Publications by authors named "Lin Li"

7,437 Publications

  • Page 1 of 1

GSG2 promotes tumor growth through regulating cell proliferation in hepatocellular carcinoma.

Biochem Biophys Res Commun 2022 Jul 31;625:109-115. Epub 2022 Jul 31.

Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, Henan, 450052, China. Electronic address:

Background: Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed malignant tumors in the world. In recent years, more and more inhibitors against gene targets have been found to be beneficial to survival. However, the function of homo-sapiens histone H3 associated protein kinase (GSG2) in HCC has not been completely understood.

Methods: The expression of GSG2 in HCC tissues was detected by immunohistochemical staining. The lentivirus-mediated short hairpin RNA (shRNA) was used to knockdown GSG2 expression in HCC cell lines Hep3B2.1-7 and SK-HEP-1. Cell proliferation and colony formation were detected by MTT assay and colony formation assay, respectively, and flow cytometry assay was used to investigate the cell apoptosis in vitro. Mice xenograft model was constructed to detect the functions of GSG2 on tumor growth in vivo. Human Apoptosis Antibody Array was conducted to find the possible mechanism.

Results: GSG2 was overexpressed in HCC tissues compared with adjacent normal tissues. The knockdown of GSG2 had the functions of inhibiting the progression of HCC, including inhibiting cell proliferation and colony formation and promoting cell apoptosis. Compared with shCtrl group, the shGSG2 group expressed higher apoptotic genes such as caspase 3, caspase 8, Fas and FasL, while lower IGF1, Bcl2 and Bcl-w.

Conclusions: Our study showed that knockdown of GSG2 suppresses the tumor growth in vitro and vivo. Therefore, GSG2 might play an oncogenic role in HCC.
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http://dx.doi.org/10.1016/j.bbrc.2022.07.093DOI Listing
July 2022

Generating an oilseed rape mutant with non-abscising floral organs using CRISPR/Cas9 technology.

Plant Physiol 2022 Aug 11. Epub 2022 Aug 11.

Key Laboratory of Plant Functional Genomics of the Ministry of Education, Yangzhou University, Yangzhou 225009, China.

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http://dx.doi.org/10.1093/plphys/kiac364DOI Listing
August 2022

SIAH1-mediated RPS3 ubiquitination contributes to chemosensitivity in epithelial ovarian cancer.

Aging (Albany NY) 2022 Aug 8;14(undefined). Epub 2022 Aug 8.

Reproductive Medicine Center, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.

The E3 ligase SIAH1 is deregulated in human cancers and correlated with poor prognosis, but its contributions to chemoresistance in epithelial ovarian cancer (EOC) are not evident. Herein we found that SIAH1 was decreased in EOC tumour tissues and cell lines and negatively correlated with the RPS3 levels. SIAH1 overexpression suppressed tumour cell growth, colony formation, invasion, metastasis, and cisplatin resistance and . SIAH1 promoted RPS3 ubiquitination and degradation using the RING-finger domain, and these steps were required for RPS3 localization to the cytoplasm, which led to subsequent NF-κB inactivation and thereby conferred chemosensitivity. Moreover, ectopic expression of RPS3 or depletion of RPS3 ubiquitination mediated by SIAH1 via the K214R mutant significantly impaired cisplatin-induced tumour suppression in cells stably expressing SIAH1. Together, our findings reveal a tumour suppressor function of SIAH1 and provide evidence showing that the SIAH1-RPS3-NF-κB axis may act as an appealing strategy for tackling treatment resistance in EOC.
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http://dx.doi.org/10.18632/aging.204211DOI Listing
August 2022

Value of Tranexamic Acid and Progressive Nursing in Accelerating Postoperative Rehabilitation After Total Knee Arthroplasty.

Altern Ther Health Med 2022 Aug 5. Epub 2022 Aug 5.

Context: Knee arthritis is the primary cause of disability in middle-aged and older adults. Total knee arthroplasty (TKA) is also a common treatment in clinics and has a remarkable effect on improving knee-joint function. However, TKA is an invasive procedure that includes a large amount of trauma. It can easily lead to an increase in perioperative blood loss coupled with a long operation time, which can increase the risk of postoperative complications, and also has a long recovery time.

Objective: The study intended to analyze the value of tranexamic acid (TXA) plus progressive nursing in accelerating the postoperative rehabilitation of patients undergoing total knee arthroplasty (TKA).

Design: The research team designed a prospective non-randomized controlled trial.

Setting: The study took place at Cangzhou Hospital of Integrated Traditional Chinese Medicine (TCM) - Western Medicine (WM) Hebei in Cangzhou, Hebei, China.

Participants: Participants were 115 patients with knee arthritis who underwent TKA at the hospital between February 2019 and October 2021.

Intervention: Of the 115 participants, 55 were assigned to the control group and received conventional nursing care, and 60 were assigned to the intervention group and after surgery received TXA plus progressive nursing.

Outcome Measures: The study measured blood loss postoperatively and identified any complications that participants experienced during treatment. At baseline and postintervention, the study also measured knee-joint range of motion (ROM), and the participants completed the Hospital for Special Surgery (HSS) knee survey, the Barthel Index for Activities of Daily Living (ADL), the Self-Rating Depression (SDS) and Self-Rating Anxiety (SAS) scales, a nursing-satisfaction survey, and the World Health Organization Quality of Life Bref (WHO-QOL-BREF) survey.

Results: Postoperatively, the blood loss in the intervention group was significantly lower than that in control group, and the knee joint ROM was significantly better in the intervention group (P < .05). In addition, the postoperative Hospital for Special Surgery (HSS) and Barthel scores in the intervention group were significantly higher, and the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) scores were significantly lower in the intervention group compared with control group (P < .05). Moreover, a lower incidence of complications and better quality of life were determined for the intervention group (P < .05).

Conclusions: Compared with conventional nursing, TXA plus progressive nursing can more effectively promote postoperative recovery of TKA patients; but the exact role of TXA and progressive nursing in TKA deserves further exploration.
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August 2022

Single-cell multiomics sequencing reveals the reprogramming defects in embryos generated by round spermatid injection.

Sci Adv 2022 Aug 10;8(32):eabm3976. Epub 2022 Aug 10.

State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, P. R. China.

Round spermatid injection (ROSI) technique holds great promise for clinical treatment of a proportion of infertile men. However, the compromised developmental potential of ROSI embryos largely limits the clinical application, and the mechanisms are not fully understood. Here, we describe the transcriptome, chromatin accessibility, and DNA methylation landscapes of mouse ROSI embryos derived from early-stage round spermatids using a single-cell multiomics sequencing approach. By interrogating these data, we identify the reprogramming defects in ROSI embryos at the pronuclear stages, which are mainly associated with the misexpression of a cohort of minor zygotic genome activation genes. We screen a small compound, A366, that can significantly increase the developmental potential of ROSI embryos, in which A366 can partially overcome the reprogramming defects by amending the epigenetic and transcriptomic states. Collectively, our study uncovers the reprogramming defects in ROSI embryos for understanding the mechanisms underlying compromised developmental potential and offers an avenue for ROSI technique optimization.
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http://dx.doi.org/10.1126/sciadv.abm3976DOI Listing
August 2022

[Corrigendum] Benzyl isothiocyanate suppresses development and metastasis of murine mammary carcinoma by regulating the Wnt/β‑catenin pathway.

Mol Med Rep 2022 Oct 10;26(4). Epub 2022 Aug 10.

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that the '1 M/Invasion' and the '2.5 M/Migration' panels shown in Fig. 3B on p. 1814 appeared to contain overlapping sections of data, such that they were potentially derived from the same original source, where these panels was intended to show the results from differently performed experiments. The authors have re‑examined their original data, and realize that Fig. 3B was inadvertently assembled incorrectly; specifically, the '2.5 M/Migration' panel was selected from the wrong data group. The revised version of Fig. 4, now containing the correct data for the '2.5 M/Migration' experiment in Fig. 3B, is shown on the next page. Note that this error did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 20: 1808‑1818, 2019; DOI: 10.3892/mmr.2019.10390].
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http://dx.doi.org/10.3892/mmr.2022.12823DOI Listing
October 2022

Subcellular analysis of nuclear and cytoplasmic redox indices differentiates breast cancer cell subtypes better than nuclear-to-cytoplasmic area ratio.

J Biomed Opt 2022 Aug;27(8)

University of Pennsylvania, Perelman School of Medicine, Department of Radiology, Britton Chance Laboratory of Redox Imaging, Philadelphia, Pennsylvania, United States, United States.

Significance: Stratification of malignancy is valuable for cancer treatment. Both optical redox imaging (ORI) indices and nuclear-to-cytoplasmic volume/area ratio (N:C ratio) have been investigated to differentiate between cancers with varying aggressiveness, but these two methods have not been directly compared. The redox status in the cell nucleus has not been studied by ORI, and it remains unknown whether nuclear ORI indices add new biological information.

Aim: We sought to compare the capacity of whole-cell and subcellular ORI indices and N:C ratio to differentiate between breast cancer subtypes with varying aggressiveness and between mitotic and nonmitotic cells.

Approach: ORI indices for whole cell, cytoplasm, and nucleus as well as the N:C area ratio were generated for two triple-negative (more aggressive) and two receptor-positive (less aggressive) breast cancer cell lines by fluorescence microscopy.

Results: We found positive correlations between nuclear and cytoplasmic ORI indices within individual cells. On average, a nuclear redox status was found to be more oxidized than cytoplasm in triple-negative cells but not in receptor-positive cells. Whole-cell and subcellular ORI indices distinguished between the receptor statuses better than the N:C ratio. However, N:C ratio was a better differentiator between nonmitotic and mitotic triple-negative cells.

Conclusions: Subcellular ORI analysis differentiates breast cancer subtypes with varying aggressiveness better than N:C area ratio.
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http://dx.doi.org/10.1117/1.JBO.27.8.086001DOI Listing
August 2022

The Association Between High CHADS-VASc Scores and Short and Long-Term Mortality for Coronary Care Unit Patients.

Clin Appl Thromb Hemost 2022 Jan-Dec;28:10760296221117969

Department of Cardiovascular Medicine, Shanghai Pudong New Area Gongli Hospital, Shanghai, P.R. China.

Background: The CHADS-VASc score has been associated with the prognosis of cardiovascular diseases. This study aimed to explore the association between the CHADS-VASc score and all-cause mortality in coronary care unit (CCU) patients.

Methods: The study was based on the Medical Information Mart for Intensive Care (MIMIC) III database. CCU patients were divided into two groups according to CHADS-VASc score: 0-3 (low risk),4-9 (intermediate and high risk). The primary outcome was 30-day mortality, and the secondary endpoints included in-hospital, 1-year, and 5-year mortality. Propensity score matching (PSM) and sensitivity analyzes for the confounders were also performed. The restricted cubic splines flexibility model was used to demonstrate the relation between red blood cell volume distribution width (RDW), blood urea nitrogen (BUN), platelet, white blood cell (WBC), hemoglobin, phosphorus, glucose, potassium, sodium and 30-day mortality in the 0-3 score versus the 4-9 score groups after PSM.

Results: Among 4491 eligible patients, 988 patients with low CHADS-VASc scores and 988 patients with intermediate and high CHADS-VASc scores had similar propensity scores and were included in the analyzes. In the survival analysis, the patients with intermediate and high CHADS-VASc scores were associated with higher 30-day mortality [hazard ratio (HR): 1.11; 95% confidence interval (CI), 1.02-1.20,  = .014], 1-year mortality [HR: 1.13; 95%CI, 1.06-1.19,  < .001], and 5-year mortality [HR: 1.13; 95%CI, 1.07-1.18,  < .001]. The interaction for 30-day mortality among subgroups was not significant between the 0-3 score versus the 4-9 score groups. The restricted cubic splines for 30-day mortality demonstrated an L-shaped trajectory for platelets and hemoglobin, a J-shaped trajectory for WBC, glucose and potassium, and a U-shaped trajectory for sodium, respectively (all nonlinear <.001).

Conclusions: A high CHADS-VASc score was an independent risk for 30-day, 1-year, and 5-year mortality for CCU patients.
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http://dx.doi.org/10.1177/10760296221117969DOI Listing
August 2022

Selection and validation of chemotherapy beneficiaries among elderly nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiation therapy (IMRT): a large real-world study.

Radiat Oncol 2022 Aug 8;17(1):138. Epub 2022 Aug 8.

Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.

Purpose: Using real-world evidence, this study aimed to identify elderly nasopharyngeal carcinoma (NPC) patients who would benefit from chemotherapy.

Methods And Materials: 1714 elderly NPC patients between April 2007 and December 2017 were identified. Recursive partitioning analysis (RPA) was used to generate risk-stratified outcomes. Prognostic factors were performed for individual comparisons of different risk groups to assess chemotherapy benefits.

Results: The median follow-up was 59.3 (0.39-170.09) months. Epstein Barr virus (EBV) DNA and T stage were included in the RPA-generated risk stratification, categorizing patients into a good-prognosis group (EBV DNA ≤ 4000 copies/mL & T1-2), and a poor-prognosis group (EBV DNA ≤ 4000 copies/mL & T3-4 and EBV DNA > 4000 copies/mL & any T). Overall survival (OS) was significantly higher in the good-prognosis group compared with the training set (HR = 0.309, 95% CI 0.184-0.517; P < 0.001), and validated in the testing set (HR = 0.276, 95% CI 0.113-0.670; P = 0.002). In the poor-prognosis group, a significantly improved OS for chemoradiotherapy (CRT) compared with RT alone was observed (HR = 0.70, 95% CI 0.55-0.88; P = 0.003). Patients who received induction chemotherapy (IC) + concurrent chemoradiotherapy (CCRT) and CCRT had a significantly improved OS compared with RT alone (IC + CCRT vs. RT alone: P = 0.002; CCRT vs. RT alone: P = 0.008) but not in the IC + RT group (P = 0.306). The 5-year OS for CRT versus RT-alone with ACE-27 scores of 0, 1 and 2 were 76.0% versus 70.0% (P = 0.014), 80.5% versus 68.2% (P = 0.150) and 58.5% versus 62.2% (P = 0.490), respectively; for those aged 60-64, 65-70 and ≥ 70 years old they were 80.9% versus 75.9% (P = 0.068), 73.3% versus 63.4% (P = 0.270) and 64.8% versus 67.1% (P = 0.820), respectively.

Conclusions: For elderly NPC patients a simple screening cutoff for chemotherapy beneficiaries might be EBV DNA < 4000 copies/ml & T3-4 and EBV DNA ≥ 4000 copies/ml & any T, but not for those > 70 years old and with an ACE-27 score > 1. IC + CCRT and CCRT were effective forms of chemotherapy.
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http://dx.doi.org/10.1186/s13014-022-02095-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358823PMC
August 2022

Porphyrin NanoMOFs as a catalytic label in a nanozyme-linked immunosorbent assay for Aflatoxin B1 detection.

Anal Biochem 2022 Aug 5:114829. Epub 2022 Aug 5.

Hunan Provincial Key Laboratory of Cytochemistry, School of Food Science and Bioengineering, Changsha University of Science & Technology, Changsha, 410114, Hunan, China. Electronic address:

Food safety is a global problem, and methods to reliably and sensitivity detect contaminants could be transformative. Herein, we synthesized a novel Porphyrin NanoMoFs (NanoPCN-223(Fe)) with excellent dispersion and peroxidase-like activity. The K value of NanoPCN-223(Fe) was 2.0 × 10 M toward the HO substrate during the catalytic process. We use the NanoPCN-223(Fe) to construct an enhanced dispersion MOF-linked immunosorbent assay (Ed-MOFLISA) to sensitive detect AFB1 in milk. The optimized Ed-MOFLISA displayed a broad quantitative range from 0.05 to 10 ng/mL and a limit of detection of 0.003 ng/mL. Spiked peanut and soy milk recovery ranged from 91.22% to 97.63%. Intra-assay and inter-assay coefficient of variation values ranged from 0.78 to 3.85%, demonstrating the outstanding reproducibility and accuracy of Ed-MOFLISA. We applied the Ed-MOFLISA assay to test the milk samples, demonstrating its potential use for monitoring food quality.
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http://dx.doi.org/10.1016/j.ab.2022.114829DOI Listing
August 2022

Non-cigarette combustible tobacco use and its associations with subsequent cessation of smoking among daily cigarette smokers: findings from the International Tobacco Control Four Country Smoking and Vaping Surveys (2016-2020).

Addiction 2022 Aug 8. Epub 2022 Aug 8.

National Addiction Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 4 Windsor Walk, Denmark Hill, London, UK.

Aims: To examine whether poly-use of cigarettes and other smoked products (poly-smoking) is predictive of quit attempts and quit success.

Design: A prospective multi-country cohort design.

Setting: Australia, Canada, England and the US.

Participants: 3983 adult daily cigarette smokers were surveyed in 2016 (Wave 1 of data collection) and were recontacted in 2018 (Wave 2) (i.e., Wave 1-Wave 2 cohort) in the International Tobacco Control Four Country Smoking and Vaping (ITC 4CV) Surveys; and 3736 smokers were surveyed in 2018 and recontacted in 2020 (Wave 3) (i.e., Wave 2-Wave 3 cohort).

Measurements: Participants were asked about their cigarette smoking and use of cigars, cigarillos, pipes, and waterpipes. Outcomes were quit attempts between two survey waves and success, defined as having quit smoking all the combustible tobacco at the subsequent survey for 1 month or more.

Findings: Levels of poly-smoking were 12.7% in the Wave 1-Wave 2 cohort and 10.5% for the Wave 2-Wave 3 cohort. Compared with cigarette-only smokers, poly-smokers were more likely to attempt between Waves 1 and 2 (54.9% vs. 42.7%, adjusted odds ratio (aOR)=1.37, 95% confidence interval [CI] 1.08-1.74, p<0.01), but not between Waves 2 and 3 (43.8% vs. 40.1%, aOR=0.94, 95%CI 0.72-1.22). Poly-smoking predicted reduced likelihood of success in both cohorts among attempters and the overall samples. Between Waves 2 and 3 there were significantly more transitions to non-daily smoking among the poly-smokers (12.4% vs. 5.3%, =40.4, p<0.001).

Conclusions: There is a consistent association between poly-smoking (use of cigarettes along with other smoked products) and reduced quit success for combustible tobacco, but it is likely due to increased likelihood of transitioning to non-daily use rather than complete cessation.
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http://dx.doi.org/10.1111/add.16023DOI Listing
August 2022

Sprayable Antibacterial Hydrogels by Simply Mixing of Aminoglycoside Antibiotics and Cellulose Nanocrystals for the Treatment of Infected Wounds.

Adv Healthc Mater 2022 Aug 6:e2201286. Epub 2022 Aug 6.

Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, China.

Antibiotic hydrogels with sustained release profiles were recognized as promising candidates to treat local bacterial infections with reduced adverse effects. However, it still remains challenging for clinical translation of these antibiotic gels due to safety concern of gel ingredients, complicated synthesis and fabrication procedures, and unsatisfactory rheological properties for practical uses in vivo. Herein, we propose the preparation of a type of sprayable hydrogels by ionic interactions between aminoglycosides and cellulose nanocrystal (CNC) for the treatment of local infections such as bacteria infected wounds. The CNC-based hydrogels are applicable for all kinds of aminoglycoside antibiotics and show excellent gel stability and rheological behaviors such as shear-thinning and fast self-healing, allowing facile administration by injection or spraying. The hydrogels exhibit efficient antibacterial activity both in vitro and in vivo, and accelerate bacteria infected wounds by spraying on the infected area. The proposed hydrogels by simply mixing of aminoglycosides and CNC provide great prospects for clinical translation in the treatment of local infections. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/adhm.202201286DOI Listing
August 2022

Recycling municipal solid waste incineration fly ash in super-lightweight aggregates by sintering with clay and using SiC as bloating agent.

Chemosphere 2022 Aug 3;307(Pt 2):135895. Epub 2022 Aug 3.

School of Environment, Tsinghua University, Beijing 100084, China. Electronic address:

Municipal solid waste incineration (MSWI) fly ash is classified as hazardous waste and requires proper treatments. Sintering of MSWI fly ash for the production of lightweight aggregate (LWA) is a promising treatment technology, while the dependence on natural bloating clay to produce high quality LWA has limited its wide application. In this study, by using SiC as a bloating agent, normal clay could be used to produce super-lightweight aggregate (bulk density <500 kg/m) with MSWI fly ash. Effects of SiC addition amount, sintering temperature and duration on LWA performance were studied. The results showed that LWA with SiC addition of 0.1-0.5 wt% had significant expansion at sintering temperature of 1120 °C-1160 °C. The optimal conditions were 0.3 wt% SiC addition and sintering at 1120 °C for 30 min, and the bulk density could reach 212 kg/m with other properties meeting the LWA standard (GB/T 17431.1-2010). Further, the heavy metal leaching toxicity was significantly decreased after sintering and met the MSWI fly ash utilization standard (HJ 1134-2020). The X-ray diffraction results revealed the formation of a complex diopside-based phase after sintering. This study provides a new approach for recycling MSWI fly ash in LWA without dependence on specific clay resources, and makes this technology wider applicability.
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http://dx.doi.org/10.1016/j.chemosphere.2022.135895DOI Listing
August 2022

An auristatin-based peptide-drug conjugate targeting Kita-Kyushu lung cancer antigen 1 for precision chemoradiotherapy in gastric cancer.

Eur J Med Chem 2022 Jul 19;241:114617. Epub 2022 Jul 19.

The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China. Electronic address:

Gastric cancer is a worldwide health problem. Chemotherapy and radiotherapy are of great importance in the management of advanced gastric cancer. However, their therapeutic efficacy is limited by off-target side effects. Peptide-drug conjugates (PDCs) are a novel strategy for tumor-targeted drug delivery to overcome the existing drug resistance mechanisms and improve antitumor effects. Kita-Kyushu lung cancer antigen 1 (KK-LC-1) is exclusively expressed in several types of cancer including gastric cancer, representing a promising target for drug delivery. Here, we suggested KK-LC-1 as a potential target for PDC design for the first time and reported the first KK-LC-1-targeting PDC product 1131-MMAE, which is composed of a KK-LC-1-targeting peptide and an antimitotic drug conjugated by an enzymatically cleavable linker. We observed that 1131-MMAE could be efficiently endocytosed by KK-LC-1 positive gastric cancer cells for subsequent drug release and arrest the cell cycle at the most radiosensitive G2/M phase. We demonstrated that 1131-MMAE could significantly delay tumor growth with reduced toxicity than free drugs as a monotherapy. We further confirmed that 1131-MMAE was also a potent radiosensitizer. 1131-MMAE could selectively enhance the radiation response of KK-LC-1 positive tumor cells and achieve improved tumor control when combined with low-dose radiation. Overall, our study proposed an optimized therapeutic regimen for precision chemoradiotherapy, which has translational potential in multiple types of cancer.
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http://dx.doi.org/10.1016/j.ejmech.2022.114617DOI Listing
July 2022

Genetically engineered bacteria-mediated multi-functional nanoparticles for synergistic tumor-targeting therapy.

Acta Biomater 2022 Aug 2. Epub 2022 Aug 2.

State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, China; Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, China. Electronic address:

Focused ultrasonic ablation surgery (FUAS) for tumor treatment has emerged as an effective non-invasive therapeutic approach, but its widespread clinical utilization is limited by its low therapeutic efficiency caused by inadequate tumor targeting, single imaging modality, and possible tumor recurrence following surgery. Therefore, this study aimed to develop a biological targeting synergistic system consisting of genetically engineered bacteria and multi-functional nanoparticles to overcome these limitations. Escherichia coli was genetically modified to carry an acoustic reporter gene encoding the formation of gas vesicles (GVs) and then target the tumor hypoxic environment in mice. After E. coli producing GVs (GVs-E. coli) colonized the tumor target area, ultrasound imaging and collaborative FUAS were performed; multi-functional nanoparticles were then enriched in the tumor target area through electrostatic adsorption. Multi-functional cationic lipid nanoparticles containing IR780, perfluorohexane, and banoxantrone dihydrochloride (AQ4N) were coloaded in the tumor to realize targeted multimodal imaging and enhance the curative effect of FUAS. AQ4N was stimulated by the tumor hypoxic environment and synergistically cooperated with FUAS to kill tumor cells. In sum, synergistic tumor therapy involving multi-functional nanoparticles mediated by genetically engineered bacteria overcomes the limitations and improves the curative effect of existing FUAS. STATEMENT OF SIGNIFICANCE: Inadequate tumor targeting, single image monitoring mode, and prone tumor recurrence following surgery remain significant challenges yet critical for tumor therapy. This study proposes a strategy for genetically engineered bacteria-mediated multifunctional nanoparticles for synergistic tumor therapy. The multifunctional genetically engineered biological targeting synergistic agent can accomplish tumor-targeting therapy, synergistic FUAS ablation, hypoxia-activated chemotherapy combined with FUAS ablation, and multiple-imaging guidance and monitoring all at the same time, thereby compensating for the shortcomings of FUAS treatment. This strategy could pave the way for the progress of tumor therapy.
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http://dx.doi.org/10.1016/j.actbio.2022.07.056DOI Listing
August 2022

Photothermal-Reagent-Triggered Visual Thermoresponsive and Quantized Photoelectrochemical Dual-Signal Assay.

ACS Sens 2022 Aug 5. Epub 2022 Aug 5.

School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, PR China.

In vitro biosensing chips are urgently needed for early-stage diagnosis and real-time surveillance of epidemic diseases. Herein, a versatile zone with photothermal effects is implanted in the miniature space of a collapsible lab-on-paper photoelectrochemical biosensor for on-site detection of microRNA-141 in body fluids, which can flexibly interconnect the traditional photocurrent signal with functional temperature response. The visualized thermoresponsive results are enhanced by the exciton energy conversion between FeO nanoparticles (FeO NPs) and formed Prussian blue nanoparticles under near-infrared irradiation, which not only presents heat energy gradient variations but also generates color changes. Significantly, the controlled release of FeO NPs is actuated by a target-triggered enzyme assist strand displacement cycle strategy to efficiently improve the accuracy of target temperature signal prediction, which can concurrently mediate photoelectric signal attenuation via promoting the rapid recombination of photoexcited charge carriers on the CuInS/CoInS electrode surface, affording dependable ultrasensitive detection results. Benefitting from the ingenious design of the versatile thermoresponsive-photoelectric sensing platform, the preliminary screening and ultrasensitive quantitative analysis can be simultaneously achieved in a single-drop sample. As a consequence, speedy prediction results and satisfied monitoring data are acquired in the ranges of 0.5 pM to 2 nM and 0.001 pM to 5 nM by measuring the temperature change and photocurrent intensity. By right of these advantages, such research paves a prospective paradigm for the manufacture of a visual, rapid, broad-spectrum, and reliable real-time surveillance platform, which allows it to be a promising candidate for epidemic disease home diagnosis and intelligent diagnosis.
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http://dx.doi.org/10.1021/acssensors.2c01162DOI Listing
August 2022

AcMYB1 Interacts With AcbHLH1 to Regulate Anthocyanin Biosynthesis in .

Front Plant Sci 2022 19;13:886313. Epub 2022 Jul 19.

Key Laboratory of South China Agricultural Plant Molecular Analysis and Gene Improvement, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou, China.

is one of the most popular foliage plants with abundant leaf phenotypes; therefore, anthocyanin coloration is a vital economic trait in . However, the molecular mechanisms underlying anthocyanin biosynthesis and its regulation remain unclear. In this study, and , transcription factor genes related to an R2R3-myeloblast (MYB) and a basic helix-loop-helix (bHLH), respectively, were isolated from "Red Valentine" and functionally characterized. AcMYB1 and AcbHLH1 were found to interact by Y2H and BiFC assay. was grouped into the AN2 subgroup and shared high homology with the known regulators of anthocyanin biosynthesis. Gene expression analysis showed that both and have similar expression patterns to anthocyanin structural genes and correlate with anthocyanin distribution in different tissues of . Light strongly promoted anthocyanin accumulation by upregulating the expression of anthocyanin-related genes in leaves. Ectopic expression of in tobacco remarkably increased anthocyanin accumulation in both vegetative and reproductive tissues at various developmental stages. These results provide insights into the regulation of anthocyanin biosynthesis in and are useful for breeding new cultivars with enhanced ornamental value.
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http://dx.doi.org/10.3389/fpls.2022.886313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344012PMC
July 2022

Protocol and Preliminary Results of the Establishment of Intracranial Aneurysm Database for Artificial Intelligence Application Based on CTA Images.

Front Neurol 2022 19;13:932933. Epub 2022 Jul 19.

Department of Roradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background And Purpose: Unruptured intracranial aneurysms (UIAs) are increasingly being detected in clinical practice. Artificial intelligence (AI) has been increasingly used to assist diagnostic techniques and shows encouraging prospects. In this study, we reported the protocol and preliminary results of the establishment of an intracranial aneurysm database for AI application based on computed tomography angiography (CTA) images.

Methods: Through a review of picture archiving and communication systems, we collected CTA images of patients with aneurysms between January 2010 and March 2021. The radiologists performed manual segmentation of all diagnosed aneurysms on subtraction CTA as the basis for automatic aneurysm segmentation. Then, AI will be applied to two stages of aneurysm treatment, namely, automatic aneurysm detection and segmentation model based on the CTA image and the aneurysm risk prediction model.

Results: Three medical centers have been included in this study so far. A total of 3,190 cases of CTA examinations with 4,124 aneurysms were included in the database. All identified aneurysms from CTA images that enrolled in this study were manually segmented on subtraction CTA by six readers. We developed a structure of 3D-Unet for aneurysm detection and segmentation in CTA images. The algorithm was developed and tested using a total of 2,272 head CTAs with 2,938 intracranial aneurysms. The recall and false positives per case (FP/case) of this model for detecting aneurysms were 0.964 and 2.01, and the Dice values for aneurysm segmentation were 0.783.

Conclusion: This study introduces the protocol and preliminary results of the establishment of the intracranial aneurysm database for AI applications based on CTA images. The establishment of a multicenter database based on CTA images of intracranial aneurysms is the basis for the application of AI in the diagnosis and treatment of aneurysms. In addition to segmentation, AI should have great potential for aneurysm treatment and management in the future.
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http://dx.doi.org/10.3389/fneur.2022.932933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343848PMC
July 2022

Near-real-time MODIS-derived vegetation index data products and online services for CONUS based on NASA LANCE.

Sci Data 2022 08 4;9(1):477. Epub 2022 Aug 4.

Center for Spatial Information Science and Systems, George Mason University, Fairfax, VA, 22030, USA.

This paper describes a set of Near-Real-Time (NRT) Vegetation Index (VI) data products for the Conterminous United States (CONUS) based on Moderate Resolution Imaging Spectroradiometer (MODIS) data from Land, Atmosphere Near-real-time Capability for EOS (LANCE), an openly accessible NASA NRT Earth observation data repository. The data set offers a variety of commonly used VIs, including Normalized Difference Vegetation Index (NDVI), Vegetation Condition Index (VCI), Mean-referenced Vegetation Condition Index (MVCI), Ratio to Median Vegetation Condition Index (RMVCI), and Ratio to previous-year Vegetation Condition Index (RVCI). LANCE enables the NRT monitoring of U.S. cropland vegetation conditions within 24 hours of observation. With more than 20 years of observations, this continuous data set enables geospatial time series analysis and change detection in many research fields such as agricultural monitoring, natural resource conservation, environmental modeling, and Earth system science. The complete set of VI data products described in the paper is openly distributed via Web Map Service (WMS) and Web Coverage Service (WCS) as well as the VegScape web application ( https://nassgeodata.gmu.edu/VegScape/ ).
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http://dx.doi.org/10.1038/s41597-022-01565-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352751PMC
August 2022

PROBER identifies proteins associated with programmable sequence-specific DNA in living cells.

Nat Methods 2022 08 4;19(8):959-968. Epub 2022 Aug 4.

Program in Epithelial Biology, Stanford University, Stanford, CA, USA.

DNA-protein interactions mediate physiologic gene regulation and may be altered by DNA variants linked to polygenic disease. To enhance the speed and signal-to-noise ratio (SNR) in the identification and quantification of proteins associated with specific DNA sequences in living cells, we developed proximal biotinylation by episomal recruitment (PROBER). PROBER uses high-copy episomes to amplify SNR, and proximity proteomics (BioID) to identify the transcription factors and additional gene regulators associated with short DNA sequences of interest. PROBER quantified both constitutive and inducible association of transcription factors and corresponding chromatin regulators to target DNA sequences and binding quantitative trait loci due to single-nucleotide variants. PROBER identified alterations in regulator associations due to cancer hotspot mutations in the hTERT promoter, indicating that these mutations increase promoter association with specific gene activators. PROBER provides an approach to rapidly identify proteins associated with specific DNA sequences and their variants in living cells.
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http://dx.doi.org/10.1038/s41592-022-01552-wDOI Listing
August 2022

The Sclerotinia sclerotiorum-inducible promoter pBnGH17D7 in Brassica napus: isolation, characterization and application in host-induced gene silencing.

J Exp Bot 2022 Aug 5. Epub 2022 Aug 5.

Key Laboratory of Plant Functional Genomics of the Ministry of Education, Yangzhou University, Yangzhou 225009, China.

Sclerotinia stem rot (SSR), caused by Sclerotinia sclerotiorum, is among the most devastating diseases in Brassica napus worldwide. Conventional breeding for SSR resistance in Brassica species is challenging due to the limited availability of resistant germplasm. Therefore, genetic engineering is an attractive means for developing SSR-resistant Brassica crops. Compared with constitutive promoter, S. sclerotiorum-inducible promoter would avoid ectopic expression of defense genes that may cause plant growth deficits. In this study, we generated a S. sclerotiorum-inducible promoter. pBnGH17D7, from the promoter of B. napus glycosyl hydrolase 17 gene (pBnGH17). Specifically, 5'-deletion and promoter activity analyses in transgenic A. thaliana plants defined a 189-bp region of pBnGH17, that was indispensable for S. sclerotiorum-induced response. Compared with pBnGH17, pBnGH17D7 showed a similar response upon S. sclerotiorum infection, but lower activity in plant tissues in the absence of S. sclerotiorum infection. Moreover, we revealed that the transcription factor BnTGA7 directly binds to the TGACG motif in pBnGH17D7 to activate BnGH17. Ultimately, pBnGH17D7 was exploited for engineering Sclerotinia-resistant B. napus via host-induced gene silencing. It induces high expression of small interfering RNAs against S. sclerotiorum pathogenic-factor gene specifically during infection, leading to increased resistance.
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http://dx.doi.org/10.1093/jxb/erac328DOI Listing
August 2022

PVR/TIGIT and PD-L1/PD-1 expression predicts survival and enlightens combined immunotherapy in lung squamous cell carcinoma.

Transl Oncol 2022 Oct 1;24:101501. Epub 2022 Aug 1.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 17 Panjiayuannanli, Beijing, China. Electronic address:

PVR/TIGIT and PD-L1/PD-1 axes play essential roles in tumor immune evasion and could be potential targets for combined immunotherapy. We aimed to evaluate the expression status of the above-mentioned immune markers in lung squamous cell carcinoma (LUSC), and investigate their survival impact and relevance with the immune microenvironment and clinicopathological features. We retrospectively collected specimens from 190 LUSC patients, who underwent pulmonary surgeries, and we performed immunohistochemistry assays of PVR, TIGIT, PD-L1, PD-1 and CD8. In our cohort, the positive rate of PVR was 85.8%, which was much higher than the positive rate of PD-L1 at 26.8%. A total of 32 (16.8%) patients demonstrated co-expression of PVR/PD-L1. High TIGIT density was correlated with positive PD-L1 expression, high PD-1 density, and high CD8 density (PD-L1, P=0.033; PD-1, P<0.001; CD8, P<0.001), and positive PVR expression was correlated with positive PD-L1 expression (P=0.046). High TIGIT density and high PVR/TIGIT expression were correlated with advanced TNM stage (TIGIT density, P=0.020; PVR/TIGIT expression, P=0.041). Patients with positive PVR expression, high TIGIT density, high PVR/TIGIT expression and PVR/PD-L1 co-expression exhibited a significantly worse prognosis (PVR, P=0.038; TIGIT, P=0.027; PVR/TIGIT, P=0.014; PVR/PD-L1, P=0.018). Multivariate analysis demonstrated that PVR/PD-L1 co-expression (Hazard ratio [HR], 1.756, 95% CI, 1.152-2.676, P=0.009) was an independent prognostic factor in LUSC patients. In conclusion, we demonstrated the expression status of PVR/TIGIT and PD-L1/PD-1 in LUSC. PVR/PD-L1 co-expression was an independent prognostic factor in LUSC patients and may serve as a potential predictive biomarker for dual-targeting immunotherapy.
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http://dx.doi.org/10.1016/j.tranon.2022.101501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352965PMC
October 2022

Fate of Oxygenated Volatile Organic Compounds in the Yangtze River Delta Region: Source Contributions and Impacts on the Atmospheric Oxidation Capacity.

Environ Sci Technol 2022 Aug 4. Epub 2022 Aug 4.

Jiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution Control, Collaborative Innovation Center of Atmospheric Environment and Equipment Technology, Nanjing University of Information Science & Technology, Nanjing 210044, China.

The Community Multiscale Air Quality model (CMAQv5.2) was implemented to investigate the sources and sinks of oxygenated volatile organic compounds (OVOCs) during a high O and high PM season in the Yangtze River Delta (YRD) region, based on constraints from observations. The model tends to overpredict non-oxygenated VOCs and underpredict OVOCs, which has been improved with adjusted emissions of all VOCs. The OVOCs in the YRD are dominated by ketones, aldehydes, and alcohols. Ketones and aldehydes mainly originate from direct emissions and secondary formation in the northern YRD, and primarily originate from secondary formation in the southern part influenced by biogenic emissions. The concentration of secondary organic aerosols (SOA) produced by OVOCs is 0.5-1.5 μg/m, with 40-80% originated from organic nitrates, 20-70% originated from dicarbonyls, and 0-20% originated from isoprene epoxydiols. The influences of OVOCs on the atmospheric oxidation capacity are dominated by the OH pathway during the day (∼350%) and by the NO pathway at night (∼150%). Consequently, O is enhanced by 30-70% in the YRD. Aerosols are also enhanced by 50-140%, 20-80%, and ∼20% for SOA, nitrate, and sulfate, respectively.
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http://dx.doi.org/10.1021/acs.est.2c00038DOI Listing
August 2022

Ivermectin induces chicken BCRP/ABCG2 expression and function: Involvement of CXR signaling pathway and mRNA stabilization.

J Vet Pharmacol Ther 2022 Aug 4. Epub 2022 Aug 4.

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.

Ivermectin is a macrocyclic lactone antiparasitic drug widely used in human and veterinary medicine. Previous studies indicated that ivermectin could interact with P-glycoprotein, being a good inducer and substrate; however, it is unknown whether ivermectin affects BCRP of chicken. In this study, we found that ivermectin distinctly affected the expression of BCRP in a time- and concentration-dependent up-regulatory way in chicken primary hepatocytes. Subsequent series of experiments showed that the BCRP induction is related with the increase of CXR expression and, promoting CXR translocations to the nucleus and enhancing the stability of Abcg2 mRNA at the post-transcriptional level by ivermectin. Furthermore, we observed that ivermectin also enhanced the stability of Abcg2 mRNA at the post-transcriptional level by Act-D chase assay. We got the similar results by in vivo test that ivermectin-induced BCRP and CXR expression in pharmacologically important tissues, and decreased the apparent permeability coefficient of florfenicol (substrate of chicken BCRP). In conclusion, the results indicated that ivermectin could induce chicken BCRP expression and function through the transcriptional CXR signaling pathway and post-transcriptional mRNA stabilization.
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http://dx.doi.org/10.1111/jvp.13090DOI Listing
August 2022

Circ_DLEU2 knockdown represses cell proliferation, migration and invasion, and induces cell apoptosis through the miR-582-5p/COX2 pathway in acute myeloid leukemia.

Histol Histopathol 2022 Aug 4:18507. Epub 2022 Aug 4.

Children's Hospital of Chongqing Medical University, Chongqing City, China.

Background: Acute myeloid leukemia (AML) is a malignant hematological neoplasm in adults. Researche indicates that circular RNAs (circRNAs) play paramount roles in the pathological process of AML. In this study, the role of circ_DLEU2 (circ_0000488) in AML is revealed.

Methods: The expression of circ_DLEU2, microRNA-582-5p (miR-582-5p) and cyclooxygenase 2 (COX2) was determined by quantitative real-time PCR. Protein expression was detected by western blot. Cell proliferation was investigated by cell cycle, 5-Ethynyl-29-deoxyuridine and 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assays. Cell apoptosis was elucidated by apoptosis analysis assay. The targeting relationship between miR-582-5p and circ_DLEU2 or COX2 was predicted by the starbase online database, and identified by a dual-luciferase reporter assay.

Results: Circ_DLEU2 and COX2 expression were substantially up-regulated, while miR-582-5p was down-regulated in AML marrow samples and cells compared with control groups. Circ_DLEU2 knockdown suppressed cell proliferation, whereas it induced cell arrest at G0/G1 phase and cell apoptosis in AML; however, these effects were attenuated by miR-582-5p inhibitor. Additionally, circ_DLEU2 was associated with miR-582-5p, and miR-582-5p bound to COX2 in AML cells. Also, we found that circ_DLEU2 regulated COX2 expression by interacting with miR-582-5p.

Conclusion: Circ_DLEU2 silencing hindered AML malignant progression via downregulating COX2 through sponging miR-582-5p. Our finding provides a theoretical basis for studying circRNA-directed therapy of AML.
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http://dx.doi.org/10.14670/HH-18-507DOI Listing
August 2022

Research progress on extraction, purification, structure and biological activity of polysaccharides.

Front Nutr 2022 18;9:965073. Epub 2022 Jul 18.

College of Food and Bioengineering, Henan Key Laboratory of Cold Chain Food Quality and Safety Control, Zhengzhou University of Light Industry, Zhengzhou, China.

Kimura et Migo () is a traditional medicinal and food homologous plant that has been used for thousands of years in folk medicine and nutritious food. Recent studies have shown that polysaccharide is one of the main biologically active components in . polysaccharides possess several biological activities, such as anti-oxidant, heptatoprotective, immunomodulatory, gastrointestinal protection, hypoglycemic, and anti-tumor activities. In the past decade, polysaccharides have been isolated from by physical and enzymatic methods and have been subjected to structural characterization and activity studies. Progress in extraction, purification, structural characterization, bioactivity, structure-activity relationship, and possible bioactivity mechanism of polysaccharides were reviewed. In order to provide reference for the in-depth study of polysaccharides and the application in functional food and biomedical research.
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http://dx.doi.org/10.3389/fnut.2022.965073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339781PMC
July 2022

Distribution, sources, and potential risks of antibiotic resistance genes in wastewater treatment plant: A review.

Environ Pollut 2022 Jul 31;310:119870. Epub 2022 Jul 31.

School of Environment, Key Laboratory for Yellow River and Huai River Water Environment and Pollution Control, Ministry of Education, Henan Key Laboratory for Environmental Pollution Control, Henan Normal University, Xinxiang, Henan, 453007, PR China. Electronic address:

Irrational use of antibiotics produces a large number of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs). Wastewater treatment plants (WWTPs) act as important sources and sinks of ARGs, and play an important role in their generation, treatment, and dissemination. This study summarizes the types, concentrations, and factors of ARGs in WWTPs, investigates the sources of ARGs in wastewater, compares the removal efficiencies of different treatment processes on ARGs, and analyzes the potential risks of ARGs accumulation in effluent, sludge and their emission into the air. The results show that the main ARGs detected in the influent of WWTPs are the genes resistant to macrolides (ermB, ermF), tetracyclines (tetW, tetA, tetC), sulfonamides (sul1, sul2), and β-lactams (bla, bla). The concentrations of ARGs in the influent of the WWTPs are 2.23 × 10-3.90 × 10 copies/mL. Wastewater quality and microbial community are the dominant factors that affect the distribution characteristics of ARGs. The accumulation of ARGs in effluent, sludge, and aerosols pose potential risks to the regional ecological environment and human health. Based on these results, research trends with respect to ARGs in WWTPs are also prospected.
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http://dx.doi.org/10.1016/j.envpol.2022.119870DOI Listing
July 2022

One new limonoid with cytotoxicity against glioma cell lines from .

Nat Prod Res 2022 Aug 3:1-6. Epub 2022 Aug 3.

School of Pharmaceutical Science, Liaoning University, Shenyang, China.

Glioma is a common malignant tumor with a high incidence rate but a low cure rate. In this paper, one previously undescribed limonoid (), along with two known cipadesin-type limonoids and , were isolated from . Their structures were established based on a comprehensive analysis of NMR and MS spectra. Compound exhibited moderate cytotoxicity against U251 and BT-325 cells with IC values of 7.32 ± 0.21 and 13.25 ± 0.35 μM, suggesting that might be a promising leading compound for the treatment of glioma.
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http://dx.doi.org/10.1080/14786419.2022.2106482DOI Listing
August 2022

Steam-assisted crystallization of highly dispersed nanosized hierarchical zeolites from solid raw materials and their catalytic performance in lactide production.

Chem Sci 2022 Jul 21;13(27):8052-8059. Epub 2022 Jun 21.

State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University 2699 Qianjin Street Changchun 130012 P. R. China

A solvent-free route based on solid raw materials affords higher product yield and lower waste production compared to the traditional hydrothermal synthesis. However, the as-made zeolites usually present blocky aggregation states, limiting their mass transfer and exposure of active sites in catalytic applications. Herein, highly dispersed nanosized hierarchical Beta zeolites with varied Si/Al ratios were prepared steam-assisted crystallization from ball-milled solid raw materials. Thanks to the sufficient mixing of solid raw materials and favorable migration of solid mixture, nanosized Beta zeolites are obtained that are assembled from nanoparticles (∼15 nm) and possess abundant interconnected intraparticle mesopores. The strategy can also be extended to synthesize nanosized hierarchical ZSM-5 zeolites. The as-prepared Beta zeolite (Si/Al = 10) exhibits outstanding catalytic performance in conversion of lactic acid to lactide (as high as 77.5% in yield). This work provides avenues for simple and cost-efficient synthesis of highly dispersed nanosized hierarchical zeolites, promising their important catalytic applications.
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http://dx.doi.org/10.1039/d2sc02823aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278505PMC
July 2022

Andrographolide suppresses breast cancer progression by modulating tumor-associated macrophage polarization through the Wnt/β-catenin pathway.

Phytother Res 2022 Aug 2. Epub 2022 Aug 2.

Central Laboratory of Yan'an Hospital Affiliated to Kunming Medical University, Kunming, People's Republic of China.

Andrographolide(ADE) has been demonstrated to inhibit tumor growth through direct cytotoxicity on tumor cells. However, its potential activity on tumor microenvironment (TME) remains unclear. Tumor-associated macrophages (TAMs), composed mainly of M2 macrophages, are the key cells that create an immunosuppressive TME by secretion of cytokines, thus enhancing tumor progression. Re-polarized subpopulations of macrophages may represent vital new therapeutic alternatives. Our previous studies showed that ADE possessed anti-metastasis and anoikis-sensitization effects. Here, we demonstrated that ADE significantly suppressed M2-like polarization and enhanced M1-like polarization of macrophages. Moreover, ADE inhibited the migration of M2 and tube formation in HUVECs under M2 stimulation. In vivo studies showed that ADE restrained the growth of MDA-MB-231 and HCC1806 human breast tumor xenografts and 4T-1 mammary gland tumors through TAMs. Wnt5a/β-catenin pathway and MMPs were particularly associated with ADE's regulatory mechanisms to M2 according to RNA-seq and bioinformatics analysis. Moreover, western blot also verified the expressions of these proteins were declined with ADE exposure. Among the cytokines released by M2, PDGF-AA and CCL2 were reduced. Our current findings for the first time elucidated that ADE could modulate macrophage polarization and function through Wnt5a signaling pathway, thereby playing its role in inhibition of triple-negative breast cancer.
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http://dx.doi.org/10.1002/ptr.7578DOI Listing
August 2022
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