Publications by authors named "Lu Yan"

1,988 Publications

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Assessment of genotoxic chemicals using chemogenomic profiling based on gene-knockout library in Saccharomyces cerevisiae.

Toxicol In Vitro 2021 Nov 26:105278. Epub 2021 Nov 26.

State Key Laboratory of Pollution Control & Resource Reuse, School of the Environment, Nanjing University, 163 Xianlin Ave., Nanjing, Jiangsu 210023, China. Electronic address:

Understanding the adverse effects of genotoxic chemicals and identifying them effectively from non-genotoxic chemicals are of great worldwide concerns. Here, Saccharomyces cerevisiae (yeast) genome-wide single-gene knockout screening approach was conducted to assess two genotoxic chemicals (4-nitroquinoline-1-oxide (4-NQO) and formaldehyde (FA)) and environmental pollutant dichloroacetic acid (DCA, genotoxicity is controversial). DNA repair was significant enriched in the gene ontology (GO) biology process (BP) terms and KEGG pathways when exposed to low concentrations of 4-NQO and FA. Higher concentrations of 4-NQO and FA influenced some RNA metabolic and biosynthesis pathways. Moreover, replication and repair associated pathways were top ranked KEGG pathways with high fold-change for low concentrations of 4-NQO and FA. The similar gene profiles perturbed by DCA with three test concentrations identified, the common GO BP terms associated with aromatic amino acid family biosynthetic process and ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. DCA has no obvious genotoxicity as there was no enriched DNA damage and repair pathways and fold-change of replication and repair KEGG pathways were very low. Five genes (RAD18, RAD59, MUS81, MMS4, and BEM4) could serve as candidate genes for genotoxic chemicals. Overall, the yeast functional genomic profiling showed great performance for assessing the signatures and potential molecular mechanisms of genotoxic chemicals.
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http://dx.doi.org/10.1016/j.tiv.2021.105278DOI Listing
November 2021

Combined first-principles statistical mechanics approach to sulfur structure in organic cathode hosts for polymer based lithium-sulfur (Li-S) batteries.

Phys Chem Chem Phys 2021 Nov 29. Epub 2021 Nov 29.

Research Group for Simulations of Energy Materials, Helmholtz-Zentrum Berlin für Materialien und Energie GmbH, Hahn-Meitner-Platz 1, Berlin 14109, Germany.

Polymer-based batteries that utilize organic electrode materials are considered viable candidates to overcome the common drawbacks of lithium-sulfur (Li-S) batteries. A promising cathode can be developed using a conductive, flexible, and free-standing polymer, poly(4-thiophen-3-yl)benzenethiol) (PTBT), as the sulfur host material. By a vulcanization process, sulfur is embedded into this polymer. Here, we present a combination of electronic structure theory and statistical mechanics to characterize the structure of the initial state of the charged cathode on an atomic level. We perform a stability analysis of differently sulfurized TBT dimers as the basic polymer unit calculated within density-functional theory (DFT) and combine this with a statistical binding model for the binding probability distributions of the vulcanization process. From this, we deduce sulfur chain length ("rank") distributions and calculate the average sulfur rank depending on the sulfur concentration and temperature. This multi-scale approach allows us to bridge the gap between the local description of the covalent bonding process and the derivation of the macroscopic properties of the cathode. Our calculations show that the main reaction of the vulcanization process leads to high-probability states of sulfur chains cross-linking TBT units belonging to different polymer backbones, with a dominant rank around = 5. In contrast, the connection of adjacent TBT units of the same polymer backbone by a sulfur chain is the side reaction. These results are experimentally supported by Raman spectroscopy.
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http://dx.doi.org/10.1039/d1cp04550dDOI Listing
November 2021

Aligned Organization of Synapses and Mitochondria in Auditory Hair Cells.

Neurosci Bull 2021 Nov 27. Epub 2021 Nov 27.

Shanghai Institute of Precision Medicine, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, China.

Recent studies have revealed great functional and structural heterogeneity in the ribbon-type synapses at the basolateral pole of the isopotential inner hair cell (IHC). This feature is believed to be critical for audition over a wide dynamic range, but whether the spatial gradient of ribbon morphology is fine-tuned in each IHC and how the mitochondrial network is organized to meet local energy demands of synaptic transmission remain unclear. By means of three-dimensional electron microscopy and artificial intelligence-based algorithms, we demonstrated the cell-wide structural quantification of ribbons and mitochondria in mature mid-cochlear IHCs of mice. We found that adjacent IHCs in staggered pairs differ substantially in cell body shape and ribbon morphology gradient as well as mitochondrial organization. Moreover, our analysis argues for a location-specific arrangement of correlated ribbon and mitochondrial function at the basolateral IHC pole.
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http://dx.doi.org/10.1007/s12264-021-00801-wDOI Listing
November 2021

Recent developments in mesoporous polydopamine-derived nanoplatforms for cancer theranostics.

J Nanobiotechnology 2021 Nov 24;19(1):387. Epub 2021 Nov 24.

The Fourth Affiliated Hospital, Zhejiang University School of Medicine, 322000, Yiwu, Zhejiang, People's Republic of China.

Polydopamine (PDA), which is derived from marine mussels, has excellent potential in early diagnosis of diseases and targeted drug delivery owing to its good biocompatibility, biodegradability, and photothermal conversion. However, when used as a solid nanoparticle, the application of traditional PDA is restricted because of the low drug-loading and encapsulation efficiencies of hydrophobic drugs. Nevertheless, the emergence of mesoporous materials broaden our horizon. Mesoporous polydopamine (MPDA) has the characteristics of a porous structure, simple preparation process, low cost, high specific surface area, high light-to-heat conversion efficiency, and excellent biocompatibility, and therefore has gained considerable interest. This review provides an overview of the preparation methods and the latest applications of MPDA-based nanodrug delivery systems (chemotherapy combined with radiotherapy, photothermal therapy combined with chemotherapy, photothermal therapy combined with immunotherapy, photothermal therapy combined with photodynamic/chemodynamic therapy, and cancer theranostics). This review is expected to shed light on the multi-strategy antitumor therapy applications of MPDA-based nanodrug delivery systems.
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http://dx.doi.org/10.1186/s12951-021-01131-9DOI Listing
November 2021

Efficacy and Safety of HLX03, an Adalimumab Biosimilar, in Patients with Moderate-to-Severe Plaque Psoriasis: A Randomized, Double-Blind, Phase III Study.

Adv Ther 2021 Nov 23. Epub 2021 Nov 23.

Department of Dermatology, Peking University People's Hospital, No. 11 Xizhimen South Avenue, Beijing, 100044, China.

Introduction: Adalimumab has been used successfully in the treatment of psoriasis. The objective of the study is to compare the efficacy, safety, and immunogenicity between HLX03, an adalimumab biosimilar, and adalimumab in Chinese patients with moderate-to-severe plaque psoriasis.

Methods: In this double-blind, active-controlled, parallel-group study, 262 patients with moderate-to-severe plaque psoriasis were randomized (1:1) to receive HLX03 or adalimumab (80 mg at week 1, 40 mg at week 2, and then 40 mg every 2 weeks) for 48 weeks. The primary endpoint was improvement in Psoriasis Area and Severity Index (PASI) score at week 16 comparing to baseline. Equivalence was demonstrated if 95% confidence interval (CI) of the between group difference fell within the equivalence margins of ± 15%. Other efficacy endpoints, safety and immunogenicity were also evaluated.

Results: In the full analysis set, PASI improvements at week 16 was 83.5% (n = 131) in the HLX03 group and 82.0% (n = 130) in the adalimumab group, with a least-square-mean difference of 1.5% (95% CI - 3.9% to 6.8%). There were no significant between-group differences in all secondary efficacy analyses including proportion of patients achieving ≥ 75% improvement from baseline PASI (PASI 75), physician global assessment (PGA) 0/1 (clear or almost clear) and change in dermatology life quality index (DLQI) score. The incidences of adverse events and the proportion of patients with antidrug antibodies were also comparable between the two treatment groups.

Conclusion: HLX03 demonstrated equivalent efficacy, similar safety and immunogenicity to reference adalimumab, supporting its development as an alternative treatment for patients with plaque psoriasis in China.

Clinical Trial Registration: Chinadrugtrials.org.cn, CTR20171123 (November 27, 2017); ClinicalTrials.gov, NCT03316781 (October 20, 2017).
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http://dx.doi.org/10.1007/s12325-021-01899-0DOI Listing
November 2021

Impact of the revised hemodynamic definition on the diagnosis of precapillary pulmonary hypertension: a retrospective single-center study in China.

Cardiovasc Diagn Ther 2021 Oct;11(5):1047-1057

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

Background: In the 6 World Symposium on Pulmonary Hypertension (PH), the hemodynamic definition of PH was reduced from a mean pulmonary artery pressure (mPAP) ≥25 to >20 mmHg. This study aimed to evaluate the impact of the revised hemodynamic definition on the diagnosis of precapillary PH.

Methods: We retrospectively enrolled patients who underwent right heart catheterization from January 2012 to December 2018. All included patients were reassessed according to the revised hemodynamic definition.

Results: A total of 1,251 patients were included for analysis, of whom 1,044 patients had precapillary PH and 182 patients had mPAP <25 mmHg. After applying the revised definition, 33 (18.1%) of 182 patients with mPAP <25 mmHg were reclassified as having PH. However, only 7 of these 33 patients had a pulmonary vascular resistance ≥3 wood units and could be considered to have precapillary PH, accounting for 0.7% of the existing precapillary PH population. More importantly, 12 patients with mPAP ≥25 mmHg were delisted from precapillary PH for pulmonary vascular resistance <3 wood units (5 patients from Group III, 4 patients from Group IV, 3 patients from Group V). Overall, there was a net 0.5% decrease [(12-7)/1044×100%] in the population with precapillary PH.

Conclusions: The revised hemodynamic definition had a minor impact on the diagnosis of precapillary PH. It should be noted that the revised definition would influence not only patients with mPAP =21-24 mmHg, but also patients with mPAP ≥25 mmHg.
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http://dx.doi.org/10.21037/cdt-21-373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569274PMC
October 2021

Screening of potential hub genes in pulmonary thromboembolism.

Exp Ther Med 2022 Jan 30;23(1):18. Epub 2021 Oct 30.

Department of Laboratory Medicine, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, P.R. China.

Pulmonary thromboembolism (PTE) is a fatal clinical syndrome that usually occurs in elderly individuals. The present study aimed to identify functional and key genes involved in the early diagnosis of PTE using bioinformatics analysis. The GSE84738 dataset was retrieved from the Gene Expression Omnibus database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were subsequently performed. In addition, Cytoscape software v.3.7.2 was used to construct a protein-protein interaction (PPI) network. Serum samples from patients with PTE and healthy individuals were collected and the expression levels of Toll-like receptor (TLR)4, TLR2, IL-1β, JUN, prostaglandin-endoperoxide synthase 2 (PTGS2), osteopontin (SPP1) and endothelin-1 (ET-1) were analyzed by reverse transcription-quantitative PCR. A total of 160 upregulated and 159 downregulated differentially expressed genes were identified between patients with PTE and healthy individuals. TNF, IL-1β, JUN, TLR4, PTGS2, vascular cell adhesion molecule 1, SPP1, ryanodine receptor 2, TLR2 and ET-1 were considered as hub genes, which are defined as the genes with the highest degree of interaction in the enrichment and PPI network analyses. The top 10 common genes with the highest degree in the PPI network and the top 10 genes in modules 1 and 2 were TLR4, TLR2, IL-1β, JUN, PTGS2, SPP1 and ET-1. Taken together, the present study suggested that TLR4, TLR2, IL-1β and SPP1 were enriched in patients with PTE, thus providing novel potential biomarkers for the diagnosis of PTE.
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http://dx.doi.org/10.3892/etm.2021.10940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593918PMC
January 2022

Long non-coding RNA HOMER3-AS1 drives hepatocellular carcinoma progression via modulating the behaviors of both tumor cells and macrophages.

Cell Death Dis 2021 Nov 23;12(12):1103. Epub 2021 Nov 23.

Department of Pathology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.

The crosstalk between cancer cells and tumor microenvironment plays critical roles in hepatocellular carcinoma (HCC). The identification of long non-coding RNAs (lncRNAs) mediating the crosstalk might promote the development of new therapeutic strategies against HCC. Here, we identified a lncRNA, HOMER3-AS1, which is over-expressed in HCC and correlated with poor survival of HCC patients. HOMER3-AS1 promoted HCC cellular proliferation, migration, and invasion, and reduced HCC cellular apoptosis. Furthermore, HOMER3-AS1 promoted macrophages recruitment and M2-like polarization. In vivo, HOMER3-AS1 significantly facilitated HCC progression. Mechanism investigations revealed that HOMER3-AS1 activated Wnt/β-catenin signaling via upregulating HOMER3. Functional rescue experiments revealed that HOMER3/Wnt/β-catenin axis mediated the roles of HOMER3-AS1 in promoting HCC cellular malignant phenotypes. Furthermore, colony stimulating factor-1 (CSF-1) was also identified as a critical downstream target of HOMER3-AS1. HOMER3-AS1 increased CSF-1 expression and secretion. Blocking CSF-1 reversed the roles of HOMER3-AS1 in inducing macrophages recruitment and M2 polarization. Furthermore, positive correlations between HOMER3-AS1 and HOMER3 expression, HOMER3-AS1 and CSF-1 expression, and HOMER3-AS1 expression and M2-like macrophages infiltration were found in human HCC tissues. In summary, our findings demonstrated that HOMER3-AS1 drives HCC progression via modulating the behaviors of both tumor cells and macrophages, which are dependent on the activation of HOMER3/Wnt/β-catenin axis and CSF-1, respectively. HOMER3-AS1 might be a promising prognostic and therapeutic target for HCC.
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http://dx.doi.org/10.1038/s41419-021-04309-zDOI Listing
November 2021

The clinical characteristics of patients with pulmonary hypertension combined with obstructive sleep apnoea.

BMC Pulm Med 2021 Nov 21;21(1):378. Epub 2021 Nov 21.

Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 BeiLiShi Road, Xicheng District, Beijing, 100037, China.

Objective: Obstructive sleep apnoea (OSA) is one cause of pulmonary hypertension (PH) and can also emerge along with PH. The clinical diagnosis and treatment of OSA in patients with PH are still controversial. The purpose of this clinical observation study was to observe and summarize the incidence and clinical characteristics of OSA in patients with PH and to explore possible predictors of PH combined with OSA.

Methods: Patients with PH diagnosed by right heart catheterization who underwent overnight cardiorespiratory monitoring from December 2018 to December 2020 were enrolled. OSA was defined as an apnoea-hypopnoea index of ≥ 5/h with ≥ 50% of apnoeic events being obstructive. Baseline clinical characteristics and parameters were collected to compare PH patients with and without OSA. Logistic regression analysis was run to determine the risk factors for OSA in PH patients.

Results: A total of 35 (25%) of 140 patients had OSA. OSA is relatively frequent in patients with PH, especially in patients with chronic thromboembolic pulmonary hypertension and patients with lung disease- or hypoxia-associated PH. The patients who had OSA were mostly male and had a higher age and a lower daytime arterial oxygen pressure. Logistic regression analysis found that older age, male sex, and lower daytime arterial blood oxygen pressure correlated with OSA in PH patients.

Conclusion: OSA is common in patients with PH. Lower daytime arterial oxygen pressure is a risk factor for OSA in older male patients with PH.
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http://dx.doi.org/10.1186/s12890-021-01755-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607599PMC
November 2021

Cancer treatment evolution from traditional methods to stem cells and gene therapy.

Curr Gene Ther 2021 Nov 18. Epub 2021 Nov 18.

Department of Anatomy, Medical College of Nantong University, Nantong 226001. China.

Background: Cancer, a malignant tumor, is caused by the failure of the mechanism that controls cell growth and proliferation. Late clinical symptoms often manifest as lumps, pain, ulcers, and bleeding. Systemic symptoms include weight loss, fatigue, and loss of appetite. It is a major disease that threatens human life and health. How to treat cancer is a long-standing problem that needs to be overcome in the history of medicine.

Method: Traditional tumor treatment methods are poorly targeted, and the side effects of treatment seriously damage the physical and mental health of patients. In recent years, with the advancement of medical science and technology, the research on gene combined with mesenchymal stem cells to treat tumors has been intensified. Mesenchymal stem cells carry genes to target cancer cells, which can achieve better therapeutic effects.

Discussion: In the text, we systematically review the cancer treatment evolution from traditional methods to novel approaches that include immunotherapy, nanotherapy, stem cell theapy, and gene therapy. We provide the latest review of the application status, clinical trials and development prospects of mesenchymal stem cells and gene therapy for cancer, as well as their integration in cancer treatment. Mesenchymal stem cells are effective carriers carrying genes and provide new clinical ideas for tumor treatment.

Conclusion: This review focuses on the current status, application prospects and challenges of mesenchymal stem cell combined gene therapy for cancer, and provides new ideas for clinical research.
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http://dx.doi.org/10.2174/1566523221666211119110755DOI Listing
November 2021

Early Enhancement of Neuroplasticity Index, the Ratio of Serum Brain-Derived Neurotrophic Factor Level to HAMD-24 Score, in Predicting the Long-Term Antidepressant Efficacy.

Front Behav Neurosci 2021 27;15:712445. Epub 2021 Oct 27.

Interdisciplinary Institute for Personalized Medicine in Brain Disorders, Jinan University, Guangzhou, China.

Current mainstream treatment of major depressive disorder (MDD) has a disadvantage in delayed onset of efficacy, making detection of early signatures predicative of the long-term treatment efficacy urgent. MDD patients were scored with HAMD-24 and serum brain-derived neurotrophic factor (BDNF) levels were measured at different times in two independent trials: a single-arm observation of Yueju pill, a clinically approved traditional multiherbal medicine, and a two-arm random placebo-controlled trial for Yueju vs escitalopram. The ratio of the BDNF level to HAMD-24 score, or neuroplasticity index (NI), and its derived parameters were used for correlation analysis and receiver operating characteristic (ROC) analysis. On both the early (4th) and final (28th) days, Yueju and escitalopram significantly reduced HAMD-24 scores, compared to baselines, but only Yueju increased BDNF at both times. For either Yueju or escitalopram treatment, NI, but not BDNF, at baseline was correlated to NIs at the early or final treatment day. NI at early time was significantly correlated to early NI enhancement from the baseline for both Yueju and escitalopram, and to final NI enhancement from the baseline for Yueju in both trials. ROC analysis supported the predictability of Yueju's final treatment efficacy from early NI enhancement. The small sample size and 28 days of treatment time may lead to the impossibility of ROC analysis of escitalopram. Early NI enhancement is useful for prediction of long-term efficacy of Yueju and presumably some other antidepressants. [www.ClinicalTrials.gov], identifier [ChiCTR1900021114].
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http://dx.doi.org/10.3389/fnbeh.2021.712445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578865PMC
October 2021

Study of Construction and Performance on Photoelectric Devices of Cs-Pb-Br Perovskite Quantum Dot.

Materials (Basel) 2021 Nov 8;14(21). Epub 2021 Nov 8.

School of Materials Science and Engineering, University of Jinan, Jinan 250022, China.

White LEDs were encapsulated using CsPbBr quantum dots and GdO:Eu red phosphor as lamp powder. Under the excitation of a GaN chip, the color coordinates of the W-LED were (0.33, 0.34), and the color temperature was 5752 K, which is close to the color coordinate and color temperature range of standard sunlight. The electric current stability was excellent with an increase in the electric current, voltage, and luminescence intensity of the quantum dots and phosphors by more than 10 times. However, the stability of the quantum dots was slightly insufficient over long working periods. The photocatalytic devices were constructed using TiO, CsPbBr, and NiO as an electron transport layer, light absorption layer, and catalyst, respectively. The Cs-Pb-Br-based perovskite quantum dot photocatalytic devices were constructed using a two-step spin coating method, one-step spin coating method, and full PLD technology. In order to improve the water stability of the device, a hydrophobic carbon paste and carbon film were selected as the hole transport layer. The TiO layer and perovskite layer with different thicknesses and film forming qualities were obtained by changing the spin coating speed. The influence of the spin coating speed on the device's performance was explored through SEM and a J-V curve to find the best spin coating process. The device constructed by the two-step spin coating method had a higher current density but no obvious increase in the current density under light, while the other two methods could obtain a more obvious light response, but the current density was very low.
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http://dx.doi.org/10.3390/ma14216716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587011PMC
November 2021

Real-time threshold determination of auditory brainstem responses by cross-correlation analysis.

iScience 2021 Nov 14;24(11):103285. Epub 2021 Oct 14.

Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai, China.

Auditory brainstem response (ABR) serves as an objective indication of auditory perception at a given sound level and is nowadays widely used in hearing function assessment. Despite efforts for automation over decades, ABR threshold determination by machine algorithms remains unreliable and thereby one still relies on visual identification by trained personnel. Here, we described a procedure for automatic threshold determination that can be used in both animal and human ABR tests. The method terminates level averaging of ABR recordings upon detection of time-locked waveform through cross-correlation analysis. The threshold level was then indicated by a dramatic increase in the sweep numbers required to produce "qualified" level averaging. A good match was obtained between the algorithm outcome and the human readouts. Moreover, the method varies the level averaging based on the cross-correlation, thereby adapting to the signal-to-noise ratio of sweep recordings. These features empower a robust and fully automated ABR test.
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http://dx.doi.org/10.1016/j.isci.2021.103285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571499PMC
November 2021

Dimethyl itaconate alleviates the pyroptosis of macrophages through oxidative stress.

BMC Immunol 2021 Nov 8;22(1):72. Epub 2021 Nov 8.

Department of Critical Care Medicine, Zhejiang Hospital, 1229 Gudun Road, Hangzhou, 310030, China.

Macrophages are involved in the pathophysiology of many diseases as critical cells of the innate immune system. Pyroptosis is a form of macrophage death that induces cytokinesis of phagocytic substances in the macrophages, thereby defending against infection. Dimethyl itaconate (DI) is an analog of itaconic acid with anti-inflammatory effects. However, the effect of dimethyl itaconate on macrophage pyroptosis has not been elucidated clearly. Thus, the present study aimed to analyze the effect of DI treatment on a macrophage pyroptosis model (Lipopolysaccharide, LPS + Adenosine Triphosphate, ATP). The results showed that 0.25 mM DI ameliorated macrophage pyroptosis and downregulated interleukin (IL)-1β expression. Then, real-time quantitative polymerase chain reaction (RT-qPCR) was used to confirm the result of RNA-sequencing of the upregulated oxidative stress-related genes (Gclc and Gss) and downregulated inflammation-related genes (IL-12β and IL-1β). In addition, Gene Ontology (GO) enrichment analysis showed that differential genes were associated with transcript levels and DNA replication. Kyoto encyclopedia of genes and genomes (KEGG) enrichment showed that signaling pathways, such as tumor necrosis factor (TNF), Jak, Toll-like receptor and IL-17, were altered after DI treatment. N-acetyl-L-cysteine (NAC) reversed the DI effect on the LPS + ATP-induced macrophage pyroptosis and upregulated the IL-1β expression. Oxidative stress-related protein Nrf2 is involved in the DI regulation of macrophage pyroptosis. Taken together, these findings suggested that DI alleviates the pyroptosis of macrophages through oxidative stress.
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http://dx.doi.org/10.1186/s12865-021-00463-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573905PMC
November 2021

The Role and Mechanism of Oxidative Stress and Nuclear Receptors in the Development of NAFLD.

Oxid Med Cell Longev 2021 27;2021:6889533. Epub 2021 Oct 27.

Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education and Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.

The overproduction of reactive oxygen species (ROS) and consequent oxidative stress contribute to the pathogenesis of acute and chronic liver diseases. It is now acknowledged that nonalcoholic fatty liver disease (NAFLD) is characterized as a redox-centered disease due to the role of ROS in hepatic metabolism. However, the underlying mechanisms accounting for these alternations are not completely understood. Several nuclear receptors (NRs) are dysregulated in NAFLD, and have a direct influence on the expression of a set of genes relating to the progress of hepatic lipid homeostasis and ROS generation. Meanwhile, the NRs act as redox sensors in response to metabolic stress. Therefore, targeting NRs may represent a promising strategy for improving oxidation damage and treating NAFLD. This review summarizes the link between impaired lipid metabolism and oxidative stress and highlights some NRs involved in regulating oxidant/antioxidant turnover in the context of NAFLD, shedding light on potential therapies based on NR-mediated modulation of ROS generation and lipid accumulation.
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http://dx.doi.org/10.1155/2021/6889533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566046PMC
October 2021

Dezocine as a potent analgesic: overview of its pharmacological characterization.

Acta Pharmacol Sin 2021 Nov 4. Epub 2021 Nov 4.

CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Dezocine, a synthetic opioid, introduced in 1970s as an analgesic, was redeveloped for relieving moderate to severe pain by Yangtze River Pharmaceutical Group in China in 2009. To date, dezocine occupies 45% of China's opioid analgesic market. Along with dezocine being a dominated painkiller, a certain amount of research was conducted to elucidate dezocine's action. In this review we summarize the current knowledge on the receptor, preclinical and clinical pharmacology of dezocine. Briefly, preclinical data show that dezocine is effective under varying pain conditions, particularly chronic neuropathic pain and cancer pain, through activation of opioid receptors, and inhibition of norepinephrine reuptake. Clinical data establish the effectiveness of dezocine either as a primary analgesic for postoperative pain management or a supplement for balanced analgesia. The receptor profile of dezocine is different from known pure μ agonists, and allows it to be used in combination with other opioids for additivity in efficacy or lower incidence of adverse effects.
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http://dx.doi.org/10.1038/s41401-021-00790-6DOI Listing
November 2021

Mechanically Activated Calcium Channel PIEZO1 Modulates Radiation-Induced Epithelial-Mesenchymal Transition by Forming a Positive Feedback With TGF-β1.

Front Mol Biosci 2021 13;8:725275. Epub 2021 Oct 13.

Department of Anesthesiology, The PLA Rocket Force Characteristic Medical Center, Beijing, China.

TGF-β-centered epithelial-mesenchymal transition (EMT) is a key process involved in radiation-induced pulmonary injury (RIPI) and pulmonary fibrosis. PIEZO1, a mechanosensitive calcium channel, is expressed in myeloid cell and has been found to play an important role in bleomycin-induced pulmonary fibrosis. Whether PIEZO1 is related with radiation-induced EMT remains elusive. Herein, we found that PIEZO1 is functional in rat primary type II epithelial cells and RLE-6TN cells. After irradiation, PIEZO1 expression was increased in rat lung alveolar type II epithelial cells and RLE-6TN cell line, which was accompanied with EMT changes evidenced by increased TGF-β1, N-cadherin, Vimentin, Fibronectin, and α-SMA expression and decreased E-cadherin expression. Addition of exogenous TGF-β1 further enhanced these phenomena . Knockdown of PIEZO1 partly reverses radiation-induced EMT . Mechanistically, we found that activation of PIEZO1 could upregulate TGF-β1 expression and promote EMT through Ca/HIF-1α signaling. Knockdown of HIF-1α partly reverses enhanced TGF-β1 expression caused by radiation. Meanwhile, the expression of PIEZO1 was up-regulated after TGF-β1 co-culture, and the mechanism could be traced to the inhibition of transcription factor C/EBPβ expression by TGF-β1. Irradiation also caused a decrease in C/EBPβ expression in RLE-6TN cells. Dual luciferase reporter assay and chromatin immunoprecipitation assay (ChIP) confirmed that C/EBPβ represses PIEZO1 expression by binding to the PIEZO1 promoter. Furthermore, overexpression of C/EBPβ by using the synonymous mutation to C/EBPβ siRNA could reverse siRNA-induced upregulation of PIEZO1. In summary, our research suggests a critical role of PIEZO1 signaling in radiation-induced EMT by forming positive feedback with TGF-β1.
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http://dx.doi.org/10.3389/fmolb.2021.725275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548710PMC
October 2021

miR-20a Overexpression in Adipose-Derived Mesenchymal Stem Cells Promotes Therapeutic Efficacy in Murine Lupus Nephritis by Regulating Autophagy.

Stem Cells Int 2021 21;2021:3746335. Epub 2021 Oct 21.

Department of Dermatology, Nanfang Hospital, Southern Medical University, China.

Objective: Lupus nephritis is the most common and severe complication of systemic lupus erythematosus. The aim of our study was to investigate the efficacy of miR-20a overexpressing adipose-derived stem cell (ADSC) transplantation in murine lupus nephritis (LN) and explore potential molecular mechanisms.

Methods: Mouse ADSCs were transfected with a miR-20a lentiviral vector to obtain miR-20a overexpression ADSCs (miR-20a-ADSCs). We first observed the influence of miR-20a on ADSC viability and apoptosis . B6.MRL/lpr mice were administered ADSC/miR-20a-ADSC intravenously every week from age 30 to 33 weeks, and the lupus and normal control groups received PBS on the same schedule.

Results: miR-20a expression increased in miR-20a-ADSC-derived exosomes, and miR-20a overexpression promoted ADSC proliferation and inhibited apoptosis. Compared with ADSCs, miR-20a-ADSC treatment significantly improved serologic and histologic abnormalities, as evidenced by reduced serum creatinine, anti-dsDNA antibody, 24 h urine protein levels, nephritis scores, and C3/IgG deposits. Furthermore, miR-20a-ADSC treatment resulted in downregulated Akt, mTOR, and p62 expression and upregulated miR-20a, Beclin 1, and LC3 II/I expression compared with ADSC treatment. After treatment with miR-20a-ADSC, a significant increase in the number of autophagosomes within podocytes was observed, along with upregulated expression of podocin and nephrin, compared with the ADSC group.

Conclusions: miR-20a-ADSC transplantation prevents the development of lupus nephritis and significantly ameliorates already-established disease, and its mechanism is related to autophagy by targeting the miR-20a-regulated mTOR pathway.
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http://dx.doi.org/10.1155/2021/3746335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553505PMC
October 2021

Skin coloration is a culturally-specific cue for attractiveness, healthiness, and youthfulness in observers of Chinese and western European descent.

PLoS One 2021 28;16(10):e0259276. Epub 2021 Oct 28.

Department of Psychology, University of Liverpool, Liverpool, United Kingdom.

Facial skin coloration signals information about an individual and plays an important role in social interactions and mate choice, due its putative association with health, attractiveness, and age. Whether skin coloration as an evolutionary significant cue is universal or specific to a particular culture is unclear and current evidence on the universality of skin color as a cue to health and attractiveness are equivocal. The current study used 80 calibrated, high-resolution, non-manipulated images of real human faces, either of Chinese or western European descent, which were rated in terms of attractiveness, healthiness, and perceived age by 44 observers, 22 western European (13 male; mean age ± SD = 24.27 ± 5.30) and 22 Chinese (7 male; mean age ± SD = 26.05 ± 3.96) observers. To elucidate the associations between skin coloration and these perceptual ratings and whether these associations are modulated by observer or image ethnicity, a linear mixed-effect model was setup with skin lightness (L*; CIELAB), redness (a*) and yellowness (b*), observer and image ethnicity as independent variables and perceived attractiveness, healthiness, and estimated age as dependent variables. We found robust positive associations between facial skin lightness (L*) and attractiveness, healthiness, and youthfulness, but only when Chinese observers judge facial images of their own ethnicity. Observers of European descent, on the other hand, associated an increase in yellowness(b*) with greater attractiveness and healthiness in Chinese facial images. We find no evidence that facial redness is positively associated with these attributes; instead, an increase in redness (a*) is associated with an increase in the estimated age of European facial images. We conclude that observers of both ethnicities make use of skin color and lightness to rate attractiveness, healthiness, and perceived age, but to a lesser degree than previously thought. Furthermore, these coloration cues are not universal and are utilized differently within the Chinese and western European ethnic groups. Our study adds to the growing body of work demonstrating the importance of skin color manipulations within an evolutionary meaningful parameter space, ideally using realistic skin models based on physical parameters.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0259276PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553160PMC
October 2021

RNA-Seq analysis in giant pandas reveals the differential expression of multiple genes involved in cataract formation.

BMC Genom Data 2021 Oct 27;22(1):44. Epub 2021 Oct 27.

Beijing Zoo, Beijing, China.

Background: The giant panda (Ailuropoda melanoleuca) is an endangered mammalian species native to China. Fewer than 2500 giant pandas are known to exist, many of which are bred in captivity as a means to preserve and repopulate the species. Like other captive mammals, giant pandas acquire age-related cataracts, reducing their quality of life. Recent comparative genome-wide methylation analysis revealed 110 differentially methylated genes associated with cataract formation including six also associated with the formation of age-related cataracts in humans.

Results: To investigate the pathological pathway in greater detail, here we used RNA-Seq analysis to investigate the differential expression profiles of genes in three giant pandas with cataracts and three healthy controls. We identified more than 700 differentially expressed genes, 29 of which were selected for further analysis based on their low q-value. We found that many of the genes encoded regulatory and signaling proteins associated with the control of cell growth, migration, differentiation and apoptosis, supporting previous research indicating a key role for apoptosis in cataract formation.

Conclusion: The identification of genes involved in the formation of age-related cataracts could facilitate the development of predictive markers, preventative measures and even new therapies to improve the life of captive animals.
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http://dx.doi.org/10.1186/s12863-021-00996-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555103PMC
October 2021

The Effectiveness of Binocular Virtual Reality Training on Repairing Visual Field Defect of Glaucoma.

Cyberpsychol Behav Soc Netw 2021 Oct;24(10):683-689

National Engineering Research Center for Healthcare Devices, Guangzhou, China.

Visual field defect caused by glaucoma seriously affects the quality of life of patients, and clinically, this type of visual field defect has been considered to be irreversible. The aim of this study is to use binocular virtual reality training (VR training) to repair visual field defect in glaucoma patients, improve the quality of life of patients, and provide a new therapeutic strategy for the rehabilitation of glaucoma. Seventy glaucoma patients (median 56, range 15-84 years) were recruited and divided into control and training groups. Fifty-four patients' data were analyzed. The training group ( = 30) received binocular VR training for 3 months. The control group ( = 24) maintained the conventional treatment without any other intervention. Their visual field index (VFI) and mean defect (MD), and retinal nerve fiber layer average thickness (RNFL) and ganglion cell layer average thickness (GCL) average thickness before training and during followup were analyzed. In the training group, the VFI value ( = 3.277;  = 0.001) and MD value ( = 3.913;  < 0.0001) were significantly improved after 1 month of training. After 3 months of training, the VFI value ( = 3.761;  < 0.0001) and MD value ( = 3.133;  = 0.002) were significantly improved. There was no significant difference with the changes of average thickness of RNFL ( = 0.350) and GCL average ( = 0.383) after 3 months of training; whereas in the control group, except for a further reduction in GCL average thickness ( = 3.158;  = 0.002) compared with the baseline data, the other followup data were not statistically significant compared with the baseline data. Our data suggested that binocular VR training can significantly improve the visual field defect of glaucoma patients but warrants further study with large sample size. Clinical Trail registration number: ChiCTR1900027909.
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http://dx.doi.org/10.1089/cyber.2021.0215DOI Listing
October 2021

Sparcl1 promotes nonalcoholic steatohepatitis progression in mice through upregulation of CCL2.

J Clin Invest 2021 10;131(20)

Department of Endocrinology and Metabolism, Fudan Institute for Metabolic Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of chronic liver disease ranging from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH). However, the molecular mechanisms of NASH progression remain incompletely understood. White adipose tissue (WAT) has emerged as an important endocrine organ and contributes not only to the initial stage of NAFLD, but also to its severity. In the current study, through transcriptomic analysis we identified increased expression of Sparcl1, a secreted glycoprotein, in the WAT from NASH mice. Plasma Sparcl1 levels were similarly elevated and positively correlated with hepatic pathological features in NASH patients. Functional studies showed that both chronic injection of recombinant Sparcl1 protein and overexpression of Sparcl1 exaggerated hepatic inflammation and liver injury in mice. In contrast, genetic ablation of Sparcl1, knockdown of Sparcl1 in WAT, and treatment with a Sparcl1-neutralizing antibody dramatically alleviated diet-induced NASH pathogenesis. Mechanistically, Sparcl1 promoted the expression of C-C motif chemokine ligand 2 (CCL2) in hepatocytes through binding to Toll-like receptor 4 (TLR4) and activation of the NF-κB/p65 signaling pathway. Genetically or pharmacologically blocking the CCL2/CCR2 pathway attenuated the hepatic inflammatory response evoked by Sparcl1. Thus, our results demonstrated an important role for Sparcl1 in NASH progression, suggesting a potential target for therapeutic intervention.
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http://dx.doi.org/10.1172/JCI144801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516465PMC
October 2021

Efficient nitrogen removal from mainstream wastewater through coupling Partial Nitritation, Anammox and Methane-dependent nitrite/nitrate reduction (PNAM).

Water Res 2021 Nov 30;206:117723. Epub 2021 Sep 30.

Australian Centre for Water and Environmental Biotechnology (ACWEB, formerly AWMC), The University of Queensland, St. Lucia, Queensland 4072, Australia. Electronic address:

The application of partial nitritation and anammox to remove nitrogen from mainstream wastewater is of great interest because of the potential to reduce energy cost and carbon dosage. However, this process confronts a dilemma of relatively high effluent nitrogen concentration (>10 mg N/L), owning to the unwanted prevalence of nitrite-oxidizing bacteria (NOB) and the intrinsic nitrate production by anammox bacteria. Here, a novel technology, named the one-stage PNAM, that integrates Partial Nitritation, Anammox and Methane-dependent nitrite/nitrate reduction reactions, was developed in a single membrane biofilm reactor (MBfR). With feeding of synthetic mainstream wastewater containing ∼50 mg NH-N/L at a hydraulic retention time of 12 h, more than 95% nitrogen was removed in the established one-stage PNAM process at a practically useful rate of 0.1 kg N/m/d. Microbial community characterization and in-situ batch tests revealed a sophisticated microbial structure consisting of ammonia-oxidizing bacteria (AOB), anammox bacteria, nitrite/nitrate-dependent anaerobic methane oxidation (n-DAMO) bacteria and archaea, and a small fraction of NOB and aerobic methanotrophs. The role of methane in removing nitrate was confirmed by switching on/off the methane supply, which relaxed the requirement for NOB suppression. In addition, the established system was relatively robust against temperature variations, evidenced by a total nitrogen removal efficiency above 80% at temperature as low as 14 ℃. The results provide a promising alternative for efficient nitrogen removal from domestic wastewater using methane as the sole carbon source.
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http://dx.doi.org/10.1016/j.watres.2021.117723DOI Listing
November 2021

Negative effects of long-term exposure to salinity, drought, and combined stresses on halophyte Halogeton glomeratus.

Physiol Plant 2021 Dec 14;173(4):2307-2322. Epub 2021 Oct 14.

State Key Laboratory of Desert and Oasis Ecology, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi, China.

Plants are subjected to salt and drought stresses concurrently but our knowledge about the effects of combined stress on plants is limited, especially on halophytes. We aim to study if some diverse drought and salt tolerance traits in halophyte may explain their tolerance to salinity and drought stresses, individual and in combination, and identify key traits that influence growth under such stress conditions. Here, the halophyte Halogeton glomeratus was grown under control, single or combinations of 60 days drought and salt treatments, and morphophysiological responses were tested. Our results showed that drought, salinity, and combination of these two stressors decreased plant growth (shoot height, root length, and biomass), leaf photosynthetic pigments content (chlorophyll a, b, a + b and carotenoids), gas exchange parameters (Net photosynthesis rate [P ], transpiration rate [E], stomatal conductance [g ]), and water potential (ψ ), and the decreases were more prominent under combined drought and salinity treatment compared with these two stressors individually performed. Similarly, combined drought and salinity treatment induced more severe oxidative stress as indicated by more hydrogen peroxide (H O ) and malondialdehyde (MDA) accumulated. Nevertheless, H. glomeratus is equipped with specific mechanisms to protect itself against drought and salt stresses, including upregulation of superoxide dismutases (SOD; EC 1.15.1.1) and catalase (CAT; EC 1.11.1.6) activities and accumulation of osmoprotectants (Na , Cl , and soluble sugar). Our results indicated that photosynthetic pigments content, gas exchange parameters, water potential, APX activity, CAT activity, soluble sugar, H O , and MDA are valuable screening criteria for drought and salt, alone or combined, and provide the tolerant assessment of H. glomeratus.
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http://dx.doi.org/10.1111/ppl.13581DOI Listing
December 2021

n-type absorber by Cd doping achieves high-performance carbon-based CsPbIBr perovskite solar cells.

J Colloid Interface Sci 2021 Sep 24;608(Pt 1):40-47. Epub 2021 Sep 24.

Engineering Research Center of Environment-Friendly Functional Materials, Ministry of Education, PR China; Fujian Key Laboratory of Photoelectric Functional Materials, PR China; College of Materials Science & Engineering, Huaqiao University, Xiamen 361021, PR China. Electronic address:

High efficiency and stability have long been the key issues faced by perovskite solar cells (PSCs). It is found that the CsPbIBr all-inorganic perovskite has a suitable band gap and satisfactory stability, so it has attracted much attention. However, the many defects in the CsPbIBr film are one of the main problems hindering the improvement of power conversion efficiency (PCE) of the CsPbIBr PSCs. The substitution of trace impurities is undoubtedly a simple, cost-effective and efficient strategy. In this work, an appropriate amount of Cd (1.0% mol of Pb) is added into the CsPbIBr precursor solution to fabricate high quality CsPbIBr film with improved crystallinity, reduced trap density, suppressed photo-generated carrier recombination, displayed n-type doping and optimized energy level alignment. The corresponding carbon-based all-inorganic Cd-doped CsPbIBr PSCs achieve a maximum PCE of 10.63% with a high open circuit voltage (V) of 1.324 V, which are much higher than those of the control one with a PCE of 8.48% and an V of 1.235 V. The unencapsulated device can still retain more than 92% of the initial PCE when stored at ambient atmosphere (25 °C, relative humidity about 30%) for 40 days.
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http://dx.doi.org/10.1016/j.jcis.2021.09.117DOI Listing
September 2021

Association of the Monocyte-to-High-Density Lipoprotein Cholesterol Ratio With Diabetic Retinopathy.

Front Cardiovasc Med 2021 21;8:707008. Epub 2021 Sep 21.

Department of Endocrinology & Metabolism, The Third Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China.

Chronic inflammation in type 2 diabetes mellitus (T2DM) is an essential contributor to the development of diabetic retinopathy (DR). The monocyte-to-high-density lipoprotein cholesterol (HDL-C) ratio (MHR) is a novel and simple measure related to inflammatory and oxidative stress status. However, little is known regarding the role of the MHR in evaluating the development of DR. A total of 771 patients with T2DM and 607 healthy controls were enrolled in this cross-sectional study. MHR determination and eye examination were performed. The association of MHR with the prevalence of DR in T2DM patients was analyzed. The MHR in patients with DR was significantly higher than that in both non-DR diabetic patients ( < 0.05) and healthy controls ( < 0.01). No significance was observed in the MHR of different DR severity grades. Moreover, the MHR was similar between patients with non-macular oedema and those with macular oedema. Logistic regression analysis demonstrated that MHR was independently associated with the prevalence of DR in diabetic patients [odds ratio (OR) = 1.438, 95% confidence interval (CI): 1.249-1.655, < 0.01]. After additional stratification by HbA1c level and diabetic duration, the MHR was still independently associated with the prevalence of DR. Our study suggests that the MHR can be used as a marker to indicate the prevalence of DR in patients with T2DM.
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http://dx.doi.org/10.3389/fcvm.2021.707008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490616PMC
September 2021

Effects of blood pressure and heart rate circadian rhythms on left atrial function.

J Hypertens 2021 11;39(11):2318-2324

Department of Cardiology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning.

Objective: We examined the associations among the circadian rhythms of blood pressure (BP), heart rate (HR) and left atrial function in essential hypertensive patients.

Methods: The study included 237 essential hypertensive patients who completed 24-h ambulatory BP, HR monitoring and two-dimensional speckle tracking echocardiography (2DSTE). The strain and strain rate images were studied, and the following parameters were measured: left atrial reservoir strain and strain rate (LAS-S and LASR-S), left atrial conduit strain and strain rate (LAS-E and LASR-E), and left atrial booster strain and strain rate (LAS-A and LASR-A). The left atrial stiffness index (LASI) was identified as the ratio of E/e' to LAS-S. All participants were divided into three groups according to the percentage of nocturnal BP dipping (dippers, nondippers and reverse dippers).

Results: The LASI was significantly higher in BP reverse dippers than in dippers and nondippers. LAS-S, LAS-E and LASR-E were significantly lower in BP reverse dippers than dippers and nondippers. Multivariate logistic regression analysis demonstrated that age, night-time mean SBP and the percentage of nocturnal HR decline were independently related to an increased LASI.

Conclusion: Impairment of the left atrial reservoir and conduit functions was correlated with abnormal BP and HR circadian rhythms in hypertension. Increased left atrial stiffness was associated with night-time SBP and the percentage of nocturnal HR decline.
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http://dx.doi.org/10.1097/HJH.0000000000002923DOI Listing
November 2021

A SARS-CoV-2 Delta variant outbreak on airplane: Vaccinated air passengers are more protected than unvaccinated.

J Travel Med 2021 Oct 5. Epub 2021 Oct 5.

Department of Communicable Diseases Control and Prevention, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China.

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http://dx.doi.org/10.1093/jtm/taab161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522384PMC
October 2021

Impact of prognostic factor distributions on mortality disparities for socioeconomically disadvantaged cancer patients.

Ann Epidemiol 2021 Oct 1;65:31-37. Epub 2021 Oct 1.

Center for Epidemiology and Healthcare Delivery Research, JPS Health Network, Fort Worth, TX; Department of Medical Education, TCU & UNTHSC School of Medicine, Fort Worth, Texas. Electronic address:

Purpose: We aimed to assess whether differences in the distributions of prognostic factors explain reported mortality disparities between urban safety-net and Surveillance, Epidemiology, and End Results (SEER) cancer populations.

Methods: We used data from SEER and a safety-net cancer center in Texas. Eligible patients were adults aged ≤64 years and diagnosed with first primary female breast, colorectal, or lung cancer between 2008 and 2016. We estimated crude and adjusted risk differences (RD) in 3- and 5-year all-cause mortality (1- and 3-year for lung cancer), where adjustment was based on entropy balancing weights that standardized the distribution of sociodemographic and tumor characteristics between the two populations.

Results: Our study populations comprised 1914 safety-net patients and 389,709 SEER patients. For breast cancer, the crude 3- and 5-year mortality RDs between safety-net and SEER populations were 7.7% (95% confidence limits [CL]: 4.3%, 11%) and 11% (95% CL: 6.7%, 16%). Adjustment for measured prognostic factors reduced the mortality RDs (3-year adjusted RD = 0.049%, 95% CL: -2.6%, 2.6%; 5-year adjusted RD = 5.6%, 95% CL: -0.83%, 12%). We observed similar patterns for colorectal and lung cancer albeit less magnitude.

Conclusions: Sociodemographic and tumor characteristics may largely explain early mortality disparities between safety-net and SEER populations but not late mortality disparities.
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http://dx.doi.org/10.1016/j.annepidem.2021.09.014DOI Listing
October 2021

Serum lipidomics reveals distinct metabolic profiles for asymptomatic hyperuricemic and gout patients.

Rheumatology (Oxford) 2021 Oct 2. Epub 2021 Oct 2.

State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.

Objectives: This study aimed to characterize the systemic lipid profile of patients with asymptomatic hyperuricemia (HUA) and gout using lipidomics, and find potential underlying pathological mechanisms therefrom.

Methods: Sera were collected from Affiliated Hospital of Nanjing University of Chinese Medicine as center 1 (discovery and internal validation sets) and Suzhou Hospital of Traditional Chinese Medicine as center 2 (external validation set) including 88 normal subjects, 157 HUA and 183 gout patients. Lipidomics was performed by UHPLC-Q Exactive MS. Differential metabolites were identifed by both variable importance in the projection ≥ 1 in orthogonal partial least-squares discriminant analysis mode and false discovery rate adjusted p ≤ 0.05. Biomarkers were found by logistic regression and receiver operating characteristic (ROC) analysis.

Results: In the discovery set, a total of 245 and 150 metabolites respectively were found for normal subjects vs HUA and normal subjects vs gout. The disturbed metabolites included DAG, TAG, PC, PE, PI, etc. We also found 116 differential metabolites for HUA vs gout. Among them, the biomarker panel of TAG 18:1-20:0-22:1 and TAG 14:0-16:0-16:1 could differentiate well between HUA and gout. The area under ROC curve was 0.8288, the sensitivity was 82%, the specificity was 78% at a 95% confidence interval from 0.747-0.9106. In internal validation set, the predictive accuracy of TAG 18:1-20:0-22:1 and TAG 14:0-16:0-16:1 panel for differentiation of HUA and gout reached 74.38%, while 84.03% in external validation set.

Conclusion: We identified serum biomarkers panel that have the potential to predict and diagnose HUA and gout patients.
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http://dx.doi.org/10.1093/rheumatology/keab743DOI Listing
October 2021
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