Publications by authors named "Xiaoxu Zhang"

75 Publications

Phase-Matching Quantum Key Distribution with Discrete Phase Randomization.

Entropy (Basel) 2021 Apr 23;23(5). Epub 2021 Apr 23.

Henan Key Laboratory of Quantum Information and Cryptography, SSF IEU, Zhengzhou 450001, China.

The twin-field quantum key distribution (TF-QKD) protocol and its variations have been proposed to overcome the linear Pirandola-Laurenza-Ottaviani-Banchi (PLOB) bound. One variation called phase-matching QKD (PM-QKD) protocol employs discrete phase randomization and the phase post-compensation technique to improve the key rate quadratically. However, the discrete phase randomization opens a loophole to threaten the actual security. In this paper, we first introduce the unambiguous state discrimination (USD) measurement and the photon-number-splitting (PNS) attack against PM-QKD with imperfect phase randomization. Then, we prove the rigorous security of decoy state PM-QKD with discrete phase randomization. Simulation results show that, considering the intrinsic bit error rate and sifting factor, there is an optimal discrete phase randomization value to guarantee security and performance. Furthermore, as the number of discrete phase randomization increases, the key rate of adopting vacuum and one decoy state approaches infinite decoy states, the key rate between discrete phase randomization and continuous phase randomization is almost the same.
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http://dx.doi.org/10.3390/e23050508DOI Listing
April 2021

Acyl fluorides as direct precursors to fluoride ketyl radicals: reductive deuteration using SmI and DO.

Chem Commun (Camb) 2021 Apr 28. Epub 2021 Apr 28.

Department of Nutrition and Health, China Agricultural University, Beijing 100193, China.

A highly chemoselective reductive deuteration of acyl fluorides to provide α,α-dideuterio alcohols with exquisite levels of deuterium incorporation was developed using SmI2 and D2O as the deuterium source. This method introduces acyl fluorides as attractive radical precursors for the generation of reactive acyl-type fluoride ketyls that should find widespread application in many synthetic strategies involving single electron transfer processes.
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http://dx.doi.org/10.1039/d1cc01381eDOI Listing
April 2021

Targeting macrophages using nanoparticles: a potential therapeutic strategy for atherosclerosis.

J Mater Chem B 2021 Apr 30;9(15):3284-3294. Epub 2021 Mar 30.

School of Basic Medicine, Qingdao University, Ningxia Road 308, Qingdao, P. R. China.

Atherosclerosis is one of the leading causes of vascular diseases, with high morbidity and mortality worldwide. Macrophages play a critical role in the development and local inflammatory responses of atherosclerosis, contributing to plaque rupture and thrombosis. Considering their central roles, macrophages have gained considerable attention as a therapeutic target to attenuate atherosclerotic progression and stabilize existing plaques. Nanoparticle-based delivery systems further provide possibilities to selectively and effectively deliver therapeutic agents into intraplaque macrophages. Although challenges are numerous and clinical application is still distant, the design and development of macrophage-targeting nanoparticles will generate new knowledge and experiences to improve therapeutic outcomes and minimize toxicity. Hence, the review aims to discuss various strategies for macrophage modulation and the development and evaluation of macrophage targeting nanomedicines for anti-atherosclerosis.
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http://dx.doi.org/10.1039/d0tb02956dDOI Listing
April 2021

Genetic Polymorphism Drives Susceptibility Between Bacteria and Bacteriophages.

Front Microbiol 2021 24;12:627897. Epub 2021 Mar 24.

Key Laboratory of Emerging Pathogens and Biosafety, Centre for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.

Phage therapy has attracted much attention for the treatment of antibiotic-resistant bacteria in recent years. However, it is common for bacteria to obtain resistance capability in short time after interaction with a lytic phage, as observed in phage therapy and co-culture of host and phage in a lab. In order to understand the mechanisms behind resistance, AB91118 and its lytic phage LQ7 were studied as a model system. A mutant strain named R1-3-1 resistant to the ancestral phage LQ7 was isolated, and then phages experimentally evolved from LQ7 were able to kill R1-3-1. Genomes of the two bacterial strains and the three phages (LQ7, ELQ7P-10, and ELQ7P-20) were analyzed based on deep sequencing data of NGS. Analyses showed that a few mutations could be identified in R1-3-1 and the evolved phages. Instead, in all the genomes of the bacteria and the phages, there exists genetic polymorphism of minor alleles, which distributes in many functional genes. Specifically, in the AB91118-LQ7 system it was found that the unique polymorphism sites in R1-3-1 associated to metabolic pathways could be inhibited by chloramphenicol (CHL). The resistant mutant R1-3-1 could become sensitive to the phage LQ7 in the presence of CHL. Combined use of CHL and the evolved phage from 20 cycles (ELQ7P-20) could produce the least resistance when killing the bacteria AB91118. The genetic polymorphism of minor alleles would be a new mechanism to drive the co-evolution between a phage and its host, which may enable the phage and the host get ready and fast response to the selective pressure from one to the other.
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http://dx.doi.org/10.3389/fmicb.2021.627897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024471PMC
March 2021

A novel tumor suppressor CECR2 down regulation links glutamine metabolism contributes tumor growth in laryngeal squamous cell carcinoma.

Clin Transl Oncol 2021 Apr 7. Epub 2021 Apr 7.

Department of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai JiaoTong University, Shanghai JiaoTong University Affiliated Sixth People's Hospital, 600 Yishan Road, Xuhui, 200233, Shanghai, China.

Purpose: Glutamine plays an important role in tumor metabolism and progression. This research aimed to find out how Gln exert their effects on laryngeal squamous cell carcinoma (LSCC).

Methods: Cell proliferation was measured by CCK8 and EdU assay, mitochondrial bioenergetic activity was measured by mitochondrial stress tests. Gene expression profiling was revealed by RNA sequencing and validated by RT-qPCR. In LSCC patients, protein expression in tumor and adjacent tissues was examined and scored by IHC staining. RNAi was performed by stably expressed shRNA in TU177 cells. In vivo tumor growth analysis was performed using a nude mouse tumorigenicity model.

Results: Gln deprivation suppressed TU177 cell proliferation, which was restored by αKG supplementation. By transcriptomic analysis, we identified CECR2, which encodes a histone acetyl-lysine reader, as the downstream target gene for Gln and αKG. In LSCC patients, the expression of CECR2 in tumors was lower than adjacent tissues. Furthermore, deficiency of CECR2 promoted tumor cell growth both in vitro and in vivo, suggesting it has tumor suppressor effects. Besides, cell proliferation inhibited by Gln withdrawal could be restored by CECR2 depletion, and the proliferation boosted by αKG supplementation could be magnified either, suggested that CECR2 feedback suppressed Gln and αKG's effect on tumor growth. Transcriptomic profiling revealed CECR2 regulated the expression of a series of genes involved in tumor progression.

Conclusion: We confirmed the Gln-αKG-CECR2 axis contributes to tumor growth in LSCC. This finding provided a potential therapeutic opportunity for the use of associated metabolites as a potential treatment for LSCC.
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http://dx.doi.org/10.1007/s12094-021-02603-yDOI Listing
April 2021

Rapid genome-wide sequence typing of African swine fever virus based on alleles.

Virus Res 2021 May 2;297:198357. Epub 2021 Mar 2.

Key Laboratory of Emerging Pathogens and Biosafety, Centre for Biosafety Mega-Sciences, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China; African Swine Fever Regional Laboratory of China (Wuhan), Jinglong Street, Jiangxia District, Wuhan, China. Electronic address:

Rapid and accurate molecular typing of African swine fever virus (ASFV) during outbreaks is important to reveal diversity and sourcing of ASFV. Here we present a new way to perform rapid genome-wide multi-locus sequence typing of ASFV using an allele calling based on gene by gene approach. Using open-accessed chewBBACA software, 41 publicly available ASFV genomes were analyzed to optimize the parameters to find the alleles. Alleles as many as 127 were found for building the phylogenetic trees, which covered more than 60 % of the whole genome. Then the method was used to analyze two ASFV genomes assembled from two metagenomic sequences of a swine whole blood and a swine spleen tissue collected in Wuhan, China. It reveals that the two ASFV genomes are the closest to that of Pig/HLJ/2018 strain and DB/LN/2018 strain, which were isolated earlier in China. This proved that the ASFV in Wuhan originated from the same source causing the earlier outbreaks in Heilongjiang and Liaoning province of China. This method could identify more informative genome regions that could be used for accurate typing than other genome-wide analysis, and with less demand on computing resources. It also showed tolerance to analyze ASFV draft genomes assembled directly from metagenomic sequences. Furthermore, the ASFV-specific genetic markers found by the allele calling could be translated into clinical diagnostics or can be used broadly to identify conserved putative therapeutic candidates.
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http://dx.doi.org/10.1016/j.virusres.2021.198357DOI Listing
May 2021

Isolation of Neuroprotective Anthocyanins from Black Chokeberry () against Amyloid-β-Induced Cognitive Impairment.

Foods 2020 Dec 29;10(1). Epub 2020 Dec 29.

Center for Viticulture and Enology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.

Black chokeberry () fruits are rich in anthocyanins, which are vital secondary metabolites that possess antioxidative properties. The aim of this study was to isolate and purify the anthocyanins from black chokeberry by simulated moving bed (SMB) chromatography, and to investigate the neuroprotective effect of SMB purified anthocyanin against Aβ-induced memory damage in rats. The parameters of the SMB process were studied and optimized. Anthocyanin extracts were identified by HPLC and UPLC-QTOF-MS, and antioxidant abilities were evaluated. The Aβ-induced animal model was established by intracerebral ventricle injection in rat brain. Through the SMB purification, anthocyanins were purified to 85%; cyanidin 3--galactoside and cyanidin 3--arabinoside were identified as the main anthocyanins by UPLC-QTOF-MS. The SMB purified anthocyanins exhibited higher DPPH and ABTS free radical scavenging abilities than the crude anthocyanins extract. Furthermore, rats receiving SMB purified anthocyanins treatment (50 mg/kg) showed improved spatial memory in a Morris water maze test, as well as protection of the cells in the hippocampus against Aβ toxicity. These results demonstrate that anthocyanins could serve as antioxidant and neuroprotective agents, with potential in the treatment of Alzheimer's disease.
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http://dx.doi.org/10.3390/foods10010063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823521PMC
December 2020

Dual-targeting tumor cells and tumor associated macrophages with lipid coated calcium zoledronate for enhanced lung cancer chemoimmunotherapy.

Int J Pharm 2021 Feb 15;594:120174. Epub 2020 Dec 15.

School of Basic Medicine, Qingdao University, Ningxia Road 308, Qingdao, PR China. Electronic address:

Lung cancer is the leading cause of cancer death among both men and women, and non-small cell lung cancer (NSCLC) accounts for almost 80% of such death. Tumor associated macrophage (TAMs) are abundant components in NSCLC. TAMs play critical roles in angiogenesis, immune escape and chemoresistance. Here we developed a dual-targeting drug delivery system (CaZOL@BMNPs) of zoledronate, which could bind to both tumor cells with overexpressed biotin receptors and macrophage mannose receptor (MMR) positive TAMs. The biotin- and mannose-modified lipid coated calcium zoledronate nanoparticles were preferentially internalized in both tumor cells and TAMs, and thereby inhibited their survivals. Our studies demonstrated that CaZOl@BMNPs treatment obviously reduced angiogenesis, reprogrammed immunosuppressive tumor microenvironment and eventually restrained tumor progression with negligible systemic toxicity. Collectively, CaZOL@BMNPs could be a promising approach by dual-targeting tumor cells and TAMs for NSCLS chemoimmunotherapy.
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http://dx.doi.org/10.1016/j.ijpharm.2020.120174DOI Listing
February 2021

Ultrahigh Adhesion Force Between Silica-Binding Peptide SB7 and Glass Substrate Studied by Single-Molecule Force Spectroscopy and Molecular Dynamic Simulation.

Front Chem 2020 27;8:600918. Epub 2020 Nov 27.

Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijng, China.

Many proteins and peptides have been identified to effectively and specifically bind on certain surfaces such as silica, polystyrene and titanium dioxide. It is of great interest, in many areas such as enzyme immobilization, surface functionalization and nanotechnology, to understand how these proteins/peptides bind to solid surfaces. Here we use single-molecule force spectroscopy (SMFS) based on atomic force microscopy to directly measure the adhesion force between a silica-binding peptide SB7 and glass surface at single molecule level. SMFS results show that the adhesion force of a single SB7 detaching from the glass surface distributes in two populations at ~220 pN and 610 pN, which is higher than the unfolding forces of most mechanically stable proteins and the unbinding forces of most stable protein-protein interactions. Molecular dynamics simulation reveals that the electrostatic interactions between positively charged arginine residues and the silica surface dominates the binding of SB7 on silica. Our study provides experimental evidence and molecular mechanism at the single-molecule level for the SB7-based immobilization of proteins on silica-based surface, which is able to withstand high mechanical forces, making it an ideal fusion tag for silica surface immobilization or peptide-base adhesive materials.
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http://dx.doi.org/10.3389/fchem.2020.600918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729015PMC
November 2020

Ischemia Reperfusion Injury: Opportunities for Nanoparticles.

ACS Biomater Sci Eng 2020 12 24;6(12):6528-6539. Epub 2020 Nov 24.

School of Basic Medicine, Qingdao University, Ningxia Road 308, Qingdao 110016, P.R. China.

Ischemia reperfusion (IR)-induced oxidative stress, accompanied by inflammatory responses, contributes to morbidity and mortality in numerous diseases such as acute coronary syndrome, stroke, organ transplantation, and limb injury. Ischemia results in profound hypoxia and tissue dysfunction, whereas subsequent reperfusion further aggravates ischemic tissue damage through inducing cell death and activating inflammatory responses. In this review, we highlight recent studies of therapeutic strategies against IR injury. Furthermore, nanotechnology offers significant improvements in this area. Hence, we also review recent advances in nanomedicines for IR therapy, suggesting them as potent and promising strategies to improve drug delivery to IR-injured tissues and achieve protective effects.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01197DOI Listing
December 2020

Targeted Delivery of Dasatinib to Deplete Tumor-Associated Macrophages by Mannosylated Mixed Micelles for Tumor Immunotherapy.

ACS Biomater Sci Eng 2020 10 16;6(10):5675-5684. Epub 2020 Sep 16.

School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016 PR China.

Tumor-associated macrophages (TAMs) are abundant in tumors and predominately show protumor M2-type fostering tumor progression. Specific depletion of TAMs is conceivably favorable for antitumor therapy. In this study, mannosylated mixed micelles (DAS-MMic) were developed to specifically deliver dasatinib (DAS) to eliminate TAMs for tumor immunotherapy. In vitro and in vivo results showed that DAS-MMic could effectively eradicate TAMs, decrease angiogenesis, reprogram the immunosuppressive tumor microenvironment, and finally suppress tumor progression. These data suggest the potential of direct elimination of TAMs by DAS-MMic for tumor immunotherapy.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01046DOI Listing
October 2020

Establishment and application of a predictive model for gefitinib-induced severe rash based on pharmacometabolomic profiling and polymorphisms of transporters in non-small cell lung cancer.

Transl Oncol 2021 Jan 19;14(1):100951. Epub 2020 Nov 19.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510080, Guangdong Province, PR China. Electronic address:

Background: Rash is a well-known predictor of survival for patients with gefitinib therapy with non-small cell lung cancer (NSCLC). However, whether patients with more severe rash obtain the more survival benefits from gefitinib is still unknown, and predicted model for severe rash is needed.

Methods: The relationship between gefitinib-induced rash and progression free survival (PFS) was primarily explored in the retrospective cohort. The association between rash and gefitinib/metabolites concentration and genetic polymorphisms were determined by pharmacometabolomic and pharmacogenomics methods in the exploratory cohort and validated in an external cohort.

Results: The survival for patients with rash was significantly higher than that of patients without rash (p = 0.0002, p = 0.0089), but no difference was found between grade 1/2 or grade 3/4. Only the concentration of gefitinib, but not its metabolites, was found to be associated with severe rash, and the cutoff value of gefitinib was 204.6 ng/mL conducted by ROC curve analysis (AUC=0.685). A predictive model for severe rash was established: gefitinib concentration (OR = 11.523, 95% CI = 2.898-64.016, p = 0.0016), SLC22A8 rs4149179(CT vs CC, OR = 3.156, 95% CI = 0.958-11.164, p = 0.0629), SLC22A1 rs4709400(CG vs CC, OR = 10.267, 95% CI = 2.067-72.465, p = 0.0087; GG vs CC, OR = 5.103, 95% CI = 1.032-33.938, p = 0.061). This model was confirmed in the validation cohort with an excellent predictive ability (AUC = 0.749, 95% CI = 0.710-0.951).

Conclusions: Our finding demonstrated that the incidence, not the severity, of gefitinib-induced rash predicted improved survival, the gefitinib concentration and polymorphisms of SLC22A8 and SLC22A1 were recommended to manage severe rash.
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http://dx.doi.org/10.1016/j.tranon.2020.100951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689337PMC
January 2021

Ethnic disparities in demographic, clinicopathologic and biological behaviours and prognosis of gastric cancer in northwest China.

Cancer Med 2020 12 20;9(24):9353-9364. Epub 2020 Oct 20.

Department of Radiology, the General Hospital, Ningxia Medical University, Yinchuan, China.

This retrospective study aimed to investigate ethnic disparities in demographic, clinicopathologic, and biological behaviours of gastric cancer (GC) in a high GC incidence area of China. There were 5022 GC patients, including 3987 Han (79.4%) and 987 Hui (14.4%) patients from Northwest China. All patient data were retrieved from 2009 to 2017. Median survival was estimated using the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards model was used to assess the impact of covariates. Similarly, low 5-year OS rates were observed in both the Hui and Han groups (23.8% and 24.2% respectively). Hui patients with stage T1 or N0 or with tumours <5 cm had 2.144-fold, 1.426-fold and 1.305-fold increased risks of poor prognosis compared with Han patients with these characteristics respectively (all p < 0.05). Further, Hui patients had 1.265-fold, 1.364-fold and 1.401-fold increased risks of poor prognosis compared with Han patients among those with high expression of Ki67, EGFR and VEGF respectively (all p < 0.05). There are ethnic disparities in the prognosis of GC patients in Northwest China. Understanding the effects of ethnicity on GC will guide reasonable evaluations of prognosis and future interventions to equalise access to high-quality care for GC patients of different ethnicities in China.
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http://dx.doi.org/10.1002/cam4.3551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774720PMC
December 2020

Photothermal and adsorption effects of silver selenide nanoparticles modified by different surfactants in nursing care of cancer patients.

Sci Technol Adv Mater 2020 Sep 1;21(1):584-592. Epub 2020 Sep 1.

Department of Nursing, Jinan People's Hospital Affiliated to Shandong First Medical University, Jinan China.

Silver selenide nanoparticles have advantages of low cytotoxicity, desirable near-infrared light response characteristics, and easy surface modification, which attract increasing attention in chemo-photothermal therapy and nursing care of cancer patients. In this contribution, we synthesized AgSe nanoparticles modified by the surfactant of cetyltrimethylammonium bromide (CTAB) using a ligand exchange strategy. Their microstructure and composition were characterized by transmission electron microscopy, X-ray diffraction, X-ray Photo-electronic Spectroscopy, and Fourier transform infrared spectroscopy. The CTAB modified AgSe nanoparticles exhibited a uniform diameter distribution centered at ~12 nm. In order to investigate the photothermal and adsorption effects of CTAB-AgSe nanocomposites, we also prepared sodium dodecyl benzene sulfonate (SDBS) modified AgSe nanoparticles to make a comparison. The CTAB-AgSe nanoparticles showed high photothermal properties, a photothermal conversion efficiency of 20.1% and a high drug adsorption performance of 48.2 μg/mg. Importantly, the CTAB-AgSe-DOX presented an MCF-7 cell activity of only 27.3% under near-infrared radiation. The results revealed that the surface-modified AgSe nanoparticles with CTAB had stronger antitumor ability.
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http://dx.doi.org/10.1080/14686996.2020.1800367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476516PMC
September 2020

Survival Advantages in Gastric Cancer Patients Receiving Preoperative SOX Regimen Chemotherapy.

Cancer Biother Radiopharm 2020 Aug 20. Epub 2020 Aug 20.

Department of Clinical Research, Shenzhen Nanshan Hospital, Huazhong University of Science and Technology, Shenzhen, China.

The objective of this study was to address whether preoperative chemotherapy (PECT) plus surgery prolongs overall survival (OS) compared with surgery plus postoperative chemotherapy (POCT) among gastric cancer (GC) patients in Northwest China. The authors included 157 GC patients confirmed histologically or by gastroscopic pathological examination treated at the General Hospital of Ningxia Medical University of China between 2012 and 2018. All patients were followed up by telephone in January 2019 within a 2-week period. The endpoint was death due to GC or its complications. Thirty-eight patients received PECT, 41 patients received POCT, 40 patients received surgery alone, and 38 patients received chemotherapy alone. Surgery was performed with R0 resection and subsequent extended lymph node dissection. Chemotherapy was performed with the S-1, oxaliplatin capecitabine regimen. Patients who received PECT had longer OS than those with POCT treatment (hazard ratio = 2.409,  = 0.037). The 5-year OS rate was 32.7% higher in the PECT group than in the POCT group. PECT was associated with better OS in GC patients and should be considered by clinicians in GC treatment, although prospective studies are needed for confirmation.
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http://dx.doi.org/10.1089/cbr.2020.3970DOI Listing
August 2020

Multi-shelled hollow cube CaTiO decorated with BiOCl towards enhancing photocatalytic performance under the visible light.

J Colloid Interface Sci 2020 Sep 6;576:21-33. Epub 2020 May 6.

School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, China. Electronic address:

It is highly desirable to combine the microstructure management and heterostructure construction technique to remold inherent wide band gap semiconductor CaTiO with the purpose of enhancing its visible light absorption capacity and photocatalytic performance. Herein, a novel multi-shelled hollow cube BiOCl/CaTiO heterostructure has been successfully synthesized by a facile template-free method for photocatalytic hydrogen production and degradation pollutants in water under the visible light. The investigations of microstructure, physicochemical property and photoelectric behaviors indicate that the multi-shelled hollow cube architecture and synergetic effect of 2D-3D structural coupling are dominant reasons to enhance phototcatalytic performance, which can significantly improve the absorption and utilization of visible light, multiply abundant active radical generation and boost the separation and migration efficiency of photoproduced electron-hole pairs. Moreover, the probable photocatalytic reaction mechanisms, the feasible migration behaviors of photo-produced charges, the influence factors of enhancing photocatalytic activities are proposed in depth. It is intended that further innovative works on the multi-shelled hollow cube architecture design of high-performance photocatalyst by facile template-free hydrothermal method can be inspired.
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http://dx.doi.org/10.1016/j.jcis.2020.05.019DOI Listing
September 2020

Application of Adaptive Evolution to Improve the Stability of Bacteriophages during Storage.

Viruses 2020 04 9;12(4). Epub 2020 Apr 9.

Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China.

Phage stability is important for the successful application of bacteriophages as alternative antibacterial agents. Considering that temperature is a critical factor in phage stability, this study aimed to explore the possibility of improving long-term phage stability through adaptive evolution to elevated temperature. Evolution of three wild-type ancestral phages ( phage Wc4 and phages CX5 and P-PSG-11) was induced by subjecting the phages to heat treatment at 60 °C for five cycles. The adapted phages showed better stability than the wild-type ancestral phages when subjected to heat treatment at 60 °C for 1 h and after 60 days of storage at 37 °C. However, the adapted phages could not withstand thermal treatment at 70 °C for 1 h. The infectivity and the lytic properties of the phages were not changed by the evolution process. Whole-genome sequencing revealed that single substitutions in the tail tubular proteins were the only changes observed in the genomes of the adapted phages. This study demonstrates that adaptive evolution could be used as a general method for enhancing the thermal stability of phages without affecting their lytic activity. Sequencing results showed that bacteriophages may exist as a population with minor heterogeneous mutants, which might be important to understand the ecology of phages in different environments.
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http://dx.doi.org/10.3390/v12040423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232334PMC
April 2020

Trapping and preconcentration of volatile organic sulfur compounds in water samples by portable and battery-powered trapping device prior to gas chromatography-sulfur chemiluminescence determination.

J Chromatogr A 2020 May 10;1619:460947. Epub 2020 Feb 10.

Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu, Sichuan 610064, China. Electronic address:

A simple, portable and battery-powered trapping device (iTrap) consisting of a purification tube, a trapping unit and a miniature air pump was developed for the pre-concentration of volatile organic sulfur compounds (VOSCs). The tested VOSCs, including methanthiol (MT), ethanethiol (ET), dimethyl sulfide (DMS), diethyl sulfide (DES) and dimethyl disulfide (DMDS), were firstly purged from water samples and then in situ pre-concentrated with the iTrap prior to their analysis by thermal desorption gas chromatography coupling with a sulfur chemiluminescence detector (TD-GC-SCD). Twenty-six adsorbents were studied to find the most suitable adsorbent for the efficient pre-concentration of VOSCs. Under optimal conditions, limits of detection of 6, 8, 6, 2 and 3 ng L were obtained for MT, ET, DMS, DES and DMDS, respectively. The precisions were better than 5.3% (relative standard deviations, RSDs). The iTrap was successfully applied for the analysis of VOSCs in Certified Reference Materials, several surface water, underground water and wastewater samples collected from Pengzhou city, Sichuan, China. Moreover, the VOSCs trapped in the iTrap were much more stable than those directly stored in water samples and the recoveries for all samples could be maintained at acceptable levels (>73%), even their preservation time as long as 8 h.
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http://dx.doi.org/10.1016/j.chroma.2020.460947DOI Listing
May 2020

Genome Analysis Reveals a Synergistic Mechanism of Ursodeoxycholic Acid and Jasminoidin in Mice Brain Repair After Ischemia/Reperfusion: Crosstalk Among Muti-Pathways.

Front Pharmacol 2019 12;10:1383. Epub 2019 Dec 12.

Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Studies have shown that combination drug therapy which corresponding treatment involves multiple genes and targets is more effective against cerebral ischemia. To identify the synergistic mechanism of ursodeoxycholic acid and jasminoidin based on differential pathway network, which protect against brain ischemia-reperfusion injury. Totally 115 mice with focal cerebral ischemia-reperfusion injury were allocated into five groups: sham, vehicle, ursodeoxycholic acid (UA), jasminoidin (JA), and JA and UA combination group (JU). The differentially expressed genes identified by microarray which consisted of 11,644 complementary DNAs were loaded to the GeneGo MetaCore™ software to analyze the enriched pathways and processes among different groups. Of the top 10 pathways and process networks, 5, 6, and 3 overlapping pathways as well as 5, 3, and 4 overlapping process networks were observed between UA and JA, UA and JU, and JA and JU, respectively. Of these, three pathways and three process networks overlapped across the three groups. Interestingly, four representative pathways and six process networks were only noted in the JU group. Gene Ontology process analysis showed 2 processes were shared by all three treatment groups in the top 10 processes. The UA and JA combination resulted in synergistic effects through affecting multi-signal transduction pathways, different locations in the same pathway, and the new signaling pathway emerged in drug combination group, those together may enhance the treatment of cerebral ischemia-reperfusion injury through promoting neural cell apoptosis, decreasing calcium levels, inhibiting inflammation, and protecting neurons.
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http://dx.doi.org/10.3389/fphar.2019.01383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920098PMC
December 2019

Volatile organic compounds fingerprinting in faeces and urine of Alzheimer's disease model SAMP8 mice by headspace-gas chromatography-ion mobility spectrometry and headspace-solid phase microextraction-gas chromatography-mass spectrometry.

J Chromatogr A 2020 03 18;1614:460717. Epub 2019 Nov 18.

College of Food Science & Nutritional Engineering, China Agricultural University, No.17 Tsinghua Dong Road,100083 Beijing, China. Electronic address:

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http://dx.doi.org/10.1016/j.chroma.2019.460717DOI Listing
March 2020

Comparison of Phenolic Compounds and the Antioxidant Activities of Fifteen Ramat cv. 'Hangbaiju' in China.

Antioxidants (Basel) 2019 Aug 20;8(8). Epub 2019 Aug 20.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China.

This study investigated the phenolic compounds of 15 Ramat cv. 'Hangbaiju', including 6 'Duoju' and 9 'Taiju', using high performance liquid chromatography (HPLC). The antioxidant activities of these 'Hangbaiju' were estimated by DPPH, ABTS and FRAP assays. Results show that a total of 14 phenolic compounds were detected in these flowers, including 3 mono-caffeoylquinic acids, 3 di-caffeoylquinic acids, 1 phenolic acid and 7 flavonoids. 'Duoju' and 'Taiju' possess different concentrations of phenolic compounds, and 'Taiju' exhibits higher caffeoylquinic acids and stronger antioxidant activities than 'Duoju'. Caffeoylquinic acids show a strong correlation with the antioxidant activities of the samples. Principal component analysis (PCA) reveals an obvious separation between 'Duoju' and 'Taiju', using phenolic compounds as variables. Apigenin-7--glucoside, 3,5-di--caffeoylquinic acid, luteolin and acacetin were found to be the key phenolic compounds to differentiate 'Duoju' from 'Taiju'.
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http://dx.doi.org/10.3390/antiox8080325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720787PMC
August 2019

Uncovering pharmacological mechanisms of Zhi-Zi-Hou-Po decoction in chronic unpredictable mild stress induced rats through pharmacokinetics, monoamine neurotransmitter and neurogenesis.

J Ethnopharmacol 2019 Oct 11;243:112079. Epub 2019 Jul 11.

Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, China. Electronic address:

Ethnopharmacological Relevance: Zhi-Zi-Hou-Po decoction (ZZHPD), a classical Chinese prescription, has been reported to improve depressive behaviors in clinic. However, definite pharmacological effects and mechanisms of ZZHPD on monoaminergic system and hippocampal neurogenesis are ambiguous. It need to be further illuminated.

Aim Of The Study: Our study is designed to reveal pharmacological mechanisms of ZZHPD on depression through pharmacokinetics, monoamine neurotransmitters and neurogenesis.

Materials And Methods: Chronic unpredictable mild stress (CUMS) is used to establish rats model of depression. Then, the antidepressant effects of ZZHPD are evaluated by detecting body weight, sucrose preference and forced swimming test. The regulatory functions of ZZHPD on monoaminergic system are assessed by measuring monoamine neurotransmitters, neurotransmitter precursor substances, synthesized rate-limiting enzymes and transporters. Finally, potential molecular mechanism of ZZHPD on hippocampal neurogenesis is evaluated by investigating newborn immature neuron and newborn mature neuron.

Results: Our results show that ZZHPD remarkably normalizes CUMS-induced decline in weight gain, decrease of sucrose consumption rate in sucrose preference test and increase of immobility time in forced swimming test. Moreover, ZZHPD significantly reverses CUMS-induced reduction of 5-hydroxytryptamine (5-HT), dopamine (DA), tryptophan (Trp), tyrosine (Tyr), tryptophan hydroxylase2 (TPH2) and tyrosine hydroxylase (TH), whereas decreases level of serotonin transporter (SERT) in CUMS-induced rats. Finally, ZZHPD obviously improves CUMS-induced decrease of newborn immature neuron and newborn mature neuron in dentate gyrus of hippocampus.

Conclusion: This study demonstrates that ZZHPD can alleviate CUMS-induced depression-like behaviors. It is probably attributed to the fact that ZZHPD could enhance monoaminergic system and hippocampal neurogenesis. Our findings provide the new perspectives on molecular targets of ZZHPD, and it will facilitate its clinical application.
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http://dx.doi.org/10.1016/j.jep.2019.112079DOI Listing
October 2019

A comparison of electronic nose and gas chromatography-mass spectrometry on discrimination and prediction of ochratoxin A content in Aspergillus carbonarius cultured grape-based medium.

Food Chem 2019 Nov 18;297:124850. Epub 2019 May 18.

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. Electronic address:

This study investigated discrimination and prediction of ochratoxin A (OTA) in three Aspergillus carbonarius strains cultured grape-based medium using E-nose technology and GC-MS analysis. Results showed that these strains cultured medium samples were divided into four groups regarding their log 10 OTA value using an equispaced normal distribution analysis. Partial least squares-discriminant analysis (PLS-DA) revealed that GC-MS PLS-DA model only separated the low OTA level medium samples from the rest OTA level samples, whereas all the OTA level samples were segregated from each other using E-nose PLS-DA model. Partial least squares regression (PLSR) analysis indicated that an excellent prediction performance was established on the accumulation of OTA in these medium samples using E-nose PLSR, whereas GC-MS PLSR model showed a screening performance on the OTA formation. These indicated that E-nose analysis could be a reliable method on discriminating and predicting OTA in A. carbonarius strains under grape-based medium.
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http://dx.doi.org/10.1016/j.foodchem.2019.05.124DOI Listing
November 2019

Targeted Delivery of Zoledronate to Tumor-Associated Macrophages for Cancer Immunotherapy.

Mol Pharm 2019 05 22;16(5):2249-2258. Epub 2019 Apr 22.

School of Pharmacy , Shenyang Pharmaceutical University , Wenhua Road No. 103 , Shenyang 110016 , PR China.

Tumor-associated macrophages (TAMs) are recruited from circulatory monocytes by tumor-derived factors, which differentiate into macrophages residing in the tumor microenvironment. TAMs play critical roles in promoting angiogenesis, invasion, metastasis and immune escape, and the direct depletion of TAMs is a promising strategy for tumor immunotherapy. In this study, we developed lipid-coated calcium zoledronate nanoparticles (CaZol@pMNPs) containing conjugated mannose, which were sterically shielded with an extracellular pH-sensitive material. The NPs specifically targeted TAMs and induced their apoptosis in vitro and in vivo. In a S180 tumor-bearing mouse model, CaZol@pMNPs effectively depleted TAMs, markedly decreased angiogenesis, reduced immune suppression, and eventually restrained tumor growth without eliciting systemic effects. The collective data indicate the potential of the direct depletion of TAMs using CaZol@pMNPs for cancer immunotherapy.
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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00261DOI Listing
May 2019

Deciphering the scalene association among type-2 diabetes mellitus, prostate cancer, and chronic myeloid leukemia via enrichment analysis of disease-gene network.

Cancer Med 2019 05 1;8(5):2268-2277. Epub 2019 Apr 1.

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.

The potential biological relationship between type-2 diabetes mellitus (T2DM) has been focused in numerous studies. To investigate the molecular associations among T2DM, prostate cancer (PCa), and chronic myeloid leukemia (CML), using a biomolecular network enrichment analysis. We obtained a list of disease-related genes and constructed disease networks. Then, GO enrichment analysis was performed to identify the significant functions and pathways of overlapping modules in the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. More than 75% of these overlapping genes were found to be consistent with the findings of previous studies. In the three diseases, we found that Sarcoglycan delta (SGCD) and Rho family GTPase 3 (RND3) were the overlapping genes and identified negative regulation of apoptotic process and negative regulation of transcription from RNA polymerase II promoter RNA as the two overlapping biological functions. CML and PCa were the most closely related, with 34 overlapping genes, five overlapping modules, 27 overlapping biological functions, and nine overlapping pathways. There were 13 overlapping genes, one overlapping modules, four overlapping biological functions and one overlapping pathway (FoxO signaling pathway) were found in T2DM and CML.And T2DM and PCa were the least related pair in our study, with only six overlapping genes, five overlapping modules, and one overlapping biological function. SGCD and RND3 were the main gene-to-gene relationship among T2DM, CML, and PCa; apoptosis, development, and transcription from RNA polymerase II promote processes were the main functional connections among T2DM, CML, and PCa by network enrichment analysis. There is a "scalene" relationship among T2DM, CML, and PCa at gene, pathway, biological process, and module levels: CML and PCa were the most closely related, the second were T2DM and PCa, and T2DM and PCa were the least related pair in our study. Our study provides a new avenue for further studies on T2DM and cancers, which may promote the discovery and development of novel therapeutic and can be used to treat multiple diseases.
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http://dx.doi.org/10.1002/cam4.1845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536925PMC
May 2019

Memantine Differentially Regulates Tau Phosphorylation Induced by Chronic Restraint Stress of Varying Duration in Mice.

Neural Plast 2019 14;2019:4168472. Epub 2019 Feb 14.

State Key Laboratory of Medical Neurobiology & Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, China.

Exposure to chronic psychiatric stress has been linked to Alzheimer's disease-related tau hyperphosphorylation and abnormalities in glutamate neurotransmission. However, the pathological relationship between glutamatergic dysfunction and tau phosphorylation in the cerebral cortex under chronic psychiatric stress is not fully understood. The present study investigated the effects of memantine (MEM, 5 and 10 mg/kg), an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, on chronic restraint stress- (CRS-) induced tau phosphorylation in mice. CRS administered for 16 or 28 consecutive days (1 h daily) induced significant tau phosphorylation in the brain. MEM treatment suppressed the elevation of phosphorylated tau (P-tau) levels induced by 16-day CRS in a dose-dependent manner. P-tau reduction was accompanied by the attenuation of the upregulation of GSK3 and CDK5 expression and the downregulation of PP2A activity induced by CRS. Additionally, MEM reduced CRS-induced upregulation of NMDA receptor subunit levels (GluN2A, GluN2B) in the frontal cortex. However, MEM markedly enhanced tau phosphorylation in the frontal cortex and other cerebral cortical regions following 28 days of CRS. The stimulatory effect of MEM on CRS-induced tau phosphorylation was correlated with increased activities of AKT, JNK, and GSK3, inactivation of PP2A, and downregulation of Pin1 and HSP70. Moreover, MEM did not effectively reverse the NMDA receptor upregulation induced by 28-day CRS and even increased GluN2B subunit levels. In contrast to the duration-dependent effects of MEM on P-tau levels, MEM produced an anxiolytic effect in both regimens as revealed by elevated plus maze testing. However, MEM did not affect the body weight reduction induced by CRS. Thus, MEM exerts distinctive effects on CRS-induced tau phosphorylation, which might be related to the expression of GluN2B. The differential effects of MEM on P-tau levels have crucial implications for its clinical application.
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http://dx.doi.org/10.1155/2019/4168472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393894PMC
May 2019

Targeted Delivery of miRNA 155 to Tumor Associated Macrophages for Tumor Immunotherapy.

Mol Pharm 2019 04 20;16(4):1714-1722. Epub 2019 Mar 20.

School of Pharmacy , Shenyang Pharmaceutical University , Shenyang 110016 , P. R. China.

Tumor associated macrophages (TAMs) are important components residing in the tumor microenvironment. They are immunosuppressive and promote tumor progression. Targeting TAMs and reprogramming their phenotype may be a promising strategy that can restore antitumor immune responses. In this study, we developed a microRNA delivery system based on lipid-coated calcium phosphonate nanoparticles (CaP/miR@pMNPs) containing conjugated mannose and sterically shielded with a pH-responsive material. The nanocarrier could respond to the low pH in the tumor microenvironment and expose mannose to promote cellular internalization in TAMs. The carrier could reactivate TAMs and reprogram their functions, reverse the immunosuppressive tumor microenvironment, and inhibit tumor growth in a tumor-bearing mouse model. In summary, redirecting the polarization of TAMs is a potential therapeutic strategy for tumor immunotherapy.
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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00065DOI Listing
April 2019

Involvement of RhoA/ROCK Signaling in Aβ-Induced Chemotaxis, Cytotoxicity and Inflammatory Response of Microglial BV2 Cells.

Cell Mol Neurobiol 2019 Jul 9;39(5):637-650. Epub 2019 Mar 9.

Department of Translational Neuroscience, Jing'an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology & Institutes of Brain Science, Fudan University, 138 Yi-Xue-Yuan Road, Shanghai, 200032, China.

Reactive microglia clustering around amyloid plaques in brain is a histopathological feature of Alzheimer's disease (AD) and reflects the contribution of neuroinflammation in AD pathogenesis. β-Amyloid peptide (Aβ) has been shown to induce a range of microglial responses including chemotaxis, cytotoxicity and inflammation, but the underlying mechanism is poorly understood. Considering the fundamental role of RhoA/ROCK signaling in cell migration and its broad implication in AD and neuroinflammation, we hypothesized that RhoA/ROCK signaling might be involved in Aβ-induced microglial responses. From in vivo mouse models including APP/PS1 transgene and fibrillar Aβ stereotactic injection, we observed the elevated expression level of RhoA in reactive microglia. Through a series in vitro cell migration, cytotoxicity and biochemistry assays, we found that RhoA/ROCK signaling plays an essential role in Aβ-induced responses of microglial BV2 cells. Small molecular agents Fasudil and Y27632 showed prominent beneficial effects, which implies the therapeutic potential of RhoA/ROCK signaling inhibitors in AD treatment.
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http://dx.doi.org/10.1007/s10571-019-00668-6DOI Listing
July 2019

A visible-light-driven Z-scheme CdS/BiGeO heterostructure with enhanced photocatalytic degradation of various organics and the reduction of aqueous Cr(VI).

J Colloid Interface Sci 2019 May 18;543:317-327. Epub 2019 Feb 18.

Key Laboratory of Preparation and Applications of Environmental Friendly Materials, Jilin Normal University, Ministry of Education, Changchun 130103, PR China. Electronic address:

A series of Z-scheme CdS/BiGeO heterostructures were successfully obtained by a simple hydrothermal method. The Z-scheme CdS/BiGeO heterostructures show outstanding photocatalytic performance for degrading the various organic pollutants of the waste water, and for the reduction of aqueous Cr(VI) under visible light. For degradation of 2-Mercaptobenzothiazole (MBT), the Z-scheme 30CdS/BiGeO heterostructure exhibits the superior rate constant, which is about 22.67 and 4.6 times higher than that of the pure BiGeO and CdS, respectively. Meanwhile, as we expected, the Z-scheme 30CdS/BiGeO heterostructure also displays the enhanced photocatalytic performance for degradation of Levofloxacin (LEV), Ciprofloxacin (CIP), Tetracycline (TC) and reduction of aqueous Cr(VI). The enhancement of photocatalytic performance is attributed to the high redox capacity and the strong interfacial interaction between CdS and BiGeO, which can effectively improve the separation of photo-induced electron-hole pairs. Additionally, the photocatalytic mechanism over the Z-scheme CdS/BiGeO heterostructure is provided. The research work may provide a promising approach to fabricate other Z-scheme heterostructures with efficient photocatalytic performance.
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http://dx.doi.org/10.1016/j.jcis.2019.02.052DOI Listing
May 2019

ClyJ Is a Novel Pneumococcal Chimeric Lysin with a Cysteine- and Histidine-Dependent Amidohydrolase/Peptidase Catalytic Domain.

Antimicrob Agents Chemother 2019 04 27;63(4). Epub 2019 Mar 27.

Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China

is one of the leading pathogens that cause a variety of mucosal and invasive infections. With the increased emergence of multidrug-resistant , new antimicrobials with mechanisms of action different from conventional antibiotics are urgently needed. In this study, we identified a putative lysin (gp20) encoded by the phage SPSL1 using the LytA autolysin as a template. Molecular dissection of gp20 revealed a binding domain (GPB) containing choline-binding repeats (CBRs) that are high specificity for By fusing GPB to the CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) catalytic domain of the PlyC lysin, we constructed a novel chimeric lysin, ClyJ, with improved activity to the pneumococcal Cpl-1 lysin. No resistance was observed in strains after exposure to incrementally doubling concentrations of ClyJ for 8 continuous days In a mouse bacteremia model using penicillin G as a control, a single intraperitoneal injection of ClyJ improved the survival rate of lethal -infected mice in a dose-dependent manner. Given its high lytic activity and safety profile, ClyJ may represent a promising alternative to combat pneumococcal infections.
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http://dx.doi.org/10.1128/AAC.02043-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437478PMC
April 2019