Research Advances in Vascular Remodeling in Choke Vessels of Perforator Flap: A Systematic Review.

BACKGROUND: As a significant bridge between perforasomes, choke vessels are the key structure of blood supply expansion, also a prerequisite for preventing distal ischemic necrosis of the multiterritory perforator flap, where the remodeling of choke vessels after flap elevation plays an essential role. This systematic review highlights the underlying mechanisms and clinical ways to promote remodeling of choke vessels, as well as experimental observation approaches to further guide researchers. METHODS: A systematic review was conducted from 1975 to 2023 through PubMed, EMBASE, Web of Science, and Cochrane database with the key words "choke vessels" and "perforator flap" to investigate the mechanisms and ways to promote remodeling of choke vessels as well as observation approaches. The inclusion criteria and exclusion criteria were set to screen the literature. RESULTS: A total of 94 literatures were obtained through database retrieval. After removing the duplicate literature, reading the title and abstract, and reviewing the full text finally, 33 articles were included in the final study. CONCLUSIONS: The underlying remodeling of choke vessels may be related to fluid shear stress, hypoxia, and inflammation. The clinical ways to promote remodeling of choke vessels include surgical delay, arterial supercharge, venous superdrainage, drugs, and stem cells. Various experimental methods of observing microvascular morphology allow for a comprehensive research of choke vessels.

Melatonin alleviates cadmium toxicity by regulating root endophytic bacteria community structure and metabolite composition in apple.

The level of cadmium (Cd) accumulation in orchard soils is increasing, and excess Cd will cause serious damage to plants. Melatonin is a potent natural antioxidant and has a potential role in alleviating Cd stress. This study aimed to investigate the effects of exogenous melatonin on a root endophyte bacteria community and metabolite composition under Cd stress. The results showed that melatonin significantly scavenged the reactive oxygen species and restored the photosynthetic system (manifested by the improved photosynthetic parameters, total chlorophyll content and the chlorophyll fluorescence parameters (Fv/Fm)), increased the activity of antioxidant enzymes (the activities of catalase, superoxide dismutase, peroxidase and ascorbate oxidase) and reduced the concentration of Cd in the roots and leaves of apple plants. High-throughput sequencing showed that melatonin increased the endophytic bacterial community richness significantly and changed the community structure under Cd stress. The abundance of some potentially beneficial endophytic bacteria (Ohtaekwangia, Streptomyces, Tabrizicola and Azovibrio) increased significantly, indicating that the plants may absorb potentially beneficial microorganisms to resist Cd stress. The metabolomics results showed that melatonin significantly changed the composition of root metabolites, and the relative abundance of some metabolites decreased, suggesting that melatonin may resist Cd stress by depleting root metabolites. In addition, co-occurrence network analysis indicated that some potentially beneficial endophytes may be influenced by specific metabolites. These results provide a theoretical basis for studying the effects of melatonin on the endophytic bacterial community and metabolic composition in apple plants.

Dopamine alleviates cadmium stress in apple trees by recruiting beneficial microorganisms to enhance the physiological resilience revealed by high-throughput sequencing and soil metabolomics.

Dopamine has demonstrated promise as a stress-relief substance. However, the function of dopamine in Cd tolerance and its mechanism remains largely unknown. The current study was performed to investigate the mechanism of dopamine on alleviating apple Cd stress through regular application of CdCl2 and dopamine solution to potting soil. The results indicated that dopamine significantly reduced reactive oxygen species (ROS) and Cd accumulation and alleviated the inhibitory effect of Cd stress on the growth of apple plants through activation of the antioxidant system, enhancement of photosynthetic capacity, and regulation of gene expression related to Cd absorption and detoxification. The richness of the rhizosphere microbial community increased, and community composition and assembly were affected by dopamine treatment. Network analysis of microbial communities showed that the numbers of nodes and total links increased significantly after dopamine treatment, while the keystone species shifted. Linear discriminant analysis effect size indicated that some biomarkers were significantly enriched after dopamine treatment, suggesting that dopamine induced plants to recruit potentially beneficial microorganisms (Pseudoxanthomonas, Aeromicrobium, Bradyrhizobium, Frankia, Saccharimonadales, Novosphingobium, and Streptomyces) to resist Cd stress. The co-occurrence network showed several metabolites that were positively correlated with relative growth rate and negatively correlated with Cd accumulation, suggesting that potentially beneficial microorganisms may be attracted by several metabolites (L-threonic acid, profenamine, juniperic acid and (3ß,5ξ,9ξ)-3,6,19-trihydroxyurs-12-en-28-oic acid). Our results demonstrate that dopamine alleviates Cd stress in apple trees by recruiting beneficial microorganisms to enhance the physiological resilience revealed. This study provides an effective means to reduce the harm to agricultural production caused by heavy metals.

Development of pteridin-7(8H)-one analogues as highly potent cyclin-dependent kinase 4/6 inhibitors: Synthesis, structure-activity relationship, and biological activity.

CDK4/6 have been validated as the cancer therapeutic targets. Here, we describe a series of pteridin-7(8H)-one analogues as potent CDK4/6 inhibitors. Among them, the most promising compound 7s demonstrated remarkable and broad-spectrum antiproliferative activities toward HCT116, HeLa, MDA-MB-231, and HT-29 cells with IC50 values of 0.65, 0.70, 0.39, and 2.53 µM, respectively, which were more potent than that of the anticancer drug Palbociclib. Interestingly, 7s also manifested the greatest inhibitory activities toward both CDK4/cyclin D3 and CDK6/cyclin D3 (IC50 = 34.0 and 65.1 nM, respectively), which was comparable with Palbociclib. Additionally, molecular simulation indicated that 7s bound efficiently at the ATPbindingsitesofCDK4 and CDK6. Further mechanistic studies revealed that compound 7s could concentration-dependently induce cell cycle arrest and apoptosis in HeLa cells. Takentogether, 7s represents a promising novel CDK4/6 inhibitor for the potential treatment of cancer.

Tumor necrosis factor-α small interfering RNA alveolar epithelial cell-targeting nanoparticles reduce lung injury in C57BL/6J mice with sepsis.

BACKGROUND: The role of tumor necrosis factor (TNF)-α small interfering (si)RNA alveolar epithelial cell (AEC)-targeting nanoparticles in lung injury is unclear. METHODS: Sixty C57BL/6J mice with sepsis were divided into normal, control, sham, 25 mg/kg, 50 mg/kg, and 100 mg/kg siRNA AEC-targeting nanoparticles groups (n = 10 per group). The wet:dry lung weight ratio, and hematoxylin and eosin staining, western blotting, and enzyme-linked immunosorbent assays for inflammatory factors were conducted to compare differences among groups. RESULTS: The wet:dry ratio was significantly lower in control and sham groups than other groups. TNF-α siRNA AEC-targeting nanoparticles significantly reduced the number of eosinophils, with significantly lower numbers in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups. The nanoparticles also significantly reduced the expression of TNF-α, B-cell lymphoma-2, caspase 3, interleukin (IL)-1ß, and IL-6, with TNF-α expression being significantly lower in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups. CONCLUSION: TNF-α siRNA AEC-targeting nanoparticles appear to be effective at improving lung injury-related sepsis, and 50 mg/kg may be a preferred dose option for administration.

Cleancap-Regulated Aggregation-Induced Emission Strategy for Highly Specific Analysis of Enzyme.

In this work, a cleancap-regulated aggregation-induced emission (AIE) strategy based on copper nanoclusters (CuNCs) was developed with stepwise recognition for highly specific analysis of the enzyme. The dissolved CuNCs with AIE characteristics in alkaline solution were prepared by using p-mercaptophenylboronic acid as the reducing agent and the stabilizing ligand. The prepared CuNCs can specifically conjugate with glucose (Glu) to connect with each other via the rapid boronate esters formation between boronic acids of CuNCs and a pair of cis-diols on Glu. The cleancap-regulated AIE strategy was further identified by modification of CuNCs with d-glucose 6-phosphate (P-Glu) as the capper and substrate. Introduction of alkaline phosphatase to the P-Glu/CuNCs complex can induce the cleavage of phosphate group to activate the 5,6-diol of Glu on the CuNCs. The decapped complexes could be aggregated through further conjugation between 5,6-diol and boronic acid of two CuNCs, resulting in strong red AIE luminescence. The dual recognitions of enzymatic cleavage and cis-diols/boronic acid conjugation endow the designed method with highly specific detection and cell imaging of enzymatic activity. The cleancap-regulated AIE strategy provides a universal tool for regulation of AIE phenomenon in trace analysis.

Progressive aggregation-induced emission strategy for imaging of aluminum ions in cellular microenvironment.

A progressive aggregation-induced emission (AIE) strategy is established based on two diverse stimulus-responsive patterns of copper nanoclusters (CuNCs) for imaging of aluminum ions (Al3+) in cellular microenvironment. The non-emissive CuNCs were facilely synthesized with l-glutathione (GSH) as both stabilizing agent and reducing agent, and demonstrated the excellent AIE characteristics in the ethanol/water mixture. Moreover, the dispersed CuNCs can be aggregated to give the AIE behavior in aqueous solutions by reducing the pH value, and could be further aggregated with 94-fold reinforce by introducing Al3+ ascribe to the strong coordination ability between Al3+ and the functional groups of GSH, demonstrating the progressive AIE process. Under endocytosis, the progressive AIE strategy can be employed to distinguish the Al3+ in the locations of lysosome against other organelles due to the acidic microenvironment of lysosome. The progressive AIE advantages of CuNCs provide a new concept for signal transduction, and have the promising applications in decoding the functions of intracellular biomolecules.

Host-guest recognition-regulated aggregation-induced emission for in situ imaging of MUC1 protein.

A host-guest recognition-regulated aggregation-induced emission (AIE) strategy is developed based on the interaction between cyclodextrin-functionalized copper nanoclusters and di(adamantan-1-yl)phosphine as a connector, which significantly improves the AIE efficiency and stability and can be applied to long-term in situ imaging of MUC1 protein.