The recent developments of the synthesis of bio-based long-chain aliphatic polyesters by the acyclic diene metathesis (ADMET) polymerization of α,ω-dienes, derived from plant oils and bio-based ...chemicals, like bis(10-undecenoate) with isosorbide, using ruthenium-carbene catalysts are reviewed. The development of subsequent (one-pot) tandem hydrogenation produced saturated polyesters under mild conditions. The polymerizations under bulk (without solvent, 80–90 °C) or in ionic liquids (50 °C) under vacuum conditions enabled the synthesis of high molar mass polymers (Mn > 30,000 g/mol). The polymerization performed by the molybdenum-alkylidene catalyst afforded the highest-molecular-weight polyesters (44,000–49,400 g/mol, in toluene at 25 °C) exhibiting promising tensile properties (strength and elongation at break) compared to polyethylene and polypropylene. Depolymerizations of these polyesters, including closed-loop chemical recycling, were also demonstrated. Catalyst developments (more active, under mild conditions) play a key role in the efficient synthesis of these materials.
Two novel metal phthalocyanines (Zn Tetra(butylformate-phenoxy)phthalocyanine (ZnTBPP) and Zn Tetra(tert-butyl-phenoxy)phthalocyanine (ZnTTPP)) were synthesized. Besides, TiO
2
nanorods (PN) are ...prepared through the hydrothermal method. The synthesized metal phthalocyanines are used to sensitize TiO
2
nanoparticles (P25) and PN. Then, four types of metal phthalocyanine-sensitized TiO
2
composite photocatalytic materials (ZnTBPP/P25, ZnTTPP/P25, ZnTBPP/PN and ZnTTPP/PN) are obtained and characterized by methods of X-ray diffraction, scanning electron microscopy, nitrogen adsorption–desorption, Fourier-transform infrared spectroscopy, UV–Vis diffuse reflectance spectroscopy, fluorescence spectra and density-functional theory. At last, the photocatalytic degradation of rhodamine B (RhB) is taken as an example to study the photocatalytic activity of composite photocatalytic materials. The results show that the photocatalytic activity of the composite photocatalytic material is stronger than that of TiO
2
. This is because in the photocatalytic process, the loading of metal phthalocyanine can expand the material’s photoresponse range and enhance its light absorption performance. At the same time, the metal phthalocyanine can optimize the energy-level structure of the material and reduce the electron–hole recombination. Besides, we found that the photocatalytic activity of nanorods is stronger than that of the nanoparticles because the nanorod structure with a large specific surface area can not only increase metal phthalocyanine load, but also expose more active sites.
Viruses need to utilize the resources from host cells to reproduce themselves. RNA translation rate, which is largely determined by codon usage, is the rate-limiting step across the life cycle of ...viruses. Adapting to the codon usage of hosts would help virus better proliferate. We retrieved the time-course mutation profile of millions of world-wide SARS-CoV-2 sequences. For synonymous mutations, we defined whether a mutation elevate or reduce the relative synonymous codon usage (RSCU). We found that if a synonymous mutation in SARS-CoV-2 increases the RSCU (calculated from human lungs), denoted as delta RSCU > 0, then this mutation is positively selected because the allele frequency (AF) of this mutation increases with time, and vice versa. The results suggest that in SARS-CoV-2, the synonymous mutations that increase codon optimality are beneficial to the virus and are favored by natural selection. For the first time, we used the dynamics of allele frequency to demonstrate that SARS-CoV-2 is continuously optimizing its codon usage to adapt to human lungs. Nevertheless, adaptation to other human tissues cannot be excluded. These results warn us that under this global pandemic, synonymous mutations in SARS-CoV-2 should not be automatically ignored since they indeed change the fitness of the virus.
Adult mammalian heart loses regeneration ability following ischemic injury due to the loss of cardiomyocyte mitosis. However, the molecular mechanisms underlying the post-mitotic nature of ...cardiomyocytes remain largely unknown.
The purpose of this study was to define the essential role of long noncoding ribonucleic acids (lncRNAs) in heart regeneration during postnatal and adult injury.
Myh6-driving cardiomyocyte-specific lncRNA-CAREL transgenic mice and adenovirus-mediated in vivo silencing of endogenous CAREL were used in this study. The effect of CAREL on cardiomyocyte replication and heart regeneration after apical resection or myocardial infarction was assessed by detecting mitosis and cytokinesis.
An lncRNA CAREL was found significantly up-regulated in cardiomyocytes from neonatal mice (P7) in parallel with loss of regenerative capacity. Cardiac-specific overexpression of CAREL in mice reduced cardiomyocyte division and proliferation and blunted neonatal heart regeneration after injury. Conversely, silencing of CAREL in vivo markedly promoted cardiac regeneration and improved heart functions after myocardial infarction in neonatal and adult mice. CAREL acted as a competing endogenous ribonucleic acid for miR-296 to derepress the expression of Trp53inp1 and Itm2a, the target genes of miR-296. Consistently, overexpression of miR-296 significantly increased cardiomyocyte replication and cardiac regeneration after injury. Decline of cardiac regenerative ability in CAREL transgenic mice was also rescued by miR-296. A short fragment containing the conserved sequence of CAREL reduced the proliferation of human induced pluripotent stem cell-derived cardiomyocytes as the full-length CAREL.
LncRNA CAREL regulates cardiomyocyte proliferation and heart regeneration in postnatal and adult heart after injury by acting as a competing endogenous ribonucleic acid on miR-296 that targets Trp53inp1 and Itm2a.
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Bortezomib (BTZ) provides one of the best treatments for multiple myeloma (MM). The efficacy of BTZ is, nevertheless, restricted by its fast clearance, low selectivity, and dose ...limiting toxicities. Here, we report on targeted BTZ therapy of MM in vivo by hyaluronic acid-shelled and core-disulfide-crosslinked biodegradable micelles (HA-CCMs) encapsulating lipophilized BTZ, bortezomib-pinanediol (BP). HA-CCMs loaded with 7.3 BTZ equiv. wt% exhibited a small size of 78 nm, good stability in 10% FBS, and glutathione-triggered drug release. MTT assays in CD44 positive LP-1 multiple myeloma cells revealed that BP encapsulated in HA-CCMs caused enhanced antiproliferative effect compared with free BP. Flow cytometry, confocal microscopy and MTT assays indicated BP-loaded HA-CCMs (HA-CCMs-BP) could actively target to LP-1 cells and induce high antitumor effect. Proteasome activity assays in vitro showed HA-CCMs-BP had a similar proteasome activity inhibition as compared to free BTZ at 18 h. The fluorescence imaging using Cy5-labeled HA-CCMs showed that HA-CCMs had a long elimination half-life and enhanced tumor accumulation via HA-mediated uptake mechanism. The therapeutic studies in LP-1 MM-bearing mice revealed better treatment efficacy of HA-CCMs-BP compared with free BTZ, in which HA-CCMs-BP at 3 mg BTZ equiv./kg brought about significant tumor growth inhibition and survival benefits. Loading of lipophilized BTZ into HA-shelled multifunctional micelles has emerged as an exciting approach for bortezomib therapy of MM.
Multiple myeloma (MM) is the second most common hematological malignancy. Bortezomib (BTZ), a potent proteasome inhibitor, provides one of the best treatments for MM. The clinical efficacy of BTZ is, however, limited by its quick clearance, poor selectivity, and significant side effects including myelosuppression and peripheral neuropathy. Here, we report on targeted BTZ therapy of MM in vivo by hyaluronic acid-shelled and core-disulfide-crosslinked biodegradable micelles (HA-CCMs) encapsulating lipophilized BTZ, bortezomib-pinanediol (BP). Our results showed that BP-loaded HA-CCMs exhibit markedly enhanced toleration, broadened therapeutic window, and significantly more effective growth suppression of CD44-overexpressed multiple myeloma in nude mice than free bortezomib. Lipophilized BTZ-loaded HA-CCMs has opened a new avenue for targeted bortezomib therapy of multiple myeloma.
Liquid crystalline elastomers (LCEs) are an emerging class of smart materials for soft actuation machines. LCE composites (LCECs), via the incorporation of fillers into LCE matrices, bring superior ...functionalities to overcome the modest robustness and mechanical actuation performance. Considering the distinctive structures, good physico-chemical and mechanical properties of some animal fibers, we propose a cost-effective design and fabrication of LCECs by dispersing cat hair fibers into a polysiloxane LCE matrix, forming a cat hair fiber reinforced polysiloxane main-chain LCEC. The cat hair fibers demonstrate good integration and compatibility properties with the matrix, and construct a reinforcement network, which can enhance the mechanical actuation properties while adapting to the large reversible deformable capability of LCE matrix due to its high flexibility. By doping the LCE matrix with a small amount of graphene, the LCECs demonstrate strong photothermal actuation performances. The modulus, tensile strength, and output driving force activated by light stimulus are remarkably enhanced. LCECs also demonstrate greatly increased resisting fatigue failure reliability under high loadings and repetitive cycles of photo actuation. The liquid crystal phase structure, mesomorphic properties, phase transition temperature and deformation ratio of LCE matrix do not change or weaken. Our LCEC design and fabrication provide a promising way for LCE application potential, and can be extended to other animal fiber incorporated LCECs, bringing more rich actuation capabilities needed by soft actuators and beyond.
This paper presents an optimized preparation process for external ointment using the Definitive Screening Design (DSD) method. The ointment is a Traditional Chinese Medicine (TCM) formula developed ...by Professor WYH, a renowned TCM practitioner in Jiangsu Province, China, known for its proven clinical efficacy. In this study, a stepwise regression model was employed to analyze the relationship between key process factors (such as mixing speed and time) and rheological parameters. Machine learning techniques, including Monte Carlo simulation, decision tree analysis, and Gaussian process, were used for parameter optimization. Through rigorous experimentation and verification, we have successfully identified the optimal preparation process for WYH ointment. The optimized parameters included drug ratio of 24.5%, mixing time of 8 min, mixing speed of 1175 rpm, petroleum dosage of 79 g, liquid paraffin dosage of 6.7 g. The final ointment formulation was prepared using method B. This research not only contributes to the optimization of the WYH ointment preparation process but also provides valuable insights and practical guidance for designing the preparation processes of other TCM ointments. This advanced DSD method enhances the screening approach for identifying the best preparation process, thereby improving the scientific rigor and quality of TCM ointment preparation processes.
Neonatal mammalian heart maintains a transient regeneration capacity after birth, whereas this regeneration ability gradually loses in the postnatal heart. Thus, the reactivation of cardiomyocyte ...proliferation is emerging as a key strategy for inducing heart regeneration in adults. We have reported that a highly conserved long noncoding RNA (lncRNA) LncDACH1 was overexpressed in the failing hearts. Here, we found that LncDACH1 was gradually upregulated in the postnatal hearts. Cardiac-specific overexpression of LncDACH1 (TG) in mice suppressed neonatal heart regeneration and worsened cardiac function after apical resection. Conversely, in vivo cardiac conditional knockout of LncDACH1 (CKO) and adenovirus-mediated silencing of endogenous LncDACH1 reactivated cardiomyocyte-proliferative potential and promoted heart regeneration after myocardial infarction (MI) in juvenile and adult mice. Mechanistically, LncDACH1 was found to directly bind to protein phosphatase 1 catalytic subunit alpha (PP1A), and in turn, limit its dephosphorylation activity. Consistently, PP1A siRNA or pharmacological blockers of PP1A abrogated cardiomyocyte mitosis induced by LncDACH1 silencing. Furthermore, LncDACH1 enhanced yes-associated protein 1 (YAP1) phosphorylation and reduced its nuclear translocation by binding PP1A. Verteporfin, a YAP1 inhibitor decreased LncDACH1 silencing-induced cardiomyocyte proliferation. In addition, targeting a conserved fragment of LncDACH1 caused cell cycle re-entry of human iPSC-derived cardiomyocytes. Collectively, LncDACH1 governs heart regeneration in postnatal and ischemic hearts via regulating PP1A/YAP1 signal, which confers a novel therapeutic strategy for ischemic heart diseases.
The in vitro antioxidant and in vivo anti-aging activities in D-galactose-induced aging mice of exopolysaccharides (EPS) and its fractions (EPS-1, EPS-2 and EPS-3) by Agrocybe cylindraceas were ...investigated presently. The scavenging effects of EPS-2 on hydroxyl (HO) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals were 97.1±4.25% and 90.23±3.25%, while the reducing power reached 1.18±0.08 at 120mg/L, which were higher than EPS, EPS-1 and EPS-3 at 1000mg/L. The EPS showed potential anti-aging activities via reducing the contents of malonaldehyde (MDA) and total cholesterol (TC), as well as increasing the activities of superoxide dismutase (SOD) activities, glutathione peroxidase (GSH-Px) activities, and total antioxidant capacity (T-AOC). Additionally, the monosaccharide analysis showed EPS contained rhamnose and glucose with the molar ratio of 2.8:1. These results demonstrated that EPS could be used as functional foods and natural drugs on preventing and mitigating the aging process.
As one of the core services of cloud computing, cloud storage could satisfy various storage and management requirements caused by the growth of data. Considering the complexity and uncontrollability ...of the cloud storage environment, many cloud auditing schemes were presented to assure the integrity of data in the cloud. However, most existing schemes have security risks, such as identity privacy and data privacy disclosure, authority abuse of group managers and collusion attacks during user revocation. To solve these problems, we propose a stateless cloud auditing scheme for non-manager dynamic group data with privacy preservation. The proposed scheme not only realizes user identity privacy preservation but also preserves data privacy security with the random masking technique. Unlike other solutions, our scheme allows <inline-formula> <tex-math notation="LaTeX">t </tex-math></inline-formula> group users to trace the user's identity cooperatively without group managers, which eliminates authority abuse of group managers and provides non-frameability. Meanwhile, utilizing the concept of Shamir Secret Sharing, our scheme divides the re-signing process into several parts to resist collusion attacks during user revocation. By the designed binary tree, group users could trace dynamic data changes and recover the latest data when existing data are damaged. Besides, both users and the third-party auditor (TPA) are stateless in our scheme; that is, they no need to maintain data index information during cloud auditing. Our scheme also achieves mutual supervision between users and cloud service providers (CSPs), which ensures data are non-repudiation on both parties. Furthermore, we construct an efficient incentive for data visitors by using the blockchain technology and design a secure data sharing model to guarantee that data owners control their data ownership. Certificateless cryptography assures that the proposed scheme avoids certificate management and key escrow problems. Finally, security analysis and performance evaluation show that our scheme is secure and efficient.
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