Publications by authors named "Xin Liang"

374 Publications

PD-1/PD-L1 immune checkpoint blockade-based combinational treatment: Immunotherapeutic amplification strategies against colorectal cancer.

Int Immunopharmacol 2021 Apr 5;96:107607. Epub 2021 Apr 5.

School of Medical and Life Sciences/Reproductive & Women-children Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, PR China. Electronic address:

Colorectal cancer (CRC) is one of the most common malignant tumours of the digestive system, and most patients are already in an advanced stage at the time of diagnosis. Moreover, current single-use immune checkpoint inhibitors (ICIs), such as programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitors, are only effective for some advanced CRC patients with microsatellite instability-high (MSI-H), and most patients may be unable to benefit from it due to a lack of CD8 T cells in the tumour microenvironment. Additionally, the subtype of CRC has emerged as a factor affecting treatment responses, with immunogenic subtypes carrying a better prognosis. In this review, we discuss bottlenecks encountered with the single use of PD-1/PD-L1 inhibitors and summarize the research status and mechanisms of PD-1/PD-L1 inhibitor-based immunotherapeutic amplification strategies, including chemotherapy, radiotherapy, photomediated therapy and other immunotherapies used for colorectal cancer.
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http://dx.doi.org/10.1016/j.intimp.2021.107607DOI Listing
April 2021

Heat shock induces cross adaptation to aluminum stress through enhancing ascorbate-glutathione cycle in wheat seedlings.

Chemosphere 2021 Mar 28;278:130397. Epub 2021 Mar 28.

MOE Key Laboratory of Environment Remediation and Ecological Health, College of Natural Resource & Environmental Sciences, Zhejiang University, Hangzhou, 310058, China.

Aluminum (Al), a neurotoxin agent, is universal in the earth crust, but its bioavailability and toxicity are manifested under acidic conditions. Up to 60% of the acid soils are distributed in tropical and subtropical regions, where crops simultaneously experience heat-shock stress. Here, we investigated the effects of heat shock-priming on Al tolerance in two different wheat genotypes. Conditioning of wheat seedlings with short period high temperature significantly alleviated Al-induced root growth inhibition, but did not significantly affect Al accumulation. However, we observed that heat shock-primed roots maintained lower levels of lipid peroxidation and higher cell viability. These priming-triggered effects were associated with reactive oxygen species (ROS) homeostasis. Furthermore, conditioning of plants with high temperature increased the contents of reduced ascorbate and glutathione, and ratios of reduced to oxidized forms of these molecules in wheat roots. However, ascorbate or glutathione biosynthesis inhibitors markedly prevented heat shock priming-induced ROS reduction accompanied by aggravated root elongation. Moreover, heat shock-priming enhanced the metabolic intensity of ascorbate-glutathione cycle, as activities of the cycle-allied enzymes were significantly increased. These results suggest that heat-shock induces cross adaptation to Al toxicity through sustaining efficient ascorbate-glutathione cycle operation in wheat plants.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130397DOI Listing
March 2021

The role of tumor-associated macrophages in osteosarcoma progression - therapeutic implications.

Cell Oncol (Dordr) 2021 Mar 31. Epub 2021 Mar 31.

Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, China.

Background: Osteosarcoma (OS) is the most common primary malignant bone tumor. Compared with previous treatment modalities, such as amputation, more recent comprehensive treatment modalities based on neoadjuvant chemotherapy combined with limb salvage surgery have improved the survival rates of patients. Osteosarcoma treatment has, however, not further improved in recent years. Therefore, attention has shifted to the tumor microenvironment (TME) in which osteosarcoma cells are embedded. Therapeutic targets in the TME may be key to improving osteosarcoma treatment. Tumor-associated macrophages (TAMs) are the most common immune cells within the TME. TAMs in osteosarcoma may account for over 50% of the immune cells, and may play important roles in tumorigenesis, angiogenesis, immunosuppression, drug resistance and metastasis. Knowledge on the role of TAMs in the development, progression and treatment of osteosarcoma is gradually improving, although different or even opposing opinions still remain.

Conclusions: TAMs may participate in the malignant progression of osteosarcoma through self-polarization, the promotion of blood vessel and lymphatic vessel formation, immunosuppression, and drug resistance. Besides, various immune checkpoint proteins expressed on the surface of TAMs, such as PD-1 and CD47, provide the possibility of the application of immune checkpoint inhibitors. Several clinical trials have been carried out and/or are in progress. Mifamotide and the immune checkpoint inhibitor Camrelizumab were both found to be effective in prolonging progression-free survival. Thus, TAMs may serve as attractive therapeutic targets. Targeting TAMs as a complementary therapy is expected to improve the prognosis of osteosarcoma. Further efforts may be made to identify potential beneficiaries of TAM-targeted therapies.
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http://dx.doi.org/10.1007/s13402-021-00598-wDOI Listing
March 2021

Matrine inhibits ovarian cancer cell viability and promotes apoptosis by regulating the ERK/JNK signaling pathway via p38MAPK.

Oncol Rep 2021 May 31;45(5). Epub 2021 Mar 31.

Xiangyang Community, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang 157000, P.R. China.

Ovarian cancer displays the highest mortality rate among all types of gynecological cancer worldwide. The survival of patients with ovarian cancer remains poor due to poor responses to anticancer treatments. The present study aimed to investigate the therapeutic effects and potential mechanism underlying matrine in ovarian cancer tissues, ovarian cancer cells and a CAOV‑3‑derived tumor‑bearing mouse model. MTT, migration, invasion, flow cytometry, immunofluorescence and immunohistochemistry assays were performed to assess the inhibitory effects of matrine on ovarian cancer. A xenograft ovarian cancer mouse model was established and treated with matrine or PBS. The results demonstrated that compared with the control group, matrine significantly induced ovarian cancer cell apoptosis by upregulating caspase‑8 and Fas cell surface death receptor (Fas) expression levels, and downregulating Bcl‑2 and Bcl‑xl expression levels. Moreover, compared with the control group, matrine significantly inhibited ovarian cancer cell viability, migration and invasion by downregulating metastasis associated protein‑1, fibronectin, angiotensin II type 2 receptor-interacting protein 3a and H high mobility group AT‑hook 2 expression levels. Compared with the control group, matrine significantly increased p38MAPK, phosphorylated (p)ERK/ERK and pJNK/JNK expression levels in ovarian cancer cells. p38MAPK knockdown significantly downregulated p38MAPK, pERK/ERK and pJNK/JNK expression levels compared with the control group, which significantly promoted ovarian cancer cell viability, migration and invasion. In vivo experiments demonstrated that compared with the control group, matrine significantly suppressed tumor growth by markedly upregulating p38MAPK, ERK and JNK expression levels. The immunohistochemistry results demonstrated that caspase‑8 and Fas expression levels were notably increased, whereas Bcl‑2 and Bcl‑xl expression levels were obviously decreased in matrine‑treated tumors compared with PBS‑treated tumors. In conclusion, the present study demonstrated that matrine inhibited ovarian cancer cell viability, migration and invasion, but induced cell apoptosis, suggesting that matrine may serve as a promising anticancer agent for the treatment of ovarian cancer.
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http://dx.doi.org/10.3892/or.2021.8033DOI Listing
May 2021

Berberine-photodynamic induced apoptosis by activating endoplasmic reticulum stress-autophagy pathway involving CHOP in human malignant melanoma cells.

Biochem Biophys Res Commun 2021 May 19;552:183-190. Epub 2021 Mar 19.

State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, PR China. Electronic address:

Malignant melanoma is a critical and aggressive skin tumor with a steeply rising incidence and a less favorable prognosis due to the lack of efficient treatment. Photodynamic therapy (PDT) is a new promising treatment for this tumor through photosensitizers-mediated oxidative cytotoxicity. In this study, we explored the role of berberine-mediated PDT (BBR-PDT) in the anti-proliferative effect on human malignant melanoma cells (MMCs). We found that there were significant differences between MMCs with BBR-PDT and MMCs with BBR or PDT only. Further research showed that BBR-PDT induced apoptosis via up-regulating the expression of cleaved caspase-3 protein. We also observed that LC3-related autophagy level was upregulated in MMCs with BBR-PDT. Besides, it was also found that BBR-PDT activated endoplasmic reticulum (ER) stress, involving a dramatic increase in reactive oxygen species (ROS). Interestingly, the knockdown of CHOP protein expression inhibited apoptosis, autophagy and ER stress levels caused by BBR-PDT, suggesting that CHOP protein may be related to apoptosis, autophagy and ER stress in MMCs with BBR-PDT. Collectively, our results indicated that BBR-PDT had an essential impact on MMCs' growth inhibition, and therefore may reveal the possibility of developing BBR-PDT into human malignant melanoma.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.147DOI Listing
May 2021

Baicalin triggers apoptosis, inhibits migration, and enhances anti-tumor immunity in colorectal cancer via TLR4/NF-κB signaling pathway.

J Food Biochem 2021 Mar 20:e13703. Epub 2021 Mar 20.

School of Medical and Life Sciences/Reproductive & Women-children Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, P.R. China.

Aberrant activation of the nuclear factor-kappa B (NF-κB) signaling pathway is closely implicated in colorectal cancer (CRC) growth, metastasis, and immune escape. In the present study, we reported natural derived compound of baicalin (BA), an efficient inhibitor of NF-κB, with good anti-tumor effect on CRC. CCK8 and colony formation assays showed that Baicalin significantly inhibit viability and proliferation in HCT-116 and CT26 cells. Additionally, Baicalin dramatically triggers mitochondria-mediated apoptosis in both HCT-116 and CT-26 cells, which is evidenced by loss of mitochondrial membrane potential and elevated cellular reactive oxygen species level. Treatment with Baicalin suppresses migration and invasion of CT26 cells by impairing TLR4/NF-κB signaling pathway. What's more, administration of Baicalin significantly retarded tumor growth rate in a subcutaneous xenograft tumor mouse model of CT26 cells. Treatment with Baicalin could ameliorate tumor immunosuppressive environment by downregulation of PD-L1 expression and proportion of myeloid-derived suppressor cells (MDSCs) and upregulation of percent of CD4 and CD8 T cells in CT26 tumors, thus improving anti-tumor immunity. In conclusion, our study demonstrated that baicalin triggers apoptosis, inhibits migration, and enhances anti-tumor immunity in colorectal cancer via TLR4/NF-κB signaling pathway, suggesting it might serve as a potential candidate drug for the treatment of CRC. PRACTICAL APPLICATIONS: In the present study, we reported natural derived compound of baicalin (BA), an efficient inhibitor of NF-κB, with good anti-tumor effect on CRC. We demonstrated that baicalin triggers mitochondria-mediated apoptosis, inhibits migration, and improves anti-tumor immunity in colorectal cancer via TLR4/NF-κB signaling pathway.
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http://dx.doi.org/10.1111/jfbc.13703DOI Listing
March 2021

Dual pH- and Glutathione-Responsive CO-Generating Nanodrug Delivery System for Contrast-Enhanced Ultrasonography and Therapy of Prostate Cancer.

ACS Appl Mater Interfaces 2021 Mar 15;13(11):12899-12911. Epub 2021 Mar 15.

Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China.

Ultrasonography (US) contrast imaging using US contrast agents has been widely applied for the diagnosis and differential diagnosis of tumors. Commercial US contrast agents have limited applications because of their large size and shorter imaging time. At the same time, the desired therapeutic purpose cannot be achieved by applying only conventional US contrast agents. The development of nanoscale US agents with US imaging and therapeutic functions has attracted increasing attention. In this study, we successfully developed DOX-loaded poly-1,6-hexanedithiol-sodium bicarbonate nanoparticles (DOX@HADT-SS-NaHCO NPs) with pH-responsive NaHCO and GSH-responsive disulfide linkages. DOX@HADT-SS-NaHCO NPs underwent acid-triggered decomposition of NaHCO to generate CO bubbles and a reduction of disulfide linkages to further promote the release of CO and DOX. The potential of DOX@HADT-SS-NaHCO NPs for contrast-enhanced US imaging and therapy of prostate cancer was thoroughly evaluated using in vitro agarose gel phantoms and a C4-2 tumor-bearing nude mice model. These polymeric NPs displayed significantly enhanced US contrast at acidic pH and antitumor efficacy. Therefore, the NaHCO and DOX-encapsulated polymeric NPs hold tremendous potential for effective US imaging and therapy of prostate cancer.
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http://dx.doi.org/10.1021/acsami.1c00077DOI Listing
March 2021

Berberine-photodynamic therapy sensitizes melanoma cells to cisplatin-induced apoptosis through ROS-mediated P38 MAPK pathways.

Toxicol Appl Pharmacol 2021 May 11;418:115484. Epub 2021 Mar 11.

State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China. Electronic address:

The clinical use of cisplatin are limited due to its drug resistance. Thus, it is urgent to find effective combination therapy that sensitizes tumor cells to this drug. The combined chemo-photodynamic therapy could increase anti-tumor efficacy while also reduce the side effects of cisplatin. Berberine is an isoquinoline alkaloid, which has been reported to show high photosensitizing activity. In this study, we have examined the effect of a combination of cisplatin and berberine-PDT in cisplatin-resistant melanoma cells. The cytotoxic effects of berberine-PDT alone or in combination with cisplatin were tested by MTT assays. We then examined the subcellular localization of berberine with confocal fluorescence microscopy. The percentage of apoptotic cells, the mitochondrial membrane potential (Δψm) and reactive oxygen species (ROS) generation assessed using flow cytometry analysis. Western blotting used in this study to determine the expression levels of MAPK signaling pathways and apoptosis-related proteins. Experimental data revealed that the mode of cell death is the caspase-dependent mitochondrial apoptotic pathways. Excessive accumulation of ROS played a key role in this process, which is confirmed by alleviation of cytotoxicity upon pretreatment with NAC. Furthermore, we found that the combined treatment activated MAPK signaling pathway. The inhibition of p38 MAPK by pretreating with SB203580 block the combined treatment-induced apoptotic cell death. In conclusion, berberine-PDT could be used as a chemo-sensitizer by promoting cell death through activation of a ROS/p38/caspase cascade.
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http://dx.doi.org/10.1016/j.taap.2021.115484DOI Listing
May 2021

Identification of Tumor Tissue of Origin with RNA-Seq Data and Using Gradient Boosting Strategy.

Biomed Res Int 2021 17;2021:6653793. Epub 2021 Feb 17.

School of Mathematics and Statistics, Hainan Normal University, Haikou 570100, China.

Background: Cancer of unknown primary (CUP) is a type of malignant tumor, which is histologically diagnosed as a metastatic carcinoma while the tissue-of-origin cannot be identified. CUP accounts for roughly 5% of all cancers. Traditional treatment for CUP is primarily broad-spectrum chemotherapy; however, the prognosis is relatively poor. Thus, it is of clinical importance to accurately infer the tissue-of-origin of CUP.

Methods: We developed a gradient boosting framework to trace tissue-of-origin of 20 types of solid tumors. Specifically, we downloaded the expression profiles of 20,501 genes for 7713 samples from The Cancer Genome Atlas (TCGA), which were used as the training data set. The RNA-seq data of 79 tumor samples from 6 cancer types with known origins were also downloaded from the Gene Expression Omnibus (GEO) for an independent data set.

Results: 400 genes were selected to train a gradient boosting model for identification of the primary site of the tumor. The overall 10-fold cross-validation accuracy of our method was 96.1% across 20 types of cancer, while the accuracy for the independent data set reached 83.5%.

Conclusion: Our gradient boosting framework was proven to be accurate in identifying tumor tissue-of-origin on both training data and independent testing data, which might be of practical usage.
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http://dx.doi.org/10.1155/2021/6653793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904362PMC
February 2021

ADAM28 from both endothelium and gastric cancer cleaves von Willebrand Factor to eliminate von Willebrand Factor-induced apoptosis of gastric cancer cells.

Eur J Pharmacol 2021 May 3;898:173994. Epub 2021 Mar 3.

State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, PR China. Electronic address:

Disintegrin and metalloproteinase 28 (ADAM28) is a member of the disintegrin and metalloprotease domain (ADAM) family. It is associated with the growth and metastasis of various malignancies in vivo, but its role in gastric cancer remains unclear. The purpose of this study was to investigate the effect of ADAM28 derived from gastric cancer and endothelium on gastric cancer cells and its related mechanisms. In this study, Western blot analysis and q-PCR results showed that ADAM28 was up-regulated in gastric cancer cell lines. The TCGA database showed that patients with high ADAM28 expression had significantly shorter overall survival than those with low ADAM28 expression. By MTT analysis, wound healing assay, and flow cytometry, we found that overexpression/knockdown of ADAM28 expression in gastric cancer cells can regulate cell proliferation, apoptosis and migration in vitro. In addition, overexpression/knockdown of ADAM28 in human umbilical vein endothelial cells (HUVECs) in the upper ventricle can regulate the apoptosis of lower ventricular gastric cancer cells in the co-culture system. Furthermore, ELISA demonstrated that knockdown of ADAM28 from endothelial cells increased the expression of von Willebrand Factor (vWF) in the supernatant. We found that ADAM28 both from gastric cancer cells and HUVECs eliminated vWF-induced apoptosis of gastric cancer cells by cleaving vWF, and the addition of the vWF knockdown plasmid eliminated the increase of integrin β3, p-TP53 and c-Casp3 caused by ADAM28 knockdown. In conclusion, ADAM28 from endothelium and gastric cancer may cleave vWF to eliminate vWF-induced apoptosis of gastric cancer cells and play an pro-metastasis effect.
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http://dx.doi.org/10.1016/j.ejphar.2021.173994DOI Listing
May 2021

Assessment of Neuroprotective Effects of Low-Intensity Transcranial Ultrasound Stimulation in a Parkinson's Disease Rat Model by Fractional Anisotropy and Relaxation Time T2 Value.

Front Neurosci 2021 9;15:590354. Epub 2021 Feb 9.

Department of Magnetic Resonance Imaging, Qinhuangdao Municipal No. 1 Hospital, Qinhuangdao, China.

Low-intensity transcranial ultrasound (LITUS) may have a therapeutic effect on Parkinson's disease (PD) patients to some extent. Fractional anisotropy (FA) and relaxation time T2 that indicate the integrity of fiber tracts and iron concentrations in brain tissue have been used to evaluate the therapeutic effects of LITUS. This study aims to use FA and T2 values to evaluate the therapeutic effects of LITUS in a PD rat model. Twenty Sprague-Dawley rats were randomly divided into a hemi-PD group ( = 10) and a LITUS group ( = 10). Single-shot spin echo echo-planar imaging and fast low-angle shot T2WI sequences at 3.0 T were used. The FA and T2 values on the right side of the substantia nigra (SN) pars compacta were measured to evaluate the therapeutic effect of LITUS in the rats. One week after PD-like signs were induced in the rats, the FA value in the LITUS group was significantly larger compared with the PD group (0.214 ± 0.027 vs. 0.340 ± 0.032, = 2.864, = 0.011). At the 5th and 6th weeks, the FA values in the LITUS group were significantly smaller compared with the PD group (5th week: 0.290 ± 0.037 vs. 0.405 ± 0.027, = 2.385, = 0.030; 6th week: 0.299 ± 0.021 vs. 0.525 ± 0.028, = 6.620, < 0.0001). In the 5th and 6th weeks, the T2 values in the injected right SN of the LITUS group were significantly higher compared with the PD group (5th week, 12.169 ± 0.826 in the LITUS group vs. 7.550 ± 0.824 in the PD group; 6th week, 11.749 ± 0.615 in the LITUS group vs. 7.550 ± 0.849 in the PD group). LITUS had neuroprotective effects and can reduce the damage of 6-OHDA-induced neurotoxicity in hemi-PD rats. The combination of FA and T2 assessments can potentially serve as a new and effective method to evaluate the therapeutic effects of LITUS.
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http://dx.doi.org/10.3389/fnins.2021.590354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900573PMC
February 2021

Fibrogranular materials function as organizers to ensure the fidelity of multiciliary assembly.

Nat Commun 2021 02 24;12(1):1273. Epub 2021 Feb 24.

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

Multicilia are delicate motile machineries, and how they are accurately assembled is poorly understood. Here, we show that fibrogranular materials (FGMs), large arrays of electron-dense granules specific to multiciliated cells, are essential for their ultrastructural fidelity. Pcm1 forms the granular units that further network into widespread FGMs, which are abundant in spherical FGM cores. FGM cores selectively concentrate multiple important centriole-related proteins as clients, including Cep131 that specifically decorates a foot region of ciliary central pair (CP) microtubules. FGMs also tightly contact deuterosome-procentriole complexes. Disruption of FGMs in mouse cells undergoing multiciliogenesis by Pcm1 RNAi markedly deregulates centriolar targeting of FGM clients, elongates CP-foot, and alters deuterosome size, number, and distribution. Although the multicilia are produced in correct numbers, they display abnormal ultrastructure and motility. Our results suggest that FGMs organize deuterosomes and centriole-related proteins to facilitate the faithful assembly of basal bodies and multiciliary axonemes.
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http://dx.doi.org/10.1038/s41467-021-21506-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904937PMC
February 2021

Primary renal large cell neuroendocrine carcinoma with horseshoe kidney: A case report.

Asian J Surg 2021 Apr 8;44(4):702-703. Epub 2021 Feb 8.

Department of Urology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2021.01.008DOI Listing
April 2021

An update review of emerging small-molecule therapeutic options for COVID-19.

Biomed Pharmacother 2021 May 3;137:111313. Epub 2021 Feb 3.

Zhuhai Jinan Selenium Source Nanotechnology Co., Ltd., Hengqin New Area, Zhuhai, 519030, PR China. Electronic address:

The SARS-CoV-2 outbreak and pandemic that began near the end of 2019 has posed a challenge to global health. At present, many candidate small-molecule therapeutics have been developed that can inhibit both the infection and replication of SARS-CoV-2 and even potentially relieve cytokine storms and other related complications. Meanwhile, host-targeted drugs that inhibit cellular transmembrane serine protease (TMPRSS2) can prevent SARS-CoV-2 from entering cells, and its combination with chloroquine and dihydroorotate dehydrogenase (DHODH) inhibitors can limit the spread of SARS-CoV-2 and reduce the morbidity and mortality of patients with COVID-19. The present article provides an overview of these small-molecule therapeutics based on insights from medicinal chemistry research and focuses on RNA-dependent RNA polymerase (RdRp) inhibitors, such as the nucleoside analogues remdesivir, favipiravir and ribavirin. This review also covers inhibitors of 3C-like protease (3CL), papain-like protease (PL) and other potentially innovative active ingredient molecules, describing their potential targets, activities, clinical status and side effects.
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http://dx.doi.org/10.1016/j.biopha.2021.111313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857046PMC
May 2021

Establishing reference ranges of serum lipid level during pregnancy and evaluating its association with perinatal outcomes: A cohort study.

Int J Gynaecol Obstet 2021 Feb 5. Epub 2021 Feb 5.

Division of Endocrinology and Metabolism, Department of Obstetrics, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.

Objective: To establish trimester-specific reference intervals (TSRIs) for blood lipid profiles in Chinese women and explore their associations with pregnancy outcomes.

Methods: Participants were women with singleton pregnancies aged 18-45 years without pre-existing chronic diseases who delivered from January 2018 to December 2018 from an ongoing cohort in Beijing, China. Baseline information and pregnancy outcomes were from the medical records. Blood lipid levels were measured at 7-13, 24-28, and 32-34 weeks of pregnancy. We estimated TSRIs for lipid profiles using an indirect Hoffmann method and evaluated their associations with pregnancy outcomes, including gestational diabetes, pregnancy-induced hypertension, macrosomia, low birth weight, large or small for gestational age, and preterm delivery.

Results: The established TSRIs were 3.21-5.38, 4.64-7.56, and 4.86-8.20 mmol/L for total cholesterol; 0.37-1.81, 1.14-3.49, and 1.61-4.63 mmol/L for triglycerides; 1.12-2.19, 1.33-2.49, and 1.24 2.31 mmol/L for high-density lipoprotein cholesterol; 1.33-2.98,1.97-4.36, and 2.02-4.92 mmol/L for low-density lipoprotein cholesterol from first trimeseter to third trimester, respectively. Both higher and lower levels of lipid profiles than TSRIs were associated with adverse pregnancy outcomes.

Conclusion: We suggested TSRIs for blood lipid levels in a Chinese population. Inappropriate lipid levels were associated with adverse pregnancy outcomes.
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http://dx.doi.org/10.1002/ijgo.13636DOI Listing
February 2021

Superresolution characterization of core centriole architecture.

J Cell Biol 2021 Apr;220(4)

State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.

The centrosome is the main microtubule-organizing center in animal cells. It comprises of two centrioles and the surrounding pericentriolar material. Protein organization at the outer layer of the centriole and outward has been studied extensively; however, an overall picture of the protein architecture at the centriole core has been missing. Here we report a direct view of Drosophila centriolar proteins at ∼50-nm resolution. This reveals a Sas6 ring at the C-terminus, where it overlaps with the C-terminus of Cep135. The ninefold symmetrical pattern of Cep135 is further conveyed through Ana1-Asterless axes that extend past the microtubule wall from between the blades. Ana3 and Rcd4, whose termini are close to Cep135, are arranged in ninefold symmetry that does not match the above axes. During centriole biogenesis, Ana3 and Rcd4 are sequentially loaded on the newly formed centriole and are required for centriole-to-centrosome conversion through recruiting the Cep135-Ana1-Asterless complex. Together, our results provide a spatiotemporal map of the centriole core and implications of how the structure might be built.
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http://dx.doi.org/10.1083/jcb.202005103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863704PMC
April 2021

The positive effects of running exercise on hippocampal astrocytes in a rat model of depression.

Transl Psychiatry 2021 Feb 1;11(1):83. Epub 2021 Feb 1.

Department of Histology and Embryology, Chongqing Medical University, 400016, Chongqing, P. R. China.

Running exercise has been shown to alleviate depressive symptoms, but the mechanism of its antidepressant effect is still unclear. Astrocytes are the predominant cell type in the brain and perform key functions vital to central nervous system (CNS) physiology. Mounting evidence suggests that changes in astrocyte number in the hippocampus are closely associated with depression. However, the effects of running exercise on astrocytes in the hippocampus of depression have not been investigated. Here, adult male rats were subjected to chronic unpredictable stress (CUS) for 5 weeks followed by treadmill running for 6 weeks. The sucrose preference test (SPT) was used to assess anhedonia of rats. Then, immunohistochemistry and modern stereological methods were used to precisely quantify the total number of glial fibrillary acidic protein (GFAP) astrocytes in each hippocampal subregion, and immunofluorescence was used to quantify the density of bromodeoxyuridine (BrdU) and GFAP cells in each hippocampal subregion. We found that running exercise alleviated CUS-induced deficit in sucrose preference and hippocampal volume decline, and that CUS intervention significantly reduced the number of GFAP cells and the density of BrdU/GFAP cells in the hippocampal CA1 region and dentate gyrus (DG), while 6 weeks of running exercise reversed these decreases. These results further confirmed that running exercise alleviates depressive symptoms and protects hippocampal astrocytes in depressed rats. These findings suggested that the positive effects of running exercise on astrocytes and the generation of new astrocytes in the hippocampus might be important structural bases for the antidepressant effects of running exercise.
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http://dx.doi.org/10.1038/s41398-021-01216-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851162PMC
February 2021

Fluoxetine Promotes Hippocampal Oligodendrocyte Maturation and Delays Learning and Memory Decline in APP/PS1 Mice.

Front Aging Neurosci 2020 13;12:627362. Epub 2021 Jan 13.

Department of Histology and Embryology, Chongqing Medical University, Chongqing, China.

Oligodendrogenesis dysfunction impairs memory consolidation in adult mice, and an oligodendrocyte abnormality is an important change occurring in Alzheimer's disease (AD). While fluoxetine (FLX) is known to delay memory decline in AD models, its effects on hippocampal oligodendrogenesis are unclear. Here, we subjected 8-month-old male amyloid precursor protein (APP)/presenilin 1 (PS1) mice to the FLX intervention for 2 months. Their exploratory behaviors and general activities in a novel environment, spatial learning and memory and working and reference memory were assessed using the open-field test, Morris water maze, and Y maze. Furthermore, changes in hippocampal oligodendrogenesis were investigated using stereology, immunohistochemistry, immunofluorescence staining, and Western blotting techniques. FLX delayed declines in the spatial learning and memory, as well as the working and reference memory of APP/PS1 mice. In addition, APP/PS1 mice exhibited immature hippocampal oligodendrogenesis, and FLX increased the numbers of 2'3'cyclic nucleotide 3'-phosphodiesterase (CNPase) and newborn CNPase oligodendrocytes in the hippocampi of APP/PS1 mice. Moreover, FLX increased the density of SRY-related HMG-box 10 protein (SOX10) cells and reduced the percentage of oligodendrocyte lineage cells displaying the senescence phenotype (CDKN2A/p16INK4a) in the hippocampus of APP/PS1 mice. Moreover, FLX had no effect on the serotonin (5-HT) 1A receptor (5-HT1AR) content or number of 5-HT1AR oligodendrocytes, but it reduced the content and activity of glycogen synthase kinase 3β (GSK3β) in the hippocampus of APP/PS1 transgenic mice. Taken together, FLX delays the senescence of oligodendrocyte lineage cells and promotes oligodendrocyte maturation in the hippocampus of APP/PS1 mice. FLX may regulate GSK3β through a mechanism other than 5-HT1AR and then inhibit the negative effect of GSK3β on oligodendrocyte maturation in the hippocampus of an AD mouse model.
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http://dx.doi.org/10.3389/fnagi.2020.627362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838348PMC
January 2021

Downregulation of miR-155-5p enhances the anti-tumor effect of cetuximab on triple-negative breast cancer cells via inducing cell apoptosis and pyroptosis.

Aging (Albany NY) 2021 01 5;13(1):228-240. Epub 2021 Jan 5.

State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, P.R. China.

Cetuximab resistance is the main obstacle for the treatment of EGFR overexpression cancer, including triple-negative breast cancer (TNBC). MicroRNA (miRNA)-155-5p is upregulated in TNBC cells; thus, the present study explored whether the downregulation of miR-155-5p enhanced the anti-tumor effect of cetuximab in TNBC cells. MDA-MB-231 and MDA-MB-468 cells were infected with lentivirus-epidermal growth factor receptor (EGFR) for 72 h to obtain EGFR-overexpressed cell lines (MDA-MB-231 and MDA-MB-468). The inhibitory effects of cetuximab on the proliferation and migration of EGFR-overexpressed MDA-MB-468 cells were enhanced following transfection with the miR-155-5p antagomir, and miR-155-5p knockdown enhanced the pro-apoptotic effect of cetuximab on EGFR-overexpressed MDA-MB-468 cells. Further, the luciferase reporter assay revealed that gasdermin E (GSDME) was the direct binding target of miR-155-5p. The combination of cetuximab with the miR-155-5p antagomir promoted pyroptosis in EGFR-overexpressed MDA-MB-468 cells via the upregulation of GSDME-N and cleaved caspase-1. Results from the experiments confirmed that the downregulation of miR-155-5p enhanced the anti-tumor effect of cetuximab in an MDA-MB-468 xenograft model and on EGFR-overexpressed TNBC cells via inducing cell apoptosis and pyroptosis. Therefore, cetuximab combination with an miR-155-5p antagomir may be a novel therapeutic strategy for the treatment of TNBC.
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http://dx.doi.org/10.18632/aging.103669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835015PMC
January 2021

Intranasal administration of α-synuclein preformed fibrils triggers microglial iron deposition in the substantia nigra of Macaca fascicularis.

Cell Death Dis 2021 Jan 13;12(1):81. Epub 2021 Jan 13.

Institute of Neuroscience, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.

Iron deposition is present in main lesion areas in the brains of patients with Parkinson's disease (PD) and an abnormal iron content may be associated with dopaminergic neuronal cytotoxicity and degeneration in the substantia nigra of the midbrain. However, the cause of iron deposition and its role in the pathological process of PD are unclear. In the present study, we investigated the effects of the nasal mucosal delivery of synthetic human α-synuclein (α-syn) preformed fibrils (PFFs) on the pathogenesis of PD in Macaca fascicularis. We detected that iron deposition was clearly increased in a time-dependent manner from 1 to 17 months in the substantia nigra and globus pallidus, highly contrasting to other brain regions after treatments with α-syn PFFs. At the cellular level, the iron deposits were specifically localized in microglia but not in dopaminergic neurons, nor in other types of glial cells in the substantia nigra, whereas the expression of transferrin (TF), TF receptor 1 (TFR1), TF receptor 2 (TFR2), and ferroportin (FPn) was increased in dopaminergic neurons. Furthermore, no clear dopaminergic neuron loss was observed in the substantia nigra, but with decreased immunoreactivity of tyrosine hydroxylase (TH) and appearance of axonal swelling in the putamen. The brain region-enriched and cell-type-dependent iron localizations indicate that the intranasal α-syn PFFs treatment-induced iron depositions in microglia in the substantia nigra may appear as an early cellular response that may initiate neuroinflammation in the dopaminergic system before cell death occurs. Our data suggest that the inhibition of iron deposition may be a potential approach for the early prevention and treatment of PD.
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http://dx.doi.org/10.1038/s41419-020-03369-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807015PMC
January 2021

Liposomes Encapsulating Neoantigens and Black Phosphorus Quantum Dots for Enhancing Photothermal Immunotherapy.

J Biomed Nanotechnol 2020 Sep;16(9):1394-1405

Colorectal cancer frustrates with high relapse after the traditional treatment including surgery and chemotherapy. Neoantigen-based therapeutic vaccine has achieved high response rate in the clinical trials rising the immunotherapy as a promising alternative for colorectal cancer. Herein, colon cancer cells derived neoantigen peptide Adpgk were employed to be co-encapsulated with black phosphorus quantum dots into liposome (Adpgk-BPQDs-liposome) as therapeutic vaccine. Adpgk-BPQDs-liposome were dispersed in F127 gel containing GM-CSF. The heat generated by black phosphorus (BP) under 808 nm near-infrared laser irradiation accelerates the F127 gel ablation and the release of GM-CSF, which recruit APC cells and prime the native T cells. The tumor bearing mice received the programmed cell death protein 1 (PD-1) checkpoint blockade antibody combined with photo-thermal gel intensively prevented the tumor progress. Furthermore, the tumor infiltrating CD8+ T cells were significantly increased which lead to the elimination of the tumor.
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http://dx.doi.org/10.1166/jbn.2020.2977DOI Listing
September 2020

Chlorogenic acid induces apoptosis, inhibits metastasis and improves antitumor immunity in breast cancer via the NF‑κB signaling pathway.

Oncol Rep 2020 Dec 9. Epub 2020 Dec 9.

School of Medical and Life Sciences/Reproductive and Women‑Children Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, P.R. China.

Breast cancer which is the most common type of diagnosed cancer among women worldwide possesses metastatic potential, multi‑drug resistance, and high mortality. The NF‑κB signaling pathway has been revealed to be abnormally activated in breast cancer cells and closely associated with high metastasis and poor prognosis. In the present study, it was reported that chlorogenic acid (CGA), a potent NF‑κB inhibitor derived from coffee, exerted antitumor activity in breast cancer. MTT and colony formation assays were conducted and it was revealed that CGA inhibited viability and proliferation in breast cancer cells. Additionally, CGA significantly induced apoptosis and suppressed migration and invasion in breast cancer cells. Notably, immunofluorescence analysis confirmed that CGA could efficiently suppress nuclear transcription of NF‑κB p65. In addition, results of western blotting demonstrated that CGA markedly impaired the NF‑κB and EMT signaling pathways. The antitumor effect of CGA was evaluated in a subcutaneous tumor mouse model of 4T1 cells, and the results revealed that CGA markedly retarded tumor growth and prolonged the survival rate of tumor‑bearing mice. Notably, CGA inhibited pulmonary metastasis of 4T1 cells by enhancing the proportion of CD4+ and CD8+ T cells in spleens of mice, which indicated an improvement of antitumor immunity. In conclusion, the present present study demonstrated that CGA improved antitumor immunity, exerting antitumor and anti‑metastatic effects by impairing the NF‑κB/EMT signaling pathway, suggesting that CGA may serve as a potential candidate for therapy of breast cancer.
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http://dx.doi.org/10.3892/or.2020.7891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757108PMC
December 2020

[Retracted] Long non-coding RNA MEG3 inhibits cell growth of gliomas by targeting miR-93 and inactivating PI3K/AKT pathway.

Oncol Rep 2021 Jan 27;45(1):407. Epub 2020 Oct 27.

Department of Neurosurgery, Yulin City Hospital of Traditional Chinese Medicine, Yulin, Shaanxi 719000, P.R. China.

Following the publication of this paper, it was drawn to the authors' attention by an interested reader that certain of the tumours featured in Fig. 6A of the above paper were strikingly similar to those featured in Fig. 8A of an article appearing in International Journal of Oncology (Fan F-Y, Deng R, Yi H, Sun H-P, Zeng Y, He G-C and Su Y: The inhibitory effect of MEG3/miR-214/AIFM2 axis on the growth of T-cell lymphoblastic lymphoma. Int J Oncol 51: 316-326, 2017). The Editor asked the authors for an explanation to account for the appearance of strikingly similar data in their paper independently, and they responded to request that the paper be retracted from Oncology Reports. All the authors agreed that the article should be retracted. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Oncology Reports 38: 2408-2416, 2017; DOI: 10.3892/or.2017.5871].
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http://dx.doi.org/10.3892/or.2020.7828DOI Listing
January 2021

Prognostic value of Ki-67 in nasopharyngeal carcinoma: a meta-analysis.

Biosci Rep 2021 Jan 4. Epub 2021 Jan 4.

Chengdu University of Traditional Chinese Medicine, Chengdu, China.

The prognostic value of Ki-67 in nasopharyngeal carcinoma (NPC) was controversial according to previous studies. We aimed to clarify the association between K-67 expression and survival in NPC through meta-analysis. We conducted a meta-analysis to explore the potential prognostic effect of Ki-67 on overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS) in NPC. A total of 13 studies comprising 1314 NPC patients were included. High Ki-67 expression was associated with poor OS (hazard ratio [HR]=2.70, 95% confidence interval [CI]=1.97-3.71, p<0.001), DFS (HR=1.93, 95% CI=1.49-2.50, p<0.001), and LRFS (HR=1.86, 95% CI=1.11-3.12, p=0.019). However, there was no significant association between Ki-67 and DMFS (HR=1.37, 95% CI=0.78-2.38, p=0.270). Furthermore, the prognostic role of Ki-67 was maintained throughout different sample sizes, analyses of HR, and study designs for OS and DFS in various subgroups. Elevated Ki-67 expression is a reliable prognostic factor for poorer survival outcomes in NPC.
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http://dx.doi.org/10.1042/BSR20203334DOI Listing
January 2021

A Machine Learning Approach for Tracing Tumor Original Sites With Gene Expression Profiles.

Front Bioeng Biotechnol 2020 24;8:607126. Epub 2020 Nov 24.

Key Laboratory of Computational Science and Application of Hainan Province, Haikou, China.

Some carcinomas show that one or more metastatic sites appear with unknown origins. The identification of primary or metastatic tumor tissues is crucial for physicians to develop precise treatment plans for patients. With unknown primary origin sites, it is challenging to design specific plans for patients. Usually, those patients receive broad-spectrum chemotherapy, while still having poor prognosis though. Machine learning has been widely used and already achieved significant advantages in clinical practices. In this study, we classify and predict a large number of tumor samples with uncertain origins by applying the random forest and Naive Bayesian algorithms. We use the precision, recall, and other measurements to evaluate the performance of our approach. The results have showed that the prediction accuracy of this method was 90.4 for 7,713 samples. The accuracy was 80% for 20 metastatic tumors samples. In addition, the 10-fold cross-validation is used to evaluate the accuracy of classification, which reaches 91%.
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http://dx.doi.org/10.3389/fbioe.2020.607126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732438PMC
November 2020

Application of in Simulated Solid-State Fermentation for Production: Changes of Microbial Community Structure and Flavor Metabolism.

Front Microbiol 2020 27;11:598758. Epub 2020 Nov 27.

Laboratory of Food Microbiology and Enzyme Engineering, Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing, China.

is conducive to the synthesis of ester compounds in brewing the Chinese liquor ; esters are crucial for the quality of . In this study, simulated solid-state fermentation for production was used to explore whether artificial addition of could improve the flavor substance in , and the underlying mechanisms. Two experimental groups were studied, in which Y3604 (Group A) and YF1503 (Group B) were added, respectively; in the control group (Group C), no was added. Adding strain Y3604 increased the content of esters in fermentation samples, especially ethyl acetate and ethyl caproate, and reduced the content of higher alcohols. Adding strain YF1503 had little effect on the ester content but decreased the content of higher alcohols. The diversity and abundance of prokaryotic genera in Group A and B samples were similar, but there were some differences compared with Group C. The correlations of genera in Group A or B samples were simple compared with group C. Although the predominant eukaryotic genera in the three groups were consistent, the abundance of each gene varied among groups. Based on our findings, bioaugmentation of fermentation with will change the ethyl acetate content and cause changes in the levels of other flavor substances. We suggest that the changes in flavor substances caused by the addition of are mainly due to changes in the microbial community structure that result from the addition of .
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http://dx.doi.org/10.3389/fmicb.2020.598758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728721PMC
November 2020

Electron Donor-Acceptor Complex-Initiated Photochemical Cyanation for the Preparation of α-Amino Nitriles.

Org Lett 2020 12 7;22(24):9638-9643. Epub 2020 Dec 7.

State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, College of Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China.

An electron donor-acceptor complex-initiated α-cyanation of tertiary amines has been described. The reaction protocol provides a novel method to synthesize various α-amino nitriles under mild conditions. The reaction can proceed smoothly without the presence of photocatalysts and transition metal catalysts, and either oxidants are unnecessary or O is the only oxidant. The practicality of this method is showcased not only by the late-stage functionalization of natural alkaloid derivatives and pharmaceutical intermediate, but also by the applicability of a stop-flow microtubing reactor.
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http://dx.doi.org/10.1021/acs.orglett.0c03703DOI Listing
December 2020

Katanin p60-like 1 sculpts the cytoskeleton in mechanosensory cilia.

J Cell Biol 2021 Jan;220(1)

Tsinghua-Peking Joint Center for Life Science, School of Life Sciences, Tsinghua University, Beijing, China.

Mechanoreceptor cells develop a specialized cytoskeleton that plays structural and sensory roles at the site of mechanotransduction. However, little is known about how the cytoskeleton is organized and formed. Using electron tomography and live-cell imaging, we resolve the 3D structure and dynamics of the microtubule-based cytoskeleton in fly campaniform mechanosensory cilia. Investigating the formation of the cytoskeleton, we find that katanin p60-like 1 (kat-60L1), a neuronal type of microtubule-severing enzyme, serves two functions. First, it amplifies the mass of microtubules to form the dense microtubule arrays inside the sensory cilia. Second, it generates short microtubules that are required to build the nanoscopic cytoskeleton at the mechanotransduction site. Additional analyses further reveal the functional roles of Patronin and other potential factors in the local regulatory network. In all, our results characterize the specialized cytoskeleton in fly external mechanosensory cilia at near-molecular resolution and provide mechanistic insights into how it is formed.
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http://dx.doi.org/10.1083/jcb.202004184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717695PMC
January 2021

Metabolomics analysis reveals potential mechanisms of phenolic accumulation in lettuce (Lactuca sativa L.) induced by low nitrogen supply.

Plant Physiol Biochem 2021 Jan 23;158:446-453. Epub 2020 Nov 23.

MOE Key Laboratory of Environment Remediation and Ecological Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, 310058, China; Key Laboratory of Subtropical Soil Science and Plant Nutrition of Zhejiang Province, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, 310058, China. Electronic address:

The roles of nitrogen availability in determining the phenolic accumulation of vegetables have been widely studied, but the underlying mechanism involved remains unknown. Thus, primary and secondary metabolites profiling of lettuce leaves were performed using non-targeted metabolomics analysis. The results showed that carbon metabolism, amino acid metabolism, and phenolic biosynthesis metabolism in lettuce were significantly affected by low nitrogen supply (LN). The phenolic content was significantly increased in LN-treated lettuce, indicating that the activated phenolic biosynthesis was triggered by the LN treatment. The reduced citrate cycle and enhanced glucose and sucrose content suggested there is a relative excess of carbon resources in LN-treated lettuce. In addition, the decreased nitrogen-rich amino acids (glutamine and aspartate acid) and the maintained phenylalanine content indicated the redirection of nitrogen resources to phenylalanine biosynthesis. Meanwhile, no significant changes of chlorophyll content were observed in LN-treated lettuce leaves. The LN-treated lettuce showed lower glutamine synthetase activity but higher glutamate synthase activity compared to control. These findings together suggest that LN treatment may increase the phenolic accumulation in lettuce by effectively redirecting more carbon and nitrogen resources to the phenolic biosynthesis pathway.
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http://dx.doi.org/10.1016/j.plaphy.2020.11.027DOI Listing
January 2021

Pyrene-porphyrin based ratiometric fluorescent sensor array for discrimination of glycosaminoglycans.

Anal Chim Acta 2021 Jan 28;1141:214-220. Epub 2020 Oct 28.

Jiangsu Key Laboratory of Pesticide Science, Department of Chemistry, College of Sciences, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, China; State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, 116024, China. Electronic address:

Accurate discrimination of common glycosaminoglycans (GAGs) before they are used in clinics is of great importance. Herein, a ratiometric sensor array Py-PP for discrimination of GAGs was constructed using three pyrene-porphyrin supramolecular complexes termed Py-PP1, Py-PP2 and Py-PP4. These complexes were readily synthesized by mixing pyrene-1-butyric acid (Py) and porphyrins PP1, PP2 and PP4 respectively. In the presence GAGs, the effective FRET from Py to porphyrin in the complex was influenced as a result of the competitive binding interactions between porphyrin and GAG. Controlled by the structural differences in the three porphyrins, complexes Py-PP1, Py-PP2 and Py-PP4 were determined to be cross-responsive towards tested GAGs including Hep, HA, Chs and DS. Distinctive fluorescence patterns were successfully generated for each GAG by the sensor array. The Py-PP sensor array was found to be powerful for discrimination of GAGs in both PBS and 5% serum media. Moreover, Py-PP was also successfully applied for reliable differentiation of Hep from other biological interferences and detection of trace GAG contaminants (0.1%, wt%) in Hep with 100% accuracy.
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http://dx.doi.org/10.1016/j.aca.2020.10.052DOI Listing
January 2021