Retinol dehydrogenase 11 (RDH11) is an 11‐cis‐retinol dehydrogenase that has a well‐characterized, albeit auxiliary role in the retinoid cycle. Diseases caused by mutations in the RDH11 gene are very ...rare, and only one affected family with eye and intelligence involvement has been reported. In the present study, we describe the clinical and genetic findings in a Chinese patient with retinitis pigmentosa (RP), juvenile cataracts, intellectual disability, and myopathy. Trio‐based whole‐exome sequencing and whole genomic copy number variation detection were performed in this family, and compound heterozygous mutations were identified in RDH11 of the patient: c.938T>C (p.Leu313Pro) derived from the father and c.75‐3C>A derived from the mother. Variant c.75‐3C>A was confirmed to be a splice‐site mutation by cDNA sequencing. It caused exon 2 skipping, resulting in a frameshift mutation and premature translation termination (p.Lys26Serfs*38). Moreover, we found mislocalization of RDH11 protein in muscle cells of the patient by using immunofluorescence staining. This is the first case reported in the Chinese population harboring mutations in RDH11 and revealing a new phenotype of syndromic RP with myopathy.
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.
Metabolic diseases are serious threats to public health and related to gut microbiota. Probiotics, prebiotics, synbiotics, and postbiotics (PPSP) are powerful regulators of gut microbiota, thus ...possessing prospects for preventing metabolic diseases. Therefore, the effects and mechanisms of PPSP on metabolic diseases targeting gut microbiota are worth discussing and clarifying. Generally, PPSP benefit metabolic diseases management, especially obesity and type 2 diabetes mellitus. The underlying gut microbial-related mechanisms are mainly the modulation of gut microbiota composition, regulation of gut microbial metabolites, and improvement of intestinal barrier function. Moreover, clinical trials showed the benefits of PPSP on patients with metabolic diseases, while the clinical strategies for gestational diabetes mellitus, optimal formula of synbiotics and health benefits of postbiotics need further study. This review fully summarizes the relationship between probiotics, prebiotics, synbiotics, postbiotics, and metabolic diseases, presents promising results and the one in dispute, and especially attention is paid to illustrates potential mechanisms and clinical effects, which could contribute to the next research and development of PPSP.
The benzylic functionalization of alkylpyridines is an important pathway for pyridine derivatives synthesis. The reaction partners, however, were mostly limited to highly reactive polar ...electrophiles. Herein, we report a potassium amide‐catalyzed selective benzylic C−H bond addition of alkylpyridines to styrenes. Potassium bis(trimethylsilyl)amide (KHMDS), a readily available Brønsted base, showed excellent catalytic activity and chemoselectivity. A series of alkylpyridine derivatives, including benzylic quaternary carbon substituted pyridines, were obtained in good to high yield. Preliminary mechanistic studies revealed that the deprotonation equilibrium is probably responsible for the excellent selectivity.
The simpler the better: A potassium amide‐catalyzed selective benzylic C−H bond addition of alkylpyridines to styrenes was achieved for the first time. Potassium bis(trimethylsilyl)amide (KHMDS), a simple and readily available Brønsted base catalyst, displayed excellent activity and selectivity for the alkylation of alkylpyridines.
Autophagy is a degradative pathway that delivers cellular components to the lysosome for degradation. The role of autophagy in cell differentiation is poorly understood. Here we show that CaMKII can ...directly phosphorylate Beclin 1 at Ser90 to promote K63-linked ubiquitination of Beclin 1 and activation of autophagy. Meanwhile, CaMKII can also promote K63-linked ubiquitination of inhibitor of differentiation 1/2 (Id-1/2) by catalyzing phosphorylation of Id proteins and recruiting TRAF-6. Ubiquitinated Id-1/Id-2 can then bind to p62 and be transported to autolysosomes for degradation. Id degradation promotes the differentiation of neuroblastoma cells and reduces the proportion of stem-like cells. Our study proposes a mechanism by which autophagic degradation of Id proteins can regulate cell differentiation. This suggests that targeting of CaMKII and the regulation of autophagic degradation of Id may be an effective therapeutic strategy to induce cell differentiation in neuroblastoma.
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.
Direct functionalization of the benzylic C−H bond of diarylmethanes is an important strategy for the synthesis of diarylmethine‐containing compounds. However, the methods developed to date for this ...purpose require a stoichiometric amount (usually more) of either a strong base or an oxidant. Reported here is the first catalytic benzylic C−H bond addition of diarylmethanes to styrenes and conjugated dienes. A potassium zincate complex, generated from potassium benzyl and zinc amide, acts as a catalyst and displays good activity and chemoselectivity. Considering the atom economy of the reaction and the ready availability of the catalyst, this reaction constitutes a practical, efficient method for diarylalkane synthesis.
‘Zinc' into it: The catalytic addition of the benzylic carbon center of diarylmethanes to styrenes and conjugated dienes was achieved for the first time by using a potassium zincate catalyst. The reaction demonstrates wide scope and high yields.
Abstract
High expression or aberrant activation of epidermal growth factor receptor (EGFR) is related to tumor progression and therapy resistance across cancer types, including non-small cell lung ...cancer (NSCLC). EGFR tyrosine kinase inhibitors (TKIs) are first-line therapy for NSCLC. However, patients eventually deteriorate after inevitable acquisition of EGFR TKI-resistant mutations, highlighting the need for therapeutics with alternative mechanisms of action. Here, we report that the elevated tribbles pseudokinase 3 (TRIB3) is positively associated with EGFR stability and NSCLC progression. TRIB3 interacts with EGFR and recruits PKCα to induce a Thr654 phosphorylation and WWP1-induced Lys689 ubiquitination in the EGFR juxtamembrane region, which enhances EGFR recycling, stability, downstream activity, and NSCLC stemness. Disturbing the TRIB3-EGFR interaction with a stapled peptide attenuates NSCLC progression by accelerating EGFR degradation and sensitizes NSCLC cells to chemotherapeutic agents. These findings indicate that targeting EGFR degradation is a previously unappreciated therapeutic option in EGFR-related NSCLC.
Fifteen new diterpenoids, namely xishaklyanes A-O (
-
), along with three known related ones (
-
), were isolated from the soft coral
collected from Xisha Islands, South China Sea. The ...stereochemistry of the new compounds was elucidated by a combination of detailed spectroscopic analyses, chemical derivatization, quantum chemical calculations, and comparison with the reported data. The absolute configuration of compound
was established by the modified Mosher's method for the first time. In bioassay, some of these compounds exhibited considerable antibacterial activities on fish pathogenic bacteria, and compound
showed the most effective activity with MIC of 0.225 μg/mL against
.
Functional passivators are conventionally utilized in modifying the crystallization properties of perovskites to minimize the non‐radiative recombination losses in perovskite light‐emitting diodes ...(PeLEDs). However, the weak anchor ability of some commonly adopted molecules has limited passivation ability to perovskites and even may desorb from the passivated defects in a short period of time, which bring about plenty of challenges for further development of high‐performance PeLEDs. Here, a multidentate molecule, formamidine sulfinic acid (FSA), is introduced as a novel passivator to perovskites. FSA has multifunctional groups (S≐O, C≐N and NH2) where the S≐O and C≐N groups enable coordination with the lead ions and the NH2 interacts with the bromide ions, thus providing the most effective chemical passivation for defects and in turn the formation of highly stable perovskite emitters. Moreover, the interaction between the FSA and octahedral PbBr64− can inhibit the formation of unfavorable low‐n domains to further minimize the inefficient energy transfer inside the perovskite emitters. Therefore, the FSA passivated green‐emitting PeLED exhibits a high external quantum efficiency (EQE) of 26.5% with fourfold enhancement in operating lifetime as compared to the control device, consolidating that the multidentate molecule is a promising strategy to effectively and sustainably passivate the perovskites.
A multidentate molecule (Formamidine Sulfinic Acid, FSA) to passivate the perovskite for efficient light‐emitting devices. Owing to its multiple roles of guaranteeing sufficient passivation durability and minimizing the energy loss, green PeLEDs based on the FSA‐perovskite films shows a superior EQE of 26.5%.
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