Publications by authors named "Xiao Han"

1,794 Publications

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Transformer-based unsupervised contrastive learning for histopathological image classification.

Med Image Anal 2022 Jul 30;81:102559. Epub 2022 Jul 30.

Tencent AI Lab, Shenzhen 518057, China. Electronic address:

A large-scale and well-annotated dataset is a key factor for the success of deep learning in medical image analysis. However, assembling such large annotations is very challenging, especially for histopathological images with unique characteristics (e.g., gigapixel image size, multiple cancer types, and wide staining variations). To alleviate this issue, self-supervised learning (SSL) could be a promising solution that relies only on unlabeled data to generate informative representations and generalizes well to various downstream tasks even with limited annotations. In this work, we propose a novel SSL strategy called semantically-relevant contrastive learning (SRCL), which compares relevance between instances to mine more positive pairs. Compared to the two views from an instance in traditional contrastive learning, our SRCL aligns multiple positive instances with similar visual concepts, which increases the diversity of positives and then results in more informative representations. We employ a hybrid model (CTransPath) as the backbone, which is designed by integrating a convolutional neural network (CNN) and a multi-scale Swin Transformer architecture. The CTransPath is pretrained on massively unlabeled histopathological images that could serve as a collaborative local-global feature extractor to learn universal feature representations more suitable for tasks in the histopathology image domain. The effectiveness of our SRCL-pretrained CTransPath is investigated on five types of downstream tasks (patch retrieval, patch classification, weakly-supervised whole-slide image classification, mitosis detection, and colorectal adenocarcinoma gland segmentation), covering nine public datasets. The results show that our SRCL-based visual representations not only achieve state-of-the-art performance in each dataset, but are also more robust and transferable than other SSL methods and ImageNet pretraining (both supervised and self-supervised methods). Our code and pretrained model are available at https://github.com/Xiyue-Wang/TransPath.
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http://dx.doi.org/10.1016/j.media.2022.102559DOI Listing
July 2022

Using machine learning models to predict acute pancreatitis in children with pancreaticobiliary maljunction.

Surg Today 2022 Aug 9. Epub 2022 Aug 9.

Department of Radiology, Children's Hospital of Soochow University, Suzhou, 215025, China.

Purpose: To develop a model to identify risk factors and predictors of acute pancreatitis in children with pancreaticobiliary maljunction (PBM).

Methods: We screened consecutive PBM patients treated at two centers between January, 2015 and July, 2021. For machine learning, the cohort was divided randomly at a 6:4 ratio to a training dataset and a validation dataset. Three parallel models were developed using logistic regression (LR), a support vector machine (SVM), and extreme gradient boosting (XGBoost), respectively. Model performance was judged primarily based on the area under the receiver operating curves (AUC).

Results: A total of 99 patients were included in the analysis, 17 of whom suffered acute pancreatitis and 82 did not. The XGBoost (AUC = 0.814) and SVM (AUC = 0.813) models produced similar performance in the validation dataset; both outperformed the LR model (AUC = 0.805). Based on the SHapley Additive exPlanation values, the most important variable in both the XGBoost and SVM models were age, protein plugs, and white blood cell count.

Conclusions: Machine learning models, especially XGBoost and SVM, could be used to predict acute pancreatitis in children with PBM. The most important contributing factor to the models were age, protein plugs, and white blood cell count.
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http://dx.doi.org/10.1007/s00595-022-02571-yDOI Listing
August 2022

Wideband signal detection in multipath environment affected by impulsive noise.

J Acoust Soc Am 2022 Jul;152(1):445

Acoustic Science and Technology Laboratory, Harbin Engineering University, Harbin 150001, China.

Detecting the presence or absence of a known signal is an important aspect of underwater acoustic (UWA) communications as it is a vital first step to process the received data. The influence of impulsive noise and multipath propagation on detection are both considered in this paper. Many robust detectors have been designed to cope with impulsive noise, but they tend to ignore the impact of multipath propagation, which may decrease the detection probability. To emphasize the role of multipath channel, we propose two-stage detection methods. In the first stage, the channel is estimated based on robust orthogonal matching pursuit, while in the second stage, detectors that use the channel estimation from the first stage, namely augmented log-likelihood ratio detector and augmented pseudo-correlation detector, are developed. The former detector is parametric and the latter one is non-parametric. The improved performance is demonstrated in simulated multipath channel and actual UWA channel with both simulated noise and recorded snapping shrimp noise, indicating that the proposed detectors are resistant to impulsive noise. It is also shown that the use of multipath information helps to improve the detection performance.
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http://dx.doi.org/10.1121/10.0012352DOI Listing
July 2022

Dopamine D2 Receptor Signaling Attenuates Acinar Cell Necroptosis in Acute Pancreatitis through the Cathepsin B/TFAM/ROS Pathway.

Oxid Med Cell Longev 2022 26;2022:4499219. Epub 2022 Jul 26.

Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Acute pancreatitis (AP) is an inflammatory disease that is associated with trypsinogen activation, mitochondrial dysfunction, cell death, and inflammation. Dopamine D2 receptor (DRD2) plays an essential role in alleviating AP, while it is unclear whether it is involved in regulating acinar cell necroptosis. Here, we found that DRD2 agonist quinpirole alleviated acinar cell necroptosis via inhibiting cathepsin B (CTSB). Moreover, CTSB inhibition by CA-074Me ameliorated AP severity by reducing necroptosis. Notably, knockdown of TFAM reversed the therapeutic effect of either quinpirole or CA-074Me. We identified a new mechanism that DRD2 signaling inhibited CTSB and promoted the expression of mitochondrial transcription factor A(TFAM), leading to reduction of ROS production in AP, which attenuated acinar cell necroptosis ultimately. Collectively, our findings provide new evidence that DRD2 agonist could be a new potential therapeutic strategy for AP treatment.
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http://dx.doi.org/10.1155/2022/4499219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345736PMC
August 2022

GDNF Promotes Astrocyte Abnormal Proliferation and Migration Through the GFRα1/RET/MAPK/pCREB/LOXL2 Signaling Axis.

Mol Neurobiol 2022 Aug 4. Epub 2022 Aug 4.

Department of Neurobiology and Anatomy, Xuzhou Key Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.

Glial cell-line derived neurotrophic factor (GDNF) is a powerful astroglioma (AG) proliferation and migration factor that is highly expressed in AG cells derived from astrocytes. However, it is still unclear whether high levels of GDNF promote AG occurrence or if they are secondary to AG formation. We previously reported that high concentrations of GDNF (200 and 500 ng/mL) can inhibit DNA damage-induced rat primary astrocytes (RA) apoptosis, suggesting that high concentrations of GDNF may be involved in the malignant transformation of astrocytes to AG cells. Here we show that 200 ng/mL GDNF significantly increased the proliferation and migration ability of RA cells and human primary astrocytes (HA). This treatment also induced RA cells to highly express Pgf, Itgb2, Ibsp, Loxl2, Lif, Cxcl10, Serpine1, and other genes that enhance AG proliferation and migration. LOXL2 is an important AG occurrence and development promotion factor and was highly expressed in AG tissues and cells. High concentrations of GDNF promote LOXL2 expression and secretion in RA cells through GDNF family receptor alpha-1(GFRα1)/rearranged during transfection proto-oncogene (RET)/mitogen-activated protein kinase (MAPK)/phosphorylated cyclic AMP response element binding protein (pCREB) signaling. GDNF-induced LOXL2 significantly promotes RA and HA cell proliferation and migration, and increases the expression of Ccl2, Gbp5, MMP11, TNN, and other genes that regulate the extracellular microenvironment in RA cells. Our results demonstrate that high concentrations of GDNF activate LOXL2 expression and secretion via the GFRα1/RET/MAPK/pCREB signal axis, which leads to remodeling of the astrocyte extracellular microenvironment through molecules such as Ccl2, Gbp5, MMP11, TNN. This ultimately results in abnormal astrocyte proliferation and migration. Collectively, these findings suggest that high GDNF concentrations may promote the malignant transformation of astrocytes to AG cells.
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http://dx.doi.org/10.1007/s12035-022-02978-1DOI Listing
August 2022

A new capnosane-type diterpenoid from the South China sea soft coral .

Nat Prod Res 2022 Aug 4:1-6. Epub 2022 Aug 4.

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, People's Republic of China.

A new rare capnosane-type diterpenoid () along with two known compounds sarcophyolides D () and arbolide C (), were isolated from the soft coral collected at Xisha Islands in the South China Sea. The structure of was established based on comprehensive spectroscopic data, literature comparison, and quantum chemical calculations. Compound exhibited moderate anti-inflammatory activities in the zebrafish model at a concentration of 20 μM.
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http://dx.doi.org/10.1080/14786419.2022.2106568DOI Listing
August 2022

Pregnancy in patients with systemic lupus erythematosus: a systematic review.

Arch Gynecol Obstet 2022 Aug 1. Epub 2022 Aug 1.

Department of Rheumatiod and Immunology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.

Systemic lupus erythematosus (SLE)-a most common disorder in women of reproductive age-has been described to be associated with adverse pregnancy outcomes. Despite the increased health risks for the mother (preeclampsia, lupus flare, arterial hypertension, gestational diabetes mellitus and thrombotic risk when antiphospholipid antibodies are present) and fetus (miscarriage, stillbirth, premature birth, intrauterine growth restriction and neonatal lupus), the majority of patients can deliver healthy neonates. With appropriate management by a multidisciplinary team, composing rheumatologists, obstetricians and neonatologists, women with SLE can achieve better pregnancy outcomes by monitoring associated predictive indicators, raising major concern for severe complications and somewhat early delivery if necessary. In this review, we summarize the latest advances in secondary infertility and pregnancy-related risk perception for lupus patients, with an emphasis on the safety of biological agents (mainly belimumab and rituximab) and traditional therapeutic regimens.
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http://dx.doi.org/10.1007/s00404-022-06718-7DOI Listing
August 2022

Depressive Symptoms and Cognitive Decline Among Chinese Rural Elderly Individuals: A Longitudinal Study With 2-Year Follow-Up.

Front Public Health 2022 13;10:939150. Epub 2022 Jul 13.

Department of Health Service Management, School of Health Service Management, Anhui Medical University, Hefei, China.

Background: Depressive symptoms and mild cognitive impairment (MCI) are highly prevalent in rural China. The study aimed to investigate the longitudinal associations between changes in depressive symptoms and cognitive decline and MCI incidence among Chinese rural elderly individuals.

Methods: A 2-year follow-up study was conducted among 1,477 participants from the Anhui Healthy Longevity Survey (AHLS). Depressive symptoms were assessed by the 9-item Patient Health Questionnaire (PHQ-9), and cognitive status was evaluated by the Mini Mental State Examination (MMSE). Multivariable linear regression and logistic regression were employed.

Results: Every 1-unit PHQ-9 score increase was significantly associated with more cognitive decline (β = 0.157, 95% CI: 0.092, 0.221, < 0.001) and a higher risk of MCI incidence (OR = 1.063, 95% CI: 1.025, 1.103, = 0.001). The participants who experienced worsening of depression symptoms had a larger decline in the 2-year MMSE score (β = 0.650, 95% CI: 0.039, 1.261, = 0.037) and elevated risks of incident MCI (OR = 1.573, 95% CI: 1.113, 2.223, = 0.010).

Limitations: Screening tools rather than standard diagnostic procedures were used in the study. Moreover, the long-term associations still need further exploration since the follow-up time was short.

Conclusions: Increased depressive symptoms were associated with more cognitive decline and higher risks of incident MCI among Chinese rural residents.
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http://dx.doi.org/10.3389/fpubh.2022.939150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326072PMC
August 2022

Perfluorononanoate and perfluorobutane sulfonate induce cardiotoxic effects in zebrafish.

Environ Toxicol Chem 2022 Jul 28. Epub 2022 Jul 28.

Clinical Research Center, Wuhan Children's Hospital (Wuhan Medical and Health Center for Women and Children), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430016, Hubei, People's Republic of China.

Globally, per- and polyfluoroalkyl substances (PFASs) are common artificial ingredients in industrial and consumer products. Recently, they have been shown to be an emerging human health risk. Perfluorononanoic acid (PFNA)/perfluorononanoate and perfluorobutane sulfonic acid (PFBS)/perfluorobutane sulfonate cause reproductive toxicity and hepatotoxicity, disrupt thyroid functions, and damage embryonic development in zebrafish. However, cardiotoxic effects of PFNA and PFBS have not been fully established. We found that PFNA and PFBS exposures repress hatchability while increasing malformation and mortality in zebrafish embryos. Hematoxylin and eosin staining as well as assessment of the transgenic zebrafish line Tg(myl7:nDsRed) revealed that exposures of embryos to PFNA increases the occurrence of severe cardiac malformations, relative to exposure to PFBS. Moreover, we evaluated the differential expressions of cardiac development-associated genes in response to PFNA and PFBS, which validated the potential cardiotoxic effects, consistent with cardiac dysfunctions. Overall, our findings reveal novel cardiotoxic effects of PFNA and PFBS in zebrafish, implying that they may exert some cardiotoxic effect in humans. To the best of our knowledge, this is the first study to show that PFNA exerts more severe cardiotoxic effects in zebrafish, when compared to PFBS. Based on these findings, studies should evaluate the mechanisms of their cardiotoxic effects. This article is protected by copyright. All rights reserved. © 2022 SETAC.
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http://dx.doi.org/10.1002/etc.5447DOI Listing
July 2022

A Nonlinear Constitutive Model for Remoulded Fine-Grained Materials Used under the Qinghai-Tibet Railway Line.

Materials (Basel) 2022 Jul 23;15(15). Epub 2022 Jul 23.

School of Civil Engineering, Harbin Institute of Technology, Harbin 150090, China.

Using undrained triaxial shear tests, this study investigates the mechanical properties of fine-grained materials (silty clay and sand) which are extensively used for China's Qinghai-Tibet Railway (QTR) under different confining pressures () and freezing temperatures (). The results show that a reduction in causes an increase in the shear strength and elastic modulus of all the materials tested in the present study. In addition, the freezing of the silty clay has no significant effect on the type of soil behaviour (strain-hardening), whereas the freezing of the sand changes its strain-hardening behaviour to strain-softening. Supposing that the deviatoric stress-strain curves of the silty clay and sand can be divided into two segments due to a reverse bending point, it was assumed that the first segment follows a hyperbolic function. Meanwhile, the second segment is also a hyperbola, with the reverse bending point as the origin and the residual strength as the asymptote. Accordingly, a nonlinear relation constitutive model that considers and is derived. All model parameters are identified. The reasonability of the new model was verified using the test results of the materials. A comparison of the predicted and test results shows that this model can well simulate the deviatoric stress-strain response in the failure process of the tested materials. In particular, it can reflect the residual deviatoric stress after the materials' failure.
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http://dx.doi.org/10.3390/ma15155119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330695PMC
July 2022

Novel read-through fusion transcript Bcl2l2-Pabpn1 in glioblastoma cells.

J Cell Mol Med 2022 Jul 27. Epub 2022 Jul 27.

Department of Neurobiology and Anatomy, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, China.

Read-through fusion transcripts have recently been identified as chimeric RNAs and have since been linked to tumour growth in some cases. Many fusion genes generated by chromosomal rearrangements have been described in glioblastoma. However, read-through fusion transcripts between neighbouring genes in glioblastoma remain unexplored. We performed paired-end RNA-seq of rat C6 glioma cells and normal cells and discovered a read-through fusion transcript Bcl2l2-Pabpn1 in which exon 3 of Bcl-2-like protein 2 (Bcl2l2) fused to exon 2 of Polyadenylate-binding protein 1 (Pabpn1). This fusion transcript was found in both human glioblastoma and normal cells. Unlike other fusions reported in glioblastoma, Bcl2l2-Pabpn1 appeared to result from RNA processing rather than genomic rearrangement. Bcl2l2-Pabpn1 fusion transcript encoded a fusion protein with BH4, BCL and RRM domains. Functionally, Bcl2l2-Pabpn1 knockdown by targeting its fusion junction decreased its expression, and suppressed cell proliferation, migration and invasion in vitro. Mechanistically, Bcl2l2-Pabpn1 blocked Bax activity and activated PI3K/AKT pathway to promote glioblastoma progression. Together, our work characterized a glioblastoma-associated Bcl2l2-Pabpn1 fusion transcript shared by humans and rats.
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http://dx.doi.org/10.1111/jcmm.17481DOI Listing
July 2022

Integration of eQTL Analysis and GWAS Highlights Regulation Networks in Cotton under Stress Condition.

Int J Mol Sci 2022 Jul 8;23(14). Epub 2022 Jul 8.

State Key Laboratory of Cotton Biology, Chinese Academy of Agricultural Sciences, Anyang 455000, China.

The genus is one of the most economically important crops in the world. Here, we used RNA-seq to quantify gene expression in a collection of seedlings and performed eGWAS on 28,382 expressed genes. We identified a total of 30,089 eQTLs in 10,485 genes, of which >90% were trans-regulate target genes. Using luciferase assays, we confirmed that different cis-eQTL haplotypes could affect promoter activity. We found ~6600 genes associated with ~1300 eQTL hotspots. Moreover, hotspot 309 regulates the expression of 325 genes with roles in stem length, fresh weight, seed germination rate, and genes related to cell wall biosynthesis and salt stress. Transcriptome-wide association study (TWAS) identified 19 candidate genes associated with the cotton growth and salt stress response. The variation in gene expression across the population played an essential role in population differentiation. Only a small number of the differentially expressed genes between South China, the Yangtze River region, and the Yellow River region sites were located in different chromosomal regions. The eQTLs found across the duplicated gene pairs showed conservative cis- or trans- regulation and that the expression levels of gene pairs were correlated. This study provides new insights into the evolution of gene expression regulation in cotton, and identifies eQTLs in stress-related genes for use in breeding improved cotton varieties.
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http://dx.doi.org/10.3390/ijms23147564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324452PMC
July 2022

Numerical Study of Fin-and-Tube Heat Exchanger in Low-Pressure Environment: Air-Side Heat Transfer and Frictional Performance, Entropy Generation Analysis, and Model Development.

Entropy (Basel) 2022 Jun 28;24(7). Epub 2022 Jun 28.

Tianjin Key Laboratory of Refrigeration Technology, Tianjin University of Commerce, Tianjin 300134, China.

Heat transfer and frictional performance at the air-side is predominant for the application and optimization of finned tube heat exchangers. For aerospace engineering, the heat exchanger operates under negative pressure, whereas the general prediction models of convective heat transfer coefficient and pressure penalty for this scenario are rarely reported. In the current study, a numerical model is developed to determine the air-side heat transfer and frictional performance. The influence of air pressure (absolute pressure) is discussed in detail, and the entropy generation considering the effect of heat transfer and pressure drop are analyzed. Furthermore, prediction models of air-side thermal and frictional factors are also developed. The results indicate that both the convective heat transfer coefficient and pressure penalty decrease significantly with decreasing air pressure, and the air-side heat transfer coefficient is decreased by 64.6~73.3% at an air pressure of 25 kPa compared with normal environment pressure. The entropy generation by temperature difference accounts for the highest proportion of the total entropy generation. The prediction correlations of Colburn -factor and friction factor show satisfactory accuracy with the absolute mean deviations of 7.48% and 9.42%, respectively. This study can provide a reference for the practical application of fined tube heat exchangers under a negative pressure environment.
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http://dx.doi.org/10.3390/e24070887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317793PMC
June 2022

Red and Blue Light Affect the Formation of Adventitious Roots of Tea Cuttings () by Regulating Hormone Synthesis and Signal Transduction Pathways of Mature Leaves.

Front Plant Sci 2022 7;13:943662. Epub 2022 Jul 7.

Tea Research Institute, Qingdao Agricultural University, Qingdao, China.

Light is an important environmental factor which affects plant growth, through changes of intensity and quality. In this study, monochromatic white (control), red (660 nm), and blue (430 nm) light-emitting diodes (LEDs) were used to treat tea short cuttings. The results showed the most adventitious roots in blue light treated tea cuttings, but the lowest roots in that treated by red light. In order to explore the molecular mechanism of light quality affecting adventitious root formation, we performed full-length transcriptome and metabolome analyses of mature leaves under three light qualities, and then conducted weighted gene co-expression network analysis (WGCNA). Phytohormone analysis showed that Indole-3-carboxylic acid (ICA), Abscisic acid (ABA), ABA-glucosyl ester (ABA-GE), trans-Zeatin (tZ), and Jasmonic acid (JA) contents in mature leaves under blue light were significantly higher than those under white and red light. A crosstalk regulatory network comprising 23 co-expression modules was successfully constructed. Among them, the "MEblue" module which had a highly positive correlation with ICA ( = 0.92, = 4e-04). KEGG analysis showed that related genes were significantly enriched in the "Plant hormone signal transduction (ko04075)" pathway. (a flavin-containing monooxygenase), , , and were identified as hub genes, and gene expression analysis showed that the expression levels of these hub genes under blue light were higher than those under white and red light. In addition, we also identified 6 auxin transport-related genes, including , , , , , and . Except , all of these genes showed the highest expression level under blue light. In conclusion, this study elucidated the molecular mechanism of light quality regulating adventitious root formation of tea short cutting through WGCNA analysis, which provided an innovation for "rapid seedling" of tea plants.
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http://dx.doi.org/10.3389/fpls.2022.943662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301306PMC
July 2022

Effect of Nitrogen Atom Introduction on the Photocatalytic Hydrogen Evolution Activity of Covalent Triazine Frameworks: Experimental and Theoretical Study.

ChemSusChem 2022 Jul 22:e202200828. Epub 2022 Jul 22.

Shandong Key Laboratory of Chemical Energy Storage and New Battery Technology, College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng, 252059, P. R. China.

The construction of high-performance photocatalyst has always been explored. Covalent organic frameworks (COFs), especially keto-amine-linked COFs, have many advantages, such as adjustable bandgaps, π-π stacking structure, excellent response ability to visible light, high specific surface area, high mobility of carrier carriers, good physical and chemical stability, and so on, showing strong potential applications in photocatalytic solar energy conversion and hydrogen production. Two analogous covalent triazine frameworks (CTFs), T3H-CTF and T3N-CTF, have been synthesized via Schiff-base condensation reactions between 2,4,6-trihydroxybenzene-1,3,5-tricarbalehyde (MOP) and the corresponding triazine-based aromatic amines under solvothermal condition. For T3N-CTF, the peripheral aromatic linker to the central triazine unit was the pyridine unit, instead of the benzene unit in the T3H-CTF unit. T3N-CTF had a hydrogen production rate (HPR) of 6485.05 μmol g  h , much higher than that of T3H-CTF (2028.06 μmol g  h ). Accordingly, T3N-CTF had a much higher apparent quantum yield (AQY) of 12.2 % than that of T3H-CTF (4.12 %) at 405 nm. The experimental and theoretical results showed that the extended light absorption range, enlarged surface area, and enhanced separation and transportation efficiencies of charge carriers of T3N-CTF compared with T3H-CTF were uniformly induced by the introduction of peripheral nitrogen atoms into the skeleton of former CTF, which eventually boosted the visible-light induced hydrogen evolution reaction (HER). The work suggests a new method for enhancing the intrinsic HER activity by modulating the electronic features of the conjugated COFs by the introduction of pyridinic N atoms.
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http://dx.doi.org/10.1002/cssc.202200828DOI Listing
July 2022

Global trends and age-specific incidence and mortality of cervical cancer from 1990 to 2019: an international comparative study based on the Global Burden of Disease.

BMJ Open 2022 07 22;12(7):e055470. Epub 2022 Jul 22.

Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Institute of Maternal and Child Health, Wuhan, Hubei, China

Objective: To describe the trends of incidence and mortality of cervical cancer in different age groups and regions from 1990 to 2019.

Design: An international comparative study based on the Global Burden of Disease (GBD) study estimates.

Participants: Data were publicly available and individuals were not involved.

Methods: We collected detailed information on cervical cancer from the GBD study between 1990 and 2019. Average annual percentage changes (AAPCs) of age-standardised incidence and mortality rate (ASIR and ASMR) in cervical cancer, by age group and region, were calculated to quantify the temporal trends.

Results: Globally, the absolute numbers of incident cases and deaths were increasing, with the most cervical cancer cases and deaths being reported in China, India and Brazil. Although the ASIR and ASMR have declined overall from 1990 to 2019, an increasing or stable trend was also observed in East Asia and Southern sub-Saharan Africa. Particularly, we found that the age-specific AAPC of incidence showed an increasing trend in the age group of 15-49 years globally, and the high Sociodemographic Index region increased the most.

Conclusions: Cervical cancer remains a concerning disease that affects women all over the world, although the ASIR and ASMR are decreasing. Efforts to control the younger trend and to reduce the disparity between regions are imminent.
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http://dx.doi.org/10.1136/bmjopen-2021-055470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316042PMC
July 2022

Goals of care documentation by medical oncologists and oncology patient end-of-life care outcomes.

Cancer 2022 Jul 22. Epub 2022 Jul 22.

Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Background: Goals of care (GOC) documentation is important but underused. We aimed to improve oncologist GOC documentation and end-of-life (EOL) care.

Methods: In April 2020, our cancer center launched a GOC note template, including optional fields for documenting discussion with the patient about: cancer natural history, goals, and/or EOL (resuscitation preferences, hospice receptivity). Associations between GOC notes and EOL care were evaluated.

Results: Among 1721 patients dying between June 1, 2020 and June 30, 2021, median days from first GOC note (± with documentation of EOL discussion) to death was 92, whereas a GOC note including EOL discussion ("GOC EOL note"), specifically, was 31. Patients with a first GOC note >60 days before death spent fewer days inpatient (6.7 vs 10.6 days, p < .001). Among patients with GOC EOL notes, those with such documentation >30 days before death had fewer inpatient (5 vs 11, p < .001) and intensive care unit days (0.5 vs 1.5, p < .001), more hospice referrals (57% vs 44%, p = .003), and less chemotherapy ≤14 days before death (6% vs 11%, p = .010). Of 925 admissions of patients dying within ≤30 days, those with GOC EOL notes were shorter (7 vs 9 days, p = .013) but not associated with more hospice discharge (30% vs 25%, p = .163). Oncologist (vs nononcologist) GOC documentation and earlier documentation of EOL discussion were associated in subset analyses with less inpatient care and more hospice referrals.

Conclusions: Documentation of GOC, including EOL discussions, is associated with favorable performance on accepted indicators of quality EOL care.
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http://dx.doi.org/10.1002/cncr.34400DOI Listing
July 2022

In-plane strain engineering in ultrathin noble metal nanosheets boosts the intrinsic electrocatalytic hydrogen evolution activity.

Nat Commun 2022 Jul 20;13(1):4200. Epub 2022 Jul 20.

Center of Advanced Nanocatalysis (CAN), Department of Applied Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, P.R. China.

Strain has been shown to modulate the electronic structure of noble metal nanomaterials and alter their catalytic performances. Since strain is spatially dependent, it is challenging to expose the active strained interfaces by structural engineering with atomic precision. Herein, we report a facile method to manipulate the planar strain in ultrathin noble metal nanosheets by constructing amorphous-crystalline phase boundaries that can expose the active strained interfaces. Geometric-phase analysis and electron diffraction profile demonstrate the in-plane amorphous-crystalline boundaries can induce about 4% surface tensile strain in the nanosheets. The strained Ir nanosheets display substantially enhanced intrinsic activity toward the hydrogen evolution reaction electrocatalysis with a turnover frequency value 4.5-fold higher than the benchmark Pt/C catalyst. Density functional theory calculations verify that the tensile strain optimizes the d-band states and hydrogen adsorption properties of the strained Ir nanosheets to improve catalysis. Furthermore, the in-plane strain engineering method is demonstrated to be a general approach to boost the hydrogen evolution performance of Ru and Rh nanosheets.
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http://dx.doi.org/10.1038/s41467-022-31971-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300738PMC
July 2022

Achieving Record-Efficiency Organic Solar Cells upon Tuning the Conformation of Solid Additives.

J Am Chem Soc 2022 Jul 20. Epub 2022 Jul 20.

College of Materials Science and Opto-Electronic Technology, Center of Materials Science and Optoelectronics Engineering, CAS Center for Excellence in Topological Quantum Computation, CAS Key Laboratory of Vacuum Physics, University of Chinese Academy of Sciences, Beijing 100190, China.

Volatile solid additives (SADs) are considered as a simple yet effective approach to tune the film morphology for high-performance organic solar cells (OSCs). However, the structural effects of the SADs on the photovoltaic performance are still elusive. Herein, two volatilizable SADs were designed and synthesized. One is SAD1 with twisted conformation, while the other one is planar SAD2 with the S···O noncovalent intramolecular interactions (NIIs). The theoretical and experimental results revealed that the planar SAD2 with smaller space occupation can more easily insert between the Y6 molecules, which is beneficial to form a tighter intermolecular packing mode of Y6 after thermal treatment. As a result, the SAD2-treated OSCs exhibited less recombination loss, more balanced charge mobility, higher hole transfer rate, and more favorable morphology, resulting in a record power conversion efficiency (PCE) of 18.85% (certified PCE: 18.7%) for single-junction binary OSCs. The universality of this study shed light on understanding the conformation effects of SADs on photovoltaic performances of OSCs.
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http://dx.doi.org/10.1021/jacs.2c05303DOI Listing
July 2022

Whole-Exome Sequencing Uncovers Specific Genetic Variation Difference Based on Different Modes of Drug Resistance in Small Cell Lung Cancer.

Front Oncol 2022 30;12:891938. Epub 2022 Jun 30.

Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

The poor survival rate of small cell lung cancer (SCLC) is mainly related to the condition that patients with SCLC often have good responses to first-line chemotherapy initially, but later on, most of these patients relapse rapidly due to resistance to further treatment. In this study, we attempted to analyze whole-exome sequencing data based on the largest sample size to date, to develop a classifier to predict whether a patient will be chemorefractory or chemosensitive and to explicate the risk of recurrence that affects the prognosis of patients. We showed the different characteristics of somatic mutational signatures, somatic mutation genes, and distinct genome instability between chemorefractory and chemosensitive SCLC patients. Amplified mutations in the chemosensitive group inhibited the regulation of the cell cycle process, transcription factor binding, and B-cell differentiation. Analysis of deletion mutation also suggested that detection of the chromosomal-level variation might influence our treatment decisions. Higher PD-L1 expressions (based on TPS methods) were mostly present among chemosensitive patients ( = 0.026), while there were no differences in PD-L1 expressions (based on CPS methods) and CD8 TILs between the two groups. According to the model determined by logistic regression, each sample was endowed with a predictive probability value (PV). The samples were divided into a high-risk group (>0.55) and a low-risk group (≤0.55), and the survival analysis showed obvious differences between the two groups. This study provides a reference basis to translate this knowledge into practice, such as formulating personalized treatment plans, which may benefit Chinese patients with SCLC.
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http://dx.doi.org/10.3389/fonc.2022.891938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280676PMC
June 2022

The chromosome-scale genome of Phoebe bournei reveals contrasting fates of terpene synthase (TPS)-a and TPS-b subfamilies.

Plant Commun 2022 Jul 14:100410. Epub 2022 Jul 14.

State Key Laboratory of Subtropical Silviculture, College of Forestry and Biotechnology, Zhejiang A&F University, Hangzhou, Zhejiang 311300, China. Electronic address:

Terpenoids, including aromatic volatile monoterpenoids and sesquiterpenoids, serve in defense against pathogens and herbivores. Phoebe trees are remarkable for their scented wood and decay resistance. Unlike other Lauraceae species investigated thus far, Phoebe species predominantly accumulate sesquiterpenoids instead of monoterpenoids. Limited genomic data restricts the elucidation of terpenoid variation and functions. Here, we presented the chromosome-scale genome assembly of a Lauraceae tree, Phoebe bournei, and identified 72 full-length terpene synthase (TPS) genes. The genome-level comparison showed pervasive lineage-specific duplication and contraction of TPS subfamilies, which contributed to the extreme terpenoid variation within Lauraceae species. Although the TPS-a and TPS-b subfamilies were both expanded via tandem duplication in P. bournei, more TPS-a copies were retained and constitutively expressed, while more TPS-b copies were lost. The TPS-a genes on chromosome 8 functionally diverged to synthesize eight highly accumulated sesquiterpenes in P. bournei. The essential oil from P. bournei and its main component β-caryophyllene exhibited antifungal activities against the three most widespread canker pathogens of trees. The TPS-a and TPS-b subfamilies experienced contrasting fates with the evolution of P. bournei. The abundant sesquiterpenoids produced by TPS-a proteins contributed to the excellent pathogen resistance of P. bournei trees. Overall, this study sheds light on the evolution and adaptation of terpenoids in Lauraceae and provides valuable resources to boost plant immunity against pathogens in various trees and crops.
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http://dx.doi.org/10.1016/j.xplc.2022.100410DOI Listing
July 2022

Aspirin inhibits the growth of hypertrophic scar in rabbit ears via regulating Wnt/β-catenin signal pathway.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2022 Jun;47(6):698-706

Department of Rehabilitation Medicine, Third Xiangya Hospital, Central South University, Changsha 410013, China.

Objectives: Steroidal anti-inflammatory drugs have certain side effects in the treatment of hypertrophic scar, and the scar recurrence is easy after withdrawal of steroid anti-inflammatory drugs. Finding reliable alternative drugs is an effective means to improve this defect. Aspirin, a traditional non-steroidal anti-inflammatory drug, is safe for topical use and has anti-inflammatory effects similar to those of steroidal anti-inflammatory drugs, which may have similar effects on the treatment of hypertrophic scar. This study aims to investigate the inhibitory effect of aspirin on the proliferation of hypertrophic scar in rabbit ears and the underlying mechanism.

Methods: The rabbit ear hypertrophic scar models were prepared. The rabbits were randomly divided into a normal skin group (group A), a blank control group (group B), a 0.9% NaCl group (group C), a 0.2% aspirin group (group D), a 0.5% aspirin group (group E), a 2% aspirin group (group F), and a triamcinolone acetonide group (group G). Macroscopic observation of hyperplasia was performed 8 weeks after local injection of the scar, followed by collecting the scar tissue samples for HE staining, Masson staining, and immunohistochemistry, respectively to assess the proliferation of fibroblasts and collagen fibers, and calculate the hypertrophic index, microvessel density, and immunohistochemical score.

Results: All rabbit ear hypertrophic scar models were successfully constructed. In groups B and C, the hypertrophic scar edge was irregular, with reddish protruding epidermis, significant contracture and hard touch. In group D, E, and F, with the increase of aspirin administration concentration, the scar became thinner and gradually flat, the proliferation of fibrocytes and collagen fibers was weakened, and the hypertrophic index was gradually decreased (<0.05). Immunohistochemistry showed that the expression of β-catenin was decreased in the group D, E and F in turn, and the immunohistochemical score was gradually decreased (<0.05). There was no significant difference in hypertrophic index, microvessel density, and immunohistochemical score (all >0.05).

Conclusions: Local injection of aspirin can reduce the generation of hypertrophic scar in a dose-dependent manner within a certain concentration range; aspirin inhibits the growth of hypertrophic scar in rabbit ears by inhibiting Wnt/β-catenin signal pathway; 2% aspirin and 40 mg/mL triamcinolone acetonide have similar curative efficacy on hypertrophic scar.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2022.220038DOI Listing
June 2022

Feasibility and safety of pedicled autologous bronchial flap reconstruction airway instead of sleeve lobectomy in partial lung cancer surgery.

Transl Lung Cancer Res 2022 Jun;11(6):1019-1026

Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: A sleeve lobectomy is a routine operation in thoracic surgery. However, sleeve lobectomy is not only a complex operation, but also has the risk of anastomotic leakage and stenosis. We used bronchial flap to reconstruct the airway instead of sleeve lobectomy. The above disadvantages can be avoided because the bronchial flap reconstruction airway has no anastomosis. This technique has not previously been reported. This paper discusses the feasibility and safety of reconstructing the bronchus with the pedicle autogenous bronchus flap in lung cancer surgery.

Methods: During the operation, when the tumor tissue had invaded ≤1/3 of the circumference of the lobar bronchus, the bronchus wall was removed at least 5 mm away from the tumor, but the contralateral healthy bronchus wall was preserved. The healthy bronchial wall was made into a "tongue-shaped" pedicled autogenous bronchial flap, approximately the size of the bronchial defect, and the flap was turned up or down to repair the root defect of the bronchus. The patients were examined every 3 months after surgery by chest computed tomography (CT) to observe the re-expansion of lung and reconstruction of the bronchus, and analyze the incidence of bronchus stenosis and local recurrence.

Results: The lobar bronchus was successfully reconstructed with the pedicled autologous bronchial flap in 45 patients; 36 males and 9 females with an average age of 56.5 years. The diameters of the tumors ranged from 3-12 cm. The pathological examination results showed that the margin of bronchus was negative. There was no perioperative death or bronchopleural fistula. The bronchoscopy showed that the reconstructed bronchus healed well, and no atelectasis or bronchostenosis was found in the follow-up period.

Conclusions: This is the first report on the application of the pedicled autogenous bronchial flap being used to reconstruct the airway instead of a sleeve lobectomy in lung cancer surgery. In the radical resection of lung cancer, the operation can simplify the operation process, and reduce the risk of anastomotic leakage or stenosis. The operation is safe and feasible, and should be more widely used.
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http://dx.doi.org/10.21037/tlcr-22-347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271431PMC
June 2022

An insight into planarian regeneration.

Cell Prolif 2022 Jul 10:e13276. Epub 2022 Jul 10.

CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.

Background: Planarian has attracted increasing attentions in the regeneration field for its usefulness as an important biological model organism attributing to its strong regeneration ability. Both the complexity of multiple regulatory networks and their coordinate functions contribute to the maintenance of normal cellular homeostasis and the process of regeneration in planarian. The polarity, size, location and number of regeneration tissues are regulated by diverse mechanisms. In this review we summarize the recent advances about the importance genetic and molecular mechanisms for regeneration control on various tissues in planarian.

Methods: A comprehensive literature search of original articles published in recent years was performed in regards to the molecular mechanism of each cell types during the planarian regeneration, including neoblast, nerve system, eye spot, excretory system and epidermal.

Results: Available molecular mechanisms gave us an overview of regeneration process in every tissue. The sense of injuries and initiation of regeneration is regulated by diverse genes like follistatin and ERK signaling. The Neoblasts differentiate into tissue progenitors under the regulation of genes such as egfr-3. The regeneration polarity is controlled by Wnt pathway, BMP pathway and bioelectric signals. The neoblast within the blastema differentiate into desired cell types and regenerate the missing tissues. Those tissue specific genes regulate the tissue progenitor cells to differentiate into desired cell types to complete the regeneration process.

Conclusion: All tissue types in planarian participate in the regeneration process regulated by distinct molecular factors and cellular signaling pathways. The neoblasts play vital roles in tissue regeneration and morphology maintenance. These studies provide new insights into the molecular mechanisms for regulating planarian regeneration.
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http://dx.doi.org/10.1111/cpr.13276DOI Listing
July 2022

Renal cell carcinoma with extensive tumor thrombus.

Am J Med Sci 2022 Jul 7. Epub 2022 Jul 7.

Department of Radiology, Yantai Affiliated Hospital of Binzhou Medical Universtiy, Yantai, Shandong, China. Electronic address:

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http://dx.doi.org/10.1016/j.amjms.2022.07.001DOI Listing
July 2022

Magnetoacoustic Wave Scattering and Dynamic Stress Concentration around the Elliptical Opening in Exponential-Gradient Piezomagnetic Materials.

Materials (Basel) 2022 Jun 29;15(13). Epub 2022 Jun 29.

College of Electrical Engineering, Zhejiang University, Hangzhou 310027, China.

Based on the theory of magnetoacoustic coupled dynamics, the purpose of this paper is to evaluate the dynamic stress concentration near an elliptical opening in exponential-gradient piezomagnetic materials under the action of antiplane shear waves. By the wave function expansion, the solutions for the acoustic wave fields and magnetic fields can be obtained. Stress analysis is performed by the complex function method and the conformal mapping method, which are used to solve the boundary conditions problem, and is used to express the dynamic stress concentration coefficient (DSCC) theoretically. As cases, numerical results of DSCCs are plotted and discussed with different incident wave numbers and material parameters by numerical simulation. Compared with circular openings, elliptical openings are widely used in material processing techniques and are more difficult to solve. Numerical results show that the dynamic stress concentration coefficient at the elliptical opening is strongly dependent on various parameters, which indicates that the elliptical opening is more likely to cause crack and damage to exponential-gradient piezomagnetic materials.
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http://dx.doi.org/10.3390/ma15134564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267831PMC
June 2022

Full-Length Transcriptome Sequencing Reveals Alternative Splicing and lncRNA Regulation during Nodule Development in .

Int J Mol Sci 2022 Jul 1;23(13). Epub 2022 Jul 1.

State Key Laboratory of Crop Stress Adaptation and Improvement, School of Life Sciences, Henan University, Kaifeng 475001, China.

Alternative splicing (AS) is a ubiquitous phenomenon among eukaryotic intron-containing genes, which greatly contributes to transcriptome and proteome diversity. Here we performed the isoform sequencing (Iso-Seq) of soybean underground tissues inoculated and uninoculated with Rhizobium and obtained 200,681 full-length transcripts covering 26,183 gene loci. It was found that 80.78% of the multi-exon loci produced more than one splicing variant. Comprehensive analysis of these identified 7874 differentially splicing events with highly diverse splicing patterns during nodule development, especially in defense and transport-related processes. We further profiled genes with differential isoform usage and revealed that 2008 multi-isoform loci underwent stage-specific or simultaneous major isoform switches after Rhizobium inoculation, indicating that AS is a vital way to regulate nodule development. Moreover, we took the lead in identifying 1563 high-confidence long non-coding RNAs (lncRNAs) in soybean, and 157 of them are differentially expressed during nodule development. Therefore, our study uncovers the landscape of AS during the soybean- interaction and provides systematic transcriptomic data for future study of multiple novel directions in soybean.
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http://dx.doi.org/10.3390/ijms23137371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266934PMC
July 2022

National Ballad Creation Education Under Artificial Intelligence and Big Data.

Front Psychol 2022 21;13:883096. Epub 2022 Jun 21.

Department of Digital Image, Sang Myung University, Seoul, South Korea.

The efficiency of manual ballad creation is low, and the status quo of music creation education still needs to be improved. Therefore, how to upgrade the creative level of students is studied to improve the creative ability of China's unique ballad culture. The concept of music theory in the process of music creation is explained, and the application of big data in the NetEase cloud music platform is excavated. Besides, the optical music organization (OMR) method based on artificial intelligence (AI) is proposed using a learning method of style imitation. This method is applied to students' ballad creation education and tested in the school creation curriculum. It is found that the novelty of the ballads created by the system is slightly better than the existing ballads by comparing the ballads created by the machine with those used as imitation templates. In addition, the students' learning interests and creative achievement are compared through the comparative experiment. The results show that students' interest in learning has been significantly improved, and their creative performance in oral language has also been enhanced compared with the control class. As a result, this system is considered to be able to be applied in students' ballad creation courses and provide some basis for AI creation in related fields.
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http://dx.doi.org/10.3389/fpsyg.2022.883096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9253618PMC
June 2022

A Novel ATM Antisense Transcript ATM-AS Positively Regulates ATM Expression in Normal and Breast Cancer Cells.

Curr Med Sci 2022 Jul 5. Epub 2022 Jul 5.

Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, 210000, China.

Objective: The ataxia telangiectasia mutated (ATM) gene is a master regulator in cellular DNA damage response. The dysregulation of ATM expression is frequent in breast cancer, and is known to be involved in the carcinogenesis and prognosis of cancer. However, the underlying mechanism remains unclear. The bioinformatic analysis predicted a potential antisense transcript ATM-antisense (AS) from the opposite strand of the ATM gene. The purpose of this study was to identify ATM-AS and investigate the possible effect of ATM-AS on the ATM gene regulation.

Methods: Single strand-specific RT-PCR was performed to verify the predicted antisense transcript ATM-AS within the ATM gene locus. qRT-PCR and Western blotting were used to detect the expression levels of ATM-AS and ATM in normal and breast cancer cell lines as well as in tissue samples. Luciferase reporter gene assays, biological mass spectrometry, ChIP-qPCR and RIP were used to explore the function of ATM-AS in regulating the ATM expression. Immunofluorescence and host-cell reactivation (HCR) assay were performed to evaluate the biological significance of ATM-AS in ATM-mediated DNA damage repair. Breast cancer tissue samples were used for evaluating the correlation of the ATM-AS level with the ATM expression as well as prognosis of the patients.

Results: The ATM-AS significantly upregulated the ATM gene activity by recruiting KAT5 histone acetyltransferase to the gene promoter. The reduced ATM-AS level led to the abnormal downregulation of ATM expression, and impaired the ATM-mediated DNA damage repair in normal breast cells in vitro. The ATM-AS level was positively correlated with the ATM expression in the examined breast cancer tissue samples, and the patient prognosis.

Conclusion: The present study demonstrated that ATM-AS, an antisense transcript located within the ATM gene body, is an essential positive regulator of ATM expression, and functions by mediating the binding of KAT5 to the ATM promoter. These findings uncover the novel mechanism underlying the dysregulation of the ATM gene in breast cancer, and enrich our understanding of how an antisense transcript regulates its host gene.
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http://dx.doi.org/10.1007/s11596-022-2585-5DOI Listing
July 2022

Isolated compounds from Dracaena angustifolia Roxb and acarbose synergistically/additively inhibit α-glucosidase and α-amylase: an in vitro study.

BMC Complement Med Ther 2022 Jul 2;22(1):177. Epub 2022 Jul 2.

Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou, 571158, People's Republic of China.

Background: As a traditional herbal medicine, Dracaena angustifolia Roxb has been used as an anti-inflammatory agent by the Li people in Hainan, China. In preliminary phytochemical studies conducted in our lab, its fractions were found to inhibit α-glucosidase in vitro, indicating a potential for alleviating glucose dysregulation.

Methods: Through in vitro enzymatic assays, the abilities of the separated components to affect α-glucosidase and α-amylase were evaluated. By establishing concentration gradients and generating Lineweaver-Burk plots, the corresponding inhibition modes together with kinetic parameters were assessed. Following the evaluation of the outcomes of their combination with acarbose, computational docking and molecular dynamic simulations were carried out to analyse the interaction mechanisms and perform virtual screening against human enzymes.

Results: Compared with acarbose, 7 compounds, including flavonoid derivatives, amides and aromatic derivatives, with higher α-glucosidase inhibitory efficiencies were confirmed. It was found that those competitive/mixed candidates and acarbose interacted synergistically or additively on α-glucosidase. Moreover, 3 of them were able to inhibit α-amylase in mixed mode, and additive effects were observed in combination with acarbose. Through in silico docking, it was found that the active site residues as well as adjacent residues were involved in α-glucosidase and α-amylase binding, which were mainly achieved through hydrogen bonding. Among those dual-function flavonoids, Compound 9 was predicted to be a considerable inhibitor of human enzymes, as the formation of ligand-enzyme complexes was mediated by the residues responsible for substrate recognition and catalysis, the stabilities of which were reiterated by molecular dynamics simulations.

Conclusion: Despite their mild effects on α-amylase, considerable α-glucosidase inhibitory efficiencies and potential synergy with acarbose were exhibited by these natural candidates. Furthermore, a stable ligand, human α-glucosidase, was predicted by the performed simulations, which provided useful information for the application of Dracaena angustifolia Roxb in diabetes treatment.
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http://dx.doi.org/10.1186/s12906-022-03649-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250238PMC
July 2022
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