Publications by authors named "He Qian"

548 Publications

Immobilization of By-product Sulfate Salt Slag from High-salt Organic Wastewater with Fly ash in Lightweight Aggregate Ceramsite.

Environ Technol 2021 Sep 24:1-17. Epub 2021 Sep 24.

Yuhuan Environmental Technology Co. LTD, Shijiazhuang 050091, Hebei Province, China.

The lightweight aggregate ceramsite (LAC) was prepared from by-product sulfate salt slag (BPSS) of high-salt organic wastewater with fly ash. The BPSS fixation rate, leaching toxicity, morphological structures and potential environmental risks of heavy metals (HMs) in LAC were investigated. BPSS can be fixed in LAC when the mass ratio of Fly ash: Kaolin: clay was 7:1:2, the addition of BPSS was 28%, the heating rate was 8 ℃·min, and the calcination temperature was 1100℃. The characteristics of the LAC met the requirements for Chinese lightweight aggregate standards (GB/T17431.2-2010). The TOC content of the aqueous leaching liquor in LAC was less than 0.5 mg·L. And the fixation rate of heavy metal was more than 99%, which meets the requirements of GB 5085.3-2007. The BPSS immobilization mechanisms were mainly related to the formation of new crystal phases, including Leucite (KAlSiO), Albite (NaO·AlO·6SiO), Potash Feldspar (KO·AlO·6SiO), Jadeite (NaAlSiO), Hauyne ([Na,Ca][Si,Al]O[SO]), Nosean (NaAlSiOSO), Sodalite (NaAlSiO[MnO]) by incorporation of heavy metals in high temperature curing reaction. This work provides an effective method for the harmless treatment and recycling of by-product salt residues from high-salt organic wastewater.
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http://dx.doi.org/10.1080/09593330.2021.1985622DOI Listing
September 2021

The Impact of Homocysteine on the Risk of Hormone-Related Cancers: A Mendelian Randomization Study.

Front Nutr 2021 24;8:645371. Epub 2021 Aug 24.

Department of Biochemistry and Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Aberrant homocysteine level is associated with metabolic disorders and DNA damage, which may be involved in the carcinogenesis of hormone-related cancers, but clinical results of observational studies are controversial. In this study, we investigated the causal relationships between plasma homocysteine and breast cancer (BRCA), prostate cancer (PrCa), and renal cell carcinoma (RCC) using Mendelian randomization (MR) analyses. To investigate the putative causal associations between homocysteine and the aforementioned three types of cancers, a two-sample MR study was employed for the study. The primary strategy for summary data analyses was the inverse-variance-weighted (IVW) approach. In our study, the single-nucleotide polymorphisms (SNPs) excluded confounding factors through Linkage Disequilibrium (LD). Phenoscanner tests were the instrumental variants (IVs), homocysteine was the exposure, and BRCA, PrCa, and RCC were the outcomes. Single-nucleotide polymorphisms associated with homocysteine were extracted from a large genome-wide association study (GWAS) meta-analysis of European participants ( = 44,147). Summary Statistics of BRCA were obtained from the latest and largest GWAS meta-analysis comprising of 82 studies from Breast Cancer Association Consortium (BCAC) studies, including women of European ancestry (133,384 cases and 113,789 controls); we obtained summary-level data from the GWAS meta-analysis of PrCa comprising 79,148 cases and 61,106 controls of European ancestry, and the dataset of RCC was a sex-specific GWAS meta-analysis comprising of two kidney cancer genome-wide scans for men (3,227 cases and 4,916 controls) and women (1,992 cases and 3,095 controls) of European ancestry. The MR-Egger and weight median analyses were applied for the pleiotropy test. The results showed null associations between plasma homocysteine levels and overall BRCA (effect = 0.97, 95% CI: 0.90-1.06, = 0.543), overall PrCa (effect = 1.01, 95% CI: 0.93-1.11, = 0.774), RCC in men (effect = 0.99, 95% CI: 0.73-1.34, = 0.929), and RCC in women (effect = 0.89, 95% CI: 0.61-1.31, = 0.563). We found no putative causal associations between homocysteine and risk of BRCA, PrCa, and RCC.
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http://dx.doi.org/10.3389/fnut.2021.645371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421785PMC
August 2021

A pH-Responsive Zwitterionic Polyurethane Prodrug as Drug Delivery System for Enhanced Cancer Therapy.

Molecules 2021 Aug 31;26(17). Epub 2021 Aug 31.

West China School of Nursing, West China Hospital, Sichuan University, Guoxue Alley No. 37, Chengdu 610041, China.

Numerous nanocarriers with excellent biocompatibilities have been used to improve cancer therapy. However, nonspecific protein adsorption of nanocarriers may block the modified nanoparticles in tumor cells, which would lead to inefficient cellular internalization. To address this issue, pH-responsive polyurethane prodrug micelles with a zwitterionic segment were designed and prepared. The micelle consisted of a zwitterionic segment as the hydrophilic shell and the drug Adriamycin (DOX) as the hydrophobic inner core. As a pH-responsive antitumor drug delivery system, the prodrug micelles showed high stability in a physiological environment and continuously released the drug under acidic conditions. In addition, the pure polyurethane carrier was demonstrated to be virtually non-cytotoxic by cytotoxicity studies, while the prodrug micelles were more efficient in killing tumor cells compared to [email protected] Furthermore, the DOX cellular uptake efficiency of prodrug micelles was proved to be obviously higher than the control group by both flow cytometry and fluorescence microscopy. This is mainly due to the modification of a zwitterionic segment with PU. The simple design of zwitterionic prodrug micelles provides a new strategy for designing novel antitumor drug delivery systems with enhanced cellular uptake rates.
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http://dx.doi.org/10.3390/molecules26175274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434572PMC
August 2021

TfO/TTBP (2,4,6-Tri--butylpyrimidine): An Alternative Amide Activation System for the Direct Transformations of Both Tertiary and Secondary Amides.

J Org Chem 2021 Sep 9. Epub 2021 Sep 9.

Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, P. R. China.

Ten types of TfO/TTBP-mediated amide transformation reactions were investigated. The results showed that compared with pyridine derivatives 2,6-di--butyl-4-methylpyridine (DTBMP) and 2-fluoropyridine (2-F-Pyr.), TTBP can serve as an alternative amide activation system for the direct transformation of both secondary and tertiary amides. For most surveyed examples, higher or comparable yields were generally obtained. In addition, TfO/TTBP combination was used to promote the condensation reactions of 2-(-butyldimethylsilyloxy)furan (TBSOF) with both tertiary and secondary amides, the one-pot reductive Bischler-Napieralski-type reaction of tertiary lactams, and Movassaghi and Hill's modern version of the Bischler-Napieralski reaction. The value of the TfO/TTBP-based methodology was further demonstrated by the concise and high-yielding syntheses of several natural products.
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http://dx.doi.org/10.1021/acs.joc.1c01572DOI Listing
September 2021

The impact of the physical form of torularhodin on its metabolic fate in the gastrointestinal tract.

Food Funct 2021 Sep 8. Epub 2021 Sep 8.

State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China 214122.

Torularhodin is a fungal carotenoid with multiple health benefits. However, the relationship between its physical form and metabolic fate in the gastrointestinal tract (GIT), which is essential to its bioavailability and health efficacy, has rarely been studied. Thus, physical forms of torularhodin including nanoemulsion powder (T-EP), capsules of the T-EP by alginate (T-EPA), and solution in MCT oil (T-oil) were used in the study. T-EP was produced through OSA-starch-mediated torularhodin emulsification and spray drying whereas the T-EPA was alginate-based capsules of the T-EP particles that were entrapped in the network structure of the alginate matrix as observed by scanning electron microscopy (SEM). The oil digestibility in the simulated small intestine was decreased from T-EP (100%), T-oil (60%) to T-EPA (40%), and the bioaccessibilities were 27%, 15% and 12%, respectively. The study using mice revealed that the content of torularhodin gradually decreased along with the digestion time in both the stomach and small intestine while a significantly higher colonic accumulation was observed in T-EPA compared to T-oil and T-EP. fecal fermentation showed that propionate (32 mM) was the predominant metabolite produced by torularhodin in the physical form of T-EPA. Thus, the physical form of torularhodin is a significant contributing factor to its GIT metabolic fate, and a health outcome-oriented design of the physical form of torularhodin or other nutraceuticals is beneficial for the development of functional foods with enhanced health benefits.
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http://dx.doi.org/10.1039/d1fo01950cDOI Listing
September 2021

Correction: Efficacy of omega-3 PUFAs in depression: A meta-analysis.

Transl Psychiatry 2021 Sep 7;11(1):465. Epub 2021 Sep 7.

Mood Disorders Psychopharmacology Unit, University Health Network; Department of Psychiatry, University of Toronto; Institute of Medical Science, University of Toronto; Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1038/s41398-021-01582-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423804PMC
September 2021

Impact of the Delta variant on vaccine efficacy and response strategies.

Expert Rev Vaccines 2021 Sep 9:1-9. Epub 2021 Sep 9.

Division of Hepatitis and Enterovirus Virus Vaccines, National Institutes for Food and Drug Control, Beijing, China.

Introduction: The Delta variant of SARS-CoV-2 has caused a new wave of the COVID-19 epidemic in many countries. It is the most infectious variant of SARS-CoV-2 to date, and its high infectivity means that a higher proportion of the population needs to be vaccinated to reduce the disease burden, which poses a substantial public health challenge.

Areas Covered: The evolution of the Delta variant is reviewed, including an overview of the Delta Plus variant with a K417N mutation in the RBD, which may confer an improved immune evasion ability. Decreases in serum neutralizing antibody titers after vaccination against Delta were greater than those against Alpha but less than those against Beta. The protective efficacy of existing vaccines against the Delta variant have declined and is related to the number of doses and the time since vaccination.

Expert Opinion: The currently used vaccines are effective against hospitalization/severe disease due to the Delta variant. Accelerating the popularization of vaccination, improving the coverage rate, and the implementation of intervention measures, such as wearing masks, are effective means to control the spread of the Delta variant and other variants. However, vaccination alone against SARS-CoV-2 without intervention measures may lead to continuous spread and the emergence of new variants.
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http://dx.doi.org/10.1080/14760584.2021.1976153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442750PMC
September 2021

Dose Correlation of and Koidz. Drug Pairs in the Chinese Medicine Prescription Based on the Copula Function.

Evid Based Complement Alternat Med 2021 24;2021:9933254. Epub 2021 Aug 24.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

Objective: and Koidz. (AMK) are widely used in treating various diseases; however, research is insufficient on measuring the relationship that exists by combining this drug pair using the copula function.

Methods: In this study, 279 traditional Chinese medicine prescriptions containing the and AMK drug pair were extracted from the prescription database for three types of screened indications, namely, diabetes mellitus, diarrhea, and insomnia. Following the principle of dose conversion, each dynasty unit was uniformly converted into a modern unit. Then, the kernel density distribution of and AMK was fitted with their empirical distribution functions. Finally, the optimal copula function was selected from the copula function family as a -copula function.

Results: The empirical distribution and probability density functions of and AMK were obtained. From the results, their Kendall rank correlation coefficients with indications of diabetes mellitus, insomnia, and diarrhea were 0.8689, 0.7858, and 0.7403, whereas their Spearman rank correlation coefficients were 0.9563, 0.9276, and 0.8958. Results also indicated that the use of the -copula function can better reflect the correlation between and AMK doses.

Conclusion: From the three indications, the dose between and AMK was positively correlated. This study, therefore, confirms the medicinal principle of Chinese medicine "combining" from the perspective of mathematical statistics. Results from this study are practical to evaluate the correlation between the drug pair doses, and AMK, using the copula function model, which provides a new model for the scientific explanation of compatibility for Chinese medicines. This study also provides a methodological basis for more drug measurement studies and clinical medications.
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http://dx.doi.org/10.1155/2021/9933254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410382PMC
August 2021

The effect of aging on beef taste, aroma and texture, and the role of microorganisms: a review.

Crit Rev Food Sci Nutr 2021 Aug 31:1-12. Epub 2021 Aug 31.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China.

The present review summarizes the advantages and disadvantages of three different aging methods (traditional dry aging, wet aging in vacuum shrink pack and dry aging in a highly moisture-permeable bag), discusses the effects of aging on beef which focus on the formation of taste-active compounds and aroma-active compounds and texture changes, and speculates the role of microbes. All these three aging methods can improve the aroma, flavor and texture of beef to varying degrees. It is concluded that the improvement in the taste during aging may be attributed to the following three aspects: First, the release of reducing sugars from the transition of glycogen and ATP; Second, the formation of free amino acids (FAAs) and peptides through proteolysis; Third, IMP, GMP, inosine and hypoxanthine which are produced by the degradation of nucleotides. The improvement of aroma is related to the volatile aroma-active components, which are produced by the thermal oxidation/degradation of fatty acids and the Maillard reaction between amino acids and reducing sugars during aging. And the change of texture is mainly owing to the degradation of cytoskeletal myofibrin and collagen with intramural connective tissue in meat by the endogenous proteolysis system. The role of microorganism in aging will be the main direction of further research.
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http://dx.doi.org/10.1080/10408398.2021.1971156DOI Listing
August 2021

Theory of the exterior-interior relationship between the lungs and the large intestine to explore the mechanism of Eriobotrya japonica leaf water extract in the treatment of cough variant asthma.

J Ethnopharmacol 2021 Aug 23;281:114482. Epub 2021 Aug 23.

College of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China. Electronic address:

Ethnopharmacological Relevance: Eriobotrya japonica (Thunb.) Lindl leaf (EJL) is used as a traditional Chinese medicine. E. japonica is a member of the Rosaceae family. EJL suppresses cough and relieves asthma and is widely used to treat lung diseases. In the present study, guided by the traditional Chinese medicine theory of the exterior-interior relationship between the lungs and the large intestine, the pathogenesis of cough variant asthma (CVA) and the treatment mechanism of EJL on CVA were explored.

Aim Of The Study: This study aimed to explore the airway remodeling effects of EJL in CVA from the perspective of the intestinal flora and the matrix metallopeptidase 9/tissue inhibitor of metalloproteinases-1 (MMP-9/TIMP-1) pathway.

Materials And Methods: The oleanolic acid and ursolic acid contents in EJL were measured by high-performance liquid chromatography (HPLC) to ensure the quality of EJL. BALB/c mice were used to establish a CVA model through ovalbumin (OVA) sensitization and atomization. EJL (at 5, 10, or 20 g/kg/day) was intragastrically administered. The body weight, ratio of total bronchial wall area (WAt) to bronchial basement membrane perimeter (Pbm) (WAt/Pbm), the number of coughs, and cough latency were measured. The pathological changes of the lung tissue were analyzed by hematoxylin and eosin (HE) staining. The expression of α-smooth muscle actin (α-SMA) was measured by immunohistochemistry (IHC). The expressions of MMP-9 and TIMP-1 were detected in the lung tissue by reverse transcription quantitative polymerase chain reaction (RT-PCR) and Western blot analysis. Additionally, an Illumina Hiseq platform was used for 16S ribosomal DNA (16S rDNA) high-throughput sequencing to detect the intestinal flora in feces samples.

Results: The results confirmed the positive effects of EJL on CVA. After administration of EJL, the number of coughs and the WAt/Pbm ratio decreased, the cough latency was prolonged, body weight was increased, and the general status was better than that of the CVA model mice. HE staining revealed that EJL decreased inflammatory cell infiltration and improved the histopathological structure of the lung tissue. EJL also showed significant inhibitory effects on the expression of α-SMA, MMP-9, and TIMP-1 and normalized the intestinal flora to a certain extent.

Conclusions: The results demonstrated that EJL alleviated airway remodeling of CVA mice, which might be related to the inhibition of the MMP-P/TIMP-1 pathway and the regulation of intestinal flora.
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http://dx.doi.org/10.1016/j.jep.2021.114482DOI Listing
August 2021

Stelleranoids A-M, guaiane-type sesquiterpenoids based on [5,7] bicyclic system from Stellera chamaejasme and their cytotoxic activity.

Bioorg Chem 2021 Oct 8;115:105251. Epub 2021 Aug 8.

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China. Electronic address:

Thirteen previously undescribed guaiane-type sesquiterpenoids based on [5,7] bicyclic system, stelleranoids A-M (1-13), along with six known analogues (14-20), were isolated from the roots of Stellera chamaejasme with chromatographic techniques. Their structures including absolute configurations were determined by HRESIMS and spectroscopic data, quantum chemical calculations, as well as X-ray crystallographic analysis. Cytotoxicity test in three cell lines indicated that compound 14 had relatively stronger cytotoxic effect against MKN-45, SKOV3, and Du145 cell lines with IC of 9.8, 17.4 and 7.3 μM, respectively; compounds 3 and 8 displayed moderate cytotoxic effect against MKN-45 and Du145 cell lines with IC ranged from 14.5 to 18.8 μM, comparable to those of the positive control. As determined by fluorescent microscopy and flow cytometry in Du145 cell line, compound 14 could promote cell apoptosis and cause cell cycle arrest at the G0/G1 phase, leading to the inhibition of cell proliferation. Further Western blot analysis revealed that this inhibitory effect was accompanied by upregulating pro-apoptosis proteins cleaved-PARP, cleaved-Caspase-9 and tumor suppressor protein p53 while downregulating anti-apoptotic protein Bcl-2 in 14-treated Du145 cells.
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http://dx.doi.org/10.1016/j.bioorg.2021.105251DOI Listing
October 2021

Discovery of an -Substituted -Cyclopropylmethyl-7α-phenyl-6,14-endoethanotetrahydronorthebaine as a Selective, Potent, and Orally Active κ-Opioid Receptor Agonist with an Improved Central Nervous System Safety Profile.

J Med Chem 2021 Aug 13;64(16):12414-12433. Epub 2021 Aug 13.

Department of Medicinal Chemistry, School of Pharmacy, Fudan University, No. 826 Zhangheng Road, Shanghai 201203, China.

The search for selective kappa opioid receptor (κOR) agonists with an improved safety profile is an area of interest in opioid research. In this work, a series of -substituted analogs were designed, synthesized, and assayed, resulting in the identification of compound () as a κOR agonist with single-digit nanomolar activities. The subtype selectivity of compound appeared to be a consequence of an enormous decrease in the affinity for μOR and δOR, rather than a significant increase in the affinity for κOR, which was not the case for , another selective and potent κOR agonist identified in our previous work. Besides reduced central nervous system effects, exhibited substantially improved physicochemical and pharmacokinetic properties compared with , with increases of over 20-fold in aqueous solubility and approximately 40-fold in oral bioavailability in rats.
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http://dx.doi.org/10.1021/acs.jmedchem.1c01082DOI Listing
August 2021

Neolignans and Sesquiterpenoid from Piper yunnanense.

Chem Biodivers 2021 Sep 9;18(9):e2100458. Epub 2021 Aug 9.

Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331, P. R. China.

Two biphenyl-type neolignans with a rare dibenzofuran skeleton, including a new one piyunneolignan A (1) and a known one piperneolignan D (2), together with a new sesquiterpenoid piyunin A (3), were isolated from the leaves and twigs of Piper yunnanense. Their structures were established on the basis of comprehensive spectroscopic data analysis and electronic circular dichroism (ECD) calculation. Piyunneolignan A (1) featured a rare C-2-C-2'/C-3-O-C-3' linkage. Compounds 1-3 were evaluated for their antimicrobial and cytotoxic activities against a panel of bacteria, fungi, and human cancer cell lines, respectively.
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http://dx.doi.org/10.1002/cbdv.202100458DOI Listing
September 2021

Reducing tetracycline antibiotics residues in aqueous environments using Tet(X) degrading enzymes expressed in Pichia pastoris.

Sci Total Environ 2021 Jul 31;799:149360. Epub 2021 Jul 31.

National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China; Guangdong Key Laboratory for Veterinary Drug Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China. Electronic address:

Tetracycline antibiotics (TCs) are massively produced and consumed in various industries resulting in large quantities of residuals in the environment. In this study, to achieve safe and efficient removal of residual TCs, a Pichia pastoris (P. pastoris) was gained to stably express glycosylated TCs degrading enzyme Tet(X) followed codon and expression parameter optimization of tet(X4). As expected, glycosylated Tet(X) still maintains efficient capacity of degrading TCs. The expressed Tet(X) maintained efficient TCs degrading ability over a pH range of 6.5 - 9.5 and temperature range of 17 - 47 °C. We tested this recombinant protein for its ability to degrade tetracycline in pond water and sewage models of tetracycline removal at starting levels of 10 mg/L substrate. 80.5 ± 3.8% and 26.2 ± 2.6% of tetracycline was degraded within 15 min in the presence of 0.2 μM Tet(X) and 50 μM NADPH, respectively. More importantly, the direct use of a Tet(X) degrading enzymes reduces the risk of gene transmission during degradation. Thus, the Tet(X) degrading enzyme expressed by P. pastoris is an effective and safe method for treating intractable TCs residues.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149360DOI Listing
July 2021

Cyclo-γ-polyglutamic acid-coated dual-responsive nanomicelles loaded with doxorubicin for synergistic chemo-photodynamic therapy.

Biomater Sci 2021 Sep 2;9(17):5977-5987. Epub 2021 Aug 2.

Department of Marine Biomedicine and Polar Medicine, Naval Special Medical Center, Naval Medical University, Shanghai 200433, China.

Nanodrug delivery systems have been used extensively to improve the tumor-targeting ability and reduce the side effects of anticancer drugs. In this study, nanomicelles responsive to dual stimuli were designed and developed as drug carriers for delivering doxorubicin (DOX). The hydrophobic group of the nanomicelles was composed of the photosensitizer protoporphyrin IX (PpIX) and the disulfide bond-containing alpha-lipoic acid (LA); the hydrophilic group was made up of the nuclear localization signal (NLS, CGGGPKKKRKVGG) peptide with a lysine linker. Furthermore, anionic cyclo-γ-polyglutamic acid (cyclo-γ-PGA) was coated on the surface of the cationic micelles to construct a multifunctional drug delivery system ([email protected]γ-PGA). Cyclo-γ-PGA, as a biological coating material, notably improved the stability of the cationic micelles by reducing nonspecific reactions with anionic groups. Additionally, the cyclo-γ-PGA coating mediated active tumor targeting and enhanced the cellular uptake of micelles via the γ-glutamyl transpeptidase (GGT) pathway. The integrated micelles not only achieved photochemical internalization (PCI) and photodynamic therapy (PDT) via light-activated reactive oxygen species (ROS) but also realized controlled intracellular drug release via the glutathione (GSH)-responsive disulfide-bond cleavage. As a result, [email protected]γ-PGA exhibited excellent synergistic chemo-photodynamic antitumor activity and fewer side effects than other therapies both in vitro and in vivo. In conclusion, this new dual-responsive drug delivery system ([email protected]γ-PGA) with improved stability and enhanced tumor-targeting ability may facilitate the development of high-efficiency and low-toxicity nanotherapeutic approaches.
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http://dx.doi.org/10.1039/d1bm00713kDOI Listing
September 2021

Daily Dose of Bovine Lactoferrin Prevents Ethanol-Induced Liver Injury and Death in Male Mice by Regulating Hepatic Alcohol Metabolism and Modulating Gut Microbiota.

Mol Nutr Food Res 2021 Sep 10;65(18):e2100253. Epub 2021 Aug 10.

School of Public Health, Medical College of Soochow University, 199 Renai Road, Suzhou, Jiangsu, 215123, China.

Scope: Lactoferrin (Lf) possess a protective potential to liver, but whether it can prevent alcoholic liver injury (ALI) remains unclear.

Methods And Results: Four groups of male C57BL/6J mice are fed with different diets, namely, AIN-93G diet for control (CON) and ethanol (EtOH) groups, and AIN-93G diet with 0.4% and 4% casein replaced by Lf for low-dose Lf (LLf) and high-dose Lf (HLf) groups, respectively. ALI is induced by giving 20% ethanol ad libitum combined with four "binges". Lf can remarkably decrease EtOH-induced mortality. Lf promotes aldehyde dehydrogenase-2 (ALDH2) expression and suppressing cytochrome P450 2E1 (CYP2E1) overexpression, resulting in the reduced hepatic superoxide and inflammation levels, which ultimately leads to the hepatic injury alleviation. However, HLf increases acetyl-CoA carboxylase and fatty acid synthase protein levels, which suggests that excessive intake may weaken the beneficial effects of Lf. Moreover, LLf increases the relative abundances of Akkermansia and Lactobacillus. Additionally, the study shows that Lf likely exerts action in its digestive product forms rather than intact Lf molecular in normal condition.

Conclusion: LLf can ameliorate ALI, which is associated with the regulation of hepatic alcohol metabolism and the modulation of gut microbiota. However, excessive Lf intake may result in a diminished benefit.
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http://dx.doi.org/10.1002/mnfr.202100253DOI Listing
September 2021

CircSCAP aggravates oxidized low-density lipoprotein-induced macrophage injury by upregulating PDE3B via miR-221-5p in atherosclerosis.

J Cardiovasc Pharmacol 2021 Jul 22. Epub 2021 Jul 22.

General Practice, The Affliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China. Health Management Center, The Second People's Hospital of Guiyang, Guiyang 550081, Guizhou, China. Emergency department, The Affliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China.

Abstract: Atherosclerosis (AS) is a major risk factor for cardiovascular disease, in which circular RNAs (circRNAs) play important regulatory roles. This research aimed to explore the biological role of circSCAP (hsa_circ_0001292) in AS development. Real-time PCR or western blot assay was conducted to analyze RNA or protein expression. Cell proliferation and apoptosis were analyzed by CCK-8 assay and flow cytometry. The levels of lipid accumulation-associated indicators and oxidative stress factors were detected using commercial kits. The levels of inflammatory cytokines were examined using enzyme-linked immunosorbent assay (ELISA). Intermolecular interaction was verified via dual-luciferase reporter analysis or RNA pull-down analysis. CircSCAP and phosphodiesterase 3B (PDE3B) levels were elevated, whereas miR-221-5p level was decreased in AS patients and oxidized low-density lipoprotein (ox-LDL)-induced THP-1 cells. CircSCAP absence suppressed lipid deposition, inflammation, and oxidative stress in ox-LDL-induced THP-1 cells. MiR-221-5p was a target of circSCAP, and anti-miR-221-5p largely reversed si-circSCAP-induced effects in ox-LDL-induced THP-1 cells. PDE3B was a target of miR-221-5p, and PDE3B overexpression largely counteracted miR-221-5p accumulation-mediated effects in ox-LDL-induced THP-1 cells. NF-κB signaling pathway was regulated by circSCAP/miR-221-5p/PDE3B axis in ox-LDL-induced THP-1 cells. In conclusion, circSCAP facilitated lipid accumulation, inflammation, and oxidative stress in ox-LDL-induced THP-1 macrophages by regulating miR-221-5p/PDE3B axis.
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http://dx.doi.org/10.1097/FJC.0000000000001118DOI Listing
July 2021

Echinacea purpurea polysaccharide prepared by fractional precipitation prevents alcoholic liver injury in mice by protecting the intestinal barrier and regulating liver-related pathways.

Int J Biol Macromol 2021 Sep 20;187:143-156. Epub 2021 Jul 20.

State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China; Synergetic Innovation Center for Food Safety and Nutrition, Jiangnan University, Wuxi 214122, China. Electronic address:

Oxidative damage and intestinal dysbiosis are regarded as crucial culprits in alcoholic liver disease (ALD). This study aimed to examine the protective effects of Echinacea purpurea polysaccharides (EPPs) against ALD and explore the underlying mechanisms based on hepatic oxidative stress, inflammation, and intestinal barrier function. Three polysaccharide fractions, namely, EPP40, EPP60, and EPP80, were obtained by stepwise ethanol precipitation, and their antioxidant activity in vitro was investigated. The results showed that EPP80 with Mw 11.82 kDa had the strongest radical-scavenging capacity against DPPH, ABTS, and •OH radicals. Besides, EPP80 comprised arabinose, galactose, glucose, mannose, galacturonic acid, and glucuronic acid in molar ratios of 13.42:25.12:10.92:8.59:2.07:0.82. The in vivo results showed that EPP80 increased the activities of antioxidant enzymes and reduced the levels of inflammatory cytokines both in mouse serum and liver. Moreover, EPP80 upregulated the expression of Occludin and ZO-1, revealing its protective effect against intestinal barrier dysfunction. Furthermore, EPP80 inhibited alcohol-induced oxidative damage by promoting the expression of Nrf2, HO-1, and NQO1 in the liver. In summary, EPP80 markedly scavenged free radicals in vitro and ameliorated alcohol-induced liver injury via Nrf2/HO-1 pathways in vivo. These findings suggested that EPP80 could provide effective supplementary support in preventing and treating ALD.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.07.095DOI Listing
September 2021

High Iodine Nutrition May Be a Risk Factor for Cervical Lymph Node Metastasis in Papillary Thyroid Cancer Patients.

Ann Nutr Metab 2021 21;77(2):90-99. Epub 2021 Jul 21.

Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, China.

Purpose: The aim of this study was to retrospectively identify the effect of iodine on the papillary thyroid cancer (PTC) process and investigate the risk clinicopathologic characteristics of cervical lymph node metastasis (CLNM) for achieving a better preventive strategy of PTC.

Methods: Totally 187 patients with CLNM and 279 without CLNM (NCLNM) were enrolled, and their urinary iodine concentration (UIC) and serum iodine concentration (SIC) were measured. Logistic regressions were used to reveal the effects of iodine nutrition on the CLNM status of PTC.

Results: The levels of thyroid-stimulating hormone (TSH) and thyroglobulin (TG) were higher in the CLNM group than in the NCLNM group. UIC and SIC were positively correlated, and both of them were correlated with TSH, free thyroxine, and TG. The proportions of UIC >300 μg/L and of SIC >90 μg/L were higher in the CLNM than in the NCLNM. Logistic analysis showed that SIC >90 μg/L was an independent predictor for CLNM in PTC. Additionally, age ≥45, female, TG, multifocality, and diameter of cancer invasion >1 cm also affected CLNM status in PTC, and their logistic regression model showed a certain diagnostic accuracy (area under the receiver-operating characteristic curve = 0.72).

Conclusions: Relatively high iodine nutrition seemed to be a significant risk factor for the occurrence of CLNM in PTC and may promote lymphatic metastasis in PTC.
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http://dx.doi.org/10.1159/000513334DOI Listing
July 2021

Cryptoyunnanones A-H, Complex Flavanones from .

J Nat Prod 2021 08 20;84(8):2209-2216. Epub 2021 Jul 20.

Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, People's Republic of China.

Eight new complex flavanones with a novel linkage, cryptoyunnanones A-H (-), together with four known α-pyrones, were isolated from the leaves and twigs of . The structures of - including their absolute configurations were characterized by spectroscopic data analysis and single-crystal X-ray crystallography. Plausible biosynthetic pathways for the formation of compounds - were proposed. Compounds - exhibited cytotoxicity against HCT-116, MDA-MB-231, and PC-3 cancer cells with IC values from 6.4 to 9.1 μM.
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http://dx.doi.org/10.1021/acs.jnatprod.1c00287DOI Listing
August 2021

Boosting with heterologous vaccines effectively improves protective immune responses of the inactivated SARS-CoV-2 vaccine.

Emerg Microbes Infect 2021 Dec;10(1):1598-1608

National Institutes for Food and Drug Control, Beijing, People's Republic of China.

Since the outbreak of COVID-19, a variety of vaccine platforms have been developed. Amongst these, inactivated vaccines have been authorized for emergency use or conditional marketing in many countries. To further enhance the protective immune responses in populations that have completed vaccination regimen, we investigated the immunogenic characteristics of different vaccine platforms and tried homologous or heterologous boost strategy post two doses of inactivated vaccines in a mouse model. Our results showed that the humoral and cellular immune responses induced by different vaccines when administered individually differ significantly. In particular, inactivated vaccines showed relatively lower level of neutralizing antibody and T cell responses, but a higher IgG2a/IgG1 ratio compared with other vaccines. Boosting with either recombinant subunit, adenovirus vectored or mRNA vaccine after two-doses of inactivated vaccine further improved both neutralizing antibody and Spike-specific Th1-type T cell responses compared to boosting with a third dose of inactivated vaccine. Our results provide new ideas for prophylactic inoculation strategy of SARS-CoV-2 vaccines.
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http://dx.doi.org/10.1080/22221751.2021.1957401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381941PMC
December 2021

Using Genetic Variants to Evaluate the Causal Effect of Plasma Phospholipid Fatty Acids on Breast Cancer and Prostate Cancer: A Mendelian Randomization Study.

Front Genet 2021 30;12:664498. Epub 2021 Jun 30.

Department of Biochemistry and Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: Observational studies indicate that phospholipid fatty acids (FAs) have an impact on the etiology in cancers, but the results are conflicting. We aimed to investigate the causal association of phospholipid FAs with breast cancer and prostate cancer.

Methods: Fourteen single nucleotide polymorphisms (SNPs) were selected as instrumental variables to predict the level of 10 phospholipid FAs from Genome-wide association studies (GWAS). We obtained the summary statistics for the latest and largest GWAS datasets for breast cancer (113,789 controls and 133,384 cases) and prostate cancer (61,106 controls and 79,148 cases) from the Breast Cancer Association Consortium (BCAC) and Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Two-sample Mendelian randomization analysis was applied.

Results: The results demonstrate that the 10 individual plasma phospholipid FAs are not significantly associated with breast cancer risk and prostate cancer risk.

Conclusion: The evidence is insufficient to support the causal association of the 10 individual plasma phospholipid FAs with breast cancer and prostate cancer.
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http://dx.doi.org/10.3389/fgene.2021.664498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278063PMC
June 2021

Analog memristive synapse based on topotactic phase transition for high-performance neuromorphic computing and neural network pruning.

Sci Adv 2021 Jul 16;7(29). Epub 2021 Jul 16.

School of Integrated Circuits, Beijing National Research Center for Information Science and Technology (BNRist), Tsinghua University, Beijing 100084, China.

Inspired by the human brain, nonvolatile memories (NVMs)-based neuromorphic computing emerges as a promising paradigm to build power-efficient computing hardware for artificial intelligence. However, existing NVMs still suffer from physically imperfect device characteristics. In this work, a topotactic phase transition random-access memory (TPT-RAM) with a unique diffusive nonvolatile dual mode based on SrCoO is demonstrated. The reversible phase transition of SrCoO is well controlled by oxygen ion migrations along the highly ordered oxygen vacancy channels, enabling reproducible analog switching characteristics with reduced variability. Combining density functional theory and kinetic Monte Carlo simulations, the orientation-dependent switching mechanism of TPT-RAM is investigated synergistically. Furthermore, the dual-mode TPT-RAM is used to mimic the selective stabilization of developing synapses and implement neural network pruning, reducing ~84.2% of redundant synapses while improving the image classification accuracy to 99%. Our work points out a new direction to design bioplausible memristive synapses for neuromorphic computing.
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http://dx.doi.org/10.1126/sciadv.abh0648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284889PMC
July 2021

Ratiometric dual-emission of Rhodamine-B grafted carbon dots for full-range solvent components detection.

Anal Chim Acta 2021 Aug 9;1174:338743. Epub 2021 Jun 9.

Key Laboratory of Carbon Materials, Institute of Coal Chemistry, Chinese Academy of Sciences, 27 Taoyuan South Road, Taiyuan, 030001, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Quick and visual detection of component contents, such as water, in a mixed solvent is important for many practical applications, and a full range detection is especially preferred. In this work, a carbon dots based ratiometric fluorescent sensor was synthesized by grafting fluorescent group (Rhodamine B, RhB) on carbon dots, and the dual emission peaks exhibited a linear ratiometric response with the change of polarity and hydrogen bond of Solvent Hansen solubility parameters. This responsive behavior is attributed to surface state photoluminescence mechanisms, and has been used for the quantitative detection of water content in ethanol with an excellent linear relationship (R = 0.996), a low detection limit (0.2%), and a full detection range (0-100%). Furthermore, a paper-based ratiometric fluorescence sensing strip is also demonstrated, which exhibits good storage stability and sensitivity. This study suggests that RhB grafted carbon dots could be feasibly and effectively used as ratiometric fluorescent sensors for solvent content detection.
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http://dx.doi.org/10.1016/j.aca.2021.338743DOI Listing
August 2021

Aloe polysaccharides ameliorate acute colitis in mice via Nrf2/HO-1 signaling pathway and short-chain fatty acids metabolism.

Int J Biol Macromol 2021 Aug 3;185:804-812. Epub 2021 Jul 3.

State Key Laboratory of Food Science and Technology, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province 214122, China; School of Food Science and Technology, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province 214122, China; International Joint Laboratory on Food Safety, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province 214122, China. Electronic address:

Aloe polysaccharides (APs) are acetyl polysaccharides. It has been reported APs could protect mice from ulcerative colitis (UC), but the complex interactions between APs and the intestinal barrier were unclear. Here, we investigated the relationship between APs and UC, and determined the synergistic effects of Nrf2/HO-1 signaling pathway and short-chain fatty acids (SCFAs) metabolism on protecting intestinal barrier in acute UC mice. Results showed APs could scavenge free radicals in vitro. In vivo, APs had the antioxidant and anti-inflammatory effect both in serum and colon. Besides, the pathological results showed APs could alleviate colonic lesions. Furthermore, our study indicated treatment with APs effectively increased SCFAs production. The inhibition of acute UC in mice was correlated with the APs-mediated effects on improving the expression of ZO-1, occludin, Nrf2, HO-I, and NQO1. Thus, APs effectively promoted the intestinal barrier via Nrf2/HO-1 signaling pathway and SCFAs metabolism, effectively ameliorating acute colitis in mice.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.07.007DOI Listing
August 2021

Gut Microbiota: A Novel Regulator of Cardiovascular Disease and Key Factor in the Therapeutic Effects of Flavonoids.

Front Pharmacol 2021 16;12:651926. Epub 2021 Jun 16.

Department of Pharmacy, Baotou Medical College, Baotou, China.

Cardiovascular disease is the main cause of death worldwide, and traditional cardiovascular risk factors cannot fully explain the occurrence of the disease. In recent years, the relationship between gut microbiota and its metabolites and cardiovascular disease has been a hot study topic. The changes in gut microbiota and its metabolites are related to the occurrence and development of atherosclerosis, myocardial infarction, heart failure, and hypertension. The mechanisms by which gut microbiota and its metabolites influence cardiovascular disease have been reported, although not comprehensively. Additionally, following ingestion, flavonoids are decomposed into phenolic acids that are more easily absorbed by the body after being processed by enzymes produced by intestinal microorganisms, which increases flavonoid bioavailability and activity, consequently affecting the onset of cardiovascular disease. However, flavonoids can also inhibit the growth of harmful microorganisms, promote the proliferation of beneficial microorganisms, and maintain the balance of gut microbiota. Hence, it is important to study the relationship between gut microbiota and flavonoids to elucidate the protective effects of flavonoids in cardiovascular diseases. This article will review the role and mechanism of gut microbiota and its metabolites in the occurrence and development of atherosclerosis, myocardial infarction, heart failure, and hypertension. It also discusses the potential value of flavonoids in the prevention and treatment of cardiovascular disease following their transformation through gut microbiota metabolism.
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http://dx.doi.org/10.3389/fphar.2021.651926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241904PMC
June 2021

Injectable Nanosponge-Loaded Pluronic F127 Hydrogel for Pore-Forming Toxin Neutralization.

Int J Nanomedicine 2021 23;16:4239-4250. Epub 2021 Jun 23.

Department of Marine Biomedicine and Polar Medicine, Naval Special Medical Center, Naval Medical University, Shanghai, 200433, People's Republic of China.

Purpose: Pore-forming toxins (PFTs) perform important functions during bacterial infections. Among various virulence-targeting therapies, nanosponges (NSs) have excellent neutralization effects on multiple PFTs. To enhance treatment efficacy, NSs tend to be incorporated into other biomaterials, such as hydrogels.

Methods: In the present work, red blood cell (RBC) vesicles were harvested to wrap polymer nanoparticles, leading to the formation of NSs, and the optimal Pluronic F127 hydrogel concentration was determined for gelation. Then, a novel detoxification system was constructed by incorporating NSs into an optimized Pluronic F127 hydrogel (NS-pGel). Next, the system was characterized by rheological and sustained release behavior as well as micromorphology. Then, the in vitro neutralization effect of NS-pGel on various PFTs was examined by a hemolysis protocol. Finally, therapeutic and prophylactic detoxification efficiency was evaluated in a mouse subcutaneous infection model in vivo.

Results: A thermosensitive, injectable detoxification system was successfully constructed by loading NSs into a 30% Pluronic F127 hydrogel. Characterization results demonstrated that the NS-pGel hybrid system sustained an ideal fluidity and viscosity at lower temperatures but exhibited a quick sol-gel transition capacity near body temperature. In addition, this hybrid system had a sustained release behavior accompanied by good biocompatibility and biodegradability. Finally, the NS-pGel system showed neutralization effects similar to those of NSs both in vitro and in vivo, indicating a good preservation of NS functionality.

Conclusion: In conclusion, we constructed a novel temperature-sensitive detoxification system with good biocompatibility and biodegradability, which may be applied to the clinical treatment of PFT-induced local lesions and infections.
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http://dx.doi.org/10.2147/IJN.S315062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238402PMC
July 2021

Prevalence and Associated Factors of Suboptimal Daily Peak Inspiratory Flow and Technique Misuse of Dry Powder Inhalers in Outpatients with Stable Chronic Airway Diseases.

Int J Chron Obstruct Pulmon Dis 2021 23;16:1913-1924. Epub 2021 Jun 23.

Department of Pharmacy, First Affiliated Hospital of Naval Medical University (Changhai Hospital), Shanghai, People's Republic of China.

Purpose: The present study aimed to investigate the prevalence and associated factors of suboptimal daily peak inspiratory flow (PIF) and technical misuse of three commonly used dry powder inhalers (DPIs) in outpatients with stable chronic airway diseases.

Patients And Methods: Included in this study were 85 outpatients with stable asthma, chronic obstructive pulmonary disease (COPD), or asthma-COPD Overlap (ACO) and had previously used any of Turbuhaler (TUR), Diskus (DIS), HandiHaler (HAN) between December 2018 and September 2019. The patient's daily PIF against the resistance of a specific DPI and operation technique was investigated by two pharmacists by using In-Check DIAL G16 and a checklist.

Results: Of the 85 patients, the proportion of patients with a suboptimal daily PIF and technical misuse was 38.8% and 65.9%, respectively. In logistic regression, we observed that the factors that increase the risk for suboptimal daily PIF were age (OR=1.06) and combination with respiratory diseases (OR = 6.59). The factor that decreases the risk for misuse was the higher education level (OR =0.63).

Conclusion: Even if patients have received training at the time of initial prescription, the standardization of the use of DPIs by patients in our center was still unoptimistic. Age and combined with respiratory diseases were associated with suboptimal PIF. Higher education level decreased the incidence of technique misuse.
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http://dx.doi.org/10.2147/COPD.S311178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236256PMC
August 2021

TMEM100 induces cell death in non‑small cell lung cancer via the activation of autophagy and apoptosis.

Oncol Rep 2021 05 29;45(5). Epub 2021 Jun 29.

Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, P.R. China.

Lung cancer is one of the most malignant type of tumors worldwide. Non‑small cell lung cancer (NSCLC), which is the most common type of lung cancer, is defined as a distinct disease that exhibits both genetic and cellular heterogeneity. Although in the past two decades significant advances in the treatment of NSCLC have besen performed, the 5‑year survival rate of patients with NSCLC remains <20%. Thus, there is an urgent requirement to gain an in‑depth understanding of the molecular mechanisms that promote NSCLC development and to identify novel therapeutic targets. In the present study, the gene expression profiles of patients with NSCLC from The Cancer Genome Atlas database were analyzed to determine potential therapeutic targets, and transmembrane protein 100 (TMEM100) was identified as a candidate tumor suppressor. TMEM100 expression level was discovered to be decreased in both NSCLC tissues and cell lines, and it was observed to be negatively associated with the TNM stage and positively associated with prognosis. Moreover, TMEM100 inhibited tumor growth and promoted cell apoptosis in A549 and H460 cells. Mechanistically, TMEM100 was demonstrated to induce autophagy in A549 cells via inhibiting the PI3K/AKT signaling pathway, whereas inhibiting autophagy using bafilomycin A1 significantly enhanced TMEM100‑induced apoptosis to compensate for the cell death. In conclusion, these findings suggested that TMEM100 may serve as a tumor suppressor in NSCLC and promote autophagy via inhibiting the PI3K/AKT signaling pathway.
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http://dx.doi.org/10.3892/or.2021.8014DOI Listing
May 2021

Iridoid Constituents of .

J Nat Prod 2021 07 24;84(7):1915-1923. Epub 2021 Jun 24.

Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, People's Republic of China.

Eleven new iridoids, brachybones A-K (-), were isolated from the twigs of . Their structures including absolute configurations were determined by spectroscopic data analysis and from the electronic circular dichroism (ECD) spectra. All of the compounds - possess one or two acetoxysenecioate substituents. Furthermore, compounds - and feature a Cl atom in the molecule, while compounds - exhibit a cagelike rigid skeleton through an unusual oxo bridge from C-3 to C-8 or C-10. The isolates were evaluated for cytotoxic activity against the HCT-116, A549, and Hela cell lines, and the results showed compounds and to be active against HCT-116 cells.
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http://dx.doi.org/10.1021/acs.jnatprod.1c00042DOI Listing
July 2021
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