Publications by authors named "Xiaofei Zhang"

475 Publications

Noninvasive thyroid histotripsy treatment: proof of concept study in a porcine model.

Int J Hyperthermia 2021 ;38(1):798-804

Department of Radiology, The University of Wisconsin, Madison, WI, USA.

Introduction: This study was performed to determine the feasibility and safety of creating superficial histotripsy treatment in a live porcine thyroid model.

Methods: The porcine thymus comparable in size, shape and location to the human thyroid was used for this study. This model has been used for thyroid surgery studies due to the diminutive size of the porcine thyroid. Four female swine underwent a total of eight histotripsy treatments performed with a prototype therapy system (HistoSonics, Inc., Ann Arbor, MI). Two treatments were performed in each animal: a spherical 1.0 × 1.0 × 1.0 cm and ovoid 1.0 × 1.0 × 2.0 cm treatment zones. MRI immediately post-procedure was evaluated for histotripsy treatment zone size and imaging appearance, followed immediately by sacrifice. Tissue was then reviewed for percent cellular destruction and precision.

Results: Treatment zones measured on post treatment MRI were similar to prescribed volumes (spherical = 0.60 (+/- 0.11) cm, ovoid = 1.23 (+/- 0.40) cm,  > 0.05 vs. prescribed). MRI demonstrated well demarcated treatment zones and imaging findings consistent with cellular destruction. Histology demonstrated sharp transitions to normal tissue (mean 0.33 (+/- 0.13) cm), and high degrees of cellular destruction (mean 76% (+/- 12.5), range of 50-100%) in the treated tissue. Edema within the overlying muscle was seen in 2/8 treatments.

Conclusion: Histotripsy is capable of safely creating precise histotripsy treatments within the superficial neck of a porcine thyroid model without evidence of considerable complications.
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http://dx.doi.org/10.1080/02656736.2021.1922762DOI Listing
July 2021

Single-cell analysis of pancreatic ductal adenocarcinoma identifies a novel fibroblast subtype associated with poor prognosis but better immunotherapy response.

Cell Discov 2021 May 25;7(1):36. Epub 2021 May 25.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

The current pathological and molecular classification of pancreatic ductal adenocarcinoma (PDAC) provides limited guidance for treatment options, especially for immunotherapy. Cancer-associated fibroblasts (CAFs) are major players of desmoplastic stroma in PDAC, modulating tumor progression and therapeutic response. Using single-cell RNA sequencing, we explored the intertumoral heterogeneity among PDAC patients with different degrees of desmoplasia. We found substantial intertumoral heterogeneity in CAFs, ductal cancer cells, and immune cells between the extremely dense and loose types of PDACs (dense-type, high desmoplasia; loose-type, low desmoplasia). Notably, no difference in CAF abundance was detected, but a novel subtype of CAFs with a highly activated metabolic state (meCAFs) was found in loose-type PDAC compared to dense-type PDAC. MeCAFs had highly active glycolysis, whereas the corresponding cancer cells used oxidative phosphorylation as a major metabolic mode rather than glycolysis. We found that the proportion and activity of immune cells were much higher in loose-type PDAC than in dense-type PDAC. Then, the clinical significance of the CAF subtypes was further validated in our PDAC cohort and a public database. PDAC patients with abundant meCAFs had a higher risk of metastasis and a poor prognosis but showed a dramatically better response to immunotherapy (64.71% objective response rate, one complete response). We characterized the intertumoral heterogeneity of cellular components, immune activity, and metabolic status between dense- and loose-type PDACs and identified meCAFs as a novel CAF subtype critical for PDAC progression and the susceptibility to immunotherapy.
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http://dx.doi.org/10.1038/s41421-021-00271-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149399PMC
May 2021

Mechanism of allergic rhinitis treated by from different geographic areas.

Pharm Biol 2021 Dec;59(1):606-618

Department of Pharmaceutics, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.

Context: The coriander plant (L.) A. Braun et Aschers (Compositae) is used for the treatment of allergic rhinitis.

Objective: Analyze the difference of the volatile oil from 7 geographic areas and its therapeutic effect on allergic rhinitis.

Materials And Methods: The volatile oils from different geographic areas were extracted and analyzed, the protein and biological pathway for the treatment of allergic rhinitis were predicted by network pharmacology. Established three groups of Sprague-Dawley rat allergic rhinitis models (n = 10). The treatment group was given 100 μL/nostril of 0.1% volatile oil, the blank and model groups were given the same amount of normal saline. After 15 days, serum inflammatory factors were detected by ELISA. Nasal mucosa tissues were examined by hematoxylineosin staining and immunuhistrochemistry.

Results: There are differences in the content of volatile oil in the seven geographic areas. Experiments showed that the concentration of TNF-α in the serum of the administration group decreased from 63.66 ± 2.06 to 51.01 ± 4.10 (pg/mL), IL-4 decreased from 41.90 ± 3.90 to 28.68 ± 3.39 (pg/mL), IgE decreased from 22.18 ± 1.40 to 17.59 ± 1.60 (pg/mL), IL-2 increased from 314.14 ± 10.32 to 355.90 ± 10.01(pg/mL). Immunohistochemistry showed that compared with the model group, the PTGS2 and MAPK3 proteins in the administration group were significantly reduced.

Discussion And Conclusions: volatile oil is a multi-target and multi-pathway in the treatment of allergic rhinitis, which provides a new research basis and reference for the treatment of allergic rhinitis.
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http://dx.doi.org/10.1080/13880209.2021.1923757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143626PMC
December 2021

The Mechanism of Lavender Essential Oil in the Treatment of Acute Colitis Based on "Quantity-Effect" Weight Coefficient Network Pharmacology.

Front Pharmacol 2021 22;12:644140. Epub 2021 Apr 22.

Department of Pharmaceutics, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.

This study aimed to introduce a new weight coefficient combined with network pharmacology to predict the potential active components, action targets, and signal pathways of lavender essential oil and to investigate the therapeutic effect of lavender essential oil on colitis through animal experiments. The component targets of lavender essential oil were mined from the Pubchem and SwissTargetPrediction databases, and the relative content of lavender essential oil was compared with OB (oral bioavailability) to establish a "quantity-effect" weight coefficient. Online databases such as GeneCards and String were used to construct a "lavender essential oil compound target disease target" network to extract the key targets of core compounds acting on diseases. The clusterProfiler package in R language programming of Rstudio software was used to analyze the enrichment of the related targets by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG), and the enriched pathways were reordered according to the "quantity-effect" weight coefficient of the targets they participated in. Following up on the findings, the pharmacodynamic test showed that, after injecting lavender essential oil into mice, the levels of inflammatory cytokines including EGFR, TNF-α, and IFN-γ in serum and colon tissue decreased, and lavender essential oil could mediate Th17 cell differentiation by reducing dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) colonic mucosal damage. The results indicated that lavender essential oil can alleviate DSS-induced colonic mucosal injury in ulcerative Colitis mice. Based on the network pharmacology of the "quantity-effect" weight coefficient, this study indicated that lavender essential oil can regulate the level of inflammatory factors, inhibit inflammatory reactions through a multicomponent and multitarget strategy, and ultimately alleviate the colonic mucosal injury of UC mice. Through the weight coefficient network pharmacology mining, it was concluded that the Th17 cell differentiation, PI3K-Akt signaling pathway, and Th1 and Th2 cell differentiation of lavender essential oil in the treatment of UC may be the key pathway for the treatment of the disease. Through the establishment of a weight coefficient combined with network pharmacology and the combination of dose and effect, it shows that network pharmacology may provide a better basis for the treatment of disease mechanism.
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http://dx.doi.org/10.3389/fphar.2021.644140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107818PMC
April 2021

Primary ovarian serous carcinomas with extensive squamous differentiation: a case report and literature review.

BMC Womens Health 2021 05 8;21(1):193. Epub 2021 May 8.

Department of Pathology, School of Medicine, Women's Hospital, Zhejiang University, Hangzhou, Zhejiang Province, China.

Background: Primary ovarian serous carcinomas (OSC) with extensive squamous differentiation is a rare, and histological diagnostic criteria and biological behavior have not been fully established. We present an extremely rare case of primary OSC of the ovary with squamous differentiation.

Case Presentation: A 58-year-old (gravidity 3, parity 2) female was admitted complaining of abdominal distention for 6 months. No apparent tumor in the cervix was found by a physical examination. Serum levels of cancer antigen 125 (CA125) was elevated (2723.0 IU/L). Macroscopically, a 7 cm tumor of the left uterine adnexa, a 5 cm tumor of the right adnexa, and a 3 cm tumor of the omentum were found. Histological and immunochemical tests confirmed a diagnosis of OSC with squamous differentiation. Debulking surgery with tumor resection was performed. The patient was subsequently received postoperative chemotherapy.

Conclusions: In summary, OSC with extensive squamous differentiation is a rare, and the inter- and intratumor heterogeneity may be the reason for this phenomenon. Histological diagnostic criteria and biological behavior have not been fully established because of the limited data.
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http://dx.doi.org/10.1186/s12905-021-01336-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106833PMC
May 2021

δ-Valerolactamic Quaternary Amino Acid Derivatives: Enantiodivergent Synthesis and Evidence for Stereodifferentiated β-Turn-Inducing Properties.

J Org Chem 2021 06 7;86(12):8041-8055. Epub 2021 May 7.

Institut des Molécules et Matériaux du Mans (IMMM) - UMR 6283 CNRS-Le Mans Université, Equipe Méthodologie et Synthèse Organique, F-72085 Le Mans Cedex 09, France.

Enantiopure () and () cyclic α,α-disubstituted amino acid derivatives displaying a δ-valerolactam side chain were prepared from a common isoxazolidine precursor. The ()-configured δ-valerolactam was converted into diastereoisomeric pseudopeptides to investigate its ability to induce secondary structures in peptidomimetics. Conformational studies of these pseudopeptides were carried out in the solid state (X-ray diffraction), in solution (NMR analyses), and (computer-aided conformational analysis), which demonstrated that such quaternary amino acids induce β-turn conformations stable enough to be retained in polar media (DMSO). Incorporation of this new type of α,α-disubstituted amino acid into a representative pseudopeptidic sequence by - then -elongation and -debenzylation is also described herein and could serve for the synthesis of various structured peptidomimetics.
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http://dx.doi.org/10.1021/acs.joc.1c00456DOI Listing
June 2021

Corrigendum to Investigations of EGFR configurations on tumor cell surface by high-resolution electron microscopy.

Biochem Biophys Res Commun 2021 Jun 30;558:239. Epub 2021 Apr 30.

Beijing Key Laboratory of Microstructure and Properties of Solids, Institute of Microstructure and Property of Advanced Materials, Beijing University of Technology, Beijing, 100124, China. Electronic address:

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http://dx.doi.org/10.1016/j.bbrc.2021.04.023DOI Listing
June 2021

The effect and prediction of diurnal temperature range in high altitude area on outpatient and emergency room admissions for cardiovascular diseases.

Int Arch Occup Environ Health 2021 Apr 26. Epub 2021 Apr 26.

Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, 730000, China.

Purpose: Diurnal temperature range (DTR) is a meteorological indicator closely associated with global climate change. Thus, we aim to explore the effects of DTR on the outpatient and emergency room (O&ER) admissions for cardiovascular diseases (CVDs), and related predictive research.

Methods: The O&ER admissions data for CVDs from three general hospitals in Jinchang of Gansu Province were collected from 2013 to 2016. A generalized additive model (GAM) with Poisson regression was employed to analyze the effect of DTR on the O&ER admissions for all cardiovascular diseases, hypertension, ischemic heart disease (IHD) and stoke. GAM was also used to preform predictive research of the effect of DTR on the O&ER admissions for CVDs.

Results: There were similar positive linear relationships between DTR and the O&ER visits with the four cardiovascular diseases. And the cumulative lag effects were higher than the single lag effects. A 1 °C increase in DTR corresponded to a 1.30% (0.99-1.62%) increase in O&ER admissions for all cardiovascular diseases. Males and elderly were more sensitivity to DTR. The estimates in non-heating season were higher than in heating season. The trial prediction accuracy rate of CVDs based on DTR was between 59.32 and 74.40%.

Conclusions: DTR has significantly positive association with O&ER admissions for CVDs, which can be used as a prediction index of the admissions of O&ER with CVDs.
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http://dx.doi.org/10.1007/s00420-021-01699-7DOI Listing
April 2021

Metal-organic frameworks as catalytic selectivity regulators for organic transformations.

Chem Soc Rev 2021 May 19;50(9):5366-5396. Epub 2021 Apr 19.

Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Department of Chemistry, Institute of Molecular Aggregation Science, Tianjin University, Tianjin 300072, China.

Selective organic transformations using metal-organic frameworks (MOFs) and MOF-based heterogeneous catalysts have been an intriguing but challenging research topic in both the chemistry and materials communities. Analogous to the reaction specificity achieved in enzyme pockets, MOFs are also powerful platforms for regulating the catalytic selectivity via engineering their catalytic microenvironments, such as metal node alternation, ligand functionalization, pore decoration, topology variation and others. In this review, we provide a comprehensive introduction and discussion about the role of MOFs played in regulating and even boosting the size-, shape-, chemo-, regio- and more appealing stereo-selectivity in organic transformations. We hope that it will be instructive for researchers in this field to rationally design, conveniently prepare and elaborately functionalize MOFs or MOF-based composites for the synthesis of high value-added organic chemicals with significantly improved selectivity.
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http://dx.doi.org/10.1039/d0cs01538eDOI Listing
May 2021

A promising nanomatrix system of simvastatin for oral delivery: Evaluation in vitro and in vivo.

Pak J Pharm Sci 2020 Nov;33(6):2489-2495

Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, PR China.

Because of the low solubility, the oral bioavailability of simvastatin (SV) was poor, which restricted the application in clinic. In order to increase the dissolution and the oral absorption of simvastatin, we prepared a novel solid nanomatrix of SV with pharmaceutical acceptable nano-sized silica and Eudragit®. The nanomatrix was prepared using solvent evaporate method and the formulation was optimized. The X-ray diffraction (XRD) and differential scanning calorimetry (DSC) were used to analyze the physicochemical characterization of the SV nanomatrix. The results indicated that the SV existed in the nanomatrix was in a state of molecule or amorphous form. The optimal formulation, consisted of SV, Eudragit® L100-55 and Sylysia 350 (1:5:5, w/w/w), significantly enhanced the dissolution of SV compared with Zocor. And the relative bioavailability was 272% to Zocor. The oral absorption of simvastatin was enhanced markedly. The SV nanomatrix after storage for 1 year displayed similar performance in vitro and in vivo with the freshly prepared nanomatrix. The stability of SV nanomatrix achieved the desired objectives. In conclusion, the nanomatrix system described here had superior performance in vitro and in vivo and was expected to have a promising future as an alternative oral drug delivery system for SV.
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November 2020

CSE1L, as a novel prognostic marker, promotes pancreatic cancer proliferation by regulating the AKT/mTOR signaling pathway.

J Cancer 2021 14;12(10):2797-2806. Epub 2021 Mar 14.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Pancreatic cancer is one of the most aggressive tumors with poor prognosis and new targetable therapies are urgently required. CSE1L (chromosome segregation 1 like) is thought to play an important role in tumorigenesis and acts as a cancer therapeutic target. However, the biological function and the underlying mechanism of CSE1L in pancreatic cancer are still not fully explicit. In the present study, we found that high CSE1L expression was related to a worse prognosis in patients with pancreatic cancer according to data from the Cancer Genome Atlas (TCGA) database. Additionally, we found that CSE1L knockdown inhibited the proliferation of pancreatic cancer cells and promoted apoptosis, while CSE1L overexpression demonstrated the opposite phenomenon. Furthermore, we discovered that CSE1L might regulate pancreatic cancer proliferation through AKT signaling pathway. In summary, we reveal that CSE1L plays a crucial role in tumor growth and may serve as a potential prognostic and therapeutic target for pancreatic cancer.
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http://dx.doi.org/10.7150/jca.54482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040880PMC
March 2021

Correlation of cooking time with water absorption and changes in relative density during boiling of cassava roots.

Int J Food Sci Technol 2021 Mar 30;56(3):1193-1205. Epub 2020 Aug 30.

CGIAR Research Program on Roots Tubers and Bananas (RTB) The Alliance of Bioversity International and the International Center for Tropical Agriculture (CIAT) Cali Colombia.

Consumers prefer cassava roots that cook quickly during boiling. Current methods to evaluate cooking time (CT) are slow and labour-intensive. This article describes improved protocols for assessing CT in roots. We evaluated CT in 36 genotypes monthly at 8-11 months after planting. CT showed differences for plant age at harvest and among genotypes. During boiling, roots absorbed water (WAB) and thus reduced their relative density (DEN). We classified three groups of genotypes with increasing CT (≤25 min, 25-40 min and >40 min), associated with decreasing WAB, respectively, 15.3 ± 3.1, 10.7 ± 1.7 and 4.9 ± 3.8% of initial root weight. A similar trend was observed for changes in DEN (46.3 ± 9.8, 54.5 ± 11.1 and 75.9 ± 6.9% of initial DEN, respectively). The highest correlations between WAB and DEN with CT (  > 0.6) were found at 30-min boiling. These alternative protocols facilitate screening large numbers of cassava genotypes for CT.
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http://dx.doi.org/10.1111/ijfs.14769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984030PMC
March 2021

Quiescin sulfhydryl oxidase 1 promotes sorafenib-induced ferroptosis in hepatocellular carcinoma by driving EGFR endosomal trafficking and inhibiting NRF2 activation.

Redox Biol 2021 05 13;41:101942. Epub 2021 Mar 13.

Liver Cancer Institute & Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis & Cancer Invasion, Fudan University & Ministry of Education, Shanghai, China. Electronic address:

Sorafenib is a first-line molecular-target drug for advanced hepatocellular carcinoma (HCC), but its clinical effects are still limited. In this study we identify Quiescin sulfhydryl oxidase 1 (QSOX1) acting as a cellular pro-oxidant, specifically in the context of sorafenib treatment of HCC. QSOX1 disrupts redox homoeostasis and sensitizes HCC cells to oxidative stress by inhibiting activation of the master antioxidant transcription factor NRF2. A negative correlation between QSOX1 and NRF2 expression was validated in tumor tissues from 151 HCC patients. Mechanistically, QSOX1 restrains EGF-induced EGFR activation by promoting ubiquitination-mediated degradation of EGFR and accelerating its intracellular endosomal trafficking, leading to suppression of NRF2 activity. Additionally, QSOX1 potentiates sorafenib-induced ferroptosis by suppressing NRF2 in vitro and in vivo. In conclusion, the data presented identify QSOX1 as a novel candidate target for sorafenib-based combination therapeutic strategies in HCC or other EGFR-dependent tumor types.
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http://dx.doi.org/10.1016/j.redox.2021.101942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024711PMC
May 2021

Islet organoid as a promising model for diabetes.

Protein Cell 2021 Mar 10. Epub 2021 Mar 10.

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.

Studies on diabetes have long been hampered by a lack of authentic disease models that, ideally, should be unlimited and able to recapitulate the abnormalities involved in the development, structure, and function of human pancreatic islets under pathological conditions. Stem cell-based islet organoids faithfully recapitulate islet development in vitro and provide large amounts of three-dimensional functional islet biomimetic materials with a morphological structure and cellular composition similar to those of native islets. Thus, islet organoids hold great promise for modeling islet development and function, deciphering the mechanisms underlying the onset of diabetes, providing an in vitro human organ model for infection of viruses such as SARS-CoV-2, and contributing to drug screening and autologous islet transplantation. However, the currently established islet organoids are generally immature compared with native islets, and further efforts should be made to improve the heterogeneity and functionality of islet organoids, making it an authentic and informative disease model for diabetes. Here, we review the advances and challenges in the generation of islet organoids, focusing on human pluripotent stem cell-derived islet organoids, and the potential applications of islet organoids as disease models and regenerative therapies for diabetes.
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http://dx.doi.org/10.1007/s13238-021-00831-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943334PMC
March 2021

Multiview Self-Supervised Segmentation for OARs Delineation in Radiotherapy.

Evid Based Complement Alternat Med 2021 5;2021:8894222. Epub 2021 Mar 5.

The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou 213003, China.

Radiotherapy has become a common treatment option for head and neck (H&N) cancer, and organs at risk (OARs) need to be delineated to implement a high conformal dose distribution. Manual drawing of OARs is time consuming and inaccurate, so automatic drawing based on deep learning models has been proposed to accurately delineate the OARs. However, state-of-the-art performance usually requires a decent amount of delineation, but collecting pixel-level manual delineations is labor intensive and may not be necessary for representation learning. Encouraged by the recent progress in self-supervised learning, this study proposes and evaluates a novel multiview contrastive representation learning to boost the models from unlabelled data. The proposed learning architecture leverages three views of CTs (coronal, sagittal, and transverse plane) to collect positive and negative training samples. Specifically, a CT in 3D is first projected into three 2D views (coronal, sagittal, and transverse planes), then a convolutional neural network takes 3 views as inputs and outputs three individual representations in latent space, and finally, a contrastive loss is used to pull representation of different views of the same image closer ("positive pairs") and push representations of views from different images ("negative pairs") apart. To evaluate performance, we collected 220 CT images in H&N cancer patients. The experiment demonstrates that our method significantly improves quantitative performance over the state-of-the-art (from 83% to 86% in absolute Dice scores). Thus, our method provides a powerful and principled means to deal with the label-scarce problem.
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http://dx.doi.org/10.1155/2021/8894222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954615PMC
March 2021

The impact of tourniquet on tibial bone cement penetration in different zones in primary total knee arthroplasty: a meta-analysis.

J Orthop Surg Res 2021 Mar 17;16(1):198. Epub 2021 Mar 17.

Department of Orthopaedic Surgery, The First Medical Centre, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China.

Background: Cement mantle penetration and the cement-bone interface strength were critical to a successful primary total knee arthroplasty (TKA). It remained unclear whether decreased blood and fat in the cancellous bone achieved with the use of a tourniquet increases tibial cement mantle penetration in different zones on AP and lateral view in TKA according to criteria defined by the Knee Society Scoring System (KSS). The purpose of this study was to determine whether tourniquet use influences tibial cement mantle penetration in different zones on AP and lateral view in TKA according to KSS.

Methods: We conducted a meta-analysis to identify studies involving the impact of tourniquet use and no tourniquet use on tibial bone cement penetration in primary TKA in electronic databases, including Web of Science, Embase, PubMed, Cochrane Controlled Trials Register, Cochrane Library, Highwire, CBM, VIP, Wanfang database, up to January 2021. Finally, we identified 1231 patients (1231 knees) assessed in twelve studies.

Results: Tourniquet use increases the cumulative cement mantle penetration (P < 0.00001), mean cement mantle penetration (P = 0.004), and cement mantle in zone 3(P < 0.0001) on AP view. However, there were no significant differences in cement mantle in zone 1(P = 0.5), zone 2(P =0 .54), zone 4(P = 0.07) on AP view, and zone 1(P = 0.32), zone 2(P = 0.38) on lateral view between two groups. There were also no significant differences in length of surgery(P = 0.7), change in hemoglobin(P = 0.4), transfusion rates(P = 0.47), and complications such as muscular calf vein thrombosis(P = 0.21), superficial infection (P = 0.72), and deep vein thrombosis (P = 0.66) between two groups.

Conclusion: The application of a tourniquet increases the thickness of the tibial bone cement penetration-the increase in the thickness of bone cement penetration mainly located in zone 3 on the anteroposterior (AP) view.
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http://dx.doi.org/10.1186/s13018-021-02345-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968365PMC
March 2021

Mycoplasma synoviae induces serum amyloid A upregulation and promotes chicken synovial fibroblast cell proliferation.

Microb Pathog 2021 May 13;154:104829. Epub 2021 Mar 13.

Key Laboratory of Veterinary Biological Engineering and Technology of Ministry of Agriculture, Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Nanjing, China; National Center for Engineering Research of Veterinary Bio-products, Jiangsu Academy of Agricultural Sciences, Nanjing, China. Electronic address:

Mycoplasma synoviae (MS) infection causes infectious synovitis and arthritis with hyperplasia of synovial cells in the chicken joint. However, its mechanism is unknown. We used primary chicken synovial fibroblast (CSF) as the research object to study the role of MS in the proliferation of MS-infected CSF and determine the mechanisms involved. Using integrated transcriptomic and proteomic analyses of the interaction between CSF and MS, we screened a proliferation-regulated factor, serum amyloid A (SAA), that may regulate proliferation of MS-infected CSF. SAA appears to be associated with MS-induced CSF proliferation. To study the role of SAA in MS-induced CSF proliferation, a eukaryotic expression vector overexpressing SAA and a small interfering RNA (siRNA) targeting Saa were constructed to manipulate the expression of SAA. Cell proliferation and apoptosis were detected via cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), or terminal deoxyribonucleotidyl transferase-mediated dUTP nick-dnd labeling (TUNEL) assays, respectively. Western blot analysis was used to examine the protein expression level of SAA, cyclin E1, and cyclin-dependent kinase 2 (CDK2). In vitro, MS significantly promoted the proliferation of CSF and increased the production of SAA. Overexpression of SAA accelerated the proliferative ability of CSF, whereas knockdown of SAA depressed the proliferative ability of CSF. A TUNEL assay indicated that MS did not induce apoptosis. Silencing of SAA suppressed the expression of cyclin E1 and CDK2. These results suggest that MS may upregulate the expression of SAA, accelerate the cell cycle, and promote proliferation of CSF.
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http://dx.doi.org/10.1016/j.micpath.2021.104829DOI Listing
May 2021

Transformation of NSCLC to SCLC after 1st- and 3rd-generation EGFR-TKI resistance and response to EP regimen and erlotinib: 2 CARE-compliant case reports.

Medicine (Baltimore) 2021 Mar;100(10):e25046

Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, People's Republic of China.

Rationale: Genotypic and histological evolution of non-small-cell lung cancer (NSCLC) into small-cell lung cancer (SCLC) has been described as a mechanism of acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy. However, the number of clinical cases is rare.

Patient Concerns: Two lung adenocarcinoma patients with EGFR mutations who recurred after radical resection transformed into SCLC under treatment with the sequential first- and third-generation EGFR-TKIs.

Diagnosis: The 2 cases were both confirmed as SCLC by pathological rebiopsy after EGFR-TKIs resistance.

Interventions: Case 1 was treated with etoposide plus cisplatin (EP) regimen and erlotinib, while case 2 was treated with erlotinib and EP followed by oral etoposide.

Outcomes: Case 1 treated with EP only achieved 3-month progression-free survival (PFS), which is the first case that reported T790 M/C797S cis-mutation for osimertinib resistance before the SCLC transformation. However, case 2 treated with erlotinib and EP followed by oral etoposide, PFS lasted for 8 months.

Lessons: The cases highlighted the importance of rebiopsy that identified pathologically SCLC transformation after EGFR-TKI resistance, and suggested the treatment of erlotinib plus EP followed by etoposide, which could provide a reference for such phenotype.
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http://dx.doi.org/10.1097/MD.0000000000025046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969239PMC
March 2021

Isotactic-Alternating, Heterotactic-Alternating, and ABAA-Type Sequence-Controlled Copolyester Syntheses via Highly Stereoselective and Regioselective Ring-Opening Polymerization of Cyclic Diesters.

J Am Chem Soc 2021 03 16;143(11):4421-4432. Epub 2021 Mar 16.

State Key Laboratory of Applied Organic Chemistry (Lanzhou University), Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, People's Republic of China.

Synthesizing different types of sequence-controlled copolyesters can enrich the diversity of copolyesters and modify their properties more precisely, but it is still a challenge to synthesize a complicated sequence-controlled copolyester using different hydroxy acids in a living polymerization manner. In this work, a highly regioselective and stereoselective catalytic system was developed to synthesize biorenewable and biodegradable copolyesters of mandelic acid and lactic acid with isotactic-alternating, heterotactic-alternating, and ABAA-type precise and complicated sequences. Because of the regular incorporation of mandelic acid into polylactide, these sequence-controlled copolymers of mandelic acid and lactic acid show higher glass-transition temperatures than polylactide and a random copolymer. A stereocomplexation interaction between two opposite enantiomeric isotactic polymer chains was also discovered in the isotactic-alternating copolymer.
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http://dx.doi.org/10.1021/jacs.1c00902DOI Listing
March 2021

Advances in CpG Island Methylator Phenotype Colorectal Cancer Therapies.

Front Oncol 2021 26;11:629390. Epub 2021 Feb 26.

Department of Medical Oncology, Dalian University Affiliated Xinhua Hospital, Dalian, China.

With the aging of the population, the incidence of colorectal cancer in China is increasing. One of the epigenetic alterations: CpG island methylator phenotype (CIMP) plays an important role in the incidence of colorectal cancer. Recent studies have shown that CIMP is closely related to some specific clinicopathological phenotypes and multiple molecular phenotypes in colorectal cancer. In this paper, the newest progress of CIMP colorectal cancer in chemotherapeutic drugs, targeted agents and small molecular methylation inhibitors are going to be introduced. We hope to provide potential clinical treatment strategies for personalized and precise treatment of colorectal cancer patients.
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http://dx.doi.org/10.3389/fonc.2021.629390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952756PMC
February 2021

The Combination of and Volatile Oils Exerts Antidepressant Effects in a CUMS-Induced Rat Model by Regulating the HPA Axis and Levels of Neurotransmitters.

Front Pharmacol 2020 24;11:614413. Epub 2021 Feb 24.

Ministry of Education, Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.

The (CX)- (MX) herbal pair is frequently used in traditional Chinese medicine prescriptions for treating depression. The volatile oil from CX and MX has been shown to have good pharmacological activities on the central nervous system, but its curative effect and mechanism in the treatment of depression are unclear. Therefore, the antidepressant effect of the volatile oil from CX-MX (CMVO) was studied in chronic unpredictable mild stress (CUMS) rats. The suppressive effects of CMVO (25, 50, 100 μL/kg) against CUMS-induced depression-like behavior were evaluated using the forced swimming test (FST), open field test (OFT) and sucrose preference test (SPT). The results showed that CMVO exhibited an antidepressant effect, reversed the decreased sugar preference in the SPT and prolongation of immobility time in the FST induced by CUMS, increased the average speed, time to enter the central area, total moving distance, and enhanced the willingness of rats to explore the environment in the OFT. Inhalational administration of CMVO decreased levels of adrenocorticotropic hormone and corticosterone in serum and the expression of corticotropin-releasing hormone mRNA in the hypothalamus, which indicated regulation of over-activation of the hypothalamic-pituitary-adrenal (HPA) axis. In addition, CMVO restored levels of 5-hydroxytryptamine (5-HT), dopamine, norepinephrine and acetylcholine in the hippocampus. The RT-PCR and immunohistochemistry results showed that CMVO up-regulated the expression of 5-HT mRNA. This study demonstrated the antidepressant effect of CMVO in CUMS rats, which was possibly mediated via modulation of monoamine and cholinergic neurotransmitters and regulation of the HPA axis.
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http://dx.doi.org/10.3389/fphar.2020.614413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943885PMC
February 2021

Comparative Genomics of and New Targets for Molecular Diagnostics.

Front Vet Sci 2021 19;8:640067. Epub 2021 Feb 19.

Key Laboratory of Veterinary Biological Engineering and Technology of Ministry of Agriculture, Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Nanjing, China.

is an important pathogen of poultry, causing significant economic losses in this industry. Analysis of the unique genes and shared genes among different strains and among related species is helpful for studying the molecular pathogenesis of and provides valuable molecular diagnostic targets to facilitate the identification of species. We selected a total of 46 strains, including six strains, from 25 major animal (including avian) species/subspecies that had complete genome sequences and annotation information published in GenBank, and used them for comparative genomic analysis. After analysis, 16 common genes were found in the 46 strains. Thirteen single-copy core genes and the 16s rRNA genes were used for genetic evolutionary analysis. was found to have a distant evolutionary relationship not only with other arthritis-causing mycoplasmas, but also with another major avian pathogen, , that shares the major virulence factor with . Subsequently, six unique coding genes were identified as shared among these strains that are absent in other species with published genome sequences. Two of the genes were found to be located in the genetically stable regions of the genomes of and were determined to be present in all isolated strains ( = 20) and -positive clinical samples ( = 48) preserved in our laboratory. These two genes were used as molecular diagnostic targets for which SYBR green quantitative PCR detection methods were designed. The two quantitative PCR methods exhibited good reproducibility and high specificity when tested on positive plasmid controls and genomic DNA extracted from different strains, other major avian pathogenic bacteria/mycoplasmas, and low pathogenic Mycoplasma species. The detection limit for the two genes was 10 copies or less per reaction. The clinical sensitivity and specificity of the quantitative PCR methods were both 100% based on testing chicken hock joint samples with positive or negative infection. This research provides a foundation for the study of species-specific differences and molecular diagnosis of .
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http://dx.doi.org/10.3389/fvets.2021.640067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933220PMC
February 2021

Hepatoprotection of Lycii Fructus Polysaccharide against Oxidative Stress in Hepatocytes and Larval Zebrafish.

Oxid Med Cell Longev 2021 18;2021:3923625. Epub 2021 Feb 18.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.

Scavenging of oxidative stress by antioxidants may provide a therapeutic strategy for nonalcoholic fatty liver disease (NAFLD). Increasing evidence is supporting the potential application of natural resourced polysaccharides as promising prevention or treatment strategies against NAFLD. In the current study, an acidic heteropolysaccharide, LFP-a1, was isolated and purified from Lycii fructus with successively hot water refluxing extraction, alcohol precipitation, protein removal, and DEAE-52 cellulose chromatographic separation. LFP-a1 was a complicated structured polysaccharide with an average MW of 4.74 × 104 Da and composed of 6 monosaccharides and 1 uronic acid. Preexposure of LFP-a1 could increase the cell viability and reverse the abnormal oxidative stress though inhibition of mitochondrial-mediated apoptotic pathway and correction of cell cycle progression against HO hepatoxicity in NAFLD model L02 cells. Consistently, study in thioacetamide- (TAA-) induced NAFLD model zebrafish larvae showed LFP-a1 preserved the liver integrity and alleviated TAA-induced oxidative stress through downregulation of abnormal apoptosis. These observations indicated the hepatoprotective activity of LFP-a1, which may be applied for the prevention or treatment of NAFLD or other oxidative stress-related diseases.
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http://dx.doi.org/10.1155/2021/3923625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906805PMC
May 2021

The RNA mA reader YTHDC1 silences retrotransposons and guards ES cell identity.

Nature 2021 03 3;591(7849):322-326. Epub 2021 Mar 3.

CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.

The RNA modification N-methyladenosine (mA) has critical roles in many biological processes. However, the function of mA in the early phase of mammalian development remains poorly understood. Here we show that the mA reader YT521-B homology-domain-containing protein 1 (YTHDC1) is required for the maintenance of mouse embryonic stem (ES) cells in an mA-dependent manner, and that its deletion initiates cellular reprogramming to a 2C-like state. Mechanistically, YTHDC1 binds to the transcripts of retrotransposons (such as intracisternal A particles, ERVK and LINE1) in mouse ES cells and its depletion results in the reactivation of these silenced retrotransposons, accompanied by a global decrease in SETDB1-mediated trimethylation at lysine 9 of histone H3 (H3K9me3). We further demonstrate that YTHDC1 and its target mA RNAs act upstream of SETDB1 to repress retrotransposons and Dux, the master inducer of the two-cell stage (2C)-like program. This study reveals an essential role for mA RNA and YTHDC1 in chromatin modification and retrotransposon repression.
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http://dx.doi.org/10.1038/s41586-021-03313-9DOI Listing
March 2021

Cathepsin B aggravates acute pancreatitis by activating the NLRP3 inflammasome and promoting the caspase-1-induced pyroptosis.

Int Immunopharmacol 2021 May 24;94:107496. Epub 2021 Feb 24.

Department of Intensive Care Unit, the Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510655, China. Electronic address:

Objectives: Cathepsin B (CTSB), nod-like receptor family pyrin domain-containing 3 (NLRP3), and caspase-1 play an important role in the development of Acute Pancreatitis (AP). Besides, the relationship between the proteins remains poorly understood. In addition, whereas previous studies have found caspase-1 activation in AP, pyroptosis, a caspase-1 induced cell death mode, has never been proposed and proved in AP.

Methods: We induced AP in mice by intraperitoneal injection of cerulein. Mice in the inhibitor group of CTSB were pretreated with injection of CA-074me, while mice in the inhibitor group of caspase-1 were of Ac-YVAD-CHO, 1 h earlier. We evaluated the inflammation of the pancreas and the detected expression of activated CTSB, NLRP3, ASC, caspase-1p20, IL-1β and IL-18. TUNEL staining was used to detect acinar cell death.

Results: The inflammation of the pancreas in the two inhibitor groups was significantly reduced compared with that in the AP group. We observed that CA-074me not only inhibits CTSB, but also suppresses the expression and activity of NLRP3, ASC and caspase-1. We found that CA-074me further inhibits the downstream event of caspase-1, including pro-inflammatory cytokine secretion and pyroptosis. Whereas Ac-YVAD-CHO inhibited caspase-1 and decreased pro-inflammatory cytokine secretion and pyroptosis, it did not down-regulate the expression and activity ofCTSB, NLRP3 and ASC.

Conclusion: The results indicate that CTSB may aggravate AP by activating the NLRP3 inflammasome and promoting Caspase-1-induced pyroptosis. These provide clues about the pathophysiological mechanisms of AP, shedding light on new ideas and potential targets for the prevention and treatment of AP.
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http://dx.doi.org/10.1016/j.intimp.2021.107496DOI Listing
May 2021

Para-aortic lymph node metastasis in lower Thoracic Esophageal Squamous Cell Carcinoma after Radical Esophagectomy: a CT-based atlas and its clinical implications for Adjuvant Radiotherapy.

J Cancer 2021 18;12(6):1734-1741. Epub 2021 Jan 18.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Our previous work showed that para-aortic lymph node (PALN) metastasis was the major failure pattern in lower thoracic esophageal squamous cell carcinoma (LTESCC) patients who presented abdominal LN failure after curative surgery. We thereby aim to generate a computerized tomography (CT)-based documentation of PALNs and to propose a clinical target volume (CTV) for this region. Sixty-five patients were enrolled. The epicentre of each PALN was drawn onto an axial CT image of a standard patient with reference to the surrounding anatomical landmarks. A CTV for PALN was generated based on the final result of node distribution, and was evaluated for dosimetric performance in three simulated patients. All the studied 248 LNs were below the level of 1.0 cm above the celiac artery (CA), and 94.76% were above the bottom of vertebra L3. Horizontally, 93.33% of the LNs in the celiac level were located within an expansion of 1.5 cm on the CA, and 94.12% of the LNs in the superior mesenteric artery (SMA) level were within 1.5 cm on the left side of the SMA. Below the SMA, all the LNs were behind the left renal vein, left to the right border of the inferior vena cava, and 98.51% of the LNs were medial to the lateral surface of the left psoas major. The proposed CTV could cover 92.74% of the LNs and was dosimetrically feasible. The proposed CTV is the first one to focus on the high-risk area of abdominal failure in LTESCC patients after surgery and can serve as a reference in the adjuvant radiotherapy for LTESCC patients.
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http://dx.doi.org/10.7150/jca.51212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890317PMC
January 2021

Rhodium-Catalyzed Redox-Neutral Olefination of Aryldiazenes with Acrylate Esters via C-H Activation and Transfer Hydrogenation.

Org Lett 2021 03 16;23(5):1687-1691. Epub 2021 Feb 16.

Key Laboratory of Applied Surface and Colloid Chemistry of MOE & School of Chemistry and Chemical Engineering, Shaanxi Normal University (SNNU), Xi'an 710062, China.

Rh(III)-catalyzed redox-neutral C-H olefination of aryldiazenecarboxylates has been realized using arylate esters as the olefinating reagents. This reaction proceeds under mild and redox-neutral conditions, resulting in integration of C-H activation and transfer hydrogenation. The chemoselectivity complements that of previously reported rhodium-catalyzed coupling of the same substrates.
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http://dx.doi.org/10.1021/acs.orglett.1c00107DOI Listing
March 2021

Association of Body Mass Index with Risk of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

COPD 2021 02 16;18(1):101-113. Epub 2021 Feb 16.

Department of Epidemiology and Health Statistics, the School of Public, Health of Qingdao University, Qingdao, Shandong Province, China.

The association between body mass index (BMI) and chronic obstructive pulmonary disease (COPD) remains controversial. Therefore, a meta-analysis was conducted to further evaluate the relationship. A comprehensive literature search was performed in PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), and Wanfang databases to identify eligible articles until July 15, 2020. Random effect model (REM) was used to compute the pooled results with 95% confidence intervals (CIs). We conducted meta-regression and subgroup analysis to explore potential sources of heterogeneity. Publication bias was evaluated by funnel plots and Egger's test. Thirty articles with 1,578,449 participants were included in the meta-analysis. The pooled OR of COPD was 1.96 (95% CI: 1.78-2.17) for the underweight group, 0.80 (95% CI: 0.73-0.87) for overweight group, and 0.86 (95% CI: 0.73-1.02) for obesity group. After further excluding 5 studies of high between-study heterogeneity in sensitivity analysis, the pooled OR of COPD was 0.77 (95% CI: 0.68-0.86) for the obesity group. This meta-analysis indicated that BMI was associated with COPD. Specifically, underweight might increase the risk of COPD; overweight and obesity might reduce the risk of COPD.
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http://dx.doi.org/10.1080/15412555.2021.1884213DOI Listing
February 2021

Improvement of Qilin pills on male reproductive function in tripterygium glycoside-induced oligoasthenospermia in rats.

Andrologia 2021 May 14;53(4):e13923. Epub 2021 Feb 14.

Department of Reproductive Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China.

This study established an oligoasthenospermic rat model using tripterygium glycosides (TGs) and investigated the mechanism by which Qilin pills (QLPs) ameliorate reproductive hypofunction. Thirty-two male Sprague Dawley rats were allocated to four equal-sized groups: (1) the control group received continuous physiological levels of saline; (2) the oligoasthenospermia model group was induced with TGs by daily intragastric administration for 28 days; (3 and 4) oligoasthenospermic rats were treated intragastrically with low dose (1.62 g kg  d ) and high dose (3.24 g kg  d ) of QLPs once daily for 60 days. The QLP-treated rats showed a marked increase (p < .05) in testicular mass, testicular index and semen parameters compared with the untreated rats. Histopathologically, the QLP-treated groups exhibited restored seminiferous tubules in contrast to the model group. Reactive oxygen species and malondialdehyde levels were dramatically decreased (p < .05) in the testes of the QLP-treated rats. QLP treatment partly reverted (p < .05) the circulatory levels of reproductive hormones (FSH, LH, testosterone, prolactin and SHBG) and hepatic and renal function (AST, Cr and urea). Our results showed that oral QLP treatment had a curative effect on the testicular mass, sperm quality, testicular pathomorphology, antioxidants, plasmatic hormones, and liver and renal function of rats.
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http://dx.doi.org/10.1111/and.13923DOI Listing
May 2021

Characterization of a transcriptional regulator PtxS from Pseudomonas plecoglossicida for regulating 2-ketogluconic acid metabolism.

Int J Biol Macromol 2021 Mar 30;174:330-338. Epub 2021 Jan 30.

The Key Laboratory of Industrial Biotechnology, National Engineering Laboratory for Cereal Fermentation Technology, School of Biotechnology, Jiangnan University, Ministry of Education, Wuxi 214122, PR China. Electronic address:

Homologs of PtxS are ubiquitous transcriptional regulators controlling the expression of the glucose dehydrogenase and kgu operon to globally regulate the 2-ketogluconic acid (2KGA) metabolism in Pseudomonas. In the present study, a PtxS from a 2KGA industrial producer Pseudomonas plecoglossicida JUIM01 (PpPtxS) was heterologously expressed in E. coli BL21(DE3), then structurally and functionally characterized. The obtained results showed that PpPtxS was a 36.65-kDa LacI-family transcriptional regulator. 2KGA was the sole effector of PpPtxS. Glucose negatively affected the molecular binding of PpPtxS and 2KGA, and gluconic acid inhibited the PpPtxS-2KGA binding reaction. PpPtxS in water solution mainly existed as a dimer and bound to two molecules of 2KGA. The effector 2KGA mainly bound to the region close to the C-terminal of PpPtxS by interacting with the 299th to the 301st amino acids (Ala, Gln, Pro, Thr, Glu and Arg). PpPtxS specifically recognized and bound to a 14-bp palindrome sequence (5'-TGAAACCGGTTTCA-3') due to its conserved HTH motif at the N-terminal. The characterization of PpPtxS in this study would provide a theoretical guidance for the industrial production of 2KGA.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.01.198DOI Listing
March 2021
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