Long-Chain Branched Bio-Based Poly(butylene dodecanedioate) Copolyester Using Pentaerythritol as Branching Agent: Synthesis, Thermo-Mechanical, and Rheological Properties.

The introduction of long-chain branched structures into biodegradable polyesters can effectively improve the melt strength and blow-molding properties of polyesters. In this study, pentaerythritol (PER) was used as a branching agent to synthesize branched poly(butylene dodecanedioate) (PBD), and the resulting polymers were characterized by Nuclear Magnetic Resonance Proton Spectra (1H NMR) and Fourier Transform Infrared spectroscopy (FT-IR). It was found that the introduction of a small amount of PER (0.25-0.5 mol%) can generate branching and even crosslinking structures. Both impact strength and tensile modulus can be greatly improved by the introduction of a branching agent. With the introduction of 1 mol% PER content in PBD, the notched impact strength of PBD has been increased by 85%, and the tensile modulus has been increased by 206%. Wide-angle X-ray diffraction and differential scanning calorimetry results showed that PER-branched PBDs exhibited improved crystallization ability compared with linear PBDs. Dynamic viscoelastics revealed that shear-thickening behaviors can be found for all branched PBD under low shear rates.

Costunolide covalently targets and inhibits CaMKII phosphorylation to reduce ischemia-associated brain damage.

BACKGROUND: Chronic cerebral hypoperfusion (CCH) is a leading cause of disability and mortality worldwide. Restoring cerebral blood flow (CBF) through vasodilatation is particularly important in the treatment of CCH. Costunolide (Cos) is a natural sesquiterpenoid compound with vasodilatory effect, but its mechanism is unclear. PURPOSE: This study aimed to investigate the vasodilatory mechanism of Cos and provide a new therapeutic regimen for treating CCH. METHODS: The therapeutic effect of Cos on CCH was assessed in a rat model of permanent common carotid artery occlusion. The direct target protein for improving CBF was identified by drug affinity responsive target stability combined with quantitative differential proteomics analysis. The molecular mechanism of Cos acting on its target protein was analyzed by multidisciplinary approaches. The signalling involved was assessed using site-directed pharmacological intervention. RESULTS: Cos has a significant therapeutic effect on ischemic brain injury by restoring CBF. Multifunctional calcium/calmodulin-dependent protein kinase II (CaMKII) was identified as a direct target of the natural small molecule Cos with a therapeutic effect on CCH. Mechanistic studies revealed that the α,ß-unsaturated-γ-lactone ring of Cos covalently binds to the Cys116 residue of CaMKII. It then inhibits the phosphorylation of CaMKII and reduces the calcium concentration in vascular smooth muscle cells, thus playing a role in vasodilation and increasing CBF. Notably, this covalent binding between Cos and CaMKII can exert a long-term vasodilator activity. CONCLUSION: We reported for the first time that Cos reduced ischemia-associated brain damage by covalently binding to the Cys116 residue of CaMKII, inhibiting CaMKII phosphorylation, and exerting long-term vasodilatory activity. This study not only found a new covalent inhibitor against the phosphorylation of CaMKII but also suggested that pharmacologically targeting CaMKII is a promising therapeutic strategy for CCH.

Synthesis of Biodegradable Polyester-Polyether with Enhanced Hydrophilicity, Thermal Stability, Toughness, and Degradation Rate.

Novel poly(butylene succinate-butylene furandicarboxylate/polyethylene glycol succinate) (PBSF-PEG) was synthesized using two-step transesterification and polycondensation in the melt. There are characterized by intrinsic viscosity, GPC, 1H NMR, DSC, TGA, tensile, water absorption tests, and water degradation at different pH. GPC analysis showed that PBSF-PEG had high molecular weight with average molecular weight (Mw) up to 13.68 × 104 g/mol. Tensile tests showed that these polymers possessed good mechanical properties with a tensile strength as high as 30 MPa and elongation at break reaching 1500%. It should be noted that the increase of PEG units improved the toughness of the polyester material. In addition, the introduction of PEG promoted the water degradation properties of PBSF, and the copolymer showed a significantly faster water degradation rate when the PEG unit content was 20%. This suggests that the amount of PEG introduced could be applied to regulate the water degradation rate of the copolymers. Hence, these new polymers have great potential for application as environmentally friendly and sustainable plastic packaging materials.

20(S)-Protopanaxatriol promotes the binding of P53 and DNA to regulate the antitumor network via multiomic analysis.

Although the tumor suppressor P53 is known to regulate a broad network of signaling pathways, it is still unclear how certain drugs influence these P53 signaling networks. Here, we used a comprehensive single-cell multiomics view of the effects of ginsenosides on cancer cells. Transcriptome and proteome profiling revealed that the antitumor activity of ginsenosides is closely associated with P53 protein. A miRNA-proteome interaction network revealed that P53 controlled the transcription of at least 38 proteins, and proteome-metabolome profiling analysis revealed that P53 regulated proteins involved in nucleotide metabolism, amino acid metabolism and "Warburg effect". The results of integrative multiomics analysis revealed P53 protein as a potential key target that influences the anti-tumor activity of ginsenosides. Furthermore, by applying affinity mass spectrometry (MS) screening and surface plasmon resonance fragment library screening, we confirmed that 20(S)-protopanaxatriol directly targeted adjacent regions of the P53 DNA-binding pocket and promoted the stability of P53-DNA interactions, which further induced a series of omics changes.

[Influence of soil salinization on soil animal community in an arid oasis of middle Heihe River basin].

An investigation was conducted on the status of soil salinization and the structure of soil animal community across six land use/cover types in an arid oasis of middle Heihe River basin, and the methods of redundancy analysis, regression analysis, and path analysis were adopted to analyze the responses of the soil animal community under different land use/cover types and different management modes to the various status of soil salinization. The six land use/cover types were 21-year old shrub land without irrigation and fertilization, 28-year old poplar and 33-year-old pine plantations with irrigation, 27- and 100-year-old farmlands with irrigation and fertilization, and natural grassland, from which all the other five land use/cover types were converted. The results demonstrated that land cover change in the absence of management practices did not lead to a significant change in the abundance and group richness of the soil animal community, while land cover change in the presence of management practices resulted in a significant change in the soil animal community. The evolvement of the soil animal community structure was co-affected by soil pH, soluble salt content, and Na+, Cl, HCO3-, and Mg2+ concentrations, among which, soil soluble salt and Na had the greatest contribution, being the key affecting factors. The abundance and group richness of the soil animal community had significant negative exponential correlations with soil soluble salt content and Na+ concentration, and significant quadratic correlations with soil Mg2+ and HCO3- concentrations. The calculated ecological threshold values of soil Mg2+ and HCO3- concentrations for the abundance and group richness of the soil animal community were 38.7-39.4 mg x kg(-1) and 324.9-335.3 mg x kg(-1), at which, the abundance and group richness reached their peaks 40-43 individuals x m(-2) and 13-14 families x m(-2), respectively. When the Mg2+ and HCO3- concentrations increased further, the abundance and group richness decreased.