Publications by authors named "Shu Wang"

1,458 Publications

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Transverse and longitudinal coupling of LSPPs in isolated triangular Al-SiO-Al hybrid nanoplates for generation of local electromagnetic fields with enhanced intensity and increased decay time.

Nanotechnology 2021 Sep 16. Epub 2021 Sep 16.

National Center for Nanoscience and Nanotechnology, No 11,Beiyitiao 11,Zhongguancun, Beijing, 100190, CHINA.

Achieving a large enhancement of local electromagnetic fields in the ultraviolet waveband is desirable for some applications such as surface-enhanced Raman scattering and surface-enhanced fluorescence. In addition, it is more significant for some applications such as plasmon-enhanced harmonic generation to enhance the intensity of local electromagnetic fields and increase their decay time at the same time. In this paper, using the finite-difference time-domain method, we numerically demonstrate that using the linearly polarized light with a wavelength of 325 nm as the illumination light, an isolated triangular Al-SiO-Al hybrid nanoplate with optimized geometric parameters can produce a local electric field enhanced by a factor of about 108 at one of its top apexes, and produce two local electric fields enhanced by a factor of about 150 at two transverse dielectric/metal interfaces of one of its longitudinal side edges. Moreover, we also numerically demonstrate that the decay time of enhanced local electric fields produced by the isolated triangular Al-SiO-Al hybrid nanoplate is about 1.6 times as large as that of enhanced local electric fields produced by an isolated triangular Al nanoplate. These unique properties of the isolated triangular Al-SiO-Al hybrid nanoplate arise because of both the transverse coupling and the longitudinal coupling of localized surface plasmon polaritons (LSPPs) in this structure. Our findings make triangular Al-SiO-Al hybrid nanoplates very promising for application in many fields such as surface-enhanced Raman scattering and plasmon-enhanced harmonic generation.
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http://dx.doi.org/10.1088/1361-6528/ac2767DOI Listing
September 2021

Morphological canalization, integration, and plasticity in response to population density in : Influences of soil conditions and growth stages.

Ecol Evol 2021 Sep 28;11(17):11945-11959. Epub 2021 Jul 28.

Northeast Institute of Geography and Agroecology Chinese Academy of Sciences Changchun China.

Phenotypic integration and developmental canalization have been hypothesized to constrain the degree of phenotypic plasticity, but little evidence exists, probably due to the lack of studies on the relationships among the three processes, especially for plants under different environments. We conducted a field experiment by subjecting plants of to three densities, under infertile and fertile soil conditions, and analyzing correlations among canalization, integration, and plasticity in a variety of measured morphological traits after 50 and 70 days, to investigate the relationships among the three variables in response to density and how these responses vary with soil conditions and growth stages. Results showed trait canalization decreased and phenotypic integration and the degree of plasticity (absolute plasticity) in traits increased with density. Phenotypic integration often positively correlated with absolute plasticity, whereas correlations between trait canalization and plasticity were insignificant in most cases, with a few positive ones between canalization and absolute plasticity at low and medium densities. As plants grew, these correlations intensified in infertile soil and attenuated in fertile soil. Our findings suggested the complexity of the relationship between canalization and plasticity: Decreased canalization is more likely to facilitate active plastic responses under more favorable conditions, whereas increased level of integration should mainly be an outcome of plastic responses. Soil conditions and growth stage may affect responses of these correlations to density via modifying plant size, competition strength, and plastic responses in traits. We also predicted that decreased canalization can be advantageous or disadvantageous, and the lack of response to stress may demonstrate a stronger ability of adaptation than passive response, thus should be adaptive plasticity as active response.
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http://dx.doi.org/10.1002/ece3.7960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427568PMC
September 2021

Fluorescence excitation-emission matrix as a novel indicator of assimilable organic carbon in wastewater: Implication from a coal chemical wastewater study.

Sci Total Environ 2021 Sep 8;804:150144. Epub 2021 Sep 8.

State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing 100084, China; Research and Application Center for Membrane Technology, School of Environment, Tsinghua University, Beijing 100084, China. Electronic address:

Assimilable organic carbon (AOC) is recognized as an important parameter to evaluate the biostability of water. Studies have been carried out to investigate the easier and faster AOC detection methods in recent years. In our study, the relationship between AOC and excitation-emission matrix (EEM) was investigated through analysis of wastewater from a coal chemical industrial corporation, including biochemical effluent, ultrafiltration effluent, and reverse osmosis concentrate. Considering the influence of water sample properties on AOC distribution, these water samples were fractionated according to their hydrophilicity and acid/base properties. Neutrals and hydrophobic acids were major components of total organic carbon and AOC concentration of these fractions was measured. EEM spectra of water samples were divided into five regions according to fluorescence peaks. Distribution of fluorescence region integration (FRI) of water samples was also calculated, as well as other fluorescence parameters. Statistical analysis showed that the concentration of AOC presented high positive correlation with the FRI in region H2, with R = 0.696. Monte Carlo simulation also proved that the proportion of significant R (p < 0.05) was high at 89.1%, suggesting that the model was reliable at least at the qualitative level. In that case, FRI in Region H2 could be an indication for AOC concentration in water samples. Our findings focus on fundamental insights into establishing relationship between spectroscopy method and AOC in wastewater and provide an easier way of accessing AOC in coal chemical industrial wastewater. Further investigation could be oriented to the dynamic analysis of AOC transformation and tracing.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150144DOI Listing
September 2021

Toxic mechanisms and pharmacological properties of euptox A, a toxic monomer from A. adenophora.

Fitoterapia 2021 Sep 10:105032. Epub 2021 Sep 10.

Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan Province, China. Electronic address:

A. adenophora (Spreng.) R.M. King & H. Rob. is as invasive plant known to cause toxicity in humans and animals. The plant's toxic activities have been associated with some toxic phytochemicals present in the plant. One of the major phytochemicals that have been reported to induce toxicity in various organs is euptox A (9-oxo-10, 11-dehydroageraphorone). Previous studies have reported that the main target organs of euptox A are the liver and spleen. Although, many studies have reported on euptox A toxicity in rats and mice, the mechanism of action and the beneficial uses of this toxin as well as it potential uses have not been fully established in literatures. Therefore, this review firstly, aims at elaborating on the toxic effects and mechanism of action of euptox A to give basic knowledge to researchers to help in the development of strategies that will reduce its toxicity to the environment. Secondly, this paper will also report on some beneficial uses of euptox A in recent years as well as suggest some future potential applications of this toxin to help in the utilization of this plant resource.
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http://dx.doi.org/10.1016/j.fitote.2021.105032DOI Listing
September 2021

Electroacupuncture Improves Clearance of Amyloid- through the Glymphatic System in the SAMP8 Mouse Model of Alzheimer's Disease.

Neural Plast 2021 26;2021:9960304. Epub 2021 Aug 26.

First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Background: Memory loss and cognitive impairment characterize the neurodegenerative disorder, Alzheimer's disease (AD). Amyloid- (A) is the key factor that triggers the course of AD, and reducing the deposition of A in the brain has been considered as a potential target for the treatment of AD. In clinical and animal studies, electroacupuncture (EA) has been shown to be an effective treatment for AD. In recent years, substantial evidence has accumulated suggesting the important role of the glymphatic system in A clearance.

Objective: The purpose of this study was to explore whether EA modifies the accumulation of A through the glymphatic system and may thus be applied to alleviate cognitive impairments.

Methods: Seven-month-old SAMP8 mice were randomized into a control group (Pc) and an electroacupuncture group (Pe). Age-matched SAMR1 mice were used as normal controls (Rc). Mice in the Pe group were stimulated on Baihui (GV20) and Yintang (GV29) for 10 min and then pricked at Shuigou (GV26) for ten times. EA treatment lasted for 8 weeks. In each week, EA would be applied once a day for the first five consecutive days and ceased at the remaining two days. After EA treatment, Morris water maze (MWM) test was used to evaluate the cognitive function; HE and Nissl staining was performed to observe the brain histomorphology; ELISA, contrast-enhanced MRI, and immunofluorescence were applied to explore the mechanisms underlying EA effects from A accumulation, glymphatic system function, reactivity of astrocytes, and AQP4 polarization, respectively.

Results: This EA regime could improve cognition and alleviate neuropathological damage to brain tissue. And EA treatment might reduce A accumulation, enhance paravascular influx in the glymphatic system, inhibit the reactivity of astrocytes, and improve AQP4 polarity.

Conclusion: EA treatment might reduce A accumulation from the brain via improving clearance performance of the glymphatic system and thereby alleviating cognitive impairment.
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http://dx.doi.org/10.1155/2021/9960304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416373PMC
August 2021

The Accuracy of Patient Specific Three-Dimensional Digital Ostectomy Template for Mandibular Angle Ostectomy.

Aesthet Surg J 2021 Sep 2. Epub 2021 Sep 2.

Department of Plastic Surgery, The Affiliated Friendship Plastic Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.

Background: Despite the three-dimensional (3D)-printed digital ostectomy template (DOT) helps surgeons perform mandibular angle ostectomy (MAO) more precisely and safely, the clinical application of DOT is problematic.

Objectives: The aim of this study was to evaluate the accuracy of DOT and improve the precision of MAO.

Methods: A total of 20 patients with a prominent mandibular angle (PMA) were allocated into two groups with 10 patients in each group. The conventional digital ostectomy template (CDOT), and the novel digital ostectomy template (NDOT) were applied to guide MAO in group A and B, respectively. The mean time taken for curved osteotomy and the volume of postoperative drainage on one side within 24 hours were recorded. The deviations between the simulated and postoperative lower border of the mandible were measured on both sides.

Results: All the patients were satisfied with the cosmetic outcomes. Statistical results showed that the mean time taken for curved osteotomy in group B was shorter than that of group A, and the volume of postoperative drainage on one side within 24 hours was similar between the two groups. The deviations at the anterior and posterior parts of the inferior border showed the accuracy of osteotomy in group B was higher than that in group A, and there was no significant difference between the two groups in the middle part.

Conclusions: The NDOT is easy to be located and fixed tightly, which reduced the operating time and increased the safety and precision of the procedures.
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http://dx.doi.org/10.1093/asj/sjab330DOI Listing
September 2021

CXCR4 and anti-BCMA CAR co-modified natural killer cells suppress multiple myeloma progression in a xenograft mouse model.

Cancer Gene Ther 2021 Sep 1. Epub 2021 Sep 1.

Department of Biological Sciences, National University of Singapore, Singapore, Singapore.

The highly restricted expression of B-cell maturation antigen (BCMA) on plasma cells makes it an ideal target for chimeric antigen receptor (CAR) immune cell therapy against multiple myeloma (MM), a bone marrow cancer. To improve the infiltration of ex vivo expanded human natural killer (NK) cells into the bone marrow, we electroporated these cells with mRNA encoding the chemokine receptor CXCR4. The CXCR4-modified NK cells displayed increased in vitro migration toward the bone marrow niche-expressing chemokine CXCL12/SDF-1α and augmented infiltration into the bone marrow compartments in mice. We further modified the CXCR4-NK cells by electroporation of mRNA encoding a CAR targeting BCMA. After the intravenous injection of the double-modified NK cells into a xenograft mouse model of MM, we observed significantly reduced tumor burden in the femur region of the living mice and the extended survival of the tumor-bearing mice. Collectively, this study provides the experimental evidence that the co-expression of CXCR4 and anti-BCMA CAR on NK cells is a possible effective way to control MM progression.
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http://dx.doi.org/10.1038/s41417-021-00365-xDOI Listing
September 2021

SNP rs4971059 predisposes to breast carcinogenesis and chemoresistance via TRIM46-mediated HDAC1 degradation.

EMBO J 2021 Aug 30:e107974. Epub 2021 Aug 30.

Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China.

Identification of the driving force behind malignant transformation holds the promise to combat the relapse and therapeutic resistance of cancer. We report here that the single nucleotide polymorphism (SNP) rs4971059, one of 65 new breast cancer risk loci identified in a recent genome-wide association study (GWAS), functions as an active enhancer of TRIM46 expression. Recreating the G-to-A polymorphic switch caused by the SNP via CRISPR/Cas9-mediated homologous recombination leads to an overt upregulation of TRIM46. We find that TRIM46 is a ubiquitin ligase that targets histone deacetylase HDAC1 for ubiquitination and degradation and that the TRIM46-HDAC1 axis regulates a panel of genes, including ones critically involved in DNA replication and repair. Consequently, TRIM46 promotes breast cancer cell proliferation and chemoresistance in vitro and accelerates tumor growth in vivo. Moreover, TRIM46 is frequently overexpressed in breast carcinomas, and its expression is correlated with lower HDAC1 expression, higher histological grades, and worse prognosis of the patients. Together, our study links SNP rs4971059 to replication and to breast carcinogenesis and chemoresistance and support the pursuit of TRIM46 as a potential target for breast cancer intervention.
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http://dx.doi.org/10.15252/embj.2021107974DOI Listing
August 2021

Effectiveness of Adding Everolimus to the First-line Treatment of Advanced Breast Cancer in Premenopausal Women Who Experienced Disease Progression While Receiving Selective Estrogen Receptor Modulators: A Phase 2 Randomized Clinical Trial.

JAMA Oncol 2021 Aug 26:e213428. Epub 2021 Aug 26.

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

Importance: The effectiveness of the mammalian target of rapamycin (mTOR) inhibitor everolimus in premenopausal women with hormone receptor (HR)-positive/ERBB2-negative advanced breast cancer who experienced disease progression while receiving selective estrogen receptor modulators (SERMs) is unknown.

Objective: To compare the effectiveness of everolimus plus letrozole vs letrozole alone in premenopausal women with HR-positive/ERBB2-negative advanced breast cancer who experienced disease progression while receiving SERMs.

Design, Setting, And Participants: The Everolimus Trial for Advanced Premenopausal Breast Cancer (MIRACLE) was a multicenter, open-label phase 2 randomized clinical trial of everolimus plus letrozole vs letrozole alone as first-line treatment conducted from December 8, 2014, to September 26, 2018. Participants included premenopausal women with HR-positive, ERBB2-negative advanced breast cancer who experienced disease progression while receiving SERMs. Analysis was performed on an intent-to-treat basis from January 5, 2015, to December 30, 2019.

Exposures: Patients were randomly assigned in a 1:1 ratio to receive everolimus (10 mg orally once daily) plus letrozole (2.5 mg orally once daily) (n = 101) or letrozole alone (2.5 mg orally once daily) (n = 98). Both groups received goserelin, 3.6 mg, subcutaneously on day 1 of each 28-day cycle. Patients in the letrozole group were permitted to cross over to receive everolimus with letrozole if disease progression occurred.

Main Outcomes And Measures: The primary end point was progression-free survival (PFS), defined as the time from randomization to confirmed disease progression or death due to any cause.

Results: A total of 199 women (mean [SD] age, 44.3 [6.3] years) were randomized. Patients receiving everolimus plus letrozole achieved a significantly longer median PFS compared with those receiving letrozole alone (19.4 months [95% CI, 16.3-22.0 months] vs 12.9 months [95% CI, 7.6-15.7 months]; hazard ratio, 0.64 [95% CI, 0.46-0.89]; P = .008). A total of 56 of the 98 patients in the letrozole group (57.1%) were crossed over to also receive everolimus. The median PFS after crossover was 5.5 months (95% CI, 3.8-8.2 months).

Conclusions And Relevance: In this randomized clinical trial, PFS was significantly longer among premenopausal patients with HR-positive/ERBB2-negative advanced breast cancer who received everolimus plus letrozole than among those who received letrozole alone. The results revealed that everolimus was effective even among patients receiving treatment with the same endocrine agent after disease progression.

Trial Registration: ClinicalTrials.gov Identifier: NCT02313051.
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http://dx.doi.org/10.1001/jamaoncol.2021.3428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391779PMC
August 2021

Spatial distribution and health risk assessment of dissolved heavy metals in groundwater of eastern China coastal zone.

Environ Pollut 2021 Aug 20;290:118016. Epub 2021 Aug 20.

College of Earth Science and Engineering, Shandong University of Science and Technology, Qingdao, 266510, China.

Environmental changes and human activities have deteriorated the quality of groundwater, which is an important source of freshwater in coastal areas. The Jiangsu Coastal Zone (JCZ), which is a typical area of the eastern China coastal zone (ECCZ), has a great demand for clean water resources due to its dense population. The groundwater in the JCZ is affected by both human activities and seawater intrusion. However, research on heavy metals in the groundwater of the JCZ is limited. This study investigated the spatial distribution characteristics and influencing factors of heavy metals in coastal groundwater of Jiangsu Province and conducted a health risk assessment (HRA). Relatively high concentrations of Cu, Cd, Pb, Co, Zn, and Ba existed in the northern JCZ, while As and B predominated in the central JCZ. The main heavy metal pollutants in the groundwater are B and As, with mean values at 0.61 mg/L and 0.02 mg/L, exceeding the standard rate reaching 48.28% and 18.07% respectively. The HRA results showed that B had the largest hazard quotient (HQ), accounting for 50.22% of the total HQs, and As was attributed to the pollutant with the largest cancer risk (CR), accounting for 99.74% of the total CRs. According to the results of the correlation analysis, heavy metals in the groundwater of JCZ mainly originated from industrial pollution, seawater intrusion, and mineral dissolution. Seawater intrusion increases the content of As and B in groundwater, leading to higher health risks. Therefore, the government should strengthen the supervision of seawater intrusion by implementing more effective water resource management policies, or adopting engineering measures such as installing subsurface physical barriers to prevent and control seawater intrusion.
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http://dx.doi.org/10.1016/j.envpol.2021.118016DOI Listing
August 2021

Full Solar-Spectrum-Driven Antibacterial Therapy over Hierarchical Sn O /PDINH with Enhanced Photocatalytic Activity.

Small 2021 Aug 21:e2102744. Epub 2021 Aug 21.

Institute for Advanced Interdisciplinary Research (iAIR), University of Jinan, Jinan, 250022, P. R. China.

Antibacterial photocatalytic therapy (APCT) is considered to be a potential treatment for administrating antibiotic-resistant bacteria. However, due to the low photocatalytic efficiency and weak ability to capture bacteria, it is not practically applied. In this work, an organic-metal oxide hybrid semiconductor heterostructure is fabricated for the photocatalytic generation of reactive oxygen species (ROS) to kill the drug-resistant bacteria. The organic semiconductor, perylene diimide (PDI), can self-assemble on Sn O nanosheets to form a "hook-and-loop" sticky surface that can capture bacteria, via large numbers of hydrogen bonding and π-π stacking interactions, which are not possible in inorganic semiconductors. This easy-to-fabricate hybrid semiconductor also possesses improved photocatalytic activity, which is owing to the formation of heterostructure that achieves full-spectrum absorption, and the reduction of the photocarrier recombination rate to produce more reactive oxygen species. It has a good promoting effect on the wounds of mice infected by Staphylococcus aureus. This work shows new ideas for fabricating smart full-spectrum inorganic-organic hybrid adhesive heterostructure photocatalysts for antibacterial photocatalytic therapy.
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http://dx.doi.org/10.1002/smll.202102744DOI Listing
August 2021

The Relationship Between "Protect People's Livelihood" and "Promote the Economy:" Provincial Evidence From China.

Front Public Health 2021 2;9:722062. Epub 2021 Aug 2.

School of Economics, Jilin University, Changchun, China.

This study focused on medical care in a single country (China) and in regions with different economic backgrounds and different economic development levels to determine the effect of healthcare expenditure on short- and long-term economic growth. The study supported some interesting conclusions: (1) For most areas of China, increasing healthcare expenditure has a negative impact on economic growth in the short term but promotes growth in the long run; (2) Under different levels of economic development within China, there is significant heterogeneity in the interaction between healthcare expenditure and economic growth; (3) The negative effects of healthcare expenditure on short-term economic growth are greater during periods of economic turbulence than during times of stability; and (4) Healthcare expenditure has a negative effect on underdeveloped areas through the accumulation of material capital, while in economically developed areas, this channel has the opposite effect. To improve the quality of medical and health protection and the quality of life and welfare, China needs to consider the development characteristics of different economic zones and establish a multilevel, systematic and diversified medical and health protection system.
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http://dx.doi.org/10.3389/fpubh.2021.722062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365510PMC
August 2021

CK-3, A Novel Methsulfonyl Pyridine Derivative, Suppresses Hepatocellular Carcinoma Proliferation and Invasion by Blocking the PI3K/AKT/mTOR and MAPK/ERK Pathways.

Front Oncol 2021 28;11:717626. Epub 2021 Jul 28.

Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, China.

Hepatocellular carcinoma (HCC) is an aggressive tumor with a poor prognosis that highly expresses phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (ERK). The PI3K/AKT/mTOR and MAPK/ERK signaling pathways play a crucial role in HCC tumor formation, cell cycle, apoptosis and survival. However, no effective targeted therapies against these pathways is available, mainly due to the extensive and complex negative feedback loops between them. Here we used CK-3, a dual blocker of the PI3K/AKT/mTOR and MAPK/ERK pathways, against HCC cell lines to verify its anti-tumor activity . CK-3 exhibited cytotoxic activity against HCC, as demonstrated with MTT and colony formation assays. The anti-metastatic potential of CK-3 was demonstrated with wound healing and cell invasion assays. The ability of CK-3 to block both the PI3K/AKT/mTOR and MAPK/ERK pathways was also confirmed. CK-3 induced the apoptosis of Hep3B cells, while Bel7402 cells died mitotic catastrophe (MC). Oral administration of CK-3 also inhibited the subcutaneous growth of BEL7402 cells in nude mice. Simultaneous PI3K/AKT/mTOR and MAPK/ERK pathway inhibition with CK-3 may be superior to single pathway monotherapies by inhibiting their feedback-regulation, and represents a potential treatment for HCC.
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http://dx.doi.org/10.3389/fonc.2021.717626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355706PMC
July 2021

Root morphological responses to population density vary with soil conditions and growth stages: The complexity of density effects.

Ecol Evol 2021 Aug 7;11(15):10590-10599. Epub 2021 Jul 7.

Northeast Institute of Geology and Agroecology Chinese Academy of Sciences Changchun China.

Aim: How plants cope with increases in population density via root plasticity is not well documented, although abiotic environments and plant ontogeny may have important roles in determining root response to density. To investigate how plant root plasticity in response to density varies with soil conditions and growth stages, we conducted a field experiment with an annual herbaceous species ().

Methods: Plants were grown at low, medium, and high densities (13.4, 36.0, and 121.0 plants m, respectively), under fertile and infertile soil conditions, and a series of root traits were measured after 30, 50, and 70 days.

Results: Root allocation increased, decreased, or canalized in response to density, depending on soil conditions and stages of plant growth, indicating the complex effects of population density, including both competitive and facilitative effects.

Main Conclusions: Root allocation was promoted by neighbor roots at early stages and in abundant resource availability, due to low-to-moderate belowground interactions among smaller plants, leading to facilitation. As plants grew, competition intensified and infertile soil aggravated belowground competition, leading to decreased root allocation in response to density. Root growth may be more likely restricted horizontally rather than vertically by the presence of neighbor, suggesting a spatial orientation effect in their responses to density. We emphasized the importance of considering effects of abiotic conditions and plant growth stages in elucidating the complexity of density effects on root traits.
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http://dx.doi.org/10.1002/ece3.7868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328429PMC
August 2021

Dilated densely connected U-Net with uncertainty focus loss for 3D ABUS mass segmentation.

Comput Methods Programs Biomed 2021 Sep 31;209:106313. Epub 2021 Jul 31.

Peking University People's Hospital, Beijing 100044, China.

Background And Objective: Accurate segmentation of breast mass in 3D automated breast ultrasound (ABUS) images plays an important role in qualitative and quantitative ABUS image analysis. Yet this task is challenging due to the low signal to noise ratio and serious artifacts in ABUS images, the large shape and size variation of breast masses, as well as the small training dataset compared with natural images. The purpose of this study is to address these difficulties by designing a dilated densely connected U-Net (DU-Net) together with an uncertainty focus loss.

Methods: A lightweight yet effective densely connected segmentation network is constructed to extensively explore feature representations in the small ABUS dataset. In order to deal with the high variation in shape and size of breast masses, a set of hybrid dilated convolutions is integrated into the dense blocks of the DU-Net. We further suggest an uncertainty focus loss to put more attention on unreliable network predictions, especially the ambiguous mass boundaries caused by low signal to noise ratio and artifacts. Our segmentation algorithm is evaluated on an ABUS dataset of 170 volumes from 107 patients. Ablation analysis and comparison with existing methods are conduct to verify the effectiveness of the proposed method.

Results: Experiment results demonstrate that the proposed algorithm outperforms existing methods on 3D ABUS mass segmentation tasks, with Dice similarity coefficient, Jaccard index and 95% Hausdorff distance of 69.02%, 56.61% and 4.92 mm, respectively.

Conclusions: The proposed method is effective in segmenting breast masses on our small ABUS dataset, especially breast masses with large shape and size variations.
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http://dx.doi.org/10.1016/j.cmpb.2021.106313DOI Listing
September 2021

TRPV1 and TRPA1 in melanocytes synergize UV-dependent and UV-independent melanogenesis.

Br J Pharmacol 2021 Aug 6. Epub 2021 Aug 6.

Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.

Background And Purpose: Melanogenesis is essential for pigmentation, and deregulated melanogenesis causes pigmentary diseases. PUVA therapy (psoralen plus ultraviolet A, UVA) strongly stimulates pigmentation, but the underlying molecular mechanisms are elusive.

Experimental Approach: Melanin content of cultured human melanocytes was spectrophotometrically measured. Patch-clamp recordings were made in human melanocytes or HEK 293 cells transiently expressing wild type or mutant human TRPV1 and TRPA1 channels. Endogenous expression of TRPV1 and TRPA1 in melanocytes was analyzed by western blotting and was knocked down with siRNA. In vivo pigmentary responses were measured by a colorimeter in mouse ear skin. The expression of TRPV1 and TRPA1 in human pigmented lesions was examined by immunohistochemical staining.

Key Results: PUVA strongly stimulated melanogenesis, and PUVA-induced TRPV1 and TRPA1 channel activation in melanocytes and the resulting Ca influx were required for the stimulated melanogenesis both in vitro and in vivo. Agonists-induced TRPV1 and TRPA1 activation alone did not stimulate melanogenesis, but it synergized UVA or intrinsic cAMP and NO signaling pathways to stimulate UV-dependent or UV-independent melanogenesis. Moreover, the expressions of TRPV1 and TRPA1 were increased in human melanocytic lesions, and inhibition of both channels decreased melanin content in melanoma cells.

Conclusion And Implications: TRPV1 and TRPA1 are key molecular sensors and enhancers of extrinsic and intrinsic melanogenic signals in both physiological and pathological conditions, and activation of both channels in melanocytes contributes to PUVA therapy-induced pigmentation. Our work provides a common mechanism of melanogenic regulation and highlights TRPV1 and TRPA1 as potential therapeutic targets for pigmentary disorders.
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http://dx.doi.org/10.1111/bph.15643DOI Listing
August 2021

Bioinspired, Nanostructure-Amplified, Subcutaneous Light Harvesting to Power Implantable Biomedical Electronics.

ACS Nano 2021 Aug 6. Epub 2021 Aug 6.

State Key Lab of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun 130012, China.

Implantable biomedical electronics hold immense promise for personalized healthy monitoring and even precise therapeutic intervention. Tremendous miniaturization of indwelling modules enables implanted biomedical devices to perform multiple functions with ultralow power consumption but exacerbates the technical challenges of supplying effective power to the devices . In this Perspective, we summarize new developments in transmitting near-infrared light from sunlight or a light-emitting diode into subcutaneously implanted photovoltaic cells, in which the light utilization efficiency can be amplified with the aid of nanostructured rear reflectors. Considering the many natural examples of nanostructure-induced structural coloration displayed by submarine animals, we wish to open up new prospects of bioinspired, nanostructure-amplified, subcutaneous light harvesting to power implanted biomedical electronics.
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http://dx.doi.org/10.1021/acsnano.1c03614DOI Listing
August 2021

Leaching behavior of polycyclic aromatic hydrocarbons (PAHs) from oil-based residues of shale gas drill cuttings.

Environ Pollut 2021 Jul 16;288:117773. Epub 2021 Jul 16.

Department of Environmental Science and Engineering, Sichuan University, Sichuan Research Center for Soil Environment Protection Engineering and Technology, Chengdu, 610065, China. Electronic address:

Cuttings are the main solid residues which are generated from drilling operations. Due to the presence of heavy and radioactive elements, the environment risk posed by cuttings has attracted increasing attention. In this work, a short-term static immersion experiment was carried out to investigate the leaching of polycyclic aromatic hydrocarbons (PAHs) from oil-based residues of shale gas drilling cuttings. Furthermore, the effects of some relevant environmental factors controlling the leaching behavior were evaluated, including the different particle sizes, pH, extraction time, solid-to-liquid (S/L) ratio and dissolved organic matter (DOM) concentration. The results showed that (1) the concentrations of leached PAHs gradually increased with prolonged leaching time, but the cumulative amount of PAHs released during leaching was less than 3% of the total. (2) The Elovich, parabolic diffusion and power function models were found to fit the experimental data better than the first-order kinetic equation, indicating that the leaching of PAHs was controlled by the coupling of diffusion and chemical reactions at the source surface. (3) Different environmental factors had different impacts on the leaching of PAHs: the shaking time and presence of DOM increased leachability, the particle size and S/L ratio decreased leachability, and the pH did not affect the leachability of PAHs. Therefore, PAHs leaching was a complex process, and it is of scientific and environmental interest to conduct the leaching tests under the simulated environmental conditions.
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http://dx.doi.org/10.1016/j.envpol.2021.117773DOI Listing
July 2021

Positron emission tomography/computed tomography hypermetabolism of Kikuchi-Fujimoto disease mimicking malignant lymphoma: a case report and literature review.

J Int Med Res 2021 Jul;49(7):3000605211032859

Department of Nuclear Medicine, 159407The First Hospital of China Medical University, The First Hospital of China Medical University, Shenyang, P.R. China.

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a benign, self-limiting inflammatory disorder of unknown etiology and pathogenesis. This report presents a rare case involving a man with F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) hypermetabolism caused by KFD mimicking malignant lymphoma. The PET/CT maximum intensity projection showed multiple hypermetabolic lymphadenopathies and homogeneous FDG uptake in the bone marrow and spleen. Malignant lymphoma was initially suspected. The patient then underwent excision biopsy of one enlarged right cervical lymph node that was selected because it showed the highest FDG uptake in PET/CT, and examination of this biopsy specimen confirmed the diagnosis of KFD. PET/CT is useful for assessing the general condition of patients and can help to select lymph nodes for excision biopsy based on the highest FDG uptake. However, KFD can predispose to localized FDG uptake and limit the specificity of PET/CT by mimicking malignancy. Thus, positive results of PET/CT should be interpreted with caution.
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http://dx.doi.org/10.1177/03000605211032859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326629PMC
July 2021

Does coffee, tea and caffeine consumption reduce the risk of incident breast cancer? A systematic review and network meta-analysis.

Public Health Nutr 2021 Jul 27:1-13. Epub 2021 Jul 27.

Department of Clinical Pharmacy, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Shenyang110016, People's Republic of China.

Objective: We aimed to evaluate the association between coffee and/or tea consumption and breast cancer (BC) risk among premenopausal and postmenopausal women and to conduct a network meta-analysis.

Design: Systematic review and network meta-analysis.

Setting: We conducted a systematic review of electronic publications in the last 30 years to identify case-control studies or prospective cohort studies that evaluated the effects of coffee and tea intake.

Results: Forty-five studies that included more than 3 323 288 participants were eligible for analysis. Network meta-analysis was performed to determine the effects of coffee and/or tea consumption on reducing BC risk in a dose-dependent manner and differences in coffee/tea type, menopause status, hormone receptor and the BMI in subgroup and meta-regression analyses. According to the first pairwise meta-analysis, low-dose coffee intake and high-dose tea intake may exhibit efficacy in preventing ER(estrogen receptor)- BC, particularly in postmenopausal women. Then, we performed another pairwise and network meta-analysis and determined that the recommended daily doses were 2-3 cups/d of coffee or ≥5 cups/d of tea, which contained a high concentration of caffeine, particularly in postmenopausal women.

Conclusions: Coffee and tea consumption is not associated with a reduction in the overall BC risk in postmenopausal women and is associated with a potentially lower risk of ER- BC. And the highest recommended dose is 2-3 cups of coffee/d or ≥5 cups of tea/d. They are potentially useful dietary protectants for preventing BC.
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http://dx.doi.org/10.1017/S1368980021000720DOI Listing
July 2021

[Retracted] MicroRNA‑718 serves a tumor‑suppressive role in non‑small cell lung cancer by directly targeting .

Int J Mol Med 2021 Sep 23;48(3). Epub 2021 Jul 23.

Department of Thoracic Oncosurgery, Jilin Province Tumor Hospital, Changchun, Jilin 130012, P.R. China.

Following the publication of this paper, the authors have contacted the Editorial Office to explain that they are unable to reproduce the results of their experiments designed to show the regulatory actions of miR‑718 on the proliferation of non‑small cell lung cancer, and consequently they wish to retract the paper. The Editor of has granted their request that the paper be retracted. All the authors agree to this retraction. The Editor and the authors apologize to the readership for any inconvenience caused. [the original article was published in 45: 33‑44, 2020; DOI: 10.3892/ijmm.2019.4396].
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http://dx.doi.org/10.3892/ijmm.2021.5013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354306PMC
September 2021

Near-Infrared-Light Remote-Controlled Activation of Cancer Immunotherapy Using Photothermal Conjugated Polymer Nanoparticles.

Adv Mater 2021 Aug 18;33(34):e2102570. Epub 2021 Jul 18.

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

Remote control of the therapeutic process is an ideal strategy for maximizing efficacy and avoiding side effects, especially for cancer immunotherapy. Herein, a conjugated polymer nanoparticles (CPNs)-mediated optogenetic system for in situ activation of immunotherapy under near-infrared laser irradiation is reported. This system is composed of photothermal CPNs and interferon-gamma (IFN-γ) plasmid driven by heat shock promoter HSP70. The photothermally responsive CPNs serve as a photo-heat nanotransducer to trigger the gene transcription of IFN-γ cytokine. The secreted IFN-γ from cancer cells can sufficiently elicit surrounding tumor-associated macrophages activation through IFN-γ-JAK-STAT1 transcription-factor signaling pathway and finally induce cancer cell killing by immunotherapy. Therefore, this synergetic optogenetic system provides a promising approach to remotely control the process of cancer immunotherapy.
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http://dx.doi.org/10.1002/adma.202102570DOI Listing
August 2021

Computing the Riemannian curvature of image patch and single-cell RNA sequencing data manifolds using extrinsic differential geometry.

Proc Natl Acad Sci U S A 2021 Jul;118(29)

Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA 02215;

Most high-dimensional datasets are thought to be inherently low-dimensional-that is, data points are constrained to lie on a low-dimensional manifold embedded in a high-dimensional ambient space. Here, we study the viability of two approaches from differential geometry to estimate the Riemannian curvature of these low-dimensional manifolds. The intrinsic approach relates curvature to the Laplace-Beltrami operator using the heat-trace expansion and is agnostic to how a manifold is embedded in a high-dimensional space. The extrinsic approach relates the ambient coordinates of a manifold's embedding to its curvature using the Second Fundamental Form and the Gauss-Codazzi equation. We found that the intrinsic approach fails to accurately estimate the curvature of even a two-dimensional constant-curvature manifold, whereas the extrinsic approach was able to handle more complex toy models, even when confounded by practical constraints like small sample sizes and measurement noise. To test the applicability of the extrinsic approach to real-world data, we computed the curvature of a well-studied manifold of image patches and recapitulated its topological classification as a Klein bottle. Lastly, we applied the extrinsic approach to study single-cell transcriptomic sequencing (scRNAseq) datasets of blood, gastrulation, and brain cells to quantify the Riemannian curvature of scRNAseq manifolds.
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http://dx.doi.org/10.1073/pnas.2100473118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307776PMC
July 2021

The role of the vaginal microbiome in distinguishing female chronic pelvic pain caused by endometriosis/adenomyosis.

Ann Transl Med 2021 May;9(9):771

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing, China.

Background: This study aimed to investigate the specific vaginal microbiome in the differential diagnosis of endometriosis/adenomyosis (EM/AM)-associated chronic pelvic pain (CPP) from other types of CPP, and to explore the role of the vaginal microbiome in the mechanism of EM/AM-associated CPP.

Methods: We recruited 37 women with EM/AM-associated CPP, 25 women with chronic pelvic pain syndrome (CPPS) without EM/AM, and 66 women without CPPS into our study. All of the participants were free from human papillomavirus (HPV) infection. Sequencing of barcoded 16S rRNA gene fragments (V4) was used to determine the vaginal microbiome composition on the Illumina HiSeq2500 System. Taxonomic and functional bioinformatics analyses were performed using -test, linear discriminant analysis effect size (LEfSe), MetaStat, and PICRUSt algorithms.

Results: At the species level, EM/AM-associated CPP was found to be associated with a predominance of , , , and , and a concomitant paucity of , , and . When the relative abundance of was over 0.001105% and that of was under 0.1911349%, the differential diagnostic sensitivity and specificity were 81.08% and 52.0%, respectively. When serum CA125 was combined, the sensitivity increased to 89.19%, but the specificity remained at 52.0%. The PICRUSt results identified 7 differentially regulated pathways within the 3 groups that may be of relevance.

Conclusions: Compared to that of CPPS patients without EM/AM and women without CPPS, the vaginal microbiome of patients with EM/AM-associated CPP shows significantly higher alpha (phylogenetic) diversity, as well as higher counts of , , , and . These differences in the vaginal microbiome may interfere with local functional pathways, which could provide a direction for innovative metabolite-specific targeted treatment. The combination of vaginal biomarkers and serum CA125 may provide an original method to differentiate EM/AM-associated CPP.
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http://dx.doi.org/10.21037/atm-20-4586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246188PMC
May 2021

Distinct chemokines selectively induce HIV-1 gp120-integrin α4β7 binding via triggering conformer-specific activation of α4β7.

Signal Transduct Target Ther 2021 Jul 16;6(1):265. Epub 2021 Jul 16.

State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.

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http://dx.doi.org/10.1038/s41392-021-00582-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282615PMC
July 2021

Comprehensive Analysis of Lysine Lactylation in Rice () Grains.

J Agric Food Chem 2021 Jul 15;69(29):8287-8297. Epub 2021 Jul 15.

College of Agronomy, Shenyang Agricultural University, Shenyang, Liaoning 110866, China.

Protein lysine lactylation is a new post-translational modification (PTM) prevalently found in fungi and mammalian cells that directly stimulates gene transcription and regulates the glycolytic flux. However, lysine lactylation sites and regulations remain largely unexplored, especially in cereal crops. Herein, we report the first global lactylome profile in rice, which effectively identified 638 lysine lactylation sites across 342 proteins in rice grains. Functional annotations demonstrated that lysine lactylation was enriched in proteins associated with central carbon metabolism and protein biosynthesis. We also observed that proteins serving as nutrition reservoirs in rice grains were frequently targeted by lactylation. Homology analyses indicated that lactylation was conserved on both histone and nonhistone proteins across plants, human cells, and fungi. In addition to lactylation, additional types of acylations could co-occur in many proteins at identical lysine residues, indicating potential cross-talks between these modifications. Our study provided a comprehensive profile of protein lysine lactylation in cereal crop grains.
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http://dx.doi.org/10.1021/acs.jafc.1c00760DOI Listing
July 2021

Effect of Combined Atropine and Patching vs Patching Alone for Treatment of Severe Amblyopia in Children Aged 3 to 12 Years: A Randomized Clinical Trial.

JAMA Ophthalmol 2021 Sep;139(9):990-996

Eye Institute, Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.

Importance: Patching is often less effective for severe amblyopia because of poor adherence. For the treatment of severe amblyopia, although combined atropine and patching therapy (CAPT) has been found to be efficacious, it is currently unknown whether CAPT is more efficacious than patching alone.

Objective: To compare the efficacy of CAPT vs patching alone in children aged 3 to 12 years with severe amblyopia.

Design, Setting, And Participants: This single-center randomized clinical trial was conducted from November 2018 to May 2020. The visual acuity (VA) examiner was masked to the treatment groups. The follow-up visits were at 3 months and 6 months. Participants aged 3 to 12 years with severe amblyopia (20/100 to 20/500) resulting from strabismus, anisometropia, or both were randomly assigned to CAPT or patching therapy.

Interventions: CAPT or patching alone for 6 months.

Main Outcomes And Measures: Change of the amblyopic eye VA from baseline to 6 months.

Results: Among 108 participants, the mean (SD) age was 5.2 (1.8) years, and 54 (50%) were female. Overall, 53 participants (49%) were randomized to CAPT and 55 (51%) were randomized to patching therapy. At baseline, the mean (SD) amblyopic eye VA was 0.95 (0.22) logMAR (approximately 20/200 [2.2 lines]). At 6 months, the CAPT group's mean improvement in amblyopic eye VA was 0.72 logMAR (7.2 lines) compared with 0.58 logMAR (5.8 lines) in the patching alone group (difference, 0.14 logMAR [1.4 lines] greater in the CAPT group; 95% CI, 0.05-0.22 logMAR [0.5-2.2 lines]; P = .002). The amblyopic eye VA improvement in the CAPT group also was greater than that in the patching alone group at 3 months (difference in the means, 0.13 logMAR [1.3 lines]; 95% CI, 0.04-0.22 logMAR [0.4-2.2 lines]; P = .004). No participants were withdrawn because of adverse effects.

Conclusions And Relevance: CAPT resulted in more mean improvement of amblyopic eye VA than patching alone among participants enrolled in this trial, although the clinical relevance of this relatively small VA difference cannot be determined from this trial.

Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1800018663.
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http://dx.doi.org/10.1001/jamaophthalmol.2021.2413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283662PMC
September 2021

Personalized Single-Cell Proteogenomics to Distinguish Acute Myeloid Leukemia from Non-Malignant Clonal Hematopoiesis.

Blood Cancer Discov 2021 07 25;2(4):319-325. Epub 2021 May 25.

Laboratory of Myeloid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 United States.

Genetic mutations associated with acute myeloid leukemia (AML) also occur in age-related clonal hematopoiesis, often in the same individual. This makes confident assignment of detected variants to malignancy challenging. The issue is particularly crucial for AML post-treatment measurable residual disease monitoring, where results can be discordant between genetic sequencing and flow cytometry. We show here, that it is possible to distinguish AML from clonal hematopoiesis and to resolve the immunophenotypic identity of clonal architecture. To achieve this, we first design patient-specific DNA probes based on patient's whole-genome sequencing, and then use them for patient-personalized single-cell DNA sequencing with simultaneous single-cell antibody-oligonucleotide sequencing. Examples illustrate AML arising from and mutated clones as well as independently. The ability to personalize single-cell proteogenomic assessment for individual patients based on leukemia-specific genomic features has implications for ongoing AML precision medicine efforts.
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http://dx.doi.org/10.1158/2643-3230.BCD-21-0046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265308PMC
July 2021

Degradation of phosphonates in Co(II)/peroxymonosulfate process: Performance and mechanism.

Water Res 2021 Sep 30;202:117397. Epub 2021 Jun 30.

Research Center for Environmental Nanotechnology (ReCENT), State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.

The increased release of phosphonates to natural waters causes global concern due to their potential threat to the aquatic environment. It is curial to mineralize phosphonates to orthophosphate (PO) before they are thoroughly removed from wastewater via conventional biological treatment. In this study, we systematically investigated the performance and mechanism of degradation of phosphonates in Co(II)-triggered peroxymonosulfate (PMS) activation process. The degradation efficiency of various phosphonates is highly dependent on their coordination with Co(II). Using 1-hydroxyethane 1,1-diphosphonic acid (HEDP) as a target pollutant, the Co(II)/PMS process is effective in a broad solution pH range from 5.0 to 10.0. Multiple experimental results imply that Co(II)-PMS complex is the primary reactive species, while hydroxyl radicals (HO), sulfate radicals (SO), singlet oxygen (O) and Co(III) play as the secondary reactive species for the degradation of HEDP. The presence of Cl, HCO, and natural organic matters (NOM) inhibits the degradation of HEDP. However, in real water samples, the selectivity and efficiency for HEDP removal in the Co(II)/PMS process are higher than that in free radicals-mediated advanced oxidation processes. This study not only sheds new lights on the mechanism of Co(II)-triggered PMS activation process, but also provides feasible technology for the degradation of phosphonates in wastewater.
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http://dx.doi.org/10.1016/j.watres.2021.117397DOI Listing
September 2021

Tetrahydrocurcumin ameliorates Alzheimer's pathological phenotypes by inhibition of microglial cell cycle arrest and apoptosis via Ras/ERK signaling.

Biomed Pharmacother 2021 Jul 8;139:111651. Epub 2021 May 8.

Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Academy of Chinese Medicine Sciences, Sichuan Institute for Translational Chinese Medicine, Chengdu 610041, China. Electronic address:

1,7-bis(4-hydroxy-3-methoxyphenyl)heptane-3,5-dione (tetrahydrocurcumin, THC) is a major bioactive metabolite of curcumin, demonstrating the potential anti-inflammatory, antioxidant and neuroprotective properties, etc. In this study, it was found that Aβ induced decreased cell viability, cell cycle arrest and apoptosis in BV-2 cells, which were ameliorated by THC. In vivo, THC administration rescued learning and memory, and reduced Aβ burden in the hippocampus of APP/PS1 mice. By proteomic analysis of the hippocampus of mice, 157 differentially expressed proteins were identified in APP/PS1 mice treated with THC (comparing with APP/PS1 mice), which also suggested that the effects of THC on the cell cycle and apoptosis were mostly related to the "Ras signaling pathway", etc. In APP/PS1 mice, the down-regulation of Gab2 and K-Ras, and the up-regulation of caspase-3, TGF-β1 and TNF-ɑ were observed; THC attenuated the abnormal expression of Gab2, K-Ras, caspase-3 and TNF-ɑ, and up-regulated TGF-β1 and Bag1 expression. In BV-2 cells, Aβ induced the down-regulation of Gab2, K-Ras and TGF-β1, and the overexpression of caspase-3, PARP1, cleaved-PARP1 and TNF-ɑ, which were restored by THC. Moreover, THC up-regulated Bag1 expression in Aβ-treated BV-2 cells. The decreased transcriptional expression of Ccnd2 and Cdkn1a were also observed in Aβ-treated BV-2 cells, and THC alleviated the down-regulation of Ccnd2. For the first time, we identified that the action of THC in preventing AD was associated with inhibition of cell cycle arrest and apoptosis of microglia via the Ras/ERK signaling pathway, shedding new light on the role of THC in alleviating the progression of AD.
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http://dx.doi.org/10.1016/j.biopha.2021.111651DOI Listing
July 2021
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