The current strategies for nanoelectrode functionalization usually involve sophisticated modification procedures, uncontrollable and unstable modifier assembly, as well as a limited variety of ...modifiers. To address this issue, we propose a versatile strategy for large‐scale synthesis of biomimetic molecular catalysts (BMCs) modified nanowires (NWs) to construct functionalized electrochemical nanosensors. This design protocol employs an easy, controllable and stable assembly of diverse BMCs‐poly(3,4‐ethylenedioxythiophene) (PEDOT) composites on conductive NWs. The intrinsic catalytic activity of BMCs combined with outstanding electron transfer ability of conductive polymer enables the nanosensors to sensitively and selectively detect various biomolecules. Further application of sulfonated cobalt phthalocyanine functionalized nanosensors achieves real‐time electrochemical monitoring of intracellular glutathione levels and its redox homeostasis in single living cells for the first time.
Versatile and large‐scale synthesis of biomimetic molecular catalyst modified nanowires provides an innovative perspective for simple and stable construction of functionalized electrochemical nanosensors. Such nanosensors enable the sensitive and selective detection of diverse biomolecules, and for the first time achieve real‐time electrochemical monitoring of intracellular glutathione levels and its redox homeostasis in single living cells.
Intraoral digital impressions have been stated to meet the clinical requirements for some teeth-supported restorations, though fewer evidences were proposed for larger scanning range. The aim of this ...study was to compare the accuracy (trueness and precision) of intraoral digital impressions for whole upper jaws, including the full dentitions and palatal soft tissues, as well as to determine the effect of different palatal vault height or arch width on accuracy of intraoral digital impressions. Thirty-two volunteers were divided into three groups according to the palatal vault height or arch width. Each volunteer received three scans with TRIOS intraoral scanner and one conventional impression of whole upper jaw. Three-dimensional (3D) images digitized from conventional gypsum casts by a laboratory scanner were chose as the reference models. All datasets were imported to a specific software program for 3D analysis by "best fit alignment" and "3D compare" process. Color-coded deviation maps showed qualitative visualization of the deviations. For the digital impressions for palatal soft tissues, trueness was (130.54±33.95)μm and precision was (55.26±11.21)μm. For the digital impressions for upper full dentitions, trueness was (80.01±17.78)μm and precision was (59.52±11.29)μm. Larger deviations were found between intraoral digital impressions and conventional impressions in the areas of palatal soft tissues than that in the areas of full dentitions (p<0.001). Precision of digital impressions for palatal soft tissues was slightly better than that for full dentitions (p = 0.049). There was no significant effect of palatal vault height on accuracy of digital impressions for palatal soft tissues (p>0.05), but arch width was found to have a significant effect on precision of intraoral digital impressions for full dentitions (p = 0.016). A linear correlation was found between arch width and precision of digital impressions for whole upper jaws (r = 0.326, p = 0.034 for palatal soft tissues and r = 0.485, p = 0.002 for full dentitions). It was feasible to use the intraoral scanner to obtain digital impressions for whole upper jaws. Wider dental arch contributed to lower precision of an intraoral digital impression. It should be confirmed in further studies that whether accuracy of digital impressions for whole upper jaws is clinically acceptable.
Nonalcoholic fatty liver disease (NAFLD), a series of liver metabolic disorders manifested by lipid accumulation within hepatocytes, has become the primary cause of chronic liver diseases worldwide. ...About 20%-30% of NAFLD patients advance to nonalcoholic steatohepatitis (NASH), along with cell death, inflammation response and fibrogenesis. The pathogenesis of NASH is complex and its development is strongly related to multiple metabolic disorders (e.g. obesity, type 2 diabetes and cardiovascular diseases). The clinical outcomes include liver failure and hepatocellular cancer. There is no FDA-approved NASH drug so far, and thus effective therapeutics are urgently needed. Bile acids are synthesized in hepatocytes, transported into the intestine, metabolized by gut bacteria and recirculated back to the liver by the enterohepatic system. They exert pleiotropic roles in the absorption of fats and regulation of metabolism. Studies on the relevance of bile acid disturbance with NASH render it as an etiological factor in NASH pathogenesis. Recent findings on the functional identification of bile acid receptors have led to a further understanding of the pathophysiology of NASH such as metabolic dysregulation and inflammation, and bile acid receptors are recognized as attractive targets for NASH treatment. In this review, we summarize the current knowledge on the role of bile acids and the receptors in the development of NAFLD and NASH, especially the functions of farnesoid X receptor (FXR) in different tissues including liver and intestine. The progress in the development of bile acid and its receptors-based drugs for the treatment of NASH including bile acid analogs and non-bile acid modulators on bile acid metabolism is also discussed.
High performance hydroxyapatite (HA) ceramics with excellent densification and mechanical properties were successfully fabricated by digital light processing (DLP) three-dimensional (3D) printing ...technology. It was found that the sintering atmosphere of wet CO
2
can dramatically improve the densification process and thus lead to better mechanical properties. HA ceramics with a relative density of 97.12% and a three-point bending strength of 92.4 MPa can be achieved at a sintering temperature of 1300 , which makes a solid foundation for application ℃ in bone engineering. Furthermore, a relatively high compressive strength of 4.09 MPa can be also achieved for a DLP-printed p-cell triply periodic minimum surface (TPMS) structure with a porosity of 74%, which meets the requirement of cancellous bone substitutes. A further cell proliferation test demonstrated that the sintering atmosphere of wet CO
2
led to improve cell vitality after 7 days of cell culture Moreover, with the possible benefit from the bio-inspired structure, the 3D-printed TPMS structure significantly improved the cell vitality, which is crucial for early osteogenesis and osteointegration.
It is usually believed that doping with photosensitizers capable of generating singlet oxygen (1O2) plays a pivotal role in enhancing the afterglow performance of semiconducting polymer nanoparticles ...(SPNs). However, the effect of doping photosensitizer bearing electron‐withdrawing groups has not been reported. Here we report the effect of doping with six photosensitizers possessing different electron‐withdrawing groups on the afterglow performance of SPNs using poly(9,9‐di(2‐ethylhexyl)‐9H‐fluo‐rene‐2,7‐vinylene)‐co‐(1‐methoxy‐4‐(2‐ethylhexyloxy)‐2,5‐phenylenevinylene) (PF‐MEHPPV) as substrate. It was found that the afterglow performance of SPNs was significantly influenced by doping with photosensitizers bearing electron‐withdrawing groups. For the doped photosensitizers with strong electron‐withdrawing groups, the stronger the electron‐withdrawing ability of the group, the worse of the afterglow performance of the SPN regardless of the 1O2 generation ability of the photosensitizer. When the doped photosensitizer exhibited weak or none electron‐withdrawing effect, the 1O2 generation ability of the photosensitizer played a dominant role on the afterglow performance of the SPNs. This work deepens the understanding of the design and synthesis of SPNs with different afterglow properties.
For the doped photosensitizers with strong electron‐withdrawing groups, the stronger the electron‐withdrawing ability of the group, the worse of the afterglow performance of the SPN regardless of the 1O2 generation ability of the photosensitizer. When the doped photosensitizer exhibited weak or none electron‐withdrawing effect, the 1O2 generation ability of the photosensitizer played a dominant role on the afterglow performance of the SPNs.
The glutathione (GSH) system is one of the most powerful intracellular antioxidant systems for the elimination of reactive oxygen species (ROS) and maintaining cellular redox homeostasis. However, ...the rapid kinetics information (at the millisecond to the second level) during the dynamic antioxidation process of the GSH system remains unclear. As such, we specifically developed a novel dual‐wire nanosensor (DWNS) that can selectively and synchronously measure the levels of GSH and ROS with high temporal resolution, and applied it to monitor the transient ROS generation as well as the rapid antioxidation process of the GSH system in individual cancer cells. These measurements revealed that the glutathione peroxidase (GPx) in the GSH system is rapidly initiated against ROS burst in a sub‐second time scale, but the elimination process is short‐lived, ending after a few seconds, while some ROS are still present in the cells. This study is expected to open new perspectives for understanding the GSH antioxidant system and studying some redox imbalance‐related physiological.
The rapid kinetics between the glutathione (GSH) system and reactive oxygen species (ROS) remain unclear. We developed a dual‐wire nanosensor that can selectively and synchronously measure intracellular GSH and ROS with a high temporal resolution, and applied it to study resveratrol (RSV)‐treated cancer cells. The GSH system is rapidly triggered by the ROS burst in a sub‐second time scale and works only for a few seconds with some residual ROS.
To develop a machine learning model for predicting acute respiratory distress syndrome (ARDS) events through commonly available parameters, including baseline characteristics and clinical and ...laboratory parameters.
A secondary analysis of a multi-centre prospective observational cohort study from five hospitals in Beijing, China, was conducted from January 1, 2011, to August 31, 2014. A total of 296 patients at risk for developing ARDS admitted to medical intensive care units (ICUs) were included. We applied a random forest approach to identify the best set of predictors out of 42 variables measured on day 1 of admission.
All patients were randomly divided into training (80%) and testing (20%) sets. Additionally, these patients were followed daily and assessed according to the Berlin definition. The model obtained an average area under the receiver operating characteristic (ROC) curve (AUC) of 0.82 and yielded a predictive accuracy of 83%. For the first time, four new biomarkers were included in the model: decreased minimum haematocrit, glucose, and sodium and increased minimum white blood cell (WBC) count.
This newly established machine learning-based model shows good predictive ability in Chinese patients with ARDS. External validation studies are necessary to confirm the generalisability of our approach across populations and treatment practices.
In recent years, although China's energy intensity has gradually decreased, the total consumption of energy commodities has increased sharply. Levying an excise tax on energy commodities is one of ...the keys to control energy consumption. This paper constructed a Computable General Equilibrium model to simulate levying an energy excise tax in Jiangsu province, which is one of China's strong economic provinces with lower endowments of energy resources. The results show that the energy excise tax is beneficial for energy saving, while levying energy will cause economic and welfare declines. When at a level tax rate of 5%, 10%, and 15%, the loss of GDP will reach 0.27%, 0.66%, and 1.13% respectively, and the incomes of inhabitants and enterprises alike will decrease. When the energy tax revenue used to compensate for the welfare losses suffered by inhabitants or enterprises, there is a double dividend effect (energy saving and increasing income). Moreover, the simulation indicated that a 5% improvement of energy efficiency brings about a “backfire” phenomenon, with an increase of 142% in energy consumption. However, when considering the cost of energy-efficiency improvements, the rebound effect will be significantly decreased. Policy suggestions are further recommended to help improve the energy policy in regard to reducing energy consumption.
•CGE model is proposed to evaluate the effect of energy excise tax.•Levying energy excise tax with refund measures could result in a double dividend.•The rebound effect of energy efficiency improvement is quantified.
For colorectal cancer (CRC), surgical resection remains essential for achieving good prognoses. Unfortunately, numerous patients with locally advanced CRC and metastatic CRC failed to meet surgical ...indications or achieve pathological complete response after surgery. Perioperative therapy has been proven to effectively lower tumor staging and reduce recurrence and metastasis. Immune checkpoint inhibitors (ICIs) have shown unprecedented prolongation of survival time and satisfactory safety in patients with high microsatellite instability/deficient mismatch repair (MSI-H/dMMR), while the therapeutic effect obtained by patients with mismatch repair-proficient or microsatellite stable (pMMR/MSS) was considered minimal. However, recent studies found that certain CRC patients with dMMR/MSI-H presented intrinsic or acquired immune resistance, and pMMR/MSS CRC patients can also achieve better efficacy. Therefore, more predictors are required for screening patients with potential clinical benefits. Since the discovery of synergistic effects between immunotherapy, chemotherapy, and radiotherapy, different immunotherapy-based therapies have been applied to the perioperative therapy of CRC in an increasing number of research. This review comprehensively summarized the past and current progress of different combinations of immunotherapy in perioperative clinical trials for CRC, focusing on the efficacy and safety, and points out the direction for future development.
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