A biosensor was created for the simultaneous monitoring of endogenous H2Sn and H2S in mouse brains and exploring their roles in activation of the TRPA1 channel under two types of brain disease ...models: ischemia and Alzheimer's disease (AD). Based on DFT calculations and electrochemical measurements, two probes, 3,4‐bis((2‐fluoro‐5‐nitrobenzoyl)oxy)‐benzoic acid (MPS‐1) and N‐(4‐(2,5‐dinitrophenoxy) phenyl)‐5‐(1, 2‐dithiolan‐3‐yl)pentanamide (MHS‐1), were synthesized for specific recognition of H2Sn and H2S. Through co‐assembly of the two probes at the mesoporous gold film with good anti‐biofouling ability and electrocatalytic activity, this microsensor showed high selectivity for H2Sn and H2S against potential biological interferences. The biosensor can simultaneously determine the concentration of H2Sn from 0.2 to 50 μm, as well as that of H2S from 0.2 to 40 μm. The expression of TRPA1 protein positively correlated with levels of H2Sn under both ischemia and AD.
A single electrochemical sensor was created for simultaneous detection of H2Sn and H2S in the brain. The expression of TRPA1 channel was found to be positively correlated with the levels of H2Sn in two brain disease models under ischemia and Alzheimer's diseases, and H2Sn is more active for expression of TRPA1 protein than that of H2S.
Highlights • This review provides updated epidemiologic data on intrahepatic cholangiocarcinoma. • Various forms of biliary inflammations, as well as many metabolic factors, are identified as risk ...factors of ICC. • We assessed the role of surgical resection and other treatment modalities, as well as their short-term and long-term outcomes.
Herein, a novel earthworm-like N, S-doped carbon nanotube-encapsulated Co9S8 hybrid was developed using the metal–organic framework (MOF) UiO-66-NH2 as a nanoscaled template via an immiscible ...two-phase incorporation. Highly efficient heteroatom-doping in graphene stacking generated a number of joints in the nanotubes, which harvested numerous defects as active sites for oxygen catalysis. Moreover, the Co9S8 nanoparticles were found to be tightly defined in the graphitic carbon shell, which were triggered by the spatial confinement of UiO-66-NH2. This nanostructure greatly enhanced the reaction kinetics and the stability of the catalyst. The carbon nanotube-Co9S8 composites via pyrolysis at 800 °C (Co9S8@CT-800) showed highly bifunctional catalytic activity for O2 catalysis processes. The low overpotential for ORR obtained for Co9S8@CT-800 was comparable to that of commercial Pt/C, and the small Tafel slope of 72 mV dec−1 for OER was better than that obtained for conventional RuO2. Density functional theory calculations revealed that the high activity of the developed nanocomposites for oxygen electrocatalysis in an alkaline medium was attributed to the synergistic effects of Co9S8 and the N-doped graphitic shell.
Heart disease is the leading cause of death worldwide. A key pathogenic factor in the development of lethal heart failure is loss of terminally differentiated cardiomyocytes. However, mechanisms of ...cardiomyocyte death remain unclear. Here, we discovered and demonstrated that ferroptosis, a programmed iron-dependent cell death, as a mechanism in murine models of doxorubicin (DOX)- and ischemia/reperfusion (I/R)-induced cardiomyopathy. In canonical apoptosis and/or necroptosis-defective Ripk3−/−, Mlkl−/−, or Fadd−/−Mlkl−/− mice, DOX-treated cardiomyocytes showed features of typical ferroptotic cell death. Consistently, compared with dexrazoxane, the only FDA-approved drug for treating DOX-induced cardiotoxicity, inhibition of ferroptosis by ferrostatin-1 significantly reduced DOX cardiomyopathy. RNA-sequencing results revealed that heme oxygenase-1 (Hmox1) was significantly up-regulated in DOX-treated murine hearts. Administering DOX to mice induced cardiomyopathy with a rapid, systemic accumulation of nonheme iron via heme degradation by Nrf2-mediated upregulation of Hmox1, which effect was abolished in Nrf2-deficent mice. Conversely, zinc protoporphyrin IX, an Hmox1 antagonist, protected the DOX-treated mice, suggesting free iron released on heme degradation is necessary and sufficient to induce cardiac injury. Given that ferroptosis is driven by damage to lipid membranes, we further investigated and found that excess free iron accumulated inmitochondria and caused lipid peroxidation on its membrane. Mitochondria-targeted antioxidant MitoTEMPO significantly rescued DOX cardiomyopathy, supporting oxidative damage of mitochondria as a major mechanism in ferroptosis-induced heart damage. Importantly, ferrostatin-1 and iron chelation also ameliorated heart failure induced by both acute and chronic I/R in mice. These findings highlight that targeting ferroptosis serves as a cardioprotective strategy for cardiomyopathy prevention.
With reduced background and high sensitivity, photoelectrochemistry (PEC) may be applied as an intracellular nanotool and open a new technological direction of single‐cell study. Nevertheless, the ...present palette of single‐cell tools lacks such a PEC‐oriented solution. Here a dual‐functional photocathodic single‐cell nanotool capable of direct electroosmotic intracellular drug delivery and evaluation of oxidative stress is devised by engineering a target‐specific organic molecule/NiO/Ni film at the tip of a nanopipette. Specifically, the organic molecule probe serves simultaneously as the biorecognition element and sensitizer to synergize with p‐type NiO. Upon intracellular delivery at picoliter level, the oxidative stress effect will cause structural change of the organic probe, switching its optical absorption and altering the cathodic response. This work has revealed the potential of PEC single‐cell nanotool and extended the boundary of current single‐cell electroanalysis.
An integrated photocathodic nanotool was fabricated for dual‐functional intracellular drug delivery and evaluation of cellular oxidative stress in single live cell.
Late‐stage hepatocellular carcinoma (HCC) usually has a low survival rate because of the high risk of metastases and the lack of an effective cure. Disulfiram (DSF) has copper (Cu)‐dependent ...anticancer properties in vitro and in vivo. The present work aims to explore the anti‐metastasis effects and molecular mechanisms of DSF/Cu on HCC cells both in vitro and in vivo. The results showed that DSF inhibited the proliferation, migration and invasion of HCC cells. Cu improved the anti‐metastatic activity of DSF, while Cu alone had no effect. Furthermore, DSF/Cu inhibited both NF‐κB and TGF‐β signalling, including the nuclear translocation of NF‐κB subunits and the expression of Smad4, leading to down‐regulation of Snail and Slug, which contributed to phenotype epithelial–mesenchymal transition (EMT). Finally, DSF/Cu inhibited the lung metastasis of Hep3B cells not only in a subcutaneous tumour model but also in an orthotopic liver metastasis assay. These results indicated that DSF/Cu suppressed the metastasis and EMT of hepatic carcinoma through NF‐κB and TGF‐β signalling. Our study indicates the potential of DSF/Cu for therapeutic use.
Dendrobium officinale Kimura et Migo is a traditional Chinese orchid herb that has both ornamental value and a broad range of therapeutic effects. Here, we report the first de novo assembled 1.35 Gb ...genome se- quences for D. officinale by combining the second-generation Illumina Hiseq 2000 and third-generation PacBio sequencing technologies. We found that orchids have a complete inflorescence gene set and have some specific inflorescence genes. We observed gene expansion in gene families related to fungus symbiosis and drought resistance. We analyzed biosynthesis pathways of medicinal components of D. officinale and found extensive duplication of SPS and SuSy genes, which are related to polysaccharide generation, and that the pathway of D. officinale alkaloid synthesis could be extended to generate 16- epivellosimine. The D. officinale genome assembly demonstrates a new approach to deciphering large complex genomes and, as an important orchid species and a traditional Chinese medicine, the D. officinale genome will facilitate future research on the evolution of orchid plants, as well as the study of medicinal components and potential genetic breeding of the dendrobe.
•Iodine species (e.g., I–, ICM, IO3−) and their occurrence in water are reviewed.•UV and UV-AOPs amend DOM and thus enhance I-DBP formation in post-disinfection.•UV deiodinates and partly mineralizes ...ICM, releases I–, but less efficiently than UV-AOPs.•UV and UV-AOPs can mineralize I-DBPs and liberate halides.•UV can reduce IO3− to I–, leading to I-DBP formation in subsequent disinfection.
Iodinated disinfection byproducts (I-DBPs) formed in water treatment are of emerging concern due to their high toxicity and the tase-and-odor problems associated with iodinated trihalomethanes (I-THMs). Iodoacetic acid and dichloroiodomethane are currently regulated in Shenzhen, China and the Ministry of Health of the People's Republic of China has also been considering regulating I-DBPs. Iodide (I–), organoiodine compounds (e.g., iodinated X-ray contrast media ICM), and iodate (IO3–) are the three common iodine sources in aquatic environment that lead to I-DBP formation. While UV irradiation effectively inactivate a wide range of microorganisms in water, it induces the transformation of these iodine sources, enabling the formation of I-DBPs. This review focuses on the fate and transformation of these iodine sources in UV-based water treatment (i.e., UV irradiation and UV-based advanced oxidation processes UV-AOPs) and the formation of I-DBPs in post-disinfection. I– released in UV-based treatments of ICM and can be oxidized in subsequent disinfection to hypoiodous acid (HOI), which reacts with natural organic matter (NOM) to produce I-DBPs. Both UV and UV-AOPs are not able to fully mineralize ICM and completely oxidize the released I– to (except UV/O3). Results reveal that UV and UV-AOPs are adequate for I-DBP degradation but require high UV doses. While the ideal I-DBP mitigation strategy awaits to be developed, understanding their sources and formation pathways aids in informed selections of water treatment processes, empowers water suppliers to meet drinking water standards, and minimizes consumers’ exposure to I-DBPs.
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RATIONALE:Human pluripotent stem cell–derived cardiovascular progenitor cells (hPSC-CVPCs) should be thoroughly investigated in large animal studies before testing in clinical trials.
OBJECTIVE:The ...main of this study is to clarify whether hPSC-CVPCs can engraft for long time in the heart of primates after myocardial infarction (MI) and compare the effectiveness and safety of immunosuppression with cyclosporine alone or multiple-drug regimen (MDR) containing cyclosporine, methylprednisolone, and basiliximab in cynomolgus monkeys that had received intramyocardial injections of 1×10 EGFP (enhanced green fluorescent protein)-expressing hPSC-CVPCs after MI. A third group of animals received the immunosuppression MDR but without cell therapy after MI (MI+MDR group).
METHODS AND RESULTS:Measurements of EGFP gene levels and EGFP immunofluorescence staining indicated that the hPSC-CVPC engraftment rate was greater in the MI+MDR+CVPC group than that in the MI+cyclosporine+CVPC group. However, even in the MI+MDR+CVPC group, no transplanted cells could be detected at 140 days after transplantation. Concomitantly, immunofluorescent analysis of CD3, CD4, and CD8 expression indicated that T-lymphocyte infiltration in the CVPC-transplanted hearts was less in the MDR-treated animals than in the cyclosporine-alone–treated animals. The recovery of left ventricular function on day 28 post-MI in the MI+MDR+CVPC group was better than that in the MI+MDR group. Apoptotic cardiac cells were also less common in the MI+MDR+CVPC group than in the MI+MDR group, although both immunosuppression regimens were associated with transient hepatic dysfunction.
CONCLUSIONS:This is the largest study of hPSCs in nonhuman primates in cardiovascular field to date (n=32). Compared with cyclosporine alone, MDR attenuates immune rejection and improves survival of hPSC-CVPCs in primates; this is associated with less apoptosis of native cardiac cells and better recovery of left ventricular function at 28 days. However, even with MDR, transplanted hPSC-CVPCs do not engraft and do not survive at 140 days after transplantation, thereby excluding remuscularization as a mechanism for the functional effect.
Hypochlorite (ClO–) and glutathione (GSH) have been reported to closely correlate with oxidative stress and related diseases; however, a clear mechanism is still unknown, mainly owing to a lack of ...accurate analytical methods for live cells. Herein we create a novel surface-enhanced Raman scattering (SERS) nanoprobe, 4-mercaptophenol (4-MP)-functionalized gold flowers (AuF/MP), for imaging and biosensing of ClO– and GSH in RAW 264.7 macrophage cells upon oxidative stress. The SERS spectra of AuF/MP change with the reaction between ClO– and 4-MP on AuFs within 1 min and then recover after reaction with GSH, resulting in the ratiometric detection of ClO– and GSH with high accuracy. The single SERS probe also shows high selectivity for ClO– and GSH detection against other reactive oxygen species and amino acids which may exist in biological systems, as well as remarkable sensitivity ascribed to a larger amount of hot spots on AuFs. The significant analytical performance of the developed nanoprobe, together with good biocompatibility and high cell-permeability, enables the present SERS probe imaging and real-time detection of ClO– and GSH in live cells upon oxidative stress.
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