Publications by authors named "Pengfei Yu"

141 Publications

An Investigation on the Occurrence and Molecular Characterization of in Meat and Meat Products in China.

Foodborne Pathog Dis 2021 Mar 25. Epub 2021 Mar 25.

Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, China.

is a common foodborne pathogen that can cause both gastrointestinal and nongastrointestinal diseases. In this study, we collected 603 meat and meat products from 39 major cities in China. The positive contamination rate of in the collected samples was 26.37% (159/603), and the contamination level in 5.03% (8/159) positive samples exceeded 1100 most probable number/g. The detection rates of virulence genes were 89.7% for the gene group, 37.1% for the gene cluster, 82.3% for , and 2.9% for . Notably, all isolates presented with multiple antibiotic resistance, and 99.43% of isolates were resistant to five classes of antibiotics. In addition, the multilocus sequence typing results indicated that all isolates were rich in genetic diversity. Collectively, we conducted a systematic investigation on the prevalence and characterization of in meat and meat products in China, providing crucial information for assessing the risk of occurrence in meat and meat products.
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http://dx.doi.org/10.1089/fpd.2020.2885DOI Listing
March 2021

Fine particulate matter induces airway inflammation by disturbing the balance between Th1/Th2 and regulation of GATA3 and Runx3 expression in BALB/c mice.

Mol Med Rep 2021 May 24;23(5). Epub 2021 Mar 24.

Department of Respiratory Medicine, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.

The present study aimed to examine the effects of 2.5 µm particulate matter (PM2.5) on airway inflammation and to investigate the possible underlying mechanism. Specifically, the focus was on the imbalance of T helper (Th)1/Th2 cells and the dysregulated expression of transcription factors, including ‑acting T cell‑specific transcription factor 3 (GATA3), runt‑related transcription factor 3 (Runx3) and T‑box transcription factor TBX21 (T‑bet). In this study, ambient PM2.5 was collected and analyzed, male BALB/c mice were sensitized and treated with PBS, ovalbumin (OVA), PM2.5 or OVA + PM2.5. The effects of PM2.5 alone or PM2.5 + OVA on immunopathological changes, the expression of transcription factors GATA3, Runx3 and T‑bet, and the imbalance of Th1/Th2 were investigated. It was found that PM2.5 + OVA co‑exposure significantly enhanced inflammatory cell infiltration, increased higher tracheal secretions in lung tissue and upregulated respiratory resistance response to acetylcholine compared with PM2.5 or OVA single exposure and control groups. In addition, higher protein and mRNA expression levels of Th2 inflammatory mediators interleukin (IL)‑4, IL‑5 and IL‑13 in bronchoalveolar lavage fluid were observed in PM2.5 + OVA treated mice, whereas the expression levels of GATA3 and STAT6 were exhibited in mice exposed to OVA + PM2.5 compared with the OVA and PM2.5 groups. By contrast, PM2.5 exposure decreased the protein and mRNA expression levels of Th1 cytokine interferon‑γ and transcription factors Runx3 and T‑bet, especially among asthmatic mice, different from OVA group, PM2.5 exposure only failed to influence the expression of T‑bet. To conclude, PM2.5 exposure evoked the allergic airway inflammation response, especially in the asthmatic mouse model and led to Th1/Th2 imbalance. These effects worked mainly by upregulating GATA3 and downregulating Runx3. These data suggested that Runx3 may play an important role in PM2.5‑aggravated asthma in BALB/c mice.
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http://dx.doi.org/10.3892/mmr.2021.12017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986036PMC
May 2021

Assessment of the toxicity and toxicokinetics of the novel potent tropomyosin receptor kinase (Trk) inhibitor LPM4870108 in rhesus monkeys.

Regul Toxicol Pharmacol 2021 Feb 6;122:104886. Epub 2021 Feb 6.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, PR China. Electronic address:

LPM4870108 is a tropomyosin receptor kinase (Trk) inhibitor that is currently under consideration for human clinical trials. We characterized the toxicity and toxicokinetic properties of LPM4870108 following its oral administration to rhesus monkeys (5, 10, or 20 mg/kg/day for 4 weeks with a 4-week recovery period). No evidence of LPM4870108 toxicity was observed over this study as reflected by an absence of difference in body weight, ophthalmoscopy, urinalysis, gross, or histopathology findings. No significant differences in toxicity-related outcomes were detected when comparing LPM4870108 and control groups, and no significant treatment-related changes in food consumption, electrocardiogram results, blood pressure, hematological parameters, biochemical values, organ weight, or bone marrow parameters were observed. Treatment caused dose-dependent effects of gait disturbance, impaired balance, poor coordination, and decreased grip strength in all LPM4870108-treated animals, with these effects being attributable to excessive on-target Trk receptor inhibition. After the 4-week recovery period, all these abnormal treatment-related findings had fully or partially resolved. The toxicokinetic study of monkeys revealed that the LPM4870108 exposure increased with dose. Overall, LPM4870108 exhibited a safety profile in treated monkeys, indicating that the Highest Non-Severely Toxic Dose (HNSTD) for LPM4870108 in monkeys was 20 mg/kg/day.
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http://dx.doi.org/10.1016/j.yrtph.2021.104886DOI Listing
February 2021

Deep Targeted Sequencing and Its Potential Implication for Cancer Therapy in Chinese Patients with Gastric Adenocarcinoma.

Oncologist 2021 Jan 29. Epub 2021 Jan 29.

Department of Gastric Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China.

Introduction: Gastric cancer (GC) has a high incidence and mortality rate, especially in East Asians, and about 90% of GCs are adenocarcinomas. Histological and etiological heterogeneity and ethnic diversity make molecular subtyping of GC complicated, thus making it difficult to determine molecular division systems and standard treatment modalities. Limited cohorts from South Korea, Singapore, Australia, and Japan have been studied; however, the mutational landscape of gastric adenocarcinomas in Chinese patients is still unknown.

Methods: We performed a targeted sequencing panel focusing on cancer-related genes and tumor-associated microorganisms of 529 gastric adenocarcinoma samples with matched blood controls. We identified 449 clinically relevant gene mutations.

Results: Approximately 47.1% of Chinese patients with GC harbored at least one actionable mutation. The top somatic mutations were TP53, ARID1A, LRP1B, PIK3CA, ERBB2, CDH1, KRAS, FAT4, CCNE1, and KMT2D. Truncation mutations of ARID1A, KMT2D, RNF43, TGFBR2, and CIC occurred in patients with high tumor mutational burden. Gene amplifications of ERBB2, CCNE1, CDK12, and CCND1 were detected in patients with low tumor mutational burden. Pathway analysis revealed common gene alterations in the Wnt and PI3K/Akt signaling pathways. The ratio of patients with high microsatellite instability was significantly lower than other cohorts, and high microsatellite instability and Epstein-Barr virus (EBV)-positive features seemed mutually inclusive in Chinese patients with GC. In 44 (8.3%) patients, 45 germline mutations were identified, among which SPINK1 mutations, all SPINK1 c.194 + 2T > C, were present in 15.9% (7/44) of patients. Microorganisms found in Chinese patients with GC included Helicobacter pylori, EBV, hepatitis B virus, and human papillomavirus types 16 and 18.

Conclusion: Identification of varied molecular features by targeted next-generation sequencing provides more insight into patient stratification and offers more possibilities for both targeted therapies and immunotherapies of Chinese patients with GC.

Implications For Practice: This study investigated the genomic alteration profile of 529 Chinese patients with gastric adenocarcinoma by deep targeting sequencing, which might be the largest Chinese cohort on the genomic research of gastric adenocarcinoma up to now.
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http://dx.doi.org/10.1002/onco.13695DOI Listing
January 2021

Study on the Kinetic Process of Asphaltene Precipitation during Crude Oil Mixing and Its Effect on the Wax Behavior of Crude Oil.

ACS Omega 2021 Jan 7;6(2):1497-1504. Epub 2021 Jan 7.

Jiangsu Key Laboratory of Oil and Gas Storage & Transportation Technology, Changzhou University, Changzhou 213164, Jiangsu, China.

As an important component of crude oil, asphaltene precipitation and deposition are harmful to petroleum production and processing. In previous research, the impacts of asphaltene precipitation on crude oil characteristics were preliminarily explored. In this paper, by mixing different types of crude oil, the dynamic process of asphaltene precipitation and its effect on the crystallization and gelation behaviors of mixed crude oil were in-depth analyzed and discussed using the high-speed centrifugation technique, microscopic observation, differential scanning calorimetry (DSC) thermal analysis, and rheological test. The results showed that the asphaltene precipitation mainly occurred in the early stage of crude oil mixing and was influenced by crude oil composition. As the precipitation time increased, the driving force for asphaltene precipitation was gradually weakened until a dynamic equilibrium between asphaltene precipitation and dissolution was reached. Meanwhile, once the asphaltene precipitation occurred, the crystallization and gelation processes of crude oil were significantly affected. It was discovered that the change in the existing state of asphaltenes due to their precipitation is an important factor affecting the interaction of asphaltenes and waxes, which is critical for the technological development of oil and gas flow assurance.
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http://dx.doi.org/10.1021/acsomega.0c05121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818607PMC
January 2021

The value of virtual bronchoscopic navigation and radial endobronchial ultrasound-guided transbronchial lung cryobiopsies for pulmonary lymphangitic carcinomatosis.

J Thorac Dis 2020 Dec;12(12):7666-7674

Department of Pulmonary and Critical Care Medicine, Yantai Yuhuangding Hospital, Yantai, China.

Background: Pulmonary lymphangitic carcinomatosis (PLC) is characterized by malignant infiltration into lung lymphatic channels from a primary site and is often observed in advanced malignant tumors. This study aimed to evaluate the diagnostic yield of transbronchial lung cryobiopsy in PLC guided by radial endobronchial ultrasound and virtual bronchoscopic navigation (VBN).

Methods: This prospective study enrolled 40 patients with clinical and radiologic features indicating PLC. The radial endobronchial ultrasound probe was initially advanced to the region of interest of the desired lobe near the pleura with guidance by VBN. Transbronchial lung biopsy and transbronchial lung cryobiopsy were both performed in the same ROI of all patients with the obtained samples being sent to the pathology laboratory for diagnostic analysis. Procedural complications were recorded.

Results: The average number of transbronchial lung biopsy and transbronchial lung cryobiopsy specimens were 4 (3 to 6) and 2 (1 to 3), respectively (t=10.43, P<0.01), with the corresponding mean diameters per biopsy being 3.7 and 8.7 mm (t=12.37, P<0.01). The diagnostic yields of transbronchial lung biopsy and transbronchial lung cryobiopsy were 70% (28/40) and 92.5% (37/40), respectively. The final positive predictive values of transbronchial lung cryobiopsy and transbronchial lung biopsy for PLC were 94.4% (34/36) and 77.8% (28/36), respectively (χ=23.94, P<0.01). Further, 52.2% (12/23) and 81.5% (22/27) of the patients in the transbronchial lung biopsy and transbronchial lung cryobiopsy groups, respectively, were diagnosed with non-small lung cancer after further molecular analysis (χ=19.56, P<0.01). Only 2 (5%) cases presented postoperative pneumothorax. Moreover, 0 (0%), 3 (7.5%), and 17 (42.5%) patients presented severe, moderate, and mild bleeding, respectively. There were no other adverse events or deaths.

Conclusions: Transbronchial lung cryobiopsy with the guidance of radial endobronchial ultrasound and VBN without fluoroscopy has a good diagnostic yield for PLC; moreover, it allows one to obtain adequate and intact tissue samples for further molecular analysis.
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http://dx.doi.org/10.21037/jtd-2020-abpd-002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797829PMC
December 2020

Adjuvant albumin-bound paclitaxel combined with S-1 vs. oxaliplatin combined with capecitabine after D2 gastrectomy in patients with stage III gastric adenocarcinoma: a phase III multicenter, open-label, randomized controlled clinical trial protocol.

BMC Cancer 2021 Jan 12;21(1):56. Epub 2021 Jan 12.

Department of Abdominal Surgery, Zhejiang Cancer Hospital (University of Chinese Academy of Sciences Cancer Hospital), Zhejiang, China.

Background: Surgery is the only treatment option for operable gastric cancer. The CLASSIC and ACTS-GC studies showed that the 5-year overall survival (OS) of patients with stage III gastric cancer undergoing D2 gastrectomy is still very low. Whether adjuvant nanoparticle albumin-bound paclitaxel (nab-paclitaxel) combined chemotherapy is more effective than the XELOX standard adjuvant chemotherapy in patients with stage III gastric cancer has not been confirmed.

Methods: This is a multicenter, open-label, phase III clinical study. In this trial, 616 patients with locally advanced stage III gastric cancer that underwent curative D2 radical surgery and achieved R0 are planned to be included. Patients will be randomized 1:1 to nab-paclitaxel combined with S-1 (AS) vs. oxaliplatin combined with capecitabine (XELOX). XELOX group: Patients assigned to the XELOX group received eight 3-week cycles of oral capecitabine (1000 mg/m) twice daily on days 1-14 of each cycle plus intravenous oxaliplatin 130 mg/m on day 1 of each cycle. AS group: AS group received eight 3-week cycles of oral S-1 (80-120 mg) (< 1.25 m, 40 mg; 1.25 to < 1.5 m, 50 mg; and > 1.5 m, 60 mg) twice daily on days 1-14 plus intravenous nab-paclitaxel 120 mg/m on days 1 and 8 of each cycle. The primary endpoint was the 3-year disease-free survival (3-year-DFS) defined as the time from randomisation to the time of recurrence of the original gastric cancer, development of a new gastric cancer, or death from any cause. The secondary endpoints were the overall survival, (defined as the time from the date of randomisation to date of death from any cause) and safety (any adverse event).

Discussion: Compared with previous studies, this study includes nab-paclitaxel based on S-1 adjuvant chemotherapy, which is expected to achieve better efficacy and lower toxicity than the standard treatment. This study is the first clinical study to evaluate the safety and efficacy of nab-paclitaxel combined with S-1 in patients with stage III gastric cancer after D2 radical resection.

Trial Registration: This clinical trial has been registered with ClinicalTrials.gov, registration number: NCT04135781 , on October 20th, 2019.
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http://dx.doi.org/10.1186/s12885-020-07772-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802165PMC
January 2021

Demethoxycucumin protects MDA-MB-231 cells induced bone destruction through JNK and ERK pathways inhibition.

Cancer Chemother Pharmacol 2021 Apr 5;87(4):487-499. Epub 2021 Jan 5.

Suzhou TCM Hospital, Affiliated to Nanjing University of Chinese Medicine, , Nanjing, China.

Bone is the most common late metastasis of breast cancer. Bone metastasis causes not only severe bone pain, but also bone-related diseases such as pathological fractures, which are closely related to osteoclasts. The effects of demethoxycurcumin (DMC) on osteoclast biology has not been investigated. In this study, we explored the effects of DMC on MDA-MB-231 cells, MCF-7 cells, and osteoclasts induced by RANKL in vitro, as well as the protective effect on bone destruction of tumor bone metastasis in vivo. DMC showed inhibitory effect on the migration and promotes the apoptosis of MDA-MB-231 and MCF-7 cells. At the same time, DMC inhibited osteoclast maturation and mature osteoclast bone resorption in a dose-dependent manner, and suppressed the expression of osteoclast marker genes TRAP, CTSK, MMP9, V-ATPase-d2 and DC-STAMP significantly. Biochemical data showed that DMC inhibited tumor cells and osteoclasts by inhibiting the early activation of ERK and JNK MAPK pathway. Consistent with the results in vitro, we confirmed that DMC protects bone destruction caused by tumor metastasis in vivo. In short, our study confirmed that DMC could be used as a potential drug for the treatment of tumor bone destruction.
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http://dx.doi.org/10.1007/s00280-020-04198-7DOI Listing
April 2021

Study on the Operation Safety and Reliability of a Waxy Hot Oil Pipeline with Low Throughput Using the Probabilistic Method.

ACS Omega 2020 Dec 16;5(51):33340-33346. Epub 2020 Dec 16.

Jiangsu Key Laboratory of Oil and Gas Storage & Transportation Technology, Changzhou University, Changzhou, Jiangsu 213164, China.

When the hot oil pipeline is running at a low throughput, it easily enters into an unstable condition, which seriously threatens the safety of the hot oil pipeline operation. In this study, the unsteady heat transfer and flow mathematical models for the hot oil pipeline system were established first by comprehensively considering the uncertainty of parameters during pipeline operation, such as the operating parameters (throughput and oil temperature), physical properties of crude oil (freezing point, viscosity, and thixotropic parameters), and environmental parameters (buried deep soil temperature and soil thermal conductivity). Then, the efficient Latin hypercube sampling (LHS) stochastic numerical algorithm was applied and further developed to quantitatively describe the operation safety of hot oil pipelines with low throughput in the form of probability. On the basis of the abovementioned research, the qualitative relationship between pipeline flowrate and friction loss is obtained. Finally, taking an actual crude oil pipeline as an example, the failure probabilities of the pipeline under different operating conditions were analyzed in detail. Combined with the target safety level of pipeline operation, the minimum allowable throughput of pipelines was determined. This study revealed the flow and heat transfer law of hot oil pipelines with low throughput and determined its operation safety and reliability under different operating conditions.
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http://dx.doi.org/10.1021/acsomega.0c05140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774277PMC
December 2020

Study of the Comprehensive Kinetic Model of Natural Gas Hydrate Formation in a Water-in-Oil Emulsion Flow System.

ACS Omega 2020 Dec 17;5(51):33101-33112. Epub 2020 Dec 17.

Department of Fuel, Army Logistics University of PLA, Chongqing 401311, People's Republic of China.

Hydrate growth is influenced by many factors, including thermodynamics, kinetics, mass and heat transfer, and so on. There is thus a practical significance in establishing a model that comprehensively considers these influencing factors for hydrate crystal growth in multiphase transportation pipelines. On this basis, this paper presents a more practical and comprehensive bidirectional growth model of hydrate shells for an actual pipeline system. Thermodynamic phase equilibrium theory and water molecule penetration theory are applied in this model to develop a method for calculating the concentration change of hydrate-forming guest molecules and the permeation rate of water molecules. The temperatures on both sides of the hydrate shell are predicted by the heat transfer model. Simultaneously, decreasing the mass transfer coefficient with continuous hydrate growth is used to describe the problem in which the mass transfer efficiency decreases with a thickened hydrate shell. Then, the hydrate growth kinetic parameters of the pipeline system are optimized according to hydrate growth experiments conducted in a high-pressure flow loop and the microscopic characteristics of the particles were provided using the PVM and FBRM probes. The improved hydrate growth model can improve the prediction accuracy of hydrate formation in slurry systems.
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http://dx.doi.org/10.1021/acsomega.0c04708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774284PMC
December 2020

Bisphenol F induces nonalcoholic fatty liver disease-like changes: Involvement of lysosome disorder in lipid droplet deposition.

Environ Pollut 2021 Feb 22;271:116304. Epub 2020 Dec 22.

Department of Hygienic Analysis and Detection, Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, NanjingMedical University, Nanjing, China. Electronic address:

Epidemiological studies have demonstrated that the general population's exposure to bisphenol A (BPA) substitutes is ubiquitous. Bisphenol F (BPF), one of the main BPA substitutes, is increasingly replacing BPA in plastics for food and beverage applications. Accumulating evidence suggests that BPA exposure is associated with nonalcoholic fatty liver disease (NAFLD)-like changes. However, the potential effects of BPF on lipid homeostasis remain poorly understood. In the present study, an epidemiological analysis with LC-MS-MS revealed that the BPF concentrations in the serum of NAFLD patients were significantly higher than those in a control group. Supporting this result, using Oil Red O, BODIPY 493/503, LipidTox Deep Red staining and gas chromatography-time-of-flight mass spectrometry (TOF-MS) assays, we found that BPF exposure induced NAFLD-like changes, with obvious lipid droplet deposition, triglyceride (TG) and fatty acids increase in mouse livers. Meanwhile, lipid droplet deposition and TG increase induced by BPF were also observed in HepG2 cells, accompanied by autophagic flux blockade, including autophagosome accumulation and the decreased degradation of SQSTM1/p62. Using adenoviruses dual-reporter plasmid RFP-GFP-LC3, RFP-GFP-PLIN2 transfection, AO staining, and EGFR degradation assays, we demonstrated that BPF treatment impaired lysosomal degradative capacity, since BPF treatment obviously impaired lysosomal acidification, manifested as decreased lysosomal hydrolase cathepsin L (CTSL) and mature cathepsin D (CTSD) in HepG2 and mouse liver issues. Additionally, v-ATPase D, a multi-subunit enzyme that mediates acidification of eukaryotic intracellular organelles, significantly decreased after BPF exposure in both the vitro and in vivo studies. This study ascertained a novel mechanism involving dysfunctional of lysosomal degradative capacity induced by BPF, which contributes to lipophagic disorders and causes lipid droplet deposition. This work provides evidence that lysosomes may be a target organelle where BPF exerts its potential toxicity; therefore, novel intervention strategies targeting lysosome are promising for BPF-induced NAFLD-like changes.
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http://dx.doi.org/10.1016/j.envpol.2020.116304DOI Listing
February 2021

Accuracy improvement of time-of-flight depth measurement by combination of a high-resolution color camera.

Appl Opt 2020 Dec;59(35):11104-11111

Time-of-flight (ToF) cameras can acquire the distance between the sensor and objects with high frame rates, offering bright prospects for ToF cameras in many applications. Low-resolution and depth errors limit the accuracy of ToF cameras, however. In this paper, we present a flexible accuracy improvement method for depth compensation and feature points position correction of ToF cameras. First, a distance-error model of each pixel in the depth image is established to model sinusoidal waves of ToF cameras and compensate for the measured depth data. Second, a more accurate feature point position is estimated with the aid of a high-resolution camera. Experiments evaluate the proposed method, and the result shows the root mean square error is reduced from 4.38 mm to 3.57 mm.
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http://dx.doi.org/10.1364/AO.405703DOI Listing
December 2020

Identification of the Cleavage Domain within Glycoprotein G of Herpes Simplex Virus Type 2.

Viruses 2020 12 12;12(12). Epub 2020 Dec 12.

Institute of Virology, Hannover Medical School, 30625 Hannover, Germany.

Glycoprotein G (gG) from herpes simplex virus type 1 and 2 (HSV-1 and HSV-2, respectively) functions as a viral chemokine binding protein (vCKBP). Soluble recombinant forms of gG of HSV-1 and HSV-2 (SgG1 and SgG2, respectively) enhance chemokine-mediated leukocyte migration, in contrast to most known vCKBPs, including those from animal alpha-herpesviruses. Furthermore, both proteins bind to nerve growth factor (NGF), but only SgG2 enhances NGF-dependent neurite outgrowth. The basis and implications of this functional difference between the two proteins are still unknown. While gG1 and gG2 are positional homologues in the genome, they share very limited sequence homology. In fact, , the open reading frame encoding gG is the most divergent genetic locus between these viruses. Full-length gG1 and gG2 are type I transmembrane proteins located on the plasma membrane of infected cells and at the viral envelope. However, gG2 is larger than gG1 and is cleaved during protein maturation, secreting the N-terminal domain to the supernatant of infected cells, whereas gG1 is not. The enzyme involved in gG2 cleavage and the functional relevance of gG2 cleavage and secretion are unknown. We aim to identify the gG2 sequence required for cleavage to determine its functional role in future experiments. Our results prove the existence of at least two cleavage motifs in gG2 within the amino acid region 314-343. Transfer of this sequence to a fusion protein results in cleavage. Finally, we show that propeptide convertases like furin are responsible for gG2 cleavage.
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http://dx.doi.org/10.3390/v12121428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763493PMC
December 2020

Neoadjuvant systemic and hyperthermic intraperitoneal chemotherapy combined with cytoreductive surgery for gastric cancer patients with limited peritoneal metastasis: a prospective cohort study.

BMC Cancer 2020 Nov 16;20(1):1108. Epub 2020 Nov 16.

Department of Gastric Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, China.

Background: There is no currently available treatment for peritoneal metastasis of gastric cancer. This phase II study aimed to evaluate the efficacy and safety of neoadjuvant systemic chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) for the treatment of these patients.

Methods: Neoadjuvant chemotherapy comprised two cycles of HIPEC and four cycles of S-1 plus paclitaxel. HIPEC was administered intraperitoneally with paclitaxel (75 mg/m). For systemic chemotherapy, paclitaxel was administered intravenously(150 mg/m) on day 1, and S-1 was administered orally(80 mg/m/day)on days 1-14 of a 3-week cycle. Another two cycles of HIPEC and four cycles of S-1 plus paclitaxel were administered after second diagnostic staging laparoscopy or CRS. The primary endpoints were treatment efficiency and safety; the secondary endpoint was 3-year overall survival (OS).

Results: A total of 40 patients were enrolled and 38 patients have been analyzed. Of these, 18 (47.4%) patients received neoadjuvant systemic chemotherapy, HIPEC and CRS (conversion therapy group), while 20 patients received only chemotherapy and HIPEC (palliative chemotherapy group). Median OS was markedly improved in the conversion therapy group (21.1 months, 95% confidence interval [CI] 16.7-25.6 months) in comparison with the palliative chemotherapy group(10.8 months, 95%CI 7.3-14.2 months, p = 0.002). After neoadjuvant systemic chemotherapy and HIPEC, a second laparoscopic exploration was performed, and the prognosis of patients with low peritoneal cancer index (PCI) (PCI < 6) was significantly better than that of patients with high PCI (PCI ≥ 6)(20.1 vs.11.3 months, p = 0.006).

Conclusion: Neoadjuvant systemic chemotherapy and HIPEC combined with CRS is safe and feasible, and could potentially improve the prognosis of gastric cancer patients with limited peritoneal metastasis. However, further clinical trials are still warranted.

Trial Registration: This study has been registered with ClinicalTrials.gov as NCT02549911 . Trial registration date: 15/09/2015.
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http://dx.doi.org/10.1186/s12885-020-07601-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667754PMC
November 2020

Assessment and molecular characterization of Bacillus cereus isolated from edible fungi in China.

BMC Microbiol 2020 10 14;20(1):310. Epub 2020 Oct 14.

Guangdong Institute of Microbiology, Guangdong Academy of Science, State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Safety and Health, Guangdong Open Laboratory of Applied Microbiology, Xianlie Zhong Road 100#, 58th Building, Guangzhou, 510070, China.

Background: Bacillus cereus is a foodborne pathogen commonly found in nature and food and can cause food spoilage and health issues. Although the prevalence of B. cereus in foods has been reported worldwide, the extent of contamination in edible fungi, which has become increasingly popular as traditional or functional food, is largely unknown. Here we investigated the prevalence, toxin genes' distribution, antibiotic resistance, and genetic diversity of B. cereus isolated from edible fungi in China.

Results: Six hundred and ninety-nine edible fungi samples were collected across China, with 198 (28.3%) samples found to be contaminated by B. cereus, with an average contamination level of 55.4 most probable number (MPN)/g. Two hundred and forty-seven B. cereus strains were isolated from the contaminated samples. Seven enterotoxin genes and one cereulide synthetase gene were detected. The detection frequencies of all enterotoxin genes were ≥ 80%, whereas the positive rate of the cesB gene in B. cereus was 3%. Most isolates were resistant to penicillins, β-lactam/β-lactamase inhibitor combinations, cephems, and ansamycins, but were susceptible to penems, aminoglycosides, macrolides, ketolide, glycopeptides, quinolones, phenylpropanol, tetracyclines, lincosamides, streptogramins, and nitrofurans. Meanwhile, 99.6% of all isolates displayed multiple antimicrobial resistance to three or more classes of antimicrobials. Using genetic diversity analysis, all isolates were defined in 171 sequence types (STs), of which 83 isolates were assigned to 78 new STs.

Conclusions: This study provides large-scale insight into the prevalence and potential risk of B. cereus in edible fungi in China. Approximately one-third of the samples were contaminated with B. cereus, and almost all isolates showed multiple antimicrobial resistance. Detection frequencies of all seven enterotoxin genes were equal to or more than 80%. These new findings may indicate a need for proper pre-/post-processing of edible fungi to eliminate B. cereus, thereby preventing the potential risk to public health.
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http://dx.doi.org/10.1186/s12866-020-01996-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557095PMC
October 2020

Beware Pathological Findings of the Stomach in Patients Undergoing Bariatric Surgery: a Systematic Review and Meta-analysis.

Obes Surg 2021 Jan 12;31(1):337-342. Epub 2020 Oct 12.

Department of Gastrointestinal Surgery, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Changlexi St. 127#, Xi'An City, Shaanxi Province, China.

Abnormal anatomic findings are a major concern before performing bariatric surgery, while pathological changes are considered less often. The present study aimed to investigate the incidences of gastric lesions warranting follow-up in patients undergoing bariatric surgery. Meta-analyses were conducted to calculate the pooled incidences of gastric lesions in patients undergoing bariatric surgery. Fifty-nine studies including 32,789 patients were included: 26 on endoscopic biopsy, 26 on pathological findings of the excised specimen, five on the intraoperative exploration results, and two on both preoperative endoscopy and postoperative specimen. Generally, atrophic gastritis (3.05% (95% CI (confidence interval) 1.53-6.09)), intestinal metaplasia (2.44% (95% CI 1.76-3.25)), and GIST (gastrointestinal stromal tumor) (0.45% (95% CI 0.31-0.60)) were not rarely found. Routine preoperative endoscopy was applied in 16 studies, and the pooled incidences of atrophic gastritis and intestinal metaplasia were 2.64% (95% CI 0.78-8.9) and 2.70% (95% CI 0.9-5.42), respectively. Hp. (Helicobacter pylori) screening and eradication were routinely performed in 10 studies, and that was related to a reduced incidence of atrophic gastritis (0.94% (95% CI 0.03-2.92)) vs. 4.31% (95% CI 2.01-9.23). GIST was more likely to be found by intraoperative exploration than by preoperative endoscopy (0.68% (95% CI 0.50-0.93) vs. 0.23% (95% CI 0.11-0.52)). Patients undergoing bariatric surgery demonstrated non-negligible incidences of gastric pathologies warranting follow-up. Preoperative endoscopy and careful intraoperative exploration should be routinely performed, and Hp. screening and eradication are suggested before endoscopy. In condition that such findings are detected, sleeve gastrectomy may be preferred over Roux-en-Y gastric bypass.
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http://dx.doi.org/10.1007/s11695-020-05029-7DOI Listing
January 2021

Persisting volcanic ash particles impact stratospheric SO lifetime and aerosol optical properties.

Nat Commun 2020 Sep 10;11(1):4526. Epub 2020 Sep 10.

Stratton Park Engineering Company, Inc, Bo ulder, CO, 80301, USA.

Volcanic ash is often neglected in climate simulations because ash particles are assumed to have a short atmospheric lifetime, and to not participate in sulfur chemistry. After the Mt. Kelut eruption in 2014, stratospheric ash-rich aerosols were observed for months. Here we show that the persistence of super-micron ash is consistent with a density near 0.5 g cm, close to pumice. Ash-rich particles dominate the volcanic cloud optical properties for the first 60 days. We also find that the initial SO lifetime is determined by SO uptake on ash, rather than by reaction with OH as commonly assumed. About 43% more volcanic sulfur is removed from the stratosphere in 2 months with the SO heterogeneous chemistry on ash particles than without. This research suggests the need for re-evaluation of factors controlling SO lifetime in climate model simulations, and of the impact of volcanic ash on stratospheric chemistry and radiation.
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http://dx.doi.org/10.1038/s41467-020-18352-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483524PMC
September 2020

Treatment of Synchronous Liver Metastases from Gastric Cancer: A Single-Center Study.

Cancer Manag Res 2020 26;12:7905-7911. Epub 2020 Aug 26.

Department of Gastric Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou 310022, People's Republic of China.

Objective: The therapeutic effects of surgical resection in gastric cancer with liver metastasis remain largely unclear. We sought to examine surgical resection combined with chemotherapy for survival benefit in cases of synchronous liver metastases from gastric cancer (LMGC), and to identify factors affecting patient prognosis.

Methods: Patients diagnosed with synchronous LMGC between January 2010 and December 2015 were enrolled in this study. The effects of gastrectomy and metastasectomy combined with chemotherapy (surgical resection group) and palliative chemotherapy (palliative chemotherapy group) on survival were comparatively assessed.

Results: Of the 132 included cases, 57 (43.2%) and 75 (56.8%) were treated with surgical resection/chemotherapy and palliative chemotherapy, respectively. Overall survival (OS) was markedly prolonged in the surgical resection group compared with the palliative chemotherapy group (33.6 vs 12.4 months, <0.001). In patients who underwent surgical resection, R0 resection resulted in prolonged OS in comparison with the non-R0 resection subgroup (45.1 vs 13.5 months, <0.001). Surgical resection (hazard ratio [HR]=0.453; 95% confidence interval [CI] 0.276-0.813; =0.009) and solitary liver metastasis (HR=0.540; 95% CI 0.315-0.796; =0.043) were independent predictors of OS.

Conclusion: Patients with synchronous LMGC might benefit from radical surgical resection combined with appropriate chemotherapy. Additional well-designed prospective studies are required to verify the above findings.
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http://dx.doi.org/10.2147/CMAR.S261353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457594PMC
August 2020

Computer-Aided Diagnosis Systems in Diagnosing Malignant Thyroid Nodules on Ultrasonography: A Systematic Review and Meta-Analysis.

Eur Thyroid J 2020 Jul 4;9(4):186-193. Epub 2019 Dec 4.

Key Laboratory of Biomedical Information Engineering of the Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.

Background: Computer-aided diagnosis (CAD) systems are being applied to the ultrasonographic diagnosis of malignant thyroid nodules, but it remains controversial whether the systems add any accuracy for radiologists.

Objective: To determine the accuracy of CAD systems in diagnosing malignant thyroid nodules.

Methods: PubMed, EMBASE, and the Cochrane Library were searched for studies on the diagnostic performance of CAD systems. The diagnostic performance was assessed by pooled sensitivity and specificity, and their accuracy was compared with that of radiologists. The present systematic review was registered in PROSPERO (CRD42019134460).

Results: Nineteen studies with 4,781 thyroid nodules were included. Both the classic machine learning- and the deep learning-based CAD system had good performance in diagnosing malignant thyroid nodules (classic machine learning: sensitivity 0.86 [95% CI 0.79-0.92], specificity 0.85 [95% CI 0.77-0.91], diagnostic odds ratio (DOR) 37.41 [95% CI 24.91-56.20]; deep learning: sensitivity 0.89 [95% CI 0.81-0.93], specificity 0.84 [95% CI 0.75-0.90], DOR 40.87 [95% CI 18.13-92.13]). The diagnostic performance of the deep learning-based CAD system was comparable to that of the radiologists (sensitivity 0.87 [95% CI 0.78-0.93] vs. 0.87 [95% CI 0.85-0.89], specificity 0.85 [95% CI 0.76-0.91] vs. 0.87 [95% CI 0.81-0.91], DOR 40.12 [95% CI 15.58-103.33] vs. DOR 44.88 [95% CI 30.71-65.57]).

Conclusions: The CAD systems demonstrated good performance in diagnosing malignant thyroid nodules. However, experienced radiologists may still have an advantage over CAD systems during real-time diagnosis.
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http://dx.doi.org/10.1159/000504390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445671PMC
July 2020

An integrated data filtering and identification strategy for rapid profiling of chemical constituents, with Arnebiae Radix as an example.

J Chromatogr A 2020 Oct 18;1629:461496. Epub 2020 Aug 18.

Expermiental Centre, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China; Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China; Shandong Provincial Key Laboratory of Traditional Chinese Medicine for Basic research, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China. Electronic address:

Profiling the chemical components of complicated herbal extracts using traditional analytical methods is time-consuming and laborious. In this study, an integrated data filtering and identification strategy was developed to efficiently identify the chemical constituents in Arnebiae Radix. The post-acquisition data processing steps with this strategy were as follows: (1) data acquisition by ultra-high performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap-MS); (2) background subtraction on the basis of the total ion chromatogram (TIC) to obtain the background-subtracted ion chromatogram; (3) construction of a diagnostic ion database based on the measured MS/MS fragment ions of reference standards and auxiliary diagnostic information according to literatures; (4) mass defect filtering (MDF) to filter the background-subtracted ion chromatogram; and (5) rapid structural identification in the MDF-processed ion chromatogram on the basis of the diagnostic ion database and further structural confirmation by analysing the retention time, fragment behaviour, and online databases (Chemspider, PubChem, and SciFinder). In this study, the herbal medicine Arnebiae Radix was used to illustrate this strategy. A total of 96 compounds were efficiently exposed and characterized from Arnebiae Radix samples obtained from 20 sources, and 13 of these compounds were confirmed by comparison with the reference standards. Thirty components with a low abundance, that remained undetected in the TIC, were identified in the MDF-processed ion chromatogram. Nine of these compounds had not been identified from Arnebiae Radix previously, and were tentatively screened as unknowns. The chemical components in traditional Chinese medicine preparations are considered to be the material basis for the effectiveness of this medical system, and are closely related to the pharmacological activities of the drugs. The pharmacodynamics of these drugs are known to be influenced by the synergistic effects of various components. Therefore, comprehensive profiling of the chemical compositions of herbal extracts is essential for systematic elucidation of the pharmacodynamics of these medicines.
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http://dx.doi.org/10.1016/j.chroma.2020.461496DOI Listing
October 2020

Prevalence, Virulence Feature, Antibiotic Resistance and MLST Typing of Isolated From Retail Aquatic Products in China.

Front Microbiol 2020 3;11:1513. Epub 2020 Jul 3.

Department of Food Science and Technology, Institute of Food Safety and Nutrition, Jinan University, Guangzhou, China.

is one of the most important foodborne pathogenic microorganisms, which can lead to gastrointestinal and non-gastrointestinal diseases. However, the potential risk of in aquatic products in China has not been comprehensively evaluated yet. In this study, a total of 860 aquatic samples from three types of retail aquatic products were collected from 39 major cities in China from 2011 to 2016. The contamination, distribution of virulence genes, antibiotic resistance and genetic diversity of isolates were measured and analyzed. Of all the samples, 219 (25.47%) were positive for and 1.83% (4/219) of the samples had contamination levels of more than 1,100 most probable number (MPN)/g. Different isolates had virulence potential, within which 59.6% (164/275) contained all three kinds of enterotoxin genes (, , and ) and 5.1% (14/275) possessed cereulide encoding gene . The antimicrobial resistance profiles revealed the universal antibiotic resistance to rifampin and most β-lactams, suggesting the necessity to continuously monitor the antibiotic resistance of in aquatic products and to control drug use in aquaculture. In sum, our study indicates the potential hazards of isolated from aquatic products to customers and may provide a reference for clinical treatment caused by .
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http://dx.doi.org/10.3389/fmicb.2020.01513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347965PMC
July 2020

High Expression of the SH3TC2-DT/SH3TC2 Gene Pair Associated With FLT3 Mutation and Poor Survival in Acute Myeloid Leukemia: An Integrated TCGA Analysis.

Front Oncol 2020 19;10:829. Epub 2020 Jun 19.

Department of Hematology, Shanghai General Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.

Fms-like tyrosine kinase 3 (FLT3) mutation is one of the most common mutations in acute myeloid leukemia (AML). However, the effect of FLT3 mutation on survival is currently still controversial and the leukemogenic mechanisms are still under further investigation. The aim of our study is to identify differentially expressed genes (DEGs) in FLT3-mutant AML and to find crucial DEGs whose expression level is related to prognosis for further analysis. By mining the TCGA-LAML dataset, 619 differentially expressed lncRNAs (DElncRNAs) and 1,428 differentially expressed mRNAs (DEmRNAs) were identified between FLT3-mutant and FLT3-wildtype samples. Through weighted gene correlation network analysis (WGCNA) and the following Cox proportional hazards regression analysis, we constructed the prognostic risk models to identify the hub DElncRNAs and DEmRNAs associated with AML prognosis. The presence of both SH3TC2 divergent transcript (SH3TC2-DT) and SH3TC2 in respective prognostic risk models promotes us to further study the significance of this gene pair in AML. SH3TC2-DT and SH3TC2 were identified to be coordinately high expressed in FLT3-mutant AML samples. High expression of this gene pair was associated with poor survival. Using logistic regression analysis, we found that high SH3TC2-DT/SH3TC2 expression was associated with FLT3 mutation, high WBC count, and intermediate cytogenetic and molecular-genetic risk. AML with SH3TC2-DT/SH3TC2 high expression showed enrichment of transcripts associated with stemness, quiescence, and leukemogenesis. Our study suggests that the SH3TC2-DT/SH3TC2 gene pair may be a possible biomarker to further optimize AML prognosis and may function in stemness or quiescence of FLT3-mutant leukemic stem cells (LSCs).
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http://dx.doi.org/10.3389/fonc.2020.00829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318790PMC
June 2020

Clinical research for whether the Traditional Chinese medicine could promote the resorption of lumbar disc herniation: a randomized controlled trial.

Medicine (Baltimore) 2020 Jul;99(27):e21069

Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai.

Lumbar disc herniation (LDH) is a common, disabling musculoskeletal disorder. Magnetic resonance imaging has clarified the natural history of lumbar disc lesions and has documented that disc lesions can become smaller and can even be completely resorbed. Previous studies have confirmed that some traditional Chinese medicine (TCM) therapies can promote resorption of the protrusion. However, high-quality research evidence is needed to support the effectiveness of the protocol.

Objective: This clinical trial aims to establish whether TCM can promote the resorption of LDH and to assess the efficacy of such therapy for LDH, thereby evaluating its clinical effect.

Methods: The present study design is for a single-center, 2-arm, open-label randomized controlled trial. A total of 150 eligible LDH patients will be randomly assigned to either a TCM treatment group or a control group in a 1:1 ratio. Patients in the TCM group will be administered a TCM decoction for 4 weeks. Patients in the conventional drug control group will be instructed to take a specific daily dose of celecoxib. The primary outcome measure is the change from baseline in the volume of the protrusion, as assessed using MR images. Secondary outcome measures include visual analog scale pain scores and Japanese Orthopaedic Association scores assessed at 3 and 6 months.

Discussion: The design and methodological rigor of this trial will allow evaluation of the basic clinical efficacy and safety data for TCM in the treatment of patients with LDH. The trial will also assess whether TCM can promote the resorption of LDH. This research will therefore help provide a solid foundation for the clinical treatment of LDH and for future research in TCM therapy.

Trial Registration: ChiCTR1900022377.
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http://dx.doi.org/10.1097/MD.0000000000021069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337462PMC
July 2020

Corrigendum: Isolated From Vegetables in China: Incidence, Genetic Diversity, Virulence Genes, and Antimicrobial Resistance.

Front Microbiol 2020 29;11:848. Epub 2020 Apr 29.

Department of Food Science and Technology, Institute of Food Safety and Nutrition, Jinan University, Guangzhou, China.

[This corrects the article DOI: 10.3389/fmicb.2019.00948.].
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http://dx.doi.org/10.3389/fmicb.2020.00848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212377PMC
April 2020

Malignant cell-specific pro-tumorigenic role of type I interferon receptor in breast cancers.

Cancer Biol Ther 2020 07 7;21(7):629-636. Epub 2020 May 7.

Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA, USA.

Within the microenvironment of solid tumors, stress associated with deficit of nutrients and oxygen as well as tumor-derived factors triggers the phosphorylation-dependent degradation of the IFNAR1 chain of type I interferon (IFN1) receptor and ensuing suppression of the IFN1 pathway. Here we sought to examine the importance of these events in malignant mammary cells. Expression of non-degradable IFNAR1 mutant in mouse mammary adenocarcinoma cells stimulated the IFN1 pathway yet did not affect growth of these cells in vitro or ability to form subcutaneous tumors in the syngeneic mice. Remarkably, these cells exhibited a notably accelerated growth when transplanted orthotopically into mammary glands. Importantly, in human patients with either ER+ or ER- breast cancers, high levels of IFNAR1 were associated with poor prognosis. We discuss the putative mechanisms underlying the pro-tumorigenic role of IFNAR1 in malignant breast cells.
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http://dx.doi.org/10.1080/15384047.2020.1750297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515508PMC
July 2020

PCC0208023, a potent SHP2 allosteric inhibitor, imparts an antitumor effect against KRAS mutant colorectal cancer.

Toxicol Appl Pharmacol 2020 07 24;398:115019. Epub 2020 Apr 24.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, PR China. Electronic address:

The non-receptor tyrosine phosphatase SHP2, encoded by PTPN11, plays an indispensable role in tumors driven by oncogenic KRAS mutations, which frequently occur in colorectal cancer. Here, PCC0208023, a potent SHP2 allosteric inhibitor, was synthesized to evaluate its inhibitory effects against the SHP2 enzyme, and the KRAS mutant colorectal cancer in vitro and in vivo, and its impart on the RAS/MAPK pathway. Consistent with an allosteric mode of inhibition, PCC0208023 can non-competitively inhibit the activity of full-length SHP2 enzyme, but lacks activity against the free catalytic domain of SHP2. Furthermore, PCC0208023 inhibited the proliferation of KRAS mutation-driven human colorectal cancer cells by inhibiting the RAS/MAPK signaling pathway in vitro. Importantly, PCC0208023 displayed good anti-tumor efficacy against KRAS-driven LS180 and HCT116 xenograft models in nude mice with the decreased Ki67 and p-ERK level, and increased cleaved caspase-3 expression in tumors. Interestingly, PCC0208023 maintained high levels in LS180 tumors within 24 h after administration and was mainly distributed in both intestines and lungs. Molecular docking studies revealed a higher affinity of PCC0208023 with key residues in the SHP2 allosteric pocket than RMC-4550. PCC0208023 deserves further optimization to identify additional low-toxic and potent SHP2 allosteric inhibitors with novel scaffolds for the treatment of patients with KRAS mutation-positive colorectal cancer.
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http://dx.doi.org/10.1016/j.taap.2020.115019DOI Listing
July 2020

Perinatal exposure to bisphenol A causes a disturbance of neurotransmitter metabolic pathways in female mouse offspring: A focus on the tryptophan and dopamine pathways.

Chemosphere 2020 Sep 9;254:126715. Epub 2020 Apr 9.

Department of Hygienic Analysis and Detection, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, No. 101 Longmian Avenue, Nanjing, 211166, China. Electronic address:

Perinatal exposure to bisphenol A (BPA) contributes to neurological disorders in offspring, but the underlying mechanisms are still poorly understood. The abnormal release of neuroactive metabolites in the tryptophan (TRP) and dopamine (DA) pathways is considered to be closely associated with some disorders. Thus, in this study, TRP and DA pathways in adult female mouse offspring were investigated when the pregnant mice were given either vehicle or BPA (2, 10, or 100 μg/kg/d) from day 6 of gestation until weaning. Then, the serum and brain samples of offspring were collected at 3, 6 and 9 months, and 12 neuroactive metabolites in the TRP and DA pathways were detected. The results showed that, in the TRP pathway, TRP levels decreased, whereas kynurenine (KYN) levels and TRP turnover increased in the brain. In the serum, TRP, KYN and 5-hydroxytryptamine (5-HT) levels decreased significantly. For the DA pathway, DA and DA metabolites, including 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT) and homovanillic acid (HVA), reduced significantly in the brain and serum. DA turnover decreased dramatically in the brain but enhanced in the serum. The disturbance of these two metabolic pathways might be one of the potential mechanisms of BPA-induced neuropsychiatric disorders.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126715DOI Listing
September 2020

Deciphering the Solvent Effect for the Solvation Structure of Ca in Polar Molecular Liquids.

J Phys Chem B 2020 04 9;124(16):3408-3417. Epub 2020 Apr 9.

State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, 865 Changning Road, Shanghai 200050, China.

Although the crystal structures for many inorganic compounds are readily available, researchers are still working hard to understand the relations between the structures and chemical properties of solutions because most of the chemical reactions take place in solutions. A huge amount of effort has been put toward modeling the ion solvation structure from the perspectives of both experiments and theories. In this study, the solvation structures of Ca ions in aqueous and alcoholic solutions at different concentrations were carefully evaluated by Ca K-edge X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) analyses. Density functional theory (DFT) calculations were also performed to correlate the results with the experimental data and then further extended to other similar systems. It was found that the number of coordinating solvent molecules decreases with increasing Ca concentration and increasing solvent molecule sizes. From the EXAFS data, it was observed that the first solvation shell of Ca splits into two Ca-O distances in a methanol solution and the counter ion Cl might also be within the first shell at high concentrations. For the first time, the effects of solvents with different polarities and sizes on the ion solvation environment were systematically evaluated.
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http://dx.doi.org/10.1021/acs.jpcb.0c02437DOI Listing
April 2020

PCC0208025 (BMS202), a small molecule inhibitor of PD-L1, produces an antitumor effect in B16-F10 melanoma-bearing mice.

PLoS One 2020 26;15(3):e0228339. Epub 2020 Mar 26.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, China.

The increased PD-L1 expression induces poorer prognosis in melanoma. The small molecule inhibitors of PD-1/PD-L1 pathways have been an encouraging drug development strategy because of good affinity and oral bioavailability without immunogenicity and immunotoxicities of PD-1/PD-L1 antibodies. In this study, we studied the effects of PCC0208025 (BMS202), a small molecule inhibitor of PD-L1, on PD-1/PD-L1 binding and the cytokines secretion in human CD3+ cells in vitro. We also investigated the antitumor and immunomodulatory activity of PCC0208025 and the pharmacokinetics properties in B16-F10 melanoma-bearing mice. The results showed that PCC0208025 inhibited the PD-1/PD-L1 proteins binding, and rescued PD-L1-mediated inhibition of IFN-γ production in human CD3+ T cells in vitro. Furthermore, in B16-F10 melanoma-bearing mice, PCC0208025 presented the antitumor effects, enhanced IFN-γ levels in plasma, increased the frequency of CD3+CD8+ T and CD8+IFN-γ+ T and the ratios of CD8+/Treg, and deceased the CD4+CD25+CD127low/- (Treg) number in tumor. Pharmacokinetics study found that PCC0208025 was absorbed and distributed into the tumors with much higher concentrations than those of the blockade against PD-1/PD-L1 binding. Our work suggests that PCC0208025 exhibited anti-tumor effects through inhibiting Treg expansion and increasing cytotoxic activity of tumor-infiltrating CD8+ T cells by the blockade of PD-1/PD-L1 binding, which may provide the pharmacological basis to develop small molecule inhibitors of PD-1/PD-L1 binding for PCC0208025 as a lead compound.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228339PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098565PMC
June 2020

Analyses of crystal growth, optical, electrical, thermal and mechanical properties of an excellent detector-grade CdMnTe: V crystal.

Sci Rep 2020 Feb 17;10(1):2749. Epub 2020 Feb 17.

School of Materials Science and Engineering, Chang'an University, Xi'an, Shaanxi, 710064, China.

A high-quality cadmium manganese tellurium (CdMnTe: V or VCMT) crystal was successfully grown via modified Te solution vertical Bridgman method with vanadium doping. The crystal structure and quality were evaluated by powder X-ray diffraction analysis. An infrared transmission spectroscope measured the transmittance of the crystal at 64%, which would suggest that the grown crystal possessed high purity and crystallinity. Ultraviolet-visible-near-infrared spectroscopy analysis obtained the forbidden band width of approximately 1.577 eV. The current-voltage test indicated that the VCMT crystal had a high resistivity of 2.07 × 10 Ω·cm. Mechanical properties were measured by a Vickers microhardness tester. Crack surface morphology around the indentation was recorded. Furthermore, mechanical properties, such as microhardness, fracture toughness, brittleness index and yield strength were investigated and discussed. The thermal stability of the VCMT single crystal was determined by thermogravimetric analysis. A VCMT detector was fabricated with planar configuration structure, which showed a resolution of 11.62% of the Am at 59.5 keV peak.
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http://dx.doi.org/10.1038/s41598-020-59612-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026162PMC
February 2020