Publications by authors named "Kui Wu"

200 Publications

Triclinic Layered AZnSiS (A = Rb and Cs) with Large Optical Anisotropy and Systematic Research on the Inherent Structure-Performance Relationship in the AMMQ Family.

Inorg Chem 2021 Jul 28. Epub 2021 Jul 28.

Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China.

Two triclinic AZnSiS (A = Rb and Cs) with layered structures were successfully synthesized, and their physicochemical performances including optical bandgap, thermal behavior, and optical anisotropy were investigated. AZnSiS could be viewed as the first discovered Si-based examples in the known AMMQ family (2-1-3-8 system; A = monovalent alkali metal; M = divalent transition metal; M = group 14 metal; Q = chalcogen). The AMMQ family members crystallize in five different space groups (1̅, 2, 2/, 222, and 3̅), and their structural transformation and optical performances (bandgap, NLO coefficient, and birefringence) were systematically studied based on the first-principles calculation among 13 AMMQ (M = Zn, Cd, and Hg) compounds without cubic β-KZnSnS. Research result shows that the above 13 compounds exhibit the layered structures, but diverse wavelike layers and their optical anisotropy (Δ) undergo an increasing trend range from the triclinic to orthorhombic systems. Moreover, 222 compounds have very weak NLO effects compared with those of the 2 compounds since the polarization directions of anionic groups (MQ and MQ) in 222 compounds are directing oppositely and almost completely canceled out by the dipole moment calculation, which further indicates that 2 compounds exhibiting the relatively strong NLO effect and large optical anisotropy could be expected as potential IR NLO candidates.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01886DOI Listing
July 2021

From thiophosphate to chalcohalide: mixed-anion AgSCl ligands concurrently enhancing nonlinear optical effects and laser-damage threshold.

Chem Commun (Camb) 2021 Jul 26. Epub 2021 Jul 26.

College of Chemistry and Environmental Science, Key Laboratory of Analytical Science and Technology of Hebei Province, Hebei University, Baoding, China.

In this study, we propose a new design strategy that introduces unique mixed-anion AgSxCly ligands into thiophosphate to afford a successful synthesis of a promising Ag5PS4Cl2 IR NLO chalcohalide. Compared with chlorine-free Ag3PS4, Ag5PS4Cl2 undergoes overall performance enhancement and achieves a good balance between large NLO effect (2.0 × Ag3PS4) and high laser damage threshold (3.8 × Ag3PS4). Theoretical analysis further indicates that AgSxCly groups are the new superior NLO-active units since they can maintain the wide bandgap while concurrently making a great contribution to the origin of NLO effects. Therefore, the incorporation of AgSxCly groups into the crystal structure can be expected to be one feasible way to design new IR NLO candidates with excellent performance.
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http://dx.doi.org/10.1039/d1cc02656aDOI Listing
July 2021

Tumor heterogeneity assessed by sequencing and fluorescence in situ hybridization (FISH) data.

Bioinformatics 2021 Jul 20. Epub 2021 Jul 20.

Computational Biology Dept, Carnegie Mellon University, Pittsburgh, PA, 15213, USA.

Motivation: Computational reconstruction of clonal evolution in cancers has become a crucial tool for understanding how tumors initiate and progress and how this process varies across patients. The field still struggles, however, with special challenges of applying phylogenetic methods to cancers, such as the prevalence and importance of copy number alteration (CNA) and structural variation (SV) events in tumor evolution, which are difficult to profile accurately by prevailing sequencing methods in such a way that subsequent reconstruction by phylogenetic inference algorithms is accurate.

Results: In the present work, we develop computational methods to combine sequencing with multiplex interphase fluorescence in situ hybridization (miFISH) to exploit the complementary advantages of each technology in inferring accurate models of clonal CNA evolution accounting for both focal changes and aneuploidy at whole-genome scales. By integrating such information in an integer linear programming (ILP) framework, we demonstrate on simulated data that incorporation of FISH data substantially improves accurate inference of focal CNA and ploidy changes in clonal evolution from deconvolving bulk sequence data. Analysis of real glioblastoma data for which FISH, bulk sequence, and single cell sequence are all available confirms the power of FISH to enhance accurate reconstruction of clonal copy number evolution in conjunction with bulk and optionally single-cell sequence data.

Availability: Source code is available on Github at https://github.com/CMUSchwartzLab/FISH_deconvolution.
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http://dx.doi.org/10.1093/bioinformatics/btab504DOI Listing
July 2021

Comparative analysis of clonal evolution among patients with right- and left-sided colon and rectal cancer.

iScience 2021 Jul 11;24(7):102718. Epub 2021 Jun 11.

BGI-Qingdao, BGI-Shenzhen, Qingdao 266555, China.

Tumor multiregion sequencing reveals intratumor heterogeneity (ITH) and clonal evolution playing a key role in tumor progression and metastases. Large-scale high-depth multiregional sequencing of colorectal cancer, comparative analysis among patients with right-sided colon cancer (RCC), left-sided colon cancer (LCC), and rectal cancer (RC), as well as the study of lymph node metastasis (LN) with extranodal tumor deposits (ENTDs) from evolutionary perspective remain weakly explored. Here, we recruited 68 patients with RCC (18), LCC (20), and RC (30). We performed high-depth whole-exome sequencing of 206 tumor regions including 176 primary tumors, 19 LN, and 11 ENTD samples. Our results showed ITH with a Darwinian pattern of evolution and the evolution pattern of LCC and RC was more complex and divergent than RCC. Genetic and evolutionary evidences found that both LN and ENTD originated from different clones. Moreover, ENTD was a distinct entity from LN and evolved later.
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http://dx.doi.org/10.1016/j.isci.2021.102718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254024PMC
July 2021

Centrosymmetric or Noncentrosymmetric? Transition Metals Talking in KTGeS(T = Co, Fe).

Inorg Chem 2021 Jul 29;60(14):10603-10613. Epub 2021 Jun 29.

Department of Chemistry, Wichita State University, Wichita, Kansas 67260, United States.

Two new quaternary sulfides KTGeS(T = Co, Fe) have been synthesized by a high-temperature solid-state routine and flux growth method. The crystal growth process of KTGeS(T = Co, Fe) was elucidated by powder X-ray diffraction and DSC thermal analysis. The millimeter-sized crystals of KTGeS(T = Co, Fe) were grown. KCoGeS crystallizes in a new structure type in centrosymmetric space group 1 (no. 2) with unit cell parameters of = 7.016(1) Å, = 7.770(1) Å, = 14.342(1) Å, α = 93.80(1)°, β = 92.65(1)°, γ = 114.04(1)°. KFeGeS crystallizes in the KFeGeSe structure type and the noncentrosymmetric space group 2 (no. 4) with unit cell parameters of = 7.1089(5)Å, = 11.8823(8) Å, = 16.7588(11) Å, β = 96.604(2)°. There is a high structural similarity between KCoGeS and KFeGeS. The larger volume coupled with higher degrees of distortion of the [FeS] tetrahedra compared to the [CoS] tetrahedra accounts for the structure's shift from centrosymmetric to noncentrosymmetric. The theory simulation confirms that [TS] tetrahedra play a crucial role in controlling the structure and properties of KTGeS(T = Co, Fe). The measured optical bandgaps of KCoGeS and KFeGeS are 2.1(1) eV and 2.6(1) eV, respectively. KFeGeS shows antiferromagnetic ordering at 24 K while no magnetic ordering was detected in KCoGeS. The magnetic measurements also demonstrate the divalent nature of transition metals in KTGeS(T = Co, Fe).
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http://dx.doi.org/10.1021/acs.inorgchem.1c01149DOI Listing
July 2021

Correction: Click activated protodrugs against cancer increase the therapeutic potential of chemotherapy through local capture and activation.

Chem Sci 2021 May 21;12(21):7583. Epub 2021 May 21.

University at Albany, SUNY 1400 Washington Ave., LS-1136 Albany NY 12222 USA

[This corrects the article DOI: 10.1039/D0SC06099B.].
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http://dx.doi.org/10.1039/d1sc90098fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171313PMC
May 2021

Click activated protodrugs against cancer increase the therapeutic potential of chemotherapy through local capture and activation.

Chem Sci 2021 Jan 5;12(4):1259-1271. Epub 2021 Jan 5.

University at Albany, SUNY 1400 Washington Ave., LS-1136 Albany NY 12222 USA

A desired goal of targeted cancer treatments is to achieve high tumor specificity with minimal side effects. Despite recent advances, this remains difficult to achieve in practice as most approaches rely on biomarkers or physiological differences between malignant and healthy tissue, and thus benefit only a subset of patients in need of treatment. To address this unmet need, we introduced a Click Activated Protodrugs Against Cancer (CAPAC) platform that enables targeted activation of drugs at a specific site in the body, , a tumor. In contrast to antibodies (mAbs, ADCs) and other targeted approaches, the mechanism of action is based on click chemistry, and is thus independent of tumor biomarker expression or factors such as enzymatic activity, pH, or oxygen levels. The CAPAC platform consists of a tetrazine-modified sodium hyaluronate-based biopolymer injected at a tumor site, followed by one or more doses of a -cyclooctene (TCO)-modified cytotoxic protodrug with attenuated activity administered systemically. The protodrug is captured locally by the biopolymer through an inverse electron-demand Diels-Alder reaction between tetrazine and TCO, followed by conversion to the active drug directly at the tumor site, thereby overcoming the systemic limitations of conventional chemotherapy or the need for specific biomarkers of traditional targeted therapies. Here, TCO-modified protodrugs of four prominent cytotoxics (doxorubicin, paclitaxel, etoposide and gemcitabine) are used, highlighting the modularity of the CAPAC platform. evaluation of cytotoxicity, solubility, stability and activation rendered the protodrug of doxorubicin, , as the most promising candidate for studies. In mice, the maximum tolerated dose (MTD) of in combination with locally injected tetrazine-modified biopolymer () was determined to be 19.1-times the MTD of conventional doxorubicin. Pharmacokinetics studies in rats show that a single injection of efficiently captures multiple protodrug doses given cumulatively at 10.8-times the MTD of conventional doxorubicin with greatly reduced systemic toxicity. Finally, combined treatment with and (together called ) showed antitumor activity in a syngeneic tumor model in mice.
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http://dx.doi.org/10.1039/d0sc06099bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179178PMC
January 2021

Single cell imaging reveals cisplatin regulating interactions between transcription (co)factors and DNA.

Chem Sci 2021 Feb 25;12(15):5419-5429. Epub 2021 Feb 25.

Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, National Centre for Mass Spectrometry in Beijing, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences Beijing 100190 People's Republic of China

Cisplatin is an extremely successful anticancer drug, and is commonly thought to target DNA. However, the way in which cisplatin-induced DNA lesions regulate interactions between transcription factors/cofactors and genomic DNA remains unclear. Herein, we developed a dual-modal microscopy imaging strategy to investigate, , the formation of ternary binding complexes of the transcription cofactor HMGB1 and transcription factor Smad3 with cisplatin crosslinked DNA in single cells. We utilized confocal microscopy imaging to map EYFP-fused HMGB1 and fluorescent dye-stained DNA in single cells, followed by the visualization of cisplatin using high spatial resolution (200-350 nm) time of flight secondary ion mass spectrometry (ToF-SIMS) imaging of the same cells. The superposition of the fluorescence and the mass spectrometry (MS) signals indicate the formation of HMGB1-Pt-DNA ternary complexes in the cells. More significantly, for the first time, similar integrated imaging revealed that the cisplatin lesions at Smad-binding elements, for example GGC(GC)/(CG) and AGAC, disrupted the interactions of Smad3 with DNA, which was evidenced by the remarkable reduction in the expression of Smad-specific luciferase reporters subjected to cisplatin treatment. This finding suggests that Smad3 and its related signalling pathway are most likely involved in the intracellular response to cisplatin induced DNA damage.
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http://dx.doi.org/10.1039/d0sc06760aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179581PMC
February 2021

Visual detection of viscosity through activatable molecular rotor with aggregation-induced emission.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Nov 25;261:120016. Epub 2021 May 25.

School of Chemistry and Chemical Engineering, Jinggangshan University, Ji'an, Jiangxi 343009, China. Electronic address:

Food safety has become one of the urgent affairs in the global public health studies, and irregular viscosity is closely associated with the food spoilage extent. In this study, one kind of activatable molecular rotor (TPA-PBZ) based on triphenylamine derivates has been synthesized via the Schiff base condensation reaction. This rotor is comprised by donor-accepter conjugated structure, with aggregation induced-emission feature and a large Stokes shift of 160 nm in water. The rotation of aromatic rings in TPA-PBZ is restricted in high-viscosity microenvironment, with the gradually increasing fluorescence emission signal at 568 nm. Significantly, this rotor TPA-PBZ has successfully been applied not only in the determination of thickening effects of food gum, but also in the detection of viscosity enhancement during the liquid food spoilage process. This molecular rotor can be utilized as an intelligent monitor platform for food quality and safety inspection in viscosity-related conditions.
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http://dx.doi.org/10.1016/j.saa.2021.120016DOI Listing
November 2021

Modifications of the Langendorff Method for Simultaneous Isolation of Atrial and Ventricular Myocytes from Adult Mice.

J Vis Exp 2021 May 13(171). Epub 2021 May 13.

Department of Cardiology, Bejing Anzhen Hospital, Capital Medical University;

A single cardiomyocyte is a vital tool in the cellular and subcellular level studies of cardiac biology and diseases as a fundamental unit of contraction and electrical activity. Hence, isolating viable, high-quality cardiomyocytes from the heart is the initial and most crucial experimental step. Comparing the various protocols for isolating the cardiomyocytes of adult mice, the Langendorff retrograde perfusion is the most successful and reproducible method reported in the literature, especially for isolating ventricular myocytes. However, isolating quality atrial myocytes from the perfused heart remains challenging, and few successful isolation reports are available. Solving this complicated problem is extremely important because apart from ventricular disease, atrial disease accounts for a large part of heart diseases. Therefore, further investigations on the cellular level to reveal the mechanisms are warranted. In this paper, a protocol based on the Langendorff retrograde perfusion method is introduced and some modifications in the depth of aorta cannulation and the steps that may affect the digestion process to isolate atrial and ventricular myocytes were simultaneously made. Moreover, the isolated cardiomyocytes are confirmed to be amenable to patch clamp investigation.
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http://dx.doi.org/10.3791/62514DOI Listing
May 2021

Personalized Variable vs Fixed-Dose Systemic Corticosteroid Therapy in Hospitalized Patients With Acute Exacerbations of COPD: A Prospective, Multicenter, Randomized, Open-Label Clinical Trial.

Chest 2021 May 21. Epub 2021 May 21.

Department of Respiratory Medicine, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, China. Electronic address:

Background: Systemic corticosteroids for the treatment of COPD exacerbations decrease treatment failure and shorten the length of hospitalization. However, the optimal dose is unclear.

Research Question: Is personalized-dose corticosteroid administered according to a dosing scale more effective than fixed-dose corticosteroid administration in hospitalized patients with COPD with exacerbations?

Study Design And Methods: This was a prospective, randomized, open-label trial. In-hospital patients with COPD with exacerbations were randomly assigned at a 1:1 ratio to either the fixed-dose group (receiving the equivalent of 40 mg of prednisolone) or the personalized-dose group for 5 days. The primary end point was a composite measure of treatment failure that included in-hospital treatment failure and medium-term (postdischarge) failure. Secondary end points were length of stay and cost.

Results: A total of 248 patients were randomly assigned to the fixed-dose group (n = 124) or personalized-dose group (n = 124). One patient in each group was not included in the intention-to-treat population because of incorrect initial COPD diagnosis. Failure of therapy occurred in 27.6% in the personalized-dose group, compared with 48.8% in the fixed-dose group (relative risk, 0.40; 95% CI, 0.24-0.68; P = .001). The in-hospital failure of therapy was significantly lower in the personalized-dose group (10.6% vs 24.4%; P = .005), whereas the medium-term failure rate, adverse event rate, hospital length of stay, and costs were similar between the two groups. After treatment failure, a lower additional dose of corticosteroids and a shorter duration of treatment were needed in the personalized-dose group to achieve control of the exacerbation. In the personalized-dose cohort, those receiving 40 mg or less had an average failure rate of 44.4%, compared with 22.9% among those receiving more than 40 mg (P = .027).

Interpretation: Personalized dosing of corticosteroids reduces the risk of failure because more patients were provided with a higher initial dose, especially > 60 mg, whereas 40 mg or less was too low in either group.

Clinical Trial Registration: ClinicalTrials.gov; No.: NCT02147015; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2021.05.024DOI Listing
May 2021

Integrating Histologic and Genomic Characteristics to Predict Tumor Mutation Burden of Early-Stage Non-Small-Cell Lung Cancer.

Front Oncol 2020 30;10:608989. Epub 2021 Apr 30.

National Clinical Research Center of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Tumor mutation burden (TMB) serves as an effective biomarker predicting efficacy of mono-immunotherapy for non-small cell lung cancer (NSCLC). Establishing a precise TMB predicting model is essential to select which populations are likely to respond to immunotherapy or prognosis and to maximize the benefits of treatment. In this study, available Formalin-fixed paraffin embedded tumor tissues were collected from 499 patients with NSCLC. Targeted sequencing of 636 cancer related genes was performed, and TMB was calculated. Distribution of TMB was significantly (p < 0.001) correlated with sex, clinical features (pathological/histological subtype, pathological stage, lymph node metastasis, and lympho-vascular invasion). It was also significantly (p < 0.001) associated with mutations in genes like , , , , , , , , , , , , , , , and . No significant correlations were found between TMB and age, neuro-invasion (p = 0.125), and tumor location (p = 0.696). Patients with p.G12 mutations and missense mutations were associated (p < 0.001) with TMB. mutations also influence TMB distribution (P < 0.001). TMB was reversely related to mutations (P < 0.001) but did not differ by mutation types. According to multivariate logistic regression model, genomic parameters could effectively construct model predicting TMB, which may be improved by introducing clinical information. Our study demonstrates that genomic together with clinical features yielded a better reliable model predicting TMB-high status. A simplified model consisting of less than 20 genes and couples of clinical parameters were sought to be useful to provide TMB status with less cost and waiting time.
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http://dx.doi.org/10.3389/fonc.2020.608989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121003PMC
April 2021

Genome-wide CRISPR screens reveal synthetic lethal interaction between CREBBP and EP300 in diffuse large B-cell lymphoma.

Cell Death Dis 2021 Apr 28;12(5):419. Epub 2021 Apr 28.

Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive lymphoid malignancy and a highly heterogeneous disease. In this study, we performed whole-genome and transcriptome sequencing, and a genome-wide CRISPR-Cas9-knockout screen to study an activated B-cell-like DLBCL cell line (RC-K8). We identified a distinct pattern of genetic essentialities in RC-K8, including a dependency on CREBBP and MDM2. The dependency on CREBBP is associated with a balanced translocation involving EP300, which results in a truncated form of the protein that lacks the critical histone acetyltransferase (HAT) domain. The synthetic lethal interaction between CREBBP and EP300 genes, two frequently mutated epigenetic modulators in B-cell lymphoma, was further validated in the previously published CRISPR-Cas9 screens and inhibitor assays. Our study suggests that integration of the unbiased functional screen results with genomic and transcriptomic data can identify both common and unique druggable vulnerabilities in DLBCL and histone acetyltransferases inhibition could be a therapeutic option for CREBBP or EP300 mutated cases.
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http://dx.doi.org/10.1038/s41419-021-03695-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080727PMC
April 2021

Increased expression of peptides from non-coding genes in cancer proteomics datasets suggests potential tumor neoantigens.

Commun Biol 2021 04 22;4(1):496. Epub 2021 Apr 22.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

Neoantigen-based immunotherapy has yielded promising results in clinical trials. However, it is limited to tumor-specific mutations, and is often tailored to individual patients. Identifying suitable tumor-specific antigens is still a major challenge. Previous proteogenomics studies have identified peptides encoded by predicted non-coding sequences in human genome. To investigate whether tumors express specific peptides encoded by non-coding genes, we analyzed published proteomics data from five cancer types including 933 tumor samples and 275 matched normal samples and compared these to data from 31 different healthy human tissues. Our results reveal that many predicted non-coding genes such as DGCR9 and RHOXF1P3 encode peptides that are overexpressed in tumors compared to normal controls. Furthermore, from the non-coding genes-encoded peptides specifically detected in cancers, we predict a large number of "dark antigens" (neoantigens from non-coding genomic regions), which may provide an alternative source of neoantigens beyond standard tumor specific mutations.
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http://dx.doi.org/10.1038/s42003-021-02007-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062694PMC
April 2021

Treatment Patterns and Survival of Patients With Advanced Non-Small Cell Lung Cancer Guided by Comprehensive Genomic Profiling: Real-World Single-Institute Study in China.

Front Oncol 2021 10;11:630717. Epub 2021 Mar 10.

Guangdong Provincial Key Laboratory of Biomedical Imaging, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.

Although the National Comprehensive Cancer Network and the Chinese Society of Clinical Oncology guidelines recommend comprehensive genomic profiling of lung adenocarcinoma, it has not been widely applied in Chinese hospitals. This observational study aimed to determine real-world evidence of whether comprehensive genomic profiling can benefit the survival of patients with lung cancer. We investigated the frequency of genomic alterations, treatment strategies, and clinical outcomes in 233 patients with advanced non-small cell lung carcinoma who were routinely screened using a 508-gene panel. The most prevalent drivers were mutations of EGFR (51%), KRAS (9%), PIK3CA (7%), ALK (7%), MET (6%), and BRAF (5%). Mutations in tumor suppressor genes included TP53, KEAP1, RB1, PTEN, and APC. Median overall survival (OS) was significantly shorter among patients harboring KRAS (mutant, n = 17; WT, n = 154) and TP53 (mutant, n = 103; WT n =68) mutations (11.3 24.0 months; P = 0.16 and 18.7 28.7 months; P = 0.018, respectively). The OS was longer among patients with tumors harboring EGFR (P = 0.069) and ALK (P = 0.51) mutations. Most patients (65.4%) with the driver gene-positive (EGFR, ALK, and ROS1) tumors were received TKI treatment, whereas those with driver gene wild tumors (53.1%) chose platinum-based therapy. Univariate and multivariate analyses associated a shorter OS among patients with tumors harboring concomitant TP53 and EGFR mutations. These findings provide additional evidence from real-world on the potential importance of targeted therapies as a treatment option in NSCLC patients harboring clinically actionable mutation.
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http://dx.doi.org/10.3389/fonc.2021.630717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988081PMC
March 2021

A series of MPS (M = Ag, Cu and Ag/Cu) thiophosphates with diamond-like structures exhibiting large second harmonic generation responses and moderate ion conductivities.

Dalton Trans 2021 Mar 18;50(12):4129-4132. Epub 2021 Mar 18.

Key laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China.

A series of thiophosphates with similar diamond-like structures, MPS (M = Ag, Cu and Ag/Cu), were successfully synthesized. Among them, AgPS and AgCuPS satisfy the phase-matching condition and display excellent second harmonic generation (SHG) responses about 1.3 and 0.8 times that of benchmark AgGaS. First-principles and dipole moment calculations indicate that their SHG effects originate from the combined action between MS and PS tetrahedra. Moreover, they also exhibit moderate ion conductivities (order of 10 to 10 S cm) between 10 and 80 °C and relatively small activation energies (E = 0.28-0.34 eV).
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http://dx.doi.org/10.1039/d1dt00366fDOI Listing
March 2021

Wearable 3D Machine Knitting: Automatic Generation of Shaped Knit Sheets to Cover Real-World Objects.

IEEE Trans Vis Comput Graph 2021 Feb 4;PP. Epub 2021 Feb 4.

Knitting can efficiently fabricate stretchable and durable soft surfaces. These surfaces are often designed to be worn on solid objects as covers, garments, and accessories. Given a 3D model, we consider a knit for it wearable if the knit not only reproduces the shape of the 3D model but also can be put on and taken off from the model without deforming the model. This '`wearability'' places additional constraints on surface design and fabrication, which existing machine knitting approaches do not take into account. We introduce the first practical automatic pipeline to generate knit designs that are both wearable and machine knittable. Our pipeline handles knittability and wearability with two separate modules that run in parallel. Specifically, given a 3D object and its corresponding 3D garment surface, our approach first converts the garment surface into a topological disc by introducing a set of cuts. The resulting cut surface is then fed into a physically-based unclothing simulation module to ensure the garment's wearability over the object. The unclothing simulation determines which of the previously introduced cuts could be sewn permanently without impacting wearability. Concurrently, the cut surface is converted into an anisotropic stitch mesh. Then, our novel, stochastic, any-time flat-knitting scheduler generates fabrication instructions for an industrial knitting machine. Finally, we fabricate the garment and manually assemble it into one complete covering worn by the target object. We demonstrate our method's robustness and knitting efficiency by fabricating models with various topological and geometric complexities.
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http://dx.doi.org/10.1109/TVCG.2021.3056101DOI Listing
February 2021

sp. nov., isolated from the faeces of greater white-fronted geese () at Poyang Lake, PR China.

Int J Syst Evol Microbiol 2021 Feb;71(2)

Jiangxi Province Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang 330006, PR China.

Two Gram-stain-positive, facultatively aerobic, non-motile and rod- to coccoid-shaped bacterial strains, 23H37-10 and 4HC-13, were isolated from the faeces of greater white-fronted geese () at Poyang Lake, Jiangxi Province, PR China. Optimal growth was observed at 35-37 °C, pH 7.0-8.0 and with 0.5-1.5 % (w/v) NaCl. The 16S rRNA gene sequences of strains 23H37-10 and 4HC-13 were identical. Phylogenetic and phylogenomic analyses indicated that strains 23H37-10 and 4HC-13 formed an independent cluster within the genus and showed 98.8, 97.4, 97.4 and 97.2 % 16S rRNA gene sequence similarity to LMM 1652, DSM 7109, DSM 44353 and NCTC 11913, respectively. Cells contained C 9, C and C as the major cellular fatty acids and MK-9 (H) as the predominant respiratory quinone. The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, phosphatidyl inositol mannosides, two unidentified phospholipids, four unidentified glycolipids and one unidentified lipid. Strain 23H37-10 contained mycolic acids, with -diaminopimelic acid and arabinose as the major whole-cell hydrolysates. The genome G+C content of strains 23H37-10 and 4HC-13 was 55.2 mol%. The digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values between strains 23H37-10 and 4HC-13 were 94.4 and 99.6 %, respectively. Strains 23H37-10 and 4HC-13 had dDDH and ANI values of less than 70 and 96 % with all available genomes of the genus , respectively. The differential genotypic inferences, together with phenotypic and biochemical characteristics, suggested that strains 23H37-10 and 4HC-13 represent a novel species within the genus , for which the name sp. nov. is proposed. The type strain is 23H37-10 (=GDMCC 1.1737=KACC 21672).
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http://dx.doi.org/10.1099/ijsem.0.004637DOI Listing
February 2021

Comprehensive evaluation of /2 variant interpretation ability among laboratories in China.

J Med Genet 2021 Jan 4. Epub 2021 Jan 4.

Department of In Vitro Diagnostic Reagent, National Institutes for Food and Drug Control, Beijing, China

High-quality interpretation of variants plays a critical role in the clinical practice of precision medicine. However, a comprehensive system to evaluate the quality and accuracy of variant interpretation has yet to be established. This study investigates the performance of an interpretation system in evaluating the capacities of interpretation among distinct laboratories in China. The evaluation system is based on a reference database that contains 750 different variants in / Evaluation was performed among 41 laboratories in China. We classified their performance into five levels. Only level A was considered qualified. This level allows for a 0.3% error rate for clinical decision-related misinterpretation; 26 of 41 laboratories (63%) met the qualified standard, while 7 laboratories were at levels D and E, which indicated egregious mistakes and systemic problems in variant interpretation. Due to strict quality demands, the interpretation of several variants was amended, which largely influenced the quality rate. The number of qualified laboratories would decrease from 26 to 17 if those incorrect recommended interpretations were not corrected. This evaluation system provides a potential approach for standardisation of variant interpretation and lowers the discordance of variant interpretation between different laboratories. A well-designed interpretation ability evaluation is essential to evaluate the interpretation level of laboratories before they provide service in real-world clinical settings.
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http://dx.doi.org/10.1136/jmedgenet-2020-107360DOI Listing
January 2021

From silicates to oxonitridosilicates: improving optical anisotropy for phase-matching as ultraviolet nonlinear optical materials.

Chem Commun (Camb) 2021 Jan;57(5):639-642

Department of Physics, Tamkang University, New Taipei City 25137, Taiwan.

Oxonitridosilicates, in which O atoms in SiO4 are partially substituted by N atoms, are proposed to improve optical anisotropies of silicates as UV NLO materials. The optical properties calculation showed that the heteroleptic SiOxN4-x (x = 1-3) tetrahedra have strong polarizability anisotropy and large hyperpolarizability. Accordingly, nine noncentrosymmetric (NCS) oxonitridosilicate crystals collected in the inorganic crystal structural database (ICSD) are evaluated by using the first principles method. Finally, Si2N2O and LiSiON are screened out owing to wide band gaps (6.49 and 6.95 eV), large birefringences (0.102 and 0.060 at 1064 nm), and large SHG coefficients (3.3 and 2.2 times that of d36(KDP)). More importantly, the cation selection and structural characteristics that are beneficial for enhancing the band gap and birefringence are identified. This study provides a novel strategy to design and find UV NLO crystals.
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http://dx.doi.org/10.1039/d0cc07269aDOI Listing
January 2021

Photoactivatable diazido Pt(IV) anticancer complex can bind to and oxidize all four nucleosides.

Dalton Trans 2020 Dec;49(47):17157-17163

Key Laboratory of Hubei Province for Coal Conversion and New Carbon Materials; School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, P. R. China.

Photoactivatable diazidodihydroxido Pt(iv) complex trans,trans,trans-[Pt(N3)2(OH)2(py)2] (1; py = pyridine) is a promising anticancer agent which can be activated by visible light to induce cancer cell death. DNA has been thought to be involved in the mechanism of action of this kind of Pt(iv) prodrug. However, the detailed photodecomposition pathways of complex 1 and its interaction modes with DNA are complex. Herein we report that upon light irradiation complex 1 can bind to all four nucleosides covalently with the reduced Pt(ii) species. Moreover, apart from the covalent coordination, various oxidation adducts of these four nucleosides induced by the reactive oxidative species (ROS) generated during the photoactivation of the complex 1 have also been identified, especially the induced oxidation of adenosine and cytidine which was firstly reported for this kind of photoactivatable Pt(iv) prodrug. Such dual-action may contribute to the highly potent photo-antiproliferativity of complex 1 towards cancer cells, which may account for the unique mechanism of action of the photoactivatable diazido Pt(iv) anticancer complexes.
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http://dx.doi.org/10.1039/d0dt03090bDOI Listing
December 2020

Utility of Radiomics for Predicting Patient Survival in Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis Treated With Stereotactic Body Radiotherapy.

Front Oncol 2020 14;10:569435. Epub 2020 Oct 14.

Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

This study aimed to develop and validate the combination of radiomic features and clinical characteristics that can predict patient survival in hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) treated with stereotactic body radiotherapy (SBRT). The prediction model was developed in a primary cohort of 70 patients with HCC and PVTT treated with SBRT, using data acquired between December 2015 and June 2017. The radiomic features were extracted from computed tomography (CT) scans. A least absolute shrinkage and selection operator regression model was used to build the model. Multivariate Cox-regression hazard models were created for analyzing survival outcomes and the radiomic features and clinical characteristics were presented with a nomogram. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the model. Participants were divided into a high-risk group and a low-risk group based on the radiomic features. A total of four radiomic features and six clinical characteristics were extracted for survival analysis. A combination of the radiomic features and clinical characteristics resulted in better performance for the estimation of overall survival (OS) [area under the curve (AUC) = 0.859 (CI: 0.770-0.948)] than that with clinical characteristics alone [AUC = 0.761 (CI: 0.641-0.881)]. These patients were divided into high-risk and low-risk groups according to the radiomic features. This study demonstrated that a nomogram of combined radiomic features and clinical characteristics can be conveniently used to assess individualized preoperative prediction of OS in patients with HCC with PVTT before SBRT.
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http://dx.doi.org/10.3389/fonc.2020.569435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594107PMC
October 2020

Genome-wide mutational signatures revealed distinct developmental paths for human B cell lymphomas.

J Exp Med 2021 Feb;218(2)

Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.

Both somatic hypermutation (SHM) and class switch recombination (CSR) are initiated by activation-induced cytidine deaminase (AID). Dysregulation of these processes has been linked to B cell lymphomagenesis. Here we performed an in-depth analysis of diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) genomes. We characterized seven genomic mutational signatures, including two B cell tumor-specific signatures, one of which is novel and associated with aberrant SHM. We further identified two major mutational signatures (K1 and K2) of clustered mutations (kataegis) resulting from the activities of AID or error-prone DNA polymerase η, respectively. K1 was associated with the immunoglobulin (Ig) switch region mutations/translocations and the ABC subtype of DLBCL, whereas K2 was related to the Ig variable region mutations and the GCB subtype of DLBCL and FL. Similar patterns were also observed in chronic lymphocytic leukemia subtypes. Thus, alterations associated with aberrant CSR and SHM activities can be linked to distinct developmental paths for different subtypes of B cell lymphomas.
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http://dx.doi.org/10.1084/jem.20200573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608067PMC
February 2021

Thrombospondin-2 is upregulated in patients with aortic dissection and enhances angiotensin II-induced smooth muscle cell apoptosis.

Exp Ther Med 2020 Dec 6;20(6):150. Epub 2020 Oct 6.

Emergency and Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing Lab for Cardiovascular Precision Medicine, Beijing 100029, P.R. China.

Thrombospondin-2 (TSP-2) is an important extracellular matrix protein that is involved in a variety of cardiovascular diseases, including viral myocarditis and abdominal aortic aneurysm. The present study aimed to investigate TSP-2 expression in patients with aortic dissection (AD). Aortas were obtained from patients with AD and healthy donors, and TSP-2 expression level in all samples was measured by western blotting and immunofluorescence assays. Blood samples were also collected from patients with AD and non-AD (NAD) subjects. Circulating TSP-2, tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels in each sample were detected using ELISAs. In addition, the effect of TSP-2 on angiotensin II (Ang II)-induced smooth muscle cell (SMC) apoptosis was assessed . Compared with healthy donors, aortic TSP-2 expression level was significantly increased in patients with AD. Furthermore, TSP-2 was secreted primarily by SMCs, but also by endothelial cells. TSP-2 plasma expression level was also elevated in patients with AD compared with non-AD subjects. Furthermore, TSP-2 serum expression level was positively correlated with TNF-α and IL-6 expression levels in patients with AD. In addition, recombinant mouse TSP-2 treatment increased Bax mRNA expression and decreased Bcl2 mRNA expression in Ang II-treated SMCs; however, the effects were reversed following treatment with the NF-κB p65 signaling pathway inhibitor JSH-23 or with the anti-TNF-α and anti-IL-6 neutralizing antibodies. The present study demonstrated that TSP-2 expression was increased in the aortic tissues and plasma of patients with AD. These findings suggested that TSP-2 may participate in the progression of AD by activating the NF-κB p65 signaling pathway and amplifying the inflammatory response.
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http://dx.doi.org/10.3892/etm.2020.9279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571314PMC
December 2020

The Association of New-Onset Atrial Fibrillation and Risk of Cancer: A Systematic Review and Meta-Analysis.

Cardiol Res Pract 2020 27;2020:2372067. Epub 2020 Sep 27.

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China.

Background: There are distinct results for the relationship between new-onset atrial fibrillation (NOAF) and subsequent incident cancer. To date, no systematic analysis has been conducted on this issue. This study aims to explore the relationship between NOAF and the risk of developing cancer through a meta-analysis with a large sample size.

Methods: Electronic databases, such as PubMed and EMBASE, were searched for published relevant studies on NOAF patients diagnosed with cancer after and during follow-ups, including reported records of baseline information and the statistical result of morbidity. Two investigators independently reviewed the articles and extracted the data using uniform standards and definitions. The meta-analysis was conducted using the Cochrane Program Review Manager.

Results: This meta-analysis consisted of five cohort studies and one case-control study, which comprised 533,514 participants. The pooled relative risk (RR) for incident cancer was 1.24 (95% CI: 1.10-1.39, =0.0003). The temporal trend analysis demonstrated that an increased risk of cancer was observed during the initial 90 days (RR: 3.44, 95% CI: 2.29-5.57, < 0.00001), but not after that. Lung cancer (RR: 1.51, 95% CI: 1.47-1.55, < 0.00001) was associated with NOAF, but not colorectal cancer and breast cancer.

Conclusion: This meta-analysis provides evidence that NOAF is associated with increased risk of cancer. The risk of incident cancer particularly increases within 90 days after NOAF diagnosis, but not after that.
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http://dx.doi.org/10.1155/2020/2372067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537679PMC
September 2020

Finding Optimal Mid-Infrared Nonlinear Optical Materials in Germanates by First-Principles High-Throughput Screening and Experimental Verification.

ACS Appl Mater Interfaces 2020 Oct 29;12(40):45023-45035. Epub 2020 Sep 29.

Department of Physics, Tamkang University, New Taipei City 25137, Taiwan.

Owing to wide infrared (IR) transparency ranges, high laser damage thresholds, and being easy to grow in open air, germanates are emerging as promising mid-infrared (mid-IR) nonlinear optical (NLO) materials. However, the germanates as NLO materials have not been investigated comprehensively and the crystals with large second harmonic generation (SHG) response have not been identified. Herein, we used the first-principles high-throughput screening pipeline for NLO materials to search for excellent NLO crystals from germanates collected in the inorganic crystal structure database. After two steps of screening, three crystals are picked out from 128 structures based on their predicted energy gaps, birefringences, and SHG coefficients. Subsequently, the three germanates are synthesized and measured. The results show that PbGaGeO and BaTiGeO exhibit a wide energy gap (>3.1 eV) and a strong phase-matchable SHG intensity that are comparable to the benchmark AgGaS (0.8 and 1.2 × AgGaS, respectively). In addition, the statistical analyses of different categories classified according to their cations show that the d-transition metal and lone pair cations are more conducive to achieving a larger SHG response and birefringence compared to other cations in germanates. It gives a guideline for exploring new mid-IR NLO materials.
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http://dx.doi.org/10.1021/acsami.0c15728DOI Listing
October 2020

Sodium-Glucose Cotransporter 2 Inhibitors Potentially Prevent Atrial Fibrillation by Ameliorating Ion Handling and Mitochondrial Dysfunction.

Front Physiol 2020 4;11:912. Epub 2020 Aug 4.

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel class of glucose-lowering agents that significantly improve the prognosis of patients with type 2 diabetes (T2D) and heart failure. SGLT2i has recently been implicated in the treatment of atrial fibrillation (AF) with clinical data demonstrating that these agents decrease the incidence of AF events in patients with T2D. Fundamental findings have suggested that SGLT2i may alleviate atrial electrical and structural remodeling. The underlying mechanisms of SGLT2i are likely associated with balancing the sodium and calcium handling disorders and mitigating the mitochondrial dysfunction in atrial myocytes. This review illustrates the advances in understanding the underlying mechanisms of SGLT2i as an evolving treatment modality for AF.
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http://dx.doi.org/10.3389/fphys.2020.00912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417344PMC
August 2020

Healthy China 2030: how to control the rising trend of unintentional suffocation death in children under five years old.

BMC Pediatr 2020 08 13;20(1):376. Epub 2020 Aug 13.

NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, 53 Xiangchun Road, Changsha, 410078, Hunan, China.

Background: To investigate the occurrence frequency, changing trends, and epidemiological distribution of unintentional suffocation in children under 5 years old.

Methods: The data were collected from the Maternal and Child Health Surveillance system from 2009 to 2018. The cause of death was classified by ICD-10. Data on unintentional suffocation death were calculated according to the characteristics of the population, time, space, cause of death and medical treatment, and constituent ratio were calculated.

Results: The mortality rate of children under 5 years old showed a downward trend, but the mortality of unintentional suffocation initially decreased and then increased. The death rate of unintentional suffocation in children less than 1-year-old was much higher than that in children aged 1 to 4 years old. The death rate of unintentional suffocation was higher in boys than in girls, and the rate was higher for rural children than for urban children. The number of low-weight and pre-term infants in the group under 1-year-old was significantly higher than that in the group of 1-4 years old. Children under 1-year-old are more likely to die at home than children aged 1 to 4 years old, and a higher proportion of younger children did not receive treatment. More than 80% of children under the age of 5 go untreated because it was too late to go to the hospital.

Conclusion: For areas and populations with a high incidence of unintentional suffocation, we suggest that priorities should include prevention, the development of a safe environment, strengthened prevention, the development of safety habits, and the popularization of first aid knowledge.
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http://dx.doi.org/10.1186/s12887-020-02281-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427067PMC
August 2020
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