Abnormal metabolism of tumour cells is closely related to the occurrence and development of breast cancer, during which the expression of NF‐E2‐related factor 2 (Nrf2) is of great significance. ...Metastatic breast cancer is one of the most common causes of cancer death worldwide; however, the molecular mechanism underlying breast cancer metastasis remains unknown. In this study, we found that the overexpression of Nrf2 promoted proliferation and migration of breast cancers cells. Inhibition of Nrf2 and overexpression of Kelch‐like ECH‐associated protein 1 (Keap1) reduced the expression of glucose‐6‐phosphate dehydrogenase (G6PD) and transketolase of pentose phosphate pathway, and overexpression of Nrf2 and knockdown of Keap1 had opposite effects. Our results further showed that the overexpression of Nrf2 promoted the expression of G6PD and Hypoxia‐inducing factor 1α (HIF‐1α) in MCF‐7 and MDA‐MB‐231 cells. Overexpression of Nrf2 up‐regulated the expression of Notch1 via G6PD/HIF‐1α pathway. Notch signalling pathway affected the proliferation of breast cancer by affecting its downstream gene HES‐1, and regulated the migration of breast cancer cells by affecting the expression of EMT pathway. The results suggest that Nrf2 is a potential molecular target for the treatment of breast cancer and targeting Notch1 signalling pathway may provide a promising strategy for the treatment of Nrf2‐driven breast cancer metastasis.
The first example of iron‐catalyzed decarboxylative (4+1) cycloaddition reactions is described in this publication. By using this method, a wide range of functionalized indoline products were ...prepared from easily available vinyl benzoxazinanones and sulfur ylides in high yields and selectivities. A possible reaction pathway involving an allylic iron intermediate is discussed based on a series of control experiments and density‐functional theory calculations.
Going in reverse: The first example of iron‐catalyzed decarboxylative formal (4+1) cycloaddition reactions, which exploit the reverse reactivity of ambident iron‐stabilized intermediates, was developed. By using this method, a wide range of functionalized indoline products were facilely prepared in generally good yields and high stereoselectivities from easily available starting materials. Ts=4‐toluenesulfonyl.
Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines ...for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi‐disciplinary team comprising of experts from all sub‐specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence‐based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow‐up of NPC, which aim to improve the management of NPC.
Three new types of lanthanide coordination polymersone-dimensional (1D) {Ln(TCMA)(HTCMA)·(DMF)·(H2O)2} n (1–2), three-dimensional (3D) {Ln(TCMA)(NO3)} n (3–4), and zero-dimensional (0D) ...Ln4(TCMA)4(OH)4(H2O)8 (5–6) (Ln = Eu, Tb) have been hydrothermally synthesized by using the ligand N,N,N-tris{(2′-carboxy1,1′-biphenyl-4-yl)methyl}methylammonium chloride (H3TCMA+Cl). Interestingly, the 1D chain and 3D Ln-MOFs can be transformed to a more stable 0D cage structure by changing temperature-induced ligand’s configuration transformation, which is attributed to the ligand’s semirigid feature. Furthermore, the crystal structures of 1–6 were characterized and confirmed by X-ray single-crystal analysis, X-ray diffraction (XRD), thermogravimetric analysis (TGA), ultimate analysis, and infrared (IR) spectroscopy. The luminescence detection results show that the 3D Eu-MOFs have good sensitivity and selectivity to detect Fe3+ ions in methanol solutions. And, with careful adjustment of metal ratios (Eu/Tb) in the reaction mixtures, color tuning was easily achieved. Moreover, lifetime data and quantum yield are reported for these complexes (1–6) prepared in this study.
During acute kidney injury (AKI), tubular cell dedifferentiation initiates cell regeneration; hepatocyte growth factor (HGF) is involved in modulating cell dedifferentiation. Mesenchymal stem cell ...(MSC)-derived microvesicles (MVs) deliver RNA into injured tubular cells and alter their gene expression, thus regenerating these cells. We boldly speculated that MVs might induce HGF synthesis via RNA transfer, thereby facilitating tubular cell dedifferentiation and regeneration. In a rat model of unilateral AKI, the administration of MVs promoted kidney recovery. One of the mechanisms of action is the acceleration of tubular cell dedifferentiation and growth. Both in vivo and in vitro, rat HGF expression in damaged rat tubular cells was greatly enhanced by MV treatment. In addition, human HGF mRNA present in MVs was delivered into rat tubular cells and translated into the HGF protein as another mechanism of HGF induction. RNase treatment abrogated all MV effects. In the in vitro experimental setting, the conditioned medium of MV-treated injured tubular cells, which contains a higher concentration of HGF, strongly stimulated cell dedifferentiation and growth, as well as Erk1/2 signaling activation. Intriguingly, these effects were completely abrogated by either c-Met inhibitor or MEK inhibitor, suggesting that HGF induction is a crucial contributor to the acceleration of cell dedifferentiation and growth. All these findings indicate that MV-induced HGF synthesis in damaged tubular cells via RNA transfer facilitates cell dedifferentiation and growth, which are important regenerative mechanisms.
Chronic heart failure is a common and fatal disease triggered by loss of normal cardiac function. Yiqi Fumai Lyophilized Injection is widely used in the treatment of cardiovascular diseases, ...especially chronic heart failure. In this study, a model of chronic heart failure in mice was established with permanent coronary artery ligation followed by Yiqi Fumai Lyophilized Injection intervention for 14 days. Then, the endogenous metabolites of mice plasma and urine samples were screened through nontargeted metabolomics techniques. The results indicated that Yiqi Fumai Lyophilized Injection treatment changed the metabolic pattern of chronic heart failure and regulated valine, leucine, and isoleucine biosynthesis, taurine and hypotaurine metabolism, histidine metabolism and arginine biosynthesis, etc. Finally, the cardioprotective mechanism of Yiqi Fumai Lyophilized Injection was further verified in the mouse model of chronic heart failure and angiotensin II‐induced cardiac fibroblasts based on metabolomics. The results showed that Yiqi Fumai Lyophilized Injection could inhibit myocardial fibrosis to improve chronic heart failure. This study firstly elucidated the metabolic network and pathways regulated by Yiqi Fumai Lyophilized Injection, which might facilitate the realization of the clinically accurate application of Yiqi Fumai Lyophilized Injection in the treatment of chronic heart failure.
Background
Hepatitis B core antibody (HBcAb) positivity is considered a prior hepatitis B virus (HBV) infection. However, little is known about the effect of HBcAb positivity on surgical safety for ...hilar cholangiocarcinoma (hCCA). The present study aims to investigate the role of HBcAb positivity on postoperative complications of hCCA.
Methods
A retrospective analysis was performed on the status of HBcAb positivity, liver fibrosis, perioperative surgical complications, and long‐term outcomes of hCCA patients with Hepatitis B surface antigen (HBsAg) negativity who underwent surgical treatment in Tongji Hospital from April 2012 to September 2019.
Results
HBcAb positivity with negative HBsAg occurs in 137 hCCA patients (63.1%). A total of 99 hCCA patients with negative HBsAg underwent extended hemihepatectomy, of whom 69 (69.7%) and 30 (30.3%) were HBcAb‐positive and HBcAb‐negative, respectively. Significant fibrosis was detected in 63.8% of the patients with HBcAb‐positive, which was markedly higher than those with HBcAb‐negative (36.7%) (p = 0.016). The postoperative complications and 90‐day mortality rates were 37.4% (37/99) and 8.1% (8/99), respectively. The incidence of postoperative complications in HBcAb‐positive patients (44.9%) was significantly higher than that in HBcAb‐negative patients (20.0%) (p = 0.018). All the patients who died within 30‐day after surgery were HBcAb‐positive. Multivariate analysis showed that the independent risk factors for complications were HBcAb positivity, preoperative cholangitis, portal occlusion >15 min, and significant fibrosis. There were no significant differences in recurrence‐free survival (RFS) and overall survival (OS) between HBcAb‐positive and HBcAb‐negative patients (p = 0.642 and p = 0.400, respectively).
Conclusions
HBcAb positivity is a common phenomenon in hCCA patients from China, a country with highly prevalent HBcAb positivity. The status of HBcAb‐positive markedly increases the incidence of postoperative complications after extended hemihepatectomy for hCCA patients.
The present study aims to evaluate the prevalence of HBcAb positivity in hCCA patients and explore the effect of HBcAb positivity on postoperative complications of hCCA patients after curative resection. Among all the 217 patients, 160 (73.7%) patients were HBcAb positive. Data of 99 HBsAg negative patients who underwent curative resection were analyzed, and the HBcAb positivity markedly increased the risk of postoperative complications and mortality after curative resection for hCCA. Surgeons should pay more attention to HBcAb status in hCCA patients with negative HBsAg, which could help them to select optimal surgical modalities.
In layered Li‐rich materials, over stoichiometric Li forms an ordered occupation of LiTM6 in transition metal (TM) layer, showing a honeycomb superstructure along 001 direction. At the atomic scale, ...the instability of the superstructure at high voltage is the root cause of problems such as capacity/voltage decay of Li‐rich materials. Here a Li‐rich material with a high Li/Ni disorder is reported, these interlayer Ni atoms locate above the honeycomb superstructure and share adjacent O coordination with honeycomb TM. These Ni─O bonds act as cable‐stayed bridge to the honeycomb plane, and improve the high‐voltage stability. The cable‐stayed honeycomb superstructure is confirmed by in situ X‐ray diffraction to have a unique cell evolution mechanism that it can alleviate interlaminar lattice strain by promoting in‐plane expansion along a‐axis and inhibiting c‐axis stretching. Electrochemical tests also demonstrate significantly improved long cycle performance after 500 cycles (86% for Li‐rich/Li half cell and 82% for Li‐rich/Si‐C full cell) and reduced irreversible oxygen release. This work proves the feasibility of achieving outstanding stability of lithium‐rich materials through superstructure regulation and provides new insights for the development of the next‐generation high‐energy‐density cathodes.
A cable‐stayed honeycomb superstructure is constructed by inducing high Li/Ni disorder in Li‐rich cathode materials. The short‐range order of the honeycomb superstructure is confirmed by the neutron pair distribution function. Benefiting from the high voltage stability and a superior crystal cell evolution mechanism of the cable‐stayed superstructure, excellent cycle performance of the Li‐rich/Si‐C full cell is achieved.
Schizandrol A (SA) is an bioactive component isolated from the Schisandra chinensis (Turcz.) Baill., which has been used as a remedy to prevent oxidative injury. However, whether the cardioprotective ...effect of SA is associated with regulating endogenous metabolites remains unclear, thus we performed comprehensive metabolomics profiling in acute myocardial ischemia (AMI) mice following SA treatment. AMI was induced in ICR mice by coronary artery ligation, then SA (6 mg·kg
·d
, ip) was administered. SA treatment significantly decreased the infarct size, preserved the cardiac function, and improved the biochemical indicators and cardiac pathological alterations. Moreover, SA (10, 100 M) significantly decreased the apoptotic index in OGD-treated H8c2 cardiomycytes in vitro. By using HPLC-Q-TOF/MS, we conducted metabonomics analysis to screen the significantly changed endogenous metabolites and construct the network in both serum and urine. The results revealed that SA regulated the pathways of glycine, serine and threonine metabolism, lysine biosynthesis, pyrimidine metabolism, arginine and proline metabolism, cysteine and methionine metabolism, valine, leucine and isoleucine biosynthesis under the pathological conditions of AMI. Furthermore, we selected the regulatory enzymes related to heart disease, including ecto-5'-nucleotidase (NT5E), guanidinoacetate N-methyltransferase (GAMT), platelet-derived endothelial cell growth factor (PD-ECGF) and methionine synthase (MTR), for validation. In addition, SA was found to facilitate PI3K/Akt activation and inhibit the expression of NOX2 in AMI mice and OGD-treated H9c2 cells. In conclusion, we have elucidated SA-regulated endogenous metabolic pathways and constructed a regulatory metabolic network map. Furthermore, we have validated the new potential therapeutic targets and underlying molecular mechanisms of SA against AMI, which might provide a reference for its future application in cardiovascular diseases.
A catalytic asymmetric allylic alkylation reaction of 3‐aryloxindoles was accomplished via a dual catalysis merging palladium catalysis and asymmetric H‐bonding catalysis for the first time. Using ...this approach, allylated oxindoles bearing chiral all‐carbon quaternary centers were produced in high yields with good enantioselectivities (up to 92 % yield and 96:4 er).
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