"Four-in-One" Nanozyme for Amplified Catalytic-Photothermal Therapy.

The cancer therapeutic efficacy of the peroxidase (POD)-mimicking nanozyme-based monotherapy is significantly hindered due to insufficient intratumoral hydrogen peroxide (H2O2) and glutathione (GSH) consumption effect on reactive oxygen species (ROS). In this study, we present the development of poly(o-phenylenediamine)@gold nanoparticles (AuNPs) (PoPD@Au) nanocomposites for multifunctional catalytic-photothermal therapy. These nanocomposites exhibit triple distinct nanozymatic activities, i.e., POD-like activity that catalyzes H2O2 to ROS, glucose oxidase (GOx)-like activity that supplements endogenous H2O2, and GSH depleting activity that decreases the ROS consumption efficiency. This open source and reduce expenditure strategy for ROS generation allows for the amplification of tumor oxidative stress, thereby enhancing anti-tumor efficiency. Additionally, the PoPD@Au nanocomposites demonstrate outstanding photothermal conversion efficiency, contributing to the synergistic effect between PoPD and AuNPs. Moreover, we reveal the improved photothermal performance of PoPD@Au triggered by the tumor microenvironment pH, which provides additional benefits for targeted catalytic-photothermal therapy. This "four-in-one" design of PoPD@Au enables efficient anti-tumor effects both in vitro and in vivo, making it a universal strategy for engineering catalytic-photothermal therapeutic nanoagents.

Optimization of Forward Collision Warning Algorithm Considering Truck Driver Response Behavior Characteristics.

Forward collision warning (FCW) systems have been widely used in trucks to alert drivers of potential road situations so they can reduce the risk of crashes. Research on FCW use shows, however, that there are differences in drivers' responses to FCW alerts under different scenarios. Existing FCW algorithms do not take differences in driver response behavior into account, with the consequence that the algorithms' minimum safe distance assessments that trigger the warnings are not always appropriate for every driver or situation. To reduce false alarms, this study analyzed truck driver behavior in response to FCW warnings, and k-means clustering was adopted to classify driver response behavior into three categories: Response Before Warning (RBW), Response After Warning (RAW), and No Response (NR). Results showed that RBW clusters tend to occur at long following distances (>19 m), and drivers applied braking before the warning. In RAW clusters, deceleration after warning is significantly more forceful than before warning. NR clusters occur at short distances, and deceleration fluctuates only slightly. To optimize the FCW algorithm, the warning distance was divided into reaction distance and braking distance. The linear support vector machine was used to fit the driver reaction distance. The long short-term memory method was used to predict braking distance based on each of the three response scenarios: R2 was 0.896 for RAW scenarios, 0.927 for RBW scenarios, and 0.980 for NR scenarios. Verification results show that the optimized truck FCW algorithm improved safety by 1 % to 5.1 %; accuracy reached 97.92 %, and the false alarm rate was 1.73 %.

Safety assessment of trucks based on GPS and in-vehicle monitoring data.

Increasingly, drivers are choosing to buy usage-based automobile insurance (UBI). Manage-how-you-drive (MHYD) insurance, a new type of UBI, incorporates active safety management to monitor driver behavior and issue warnings as needed. While researchers have introduced telematics data into automobile insurance pricing, the specific effect of in-vehicle active safety management on driver risk assessment has been neglected, especially for truck drivers, whose crashes have more serious consequences. This study uses telematics and in-vehicle monitoring features to examine the key factors underlying large commercial truck crashes, and quantifies the effect of these factors on crash risk. Data from 2,185 trucks in Shanghai, China, were collected for a total of 105,786 trips and 465,555 in-vehicle warnings to investigate three types of factors affecting risk: travel characteristics, driving behavior, and in-vehicle warnings. A zero-inflated Poisson (ZIP) regression model was built, and a ZIP model without the warning variables as well as a basic Poisson model with warnings were considered for comparison. It was found that the ZIP model considering in-vehicle warning information performed significantly better than the other models. The standardized regression coefficient method was used to identify the most important variables. In-vehicle yawn and smoking warnings had significantly more association with the number of crashes than did the travel characteristics and driving behavior variables, though freeway distance traveled, average freeway speed, percentage of trips on sunny days, and percentage of trips at night also correlated significantly with crash risk. These results can provide a reference for UBI insurance professionals considering in-vehicle active safety management, as well as support freight companies in drafting appropriate working regulations.

Comparative study of two poly(amino acid)-based photosensitizer-delivery systems for photodynamic therapy.

The photosensitizers (PS) play a vital role in photodynamic therapy (PDT), but the clinical therapeutic effect is limited by its low solubility, easy aggregation and lack of selective tumor uptake. Hence, some biocompatible materials such as poly(amino acid) have been chosen to deliver PS to solve these problems. In this study, we fabricated two kind of poly(amino acid)-based PS delivery systems by using poly (L-glutamic acid) (PLG) as the backbone material to physically encapsulate (P(T)) and chemically conjugate PS (PT), respectively. Moreover, the anticancer effect of these two PS delivery systems had been comparatively investigated. In vitro experiments verified that the delivery system of PT exhibited more effective treatment effect than that of P(T) because PS was chemically conjugated with PLG in PT which could obviously avoid the π-π stacking effect of PS and induced the aggregation. The less aggregation avoiding the quenching effect could result in an enhanced generation ability of reactive oxygen species to improve PDT treatment effect. Contrarily, the treatment effect of P(T) was lower due to the rigid structure and hydrophobic π-π stacking effect, in which the physically encapsulated PS was easier to aggregate and quench. Hence, the way how to combine carrier with drug is significant for satisfied treatment effect.

Poly(L-Glutamic Acid)-Drug Conjugates for Chemo- and Photodynamic Combination Therapy.

Despite the polymeric vascular disrupting agent (poly(L -glutamic acid)-graft-methoxy poly(ethylene glycol)/combretastatin A4) nanoparticles can efficiently inhibit cancer growth, their further application is still a challenge owing to the tumor recurrence and metastasis after treatment. In this study, two poly(L -glutamic acid)-drug conjugates for chemo-and photodynamic combination therapy are fabricated. PLG-g-mPEG-CA4 nanoparticles are prepared by combretastatin A4 (CA4) and poly(L -glutamic acid)-graft-methoxy poly(ethylene glycol) (PLG-g-mPEG) using the Yamaguchi esterification reaction. PLG-g-mPEG-TPP (TPP: 5, 10, 15, 20-tetraphenylporphyrin) nanoparticles are constructed using PLG-g-mPEG and amine porphyrin through condensation reaction between carboxyl group of PLG-g-mPEG and amino group of porphyrin. The results showed that PLG-g-mPEG-CA4 nanoparticles have good antitumor ability. PLG-g-mPEG-TPP nanoparticles can produce singlet oxygen under the laser irradiation. Moreover, the combined therapy of PLG-g-mPEG-CA4 and PLG-g-mPEG-TPP nanoparticles has higher antitumor effect than the single chemotherapy or the single photodynamic therapy in vitro. The combination of CA4 nondrug and photodynamic therapy provides a new insight for enhancing the tumor therapeutic effect with vascular disrupting agents and other therapy.

Competitive intelligence and its impact on innovations in tourism industry of China: An empirical research.

Competitive intelligence (CI) has attracted much attention in innovation research, but most of existing literature studies CI in technological innovations in manufacturing industry, with little empirical research in context of service businesses. This paper first analyzes CI of service businesses and then uses covariance-based structural equation modeling (SEM) on a data of 333 got from the survey in tourism enterprises of east China to test the effect of customer CI, opponent CI, and supplier CI on service innovations in China's service industry. Results show that opponent CI and supplier CI have positive influence on both exploratory and exploitative service innovation. Customer CI has more obvious positive influence on exploratory service innovation than on exploitative service innovation.

Acid-responsive dextran-based therapeutic nanoplatforms for photodynamic-chemotherapy against multidrug resistance.

Limited by multidrug resistance (MDR) and nonspecific selectivity, free molecular chemotherapies still are inefficient in clinical cancer treatment. Nanoscale therapeutics delivery systems with controllable release capacity have been developed to reverse multidrug resistance and improve anticancer efficacy. Herein, we constructed acid-sensitive dextrin-based nanoplatforms (THDP) to deliver chemotherapies via supramolecular coordination between tetra sodium meso-tetra (sulfonatophenyl)-porphyrin zinc (II) (Zn-TPPS) and histidine modified dextrin-graft-poly (ethylene glycol) (HDP) to reverse multidrug resistance through photodynamic-chemotherapy. The introductions of hydrophilic poly (ethylene glycol) (PEG) not only prevent undesired aggregation under physiological conditions but also enhanced cellular endocytosis effect. Doxorubicin loaded nanoplatforms (THDP@DOX) with a relatively uniform size of average 63 nm exhibited excellent stability in blood circulation. When THDP@DOX was internalized, the acidic intercellular environment could control the chemotherapies release. Moreover, the generated reactive oxygen species by photosensitizer Zn-TPPS with light irradiation could obviously block DOX efflux and ultimately induce apoptosis to effectively reverse multidrug resistance of tumor cells. Meanwhile, the combination of photosensitizers and chemotherapies obviously created an enhanced MDR reversal effect, providing a promising approach for MDR reversal to achieve highly efficient cancer therapeutics.

Acid-sensitive ROS-triggered dextran-based drug delivery system for advanced chemo-photodynamic synergistic therapy.

In order to improve the treatment efficacy and reduce the side effects, the synergistic therapy has been effectively exploited in cancer treatment. Herein, we fabricated a kind of acid-sensitive ROS-triggered dextran-based drug delivery system (DHTD/Zn-TPP) for synergistic therapy, in which chemotherapeutics doxorubicin was conjugated to the dextran backbone via ROS cleavable thioketal conjugates while photosensitizer porphyrin (Zn-TPP) was encapsulated via acid-responsive metallic coordinated interaction. The structure and acid-responsive self-assemble behavior of DHTD/Zn-TPP were measured by 1 H NMR, Fourier transform infrared, dynamic laser scattering, and transmission electron microscopy. Further, the in vivo ROS-triggered DOX release and anticancer efficiency were evaluated toward HeLa cells and MCF-7 cells. All the data obtained verified that DHTD/Zn-TPP had a significantly improved cell growth inhibitory effect with light irritation due to the combined application of photodynamic-chemotherapy.

Tumor regression and potentiation of polymeric vascular disrupting therapy through reprogramming of a hypoxia microenvironment with temsirolimus.

Although the polymeric vascular disrupting agent (poly(l-glutamic acid)-graft-methoxy poly(ethylene glycol)/combretastatin A4) nanoparticles (CA4-NPs) has great potential to inhibit cancer growth, it is still a challenge to avert tumor recurrence and metastasis after treatment. It is mainly tightly associated with hypoxia induced by CA4-NPs, which can activate many downstream genes regulating tumor growth and metastasis. Herein, to relieve a tumor hypoxia microenvironment, the mTOR inhibitor temsirolimus was employed to modulate the tumor microenvironment when treated with CA4-NPs. In vitro MTT experiments strongly verified that the combination of temsirolimus with polymeric CA4-NPs exhibited an additive toxicity to 4T1 cells. An in vivo study with the 4T1 mammary adenocarcinoma model revealed that consistent with the proposed scenario, combination therapy with CA4-NPs plus temsirolimus suppressed tumor growth significantly more strongly compared to either CA4-NPs or temsirolimus monotherapy, and the inhibition rate to 4T1 tumor with a volume of 300 mm3 was 71%. The mechanism underling combination treatment was confirmed by western blotting and immunofluorescence staining, and the results demonstrated that temsirolimus could inhibit HIF1α expression. Thus, this work provides a mechanistic rationale for the use of VDAs in combination with the mTOR inhibitor to enhance anticancer efficacy, delaying tumor recurrence and inhibiting tumor metastasis.

Preliminary study on the application of an umbrella-like abdominal wall-lifting device in gasless laparoscopic surgery.

UNLABELLED: Abstract Background: In laparoscopic surgery with CO2 pneumoperitoneum, serious complications often occur for elderly patients and those who undergo long operations. These complications mainly include respiratory and circulatory system changes. In patients with tumors, release of free tumor cells into the abdominal cavity is believed to be possible. Gasless laparoscopic techniques can avoid these complications of CO2 pneumoperitoneum. Currently, the main shortcoming of gasless laparoscopic techniques is inadequate operative space. Because of this shortcoming, gasless techniques have not been widely applied in clinical practice. MATERIALS AND METHODS: We herein describe a new technique of gasless laparoscopic cholecystectomy in pigs using a self-designed umbrella-like abdominal wall-lifting device. This device lifts up the anterior abdominal wall by opening the umbrella leaf in the abdominal cavity. RESULTS: Five pigs underwent laparoscopic cholecystectomy using this technique. The operation times were 85, 40, 28, 21, and 24 minutes. The corresponding bleeding volumes were 11, 20, 5, 2, and 8 mL. CONCLUSIONS: These preliminary outcomes suggest that the umbrella-like abdominal wall-lifting technique is safe and feasible in gasless laparoscopic surgery and can provide sufficient exposure of the operative field. Further study in the form of randomized controlled trials is needed to investigate the advantages of this new technique.