Patients with locally advanced colorectal cancer (LACRC) have a high risk of recurrence and metastasis, although neoadjuvant therapy may provide some benefit. However, patients with high ...microsatellite instability/deficient mismatch repair (MSI-H/dMMR) LACRC receive little benefit from neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant chemotherapy (nCT). The 2015 KEYNOTE-016 trial identified MSI-H/dMMR as a biomarker indicative of immunotherapy efficacy, and pointed to the potential use of immune checkpoint inhibitors (ICIs). In 2017, the FDA approved two ICIs (pembrolizumab and nivolumab) for treatment of MSI-H/dMMR metastatic CRC (mCRC). In 2018, the CheckMate-142 trial demonstrated successful treatment of mCRC based on "double immunity" provided by nivolumab with ipilimumab, a regimen that may become a standard first-line treatment for MSI-H mCRC. In 2018, the FDA approved nivolumab alone or with ipilimumab for patients who progressed to MSI-H/dMMR mCRC after standard chemotherapy. The FDA then approved pembrolizumab alone as a first-line treatment for patients with MSI-H/dMMR CRC that was unresectable or metastatic. There is now interest in using these drugs in neoadjuvant immunotherapy (nIT) for patients with MSI-H/dMMR non-mCRC. In 2020, the NICHE trial marked the start of using nIT for CRC. This novel treatment of MSI-H/dMMR LACRC may change the approaches used for neoadjuvant therapy of other cancers. Our review of immunotherapy for CRC covers diagnosis and treatment, clinical prognostic characteristics, the mechanism of nIT, analysis of completed prospective and retrospective studies, and ongoing clinical trials, and the clinical practice of using nIT for MSI-H/dMMR LACRC. Our team also proposes a new organ-preservation strategy for patients with MSI-H/dMMR low LARC.
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•Peroxidase-like activity of Glutathione-Ag nanoparticles (GSH-AgNPs) was investigated.•The GSH-AgNPs nanozyme follows Michaelis-Menten behaviors and shows strong affinity to ...H2O2.•Vitamin B1 can inhibit the catalytic activity of GSH-AgNPs.•Lable-free colorimetric sensors for the detection ofVitamin B1 was developed with excellent sensitivity and selectivity.
A label-free sensing strategy based on the enzyme-mimicking property of Glutathione-Ag nanoparticles (GSH-AgNPs) was demonstrated for colorimetric detection of vitamin B1 (VB1). Firstly, obvious blue color accompanied with an absorption peak at 652 nm was observed due to the high peroxidase-like activity of GSH-AgNPs towards 3,3′,5,5′-tetramethylbenzidine (TMB). Then, in the presence of VB1, the mimetic activity of GSH-AgNPs could be strongly restrained, evidenced as a promiment colorimetric change to colorless, which can be used to achieve the visualization detection VB1. Linear relationship between absorbance response and VB1 concentration from 0 to 0.2 µM were obtained. The detection limit was calculated as low as 40 nM. The inhibition reasons were thoroughly discussed. Considering the advantages of rapid response, easy procedure and high selectivity, the proposed method possesses potential application in environment and biological analysis for VB1 detection.
Background. Chronic heart failure (CHF) is the end stage of cardiac disease with a 5-year mortality rate reaching 50%. Simvastatin is an antioxidant with lipid-lowering effects, which is commonly ...used to treat CHF. Resistance training is a nondrug treatment for CHF and exerts a positive effect on both the myocardial structure and function. Objective. This study is aimed at exploring the effects and outcomes of simvastatin combined with resistance training on the mitochondrial membrane potential (MMP) of peripheral blood lymphocytes and the Janus kinase/signal transducer and activator of the transcription 3 (JAK/STAT3) signaling pathway in patients with CHF. Methods. One hundred and eleven patients with CHF were allocated to the control group (CNG) (n=55) and intervention group (IG) (n=56) using the random number table method. The CNG received simvastatin treatment only, whereas the IG received simvastatin treatment plus resistance training. Treatment efficacy, diastolic interventricular septal thickness (IVST), left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVDD), MMP fluorescence intensity, JAK mRNA and STAT3 mRNA relative expression levels, serum C-reactive protein (CRP), galectin-3, interleukin-6 (IL-6), N-terminal–probrain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and heart-type fatty acid-binding protein (H-FABP) levels were compared in both groups. Results. After 6 months of treatment, diastolic IVST, LVDD, and serum levels of CRP, galectin-3, IL-6, NT-proBNP, hs-cTnT, and H-FABP decreased in both groups and were lower in the IG than in the CNG (P<0.05), whereas LVEF, JAK and STAT3 mRNA relative expression levels, and MMP fluorescence intensity of peripheral blood lymphocytes were higher in the IG than in the CNG (P<0.05). Conclusion. Simvastatin combined with resistance training improves heart function and reduces myocardial damage as well as the occurrence of adverse cardiac events compared with simvastatin alone. The mechanism may be related to the increase of expression of MMP, JAK, and STAT3, the regulation of MMP and JAK/STAT3 signaling pathways in peripheral lymphocytes, the alleviation of mitochondrial damage, and the inhibition of inflammatory response.
Lipid droplets (LDs) polarity is intricately linked to diverse biological processes and diseases. The visualization of LDs-polarity is of vital importance but challenging due to the lack of ...high-specificity, high-sensitivity and large-Stokes shift probes for real-time tracking LDs-polarity in biological systems.
Four D-π-A based fluorescent probes (TPA-TCF1-TPA-TCF4) have been developed by combining tricyanofuran (an electron acceptor, A) and triphenylamine (an electron donor, D) derivatives with different terminal groups. Among them, TPA-TCF1 and TPA-TCF4 exhibit excellent polar sensitivity, large Stokes shift (≥182 nm in H2O), and efficient LDs targeting ability. In particular, TPA-TCF4 is capable of monitoring the change of LDs-polarity during ferroptosis, inflammation, apoptosis of cancer cell, and fatty liver.
All these features render TPA-TCF4 a versatile tool for pharmacodynamic evaluation of anti-cancer drugs, in-depth understanding of the biological effect of LDs on ferroptosis, and medical diagnosis of LDs-polarity related diseases.
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•TPA-TCF4 has a large Stokes shift and targets LDs via a “washing-free” procedure.•TPA-TCF4 can reflect the change of LDs polarity in ferroptosis and inflammation.•TPA-TCF4 can be used to evaluate the efficacy of anticancer drugs.•TPA-TCF4 can detect fatty liver at tissue, organ and even in vivo levels.
Fine metal nanoparticles (2–3 nm; Au, Pt, and alloyed Au–Pt) with a narrow size distribution were deposited on active TiO2 through a facile chemical reduction method. Compared to the bare TiO2, a ...remarkable enhancement of up to 10-fold for photocatalytic hydrogen evolution was achieved on the alloyed nanocomposites. By using core level and valence band XPS analysis, two electronic properties are shown to contribute to the promoted photocatalytic activity: stronger metal–support interaction between the alloyed structures and TiO2 and higher electron population on the Au–Pt/TiO2 photocatalysts in comparison with the bare TiO2. Moreover, an improved charge separation over TiO2 using Au–Pt nanoparticles was clearly evidenced by the significant increase of photocurrent responses obtained from the photoelectrochemical measurements. For the first time, in situ 13C and 1H NMR spectroscopy was applied to monitor the gas–liquid–solid photocatalytic reactions under real working conditions. Via a two-electron oxidation pathway, the surface-adsorbed methanol was first oxidized to formaldehyde, followed by spontaneous hydrolysis and methanolysis to methanediol and methoxymethanol, rather than methyl formate and formic acid that have been previously reported in gaseous CH3OH photocatalysis. The in situ monitoring also revealed that deposition of metal NPs would not alter the reaction pathways while making the reaction faster compared to the bare TiO2.
Thin films of high entropy alloys (HEAs) are of great interest for surface engineering applications due to their exceptional properties including superior hardness, resistance to oxidation and ...corrosion, high temperature stability and high hydrophobicity. The microstructural and the physical properties of high entropy nitride (HEN) thin films, that are chemically inert and possess superior properties, can be effectively tunned using magnetron sputtering processes in the reactive mode. In this study, high entropy nitride thin films of AlCoCrCu0.5FeNi were deposited using RF reactive magnetron sputtering with three different nitrogen gas flow fractions (RN) of 6.25, 12.5, and 25%. X-ray diffraction technique and transmission electron microscopy revealed that the crystallinity of the HEN films changed from a mixed cubic FCC and BCC to a partially amorphous phase with increasing RN due to the accumulation of more interstitial nitrogen atoms in the film. Modifications of film morphology, such as decreases in grain size and surface roughness, were observed from scanning electron microscopy and atomic force microscopy, respectively. Energy dispersive spectroscopy recorded the highest nitrogen concentration of 10.6% for the film deposited at an intermediate RN of 12.5%. X-ray photoelectron spectroscopy detected significant levels of surface protective oxides (such as Al2O3 and Cr2O3) and nitrides (such as AlN and CrN) for the HEN thin films deposited at higher gas fractions of 12.5 and 25%. According to nanoindentation results, the film deposited at the RN of 25% attained a hardness of 9.8 GPa. The highest hardness, significant oxidation resistance and the highest hydrophobicity with a WCA of 112° were achieved for the HEN film deposited using the highest RN of 25%. Such high entropy nitride films deposited by reactive magnetron sputtering have important implications as protective coatings for a wide range of applications including turbines, engine blades and aircraft bodies used in aerospace industries.
•High entropy nitride thin films were deposited at various nitrogen flow fractions.•Transition from a mixed FCC and BCC to a partially amorphous phase was observed.•Higher nitrogen flow fractions modified the surface morphology of the films.•Significant presence of surface protective binary oxides and nitrides were evident.•Films attained high hardness, improved oxidation resistance and high hydrophobicity.
There are many influencing factors for deep thermal environment, which will interact with each other. The analytic hierarchy process (AHP) and fuzzy comprehensive evaluation (FCE) are introduced to ...construct the evaluation model. Based on the comprehensive evaluation of the underground heat source and its thermal contribution rate, some suggestions on thermal stress control are put forward. The results showed that the average thermal contribution rates of surrounding rock, air self-compression, equipment, and personnel were 56.28%, 27.44%, 15.23% and 1.04%, respectively. SSD and HSI (heat stress index) of −652 m and deep workface are far higher than the maximum heat overload tolerated by human body. The nine evaluation indexes show that the degree of heat stress increases significantly with the increasing of depth. Among them, temperature, surrounding rock heat release and dress sensitivity are the main influencing factors of thermal environment evaluation. The severity of thermal stress was determined by comparing the difference in standard score and standard deep thermal environment parameters. Therefore, corresponding cooling technology is adopted to provide a new approach for deep thermal environment treatment.
The microstructure and adhesion force between dust particles determine the dust starting and migration to a certain extent. By use of scanning electron microscopy, the BET method, and the abruption ...technique, the microstructure and adhesion force of dust on the soil pavement of an open-pit mine were examined. The results indicate that the dust shape of soil pavement is mainly irregular quadrilateral, pentagonal and circular. The adhesion of dust particles in soil pavement reduces as particle size and temperature increase. When the particle size grows from 22 to 30 μm and the ambient temperature rises from 25 to 30 ℃, the adhesion force of dust particles in soil pavement drops dramatically. The adhesion force of dust particles in the soil pavement of open-pit mine increases as environmental humidity and pressure rise. When the environmental humidity exceeds 70% and pressure exceeds 24.79 kPa, the adhesion of dust particles increases dramatically. On the basis of the multiple regression method, a prediction model for the dust adhesion force of open-pit mines’ soil pavement has been developed. However, its accuracy needs to be further enhanced.
The illustration of the correlation between lipid droplets (LDs) variation and nonalcoholic fatty liver disease (NAFLD) is a challenging and important work in biomedical research. Herein, a red ...emission fluorophore LD-HW containing donor-π-bridge-acceptor (D-π-A) structure was readily constructed and systematically investigated. It was found that LD-HW could selectively identify polarity variation accompanying with an obvious blue-shift (around 80 nm) in fluorescence spectra, and a sharp enhancement (about 440-fold) in fluorescence quantum yield (QY) over the solvent polarity ranging from water (polarity parameter Δf = 0.3200) to 1,4-dioxane (Δf = 0.0205). In addition, probe LD-HW could precisely light up LDs within a short time (≤5 min) through a wash-free procedure and real-time monitor the dynamic behavior of cellular LDs. More importantly, LD-HW exhibited an excellent performance in differentiating fatty liver through in vivo imaging the change of cellular LDs. The in situ fluorescence spectra of corresponding tissue section proved that polarity level in the liver of NAFLD mice was lower than that in normal mice. Taken together, probe LD-HW presented great potential in non-invasive diagnosis of fatty liver through in vivo imaging.
Organic-inorganic halide perovskites have attracted much attention thanks to their excellent optoelectronic performances. Here, a bulk CH3NH3PbBr3 (MAPbBr3) single crystal (SC) was fabricated, whose ...temperature and light polarization dependence was investigated by measuring photoluminescence. The presence of obvious band tail states was unveiled when the applied temperature was reduced from room temperature to 78 K. Temperature dependence of the bandgap of the MAPbBr3 SC was found to be abnormal compared with those of traditional semiconductors due to the presence of instabilization of out-of-phase tail states. The MAPbBr3 SC revealed an anisotropy light absorption for linearly polarized light with an anisotropy ratio of 1.45, and a circular dichroism ratio of up to 9% was discovered due to the spin-orbit coupling in the band tail states, exhibiting great polarization sensitivity of the MAPbBr3 SC for the application of light sensors. These key findings shed light on the development of potential optoelectronic and spintronic applications based on large-scaled organic-inorganic perovskite SCs.
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