The integration of heterometallic units and nanostructures into metal–organic frameworks (MOFs) used for the oxygen evolution reaction (OER) can enhance the electrocatalytic performance and help ...elucidate underlying mechanisms. We have synthesized a series of stable MOFs (CTGU‐10a1–d1) based on trinuclear metal carboxylate clusters and a hexadentate carboxylate ligand with a (6,6)‐connected nia net. We also present a strategy to synthesize hierarchical bimetallic MOF nanostructures (CTGU‐10a2–d2). Among these, CTGU‐10c2 is the best material for the OER, with an overpotential of 240 mV at a current density of 10 mA cm−2 and a Tafel slope of 58 mV dec−1. This is superior to RuO2 and confirms CTGU‐10c2 as one of the few known high‐performing pure‐phase MOF‐OER electrocatalysts. Notably, bimetallic CTGU‐10b2 and c2 show an improved OER activity over monometallic CTGU‐10a2 and d2. Both DFT and experiments show that the remarkable OER performance of CTGU‐10c2 is due to the presence of unsaturated metal sites, a hierarchical nanobelt architecture, and the Ni–Co coupling effect.
Finding the right balance: The integration of heterometallic clusters and nanostructures into stable hierarchical nanosheet‐based bimetal–organic frameworks allows to increase the oxygen evolution reaction performance of electrocatalysts. The ideal ratio between Co and Ni leads to one of the best performances of pure‐phase MOF–OER electrocatalysts.
Traditional Chinese medicine (TCM) has attracted increasing interest throughout the world because of its potential complementary therapy and an abundant source for new drug discovery. TCM possesses ...the significant bioactivity of the use of multi-component drugs and can act multiple targets by multiple components. Metabolomics is a holistic investigation of numerous metabolite responses of complex biology systems to pathological stimuli and drug treatments based on the global metabolic profiles in complex biological matrixes. It provides variation of systematic metabolic networks for characterizing pathological states in animal models and clinical studies. In agreement with the holistic thinking of TCM, metabolomics has shown potential in bioactivity evaluation and action mechanism of TCM as well as pharmaceutical research and development. Recently, different metabolomic technologies have been applied to the modernization of TCM and treatments of different diseases such as cardiovascular disease, kidney disease, liver disease and metabolic disease. Based on the reported literature, this paper introduced the application of metabolomics in efficacy evaluation of TCM and its biochemical action mechanism.
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•Traditional Chinese medicine was widely used for disease prevention and treatment.•Metabolomics has been applied to bioactivity study of traditional Chinese medicine.•Metabolomics in bioactive evaluation of traditional Chinese medicine are discussed.•Metabolomics highlights therapeutic mechanism of traditional Chinese medicine.
Transport through the cell membrane can be divided into active, passive and vesicular types (exosomes). Exosomes are nano‐sized vesicles released by a variety of cells. Emerging evidence shows that ...exosomes play a critical role in cancers. Exosomes mediate communication between stroma and cancer cells through the transfer of nucleic acid and proteins. It is demonstrated that the contents and the quantity of exosomes will change after occurrence of cancers. Over the last decade, growing attention has been paid to the role of exosomes in the development of breast cancer, the most life‐threatening cancer in women. Breast cancer could induce salivary glands to secret specific exosomes, which could be used as biomarkers in the diagnosis of early breast cancer. Exosome‐delivered nucleic acid and proteins partly facilitate the tumorigenesis, metastasis and resistance of breast cancer. Exosomes could also transmit anti‐cancer drugs outside breast cancer cells, therefore leading to drug resistance. However, exosomes are effective tools for transportation of anti‐cancer drugs with lower immunogenicity and toxicity. This is a promising way to establish a drug delivery system.
Exosomes are nano‐sized vesicles released by a variety of cells. Exosomes function as versatile promoters in the tumorigenesis, metastasis and drug resistance of breast cancer. In this review, we summarize the current knowledge about the functions of exosomes in the diagnosis, tumorigenesis, metastasis, microenvironment, drug resistance and therapy of breast cancer.
To study the role of hsa_circ_0072995 in regulating the invasion and migration of breast cancer cells.
Hsa_circ_0072995 expression was confirmed by quantitative real-time PCR; evaluating the ...migration and invasion of breast cancer cells through transwell assay; predicating circRNA/microRNAs interaction using the miRanda and RNAhybrid software; identifying the relationship between hsa_circ_0072995 and miR-30c-2-3p by luciferase activity assay; detecting the location of hsa_circ_0072995 by Fluorescence
hybridization assay.
Hsa_circ_0072995 was significantly upregulated in MDA-MB-231 cells compared with MCF-7 cells. Hsa_circ_0072995 regulated the invasion and migration of breast cancer cells. Hsa_circ_0072995 existed in the nucleus and cytoplasm, and the proportion of the two was roughly equal. Hsa_circ_0072995 bound to miR-30c-2-3p. Overexpression of miR-30c-2-3p inhibited breast cancer cells migration and invasion. Low expression of miR-30c-2-3p was correlated with poor overall survival by The Cancer Genome Atlas database.
Hsa_circ_0072995 may be a novel biomarker for breast cancer, and may function in metastasis of breast cancer.
Objective
To review of our hospital's experiences in transvaginal natural orifice transluminal endoscopic surgery (vNOTES) and challenges we encountered in performance of the procedure, so as to ...provide help to medical institutions who are preparing to carry out vNOTES.
Methods
We retrospectively analyzed the data of all patients receiving vNOTES in our hospital from April 2018 to May 2021. Data we collected cover the general characteristics, perioperative outcomes, and complications of the patients.
Results
A total of 1147 patients underwent vNOTES in the past 3 years at our hospital. The total numbers of adnexal surgery, myomectomy, hysterectomy, pelvic floor reconstruction surgery, and malignant tumor surgery performed via vNOTES were 902, 98, 82, 51, and 14, respectively. Eighteen patients were converted to transabdominal laparoscopic surgery. A total of 38 patients had complications according to Clavien‐Dindo classification, and the total complication rate was 3.31%. Among these cases of complications, 27 were Grade I, 4 were Grade II, and 7 were Grade III. No complications of Grade IV or V were reported.
Conclusion
The application of vNOTES is safe and feasible for most gynecological surgeries. Moreover, hospitals with traditional laparoscopic equipment are advised to try this technique as there is no need to purchase additional expensive equipment. However, since vNOTES represents a novel approach, the long‐term complications and efficacy associated with this technique are pending to be verified through large‐scale prospective multicenter randomized controlled studies.
Several studies have examined the functions of nucleic acids in small extracellular vesicles (sEVs). However, much less is known about the protein cargos of sEVs and their functions in recipient ...cells. This study demonstrates the presence of lysine‐specific demethylase 1 (LSD1), which is the first identified histone demethylase, in the culture medium of gastric cancer cells. We show that sEVs derived from gastric cancer cells and the plasma of patients with gastric cancer harbor LSD1. The shuttling of LSD1‐containing sEVs from donor cells to recipient gastric cancer cells promotes cancer cell stemness by positively regulating the expression of Nanog, OCT4, SOX2, and CD44. Additionally, sEV‐delivered LSD1 suppresses oxaliplatin response of recipient cells in vitro and in vivo, whereas LSD1‐depleted sEVs do not. Taken together, we demonstrate that LSD1‐loaded sEVs can promote stemness and chemoresistance to oxaliplatin. These findings suggest that the LSD1 content of sEV could serve as a biomarker to predict oxaliplatin response in gastric cancer patients.
Synopsis
Lysine specific demethylase 1 is not only a nuclear protein but is also secreted. Gastric cancer cells release sEVs that contain LSD1, thereby promoting cancer cell stemness and oxaliplatin resistance.
LSD1 is a component of small extracellular vesicles (sEVs) from gastric cancer cells and gastric cancer patient plasma.
LSD1‐containing sEVs increase the expression of Nanog, OCT4, SOX2 and CD44, and promote oxaliplatin resistance.
sEVs‐delivered LSD1 may serve as a potential biomarker to predict oxaliplatin response in the clinic.
Lysine specific demethylase 1 is not only a nuclear protein but is also secreted. Gastric cancer cells release sEVs that contain LSD1, thereby promoting cancer cell stemness and oxaliplatin resistance.
Summary
This is a meta‐analysis of the pooled prevalence of sleep disturbances and its associated factors in Chinese university students. English (PubMed, PsycINFO, Embase) and Chinese (SinoMed, Wan ...Fang Database and Chinese National Knowledge Infrastructure) databases were systematically and independently searched from inception until 16 August 2016. The prevalence of sleep disturbances was pooled using random‐effects model. Altogether 76 studies involving 112 939 university students were included. The overall pooled prevalence of sleep disturbances was 25.7% (95% CI: 22.5–28.9%). When using the screening scales Pittsburgh Sleep Quality Index, Athens Insomnia Scale and Self‐Rating Sleeping State Scale, and the diagnostic criteria of the Chinese Classification of Mental Disorders (Second Edition), the pooled prevalence of sleep disturbances was 24.1% (95% CI: 21.0–27.5%) and 18.1% (95% CI: 16.4–20.0%), respectively. The percentages of students dissatisfied with sleep quality and those suffering from insomnia symptoms were 20.3% (95% CI: 13.0–30.3%) and 23.6% (95% CI: 18.9–29.0%), respectively. Subgroup analyses revealed that medical students were more vulnerable to sleep disturbances than other student groups. There was no significant difference between males and females, and across geographic locations. Sleep disturbances are common in Chinese university students. Appropriate strategies for prevention and treatment of sleep disturbances in this population need greater attention.
Objectives
Colorectal cancer is one of the most common malignancies both in men and women. Owing to metastasis and resistance, the prognosis of colorectal cancerCRC patients remains extremely poor ...with chemotherapy. A disintegrin and metalloproteinase 17 (ADAM17) induces the activation of Notch pathway and contributes to the chemoresistance. This study aimed to discover a novel ADAM17 inhibitor and investigate the chemosensitization effect.
Materials and methods
Pharmacophore model, western blot and enzymatic assay were used to discover ZLDI‐8. Cell proliferation was determined by MTT and colony formation assay. Cell migratory and invasive ability were determined by wound healing scratch and transwell assay. Immunofluorescence images and western blot analysed the expression of Notch or epithelial‐mesenchymal transition (EMT) pathway markers. Xenografts were employed to evaluate the chemosensitization effect of ZLDI‐8 in vivo.
Results
We found that ZLDI‐8 cell‐specifically inhibited the proliferation of CRC, and this effect was due to abrogation of ADAM17 and Notch pathway. Meanwhile, we reported for the first time that ZLDI‐8 synergistically improved the anti‐tumour and anti‐metastasis activity of 5‐fluorouracil or irinotecan by reversing Notch and EMT pathways. Interestingly, in vivo studies further demonstrated that ZLDI‐8 promoted the anti‐tumour effect of 5‐fluorouracil through Notch and EMT reversal.
Conclusions
A novel ADAM17 inhibitor ZLDI‐8 may be a potential chemosensitizer which sensitized CRC cells to 5‐fluorouracil or irinotecan by reversing Notch and EMT pathways.
The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global crisis. Replication of SARS-CoV-2 requires the viral ...RNA-dependent RNA polymerase (RdRp) enzyme, a target of the antiviral drug remdesivir. Here we report the cryo-electron microscopy structure of the SARS-CoV-2 RdRp, both in the apo form at 2.8-angstrom resolution and in complex with a 50-base template-primer RNA and remdesivir at 2.5-angstrom resolution. The complex structure reveals that the partial double-stranded RNA template is inserted into the central channel of the RdRp, where remdesivir is covalently incorporated into the primer strand at the first replicated base pair, and terminates chain elongation. Our structures provide insights into the mechanism of viral RNA replication and a rational template for drug design to combat the viral infection.
Melatonin can increase plant resistance to stress, and exogenous melatonin has been reported to promote stress resistance in plants. In this study, a melatonin biosynthesis-related
gene was cloned ...from tomato (
Mill. cv.
), which is highly expressed in fruits compared with other organs. The protein was found to locate in the cytoplasm. Melatonin content in
overexpression transgenic tomato plants was significantly higher than that in wild-type plants. Under 800 mM NaCl stress, the transcript level of
in tomato leaf was positively related to the melatonin contents. Furthermore, compared with that in wild-type plants, levels of superoxide and hydrogen peroxide were lower while the content of proline was higher in
transgenic tomatoes. Therefore,
was closely associated with melatonin biosynthesis confers the significant salt tolerance, providing a clue to cope with the growing global problem of salination in agricultural production.