Mitochondria are the major cellular energy‐producing organelles and intracellular source of reactive oxygen species. These organelles are responsible for driving cell life and death through ...mitochondrial network structure homeostasis, which is determined by a balance of fission and fusion. Recent advances revealed that a number of components of the fission and fusion machinery, including dynamin‐related protein 1 (Drp1), mitofusin1/2 (Mfn1/2) and Optic atrophy 1 (OPA1), that have been implicated in mitochondrial shape changes are indispensible for autophagy, apoptosis and necroptosis. Drp1 is the main regulator of mitochondrial fission and has become a key point of contention. The controversy focuses on whether Drp1 is directly involved in the regulation of cell death and, if involved, whether is it a stimulator or a negative regulator of cell death. Here, we examine the relevance of the homeostasis of the mitochondrial network structure in 3 different types of cell death, including autophagy, apoptosis and necroptosis. Furthermore, a variety of cancers often exhibit a fragmented mitochondrial phenotype. Thus, the fragmented ratio can reflect tumor progression that predicts prognosis and therapeutic response. In addition, we investigate whether the targeting of the mitochondrial fission protein Drp1 could be a novel therapeutic approach.
Here, we examine the relevance of the homeostasis of the mitochondrial network structure in 3 different types of cell death, including autophagy, apoptosis and necroptosis. Furthermore, a variety of cancers often exhibit a fragmented mitochondrial phenotype. Targeting the mitochondrial fission protein Drp1or other shaping proteins is becoming a topic of interest. Further studies are needed to understand the differential effects of oncogenic signaling pathways on mitochondrial dynamics and to identify additional new signaling axes that regulate mitochondrial network structure homeostasis.
A metal‐, base‐ and reductant‐free approach for the efficient synthesis of various N‐acylated 2‐aminoquinolines was reported. In this work, readily available nitriles are used as the amide source, ...and methyl carbazate as both the radical activating reagent and oxygen source. This is the first report on the ester‐radical‐activated highly regioselective addition of nitriles to quinolone N‐oxides. This procedure is expected to complement the current methods for functionalization of N‐oxides via an electrophilic activation mechanism.
The slow reaction kinetics and structural instability of organic electrode materials limit the further performance improvement of aqueous zinc‐organic batteries. Herein, we have synthesized a ...Z‐folded hydroxyl polymer polytetrafluorohydroquinone (PTFHQ) with inert hydroxyl groups that could be partially oxidized to the active carbonyl groups through the in situ activation process and then undertake the storage/release of Zn2+. In the activated PTFHQ, the hydroxyl groups and S atoms enlarge the electronegativity region near the electrochemically active carbonyl groups, enhancing their electrochemical activity. Simultaneously, the residual hydroxyl groups could act as hydrophilic groups to enhance the electrolyte wettability while ensuring the stability of the polymer chain in the electrolyte. Also, the Z‐folded structure of PTFHQ plays an important role in reversible binding with Zn2+ and fast ion diffusion. All these benefits make the activated PTFHQ exhibit a high specific capacity of 215 mAh g−1 at 0.1 A g−1, over 3400 stable cycles with a capacity retention of 92 %, and an outstanding rate capability of 196 mAh g−1 at 20 A g−1.
A hydroxyl polymer PTFHQ has been designed to obtain electrochemical activity through an in situ electrochemical activation process. The synergistic effects of the different functional groups (C=O, −OH, and −S−) and the unique Z‐folded structure of the activated PTFHQ effectively improve its electrochemical activity and contribute to the rapid reaction kinetics, realizing the construction of high‐performance zinc‐organic batteries.
Oral cancer (OC) poses a threat to human health and imposes a heavy burden on countries. We assessed the burden imposed by OC on Asian nations from 1990 to 2019 based on gender and age.
We collected ...oral cancer data from the 2019 Global Burden of Disease study from 1990 to 2019 in 45 Asian countries and territories. Annual case data and age-standardised rates (ASRs) were used to investigate the incidence, mortality, and disability-adjusted life-years (DALYs) of OC based on age and gender from 1990 to 2019 in 45 Asian countries and territories. Estimated annual percentage changes (EAPCs) were used to assess incidence rate, mortality, and trends in DALYs.
The age-standardised incidence rate (ASIR) of OC increased from 1990 to 2019 with an EAPC of 0.32 (95% CI, 0.19-0.46), and the age-standardised death rate of OC remained stable at an EAPC of 0.08 (95%CI, from -0.06 to 0.21). The age-standardised DALYs of OC decreased at an EAPC of -0.16 (95%CI, from -0.30 to -0.02). The proportion of patients older than 70 years increased yearly in terms of incidence, mortality, and DALYs from 1990 to 2019. Of the DALYs, smoking was the main contributor in the Asian regions, and the largest contributor to DALYs in most Asian regions. Other contributors were alcohol use and chewing tobacco.
Although the burden of OC was declining in Asia, South Asia remained the region with the highest burden. OC caused the greatest burden in Pakistan, Taiwan China, and India. Therefore, measures should be taken to reduce the burden of oral cancer in high-risk regions and countries with attributable risk factors.
Evodia rutaecarpa, a well-known herb medicine in China, is extensively applied in traditional Chinese medicine (TCM). The plant has the effects of dispersing cold and relieving pain, arresting ...vomiting, and helping Yang and stopping diarrhea. Modern research demonstrates that evodiamine, the main component of Evodia rutaecarpa, is the material basis for its efficacy.
This paper is primarily addressed to summarize the current studies on evodiamine. The progress in research on the pharmacology, toxicology, pharmacokinetics, preparation researches and clinical application are reviewed. Moreover, outlooks and directions for possible future studies concerning it are also discussed.
The information of this systematic review was conducted with resources of multiple literature databases including PubMed, Google scholar, Web of Science and Wiley Online Library and so on, with employing a combination of keywords including “pharmacology”, “toxicology”, “pharmacokinetics” and “clinical application”, etc.
As the main component of Evodia rutaecarpa, evodiamine shows considerable pharmacological activities, such as analgesic, anti-inflammatory, anti-tumor, anti-microbial, heart protection and metabolic disease regulation. However, it is also found that it has significant hepatotoxicity and cardiotoxicity, thereby it should be monitored in clinical. In addition, available data demonstrate that the evodiamine has a needy solubility in aqueous medium. Scientific and reasonable pharmaceutical strategies should be introduced to improve the above defects. Meanwhile, more efforts should be made to develop novel efficient and low toxic derivatives.
This review summarizes the results from current studies of evodiamine, which is one of the valuable medicinal ingredients from Evodia rutaecarpa. With the assistance of relevant pharmacological investigation, some conventional application and problems in pharmaceutical field have been researched in recent years. In addition, unresolved issues include toxic mechanisms, pharmacokinetics, novel pharmaceutical researches and relationship between residues and intestinal environment, which are still being explored and excavate before achieving integration into clinical practice.
Reirradiation in standard fractionation for locally advanced recurrent nasopharyngeal carcinoma after a previous course of high-dose radiotherapy is often associated with substantial late toxicity, ...negating its overall benefit. We therefore aimed to investigate the efficacy and safety of hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy.
This multicentre, randomised, open-label, phase 3 trial was done in three centres in Guangzhou, China. Eligible patients were aged 18–65 years with histopathologically confirmed undifferentiated or differentiated, non-keratinising, advanced locally recurrent nasopharyngeal carcinoma. Participants were randomly assigned (1:1) to either receive hyperfractionation (65 Gy in 54 fractions, given twice daily with an interfractional time interval of at least 6 h) or standard fractionation (60 Gy in 27 fractions, given once a day). Intensity-modulated radiotherapy was used in both groups. A computer program generated the assignment sequence and randomisation was stratified by treatment centre, recurrent tumour stage (T2–T3 vs T4), and recurrent nodal stage (N0 vs N1–N2), determined at the time of randomisation. The two primary endpoints were the incidence of severe late complications defined as the incidence of grade 3 or worse late radiation-induced complications occurring 3 months after the completion of radiotherapy until the latest follow-up in the safety population, and overall survival defined as the time interval from randomisation to death due to any cause in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02456506.
Between July 10, 2015, and Dec 23, 2019, 178 patients were screened for eligibility, 144 of whom were enrolled and randomly assigned to hyperfractionation or standard fractionation (n=72 in each group). 35 (24%) participants were women and 109 (76%) were men. After a median follow-up of 45·0 months (IQR 37·3–53·3), there was a significantly lower incidence of grade 3 or worse late radiation-induced toxicity in the hyperfractionation group (23 34% of 68 patients) versus the standard fractionation group (39 57% of 68 patients; between-group difference –23% 95% CI –39 to –7; p=0·023). Patients in the hyperfractionation group had better 3-year overall survival than those in the standard fractionation group (74·6% 95% CI 64·4 to 84·8 vs 55·0% 43·4 to 66·6; hazard ratio for death 0·54 95% CI 0·33 to 0·88; p=0·014). There were fewer grade 5 late complications in the hyperfractionation group (five 7% nasal haemorrhage) than in the standard fractionation group (16 24%, including two 3% nasopharyngeal necrosis, 11 16% nasal haemorrhage, and three 4% temporal lobe necrosis).
Hyperfractionated intensity-modulated radiotherapy could significantly decrease the rate of severe late complications and improve overall survival among patients with locally advanced recurrent nasopharyngeal carcinoma. Our findings suggest that hyperfractionated intensity-modulated radiotherapy could be used as the standard of care for these patients.
Key-Area Research and Development of Guangdong Province, the National Natural Science Foundation of China, the Special Support Program for High-level Talents in Sun Yat-sen University Cancer Center, the Guangzhou Science and Technology Plan Project, and the National Ten Thousand Talents Program Science and Technology Innovation Leading Talents, Sun Yat-Sen University Clinical Research 5010 Program.
A mild and eco-friendly visible-light-induced decarboxylative acylation of quinoxalin-2(1
H
)-ones and α-oxo carboxylic acids with ambient air as the sole oxidant at room temperature was established. ...The reaction proceeded efficiently without any metal catalysts, strong oxidants or external-photosensitizers, ultimately reducing the generation of waste.
An eco-friendly visible-light-induced decarboxylative acylation of quinoxalin-2(1
H
)-ones and α-oxo carboxylic acids with air as the oxidant under external-photocatalyst-free conditions was established.
The first example of visible-light-induced deoxygenative C2-sulfonylation of quinoline
N
-oxides with sulfinic acids in the presence of an organic dye as the catalyst was developed. The reaction ...conditions are eco-friendly and mild, employing ambient air as the sole oxidant and aqueous acetone solution as the solvent. This approach requires only a very low catalyst loading, allowing gram-scale preparation as well as late-stage modification of biologically active compounds bearing quinoline groups.
Organic electrode materials (OEMs) have gathered extensive attention for aqueous zinc‐ion batteries (AZIBs) due to their structural diversity and molecular designability. However, the reported ...research mainly focuses on the design of the planar configuration of OEMs and does not take into account the important influence of the spatial structure on the electrochemical properties, which seriously hamper the further performance liberation of OEMs. Herein, this work has designed a series of thioether‐linked naphthoquinone‐derived isomers with tunable spatial structures and applied them as the cathodes in AZIBs. The incomplete conjugated structure of the elaborately engineered isomers can guarantee the independence of the redox reaction of active groups, which contributes to the full utilization of active sites and high redox reversibility. In addition, the position isomerization of naphthoquinones on the benzene rings changes the zincophilic activity and redox kinetics of the isomers, signifying the importance of spatial structure on the electrochemical performance. As a result, the 2,2′‐(1,4‐phenylenedithio) bis(1,4‐naphthoquinone) (p‐PNQ) with the smallest steric hindrance and the most independent redox of active sites exhibits a high specific capacity (279 mAh g−1), an outstanding rate capability (167 mAh g−1 at 100 A g−1), and a long‐term cycling lifetime (over 2800 h at 0.05 A g−1).
The naphthoquinone derivative isomers with nonplanar and partially conjugated structures have been designed to guarantee high structure stability and redox unit independence, realizing the construction of Zn‐organic batteries with high achievable capacity, stable cycling performance, and ultrarapid rate capability.
A new and efficient visible-light-mediated strategy has been developed for the synthesis of 3-sulfenylated quinoxalin-2(1H)-ones via direct C–H sulfenylation of quinoxalin-2(1H)-ones with thiols in ...air at room temperature. Through this photochemical reaction, various 3-sulfenylated quinoxalin-2(1H)-ones can be efficiently and conveniently obtained in excellent yields with good functional group tolerance by simple use of rhodamine B as the cheap photocatalyst and air as the green oxidant.
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