Iron‐nitrogen‐carbon materials are being intensively studied as the most promising substitutes for Pt‐based electrocatalysts for the oxygen reduction reaction (ORR). A rational design of the ...morphology and porous structure can promote the accessibility of the active site and the reactants/products transportation, accelerating the reaction kinetics. Herein, 1D porous iron/nitrogen‐doped carbon nanorods (Fe/N‐CNRs) with a hierarchically micro/mesoporous structure are prepared by pyrolyzing the in situ polymerized pyrrole on the surface of Fe‐MIL‐88B‐derived 1D Fe2O3 nanorods (MIL: Material Institut Lavoisier). The Fe2O3 nanorods not only partially dissolve to generate Fe3+ for initiating polymerization but serve as templates to form the 1D structure during polymerization. Furthermore, the pyrrole coated Fe2O3 nanorod architecture prevents the porous structure from collapsing and protects Fe from aggregation to yield atomic Fe‐N4 moieties during carbonization. The obtained Fe/N‐CNRs display exceptional ORR activities (E1/2 = 0.90 V) and satisfactory long‐term durabilities, exceeding those for Pt/C. Furthermore, the unprecedented Fe/N‐CNRs catalytic performance is demonstrated with Zn‐air batteries, including a superior maximum power density (181.8 mW cm−2), specific capacity (998.67 W h kg−1), and long‐term durability over 100 h. The prominent performance stems from the unique 1D structure, hierarchical pore system, high surface area, and homogeneously dispersed single‐atom Fe‐N4 moieties.
1D iron/nitrogen (Fe/N)‐doped hierarchically porous carbon nanorods (Fe/N‐CNRs) catalysts with atomically dispersed Fe‐N4 sites are prepared via an in situ polymerization strategy. The obtained Fe/N‐CNRs catalyst displays excellent catalytic performance towards oxygen reduction reaction and Zn‐air batteries, surpassing commercial Pt/C, which indicates that the prepared catalyst possesses the potential of practical application in electrochemical devices.
Maintaining the structure of protein and peptide drugs has become one of the most important goals of scientists in recent decades. Cold and thermal denaturation conditions, lyophilization and freeze ...drying, different pH conditions, concentrations, ionic strength, environmental agitation, the interaction between the surface of liquid and air as well as liquid and solid, and even the architectural structure of storage containers are among the factors that affect the stability of these therapeutic biomacromolecules. The use of genetic engineering, side-directed mutagenesis, fusion strategies, solvent engineering, the addition of various preservatives, surfactants, and additives are some of the solutions to overcome these problems. This article will discuss the types of stress that lead to instabilities of different proteins used in pharmaceutics including regulatory proteins, antibodies, and antibody-drug conjugates, and then all the methods for fighting these stresses will be reviewed. New and existing analytical methods that are used to detect the instabilities, mainly changes in their primary and higher order structures, are briefly summarized.
Background and Aims
Surgical resection is the primary treatment for HCC; however, it is associated with a high rate of recurrence and death. We conducted this phase 2 study to investigate the ...efficacy and safety of postoperative intensity‐modulated radiotherapy (IMRT) for HCC after narrow‐margin hepatectomy.
Approach and Results
We designed a single‐arm, prospective phase 2 trial to evaluate overall survival (OS), disease‐free survival (DFS), recurrence patterns, and toxicity in patients receiving adjuvant radiotherapy. The eligibility criteria included the following: pathological diagnosis of HCC after hepatectomy, with narrow pathological margins (< 1 cm); age > 18 years; and Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients received IMRT within 4‐6 weeks after surgical resection. This trial was registered at ClinicalTrials.gov (NCT01456156). Between 2008 and 2016, a total of 76 eligible patients who underwent narrow‐margin resection were enrolled. The median follow‐up duration was 70 months; the 3‐year OS and DFS rates were 88.2% and 68.1%, respectively; and the 5‐year OS and DFS rates were 72.2% and 51.6%, respectively. Intrahepatic recurrence was the primary recurrence pattern. No marginal recurrence was found. Intrahepatic, extrahepatic, and combined recurrences at the first relapse were found in 33, 5, and 1 patient, respectively. The most common radiation‐related grade‐3 toxicities were leukopenia (7.9%), elevated alanine aminotransferase (3.9%) and aspartate aminotransferase (2.6%) levels, and thrombocytopenia (1.3%). Classical or nonclassical radiation‐induced liver disease was not noted.
Conclusions
Adjuvant radiotherapy is an effective, well‐tolerated, and promising adjuvant regimen in patients with HCC who have undergone narrow‐margin hepatectomy. Our trial provides evidence and a rationale for planning a future phase 3 trial.
Electrospray ionization (ESI) and desorption electrospray ionization (DESI) are common soft ionization method of mass spectrometry (MS). However, recent studies revealed that some chemical reactions ...can be induced or greatly accelerated in the sprayed microdroplets compared to the same reaction in the bulk. These open a new area in using microdroplet MS to explore new chemistry and develop new applications. This minireview will introduce microdroplet chemistries and explore various microdroplet techniques most of which are ESI‐ or DESI‐based extensions by incorporating transfer tube, supersonic nebulizing gas, droplet fusion, spray extraction, laser irradiation, or laser ablation for online/offline MS analysis. Potential applications associated with new techniques, including real‐time reaction monitoring, high‐throughput reaction screening, protein identification, and protein characterization, are also described. Future outlook, such as coupling microdroplet MS with separation techniques, is proposed and discussed.
Hepatocellular carcinoma (HCC) is the most predominant primary malignancy in the liver. Genotoxic and genetic models have revealed that HCC cells are derived from hepatocytes, but where the critical ...region for tumor foci emergence is and how this transformation occurs are still unclear. Here, hyperpolyploidization of hepatocytes around the centrilobular (CL) region is demonstrated to be closely linked with the development of HCC cells after diethylnitrosamine treatment. We identify the CL region as a dominant lobule for accumulation of hyperpolyploid hepatocytes and preneoplastic tumor foci formation. We also demonstrate that upregulation of Aurkb plays a critical role in promoting hyperpolyploidization. Increase of AURKB phosphorylation is detected on the midbody during cytokinesis, causing abscission failure and hyperpolyploidization. Pharmacological inhibition of AURKB dramatically reduces nucleus size and tumor foci number surrounding the CL region in diethylnitrosamine-treated liver. Our work reveals an intimate molecular link between pathological hyperpolyploidy of CL hepatocytes and transformation into HCC cells.
The assembly of spherical fullerenes, or buckyballs, into single crystals for crystallographic identification often suffers from disordered arrangement. Here we show a chiral configuration of ...decapyrrylcorannulene that has a concave 'palm' of corannulene and ten flexible electron-rich pyrryl group 'fingers' to mimic the smart molecular 'hands' for self-adaptably cradling various buckyballs in a (+)hand-ball-hand(-) mode. As exemplified by crystallographic identification of 15 buckyball structures representing pristine, exohedral, endohedral, dimeric and hetero-derivatization, the pyrryl groups twist with varying dihedral angles to adjust the interaction between decapyrrylcorannulene and fullerene. The self-adaptable electron-rich pyrryl groups, susceptible to methylation, are theoretically revealed to contribute more than the bowl-shaped palm of the corannulene in holding buckyball structures. The generality of the present decapyrrylcorannulene host with flexible pyrryl groups facilitates the visualization of numerous unknown/unsolved fullerenes by crystallography and the assembly of the otherwise close-packed spherical fullerenes into two-dimensional layered structures by intercalation.
6,6‐phenyl‐C61‐butyric acid methyl ester remains indispensable as the electron transport material (ETM) for perovskite solar cells (PSCs), but its synthesis involves complicated multisteps with low ...productivity. In contrast, the potential of synthesizing simpler fulleropyrrolidine derivatives has long been overlooked, and little has been understood regarding their structure‐dependent effects on photovoltaic (PV) performance. Herein, seven novel fulleropyrrolidine derivatives (F1–F7) are deliberately designed, synthesized, and comprehensively characterized in both solution and thin‐film states and subsequently investigated as ETMs for PSCs. Notably, the F4 delivers the highest power conversion efficiencies over 20% of devices, which surpass all reported fulleropyrrolidine ETMs due to its optimal photoelectric property. Moreover, the structure‐dependent effects of the fullerenes on PV parameters are uncovered, including solubility, intermolecular interaction, packing structure, and charge‐transfer ability, which can guide the future design of high‐performance and stable fullerene ETMs for PSCs.
A novel fullerene molecular template with a solubility enhancer arm (R1) and a π–π interaction inducer arm (R2) is deliberately proposed. This design effort delivers the highest power conversion efficiency over 20% of the device with corresponding fulleropyrrolidine electron transport material for the first time.
High-fat diet (HFD)-induced obesity is a primary risk factor for serious health problems. Although much research has been performed at the genomic level, lipidomic studies were limited. In this ...study, we aim to obtain a comprehensive profile of circulating plasma lipids, which are altered in rodent rat obesity by untargeted liquid chromatography–mass spectrometry. Rats fed with HFD for 8 weeks had increased body weight, liver and adipose tissue weight. The analysis results revealed that polyunsaturated fatty acids (PUFAs) and their corresponding phosphatidylcholine, phosphatidylinositol, and phosphatidylserine were significantly decreased in rats fed with HFD. In contrast, less unsaturated and ether type phosphatidylglycerols were increased. The triacylglycerides (TAGs) having saturated FA were increased in the HFD condition, whereas TAGs having PUFA were decreased. The levels of many plasma lipids were altered, and interestingly PUFA derived lipids were negatively associated with obesity. This signifies the importance of a PUFAs enriched diet to overwhelm obesity associated diseases.
A green synthesis strategy of 2‐arylquinoxalines and 3‐arylquinoxalin‐2(1H)‐ones via ball milling, which could avoid copious solvent waste, was accomplished in this work. Aryl radicals were produced ...from aryldiazonium salts by using a solvent‐free or catalyst‐free single electron transfer process induced by mechanical force, affording a series of 2‐arylquinoxalines and 3‐arylquinoxalin‐2(1H)‐ones with 28%–85 yield.
Sirtuin3 (Sirt3) is a member of the silent information regulator 2 (Sir2) family of proteins located in mitochondria that influences almost every major aspect of mitochondrial biology, including ATP ...generation and reactive oxygen species (ROS) production. Our previous study showed that Sirt3 exerts protective effects against oxidative stress in neuronal cells. In this study, we investigated the role of Sirt3 in neuronal ischemia using an oxygen and glucose deprivation (OGD) model. Sirt3 was up-regulated by OGD and overexpression of Sirt3 through lentivirus transfection significantly reduced OGD-induced lactate dehydrogenase (LDH) release and neuronal apoptosis. These effects were accompanied by reduced hydrogen dioxide (H2O2) production, enhanced ATP generation and preserved mitochondrial membrane potential (MMP). The results of immunocytochemistry and electron microscopy showed that Sirt3 increased autophagy in OGD-injured neurons, which was also confirmed by the increased expression of Beclin-1 as well as LC3-I to LC3-II conversion. In addition, the autophagy inhibitor 3-MA and bafilomycin A1 partially prevented the effects of Sirt3 on LDH release and apoptosis after OGD. The results of western blotting showed that overexpression of Sirt3 in cortical neurons markedly increased the phosphorylation of AMPK, whereas the phosphor-mTOR (p-mTOR) levels decreased both in the presence and absence of OGD insult. Furthermore, pre-treatment with the AMPK inhibitor compound C partially reversed the protective effects of Sirt3. Taken together, these findings demonstrate that Sirt3 protects against OGD insult by inducing autophagy through regulation of the AMPK-mTOR pathway and that Sirt3 may have therapeutic value for protecting neurons from cerebral ischemia.
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•Overexpression of Sirt3 attenuates OGD-induced neuronal injury.•Sirt3 preserves mitochondrial function and cellular bioenergetics.•Sirt3 promotes autophagy following neuronal ischemia.•Autophagy contributes to the neuroprotective effect of Sirt3.•Sirt3-induced protection is mediated by the AMPK-mTOR pathway.
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