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(1) Background: Dyes play an important role in food, medicine, textile, and other industries, which make human life more colorful. With the increasing demand for food safety, the development of natural dyes becomes more and more attractive. (2) Methods: The literature was searched using the electronic databases PubMed, Web of Science, and SciFinder and this scoping review was carried out following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). (3) Results: 248 articles were included in this review. This review summarizes the research progress on natural dyes in the last ten years. According to structural features, natural dyes mainly include carotenoids, polyphenols, porphyrins, and alkaloids, and some of the newest dyes are summarized. Some pharmacological activities of carotenoids, anthocyanin, curcumin, and betalains in the last 10 years are summarized, and the biological effects of dyes regarding illumination conditions. The disadvantages of natural dyes, including sources, cost, stability, and poor bioavailability, limit their application. Here, some feasible strategies (potential resources, biotechnology, new extraction and separation strategies, strategies for improving stability) are described, which will contribute to the development and utilization of natural dyes. (4) Conclusion: Natural dyes show health benefits and potential in food additives. However, it is necessary for natural dyes to pass toxicity tests and quality tests and receive many regulatory approvals before their final entry into the market as food colorants or as drugs.

(1) Background: Orthosiphon stamineus Benth. is a traditional medicine used in the treatment of diabetes and chronic renal failure in southern China, Malaysia, and Thailand. Diabetes is a chronic metabolic disease and the number of diabetic patients in the world is increasing. This review aimed to systematically review the effects of O. stamineus in the treatment of diabetes and its complications and the pharmacodynamic material basis. (2) Methods: This systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), using the databases ScienceDirect, PubMed, and Web of Science. (3) Results: Thirty-one articles related to O. stamineus and diabetes were included. The mechanisms of O. stamineus in the treatment of diabetes and its complications mainly included inhibiting α-amylase and α-glucosidase activities, antioxidant and anti-inflammatory activities, regulating lipid metabolism, promoting insulin secretion, ameliorating insulin resistance, increasing glucose uptake, promoting glycolysis, inhibiting gluconeogenesis, promoting glucagon-likepeptide-1 (GLP-1) secretion and antiglycation activity. Phenolic acids, flavonoids and triterpenoids might be the main components for hypoglycemia effects in O. stamineus. (4) Conclusion: O. stamineus could be an antidiabetic agent to treat diabetes and its complications. However, it needs further study on a pharmacodynamic substance basis and the mechanisms of effective constituents.

In order to investigate the physicochemical properties and bioactivities of AgNPs prepared using green and chemical approaches and further explore the related antibacterial mechanism, one kind of chemical AgNPs (C-AgNPs) and three kinds of green AgNPs (G-AgNPs) mediated with aqueous extracts of Morus alba L. were prepared and characterized. All G-AgNPs displayed higher antioxidant activities in DPPH radical scavenging, reducing power and total antioxidant assays than C-AgNPs and extracts. Meanwhile, all G-AgNPs exerted significantly (P < 0.05) enhanced antimicrobial activities against various pathogens compared with C-AgNPs and extracts. Among prepared AgNPs, ML-AgNPs mediated with aqueous extract of Morus alba L. leaves exhibited the most powerful antibacterial effect with the largest inhibition zones (13.11 ± 0.76 mm for S. aureus , 13.27 ± 0.22 mm for E. coli ) and the lowest minimum inhibition concentrations against S. aureus (6.125 μg/ml) and E. coli (3.125 μg/ml). ML-AgNPs could inhibit the growths of S. aureus and E. coli in time- and dose-dependent modes, and even could disrupt the bacterial structure integrality resulting in the leakage of intracellular contents. G-AgNPs, especially ML-AgNPs, with remarkable bioactivities could replace C-AgNPs as related agents applied in agriculture and medicine.

Reversible phosphorylation has emerged as an important mechanism for regulating 26S proteasome function in health and disease. Over 100 phospho-tyrosine sites of the human proteasome have been detected, and yet their function and regulation remain poorly understood. Here we show that the 19S subunit Rpt2 is phosphorylated at Tyr439, a strictly conserved residue within the C-terminal HbYX motif of Rpt2 that is essential for 26S proteasome assembly. Unexpectedly, we found that Y439 phosphorylation depends on Rpt2 membrane localization mediated by its N-myristoylation. Multiple receptors tyrosine kinases can trigger Rpt2–Y439 phosphorylation by activating Src, a N-myristoylated tyrosine kinase. Src directly phosphorylates Rpt2–Y439 in vitro and negatively regulates 26S proteasome activity at cellular membranes, which can be reversed by the membrane-associated isoform of protein tyrosine phosphatase nonreceptor type 2 (PTPN2). In H1975 lung cancer cells with activated Src, blocking Rpt2–Y439 phosphorylation by the Y439F mutation conferred partial resistance to the Src inhibitor saracatinib both in vitro and in a mouse xenograft tumor model, and caused significant changes of cellular responses to saracatinib at the proteome level. Our study has defined a novel mechanism involved in the spatial regulation of proteasome function and provided new insights into tyrosine kinase inhibitor-based anticancer therapies.

The Hippo-YAP pathway responds to diverse environmental cues to manage tissue homeostasis, organ regeneration, tumorigenesis, and immunity. However, how phosphatase(s) directly target Yes-associated protein (YAP) and determine its physiological activity are still inconclusive. Here, we utilized an unbiased phosphatome screening and identified protein phosphatase magnesium-dependent 1A (PPM1A/PP2Cα) as the bona fide and physiological YAP phosphatase. We found that PPM1A was associated with YAP/TAZ in both the cytoplasm and the nucleus to directly eliminate phospho-S127 on YAP, which conferring YAP the nuclear distribution and transcription potency. Accordingly, genetic ablation or depletion of PPM1A in cells, organoids, and mice elicited an enhanced YAP/TAZ cytoplasmic retention and resulted in the diminished cell proliferation, severe gut regeneration defects in colitis, and impeded liver regeneration upon injury. These regeneration defects in murine model were largely rescued via a genetic large tumor suppressor kinase 1 (LATS1) deficiency or the pharmacological inhibition of Hippo-YAP signaling. Therefore, we identify a physiological phosphatase of YAP/TAZ, describe its critical effects in YAP/TAZ cellular distribution, and demonstrate its physiological roles in mammalian organ regeneration.

Abstract Reversible phosphorylation has emerged as an important mechanism for regulating 26S proteasome function in health and disease. Over 100 phospho-tyrosine (pTyr) sites of the human proteasome have been detected, and yet their function and regulation remain poorly understood. Here we show that the 19S subunit Rpt2 is phosphorylated at Tyr439, a strictly conserved residue within the C-terminal HbYX motif of Rpt2 that is essential for 26S proteasome assembly. Unexpectedly, we found that Y439 phosphorylation depends on Rpt2 membrane localization mediated by its N-myristoylation. Multiple receptor tyrosine kinases (RTKs) can trigger Rpt2-Y439 phosphorylation by activating Src, a N-myristoylated tyrosine kinase. Src directly phosphorylates Rpt2-Y439 in vitro and negatively regulates 26S proteasome integrity and activity at cellular membranes, which can be reversed by the membrane-associated isoform of protein tyrosine phosphatase non-receptor type 2 (PTPN2). In H1975 lung cancer cells with activated Src, blocking Rpt2-Y439 phosphorylation by the Y439F mutation conferred partial resistance to the Src inhibitor saracatinib both in vitro and in a mouse xenograft tumor model, and caused significant changes of cellular responses to saracatinib at the proteome level. Our study has defined a novel mechanism involved in the spatial regulation of proteasome function and provided new insights into tyrosine kinase inhibitor-based anti-cancer therapies. Competing Interest Statement The authors have declared no competing interest. Footnotes * http://uaalink.com/download/Guo_FASP.zip