Publications by authors named "Xiaoqing Liu"

632 Publications

KSHV Reprogramming of Host Energy Metabolism for Pathogenesis.

Front Cell Infect Microbiol 2021 12;11:621156. Epub 2021 May 12.

Ministry of Education (MOE) & National Health Committee (NHC) & Chinese Academy of Medical Science (CAMS), Key Laboratory of Medical Molecular Virology, Department of Medical Microbiology and Parasitology, School of Basic Medicine, Shanghai Medical College, Fudan University, Shanghai, China.

Reprogramming of energy metabolism is a key for cancer development. Kaposi's sarcoma-associated herpesvirus (KSHV), a human oncogenic herpesvirus, is tightly associated with several human malignancies by infecting B-lymphocyte or endothelial cells. Cancer cell energy metabolism is mainly dominated by three pathways of central carbon metabolism, including aerobic glycolysis, glutaminolysis, and fatty acid synthesis. Increasing evidence has shown that KSHV infection can alter central carbon metabolic pathways to produce biomass for viral replication, as well as the survival and proliferation of infected cells. In this review, we summarize recent studies exploring how KSHV manipulates host cell metabolism to promote viral pathogenesis, which provides the potential therapeutic targets and strategies for KSHV-associated cancers.
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http://dx.doi.org/10.3389/fcimb.2021.621156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153180PMC
May 2021

Using Recursive Feature Selection with Random Forest to Improve Protein Structural Class Prediction for Low-Similarity Sequences.

Comput Math Methods Med 2021 7;2021:5529389. Epub 2021 May 7.

College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China.

Many combinations of protein features are used to improve protein structural class prediction, but the information redundancy is often ignored. In order to select the important features with strong classification ability, we proposed a recursive feature selection with random forest to improve protein structural class prediction. We evaluated the proposed method with four experiments and compared it with the available competing prediction methods. The results indicate that the proposed feature selection method effectively improves the efficiency of protein structural class prediction. Only less than 5% features are used, but the prediction accuracy is improved by 4.6-13.3%. We further compared different protein features and found that the predicted secondary structural features achieve the best performance. This understanding can be used to design more powerful prediction methods for the protein structural class.
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http://dx.doi.org/10.1155/2021/5529389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123985PMC
May 2021

Development and Validation of a Polygenic Risk Score for Stroke in the Chinese Population.

Neurology 2021 May 24. Epub 2021 May 24.

Key Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.

Objective: To construct a polygenic risk score (PRS) for stroke and evaluate its utility in risk stratification and primary prevention for stroke.

Methods: Using meta-analytic approach and large genome-wide association results for stroke and stroke-related traits in East Asians, we generated a combined PRS (metaPRS) by incorporating 534 genetic variants in a training set of 2,872 patients with stroke and 2,494 controls. We then validated its association with incident stroke using Cox regression models in large Chinese population-based prospective cohorts comprising 41,006 individuals.

Results: During a total of 367,750 person-years (mean follow-up 9.0 years), 1,227 participants developed stroke before age of 80 years. Individuals with high polygenic risk had an about 2-fold higher risk of incident stroke compared with those with low polygenic risk (HR: 1.99, 95% CI: 1.66-2.38), with the lifetime risk of stroke being 25.2% (95% CI: 22.5%-27.7%) and 13.6% (95% CI: 11.6%-15.5%), respectively. Individuals with both high polygenic risk and family history displayed the lifetime risk as high as 41.1% (95% CI: 31.4%-49.5%). Moreover, individuals with high polygenic risk achieved greater benefits in terms of absolute risk reductions from adherence to ideal fasting blood glucose and total cholesterol than those with low polygenic risk. Maintaining favorable cardiovascular health (CVH) profile could substantially mitigate the increased risk conferred by high polygenic risk to the level of the low polygenic risk (from 34.6 % to 13.2%).

Conclusions: Our metaPRS has great potential for risk stratification of stroke and identification of individuals who may benefit more from maintaining ideal CVH.

Classification Of Evidence: This study provides Class I evidence that a meta-polygenic risk score is predictive of stroke risk.
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http://dx.doi.org/10.1212/WNL.0000000000012263DOI Listing
May 2021

Transcriptomic and metabolomic joint analysis reveals distinct flavonoid biosynthesis regulation for variegated testa color development in peanut (Arachis hypogaea L.).

Sci Rep 2021 May 21;11(1):10721. Epub 2021 May 21.

North China Key Laboratory for Crop Germplasm Resources of Education Ministry, College of Agronomy, Hebei Agricultural University, Baoding, 071001, China.

Peanut is one of the important oil and economic crops, among which the variegated testa peanut is a unique member. The molecular mechanisms underlying the pigment synthesis in variegated testa are still unclear. Differentially expressed genes (DEGs) in the flavonoid metabolism pathway in pigmented areas indicated that there were 27 DEGs highly related to the synthesis of variegated testa color among 1,050 DEGs. Of these 27, 13 were up-regulated and 14 were down-regulated, including 3 PALs, 1 C4H, 2 CHSs, 1 F3H, 1 F3'H, 2 DFRs, 2 LARs, 2 IAAs, 4 bHLHs, and 9 MYBs. GO (Gene Ontology) analysis indicated that DEGs were similarly enriched in three branches. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis suggested flavonoid biosynthesis is the most direct metabolic pathway for the synthesis of testa variegation. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) results showed that cyanidin and delphinidin were the primary metabolites that caused the color differences between the pigmented and the non-pigmented areas. Through the verification of 20 DEGs via qPCR, the results were consistent with transcriptome sequencing in four comparison groups. The results in this study lay the foundation for revealing the molecular regulation mechanisms of flavonoid synthesis in variegated testa peanut.
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http://dx.doi.org/10.1038/s41598-021-90141-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140124PMC
May 2021

On the association of frustrated Lewis pairs in ionic liquids: a molecular dynamics simulation study.

Phys Chem Chem Phys 2021 Jun 17;23(22):12541-12548. Epub 2021 May 17.

School of Environment and Safety Engineering, North University of China, Taiyuan, 030051, P. R. China.

Sterically hindered frustrated Lewis pairs (FLPs) have the ability to activate hydrogen molecules, and their reactivity is strongly determined by the geometric parameters of the Lewis acids and bases. A recent experimental study showed that ionic liquids (ILs) could largely improve the effective configuration of FLPs. However, the detailed mechanistic profile is still unclear. Herein, we performed molecular dynamics (MD) simulations to reveal the effects of ILs on the structures of FLPs, in particular, the association of Lewis acids and bases. For this purpose, mixed systems were adopted consisting of the ILs [Cmim][NTf] (n = 6, 10, 14), [Cmim][PF] and [Cmim][CTf] and the typical FLP (tBu)P/B(CF) for MD simulations. Radial distribution functions (RDFs) results show that toluene competes with (tBu)P to interact with B(CF), resulting in a relatively low effective (tBu)P/B(CF) complex, while [Cmim][NTf] shows less competition with (tBu)P, which increases the amount of effective FLPs. Spatial distribution functions (SDFs) results show that toluene forms a continuum solvation-shell, which hinders the interactions between (tBu)P and B(CF), while [Cmim][NTf] leaves relatively large empty spaces, which are accessible for (tBu)P or B(CF) molecules, resulting in higher probabilities of effective FLP structures. Lastly, we find that the longer alkyl chain length of [Cmim] cations, the higher the amount of effective (tBu)P/B(CF) pairs, and the anion [CTf] shows negative effects, for which even less effective (tBu)P/B(CF) pairs have been found compared to those of toluene.
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http://dx.doi.org/10.1039/d1cp00479dDOI Listing
June 2021

Water-Triggered Transformation of Ligand-Free Lead Halide Perovskite Nanocrystal-Embedded Pb(OH)Br with Ultrahigh Stability.

ACS Appl Mater Interfaces 2021 May 11;13(20):23960-23969. Epub 2021 May 11.

State Key Laboratory of Silicate Materials for Architectures, Wuhan University of Technology, No. 122, Luoshi Road, Wuhan 430070, P. R. China.

Lead halide perovskite (LHP) nanomaterials have attracted tremendous attention owing to their remarkable optoelectronic properties. However, they are extremely unstable under moist environments, high temperatures, and light illumination due to their intrinsic structural lability, which has been the critical unsolved problem for practical applications. To address this issue, we propose a facile and environmentally friendly ligand-free approach to design and synthesize rod-like CsPbBr-embedded Pb(OH)Br with excellent stability under various harsh environments such as soaking in water, heating, and ultraviolet (UV) illumination. Plate-like CsPbBr- and CsPbBr-embedded Pb(OH)Br powders are first formed by evaporating the solvent in a dispersion of ethanol (or methanol, isopropanol), CsCO, and PbBr. Upon soaking in water, the plate-like sample undergoes phase transformation from CsPbBr and CsPbBr to CsPbBr and shape conversion from nanoplate to a microrod, leading to the formation of rod-like CsPbBr-embedded Pb(OH)Br. The stable Pb(OH)Br coating effectively prevents the luminescent CsPbBr nanocrystals from reacting with water, leading to extremely high aqueous stability of the CsPbBr-embedded Pb(OH)Br. The photoluminescence (PL) intensity of the representative CsPbBr-embedded Pb(OH)Br sample can maintain 92.2% of the initial PL intensity value even after soaking in room-temperature water for 165 days; in the meantime, the phase and shape are preserved. The typical sample also shows outstanding stability under hot water, UV illumination, and annealing conditions. The ultrahigh aqueous stability, thermal stability, and photostability of the CsPbBr-embedded Pb(OH)Br nanomaterials suggest an effective, facile, and environmentally friendly technique to grow perovskite-based nanomaterials for promising practical applications in the optoelectronic field.
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http://dx.doi.org/10.1021/acsami.1c06627DOI Listing
May 2021

Efficacy and Safety of Niraparib as Maintenance Treatment in Patients with Extensive-Stage Small Cell Lung Cancer after First-Line Chemotherapy: A Randomized, Double-Blind, Phase 3 Study.

J Thorac Oncol 2021 Apr 26. Epub 2021 Apr 26.

The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Introduction: ZL-2306-005 is a randomized, double-blind, multicenter phase 3 study evaluating the efficacy and safety of niraparib, a poly(ADP-ribose) polymerase inhibitor, as first-line maintenance therapy in Chinese patients with platinum-responsive, extensive-stage small cell lung cancer (ES-SCLC).

Methods: Patients with complete/partial response (CR/PR) to standardized, platinum-based first-line chemotherapy were randomized 2:1 to receive niraparib or placebo (300 mg [baseline body weight ≥77 kg, platelet count ≥150,000/μL] or 200 mg) once daily until progression or unacceptable toxicity. Primary endpoints were progression-free survival (PFS) (blinded independent central review, BICR) and overall survival (OS) (sample size planned: 591 patients). Secondary endpoints included investigator-assessed PFS and safety.

Results: ZL-2306-005 was terminated early due to ES-SCLC treatment landscape changes (data cut-off: 20 Mar 2020). During July 2018-February 2020, 185 of 272 patients screened were randomized (niraparib: n=125 [CR=1, PR=124]; placebo: n=60 [CR=1, PR=59]). Median (95% confidence interval [CI]) PFS (BICR) was 1.54 months (1.41-2.69, niraparib) and 1.36 months (1.31-1.48, placebo); hazard ratio [HR]=0.66 (95% CI: 0.46-0.95; p=0.0242). Median OS was 9.92 months (9.33-13.54, niraparib) and 11.43 months (9.53-not estimable, placebo); HR=1.03 (95% CI: 0.62-1.73; p=0.9052). Median investigator-assessed PFS was 1.48 months (1.41-2.56, niraparib) and 1.41 months (1.31-2.00, placebo); HR=0.88 (95% CI: 0.61-1.26; p=0.4653). Grade ≥3 adverse events occurred in 34.4% (niraparib) and 25.0% (placebo) of patients.

Conclusions: ZL-2306-005 did not reach primary endpoints. However, niraparib as maintenance therapy modestly improved PFS in patients with platinum-responsive ES-SCLC, with acceptable tolerability profile and no new safety signal.
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http://dx.doi.org/10.1016/j.jtho.2021.04.001DOI Listing
April 2021

Pazopanib ameliorates acute lung injuries via inhibition of MAP3K2 and MAP3K3.

Sci Transl Med 2021 Apr;13(591)

Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA.

Acute lung injury (ALI) causes high mortality and lacks any pharmacological intervention. Here, we found that pazopanib ameliorated ALI manifestations and reduced mortality in mouse ALI models and reduced edema in human lung transplantation recipients. Pazopanib inhibits mitogen-activated protein kinase kinase kinase 2 (MAP3K2)- and MAP3K3-mediated phosphorylation of NADPH oxidase 2 subunit p47 at Ser to increase reactive oxygen species (ROS) formation in myeloid cells. Genetic inactivation of MAP3K2 and MAP3K3 in myeloid cells or hematopoietic mutation of p47 Ser to alanine attenuated ALI manifestations and abrogates anti-ALI effects of pazopanib. This myeloid MAP3K2/MAP3K3-p47 pathway acted via paracrine HO to enhance pulmonary vasculature integrity and promote lung epithelial cell survival and proliferation, leading to increased pulmonary barrier function and resistance to ALI. Thus, pazopanib has the potential to be effective for treating ALI.
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http://dx.doi.org/10.1126/scitranslmed.abc2499DOI Listing
April 2021

Orthogonal Demethylase-Activated Deoxyribozyme for Intracellular Imaging and Gene Regulation.

J Am Chem Soc 2021 May 27;143(18):6895-6904. Epub 2021 Apr 27.

College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P. R. China.

The epigenetic modification of nucleic acids represents a versatile approach for achieving high-efficient control over gene expression and transcription and could dramatically expand their biosensing and therapeutic applications. Demethylase-involved removal of N6-methyladenine (mA) represents one of the vital epigenetic reprogramming events, yet its direct intracellular evaluation and as-guided gene regulation are extremely rare. The endonuclease-mimicking deoxyribozyme (DNAzyme) is a catalytically active DNA that enables the site-specific cleavage of the RNA substrate, and several strategies have imparted the magnificent responsiveness to DNAzyme by using chemical and light stimuli. However, the epigenetic regulation of DNAzyme has remained largely unexplored, leaving a significant gap in responsive DNA nanotechnology. Herein, we reported an epigenetically responsive DNAzyme system through the selection of an exquisite mA-caged DNAzyme that could be specifically activated by FTO (fat mass and obesity-associated protein) demethylation for precise intracellular imaging-directed gene regulation. Based on a systematic investigation, the active DNAzyme configuration was potently disrupted by the site-specific incorporation of mA modification and subsequently restored into the intact DNAzyme structure via the tunable FTO-specific removal of mA-caging groups under a variety of conditions. This orthogonal demethylase-activated DNAzyme amplifier enables the robust and accurate monitoring of FTO and its inhibitors in live cells. Moreover, the simple demethylase-activated DNAzyme facilitates the assembly of an intelligent self-adaptive gene regulation platform for knocking down demethylase with the ultimate apoptosis of tumor cells. As a straightforward and scarless mA removal strategy, the demethylase-activated DNAzyme system offers a versatile toolbox for programmable gene regulation in synthetic biology.
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http://dx.doi.org/10.1021/jacs.1c00570DOI Listing
May 2021

Fruit and vegetable consumption, cardiovascular disease, and all-cause mortality in China.

Sci China Life Sci 2021 Apr 20. Epub 2021 Apr 20.

Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.

Evidence about the response patterns of fruit and vegetable consumption with the risk of cardiovascular disease (CVD) and all-cause mortality was inconsistent. These associations were examined using a large-scale, population-based Chinese cohort comprising 100,728 participants. A food-frequency questionnaire was used to assess fruit and vegetable consumption. Outcomes were ascertained by interviewing individuals or their proxies and checking hospital records or death certificates. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). At the 736,668 person-years of follow-up, 3,677 CVD cases and 5,466 deaths were identified. The multivariable-adjusted HRs for CVD across increasing quartiles of total fruit and vegetable consumption were 1 (reference), 0.94 (95%CI=0.85-1.04), 0.89 (95%CI=0.80-0.98), and 0.85 (95% CI=0.11-0.95). Moreover, participants in the highest quartile displayed a 13% lower risk of all-cause mortality (HR=0.81; 95% CI=0.80-0.95). A nonlinear dose-response relation was found for CVD, without additional benefits beyond a consumption of 600 g d, whereas the all-cause mortality risk decreased along with higher consumption, with a linear trend. These associations remained significant for fruit consumption but not for vegetable consumption. Our findings indicated that greater fruit and vegetable consumption was significantly associated with a lower risk of CVD and all cause mortality. Increasing fruit and vegetable consumption, especially fruit, in the general population would prevent CVD and premature mortality.
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http://dx.doi.org/10.1007/s11427-020-1896-xDOI Listing
April 2021

Gestational exposure to perfluoroalkyl substances and congenital heart defects: A nested case-control pilot study.

Environ Int 2021 Sep 23;154:106567. Epub 2021 Apr 23.

Department of Epidemiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, #96 Dongchuan Road, Guangzhou 510080, China. Electronic address:

Background: Accumulating evidence suggests that environmental pollutants may contribute to the occurrence of congenital heart defects (CHDs). However, no previous studies have evaluated the impact of perfluoroalkyl substances (PFAS), persistent environmental pollutants, on CHDs. This exploratory study aimed to generate testable hypotheses of the association between gestational PFAS and the risk of CHDs.

Methods: A nested case-control study was conducted in a cohort of 11,578 newborns. Exposure odds ratios were compared between 158 CHD cases and 158 non-malformed controls delivered at the same hospital, individually matched by maternal age (±5 years) and parity. Concentrations of 27 PFAS, including linear and branched isomers, were determined in maternal peripheral blood and cord blood plasma collected before and during delivery using a ultra-performance liquid chromatography coupled to mass spectrometry. Conditional logistic regression was utilized to evaluate associations between individual PFAS and the risk of CHDs, adjusted for confounding variables.

Results: Maternal gestational exposure to the highly branched perfluorooctanesulfonate (PFOS) isomer potassium 6-trifluoromethyperfluoroheptanesulfonate [6 m-PFOS, adjusted odds ratio (aOR) (95% CI) = 2.47(1.05,5.83)] and perfluorodecanoic acid [PFDA, aOR (95% CI) = 2.33(1.00,5.45)] were associated with increased odds of septal defects with statistical significance, while linear PFOS [aOR (95% CI) = 3.65(1.09,12.16)] and perfluoro-n-dodecanoic acid [PFDoA, aOR (95% CI) = 6.82(1.75, 26.61)] were associated with conotruncal defects. Effect estimates also suggested associations for higher maternal 6 m-PFOS and PFDA concentrations with ventricular septal defect. However, we did not observe these associations in cord blood.

Conclusion: These exploratory findings suggested that gestational exposure to most PFAS, especially linear PFOS, 6 m-PFOS, PFDA, and PFDoA, was associated with greater risks for septal and conotruncal defects. However, a larger, adequately powered study is needed to confirm our findings, and to more comprehensively investigate the potential teratogenic effects of other more recently introduced PFAS, and on associations with individual CHD subtypes.
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http://dx.doi.org/10.1016/j.envint.2021.106567DOI Listing
September 2021

Adverse associations of sedentary behavior with cancer incidence and all-cause mortality: A prospective cohort study.

J Sport Health Sci 2021 Apr 18. Epub 2021 Apr 18.

Key Laboratory of Cardiovascular Epidemiology, Chinese Academy of Medical Sciences, Beijing 100037, China; Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China; School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China. Electronic address:

Background: Inconsistent results have been reported in developed countries for relationships between sedentary behavior and cancer incidence and mortality, and evidence from the Chinese population is scarce. This study aimed to investigate such relationships in large Chinese population-based prospective cohorts and to explore the joint effect and interaction of sedentary behavior and moderate-to-vigorous physical activity (MVPA) on these relationships.

Methods: We included 95,319 Chinese adults without cancer from 3 large cohorts and assessed their sedentary behavior and physical activity with a unified questionnaire. Cancer incidence and mortality were confirmed by interviewing participants or their proxies and checking hospital records and death certificates. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) for cancer and mortality were estimated using Cox proportional hazards regression models.

Results: During 559,002 person-years of follow-up, 2388 cancer events, 1571 cancer deaths, and 4562 all-cause deaths were recorded. Sedentary behavior was associated with increased risk of developing cancer and deaths in a dose-response manner. The multivariable-adjusted HRs (95%CIs) were the following: HR = 1.16, 95%CI: 1.01‒1.33; HR = 1.24, 95%CI: 1.04‒1.48; and HR = 1.15, 95%CI: 1.04‒1.28 for cancer incidence, cancer mortality, and all-cause mortality, respectively, for those having ≥10 h/day of sedentary time compared to those having <6 h/day of sedentary time. Sedentary populations (≥10 h/day) developed cancer or died 4.09 and 2.79 years earlier, respectively, at the index age of 50 years. Failure to achieve the recommended level of MVPA may further aggravate the adverse associations, with the highest cancer and mortality risks being observed among participants with both ≥10 h/day of sedentary time and <150 min/week of MVPA. Limitations of this study include the fact that physical activity information was obtained via questionnaire instead of objective measurement and that there were insufficient incident cases for the analysis of associations between sedentary behavior and site-specific cancers.

Conclusion: Sedentary behavior was associated with an increased risk of cancer and all-cause mortality among Chinese adults, especially for those with ≥10 h/day of sedentary time. It is necessary to reduce sedentary time, in addition to increasing MVPA levels, for the prevention of cancer and premature death.
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http://dx.doi.org/10.1016/j.jshs.2021.04.002DOI Listing
April 2021

Response to "Reply to 'A deep learning-based smartphone platform for cutaneous lupus erythematosus classification assistance: Simplifying the diagnosis of complicated diseases.' Has the complicated disease been simplified too much?" Artificial intelligence system is helpful for diagnosis of cutaneous lupus erythematosus.

J Am Acad Dermatol 2021 Apr 20. Epub 2021 Apr 20.

Department of Dermatology, Second Xiangya Hospital, Hunan Key Laboratory of Medical Epigenomics, Central South University, Changsha, Hunan, China; Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China; Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, Jiangsu, China. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.04.014DOI Listing
April 2021

Facile, Smart, and Degradable Metal-Organic Framework Nanopesticides Gated with Fe-Tannic Acid Networks in Response to Seven Biological and Environmental Stimuli.

ACS Appl Mater Interfaces 2021 Apr 15;13(16):19507-19520. Epub 2021 Apr 15.

Key Laboratory of Mesoscopic Chemistry (Ministry of Education), State Key Laboratory of Coordination Chemistry, and School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, People's Republic of China.

Nanopesticides were selected as one of the top 10 emerging technologies in chemistry that will change our world in 2019. Facile, smart, and degradable metal-organic framework MIL-101(Fe) nanopesticides gated with Fe-tannic acid (TA) networks are created using a universal strategy. The capping of the Fe-TA network gatekeepers is instinctively oriented by the coordinatively unsaturated Fe sites on the surfaces of the MIL-101(Fe) nanocarriers; thus, their combination is perfectly matched. This is the first example that one smart gated nanoparticle is integrated with seven stimuli-responsive performances to meet the diverse controlled release of encapsulated cargos by the disassembly of the gatekeepers and/or the degradation of the nanocarriers. More importantly, each of the seven stimuli (acidic/alkaline pH, HO, glutathione, phosphates, ethylenediaminetetraacetate, and near-infrared light of sunlight) is closely related to the biological and natural environments of crops, and the biocompatible nanocarriers are eventually degraded against bioaccumulation even if the nanopesticides enter crops. These mechanisms of the stimuli-responsive controlled release are identified and clearly elaborated. It is found that the natural polyphenol can improve the wettability of aqueous droplets of nanopesticides on model hydrophobic foliage for pesticide adhesion and retention. The nanopesticides encapsulated with the fungicide tebuconazole show high fungicidal activities against pathogenic fungi (rice sheath blight) and (wheat head blight); good safety on seed germination, seedling emergence, and plant height of wheat by seed dressing; and satisfactory control efficacy in wheat powdery mildew caused by in the greenhouse. The nanopesticides have potential applications in the field for high quality and yield of agricultural production.
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http://dx.doi.org/10.1021/acsami.1c04118DOI Listing
April 2021

Single Transition Metal Atom Bound to the Unconventional Phase of the MoS Monolayer for Catalytic Oxygen Reduction Reaction: A First-Principles Study.

ACS Appl Mater Interfaces 2021 Apr 12;13(15):17412-17419. Epub 2021 Apr 12.

College of Optoelectronic Engineering, Chongqing University, Chongqing 400044, P. R. China.

Supported single-atom catalysts (SACs) have received a lot of attention due to their super-high atom utilization and outstanding catalytic performance. However, the instability of the supported transition-metal (TM) atoms hampers their widespread applications. Exploration of an appropriate substrate to stabilize the supported single atom is crucial for the future implementation of SACs. In recent years, two-dimensional materials have been proposed as possible substrates due to their large specific surface areas, but their chemically inert surfaces are difficult to stabilize TM atoms without defecting or doping. Herein, by means of systematic first-principles calculations, we demonstrate that the defect-free MoS monolayer in the unconventional phase (1T') can effectively immobilize single TM atoms owing to its unique electrophilic property as compared to the conventional 2H phase. As a prototype probe, we investigated oxygen reduction reaction (ORR) catalyzed by a total of 21 single TM atoms stabilized on 1T'-MoS and successfully screened out two candidates, Cu and [email protected]'-MoS, which have a low overpotential of 0.41 and 0.32 V respectively, outperforming most of the previously reported ORR catalysts. Furthermore, we reveal that the adsorption energy of the ORR intermediate, *OH, provides an excellent descriptor to assess the ORR activity, which is further determined by the -band center of the supported TM adatoms, thus being a great advantage for future design of stable and high-performance SACs.
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http://dx.doi.org/10.1021/acsami.0c21597DOI Listing
April 2021

Functional disability and post-traumatic stress disorder in survivors of mechanical ventilation: a cross-sectional study in Guangzhou, China.

J Thorac Dis 2021 Mar;13(3):1564-1575

Department of Critical Care Medicine, Guangzhou Institute of Respiratory Health, The 1st Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: Critical illness is associated with cognitive, physical, and psychological impairments; however, evidence of the severity and frequency of impairments in Chinese survivors of mechanical ventilation in an intensive care unit (ICU) remains limited. Our aim was to investigate the incidence and severity of impairments in Chinese survivors of mechanical ventilation in ICU and to explore risk factors influencing specific impairments.

Methods: Patients discharged alive after mechanical ventilation in a large general ICU for ≥2 days were enrolled in this single-center cross-sectional study. Survivors were evaluated using measures of functional disability (Activity of Daily Living Scale), and post-traumatic stress disorder (PTSD, The Impact of Event Scale-Revised) via telephone interview. Multivariable analysis was conducted.

Results: Data were obtained from 130 consenting survivors. At follow-up (mean: 19.64 months), among those in part-time or full-time employment prior to admission, only 45.1% had returned to work. Further, 29.2% of survivors had clear disabilities affecting daily living. Deficits in activities of daily living (ADL) were mainly characterized by impairment of instrumental ADL. Predictors of ADL in mechanically ventilated survivors included age, ICU admission diagnosis, and Acute Physiology And Chronic Health Evaluation II (APACHE II) score, which accounted for 33.5% of total variance. Furthermore, 17.7% of participants had symptoms consistent with PTSD. ICU length of stay was the only predictor of PTSD, and accounted for 7.5% of total variance.

Conclusions: ICU survivors of mechanical ventilation in China face negative impacts on employment, and commonly have ADL impairment and PTSD. Age, ICU admission diagnosis, and APACHE II score were key factors influencing ADL, while ICU length of stay was the only factor affecting PTSD. These findings suggest that some survivors who have had certain exposures may warrant closer follow-up, and systematic interventions for these high-risk survivors should be developed in China.
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http://dx.doi.org/10.21037/jtd-20-2622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024792PMC
March 2021

Maternal exposure to ambient air pollution and congenital heart defects in China.

Environ Int 2021 Aug 7;153:106548. Epub 2021 Apr 7.

Guangdong Provincial Engineering Technology Research Center of Environmental and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China. Electronic address:

Background: Evidence of maternal exposure to ambient air pollution on congenital heart defects (CHD) has been mixed and are still relatively limited in developing countries. We aimed to investigate the association between maternal exposure to air pollution and CHD in China.

Method: This longitudinal, population-based, case-control study consecutively recruited fetuses with CHD and healthy volunteers from 21 cities, Southern China, between January 2006 and December 2016. Residential address at delivery was linked to random forests models to estimate maternal exposure to particulate matter with an aerodynamic diameter of ≤ 1 µm (PM), ≤2.5 µm, and ≤10 µm as well as nitrogen dioxides, in three trimesters. The CHD cases were evaluated by obstetrician, pediatrician, or cardiologist, and confirmed by cardia ultrasound. The CHD subtypes were coded using the International Classification Diseases. Adjusted logistic regression models were used to assess the associations between air pollutants and CHD and its subtypes.

Results: A total of 7055 isolated CHD and 6423 controls were included in the current analysis. Maternal air pollution exposures were consistently higher among cases than those among controls. Logistic regression analyses showed that maternal exposure to all air pollutants during the first trimester was associated with an increased odds of CHD (e.g., an interquartile range [13.3 µg/m] increase in PM was associated with 1.09-fold ([95% confidence interval, 1.01-1.18]) greater odds of CHD). No significant associations were observed for maternal air pollution exposures during the second trimester and the third trimester. The pattern of the associations between air pollutants and different CHD subtypes was mixed.

Conclusions: Maternal exposure to greater levels of air pollutants during the pregnancy, especially the first trimester, is associated with higher odds of CHD in offspring. Further longitudinal well-designed studies are warranted to confirm our findings.
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http://dx.doi.org/10.1016/j.envint.2021.106548DOI Listing
August 2021

Identification of pediatric respiratory diseases using a fine-grained diagnosis system.

J Biomed Inform 2021 May 6;117:103754. Epub 2021 Apr 6.

National Clinical Research Center for Child Health, China. Electronic address:

Respiratory diseases, including asthma, bronchitis, pneumonia, and upper respiratory tract infection (RTI), are among the most common diseases in clinics. The similarities among the symptoms of these diseases precludes prompt diagnosis upon the patients' arrival. In pediatrics, the patients' limited ability in expressing their situation makes precise diagnosis even harder. This becomes worse in primary hospitals, where the lack of medical imaging devices and the doctors' limited experience further increase the difficulty of distinguishing among similar diseases. In this paper, a pediatric fine-grained diagnosis-assistant system is proposed to provide prompt and precise diagnosis using solely clinical notes upon admission, which would assist clinicians without changing the diagnostic process. The proposed system consists of two stages: a test result structuralization stage and a disease identification stage. The first stage structuralizes test results by extracting relevant numerical values from clinical notes, and the disease identification stage provides a diagnosis based on text-form clinical notes and the structured data obtained from the first stage. A novel deep learning algorithm was developed for the disease identification stage, where techniques including adaptive feature infusion and multi-modal attentive fusion were introduced to fuse structured and text data together. Clinical notes from over 12000 patients with respiratory diseases were used to train a deep learning model, and clinical notes from a non-overlapping set of about 1800 patients were used to evaluate the performance of the trained model. The average precisions (AP) for pneumonia, RTI, bronchitis and asthma are 0.878, 0.857, 0.714, and 0.825, respectively, achieving a mean AP (mAP) of 0.819. These results demonstrate that our proposed fine-grained diagnosis-assistant system provides precise identification of the diseases.
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http://dx.doi.org/10.1016/j.jbi.2021.103754DOI Listing
May 2021

Analysis of pathological changes in the epithelium in COVID-19 patient airways.

ERJ Open Res 2021 Apr 6;7(2). Epub 2021 Apr 6.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

https://bit.ly/2M2NcdO.
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http://dx.doi.org/10.1183/23120541.00690-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898030PMC
April 2021

Enhanced luminescence of Si(111) surface by localized surface plasmons of silver islands.

Nanotechnology 2021 Apr 30;32(29). Epub 2021 Apr 30.

Department of Physics, Nanchang University, Nanchang 330031, People's Republic of China.

The role of silver localized surface plasmons (LSPs) on the luminescence of a Si(111)-(7 × 7) surface has been investigated by scanning tunneling microscopy (STM) with a silver tip at 77 K. On a bare Si(111)-(7 × 7) surface, a characteristic peak at 1.85 eV dominates the STM-induced luminescence spectrum, although the luminescence intensity is extremely weak. Once Ag atoms are deposited onto the Si surface to form islands with a few atomic layers, it is found that the intensity of the characteristic peak from the Si surface underneath the Ag islands is significantly enhanced by about one order. In addition to the luminescence from the Si surface, light emission originating from the irradiation decay of the Ag plasmons is also detected. Such great enhancement of the luminescence from the Si surface is attributed to the strong coupling between the surface states of the Si and the LSPs of the Ag islands.
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http://dx.doi.org/10.1088/1361-6528/abf3f0DOI Listing
April 2021

Cascaded Amplifier Nanoreactor for Efficient Photodynamic Therapy.

ACS Appl Mater Interfaces 2021 Apr 31;13(14):16075-16083. Epub 2021 Mar 31.

College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P. R. China.

Photodynamic therapy (PDT) utilizes reactive oxygen species (ROS) to treat established diseases and has attracted growing attention in the field of cancer therapy. However, in a tumor microenvironment (TME), the inherent hypoxia and high level of antioxidants severely hamper the efficacy of ROS generation. Here, we describe a cascaded amplifier nanoreactor based on self-assembled nanofusiforms for persistent oxygenation to amplify ROS levels. The nanofusiform assembly is capable of photothermal and photodynamic treatment and regulation of redox oxidation stress by antioxidant depletion to prevent ROS tolerance. The Pt nanozyme decoration of the nanofusiform enables efficient oxygen supplements Pt nanozyme-catalyzed decomposition of HO overexpressed in TME and generation of O. Furthermore, the temperature elevation resulted from the photothermal effect of the nanofusiform increases the catalase-like catalytic activity of the Pt nanozyme for boosted oxygen generation. Thus, such a triple cascade strategy using nanozyme-based nanofusiforms amplifies the ROS level by continuous oxygenation, enhancing the efficacy of PDT and . Meanwhile, an multi-modal imaging including near-infrared fluorescence imaging, photothermal imaging, and magnetic resonance imaging achieves precise tumor diagnosis. The rationally designed nanofusiform acts as an efficient ROS amplifier through multidimension strengthening of continuous oxygenation, providing a potential smart nanodrug for cancer therapy.
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http://dx.doi.org/10.1021/acsami.1c01683DOI Listing
April 2021

Metabolic engineering of astaxanthin-rich maize and its use in the production of biofortified eggs.

Plant Biotechnol J 2021 Mar 29. Epub 2021 Mar 29.

Crop Functional Genome Research Center, Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China.

Production of the high-value carotenoid astaxanthin, which is widely used in food and feed due to its strong antioxidant activity and colour, is less efficient in cereals than in model plants. Here, we report a new strategy for expressing β-carotene ketolase and hydroxylase genes from algae, yeasts and flowering plants in the whole seed using a seed-specific bidirectional promoter. Engineered maize events were backcrossed to inbred maize lines with yellow endosperm to generate progenies that accumulate astaxanthin from 47.76 to 111.82 mg/kg DW in seeds, and the maximum level is approximately sixfold higher than those in previous reports (16.2-16.8 mg/kg DW) in cereals. A feeding trial with laying hens indicated that they could take up astaxanthin from the maize and accumulate it in egg yolks (12.10-14.15 mg/kg) without affecting egg production and quality, as observed using astaxanthin from Haematococcus pluvialis. Storage stability evaluation analysis showed that the optimal conditions for long-term storage of astaxanthin-rich maize are at 4 °C in the dark. This study shows that co-expressing of functional genes driven by seed-specific bidirectional promoter could dramatically boost astaxanthin biosynthesis in every parts of kernel including embryo, aleurone layer and starch endosperm other than previous reports in the starch endosperm only. And the staple crop maize could serve as a cost-effective plant factory for reliably producing astaxanthin.
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http://dx.doi.org/10.1111/pbi.13593DOI Listing
March 2021

Effects of Ionic Liquids on the Thermodynamics of Hydrogen Activation by Frustrated Lewis Pairs: A Density Functional Theory Study*.

Chemphyschem 2021 May 16;22(10):968-974. Epub 2021 Apr 16.

Beijing Key Laboratory of Ionic Liquids Clean Process, Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100049, China.

Nowadays, hydrogen activation by frustrated Lewis pairs (FLPs) and their applications are one of the emerging research topics in the field of catalysis. Previous studies have shown that the thermodynamics of this reaction is determined by electronic structures of FLPs and solvents. Herein, we investigated systems consisting of typical FLPs and ionic liquids (ILs), which are well known by their large number of types and excellent solvent effects. The density functional theory (DFT) calculations were performed to study the thermodynamics for H activation by both inter- and intra-molecular FLPs, as well as the individual components. The results show that the computed overall Gibbs free energies in ILs are more negative than that computed in toluene. Through the thermodynamics partitioning, we find that ILs favor the H-H cleavage elemental step over the elemental steps of proton attachment, hydride attachment and zwitterionic stabilization. Moreover, the results show that these effects are strongly dependent on the type of FLPs, where intra-molecular FLPs are more affected compared to the inter-molecular FLPs.
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http://dx.doi.org/10.1002/cphc.202100093DOI Listing
May 2021

User-safe and efficient chitosan-gated porous carbon nanopesticides and nanoherbicides.

J Colloid Interface Sci 2021 Jul 9;594:20-34. Epub 2021 Mar 9.

Key Laboratory of Mesoscopic Chemistry (Ministry of Education), State Key Laboratory of Coordination Chemistry, and School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, People's Republic of China. Electronic address:

Nanopesticides are selected as one of ten chemical innovations that will change our world. Carboxylated porous carbon nanoparticles (PCNs) were used to encapsulate water-insoluble pesticides and subsequently capped with chitosan (CS) to prepare the CS-gated PCN ([email protected]) nanopesticides for the controlled release of pesticides in response to acidic pH and elevated temperature with good fungicidal efficacy. To resolve the issue of gastrointestinal absorption of PQ upon ingestion of PQ formulation, it is an innovative strategy to select the carboxylated PCNs as the paraquat (PQ) nanocarriers to inhibit PQ release in the gastrointestinal tract from the origin. The PQ-loaded [email protected] nanoherbicides showed very low cytotoxicity to human normal cells and high survival rate in mice because the strong π-π interactions between the electron-deficient PQ and the electron-rich PCNs almost inhibited the release of PQ at both acidic and alkaline pH values. The controlled release of PQ from the nanoherbicides was realized at elevated temperatures owing to the weakening of the strong π-π interactions, aiming to eliminate weeds via the photothermal effect of PCNs under natural sunlight. The user-safe PCN-based PQ formulation can inhibit PQ release in the gastrointestinal tract and keep the PQ herbicidal efficacy in the practical application.
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http://dx.doi.org/10.1016/j.jcis.2021.03.001DOI Listing
July 2021

Rab26 suppresses migration and invasion of breast cancer cells through mediating autophagic degradation of phosphorylated Src.

Cell Death Dis 2021 03 17;12(4):284. Epub 2021 Mar 17.

School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, 361005, Fujian, China.

Rab proteins play crucial roles in membrane trafficking. Some Rab proteins are implicated in cancer development through regulating protein sorting or degradation. In this study, we found that the expression of Rab26 is suppressed in the aggressive breast cancer cells as compared to the levels in non-invasive breast cancer cells. Over-expression of Rab26 inhibits cell migration and invasion, while Rab26 knockdown significantly promotes the migration and invasion of breast cancer cells. Rab26 reduces focal adhesion association of Src kinase and induces endosomal translocation of Src. Further experiments revealed that Rab26 mediates the autophagic degradation of phosphorylated Src through interacting with ATG16L1, consequently, resulting in the suppression of the migration and invasion ability of breast cancer cells.
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http://dx.doi.org/10.1038/s41419-021-03561-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969620PMC
March 2021

Polymorphic Pairing Configurations of Guanine and Cytosine at the Water-HOPG Interface.

Langmuir 2021 03 16;37(12):3761-3765. Epub 2021 Mar 16.

Department of Physics, Nanchang University, Nanchang 330031, China.

A series of nucleobases guanine (G) and cytosine (C) pairing configurations have been fabricated on highly oriented pyrolytic graphite (HOPG) surface by controlling the molar ratio of G and C in water solution. Watson-Crick (WC) base pairing governs the association of C and G nucleobases when the molar ratio of C/G is adjusted to 1:1. Nucleobase-rich is preferentially hydrogen-bonded to the sites exposed around WC motifs with the adjustment of the C/G molar ratio. At a higher C/G molar ratio imbalance, the pairing configurations depend on the combination of interspace and sites of hydrogen binding between G and C bases. The systematic analysis of the high-resolution STM images and DFT calculations reveal that hydrogen bonding plays a dominant role in the formation of these pairing configurations and that the competition between the priority and diversity of hydrogen-bonded configurations bonding between G and C is the key for the pairing structural polymorphism.
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http://dx.doi.org/10.1021/acs.langmuir.1c00296DOI Listing
March 2021

Safety and efficacy of first-line dacomitinib in Asian patients with EGFR mutation-positive non-small cell lung cancer: Results from a randomized, open-label, phase 3 trial (ARCHER 1050).

Lung Cancer 2021 04 23;154:176-185. Epub 2021 Feb 23.

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China. Electronic address:

Objectives: To compare efficacy and safety of dacomitinib versus gefitinib as first-line therapy for EGFR mutation-positive advanced NSCLC in Asian patients enrolled in the ongoing ARCHER 1050 trial.

Materials And Methods: In this ongoing, randomized, open-label, phase 3 trial (NCT01774721), eligible patients with newly diagnosed advanced EGFR mutation-positive NSCLC were randomized (1:1) to receive oral dacomitinib 45 mg/day or oral gefitinib 250 mg/day. Randomization, by a central computer system, was stratified by race and EGFR mutation type (exon 19 deletion mutation/exon 21 L858R substitution mutation). The primary endpoint was PFS by blinded independent review.

Results: Of 346 Asian patients, 170 were randomized to dacomitinib and 176 to gefitinib. The hazard ratio (HR) for PFS with dacomitinib versus gefitinib was 0.509 (95 % confidence interval [CI]: 0.391-0.662; 1-sided p < 0.0001; median 16.5 months [95 % CI: 12.9-18.4] vs. 9.3 months [95 % CI: 9.2-11.0]). HR for OS with dacomitinib versus gefitinib was 0.759 (95 % CI: 0.578-0.996; median 37.7 months [95 % CI: 30.2-44.7] vs. 29.1 months [95 % CI: 25.6-36.0]). The OS benefit was still maintained in those patients who had a stepwise dose reduction of dacomitinib (to 30 and 15 mg/day). The most common adverse events (AEs) were diarrhea (154 [90.6 %] patients), paronychia (110 [64.7 %]), dermatitis acneiform (96 [56.5 %]), and stomatitis (87 [51.2 %]) with dacomitinib, and diarrhea (100 [56.8 %]), alanine aminotransferase increased (81 [46.0 %]), and aspartate aminotransferase increased (75 [42.6 %]) with gefitinib. Treatment-related serious AEs were reported in 16 (9.4 %) and 8 (4.5 %) patients treated with dacomitinib and gefitinib, respectively.

Conclusion: First-line dacomitinib was associated with significant prolongation of PFS and improved OS compared with gefitinib in Asian patients with EGFR mutation-positive advanced NSCLC. The AE profiles of dacomitinib and gefitinib in Asian patients were consistent with the overall ARCHER 1050 population.
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http://dx.doi.org/10.1016/j.lungcan.2021.02.025DOI Listing
April 2021

Docetaxel maintenance therapy versus best supportive care after first-line chemotherapy with different dose docetaxel plus cisplatin for advanced non-small cell lung cancer (TFINE study, CTONG-0904): an open-label, randomized, phase III trial.

Ann Transl Med 2021 Feb;9(4):338

Sanofi (China) Investment Co., Ltd. Shanghai Branch, Shanghai, China.

Background: Maintenance therapy is important in the management of advanced non-small cell lung cancer (NSCLC). The present TFINE study assessed the efficacy and safety of docetaxel continuation maintenance (DCM) therapy after first-line treatment with different doses of docetaxel plus cisplatin.

Methods: In this open-label, randomized, phase III study, newly diagnosed patients with advanced NSCLC were initially randomized (R1, 1:1) to receive first-line treatment with cisplatin 75 mg/m plus docetaxel 75 mg/m (DC75) or 60 mg/m (DC60) for up to 4 cycles. Patients without progression were further randomized (R2, 1:2) to best supportive care (BSC) or DCM (60 mg/m) for up to 6 cycles. The primary endpoint was progression-free survival (PFS) after R2, and the secondary endpoints included best response rate in first-line treatment, overall survival (OS), time to progression (TTP), and toxicities.

Results: A total of 375 patients were enrolled in R1 and 184 of these patients continued in R2. DCM significantly prolonged PFS compared to BSC (HR =0.57, median PFS =5.8 . 3.0 months, P=0.002). The response rates were 30.2% and 23.9% in the DC75 and DC60 groups, respectively (P=0.17). There was no significant difference in OS (12.3 . 13.7 months, P=0.77). Additionally, 47.8% and 45.7% of patients reported AEs in the DC75 and DC60 groups, respectively. Diarrhea was more frequent with DC75 than with DC60 (8.6% . 3.2%, P=0.029). Other toxicities were comparable between the 2 docetaxel dose groups.

Conclusions: Continuation maintenance treatment with docetaxel is well tolerated and improves PFS in patients with NSCLC. The docetaxel dose of 60 mg/m may be preferred due to similar efficacy and less diarrhea.

Trial Registration: NCT01038661.
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http://dx.doi.org/10.21037/atm-20-8078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944306PMC
February 2021

Ambient extreme heat exposure in summer and transitional months and emergency department visits and hospital admissions due to pregnancy complications.

Sci Total Environ 2021 Jul 1;777:146134. Epub 2021 Mar 1.

Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, One University Place, Rensselaer, Albany, NY 12144, USA; Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, State University of New York, One University Place, Rensselaer, Albany, NY 12144, USA. Electronic address:

Although extreme heat exposure (EHE) was reported to be associated with increased risks of multiple diseases, little is known about the effects of EHE on pregnancy complications. We examined the EHE-pregnancy complications associations by lag days, subtypes, sociodemographic characteristics, and areas in New York State (NYS). We conducted a case-crossover analysis to assess the EHE-pregnancy complications associations in summer (June-August) and transitional months (May and September). All emergency department (ED) visits and hospital admissions due to pregnancy complications (ICD 9 codes: 630-649) from 2005 to 2013 in NYS were included. Daily mean temperature > 90th percentile of the monthly mean temperature in each county was defined as an EHE. We used conditional logistic regression while controlling for other weather factors, air pollutants and holidays to assess the EHE-pregnancy complications associations. EHE was significantly associated with increased ED visits for pregnancy complications in summer (ORs ranged: 1.01-1.04 from lag days 0-5). There was also a significant and stronger association in transitional months (ORs ranged: 1.02-1.06, Lag 0). Furthermore, we found EHE affected multiple subtypes of pregnancy complications, including threatened/spontaneous abortion, renal diseases, infectious diseases, diabetes, and hypertension (ORs range: 1.13-1.90) during transitional months. A significant concentration response effect between the number of consecutive days of EHE and ED visits in summer (P for trend <0.001), ED visits in September (P for trend =0.03), and hospital admission in May (P for trend<0.001) due to pregnancy complications was observed, respectively. African Americans and residents in lower socioeconomic position (SEP) counties were more susceptible to the effects of EHE. In conclusion, we found an immediate and prolonged effect of EHE on pregnancy complications in summer and a stronger, immediate effect in transitional months. These effects were stronger in African Americans and counties with lower SEP. Earlier warnings regarding extreme heat are recommended to decrease pregnancy complications.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146134DOI Listing
July 2021

Eltrombopag restores erythropoiesis in refractory adult acquired pure red cell aplasia.

Int J Hematol 2021 Jul 21;114(1):124-128. Epub 2021 Feb 21.

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China.

Acquired pure red cell aplasia is a rare condition characterized by normocytic normochromic anemia with severe reticulocytopenia. In refractory acquired pure red cell aplasia, the low response rate of immunosuppressive therapy also constitutes a challenge. We herein report the case of a 58-year-old male with refractory acquired pure red cell aplasia that was successfully treated by eltrombopag at a dose of 75 mg/day. After application of eltrombopag, the patient achieved complete remission and tolerated the treatment very well, with only mild bilirubin elevation. These preliminary findings showed that eltrombopag may be effective and well tolerated in adult patients with refractory acquired pure red cell aplasia.
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http://dx.doi.org/10.1007/s12185-021-03100-2DOI Listing
July 2021