Publications by authors named "Zhe Wang"

2,589 Publications

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Young population consume twice as much artificial sweetener than the general population - A wastewater-based assessment in China.

Sci Total Environ 2022 May 23:156200. Epub 2022 May 23.

Queensland Alliance for Environmental Health Sciences (QAEHS), The University of Queensland, 20 Cornwall Street, Woolloongabba, 4102, Queensland, Australia.

Understanding artificial sweetener consumption patterns and levels in different demographics is important for formulating public health policies on controlling sugar consumption. There is a considerable knowledge gap with respect to the pattern of artificial sweetener consumption in China. To narrow this gap, wastewater analysis was used to assess the temporal patterns of consumption of seven artificial sweeteners in an urban population and a university town in a megacity in South China over a one-year period. Daily influent wastewater samples were collected from an urban catchment and weekly samples collected from a university sub-catchment. Population normalized per capita consumption of the four detected artificial sweeteners (cyclamate, acesulfame, sucralose and saccharin) in the university catchment (1.0-5.9 mg d p) was much higher than those in urban catchment (0.5-1.3 mg d p), indicating younger population consume more artificial sweeteners than the general population. The daily consumption of artificial sweeteners was found to be stable throughout the week in the urban catchment. Time-series analysis showed that an average increase in temperature of 1 °C was associated with an increase consumption of 33 μg d p for acesulfame, 15 μg d p for sucralose and 14 μg d p for saccharin. This was the first study that objectively quantified the greater consumption of artificial sweeteners (proxy for consumption of artificially sweetened food and beverages) in a younger age group when compared to the general population, which could potentially pose a risk of health related diseases.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156200DOI Listing
May 2022

Dual-Layer Multichannel Hydrogel Evaporator with High Salt Resistance and a Hemispherical Structure toward Water Desalination and Purification.

ACS Appl Mater Interfaces 2022 May 25. Epub 2022 May 25.

Department of Macromolecular Materials and Engineering, School of Chemistry and Materials Science, Heilongjiang University, Harbin 150080, China.

Interfacial solar steam generation technology has been considered as one of the most promising methods for seawater desalination. However, in practical applications, salt precipitation on the evaporation surface reduces the evaporation rate and impairs long-term stability. Herein, a dual-layer hydrogel-based evaporator that contains a microchannel-structured water-supplying layer and a nanoporous light-absorbing layer was synthesized via sol-gel transition and "hot-ice" template methods. Contributed by the designed structure-induced accelerated salt ion exchange, the hemispherical dual-layer hydrogel evaporator showed excellent salt formation resistance property, as well as a high evaporation rate reaching 2.03 kg m h even under high brine concentration conditions. Furthermore, the hydrogel-based evaporator also demonstrated excellent ion rejection, high/low pH tolerance, and excellent purification properties toward heavy metals and organic dyes. It is believed that this type of dual-layer multichannel evaporator is promising to be used in seawater desalination, water pollution treatment, and other environmental remediation-related applications.
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http://dx.doi.org/10.1021/acsami.2c06370DOI Listing
May 2022

Neurosurgery Research Output in Ethiopia: A Scoping Review.

World Neurosurg 2022 May 21. Epub 2022 May 21.

Neurosurgery Units, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia; Department of Clinical Medicine, University of Bergen, Bergen, Norway.

Introduction: Neurosurgery-specific research plays a critical role in improving outcomes in patients with neurosurgical diseases. Despite the high burden of neurosurgical pathologies in Ethiopia, little is known on types of neurosurgical research coming from Ethiopia. The goal of this scoping review is to assess the quantity and types of neurosurgical research published in peer-reviewed journals by authors from Ethiopia.

Methods: PubMed, CINAHL, Embase, and Scopus were searched for Ethiopian neurosurgery literature published from 2001 to 2021. We selected articles based on the following criteria: articles must (1) discuss topics within neurosurgery, and (2) focus on clinical practice and/or public health in Ethiopia. We collected data on research originality, study designs, and clinical vs public health research. The frequencies and percentages of categorical variables were reported. All analyses were conducted using Jamovi software.

Results: Of the total of 362 results, 89 neurosurgical research papers were included in the final analysis. Of the 89 publications, case reports/ series were most common (28.7%), followed by retrospective cohort (20.7%) and prospective cohort studies (18.4%). There were 8 (9.2%) literature reviews and 1 (1.1%) systematic review and meta-analysis. No randomized controlled trial (RCT) was found. Of all articles, 66 (75.9%) focused on clinical practice, and 21 (23.6%) were related to the public health aspect of neurosurgery. Forty-two (48.3%) articles included authors only from Ethiopia; 37 (42.5%) articles involved collaboration between Ethiopian and authors from another country, and 8 articles (9.2%) did not have Ethiopian authors.

Conclusion: Neurosurgery research from Ethiopia is lacking, despite its high disease burden. Case reports/series and cohort studies remain to be the mainstay, with few systematic reviews and no RCT. International collaboration accounts for approximately half of Ethiopian neurosurgery research output. Further research support and infrastructure should be developed to encourage neurosurgery publications from Ethiopia.
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http://dx.doi.org/10.1016/j.wneu.2022.05.053DOI Listing
May 2022

Multiagent off-screen behavior prediction in football.

Sci Rep 2022 May 23;12(1):8638. Epub 2022 May 23.

DeepMind, London, UK.

In multiagent worlds, several decision-making individuals interact while adhering to the dynamics constraints imposed by the environment. These interactions, combined with the potential stochasticity of the agents' dynamic behaviors, make such systems complex and interesting to study from a decision-making perspective. Significant research has been conducted on learning models for forward-direction estimation of agent behaviors, for example, pedestrian predictions used for collision-avoidance in self-driving cars. In many settings, only sporadic observations of agents may be available in a given trajectory sequence. In football, subsets of players may come in and out of view of broadcast video footage, while unobserved players continue to interact off-screen. In this paper, we study the problem of multiagent time-series imputation in the context of human football play, where available past and future observations of subsets of agents are used to estimate missing observations for other agents. Our approach, called the Graph Imputer, uses past and future information in combination with graph networks and variational autoencoders to enable learning of a distribution of imputed trajectories. We demonstrate our approach on multiagent settings involving players that are partially-observable, using the Graph Imputer to predict the behaviors of off-screen players. To quantitatively evaluate the approach, we conduct experiments on football matches with ground truth trajectory data, using a camera module to simulate the off-screen player state estimation setting. We subsequently use our approach for downstream football analytics under partial observability using the well-established framework of pitch control, which traditionally relies on fully observed data. We illustrate that our method outperforms several state-of-the-art approaches, including those hand-crafted for football, across all considered metrics.
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http://dx.doi.org/10.1038/s41598-022-12547-0DOI Listing
May 2022

Use of machine-learning algorithms to aid in the early detection of leptospirosis in dogs.

J Vet Diagn Invest 2022 May 21:10406387221096781. Epub 2022 May 21.

Department of Medicine and Epidemiology, University of California-Davis, Davis, CA, USA.

Leptospirosis is a life-threatening, zoonotic disease with various clinical presentations, including renal injury, hepatic injury, pancreatitis, and pulmonary hemorrhage. With prompt recognition of the disease and treatment, 90% of infected dogs have a positive outcome. Therefore, rapid, early diagnosis of leptospirosis is crucial. Testing for -specific serum antibodies using the microscopic agglutination test (MAT) lacks sensitivity early in the disease process, and diagnosis can take >2 wk because of the need to demonstrate a rise in titer. We applied machine-learning algorithms to clinical variables from the first day of hospitalization to create machine-learning prediction models (MLMs). The models incorporated patient signalment, clinicopathologic data (CBC, serum chemistry profile, and urinalysis = blood work [BW] model), with or without a MAT titer obtained at patient intake (=BW + MAT model). The models were trained with data from 91 dogs with confirmed leptospirosis and 322 dogs without leptospirosis. Once trained, the models were tested with a cohort of dogs not included in the model training (9 leptospirosis-positive and 44 leptospirosis-negative dogs), and performance was assessed. Both models predicted leptospirosis in the test set with 100% sensitivity (95% CI: 70.1-100%). Specificity was 90.9% (95% CI: 78.8-96.4%) and 93.2% (95% CI: 81.8-97.7%) for the BW and BW + MAT models, respectively. Our MLMs outperformed traditional acute serologic screening and can provide accurate early screening for the probable diagnosis of leptospirosis in dogs.
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http://dx.doi.org/10.1177/10406387221096781DOI Listing
May 2022

A comprehensive analysis of potential gastric cancer prognostic biomarker ITGBL1 associated with immune infiltration and epithelial-mesenchymal transition.

Biomed Eng Online 2022 May 20;21(1):30. Epub 2022 May 20.

Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Putuo District, Shanghai, 200065, People's Republic of China.

Background: Integrin, beta-like 1 (ITGBL1) is involved in a variety of human malignancies. However, the information on the involvement of ITGBL1 in gastric carcinoma (GC) is limited. Hence, this study aimed further to explore the functions and mechanisms of ITGBL1 in GC.

Methods: First, multiple bioinformatics databases, including Oncomine, Tumor Immune Estimation Resource, UALCAN, and Kaplan-Meier Plotter, were used to predict the expression level and prognostic value of ITGBL1, as well as its association with immune infiltration and epithelial-mesenchymal transition (EMT) in GC. Quantitative reverse transcription-polymerase chain reaction and immunohistochemical analysis were used to detect the expression of ITGBL1 in both GC tissues and cells. Then, targeted silencing of ITGBL1 in GC cells was further used to examine the biological functions of ITGBL1.

Results: These databases revealed that ITGBL1 was overexpressed and affected the overall survival in GC. Besides, the expression of ITGBL1 positively correlated with immune-infiltrating cells and EMT-related markers. Subsequently, molecular biology experiments verified these predictions. In GC tissues and cells, ITGBL1 was notably overexpressed. Loss-of-function studies showed that the knockdown of ITGBL1 significantly suppressed migration and invasion but promoted apoptosis in MGC803 GC cells. Furthermore, the inhibition of ITGBL1 resulted in remarkably increased protein expression levels of cadherin 1, while the expression of Vimentin, Snail, and transforming growth factor-β1 was downregulated, indicating the initiation and progression of GC caused by ITGBL1 partly via inducing EMT.

Conclusions: To sum up, the findings indicated that ITGBL1 acted as a valuable oncogenic factor in GC.
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http://dx.doi.org/10.1186/s12938-022-00998-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9123716PMC
May 2022

Isoleucine stimulates mTOR and SREBP-1c gene expression for milk synthesis in mammary epithelial cells through BRG1-mediated chromatin remodeling.

Br J Nutr 2022 May 20:1-33. Epub 2022 May 20.

College of Animal Science, Yangtze University, Jingzhou, 434023, China.

Several amino acids can stimulate milk synthesis in mammary epithelial cells (MECs), however, the regulatory role of isoleucine (Ile) and underlying molecular mechanism remain poorly understood. In this study, we aimed to evaluate the regulatory effects of Ile on milk protein and fat synthesis in MECs and reveal the mediation mechanism of Brahma-related gene 1 (BRG1) on this regulation. Ile dose-dependently affected milk protein and fat synthesis, mTOR phosphorylation, SREBP-1c expression and maturation, and BRG1 protein expression in bovine MECs. PI3K inhibition by LY294002 treatment blocked the stimulation of Ile on BRG1 expression. BRG1 knockdown and gene activation experiments showed that it mediated the stimulation of Ile on milk protein and fat synthesis, mTOR phosphorylation, and SREBP-1c expression and maturation in MECs. ChIP-PCR analysis detected that BRG1 bound to the promoters of mTOR and SREBP-1c, and ChIP-qPCR further detected that these binding were increased by Ile stimulation. In addition, BRG1 positively regulated the binding of H3K27ac to these two promoters, while it negatively affected the binding of H3K27me3 to these promoters. BRG1 knockdown blocked the stimulation of Ile on these two gene expression. The expression of BRG1 was higher in mouse mammary gland in the lactating period, compared with that in the puberty or dry period. Taken together, these experimental data reveal that Ile stimulates milk protein and fat synthesis in MECs via the PI3K-BRG1-mTOR/SREBP-1c pathway.
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http://dx.doi.org/10.1017/S0007114522001544DOI Listing
May 2022

The Value of Rare Genetic Variation in the Prediction of Common Obesity in European Ancestry Populations.

Front Endocrinol (Lausanne) 2022 3;13:863893. Epub 2022 May 3.

Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, United States.

Polygenic risk scores (PRSs) aggregate the effects of genetic variants across the genome and are used to predict risk of complex diseases, such as obesity. Current PRSs only include common variants (minor allele frequency (MAF) ≥1%), whereas the contribution of rare variants in PRSs to predict disease remains unknown. Here, we examine whether augmenting the standard common variant PRS (PRS) with a rare variant PRS (PRS) improves prediction of obesity. We used genome-wide genotyped and imputed data on 451,145 European-ancestry participants of the UK Biobank, as well as whole exome sequencing (WES) data on 184,385 participants. We performed single variant analyses (for both common and rare variants) and gene-based analyses (for rare variants) for association with BMI (kg/m), obesity (BMI ≥ 30 kg/m), and extreme obesity (BMI ≥ 40 kg/m). We built PRSs and PRSs using a range of methods (Clumping+Thresholding [C+T], PRS-CS, lassosum, gene-burden test). We selected the best-performing PRSs and assessed their performance in 36,757 European-ancestry unrelated participants with whole genome sequencing (WGS) data from the Trans-Omics for Precision Medicine (TOPMed) program. The best-performing PRS explained 10.1% of variation in BMI, and 18.3% and 22.5% of the susceptibility to obesity and extreme obesity, respectively, whereas the best-performing PRS explained 1.49%, and 2.97% and 3.68%, respectively. The PRS was associated with an increased risk of obesity and extreme obesity (OR = 1.37 per SD, = 1.7x10; OR = 1.55 per SD, = 3.8x10), which was attenuated, after adjusting for PRS (OR = 1.08 per SD, = 9.8x10; OR= 1.09 per SD, = 0.02). When PRS and PRS are combined, the increase in explained variance attributed to PRS was small (incremental Nagelkerke R = 0.24% for obesity and 0.51% for extreme obesity). Consistently, combining PRS to PRS provided little improvement to the prediction of obesity (PRS AUC = 0.591; PRS AUC = 0.708; PRS AUC = 0.710). In summary, while rare variants show convincing association with BMI, obesity and extreme obesity, the PRS provides limited improvement over PRS in the prediction of obesity risk, based on these large populations.
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http://dx.doi.org/10.3389/fendo.2022.863893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9110787PMC
May 2022

Acellular Dermal Matrix Prevents Esophageal Stricture After Full Circumferential Endoscopic Submucosal Dissection in a Porcine Model.

Front Bioeng Biotechnol 2022 2;10:884502. Epub 2022 May 2.

Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China.

Esophageal stricture is a common complication after endoscopic submucosal dissection (ESD), especially in full circumferential ESD. This study investigated fully covered self-expanding metal stent (FCSEMS) placement with an acellular dermal matrix (ADM) for preventing post-ESD esophageal stricture. Twelve Bama minipigs were randomly divided into two groups, which underwent full circumferential ESD in the distal esophagus. In group A, an FCSEMS with ADM was placed at the mucosal defect, whereas group B underwent standard FCSEMS placement. The stent was removed during gastroscopy 2 weeks after the ESD procedure. At the fourth week, gastroscopy was repeated to evaluate local healing and stenosis. The animals were sacrificed, esophageal specimens were obtained for macroscopic and histological evaluation, and serum C-reactive protein (CRP) levels were quantified. Four weeks post ESD dysphagia occurrence was lesser in group A than in group B. Group A demonstrated lesser esophageal stricture on macroscopic evaluation (21.02 ± 16.65% vs. 57.41 ± 8.48%, = 0.001) in the form of enhanced re-epithelization (99.13 ± 0.98% vs. 96.63 ± 1.64%, = 0.009), diminished submucosal fibrosis (1117.53 ± 188.83 um vs. 1834.69 ± 421.99 um, = 0.003), and attenuated inflammatory infiltration (121.00 ± 30.66 vs. 188.17 ± 64.92, = 0.045). The increase in the serum CRP level was lower in group A than in group B at 4 weeks post-ESD. FCSEMS combined with ADM can enhance re-epithelization in the process of wound healing and significantly reduce the degree of esophageal stenosis after circumferential ESD. This study provided important preclinical findings for subsequent clinical trials.
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http://dx.doi.org/10.3389/fbioe.2022.884502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108161PMC
May 2022

A nonendemic analysis of the patterns and prognosis of de novo metastatic nasopharyngeal carcinomas in older patients aged ≥ 65 years.

Sci Rep 2022 May 18;12(1):8321. Epub 2022 May 18.

Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510062, China.

This study aimed to investigate the prognostic factors related to overall survival (OS) and cancer-specific survival (CSS) in patients with de novo metastatic nasopharyngeal carcinoma (NPC) aged ≥ 65 years in nonendemic areas. The Surveillance, Epidemiology, and End Results database was queried for elderly patients with M1 stage NPC at initial diagnosis between 2004 and 2016. This study examined 100 patients and evaluated the relationship of sex, age, race, pathological grade, T stage, N stage, sequence number, site of metastasis, number of metastatic organs, and other related factors with OS and CSS. The median survival and follow-up time were 10 and 48 months, respectively. The survival curves for race, bone metastasis, radiation, and chemotherapy significantly affected OS on the log-rank test. Advanced N stage and liver metastasis may be associated with poor survival. Race, bone metastasis, and chemotherapy were independent prognostic factors of OS. Bone metastasis was associated with poor survival. The survival curves for CSS were significantly different between races, N stage, sequence number, and bone metastasis. In Cox regression multivariate analysis, only sequence number had an independent effect on prognosis. This study revealed that chemotherapy prolonged survival in elderly patients with metastatic NPC, whereas bone metastasis shortened survival.
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http://dx.doi.org/10.1038/s41598-022-12368-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117287PMC
May 2022

fastDRH: a webserver to predict and analyze protein-ligand complexes based on molecular docking and MM/PB(GB)SA computation.

Brief Bioinform 2022 May 18. Epub 2022 May 18.

Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, College of Pharmaceutical Sciences and Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310058, China.

Predicting the native or near-native binding pose of a small molecule within a protein binding pocket is an extremely important task in structure-based drug design, especially in the hit-to-lead and lead optimization phases. In this study, fastDRH, a free and open accessed web server, was developed to predict and analyze protein-ligand complex structures. In fastDRH server, AutoDock Vina and AutoDock-GPU docking engines, structure-truncated MM/PB(GB)SA free energy calculation procedures and multiple poses based per-residue energy decomposition analysis were well integrated into a user-friendly and multifunctional online platform. Benefit from the modular architecture, users can flexibly use one or more of three features, including molecular docking, docking pose rescoring and hotspot residue prediction, to obtain the key information clearly based on a result analysis panel supported by 3Dmol.js and Apache ECharts. In terms of protein-ligand binding mode prediction, the integrated structure-truncated MM/PB(GB)SA rescoring procedures exhibit a success rate of >80% in benchmark, which is much better than the AutoDock Vina (~70%). For hotspot residue identification, our multiple poses based per-residue energy decomposition analysis strategy is a more reliable solution than the one using only a single pose, and the performance of our solution has been experimentally validated in several drug discovery projects. To summarize, the fastDRH server is a useful tool for predicting the ligand binding mode and the hotspot residue of protein for ligand binding. The fastDRH server is accessible free of charge at http://cadd.zju.edu.cn/fastdrh/.
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http://dx.doi.org/10.1093/bib/bbac201DOI Listing
May 2022

Non-rapid eye movement sleep and wake neurophysiology in schizophrenia.

Elife 2022 May 17;11. Epub 2022 May 17.

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, United States.

Motivated by the potential of objective neurophysiological markers to index thalamocortical function in patients with severe psychiatric illnesses, we comprehensively characterized key non-rapid eye movement (NREM) sleep parameters across multiple domains, their interdependencies, and their relationship to waking event-related potentials and symptom severity. In 72 schizophrenia (SCZ) patients and 58 controls, we confirmed a marked reduction in sleep spindle density in SCZ and extended these findings to show that fast and slow spindle properties were largely uncorrelated. We also describe a novel measure of slow oscillation and spindle interaction that was attenuated in SCZ. The main sleep findings were replicated in a demographically distinct sample, and a joint model, based on multiple NREM components, statistically predicted disease status in the replication cohort. Although also altered in patients, auditory event-related potentials elicited during wake were unrelated to NREM metrics. Consistent with a growing literature implicating thalamocortical dysfunction in SCZ, our characterization identifies independent NREM and wake EEG biomarkers that may index distinct aspects of SCZ pathophysiology and point to multiple neural mechanisms underlying disease heterogeneity. This study lays the groundwork for evaluating these neurophysiological markers, individually or in combination, to guide efforts at treatment and prevention as well as identifying individuals most likely to benefit from specific interventions.
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http://dx.doi.org/10.7554/eLife.76211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9113745PMC
May 2022

Exposure of the Heart in Lung Cancer Radiation Therapy: A Systematic Review of Heart Doses Published During 2013 to 2020.

Radiother Oncol 2022 May 13. Epub 2022 May 13.

St Luke's Radiation Oncology Network, St. Luke's Hospital, Dublin, Ireland; School of Medicine, Trinity College Dublin, Ireland; Trinity St James's Cancer Institute, St. James's Hospital, Dublin, Ireland.

Background And Purpose: Lung cancer radiotherapy increases the risk of cardiotoxicity and heart radiation dose is an independent predictor of poor survival. This study describes heart doses and strategies aiming to reduce exposure.

Materials And Methods: A systematic review of lung cancer dosimetry studies reporting heart doses published 2013-2020 was undertaken. Doses were compared according to laterality, region irradiated, treatment modality (stereotactic ablative body radiotherapy (SABR) and non-SABR), planning technique, and respiratory motion management.

Results: For 392 non-SABR regimens in 105 studies, the average MHD was 10.3 Gy (0.0-48.4) and was not significantly different between left and right-sided tumours. It was similar between IMRT and 3DCRT (10.9 Gy versus 10.6 Gy) and lower with particle beam therapy (proton 7.0 Gy; carbon-ion 1.9 Gy). Active respiratory motion management reduced exposure (7.4 Gy versus 9.3 Gy). For 168 SABR regimens in 35 studies, MHD was 4.0 Gy (0.0-32.4). Exposure was higher in central and lower lobe lesions (6.3 and 5.8 Gy respectively). MHD was lowest for carbon ions (0.5 Gy) compared to other techniques. Active respiratory motion management reduced exposure (2.4 Gy versus 5.0 Gy). Delineation guidelines and Dose Volume Constraints for the heart varied substantially.

Conclusions: There is scope to reduce heart radiation dose in lung cancer radiotherapy. Consensus on planning objectives, contouring and DVCs for the heart may lead to reduced heart doses in the future. For IMRT, more stringent optimisation objectives may reduce heart dose. Active respiratory motion management or particle therapy may be considered in situations where cardiac dose is high.
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http://dx.doi.org/10.1016/j.radonc.2022.05.007DOI Listing
May 2022

SIRT5 is involved in the proliferation and metastasis of breast cancer by promoting aerobic glycolysis.

Pathol Res Pract 2022 May 11;235:153943. Epub 2022 May 11.

State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, China. Electronic address:

Objective: Breast cancer (BC) is the most commonly diagnosed cancer among females and has a poor prognosis, breast invasive ductal carcinoma is the most common histological type. The occurrence and development of BC is closely related to aberrant glucose metabolism. In the hyperglycemic environment caused by abnormal glucose metabolism, hypoxia-inducible factor-1 alpha (HIF-1α) enables tumor cells to absorb large amounts of glucose and enhance glycolysis by inducing the expression of glucose transporter type1 (GLUT1) and glycolysis genes, thus promoting tumor cell proliferation and metastasis. Mitochondrial Sirtuin5 (SIRT5) plays a role in the rewiring of glucose metabolism during the progression of cancers. Thus, we aimed to elucidate whether SIRT5 promotes BC proliferation and metastasis by facilitating aerobic glycolysis in BC.

Methods: The expression of SIRT5 in breast carcinoma tissue and cells was evaluated using immunohistochemical staining, western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis to confirm the biological role of SIRT5 in breast carcinoma. We established a stable cell line with SIRT5 knockdown using lentiviral transduction in T47D cells to reduce SIRT5 expression and then evaluated the effect of SIRT5 on cells cultured in the presence of high glucose (4500 mg/L) and normal glucose (2000 mg/L) concentrations. Cell proliferation was detected using the CCK-8 assay, the cell cycle and cell apoptosis were measured using flow cytometry and Annexin V staining, and cell migration was tested by performing Celigo scratch and Transwell assays. The expression of PKM2, HK2, mTOR and HIF-1α, which play roles in aerobic glycolysis, was investigated using western blot.

Results: SIRT5 was overexpressed in BC tissues compared with paired normal tissues. Prognostic and OS analyses showed that the SIRT5 expression level was an individual prognostic factor for patients with BC. SIRT5 knockdown inhibited proliferation and metastasis and slightly increased apoptosis in T47D cells under high-glucose conditions. Furthermore, the downregulation of HK2 and HIF-1α caused by SIRT5 knockdown was a high glucose-dependent process, while the downregulation of PKM2 was mediated by a high glucose-independent process.

Conclusions: SIRT5 is an independent prognostic factor for BC and contributes to cell proliferation and metastasis in a high glucose-dependent manner to some degree, which might be mediated by promoting aerobic glycolysis.
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http://dx.doi.org/10.1016/j.prp.2022.153943DOI Listing
May 2022

Mono-Sized Anion-Exchange Magnetic Microspheres for Protein Adsorption.

Int J Mol Sci 2022 Apr 29;23(9). Epub 2022 Apr 29.

School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 102488, China.

In this study, mono-sized anion-exchange microspheres with polyglycidylmethacrylate were engineered and processed to introduce magnetic granules by penetration-deposition approaches. The obtained magnetic microspheres showed a uniform particle diameter of 1.235 μm in average and a good spherical shape with a saturation magnetic intensity of 12.48 emu/g by VSM and 12% magnetite content by TGA. The magnetic microspheres showed no cytotoxicity when the concentration was below 10 μg/mg. The magnetic microspheres possess respective adsorption capacity for three proteins including Bovine albumin, Hemoglobin from bovine blood, and Cytochrome C. These magnetic microspheres are also potential biomaterials as targeting medicine carriers or protein separation carriers at low concentration.
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http://dx.doi.org/10.3390/ijms23094963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9099793PMC
April 2022

IFNγ regulates ferroptosis with fatty acids.

Authors:
Zhe Wang

Nat Cell Biol 2022 May;24(5):601

Nature Cell Biology, .

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http://dx.doi.org/10.1038/s41556-022-00921-zDOI Listing
May 2022

Identification of multi-target anti-cancer agents from TCM formula by in silico prediction and in vitro validation.

Chin J Nat Med 2022 May;20(5):332-351

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address:

Cancer is a complex disease associated with multiple gene mutations and malignant phenotypes, and multi-target drugs provide a promising therapy idea for the treatment of cancer. Natural products with abundant chemical structure types and rich pharmacological characteristics could be ideal sources for screening multi-target antineoplastic drugs. In this paper, 50 tumor-related targets were collected by searching the Therapeutic Target Database and Thomson Reuters Integrity database, and a multi-target anti-cancer prediction system based on mt-QSAR models was constructed by using naïve Bayesian and recursive partitioning algorithm for the first time. Through the multi-target anti-cancer prediction system, some dominant fragments that act on multiple tumor-related targets were analyzed, which could be helpful in designing multi-target anti-cancer drugs. Anti-cancer traditional Chinese medicine (TCM) and its natural products were collected to form a TCM formula-based natural products library, and the potential targets of the natural products in the library were predicted by multi-target anti-cancer prediction system. As a result, alkaloids, flavonoids and terpenoids were predicted to act on multiple tumor-related targets. The predicted targets of some representative compounds were verified according to literature review and most of the selected natural compounds were found to exert certain anti-cancer activity in vitro biological experiments. In conclusion, the multi-target anti-cancer prediction system is very effective and reliable, and it could be further used for elucidating the functional mechanism of anti-cancer TCM formula and screening for multi-target anti-cancer drugs. The anti-cancer natural compounds found in this paper will lay important information for further study.
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http://dx.doi.org/10.1016/S1875-5364(22)60180-8DOI Listing
May 2022

Postoperative avascular necrosis of the femoral head in pediatric femoral neck fractures.

PLoS One 2022 12;17(5):e0268058. Epub 2022 May 12.

Department of Pediatric Surgery, Qilu Hospital of Shandong University, Shandong, China.

This study aimed to evaluate the relevant factors of postoperative avascular necrosis of the femoral head (AVN) in children with femoral neck fracture. This study retrospectively analyzed the clinical data of 28 children with femoral neck fractures treated at our center between July 2016 and January 2019. The average age was 9.3 (range, 4.4-14) years with 75% male participants. Fracture classification was based on the Delbet classification: there were four, seven, 15, and two cases of type I, II, III, and IV fractures, respectively. Displacement degree was based on the Garden classification. Sixteen cases had insignificant displacement (Garden types I and II), six had medium displacement (Garden type III), and six had significant displacement (Garden type IV). There were six early (≤24 hours) and 22 delayed (>24 hours) surgeries. Twenty-three patients had satisfactory reduction, and five had unsatisfactory reduction. The mean postoperative follow-up period was 15.7 (range, 12-36) months. Follow-up was evaluated using the Ratliff scoring standards. The correlation between age, fracture classification, displacement degree, surgery timing, reduction quality, and other factors and AVN occurrence was statistically analyzed. Among 28 children, AVN was found in six cases. There were statistically significant differences in displacement degree (P = 0.001) and reduction quality (P = 0.001), while the occurrence of AVN did not significantly differ with sex (P = 0.117), age distribution (P = 0.218), fracture classification (P = 0.438), surgery timing (P = 0.255), and mechanism of injury (P = 0.436). The results of logistic regression analysis showed that displacement degree was a relevant risk factor (P = 0.049, odds ratio [OR] = 8.391, 95% confidence interval [CI]: 1.004-70.117), while reduction quality was not (P = 0.075, OR = 14.536, 95% CI: 0.757-278.928). Although the development of AVN in children with femoral neck fractures may be related to many factors, the results of this research suggest that there is a significant correlation between displacement degree and AVN occurrence.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0268058PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098045PMC
May 2022

Identification of a novel autophagy-related prognostic signature and small molecule drugs for glioblastoma by bioinformatics.

BMC Med Genomics 2022 May 12;15(1):111. Epub 2022 May 12.

Department of Pediatrics, The First Hospital of Jilin University, Changchun, 130021, Jilin, China.

Objective: To explore the autophagy-related prognostic signature (ARPs) via data mining in gene expression profiles for glioblastoma (GBM).

Methods: Using the Cancer Genome Atlas (TCGA) database, we obtained 156 GBM samples and 5 adjacent normal samples, and denoted them as discovery cohort. Univariate Cox regression analysis was used to screen autophagy genes that related to GBM prognosis. Then, the least absolute shrinkage and selection operator Cox regression model was used to construct an autophagy-based ARPs, which was validated in an external cohort containing 80 GBM samples. The patients in the above-mentioned cohorts were divided into low-risk group and high-risk group according to the median prognostic risk score, and the diagnostic performance of the model was assessed by receiver operating characteristic curve analyses. The gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analyses were performed between the high-risk and low-risk patients. Additionally, the genetic features of ARPs, such as genetic variation profiles, correlations with tumor-infiltrating lymphocytes (TILs), and potential drug sensitivity, were further assessed in the TCGA-GBM data set.

Results: A signature of ARPs including NDUFB9, BAK1, SUPT3H, GAPDH, CDKN1B, CHMP6, and EGFR were detected and validated. We identified a autophagy-related prognosis 7-gene signature correlated survival prognosis, immune infiltration, level of cytokines, and cytokine receptor in tumor microenvironment. Furthermore, the signature was tested in several pathways related to disorders of tumor microenvironment, as well as cancer-related pathways. Additionally, a range of small molecular drugs, shown to have a potential therapeutic effect on GBM.

Conclusions: We constructed an autophagy-based 7-gene signature, which could serve as an independent prognostic indicator for cases of GBM and sheds light on the role of autophagy as a potential therapeutic target in GBM.
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http://dx.doi.org/10.1186/s12920-022-01261-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097333PMC
May 2022

Anti-inflammatory activities of natural cyclopeptide RA-XII in colitis-associated colon cancer mouse model and its effect on gut microbiome.

Phytother Res 2022 May 10. Epub 2022 May 10.

State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China.

Colorectal cancer (CRC), the third most common cancer globally, is associated with intestinal inflammation that leads to poor prognosis. RA-XII, a natural cyclopeptide, has previously been reported to possess anti-tumor activities. Here, the anti-inflammatory activities of RA-XII were investigated in colitis-associated colon cancer mice and a co-culture in vitro model, in which colon cancer cells HCT116 and macrophages RAW264.7 were grown together to mimic the inflammatory microenvironment of CRC. Changes of inflammatory-related molecules and protein expressions in cells were evaluated after RA-XII incubation. Besides, azoxymethane and dextran sulfate sodium-induced colitis-associated colon cancer mice were treated with RA-XII for 24 days, inflammatory parameters and gut microbiome alterations were studied. Our results showed that RA-XII reversed the inflammatory responses of RAW264.7 cells induced by LPS and modulated the protein expressions of AKT, STAT3/p-STAT3, P70S6K, NF-κB and GSK3β and suppressed the expression of LC3A/B in HCT116 cells in co-culture system. RA-XII treatment restored the colitis damage in colon, reduced colon tumors numbers and decreased inflammatory factors (IL-6, IL-10 and TNF-α). The role of RA-XII on regulating gut microbiome was also demonstrated for the first time. In conclusion, our findings provided new scientific evidence for developing RA-XII as a potent anti-inflammatory agent for CRC.
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http://dx.doi.org/10.1002/ptr.7482DOI Listing
May 2022

Deciphering the tumor cell-infiltrating landscapes reveal microenvironment subtypes and therapeutic potentials for nonsquamous NSCLC.

JCI Insight 2022 May 5. Epub 2022 May 5.

Key Laboratory of Engineering of Shandong Province, Shandong Provincial Hospital, Jinan, China.

Recent studies highlighted the clinicopathologic importance of tumor microenvironment (TME) in delineating molecular attributes and therapeutic potentials. However, the overall TME cell-infiltration landscape in non-squamous NSCLC have not been comprehensively recognized. In this study, we employed consensus non-negative matrix factorization (NMF) molecular subtyping to determine the TME cell infiltration patterns and identified three TME clusters (TME-C1, -C2, -C3) characterized by distinct clinicopathologic features, infiltrating cells, and biological processes. Proteomics analyses revealed that cGAS-STING immune signaling mediated protein and phosphorylation level were significantly upregulated in inflamed-related TME-C2 clusters. The TMEsig-score extracted from the TME-related signature divided NSCLC patients into high- and low-score subgroups, where a high score was associated with favorable prognosis and immune infiltration. Genomic landscape revealed that patients with low TMEsig-score harbored greater somatic copy number alternations and higher mutation frequency of driver genes involving STK11, KEAP1 and SMARCA4 et al. Drug sensitivity analyses suggested that tumors with high TMEsig-score were responsible for favorable clinical response to immune check-point inhibitors (ICI) treatment. In summary, this study highlights that comprehensive recognizing of the TME cell infiltration landscape will contribute to enhance our understanding of TME immune regulation and promote effectiveness of precision biotherapy strategies.
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http://dx.doi.org/10.1172/jci.insight.152815DOI Listing
May 2022

Self-Constructing Fuzzy Neural Fractional-Order Sliding Mode Control of Active Power Filter.

IEEE Trans Neural Netw Learn Syst 2022 May 4;PP. Epub 2022 May 4.

In this article, a fractional-order sliding mode control (FOSMC) scheme is proposed for mitigating harmonic distortions in the power system, whereby a self-constructing recurrent fuzzy neural network (SCRFNN) is used to weaken the effect of compound nonlinearity caused by unknown uncertainties and environmental fluctuations. The fractional-order sliding mode controller (SMC) is constructed to maintain the control system to be asymptotically stable and a fractional-order calculus is introduced into an SMC to soften the sliding manifold design and realize chattering reduction. Considering parameter variations existing in the power system model, SCRFNN is adopted to approximate the unknown dynamics, which is able to dynamically update network structure by optimizing the fuzzy division, and a feedback connection is incorporated into the feedforward neural network, which is regarded as a storage unit to enhance the capability of coping with temporal problem. The control scheme combining the FOSMC with the SCRFNN can make the tracking error and its time derivative converge to zero. Experimental studies demonstrate the validity of the designed scheme, and comprehensive comparisons illustrate its superiority in harmonic suppression and high robustness.
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http://dx.doi.org/10.1109/TNNLS.2022.3169518DOI Listing
May 2022

Validation analysis of EMDB entries.

Acta Crystallogr D Struct Biol 2022 May 20;78(Pt 5):542-552. Epub 2022 Apr 20.

European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton CB10 1SD, United Kingdom.

The Electron Microscopy Data Bank (EMDB) is the central archive of the electron cryo-microscopy (cryo-EM) community for storing and disseminating volume maps and tomograms. With input from the community, EMDB has developed new resources for the validation of cryo-EM structures, focusing on the quality of the volume data alone and that of the fit of any models, themselves archived in the Protein Data Bank (PDB), to the volume data. Based on recommendations from community experts, the validation resources are developed in a three-tiered system. Tier 1 covers an extensive and evolving set of validation metrics, including tried and tested metrics as well as more experimental ones, which are calculated for all EMDB entries and presented in the Validation Analysis (VA) web resource. This system is particularly useful for cryo-EM experts, both to validate individual structures and to assess the utility of new validation metrics. Tier 2 comprises a subset of the validation metrics covered by the VA resource that have been subjected to extensive testing and are considered to be useful for specialists as well as nonspecialists. These metrics are presented on the entry-specific web pages for the entire archive on the EMDB website. As more experience is gained with the metrics included in the VA resource, it is expected that consensus will emerge in the community regarding a subset that is suitable for inclusion in the tier 2 system. Tier 3, finally, consists of the validation reports and servers that are produced by the Worldwide Protein Data Bank (wwPDB) Consortium. Successful metrics from tier 2 will be proposed for inclusion in the wwPDB validation pipeline and reports. The details of the new resource are described, with an emphasis on the tier 1 system. The output of all three tiers is publicly available, either through the EMDB website (tiers 1 and 2) or through the wwPDB ftp sites (tier 3), although the content of all three will evolve over time (fastest for tier 1 and slowest for tier 3). It is our hope that these validation resources will help the cryo-EM community to obtain a better understanding of the quality and of the best ways to assess the quality of cryo-EM structures in EMDB and PDB.
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http://dx.doi.org/10.1107/S205979832200328XDOI Listing
May 2022

Oral hymecromone decreases hyaluronan in human study participants.

J Clin Invest 2022 May;132(9)

Division of Infectious Diseases and Geographic Medicine, Department of Medicine.

BACKGROUNDHyaluronan (HA), an extracellular matrix glycosaminoglycan, has been implicated in the pathophysiology of COVID-19 infection, pulmonary hypertension, pulmonary fibrosis, and other diseases, but is not targeted by any approved drugs. We asked whether hymecromone (4-methylumbelliferone [4-MU]), an oral drug approved in Europe for biliary spasm treatment that also inhibits HA in vitro and in animal models, could be repurposed as an inhibitor of HA synthesis in humans.METHODSWe conducted an open-label, single-center, dose-response study of hymecromone in healthy adults. Subjects received hymecromone at 1200 (n = 8), 2400 (n = 9), or 3600 (n = 9) mg/d divided into 3 doses daily, administered orally for 4 days. We assessed safety and tolerability of hymecromone and analyzed HA, 4-MU, and 4-methylumbelliferyl glucuronide (4-MUG; the main metabolite of 4-MU) concentrations in sputum and serum.RESULTSHymecromone was well tolerated up to doses of 3600 mg/d. Both sputum and serum drug concentrations increased in a dose-dependent manner, indicating that higher doses lead to greater exposures. Across all dose arms combined, we observed a significant decrease in sputum HA from baseline after 4 days of treatment. We also observed a decrease in serum HA. Additionally, higher baseline sputum HA levels were associated with a greater decrease in sputum HA.CONCLUSIONAfter 4 days of exposure to oral hymecromone, healthy human subjects experienced a significant reduction in sputum HA levels, indicating this oral therapy may have potential in pulmonary diseases where HA is implicated in pathogenesis.TRIAL REGISTRATIONClinicalTrials.gov NCT02780752.FUNDINGStanford Medicine Catalyst, Stanford SPARK, Stanford Innovative Medicines Accelerator program, NIH training grants 5T32AI052073-14 and T32HL129970.
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http://dx.doi.org/10.1172/JCI157983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9057598PMC
May 2022

Four bioactive new steroids from the soft coral collected in South China Sea.

Beilstein J Org Chem 2022 8;18:374-380. Epub 2022 Apr 8.

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, People's Republic of China.

Four new polyhydroxylated steroids lobophysterols E-H (-), together with three known compounds (-), were isolated from the soft coral collected at Xisha Island, China. The structures of the new compounds were elucidated by extensive spectroscopic analysis and comparison with NMR data of structurally related compounds reported in the literature. The absolute configuration of - was determined by X-ray diffraction. All the compounds have assessed the cytotoxicity against HL-60, K562, and Hela cells. Compound showed weak cytotoxicity against K562 cells with an IC value of 19.03 μM. In addition, compound also showed a moderate anti-inflammatory effect in zebrafish.
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http://dx.doi.org/10.3762/bjoc.18.42DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016341PMC
April 2022

Effection of monoplanar pedicle screw on facet joint degeneration in thoracolumbar vertebral fractures.

BMC Musculoskelet Disord 2022 Apr 30;23(1):407. Epub 2022 Apr 30.

Department of Orthopedics, Xijing Hospital, Air Force Medical University of PLA, No. 169 West Changle Road, Shaanxi Province, 710032, Xi'an, China.

Background: This study aimed to compare the clinical outcomes and effect on instrument-related facet joints between fixed-axis pedicle screw (FAPS) and monoplanar pedicle screw (MPPS).

Methods: 816 pedicle screws of 204 patients with thoracolumbar vertebral fractures (TLVF) who underwent internal fixation surgery were analyzed in this retrospective study. All patients were divided into two groups (FAPS and MPPS). Preoperative, immediate postoperative, and 12-18-months postoperative CT and X-ray, and clinical data, including demographics, preoperative and immediate postoperative Visual Analogue Scale (VAS), blood loss (BL), operation time (OT) and hospital stay time (HST), were collected. Facet joint violation and degeneration grade were evaluated by CT according to Babu's criteria and Weishaupt's criteria respectively, and preoperative, immediate postoperative and 12-18-months postoperative anterior body compression index (ABCI) were measured by X-ray.

Results: Postoperative VAS of two groups was lower than preoperative VAS (p < 0.05). BL, OT, and HST were less in MPPS than FAPS, and the difference was statistically significant in BL and HST (p < 0.05) but no in OT (p > 0.05). Immediate postoperative and 12-18-months postoperative ABCI were significantly higher than preoperative (p < 0.05), and the difference of ABCI between immediate postoperative and 12-18-months postoperative were not significant in two groups (p > 0.05). Total violation rate (VR) was about 1.35% (11/816) and FAPS had a lower VR than MPPS, but no significant (p > 0.05). Weishaupt's criteria revealed that average class (AC) was 0.69 in FAPS and 0.67 in MPPS, and the distribution of degenerated facet joints in two groups did not differ preoperatively (p > 0.05). In 12-18 months postoperatively, AC was significantly higher in FAPS than in MPPS, and the distribution of degenerated facet joints in two groups was significantly different (p < 0.05). The comparison of cranial to caudal joints in two groups revealed that cranial joints had more severe degeneration than caudal joints.

Conclusions: The findings suggested that both MPPS and FAPS were effective for patients with TLVF, but MPPS by percutaneous may be a better choice to avoid adjacent segment degeneration, especially the surgery-involved facet joints degeneration.
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http://dx.doi.org/10.1186/s12891-022-05360-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9055697PMC
April 2022

Frame-Level Teacher-Student Learning With Data Privacy for EEG Emotion Recognition.

IEEE Trans Neural Netw Learn Syst 2022 Apr 29;PP. Epub 2022 Apr 29.

Recently, electroencephalogram (EEG) emotion recognition has gradually attracted a lot of attention. This brief designs a novel frame-level teacher-student framework with data privacy (FLTSDP) for EEG emotion recognition. The framework first proposes a teacher-student network without prior professional information for automated filtering of useful frame-level features by a gated mechanism and extracting high-level features by using knowledge distillation to capture the results of EEG emotion recognition from a teacher network and student networks. Then, the results from subnetworks are integrated by using the novel decision module, which, motivated by the voting mechanism, adjusts the composition of feature vectors and improves the weight of accurate prediction to optimize the integration effect. During training, an innovative data privacy protection mechanism is applied for avoiding data sharing, where each student network only inherits weights from all trained networks and does not inherit the training dataset. Here, the framework can be repeatedly optimized and improved by only training the next student subnetwork on new EEG signals. Experimental results show that our framework improves the accuracy of EEG emotion recognition by more than 5% and gets state-of-the-art performance for EEG emotion recognition in the subject-independent mode.
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http://dx.doi.org/10.1109/TNNLS.2022.3168935DOI Listing
April 2022

Use of dissociation degree in lysosomes to predict metal oxide nanoparticle toxicity in immune cells: Machine learning boosts nano-safety assessment.

Environ Int 2022 Jun 25;164:107258. Epub 2022 Apr 25.

Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), Dalian Key Laboratory on Chemicals Risk Control and Pollution Prevention Technology, School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024, China.

Potential immune responses resulting from exposure to metal oxide nanoparticles (MeONPs) have been the subject of intensive discussion in the last decade. Despite the extensive use of MeONPs in several applications, their toxic effects on immune cells have rarely been predicted in silico because of the complexity of immune responses and the complicated properties of MeONPs. In the present study, machine learning (ML) methods coupled with high-throughput in vitro bioassays were used to develop models for predicting the toxicity of MeONPs in immune cells. An ML model with a high prediction accuracy (97% and 96% in the training and test sets, respectively) was constructed by resolving the class imbalance problem in training and applying an ensembled algorithm. Further, to verify the model, MeONPs outside the scope of the datasets were selected to examine their cytotoxicity experimentally. The model was validated against independent MeONPs, with an accuracy of 91%. ML methods coupled with intracellular imaging revealed that the toxic ions released in the lysosome were an important determinant of toxicity in immune cells. Furthermore, ζ-potential, electronegativity, and size are crucial factors for predicting nanotoxicity. We believe the established modeling framework will provide useful insights for designing and applying safe nanoparticles and facilitating decision-making for environmental and health protection.
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http://dx.doi.org/10.1016/j.envint.2022.107258DOI Listing
June 2022

The genome of Corydalis reveals the evolution of benzylisoquinoline alkaloid biosynthesis in Ranunculales.

Plant J 2022 Apr 27. Epub 2022 Apr 27.

Key Lab of Chinese Medicine Resources Conservation, State Administration of Traditional Chinese Medicine of the People's Republic of China, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China.

Species belonging to the order Ranunculales have attracted much attention because of their phylogenetic position as a sister group to all other eudicot lineages and their ability to produce unique yet diverse benzylisoquinoline alkaloids (BIAs). The Papaveraceae family in Ranunculales is often used as a model system for studying BIA biosynthesis. Here, we report the chromosome-level genome assembly of Corydalis tomentella, a species of Fumarioideae, one of the two subfamilies of Papaveraceae. Based on comparisons of sequenced Ranunculalean species, we present clear evidence of a shared whole-genome duplication (WGD) event that has occurred before the divergence of Ranunculales but after its divergence from other eudicot lineages. The C. tomentella genome enabled us to integrate isotopic labeling and comparative genomics to reconstruct the BIA biosynthetic pathway for both sanguinarine biosynthesis shared by papaveraceous species and the cavidine biosynthesis that is specific to Corydalis. Also, our comparative analysis revealed that gene duplications, especially tandem gene duplications, underlie the diversification of BIA biosynthetic pathways in Ranunculales. In particular, tandemly duplicated berberine bridge enzyme-like genes appear to be involved in cavidine biosynthesis. In conclusion, our study of the C. tomentella genome provides important insights into the occurrence of WGDs during the early evolution of eudicots, as well as into the evolution of BIA biosynthesis in Ranunculales.
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http://dx.doi.org/10.1111/tpj.15788DOI Listing
April 2022
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