Publications by authors named "Ting Zhu"

525 Publications

Cesarean Scar Pregnancies Treated by Uterine Artery Chemotherapy Embolization Combined With Ultrasound-Guided Dilation and Curettage: A Retrospective Study.

J Ultrasound Med 2022 Jul 2. Epub 2022 Jul 2.

Department of Ultrasound, Shuguang Hospital affiliated to Shanghai Universtity of Traditional Chinese Medicine, Shanghai, China.

Objectives: To explore the effect of cesarean scar pregnancy (CSP) treatment by comparing uterine artery chemotherapy embolization (UACE) combined with dilation and curettage (D&C) with or without ultrasound guidance.

Methods: CSP patients treated with UACE combined with D&C from January 2013 to December 2020 at Shuguang Hospital, affiliated to Shanghai University of Traditional Chinese Medicine were included in this retrospective study. The patients were divided into groups A and B according to whether D&C was guided by ultrasound.

Results: Forty-eight patients with CSP diagnosed by transvaginal ultrasound were included in this study, whose gestational age was <8 weeks. There were no significant differences in the basic clinical characteristics of the two groups. The success rates of the 2 groups were no significant difference, 100% (27/27) in group A and 85.7% (18/21) in group B. The maximal intraoperative blood loss of group A was 100 mL and that of group B was 150 mL. There was no uterine perforation during the operation. Ultrasound guidance can shorten the D&C operation time, reduce intraoperative bleeding during D&C, and decrease the residual rate of trophoblastic tissue after D&C.

Conclusions: Ultrasound guidance can improve the safety and efficiency of UACE combined with D&C in the treatment of CSP and reduce its complications. We believe it is an optimal treatment for CSP patients who do not plan to have children in the future.
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http://dx.doi.org/10.1002/jum.16050DOI Listing
July 2022

Identification of Cigarette Smoking-Related Novel Biomarkers in Lung Adenocarcinoma.

Biomed Res Int 2022 19;2022:9170722. Epub 2022 Jun 19.

Department of Preventive Medicine of Traditional Chinese medicine, Jiangnan Hospital Affiliated to Zhejiang Chinese Medical University (Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine), Hangzhou 310000, Zhejiang, China.

Objective: The aims of this study were to screen the gene mutations that are able to predict the risk of cigarette smoking-related lung adenocarcinoma (LUAD) and to evaluate its prognostic significance.

Methods: Clinical data and genetic information were retrieved from the TCGA database, and the patients with LUAD were divided into three groups including never smoking, light smoking, and heavy smoking according to cigarette smoking dose. Differentially mutated genes (DMGs) of each group were analyzed. At the same time, the function of DMGs in three smoking groups was evaluated by GO function and KEGG pathway analysis. The driver genes and protein variation effect of DMGs were performed to further screen key genes. The survival characteristics of the gene expression and mutation of those genes were analyzed and plotted to visualize by the Kaplan-Meier model.

Result: The DMGs for different smoking doses were identified. The driver and deleterious mutation in the DMGs were screened and gene interaction network was constructed. The DMGs with driver mutations and deleterious mutations that were associated with the overall survival in the heavy smoking patients were considered as the candidate genes for novel markers of smoking-related LUAD. The final novel risk factor gene was identified as MYH7 and the high express of MYH7 in LUAD correlation with patients' gender, lymph node metastasis, T stage, and clinical stage.

Conclusions: In summary, it can be concluded that MYH7 is a novel biomarker for heavy smoking-related LUAD and it is significantly correlated with the prognosis of lung cancer and is related to the clinical characteristics of lung cancer.
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http://dx.doi.org/10.1155/2022/9170722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234045PMC
July 2022

Proteomic and Phosphoproteomic Analyses Reveal a Complex Network Regulating Pollen Abortion and Potential Candidate Proteins in TCMS Wheat.

Int J Mol Sci 2022 Jun 8;23(12). Epub 2022 Jun 8.

College of Agronomy, Northwest A&F University, Yangling 712100, China.

Thermosensitive sterile lines are natural materials for exploring the effects of anther development on male fertility. To study the possible molecular mechanisms regulating protein activity during the induction of male sterility, proteomic and phosphoproteomic analyses with tandem mass tags (TMTs) were used to study the binucleate anther of the thermosensitive sterile wheat line YS3038. A total of 9072 proteins, including 5019 phosphoproteins, were identified. Enrichment analyses of differentially abundant proteins (DAPs) and phosphoproteins (DAPPs) in metabolic pathways showed that both were mainly related to energy metabolism. Soluble sugar and ATP content were significantly decreased, free fatty acid content was significantly increased, and ROS was abnormally accumulated in male sterile YS3038-A. In addition, 233 kinase-substrate pairs involved in potential phosphorylation control networks were predicted to regulate fertility. Candidate proteins were identified, and a quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to validate the TMT results. is likely to be involved in fertility conversion of YS3038 by barley stripe mosaic virus-induced gene silencing (BSMV-VIGS). Our data provide new insights into the mechanism of TCMS, which has value for identifying potential candidate proteins associated with the formation or abortion of pollen and promotion of wheat heterosis utilization.
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http://dx.doi.org/10.3390/ijms23126428DOI Listing
June 2022

Impaired regulation of MMP2/16-MLCK3 by miR-146a-5p increased susceptibility to myocardial ischemic injury in aging mice.

Cardiovasc Res 2022 Jun 21. Epub 2022 Jun 21.

Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Department of Pathophysiology, Shenzhen University Health Science Center, Shenzhen, China.

Aims: Aging impairs cardiac function and increases susceptibility to myocardial ischemic injury. Cardiac myosin light chain kinase (MLCK3) phosphorylates cardiac myosin regulatory light chain (MLC2), controlling sarcomere organization and cardiomyocyte contraction. Dysregulation of MLCK3 and phosphorylated MLC2 (p-MLC2) contributes to heart failure after myocardial infarction (MI). We aimed at exploring how the MLCK3-p-MLC2 axis changes in aging hearts post MI and at investigating the underlying regulatory mechanisms.

Methods And Results: We generated adult (3 months) and aged (30 months) MI mouse models to compare their cardiac performance, and then detected MLCK3 expression and MLC2 activity. Aging increased the size of MI-induced infarctions and promoted cardiac contractile dysfunction. Furthermore, MLCK3 expression and MLC2 activity increased in adult hearts after MI, but not in aged hearts. miR-146a was found consistently increased in adult and aged hearts post-MI. Mechanistic analyses performed in vitro demonstrated that miR-146a-5p downregulated matrix metalloprotease (MMP)2/16 expression in cardiomyocytes. This downregulation in turn increased MLCK3 expression and MLC2 activity. However, miR-146a-5p failed to regulate the MMP2/16-MLCK3-p-MLC2 axis in senescent cardiomyocytes or in cardiac miR-146a conditional knockout mice, with the latter experiencing an exacerbated deterioration of cardiac function post-MI.

Conclusion: These results suggest that increase of MLCK3 and p-MLC2 contents through decreasing MMP2/16 by miR-146a-5p represents a compensatory mechanism that can protect cardiac contractile function after MI. Aging impairs this miR-146a-5p-regulated MMP2/16-MLCK3-p-MLC2 contractile axis, leading to compromised contractile function and increased susceptibility to heart failure.
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http://dx.doi.org/10.1093/cvr/cvac104DOI Listing
June 2022

Short-term wind speed prediction based on FEEMD-PE-SSA-BP.

Environ Sci Pollut Res Int 2022 Jun 16. Epub 2022 Jun 16.

School of Science, Wuhan University of Science and Technology, Wuhan, 430081, China.

As one of the renewable energy power generation methods, wind power generation shows a high growth trend. However, while wind power is connected to the grid, the volatility and instability of wind power make the power system produce a lot of uncertain fluctuations, which greatly affects the power quality and jeopardizes the stable operation of the power system. Therefore, high wind speed forecasting accuracy can provide a solid basis for grid management, improve the power system's ability to consume wind power, and ensure the safety and stabilization of the power system. In order to solve the problem of inaccurate prediction caused by the non-linearity and unsteadiness of wind speed series, this paper proposes a Fractal Ensemble Empirical Mode Decomposition (FEEMD)-Permutation Entropy (PE)-Sparrow Search Algorithm (SSA)-Error Back Propagation (BP) neural network method for short-term wind speed prediction. This method first uses FEEMD to decompose the original wind speed in order from high to low frequency; then calculates the entropy value of each component, and merges the components with similar entropy values to effectively reduce the computation; and finally, the new sub-series are predicted by SSA-BP model, and the predicted value of the merged new sub-sequences are accumulated to obtain the final wind speed prediction results. The simulation study shows that the proposed prediction model is not only fast and accurate, but also suitable for short-term wind speed prediction.
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http://dx.doi.org/10.1007/s11356-022-21414-4DOI Listing
June 2022

Identification of the Active Compound of Liu Wei Di Huang Wan for Treatment of Gestational Diabetes Mellitus via Network Pharmacology and Molecular Docking.

J Diabetes Res 2022 28;2022:4808303. Epub 2022 May 28.

Department of Obstetrics and Gynaecology, Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, Shanghai 200120, China.

Liu Wei Di Huang Wan (LWDHW) is a well-known Chinese herbal compound, which has been prescribed for the treatment of gestational diabetes mellitus (GDM). We sought to clarify the potential therapeutic effects of LWDHW against GDM. Differentially expressed genes (DEGs) in GDM were firstly identified from the Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to reveal the biological functions of the DEGs. Subsequently, the LWDHW-compound-target network was constructed based on public databases to identify the relationship between the active components in LWDHW and the corresponding targets. Furthermore, gene functional analysis and protein-protein interaction (PPI) network construction were applied to investigate the function of potential targets and to evaluate hub genes. Finally, molecular docking was used to verify the binding activities between active ingredients and hub targets. Thirteen active components and 39 corresponding therapeutic target genes were obtained via network pharmacology analysis. The enrichment analysis demonstrated that the anti-GDM effect of LWDHW included oxidoreductase activity, involvement in renal system process, and regulation of blood pressure, which may be achieved through regulation of serotonergic synapses, vascular smooth muscle contraction, and neuroactive ligand-receptor interaction pathways. Additionally, molecular docking revealed that the main active component, Mu Dan Pi, exhibited the best affinity for proteins encoded by hub genes. This study applied network pharmacology analysis and molecular docking to display the multicomponent and multitarget characteristics of LWDHW in the treatment of GDM. Our findings provide novel insights into the pathogenesis of GDM and the therapeutic mechanisms of LWDHW against GDM.
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http://dx.doi.org/10.1155/2022/4808303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9167086PMC
June 2022

Directed evolution and selection of biostable L-DNA aptamers with a mirror-image DNA polymerase.

Nat Biotechnol 2022 Jun 6. Epub 2022 Jun 6.

School of Life Sciences, Tsinghua-Peking Center for Life Sciences, Beijing Frontier Research Center for Biological Structure, Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing, China.

Mirror-image aptamers made from chirally inverted nucleic acids are nuclease-resistant and exceptionally biostable, opening up opportunities for unique applications. However, the directed evolution and selection of mirror-image aptamers directly from large randomized L-DNA libraries has, to our knowledge, not been demonstrated previously. Here, we developed a 'mirror-image selection' scheme for the directed evolution and selection of biostable L-DNA aptamers with a mirror-image DNA polymerase. We performed iterative rounds of enrichment and mirror-image polymerase chain reaction (PCR) amplification of L-DNA sequences that bind native human thrombin, in conjunction with denaturing gradient gel electrophoresis (DGGE) to isolate individual aptamers and L-DNA sequencing-by-synthesis to determine their sequences. Based on the selected L-DNA aptamers, we designed biostable thrombin sensors and inhibitors, which remained functional in physiologically relevant nuclease-rich environments, even in the presence of human serum that rapidly degraded D-DNA aptamers. Mirror-image selection of biostable L-DNA aptamers directly from large randomized L-DNA libraries greatly expands the range of biomolecules that can be targeted, broadening their applications as biostable sensors, therapeutics and basic research tools.
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http://dx.doi.org/10.1038/s41587-022-01337-8DOI Listing
June 2022

Uncovering BTB and CNC Homology1 (BACH1) as a Novel Cancer Therapeutic Target.

Front Genet 2022 16;13:920911. Epub 2022 May 16.

Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.

BTB and CNC homology1 (BACH1), working as a transcriptional factor, is demonstrated to function on the regulation of epigenetic modifications by complex regulatory networks. Although BACH1 is reported as an oncogene, the overall analysis of its role remains lacking. In this study, we uncovered the capacity of BACH1 as a new pan-cancer therapeutic target. We found that BACH1 is highly expressed in abundant cancers and correlated with the poor prognosis of most cancers. The mutation sites of BACH1 varied in different cancer types and correlated to patients' prognoses. The tumor mutation burden (TMB) in four cancer species and up to six tumor infiltrated immune cells had a significant relevance with BACH1. The enrichment analysis showed that the BACH1-associated genes were significantly enriched in the pathways of PD-1/L1 expression, ubiquitin-mediated proteolysis, T cell receptor, Th17 cell differentiation. We then demonstrated that BACH1 is positively correlated with the expression of many candidate genes, incluing SRPK2, GCLM, SLC40A1, and HK2 but negatively correlated with the expression of KEAP1 and GAPDH. Overall, our data shed light on BACH1's effect on latent utility in cancer targeting therapy.
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http://dx.doi.org/10.3389/fgene.2022.920911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149251PMC
May 2022

Disulfiram bolsters T-cell anti-tumor immunity through direct activation of LCK-mediated TCR signaling.

EMBO J 2022 May 31:e110636. Epub 2022 May 31.

Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Activation of the T-cell antigen receptor (TCR)-CD3 complex is critical to induce the anti-tumor response of CD8 T cells. Here, we found that disulfiram (DSF), an FDA-approved drug previously used to treat alcohol dependency, directly activates TCR signaling. Mechanistically, DSF covalently binds to Cys20/Cys23 residues of lymphocyte-specific protein tyrosine kinase (LCK) and enhances its tyrosine 394 phosphorylation, thereby promoting LCK kinase activity and boosting effector T cell function, interleukin-2 production, metabolic reprogramming, and proliferation. Furthermore, our in vivo data revealed that DSF promotes anti-tumor immunity against both melanoma and colon cancer in mice by activating CD8 T cells, and this effect was enhanced by anti-PD-1 co-treatment. We conclude that DSF directly activates LCK-mediated TCR signaling to induce strong anti-tumor immunity, providing novel molecular insights into the therapeutic effect of DSF on cancer.
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http://dx.doi.org/10.15252/embj.2022110636DOI Listing
May 2022

Exogenous nitrogen from riverine exports promotes soil methane production in saltmarshes in China.

Sci Total Environ 2022 Sep 23;838(Pt 2):156203. Epub 2022 May 23.

Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, National Observations and Research Station for Wetland Ecosystems of the Yangtze Estuary, Institute of Biodiversity Science and Institute of Eco-Chongming, School of Life Sciences, Fudan University, Shanghai 200438, China; Yunnan Key Laboratory of Plant Reproductive Adaptation and Evolutionary Ecology and Centre for Invasion Biology, Institute of Biodiversity, School of Ecology and Environmental Science, Yunnan University, Kunming 650504, Yunnan, China. Electronic address:

Methane emissions from saltmarshes can potentially promote climate warming. Soil methane production is positively correlated with methane emissions from saltmarshes. Understanding the factors influencing soil methane production will improve the prediction of methane emissions, but an investigation of these factors has not been conducted in saltmarshes in China. We collected soils from native Phragmites australis and invasive Spartina alterniflora saltmarshes along the coast of China; the soil potential methane production (PMP) was determined by incubation experiments. The large-scale investigation results showed that the ratios of methanogens relative to sulfate-reducing bacteria (RMRS) and total organic carbon (TOC) were positively correlated with soil PMP for both species. Dissolved inorganic nitrogen (DIN) was positively correlated with the soil PMP of P. australis saltmarshes, and plant biomass was positively correlated with the soil PMP of S. alterniflora saltmarshes. Our results showed that exogenous nitrogen from riverine exports was positively correlated with DIN and plant biomass in both P. australis and S. alterniflora saltmarshes. In addition, exogenous nitrogen was also positively correlated with TOC in S. alterniflora saltmarshes. Consequently, exogenous nitrogen indirectly promoted soil methane production in P. australis saltmarshes by increasing the DIN and promoted soil methane production in S. alterniflora saltmarshes by enhancing the TOC and plant biomass. Moreover, we found that the promoting effect of DIN on the soil PMP of P. australis saltmarshes increased when the incubation temperature increased from 15 °C to 25 °C. Thus, the promoting effect of exogenous nitrogen on the soil methane production in P. australis saltmarshes might be strengthened in the peak of growing season. Our findings are the first to confirm that exogenous nitrogen inputs from rivers indirectly promote soil methane production in P. australis and S. alterniflora saltmarshes and provide new insights into the factors responsible for soil methane production in saltmarshes.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156203DOI Listing
September 2022

Discovery of novel coumarin-indole derivatives as tubulin polymerization inhibitors with potent anti-gastric cancer activities.

Eur J Med Chem 2022 Aug 18;238:114467. Epub 2022 May 18.

Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China; School of Pharmaceutical Sciences, Institute of Drug Discovery & Development, Key Laboratory of Advanced Drug Preparation Technologies (Ministry of Education), Zhengzhou University, Zhengzhou, Henan, 450001, China. Electronic address:

Novel coumarin-indole derivatives were designed, synthesized and evaluated as tubulin polymerization inhibitors targeting the colchicine binding site. Among these compounds, compound MY-413 displayed the most potent inhibitory activities against gastric cancer cell line MGC-803 with an IC value of 0.011 μM. Furthermore, the IC values of compound MY-413 was less than 0.1 μM for other 17 cancer cell lines and less than 0.05 μM for other 8 cancer cell lines. Compound MY-413 effectively inhibited the tubulin polymerization (IC = 2.46 μM) by binding to the colchicine site. Screening for the inhibitory effects of compound MY-413 on 61 kinases, it was found that compound MY-413 could inhibit MAPK pathways-related kinases. Because of the inhibitory effects of compound MY-413 on tubulin polymerization and MAPK signaling pathway, compound MY-413 induced cell apoptosis, arrested the cell cycle in the G2/M phase, induced the inhibition of cell proliferation and migration in gastric cancer cells MGC-803 and HGC-27. In addition, compound MY-413 could significantly inhibit tumor growth in MGC-803 xenograft tumor models with tumor growth inhibition (TGI) rates of 70% (15 mg/kg) and 80% (30 mg/kg) without obvious toxicity. Consistent with the in vitro results, compound MY-413 also inhibited MAPK signaling pathway, and induced apoptosis and proliferation inhibition in vivo. In conclusion, this work indicated that compound MY-413 was a promising lead compound for the further investigation as a potential anti-gastric cancer agent.
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http://dx.doi.org/10.1016/j.ejmech.2022.114467DOI Listing
August 2022

HBV pgRNA profiles in Chinese HIV/HBV coinfected patients under pre- and posttreatment: a multicentre observational cohort study.

J Viral Hepat 2022 May 18. Epub 2022 May 18.

Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Data on hepatitis B virus (HBV) pregenomic (pgRNA) levels in HIV/HBV coinfected patients pre- and post-combined antiretroviral therapy (cART) are limited. This study aimed to evaluate the distribution of HBV pgRNA levels in treatment-naive coinfected patients and explore the changes that occur after the initiation of cART by examining patients from multicentre cohort studies performed in China. We included HIV/HBV coinfected subjects from the China AIDS Clinical Trial cohorts established from 2008 to 2014. Clinical and serological markers of HIV and HBV infection and biochemical data were acquired at baseline and after 96 and 240-480 weeks of cART. The correlations between HBV pgRNA and HBV DNA levels as well as HBsAg levels were calculated using Spearman's bivariate correlation analysis, and multivariate regression analysis was performed to determine factors associated with undetectable HBV pgRNA levels before cART and HBeAg loss after cART. A total of 132 HIV/HBV coinfected patients were enrolled, and 100 individuals were HBeAg-negative. A total of 34.4% (32/93) of patients were positive for HBV pgRNA, and the median HBV pgRNA level was 4.92 (IQR: 4.21-6.12) log copies/mL before cART. The median HBV pgRNA level was significantly lower in HBeAg-negative individuals than in HBeAg-positive individuals (4.22 (IQR: 2.70-4.84) log copies/mL vs. 5.77 (IQR: 4.63-6.55) log copies/mL, p = 0.002). HBV pgRNA was moderately correlated with HBsAg (r = 0.594, p = 0.001), and positively associated with HBV DNA (r = 0.445, p = 0.011). The factors independently associated with undetectable HBV pgRNA level before cART were HBV DNA (OR: 5.61, 95% CI: 1.50-20.96, p = 0.01) and HBeAg status (OR: 5.95, 95% CI: 1.52-23.25, p = 0.01). A total of 87.5% (28/32) of patients were followed for a median duration of 138 (IQR: 54-240) weeks, and the HBV pgRNA levels became undetectable in seven patients. The 132 patients were observed for 695.5 person-years, and no HBsAg loss occurred. Thirteen individuals achieved HBeAg loss, four patients had undetectable levels of HBV pgRNA pre-cART, and the level of six individuals became undetectable during the 48-week (IQR: 48-264) follow-up period. HBeAg status was significantly associated with HBV pgRNA level in HIV/HBV coinfected patients pre- and post-cART. Additionally, undetectable HBV pgRNA level may be associated with HBeAg loss after cART.
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http://dx.doi.org/10.1111/jvh.13704DOI Listing
May 2022

Contributions of species shade tolerance and individual light environment to photosynthetic induction in tropical tree seedlings.

Tree Physiol 2022 May 14. Epub 2022 May 14.

Department of Ecology and Key Laboratory for Earth Surface Processes of Ministry of Education, College of Urban and Environmental Sciences, Peking University, Beijing, China.

It has long been debated whether tree leaves from shady environments exhibit higher photosynthetic induction efficiency than those from sunny environments and how the shade tolerance of tree species and the light environment of leaves contribute to the dynamics of photosynthesis. To address these questions, we investigated leaf photosynthetic responses to simulated changes of light intensity in seedlings of six tree species with differential shade tolerance. The seedlings were growing under different light environments in a lowland tropical forest. We proposed an index of relative shade tolerance (RST) to assess species-specific capacity to tolerate shade, and we quantified the light environment of individual leaves by the index of daily light integral (DLI), the averaged daily total light intensity. We obtained the following results. Photosynthetic induction efficiency (IE), which is the ratio of the achieved carbon gain to the expected carbon gain, was significantly higher for species with a higher RST than for that with a lower RST. The impacts of light environment on the IE of individual leaves within the same species varied largely among different species. In the three species with relatively low RST, the IE of individual leaves decreased at higher DLIs when DLI < 10 mol m-2 d-1. Seedlings with high initial stomatal conductance before induction (gs50) possessed a higher IE than those with low gs50 from the same species. A trade-off existed between IE and steady-state photosynthetic rates. These results suggest a complex interaction between the shade tolerance of species and the light environments of individual leaves for photosynthetic induction, and provide new insights into the adaptation strategy for understory seedlings under sunfleck environments.
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http://dx.doi.org/10.1093/treephys/tpac056DOI Listing
May 2022

Lactate Transporter SLC16A3 (MCT4) as an Onco-Immunological Biomarker Associating Tumor Microenvironment and Immune Responses in Lung Cancer.

Int J Gen Med 2022 27;15:4465-4474. Epub 2022 Apr 27.

Department of Radiotherapy and Chemotherapy, Ningbo First Hospital, Ningbo, People's Republic of China.

Purpose: Lactate, a marker of tumor metabolic reprogramming, maintains the acidic microenvironment and also affects the metabolism and function of immune cells. SLC16A3 is responsible for the extracellular transport of lactate, which is a key component of glycolysis. However, the role of SLC16A3 in immune infiltration and immunosuppression of lung cancer is largely unknown. Our study explored the therapeutic and prognostic value of SLC16A3 in predicting immune infiltration and immune checkpoint efficacy of lung cancer.

Methods: SLC16A3 expression was evaluated with TCGA database. Kaplan-Meier analysis was performed for survival rates. GO and KEEG enrichment was conducted to determine predictive signaling pathways. We utilized TIMER and CIBERSORT to analyze the correlation between SLC16A3 and immunocyte infiltration as well as immune checkpoint. Interleukin and HIF-1a expression was measured with ELISA kit and flow cytometry separately.

Results: In comparison with normal tissues, SLC16A3 expression was significantly upregulated in both lung adenocarcinoma (LUAD) and squamous carcinoma (LUSC), which was closely related to poor prognosis. GO analysis indicated that SLC16A3 involved in different signal pathways in LUAD and LUSC and linked to HIF-1 signaling in LUAD. High SLC16A3 was correlated with immunosuppressive cells (Treg, Th2 and iDC), immune checkpoint (PD1, PD-L1, PVR, Tim-3, ITGAM) and immunosuppressive factors (foxp3, TGF-β) in LUAD not LUSC. Furthermore, SLC16A3 was identified to tightly interact with IL-8 which may induce microenvironment immune tolerance. Based on the clinical prediction, we performed experiments with LUAD A549 cells and showed reduced IL-8 and HIF-1a when treated with SLC16A3 knockdown. HIF-1a stimulation by dimethyloxalylglycine (DMOG) could restore IL-8 secretion in SLC16A3 downregulated cells.

Conclusion: Taken together, our results suggest that SLC16A3 contributes to a worse prognosis in lung cancer and may play an important role in immune microenvironment and evasion through HIF-1a-IL8 axis, which could be a novel therapeutic target for immunotherapy in lung cancer.
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http://dx.doi.org/10.2147/IJGM.S353592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9059363PMC
April 2022

Exosomal LncRNA RP5-977B1 as a novel minimally invasive biomarker for diagnosis and prognosis in non-small cell lung cancer.

Int J Clin Oncol 2022 Jun 28;27(6):1013-1024. Epub 2022 Apr 28.

Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhouda Road, Guangzhou, 510515, Guangdong, China.

Background: Lung cancer is the leading cause of cancer-related deaths in the world. Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases. For lack of conveniently sensitive and specific biomarkers, the majority of patients are in the late stage at initial diagnosis. Long non-coding RNAs (LncRNAs), a novel type of non-coding RNA, have recently been recognized as critical factors in tumor initiation and progression, but the role of exosomal LncRNAs has not been thoroughly excavated in NSCLC yet.

Methods: We isolated exosomes from the serum of patients with NSCLC and healthy controls. Exosome RNA deep sequencing was subsequently performed to detect differentially expressed exosomal LncRNAs. qRT-PCR assay was then utilized to validate dysregulated LncRNAs in both testing and multicentric validation cohort. Receiver operating characteristic (ROC) curve was used to detect the diagnostic capability of exosomal biomarkers. Furthermore, Kaplan-Meier analysis was applied to evaluate the prognostic values of these molecules.

Results: On the basis of analysis, we found that novel exosomal LncRNA RP5-977B1 exhibited higher levels in NSCLC than that in the healthy controls. The area under the curve (AUC) value of exosomal RP5-977B1 was 0.8899 and superior to conventional biomarkers CEA and CYFRA21-1 both in testing and multicentric validation cohort. Interestingly, the diagnostic capability of exosomal RP5-977B1 was also validated in early-stage patients with NSCLC. Furthermore, high expression of exosomal RP5-977B1was closely related with worse prognosis in NSCLC (P = 0.036).

Conclusions: Our results suggested that exosomal RP5-977B1 might serve as a novel "liquid biopsy" diagnostic and prognostic biomarker to monitor NSCLC and improve possible therapy.
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http://dx.doi.org/10.1007/s10147-022-02129-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120093PMC
June 2022

Polyphenols from Chinese Herbal Medicine: Molecular Mechanisms and Therapeutic Targets in Pulmonary Fibrosis.

Am J Chin Med 2022 26;50(4):1063-1094. Epub 2022 Apr 26.

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

Pulmonary fibrosis (PF) is a highly confounding and fatal pathological process with finite treatment options. Multiple factors such as oxidative and immune/inflammation involve key pathological processes in chronic lung disease, and their intimate interactions mediate chronic lung damage, denudation of the alveolar epithelium, hyperproliferation of type II alveolar epithelial cells (AECIIs), proliferation and differentiation of fibroblasts, and the permeability of microvessels. We reviewed the classic mechanism of PF and highlighted a few emerging mechanisms for studying complex networks in lung disease pathology. Polyphenols, as a multi-target drug, has excellent potential in the treatment of pulmonary fibrosis. We then reviewed recent advances in discovering phenolic compounds from fruits, tea, and medical herbs with the bioactivities of simultaneously regulating multiple factors (e.g., oxidative stress, inflammation, autophagy, apoptosis, pyroptosis) for minimizing pulmonary fibrosis injury. These compounds include resveratrol, curcumin, salvianolic acid B, epigallocatechin-3-gallate, gallic acid, corilagin. Each phenolic compound can exert its anti-PF effect through various mechanisms, and the signaling pathways involved in different phenolic compounds are not the same. This review summarized the available evidence on phenolic compounds' effectiveness in pulmonary diseases and explored the molecular mechanisms and therapeutic targets of phenolic compounds from Chinese herbal medicine with the properties of inhibition of ongoing fibrogenesis and resolution of existing fibrosis.
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http://dx.doi.org/10.1142/S0192415X22500434DOI Listing
June 2022

Individualized prediction of psychiatric readmissions for patients with major depressive disorder: a 10-year retrospective cohort study.

Transl Psychiatry 2022 04 23;12(1):170. Epub 2022 Apr 23.

West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China.

Patients with major depressive disorder (MDD) are at high risk of psychiatric readmission while the factors associated with such adverse illness trajectories and the impact of the same factor at different follow-up times remain unclear. Based on machine learning (ML) approaches and real-world electronic medical records (EMR), we aimed to predict individual psychiatric readmission within 30, 60, 90, 180, and 365 days of an initial major depression hospitalization. In addition, we examined to what extent our prediction model could be made interpretable by quantifying and visualizing the features that drive the predictions at different follow-up times. By identifying 13,177 individuals discharged from a hospital located in western China between 2009 and 2018 with a recorded diagnosis of MDD, we established five prediction-modeling cohorts with different follow-up times. Four different ML models were trained with features extracted from the EMR, and explainable methods (SHAP and Break Down) were utilized to analyze the contribution of each of the features at both population-level and individual-level. The model showed a performance on the holdout testing dataset that decreased over follow-up time after discharge: AUC 0.814 (0.758-0.87) within 30 days, AUC 0.780 (0.728-0.833) within 60 days, AUC 0.798 (0.75-0.846) within 90 days, AUC 0.740 (0.687-0.794) within 180 days, and AUC 0.711 (0.676-0.747) within 365 days. Results add evidence that markers of depression severity and symptoms (recurrence of the symptoms, combination of key symptoms, the number of core symptoms and physical symptoms), along with age, gender, type of payment, length of stay, comorbidity, treatment patterns such as the use of anxiolytics, antipsychotics, antidepressants (especially Fluoxetine, Clonazepam, Olanzapine, and Alprazolam), physiotherapy, and psychotherapy, and vital signs like pulse and SBP, may improve prediction of psychiatric readmission. Some features can drive the prediction towards readmission at one follow-up time and towards non-readmission at another. Using such a model for decision support gives the clinician dynamic information of the patient's risk of psychiatric readmission and the specific features pulling towards readmission. This finding points to the potential of establishing personalized interventions that change with follow-up time.
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http://dx.doi.org/10.1038/s41398-022-01937-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035153PMC
April 2022

Investigation of serum markers of esophageal squamous cell carcinoma based on machine learning methods.

J Biochem 2022 Jun;172(1):29-36

Department of Thoracic Surgery, Shaoxing People's Hospital, Shaoxing, Zhejiang Province, China, 312000.

Esophageal squamous cell carcinoma (ESCC) is one of the malignant tumors with high mortality in humans, and there is a lack of effective and convenient early diagnosis methods. By analyzing the serum miRNA expression data in ESCC tumor samples and normal samples, on the basis of the maximal relevance and minimal redundancy (mRMR) feature selection and the incremental feature selection method, a random forest classifier constructed by five-feature miRNAs was acquired in our study. The receiver operator characteristic curve showed that the model was able to distinguish samples. Principal component analysis (PCA) and sample hierarchical cluster analysis showed that five-feature miRNAs could well distinguish ESCC patients from healthy individuals. The expression levels of miR-663a, miR-5100 and miR-221-3p all showed a higher expression level in ESCC patients than those in healthy individuals. On the contrary, miR-6763-5p and miR-7111-5p both showed lower expression levels in ESCC patients than those in healthy individuals. In addition, the collected clinical serum samples were used for qRT-PCR analysis. It was uncovered that the expression trends of the five-feature miRNAs followed a similar pattern with those in the training set. The above findings indicated that the five-feature miRNAs may be serum tumor markers of ESCC. This study offers new insights for the early diagnosis of ESCC.
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http://dx.doi.org/10.1093/jb/mvac030DOI Listing
June 2022

Synchronous Defect and Interface Engineering of NiMoO Nanowire Arrays for High-Performance Supercapacitors.

Nanomaterials (Basel) 2022 Mar 26;12(7). Epub 2022 Mar 26.

Yunnan Key Laboratory of Optoelectronic Information Technology, College of Physics and Electronics Information, Yunnan Normal University, Kunming 650500, China.

Developing high-performance electrode materials is in high demand for the development of supercapacitors. Herein, defect and interface engineering has been simultaneously realized in NiMoO nanowire arrays (NWAs) using a simple sucrose coating followed by an annealing process. The resultant hierarchical oxygen-deficient [email protected] NWAs (denoted as "[email protected]") are grown directly on conductive ferronickel foam substrates. This composite affords direct electrical contact with the substrates and directional electron transport, as well as short ionic diffusion pathways. Furthermore, the coating of the amorphous carbon shell and the introduction of oxygen vacancies effectively enhance the electrical conductivity of NiMoO. In addition, the coated carbon layer improves the structural stability of the NiMoO in the whole charging and discharging process, significantly enhancing the cycling stability of the electrode. Consequently, the [email protected] electrode delivers a high areal capacitance of 2.24 F cm (1720 F g) at a current density of 1 mA cm and superior cycling stability of 84.5% retention after 6000 cycles at 20 mA cm. Furthermore, an asymmetric super-capacitor device (ASC) has been constructed with [email protected] as the positive electrode and activated carbon (AC) as the negative electrode. The as-assembled ASC device shows excellent electrochemical performance with a high energy density of 51.6 W h kg at a power density of 203.95 W kg. Moreover, the NiMoO//AC ASC device manifests remarkable cyclability with 84.5% of capacitance retention over 6000 cycles. The results demonstrate that the [email protected] composite is a promising material for electrochemical energy storage. This work can give new insights on the design and development of novel functional electrode materials via defect and interface engineering through simple yet effective chemical routes.
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http://dx.doi.org/10.3390/nano12071094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000437PMC
March 2022

Hypoxia Promotes Human Umbilical Vein Smooth Muscle Cell Phenotypic Switching via the ERK 1/2/c-fos/NF-κB Signaling Pathway.

Ann Vasc Surg 2022 Apr 9. Epub 2022 Apr 9.

Department of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address:

Background: Vein wall hypoxia has long been suggested as a key factor for the development of varicose veins (VVs) and accumulating evidence has revealed the phenotypic transformation of vascular smooth muscle cells (VSMCs) under hypoxic conditions. However, the underlying molecular mechanisms of this process remain poorly understood. Our previous study revealed a positive correlation between c-fos expression and VSMC functional disturbance of VVs. This study aimed to further explore the role of c-fos in the phenotypic switching of VSMCs under hypoxic conditions.

Methods: Human umbilical vein smooth muscle cells (HUVSMCs) were cultured under hypoxia or normoxia. PD0325901 (10 μmol/L) and pyrrolidine dithiocarbamate (PDTC) (10 μmol/L) were used to inhibit the extracellular signal-regulated kinase 1/2 (ERK1/2) and nuclear factor-κ B (NF-κB) signaling pathways, respectively. HUVSMCs stably overexpressing c-fos were constructed to explore the underlying mechanism. The Western blot analysis was performed to detect the protein expression levels of c-fos, phosphorylated p65 (p-p65), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), osteopontin (OPN), and α-smooth muscle actin (α-SMA). Cell proliferation and migration capacity were detected by a Cell Counting Kit 8 (CCK-8) assay and a wound-healing assay, respectively. The cell apoptotic rate was determined using the Annexin V-FITC Apoptosis Detection Kit.

Results: Hypoxic exposure increased the expression levels of indicators of the p-ERK1/2/c-fos and NF-κB signaling pathways, which was accompanied by altered levels of phenotypic biomarkers (α-SMA and OPN). Cells exposed to hypoxia were characterized by a greater proliferative and migratory ability. No significant differences were observed in the rate of cell apoptosis between the normal group and the hypoxic group. In addition, inhibition of the ERK1/2/c-fos signaling pathway by PD0325901 (10 μmol/L) reduced the expression of inflammatory cytokines and attenuated hypoxia-mediated phenotypic transformation. Furthermore, inhibition of the NF-κB signaling pathway by PDTC (10 μmol/L) downregulated the expression level of OPN and reduced the migration of HUVSMCs under hypoxia exposure. However, pretreatment with PDTC did not suppress the expression of c-fos or cell proliferation. Finally, the introduction of exogenous c-fos in HUVSMCs induced increased protein expression levels of p-p65, COX-2, and OPN, accompanied by a remarkable increase in HUVSMC proliferation and migration.

Conclusions: Our research demonstrated that hypoxia could promote the phenotypic transformation of HUVSMCs partially through the ERK1/2/c-fos/NF-κB signaling pathway, which provided a novel insight into hypoxia-associated venous wall remodeling to further aid the development of a novel therapeutic target for the prevention or treatment of VVs.
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http://dx.doi.org/10.1016/j.avsg.2022.03.038DOI Listing
April 2022

Construction of a prognostic risk assessment model for lung adenocarcinoma based on Integrin β family-related genes.

J Clin Lab Anal 2022 Jun 11;36(6):e24419. Epub 2022 Apr 11.

Department of Thoracic Surgery, Shaoxing People's Hospital, Shaoxing, China.

Background: Integrin β (ITGB) superfamily plays an essential role in the intercellular connection and signal transmission. It was exhibited that overexpressing of ITGB family members promotes the malignant progression of lung adenocarcinoma (LUAD), but the relationship between ITGB superfamily and the LUAD prognosis remains unclear.

Methods: In this study, the samples were assigned to different subgroups utilizing non-negative matrix factorization clustering according to the expression of ITGB family members in LUAD. Kaplan-Meier (K-M) survival analysis revealed the significant differences in the prognosis between different ITGB subgroups. Subsequently, we screened differentially expressed genes among different subgroups and conducted univariate Cox analysis, random forest feature selection, and multivariate Cox analysis. 9-feature genes (FAM83A, AKAP12, PKP2, CYP17A1, GJB3, TMPRSS11F, KRT81, MARCH4, and STC1) in the ITGB superfamily were selected to establish a prognostic assessment model for LAUD.

Results: In accordance with the median risk score, LUAD samples were divided into high- and low-risk groups. The receiver operating characteristic (ROC) curve of LUAD patients' survival was predicted via K-M survival curve and principal component analysis dimensionality reduction. This model was found to have a favorable performance in LUAD prognostic assessment. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of differentially expressed genes between groups and Gene Set Enrichment Analysis (GSEA) of intergroup samples confirmed that the high- and low-risk groups had evident differences mainly in the function of extracellular matrix (ECM) interaction. Risk score and univariate and multivariate Cox regression analyses of clinical factors showed that the prognostic model could be applied as an independent prognostic factor for LUAD. Then, we draw the nomogram of 1-, 3-, and 5-year survival of LUAD patients predicted with the risk score and clinical factors. Calibration curve and clinical decision curve proved the favorable predictive ability of nomogram.

Conclusion: We constructed a LUAD prognostic risk model based on the ITGB superfamily, which can provide guidance for clinicians on their prognostic judgment.
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http://dx.doi.org/10.1002/jcla.24419DOI Listing
June 2022

A Highly Efficient Sulfur Host Enabled by Nitrogen/Oxygen Dual-Doped Honeycomb-Like Carbon for Advanced Lithium-Sulfur Batteries.

Small 2022 Apr 25;18(17):e2107380. Epub 2022 Mar 25.

State Key Laboratory for Mechanical Behavior of Materials, School of Material Science and Engineering, Xi'an Jiaotong University, Xi'an, 710049, P. R. China.

High energy density and long cycle life of lithium-sulfur (Li-S) batteries suffer from the shuttle/expansion effect. Sufficient sulfur storage space, local fixation of polysulfides, and outstanding electrical conductivity are crucial for a robust cathode host. Herein, a modified template method is proposed to synthesize a highly regular and uniform nitrogen/oxygen dual-doped honeycomb-like carbon as sulfur host (N/O-HC-S). The unique structure not only offers physical entrapment for polysulfides (LiPSs) but also provides chemical adsorption and catalytic conversion sites of polysulfides. In addition, this structure offers enough space for loading sulfur, and a regular space of nanometer size can effectively prevent sulfur particles from accumulating. As expected, the as-prepared N/O-HC900-S with high areal sulfur loading (7.4 mg cm ) shows a high areal specific capacity of 7.35 mAh cm at 0.2 C. Theoretical calculations also reveal that the strong chemical immobilization and catalytic conversion of LiPSs attributed to the spin density and charge distribution of carbon atoms will be influenced by the neighbor nitrogen/oxygen dopants. This structure that provides cooperative chemical adsorption, high lithium ions flux, and catalytic conversion for LiPSs can offer a new strategy for constructing a polysulfide confinement structure to achieve robust Li-S batteries.
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http://dx.doi.org/10.1002/smll.202107380DOI Listing
April 2022

Tracking the sliding of grain boundaries at the atomic scale.

Science 2022 Mar 17;375(6586):1261-1265. Epub 2022 Mar 17.

Institute of Microstructure and Property of Advanced Materials, Beijing Key Lab of Microstructure and Property of Advanced Materials, Beijing University of Technology, Beijing 100124, China.

Grain boundaries (GBs) play an important role in the mechanical behavior of polycrystalline materials. Despite decades of investigation, the atomic-scale dynamic processes of GB deformation remain elusive, particularly for the GBs in polycrystals, which are commonly of the asymmetric and general type. We conducted an in situ atomic-resolution study to reveal how sliding-dominant deformation is accomplished at general tilt GBs in platinum bicrystals. We observed either direct atomic-scale sliding along the GB or sliding with atom transfer across the boundary plane. The latter sliding process was mediated by movements of disconnections that enabled the transport of GB atoms, leading to a previously unrecognized mode of coupled GB sliding and atomic plane transfer. These results enable an atomic-scale understanding of how general GBs slide in polycrystalline materials.
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http://dx.doi.org/10.1126/science.abm2612DOI Listing
March 2022

The dynamic behavior and mechanism of uranium (VI) biomineralization in Enterobacter sp. X57.

Chemosphere 2022 Jul 8;298:134196. Epub 2022 Mar 8.

Key Laboratory of Radiation Physics and Technology of the Ministry of Education, Institute of Nuclear Science and Technology, Sichuan University, Chengdu, 610064, PR China.

The important role of microbes in the biomineralization and migration behavior of uranium in the field of environmental chemistry has been well emphasized in previous work. However, limited work on mineralization processes of indigenous microorganism has prevented us from a deeper understanding of the process and mechanisms of uranium biomineralization. In this work, the dynamic process and mechanism of uranium biomineralization in Enterobacter sp. X57, a novel uranium-tolerant microorganism separated from uranium contaminated soil, were systematically investigated. Enterobacter sp. X57 can induce intracellular mineralization of U (VI) to Uramphite (NHUOPO·3HO) under neutral conditions by alkaline phosphatase. In this biomineralization process, soluble U (VI) first bonded with the amino and phosphate groups on the plasma membrane, providing initial nucleation site for the formation of U (VI) biominerals. Then the impairment of cell barrier function and the enhancement of alkaline phosphatase metabolism occurred with the accumulation of uranium in cells, creating a possible pathway for soluble U (VI) to diffuse into the cell and be further mineralized into U (VI)-phosphate minerals. All the results revealed that the intracellular biomineralization of uranium by Enterobacter sp. X57 was a combined result of biosorption, intracellular accumulation and phosphatase metabolism. These findings may contribute to a better understanding of uranium biomineralization behavior and mechanism of microorganisms, as well as possible in-situ bioremediation strategies for uranium by indigenous microorganisms.
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http://dx.doi.org/10.1016/j.chemosphere.2022.134196DOI Listing
July 2022

Reversible Mechanochromisms via Manipulating Surface Wrinkling.

Nano Lett 2022 Mar 2;22(6):2261-2269. Epub 2022 Mar 2.

State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an, 710049, P.R. China.

Mechanochromic structural-colored materials have promising applications in various domains. In this Letter, we report three types of reversible mechanochromisms in simple material systems by harnessing mechano-responsive wrinkling dynamics including (i) brightness mechanochromism (BM), (ii) hue change mechanochromism (HCM), and (iii) viewable angle mechanochromism (VAM). Upon stretching, the BM device exhibits almost a constant hue but reduces light brightness due to the postbuckling mechanics-controlled deformation, while the HCM device can change the hue from blue to red with almost constant intensity because of the linear elastic mechanics-controlled deformation. The VAM device shows a constant hue because of the thin film interference effect. However, the viewable angles decrease with increasing applied strain owing to the light scattering of wrinkles. All of the mechanochromic behaviors exhibit good reversibility and durability. We clearly elucidated the underlying mechanisms for different mechanochromisms and demonstrated their potential applications in smart displays, stretchable strain sensors, and antipeeping/anticounterfeiting devices.
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http://dx.doi.org/10.1021/acs.nanolett.1c04494DOI Listing
March 2022

Exploiting the Twisted Intramolecular Charge Transfer Effect to Construct a Wash-Free Solvatochromic Fluorescent Lipid Droplet Probe for Fatty Liver Disease Diagnosis.

Anal Chem 2022 03 22;94(9):3881-3887. Epub 2022 Feb 22.

State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100, P. R. China.

The prominent pathological feature of fatty liver disease lesions is excessive fat accumulation in lipid droplets in hepatocytes. Thus, developing fluorescent lipid droplet-specific probes with high permeability and a high imaging contrast provides a robust tool for diagnosing fatty liver diseases. Herein, we rationally developed a novel donor-acceptor lipophilic fluorescent probe ANI with high photostability for wash-free visualization of lipid droplets and fatty liver disease characteristics. ANI showed a typical twisted intramolecular charge transfer effect with very faint fluorescence in high-polar solvents, but dramatically boosted emissions in low-polar environments. The solvatochromic probe can selectively light up lipid droplets with a high contrast in a wash-free manner. Further use of ANI to reveal the excessive accumulation of lipid droplets with a significantly large size in the liver tissues from the fatty liver disease model mice was successfully demonstrated. The remarkable imaging performances rendered ANI an alternative tool for accurately evaluating fatty liver disease in intraoperative diagnosis.
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http://dx.doi.org/10.1021/acs.analchem.1c04847DOI Listing
March 2022

Photonic Nanojet-Mediated Optogenetics.

Adv Sci (Weinh) 2022 04 20;9(12):e2104140. Epub 2022 Feb 20.

Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR, 999077, China.

Optogenetics has become a widely used technique in neuroscience research, capable of controlling neuronal activity with high spatiotemporal precision and cell-type specificity. Expressing exogenous opsins in the selected cells can induce neuronal activation upon light irradiation, and the activation depends on the power of incident light. However, high optical power can also lead to off-target neuronal activation or even cell damage. Limiting the incident power, but enhancing power distribution to the targeted neurons, can improve optogenetic efficiency and reduce off-target effects. Here, the use of optical lenses made of polystyrene microspheres is demonstrated to achieve effective focusing of the incident light of relatively low power to neighboring neurons via photonic jets. The presence of microspheres significantly localizes and enhances the power density to the target neurons both in vitro and ex vivo, resulting in increased inward current and evoked action potentials. In vivo results show optogenetic stimulation with microspheres that can evoke significantly more motor behavior and neuronal activation at lowered power density. In all, a proof-of-concept of a strategy is demonstrated to increase the efficacy of optogenetic neuromodulation using pulses of reduced optical power.
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http://dx.doi.org/10.1002/advs.202104140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036029PMC
April 2022

Therapeutic targets of neuroprotection and neurorestoration in ischemic stroke: Applications for natural compounds from medicinal herbs.

Biomed Pharmacother 2022 Apr 12;148:112719. Epub 2022 Feb 12.

Institute of Neuroregeneration & Neurorehabilitation, Department of Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao 266071, China. Electronic address:

Neuroprotective and neurorestorative therapy represent two major drug intervention strategies for ischemic stroke. Multiple factors such as excitotoxicity, inflammation, angiogenesis, and neurogenesis are the main pathological processes that underlie acute and chronic ischemic brain injury. Furthermore, their intimate interactions mediate blood-brain barrier permeability, increase neurovascular unit structural damage as well as a hemorrhagic transformation during ischemic stroke. We aimed to review the current understandings of the underlying mechanisms of neuroprotection and neurorestoration in ischemic stroke. Notably, traditional Chinese medicine (TCM) has notable advantages in the comprehensive treatment and overall regulation of multi-site and multi-target diseases. Therefore, we reviewed the recent advances in natural compounds from medicinal herbs that possess the bioactivities of simultaneously promoting neuroprotection (e.g., excitotoxicity, oxidative stress, apoptosis, inflammation, and autophagy) and neurorestoration (e.g., angiogenesis, neurogenesis, and axonal sprouting) following brain ischemia injury. These natural compounds were divided into glycosides (astragaloside IV, gastrodin, ginsenoside Rg1 and salidroside), flavonoids (baicalin, icariin, puerarin and breviscapine), phenols (resveratrol, curcumin and salvianolic acid B), and terpenes (ginkgolide B and catalpol). We found that all compounds exhibited anti-brain ischemia activities in vivo and in vitro experiments by promoting neuroprotection and, or neurorestoration. This review tracks and summarizes the progress of the past five years to explore the active compounds and the underlying molecular mechanisms of TCMs that produce pro-neuroprotection and pro-neurorestoration. Additionally, we provide another basis of reference supporting the advantages of TCMs, which could ultimately lead to the development of precise clinical medications for ischemic stroke treatment.
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http://dx.doi.org/10.1016/j.biopha.2022.112719DOI Listing
April 2022

Irisin/FNDC5 inhibits the epithelial-mesenchymal transition of epithelial ovarian cancer cells via the PI3K/Akt pathway.

Arch Gynecol Obstet 2022 Feb 14. Epub 2022 Feb 14.

Department of Gynecology, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, 266011, People's Republic of China.

Purpose: This study explored the role of irisin/fibronectin type III domain-containing protein 5 (FNDC5) in epithelial ovarian cancer and investigated its underlying mechanisms.

Methods: Immunohistochemistry was performed to analyze the expression of irisin/FNDC5 in epithelial ovarian cancer and normal ovarian tissues. Cell Counting Kit-8, transwell, and wound-healing assays were performed to examine the effect of irisin on the viability, migration, and invasion of ovarian cancer cells, respectively. Western blotting was used to detect the changes of epithelial-mesenchymal transition (EMT)-related proteins and phosphatidylinositol 3-kinase (PI3K)/Akt pathway proteins. Ovarian cancer cells were treated in vitro with the PI3K agonist (740Y-P) in combination with irisin to explore the mechanism of irisin in ovarian cancer.

Results: The expression of irisin/FNDC5 in epithelial ovarian cancer tissue was significantly higher than that in normal ovarian tissues, and the expression in late stage patients with lymph node metastasis was lower than that in early stage patients without metastasis. Irisin inhibited the proliferation, invasion, and migration of epithelial ovarian cancer cells, down-regulated phosphorylated Akt, and inhibited EMT progression. The PI3K agonist, 740Y-P, partially reversed the effects of irisin on the invasion, migration, and EMT of ovarian cancer cells.

Conclusion: These findings show that irisin/FNDC5 was highly expressed in ovarian cancer tissues, which may regulate the EMT through the PI3K/Akt signaling pathway and inhibit the proliferation, invasion, and migration of epithelial ovarian cancer.
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http://dx.doi.org/10.1007/s00404-022-06427-1DOI Listing
February 2022

Genome-wide identification and characterization of NLR genes in lamprey (Lethenteron reissneri) and their responses to lipopolysaccharide/poly(I:C) challenge.

Mol Immunol 2022 03 4;143:122-134. Epub 2022 Feb 4.

College of Life Sciences, Liaoning Normal University, Dalian 116081, China; Lamprey Research Center, Liaoning Normal University, Dalian 116081, China; Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116081, China. Electronic address:

The nucleotide oligomerization domain (NOD)-like receptor (NLR) is a relatively conserved receptor family involved in natural immunity that plays a key role in the resistance to pathogen invasion and regulation of the innate immune response. Lethenteron reissneri (lamprey) is a representative species of existing ancient jawless vertebrates. Studies of the evolutionary relationship of immune system-related molecules in lampreys can provide an important reference for the origin and evolution of innate immunity. However, the characterization and evolutionary patterns of the NLR family remain unclear in the lamprey genome. Based on the genome database of L. reissneri, we identified nine NLR genes, characterized their functional domains and chromosomal positions, and constructed a network comprising the results of gene structure and gene-collinearity analyses. Comparative genomics studies suggest that Lr-NODa and Lr-NODb most likely share the common ancestor of NOD1 and NOD2 in jawed vertebrates, and that Lr-NODb may have been generated by lamprey-specific tandem duplication of Lr-NODa. Additionally, phylogenetic analysis of the NLRC subfamily suggests that Lr-NLRC3a has ancestral traits and may be derived from the common ancestor of another vertebrate NLRC subfamily. Further analysis of the formation of the NLRC subfamily has shown that exon shuffling, domain recombination, and chromosome rearrangement play important roles in its structural evolution. Furthermore, real-time quantitative polymerase chain reaction shows that most NLR genes in lamprey are highly expressed in the immune tissues of the heart, gill, and supraneural body, with these genes also showing significant responses to polyinosinic-polycytidylic acid infection. These results indicate that NLR genes are involved in the immune protection of L. reissneri and provide an important theoretical foundation for studies of the functional evolution of vertebrate NLRs involved in the innate immune system.
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http://dx.doi.org/10.1016/j.molimm.2022.01.014DOI Listing
March 2022
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