Publications by authors named "Cheng Zhu"

477 Publications

Duration of antibiotic therapy in systemic lupus erythematosus patients with hospital-acquired bacterial pneumonia in eastern China.

Ann Palliat Med 2021 Feb 8. Epub 2021 Feb 8.

Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: To investigate the duration of antibiotic therapy and its influencing factors in treating systemic lupus erythematosus (SLE) patients with hospital-acquired bacterial pneumonia (HABP).

Methods: Clinical data of SLE patients with HABP from January 2015 to December 2019 were collected. Duration of antibiotic treatment and its correlations with the severity of pneumonia, status of SLE and the time to clinical stability (TCS) were analysed. A logistic regression model was performed to screen the risk factors influencing the total antibiotic treatment course >7 days.

Results: Three hundred and forty-four patients were finally enrolled in the study and the mean duration of total antibiotic therapy was 9.5 days. The TCS was related to the duration of antibiotic therapy (R2 =0.76, P<0.0001). More patients with multidrug-resistant pathogen infection and Candida colonization were found in the total duration >7 days group. SLE disease activity index (SLEDAI) [odds ratio (OR) =5.52, 95% confidence interval (CI): 3.59-7.28], taking immunosuppressants during HABP treatment (OR =5.29, 95% CI: 3.93-7.09) and multidrug-resistant pathogen infection (OR =4.91, 95% CI: 1.45-6.87) were greatly impacted risk factors (P<0.05, respectively).

Conclusions: The duration of antibiotic therapy in SLE patients with HABP was longer than the course recommended by practice guidelines. The severity of the disease and the host's immune status might influence the duration of treatment.
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http://dx.doi.org/10.21037/apm-20-584DOI Listing
February 2021

Experimental and simulated evaluations of airborne contaminant exposure in a room with a modified localized laminar airflow system.

Environ Sci Pollut Res Int 2021 Feb 15. Epub 2021 Feb 15.

Department of Energy and Environmental System Engineering, Zhejiang University of Science and Technology, Hangzhou, 310023, People's Republic of China.

The traditional mixing ventilation is not an energy effective approach to remove indoor air pollutants, maintain breath zone air quality, and control the airborne transmission. This study investigated the potential of a localized laminar airflow ventilation system to alleviate human exposure to pollutants. Breathing thermal manikins with sitting posture and supine posture were used to simulate the human. NO was used as the tracer gas to simulate the indoor pollutant emission. The contaminant exposure index (ε) and intake fraction index (IF) were used to assess the risk of human pollutant exposure for various supply air velocities given different emission source positions. Enhanced pollutant removal efficiency (E) (from the result) showed the qualification and desirability of the localized laminar airflow ventilation system in improving the breath zone air quality. The results showed that the CFD results could fit well with the experimental data and found out the interaction between thermal plume and supply air. The results also indicated a low ε and IF, with over 90%, all of which were highly correlated with the supply velocity. Human's different breathing methods have little influence on the pollutant exposure so as to the location of the pollution source. This study found that localized laminar airflow ventilation system could efficiently provide fresh air to the breathing zone without sacrificing the thermal environment around human. It can be used for small region air quality control such as that in the bedroom and living room where desired air quality is favored.
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http://dx.doi.org/10.1007/s11356-021-12685-4DOI Listing
February 2021

ImmunoPET imaging of human CD8 T cells with novel Ga-labeled nanobody companion diagnostic agents.

J Nanobiotechnology 2021 Feb 9;19(1):42. Epub 2021 Feb 9.

Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai, 200127, China.

Background: Although immunotherapy has revolutionized treatment strategies for some types of cancers, most patients failed to respond or obtain long-term benefit. Tumor-infiltrating CD8 T lymphocytes are closely related to the treatment outcome and prognosis of patients. Therefore, noninvasive elucidation of both systemic and tumor-infiltrating CD8 T lymphocytes is of extraordinary significance for patients during cancer immunotherapy. Herein, a panel of Ga-labeled Nanobodies were designed and investigated to track human CD8 T cells in vivo through immuno-positron emission tomography (immunoPET).

Results: Among the screened Nanobodies, SNA006a showed the highest binding affinity and specificity to both human CD8 protein and CD8 cells in vitro, with the equilibrium dissociation constant (K) of 6.4 × 10 M and 4.6 × 10 M, respectively. Ga-NOTA-SNA006 was obtained with high radiochemical yield and purity, and stayed stable for at least 1 h both in vitro and in vivo. Biodistribution and Micro-PET/CT imaging studies revealed that all tracers specifically concentrated in the CD8 tumors with low accumulation in CD8 tumors and normal organs except the kidneys, where the tracer was excreted and reabsorbed. Notably, the high uptake of Ga-NOTA-SNA006a in CD8 tumors was rapid and persistent, which reached 24.41 ± 1.00% ID/g at 1.5 h after intravenous injection, resulting in excellent target-to-background ratios (TBRs). More specifically, the tumor-to-muscle, tumor-to-liver, and CD8 to CD8 tumor was 28.10 ± 3.68, 5.26 ± 0.86, and 19.58 ± 2.70 at 1.5 h, respectively. Furthermore, in the humanized PBMC-NSG and HSC-NPG mouse models, Ga-NOTA-SNA006a accumulated in both CD8 tumors and specific tissues such as liver, spleen and lung where human CD8 antigen was overexpressed or CD8 T cells located during immunoPET imaging.

Conclusions: Ga-NOTA-SNA006a, a novel Nanobody tracer targeting human CD8 antigen, was developed with high radiochemical purity and high affinity. Compared with other candidates, the long retention time, low background, excellent TBRs of Ga-NOTA-SNA006a make it precisely track the human CD8 T cells in mice models, showing great potential for immunotherapy monitoring and efficacy evaluation.
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http://dx.doi.org/10.1186/s12951-021-00785-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871532PMC
February 2021

Continuous Glucose Monitoring in Patients With Insulinoma Treated by Endoscopic Ultrasound-Guided Ethanol Injection.

Pancreas 2021 Feb;50(2):183-188

From the Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission Departments of Gastroenterology Pharmacy, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China.

Objectives: The aims of this study were to analyze the continuous glucose monitoring (CGM) profiles of patients with insulinoma before and after treatment with endoscopic ultrasound-guided ethanol injection and assess the value of CGM in curative effect evaluating.

Methods: We included 8 patients, and CGM was performed for 3 to 5 days before and after treatment.

Results: The proportion of monitoring points at which the glucose level was lower than 3.9 mmol/L after treatment decreased in patient 5 (from 4% to 3%) and patient 8 (from 30% to 12%), whereas the proportion increased in patient 1 (from 1% to 16%), patient 3 (from 5% to 23%), and patient 7 (from 7% to 63%). There was no mean significant difference between CGM values (5.75 [standard deviation, 2.49] mmol/L) and self-monitoring of blood glucose values (5.76 [standard deviation, 2.32] mmol/L) (P > 0.05). Pearson correlation analysis showed positive correlation between CGM values and self-monitoring of blood glucose values (r = 0.88, P < 0.05). Clarke Error Grid Analysis showed that 91.5% of pairs were located in areas A and B.

Conclusions: Continuous glucose monitoring is useful for detecting hypoglycemia and evaluating curative effect, but the correction of fingertip blood glucose is necessary when the blood glucose is relatively low.
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http://dx.doi.org/10.1097/MPA.0000000000001735DOI Listing
February 2021

[Screening of tomato cultivars in cadmium-polluted areas and study on their antioxidant capacity].

Sheng Wu Gong Cheng Xue Bao 2021 Jan;37(1):242-252

Key Laboratory of Marine Food Quality and Hazard Controlling Technology of Zhejiang Province, Zhejiang Provincial Key Laboratory of Biometrology and Inspection & Quarantine, College of Life Sciences, China Jiliang University, Hangzhou 310018, Zhejiang, China.

To screen the available tomato pollution-safe cultivar varieties and reduce the potential food safety risks in Cd-polluted areas, the differences of Cd accumulation in different tomato (Solanum lycopersicum) varieties in southern China were studied by soil culture and hydroponic experiments. Firstly, the high and low accumulation varieties were selected from 25 tomato varieties under 2.94 mg/kg Cd stress by soil culture test, and then the responses of high and low accumulation tomato varieties to Cd stress were determined by hydroponic experiments. The results of soil culture test show that under 2.94 mg/kg Cd stress, there were significant differences in plant height, total biomass and yield among 25 tomato cultivars, and the Cd contents of fruits of all 25 tomato cultivars exceeded the highest limit value (0.05 mg/kg) of CAC (Codex alimentarius commission). Through cluster analysis, 7, 4 and 14 varieties accumulating relatively high, medium, and low concentrations of Cd in the fruits were screened, among which the highest, the lowest, and the average Cd contents in the fruits were 3.06 mg/kg DW, 1.47 mg/kg DW, and 2.21 mg/kg DW, respectively. The results of hydroponic experiment show that under the same concentration of Cd stress, Qiantangxuri F1, a high Cd accumulating variety, absorbed Cd faster, accumulated more Cd, used shorter oxidative stress response time and had stronger tolerance to Cd than Zhefen 3053, a low Cd accumulating variety. The typical high and low Cd accumulating varieties can provide a reference for agricultural production in heavy metal polluted areas and the development of molecular-assisted breeding methods of PSC. At present, cultivating low Cd accumulating PSC varieties and dynamic monitoring of Cd contents in tomato fruits are feasible methods in medium and light Cd-polluted areas.
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http://dx.doi.org/10.13345/j.cjb.200242DOI Listing
January 2021

Expansion and Functional Diversification of TFIIB-Like Factors in Plants.

Int J Mol Sci 2021 Jan 23;22(3). Epub 2021 Jan 23.

College of Life Sciences, China Jiliang University, 258 Xueyuan Street, Hangzhou 310018, China.

As sessile organisms, plants have evolved unique patterns of growth and development, elaborate metabolism and special perception and signaling mechanisms to environmental cues. Likewise, plants have complex and highly special programs for transcriptional control of gene expression. A case study for the special transcription control in plants is the expansion of general transcription factors, particularly the family of Transcription Factor IIB (TFIIB)-like factors with 15 members in Arabidopsis. For more than a decade, molecular and genetic analysis has revealed important functions of these TFIIB-like factors in specific biological processes including gametogenesis, pollen tube growth guidance, embryogenesis, endosperm development, and plant-microbe interactions. The redundant, specialized, and diversified roles of these TFIIB-like factors challenge the traditional definition of general transcription factors established in other eukaryotes. In this review, we discuss general transcription factors in plants with a focus on the expansion and functional analysis of plant TFIIB-like proteins to highlight unique aspects of plant transcription programs that can be highly valuable for understanding the molecular basis of plant growth, development and responses to stress conditions.
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http://dx.doi.org/10.3390/ijms22031078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865254PMC
January 2021

Cargo Recognition and Function of Selective Autophagy Receptors in Plants.

Int J Mol Sci 2021 Jan 20;22(3). Epub 2021 Jan 20.

College of Life Sciences, China Jiliang University, Hangzhou 310018, China.

Autophagy is a major quality control system for degradation of unwanted or damaged cytoplasmic components to promote cellular homeostasis. Although non-selective bulk degradation of cytoplasm by autophagy plays a role during cellular response to nutrient deprivation, the broad roles of autophagy are primarily mediated by selective clearance of specifically targeted components. Selective autophagy relies on cargo receptors that recognize targeted components and recruit them to autophagosomes through interaction with lapidated autophagy-related protein 8 (ATG8) family proteins anchored in the membrane of the forming autophagosomes. In mammals and yeast, a large collection of selective autophagy receptors have been identified that mediate the selective autophagic degradation of organelles, aggregation-prone misfolded proteins and other unwanted or nonnative proteins. A substantial number of selective autophagy receptors have also been identified and functionally characterized in plants. Some of the autophagy receptors in plants are evolutionarily conserved with homologs in other types of organisms, while a majority of them are plant-specific or plant species-specific. Plant selective autophagy receptors mediate autophagic degradation of not only misfolded, nonactive and otherwise unwanted cellular components but also regulatory and signaling factors and play critical roles in plant responses to a broad spectrum of biotic and abiotic stresses. In this review, we summarize the research on selective autophagy in plants, with an emphasis on the cargo recognition and the biological functions of plant selective autophagy receptors.
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http://dx.doi.org/10.3390/ijms22031013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864022PMC
January 2021

Adaptive model-parameter-free fault-tolerant trajectory tracking control for autonomous underwater vehicles.

ISA Trans 2021 Jan 7. Epub 2021 Jan 7.

Science and Technology on Underwater Vehicle Laboratory, Harbin Engineering University, Harbin 150001, China.

This paper provides a model-parameter-free control strategy for the trajectory tracking problem of the autonomous underwater vehicle exposed to external disturbances and actuator failures. Two control architectures have been constructed such that the system states could be forced to the desired trajectories with acceptable performance. By combining sliding mode control (SMC) technology and adaptive algorithm, the first control architecture is developed for tracking missions under healthy actuators. Taking actuator failures scenario into account, system reliability is improved considerably by the utilization of a passive fault-tolerant technology in the second controller. Benefitting from properties of Euler-Lagrange systems, the nonlinear dynamics of the underwater vehicles could be handled properly such that the proposed controllers could be developed without model parameters. Finally, the validity of the proposed controllers is demonstrated by theoretical analysis and numerical simulations.
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http://dx.doi.org/10.1016/j.isatra.2020.12.059DOI Listing
January 2021

Strategically positioning cooperators can facilitate the contagion of cooperation.

Sci Rep 2021 Jan 13;11(1):1127. Epub 2021 Jan 13.

Faculty of Natural Sciences and Mathematics, University of Maribor, Koroška cesta 160, 2000, Maribor, Slovenia.

The spreading of cooperation in structured population is a challenging problem which can be observed at different scales of social and biological organization. Generally, the problem is studied by evaluating the chances that few initial invading cooperators, randomly appearing in a network, can lead to the spreading of cooperation. In this paper we demonstrate that in many scenarios some cooperators are more influential than others and their initial positions can facilitate the spreading of cooperation. We investigate six different ways to add initial cooperators in a network of cheaters, based on different network-based measurements. Our research reveals that strategically positioning the initial cooperators in a population of cheaters allows to decrease the number of initial cooperators necessary to successfully seed cooperation. The strategic positioning of initial cooperators can also help to shorten the time necessary for the restoration of cooperation. The optimal ways in which the initial cooperators should be placed is, however, non-trivial in that it depends on the degree of competition, the underlying game, and the network structure. Overall, our results show that, in structured populations, few cooperators, well positioned in strategically chosen places, can spread cooperation faster and easier than a large number of cooperators that are placed badly.
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http://dx.doi.org/10.1038/s41598-020-80770-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806618PMC
January 2021

Study on the decay characteristics and transmission risk of respiratory viruses on the surface of objects.

Environ Res 2021 Jan 6;194:110716. Epub 2021 Jan 6.

MOE Key Laboratory of Deep Earth Science and Engineering, College of Architecture and Environment, Sichuan University, Chengdu, China; Institute for Disaster Management and Reconstruction, Sichuan University, Chengdu, China. Electronic address:

The complex and changeable environment is a brand-new living condition for the viruses and pathogens released by the infected people to the indoor air or deposited on the surface of objects, which is an important external condition affecting the decay and transmission risk of the viruses. Exposure to contaminated surfaces is one of the main routes of respiratory diseases transmission. Therefore, it is very important for epidemic prevention and control to study the law of virus decay and the environmental coupling effect on various surfaces. Based on the analysis of the influencing mechanism, a large amount of experimental evidence on the survival of viruses on the surface of objects were excavated in this paper, and the effects of various factors, such as surface peripheral temperature, relative humidity, virus-containing droplet volume, surface materials and virus types, on the decay rate constants of viruses were comprehensively analyzed. It was found that although the experimental methods, virus types and experimental conditions varied widely in different experiments, the virus concentrations on the surface of objects all followed the exponential decay law, and the coupling effect of various factors was reflected in the decay rate constant k. Under different experimental conditions, k values ranged from 0.001 to 100 h, with a difference of 5 orders of magnitude, corresponding to the characteristic time t between 500 and 0.1 h when the virus concentration decreased by 99%. This indicates a large variation in the risk of virus transmission in different scenarios. By revealing the common law and individuality of the virus decay on the surface of objects, the essential relationship between the experimental observation phenomenon and virus decay was analyzed. This paper points out the huge difference in virus transmission risk on the surface at different time nodes, and discusses the prevention and control strategies to grasp the main contradictions in the different situations.
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http://dx.doi.org/10.1016/j.envres.2021.110716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834477PMC
January 2021

High-Resolution Melting Analysis of Sequences Distinguishes Pufferfish Species ( spp.) in China.

J Agric Food Chem 2021 Jan 5;69(2):794-804. Epub 2021 Jan 5.

Key Laboratory of Marine Food Quality and Hazard Controlling Technology of Zhejiang Province, College of Life Sciences, China Jiliang University, Hangzhou 310018, China.

Pufferfish is a traditional, delicious dish in Asia. However, eating wild or improperly processed pufferfish causes serious poisoning. This study aimed to exploit the high-resolution melting (HRM) method for authenticating four species of pufferfish (, , , and ). Candidate DNA barcodes, including the cytochrome c oxidase subunit I (), cytochrome oxidase b (), and the control region (D-loop), were analyzed, with selected as the optimal DNA barcode. An HRM method was developed to identify 57 commercial fish samples in China, including 33 commercial pufferfish products and 24 unlabeled fish products. The findings revealed that the pufferfish products were or , and four samples were detected in unlabeled fish products. These results showed that DNA barcode coupled with HRM analysis was a rapid and efficient tool to identify pufferfish, which might aid in the prevention of consumer fraud or mislabeling of fish products.
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http://dx.doi.org/10.1021/acs.jafc.0c06584DOI Listing
January 2021

Corrigendum to "In vitro and in vivo anti-biofilm effects of silver nanoparticles immobilized on titanium" [Biomaterials (2014) 9114-9125].

Biomaterials 2021 Feb 29;269:120615. Epub 2020 Dec 29.

Department of Physics & Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China.

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http://dx.doi.org/10.1016/j.biomaterials.2020.120615DOI Listing
February 2021

Impact of permissive hypercapnia on regional cerebral oxygen saturation and postoperative cognitive function in patients undergoing cardiac valve replacement.

Ann Palliat Med 2020 Nov;9(6):4066-4073

Department of Anesthesiology, Nanjing Frist Hospital, Nanjing Medical University, Nanjing, China.

Background: Cardiac valve replacement (CVR) is currently the main surgical treatment for patients with valvular heart diseases (VHD). Postoperative cognitive dysfunction (POCD) is one of the most serious complications of cardiac surgery. Permissive hypercapnia (PHC), an important lung-protective ventilation strategy, has protective effects on vital organs, including the heart, lungs, and central nervous system (CNS). The main objective of this study is to assess the effect of the PHC ventilation strategy on rSO2 and postoperative cognitive function in patients undergoing CVR.

Methods: A total of 66 patients undergoing CVR were included and randomly divided into the PHC ventilation group (Group H, n=33) and conventional ventilation group (Group C, n=33). Patients of both groups were subjected to conventional ventilation before cardiopulmonary bypass (CPB). patients in Group H were subjected to the PHC ventilation strategy to keep the partial pressure of carbon dioxide (PaCO2) at 46-60 mmHg.

Results: (I) Group H had a lower HR at T0 and T1 (P<0.05) and higher CO at T3 and T4 (P<0.05) than Group C. (II) Group H had higher rSO2 at T4 (P<0.05), lower pH and lactate (Lac) at T4 (P<0.05), higher PaCO2 at T3 and T4 (P<0.05), and lower PaO2 at T3 and T4 (P<0.05). (III) Compared to 1 d before surgery, the MMSE scores of both groups were lower 24 h after surgery (P<0.05).

Conclusions: PHC can increase the rSO2 of patients undergoing CVR, increase cerebral blood flow, improve the cerebral oxygen supply/consumption balance, and play a protective role in the brain. It has no significant impact on the incidence of POCD.
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http://dx.doi.org/10.21037/apm-20-2090DOI Listing
November 2020

Salicylic acid application alleviates cadmium accumulation in brown rice by modulating its shoot to grain translocation in rice.

Chemosphere 2021 Jan 29;263:128034. Epub 2020 Aug 29.

Key Laboratory of Marine Food Quality and Hazard Controlling Technology of Zhejiang Province, College of Life Sciences, China Jiliang University, Hangzhou, 310018, China. Electronic address:

Cadmium (Cd) contamination, which poses a serious threat to human health, has been recognized as a major threat to the agricultural system and crop production. Salicylic acid (SA) is a signaling molecule that plays an important role in against Cd toxicity. Previously, we found that spraying rice with SA could reduce the Cd accumulation in rice grains grown in Cd-contaminated soil. In this study, we studied the specific mechanism of SA spray on reducing Cd accumulation in rice grain. The results showed that treatment with SA could alleviate Cd toxicity in rice by increasing the activities of antioxidant enzymes that reduce hydrogen peroxide (HO) accumulation, but not by changing the pH, or total or available Cd of the soil. The key factor by which SA treatment reduced Cd accumulation in rice grains was by decreasing the Cd content in rice leaves at the flowering stage. This indicated that SA could modulate the Cd accumulation in shoots, reducing the Cd translocation to rice grains. Furthermore, SA could increase the HO content, activating the SA-signaling pathway and modulating the expression levels of Cd transporters (OsLCT1 and OsLCD) in rice leaves to increase Cd tolerance and reduce Cd accumulation in the rice grain. Thus, spraying rice with SA may be effective measure to cope with Cd contamination in paddy soils.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128034DOI Listing
January 2021

Scanning Ion Conductance Microscopy.

Chem Rev 2020 Dec 9. Epub 2020 Dec 9.

Department of Chemistry, Indiana University, 800 E. Kirkwood Avenue, Bloomington, Indiana 47405, United States.

Scanning ion conductance microscopy (SICM) has emerged as a versatile tool for studies of interfaces in biology and materials science with notable utility in biophysical and electrochemical measurements. The heart of the SICM is a nanometer-scale electrolyte filled glass pipette that serves as a scanning probe. In the initial conception, manipulations of ion currents through the tip of the pipette and appropriate positioning hardware provided a route to recording micro- and nanoscopic mapping of the topography of surfaces. Subsequent advances in instrumentation, probe design, and methods significantly increased opportunities for SICM beyond recording topography. Hybridization of SICM with coincident characterization techniques such as optical microscopy and faradaic electrodes have brought SICM to the forefront as a tool for nanoscale chemical measurement for a wide range of applications. Modern approaches to SICM realize an important tool in analytical, bioanalytical, biophysical, and materials measurements, where significant opportunities remain for further exploration. In this review, we chronicle the development of SICM from the perspective of both the development of instrumentation and methods and the breadth of measurements performed.
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http://dx.doi.org/10.1021/acs.chemrev.0c00962DOI Listing
December 2020

Dynamic Defense against Stealth Malware Propagation in Cyber-Physical Systems: A Game-Theoretical Framework.

Entropy (Basel) 2020 Aug 15;22(8). Epub 2020 Aug 15.

Science and Technology on Information Systems Engineering Laboratory, National University of Defense Technology, Changsha 410073, China.

Stealth malware is a representative tool of advanced persistent threat (APT) attacks, which poses an increased threat to cyber-physical systems (CPS) today. Due to the use of stealthy and evasive techniques, stealth malwares usually render conventional heavy-weight countermeasures inapplicable. Light-weight countermeasures, on the other hand, can help retard the spread of stealth malwares, but the ensuing side effects might violate the primary safety requirement of CPS. Hence, defenders need to find a balance between the gain and loss of deploying light-weight countermeasures, which normally is a challenging task. To address this challenge, we model the persistent anti-malware process as a shortest-path tree interdiction (SPTI) Stackelberg game with both static version (SSPTI) and multi-stage dynamic version (DSPTI), and safety requirements of CPS are introduced as constraints in the defender's decision model. The attacker aims to stealthily penetrate the CPS at the lowest cost (e.g., time, effort) by selecting optimal network links to spread, while the defender aims to retard the malware epidemic as much as possible. Both games are modeled as bi-level integer programs and proved to be NP-hard. We then develop a Benders decomposition algorithm to achieve the Stackelberg equilibrium of SSPTI, and design a Model Predictive Control strategy to solve DSPTI approximately by sequentially solving an 1+δ approximation of SSPTI. Extensive experiments have been conducted by comparing proposed algorithms and strategies with existing ones on both static and dynamic performance metrics. The evaluation results demonstrate the efficiency of proposed algorithms and strategies on both simulated and real-case-based CPS networks. Furthermore, the proposed dynamic defense framework shows its advantage of achieving a balance between fail-secure ability and fail-safe ability while retarding the stealth malware propagation in CPS.
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http://dx.doi.org/10.3390/e22080894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517520PMC
August 2020

Gas phase identification of the elusive oxaziridine (cyclo-HCONH) - an optically active molecule.

Chem Commun (Camb) 2020 Dec 7;56(100):15643-15646. Epub 2020 Dec 7.

Department of Chemistry, University of Hawaii, 2545 McCarthy Mall, Honolulu, HI 96822, USA.

The hitherto elusive oxaziridine molecule (cyclo-HCONH) - an optically active, high energy isomer of nitrosomethane (CHNO) - is prepared in processed methane-nitrogen monoxide ices and detected upon sublimation in the gas phase. Electronic structure calculations reveal likely routes via addition of carbene (CH) to the nitrogen-oxygen double bond of nitrosyl hydride (HNO). Our findings provide a fundamental framework to explore the preparation and stability of racemic oxaziridines exploited in chiral substrate-controlled diastereoselective preparation such as Sharpless asymmetric epoxidation, thus advancing our fundamental understanding of the preparation and chemical bonding of strained rings in small organic molecules.
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http://dx.doi.org/10.1039/d0cc06760aDOI Listing
December 2020

Systematic review of radiomic biomarkers for predicting immune checkpoint inhibitor treatment outcomes.

Methods 2020 Dec 1. Epub 2020 Dec 1.

Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, the Netherlands.

Background: Systemic therapy agents targeting immune checkpoint inhibitors have been approved for use since 2011. This type of therapy aims to trigger a patient's immune response to attack tumor cells, rather than acting against the tumor directly. Radiomics is an automated method of medical image analysis that is now being actively investigated for predictive markers of treatment response in immunotherapy.

Objective: To conduct an early systematic review determining the current status of radiomic features as potential predictive markers of immunotherapy response. Provide a detailed critical appraisal of methodological quality of models, as this informs the degree of confidence about current reports of model performance. In addition, to offer some recommendations for future studies that could establish robust evidence for radiomic features as immunotherapy response markers.

Method: A PubMed citation search was conducted for publications up to and including April 2020, followed by full-text screening. A total of seven articles meeting the eligibility criteria were examined in detail for study characteristics, model information and methodological quality. The review was conducted in the Cochrane style but has not been prospectively registered. Results are reported following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) guidelines.

Results: A total of seven studies were examined in detail, comprising non-small cell lung cancer, metastatic melanoma and a diverse assortment of solid tumors. Methodological robustness of reviewed studies varied greatly. Principal shortcomings were lack of prospective registration, and deficiencies in feature selection and dimensionality reduction, model calibration, clinical utility and external validation. A few studies with overall moderate to good methodological quality were identified. These results suggest that current state-of-the-art performance of radiomics in regards to discrimination (area under the curve or concordance index) is in the vicinity of 0.7, but the very small number of studies to date prevents any conclusive remarks to be made. We recommended future improvements in regards to prospective study registration, clinical utility, methodological procedure and data sharing.

Conclusions: Radiomics has a potentially significant role for predicting immunotherapy response. Additional multi-institutional studies with robust methodological underpinning and repeated external validations are required to establish the (added) value of radiomics within the pantheon of clinical tools for decision-making in immunotherapy.
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http://dx.doi.org/10.1016/j.ymeth.2020.11.005DOI Listing
December 2020

Bi-Layer Shortest-Path Network Interdiction Game for Internet of Things.

Sensors (Basel) 2020 Oct 21;20(20). Epub 2020 Oct 21.

Science and Technology on Information Systems Engineering Laboratory, National University of Defense Technology, Changsha 410073, China.

Network security is a crucial challenge facing Internet-of-Things (IoT) systems worldwide, which leads to serious safety alarms and great economic loss. This paper studies the problem of malicious interdicting network exploitation of IoT systems that are modeled as a bi-layer logical-physical network. In this problem, a virtual attack takes place at the logical layer (the layer of Things), while the physical layer (the layer of Internet) provides concrete support for the attack. In the interdiction problem, the attacker attempts to access a target node on the logical layer with minimal communication cost, but the defender can strategically interdict some key edges on the physical layer given a certain budget of interdiction resources. This setting generalizes the classic single-layer shortest-path network interdiction problem, but brings in nonlinear objective functions, which are notoriously challenging to optimize. We reformulate the model and apply Benders decomposition process to solve this problem. A layer-mapping module is introduced to improve the decomposition algorithm and a random-search process is proposed to accelerate the convergence. Extensive numerical experiments demonstrate the computational efficiency of our methods.
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http://dx.doi.org/10.3390/s20205943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589153PMC
October 2020

Corrigendum: Diverse Mobile Genetic Elements and Conjugal Transferability of Sulfonamide Resistance Genes () in Isolates From and Pork From Large Markets in Zhejiang, China.

Front Microbiol 2020 17;11:1793. Epub 2020 Aug 17.

Key Laboratory of Marine Food Quality and Hazard Controlling Technology of Zhejiang Province, College of Life Sciences, China Jiliang University, Hangzhou, China.

[This corrects the article DOI: 10.3389/fmicb.2019.01787.].
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http://dx.doi.org/10.3389/fmicb.2020.01793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461888PMC
August 2020

Identification of risk factors for mortality associated with COVID-19.

PeerJ 2020 1;8:e9885. Epub 2020 Sep 1.

Department of Emergency Medicine, Sir Run Run Shaw hospital; Zhejiang University School of Medicine, Hangzhou, China.

Objectives: Coronavirus Disease 2019 (COVID-19) has become a pandemic outbreak. Risk stratification at hospital admission is of vital importance for medical decision making and resource allocation. There is no sophisticated tool for this purpose. This study aimed to develop neural network models with predictors selected by genetic algorithms (GA).

Methods: This study was conducted in Wuhan Third Hospital from January 2020 to March 2020. Predictors were collected on day 1 of hospital admission. The primary outcome was the vital status at hospital discharge. Predictors were selected by using GA, and neural network models were built with the cross-validation method. The final neural network models were compared with conventional logistic regression models.

Results: A total of 246 patients with COVID-19 were included for analysis. The mortality rate was 17.1% (42/246). Non-survivors were significantly older (median (IQR): 69 (57, 77) vs. 55 (41, 63) years; < 0.001), had higher high-sensitive troponin I (0.03 (0, 0.06) vs. 0 (0, 0.01) ng/L; < 0.001), -reactive protein (85.75 (57.39, 164.65) vs. 23.49 (10.1, 53.59) mg/L; < 0.001), -dimer (0.99 (0.44, 2.96) vs. 0.52 (0.26, 0.96) mg/L; < 0.001), and α-hydroxybutyrate dehydrogenase (306.5 (268.75, 377.25) vs. 194.5 (160.75, 247.5); < 0.001) and a lower level of lymphocyte count (0.74 (0.41, 0.96) vs. 0.98 (0.77, 1.26) × 10/L; < 0.001) than survivors. The GA identified a 9-variable (NNet1) and a 32-variable model (NNet2). The NNet1 model was parsimonious with a cost on accuracy; the NNet2 model had the maximum accuracy. NNet1 (AUC: 0.806; 95% CI [0.693-0.919]) and NNet2 (AUC: 0.922; 95% CI [0.859-0.985]) outperformed the linear regression models.

Conclusions: Our study included a cohort of COVID-19 patients. Several risk factors were identified considering both clinical and statistical significance. We further developed two neural network models, with the variables selected by using GA. The model performs much better than the conventional generalized linear models.
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http://dx.doi.org/10.7717/peerj.9885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473053PMC
September 2020

Application of exogenous salicylic acid reduces Cd toxicity and Cd accumulation in rice.

Ecotoxicol Environ Saf 2021 Jan 6;207:111198. Epub 2020 Sep 6.

Key Laboratory of Marine Food Quality and Hazard Controlling Technology of Zhejiang Province, College of Life Sciences, China Jiliang University; Hangzhou, 310018, China. Electronic address:

Cd pollution in farmland is becoming a serious problem because it affects the safety of rice production and human health. Salicylic acid (SA) plays crucial roles in plant development and mediates plant responses to biotic and abiotic stress. This study assessed the molecular and physiological mechanisms of SA spraying effects on Cd tolerance and Cd accumulation in rice. Spraying of 0.1 mM SA had no great effect on the agronomic traits of rice, but significantly decreased Cd accumulation in rice grains, and SA spraying increased the Cd contents in leaves (only at the mature stage) and decreased the Cd contents in panicles (only at the filling and mature stage), but had no evident impact on the Cd content of other tissues and other growth stages. SA spraying reduced Cd accumulation in rice grains by promoting the deposition and fixation of Cd in the cell wall of leaves, thus preventing Cd being transferred from leaves to rice grains at the filling stage. SA spraying also decreased Cd toxicity by reducing HO and MDA accumulation and increasing the chlorophyll content in rice leaves. Furthermore, SA spraying remarkably decreased Cd accumulation in rice grains by modulating the expression level of the genes associated with Cd translocation and accumulation to control the Cd accumulation in rice. Hence, SA spraying reduced the inhibition of Cd on the plant height caused by Cd and increased the dry weight of shoots in the vegetative growth period of rice seedlings, and it reduced Cd transport from leaves to grains, thus reducing Cd content in rice. These findings provide a novel perspective and a new method for reducing Cd accumulation in rice.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111198DOI Listing
January 2021

Combination of metformin and cold atmospheric plasma induces glioma cell death to associate with c-Fos.

Neoplasma 2021 Jan 3;68(1):126-134. Epub 2020 Sep 3.

Jiangsu Key Lab of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China.

Glioma is the most common type of brain cancer. Chemotherapy combination with surgery and radiotherapy is a standard treatment for patients. Although there are many advances in glioma therapy, the prognosis of glioma patients has not significantly been improved over the past decades. Hence, there is still an urgent need to develop a new therapy to treat glioma. Cell viability was assessed by CellTiter Blue assay; flow cytometry (FCM) was used for detecting cell apoptosis; ROS detection was detected by ROS Assay; H2O2 detection was performed by hydrogen peroxide detection kits; real-time PCR and WB were used to determine gene expression. Using the glioma cell line U251 and U87, we investigated a possible combination inhibitory effect includes metformin and cold atmospheric plasma (CAP). The combination treatment showed a synergistic inhibitory effect on cell viability, significantly inducing cell apoptosis. Furthermore, we also found H2O2 produced by CAP has an important role in the synergistic inhibitory effect, eliminating H2O2 with catalase reversed the synergistic inhibitory effect. In addition, the transcript and protein levels of c-FOS were robustly increased after co-treated with metformin and CAP. Taken together, we propose that pre-treatment of glioma cells with metformin sensitize tumor cells to CAP, which may serve as a potential therapeutic strategy for glioma.
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http://dx.doi.org/10.4149/neo_2020_200325N307DOI Listing
January 2021

MicroRNAs as Important Regulators of Heat Stress Responses in Plants.

J Agric Food Chem 2020 Oct 29;68(41):11320-11326. Epub 2020 Sep 29.

Key Laboratory of Marine Food Quality and Hazard Controlling Technology of Zhejiang Province, College of Life Sciences, China Jiliang University, Hangzhou, Zhejiang 310018, People's Republic of China.

Heat stress is a major abiotic stress that significantly affects plant growth and productivity. Plants have, however, evolved complex adaptive mechanisms to cope with heat stress. MicroRNAs (miRNAs) are important molecules that regulate gene expression through the post-transcriptional degradation of target mRNA molecules or by repressing translation. Plant miRNAs play essential roles in development and a variety of stress responses. Recent advances in high-throughput sequencing technologies have enabled the identification and characterization of an increasing number of heat-responsive miRNAs in diverse plant species. Heat-regulated miRNAs combined with their target genes constitute large regulatory networks that control various metabolic pathways, including protein refolding, antioxidant defense, maintenance of photosynthetic systems, protection of reproductive tissues, regulation of flowering time, and miRNA biogenesis. In this review, we summarize the information acquired to date about the significance of plant miRNAs and their target genes in heat stress tolerance, thereby helping to identify the regulatory mechanisms that underlie heat stress responses in plants.
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http://dx.doi.org/10.1021/acs.jafc.0c03597DOI Listing
October 2020

The elusive cyclotriphosphazene molecule and its Dewar benzene-type valence isomer (PN).

Sci Adv 2020 Jul 22;6(30):eaba6934. Epub 2020 Jul 22.

Department of Chemistry, University of Hawaii at Manoa, 2545 McCarthy Mall, Honolulu, HI 96822, USA.

Although the chemistry of phosphorus and nitrogen has fascinated chemists for more than 350 years, the Hückel aromatic cyclotriphosphazene (PN, ) molecule-a key molecular building block in phosphorus chemistry-has remained elusive. Here, we report a facile, versatile pathway producing cyclotriphosphazene and its Dewar benzene-type isomer (PN, ) in ammonia-phosphine ices at 5 K exposed to ionizing radiation. Both isomers were detected in the gas phase upon sublimation via photoionization reflectron time-of-flight mass spectrometry and discriminated via isomer-selective photochemistry. Our findings provide a fundamental framework to explore the preparation of inorganic, isovalent species of benzene (CH) by formally replacing the C─H moieties alternatingly through phosphorus and nitrogen atoms, thus advancing our perception of the chemical bonding of phosphorus systems.
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http://dx.doi.org/10.1126/sciadv.aba6934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439403PMC
July 2020

A bibliometric analysis using VOSviewer of publications on COVID-19.

Ann Transl Med 2020 Jul;8(13):816

Department of Emergency Medicine, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: As a global pandemic, COVID-19 has aroused great concern in the last few months and a growing number of related researches have been published. Therefore, a bibliometric analysis of these publications may provide a direction of hot topics and future research trends.

Methods: The global literatures about COVID-19 published between 2019 and 2020 were scanned in the Web of Science collection database. "COVID-19" "Novel Coronavirus" "2019-nCoV" and "SARS-CoV-2" were used as the keywords to reach the relevant publications. VOSviewer was applied to perform the bibliometric analysis of these articles.

Results: Totally 3,626 publications on the topic of COVID-19 were identified and "COVID-19" with a total link strength of 2,649 appeared as the most frequent keyword, which had a strong link to "pneumonia" and "epidemiology". The mean citation count of the top 100 most cited articles was 96 (range, 26-883). Most of them were descriptive studies and concentrated on the clinical features. The highest-ranking journal was British medical journal with 211 publications and the most cited journal was Lancet with 2,485 citation counts. Eleven articles written by Christian Drosten from Berlin Institute of Virology have been cited for 389 times and 40 articles from Chinese Academy of Sciences have been cited for 1,597 times which are the most cited author and organization. The number of collaborators with China is 44 and the total link strength is 487. The main partners of China are USA, England and Germany. The published literatures have focused on three topics: disease management, clinical features and pathogenesis.

Conclusions: The current growth trends predict a large increase in the number of global publications on COVID-19. China made the most outstanding contribution within this important field. Disease treatment, spike protein and vaccine may be hotspots in the future.
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http://dx.doi.org/10.21037/atm-20-4235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396244PMC
July 2020

Silencing of RGS2 enhances hippocampal neuron regeneration and rescues depression-like behavioral impairments through activation of cAMP pathway.

Brain Res 2020 11 15;1746:147018. Epub 2020 Jul 15.

Department of Psychiatry, The Affiliated Kangning Hospital to Wenzhou Medical University, Wenzhou 325000, PR China.

Depression is one of the most common mental disorders with an increasing incidence. However, factors involved in depression are so complex, thus it is difficult to find effective strategies to reverse the impairments. This study aims to verify the role of regulator of G protein signaling 2 (RGS2) in the mouse mode of unpredictable mild stress-induced depression-like behaviors. Knockdown of RGS2 was achieved by transfection of siRNA-RGS2 in mouse hippocampal (HT-22) cells in vitro and injection of recombinant adenovirus expressing siRNA-RGS2 in mice in vivo. An aberrant high expression of RGS2 was found in mice with depression-like behaviors through immunohistochemical analysis. Silencing of RGS2 or Forskolin (activator of cAMP pathway) developed sweet water consumption, reduced inflammation and oxidative stress injury, and attenuated cognitive impairment and neuronal damage in mice with depression-like behaviors. Furthermore, regeneration was enhanced and apoptosis was repressed in mouse hippocampal neurons in the presence of RGS2 knockdown and Forskolin. Mechanistic studies indicated that silencing of RGS2 promoted the activation of cAMP pathway, thus rescuing depression-like behaviors of mice. Collectively, our study uncovered the role of RGS2-dependent cAMP pathway in regulation of cognitive impairment and hippocampal neuron regeneration in depression-like behaviors of mice, which may be a potential therapeutic target for impairments and symptoms associated with depression.
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http://dx.doi.org/10.1016/j.brainres.2020.147018DOI Listing
November 2020

Co-occurrence of Antibiotic and Heavy Metal Resistance and Sequence Type Diversity of Isolated From at Freshwater Farms, Seawater Farms, and Markets in Zhejiang Province, China.

Front Microbiol 2020 26;11:1294. Epub 2020 Jun 26.

Key Laboratory of Marine Food Quality and Hazard Controlling Technology of Zhejiang Province, College of Life Sciences, China Jiliang University, Hangzhou, China.

is the leading cause of seafood-borne bacterial poisoning in China and is a threat to human health worldwide. The aim of this study was to assess the antibiotic resistance profiles and distribution of heavy metal resistance of isolates from from freshwater farms, seawater farms, and their corresponding markets in Zhejiang, China and to assess the relationship between multidrug resistance (MDR) and multi-heavy metal resistance (MHMR). Of the 360 samples that we tested, 90 (25.00%) were positive, but the occurrence of pathogenic isolates carrying the toxin genes (4.44%) and (3.33%) was low. None of the tested isolates harbored both the and genes. However, antibiotic resistance profiles varied among different sampling locations, levels of resistance to the antibiotics ampicillin (76.67%) and streptomycin (74.44%) were high overall, and MDR isolates were common (40.00% of all isolates). Heavy metal resistance patterns were similar among the different sampling locations. Overall, the majority of isolates displayed tolerance to Cd (60.00%), and fewer were resistant to Cu (40.00%), Zn (38.89%), Ni (24.44%), Cr (14.44%), and Co (8.89%). In addition, 34.44% (31/90) of isolates tested in this study were found to be MHMR. Using Pearson's correlation analysis, MDR and MHMR were found to be positively correlated ( = 0.004; = 0.759). The 18 isolates that were both MDR and MHMR represented 18 sequence types, of which 12 were novel to the PubMLST database, and displayed a high level of genetic diversity, suggesting that dissemination may be affected by mobile genetic elements via horizontal gene transfer. However, a low percentage of class 1 integrons without gene cassettes and no class 2 or 3 integrons were detected in the 18 MDR and MHMR isolates or in the 90 isolates overall. Thus, we suggest that future research focus on elucidating the mechanisms that lead to a high prevalence of resistance determinants in . The results of this study provide data that will support aquatic animal health management and food safety risk assessments in the aquaculture industry.
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http://dx.doi.org/10.3389/fmicb.2020.01294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333440PMC
June 2020

Correction of cilia structure and function alleviates multi-organ pathology in Bardet-Biedl syndrome mice.

Hum Mol Genet 2020 Aug;29(15):2508-2522

Rare and Neurologic Diseases Research, Sanofi, Framingham, MA 01701, USA.

Bardet-Biedl syndrome (BBS) is a pleiotropic autosomal recessive ciliopathy affecting multiple organs. The development of potential disease-modifying therapy for BBS will require concurrent targeting of multi-systemic manifestations. Here, we show for the first time that monosialodihexosylganglioside accumulates in Bbs2-/- cilia, indicating impairment of glycosphingolipid (GSL) metabolism in BBS. Consequently, we tested whether BBS pathology in Bbs2-/- mice can be reversed by targeting the underlying ciliary defect via reduction of GSL metabolism. Inhibition of GSL synthesis with the glucosylceramide synthase inhibitor Genz-667161 decreases the obesity, liver disease, retinal degeneration and olfaction defect in Bbs2-/- mice. These effects are secondary to preservation of ciliary structure and signaling, and stimulation of cellular differentiation. In conclusion, reduction of GSL metabolism resolves the multi-organ pathology of Bbs2-/- mice by directly preserving ciliary structure and function towards a normal phenotype. Since this approach does not rely on the correction of the underlying genetic mutation, it might translate successfully as a treatment for other ciliopathies.
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http://dx.doi.org/10.1093/hmg/ddaa138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471507PMC
August 2020

Salinomycin and Sulforaphane Exerted Synergistic Antiproliferative and Proapoptotic Effects on Colorectal Cancer Cells by Inhibiting the PI3K/Akt Signaling Pathway in vitro and in vivo.

Onco Targets Ther 2020 3;13:4957-4969. Epub 2020 Jun 3.

Department of Geriatric Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, People's Republic of China.

Background: Both salinomycin (SAL) and sulforaphane (SFN) exert their antitumorigenic effects in various types of cancer We investigated whether combining salinomycin (SAL, an antibiotic ionophore) with sulforaphane (SFN, a phytochemical) exerted synergistic antiproliferative and proapoptotic activities in colorectal cancer (CRC) cells in vitro and in vivo by evaluating the proliferative and apoptotic responses of two CRC cell lines.

Materials And Methods: The combination index (CI) was calculated using the Chou-Talalay method, and the effects of the synergistic combination (CI<1) of lower doses of SAL and SFN were selected for further studies. Anti-tumor effect of the combination of SAL and SFN was tested both in vitro and in vivo.

Results: Cotreatment effectively inhibited proliferation, migration and invasion and enhanced apoptosis. The xenograft model also showed similar results. Furthermore, we evaluated the molecular mechanism behind SAL- and SFN-mediated CRC cell apoptosis. The combination treatment induced apoptosis in Caco-2 and CX-1 cells by inhibiting the PI3K/Akt pathway, which increased the expression of the tumor suppressor protein p53. The treatment also decreased the expression of the survival protein Bcl-2 and increased the expression of the proapoptotic protein Bax, which increased the Bax/Bcl-2 ratio, as well as enhanced poly ADP-ribose polymerase (PARP) cleavage. Upon inhibiting the PI3K/Akt pathway with LY294002 prior to cotreatment, we detected enhanced PARP cleavage compared to that in the cotreatment only group.

Conclusion: We investigated whether the combination of SAL and SFN had antiproliferative and proapoptotic effects in CRC cells both in vitro and in vivo. Cotreatment also significantly decreased migration and invasion compared to that of the control and SAL or SFN monotherapies. This novel combination of SAL and SFN might provide a potential strategy to treat CRC.
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http://dx.doi.org/10.2147/OTT.S246706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276212PMC
June 2020