Publications by authors named "Yanyan Li"

690 Publications

Dl-3-N-Butylphthalide Promotes Angiogenesis in an Optimized Model of Transient Ischemic Attack in C57BL/6 Mice.

Front Pharmacol 2021 29;12:751397. Epub 2021 Sep 29.

Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Transient ischemic attack (TIA) has been widely regarded as a clinical entity. Even though magnetic resonance imaging (MRI) results of TIA patients are negative, potential neurovascular damage might be present, and may account for long-term cognitive impairment. Animal models that simulate human diseases are essential tools for in-depth study of TIA. Previous studies have clarified that Dl-3-N-butylphthalide (NBP) promotes angiogenesis after stroke. However, the effects of NBP on TIA remain unknown. This study aims to develop an optimized TIA model in C57BL/6 mice to explore the microscopic evidence of ischemic injury after TIA, and investigate the therapeutic effects of NBP on TIA. C57BL/6 mice underwent varying durations (7, 8, 9 or 10 min) of middle cerebral artery occlusion (MCAO). Cerebral artery occlusion and reperfusion were assessed by laser speckle contrast imaging. TIA and ischemic stroke were distinguished by neurological testing and MRI examination at 24 h post-operation. Neuronal apoptosis was examined by TUNEL staining. Images of submicron cerebrovascular networks were obtained micro-optical sectioning tomography. Subsequently, the mice were randomly assigned to a sham-operated group, a vehicle-treated TIA group or an NBP-treated TIA group. Vascular density was determined by immunofluorescent staining and fluorescein isothiocyanate method, and the expression of angiogenic growth factors were detected by western blot analysis. We found that an 8-min or shorter period of ischemia induced neither permanent neurological deficits nor MRI detectable brain lesions in C57BL/6 mice, but histologically caused neuronal apoptosis and cerebral vasculature abnormalities. NBP treatment increased the number of CD31 microvessels and perfused microvessels after TIA. NBP also up-regulated the expression of VEGF, Ang-1 and Ang-2 and improved the cerebrovascular network. In conclusion, 8 min or shorter cerebral ischemia induced by the suture MCAO method is an appropriate TIA model in C57BL/6 mice, which conforms to the definition of human TIA, but causes microscopic neurovascular impairment. NBP treatment increased the expression of angiogenic growth factors, promoted angiogenesis and improved cerebral microvessels after TIA. Our study provides new insights on the pathogenesis and potential treatments of TIA.
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http://dx.doi.org/10.3389/fphar.2021.751397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513739PMC
September 2021

Development and validation of a liquid chromatography-tandem mass spectrometry method with triple-stage fragmentation to determine levetiracetam in epileptic patient serum and its application in therapeutic drug monitoring.

J Sep Sci 2021 Oct 14. Epub 2021 Oct 14.

Department of Laboratory Medicine, the First Hospital of Jilin University, Changchun, P. R. China.

Levetiracetam is an antiepileptic drug that is primarily approved by the Food and Drug Administration for the treatment of focal and generalized seizures. This study describes the development and validation of a highly selective and sensitive liquid chromatography-tandem mass spectrometry method with triple-stage fragmentation to determine levetiracetam in epileptic patient serum. After simple protein precipitation, the analytes were separated on a short reversed-phase column (Agilent Poroshell 120 SB-C18 column, 4.6 × 50 mm, 2.7 μm) using isocratic elution with 25% 0.1% formic acid in water (solvent A) and 75% methanol (solvent B) at a flow rate of 0.8 ml/min. The linear range is 0.5-50 μg/mL (R > 0.99). All the validation data, such as lower limit of quantification, linearity, specificity, recoveries, matrix effects, and other parameters, fit the request of biological method validation guidance. Passing-Bablok regression coefficients demonstrated that there is no constant bias and no proportional bias between the liquid chromatography-tandem mass spectrometry methods with triple-stage fragmentation and liquid multiple reaction monitoring. Bland-Altman plot showed that the developed liquid chromatography-tandem mass spectrometry method with triple-stage fragmentation method is reliable and accurate to determine levetiracetam in human serum.
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http://dx.doi.org/10.1002/jssc.202100639DOI Listing
October 2021

Predictive value of ACEF II score in patients with multi-vessel coronary artery disease undergoing one-stop hybrid coronary revascularization.

BMC Cardiovasc Disord 2021 Oct 10;21(1):489. Epub 2021 Oct 10.

Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, No. 8 Gongti South Road, Beijing, 100020, China.

Background: We aimed to investigate the predictive value of recently updated ACEF II score on major adverse cardiac and cerebrovascular events (MACCE) in patients with multi-vessel coronary artery disease (MVCAD) undergoing one-stop hybrid coronary revascularization (HCR).

Methods: Patients with MVCAD undergoing one-stop HCR were retrospectively recruited from March 2018 to September 2020. Several prediction risk models, including ACEF II score, were calculated for each patient. Kaplan-Meier curve was used to evaluate freedom from cardiac death and MACCE survival rates. Differences of prediction performance among risk scores for predicting MACCE were compared by receiver operating characteristic (ROC) curve.

Results: According to the ACEF II score, a total of 120 patients undergoing one-stop HCR were assigned to low-score group (80 cases) and high-score group (40 cases). During the median follow-up time of 18 months, the incidence of MACCE in the low-score group and high-score group were 8.8 % and 37.5 %, respectively (p < 0.001); and the cardiac death rate of the two were 2.5% and 12.5%, respectively (p < 0.05). Moreover, the cumulative freedom from cardiac death (97.5% vs. 86.8, p < 0.05) and MACCE (75.2% vs. 52.8%, p < 0.001) survival rates in the high-score group were significantly lower than in the low-score group. According to the Cox proportional hazards regression, the ACEF II score was an independent prognostic indicator for MACCE with hazards ratio (HR) 2.24, p = 0.003. The ROC curve analysis indicated that the areas under the curve (AUC) of MACCE from the ACEF II score was 0.740 (p < 0.001), while the AUC of MACCE from the SYNTAX score II CABG was 0.621 (p = 0.070) and the AUC from the EuroSCORE II was 0.703 (p < 0.001). Thus, the accurate predictive value of ACEF II score was similar to the EuroSCORE II but much higher than the SYNTAX score II CABG.

Conclusions: The updated ACEF II score is a more convenient and validated prediction tool for MACCE in patients with MVCAD undergoing one-stop HCR comparing to other risk models.
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http://dx.doi.org/10.1186/s12872-021-02299-6DOI Listing
October 2021

1.7-μm Tm-doped fiber laser intracavity-pumped by an erbium/ytterbium-codoped fiber laser.

Opt Express 2021 Aug;29(16):25280-25289

In this paper, we demonstrate an efficient 1.7-μm Tm-doped fiber laser whose cavity was embedded in a 1560 nm erbium/ytterbium-codoped fiber laser cavity, which enabled bidirectional pumping and made full use of the circulating pump in the parent laser cavity. A rate equation model was developed to optimize the fiber length and output coupling for a desired output power. In the experiment, a maximum output power at 1720 nm of 1.13 W was obtained under 10 W of 976 nm diode pump power, which correlated well with our modeling. The slope efficiency from the multimode 976 nm diode pump to 1720 nm output was 13.5%, while the slope efficiency in terms of launched 1560 nm pump power reached 62.5%. By using a short Tm-doped fiber to minimize signal reabsorption, a high signal-to-noise ratio over 65 dB was achieved. The prospect for further power scaling was also discussed based on our developed model.
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http://dx.doi.org/10.1364/OE.432898DOI Listing
August 2021

Few-cycle mid-infrared laser based on nonlinear self-compression in solid thin plates.

Opt Lett 2021 Oct;46(19):5075-5078

A few-cycle mid-infrared (MIR) laser is demonstrated via nonlinear self-compression in solid thin plates. In this novel solution, the anomalous material dispersion in the MIR band and the chirp induced by self-phase modulation are mutually compensated, which can achieve self-compression. Finally, with the 4 µm laser injection with 4.8 mJ/155 fs and few-cycle pulses with 3.44 mJ, 29.4 fs are generated with a high efficiency of 71.7%, and the system maintains very good spectral stability in 10 days. Compared with other post-compression methods, this self-compression technique has the advantages of high efficiency and robust and large energy expansion scale, which can be further extended to MIR lasers with other wavelengths and higher peak power.
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http://dx.doi.org/10.1364/OL.442105DOI Listing
October 2021

Cancer death and potential years of life lost in Feicheng City, China: Trends from 2013 to 2018.

Medicine (Baltimore) 2021 Oct;100(39):e27370

Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.

Abstract: This study aimed to evaluate the impact of cancer-related mortality on life expectancy in Feicheng City.We extracted the death records and population data of Feicheng City from 2013 to 2018 through the Feicheng Center for Disease Control and Prevention. The mortality, premature mortality, cause-eliminated life expectancy, potential years of life lost (PYLL), average potential years of life lost (APYLL), annual change percentage (APC), and other indicators of cancer were calculated. The age-standardized rates were calculated using the sixth national census (2010).From 2013 to 2018, the mortality rate of cancer in Feicheng City was 221.55/100,000, and the standardized mortality rate was 166.37/100,000. The standardized mortality rate increased from 2013 to 2014 and then decreased annually. The premature mortality of cancer was 8.98% and showed a downward trend (APC = -2.47%, t = -3.10, P = .04). From 2013 to 2018, the average life expectancy of residents in Feicheng City was 78.63 years. Eliminating the impact of cancer, life expectancy could increase by 3.72 years. The rate of life loss caused by cancer in men was higher than that in women. The total life loss caused by cancer deaths was 126,870.50 person-years, the potential life loss rate was 22.51‰, and the average potential life loss was 13.30 years. The standardized potential years of life lost rate showed a downward trend (APC = -2.96%, t = -3.72, P = .02), and APYLL decreased by 1.98% annually (t = -5.44, P = .01). The top 5 malignant tumors in APYLL were leukemia, breast cancer, brain tumor, liver cancer, and ovarian cancer.Lung cancer, esophageal cancer, female breast cancer, and childhood leukemia have a great impact on the life expectancy of residents in Feicheng City. Effective measures need to be taken to reduce the disease burden of malignant tumors.
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http://dx.doi.org/10.1097/MD.0000000000027370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483870PMC
October 2021

Development and application of sequential window acquisition of all theoretical mass spectra data acquisition modes on ultra-high-performance liquid chromatography triple-quadrupole/time-of-flight mass spectrometry for metabolic profiling of amino acids in human plasma.

J Sep Sci 2021 Sep 30. Epub 2021 Sep 30.

Department of Laboratory Medicine, the First Hospital of Jilin University, Jilin University, Changchun, P. R. China.

Accumulating evidence suggests that amino acids are important indicators of nutritional and metabolic status. A high-resolution mass spectrometry method based on sequential window acquisition of all theoretical mass spectra acquisition was developed for the simultaneous determination of 16 amino acids in human plasma. Sample preparation by protein precipitation using a mixture of acetonitrile and formic acid was followed by a BEH Amide column. The superiority of this method was investigated by comparing it to time-of-flight scan and multiple reaction monitoring modes. The limit of detection in sequential window acquisition of all theoretical mass spectra mode for threonine, methionine, histidine, citrulline, and tryptophan is 0.1 ng on the column; for lysine and asparagine is 0.2 ng; for alanine, pyroglutamic acid, leucine, ornithine, and aspartate is 0.5 ng, for arginine is 1.0 ng; for glutamate and serine is 2.0 ng; for glutamine is 10.0 ng. This method was linear in the range 0.8-40 μg/mL for arginine, citrulline, glutamate, histidine, leucine, methionine, pyroglutamic acid, threonine, tryptophan; 2-100 μg/mL for asparagine, aspartate, lysine, ornithine, serine; and 4-200 μg/mL for alanine, glutamine with good accuracy and precision. Significantly different levels in 11 amino acids were observed between childhood and adulthood, representing the growth and development of individuals relating to the level of amino acids.
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http://dx.doi.org/10.1002/jssc.202100573DOI Listing
September 2021

Estimating the Long-Term Epidemiological Trends and Seasonality of Hemorrhagic Fever with Renal Syndrome in China.

Infect Drug Resist 2021 21;14:3849-3862. Epub 2021 Sep 21.

Department of Epidemiology and Health Statistics, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, People's Republic of China.

Objective: We aim to examine the adequacy of an innovation state-space modeling framework (called TBATS) in forecasting the long-term epidemic seasonality and trends of hemorrhagic fever with renal syndrome (HFRS).

Methods: The HFRS morbidity data from January 1995 to December 2020 were taken, and subsequently, the data were split into six different training and testing segments (including 12, 24, 36, 60, 84, and 108 holdout monthly data) to investigate its predictive ability of the TBATS method, and its forecasting performance was compared with the seasonal autoregressive integrated moving average (SARIMA).

Results: The TBATS (0.27, {0,0}, -, {<12,4>}) and SARIMA (0,1,(1,3))(0,1,1) were selected as the best TBATS and SARIMA methods, respectively, for the 12-step ahead prediction. The mean absolute deviation, root mean square error, mean absolute percentage error, mean error rate, and root mean square percentage error were 91.799, 14.772, 123.653, 0.129, and 0.193, respectively, for the preferred TBATS method and were 144.734, 25.049, 161.671, 0.203, and 0.296, respectively, for the preferred SARIMA method. Likewise, for the 24-, 36-, 60-, 84-, and 108-step ahead predictions, the preferred TBATS methods produced smaller forecasting errors over the best SARIMA methods. Further validations also suggested that the TBATS model outperformed the Error-Trend-Seasonal framework, with little exception. HFRS had dual seasonal behaviors, peaking in May-June and November-December. Overall a notable decrease in the HFRS morbidity was seen during the study period (average annual percentage change=-6.767, 95% confidence intervals: -10.592 to -2.778), and yet different stages had different variation trends. Besides, the TBATS model predicted a plateau in the HFRS morbidity in the next ten years.

Conclusion: The TBATS approach outperforms the SARIMA approach in estimating the long-term epidemic seasonality and trends of HFRS, which is capable of being deemed as a promising alternative to help stakeholders to inform future preventive policy or practical solutions to tackle the evolving scenarios.
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http://dx.doi.org/10.2147/IDR.S325787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464322PMC
September 2021

The Significance of MET Expression and Strategies of Targeting MET Treatment in Advanced Gastric Cancer.

Front Oncol 2021 7;11:719217. Epub 2021 Sep 7.

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

Background: Accurate assessment of predictive biomarker expression is critical in patient selection in clinical trials or clinical practice. However, changes in biomarker expression may occur after treatment. The aim of the present study was to evaluate the effects of chemotherapy on MET expression in gastric cancer (GC).

Methods: MET expression was examined immunohistochemically before and after treatment in 122 patients with unresectable or recurrent GC, and was evaluated according to H-score or the scoring criteria used in the MetMAb trial. gene amplification was assessed by chromogenic hybridization (CISH). The antitumor effect of MET targeted therapy was investigated in human gastric cancer cells and , and the underlying molecular mechanisms were analyzed by western blot.

Results: MET expression was associated with Lauren classification as well as tumor differentiation by either scoring system. MET amplification was not associated with clinical characteristics. Of the 71 patients who had paired pre- and post-treatment tumor tissues, 28 patients (39%) were initially positive for MET expression, and 43 (61%) were negative. Twenty-five patients (35%) showed significant changes in MET expression after treatment (P=0.007). Additionally, there was a concomitant overexpression of MET and HER2 in a subset of GC patients. MET inhibitor volitinib could significantly inhibit cell proliferation and xenograft growth and in MKN45 cells with MET and phosphorylated MET (pMET) high expressions suppressing downstream PI3K/Akt and MAPK signaling pathways. Furthermore, combination therapy targeting both MET and HER2 demonstrated a synergistic antitumor activity.

Conclusions: MET expression is altered post chemotherapy and MET status should be evaluated in real-time. Both MET and pMET expressions might need to be considered for patients suitable for volitinib treatment.
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http://dx.doi.org/10.3389/fonc.2021.719217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453156PMC
September 2021

USP7 inhibition induces apoptosis in glioblastoma by enhancing ubiquitination of ARF4.

Cancer Cell Int 2021 Sep 23;21(1):508. Epub 2021 Sep 23.

Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Jiangsu, Suzhou, People's Republic of China.

Background: Glioblastomas (GBMs) are grade IV central nervous system tumors characterized by a poor prognosis and a short median overall survival. Effective induction of GBM cell death is difficult because the GBM cell population is genetically unstable, resistant to chemotherapy and highly angiogenic. In recent studies, ubiquitin-specific protease 7 (USP7) is shown to scavenge ubiquitin from oncogenic protein substrates, so effective inhibition of USP7 may be a potential key treatment for GBM.

Methods: Immunohistochemistry and western blotting were used to detect the expression of USP7 in GBM tissues. In vitro apoptosis assay of USP7 inhibition was performed by western blotting, immunofluorescence, and flow cytometry. Anti-apoptotic substrates of USP7 were defined by Co-IP and TMT proteomics. Western blotting and IP were used to verify the relationship between USP7 and its substrate. In an in vivo experiment using an intracranial xenograft model in nude mice was constructed to assess the therapeutic effect of target USP7.

Results: Immunohistochemistry and western blotting confirmed that USP7 was significantly upregulated in glioblastoma samples. In in vitro experiments, inhibition of USP7 in GBM induced significant apoptosis. Co-IP and TMT proteomics identified a key anti-apoptotic substrate of USP7, ADP-ribosylation factor 4 (ARF4). Western blotting and IP confirmed that USP7 interacted directly with ARF4 and catalyzed the removal of the K48-linked polyubiquitinated chain that binded to ARF4. In addition, in vivo experiments revealed that USP7 inhibition significantly suppressed tumor growth and promoted the expression of apoptotic genes.

Conclusions: Targeted inhibition of USP7 enhances the ubiquitination of ARF4 and ultimately mediates the apoptosis of GBM cells. In a clinical sense, P5091 as a novel specific inhibitor of USP7 may be an effective approach for the treatment of GBM.
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http://dx.doi.org/10.1186/s12935-021-02208-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461901PMC
September 2021

LncRNA NEAT1 Promotes Gastric Cancer Progression Through miR-17-5p/TGFβR2 Axis Up-Regulated Angiogenesis.

Front Cell Dev Biol 2021 6;9:705697. Epub 2021 Sep 6.

Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

Background: Long non-coding RNAs (lncRNAs) have been indicated to play critical roles in gastric cancer (GC) tumorigenesis and progression. However, their roles in GC remain to be further elucidated.

Methods: RT-qPCR and fluorescence hybridzation (FISH) were conducted to detect the expression of lncRNA NEAT1 in GC tissues and cell lines. Gene Set Enrichment Analysis (GSEA) was performed to screen out potential phenotypes and pathways that NEAT1 may participate in. NEAT1-silenced AGS and MGC803 cells were constructed and a series of functional experiments to investigate the roles of NEAT1 in GC angiogenesis both and . RNA pull down and luciferase reporter assays were utilized to illustrate the mechanisms underlying the functions of NEAT1 in GC.

Results: We observed that NEAT1 was upregulated in most GC specimens and cell lines. NEAT1 high was correlated with poor prognosis of GC patients. experiments showed that NEAT1 promoted GC angiogenesis by enhancing proliferation, migration, and tube formation ability of endothelial cells. Mechanism researches revealed that NEAT1 could competitively sponge miR-17-5p which targeted TGFβR2 directly. Subsequently, activate TGFβ/Smad pathway by following with upregulation of a series of classical proangiogenic factors especially VEGF.

Conclusion: The study unveiled that the LncRNA NEAT1/miR-17-5p/TGFβR2 axis is a novel mechanism in GC angiogenesis. Disrupting this axis may be a potential strategy for GC treatment.
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http://dx.doi.org/10.3389/fcell.2021.705697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452045PMC
September 2021

Solution-based fabrication of mechanically transformative materials for implantable applications.

Biomater Sci 2021 Oct 12;9(20):6950-6956. Epub 2021 Oct 12.

College of Engineering and Applied Sciences and Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing 210046, China.

Implantable probes and needles represent multifunctional biomedical platforms by integrating sensing, stimulation, and drug delivery capabilities. Conventional rigid probes often result in inflammatory responses due to large mechanical mismatch with soft biological tissues, whereas soft probes with improved long-term performances are difficult to be inserted deep into the compliant biological tissues. An emerging class of mechanically transformative materials addresses the challenge by embedding a phase-change material of gallium within an elastomeric matrix. These materials exhibit high stiffness under ambient conditions to enable facile insertion and compliant mechanical properties after implantations. The widespread implementation of mechanically transformative materials is primarily hindered by the lack of facile fabrication techniques for delicate gallium features. In this study, we introduce a solution-based approach for scalable fabrication of gallium-based mechanically transformative materials, which exhibit bistable mechanical properties with large modulations in the modulus by five orders of magnitude. In a solution-based coating process, gallium features are created based on a patterned copper film and then encapsulated with elastomers to form mechanically transformative materials. The height profile of the gallium feature is controlled by the two-dimensional design of the copper pattern, which provides access to delicate and complex three-dimensional features as exemplified by mechanically transformative indwelling needles with sharp tips. The practical suitability is demonstrated by the implementation of the indwelling needles for long-term chemotherapy. The excellent biocompatibility enables applications of mechanically transformative biomedical devices in chronic implantable systems.
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http://dx.doi.org/10.1039/d1bm00808kDOI Listing
October 2021

SmProt: A Reliable Repository with Comprehensive Annotation of Small Proteins Identified from Ribosome Profiling.

Genomics Proteomics Bioinformatics 2021 Sep 15. Epub 2021 Sep 15.

College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address:

Small proteins specifically refer to proteins consisting of less than 100 amino acids translated from small open reading frames (sORFs), which were usually missed in previous genome annotation. The significance of small proteins has been revealed in current years, along with the discovery of their diverse functions. However, systematic annotation of small proteins is still insufficient. SmProt was specially developed to provide valuable information on small proteins for scientific community. Here we present the update of SmProt, which emphasizes reliability of translated sORFs, genetic variants in translated sORFs, disease-specific sORF translation events or sequences, and remarkably increased data volume. More components such as non-ATG translation initiation, function, and new sources are also included. SmProt incorporated 638,958 unique small proteins curated from 3,165,229 primary records, which were computationally predicted from 419 ribosome profiling (Ribo-seq) datasets or collected from literature and other sources from 370 cell lines or tissues in 8 species (Homo sapiens, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Danio rerio, Saccharomyces cerevisiae, Caenorhabditis elegans, and Escherichia coli). In addition, small protein families identified from human microbiomes were also collected. All datasets in SmProt are free to access, and available for browse, search, and bulk downloads at http://bigdata.ibp.ac.cn/SmProt/.
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http://dx.doi.org/10.1016/j.gpb.2021.09.002DOI Listing
September 2021

The resting-state cerebro-cerebellar function connectivity and associations with verbal working memory performance.

Behav Brain Res 2021 Sep 15;417:113586. Epub 2021 Sep 15.

Military Medical Psychology School , Fourth Military Medical University, Xi'an, China. Electronic address:

The cerebellum plays an important role in cognitive functions through connecting with the cerebral cortical areas. However, the relationship between the resting-state functional connectivity (FC) pattern of human cerebro-cerebellar circuits and cognition is not fully understood. The present study investigated the FC patterns of human cerebro-cerebellar circuits and their associations with verbal working memory performance (an n-back task with three subtasks: 0-back, 1-back, and 2-back) through resting-state functional magnetic resonance imaging (fMRI) data from 34 healthy subjects. The whole-brain connectivity analysis was used to identify the cortical hubs as regions of interest (ROI). Then ROI-based FC analysis was performed to investigate the connectivity characteristics within the key cortical hubs and their associations with n-back task performance. The results showed that the bilateral cerebellum lobule VI as central hubs had increased FC with the default mode network (DMN) node (e.g., right posterior cingulate cortex) and salient network (SN) node (e.g., right anterior cingulate cortex), while decreased FC with the executive control network (ECN) node (e.g., the bilateral superior frontal gyrus). Furthermore, FC values of the cerebellum lobule VI with DMN and ECN nodes correlated with verbal working memory performance (response time of 2-back task). The results suggest that the cerebro-cerebellar circuits involve the underlying neural basis of verbal working memory processing during the resting state.
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http://dx.doi.org/10.1016/j.bbr.2021.113586DOI Listing
September 2021

RNA-seq analysis reveals the positive role of KLF5 in the differentiation of subcutaneous adipocyte in goats.

Gene 2021 Sep 14;808:145969. Epub 2021 Sep 14.

Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization of Education Ministry, Southwest Minzu University, Chengdu, China; Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Exploitation of Sichuan Province, Southwest Minzu University, Chengdu, China; College of Animal & Veterinary Science, Southwest Minzu University, China. Electronic address:

As the largest energy storage reservoir, subcutaneous adipose tissue (SAT) stores excess lipids by adipocytes enlargement and/or recruitment of new precursor cells. Energy overload can cause ectopic fat deposition and metabolic diseases. In this study, 6814 differentially expressed genes (DEGs) were screened in goat subcutaneous preadipocytes and mature adipocytes by RNA-seq technique. The relative expression of the DEGs were verified by qPCR, such as PLIN2, MECR, ADCY7, PEBP1 and KLF5, and their expression level was found to be consistent with the trend of RNA-seq analysis. The KLF5 was selected for further functional verification. Overexpression of KLF5 promoted both the adipogenesis and the differentiation of preadipocytes, while the expression of preadipocyte marker gene: preadipocyte factor 1(Pref1) was decreased, as well as, peroxisome proliferator activation Receptor γ(PPARγ), CCAAT enhancer binding protein β(C/EBPβ) and Sterol regulatory element binding protein isoform 1(SREBP1) were increased. On the contrary, the interference of KLF5 could reduce adipogenesis, enhance the expression of Pref1, and reduce the expression of C/EBPβ and SREBP1. Our research provides a basic reference for revealing the mechanism of subcutaneous adipocyte differentiation in goats.
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http://dx.doi.org/10.1016/j.gene.2021.145969DOI Listing
September 2021

Emerging onsite electron donors for advanced nitrogen removal from anammox effluent of leachate treatment: A review and future applications.

Bioresour Technol 2021 Dec 8;341:125905. Epub 2021 Sep 8.

School of Environmental and Chemical Engineering, Shanghai University, 333 Nanchen Road, Shanghai 200444, China. Electronic address:

Partial nitrification-anammox process is promising in leachate treatment, but the 11% residue nitrate limits the total nitrogen removal efficiency. Denitrification or partial denitrification and anammox are both practical polishing processes of anammox effluent, requiring extra electron donors. Fortunately, there are organic matter, sulfide and methane in leachate or produced by leachate treatment, which can serve as onsite electron donors. In this review, the mechanisms and processes using these three kinds of electron donors for residue nitrate reduction in anammox effluent of leachate are systematically summarized and discussed. It can be concluded that, biodegradable organic matter is an effective electron donor, sulfide is a promising electron donor, methane is a potential electron donor. Two possible applications in future based on anammox treatment of fresh and mature leachate using sulfide and methane as onsite electron donors are proposed. Through sulfide reutilization, energy-saving with about 14% of aeration reduction can be achieved.
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http://dx.doi.org/10.1016/j.biortech.2021.125905DOI Listing
December 2021

Comparison of LC-MS and LC-MRM strategy for quantification of methotrexate in human plasma and its application in therapeutic drug monitoring.

J Pharm Biomed Anal 2021 Oct 30;205:114345. Epub 2021 Aug 30.

Department of Laboratory Medicine, The First Hospital of Jilin University, Jilin University, Xinmin Street, Changchun 130061, PR China. Electronic address:

A simple, highly selective and high throughput liquid chromatography tandem mass spectrometry cubed (LC/MS) method was developed and validated for quantification of methotrexate in human plasma. The MS detection is a scanning mode of QTrap MS systems or ion trap MS systems. After simple protein precipitation with methanol, methotrexate and methotrexate-d were separated on an Agilent Poroshell 120 SB-C18 column (4.6 × 50 mm, 2.7 µm) using isocratic elution with a mobile phase consisting of 60% 0.1% formic acid in water and 40% 0.1% formic acid in acetonitrile. The flow rate is 0.8 mL/min. MS detection in positive ion mode used the MRM transitions at m/z 455.2→308.2→175.1 for quantification of methotrexate and m/z 458.2→311.2→175.1 for quantification of methotrexate-d. The total run time was only 3 min for each sample. The LC/MS assay was linear in the concentration range 10-3000 ng/mL(R ≥ 0.995) and the intra- and inter-day accuracies were< 3.72% and precisions were< 7.78% at all concentrations. The absolute recoveries (%) and matrix effect (%) for methotrexate in human plasma were between 92.6 and 114.3. The novelty of the presented methodology is the MS technique resulting in enhanced selectivity and sensitivity. The application of this LC-MS method was successfully completed on 46 human plasma samples and the quantitative results of identical human plasma samples were compared with another LC-MRM based method. Passing-Bablok regression coefficients demonstrated that there is no significant difference between the LC-MS method and LC-MRM method. Bland-Altman plots showed a concordant results, supporting the developed LC-MS method is a reliable and accurate assay for determination of methotrexate in human plasma. This work is also a proof of concept for using LC-MS technique to determination of chemicals in biological samples.
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http://dx.doi.org/10.1016/j.jpba.2021.114345DOI Listing
October 2021

miR-10a-5p Inhibits the Differentiation of Goat Intramuscular Preadipocytes by Targeting KLF8 in Goats.

Front Mol Biosci 2021 13;8:700078. Epub 2021 Aug 13.

Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization of Education Ministry, Southwest Minzu University, Chengdu, China.

Intramuscular fat contributes to the improvement of meat quality of goats. MicroRNAs (miRNAs) have been reported to regulate adipocyte differentiation and maturation. The aim of our study was to clarify whether miR-10a-5p regulates goat intramuscular preadipocyte (GIPC) differentiation and its direct downstream signaling pathway. GIPCs were isolated from longissimus dorsi, whose miR-10a-5p level was measured at different time point of differentiation induction. Adipogenic differentiation of the GIPCs was evaluated by Oil Red O and BODIPY staining, and the expression changes of adipogenic genes like ACC, ATGL, CEBPβ, PPARγ, etc. Related mechanisms were verified by qPCR, a bioinformatic analysis, a dual-luciferase reporter assay, overexpression, and siRNA transfection. Oil Red O and BODIPY staining both with adipogenic gene detection showed that miR-10a-5p suppressed the accumulation of lipid droplets in GIPCs and inhibited its differentiation. The dual-luciferase reporter assay experiment revealed that miR-10a-5p regulates GIPC differentiation by directly binding to KLF8 3'UTR to regulate its expression. Thus, the results indicated that miR-10a-5p inhibits GIPC differentiation by targeting KLF8 and supply a new target for fat deposition and meat quality improvement.
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http://dx.doi.org/10.3389/fmolb.2021.700078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418121PMC
August 2021

Identification of Immune-Related Genes in Sepsis due to Community-Acquired Pneumonia.

Comput Math Methods Med 2021 26;2021:8020067. Epub 2021 Aug 26.

Department of Emergency, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Minhang District, Shanghai 201199, China.

Background: Immunosuppression has a key function in sepsis pathogenesis, so it is of great significance to find immune-related markers for the treatment of sepsis.

Methods: Datasets of community-acquired pneumonia (CAP) with sepsis from the ArrayExpress database were extracted. Differentially expressed genes (DEGs) between the CAP group and normal group by Limma package were performed. After calculation of immune score through the ESTIMATE algorithm, the DEGs were selected between the high immune score group and the low immune score group. Enrichment analysis of the intersected DEGs was conducted. Further, the protein-protein interaction (PPI) of the intersected DEGs was drawn by Metascape tools. Related publications of the key DEGs were searched in NCBI PubMed through Biopython models, and RT-qPCR was used to verify the expression of key genes.

Results: 360 intersected DEGs (157 upregulated and 203 downregulated) were obtained between the two groups. Meanwhile, the intersected DEGs were enriched in 157 immune-related terms. The PPI of the DEGs was performed, and 8 models were obtained. In sepsis-related research, eight genes were obtained with degree ≥ 10, included in the models.

Conclusion: CXCR3, CCR7, HLA-DMA, and GPR18 might participate in the mechanism of CAP with sepsis.
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http://dx.doi.org/10.1155/2021/8020067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413041PMC
August 2021

Positive regulation of TFEB and mitophagy by PGC-1α to alleviate LPS-induced acute lung injury in rats.

Biochem Biophys Res Commun 2021 Nov 24;577:1-5. Epub 2021 Aug 24.

Department of Respiratory, The Second Affiliated Hospital, The Air Force Military Medical University, Xi'an, 710038, ShaanXi, China. Electronic address:

Aim Of The Study: Acute lung injury (ALI) exhibits the features of noncardiogenic pulmonary edema and acute inflammatory process, and it also displays significant morbidity and mortality rates. This work focused on identifying how overexpression of PPARγ coactivator 1α (PGC-1α) positively regulated TFEB and mitophagy for resisting the lipopolysaccharide (LPS)-mediated ALI.

Materials And Methods: The levels of autophagic proteins and inflammatory factors in LPS-induced ALI rats and primary type II alveolar epithelial cells were measured, respectively. Lung wet/dry ratios were calculated. Protein co-immunoprecipitation of PGC-1α and TFEB was detected. To explore the interaction between TFEB and PGC-1α, a luciferase reporter assay was conducted.

Results: The results showed that overexpression of PGC-1α decreases IL-1 and IL-6 but increases IL-10 in LPS-mediated ALI rats and type II alveolar epithelial cells (P < 0.05). Overexpression of PGC-1α can reduce lung edema in LPS-mediated ALI rats (P < 0.05). Overexpression of PGC-1α upregulates mitophagy-related proteins, such as TFEB, LC3B, Beclin, and LAMP1, and improves mitophagy in LPS-induced ALI. Protein immunoprecipitation indicated that TFEB and PGC-1α are interacting proteins. The luciferase reporter assay demonstrated that PGC-1α positively regulated TFEB in the LPS-induced primary type II alveolar epithelial cells.

Conclusion: PGC-1α protects LPS-induced ALI by decreasing inflammation and alleviating lung edema. The mechanism might be positive regulation of TFEB directly and then upregulation of mitophagy in LPS-induced ALI.
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http://dx.doi.org/10.1016/j.bbrc.2021.08.064DOI Listing
November 2021

Hyaluronic Acid Coating Reduces the Leakage of Melittin Encapsulated in Liposomes and Increases Targeted Delivery to Melanoma Cells.

Pharmaceutics 2021 Aug 11;13(8). Epub 2021 Aug 11.

Department of Pharmaceutics, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Melittin is a promising antitumor substance; however, it is a nonspecific cytolytic peptide, which limits its clinical application. In this study, melittin liposomes (Mel-Lip) and hyaluronic acid (HA)-modified Mel-Lip (Mel-HA-Lip) were designed to reduce the toxicity and increase the anti-tumor effects of melittin. The optimal preparation procedure was evaluated using a uniform design based on the single factor method, and the concentration of HA was determined based on the cellular uptake of coumarin 6 labeled HA-Lip. Liposomes and HA-modified liposomes were evaluated in vitro by assessing cytotoxicity, cellular uptake, and release behavior. Liposomes prepared in the optimum formulation improved stability, with a particle size of 132.7 ± 1.55 nm, zeta potential of -11.5 ± 1.51 mV, entrapment efficiency of 86.25 ± 1.28%, and drug-loading efficiency of 3.91 ± 0.49%. Cellular uptake tests revealed that the uptake of nanoparticles significantly increased with HA modification, suggesting that HA modification enhanced the internalization of liposomes within cells, which was consistent with the results of the cytotoxicity analysis. Furthermore, in vitro release experiments showed that Mel-HA-Lip possessed a stronger sustained-release effect compared with Mel-Lip. The results of this experiment provide insight into the potential tumor-targeting effects of melittin.
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http://dx.doi.org/10.3390/pharmaceutics13081235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398362PMC
August 2021

Towards the sustainable discovery and development of new antibiotics.

Nat Rev Chem 2021 Aug 19:1-24. Epub 2021 Aug 19.

Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), and Department of Pharmacy, Saarland University Campus E8.1, Saarbrücken, Germany.

An ever-increasing demand for novel antimicrobials to treat life-threatening infections caused by the global spread of multidrug-resistant bacterial pathogens stands in stark contrast to the current level of investment in their development, particularly in the fields of natural-product-derived and synthetic small molecules. New agents displaying innovative chemistry and modes of action are desperately needed worldwide to tackle the public health menace posed by antimicrobial resistance. Here, our consortium presents a strategic blueprint to substantially improve our ability to discover and develop new antibiotics. We propose both short-term and long-term solutions to overcome the most urgent limitations in the various sectors of research and funding, aiming to bridge the gap between academic, industrial and political stakeholders, and to unite interdisciplinary expertise in order to efficiently fuel the translational pipeline for the benefit of future generations.
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http://dx.doi.org/10.1038/s41570-021-00313-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374425PMC
August 2021

KLF4 Inhibits the Differentiation of Goat Intramuscular Preadipocytes Through Targeting C/EBPβ Directly.

Front Genet 2021 4;12:663759. Epub 2021 Aug 4.

Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu, China.

Intramuscular fat (IMF) deposition is a complicated process, and most of the underlying regulators of this biological process are unknown. Here, we cloned the intact CDS of gene, investigated the role of KLF4 by gaining or losing function and further explored the pathways of KLF4 regulating differentiation of intramuscular preadipocytes in goat. Our results show that goat gene consists of 1,536 bp encoding a protein of 486 amino acids. The expression of KLF4 is higher in the lung while lower in the heart and muscle in goat. Knockdown of KLF4 mediated by siRNA technique significantly promotes intramuscular preadipocyte lipid accumulation and upregulates mRNA expression of adipogenic related genes including C/EBPα, C/EBPβ, and PPARγ cultured cells. Consistently, overexpression of KLF4 inhibits intramuscular adipocyte lipid accumulation and significantly downregulation gene expression of C/EBPβ, PPARγ, , and Pref-1. Further, we found that other members of KLFs were upregulated or downregulated after interference or overexpression of KLF4, including KLF2 and KLF5-7. We also found that C/EBPβ was a potential target of KLF4, because it had an opposite expression pattern with KLF4 during the differentiation of intramuscular preadipocytes and had putative binding sites of KLF4. The dual-luciferase reporter assay indicated that overexpression of KLF4 inhibited the transcriptional activity of C/EBPβ. These results demonstrate that KLF4 inhibits the differentiation of intramuscular preadipocytes in goat by targeting C/EBPβ.
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http://dx.doi.org/10.3389/fgene.2021.663759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373462PMC
August 2021

Exploring the relationship between urbanization and water environment based on coupling analysis in Nanjing, East China.

Environ Sci Pollut Res Int 2021 Aug 19. Epub 2021 Aug 19.

College of Urban and Environmental Sciences, Jiangsu Second Normal University, Nanjing, 210013, China.

The degradation of water environment (WE) has constrained the sustainable development of cities, while the rapid urbanization also exacerbates water environment change. However, the complicated relationship between urbanization and WE is far from clearly understood. In this study, a comprehensive index system for urbanization and WE was applied along with the System Index Evaluation Model (SIEM) and a Coupling Coordination Degree Model (CCDM) to analyze the coupling between urbanization and WE in Nanjing, East China, from 1990 to 2018. The comprehensive index of urbanization increased from 0.0392 in 1990 to 0.9890 in 2018, showing a clear increasing trend. Demographic and spatial urbanization made the largest contribution to urbanization development from 1990 to 2010, while economic urbanization became the largest contributor to urbanization development between 2011 and 2018. Under the combined effects of pressure, state, and response subsystems, the comprehensive WE index showed an upward trend with some fluctuations from 1990 to 2018. The degree of coupling coordination between urbanization and WE displayed an overall upward tendency, growing from 0.18 in 1990 to 0.95 in 2018. The coupling coordination state transitioned from a serious imbalance during the low coupling period (1990-1992) into the superior coordination of the highly coupled period (2011-2018). With the continuous urbanization in the future, in addition to ensuring the optimal management of surface water, protection of groundwater should be reinforced. The results advance our understanding of the dynamic relationship between urbanization and WE and provide important implications for urban planning and water resource protection.
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http://dx.doi.org/10.1007/s11356-021-15161-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374037PMC
August 2021

Analysis of Prevalence, Influencing Factors, and Countermeasures of Short Stature in Children and Adolescents Aged 6∼14 in Furong District, Changsha City, in 2020.

Evid Based Complement Alternat Med 2021 6;2021:3933854. Epub 2021 Aug 6.

Department of Pediatric Orthopedics, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, Guangdong, China.

In recent years, children's and adolescents' growth and development issues have received increasing attention with the socioeconomic development. The etiology of child short stature involves heredity, race, sex, nutrition, and a variety of endocrine hormones, which is very complex. The age of 6∼14 is the key period of children's development. Understanding the height characteristics, the prevalence of short stature, and its influencing factors at this stage and formulating preventive measures as soon as possible are conducive to improving the average height of children and reducing the incidence of short stature. In this study, cluster sampling was used to select 56,865 children and adolescents aged 6∼14 years old from 40 primary and secondary schools in Furong District of Changsha City, and the height of each child and adolescent was measured. The results showed that the overall crude prevalence of short stature in children aged 6∼14 in Furong District of Changsha is 2.82%. Growth hormone level <10 g/L, pubertal retardation, familial short stature, low egg intake, and intrauterine growth retardation are independent risk factors affecting the occurrence of short stature. In order to improve the status quo of short stature of children aged 6∼14 in Furong District, Changsha City, targeted intervention should be strengthened for people with combined high risk factors.
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http://dx.doi.org/10.1155/2021/3933854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367590PMC
August 2021

A novel multi-functionalized multicellular nanodelivery system for non-small cell lung cancer photochemotherapy.

J Nanobiotechnology 2021 Aug 14;19(1):245. Epub 2021 Aug 14.

Department of Pharmaceutical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

Background: A red blood cell membrane (RBCm)-derived drug delivery system allows prolonged circulation of an antitumor treatment and overcomes the issue of accelerated blood clearance induced by PEGylation. However, RBCm-derived drug delivery systems are limited by low drug-loading capacities and the lack of tumor-targeting ability. Thus, new designs of RBCm-based delivery systems are needed.

Results: Herein, we designed hyaluronic acid (HA)-hybridized RBCm (HA&RBCm)-coated lipid multichambered nanoparticles (HA&RBCm-LCNPs) to remedy the limitations of traditional RBCm drug delivery systems. The inner core co-assembled with phospholipid-regulated glycerol dioleate/water system in HA&RBCm-LCNPs met the required level of blood compatibility for intravenous administration. These newly designed nanocarriers had a honeycomb structure with abundant spaces that efficiently encapsulated paclitaxel and IR780 for photochemotherapy. The HA&RBCm coating allowed the nanocarriers to overcome the reticuloendothelial system barrier and enhanced the nanocarriers specificity to A549 cells with high levels of CD44. These properties enhanced the combinatorial antitumor effects of paclitaxel and IR780 associated with microtubule destruction and the mitochondrial apoptotic pathway.

Conclusions: The multifunctional HA&RBCm-LCNPs we designed expanded the functionality of RBCm and resulted in a vehicle for safe and efficient antitumor treatment.
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http://dx.doi.org/10.1186/s12951-021-00977-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364713PMC
August 2021

Integrated biocontrol of tobacco bacterial wilt by antagonistic bacteria and marigold.

Sci Rep 2021 08 11;11(1):16360. Epub 2021 Aug 11.

State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Science, Hubei University, Wuhan, 430062, China.

Tobacco bacterial wilt (TBW) is seriously damages the growth of tobacco. There is an urgent need to find a safer and more effective measure to control TBW. In this study, B. amyloliquefaciens ZM9 and marigold powder were applied to the tobacco roots alone or in combination, and the potential inhibition of TBW was assessed. On the other hand, the effects of these treatments on soil physicochemical properties, rhizosphere microbial community and soil metabolites were also evaluated. The results showed that the application of B. amyloliquefaciens ZM9 or marigold powder alone significantly reduced the abundance of R. solanacearum in rhizosphere soil, while the integrated treatment showed the strongest inhibitory effect. Moreover, the integrated treatment can inhibit the secretion of chemoattractants, and affect the change of rhizosphere soil microbial composition. In conclusion, the combination of antagonistic bacteria agent B. amyloliquefaciens ZM9 with marigold powder can enhance the suppression of TBW. Furthermore, B. amyloliquefaciens ZM9 and marigold have synergistic effects on suppressing TBW by regulation soil physicochemical properties, soil metabolites and microbial structure. This study provide a promising strategy for TBW control by integrated applying of B. amyloliquefaciens ZM9 and marigold powder.
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http://dx.doi.org/10.1038/s41598-021-95741-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357815PMC
August 2021

The effects of sacubitril/valsartan on heart failure with preserved ejection fraction: a meta-analysis.

Acta Cardiol 2021 Aug 11:1-9. Epub 2021 Aug 11.

Department of Cardiovascular Diseases, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, P.R. China.

Background: Compared with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, Sacubitril/Valsartan has been reported to have superior results. However, the effects of sacubitril/valsartan on heart failure with preserved ejection fraction (HFpEF) are still in dispute.

Objectives: This study aims to evaluate the effects of sacubitril/valsartan on the treatment of HFpEF patients.

Methods: PubMed, Embase, Web of Science, Cochrane Library, and Clinicaltrials.gov were used to search for randomised controlled trials of sacubitril/valsartan in HFpEF patients from inception to 7 December 2020.

Results: Four studies, with a total of 7739 participants, met the inclusion criteria. The present meta-analysis results showed that compared with the control group, sacubitril/valsartan reduced the hospitalisation rate of HF in HFpEF patients [Risk Ratio(RR): 0.85; 95% confidence interval (CI): 0.79-0.93;  = 0.0002). Regarding all-cause mortality, cardiovascular mortality, and the improvement in NYHA class, sacubitril/valsartan did not show apparent advantages. Although sacubitril/valsartan was linked to increasing the risk of symptomatic hypotension (RR: 1.44; 95% CI: 1.25-1.66; ﹤0.00001), there was no evidence supporting the incidence of renal function worsening and hyperkalemia.

Conclusion: Our study shows that compared with valsartan or individualised medical therapy (IMT), there were not different between the two groups except for the hospitalisation rate which was favoured by Sacubitril/Valsartan treatment group for HFpEF patients.
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http://dx.doi.org/10.1080/00015385.2021.1963101DOI Listing
August 2021

Intrinsic bioactivity of black phosphorus nanomaterials on mitotic centrosome destabilization through suppression of PLK1 kinase.

Nat Nanotechnol 2021 Oct 5;16(10):1150-1160. Epub 2021 Aug 5.

Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.

Although nanomaterials have shown promising biomedical application potential, incomplete understanding of their molecular interactions with biological systems prevents their inclusion into mainstream clinical applications. Here we show that black phosphorus (BP) nanomaterials directly affect the cell cycle's centrosome machinery. BP destabilizes mitotic centrosomes by attenuating the cohesion of pericentriolar material and consequently leads to centrosome fragmentation within mitosis. As a result, BP-treated cells exhibit multipolar spindles and mitotic delay, and ultimately undergo apoptosis. Mechanistically, BP compromises centrosome integrity by deactivating the centrosome kinase polo-like kinase 1 (PLK1). BP directly binds to PLK1, inducing its aggregation, decreasing its cytosolic mobility and eventually restricting its recruitment to centrosomes for activation. With this mechanism, BP nanomaterials show great anticancer potential in tumour xenografted mice. Together, our study reveals a molecular mechanism for the tumoricidal properties of BP and proposes a direction for biomedical application of nanomaterials by exploring their intrinsic bioactivities.
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http://dx.doi.org/10.1038/s41565-021-00952-xDOI Listing
October 2021
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