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The abrogation of the self-adaptive redox evolution of tumors is promising for improving therapeutic outcomes. In this study, we designed a novel trimetallic alloy nanozyme AuCuPt-PpIX (ACPP), which mimics up to five naturally occurring enzymes—glucose oxidase (GOD), superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and glutathione peroxidase (GPx). Facilitated by these enzyme-mimicking traits, the constructed ACPP nanozymes can not only disrupt the established redox homeostasis in tumors through a series of enzymatic cascade reactions but also achieve cyclic regeneration of the relevant enzyme substrates. Density functional theory (DFT) calculations have theoretically explained the synergistic effect of multi-metallic doping and the possible mechanism of enzymatic catalysis. The doped Cu and Pt sites are conducive to the adsorption, activation, and dissociation of reactant molecules, whereas the Au sites are conducive to desorption, which significantly improves catalytic efficiency via a synergistic effect. Additionally, ACPP nanozymes can improve the effect of protoporphyrin (PpIX)-enabled sonodynamic therapy (SDT) by alleviating hypoxia and initiating ferroptosis by inducing lipid peroxidation (LPO) and inhibiting GPX4 activity, thus achieving multi-modal synergistic therapy. This study presents a typical paradigm to enable the use of multi-metallic alloy nanozymes for the treatment of tumor cells with self-adaptive properties.

Yaolin Wang,1– 3,&ast; Kai Zhao,4,5,&ast; Nanling Wu,1– 3 Tao Ji,1– 3 Gaowei Su,1– 3 Xiaojie Cui,1– 3 Yushan Dong,1– 3 Xiuxia Chen1– 3 1NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 3Department of Anesthesiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 4Department of Anesthesiology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Hefei, Anhui, People’s Republic of China; 5Department of Anesthesiology, Anhui Provincial Hospital, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiuxia Chen, Department of Anesthesiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China, Tel +86 18052268332, Email cxxlxy@sina.comPurpose: This study was designed to investigate the effects of different doses of butorphanol on postoperative shivering and quality of recovery in elderly patients.Patients and Methods: A total of 147 elderly patients (aged 60 or older) scheduled for elective transurethral resection of the prostate were enrolled in the current study. Patients were randomly and evenly assigned into four groups: Group C (0.9% normal saline), Group B1 (butorphanol 0.01 mg/kg), Group B2 (butorphanol 0.02 mg/kg) and Group B3 (butorphanol 0.03 mg/kg). All drugs were diluted to 5mL and injected intravenously slowly 5 min before induction of anesthesia. The primary outcome measure was the incidence of postoperative shivering in the post-anesthesia care unit. Quality of Recovery-40 (QoR-40) scores were assessed on postoperative day (POD) 1, 2 and 3. Perioperative core and skin temperature, extubation time and adverse events were also recorded.Results: Patients among the four groups had comparable baseline characteristics. Compared with Group C, the incidence of shivering was significantly lower in Group B2 and B3 (P = 0.006 and P = 0.005, respectively). The QoR-40 scores on POD1 were significantly higher in all butorphanol groups than that in Group C (P < 0.0083). In Group B2 and B3, patients experienced lower pain intensity (P < 0.001). In addition, the incidence of catheter-related bladder discomfort (CRBD) was lower in all butorphanol groups than in Group C (P < 0.0083).Conclusion: Butorphanol 0.02 or 0.03 mg/kg could effectively prevent the occurrence of postoperative shivering in elderly patients scheduled for transurethral resection of the prostate, provided effective postoperative recovery and postoperative analgesia.Keywords: butorphanol, elderly patients, postoperative shivering, recovery quality, postoperative pain

As the least toxic heavy metal, monoelemental bismuth nanomaterials with several superiorities are the ideal theranostic agents. However, bismuth nanoparticles are easily oxidized by oxygen in air or media, limiting their clinical application. In contrast, the oxidization of Bi

Kai Zhao,1,&ast; Yushan Dong,1,&ast; Gaowei Su,1 Yaolin Wang,1 Tao Ji,1 Nanling Wu,1 Xiaojie Cui,1 Wenzhan Li,1 Yanming Yang,1 Xiuxia Chen1,2 1Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiuxia Chen, Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China, Tel +86 18052268332, Fax +0516-8346-9496, Email cxxlxy@sina.comPurpose: Lidocaine has been gradually used in general anesthesia. This study was designed to investigate the effect of systemic lidocaine on postoperative quality of recovery (QoR) in patients undergoing supratentorial tumor resection, and to explore its brain-injury alleviation effect in neurosurgical anesthesia.Patients and Methods: Sixty adult patients undergoing elective supratentorial tumor resection. Patients were randomly assigned either to receive lidocaine (Group L: 1.5 mg/kg bolus completed 10 min before anesthesia induction followed by an infusion at 2.0 mg/kg/h) or to receive normal saline (Group C: received volume-matched normal saline at the same infusion rate). Primary outcome measures were Quality of Recovery-40 (QoR-40) scores on postoperative day (POD) 1 and 2. Plasma concentrations of S100B protein (S100B), neuron specific enolase (NSE), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) before anesthesia induction and at the end of surgery were assessed. Visual Analogue Scale (VAS) scores were assessed at 1, 2, 6, 12, 24 and 48 h after surgery. Perioperative parameters and adverse events were also recorded.Results: Patients between two groups had comparable baseline characteristics. Global QoR-40 scores on POD 1 and POD 2 were significantly higher (P < 0.001) in group L (165.5± 3.8 vs 173.7± 4.7) than those in group C (155.6± 4.0 vs 163.2± 4.5); and scores of physical comfort, emotional state, and pain in group L were superior to those in group C (P < 0.05). In group L, patients possessed lower plasma concentration of pro-inflammatory factors (IL-6, TNF-α) and brain injury-related factors (S100B, NSE) (P < 0.05), consumed less remifentanil and propofol, and experienced lower pain intensity. Multiple linear regression analysis demonstrated age and pain were correlated with postperative recovery quality.Conclusion: Systemic lidocaine improved early recovery quality after supratentorial tumor resection with general anesthesia, and had certain brain-injury alleviation effects. These benefits may be attributed to the inflammation-alleviating and analgesic properties of lidocaine.Keywords: lidocaine, brain neoplasm, supratentorial tumor resection, recovery quality, brain protection, postoperative pain

The construction of nanoplatforms with combined photothermal property and cascade enzymatic activities has become one of hot spots in anticancer research. However, the overheat of photothermal therapy (PTT) and the specific properties of tumor microenvironment (TME) greatly impaired the therapeutic efficiency. Herein, we rationally fabricated a virus-like SiOx/CeO2/VOx (SCV) nanoplatform for 1064 nm near-infrared (NIR) triggered mild-temperature PTT and nanozyme catalytic therapy. Firstly, the virus-like shape of SiOx/CeO2/VOx made it favorable for cell adhesion and had a better phagocytosis in cells, and the SCV generated effective PTT effect upon 1064 nm laser irradiation. Particularly, the produced VO2+ in TME could be used as a heat shock protein inhibitor to inhibit the expression of heat shock protein 60 (HSP60) to enhance the PTT efficiency. Moreover, SCV nanozyme exhibited obvious peroxidase-mimic (POD) catalytic activity, which could generate highly toxic free radical ion (•OH) under acidic conditions. The mild-temperature heat and •OH produced by enzymatic catalysis effectively blocked the tumor growth, verified firmly by the in vitro and in vivo tests. Our designed virus-like SCV nanozyme with POD mimic enzyme activity and mild photothermal effect may provide a new way of thinking for the combination therapy model.

Mitochondria are the "power plant" of the cell, providing a constant source of energy, and are involved in a variety of intracellular signaling pathways. Among these pathways, Ca2+ homeostasis is closely related to the normal function of mitochondria. By destroying the Ca2+ steady state of mitochondria and disrupting their multiple cellular activities, tumor cell killing can be achieved. In addition, the presence of an intracellular oxidative stress state triggers the closure of cellular calcium channels, which leads to intracellular Ca2+ retention and enrichment. We designed a targeted and tumor microenvironment (TME)-responsive CaO2-based nanosystem that can selectively target cancer cells for pH-controlled degradation and drug release, alter cellular physiological mechanisms by disrupting Ca2+ homeostasis in an artificial manner, and introduce mitochondrial Ca2+ excess-mediated apoptosis. Meanwhile, the production of Ca(OH)2 will raise the pH of the microenvironment and subsequently promote the oxidation process of glutathione by H2O2 released from CaO2 degradation, achieving the goal of remodeling TME. Moreover, calcium overload of tumor cells and calcification of tissues can both inhibit tumor growth and act as a contrast agent for computed tomography imaging.

Dried Lycium ruthenicum Murray (LM) fruits were ground by three different methods. The results showed that LM powders produced by superfine-grinding had smaller particle size (1.78–200.00 μm) as compared to shear-breaking and ball-milling. As a consequence, its bulk density, angle of repose and angle of slide were increased to 0.71 g/mL, 52.99° and 60.38°, respectively. Moreover, the superfine-ground LM powders displayed good dispersibility and infusion properties, showing improved water holding capacity and water solubility index than other powders during infusion. Consequently, the phytochemicals present in the superfine-ground LM powders could be released more easily, leading to the powders with higher anthocyanin and polysaccharide contents (24.50 and 160.54 mg/g) and antioxidant activities (DPPH, ABTS and FRAP: 34.53, 42.19 and 40.25 mM TE/g, respectively) than other powders. The results suggested that superfine-grinding could be a promising method for producing LM powders with higher contents of bioactive compounds and bioactivity.

Trait stability of Lactobacillus plantarum was studied following daily subculture over a 90-d period. Acid and bile tolerance, self-aggregation ability, cell hydrophobicity, pathogen inhibition activity, and cholesterol removal ability of cultures subcultured 30 (Lp30), 60 (Lp60), or 90 (Lp90) times were not significantly different from the original strain (Lp0). However, carbohydrate metabolism patterns did change; the Lp0 culture was unable to use d-sorbitol, α-methyl-d-mannose, and d-raffinose, whereas Lp30, Lp60, and Lp90 cultures could. Furthermore, gluconate and gentiobiose were fully used by the Lp0 culture but only poorly used by the Lp30, Lp60, and Lp90 cultures. Milk fermentation test confirmed that L. plantarum was unable to use lactose throughout laboratory evolution. Six non-synonymous mutations in genome of the Lp30, Lp60, and Lp90 cultures were identified by whole-genome sequencing, including mutant gene encoding the phosphoglycerate mutase, which is closely related to the transport and metabolism of carbohydrates. These mutations may play an important role in changes of carbohydrate metabolism patterns observed. Understanding the evolutionary characteristics of L. plantarum will help in development for food industry.

Although nanocatalytic therapy has become an emerging strategy for tumor treatment, the therapeutic effects of reactive oxygen species (ROS)-mediated treatment are still seriously limited by the inherent flaws of the enzymatic activities and the specific physicochemical properties of the tumor microenvironment (TME). Herein, we report an ultrasmall bimetallic oxide nanozyme (CuFe

The construction of nanoplatforms with combined photothermal properties and cascading enzymatic activities has become an active area of anticancer research. However, the overheating of photothermal therapy (PTT) and the specific properties of tumor microenvironment (TME) greatly impaired the therapeutic efficiency. Herein, we rationally fabricated a virus-like SiO

Clinical applications of nanozyme-initiated chemodynamic therapy (NCDT) have been severely limited by poor catalytic efficiency of nanozymes, insufficient endogenous H2O2 content, and off-target consumption. Herein, we develop hollow mesoporous Mn/Zr-co-doped CeO2 tandem nanozyme (PHMZCO-AT) with elaborately regulated multi-enzymatic activities, i.e., simultaneously enhancing superoxide dismutase (SOD)-like and peroxidase (POD)-like activities and inhibiting catalase (CAT)-like activity, serving as an H2O2 homeostasis disruptor to promote H2O2 evolvement and restrain off-target elimination of H2O2 for achieving intensive NCDT. PHMZCO-AT nanozymes with SOD-like activity can catalyze endogenous O2·– into H2O2 in the tumor region. The suppression of CAT activity and depletion of glutathione by PHMZCO-AT largely weaken the off-target decomposition of H2O2 to H2O. Elevated H2O2 is then exclusively catalyzed by the downstream POD-like activity of PHMZCO-AT to generate toxic hydroxyl radicals, further inducing tumor apoptosis and death. T1-weighted magnetic resonance imaging and high-contrast X-ray computed tomography imaging are also achieved using PEG/PHMZCO-AT nanozymes due to the existence of paramagnetic Mn2+ species and high X-ray attenuation ability of elemental Zr, permitting in vivo tracking of the therapeutic process. This work presents a powerful paradigm to achieve intensive NCDT efficacy by simultaneously regulating multi-enzymatic activities of Ce-based nanozymes and perturbing the H2O2 homeostasis in tumor microenvironment. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) Submitted/Accepted version The work was supported by the MOST Grant (2016YFA0101202), the National Natural Science Foundation of China (51972075 and 51772059), the Singapore Agency for Science, Technology and Research (A*STAR) AME IRG grant (A20E5c0081), the Singapore National Research Foundation Investigatorship (NRF-NRFI2018-03), and the Fundamental Research Funds for the Central Universities.

Reducing the scavenging capacity of reactive oxygen species (ROS) and elevating ROS production are two primary goals of developing novel sonosensitizers for sonodynamic therapy (SDT). Hence, ultrathin 2D Bi

The development of a stimulus-responsive nanosystem provides an effective method for improving the accuracy and efficiency of chemotherapy. Meanwhile, traditional photodynamic therapy (PDT) has been substantially restricted by the low dosage of photosensitizer and limited penetration depth of the ultraviolet (UV) or visible light used for excitation. Here, we designed a smart multifunctional nanoplatform by coating core-shell composite mesoporous silica-encapsulated upconversion nanoparticles and chlorin e6 (Ce6) with degradable calcium phosphate, followed by the loading of doxorubicin (DOX). In our structure, the as-synthesized nanoplatform exhibits high responsiveness to a low pH value and degrades rapidly in the weakly acidic tumor microenvironment, allowing the quick release of loaded DOX in tumor sites. Interestingly, the loaded DOX, whose release depends on the pH value and positively correlates with the calcium-ion concentration, enables drug release to be monitored in real time. Combined with photosensitizer Ce6-induced PDT triggered by an 808 nm near-infrared light, synergistic chemo-photodynamic therapy is achieved, thus leading to a highly efficient anticancer treatment in vitro and in vivo. Importantly, the inherent properties of rare earth ions (Gd3+, Yb3+, and Nd3+) make the nanoplatform possess UCL, MRI, and CT trimode imaging capabilities, thus achieving a multiple imaging modality-guided synergistic therapy.

Gasotransmitters with high therapeutic efficacy and biosafety have been drawing the attention of researchers. Nevertheless, how to effectively deliver gases to and precisely control their generation at the lesion as well as integrate them with other therapies to realize precision therapy have remained elusive. Herein, we report a versatile Cu2+-initiated nitric oxide (NO) nanocomposite for multimodal imaging-guided synergistic chemodynamic/photodynamic/gas therapy. After the nanomedicine was ingested by tumor cells, the acidic tumor microenvironment accelerated the decomposition of CuO2 and simultaneously triggered the Fenton-like catalytic reaction of Cu2+ and H2O2 to produce highly toxic ˙OH. By virtue of the NO generation and glutathione depletion, UMNOCC-PEG can relieve the antioxidant capacity and hypoxia of the tumor to improve the efficiency of chemodynamic therapy (CDT) and photodynamic therapy (PDT). Importantly, NO and reactive oxygen species (ROS) can generate reactive nitrogen species (RNS), which can result in DNA damage, further improving the therapeutic effect (cell apoptosis rate up to 93.4%). Moreover, the inherent properties of lanthanide ions endow UMNOCC-PEG with upconversion luminescence (UCL), CT and MRI trimodal imaging capability, achieving precise cancer treatment. By taking advantage of these features, the strategy developed here may provide a promising application foreground to conquer malignant tumors.

The development of near-infrared (NIR) laser triggered phototheranostics for multimodal imaging-guided combination therapy is highly desirable. However, multiple laser sources, as well as inadequate therapeutic efficacy, impede the application of phototheranostics. Here, we develop an all-in-one theranostic nanoagent PEGylated DCNP@DMSN-MoO

The therapeutic effect of traditional chemodynamic therapy (CDT) agents is severely restricted by their weakly acidic pH and glutathione (GSH) overexpression in the tumor microenvironment. Here, fusiform-like copper(II)-based tetrakis(4-carboxy phenyl)porphyrin (TCPP) nanoscale metal-organic frameworks (nMOFs) were designed and constructed for the first time (named PCN-224(Cu)-GOD@MnO2). The coated MnO2 layer can not only avoid conjugation of glucose oxidase (GOD) to damage normal cells but also catalyzes the generation of O2 from H2O2 to enhance the oxidation of glucose (Glu) by GOD, which also provides abundant H2O2 for the subsequent Cu+-based Fenton-like reaction. Meanwhile, the Cu2+ chelated to the TCPP ligand is converted to Cu+ by the excess GSH in the tumor, which reduces the tumor antioxidant activity to improve the CDT effect. Next, the Cu+ reacts with the plentiful H2O2 by enzyme catalysis to produce a toxic hydroxyl radical (•OH), and singlet oxygen (1O2) is synchronously generated from combination with Cu+, O2, and H2O via the Russell mechanism. Furthermore, the nanoplatform can be used for both TCPP-based in vivo fluorescence imaging and Mn2+-induced T1-weighted magnetic resonance imaging. In conclusion, fusiform-like PCN-224(Cu)-GOD@MnO2 nMOFs facilitate the therapeutic efficiency of chemodynamic and starvation therapy via combination with relief hypoxia and GSH depletion after acting as an accurate imaging guide.

In the process of the transformer substation construction, efficient management technology is needed to ensure the safety, reliability and normal progress of the field operation. At present, the management means are more to standardize people’s behavior quality by combining the manual inspection and the management system. The management means are relatively single, and the utilization efficiency of the human resources is low. It is proposed to use the three-dimensional panoramic technology to visualize the management of the substation. The UAV can collect the multi-directional images of the whole substation and acquire the three-dimensional panorama through processing. Based on this, the open and transparent management can be carried out to improve the management efficiency, and the construction process information database and the three-dimensional panoramic information database can be formed in the entire construction cycle.

The strategy of diagnosis-to-therapy to realize the integration of imaging and high antitumor efficiency has become the most promising method. Light-induced therapeutic technologies have drawn considerable interest. However, the limited penetration depth of UV/vis excitation and relatively low efficiency are the main obstacles for its further clinic application. For this concern, we presented a facile method to anchor ultrasmall ZnFe2O4 nanoparticles and upconversion luminescence nanoparticles (UCNPs) on graphene oxide (GO) nanosheets (GO/ZnFe2O4/UCNPs, abbreviated as GZUC). To solve the penetration question, here we introduced Tm3+-doped UCNPs to convert the high-penetrated near-infrared (NIR) light into UV/vis photons to activate the photodynamic process. In this system, the dual phototherapy from GO and ZnFe2O4 has been realized upon NIR laser irradiation. Combined with the photodynamic therapy (PDT) based on Fenton reaction that ZnFe2O4 nanoparticles react with excessive H2O2 in tumor microenvironment...

The development of the advanced imaging probe holds the key to the achievement of target imaging and metastasis tracing. The bismuth based nanoprobe has been regarded as the most promising X-ray computed tomography probe due to its largest X-ray attenuation coefficient. Accordingly, the bismuth nanoparticles with controllable size distribution and light weight have been fabricated through a one pot synthesis strategy. The surface modification can be easily conducted with the polyethylene glycol to make the nanoparticles hydrosoluble and biocompatible. More importantly, the Bi nanoparticles can be excited by light to conduct excitation wavelength dependent emission in the visible (Vis) and near-infrared (NIR) region, which makes it possible to utilize it for fluorescence imaging. Under the detection of the multimode CT/fluorescence imaging, the long circulation time of the Bi nanoparticles and its specific accumulation at the liver and intestine can be visually displayed. The facile and large scale prepara...

The tumor microenvironment (TME) is complex in composition and unique in nature, and is closely related to the growth, invasion and metastasis of tumor cells. Improving and remodeling the TME to return it to a normalized state can fundamentally disrupt the environment and/or nutrient supply on which tumor cells depend. To achieve this goal, based on the unique physicochemical properties and biological effects of CaO2, we designed and constructed a Ca2+ nanogenerator (named as CaO2-Cu/ICG@PCM) that enables H2O2/O2 self-supplementation and GSH depletion. The 808 nm laser induces the heat generation of photosensitizer indocyanine green (ICG) to initiate a series of reactions, followed by the production of copper ions, H2O2, O2 and large amounts of Ca2+, which can eventually lead to the combined treatment of photodynamic therapy (PDT), chemodynamic therapy (CDT) and calcium overload. Additionally, the reaction process is accompanied by the generation of Ca(OH)2, which greatly improves the acidic environment of TME and effectively promotes the oxidation process of GSH by H2O2, achieving the purpose of remodeling TME. It is worth mentioning that a large amount of free Ca2+ accumulating in tumor cells can rapidly initiate the process of calcium overload and calcification, which can not only play a role in tumor suppression, but also assist CT imaging to detect the effect of treatment. Thus, CaO2-Cu/ICG@PCM could be a promising candidate for bioimaging and tumor therapy.

Reducing the scavenging capacity of reactive oxygen species (ROS) and elevating ROS production are two primary goals of developing novel sonosensitizers for sonodynamic therapy (SDT). Hence, ultrathin 2D Bi2 MoO6 -poly(ethylene glycol) nanoribbons (BMO NRs) are designed as piezoelectric sonosensitizers for glutathione (GSH)-enhanced SDT. In cancer cells, BMO NRs can consume endogenous GSH to disrupt redox homeostasis, and the GSH-activated BMO NRs (GBMO) exhibit an oxygen-deficient structure, which can promote the separation of electron-hole pairs, thereby enhancing the efficiency of ROS production in SDT. The ultrathin GBMO NRs are piezoelectric, in which ultrasonic waves introduce mechanical strain to the nanoribbons, resulting in piezoelectric polarization and band tilting, thus accelerating toxic ROS production. The as-synthesized BMO NRs enable excellent computed tomography imaging of tumors and significant tumor suppression in vitro and in vivo. A piezoelectric Bi2 MoO6 sonosensitizer-mediated two-step enhancement SDT process, which is activated by endogenous GSH and amplified by exogenous ultrasound, is proposed. This process not only provides new options for improving SDT but also broadens the application of 2D piezoelectric materials as sonosensitizers in SDT.

The goal of this work was to use laboratory evolution assays and whole-genome sequencing to develop and test the safety of a probiotic, Lactobacillus plantarum, with high-level of resistance to gentamicin. The evolution of L. plantarum was evaluated under the selective pressure from gentamicin and subsequently when the selective pressure was removed. After 30 days of selective pressure from gentamicin, the minimum inhibitory concentration (MIC) of L. plantarum to gentamicin increased from 4 to 512 μg/mL and remained stable at this level. After removing the selective pressure, the resistance of L. plantarum to gentamicin decreased to 64 μg/mL after 20 days, and remained stable thereafter. Although the MIC declined it was still higher than the cut-off value recommended by EFSA, indicating that the acquisition of gentamicin-resistance was an irreversible process. Using whole-genome sequencing, gene mutations were identified in the strains that had undergone selection pressure from gentamicin as well as in the strains where the selection pressure was subsequently removed. Specifically, four non-synonymous mutations were detected including one single nucleotide polymorphism (SNP), one insertion, and two structural variants (SVs), of which the mutations in genes encoding the drug resistance MFS transporter and transcriptional regulator of AraC family were only detected in the strains under selective pressure from gentamicin. The results indicate that these mutations play an important role in increasing the resistant levels of L. plantarum to gentamicin. The mobility analysis of mutant genes confirmed that they were not located on mobile elements of the genome of highly resistant L. plantarum, indicating that horizontal gene transfer was not possible.

The goal of this work was to use laboratory evolution assays and whole-genome sequencing to develop and test the safety of a probiotic, Lactobacillus plantarum, with high-level of resistance to gentamicin. The evolution of L. plantarum was evaluated under the selective pressure from gentamicin and subsequently when the selective pressure was removed. After 30 days of selective pressure from gentamicin, the minimum inhibitory concentration (MIC) of L. plantarum to gentamicin increased from 4 to 512 μg/mL and remained stable at this level. After removing the selective pressure, the resistance of L. plantarum to gentamicin decreased to 64 μg/mL after 20 days, and remained stable thereafter. Although the MIC declined it was still higher than the cut-off value recommended by EFSA, indicating that the acquisition of gentamicin-resistance was an irreversible process. Using whole-genome sequencing, gene mutations were identified in the strains that had undergone selection pressure from gentamicin as well as in the strains where the selection pressure was subsequently removed. Specifically, four non-synonymous mutations were detected including one single nucleotide polymorphism (SNP), one insertion, and two structural variants (SVs), of which the mutations in genes encoding the drug resistance MFS transporter and transcriptional regulator of AraC family were only detected in the strains under selective pressure from gentamicin. The results indicate that these mutations play an important role in increasing the resistant levels of L. plantarum to gentamicin. The mobility analysis of mutant genes confirmed that they were not located on mobile elements of the genome of highly resistant L. plantarum, indicating that horizontal gene transfer was not possible.

Photodynamic therapy (PDT) and photothermal therapy (PTT) combined treatment guided by imaging diagnosis has brought the cancer treatment into a new stage. But simple nanoplatforms with multifunctional therapeutic performance are rarely designed. Herein, we adopt ball-milling method to fabricate spherical BiAgOS nanoparticles as photosensitizer to apply for 808 nm near-infrared (NIR) light triggered PDT and PTT co-therapy. The polyethylene glycol (PEG) modified BiAgOS NPs show a great absorption in the range of visible light to near-infrared region. Under 808 nm laser irradiation, BiAgOS-PEG NPs have obvious photothermal and photosensitive effects together with excellent X-ray computed tomography (CT) imaging function. The in vitro and in vivo experiments exhibit that the BiAgOS-PEG NPs have good biocompatibility, excellent tumor cells inhibition effects simultaneously. Our finding described the first use of BiAgOS-PEG NPs as a semiconductor photosensitizer for anti-cancer treatment, providing a promising strategy to fabricate this kind of material for imaging guided NIR light induced combined tumor treatment.

Synergistic therapy with different treatment mechanisms is an emerging strategy to improve antitumor efficiency. Here, a diversified nanoplatform (Ag2S@MSN-TGF) is synthesized by coating mesoporous silica on Ag2S nanoparticles (NPs), followed by loading hypoxia-active prodrug (tirapazamine) insides the mesoporous silica and coating glucose oxidase (GOx) on the surface. Considering that the degree of hypoxia in tumors is not high enough, GOx is combined with hypoxia-active tirapazamine prodrug, and two important functions are realized. One is the consumption of oxygen to enhance the hypoxic environment and promote the curative effect of tirapazamine, and the other is the consumption of glucose to achieve starvation treatment. Additionally, we take the lead in using Ag2S NPs for second near-infrared (NIR-II, 1064 nm) excited photothermal therapy (PTT). The photothermal conversion efficiency (44.7%) of Ag2S@MSN-TGF is even better than that under 808 nm laser irradiation (38.2%). Finally, in vivo NIR-II fluorescence imaging well demonstrated that Ag2S@MSN-TGF can offer an obvious tracking effect for the therapeutic process. Therefore, superior to any single therapeutic mode, our designed Ag2S@MSN-TGF demonstrates an excellent tumor inhibition effect in vitro and in vivo due to synergistic starvation, hypoxia-active prodrug treatment and PTT effect, suggesting the significant prospect of NIR-II imaging guided antitumor therapy.

Nanocatalytic therapy, using artificial nanoscale enzyme mimics (nanozymes), is an emerging technology for therapeutic treatment of various malignant tumors. However, the relatively deficient catalytic activity of nanozymes in the tumor microenvironment (TME) restrains their biomedical applications. Here, a versatile and bacteria-like PEG/Ce-Bi@DMSN nanozyme is developed by coating uniform Bi2 S3 nanorods (NRs) with dendritic mesoporous silica (Bi2 S3 @DMSN) and then decorating ultrasmall ceria nanozymes into the large mesopores of Bi2 S3 @DMSN. The nanozymes exhibit dual enzyme-mimic catalytic activities (peroxidase-mimic and catalase-mimic) under acidic conditions that can regulate the TME, that is, simultaneously elevate oxidative stress and relieve hypoxia. In addition, the nanozymes can effectively consume the overexpressed glutathione (GSH) through redox reaction. Photothermal therapy (PTT) is introduced to synergistically improve the dual enzyme-mimicking catalytic activities and depletion of the overexpressed GSH in the tumors by photonic hyperthermia. This is achieved by taking advantage of the desirable light absorbance in the second near-infrared (NIR-II) window of the PEG/Ce-Bi@DMSN nanozymes. Subsequently the reactive oxygen species (ROS)-mediated therapeutic efficiency is significantly improved. Therefore, this study provides a proof of concept of hyperthermia-augmented multi-enzymatic activities of nanozymes for tumor ablation.

The strategy of diagnosis-to-therapy to realize the integration of imaging and high antitumor efficiency has become the most promising method. Light-induced therapeutic technologies have drawn considerable interest. However, the limited penetration depth of UV/vis excitation and relatively low efficiency are the main obstacles for its further clinic application. For this concern, we presented a facile method to anchor ultrasmall ZnFe

This study aimed to investigate the effect of Modified Sanzi Yangqin Decoction on tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) in skeletal muscle of type 2 diabetic rats. The rat model of type 2 diabetes was induced by high-fat diet and multiple low-dose streptozotocin injections. Diabetic model rats were randomly divided into 5 groups: the model control group, the metformin group, and Modified Sanzi Yangqin Decoction groups of low, medium, and high doses. OGTT was conducted every two weeks during treatment period. At the end of the treatment, the fasting blood glucose (FBG) level and the fasting C-peptide level were measured to calculate insulin resistance index. The levels of IRS-1, p-IRS-1Tyr895, and protein tyrosine phosphates 1B (PTP1B) in skeletal muscle were also measured. Modified Sanzi Yangqin Decoction significantly reduced the FBG level, increased the fasting C-peptide level, and lowered the insulin resistance index in type 2 diabetic rats. It also significantly increased the protein level of p-IRS-1Tyr895 and reduced the PTP1B protein level in skeletal muscle of type 2 diabetic rats. Modified Sanzi Yangqin Decoction increases tyrosine phosphorylation of IRS-1 in skeletal muscle of type 2 diabetic rats, which results from the increase of p-IRS-1Tyr895 protein and is related to the suppression of PTP1B protein.

The chemical compositions and α-glucosidase inhibitory activities of anthocyanins extracted from blueberry, blackcurrant and blue honeysuckle fruits and their acid hydrolysates (anthocyanidins) were analysed. Those anthocyanins were glycosidic anthocyanins that converted to anthocyanidins during acid hydrolysis, leading to increases in their α-glucosidase inhibitory activities (expressed as IC50 values) from 0.232, 0.152 and 0.188 to 0.113 to 0.005 and 0.025 mg/mL. The potential inhibitory mechanism of these anthocyanidins was then investigated through inhibition kinetics, fluorescence quenching and docking simulations. The results showed the following: 1) all anthocyanidins were mixed-type inhibitors of α-glucosidase and they bind more tightly to free α-glucosidase as compared to the α-glucosidase-substrate complex; 2) anthocyanidin inhibition of α-glucosidase was a static procedure, presumably driven by hydrophobic associations and hydrogen bonding; and 3) all anthocyanidins were inserted into the active site of α-glucosidase and avoided the entrance of p-nitrophenyl-a-D-glucopyranoside. This study is valuable for anthocyanidins as potential α-glucosidase inhibitors.

A theory for dressed quantum ion acoustic waves (QIAWs), which includes higher-order corrections when QIAWs are investigated by the reductive perturbation method, is presented for unmagnetized plasmas containing positive and negative ions and weakly relativistic electron beams. The properties of the QIAWs are investigated using a quantum hydrodynamic model, from which a Korteweg–de Vries equation is derived using the reductive perturbation method. An equation including higher-order dispersion and nonlinearity corrections is also derived, and the physical parameter space is discussed for the importance of these corrections.

Stencil computations are a class of computational kernels which update array elements according to some stencil patterns, and they have drawn more attentions recently. The Intel Xeon Phi coprocessor, which is designed for high performance computing, has not been fully evaluated for stencil computations. In this paper, we present a series of optimizations to accelerate the 3-D 7-point stencil code on Intel Xeon Phi coprocessor. We focus on how to exploit the performance potential of many cores and wide-vector unit in each core. In order to exploit data locality, we use loop tiling and we propose a method for calculating the block size while tiling. The achieved performance brings a speedup of 211.6 in comparison with the serial code.

The ARMv8 64-bit platform has been considered as an alternative for high performance computing (HPC). Stencil computations are a class of iterative kernels which update array elements according to a stencil. In this paper, we evaluate the performance and scalability of one ARMv8 64-bit Multi-Core Processor with 7-point 3D stencil code, and a series of optimization are devised for the stencil code. In the optimization, we mainly focus on how to parallelize the kernel and how to exploit data locality with loop tiling, also we improve the calculation of the block size in tiling. The achieved performance differs with the grid size of stencil, and the optimal performance is 24.4 % of the peak DP Flops for the grid size of \(64^{3}\). Comparing with Intel Xeon processor, the performance of the ARMv8 64-bit processor is about 40 % of that of Sandy Bridge for the stencil code with the grid size of \(512^{3}\), but this ARMv8 64-bit processor shows better scalability.