Publications by authors named "Yaping Xu"

176 Publications

Radiosensitizing effect of c-Met kinase inhibitor BPI-9016M in esophageal squamous cell carcinoma cells and .

Ann Transl Med 2021 Dec;9(24):1799

First Clinical Medical School, Wenzhou Medical University, Wenzhou, China.

Background: c-Met is the receptor of hepatocyte growth factor (HGF) which plays a key role in inhibiting apoptosis. BPI-9016M is a small-molecule c-Met inhibitor that can promote apoptosis and enhance the cytotoxicity of various DNA-damaging agents. Here, we evaluated the radiosensitizing potential of BPI-9016M in Eca109 human esophageal squamous cell carcinoma (ESCC) cells and .

Methods: Cell Counting Kit-8 (CCK-8) assay was used to measure cell viability. Clonogenic survival assay and a murine tumor xenograft in male nude mice were used to evaluate the radiosensitizing effect of BPI-9016M. Apoptosis was determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and flow cytometry experiment. Apoptosis-related proteins were detected by western blot. By evaluating the activation of the ATR-Chk1/ATM-Chk2 pathway to detect radiation-induced DNA double-strand break and homologous recombination repair. BPI-9016M induced a radiosensitizing effect in Eca109 cells and reduced the survival rate of clone formation .

Results: The combination of BPI-9016M with irradiation (IR) significantly delayed the growth of ESCC tumor xenografts than treatment alone (P<0.05). The radiosensitizing effects of BPI-9016M were due to increased apoptosis, such as the up-regulation of cleaved-caspase 3 and 9, down-regulation of mutant P53 and Bcl-2, the decreased of phosphorylation of ATR and ATM, and the inhibition of γ-H2AX accumulation and .

Conclusions: These findings indicated that BPI-9016M exerts a radiosensitizing effect and enhances apoptosis by inhibiting homologous recombination DNA repair in irradiated ESCC cells.
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http://dx.doi.org/10.21037/atm-21-6586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8756247PMC
December 2021

Genetic Blockade of NAAA Cell-specifically Regulates Fatty Acid Ethanolamides (FAEs) Metabolism and Inflammatory Responses.

Front Pharmacol 2021 7;12:817603. Epub 2022 Jan 7.

CAS Key Laboratory of Design and Assembly of Functional Nanostructures and Fujian Provincial Key Laboratory of Nanomaterials, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fujian, China.

N-Acylethanolamine acid amidase (NAAA) is a lysosomal enzyme responsible for the hydrolysis of fatty acid ethanolamides (FAEs). However, the role of NAAA in FAEs metabolism and regulation of pain and inflammation remains mostly unknown. Here, we generated NAAA-deficient (NAAA) mice using CRISPR-Cas9 technique, and found that deletion of NAAA increased PEA and AEA levels in bone marrow (BM) and macrophages, and elevated AEA levels in lungs. Unexpectedly, genetic blockade of NAAA caused moderately effective anti-inflammatory effects in lipopolysaccharides (LPS)-induced acute lung injury (ALI), and poor analgesic effects in carrageenan-induced hyperalgesia and sciatic nerve injury (SNI)-induced mechanical allodynia. These data contrasted with acute (single dose) or chronic NAAA inhibition by F96, which produced marked anti-inflammation and analgesia in these models. BM chimera experiments indicated that these phenotypes were associated with the absence of NAAA in non-BM cells, whereas deletion of NAAA in BM or BM-derived cells in rodent models resulted in potent analgesic and anti-inflammatory phenotypes. When combined, current study suggested that genetic blockade of NAAA regulated FAEs metabolism and inflammatory responses in a cell-specifical manner.
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http://dx.doi.org/10.3389/fphar.2021.817603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777083PMC
January 2022

Sustainability Trait Modeling of Field-Grown Switchgrass () Using UAV-Based Imagery.

Plants (Basel) 2021 Dec 11;10(12). Epub 2021 Dec 11.

Department of Plant Sciences, University of Tennessee, Knoxville, TN 37996, USA.

Unmanned aerial vehicles (UAVs) provide an intermediate scale of spatial and spectral data collection that yields increased accuracy and consistency in data collection for morphological and physiological traits than satellites and expanded flexibility and high-throughput compared to ground-based data collection. In this study, we used UAV-based remote sensing for automated phenotyping of field-grown switchgrass (), a leading bioenergy feedstock. Using vegetation indices calculated from a UAV-based multispectral camera, statistical models were developed for rust disease caused by , leaf chlorophyll, nitrogen, and lignin contents. For the first time, UAV remote sensing technology was used to explore the potentials for multiple traits associated with sustainable production of switchgrass, and one statistical model was developed for each individual trait based on the statistical correlation between vegetation indices and the corresponding trait. Also, for the first time, lignin content was estimated in switchgrass shoots via UAV-based multispectral image analysis and statistical analysis. The UAV-based models were verified by ground-truthing via correlation analysis between the traits measured manually on the ground-based with UAV-based data. The normalized difference red edge (NDRE) vegetation index outperformed the normalized difference vegetation index (NDVI) for rust disease and nitrogen content, while NDVI performed better than NDRE for chlorophyll and lignin content. Overall, linear models were sufficient for rust disease and chlorophyll analysis, but for nitrogen and lignin contents, nonlinear models achieved better results. As the first comprehensive study to model switchgrass sustainability traits from UAV-based remote sensing, these results suggest that this methodology can be utilized for switchgrass high-throughput phenotyping in the field.
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http://dx.doi.org/10.3390/plants10122726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709265PMC
December 2021

Assessing health-related quality-of-life in patients with symptomatic obstructive hypertrophic cardiomyopathy: EQ-5D-based utilities in the EXPLORER-HCM trial.

J Med Econ 2022 Jan-Dec;25(1):51-58

University of Washington, Seattle, WA, USA.

Aims: To assess the effects of mavacamten on health-related quality-of-life (HRQoL) in symptomatic obstructive hypertrophic cardiomyopathy (HCM) and estimate health utilities by New York Heart Association (NYHA) functional class.

Materials And Methods: Patients with symptomatic obstructive HCM were randomized to 30 weeks of mavacamten or to placebo treatment, with or without beta-blocker or calcium channel blocker monotherapy, in EXPLORER-HCM (ClinicalTrials.gov identifier: NCT03470545). Health utility was measured using the EuroQoL 5-dimension 5-level (EQ-5D-5L) index score with the US value set. The 30-week changes in EQ-5D-5L index score and EuroQoL visual analog scale (EQ-VAS) score were compared between the two arms using linear regression, and the proportions of patients with a meaningful improvement were compared using logistic regression. The meaningful change thresholds were estimated using both distribution- and anchor-based approaches. Mean utilities by NYHA class were estimated for each arm using a generalized estimating equation.

Results: Compared with placebo ( = 89), patients receiving mavacamten ( = 96) had significantly greater 30-week improvement in EQ-5D-5L index score (mavacamten = 0.084; placebo = 0.009; adjusted difference = 0.073 [95% confidence interval = 0.027-0.118]) and EQ-VAS score (mavacamten = 8.5; placebo = 0.7; adjusted difference = 7.5 [95% confidence interval = 1.8-13.2]), and a significantly higher proportion of these patients showed meaningful improvement in EQ-5D-5L index score and EQ-VAS score. Both outcomes were correlated with the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS) and HCM Symptom Questionnaire Shortness-of-Breath (HCMSQ SoB) subscore, two patient-reported anchor variables. Additionally, mean utilities significantly decreased with higher NYHA functional class (values for NYHA class I, II, and III/IV - mavacamten = 0.950, 0.866, and 0.708; placebo = 0.952, 0.850, and 0.704).

Conclusions: Compared with placebo, mavacamten significantly improved EQ-5D-5L index score and EQ-VAS score - and thus HRQoL - among patients with symptomatic obstructive HCM. Patients with a higher NYHA functional class had a lower health utility value.
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http://dx.doi.org/10.1080/13696998.2021.2011301DOI Listing
December 2021

A Radiomics Nomogram for Preoperative Prediction of Clinical Occult Lymph Node Metastasis in cT1-2N0M0 Solid Lung Adenocarcinoma.

Cancer Manag Res 2021 28;13:8157-8167. Epub 2021 Oct 28.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People's Republic of China.

Background: Clinical occult lymph node metastasis (cOLNM) means that the lymph node is negatively diagnosed by preoperative computed tomography (CT), but has been proven to be positive by postoperative pathology. The aim of this study was to establish and validate a nomogram based on radiomics features for the preoperative prediction of cOLNM in early-stage solid lung adenocarcinoma patients.

Methods: A total of 244 patients with clinical T1-2N0M0 solid lung adenocarcinoma who underwent preoperative contrast-enhanced chest CT were divided into a primary group (n = 160) and an independent validation group from another hospital (n = 84). The records of 851 radiomics features of each primary tumor were extracted. LASSO analysis was used to reduce the data dimensionality and select features. Multivariable logistic regression was utilized to identify independent predictors of cOLNM and develop a predictive nomogram. The performance of the predictive model was assessed by its calibration and discrimination. Decision curve analysis (DCA) was performed to estimate the clinical usefulness of the nomogram.

Results: The predictive model consisted of a clinical factor (CT-reported tumor size) and a radiomics feature (Rad-score). The nomogram presented good discrimination, with a C-index of 0.782 (95% CI, 0.768-0.796) in the primary cohort and 0.813 (95% CI, 0.787-0.839) in the validation cohort, and good calibration. DCA showed that the radiomics nomogram was clinically useful.

Conclusion: This study develops and validates a nomogram that incorporates clinical and radiomics factors. It can be tailored for the individualized preoperative prediction of cOLNM in early-stage solid lung adenocarcinoma patients.
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http://dx.doi.org/10.2147/CMAR.S330824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560059PMC
October 2021

Genomic Landscape in Neoplasm-Like Stroma Reveals Distinct Prognostic Subtypes of Pancreatic Ductal Adenocarcinoma.

Front Oncol 2021 18;11:771247. Epub 2021 Oct 18.

Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

As a main component of the tumor microenvironment, the stroma is critical in development, progression, and metastasis of pancreatic ductal adenocarcinoma (PDAC). The genomic status and its relationship of neoplastic and stromal components remain unclear in PDAC. We performed targeted sequencing for 1,021 cancer-suspected genes on parallel microdissected stromal and neoplastic components from 50 operable PDAC patients. Clonality analysis of mutations was conducted to reconstruct the evolutionary trajectory, and then molecular subtypes were established. Multi-lineage differentiation potential and mesenchymal transformation of -mutant cell line Panc1 were evaluated using RT-PCR and immunofluorescence staining. In this study, 39 (78.0%) were genomically altered in stroma, with (71.8%), (61.5%), and (23.1%) as the most commonly mutated genes. The majority of stromal mutations (89.8%) were detected in matched neoplastic components. Patients with -mut stroma demonstrated a higher tumor cell fraction (TCF) than did those with wild-type (WT) stroma ( = 0.0371, = 0.0014). In both components, mutants and often occurred as clonal events, and the allele frequencies presented linear correlation in the same specimen. All neoplasm-like stroma (characterized with all or initial neoplastic clones and driver events in stroma) harbored or mutations. Neoplasm-like and -mutant stroma was associated with shorter disease-free survival. It is a new finding for the existence of driver gene mutations in PDAC stroma. These data suggest that genomic features of stromal components may serve as prognostic biomarkers in resectable PDAC and might help to guide a more precise treatment paradigm in therapeutic options.
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http://dx.doi.org/10.3389/fonc.2021.771247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558555PMC
October 2021

Efficient A·T to G·C Base Conversions in Dicots Using Adenine Base Editors Expressed under the Tomato EF1α Promoter.

Plant Biotechnol J 2021 Oct 25. Epub 2021 Oct 25.

Shanghai Center for Plant Stress Biology, and National Key Laboratory of Plant Molecular Genetics, Center of Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai, 200032, China.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas systems have revolutionized plant breeding. Different Cas enzymes have been widely used to introduce deletions or insertions into plant genomes. However, many important agronomical traits in plants are associated with single nucleotide polymorphisms. For example, the Lin5 SNP causes an Asn366 to Asp change, resulting in a higher sugar content in tomato fruits (Tieman et al., 2017). Thus, it is important to develop tools to efficiently introduce precise base changes in crops.
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http://dx.doi.org/10.1111/pbi.13736DOI Listing
October 2021

NAAA inhibitor F96 attenuates BBB disruption and secondary injury after traumatic brain injury (TBI).

Eur J Pharmacol 2021 Dec 13;912:174561. Epub 2021 Oct 13.

CAS Key Laboratory of Design and Assembly of Functional Nanostructures, And Fujian Provincial Key Laboratory of Nanomaterials, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, China; Xiamen Institute of Rare-earth Materials, Haixi Institutes, Chinese Academy of Sciences, Fujian, 361005, China; Key Laboratory of Functional and Clinical Translational Medicine, Fujian Province University, Xiamen Medical College, China. Electronic address:

Traumatic brain injury (TBI) is a leading cause of death worldwide, for which there is currently no comprehensive treatment available. Preventing blood-brain barrier (BBB) disruption is crucial for TBI treatment. N-acylethanolamine acid amidase (NAAA)-regulated palmitoylethanolamide (PEA) signaling play an important role in the control of inflammation. However, the role of NAAA in BBB dysfunction following TBI remains unclear. In the present study, we found that TBI induces the increase of PEA levels in the injured cortex, which prevent the disruption of BBB after TBI. TBI also induces the infiltration of NAAA-contained neutrophils, increasing the contribution of NAAA to the PEA degradation. Neutrophil-derived NAAA weakens PEA/PPARα-mediated BBB protective effects after TBI, facilitates the accumulation of immune cells, leading to secondary expansion of tissue injury. Inactivation of NAAA increased PEA levels in injured site, prevents early BBB damage and improves secondary injury, thereby eliciting long-term functional improvements after TBI. This study identified a new role of NAAA in TBI, suggesting that NAAA is a new important target for BBB dysfunction related CNS diseases.
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http://dx.doi.org/10.1016/j.ejphar.2021.174561DOI Listing
December 2021

Lung cancer-associated T cell repertoire as potential biomarker for early detection of stage I lung cancer.

Lung Cancer 2021 12 28;162:16-22. Epub 2021 Sep 28.

Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, China; Xiangya Lung Cancer Center, Xiangya Hospital, Central South University, Changsha, China; Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Changsha, China. Electronic address:

Background: Early detection of lung cancer in asymptomatic patients remains challenging, especially for stage I. Considering the substantial interaction with tumor immunogenicity, we hypothesized that lung cancer-associated TCR (LC-aTCR) may serve as potential biomarker in early detection of stage I lung cancer.

Methods: Individuals who received low-dose computed tomography (LDCT) screening were enrolled in the study. Surgical tissues and peripheral blood specimens were collected and performed with DNA-based T cell repertoire (TCR) sequencing. The motif-based algorithm was used to deconstruct specific lung cancer-associated TCRs (LC-aTCRs).

Results: A total of 146 individuals participating in the real-world LDCT screening project were enrolled in this study, including 52 patients with pathologically-confirmed stage I lung cancer and 94 non-cancer controls. We developed a motif-based algorithm to define 80 LC-aTCRs in the training cohort. Moreover, in the validation cohort, high sensitivity and specificity was showed in stage I lung cancer with 72% and 91% respectively, and the AUC of the ROC curve was 0.91 (95% CI: 0.85 ∼ 0.96).

Conclusion: This work provides inspiration for stage I lung cancer detection by using blood TCR profiling data. The combination of TCR-based assay and routine screening deserves further testing in larger cohorts.
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http://dx.doi.org/10.1016/j.lungcan.2021.09.017DOI Listing
December 2021

A Propensity-Matched Analysis of Survival of Clinically Diagnosed Early-Stage Lung Cancer and Biopsy-Proven Early-Stage Non-Small Cell Lung Cancer Following Stereotactic Ablative Radiotherapy.

Front Oncol 2021 24;11:720847. Epub 2021 Aug 24.

Department of Radiation Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.

Purpose: Stereotactic body radiotherapy (SBRT) has been increasingly regarded as a reasonable option for early-stage lung cancer patients without pretreatment pathologic results, but the efficacy and safety in a Chinese population remains unclear. The aim of this study was to compare survival outcomes and toxicities between patients with clinically diagnosed early-stage lung cancer or biopsy-proven early-stage non-small cell lung cancer and to demonstrate the rationality of this treatment.

Material And Methods: From May 2012 to December 2018, 56 patients with clinically diagnosed early-stage lung cancer and 60 patients with early-stage biopsy-proven were selected into non-pathological group and pathological group, respectively. Propensity score matching (PSM) was performed to reduce patient selection bias. Survival analysis with log-rank test was used to assess the differences of treatment outcomes, which included local control (LC), progression-free survival (PFS), and overall survival (OS).

Results: The median age was 76 (range 47-93) years, and the median follow-up time was 58.3 (range 4.3-95.1) months in the cohort without pathologic results. The median age was 74 (range 57-88) years, and the median follow-up time was 56.3 (range 2.6-94) months in the cohort with pathologic results. 45 matched-pair were analyzed. The 5-year LC, PFS, and OS rates in matched-pair patients with or without pathologic biopsy were 85.5% and 89.8%, 40.6% and 70.9%, and 63.2% and 76.1%, respectively. On Kaplan-Meier survival analysis after PSM analysis, there was no significant difference between patients with pathologic results versus patients with no pathologic results in terms of LC (P= 0.498) and OS (P=0.141). Of the matched-pair patients treated with SBRT, only 1 patient experienced grade 3 or above radiation pneumonitis.

Conclusion: For early-stage lung cancer patients with medically inoperable or not suitable for invasive diagnosis, SBRT may be a good local treatment.
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http://dx.doi.org/10.3389/fonc.2021.720847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421845PMC
August 2021

Multiomics Analysis Reveals Distinct Immunogenomic Features of Lung Cancer with Ground-Glass Opacity.

Am J Respir Crit Care Med 2021 11;204(10):1180-1192

Department of Thoracic Surgery and.

Ground-glass opacity (GGO)-associated lung cancers are common and radiologically distinct clinical entities known to have an indolent clinical course and superior survival, implying a unique underlying biology. However, the molecular and immune characteristics of GGO-associated lung nodules have not been systemically studied. To provide mechanistic insights for the treatment of these radiologically distinct clinical entities. We initiated a prospective cohort study to collect and characterize pulmonary nodules with GGO components (nonsolid and part-solid nodules) or without GGO components, as precisely quantified by using three-dimensional image reconstruction to delineate the molecular and immune features associated with GGO. Multiomics assessment conducted by using targeted gene panel sequencing, RNA sequencing, TCR (T-cell receptor) sequencing, and circulating tumor DNA detection was performed. GGO-associated lung cancers exhibited a lower tumor mutation burden than solid nodules. Transcriptomic analysis revealed a less active immune environment in GGO components and immune pathways, decreased expression of immune activation markers, and less infiltration of most immune-cell subsets, which was confirmed by using multiplex immunofluorescence. Furthermore, T-cell repertoire sequencing revealed lower T-cell expansion in GGO-associated lung cancers. HLA loss of heterozygosity was significantly less common in lung adenocarcinomas with GGO components than in those without. Circulating tumor DNA analysis suggested that the release of tumor DNA to the peripheral blood was correlated with the tumor size of non-GGO components. Compared with lung cancers presenting with solid lung nodules, GGO-associated lung cancers are characterized by a less active metabolism and a less active immune microenvironment, which may be the mechanisms underlying their indolent clinical course. Clinical trial registered with www.clinicaltrials.gov (NCT03320044).
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http://dx.doi.org/10.1164/rccm.202101-0119OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759311PMC
November 2021

Genomic Landscape and Tumor Mutational Burden Determination of Circulating Tumor DNA in Over 5,000 Chinese Patients with Lung Cancer.

Clin Cancer Res 2021 11 26;27(22):6184-6196. Epub 2021 Aug 26.

Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Purpose: Having emerged as a noninvasive and clinically applicable approach for molecular determination of lung cancer, a genomic overview of circulating tumor DNA (ctDNA) of large-scale cohort may be helpful in novel biomarker development and therapeutic innovation.

Experimental Design: Primary cohort encompasses 5,671 blood samples from 4,892 patients with lung cancer. Pair-wise tissue samples from 579 patients and additional 358 sample pairs were collected to evaluate the correlation between blood and tissue tumor mutational burden (TMB). Parallel sequencing with plasma/tissue and white blood cells was performed using a 1,021-gene panel.

Results: Histologic subtyping was the most relevant to ctDNA detectability independent of other demographic characteristics, with small cell lung cancer showing the highest detectability, ctDNA abundance, and blood TMB (bTMB). Mutational landscape demonstrated significant differences, and integrated clonality analysis highlighted distinct driver-pattern and functional pathway interaction among various subtypes. The clonality and concurrent genes of mutations could predict the therapeutic efficacy of tyrosine kinase inhibitors (TKI), and mutations in non-small cell lung cancer characterized a subset with high bTMB, elevated ctDNA level, and potential small cell transformation. Most importantly, we developed an adjusted algorithm for bTMB in samples with extremely low ctDNA level and validated its correlation with tissue TMB in an independent cohort.

Conclusions: ctDNA could serve as a promising alternative in genomic profiling for lung cancer. The novel identification of ctDNA clonality and adjusted bTMB might improve therapeutic and prognostic evaluation. This dataset was also a valuable resource for the development of new therapeutic targets and new genomically guided clinical trials.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-1537DOI Listing
November 2021

The retinoid X receptor α modulator K-80003 suppresses inflammatory and catabolic responses in a rat model of osteoarthritis.

Sci Rep 2021 08 20;11(1):16956. Epub 2021 Aug 20.

Key Laboratory of Functional and Clinical Translational Medicine, Fujian Province University, Xiamen Medical College, Xiamen, China.

Osteoarthritis (OA), a most common and highly prevalent joint disease, is closely associated with dysregulated expression and modification of RXRα. However, the role of RXRα in the pathophysiology of OA remains unknown. The present study aimed to investigate whether RXRα modulator, such as K-80003 can treat OA. Experimental OA was induced by intra-articular injection of monosodium iodoacetate (MIA) in the knee joint of rats. Articular cartilage degeneration was assessed using Safranin-O and fast green staining. Synovial inflammation was measured using hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assay (ELISA). Expressions of MMP-13, ADAMTS-4 and ERα in joints were analyzed by immunofluorescence staining. Western blot, RT-PCR and co-Immunoprecipitation (co-IP) were used to assess the effects of K-80003 on RXRα-ERα interaction. Retinoid X receptor α (RXRα) modulator K-80003 prevented the degeneration of articular cartilage, reduced synovial inflammation, and alleviated osteoarthritic pain in rats. Furthermore, K-80003 markedly inhibited IL-1β-induced p65 nuclear translocation and IκBα degradation, and down-regulate the expression of HIF-2α, proteinases (MMP9, MMP13, ADAMTS-4) and pro-inflammatory factors (IL-6 and TNFα) in primary chondrocytes. Additionally, knockdown of ERα with siRNA blocked these effects of K-80003 in chondrocytes. In conclusion, RXRα modulators K-80003 suppresses inflammatory and catabolic responses in OA, suggesting that targeting RXRα-ERα interaction by RXRα modulators might be a novel therapeutic approach for OA treatment.
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http://dx.doi.org/10.1038/s41598-021-96517-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379249PMC
August 2021

PtSe /Pt Heterointerface with Reduced Coordination for Boosted Hydrogen Evolution Reaction.

Angew Chem Int Ed Engl 2021 Oct 17;60(43):23388-23393. Epub 2021 Sep 17.

School of Advanced study, Taizhou University, Taizhou, China.

PtSe is a typical noble metal dichalcogenide (NMD) that holds promising possibility for next-generation electronics and photonics. However, when applied in hydrogen evolution reaction (HER), it exhibits sluggish kinetics due to the insufficient capability of absorbing active species. Here, we construct PtSe /Pt heterointerface to boost the reaction dynamics of PtSe , enabled by an in situ electrochemical method. It is found that Se vacancies are induced around the heterointerface, reducing the coordination environment. Correspondingly, the exposed Pt atoms at the very vicinity of Se vacancies are activated, with enhanced overlap with H 1s orbital. The adsorption of H intermediate is thus strengthened, achieving near thermoneutral free energy change. Consequently, the as-prepared PtSe /Pt exhibits extraordinary HER activity even superior to Pt/C, with an overpotential of 42 mV at 10 mA cm and a Tafel slope of 53 mV dec . This work raises attention on NMDs toward HER and provides insights for the rational construction of novel heterointerfaces.
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http://dx.doi.org/10.1002/anie.202110335DOI Listing
October 2021

Self-paired dumbbell DNA -assisted simple preparation of stable circular DNAzyme and its application in Pb sensor.

Anal Chim Acta 2021 Aug 8;1175:338733. Epub 2021 Jun 8.

Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, Nankai University, Tianjin, 300071, PR China.

During its development in recent decades, DNAzyme has become a promising candidate for application in biosensor field. However, it still suffers from the problem of thermodynamic and biological instability such as nuclease digestion, which limits its applications in complex samples. Here we have presented a simple and common strategy to resolve this problem by engineering the linear DNAzyme into a circular shape DNAzyme based on the integration of substrate and enzyme parts into one single-stranded sequence. This circular DNAzyme system is indeed endowed with excellent stability due to the stable intramolecular double-stranded formation and extraordinary resistance to nuclease digestion due to the closed structure. We demonstrated that this circular DNAzyme system gained excellent stability and could active under conditions across a broader range of temperature, salt concentrations, and pH. Depending on this circular DNAzyme, combing with Terminal deoxynucleotidyl transferase (TdT)-generated G-quadruplexes, a label free colorimetric sensing platform for Pb quantitation was developed, and a detection limit of 0.085 nM was achieved. Then the enzyme digestion cycle amplification was introduced to further improve the sensitivity of the sensing system, an ultralow detection limit of 0.0015 nM for this fluorescence method was achieved. Based on the two sensing platforms, ultrasensitive analysis of Pb in environmental water and food samples was successfully realized. It is anticipated that this stable circular DNAzyme design will be helpful for trace detection in complex samples.
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http://dx.doi.org/10.1016/j.aca.2021.338733DOI Listing
August 2021

Exosomes derived from astrocytes after oxygen-glucose deprivation promote differentiation and migration of oligodendrocyte precursor cells in vitro.

Mol Biol Rep 2021 Jul 26;48(7):5473-5484. Epub 2021 Jul 26.

Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, People's Republic of China.

Background: Excessive release of glutamate, oxidative stress, inflammation after ischemic brain injury can lead to demyelination. Astrocytes participate in the maturation and differentiation of oligodendrocyte precursor cells (OPCs), and play multiple roles in the process of demyelination and remyelination. Here, we studied the role of Astrocyte-derived exosomes (AS-Exo) under ischemic conditions in proliferation, differentiation and migration of OPCs in vitro.

Methods And Results: Exosomes were collected from astrocytes supernatant by differential centrifugation from control astrocytes (CT), mild hypoxia astrocytes (O2R24) which were applied oxygen-glucose deprivation for 2 h and reperfusion for 24 h (OGD2hR24h) and severe hypoxia astrocytes (O4R24) which were applied oxygen-glucose deprivation for 4 h and reperfusion for 24 h (OGD4hR24h). Exosomes (20 µg/ml) were co-cultured with OPCs for 24 h and their proliferation, differentiation and migration were detected. The results showed that AS-Exo under severe hypoxia (O4R24) inhibit the proliferation of OPCs. Meanwhile, all exosomes from three groups can promote OPCs differentiation and migration. Compared to control, the expressions of MAG and MBP, markers of mature oligodendrocytes, were significantly increased in AS-Exo treatment groups. AS-Exo treatment significantly increased chemotaxis for OPCs.

Conclusions: AS-Exo improve OPCs' differentiation and migration, whereas AS-Exo with severe hypoxic precondition suppress OPCs' proliferation. AS-Exo may be a potential therapeutic target for myelin regeneration and repair in white matter injury or other demyelination related diseases.
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http://dx.doi.org/10.1007/s11033-021-06557-wDOI Listing
July 2021

Social Cognitive Correlates of Physical Activity among Chinese University Employees: A Cross-Sectional Study.

Int J Environ Res Public Health 2021 07 2;18(13). Epub 2021 Jul 2.

Department of Physical and Art Education, Zhejiang University, Hangzhou 310098, China.

Despite the well-documented benefits of leisure time physical activity, university employees are often reported to be at high risk of physical inactivity and low fitness levels. However, few efforts have been made to identify modifiable correlates of physical activity among this population. From the perspective of Social Cognitive Theory (SCT), the current study aims to examine the relationship between physical activity and a series of demographic variables (e.g., age, gender, income, education), self-reported fitness, and social cognitive variables. Data were collected through mail-based surveys from a convenience sample consisting of 116 Chinese university employees (age = 36.59 ± 8.7 y). An array of SCT variables, namely, exercise self-efficacy ( = 0.55, < 0.01), barrier self-efficacy ( = 0.35, < 0.01), exercise social support ( = 0.37, < 0.01), importance of physical self ( = 0.30, < 0.01), outcome expectations ( = 0.24, < 0.05), and satisfaction with health( = 0.32, < 0.01) were found to be positively correlated with physical activity in Chinese faculty and staff, and most of the correlations were moderate to large in magnitude. Further regression analyses indicate that exercise self-efficacy ( = 0.29, < 0.01) and exercise social support from friends ( = 0.70, < 0.01) emerge as significant predictors of physical activity after controlling for age, gender, occupation (faculty or staff), and self-reported fitness. It is concluded that these SCT variables are important correlates of university employees' physical activity behavior. Future physical activity promotion interventions in this population should incorporate strategies to improve one's confidence in maintaining regular physical activity and enhance social support from friends, which are likely to increase the effectiveness of these programs.
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http://dx.doi.org/10.3390/ijerph18137116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297127PMC
July 2021

Multi-Center in-Depth Screening of Neonatal Deafness Genes: Zhejiang, China.

Front Genet 2021 2;12:637096. Epub 2021 Jul 2.

Beijing Genomics Institute, Shenzhen, China.

Purpose: The conventional genetic screening for deafness involves 9-20 variants from four genes. This study expands screening to analyze the mutation types and frequency of hereditary deafness genes in Zhejiang, China, and explore the significance of in-depth deafness genetic screening in newborns.

Methods: This was a multi-centre study conducted in 5,120 newborns from 12 major hospitals in the East-West (including mountains and islands) of Zhejiang Province. Concurrent hearing and genetic screening was performed. For genetic testing, 159 variants of 22 genes were screened, including , , , , , , , , , , , , , , , , , , , , , and using next-generation sequencing. Newborns who failed to have genetic mutations or hearing screening were diagnosed audiologically at the age of 6 months.

Results: A total of 4,893 newborns (95.57%) have passed the initial hearing screening, and 7 (0.14%) have failed in repeated screening. Of these, 446 (8.71%) newborns carried at least one genetic deafness-associated variant. High-risk pathogenic variants were found in 11 newborns (0.21%) (nine homozygotes and two compound heterozygotes), and eight of these infants have passed the hearing screening. The frequency of mutations in , , , , and was 5.43%, 0.59%, 1.91%, 0.98%, and 0.02%, respectively. The positive rate of in-depth screening was significantly increased when compared with 20 variants in four genes of traditional testing, wherein was increased by 97.2%, by 21% and by 150%. The most common mutation variants were GJB2c.235delC and SLC26A4c.919-2A > G, followed by GJB2c.299_300delAT. Homoplasmic mutation in was the most common, including m.1555A > G, m.961T > C, m.1095T > C. All these infants have passed routine hearing screening. The positive rate of mutation was significantly higher in newborns with high-risk factors of maternal pregnancy.

Conclusion: The positive rate of deafness gene mutations in the Zhejiang region is higher than that of the database, mainly in GJB2c.235delC, SLC26A4 c.919-2A > G, and m.1555A > G variants. The expanded genetic screening in the detection rate of diseasecausing variants was significantly improved. It is helpful in identifying high-risk children for follow-up intervention.
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http://dx.doi.org/10.3389/fgene.2021.637096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282931PMC
July 2021

The margin of internal risk volume on atrial septal and ventricular septal based on electrocardiograph gating 4DCT.

Ann Transl Med 2021 May;9(10):842

Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Background: The aim of this study was to quantify the margin of internal risk volume (IRV) on the atrial septum (AS) and ventricular septum (VS) based on electrocardiograph gating (ECG-gating) 4DCT.

Methods: Twenty patients were enrolled and received an ECG-gating 4DCT scan performed in breath-hold, and CT images were reconstructed at 5% intervals of the cardiac cycle for a total of 20 phases (0-95%). The contouring of the AS and VS were delineated in each phase, and the displacements and margin of the AS and VS were calculated. We fused the total of the AS and VS (0-95% phase), which were recorded as AS and VS. The margins were applied to the AS and VS in every phase and revised according to the cover rate of AS and VS.

Results: (I) The margins of the AS and VS according to displacements in the left-right, cranio-caudal, and antero-posterior direction were 3 mm, 3 mm, and 3 mm; and 3 mm, 3 mm, and 2 mm, respectively. (II) The volume of AS was (11.80±3.72) cm, which was 2.9 times larger than the maximum volume of the AS. The volume of VS was (60.45±12.92) cm, which was 1.6 times larger than the maximum volume of the VS. (III) The emendatory margins of the AS and VS in the left-right, cranio-caudal, and antero-posterior direction were 7 mm, 10 mm, and 7 mm; and 5 mm, 3 mm, and 4 mm, respectively. The emendatory margins were added to the AS and VS, and the coverage rates were (95.88±3.29)% and (95.24±2.54)%, respectively.

Conclusions: The margin of IRV on the AS and VS could cover the movement of AS and VS induced by heartbeat in the left-right, cranio-caudal, and antero-posterior direction respectively during thoracic radiotherapy.
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http://dx.doi.org/10.21037/atm-21-1162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184443PMC
May 2021

The association between the ERCC1/2 polymorphisms and radiotherapy efficacy in 87 patients with non-small cell lung cancer.

J Thorac Dis 2021 May;13(5):3126-3136

Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Background: This study sought to investigate the association between the ERCC1/2 single-nucleotide polymorphisms (SNPs) and the efficacy of radiotherapy and prognosis in patients with non-small cell lung cancer (NSCLC).

Methods: We examined 6 SNPs in the ERCC1 and ERCC2 genes in 87 consecutive patients with NSCLC who were treated with definitive radiotherapy. The objective remission rates (ORR), overall survival (OS), and progressive-free survival (PFS) were assessed. A Cox regression analysis was conducted to analyze the independent factors related to death and recurrence.

Result: Patients with the G allele had better OS than patients with the A allele, and there was a statistical difference between the two groups (30.9 16.2 months; P=0.003). Patients with the genotype had significantly worse OS than patients with the or genotypes (6.8 19.8 30.9 months, respectively; P=0.000). The median PFS of the G allele was 18.9 months, which was significantly better than that of the allele (P=0.040). The median PFS of patients with the genotype, the genotype, and the genotype was 18.9, 11.3, and 5.1 months, respectively; the difference among the three groups was statistically significant (P=0.019). Patients with the allele also had better PFS than those with the allele (18.9 11.3 months, P=0.040). The multivariate cox proportional hazard analysis showed that the ERCC1 gene was an independent survival indicator [HR: 1.623, 95% confidence interval (CI): 1.018-2.591, P=0.042] but not an independent recurrence indicator (HR: 1.497, 95% CI: 0.932-2.404, P=0.095).

Conclusions: The ERCC1 SNP may be a potential biomarker for predicting survival prognosis in Chinese NSCLC patients who have undergone definitive radiotherapy. Patients with the allele had better OS than those with the allele.
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http://dx.doi.org/10.21037/jtd-21-755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182509PMC
May 2021

PEA prevented early BBB disruption after cerebral ischaemic/reperfusion (I/R) injury through regulation of ROCK/MLC signaling.

Biochem Biophys Res Commun 2021 08 11;566:164-169. Epub 2021 Jun 11.

Institute of Respiratory Diseases Xiamen Medical College, Xiamen, Fujian, 361002, China; Key Laboratory of Functional and Clinical Translational Medicine, Fujian Province University, Xiamen Medical College, Xiamen, Fujian, 361002, China. Electronic address:

Palmitoylethanolamide (PEA) offers a strong protection against BBB disruption and neurological deficits after cerebral ischaemic/reperfusion (I/R) injury. To date, these BBB protective effects of PEA are mainly attributed to PPARα-mediated actions. However, whether PEA protects against BBB disruption through direct regulation of cytoskeletal microfilaments remains unknown. Here, we identified PEA as a Rho-associated protein kinase (ROCK2) inhibitor (IC = 38.4 ± 4.8 μM). In vitro data suggested that PEA reduced the activation of ROCK/MLC signaling and stress fiber formation within microvascular endothelial cells (ECs) after oxygen-glucose deprivation (OGD), and consequently attenuated early (0-4 h) EC barrier disruption. These actions of PEA could not be blocked by the PPARα antagonist GW6471. In summary, the present study described a previously unexplored role of PEA as a ROCK2 inhibitor, and propose a PPARα-independent mechanism for pharmacological effects of PEA.
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http://dx.doi.org/10.1016/j.bbrc.2021.06.019DOI Listing
August 2021

Serial circulating tumor DNA identification associated with the efficacy and prognosis of neoadjuvant chemotherapy in breast cancer.

Breast Cancer Res Treat 2021 Aug 18;188(3):661-673. Epub 2021 May 18.

Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No.1 Shuaifu Garden, Dongcheng District, Beijing, 100010, China.

Background: Circulating tumor DNA (ctDNA) provides a promising noninvasive alternative to evaluate the efficacy of neoadjuvant chemotherapy (NCT) in breast cancer.

Methods: Herein, we collected 63 tissue (aspiration biopsies and resected tissues) and 206 blood samples (baseline, during chemotherapy (Chemo), after chemotherapy (Post-Chemo), after operation (Post-Op), during follow-up) from 32 patients, and preformed targeted deep sequencing with a customed 1021-gene panel.

Results: As the results, TP53 (43.8%) and PIK3CA (40.6%) were the most common mutant genes in the primary tumors. At least one tumor-derived mutation was detected in the following number of blood samples: 21, baseline; 3, Chemo; 9, Post-Chemo; and 5, Post-Op. Four patients with pathologic complete response had no tissue mutation in Chemo and Post-Chemo blood. Compared to patients with mutation-positive Chemo or Post-Chemo blood, the counterparts showed a superior primary tumor decrease (median, 86.5% versus 54.6%) and lymph involvement (median, 1 versus 3.5). All five patients with mutation-positive Post-Op developed distant metastases during follow-up, and the sensitivity of detecting clinically relapsed patients was 71.4% (5/7). The median DFS was 9.8 months for patients with mutation-positive Post-Op but not reached for the others (HR 23.53; 95% CI, 1.904-290.9; p < 0.0001).

Conclusions: Our study shows that sequential monitoring of blood ctDNA was an effective method for evaluating NCT efficacy and patient recurrence. Integrating ctDNA profiling into the management of LABC patients might improve clinical outcome.

Trial Registration: This prospective study recruited LABC patients at Peking Union Medical College Hospital (ClinicalTrials.gov Identifier: NCT02797652).
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http://dx.doi.org/10.1007/s10549-021-06247-yDOI Listing
August 2021

Circulating Tumor DNA Analyses Predict Disease Recurrence in Non-Muscle-Invasive Bladder Cancer.

Front Oncol 2021 28;11:657483. Epub 2021 Apr 28.

Health Science Center, The First Affiliated Hospital of Shenzhen University, and Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, Shenzhen Second People's Hospital, Shenzhen, China.

Circulating tumor DNA (ctDNA) can be a prognostic biomarker for non-muscle-invasive bladder cancer (NMIBC); however, targeted sequencing has not been performed to detect ctDNA in NMIBC. We applied targeted sequencing based on an 861-gene panel to determine mutations in tumor tissue DNA and plasma ctDNA in 82 NMIBC patients receiving transurethral resection (TUR) of bladder followed by immunotherapy. We detected 476 and 165 somatic variants in tumor DNA from 82 NMIBC patients (100%) and ctDNA from 54 patients (65.85%), respectively. Patients with high heterogeneity in tumor DNA had a significantly shorter disease-free survival than those with low heterogeneity. Tumor-derived alterations were detectable in plasma of 43 patients (52.44%). The concordance of somatic variants between tumor DNA and plasma ctDNA were higher in patients with T1 stage (p < 0.0001) and tumor size ≥3 cm (p = 0.0002). Molecular tumor burden index (mTBI) in ctDNA positively correlated with larger tumor size (p = 0.0020). A higher mTBI was an independent predictor of recurrence after TUR of bladder followed by immunotherapy. Analysis of ctDNA based on targeted sequencing is a promising approach to predict disease recurrence for NMIBC patients receiving TUR of bladder followed by immunotherapy.
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http://dx.doi.org/10.3389/fonc.2021.657483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114939PMC
April 2021

Identifying Genomic Alterations in Small Cell Lung Cancer Using the Liquid Biopsy of Bronchial Washing Fluid.

Front Oncol 2021 26;11:647216. Epub 2021 Apr 26.

Department of Respiratory Ward One, Shanxi Provincial Cancer Hospital, Taiyuan, China.

With the rapid development of cancer genomics and immunomics, some new treatments of small cell lung cancer (SCLC) are emerging. However, there are limitations to the clinical use of tumor tissue. Our study aimed to evaluate the potential use of bronchial washing fluid (BWF) in the liquid biopsy of SCLC. Twenty-one extensive SCLC (ES-SCLC) patients were enrolled in this study. For all patients, four sample types, BWF supernatant (BWFs), BWF precipitate (BWFp), plasma and tumor tissue, were collected before receiving chemotherapy, and one type, plasma, was collected after chemotherapy. All samples were conducted to NGS using the 1021-gene panel. The concordance rates of genomic profiling using NGS in the four types of samples were evaluated. Multiple clinical information was analyzed for correlation. We successfully tested 20 BWFs samples, 21 BWFp samples, 21 tumor tissue samples, 20 pre-treatment plasma, and 13 post-treatment plasma of these 21 patients. The detectability of somatic mutations was 100% for BWFs, BWFp, tumor tissues, and post-treatment plasma, and only one pre-treatment plasma was absent with any mutation. Matched tumor tissue, BWFs, BWFp, and pre-treatment plasma samples were subsistent for 19 patients. For these patients, 204 genomic alterations were identified in tissue samples, while 189 (92.6%), 175 (85.5%), and 163 (79.9%) alterations were detected in the matched BWFs, BWFp, and pre-treatment plasma, respectively. Moreover, we found that the three tumor markers associated with SCLC have a lower sensitivity than genomic alterations. The endocrine resistance pathway was found enriched in hyponatremia patients which may be related to the hyponatremia. The TMBs of BWF, BWFp, and pre-treatment plasma samples all had a strong correlation with that of tissue samples. Both the VAF and the MVAF of mutations in post-treatment plasma were less than those in pre-treatment plasma, which was in accordance with the evaluation of curative effect. For ES-SCLC patients, the liquid biopsy of BWF showed a highly potential advantage to identify DNA alterations, which suggested that genomic analysis of BWF liquid biopsy may have clinical value as a supplement for tissue and blood detection. Through the restricted validation, it can be widely used in routine clinical practice.
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http://dx.doi.org/10.3389/fonc.2021.647216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110515PMC
April 2021

Deep Neural Networks for Depression Recognition Based on 2D and 3D Facial Expressions Under Emotional Stimulus Tasks.

Front Neurosci 2021 23;15:609760. Epub 2021 Apr 23.

School of Information Science Engineering, Lanzhou University, Lanzhou, China.

The proportion of individuals with depression has rapidly increased along with the growth of the global population. Depression has been the currently most prevalent mental health disorder. An effective depression recognition system is especially crucial for the early detection of potential depression risk. A depression-related dataset is also critical while evaluating the system for depression or potential depression risk detection. Due to the sensitive nature of clinical data, availability and scale of such datasets are scarce. To our knowledge, there are few extensively practical depression datasets for the Chinese population. In this study, we first create a large-scale dataset by asking subjects to perform five mood-elicitation tasks. After each task, subjects' audio and video are collected, including 3D information (depth information) of facial expressions via a Kinect. The constructed dataset is from a real environment, i.e., several psychiatric hospitals, and has a specific scale. Then we propose a novel approach for potential depression risk recognition based on two kinds of different deep belief network (DBN) models. One model extracts 2D appearance features from facial images collected by an optical camera, while the other model extracts 3D dynamic features from 3D facial points collected by a Kinect. The final decision result comes from the combination of the two models. Finally, we evaluate all proposed deep models on our built dataset. The experimental results demonstrate that (1) our proposed method is able to identify patients with potential depression risk; (2) the recognition performance of combined 2D and 3D features model outperforms using either 2D or 3D features model only; (3) the performance of depression recognition is higher in the positive and negative emotional stimulus, and females' recognition rate is generally higher than that for males. Meanwhile, we compare the performance with other methods on the same dataset. The experimental results show that our integrated 2D and 3D features DBN is more reasonable and universal than other methods, and the experimental paradigm designed for depression is reasonable and practical.
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http://dx.doi.org/10.3389/fnins.2021.609760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102822PMC
April 2021

Risk factors for radiation pneumonitis in lung cancer patients with subclinical interstitial lung disease after thoracic radiation therapy.

Radiat Oncol 2021 Apr 13;16(1):70. Epub 2021 Apr 13.

Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Yangpu District, Shanghai, 200433, People's Republic of China.

Background: Previous studies have found that patients with subclinical interstitial lung disease (ILD) are highly susceptible to developing radiation pneumonitis (RP) after thoracic radiation therapy. In the present study we aimed to evaluate the incidence of and risk factors for RP after thoracic intensity-modulated radiation therapy in lung cancer patients with subclinical ILD.

Methods: We retrospectively analyzed data from lung cancer patients with subclinical ILD who were treated with thoracic intensity-modulated radiation therapy with a prescribed dose of ≥ 50 Gy in our institution between January 2016 and December 2017.

Results: Eighty-seven consecutive lung cancer patients with subclinical ILD were selected for the study. The median follow-up period was 14.0 months. The cumulative incidence of grades ≥ 2 and ≥ 3 RP at one year was 51.0% and 20.9%, respectively. In the multivariate analysis, a mean lung dose ≥ 12 Gy was a significant risk factor for grade ≥ 2 RP (p = 0.049). Chemotherapy with gemcitabine in the past, V5 ≥ 50%, and subclinical ILD involving ≥ 25% of the lung volume were significantly associated with grade ≥ 3 RP (p = 0.046, p = 0.040, and p = 0.024, respectively).

Conclusion: Mean lung dose is a significant risk factor for grade ≥ 2 RP. Lung cancer patients who have received chemotherapy with gemcitabine in the past, V5 ≥ 50%, and those with subclinical ILD involving ≥ 25% of lung volume have an increased risk of grade ≥ 3 RP in lung cancer patients with subclinical ILD.
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http://dx.doi.org/10.1186/s13014-021-01798-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045204PMC
April 2021

Hierarchical Self-Assembly of Nanowires on the Surface by Metallo-Supramolecular Truncated Cuboctahedra.

J Am Chem Soc 2021 04 13;143(15):5826-5835. Epub 2021 Apr 13.

College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, Guangdong 518060, China.

Parastichy, the spiral arrangement of plant organs, is an example of the long-range apparent order seen in biological systems. These ordered arrangements provide scientists with both an aesthetic challenge and a mathematical inspiration. Synthetic efforts to replicate the regularity of parastichy may allow for molecular-scale control over particle arrangement processes. Here we report the packing of a supramolecular truncated cuboctahedron (TCO) into double-helical (DH) nanowires on a graphite surface with a non-natural parastichy pattern ascribed to the symmetry of the TCOs and interactions between TCOs. Such a study is expected to advance our understanding of the design inputs needed to create complex, but precisely controlled, hierarchical materials. It is also one of the few reported helical packing structures based on Platonic or Archimedean solids since the discovery of the Boerdijk-Coxeter helix. As such, it may provide experimental support for studies of packing theory at the molecular level.
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http://dx.doi.org/10.1021/jacs.1c00625DOI Listing
April 2021

DNA damage response as a prognostic indicator in metastatic breast cancer via mutational analysis.

Ann Transl Med 2021 Feb;9(3):220

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: High tumor heterogeneity contributes to breast cancer recurrence and metastasis. However, the lack of indicators to serve as precise and reliable means of predicting breast cancer prognosis has yet to be addressed. This study aims to reveal the prognostic relevance of mutations in metastatic breast cancer (MBC) by large-scale circulating tumor DNA (ctDNA) analysis in China.

Methods: We performed ctDNA panel-captured sequencing of 958 blood samples from MBC patients including 494 hormone receptor (HR)-positive cases, 130 human epidermal growth factor receptor 2-positive cases, and 177 triple-negative breast cancer (TNBC) cases. The somatic mutations and potential targets were assessed. Progression-free survival (PFS) was analyzed using the Kaplan-Meier method.

Results: In 801 of the 958 MBC blood samples, 663 mutated genes and 5,829 nonsynonymous alterations were identified. Mutated genes of the highest frequency were tumor protein p53 (, 54%), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (, 41%), estrogen receptor 1 (, 12%), myeloid/lymphoid or mixed-lineage leukemia protein 3 (, 11%), DNA (cytosine-5)-methyltransferase 3A (, 10%), erb-b2 receptor tyrosine kinase 2 (, 10%), GATA binding protein 3 (, 8%), FAT atypical cadherin 1 (, 7%), phosphatase and tensin homolog (, 6%), and mitogen-activated protein kinase kinase kinase 1 (, 6%). Enriched mutations and driver genes in MBC varied across stages and in multiple subtypes. Moreover, , , or coexisting / mutations in MBC were remarkably related with shorter PFS. Mutated DNA damage response (DDR) genes were significantly associated with tumor mutation burden and mutant-allele tumor heterogeneity score, as well as with worse clinical outcome.

Conclusions: Our findings indicate that the mutations of , , , and in particular, DDR genes, in MBC might be relevant indicators of unfavorable prognosis in MBC.
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http://dx.doi.org/10.21037/atm-20-2137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940884PMC
February 2021

Tumor mutation burden as a biomarker in resected gastric cancer via its association with immune infiltration and hypoxia.

Gastric Cancer 2021 07 9;24(4):823-834. Epub 2021 Mar 9.

Department of Medical Oncology, Jiangsu Province Hospital, Nanjing, China.

Background: Tumor mutation burden (TMB) predicts immunotherapy efficacy in solid tumors. However, the biomarker role of TMB is still conflicting in resected tumors. We aimed to examine the association of TMB with prognosis and postoperative chemotherapy (CT) or radiochemotherapy (RCT) efficacy in resected gastric cancer (GC).

Methods: Whole-exome sequencing (WES) was performed in 73 resected GC specimens. Validation cohorts included 352 patients from The Cancer Genome Atlas (TCGA) and 222 patients from the Asian Cancer Research Group (ACRG). Immune infiltration and hypoxia were evaluated by transcriptome data and immunohistochemistry assay.

Results: TMB-high GC had favorable overall survival (OS) and disease-free survival (DFS), but the OS and DFS benefits with postoperative CT/RCT were more pronounced in TMB-low GC. These findings were consistent among all three cohorts and were maintained in the pooled cohort. Stratified by stages in the pooled cohort, stage III GC benefited from postoperative CT/RCT regardless of TMB level while stage Ib/II GC benefited from postoperative CT/RCT in TMB-low but not in TMB-high subgroup. TMB positively correlated with immune infiltration which was characterized by NK cell rather than CD8 + T cell enrichment. TMB-high GC was more hypoxic than TMB-low GC, and TMB-high stage Ib/II GC was the most hypoxic.

Conclusions: High TMB may predict favorable prognosis in resected GC but poor response to postoperative CT/RCT in stage Ib/II subgroup, which may be determined by TMB-associated immune infiltration and hypoxia, respectively.
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http://dx.doi.org/10.1007/s10120-021-01175-8DOI Listing
July 2021

High-Intensity Focused Ultrasound Combined With Gonadotropin-Releasing Hormone Agonist or Levonorgestrel-Releasing Intrauterine System in Treating Dysmenorrhea of Severe Adenomyosis.

J Comput Assist Tomogr 2021 Mar-Apr 01;45(2):224-231

From the Department of Gynaecology, General Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin.

Objective: The objective of this study was to investigate the efficacy of high-intensity focused ultrasound (HIFU) combined with gonadotropin-releasing hormone agonist or levonorgestrel-releasing intrauterine system (LNG-IUS) in treating dysmenorrhea in patients with severe adenomyosis.

Methods: A retrospective analysis was performed on 243 patients diagnosed with severe adenomyosis. Patients were divided into H (received HIFU alone), H-G (received HIFU combined with gonadotropin-releasing hormone agonist), and H-L (received HIFU combined with LNG-IUS) groups. Their clinical results were compared at 3 months, 6 months, and 12 months after treatment.

Results: The effective rates of dysmenorrhea relief in the 3 groups after 3 months were 95.24% in the H group, 98.8% in the H-G group, and 94.74% in the H-L group; those after 6 months were 88.10% in the H group, 95.18% in the H-G group, and 84.21% in the H-L group; those after 12 months were 77.38% in the H group, 79.52% in the H-G group, and 96.05% in the H-L group. There was significant difference in effective rates of dysmenorrhea relief among 3 groups after 12 months of treatment, but not 3 or 6 months. In addition, at 12 months after treatment, there were significant differences in the efficacy of dysmenorrhea between patients of different ages or different ablation rates in group H. However, there was no significant difference in the H-G group and the H-L group.

Conclusions: High-intensity focused ultrasound alone is effective in alleviating the symptoms of dysmenorrhea in short term. However, HIFU combined with LNG-IUS improves the therapeutic effect for a longer period.
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http://dx.doi.org/10.1097/RCT.0000000000001138DOI Listing
April 2021
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