Publications by authors named "Wei Du"

1,183 Publications

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Economic Impact of Preoperative Meloxicam IV Administration in Total Knee Arthroplasty: A Randomized Trial Sub-Study.

J Pain Palliat Care Pharmacother 2021 Jul 19:1-13. Epub 2021 Jul 19.

We evaluated the economic impact associated with preoperative meloxicam IV 30 mg vs placebo administration among adult total knee arthroplasty (TKA) recipients enrolled in Phase IIIB NCT03434275 trial. Data on total hospital costs and length of stay (LOS) obtained from the trial were compared between meloxicam IV 30 mg and placebo groups. Patients in the meloxicam IV 30 mg vs placebo group (n = 93 vs 88) incurred an adjusted $2,266 (95% CI: -$1,035, $5,116; p = 0.1689) lower total hospital costs and an adjusted 8.6% (95% confidence interval [CI]: -2.0%, 18.1%; p = 0.1082) shorter LOS. While statistically non-significant, based on 95% CIs, the results from this sub-study may suggest a favorable impact associated with meloxicam IV 30 mg on hospital costs and LOS.
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http://dx.doi.org/10.1080/15360288.2021.1883789DOI Listing
July 2021

miR‑367‑3p downregulates Rab23 expression and inhibits Hedgehog signaling resulting in the inhibition of the proliferation, migration, and invasion of prostate cancer cells.

Oncol Rep 2021 Sep 19;46(3). Epub 2021 Jul 19.

Department of Urology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, P.R. China.

MicroRNAs play an important role in tumor cell proliferation, invasion, and Rab23 is a member of the Ras‑related small GTPase family and plays a critical role in the progression of may types of tumors. The present study was designed to investigate the inhibitory effect of microRNA (miR)‑367‑3p on the proliferation, invasion, and metastasis of prostate cancer cells. qRT‑PCR was used to detect the expression of miR‑367‑3p in prostate cancer and adjacent tissues. Cell proliferation, scratch, and Transwell assays were performed to verify the inhibitory effect of miR‑367‑3p overexpression or Ras‑related protein Rab 23 () knockdown on prostate cancer. Double luciferase reporter assay was utilized to verify whether miR‑367‑3p could target the Rab23 3'‑untranslated region (UTR). The expression levels of Rab23, Gli1, and Gli2 in prostate cancer cells transfected with the miR‑367‑3p mimic were detected via qRT‑PCR analysis. miR‑367‑3p expression in the prostate cancer tissues was downregulated compared with that in the para‑cancer control tissues. miR‑367‑3p expression in DU145 and PC3 cells was also downregulated compared with that in the human prostate epithelial cell line RWPE‑1. The overexpression of miR‑367‑3p or the knockdown of Rab23 inhibited the proliferation, invasion, and metastasis of prostate cancer cells. The results of the luciferase reporter assay confirmed that Rab23 was a target gene that was regulated by miR‑367‑3p. miR‑367‑3p specifically bound to the 3'‑UTR of Rab23 mRNA. The overexpression of miR‑367‑3p inhibited Rab23 expression and the Hedgehog pathway. Cell function experiments confirmed that the overexpression of Rab23 reversed the anticancer effect of miR‑367‑3p. miR‑367‑3p was able to inhibit the Hedgehog pathway by targeting the expression of the Rab23 gene, thus inhibiting the proliferation, invasion, and metastasis of prostate cancer cells.
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http://dx.doi.org/10.3892/or.2021.8143DOI Listing
September 2021

Mediastinal Low-Grade Fibromyxoid Sarcoma With FUS-CREB3L2 Gene Fusion.

Cureus 2021 Jun 11;13(6):e15606. Epub 2021 Jun 11.

Oncology, Charleston Area Medical Center (CAMC), Charleston, USA.

Low-grade fibromyxoid sarcoma (LGFMS) is a rare subclass of sarcoma. Histologically, they are characterized by bland-appearing fibroblastic spindle cells and are similar to sclerosing epithelioid fibrosarcoma (SEF) subtype. The standard treatment of this aggressive tumor subtype is surgical removal with wide excision in conjunction with doxorubicin chemotherapy. Due to the rarity of this disease, effective systemic therapies are lacking and patient outcomes remain poor. Herein, we report on a 50-year-old male who presented with severe shortness of breath. Subsequent imaging revealed pericardial effusion and large mediastinal mass consistent with locally advanced disease. Fine needle biopsy demonstrated malignant, Ewing-like round tumor cells. Further genetic analysis affirmed the presence of FUS-CREB3L2 gene fusion. The patient was treated with doxorubicin and survival time from the initial presentation was five months. To date, there are limited reports of this disease. Few targeted therapies or immunotherapies for LGFMS exist, and a dire need for new therapy development remains.
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http://dx.doi.org/10.7759/cureus.15606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273027PMC
June 2021

Interaction of different-sized ZnO nanoparticles with maize (Zea mays): Accumulation, biotransformation and phytotoxicity.

Sci Total Environ 2021 Jul 9;796:148927. Epub 2021 Jul 9.

School of Agriculture and Food Sciences, The University of Queensland, St. Lucia, Queensland 4072, Australia.

This study aimed to investigate the biotransformation of ZnO nanoparticles (NPs) in maize grown in hydroponics for ecotoxicity assessment. Maize seedlings grown for 14 days were exposed to a solution of 9 nm ZnO NPs, 40 nm ZnO NPs, and ZnSO at a Zn concentration of 300 mg L for 1, 3, and 7 days, respectively. The results of in-situ Zn distribution in maize (Zea mays) showed that 9 nm ZnO NPs could quickly enter the roots of maize and reach the center column transport system of the stem. The results of transmission electron microscopy combined with energy dispersive X-ray spectroscopy revealed that ZnO NPs were accumulated in the vacuoles of the roots, and then transformed and transported through vesicles. Simulated studies showed that low pH (5.6) played a critical role in the transformation of ZnO NPs, and organic acids (K = 10) could promote particle dissolution. Visual MINTEQ software simulated the species of Zn after the entry of ZnO NPs or Zn into plants and found that the species of Zn was mainly Zn when the Zn content of plants reached 200-300 ppm. Considering that the lowest Zn content of the roots in treatments was 1920 mg kg, combination of the result analysis of root effects showed that the toxicity of roots in most treatments had a direct relationship with Zn. However, treatment with 9 nm ZnO NPs exhibited significantly higher toxicity than ZnSO treatment on day 1 when the Zn concentration difference was not significant, which was mainly due to the large amount of ZnO NPs deposited in the roots. To the authors' knowledge, this study was the first to confirm the process of biotransformation and explore the factors affecting the toxicity of ZnO NPs in depth.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148927DOI Listing
July 2021

Mass Absorption Efficiency of Black Carbon from Residential Solid Fuel Combustion and Its Association with Carbonaceous Fractions.

Environ Sci Technol 2021 Jul 16. Epub 2021 Jul 16.

Laboratory for Earth Surface Process, College of Urban and Environmental Sciences, Peking University, Beijing 100871, People's Republic of China.

Black carbon (BC) emissions, derived primarily from incomplete fuel combustion, significantly affect the global and regional climate. Mass absorption efficiency (MAE) is one important parameter in evaluating the climate impacts of BC. Here, values and variabilities in the MAE of BC (MAE) from real-world residential emissions were investigated from a field campaign covering 163 burning events for different fuel-stove combinations. MAE (average: 12 ± 5 m/g) was normally distributed and varied greatly by 2 orders of magnitude. Statistically significant differences in MAE were found for various fuels, while no significant differences were observed among different stoves. The fuel difference explained 72 ± 7% of the MAE variation. MAE did not correlate with the modified combustion efficiency but positively correlated with the ratio of organic carbon (OC) to elemental carbon (EC) and negatively correlated with char-EC. The OC/EC ratio was not always lower in coal emissions in comparison to biomass burning emissions. Coal- and biomass-burning emissions had different profiles of carbon fractions. Char-EC, OC, OC/EC, and char-EC/soot-EC can explain 68.7% of the MAE variation, providing the potential for predicting MAE from the carbon fractions, since they are more commonly measured and available.
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http://dx.doi.org/10.1021/acs.est.1c02689DOI Listing
July 2021

Configurable topological phonon polaritons in twisted hBN metasurfaces.

Appl Opt 2021 Jul;60(19):5735-5741

Phonon polaritons are hybrid excitations that originate from coupling of photons with optical phonons in polar crystals. Hexagonal boron nitride (hBN) is a representative phonon polariton material in mid-infrared that exhibits long lifetimes and ultraslow propagation. However, due to in-plane isotropic permittivities, the dispersion engineering and highly canalized ray-like propagation along the in-plane surface required in photonic and optoelectronic applications cannot be realized in a bare hBN structure. In this paper, we theoretically investigate phonon polaritons in twisted hBN metasurfaces. Due to interactions between different propagating polaritons in the top and bottom metasurfaces, configurable polaritons can be hybridized. Importantly, the hybridized polariton dispersion can be changed from the hyperbolic type to elliptical type via tuning the twisting angle. The demonstrated steerable dispersion evolution and highly canalized propagating polaritons hold promise for nano-optical applications such as in-plane hyperlensing, waveguiding, and focusing.
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http://dx.doi.org/10.1364/AO.428388DOI Listing
July 2021

Nonsmoking and Nondrinking Oral Squamous Cell Carcinoma Patients: A Different Entity.

Front Oncol 2021 28;11:558320. Epub 2021 Jun 28.

Department of Head Neck and Thyroid Surgery, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.

Objective: Our goal was to analyze the demographic and pathologic characteristics as well as prognosis in nonsmoking and nondrinking (NSND) oral squamous cell carcinoma (SCC) patients compared with typical oral SCC patients.

Patients And Methods: A total of 353 patients were retrospectively enrolled and divided into two groups: the NSND group and the current smoking/current drinking (CSCD) group. Demographic, pathologic, and molecular data were compared between the two groups. The main research endpoints were locoregional control (LRC) and disease-specific survival (DSS).

Results: In the NSND group, 16.3%, 41.9%, and 53.5% of patients were aged no more than 40 years, were female, and had an educational background of high school or above compared to 3.7%, 6.0%, and 38.2% of patients in the CSCD group, respectively. A total of 15.1% of the NSND patients had SCC of the lower gingiva and floor of the mouth, which was lower than the 35.6% of patients in the CSCD group. CSCD patients were likely to have an advanced disease stage (48.7% vs 32.5%, p=0.042) and poorly differentiated cancer (26.6% vs 16.3%, p=0.042). The NSND patients had a mean Ki-67 index of 24.5%, which was lower than the mean of 35.7% in the CSCD patients. The two groups had no HPV infection and similar p16 expression (4.7% vs 10.1%, p=0.132), but there was higher expression of p53 (38.6% vs 17.4%, p<0.001) and p63 (59.9% vs 29.1%, p<0.001) in the CSCD group. The 5-year LRC rates for NSND patients and CSCD patients were 48% and 38%, respectively, and the difference was significant (p=0.048). The 5-year DSS rates for NSND patients and CSCD patients were 56% and 39%, respectively, and the difference was significant (p=0.047). Further, a Cox model confirmed the independence of smoking and drinking status for affecting LRC and DSS.

Conclusion: NSND oral SCC patients are a different entity. HPV infection has a limited role in carcinogenesis in NSND patients, and p16 expression is associated with worse locoregional control.
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http://dx.doi.org/10.3389/fonc.2021.558320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273760PMC
June 2021

Combination of Sulindac and Eflornithine Delays the Need for Lower Gastrointestinal Surgery in FAP Patients: Post-Hoc Analysis of a Randomized Clinical Trial.

Dis Colon Rectum 2021 Jul 12. Epub 2021 Jul 12.

Department of Gastroenterology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA Department of Gastroenterology, Hepatology & Nutrition, Cleveland Clinic, Cleveland, OH, USA Department of Gastroenterology & Hepatology, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, The Netherlands Division of Gastroenterology & Hepatology, Mayo Clinic, Phoenix, AZ, USA University Hospital Gasthuisberg, Leuven, Belgium Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX, USA Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA Department of Internal Medicine I, University of Bonn, Bonn, Germany National Center for Hereditary Tumor Syndromes, Bonn, Germany Division of Population Sciences, Dana-Farber Cancer Institute, Boston, MA, USA Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, MA, USA Harvard Medical School, Boston, MA USA Cancer Prevention Pharmaceuticals, Inc., Tucson, AZ, USA Clinical Statistics Consulting, Blue Bell, PA, USA.

Background: Colectomy and proctocolectomy are the initial standard of care for patients with familial adenomatous polyposis. Pharmacotherapy to prevent progression of polyposis and surgeries in the lower gastrointestinal tract would be beneficial to patients with this disease.

Objective: This analysis aimed to evaluate the impact of eflornithine-sulindac combination versus monotherapy in delaying time to disease progression in the lower gastrointestinal tract of patients with familial adenomatous polyposis.

Design: This is a post-hoc analysis of a randomized phase 3 trial.

Setting: Twenty-one hospitals in 7 countries treating patients with familial adenomatous polyposis.

Patients: Adults with familial adenomatous polyposis were randomized 1:1:1 into 3 arms.

Interventions: Patients received either eflornithine (750 mg), sulindac (150 mg), or both once daily for up to 48 months.

Main Outcome Measures: Efficacy was evaluated as time from randomization to predefined primary disease progression endpoints.

Results: Results are reported for the study population excluding patients who had undergone permanent ileostomies (n = 158). Disease progression was observed in 2/54 (3.7%), 9/53 (17.0%), and 10/51 (19.6%) patients with at least partial lower gastrointestinal tract in the combination, sulindac, and eflornithine arms, respectively, corresponding to risk reductions of 80% (p = 0.02) and 83% (p = 0.01) between combination and sulindac or eflornithine, respectively. When endoscopic excision of adenomas ≥10 mm in size were censored, the need for major surgery was observed in 0/54, 7/53 (13.2%), and 8/51 (15.7%) patients in the combination, sulindac, and eflornithine arms, respectively, corresponding to risk reductions approaching 100% between combination and sulindac (p = 0.005) or combination and eflornithine (p = 0.003).

Limitations: This was a post-hoc analysis, the sample size was small, and there were fewer than expected events.

Conclusions: Eflornithine-sulindac combination therapy was superior to either drug alone in delaying or preventing the need for lower gastrointestinal tract surgery in patients with familial adenomatous polyposis. See Video Abstract at http://links.lww.com/DCR/B658 .
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http://dx.doi.org/10.1097/DCR.0000000000002095DOI Listing
July 2021

Water-induced release of recalcitrant polycyclic aromatic hydrocarbons from soil organic matter during microwave-assisted solvent extraction.

Environ Pollut 2021 Sep 3;284:117493. Epub 2021 Jun 3.

College of Urban and Environmental Sciences, Laboratory for Earth Surface Processes, Sino-French Institute for Earth System Science, Peking University, Beijing, 100871, China.

Polycyclic aromatic hydrocarbons (PAHs) in soil can be recalcitrant to solvent extraction after aging. We showed in this study that mixing a small amount of water in the extracting solvent during microwave-assisted extraction (MAE) can release recalcitrant PAHs, resulting in significant improvement in the analyzed concentrations. The improvement factor (F) for the total of 16 priority PAHs (∑PAH16) listed by the United States Environmental Protection Agency was 1.44-1.55 for field soils. By comparing the F values for different soil organic components, we demonstrated that the recalcitrant PAHs were primarily associated with biochar, humic acid (HA), and humin (HM), with the F values for ∑PAH16 of 1.94, 6.62, and 4.59, respectively. The results showed that the recalcitrant PAHs comprised a sequestered fraction and a desorption-limited fraction. NMR spectra showed that water worked alone at elevated temperature to promote hydrolysis of biochar and destroy the macromolecular structure, thus causing the release of the otherwise sequestered PAHs during MAE. The substantial reduction in F values for HA and HM after demineralization indicated sequestration of PAHs in organic-mineral complexes, which can be destroyed by hot water treatment. The release of the sequestered fraction was nonselective and independent of compound hydrophobicity. In comparison, the release of the desorption-limited fraction was positively affected by the hydrophobicity of PAHs and was facilitated by the presence of water in the extracting solvent. The results of this study provide important insights into the sequestration and release of recalcitrant PAHs in soil.
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http://dx.doi.org/10.1016/j.envpol.2021.117493DOI Listing
September 2021

Assessment on chronic and transgenerational toxicity of methamphetamine to Caenorhabditis elegans and associated aquatic risk through toxicity indicator sensitivity distribution (TISD) analysis.

Environ Pollut 2021 Jul 2;288:117696. Epub 2021 Jul 2.

MOE Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, Tianjin, 300350, PR China.

Evidence about the adverse effects of methamphetamine (METH) on invertebrates is scarce. Hence, C. elegans, a representative invertebrate model, was exposed to METH at environmental levels to estimate chronic and transgenerational toxicity. The results of chronic exposure were integrated into an underlying toxicity framework of METH in invertebrates (e.g., benthos) at environmentally relevant concentrations. The induction of cellular oxidative damage-induced apoptosis and fluctuation of ecologically important traits (i.e., feeding and locomotion) might be attributed by the activation of the longevity regulating pathway regulated by DAF-16/FOXO, and detoxification by CYP family enzymes. The adverse effects to the organism level included impaired viability and decreased fecundity. The results from transgenerational exposure elucidated the cumulative METH-induced damage in invertebrates. Finally, a new risk assessment method named toxicity indicator sensitivity distribution (TISD) analysis was proposed by combining multiple toxicity indicator test data (EC) to derive the hazardous concentration for 10% indicators (C) of one species. The risk quotient (RQ) values calculated by measured environmental concentrations and C in southern China, southeastern Australia, and the western US crossed the alarm line (RQ = 5), suggesting a need for long-term monitoring.
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http://dx.doi.org/10.1016/j.envpol.2021.117696DOI Listing
July 2021

Enhancing effect of NO on the formation of light-absorbing secondary organic aerosols from toluene photooxidation.

Sci Total Environ 2021 Jun 27;794:148714. Epub 2021 Jun 27.

Institute of Urban Meteorology, China Meteorological Administration, Beijing 100089, China.

Aromatic hydrocarbons are one of the major precursors of atmospheric brown carbon (BrC) and both abundantly co-exist with NO in the urban atmosphere especially in winter haze period. However, the impact of NOx on the formation of BrC derived from aromatic hydrocarbons is still not fully understood. In this study, the yield and light absorption of secondary organic aerosols (SOA) from toluene photooxidation under various nitrogen oxides (NO) levels were investigated by using a 5 m photooxidation smog chamber. A trend of increase at first and then decrease in the SOA yield with an increasing NO concentration was observed. The acid-catalyzed heterogeneous reactions lead to the increase of SOA yield in the low-NO regime. The formation of low-volatility species might be suppressed at high-NO conditions is responsible for the decreased SOA yield. In contrast, light absorption and mass absorption coefficient (MAC) of the toluene-derived SOA continuously increased with the increasing NO concentrations. HR-ToF-AMS results showed that nitrogen-containing organic compounds (NOCs) are the main species that lead to the increase of the SOA light absorption. The ratio of CHN family to the total NOCs, which are derived from the nitro compounds, also increased dominantly with the increasing NO levels and accounted for more than half of the total NOCs when the NO concentration increased to 495 ppbv, indicating that nitro compounds rather than organic nitrates are the major light-absorbing species and preferably formed in the toluene oxidation process.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148714DOI Listing
June 2021

Hydrated cation-π interactions of π-electrons with hydrated Li, Na, and K cations.

Phys Chem Chem Phys 2021 Jul;23(27):14662-14670

Department of Physics, East China University of Science and Technology, Shanghai 200237, China. and Shanghai Synchrotron Radiation Facility, Zhangjiang Laboratory, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201204, China.

Cation-π interactions are essential for many chemical, biological, and material processes, and these processes usually involve an aqueous salt solution. However, there is still a lack of a full understanding of the hydrated cation-π interactions between the hydrated cations and the aromatic ring structures on the molecular level. Here, we report a molecular picture of hydrated cation-π interactions, by using the calculations of density functional theory (DFT). Specifically, the graphene sheet can distort the hydration shell of the hydrated K+ to interact with K+ directly, which is hereafter called water-cation-π interactions. In contrast, the hydration shell of the hydrated Li+ is quite stable and the graphene sheet interacts with Li+ indirectly, mediated by water molecules, which we hereafter call the cation-water-π interactions. The behavior of hydrated cations adsorbed on a graphene surface is mainly attributed to the competition between the cation-π interactions and hydration effects. These findings provide valuable details of the structures and the adsorption energy of hydrated cations adsorbed onto the graphene surface.
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http://dx.doi.org/10.1039/d1cp01609aDOI Listing
July 2021

[Pollution Characteristics and Sources of Wintertime Atmospheric Brown Carbon at a Background Site of the Yangtze River Delta Region in China].

Huan Jing Ke Xue 2021 Jul;42(7):3127-3135

Key Laboratory of Geographic Information Sciences, Ministry of Education, School of Geographic Sciences, East China Normal University, Shanghai 200241, China.

To investigate the pollution characteristics and sources of atmospheric brown carbon (BrC) in Chongming Island, a background site of the Yangtze River Delta (YRD) region in China, PM samples collected from December 2018 to January 2019 were analyzed to determine their chemical compositions and optical properties. The results showed that the light absorption coefficient (Abs) of BrC extracted by methanol at 365 nm was (5.39±3.33) M·m, which was 1.3 times of the water extracted BrC. Both increased significantly with the increase of pH values, suggesting that less acidic conditions can enhance the light absorption ability of BrC. In winter, both Abs and MAE (mass absorption efficiency) were higher in the nighttime than in the daytime. A strong linear correlation observed between Abs and levoglucosan (=0.72) indicated that many light absorbing substances in Chongming Island were derived from biomass burning emissions. During the campaign, nitro-aromatic compounds (NACs) and PAHs accounted for (1.5±1.1) ng·m and (8.3±4.7) ng·m, respectively, contributing to 0.1% and 0.067% of the absorption of the total BrC at 365 nm, respectively. Positive matrix factorization (PMF) analysis further showed that biomass and fossil fuel combustions were the main sources of BrC in Chongming Island in winter, accounting for 56% of the total BrC, followed by secondary formation, accounting for 24% of the total BrC, with road dust contributing only 6%.
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http://dx.doi.org/10.13227/j.hjkx.202012002DOI Listing
July 2021

Advances in Enzyme and Ionic Liquid Immobilization for Enhanced in MOFs for Biodiesel Production.

Molecules 2021 Jun 9;26(12). Epub 2021 Jun 9.

Chemical and Petroleum Engineering Department, UAE University, Al Ain 15551, United Arab Emirates.

Biodiesel is a promising candidate for sustainable and renewable energy and extensive research is being conducted worldwide to optimize its production process. The employed catalyst is an important parameter in biodiesel production. Metal-organic frameworks (MOFs), which are a set of highly porous materials comprising coordinated bonds between metals and organic ligands, have recently been proposed as catalysts. MOFs exhibit high tunability, possess high crystallinity and surface area, and their order can vary from the atomic to the microscale level. However, their catalytic sites are confined inside their porous structure, limiting their accessibility for biodiesel production. Modification of MOF structure by immobilizing enzymes or ionic liquids (ILs) could be a solution to this challenge and can lead to better performance and provide catalytic systems with higher activities. This review compiles the recent advances in catalytic transesterification for biodiesel production using enzymes or ILs. The available literature clearly indicates that MOFs are the most suitable immobilization supports, leading to higher biodiesel production without affecting the catalytic activity while increasing the catalyst stability and reusability in several cycles.
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http://dx.doi.org/10.3390/molecules26123512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226643PMC
June 2021

Distribution and partitioning of pyrethroid insecticides in agricultural lands: Critical influencing factors.

Environ Int 2021 Jun 28;156:106736. Epub 2021 Jun 28.

Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China.

Pyrethroid insecticides are widely applied due to the broad spectrum and high efficiency in pest control and detected in various environmental media, but the key factor affecting their occurrence and distribution in agricultural lands is still not clear. Here, we measured pyrethroid residues in 644 surface soil and 630 surface water samples and quantified the impacts of various factors on the distribution and partition of pyrethroids through a large-scale field study in Southeast China during 2015-2017. The pyrethroid residues were widely detected in the studied areas, and the mean concentration of seven individual pyrethroids in surface soil and water ranged from 0.10 (cyfluthrin, (CYF)) to 12.14 ng/g (bifenthrin, (BIF)) and 0.18 (CYF) to 3.36 µg/L (BIF) respectively, which were higher than other regions in China and some other countries. Using a generalized linear model coupled with dominance analysis, we found that the crop type and season were significantly associated with pyrethroid residues in surface soil and water (p < 0.05). The crop difference dominated the variances of the distribution of pyrethroid residues in the surface soil and water with a contribution of more than 55% and followed by the factor of season difference. The findings provide new insight into the distribution and partitioning of pyrethroids in agricultural lands and insecticide control on ecological safety and public health.
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http://dx.doi.org/10.1016/j.envint.2021.106736DOI Listing
June 2021

Bifunctional μ opioid and σ receptor ligands as novel analgesics with reduced side effects.

Eur J Med Chem 2021 Jun 18;223:113658. Epub 2021 Jun 18.

Jiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China. Electronic address:

Opioid analgesics are highly effective painkillers for the treatment of moderate or severe pain, but they are associated with a number of undesirable adverse effects, including the development of tolerance, addiction, constipation and life-threatening respiratory depression. The development of new and safer analgesics with innovative mechanisms of action, which can enhance the efficacy in comparison to available treatments and reduce their side effects, is urgently needed. The sigma-1 receptor (σR), a unique Ca-sensing chaperone protein, is expressed throughout pain-modulating tissues and affects neurotransmission by interacting with different protein partners, including molecular targets that participate in nociceptive signalling, such as the μ-opioid receptor (MOR), N-methyl-d-aspartate receptor (NMDAR) and cannabinoid 1 receptor (CBR). Overwhelming pharmacological and genetic evidence indicates that σR antagonists induce anti-hypersensitive effects in sensitising pain conditions (e.g. chemically induced, inflammatory and neuropathic pain) and enhance opioid analgesia but not opioid-mediated detrimental effects. It has been suggested that balanced modulation of MORs and σRs may improve both the therapeutic efficacy and safety of opioids. This review summarises the functional profiles of ligands with mixed MOR agonist and σR antagonist activities and highlights their therapeutic potentials for pain management. Dual MOR agonism/σR antagonism represents a promising avenue for the development of potent and safer analgesics.
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http://dx.doi.org/10.1016/j.ejmech.2021.113658DOI Listing
June 2021

Insights into the accelerated venlafaxine degradation by cysteine-assisted Fe/persulfate: Key influencing factors, mechanisms and transformation pathways with DFT study.

Sci Total Environ 2021 Jun 22;793:148555. Epub 2021 Jun 22.

Key Laboratory of Integrated Regulation and Resource Development on Shallow Lakes, Ministry of Education, Hohai University, Nanjing 210098, China; College of Environment, Hohai University, Nanjing 210098, China. Electronic address:

The effective removal of refractory antidepressant in wastewater is challenging. In this study, a novel strategy of cysteine-assisted Fe/persulfate system (Fe/Cys/PS) was applied for the venlafaxine (Ven, as a typical antidepressant) degradation. The obtained results revealed that the Ven removal was evidently accelerated and enhanced in Fe/Cys/PS process, and achieved complete degradation in 5 min with optimal dosage. Further analysis indicated that the Ven degradation efficiency was associated with the chemical concentrations (i.e. Fe, Cys and PS) and operational conditions (i.e. pH and temperature). Moreover, the reactions were not impacted by the co-occurring organic matters (i.e. fulvic acid) and inorganic ions (i.e. Cl) potentially existing in real wastewater matrices. Mechanistic explorations demonstrated that the presence of Cys promoted the Fe/Fe redox cycle, and thus enhanced the reactive oxygen species yields (ROS). The OH was considered as the primary ROS in Fe/Cys/PS process for Ven degradation via the radical scavenger verification. Also, the main intermediates of Ven degradation were identified, and the possible transformation pathway was proposed, in which the hydroxylation attacked by the OH was the main reaction. Moreover, the active reaction sites in Ven were calculated with the density function theory (DFT), which was consistent with the observed metabolic routes.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148555DOI Listing
June 2021

A 3D visualization layered anatomy for acromial arterial rete and flap design.

Surg Radiol Anat 2021 Jun 22. Epub 2021 Jun 22.

Department of Anatomy, Institute of Clinical Applied Anatomy, School of Basic Medical Sciences, Basic Medical College, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.

Background: The acromial arterial rete (AAR) is the junction between the skin blood supply of the cervical side and that of the upper arm, and it is the only site crossed by the trans-regional blood supply of the cervico-humeral flap (CHF). The aim of this study was to explore the structures of AAR to optimizing flap design.

Methods: A body arteriography and spiral CT scan were performed on 33 whole adult corpses. The 3D reconstruction was used to perform continuous digital layered anatomy of the shoulder and upper chest; the acromion and acromioclavicular joint were used as the center to observe the source, route and distribution characteristics of a perforating branch and their anastomosis.

Results: The perforating branches were separated from an acromial branch of the transverse cervical artery (97%), posterior humeral circumflex artery (95%), a deltoid branch of the thoracoacromial artery (95%), and the acromial branch of the thoracoacromial artery (93%). The diameter of the acromial branch of the transverse cervical artery at its initial location was 1.18 ± 0.37 mm; the trunk length was 12.53 ± 3.83 cm, and it was anastomosed with other blood vessels in three forms.

Conclusion: Deep fascia should be included in the flap design. Three kinds of pedicled transfer flaps can be designed with the acromial branch of transverse carotid artery as the vascular pedicle. Free flaps can be designed with the acromial branch of thoracoacromial artery as the vascular pedicle.
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http://dx.doi.org/10.1007/s00276-021-02781-yDOI Listing
June 2021

Elucidation of the Regulatory Network of Flavonoid Biosynthesis by Profiling the Metabolome and Transcriptome in Tartary Buckwheat.

J Agric Food Chem 2021 Jun 21;69(25):7218-7229. Epub 2021 Jun 21.

College of Agriculture, Institute of Agricultural Bioengineering, Shanxi Agricultural University, 030801 Taigu, Shanxi, China.

The characteristics of flavonoid metabolism in different Tartary buckwheat (TB) tissues and the related gene regulation network are still unclear at present. One hundred forty-seven flavonoids were identified from six TB tissues using the ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. The roadmap of the rutin synthesis pathway was revealed. Through transcriptomic analysis it was revealed that the differentially expressed genes (DEGs) are mainly enriched in the "Phenylpropanoid biosynthesis" pathway. Fifty-two DEGs involved in the "flavonol synthesis" pathway were identified. The weighted gene correlation network analysis revealed four co-expression network modules correlated with six flavonol metabolites. Eventually, 74 genes revealed from MEblue and MElightsteelblue modules were potentially related to flavonol synthesis. Of them, 7 MYB transcript factors had been verified to regulate flavonoid synthesis. Furthermore, overexpressed enhanced the rutin content . The present findings provide a dynamic flavonoid metabolism profile and co-expression network related to rutin synthesis and are thus valuable in understanding the molecular mechanisms of rutin synthesis in TB.
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http://dx.doi.org/10.1021/acs.jafc.1c00190DOI Listing
June 2021

Alteration of the PKA-CREB cascade in the mPFC accompanying prepulse inhibition deficits: evidence from adolescent social isolation and chronic SKF38393 injection during early adolescence.

Behav Pharmacol 2021 Jun 18. Epub 2021 Jun 18.

School of Psychological and Cognitive Science, Beijing Key Laboratory of Behavior and Mental Health, Peking University, Beijing Key Research Base of Humanities and Social Sciences of the Ministry of Education, Academy of Psychology and Behavior, Tianjin Normal University Faculty of Psychology, Tianjin Normal University Tianjin Social Science Laboratory of Students' Mental Development and Learning, Tianjin Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences The University of Chinese Academy of Sciences, Beijing, China.

Prepulse inhibition (PPI) refers to the inhibition of the startle reflex that occurs when the startling stimulus is preceded by a weak prestimulus. Altered adolescent mPFC circuitry induced by early-life adversity might be a key source of PPI deficits. The current study focused on variations in the cyclic AMP (cAMP)/protein kinase A (PKA)-cAMP-response element-binding protein (CREB) pathway in the medial prefrontal cortex (mPFC). We found a negative relationship between PPI and the PKA-CREB cascade during adolescence by employing both developmental and pharmacologic manipulations. Experiment 1, with the early adolescent social isolation model [postnatal days (PNDs), 21-34), displayed a disrupted PPI at PND 35 and significantly altered PKA, phosphorylated CREB (p-CREB) and the ratio of p-CREB to CREB. In particular, the level of p-CREB was negatively related to PPI performance. In Experiment 2, SKF38393, a well-characterized activator of adenylate cyclase and cAMP/PKA, was chronically injected during early adolescence (PNDs 28-34). We sought to mimic potential biochemical changes, particularly PKA activation, which is possibly altered by adolescent social isolation, and to determine if PPI was disrupted, similar to the disruption associated with adolescent social isolation. On PND 35, PPI deficits were detected, as well as increased PKA, marginally increased CREB and no change occurred in p-CREB or the ratio of p-CREB to CREB. In particular, PKA activity was negatively related to PPI performance. Although these results are limited in suggesting a causal link between PPI deficits and PKA-CREB signaling, they may help to elucidate the role played by PKA-CREB in the mPFC in regulating PPI.
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http://dx.doi.org/10.1097/FBP.0000000000000643DOI Listing
June 2021

Phytoremediation of antibiotic-contaminated wastewater: Insight into the comparison of ciprofloxacin absorption, migration, and transformation process at different growth stages of E. crassipes.

Chemosphere 2021 Jun 14;283:131192. Epub 2021 Jun 14.

School of Environment, Nanjing Normal University, Nanjing, 210023, China. Electronic address:

The selection of aquatic plants at different growth stages and their absorption, migration, and transformation mechanisms has yet to be clarified. In this study, Eichhornia crassipes at the seedling and mature stages were selected to uptake antibiotics under hydroponic conditions. The results showed that the enrichment of ciprofloxacin (CIP) in roots at the seedling and mature stages were 7.72~2114.39 μg g and 0.07~3711.33 μg g, respectively. The enrichment of CIP in aerial parts at the seedling and mature stages were 16.38~24.24 μg g and 9.55~20.13 μg g, respectively. The translocation from roots to aerial parts at the seedling stage was high, as evidenced by the relatively higher transfer factor (TF). In addition, eight and ten major metabolic products were observed in the tissues of seeding and mature stage of E. crassipes, respectively. The metabolic pathway of CIP was short at the maturity stage, and CIP had a strong upward migration ability at the seedling stage, facilitating long-time photodegradation. However, E. crassipes exhibited a poor CIP tolerance at the mature stage and decayed relatively early. Therefore, the seedling stage of E. crassipes was proposed to be applied for phytoremediation, and these findings might improve the ability to phytoremediation of antibiotic-contaminated water.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131192DOI Listing
June 2021

USP4 is pathogenic in allergic airway inflammation by inhibiting regulatory T cell response.

Life Sci 2021 Jun 16;281:119720. Epub 2021 Jun 16.

Department of Pulmonary and Critical Care Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Respiratory Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Aims: Asthma is characterized by chronic inflammation and airway hyperresponsiveness (AHR). It is controllable, but not curable. Ubiquitin-specific peptidase 4 (USP4) has been verified as a regulator of regulatory T (Treg) cells and Th17 cells in vitro. In this study, we aim to investigate whether USP4 could serve as a therapeutic target for asthma.

Main Methods: Age-matched USP4 wild-type and knockout mice received an intraperitoneal injection of 100 μg ovalbumin (OVA) mixed in 2 mg aluminum hydroxide in 1 × PBS on days 0, 7 and 14. On days 21 to 27, the mice were challenged with aerosolized 1% OVA in 1 × PBS for 30 min. Tissue histology, ELISA and flow cytometry were applied 24 h after the last OVA challenge.

Key Findings: USP4 deficiency protected mice from OVA-induced AHR and decreased the production of several inflammatory cytokines in T cells in vivo. Compared to the lung cells isolated from WT mice, Usp4 lung cells decreased secretion of IL-4, IL-13 and IL-17A upon stimulation in vitro. Meanwhile, the percentage of CD4Foxp3 Treg cells was elevated, with more CCR6Foxp3 Treg cells accumulating in the lungs of OVA-challenged USP4 deficient mice than in their wild-type counterparts. Treatment with the USP4 inhibitor, Vialinin A, reduced inflammatory cell infiltration in the lungs of OVA-challenged mice in vivo.

Significance: We found USP4 deficiency contributes to attenuated airway inflammation and AHR in allergen-induced murine asthma, and Vialinin A treatment alleviates asthma pathogenesis and may serve as a promising therapeutic target for asthma.
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http://dx.doi.org/10.1016/j.lfs.2021.119720DOI Listing
June 2021

Spi-B Promotes the Recruitment of Tumor-Associated Macrophages Enhancing CCL4 Expression in Lung Cancer.

Front Oncol 2021 1;11:659131. Epub 2021 Jun 1.

Department of Immunology, Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, China.

Tumor immune escape plays a critical role in malignant tumor progression and leads to the failure of anticancer immunotherapy. Spi-B, a lymphocyte lineage-specific Ets transcription factor, participates in mesenchymal invasion and favors metastasis in human lung cancer. However, the mechanism through which Spi-B regulates the tumor immune environment has not been elucidated. In this study, we demonstrated that Spi-B enhanced the infiltration of tumor-associated macrophages (TAMs) in the tumor microenvironment using subcutaneous mouse models and clinical samples of human lung cancer. Spi-B overexpression increased the expression of TAM polarization- and recruitment-related genes, including . Moreover, deleting inhibited the ability of Spi-B promoting macrophage infiltration. These data suggest that Spi-B promotes the recruitment of TAMs to the tumor microenvironment upregulating expression, which contributes to the progression of lung cancer.
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http://dx.doi.org/10.3389/fonc.2021.659131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205110PMC
June 2021

Multiple reflection and scattering effects of the lotus seedpod-based activated carbon decorated with CoO microwave absorbent.

J Colloid Interface Sci 2021 Jun 9;602:344-354. Epub 2021 Jun 9.

School of Environmental and Material Engineering, Yantai University, No. 30 Qingquan Road, Yantai 264005, PR China. Electronic address:

The lotus seedpod-based activated carbon (LSAC) is derived from pyrolysis of lotus seedpod as biomass carbon precursor, and CoO is then deposited to LSAC by oxidation-precipitation and crystallization process of Co ions from Co(NO) solution. The CoO particles uniformly decorate on the surface and/or the inner channels of LSAC. The optimal reflection loss (RL) value of LSAC/CoO-paraffin wax (PW) composite reaches -39.8 dB, and the bandwidth for RL below -10 dB and -20 dB are 10.3 and 3.0 GHz, respectively, much better than that of LSAC-PW composite for the higher magnetic loss. The addition of CoO particles in LSAC-PW composite significantly enhance the RL values in various thicknesses. The channels of the LSAC and decorated CoO can improve the abilities of multiple scattering, dipole polarization, interface polarization and magnetic loss. This composite provides a promising method to construct high performance absorbers by using biomass carbon to tune the dielectric properties of the ferromagnetic materials.
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http://dx.doi.org/10.1016/j.jcis.2021.06.048DOI Listing
June 2021

Enhanced Reversible Zinc Ion Intercalation in Deficient Ammonium Vanadate for High-Performance Aqueous Zinc-Ion Battery.

Nanomicro Lett 2021 Apr 30;13(1):116. Epub 2021 Apr 30.

Department of Materials Science and Engineering, University of Washington, Seattle, WA, 98195, USA.

Ammonium vanadate with bronze structure (NHVO) is a promising cathode material for zinc-ion batteries due to its high specific capacity and low cost. However, the extraction of [Formula: see text] at a high voltage during charge/discharge processes leads to irreversible reaction and structure degradation. In this work, partial [Formula: see text] ions were pre-removed from NHVO through heat treatment; NHVO nanosheets were directly grown on carbon cloth through hydrothermal method. Deficient NHVO (denoted as NVO), with enlarged interlayer spacing, facilitated fast zinc ions transport and high storage capacity and ensured the highly reversible electrochemical reaction and the good stability of layered structure. The NVO nanosheets delivered a high specific capacity of 457 mAh g at a current density of 100 mA g and a capacity retention of 81% over 1000 cycles at 2 A g. The initial Coulombic efficiency of NVO could reach up to 97% compared to 85% of NHVO and maintain almost 100% during cycling, indicating the high reaction reversibility in NVO electrode.
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http://dx.doi.org/10.1007/s40820-021-00641-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087727PMC
April 2021

Cell-Penetrating Mitochondrion-Targeting Ligands for the Universal Delivery of Small Molecules, Proteins and Nanomaterials.

Chemistry 2021 Jun 11. Epub 2021 Jun 11.

Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543, Singapore.

Mitochondria are key organelles that perform vital cellular functions such as those related to cell survival and death. The targeted delivery of different types of cargos to mitochondria is a well-established strategy to study mitochondrial biology and diseases. Of the various existing mitochondrion-transporting vehicles, most suffer from poor cytosolic entry, low delivery efficiency, limited cargo types, and cumbersome preparation protocols, and none was known to be universally applicable for mitochondrial delivery of different types of cargos (small molecules, proteins, and nanomaterials). Herein, two new cell-penetrating, mitochondrion-targeting ligands (named Mito ) that are capable of effectively "tagging" small-molecule drugs, native proteins and nanomaterials are disclosed, as well as their corresponding chemoselective conjugation chemistry. Upon successful cellular delivery and rapid endosome escape, the released native cargos were found to be predominantly localized inside mitochondria. Finally, by successfully delivering doxorubicin, a well-known anticancer drug, to the mitochondria of HeLa cells, we showed that the released drug possessed potent cell cytotoxicity, disrupted the mitochondrial membrane potential and finally led to apoptosis. Our strategy thus paves the way for future mitochondrion-targeted therapy with a variety of biologically active agents.
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http://dx.doi.org/10.1002/chem.202101989DOI Listing
June 2021

Folate metabolic profiling and expression of folate metabolism-related genes during panicle development in foxtail millet (Setaria italica (L.) P. Beauv).

J Sci Food Agric 2021 Jun 9. Epub 2021 Jun 9.

College of Agriculture, Institute of Agricultural Bioengineering, Shanxi Agricultural University, Taigu, China.

Background: Foxtail millet grain has higher folate content than other cereal crops. However, the folate metabolite content and the expression patterns of folate metabolite-related genes are unknown.

Results: Liquid chromatography-mass spectrometry was used to investigate 12 folate metabolites in a foxtail millet panicle. The content of total folate and derivatives gradually decreased during panicle development. Polyglutamate 5-formyl-tetrahydrofolate was the major form. Twenty-eight genes involved in the folate metabolic pathway were identified through bioinformatic analysis. These genes in Setaria italica, S. viridis and Zea mays showed genomic collinearity. Phylogenetic analysis revealed that the folate-related genes were closely related among the C4 plants compared to C3 plants. The gene expressions were then studied at three panicle development stages. The gene expression patterns were classified into two groups, namely SiADCL1 and SiGGH as two key enzymes, which are responsible for folate synthesis and degradation; their expression levels were highest at the early panicle development stage, up to 179.11- and 163.88-fold, respectively. Their expression levels had a similar downward trend during panicle development and were significantly positively correlated with the concentration of total folate and folate derivatives. However, SiSHMT3 expression levels were significantly negatively correlated with total folate concentration.

Conclusion: Besides being the major determinants of folate and folate derivatives accumulation, SiADCL1 and SiGGH expression levels are key limiting factors in the foxtail millet panicle. Therefore, SiADCL1 and SiGGH expression levels can be targeted in genetic modification studies to improve folate content in foxtail millet seeds in the future. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.11355DOI Listing
June 2021

Ligand-Controlled Regiodivergent Asymmetric [5 + 2] and [3 + 2] Annulations of Vinyl Indoloxazolidones Catalyzed by Palladium.

Org Lett 2021 Jun 9;23(12):4791-4795. Epub 2021 Jun 9.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Ministry of Education and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.

Here, we present palladium-catalyzed regiodivergent asymmetric annulations of vinyl indoloxazolidones, which can act as 1,5-carbodipoles or 1,3-carbodipoles by tuning the chiral ligands and conditions, in the assemblies with sulfamate-derived cyclic imines and even activated alkenes. A diversity of polycyclic products are generally constructed with high regio- and enantioselectivity.
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http://dx.doi.org/10.1021/acs.orglett.1c01507DOI Listing
June 2021

circ0101675 promotes malignant process via sponging miR-1278 and upregulating WNT3A/5A in non-small cell lung cancer.

J Cancer 2021 17;12(14):4209-4217. Epub 2021 May 17.

Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Cancer Research Institute, University of South China, Hengyang 421001, Hunan Province, China.

Circular RNAs (circRNAs) is one type of non-coding RNAs (ncRNAs) which have many roles in biological processes, as well as modulation intracellular gene expression modulation. Nonethless, the roles along with expression status of the most circRNAs in NSCLC (non-small cell lung cancer) remain unknown. Herein, we conducted a high-throughput microarray sequencing to identify abnormal expressed circRNAs. Circ0101675 was found upregulated in NSCLC cell lines and tissues. We carried out colony formation, transwell, CCK-8, and animal assays to investigate the functions of circ0101675. Silence of circ0101675 inhibited the migration and proliferation of NSCLC. To elucidate the mechanism, RNA immunoprecipitation assays along with luciferase enzyme reporter assays were further employed to explore the cross-talk between circ0101675 and other molecules. We discovered that circ0101675 facilitates the malignant process of growth and migration via sponging miR-1278 and upregulating WNT3A/5A expression. In conclusion, we revelaed the vital role of circ0101675-miR-1278-WNT3A/5A signaling in NSCLC progression via the competing endogenous RNAs mechanism. Therefore, circ0101675 can be used as a new and useful biomarker for monitoring and treating NSCLC.
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http://dx.doi.org/10.7150/jca.57255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176403PMC
May 2021

Baseline and early changes in circulating Serum Amyloid A (SAA) predict survival outcomes in advanced non-small cell lung cancer patients treated with Anti-PD-1/PD-L1 monotherapy.

Lung Cancer 2021 Aug 28;158:1-8. Epub 2021 May 28.

State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address:

Background: Systemic inflammation plays an important role in carcinogenesis and is associated with overall survival in patients with different cancer types, including those treated with immune checkpoint blockade (ICB). Serum Amyloid A (SAA) is an acute-phase protein and a marker of persistent inflammation. We hypothesized that circulating SAA may predict outcomes in advanced non-small cell lung (aNSCLC) patients treated with PD-1/PD-L1 ICB.

Materials And Methods: This retrospective study included 91 aNSCLC patients who received anti-PD-(L)1 monotherapy in Sun Yat-sen University Cancer Center (Guangzhou, China) between August 2016 and June 2018. We examined the impact of circulating SAA at baseline and 8 (±2) weeks later on overall survival (OS). X-tile program was used to determine the cut-off values which optimized the significance of the split between Kaplan-Meier survival curves. Kaplan-Meier methodology and Cox regression analyses were conducted for survival analyses.

Results: The optimal cut-off value of baseline SAA for OS stratification was 137.6 mg/L. In univariate analysis, both high level of baseline SAA (hazard ratio [HR], 2.76; 95% confidence interval [CI], 1.47-5.18; P = 0.002) and lack of early SAA descent (HR, 1.51; 95% CI, 1.11-2.06; P = 0.009) were significantly associated with inferior OS. In multivariate analysis, gender, smoking status, performance status, liver metastasis, neutrophil-to-lymphocyte ratio, baseline SAA and early changes in SAA independently predicted OS (all with P < 0.05). A combined baseline SAA ≥ 137.6 mg/L and without early SAA descent identified a small cohort with remarkably worse OS (median, 3.2 months).

Conclusions: Both high baseline and lack of early decline in circulating SAA are significantly associated with inferior outcomes in aNSCLC patients treated with PD-1/PD-L1 ICB. Combined these two SAA indexes provided improved risk stratification. The prognostic value of this simple, readily-available, and cost-effective biomarker warrants larger, prospective validation before definitive recommendation can be made.
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http://dx.doi.org/10.1016/j.lungcan.2021.05.030DOI Listing
August 2021