Publications by authors named "Ling Huang"

913 Publications

Novel Polarity Fluorescent Probe for Dual-Color Visualization of Lysosomes and Plasma Membrane during Apoptosis.

Anal Chem 2022 Aug 9. Epub 2022 Aug 9.

Guangxi Key Laboratory of Electrochemical Energy Materials, Institute of Optical Materials and Chemical Biology, School of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi 530004, P. R. China.

Apoptosis plays a crucial role in the occurrence of cancer and other diseases. Real-time monitoring of the cell apoptosis process has great significance for cell viability and drug screening. Herein, a novel fluorescent probe was constructed based on the fluorescence resonance energy transfer mechanism, which track the sensitivity of polarity changes, as well as detect the drug-induced cell apoptosis process in a dual-color mode. Importantly, the change of cellular microenvironmental polarity makes it possible to dynamically visualize the process of drug-induced cell apoptosis. More significantly, the designed probe targeted the lysosomes in the living cells to give a blue emission, and it accumulated on the plasma membrane to display red fluorescence during the drug-induced cell apoptosis process. Thus, cell viability could be monitored by both the localization and emission colors of the robust probe. We expect that the unique probe can provide a new blueprint for evaluating and screening apoptosis-related drugs.
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http://dx.doi.org/10.1021/acs.analchem.2c02207DOI Listing
August 2022

Dye doped Metal-organic Frameworks for Enhanced Phototherapy.

Adv Drug Deliv Rev 2022 Aug 3:114479. Epub 2022 Aug 3.

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, United States.

Phototherapy is a noninvasive cancer treatment that relies on the interaction between light and photoactive agents. These photoactive agents are typically organic dyes, but their hydrophobic nature and self-aggregation tendency in biological media greatly restricts the development of highly effective phototherapeutic systems. In the past decade, functional dye-doped metal-organic framework (MOF)-based phototherapy has attracted enormous interest because organic dyes can be encapsulated and isolated within the MOF structure to show superior treatment efficacy. In addition to incorporating the reported phototherapeutic dyes into MOF as the ligand or the guest in the pores, the construction of an MOF-based phototherapy agent can also be extended to these dye units that are previously inactive for phototherapy. Thus, this review focuses on the emerging development of phototherapeutic MOFs that exhibited better performance than the involving dye units due to the controlled dye aggregation within the MOF. The related mechanisms and some emerging future directions of dye-doped MOF-based phototherapy are also discussed and summarized.
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http://dx.doi.org/10.1016/j.addr.2022.114479DOI Listing
August 2022

5-Aminosalicylic acid ameliorates dextran sulfate sodium-induced colitis in mice by modulating gut microbiota and bile acid metabolism.

Cell Mol Life Sci 2022 Aug 1;79(8):460. Epub 2022 Aug 1.

College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan, 430065, People's Republic of China.

Colitis develops via the convergence of environmental, microbial, immunological, and genetic factors. The medicine 5-aminosalicylic acid (5-ASA) is widely used in clinical practice for colitis (especially ulcerative colitis) treatment. However, the significance of gut microbiota in the protective effect of 5-ASA on colitis has not been explored. Using a dextran sulfate sodium (DSS)-induced colitis mouse model, we found that 5-ASA ameliorated colitis symptoms in DSS-treated mice, accompanied by increased body weight gain and colon length, and a decrease in disease activity index (DAI) score and spleen index. Also, 5-ASA alleviated DSS-induced damage to colonic tissues, as indicated by suppressed inflammation and decreased tight junction, mucin, and water-sodium transport protein levels. Moreover, the 16S rDNA gene sequencing results illustrated that 5-ASA reshaped the disordered gut microbiota community structure in DSS-treated mice by promoting the abundance of Bifidobacterium, Lachnoclostridium, and Anaerotruncus, and reducing the content of Alloprevotella and Desulfovibrio. Furthermore, 5-ASA improved the abnormal metabolism of bile acids (BAs) by regulating the Farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5 (TGR5) signaling pathways in DSS-treated mice. In contrast, 5-ASA did not prevent the occurrence of colitis in mice with gut microbiota depletion, confirming the essential role of gut microbiota in colitis treatment by 5-ASA. In conclusion, 5-ASA can ameliorate DSS-induced colitis in mice by modulating gut microbiota and bile acid metabolism. These findings documented the new therapeutic mechanisms of 5-ASA in clinical colitis treatment.
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http://dx.doi.org/10.1007/s00018-022-04471-3DOI Listing
August 2022

Sharp Enhancement of Birefringence in Antimony Oxalates Achieved by the Cation-Anion Synergetic Interaction Strategy.

Inorg Chem 2022 Aug 27;61(31):12481-12488. Epub 2022 Jul 27.

College of Chemistry, Sichuan University, Chengdu 610065, P. R. China.

Birefringent materials with large birefringence play an important role in in laser science and technology owing to their ability to modulate polarized light. However, the lack of systematic and effective synthesis strategies severely hinders the development of novel superior birefringent materials. Herein, the cation-anion synergetic interaction strategy was proposed to successfully synthesize two excellent UV birefringent materials, RbSb(CO)F·HO and [C(NH)]Sb(CO)F·HO. Both compounds feature unprecedented [Sb(CO)F] anionic chains composed of planar π-conjugated [CO] units and a distorted SbOF complex with stereochemically active lone pairs, which induce a large optical anisotropy. Remarkably, further enhancement of birefringence in [C(NH)]Sb(CO)F·HO was achieved via cation-anion synergetic interactions between the [C(NH)] cationic groups and [Sb(CO)F] anionic chains. It exhibited a giant birefringence of [email protected] nm, twice larger than that of its analogue RbSb(CO)F·HO ([email protected] nm). A detailed structural analysis and theoretical calculations revealed that the cation-anion synergetic interaction strategy is an effective strategy for the efficient exploration of superior birefringent materials, which will guide the further exploration of new structure-driven functional materials.
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http://dx.doi.org/10.1021/acs.inorgchem.2c02262DOI Listing
August 2022

Composition of Pinot Noir Wine from Grapevine Red Blotch Disease-Infected Vines Managed with Exogenous Abscisic Acid Applications.

Molecules 2022 Jul 15;27(14). Epub 2022 Jul 15.

Department of Food Science and Technology, Oregon State University, Corvallis, OR 97331, USA.

Grapevine red blotch disease (GRBD) has negative effects on grape development and impacts berry ripening. Abscisic acid (ABA) is a plant growth regulator involved in the initiation of berry ripening. Exogenous abscisic acid application was compared to an unsprayed control on GRBD-positive Pinot noir vines during two vintages, and the total monomeric anthocyanin, total phenolics, phenolic composition, and volatile profile were measured in wines. In addition, untargeted metabolites were profiled using high-resolution LC-MS/MS. Results showed that the wine composition varied by vintage year and was not consistent with ABA application. Wines from the ABA treatment had a lower total anthocyanin and total phenolic content in one year. The untargeted high-resolution LC-MS/MS analysis showed a higher abundance of phenolic compounds in ABA wines in 2019, but lower in 2018. The wine volatile compounds of ABA treatments varied by vintage. There were higher levels of free β-damascenone, β-ionone, nerol, and several fermentation-derived esters, acids, and alcohols in ABA wines, but these were not observed in 2019. Lower 3-isobutyl-2-methoxypyrazine (IBMP) was also observed in wines with ABA treatment in 2019. The results demonstrated that ABA application to the fruit zones did not consistently mitigate the adverse impacts of GRBD on Pinot noir wines.
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http://dx.doi.org/10.3390/molecules27144520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321972PMC
July 2022

Genomic signature of MTOR could be an immunogenicity marker in human colorectal cancer.

BMC Cancer 2022 Jul 26;22(1):818. Epub 2022 Jul 26.

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Background: The mTOR signaling pathway plays an important role in cancer. As a master regulator, the status of MTOR affects pathway activity and the efficacy of mTOR inhibitor therapy. However, little research has been performed to explore MTOR in colorectal cancer (CRC).

Methods: In this study, gene expression and clinical data were analyzed using The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Signaling pathways related to MTOR in CRC were identified by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). Somatic mutation data were downloaded from TCGA and analyzed using the maftools R package. Tumor Immune Estimation Resource (TIMER) and CIBERSORT were used to analyze correlations between MTOR and tumor-infiltrating immune cells (TIICs). Finally, we detected MTOR mutations in a CRC cohort from our database using whole-exome sequencing.

Results: We found that MTOR was overexpressed in Asian CRC patients and associated with a poor prognosis. Enrichment analysis showed that MTOR was involved in metabolism, cell adhesion, and translation pathways in CRC. High MTOR expression was correlated with high tumor mutation burden (TMB) and several TIICs. Finally, we found that the mTOR signaling pathway was activated in CRC lines characterized by microsatellite instability (MSI), and the frequency of MTOR mutations was higher in MSI-high (MSI-H) patients than in microsatellite stable (MSS) patients.

Conclusions: MTOR may represent a comprehensive indicator of prognosis and immunological status in CRC. The genomic signatures of MTOR may provide guidance for exploring the role of mTOR inhibitors in CRC.
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http://dx.doi.org/10.1186/s12885-022-09901-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327395PMC
July 2022

Thermal Enhancement of Luminescence for Negative Thermal Expansion in Molecular Materials.

J Am Chem Soc 2022 Aug 25;144(30):13688-13695. Epub 2022 Jul 25.

Beijing Advanced Innovation Center for Materials Genome Engineering, Institute of Solid State Chemistry, University of Science and Technology Beijing, Beijing 100083, China.

Overcoming thermal quenching is an essential issue in the practical application of luminescent materials. Herein, we found that negative thermal expansion (NTE) can achieve the thermal enhancement of luminescence in molecular materials based on three metal-organic frameworks CuX-bpy (X = Cl, Br, I; bpy = 4,4'-bipyridine). All complexes exhibit NTE on the -axis, and the strongest NTE leads to a contraction of the Cu...Cu distance in CuCl-bpy, which further intensifies the luminescence emission. This phenomenon indicates the existence of thermally enhanced charge transfer. Moreover, the origin of the distinction in charge transfer attributed to the different valence states of the copper is investigated through the combined studies of X-ray photoelectron spectroscopy, X-ray absorption near-edge structure, and density functional theory calculations. This research provides a new approach to modulating the luminescence thermal enhancement by NTE.
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http://dx.doi.org/10.1021/jacs.2c04316DOI Listing
August 2022

Efficacy analysis of Cheng's GIRAFFE reconstruction after proximal gastrectomy for adenocarcinoma of esophagogastric junction.

Chin J Cancer Res 2022 Jun;34(3):289-297

Department of Gastric Surgery, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China.

Objective: Reconstruction of the digestive tract for adenocarcinoma of esophagogastric junction (AEG) is in dispute. This study evaluated Cheng's gastric tube interposition esophagogastrostomy with reconstruction of His angle and fundus (Cheng's GIRAFFE anastomosis) in laparoscopic/open proximal gastrectomy for Siewert type II AEG, which was performed at Zhejiang Cancer Hospital and the First Affiliated Hospital of Zhejiang Chinese Medical University. Here, we discuss the preliminary results of gastric emptying and anti-reflux.

Methods: From a retrospective database, 74 patients with advanced Siewert type II AEG underwent curative proximal gastrectomy with GIRAFFE anastomosis, and their gastric emptying and anti-reflux outcomes were evaluated by the Reflux Disease Questionnaire (RDQ) score, nuclide gastric emptying, 24-h impedance-pH monitoring and gastroscopy.

Results: Seventy-four patients successfully completed proximal partial gastrectomy with Cheng's GIRAFFE esophagogastric anastomosis. RDQ score six months after the operation was 2.2±2.5. Results of nuclide gastric emptying examinations showed that the gastric half-emptying time was 67.0±21.5 min, the 1-h residual rate was (52.2±7.7)%, the 2-h residual rate was (36.4±5.1)%, and the 3-h residual rate was (28.8±3.6)%; 24-h impedance-pH monitoring revealed that the mean DeMeester score was 5.8±2.9. Reflux esophagitis was observed by gastroscopy in 7 patients six months after surgery.

Conclusions: Cheng's GIRAFFE anastomosis is safe and feasible for Siewert type II AEG.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2022.03.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273578PMC
June 2022

Discovery of a novel class of benzoxazole derivatives as histamine H receptor ligands for the treatment of neuropathic pain.

Bioorg Chem 2022 Oct 19;127:106039. Epub 2022 Jul 19.

Jiangsu Institute of Marine Resources Development, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Ocean University, Lianyungang 222005, China; Grand Life Sciences (Wuhan) Co., Ltd., Wuhan 430040, China. Electronic address:

To discover effective analgesics, we summarize the synthesis, optimization, and pharmacological anti-nociceptive effects of a novel series of benzoxazole derivatives targeting H receptor (HR). The new benzoxazoles were assayed in vitro for histamine HR and HR binding affinity. The best compound 8d (2-methyl-6-(3-(4-methylpiperazin-1-yl)propoxy)benzo[d]oxazole) exhibited high affinity for HR (K = 19.7 nM), high selectivity for ten other off-target receptors, and negligible effects on human ether-a-go-go-related gene (hERG, cardiac ion channel). In rodent animals, compound 8d dose-dependently reversed formalin-evoked pain (Phase I, ED = 6.0 mg/kg; Phase II, ED = 7.8 mg/kg) and CCI-induced neuropathic pain (chronic constriction injury, ED = 15.6 mg/kg). Furthermore, compound 8d showed an excellent safety profile in acute toxicity test (LD > 2000 mg/kg) with a therapeutic index (TI = LD/ED) > 250 and showed a desirable drug-like pharmacokinetic profile. Above characteristics indicate that compound 8d represents a promising candidate analgesic for the treatment of neuropathic pain.
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http://dx.doi.org/10.1016/j.bioorg.2022.106039DOI Listing
October 2022

Landscape of somatic alterations in large-scale solid tumors from an Asian population.

Nat Commun 2022 Jul 23;13(1):4264. Epub 2022 Jul 23.

Department of Gastrointestinal Oncology, Huifuxi Branch of Guangdong Provincial People's Hospital, Guangzhou, China.

Extending the benefits of tumor molecular profiling for all cancer patients requires a comprehensive analysis of tumor genomes across distinct patient populations worldwide. In this study, we perform deep next-generation DNA sequencing (NGS) from tumor tissues and matched blood specimens from over 10,000 patients in China by using a 450-gene comprehensive assay, developed and implemented under international clinical regulations. We perform a comprehensive comparison of somatically altered genes, the distribution of tumor mutational burden (TMB), gene fusion patterns, and the spectrum of various somatic alterations between Chinese and American patient populations. Here, we show 64% of cancers from Chinese patients in this study have clinically actionable genomic alterations, which may affect clinical decisions related to targeted therapy or immunotherapy. These findings describe the similarities and differences between tumors from Chinese and American patients, providing valuable information for personalized medicine.
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http://dx.doi.org/10.1038/s41467-022-31780-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308789PMC
July 2022

Personalized tumor vaccine for pancreatic cancer.

Cancer Immunol Immunother 2022 Jul 14. Epub 2022 Jul 14.

Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA, 02215, USA.

Background: Pancreatic cancer is a highly lethal malignancy often presenting with advanced disease and characterized by resistance to standard chemotherapy. Immune-based therapies such checkpoint inhibition have been largely ineffective such that pancreatic cancer is categorized as an immunologically "cold tumor". In the present study, we examine the therapeutic efficacy of a personalized cancer vaccine in which tumor cells are fused with dendritic cells (DC) resulting in the broad induction of antitumor immunity.

Results: In the KPC spontaneous pancreatic cancer murine model, we demonstrated that vaccination with DC/KPC fusions led to expansion of pancreatic cancer specific lymphocytes with an activated phenotype. Remarkably, vaccination led to a reduction in tumor bulk and near doubling of median survival in this highly aggressive model. In a second murine pancreatic model (Panc02), vaccination with DC/tumor fusions similarly led to expansion of tumor antigen specific lymphocytes and their infiltration to the tumor site. Having shown efficacy in immunocompetent murine models, we subsequently demonstrated that DC/tumor fusions generated from primary human pancreatic cancer and autologous DCs potently stimulate tumor specific cytotoxic lymphocyte responses.

Conclusions: DC/tumor fusions induce the activation and expansion of tumor reactive lymphocytes with the capacity to infiltrate into the pancreatic cancer tumor bed.
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http://dx.doi.org/10.1007/s00262-022-03237-xDOI Listing
July 2022

Effects of Nitrogen Fertilizer Ratio on Microbial Diversity of Rice Rhizosphere Soil in Cold Region.

Cell Mol Biol (Noisy-le-grand) 2022 Feb 27;67(6):107-116. Epub 2022 Feb 27.

School of Life Science and Technology, Henan Institute of Science and Technology, Xinxiang, 453003, China.

The experiment was conducted in the paddy field of a scientific and technological park of an agricultural reclamation farm in Xinxiang province from 2017 to 2019. The soil quality of the experimental field was the rhizosphere soil of rice in the cold region, and Longjing 31 was used as the experimental material. The effects of nitrogen application ratio on microbial diversity of rice rhizosphere soil in the cold region were studied. The aim is to provide a theoretical basis for rational fertilization, improving soil environment and high yield and efficiency. The results showed that: (a) the microbial diversity index of rice rhizosphere soil in the cold region was the best after the second nitrogen application; (b) under the ratio of N4 nitrogen application, the activity of bacteria, fungi and actinomycetes in rice rhizosphere soil in a cold region and their survival were the best; (c) under intensive cultivation conditions, the microbial diversity was the highest under SF1 treatment. SF0 treatment had the highest fungal diversity and SF3 treatment had the highest actinomycete diversity. (d) There was no significant effect on the microbial diversity of rice rhizosphere soil in the cold region without nitrogen fertilizer application in a single season.
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http://dx.doi.org/10.14715/cmb/2021.67.6.15DOI Listing
February 2022

Homochiral Hybrid Organic-Inorganic Cadmium Chlorides Directed by Enantiopure Amino Acids.

Inorg Chem 2022 Jul 10;61(29):11032-11035. Epub 2022 Jul 10.

College of Chemistry, Sichuan University, Chengdu 610064, China.

Homochiral cadmium chlorides were prepared under mild conditions using enantiopure amino acids as structure-directing agents. They feature a lacunary hexagonal CdCl lattice as well as a one-dimensional perovskite structure. The coexistence of protonated and zwitterionic amino acids between cadmium chloride chains is quite rare. These compounds are nonlinear optically active solids showing a moderate second-harmonic-generation response. Theoretical calculations were performed to reveal the origin of their nonlinear-optical properties.
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http://dx.doi.org/10.1021/acs.inorgchem.2c01782DOI Listing
July 2022

Integrated Single-Cell RNA-Sequencing Analysis of Gastric Cancer Identifies FABP1 as a Novel Prognostic Biomarker.

J Oncol 2022 28;2022:4761403. Epub 2022 Jun 28.

Hainan Province Key Laboratory for Drug Preclinical Study of Pharmacology and Toxicology Research, Hainan Medical University, Haikou 571199, China.

Gastric cancer (GC) is usually diagnosed in an advanced stage at the first visit due to the atypical clinical symptoms. The low surgical resection rate and chemotherapy sensitivity result in dismal survival. Therefore, it is urgent to develop novel biomarkers with high sensitivity and specificity to accurately assess the prognosis of GC patients. In the present study, 3385 differentially expressed genes (DEGs) were obtained from the single-cell RNA sequencing data of GC specimens. Using the unsupervised dimensionality reduction, we further found 3 subsets of cells including gastric cells, plasmacytoid dendritic cells, and memory T cells. Based on the cell clustering, we explored the key regulatory genes for GC progression by pseudo-time analysis and functional enrichment analysis. According to the results, the significant differentially expressed fatty acid-binding protein 1 (FABP1) verified by pseudo-time analysis was identified as the hub gene of GC progression. FABP1 was shown to be closely related to the long-term survival and the age at diagnosis of patients with GC in analysis based on the TCGA (The Cancer Genome Atlas) database. To further verify the role of FABP1 in GC, we performed immunohistochemical (IHC) analysis using the GC tissue microarray and found that the expression level of FABP1 was higher in GC tissues than in the adjacent tissues. Moreover, GC patients with higher expression of FABP1 had a worse clinical outcome. In summary, our study revealed that FABP1 is a potential effective biomarker for the prognosis of GC, and high expression of FABP1 predicts unsatisfactory survival.
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http://dx.doi.org/10.1155/2022/4761403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9256400PMC
June 2022

Investigation of stress distribution within an endodontically treated tooth restored with different restorations.

J Dent Sci 2022 Jul 21;17(3):1115-1124. Epub 2022 Feb 21.

Department of Fixed Prosthodontics, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

Background/purpose: Recently, metal-free restoration has become the standard in prosthetic treatment. However, it is still unclear which combination is most effective in preventing root fracture and secondary caries. The purpose of this study was to evaluate the influence of different post systems, crown materials, crown thickness and luting agents on the stress distribution around the crown margins, cervical dentin and the tip of the post.

Materials And Methods: Ninety-six mandibular first premolar models were developed and analyzed using finite element analysis (FEA). Two designs of crowns, six kinds of crown materials, four types of post and core systems and two kinds of luting agents were included and evaluated for the stress distribution within the abutment teeth. The Von Mises stress magnitudes were compared among all models.

Results: The stress at the tip of the post decreased as the young's modulus of luting agent decreased; The stress concentrated more at the cervical area (dentin and crown), as the physical properties of the crown material increased.

Conclusion: Crowns fabricated using polyetheretherketone (PEEK) can reduce the stress concentration at the cervical area, so it may be possible to reduce the amount of tooth reduction during abutment tooth preparation. The stress distribution around the post tip is affected by the post and core systems and luting agent, regardless of crown materials and thickness. When inserting a post of the higher Young's modulus such as zirconia post, methyl methacrylate luting cement can reduce the stress concentration at the tip of the post.
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http://dx.doi.org/10.1016/j.jds.2022.01.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9236959PMC
July 2022

Lipid Profile in Patients With Primary Ovarian Insufficiency: A Systematic Review and Meta-Analysis.

Front Endocrinol (Lausanne) 2022 10;13:876775. Epub 2022 Jun 10.

Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

Backgrounds: A large number of studies have investigated the effect of early menopause on cardiovascular disease (CVD) outcomes and the relationship between the levels of lipid profile and primary ovarian insufficiency (POI). However, the results are inconsistent. The aim of this meta-analysis was to assess whether the levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) changed in women with POI relative to healthy controls.

Methods: To identify eligible studies, references published prior to December 2021 were searched in the PubMed, Embase, Cochrane Library and Web of Science databases. DerSimonian-Laird random-effects model was used to estimate the overall standard mean difference (SMD) between POI and healthy control subjects. Subgroup analysis and sensitivity analysis were preformed, and publication bias was assessed.

Results: A total of 12 studies featuring 846 women with primary ovarian insufficiency and 959 healthy women were selected for analysis. The meta-analysis showed that the levels of TC (SMD: 0.60; 95% CI: 0.32 to 0.89; <0.0001), TG (SMD: 0.36; 95% CI: 0.12 to 0.60; 0.003), LDL (SMD: 0.46; 95% CI: 0.16 to 0.76; 0.003) were significantly increased in women with POI. There was no significant change in the level of HDL (SMD: 0.25; 95% CI: -0.12 to 0.61; 0.19). Subgroup analysis showed that the heterogeneity in this meta-analysis of the correlation between lipid profile and POI might come from by region, sample size, number of cases, mean body mass index (BMI) value of cases and mean age of cases.

Conclusions: Scientific evidence suggests that the lipid profile levels were altered in patients with primary ovarian insufficiency compared to healthy controls. Therefore, we recommend that early medical intervention (e.g., hormone replacement therapy) to minimize the risk of CVD morbidity and mortality associated with dyslipidemia in patients with POI.

Systematic Review Registration: PROSPERO, identifier CRD42021297088.
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http://dx.doi.org/10.3389/fendo.2022.876775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226361PMC
June 2022

Huaier Inhibits Gastric Cancer Growth and Hepatic Metastasis by Reducing Syntenin Expression and STAT3 Phosphorylation.

J Oncol 2022 15;2022:6065516. Epub 2022 Jun 15.

The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China.

Gastric cancer (GC) is a common malignant tumor worldwide and poses a serious threat to human health. As a traditional Chinese medicine, Huaier ( Murr.) has been used in the clinical treatment of GC. However, the mechanism underlying the anticancer effect of Huaier remains poorly understood. In this study, we used imaging technology to determine the anticancer effect of the Huaier n-butanol extract (HBE) on orthotopic and hepatic metastasis of GC mouse models. We found that HBE suppressed tumor growth and metastasis without causing apparent host toxicity. Proteomic analysis of GC cells before and after HBE intervention revealed syntenin to be one of the most significantly downregulated proteins after HBE intervention. We further demonstrated that HBE suppressed the growth and metastasis of GC by reducing the expression of syntenin and the phosphorylation of STAT3 at Y705 and reversing the epithelial-mesenchymal transition (EMT). In addition, we confirmed that syntenin was highly expressed in GC tissue and correlated with metastasis and poor prognosis. In conclusion, our results suggest that Huaier, a clinically used anticancer drug, may inhibit the growth and liver metastasis of GC by inhibiting the syntenin/STAT3 signaling pathway and reversing EMT.
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http://dx.doi.org/10.1155/2022/6065516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9217535PMC
June 2022

Risk factors for midcourse correction during treatment of first series of aligners with Invisalign.

Am J Orthod Dentofacial Orthop 2022 Aug 23;162(2):e96-e102. Epub 2022 Jun 23.

Department of Orthodontics, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China. Electronic address:

Introduction: This study aimed to analyze risk factors for midcourse correction (MC) during the first series of aligners in treatments with Invisalign (Align Technology, Santa Clara, Calif).

Methods: Three hundred and fourteen patients treated with Invisalign were divided into MC and non-midcourse correction groups according to whether they completed the first series of aligners. Differences between these groups were compared with independent sample t tests, chi-square tests, and Wilcoxon rank sum tests. A multivariate logistic regression analysis was performed to identify independent risk factors, including gender, age, extraction treatment, interproximal reduction, correction steps (steps in first series treatment), overbite, overjet, the curve of Spee, Angle classification, and crowding.

Results: The percentage of females (86.3%), Angle Class I malocclusion (62.4%), and nonextraction (56.1%) was relatively higher in all 314 patients. More than half of the patients (73.6%) completed the first series of aligners. Differences between the groups in the number of patients with extraction, correction steps, and the curve of Spee were significant (P <0.05). The proportions of MC were 41.3% and 14.8% in extraction and nonextraction patients, respectively. More initially planned correction steps were seen in the MC group (53.4 ± 15.6 steps). Extraction (adjusted odds ratio, 0.375; P = 0.001) and correction steps (adjusted odds ratio, 1.06; P <0.001) were independent risk factors for MC.

Conclusions: Extraction and the number of initially planned correction steps are independent risk factors for MC. In patients with complex dentofacial abnormalities, such as extraction, MC may be needed to achieve predicted changes.
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http://dx.doi.org/10.1016/j.ajodo.2021.12.018DOI Listing
August 2022

Wiskott-Aldrich syndrome protein forms nuclear condensates and regulates alternative splicing.

Nat Commun 2022 06 25;13(1):3646. Epub 2022 Jun 25.

Department of Research Laboratories and Director of Center for Stem Cell and Cell Therapy, Instituto G. Gaslini Children Hospital Scientific Institute, 16147, Genova, Italy.

The diverse functions of WASP, the deficiency of which causes Wiskott-Aldrich syndrome (WAS), remain poorly defined. We generated three isogenic WAS models using patient induced pluripotent stem cells and genome editing. These models recapitulated WAS phenotypes and revealed that WASP deficiency causes an upregulation of numerous RNA splicing factors and widespread altered splicing. Loss of WASP binding to splicing factor gene promoters frequently leads to aberrant epigenetic activation. WASP interacts with dozens of nuclear speckle constituents and constrains SRSF2 mobility. Using an optogenetic system, we showed that WASP forms phase-separated condensates that encompasses SRSF2, nascent RNA and active Pol II. The role of WASP in gene body condensates is corroborated by ChIPseq and RIPseq. Together our data reveal that WASP is a nexus regulator of RNA splicing that controls the transcription of splicing factors epigenetically and the dynamics of the splicing machinery through liquid-liquid phase separation.
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http://dx.doi.org/10.1038/s41467-022-31220-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233711PMC
June 2022

Copper Substitution in P2-Type Sodium Layered Oxide To Mitigate Phase Transition and Enhance Cyclability of Sodium-Ion Batteries.

ACS Appl Mater Interfaces 2022 Jul 24;14(26):29813-29821. Epub 2022 Jun 24.

State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

Development of high-performance cathode materials is one of the key challenges in the practical application of sodium-ion batteries. Among all the cathode materials, layered sodium transition-metal oxides are particularly attractive. However, undesired phase transitions are often reported and have detrimental effects on the structure stability and electrochemical performance. Cu substitution of zinc in the P2-type NaMnNiZnCuO ( = 0, 0.075, and 0.15) composites was investigated in this study for mitigating the biphase transition and enhancing the electrochemical performance of sodium-ion batteries. The coupling effect of Zn and Cu enables an excellent capacity retention of 96.4% of the initial discharge capacity after 150 cycles at 0.1 C in the Na/NaMnNiZnCuO cell. The biphase transition that occurred in the high voltage range has been significantly suppressed after the incorporation of Cu in NaMnNiZnO, which was confirmed by in situ X-ray diffraction studies. Moreover, the substitution of the inert element Zn with electrochemically active Cu leads to the suppression of anionic redox and the occurrence of Cu redox reaction, and the electrolyte decomposition is impeded after the introduction of electrochemically active Cu in the NaMnNiZnCuO composite cathode. The enhanced electrochemical performance in the NaMnNiZnCuO electrode can be ascribed to the coexistence of Zn and Cu and alleviated volumetric change as well as suppressed electrode/electrolyte side reaction after Cu substitution.
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http://dx.doi.org/10.1021/acsami.2c05521DOI Listing
July 2022

The Rapid Emergence of Ceftazidime-Avibactam Resistance Mediated by KPC Variants in Carbapenem-Resistant in Zhejiang Province, China.

Antibiotics (Basel) 2022 May 30;11(6). Epub 2022 May 30.

Department of Clinical Laboratory, School of Medicine, Second Affiliated Hospital of Zhejiang University, Hangzhou 310000, China.

Ceftazidime-avibactam (CAV) is a new treatment option against carbapenem-resistant (CRKP) infections. However, the rapid emergence of CAV resistance mediated by KPC variants has posed a severe threat to healthcare after its clinical application. The characteristics of CAV resistance in CRKP strains needs to be determined in China. A total of 477 CRKP isolates were collected from 46 hospitals in Zhejiang Province from 2018 to 2021. The results demonstrated that CAV had a potent activity against 94.5% of all CRKP (451/477, 95% CI: 93.0-96.1%) and 86.0% of CRKP strains carrying genes (410/477, 95% CI: 83.5-88.4%). A total of 26 CAV-resistant strains were found. Among these strains, sixteen harbored metallo-β lactamases, and two carried KPC-2 carbapenemase and mutated and . Eight CRKP strains encoded KPC-33 or KPC-93, belonging to ST11, among which seven strains were detected in patients hospitalized in 2021 after exposure to CAV and one strain was associated with intra-hospital spread. CAV is a potent agent in vitro against CRKP strains. The rapid development of CAV resistance mediated by various KPC variants after a short period of CAV treatment has increased and brought difficulties in treating infections caused by CRKP strains, especially those belonging to ST11. The surveillance of bacterial resistance against CAV is highly recommended due to the steep development of CAV resistance and rapid evolution of KPC enzymes.
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http://dx.doi.org/10.3390/antibiotics11060731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219983PMC
May 2022

Circulating folate concentrations and the risk of mild cognitive impairment: A prospective study on the older Chinese population without folic acid fortification.

Eur J Neurol 2022 Jun 23. Epub 2022 Jun 23.

Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.

Background: The longitudinal association between serum folate concentrations and the risk of cognitive impairment remains unclear in populations with low folate levels. We examined the association between serum folate concentrations and mild cognitive impairment (MCI) in older adults in China, where mandatory fortification of foods with folic acid has not been implemented. We further explored if homocysteine (Hcy) and leukocyte telomere length (LTL) mediate the association between serum folate and MCI.

Methods: We performed a longitudinal analysis of 3974 participants aged ≥60 years from the Tianjin Elderly Nutrition and Cognition (TENC) cohort study. The associations between serum folate level and the risk of cognitive impairment overall and stratified by apolipoprotein E (APOE) ε4 genotypes were evaluated using multivariable Cox proportional hazards models. The mediating effects of Hcy and LTL on the folate-MCI association were explored via a path analysis approach.

Results: Within a 3-year follow-up, we documented 560 incident MCI cases. After multivariable adjustment, higher serum folate concentrations were associated with lower incidence of MCI, with hazard ratios (95% confidence interval) across quartiles of folate (from lowest to highest concentrations) of 1.00 (reference), 0.66 (0.52, 0.83), 0.57 (0.45, 0.73), 0.66 (0.52, 0.84), respectively (p for trend <0.001). In mediation analyses, the status of serum folate deficiency and MCI were correlated via two intermediary pathways, Hcy and Hcy-telomere (p < 0.05).

Conclusions: Lower folate concentrations, independently of APOE genotype, were associated with increased risk of MCI among elderly Chinese people, a population with relatively low folate intake. Our data were compatible with the mediation hypothesis that the association between folate status and MCI was mediated by Hcy and LTL.
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http://dx.doi.org/10.1111/ene.15474DOI Listing
June 2022

Epidemiological and genetic characteristics of clinical carbapenem-resistant strains collected countrywide from hospital intensive care units (ICUs) in China.

Emerg Microbes Infect 2022 Dec;11(1):1730-1741

School of Medicine, Department of Clinical Laboratory, Second Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China.

is one of the key Gram-negative pathogens that can cause serious nosocomial infections. In China, a large proportion of clinical strains are multidrug resistant, among which strains resistant to carbapenems are particularly worrisome, as infections caused by such strains may limit the choice of existing antibiotics. We conducted a nationwide and genome-based surveillance on the prevalence and antibiotic susceptibility profile of carbapenem-resistant (CRAB) strains collected from intensive care units (ICUs) in hospitals in different provinces and investigated the routes of transmission and mechanism of resistance by whole-genome sequencing and phylogenetic analysis. We found that CRAB strains were prevalent in 71.4% (55/77) of the ICUs surveyed. Clonal spread of CRAB was found in 37.6% (29/77) of ICUs and a total of 22 different clones were identified. Most clones were transmissible within one ICU, but up to six clones could be detected in at least three hospitals. In addition, carbapenem-hydrolysing class D β-lactamases (CHDL) were found to be mainly responsible for carbapenem-resistance in and the ST2 global-clone is the predominant type of CRAB in China. Importantly, we found that CRAB isolates currently exhibited an extremely low rate of resistance to colistin (0.4%) and tigecycline (2.5%), but a high rate of resistance to ceftazidime-avibactam (70.2%). Findings in this work shall facilitate development of appropriate antimicrobial regimens for treatment of CRAB infections. Further surveillance and research on the evolutionary and epidemiological features of clinical CRAB strains are necessary.
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http://dx.doi.org/10.1080/22221751.2022.2093134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258068PMC
December 2022

Transcriptomics combined with metabolomics analysis of the mechanism of agmatine in the treatment of septic liver injury.

Ann Transl Med 2022 May;10(10):578

State Key Laboratory of Trauma, Burns and Combined Injury, Department of Wound Infection and Drug, Daping Hospital, Army Medical University, Chongqing, China.

Background: Acute liver injury can occur at any stage of sepsis and is an important sign of multiple organ dysfunction syndrome (MODS). Studies have shown that agmatine (AGM) can effectively improve liver injury caused by sepsis. However, due to the numerous metabolites and metabolic pathways of AGM in the human body, its mechanism in treating septic liver injury is unclear.

Methods: In this study, a liver injury model of septic Sprague-Dawley rats was established by cecal ligation and perforation (CLP). After AGM treatment, transcriptomics combined with metabolomics was employed to analyze the gene expression levels and metabolite changes.

Results: The results showed that AGM decreased the expression levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), procalcitonin (PCT), and inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)] in the serum of septic rats. It also reduced liver inflammatory cell infiltration and abnormal lipid metabolism, and promoted the survival rate of septic rats. In addition, 17 differentially-expressed genes were identified by transcriptomics, mainly in arginine and proline metabolism, the arachidonic acid metabolism pathway, as well as the nuclear factor kappa B (NF-κB) and AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor α (PPARα) signal transduction pathways. Metabolomics analysis was carried out to study the potential liver metabolism spectrum changes induced by AGM treatment. The results showed significant changes in 26 metabolites in the rat liver samples, mainly involved in arginine and proline metabolism, arachidonic acid metabolism, linoleic acid metabolism, and fatty acid metabolism.

Conclusions: The integrated transcriptomics and metabolomics analysis demonstrated that AGM improved septic liver injury by regulating lipid metabolism, and reduced the inflammatory reaction by affecting fatty acid metabolism, amino acid metabolism, and the arachidonic acid metabolism pathway. The integration of transcriptomics and metabolomics provides an effective means to elucidate AGM's therapeutic pathways and biomarkers.
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http://dx.doi.org/10.21037/atm-22-2103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201151PMC
May 2022

Modification of Microfluidic Paper-Based Devices with an Oxidant Layer for Distance Readout of Reducing Substances.

ACS Omega 2022 Jun 2;7(23):20383-20389. Epub 2022 Jun 2.

School of Chemistry and Environmental Engineering, Hanshan Normal University, Chaozhou, Guangdong 521041, China.

We developed a novel strategy for modification of paper cellulose with water-insoluble oxidants for distance readout of reducing substances on microfluidic paper-based analytical devices (μPADs). Water-insoluble oxidants were formed and modified onto paper cellulose through the redox reaction that occurred between paper cellulose and potassium permanganate deposited on the paper channel, developing a yellowish-brown color on the channel. As aqueous solutions containing reducing substances flowed along the channel, reducing substances were consumed owing to the redox reaction that occurred between oxidants and reducing substances until the reducing substances were depleted, forming a discolored zone on the yellowish-brown channel. The redox reaction between insoluble oxidants and reducing substances on the paper cellulose could be used for distance-based detection of a wide variety of reducing substances, which is similar to the classical potassium permanganate titration that employs the redox reaction that occurred between potassium permanganate and reducing substances. We believe that this method will broaden the analytical applications of distance-based detection on μPADs. This method was applied to ascorbic acid assay and captopril assay in real samples with analytical results comparing well with the labeled values, demonstrating its great potential in real sample analysis.
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http://dx.doi.org/10.1021/acsomega.2c02537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202063PMC
June 2022

Development of the Practice of Pharmaceutical Care for Cancer Pain Management in Outpatient Clinics Using the Delphi Method.

Front Pharmacol 2022 2;13:840560. Epub 2022 Jun 2.

Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China.

There exists no broad agreement of experts on the practice of pharmaceutical care for cancer pain management in outpatient clinics. This study aimed to use the Delphi consensus process to provide expert recommendations on the practice of cancer pain management in outpatient clinics from the point of view of pharmaceutical care in clinical practice and future clinical trials. A comprehensive literature review was conducted to draft the initial practice. In this process, 30-40 senior experts from various provinces in China were invited to rank the items of practice during the two Delphi consultations. The definitions of consensus included a combination with an average score of ≥4, the percentage of experts rating the scores at >4 points, and the coefficient of variation of the scores. The expert panel comprised 18 pharmacists, 3 anesthesiologists, 6 oncologists, and 9 nurses. As a result of a comprehensive review, 33 items were initially formed. Among them, the consensus was reached for 27 items after the first Delphi round. The other six items and a total of five items for supplementation entered the second round, among which consensus was reached for eight items and three items were excluded. Expert consensus was achieved on 35 items after two rounds of consultation, which involved the collection of patient basic information, comprehensive pain assessment, breakthrough or neuropathic pain assessment, analgesic treatment evaluation, out-of-hospital follow-up, medical records, and evidence-based documents for reference. The final list of 35 items could be used to develop the practice of pharmaceutical care for cancer pain management in outpatient clinics in China. The practice may aid in the standardization of pharmaceutical care for pain, relieve pain to the greatest extent possible, and enhance the level of pain management in China.
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http://dx.doi.org/10.3389/fphar.2022.840560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201566PMC
June 2022

Copper Doped Carbon Dots for Addressing Bacterial Biofilm Formation, Wound Infection, and Tooth Staining.

ACS Nano 2022 Jun 17. Epub 2022 Jun 17.

State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Fiber Laser Materials and Applied Techniques, School of Materials Science and Engineering, School of Physics, South China University of Technology, Guangzhou 510640, China.

Oral infectious diseases and tooth staining, the main challenges of dental healthcare, are inextricably linked to microbial colonization and the formation of pathogenic biofilms. However, dentistry has so far still lacked simple, safe, and universal prophylactic options and therapy. Here, we report copper-doped carbon dots (Cu-CDs) that display enhanced catalytic (catalase-like, peroxidase-like) activity in the oral environment for inhibiting initial bacteria () adhesion and for subsequent biofilm eradication without impacting the surrounding oral tissues via oxygen (O) and reactive oxygen species (ROS) generation. Especially, Cu-CDs exhibit strong affinity for lipopolysaccharides (LPS) and peptidoglycans (PGN), thus conferring them with excellent antibacterial ability against Gram-positive bacteria () and Gram-negative bacteria (), such that they can prevent wound purulent infection and promoting rapid wound healing. Additionally, the Cu-CDs/HO system shows a better performance in tooth whitening, compared with results obtained with other alternatives, e.g., CDs and clinically used HO, particularly its negligible enamel and dentin destruction. It is anticipated that the biocompatible Cu-CDs presented in this work are a promising nano-mouthwash for eliminating oral pathogenic biofilms, prompting wound healing as well as tooth whitening, highlighting their significance in oral health management.
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http://dx.doi.org/10.1021/acsnano.2c02518DOI Listing
June 2022

Stabilizing Li-O Batteries with Multifunctional Fluorinated Graphene.

Nano Lett 2022 Jun 10;22(12):4985-4992. Epub 2022 Jun 10.

State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, P.R. China.

As a full cell system with attractive theoretical energy density, challenges faced by Li-O batteries (LOBs) are not only the deficient actual capacity and superoxide-derived parasitic reactions on the cathode side but also the stability of Li-metal anode. To solve simultaneously intrinsic issues, multifunctional fluorinated graphene (CF, = 1, F-Gr) was introduced into the ether-based electrolyte of LOBs. F-Gr can accelerate O transformation and O-participated oxygen reduction reaction (ORR) process, resulting in enhanced discharge capacity and restrained O-derived side reactions of LOBs, respectively. Moreover, F-Gr induced the F-rich and O-depleted solid electrolyte interphase (SEI) film formation, which have improved Li-metal stability. Therefore, energy storage capacity, efficiency, and cyclability of LOBs have been markedly enhanced. More importantly, the method developed in this work to disperse F-Gr into an ether-based electrolyte for improving LOBs' performances is convenient and significant from both scientific and engineering aspects.
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http://dx.doi.org/10.1021/acs.nanolett.2c01713DOI Listing
June 2022

[Characteristics of Soil NO Emissions in the Yangtze River Delta Region for Year 2018].

Huan Jing Ke Xue 2022 Jun;43(6):3357-3364

Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China.

Soil NO emissions represent an important source of atmospheric nitric oxide (NO) and play an important role in atmospheric chemistry. Based on the latest BDSNP algorithm, this study estimated the soil NO emissions over the Yangtze River Delta region for the year 2018 and further analyzed the associated temporal and spatial variations and uncertainties. The results showed that the annual soil NO emissions in 2018 over the YRD region was 213.6 kt, accounting for 7.3% of the total anthropogenic NO emissions. Areas with high emissions were mainly concentrated in northern Anhui Province and most parts of Jiangsu Province. In terms of monthly variations, soil NO emissions peaked in June, accounting for 19.9% of the annual emissions and 19.7% of anthropogenic NO emissions in June. In terms of daily variations, soil NO emissions peaked around 16:00 and accounted for 5.5% of daily emissions. Soil NO emissions came from three components:soil background, nitrogen fertilizer application, and nitrogen deposition. Nitrogen fertilizer application was the main source of soil NO emissions, accounting for up to 77.8%. With the in-depth reduction in NO emissions from motor vehicles and industries, the importance of soil NO emissions will become increasingly prominent.
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http://dx.doi.org/10.13227/j.hjkx.202109015DOI Listing
June 2022

Murr Sensitizes Gastric Cancer Cells to 5-Fluorouracil by Modulating Tumor Microenvironment.

Front Pharmacol 2022 17;13:911663. Epub 2022 May 17.

The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.

(TRM) is a traditional Chinese medicine which has been used in clinics for enhancing immunity and improving the efficacy of chemotherapy. However, the mechanisms of action of TRM are unknown. In the previous study, we found that the n-butanol extract (TRMBE) comprises the major bioactive components of TRM. In the present study, we aimed to assess the combinational effects of TRMBE and 5-fluorouracil (5-FU) on the treatment of gastric cancer (GC) and explore its mechanism of action. It was found that TRMBE significantly potentiated the anticancer activity of 5-FU and prolonged the survival time of mice bearing Mouse Forestomach Carcinoma (MFC) xenograft tumors. We observed that the combination of TRMBE and 5-FU decreased the risk of liver metastasis . Furthermore, the combination of TRMBE and 5-FU reduced the levels of immune cytokines IL-6, IL-10, and TGF-β and increased the level of IFN-γ in peripheral blood. This combination therapy also significantly decreased the levels of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and PD-1-positive CD8 T cells and increased the levels of NK cells in tumor microenvironment (TME). However, TRMBE treatment was unable to enhance the chemosensitivity of GC to 5-FU after the depletion of CD8 T and NK cells. Taken together, our results demonstrate that TRMBE can reshape the TME of GC by regulating PMN-MDSCs, CD8 T cells, and NK cells, therefore improving the therapeutic effects of 5-FU. This study suggests that the combination of TRMBE and 5-FU could enhance immunity and could be a promising approach for GC treatment.
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http://dx.doi.org/10.3389/fphar.2022.911663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152117PMC
May 2022
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