Publications by authors named "Xiaofei Shen"

66 Publications

Comparative short-term and long-term outcomes between internal and external intestinal plication in the management of small bowel obstruction.

BMC Surg 2021 Jul 12;21(1):309. Epub 2021 Jul 12.

Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, 321 Zhongshan RD, Nanjing, China.

Background: Small bowel obstruction (SBO) is common and usually requires surgical intervention. Intestinal plication is a traditional but critical strategy for SBO in certain scenarios. This study is to compare the short-term and long-term outcome between internal and external plications in the management of SBO.

Methods: All patients receiving intestinal plication in our hospital were retrospectively collected. Short-term outcome including postoperative complications, reoperation, postoperative ICU stay, starting day of liquid diet and postoperative hospitalization, as well as long-term outcome including recurrence of obstruction, readmission, reoperation and death were compared between groups. Gut function at annual follow-up visits was evaluated as well.

Results: Nine internal and 11 external candidates were recruited into each group. The major causes of plication were adhesive obstruction, abdominal cocoon, volvulus and intussusception. Lower incidence of postoperative complication (p = 0.043) and shorter postoperative hospitalization (p = 0.049) was observed in internal group. One patient receiving external plication died from anastomosis leakage. During the 5-year follow-up period, the readmission rate was low in both groups (22.2 % vs. 9.1 %), and none of patients required reoperation or deceased. None of patients exhibited gut dysfunction, and all patients restored normal gut function after 4 years. Patients in external group demonstrated accelerated recovery of gut function after surgery.

Conclusions: This study compares short-term and long-term outcome of patients receiving internal or external intestinal plication. We suggest a conservative attitude toward external plication strategy. Surgical indication for intestinal plication is critical and awaits future investigations.
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http://dx.doi.org/10.1186/s12893-021-01304-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276395PMC
July 2021

What group 2 innate lymphoid cells tell themselves: autocrine signals play essential roles in mucosal immunity.

Signal Transduct Target Ther 2021 Jul 9;6(1):261. Epub 2021 Jul 9.

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

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http://dx.doi.org/10.1038/s41392-021-00685-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270981PMC
July 2021

Robotics Dexterous Grasping: The Methods Based on Point Cloud and Deep Learning.

Front Neurorobot 2021 9;15:658280. Epub 2021 Jun 9.

The State Key Laboratory for Management and Control of Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, China.

Dexterous manipulation, especially dexterous grasping, is a primitive and crucial ability of robots that allows the implementation of performing human-like behaviors. Deploying the ability on robots enables them to assist and substitute human to accomplish more complex tasks in daily life and industrial production. A comprehensive review of the methods based on point cloud and deep learning for robotics dexterous grasping from three perspectives is given in this paper. As a new category schemes of the mainstream methods, the proposed generation-evaluation framework is the core concept of the classification. The other two classifications based on learning modes and applications are also briefly described afterwards. This review aims to afford a guideline for robotics dexterous grasping researchers and developers.
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http://dx.doi.org/10.3389/fnbot.2021.658280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221534PMC
June 2021

Dencichine prevents ovariectomy-induced bone loss and inhibits osteoclastogenesis by inhibiting RANKL-associated NF-κB and MAPK signaling pathways.

J Pharmacol Sci 2021 Aug 3;146(4):206-215. Epub 2021 May 3.

Department of Orthopaedics, Yancheng City No.1 People's Hospital, Yancheng, Jiangsu 224006, China. Electronic address:

Aims: To investigate the effect of dencichine on osteoclastogenesis in vivo and in vitro.

Methods: RANKL-induced osteoclastogenesis were treated with different concentrations of dencichine. Pit forming assays were applied to evaluate the degree of bone resorption. Osteoclastogenic markers were detected by real-time quantitative PCR (RT-qPCR) and Western blot. Micro CT was conducted to investigate the effects of dencichine on osteoclastogenesis in ovariectomized (OVX) mice.

Results: Dencichine suppressed osteoclastogenesis through the inhibition of phosphorylation of p65, p50 (NF-κB pathway), p38, ERK and JNK (MAPKs pathway) in vitro. Furthermore, dencichine inhibited the function of osteoclasts in a dose-dependent manner. In addition, the expression levels of the nuclear factor of activated T cells 1 (NFATc1) and osteoclastogenesis markers were decreased by dencichine, including MMP-9, Cathepsin K (CTSK), Tartrate-Resistant Acid Phosphatase (TRAP), C-FOS, dendritic cell specific transmembrane protein (DC-STAMP). In vivo data proved that dencichine alleviated ovariectomy-induced bone loss and osteoclastogenesis in mice.

Conclusion: Our results demonstrate that dencichine alleviates OVX-induced bone loss in mice and inhibits RANKL-mediated osteoclastogenesis via inhibition of NF-κB and MAPK pathways in vitro, suggesting that dencichine might serve as a promising candidate for treatment of bone loss diseases, including PMOP and rheumatoid arthritis.
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http://dx.doi.org/10.1016/j.jphs.2021.04.004DOI Listing
August 2021

Distribution of fluoroquinolone resistance determinants in Carbapenem-resistant Klebsiella pneumoniae clinical isolates associated with bloodstream infections in China.

BMC Microbiol 2021 Jun 2;21(1):164. Epub 2021 Jun 2.

Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200082, P. R. China.

Background: The rate of fluoroquinolone (FQ) resistance among carbapenem-resistant Klebsiella pneumoniae (CRKP) is high. The present study aimed to investigate the distribution of fluoroquinolone resistance determinants in clinical CRKP isolates associated with bloodstream infections (BSIs).

Results: A total of 149 BSI-associated clinical CRKP isolates collected from 11 Chinese teaching hospitals from 2015 to 2018 were investigated for the prevalence of fluoroquinolone resistance determinants, including plasmid-mediated quinolone resistance (PMQR) genes and spontaneous mutations in the quinolone resistance-determining regions (QRDRs) of the gyrA and parC genes. Among these 149 clinical CRKP isolates, 117 (78.5%) exhibited resistance to ciprofloxacin. The GyrA substitutions (Ser83 → IIe/Phe) and (Asp87 → Gly/Ala) were found among 112 (75.2%) of 149 isolates, while the substitution (Ser80 → IIe) of ParC was found in 111 (74.5%) of the 149 isolates. In total, 70.5% (105/149) of the CRKP isolates had at least two mutations within gyrA as well as a third mutation in parC. No mutations in the QRDRs were found in 31 ciprofloxacin susceptible CRKP isolates. Eighty-nine (56.9%) of 149 were found to carry PMQR genes including qnrS1 (43.0%), aac(6')-Ib-cr (16.1%), qnrB4 (6.0%), qnrB2 (2.7%), and qnrB1 (1.3%). Nine isolates contained two or more PMQR genes, with one carrying four [aac(6')-Ib-cr, qnr-S1, qnrB2, and qnrB4]. The co-existence rate of PMQR determinants and mutations in the QRDRs of gyrA and parC reached 68.5% (61/89). Seventy-four (83.1%, 74/89) PMQR-positive isolates harbored extended-spectrum beta-lactamase (ESBL)-encoding genes. Multilocus sequence typing (MLST) analysis demonstrated that the ST11 was the most prevalent STs in our study.

Conclusions: Mutations in the QRDRs of gyrA and parC were the key factors leading to the high prevalence of fluoroquinolone resistance among BSI-associated CRKP. The co-existence of PMQR genes and mutations in the QRDRs can increase the resistance level of CRKP to fluoroquinolones in clinical settings. ST11 CRKP isolates with identical QRDR substitution patterns were found throughout hospitals in China.
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http://dx.doi.org/10.1186/s12866-021-02238-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173869PMC
June 2021

Model-based analysis uncovers mutations altering autophagy selectivity in human cancer.

Nat Commun 2021 05 31;12(1):3258. Epub 2021 May 31.

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu, China.

Autophagy can selectively target protein aggregates, pathogens, and dysfunctional organelles for the lysosomal degradation. Aberrant regulation of autophagy promotes tumorigenesis, while it is far less clear whether and how tumor-specific alterations result in autophagic aberrance. To form a link between aberrant autophagy selectivity and human cancer, we establish a computational pipeline and prioritize 222 potential LIR (LC3-interacting region) motif-associated mutations (LAMs) in 148 proteins. We validate LAMs in multiple proteins including ATG4B, STBD1, EHMT2 and BRAF that impair their interactions with LC3 and autophagy activities. Using a combination of transcriptomic, metabolomic and additional experimental assays, we show that STBD1, a poorly-characterized protein, inhibits tumor growth via modulating glycogen autophagy, while a patient-derived W203C mutation on LIR abolishes its cancer inhibitory function. This work suggests that altered autophagy selectivity is a frequently-used mechanism by cancer cells to survive during various stresses, and provides a framework to discover additional autophagy-related pathways that influence carcinogenesis.
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http://dx.doi.org/10.1038/s41467-021-23539-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166871PMC
May 2021

Comment on "Genomic Alteration and Immunity-Implications In Esophageal Cancer".

Ann Surg 2021 May 24. Epub 2021 May 24.

Medical Department of General Surgery, Chinese PLA General Hospital, Beijing, China Department of General Surgery, the 7 Medical Center, Chinese PLA General Hospital, Beijing, China The Second School of Clinical Medicine, Southern Medical University, Guangdong, China Faculty of Hepato-Pancreato-Biliary Surgery, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.

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http://dx.doi.org/10.1097/SLA.0000000000004952DOI Listing
May 2021

Comment on "Circulating Tumor Cells-New Indicator For Clinical Staging Of Patients With Esophageal Cancer".

Ann Surg 2021 May 24. Epub 2021 May 24.

Medical Department of General Surgery, Chinese PLA General Hospital, Beijing, China Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China Faculty of Hepato-Pancreato-Biliary Surgery, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.

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http://dx.doi.org/10.1097/SLA.0000000000004948DOI Listing
May 2021

Anti-Apoptotic Role of Sanhuang Xiexin Decoction and Anisodamine in Endotoxemia.

Front Pharmacol 2021 21;12:531325. Epub 2021 Apr 21.

Innovative Institutes of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Endotoxemia is characterized by initial uncontrollable inflammation, terminal immune paralysis, significant cell apoptosis and tissue injury, which can aggravate or induce multiple diseases and become one of the complications of many diseases. Therefore, anti-inflammatory and anti-apoptotic therapy is a valuable strategy for the treatment of endotoxemia-induced tissue injury. Traditional Chinese medicine exhibits great advantages in the treatment of endotoxemia. In this review, we have analyzed and summarized the active ingredients and their metabolites of Sanhuang Xiexin Decoction, a famous formula in endotoxemia therapy. We then have summarized the mechanisms of Sanhuang Xiexin Decoction against endotoxemia and its mediated tissue injury. Furthermore, silico strategy was used to evaluate the anti-apoptotic mechanism of anisodamine, a well-known natural product that widely used to improve survival in patients with septic shock. Finally, we also have summarized other anti-apoptotic natural products as well as their therapeutic effects on endotoxemia and its mediated tissue injury.
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http://dx.doi.org/10.3389/fphar.2021.531325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099151PMC
April 2021

Targeting Neutrophils in Sepsis: From Mechanism to Translation.

Front Pharmacol 2021 12;12:644270. Epub 2021 Apr 12.

Medical Department of General Surgery, The 1st Medical Center of Chinese PLA General Hospital, Beijing, China.

Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Although our understanding in the pathophysiological features of sepsis has increased significantly during the past decades, there is still lack of specific treatment for sepsis. Neutrophils are important regulators against invading pathogens, and their role during sepsis has been studied extensively. It has been suggested that the migration, the antimicrobial activity, and the function of neutrophil extracellular traps (NETs) have all been impaired during sepsis, which results in an inappropriate response to primary infection and potentially increase the susceptibility to secondary infection. On the other hand, accumulating evidence has shown that the reversal or restoration of neutrophil function can promote bacterial clearance and improve sepsis outcome, supporting the idea that targeting neutrophils may be a promising strategy for sepsis treatment. In this review, we will give an overview of the role of neutrophils during sepsis and discuss the potential therapeutic strategy targeting neutrophils.
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http://dx.doi.org/10.3389/fphar.2021.644270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072352PMC
April 2021

Cancer Therapy with Nanoparticle-Medicated Intracellular Expression of Peptide CRM1-Inhibitor.

Int J Nanomedicine 2021 14;16:2833-2847. Epub 2021 Apr 14.

Department of Pathology and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Centre for Biotherapy, Chengdu, 610041, People's Republic of China.

Introduction: Peptides can be rationally designed as non-covalent inhibitors for molecularly targeted therapy. However, it remains challenging to efficiently deliver the peptides into the targeted cells, which often severely affects their therapeutic efficiency.

Methods: Herein, we created a novel non-covalent peptide inhibitor against nuclear export factor CRM1 by a structure-guided drug design method and targetedly delivered the peptide into cancer cells by a nanoparticle-mediated gene expression system for use as a cancer therapy.

Results: The nuclear export signal (NES)-optimized CRM1 peptide inhibitor colocalized with CRM1 to the nuclear envelope and inhibited nuclear export in cancer cell lines in vitro. The crystal structures of the inhibitors complexed with CRM1 were solved. In contrast to the covalent inhibitors, the peptides were similarly effective against cells harboring the CRM1 C528S mutation. Moreover, a plasmid encoding the peptides was delivered by a iRGD-modified nanoparticle to efficiently target and transfect the cancer cells in vivo after intravenous administration. The peptides could be selectively expressed in the tumor, resulting in the efficient inhibition of subcutaneous melanoma xenografts without obvious systemic toxicity.

Discussion: This work provides an effective strategy to design peptide-based molecularly targeted therapeutics, which could lead to the development of future targeted therapy.
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http://dx.doi.org/10.2147/IJN.S266398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054660PMC
May 2021

Targeting Endosomal Recycling Pathways by Bacterial and Viral Pathogens.

Front Cell Dev Biol 2021 4;9:648024. Epub 2021 Mar 4.

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China.

Endosomes are essential cellular stations where endocytic and secretory trafficking routes converge. Proteins transiting at endosomes can be degraded via lysosome, or recycled to the plasma membrane, trans-Golgi network (TGN), or other cellular destinations. Pathways regulating endosomal recycling are tightly regulated in order to preserve organelle identity, to maintain lipid homeostasis, and to support other essential cellular functions. Recent studies have revealed that both pathogenic bacteria and viruses subvert host endosomal recycling pathways for their survival and replication. Several host factors that are frequently targeted by pathogens are being identified, including retromer, TBC1D5, SNX-BARs, and the WASH complex. In this review, we will focus on the recent advances in understanding how intracellular bacteria, human papillomavirus (HPV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijack host endosomal recycling pathways. This exciting work not only reveals distinct mechanisms employed by pathogens to manipulate host signaling pathways, but also deepens our understanding of the molecular intricacies regulating endosomal receptor trafficking.
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http://dx.doi.org/10.3389/fcell.2021.648024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970000PMC
March 2021

Identification of the featured-element in fine road dust of cities with coal contamination by geochemical investigation and isotopic monitoring.

Environ Int 2021 07 12;152:106499. Epub 2021 Mar 12.

School of Ecology and Environment, Anhui Normal University, Wuhu 241000, Anhui, China.

The exploitation of coal releases large amounts of contaminants into the environment. However, the featured pollutants of coal utilization as well as the scope and degree of their impact remain to be revealed. To identify the featured-element of coal contamination in a complex environment, a typical coal resource city was selected, and the major elements, 18 trace elements, as well as δC, δN, and δS in the fine road dust and certain source materials were analyzed. Through multiple analysis methods, the featured-element was determined step-by-step: firstly, elements with enrichment coefficients greater than two in road dust were focused: Zn, Hg, Pb, Cu, Cd, and Cr; secondly, difference analysis showed a significant difference (p < 0.05) of Hg and Cu concentration at different distance from the coal-fired power plant, making Hg and Cu the only candidates for the featured-element; finally, through coal-related source materials determination, Cu was not qualified as a featured-element. Therefore, Hg was the only left element to be considered as the featured-element. To be more convincing, more analyses were performed to support Hg as the featured-element: cluster analysis and isotope monitoring indicated Hg in road dust could originate from coal combustion; X-ray photoelectron spectroscopy was also conducted, where the forms of Hg in road dust with possible source materials were compared, and the presence of HgO and Hg only in the road dust near the power plant indicated the impact of the power plant on the surrounding dust. Through the health risk assessment, it was found that Hg in the road dust had no health risk, though the study area still had Pb, Cr, and As risks, which were not closely related to the pollutants released by coal-related sources.
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http://dx.doi.org/10.1016/j.envint.2021.106499DOI Listing
July 2021

Circulating Tumor DNA Detection Using Digital Polymerase Chain Reaction-Promising But Needs Improvement.

Gastroenterology 2021 Jul 25;161(1):366-367. Epub 2021 Feb 25.

Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital, Beijing, China.

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http://dx.doi.org/10.1053/j.gastro.2021.02.048DOI Listing
July 2021

A Polyclonal Spread Emerged: Characteristics of Carbapenem-Resistant Isolates from the Intensive Care Unit in a Chinese Tertiary Hospital.

Pol J Microbiol 2020 Sep 8;69(3):311-319. Epub 2020 Sep 8.

Emergency Intensive Care Unit, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Carbapenem-resistant (CRKP) isolates often cause nosocomial infections with limited therapeutic options and spread rapidly worldwide. In this study, we revealed a polyclonal emergence of CRKP isolates from the intensive care unit in a Chinese tertiary hospital. We applied a series of methods including automated screening, antimicrobial susceptibility testing, the modified carbapenem inacti vation method (mCIM), PCR amplification, DNA sequencing, and multilocus sequence typing (MLST) to characterize 30 non-duplicated CRKP isolates along with the collection of the related medical records. The results showed the polyclonal spread of CRKP isolates belonged to ST722, ST1446, ST111, ST896, ST290, and ST11. Among them, ST722 and ST1446 were two novel types of , and ST896 isolate harboring was also found for the first time. Since the polyclonal spread of CRKP in the same ward is rare, the silent clonal evolution with the switching genotypes prompts us to stay alert for outbreaks caused by novel subclones.
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http://dx.doi.org/10.33073/pjm-2020-034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810120PMC
September 2020

Estrogen Receptor Beta Prevents Signet Ring Cell Gastric Carcinoma Progression in Young Patients by Inhibiting Pseudopodia Formation via the mTOR-Arpc1b/EVL Signaling Pathway.

Front Cell Dev Biol 2020 21;8:592919. Epub 2021 Jan 21.

Department of General Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

Signet ring cell gastric carcinoma (SRCGC) is a poorly differentiated malignancy, and can be highly dangerous in the progression stage. There is a higher male to female ratio among patients with signet ring cell carcinoma as compared to patients with non-SRCGC. ERβ has been found to express in stomach adenocarcinoma, but how it affects tumor progression remains unclear. Here, we studied estrogen receptor beta (ERβ) to explore the role of sex-associated factors in SRCGC. We analyzed the clinicopathological statistics of patients with SRCGC, and conducted a series of experiments. Immunohistochemistry showed that patients with low ERβ expression were at risk of poor prognosis and higher T stage. assays indicated that ERβ might prevent SRCGC progression by inhibiting cell proliferation and invasiveness and by promoting anoikis. Western blotting and quantitative RT-PCR proved that the mTOR-Arpc1b/EVL signaling pathway might participate in the negative regulatory role of ERβ. In conclusion, our findings show that ERβ might inhibit the malignancy of signet ring cells in patients with SRCGC, indicating that ERβ might be a potential target in adjuvant treatment.
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http://dx.doi.org/10.3389/fcell.2020.592919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859346PMC
January 2021

IL-33 in Gastric Metaplasia-Implications for Therapeutic Targets.

Gastroenterology 2021 Jun 3;160(7):2629-2630. Epub 2021 Feb 3.

Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital, Beijing, China.

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http://dx.doi.org/10.1053/j.gastro.2021.01.231DOI Listing
June 2021

Retraction notice to "2D NMR assisted structure elucidation of three cyanoethylated cellulose derivatives and correlated with their properties" [Carbohydr. Res. 487(2020) 107861].

Carbohydr Res 2020 Dec 21;498:108177. Epub 2020 Oct 21.

Department of Polymer Science and Engineering, School of Chemistry and Chemical Engineering, Hefei University of Technology, Hefei, Anhui Province, 230009, China. Electronic address:

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief who would like to withdraw this accepted article, due to serious errors in authorship and affiliations which breach the journal's ethical policies.
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http://dx.doi.org/10.1016/j.carres.2020.108177DOI Listing
December 2020

Resveratrol enhances the antimicrobial effect of polymyxin B on Klebsiella pneumoniae and Escherichia coli isolates with polymyxin B resistance.

BMC Microbiol 2020 10 12;20(1):306. Epub 2020 Oct 12.

Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200082, China.

Background: Multidrug resistant (MDR) Gram-negative bacterial infections are a serious threat to human health due to the lack of effective treatments. In this study, we selected 50 Gram-negative bacterial strains, including 26 strains of Klebsiella pneumoniae and 24 strains of Escherichia coli, to explore whether resveratrol and polymyxin B have a synergistic killing effect.

Results: MIC values against polymyxin B were ≥ 4 μg/mL for 44 of the strains and were 2 μg/mL for the other 6 strains. MICs against polymyxin B in the isolates tested were significantly reduced by the addition of resveratrol. The degree of decline depended on the bacteria, ranging from 1/2 MIC to 1/512 MIC, and the higher the concentration of resveratrol, the greater the decrease. Checkerboard analysis indicated a synergistic effect between resveratrol and polymyxin B; the optimal drug concentration for different bacteria was different, that of resveratrol ranging from 32 μg/mL to 128 μg/mL. Subsequent time-kill experiments showed that a combination of polymyxin B and resveratrol was more effective in killing bacteria.

Conclusions: Our in vitro studies have shown that resveratrol can increase the sensitivity of MDR bacterial strains to polymyxin B, suggesting a potential new approach to the treatment of MDR infections.
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http://dx.doi.org/10.1186/s12866-020-01995-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552488PMC
October 2020

Effects of prepubertal exposure to forchlorfenuron through prenatal and postnatal gavage administration in developing Sprague-Dawley rats.

Reprod Toxicol 2020 12 28;98:157-164. Epub 2020 Sep 28.

Center for Drug Safety Evaluation and Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address:

Forchlorfenuron (CPPU), a plant growth regulator, is widely used in agriculture. However, its long-term exposure effects on humans, especially neonates, remain unclear. Therefore, we investigated the developmental toxicity of prenatal and postnatal gavage administration of CPPU in rats. Pregnant Sprague-Dawley rats were administered 300 mg/kg/day CPPU by gavage from day 6 of gestation to the cessation of nursing. During weaning, rat offspring were administered 0, 30, 100, or 300 mg/kg/day CPPU for 4 weeks, followed by a 4-week CPPU-free recovery period. There were no significant differences in clinical symptoms, body weight, development indicators, serum biochemical parameters, sex hormone levels, sperm motility, relative organ weights, and histopathological changes among the 0-100 mg/kg/day CPPU groups. In the 300 mg/kg/day CPPU group, female rats exhibited decreased body weight, earlier time of vaginal opening (VO) and first estrus time (FE), elevated estradiol and blood urea nitrogen (BUN) levels, and upregulation of estrogen receptor 1 gene expression, whereas male rats only exhibited increases in serum BUN, creatinine, and glucose levels. Most changes were reversed after the recovery period. Furthermore, the endometrial epithelial height was significantly increased in female rats despite the absence of significant changes in uterine wall thickness and endometrial glands. Thus, CPPU may promote estradiol secretion, resulting in altered VO and FE and adverse effects in prepubertal female rats. These findings may be applied for risk assessment following CPPU exposure in humans.
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http://dx.doi.org/10.1016/j.reprotox.2020.09.009DOI Listing
December 2020

High Prevalence of 16S rRNA Methyltransferase Genes in Carbapenem-Resistant Clinical Isolates Associated with Bloodstream Infections in 11 Chinese Teaching Hospitals.

Infect Drug Resist 2020 9;13:2189-2197. Epub 2020 Jul 9.

Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200082, People's Republic of China.

Objective: The 16S rRNA methylase-mediated high-level resistance to aminoglycosides has become a great concern. The purpose of the study was to investigate the occurrence of 16S rRNA methyltransferase (RMTase) genes in carbapenem-resistant (CRKP) clinical isolates associated with bloodstream infections (BSIs) in China.

Methods: From July 2015 to December 2018, a total of 137 unique CRKP clinical isolates associated with BSIs were collected from 11 Chinese teaching hospitals. PCR and DNA sequencing were used to identify 16S RMTase genes. Whole-genome sequencing (WGS) was performed on all CRKP clinical isolates. Relevant information was extracted from WGS data (antibiotic resistance determinants, K-type and wzi allelic types). All 16S RMTase-producing CRKP clinical isolates were characterized by antimicrobial susceptibility testing, multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE).

Results: In this study, 137 CRKPs were found to harbor at least one carbapenemase gene. Among 137 CRKPs, 78 (56.9%, 78/137) were positive for 16S RMTase genes (5 for armA, 70 for rmtB, 3 for both armA and rmtB) and highly resistant to gentamicin and amikacin (MICs ≥256 mg/L). Seventy-five isolates harboring 16S RMTase genes also produced ESBLs. In this study, 5 sequence types (STs) and 6 capsule serotypes were found among 78 isolates positive for 16S RMTases genes, while 14 STs and 6 capsule serotypes were found among 59 isolates negative for 16S RMTases genes. Compared with the isolates negative for 16S RMTases genes, the STs and capsular serotypes of 16S RMTases-positive strains are more concentrated. Among 78 16S RMTases-positive strains, the most prevalent clone type is ST11-PFGE-B-KL64-wzi64 (62.8%, 49/78), which mainly carries the rmtB and bla genes and is distributed in 7 provinces in China.

Conclusion: A high prevalence of 16S RMTase genes was found among CRKP clinical isolates associated with BSIs from Chinese teaching hospitals, which was attributed to the dissemination of the ST11-PFGE-B-KL64-wzi64 clone.
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http://dx.doi.org/10.2147/IDR.S254479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367928PMC
July 2020

Mechanism of cargo recognition by retromer-linked SNX-BAR proteins.

PLoS Biol 2020 03 9;18(3):e3000631. Epub 2020 Mar 9.

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu, China.

Endocytic recycling of internalized transmembrane proteins is essential for many important physiological processes. Recent studies have revealed that retromer-related Sorting Nexin family (SNX)-Bin/Amphiphysin/Rvs (BAR) proteins can directly recognize cargoes like cation-independent mannose 6-phosphate receptor (CI-MPR) and Insulin-like growth factor 1 receptor (IGF1R); however, it remains poorly understood how SNX-BARs select specific cargo proteins and whether they recognize additional ligands. Here, we discovered that the binding between SNX-BARs and CI-MPR or IGF1R is mediated by the phox-homology (PX) domain of SNX5 or SNX6 and a bipartite motif, termed SNX-BAR-binding motif (SBM), in the cargoes. Using this motif, we identified over 70 putative SNX-BAR ligands, many of which play critical roles in apoptosis, cell adhesion, signal transduction, or metabolite homeostasis. Remarkably, SNX-BARs could cooperate with both SNX27 and retromer in the recycling of ligands encompassing the SBM, PDZ-binding motif, or both motifs. Overall, our studies establish that SNX-BARs function as a direct cargo-selecting module for a large set of transmembrane proteins transiting the endosome, in addition to their roles in phospholipid recognition and biogenesis of tubular structures.
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http://dx.doi.org/10.1371/journal.pbio.3000631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082075PMC
March 2020

Subinhibitory Concentrations of Fusidic Acid May Reduce the Virulence of by Down-Regulating and to Reduce Biofilm Formation and α-Toxin Expression.

Front Microbiol 2020 14;11:25. Epub 2020 Feb 14.

Department of Clinical Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

is an important pathogen in hospital and community infections. Fusidic acid is particularly effective in treating skin and wound infections caused by staphylococci. The purpose of our study was to clarify the effect of fusidic acid on the biofilm formation and α-toxin expression of at subinhibitory concentrations [1/64, 1/32, and 1/16 × minimum inhibitory concentration (MIC)]. A total of 504 genes greater than a twofold or less than twofold change in expression of effected by subinhibitory concentrations of fusidic acid were found, including 232 up-regulated genes and 272 down-regulated genes, which were determined by transcriptome sequencing. Our results showed subinhibitory concentrations of fusidic acid significantly inhibited the expression of , , , and at the mRNA level in clinical strains tested. And subinhibitory concentrations of fusidic acid can significantly reduce the hemolysis activity and α-toxin production of . In addition, the subinhibitory concentrations of fusidic acid significantly inhibited biofilm formation, autolysis, cell aggregation, and polysaccharide intercellular adhesin (PIA) production of . Moreover, fusidic acid effectively reduces the damage of mouse skin lesion area. Furthermore, fusidic acid reduced the expression of the two-component regulatory system and staphylococcal accessory gene regulator (). In conclusion, our results suggested that the subinhibitory concentrations of fusidic acid may reduce the virulence of by down-regulating and to reduce biofilm formation and α-toxin expression, which will provide a theoretical basis for the clinical treatment of infection. This is the first report that fusidic acid has an inhibitory effect on the virulence of , and this broadens the clinical application of fusidic acid.
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http://dx.doi.org/10.3389/fmicb.2020.00025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033611PMC
February 2020

Allosteric inhibitors of the STAT3 signaling pathway.

Eur J Med Chem 2020 Mar 7;190:112122. Epub 2020 Feb 7.

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, 610041, China. Electronic address:

Over-expression and/or hyperactivation of signal transducer and activator of transcription 3 (STAT3) signaling are found in various human diseases, including cancer, autoimmune disorders, and inflammatory diseases. Therefore, STAT3 represents a highly promising therapeutic target for the treatment of these diseases. However, the traditional orthosteric inhibitors of STAT3 exhibit limited clinical efficacy, with low selectivity, numerous side effects, and emerging acquired resistance. Allosteric inhibitors targeting STAT3 or its upstream molecules have emerged as a promising approach to overcome these barriers. In this review, we summarize the recent advances in the development of these inhibitors as well as their applications.
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http://dx.doi.org/10.1016/j.ejmech.2020.112122DOI Listing
March 2020

Downregulation of CLDN6 inhibits cell proliferation, migration, and invasion via regulating EGFR/AKT/mTOR signalling pathway in hepatocellular carcinoma.

Cell Biochem Funct 2020 Jul 13;38(5):541-548. Epub 2020 Feb 13.

Institute of Laboratory Animals of Sichuan Academy of Medical Science, Sichuan Provincial People's Hospital, Chengdu, China.

Accumulating evidence showed that the claudin-6 (CLDN6) expression was abnormal in many cancers, while its expression and biological functions in hepatocellular carcinoma (HCC) is still unclear. The present study demonstrated that CLDN6 was upregulated in HCC tissues compared with tumour-adjacent tissues. CLDN6 silencing was significantly inhibited proliferation, migration, and invasion of HepG2 cells. Meanwhile, downregulation of CLDN6 remarkably inhibited the activation of EGFR/AKT/mTOR signalling pathway. Interestingly, the effect of CLDN6 overexpression on HepG2 cell proliferation and invasion could be inhibited by EGFR/AKT/mTOR signalling pathway inhibitor (AG1478). SIGNIFICANCE OF THE STUDY: These findings suggested that CLDN6 may act as an oncogene in HCC and improve HepG2 cell proliferation, migration, and invasion may via EGFR/AKT/mTOR signalling pathway.
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http://dx.doi.org/10.1002/cbf.3489DOI Listing
July 2020

Knockdown Of lncRNA NCK-AS1 Regulates Cisplatin Resistance Through Modulating miR-137 In Osteosarcoma Cells.

Onco Targets Ther 2019 16;12:11057-11068. Epub 2019 Dec 16.

Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, People's Republic of China.

Purpose: Long non-coding RNAs (lncRNAs) have been proved to act crucial parts in the progress of human tumor. However, the role of lncRNAs in drug resistance of tumor cells remains to be further elucidated. The present study aimed to explore whether lncRNA NCK-AS1 could affect the cisplatin (DDP) resistance in human osteosarcoma cell and the underlying molecular mechanism.

Methods: The expression of NCK1-AS1 and miR-137 in osteosarcoma cells was detected by qRT-PCR. CCK-8 assay, colony formation assay, Western blotting, wound healing assay and transwell assay were employed to assess the cell proliferation, migration and invasion. In addition, CCK-8 assay, flow cytometry, qRT-PCR and resistance gene activity analysis were performed to assess the DDP sensitivity of osteosarcoma cells. The interaction between NCK1-AS1 and miR-137 was identified using a dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay.

Results: The results revealed that NCK1-AS1 was significantly upregulated in osteosarcoma cells, as well as in DDP-resistant osteosarcoma cells. NCK1-AS1 silence inhibited the proliferation, migration and invasion of osteosarcoma cells, whereas enhanced the sensitivity of osteosarcoma cells to DDP. Furthermore, NCK1-AS1 directly interacted with miR-137 and overexpression of miR-137 suppressed the proliferation, migration and invasion of osteosarcoma cells. Most importantly, miR-137 overexpression enhanced the sensitivity of osteosarcoma cells to DDP, and high expression of NCK1-AS1 reversed the influences of miR-137 overexpression on DDP-resistant cells.

Conclusion: In short, NCK1-AS1 knockdown enhanced DDP sensitivity of osteosarcoma cells by regulating miR-137, which may be a novel potential target for anti-DDP resistance in human osteosarcoma.
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http://dx.doi.org/10.2147/OTT.S228199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924660PMC
December 2019

Helical poly(phenyl isocyanide)s grafted selectively on C-6 of cellulose for improved chiral recognition ability.

Carbohydr Polym 2020 Mar 12;231:115737. Epub 2019 Dec 12.

Biomass Molecular Engineering Center, Department of Material Science and Engineering, Anhui Agricultural University, Hefei, Anhui, 230036, China.

Cellulose graft copolymers are an effective way to endow new properties to cellulose substrate, as well the rigidity, regularity, and helicity of the cellulose backbone could induce the self-assembly of supramolecular structures. In this work, right-handed helical poly(phenyl isocyanide)s (PPI) were grafted selectively onto C-6-cellulose. Alkyne-terminated PPI was synthesized by living polymerization of right-handed phenyl isocyanide monomer using an alkyne-terminated palladium(II) complex as an initiator/catalyst, and were grafted onto the C-6 of the cellulose backbone (Cell-6-g-PPI) at various chain lengths using copper-catalyzed alkyne-azide cycloaddition (CuAAC) "click" chemistry. We confirmed the successful grafting by liquid H NMR and C NMR, as well as solid C NMR, FTIR, and GPC. After grafting onto cellulose, the right-handed chirality of PPI was significantly increased by 111.2%. Additionally, the Cell-6-g-PPI exhibited better chiral recognition of L-Phe-DNSP than PPI alone. Therefore, the helical cellulose backbone has enhanced effect on preferred helix of PPI.
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http://dx.doi.org/10.1016/j.carbpol.2019.115737DOI Listing
March 2020

Mucosal-associated invariant T cells restrict allergic airway inflammation.

J Allergy Clin Immunol 2020 05 23;145(5):1469-1473.e4. Epub 2019 Dec 23.

Department of Immunology & Microbial Diseases, Albany Medical College, Albany, NY; Division of Allergy and Immunology, Department of Medicine, Albany Medical College, Albany, NY. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2019.12.891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214121PMC
May 2020

Coexistence of and on a Transferrable Plasmid of a Novel ST192 Clinical Isolate.

Infect Drug Resist 2019 13;12:3883-3891. Epub 2019 Dec 13.

Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200082, People's Republic of China.

Introduction: The occurrence and development of antibiotic resistance are mainly caused by the spread of large plasmids carrying multiple antibiotic resistance genes. Recently, the association between 16S rRNA methyltransferase genes and β-lactamase genes carried by the same plasmid is of concern.

Methods: The 1564 was isolated from the catheter tip of a patient in a tertiary hospital, Shanghai, China. The presence of the and genes were assessed by PCR. Complete sequence of plasmid p1564 was determined. The 1564 was characterized by antimicrobial susceptibility testing, Carbapenemase phenotype confirmation testing, conjugation experiment, S1-PFGE and multilocus sequence typing (MLST).

Results: Herein, we found that a New Delhi Metallo-β-lactamase-1 gene ( ) and a 16S rRNA methyltransferase gene () coexisted on a transferrable plasmid of a carbapenem-resistant clinical isolate. The clinical isolate was found to belong to a novel sequence type 192 (ST192) determined by MLST. The sequencing results of the plasmid p1564 carrying gene and gene showed that the size and guanine-cytosine content of the plasmid were 136, 902 bp and 51.8%, with 164 putative ORFs and two multidrug resistance gene islands. In addition to and , the plasmid contained bleomycin resistance gene ( ), CMY-6β-lactamase gene ( ), quaternary ammonium compound resistance gene (), truncated quaternary ammonium compound resistance gene (), aminoglycoside resistance gene () and sulfonamide resistance gene (). By comparison, p1564 has high homology with pHS36-NDM from subsp. serovar Stanley reported in China, with similar size and both belonging to plasmid incompatibility group A/C.

Conclusion: The present study demonstrated for the first time the co-existence of and in a novel ST192 . The spread of plasmids harboring both and may occur among Enterobacteriaceae in China.
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http://dx.doi.org/10.2147/IDR.S228130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6916698PMC
December 2019

A critical role for c-Myc in group 2 innate lymphoid cell activation.

Allergy 2020 04 29;75(4):841-852. Epub 2020 Jan 29.

Department of Immunology & Microbial Diseases, Albany Medical College, Albany, NY, USA.

Background: Asthma is a complicated chronic inflammatory disorder characterized by airway inflammation and bronchial hyperresponsiveness. Group 2 innate lymphoid cells (ILC2) are tissue-resident innate effector cells that can mediate airway inflammation and hyperresponsiveness through production of IL-5, IL-13 and VEGFA. ILC2 in asthma patients exhibit an activated phenotype. However, molecular pathways that control ILC2 activation are not well understood.

Methods: MYC expression was examined in ILC2 sorted from peripheral blood of healthy controls and asthma patients or cultured with or without activating cytokines. CRISPR knockout technique was used to delete c-Myc in primary murine lung ILC2 or an ILC2 cell line. Cell proliferation was examined, gene expression pattern was profiled by genome-wide microarray analysis, and direct gene targets were identified by Chromatin immunoprecipitation (ChIP). ILC2 responses, airway inflammation and airway hyperresponsiveness were examined in Balb/c mice challenged with Alternaria extracts, with or without treatment with JQ1.

Results: ILC2 from asthma patients expressed increased amounts of MYC. Deletion of c-Myc in ILC2 results in reduced proliferation, decreased cytokine production, and reduced expression of many lymphocyte activation genes. ChIP identified Stat6 as a direct gene target of c-Myc in ILC2. In vivo inhibition of c-Myc by JQ1 treatment repressed ILC2 activity and suppressed Alternaria-induced airway inflammation and AHR.

Conclusion: c-Myc expression is upregulated during ILC2 activation. c-Myc is essential for ILC2 activation and their in vivo pathogenic effects. These findings suggest that targeting c-Myc may unlock novel strategies to combat asthma or asthma exacerbation.
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http://dx.doi.org/10.1111/all.14149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176544PMC
April 2020
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