Ruirui Zhang

Oxidative side reaction is one of the major factors hindering the development of hemoglobin-based oxygen carriers (HBOCs). To avoid the oxidative toxicity, we designed and synthesized polydopamine-coated hemoglobin (Hb-PDA) nanoparticles via simple one-step assemblage without any toxic reagent. Hb-PDA nanoparticles showed oxidative protection of Hb by inhibiting the generation of methemoglobin (MetHb) and ferryl (Fe IV) Hb, as well as excellent antioxidant properties by scavenging free radicals and reactive oxygen species (ROS). Interestingly, the scavenging rate of Hb-PDA nanoparticles for ABTS+ radical is at most 89%, while for DPPH radical it reaches 49%. In addition, Hb-PDA efficiently reduced the intracellular H2O2-induced ROS generation. Moreover, Hb-PDA nanoparticles exhibited high oxygen affinity, low effect on blood constituents, and low cytotoxicity. The results indicate that polydopamine-coated hemoglobin might be a promising approach for constructing novel oxygen carriers with the capacity to reduce oxidative side reaction.

Metastatic relapse is a leading cause of cancer-associated death and one of the major obstacles for effective therapy against triple-negative breast cancer. To address this problem, a miRNA-delivering nanocapsule technology based on hyaluronic acid (HA)/protamine sulfate (PS) interpolyelectrolyte complexes (HP-IPECs) is developed for efficient encapsulation and intracellular delivery microRNA-34a (miR-34a), which is a potent endogenous tumor suppressor of breast cancer. The nanocapsules are successfully generated through a self-assembly approach mediated by an electrostatic interaction. In vitro and in vivo experiments illustrate that miR-34a can be efficiently encapsulated into HP-IPECs and delivered into breast cancer cells or breast cancer tissues. Nanocomplex-assisted delivery of miR-34a induces cell apoptosis and suppresses migration, proliferation, and tumor growth of breast cancer cells via targeting CD44 and a Notch-1-signaling pathway. The obtained results suggest that HP-IPECs have a great potential as a biodegradable vector for microRNA-based therapy against triple-negative breast cancer.

BACKGROUND: Metastasis is the leading cause of death in patients with bladder cancer (BC). However, current available treatments exert little effects on metastatic BC. Moreover, traditional grading and staging have only a limited ability to identify metastatic BC. Accumulating evidence indicates that the aberrant expression of microRNA is intimately associated with tumor progression. So far, many miRNAs have been identified as molecular targets for cancer diagnosis and therapy. This study focused on the role of miR-516a-5p (miR-516a) in BC. METHODS: MiR-516a expression and its downstream signaling pathway were detected using molecular cell biology and biochemistry approaches and techniques. Fresh clinical BC tissue was used to study the clinicopathological characteristics of patients with different miR-516a expression. The biological functions of miR-516a in BC were tested both in vivo and in vitro. RESULTS: A more invasive BC phenotype was significantly and positively correlated with miR-516a overexpression in BC patients. MiR-516a inhibition significantly decreased BC cell invasion and migration in vitro and in vivo. Furthermore, miR-516a attenuated the expression of PH domain leucine-rich repeat-containing protein phosphatase 2 protein and inhibited SMAD-specific E3 ubiquitin protein ligase 1 transcription by activating the AKT/Forkhead box O3 signaling pathway, which stabilized MMP9 and slowed down its proteasomal degradation, ultimately promoting BC motility and invasiveness. CONCLUSIONS: Our findings reveal the crucial function of miR-516a in promoting BC metastasis, and elucidate the molecular mechanism involved, suggesting that miR-516a may be a promising novel diagnostic and therapeutic target for BC.

BACKGROUND: Post-transcriptional regulation of gene expression can be achieved through the control of mRNA stability, cytoplasmic compartmentalization, 3' UTR length and translational efficacy. Spermiogenesis, a process through which haploid male germ cells differentiate into spermatozoa, represents an ideal model for studying post-transcriptional regulation in vivo because it involves a large number of transcripts that are physically sequestered in ribonucleoprotein particles (RNPs) and thus subjected to delayed translation. To explore how small RNAs regulate mRNA fate, we conducted RNA-Seq analyses to determine not only the levels of both mRNAs and small noncoding RNAs, but also their cytoplasmic compartmentalization during spermiogenesis. RESULT: Among all small noncoding RNAs studied, miRNAs displayed the most dynamic changes in both abundance and subcytoplasmic localization. mRNAs with shorter 3' UTRs became increasingly enriched in RNPs from pachytene spermatocytes to round spermatids, and the enrichment of shorter 3' UTR mRNAs in RNPs coincided with newly synthesized miRNAs that target these mRNAs at sites closer to the stop codon. In contrast, the translocation of longer 3' UTR mRNAs from RNPs to polysomes correlated with the production of new miRNAs that target these mRNAs at sites distal to the stop codon. CONCLUSIONS: miRNAs appear to control cytoplasmic compartmentalization of mRNAs based on 3' UTR length. Our data suggest that transcripts with longer 3' UTRs tend to contain distal miRNA binding sites and are thus targeted to polysomes for translation followed by degradation. In contrast, those with shorter 3' UTRs only possess proximal miRNA binding sites, which, therefore, are targeted into RNPs for enrichment and delayed translation.

The impact of China’s green finance policies on renewable energy, clean energy, and other green companies is a hot topic of concern. This study uses the difference-in-differences (DID) model to examine the incentive effect of the Green Credit Guidelines (GCG) on the technological innovation and financial performance of Chinese listed green enterprises. The heterogeneity analysis is carried out from the level of digital finance, green development, and marketization. This study finds that: (1) Green finance is conducive to stimulating the technological innovation and financial performance of green enterprises. (2) Green enterprises in areas with high digital finance levels have a more significant incentive effect on green finance policies, compared to areas with less-developed digital finance. (3) Green enterprises in areas with high levels of green development are more significantly positively affected by green finance policies, compared to areas with less-developed digital finance. (4) The incentive effect of green credit policies on green enterprises in areas with a high degree of marketization is more significant, compared with regions with a lower level of green development. Finally, some policy implications are proposed to provide a reference for China to improve the green financial system to facilitate the financing of green enterprises.