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SUMMARY: The mechanistic basis by which boron (B) deprivation inhibits root growth via the mediation of root apical auxin transport and distribution remains elusive. This study showed that B deprivation repressed root growth of wild‐type Arabidopsis seedlings, which was related to higher auxin accumulation (observed with DII‐VENUS and DR5‐GFP lines) in B‐deprived roots. Boron deprivation elevated the auxin content in the root apex, coinciding with upregulation of the expression levels of auxin biosynthesis‐related genes (TAA1, YUC3, YUC9, and NIT1) in shoots, but not in root apices. Phenotyping experiments using auxin transport‐related mutants revealed that the PIN2/3/4 carriers are involved in root growth inhibition caused by B deprivation. B deprivation not only upregulated the transcriptional levels of PIN2/3/4, but also restrained the endocytosis of PIN2/3/4 carriers (observed with PIN‐Dendra2 lines), resulting in elevated protein levels of PIN2/3/4 in the plasma membrane. Overall, these results suggest that B deprivation not only enhances auxin biosynthesis in shoots by elevating the expression levels of auxin biosynthesis‐related genes but also promotes the polar auxin transport from shoots to roots by upregulating the gene expression levels of PIN2/3/4, as well as restraining the endocytosis of PIN2/3/4 carriers, ultimately resulting in auxin accumulation in root apices and root growth inhibition. Significance Statement: While boron (B) deprivation‐induced root growth inhibition is causally associated with auxin accumulation and transport, the underlying mechanisms remain unknown. This work showed that enhanced auxin biosynthesis resulting from upregulation of the expression levels of auxin biosynthesis‐related genes in shoots and increased protein levels of PIN2/3/4 carriers in the plasma membrane mediated by increased transcript levels of PIN2/3/4 genes in roots combined with restrained endocytosis of PIN2/3/4 carriers result in auxin overaccumulation in root apices and consequently root growth inhibition. [ABSTRACT FROM AUTHOR]

This study examines the key influencing factors of voluntary dual ratings selection in corporate bond financing and the effect of dual ratings on risk premium and default risk, based on corporate bond data issued from 2016 to 2021. It shows that the worse the bond issuers' credit qualifications, the more likely they are to seek dual ratings before issuance. Compared to a single credit rating, the risk premium for a bond with dual ratings is lower, and the effect becomes more significant in the low-rated and non-listed company samples. There are dual ratings before bond issuance, and the higher the average credit rating level of the bond, the lower the bond's default risk. The research findings provide a theoretical basis and empirical evidence for the practice of voluntary dual ratings in China, expand research on the influencing mechanism of bond issuance pricing in the context of voluntary dual ratings selection, and examine the information content of credit ratings from the perspective of their ability to predict bond default. [ABSTRACT FROM AUTHOR]

Autophagy plays an important role in tissue remodeling during insect development. The interplay between autophagy‐related (ATG) proteins and caspases regulates the autophagic activity of ATGs, thereby modulating the process of autophagy. Our previous study characterized BmCaspase‐8‐like (BmCasp8L) as a caspase suppressor that inhibits apoptosis and immune signaling by suppressing the activation of death‐related ced‐3/Nedd2‐like caspase (DREDD), a caspase‐8 homolog in silkworm. In this study, we explored the regulatory role of BmCasp8L in autophagy. We found that the expression of Bmcasp8l increased from the late spinning stage to the pupa stage in the posterior silk gland (PSG), correlating with the expression patterns of Bmatg8 and Bmatg6. RNA interference‐mediated downregulation of BmCasp8L expression significantly decreased starvation‐induced autophagic influx as determined by the levels of BmATG8–phosphatidylethanolamine and the percentage of cells displaying punctate enhanced green fluorescent protein‐BmATG8. Conversely, the overexpression of BmCasp8L significantly increased autophagic influx. We also found that BmCasp8L underwent autophagic degradation induced by starvation and that it was colocalized with BmATG8. Lastly, we demonstrated that BmDREDD attenuated autophagy and BmCasp8L suppressed BmDREDD‐mediated cleavage of BmATG6. Taken together, our results demonstrated that BmCasp8L is a novel proautophagic molecule which suppresses BmDREDD‐mediated cleavage of BmATG6 and is a target for autophagy. [ABSTRACT FROM AUTHOR]

Objectives: To explore the impact of lymph node diameter on the efficacy and safety of ultrasound-guided microwave ablation (MWA) in the treatment of cervical metastatic lymph nodes (CMLNs) from thyroid cancer., Methods: A total of 32 patients with 58 CMLNs from thyroid cancer underwent ultrasound-guided MWA and were included in the retrospective study. Patients were divided into three groups based on the mean largest diameter of the CMLNs: Group A (diameter ≤10mm), Group B (10mm < diameter ≤20mm), and Group C (diameter >20mm). The research involved comparing changes in cervical metastatic lymph nodes and serum thyroglobulin (sTg) levels, as well as the incidence of complications, before and after microwave ablation across three groups of patients., Results: The technical success rate of this study was 100% (32/32), and they showed no major complications. Compared with measurements taken before MWA, the mean largest diameter and volume of CMLNs, as well as the sTg level, showed significant reductions ( p < 0.05) at the last follow-up in all three patient groups. Group A and B exhibited higher lymph node volume reduction rates and complete disappearance rates compared to Group C. However, the recurrence rate in the three groups were in the following order: Group C > Group B > Group A. The occurrence rate of mild complications was Group A > Group C > Group B., Conclusion: MWA is a safe and effective method for treating CMLNs, with advantages for localized nodes but limitations for larger ones. Careful consideration and personalized plans are advised, based on comprehensive evidence assessment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xiao, Chen, Li, Li and Zhu.)

Purpose: Given the potent immunostimulatory effects of bacterial outer membrane vesicles (OMVs) and the significant anti-colon tumor properties of Parabacteroides distasonis ( Pd ), this study aimed to elucidate the role and potential mechanisms of Pd -derived OMVs ( Pd -OMVs) against colon cancer., Methods: This study isolated and purified Pd -OMVs from Pd cultures and assessed their characteristics. The effects of Pd -OMVs on CT26 cell uptake, proliferation, and invasion were investigated in vitro. In vivo, a CT26 colon tumor model was used to investigate the anti-colon tumor effects and underlying mechanisms of Pd -OMVs. Finally, we evaluated the biosafety of Pd -OMVs., Results: Purified Pd -OMVs had a uniform cup-shaped structure with an average size of 165.5 nm and a zeta potential of approximately -9.56 mV, and their proteins were associated with pathways related to immunity and apoptosis. In vitro experiments demonstrated that CT26 cells internalized the Pd -OMVs, resulting in a significant decrease in their proliferation and invasion abilities. Further in vivo studies confirmed the accumulation of Pd -OMVs in tumor tissues, which significantly inhibited the growth of colon tumors. Mechanistically, Pd -OMVs increased the expression of CXCL10, promoting infiltration of CD8 + T cells into tumor tissues and expression of pro-inflammatory factors TNF-α, IL-1β, and IL-6. Notably, Pd -OMVs demonstrated a high level of biosafety., Conclusion: This paper elucidates that Pd -OMVs can exert significant anti-colon tumor effects by upregulating the expression of the chemokine CXCL10, thereby increasing the infiltration of CD8 + T cells into tumors and enhancing antitumor immune responses. This suggests that Pd -OMVs may be developed as a novel nanoscale potent immunostimulant with great potential for application in tumor immunotherapy. As well as developed as a novel nano-delivery carrier for combination with other antitumor drugs., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Liang et al.)

In this research, we studied the formation of Drosophila melanogaster FADD (Fas-associated death domain-containing protein) amyloid fiber and its influence on signal transduction in IMD (Immune deficiency) signaling pathway to better understand the regulation mechanism of Drosophila innate immune signaling pathway, which will provide reference for the immune regulation in other species. First, we purified dFADD protein expressed in Escherichia coli and performed Sulfur flavin T binding and transmission electron microscopy to identify the dFADD amyloid fibers formed in vitro. Then we investigated the formation of dFADD polymers in S2 cells using SDD-AGE and confocal microscope. We also constructed dFADD mutants to find out which domain is essential to fiber formation and its effect on IMD signal transduction. Our results revealed that dFADD could be polymerized to form amyloid fiber polymers in vitro and inside the cells. Formation of fibers relies on DED (Death-effector domain) domain of dFADD, since DED domain-deleted mutant existed as a monomer. Dual luciferase reporter assay showed that intact DED domain was required for the induction of downstream antimicrobial peptides, indicating that fiber formation was the key to IMD signal transduction. Our study revealed the role of dFADD in mediating the cascade between IMD and Dredd in the IMD signaling pathway by forming amyloid fibers, suggesting an evolutionarily conserved regulatory mechanism of innate immune signaling pathway.

Purpose: To review the clinical data and treatment efficacy of bevacizumab in Chinese patients with metastatic colorectal cancer (mCRC)., Patients and Methods: A total of 96 patients with mCRC treated by chemotherapy plus bevacizumab in the PLA General Hospital between December 2005 and August 2012 were analyzed retrospectively by overall response rate, disease-control rate, progression-free survival (PFS), and overall survival (OS). The tumor responses were assessed by the Response Evaluation Criteria in Solid Tumors guidelines., Results: A total of 96 patients with mCRC were identified. Median age was 53.6 years. Eastern Cooperative Oncology Group performance status was 0-2. By the end of follow-up (August 20, 2012), 54 patients exhibited progression (56.3%), and 39 (40.6%) patients had died. A total of 27 (28.1%) achieved partial response, and 48 patients (50.0%) had stable disease, exhibiting an overall response rate of 28.1% and a disease-control rate of 78.1%. The response rates of the first-line, second-line, and third-line (or later) therapy were 41.7%, 21.9%, and 15.8%, respectively. The median durations of the PFS and OS were 8.13 months and 14.80 months, respectively. The median durations of the PFS were 12.70 months, 8.30 months, and 6.40 months for first-line, second-line, and third-line (or later) therapy, respectively, and the median durations of the OS were 24.03 months, 14.90 months, and 11.03 months for first-line, second-line, and third-line (or later) therapy, respectively., Conclusion: A bevacizumab-containing chemotherapy regimen was well tolerated and effective in Chinese patients with mCRC.