Growth Characteristics of Ramet System in Phyllostachys praecox Forest under Mulch Management.

The ramet system is a typical structural type in the life history of clonal plants. This massive structure is formed by many similar ramets connected by underground rhizomes, which are independent and mutually influential. Therefore, the ramet system is unique to bamboo forests, and its role in the construction, maintenance, and productivity of bamboo populations is irreplaceable. Mulch management is a high-level cultivation model for bamboo forests that is used to cultivate bamboo shoots. However, the basic conditions of bamboo ramet systems in this managed model are poorly understood. This study analyzed the underground rhizome morphology, bud bank, and branching of bamboo ramets in a Phyllostachys praecox C.D. Chu et C.S. Chao 'Prevernalis' forest to explore the growth patterns of bamboo ramets in high-level management fields. In mulched bamboo forests, the bamboo rhizomes, distributed in intermediate positions of the bamboo ramet system, were long with many lateral buds and branches, and those at the initial and distal ends were short with few lateral buds and branches. The initial end of the ramet system reduced the ramet system, the intermediate part expanded the ramet system, and the distal end promoted ramet system regeneration. Owing to the continuous reduction, expansion, and renewal of ramet systems, the bamboo rhizome system demonstrates mobility and adaptability. This study found that a higher level of bamboo forest management increased the possibility of artificial fragmentation of the ramet system and that improving the efficiency of the ramet system was beneficial for maintaining its high vitality. Thus, this study provides a crucial reference for guiding the precise regulation of bamboo ramet systems in artificial bamboo forests.

LncRNA RGMB-AS1 inhibits HMOX1 ubiquitination and NAA10 activation to induce ferroptosis in non-small cell lung cancer.

Ferroptosis, an iron-dependent regulated cell death caused by excessive lipid peroxide accumulation, has emerged as a promising therapeutic target in various cancers, including non-small cell lung cancer (NSCLC). In this study, we identified the long non-coding RNA RGMB-AS1 as a key regulator of ferroptosis in NSCLC. Mechanistically, RGMB-AS1 interacted with heme oxygenase 1 (HMOX1) and prevented its ubiquitination by the E3 ligase TRC8, leading to increased HMOX1 stability and enhanced ferroptosis. Additionally, RGMB-AS1 bound to the 82-87 amino acid region of N-alpha-acetyltransferase 10 (NAA10), stimulating its acetyltransferase activity and promoting the conversion of acetyl-CoA to HMG-CoA, further contributing to ferroptosis. The RGMB-AS1-HMOX1 and RGMB-AS1-NAA10 axes synergistically inhibited NSCLC growth both in vitro and in vivo. Clinically, low RGMB-AS1 expression was associated with advanced tumor stage and poor overall survival in NSCLC patients. Furthermore, adeno-associated virus-mediated RGMB-AS1 overexpression significantly suppressed tumor growth in mouse xenograft models. Our findings uncover a novel lncRNA-mediated regulatory mechanism of ferroptosis and highlight the potential of RGMB-AS1 as a prognostic biomarker and therapeutic target in NSCLC.

Polyphyllin D punctures hypertrophic lysosomes to reverse drug resistance of hepatocellular carcinoma by targeting acid sphingomyelinase.

Hypertrophic lysosomes are critical for tumor progression and drug resistance; however, effective and specific lysosome-targeting compounds for cancer therapy are lacking. Here we conducted a lysosomotropic pharmacophore-based in silico screen in a natural product library (2,212 compounds), and identified polyphyllin D (PD) as a novel lysosome-targeted compound. PD treatment was found to cause lysosomal damage, as evidenced by the blockade of autophagic flux, loss of lysophagy, and the release of lysosomal contents, thus exhibiting anticancer effects on hepatocellular carcinoma (HCC) cell both in vitro and in vivo. Closer mechanistic examination revealed that PD suppressed the activity of acid sphingomyelinase (SMPD1), a lysosomal phosphodieserase that catalyzes the hydrolysis of sphingomyelin to produce ceramide and phosphocholine, by directly occupying its surface groove, with Trp148 in SMPD1 acting as a major binding residue; this suppression of SMPD1 activity irreversibly triggers lysosomal injury and initiates lysosome-dependent cell death. Furthermore, PD-enhanced lysosomal membrane permeabilization to release sorafenib, augmenting the anticancer effect of sorafenib both in vivo and in vitro. Overall, our study suggests that PD can potentially be further developed as a novel autophagy inhibitor, and a combination of PD with classical chemotherapeutic anticancer drugs could represent a novel therapeutic strategy for HCC intervention.

Targeting ARF1-IQGAP1 interaction to suppress colorectal cancer metastasis and vemurafenib resistance.

INTRODUCTION: Acquired resistance to BRAF inhibitor vemurafenib is frequently observed in metastatic colorectal cancer (CRC), and it is a thorny issue that results in treatment failure. As adaptive responses for vemurafenib treatment, a series of cellular bypasses are response for the adaptive feedback reactivation of ERK signaling, which warrant further investigation. OBJECTIVES: We identified ARF1 (ADP-ribosylation factor 1) as a novel regulator of both vemurafenib resistance and cancer metastasis, its molecular mechanism and potential inhibitor were investigated in this study. METHODS: DIA-based quantitative proteomics and RNA-seq were performed to systematic analyze the profiling of vemurafenib-resistant RKO cells (RKO-VR) and highly invasive RKO cells (RKO-I8), respectively. Co­immunoprecipitation assay was performed to detect the interaction of ARF1 and IQGAP1 (IQ-domain GTPase activating protein 1). An ELISA-based drug screen system on FDA-approved drug library was established to screen the compounds against the interaction of ARF1-IQGAP1.The biological functions of ARF1 and LY2835219 were determined by transwell, western blotting, Annexin V-FITC/PI staining and in vivo experimental metastasis assays. RESULTS: We found that ARF1 strongly interacted with IQGAP1 to activate ERK signaling in VR and I8 CRC cells. Deletion of IQGAP1 or inactivation of ARF1 (ARF-T48S) restored the invasive ability induced by ARF1. As ARF1-IQGAP1 interaction is essential for ERK activation, we screened LY2835219 as novel inhibitor of ARF1-IQGAP1 interaction, which inactivated ERK signaling and suppressed CRC metastasis and vemurafenib-resistance in vitro and in vivo with no observed side effect. Furthermore, LY2835219 in combined treatment with vemurafenib exerted significantly inhibitory effect on ARF1-mediated cancer metastasis than used independently. CONCLUSION: This study uncovers that ARF1-IQGAP1 interaction-mediated ERK signaling reactivation is critical for vemurafenib resistance and cancer metastasis, and that LY2835219 is a promising therapeutic agent for CRC both as a single agent and in combination with vemurafenib.

Evaluating the Rhizosphere and Endophytic Microbiomes of a Bamboo Plant in Response to the Long-Term Application of Heavy Organic Amendment.

Root-associated bacteria play a major role in plant health and productivity. However, how organic amendment influences root-associated bacteria is uncertain in Lei bamboo (Phyllostachys praecox) plantations. Here, we compared the rhizosphere and endophytic microbiomes in two Lei bamboo plantations with (IMS) and without (TMS) the application of organic amendment for 16 years. The results showed IMS significantly increased (p < 0.05) the relative abundance of Proteobacteria and significantly decreased (p < 0.05) the relative abundance of Acidobacteria, Bacteroidetes, and Verrucomicrobiota. The root endophytic Proteobacteria and Acidobacteria were significantly higher in abundance (p < 0.05) in the IMS than in the TMS, while Actinobacteria and Firmicutes were significantly lower in abundance. Five taxa were assigned to Proteobacteria and Acidobacteria, which were identified as keystones in the rhizosphere soil microbiome, while two species taxonomically affiliated with Proteobacteria were identified as keystones in the root endophytic microbiota, indicating this phylum can be an indicator for a root-associated microbiome in response to IMS. The soil pH, soil total organic carbon (TOC), total nitrogen (TN), total phosphorus (TP), available potassium (AK), and TOC:TP ratio were significantly correlated (p < 0.05) with the bacterial community composition of both rhizosphere soils and root endophytes. TMS increased the microbial network complexity of root endophytes but decreased the microbial network complexity of rhizosphere soil. Our results suggest IMS shapes the rhizosphere and endophytic bacterial community compositions and their interactions differently, which should be paid attention to when designing management practices for the sustainable development of forest ecosystems.

Highly bioactive iridium metal-complex alleviates spinal cord injury via ROS scavenging and inflammation reduction.

Generation of a promising antioxidative reagent with superior biocompatibility is urgently needed to remedy spinal cord injuries (SCI), repair the damaged neurons and restrain the secondary injuries caused by inflammation-induced oxidative stress. Inhibitory elements in the injury sites and necessitous inherent neural regeneration ability were major challenges for functional recovery after spinal cord injuries. We here developed a highly bioactive iridium complex (IrFPHtz) with enhanced antioxidative activities and improved SCI therapeutic efficacy. Both in vivo and in vitro, IrFPHtz has exhibited neuroprotective and anti-inflammatory properties. Mechanically, IrFPHtz directly targets SOD1 and upregulates the expression of SOD1 to eliminate the excess Reactive Oxygen Species (ROS) production induced by SCI, and thus protecting neuron cells from further damage. As a result, IrFPHtz safeguarded the neurons and myelin sheaths against trauma, lessened glial scar conformations and facilitated the repair of neurons and long axon expansion in the glial scar. Furthermore, IrFPHtz significantly ameliorated the behavioral functions of SCI mice and promoted a satisfactory curative effect. Therefore, this study sheds light on a novel method for SCI treatment using IrFPHtz as a potential drug and implicates the clinical significance of metal complexes in diseases featuring with upregulated ROS species.

Inhibition of BAG3 enhances the anticancer effect of shikonin in hepatocellular carcinoma.

Human hepatocellular carcinoma (HCC) is the most frequent cancer worldwide with a poor prognosis. Tumor-specific pyruvate kinase M2 (PKM2) is essential for cancer metabolism and tumorigenesis. Shikonin, a specific inhibitor of PKM2, but not PKM1, exhibits significant anticancer effect in HCC, and was deemed as a promising drug for cancer therapy. However, shikonin-mediated bypass signaling in HCC remained unclear. Here, we performed forward/reverse stable isotope labeling with amino acids in cell culture (SILAC)-based proteomics to identify the early molecular events controlled by shikonin. We demonstrated for the first time that shikonin could induce the nuclear translocation of PKM2 for recruiting Nrf2, and transcriptionally activated Nrf2 downstream target gene BAG3, therefore increasing protective effect to sustain cell survival. Knockdown of BAG3 by si-RNA significantly potentiated the anticancer effect of shikonin. These findings provided the first evidence of a new noncanonical function of inhibited PKM2 could act as a transcriptional coactivator of Nrf2 in cancer survival, highlight that shikonin in combined with BAG3 inhibitor could be a promising therapeutic strategy for HCC therapy.

Post-translational modifications of CDK5 and their biological roles in cancer.

Post-translational modifications (PTMs) of Cyclin-dependent kinase 5 (CDK5) have emerged as important regulatory mechanisms that modulate cancer development in patients. Though CDK5 is an atypical member of the cyclin-dependent kinase family, its aberrant expression links to cell proliferation, DNA damage response, apoptosis, migration and angiogenesis in cancer. Current studies suggested that, new PTMs on CDK5, including S-nitrosylation, sumoylation, and acetylation, serve as molecular switches to control the kinase activity of CDK5 in the cell. However, a majority of these modifications and their biological significance in cancer remain uncharacterized. In this review, we discussed the role of PTMs on CDK5-mediated signaling cascade, and their possible mechanisms of action in malignant tumors, as well as the challenges and future perspectives in this field. On the basis of the newly identified regulatory signaling pathways of CDK5 related to PTMs, researchers have investigated the cancer therapeutic potential of chemical compounds, small-molecule inhibitors, and competitive peptides by targeting CDK5 and its PTMs. Results of these preclinical studies demonstrated that targeting PTMs of CDK5 yields promising antitumor effects and that clinical translation of these therapeutic strategies is warranted.

Responses of soil nutrients and microbial communities to intercropping medicinal plants in moso bamboo plantations in subtropical China.

Bamboo forests are one of the most important forest resources in subtropical China. A pure, single-layer bamboo forest is considered an optimal habitat for intercropping medicinal herbs. Soil microorganisms have an important role in various ecological processes and respond quickly to environmental changes. However, changes in soil nutrients and microbial communities associated with agroforestry cultivation methods remain poorly documented. In the present study, a pure moso bamboo (Phyllostachys edulis) forest (Con) and three adjacent moso bamboo-based agroforestry (BAF) systems (moso bamboo-Paris polyphylla (BP), moso bamboo-Tetrastigma hemsleyanum (BT) and moso bamboo-Bletilla striata (BB)) were selected; and their soil chemical properties and bacterial communities were studied and compared to evaluate the effects of agroforestry on soil bacterial communities and the relationship between soil properties and bacterial communities in BAF systems. Results showed that compared with soils under the Con, soils under the BAF systems had more (p < 0.05) soil organic carbon (SOC) and available nitrogen (AN) but lower (p < 0.05) pH and available potassium (AK). In addition, compared with the Con system, the BB and BT systems had significantly greater (p < 0.05) available phosphorus (AP). Compared with that in the Con system, the Shannon index in the BAF systems was significantly greater (p < 0.05), but the Chao1 index not different. On the basis of relative abundance values, compared with the Con soils, the BAF soils had a significantly greater abundance of (p < 0.05) Bacteroidetes and Planctomyces but a significantly lower abundance of (p < 0.05) Verrucomicrobia, Gemmatimonadetes and Candidatus Xiphinematobacter. Moreover, compared with the Con system, the BB and BT systems had a greater (p < 0.05) abundance of Actinobacteria, Rhodoplanes, Candidatus Solibacter and Candidatus Koribacter. Redundancy analysis (RDA) revealed that soil pH, SOC and AP were significantly correlated with bacterial community composition. Results of this study suggest that intercropping medicinal herbs can result in soil acidification and potassium (K) depletion; thus, countermeasures such as applications of K fertilizer and alkaline soil amendments are necessary for BAF systems.

Changes of Root Endophytic Bacterial Community Along a Chronosequence of Intensively Managed Lei Bamboo (Phyllostachys praecox) Forests in Subtropical China.

Endophytic bacteria widely exist inside plant tissues and have an important role in plant growth and development and the alleviation of environmental stress. However, little is known about the response of root-associated bacterial endophytes of Lei bamboo (Phyllostachys praecox) to intensive management, which is a common management practice for high bamboo shoot production in subtropical China. In this study, we comparatively investigated the root endophytic bacterial community structures in a chronosequence of intensively managed (5a, 10a, 15a, and 20a) and extensively managed plantations (as control, Con). The results showed that endophytic Proteobacteria was the dominant bacterial phylum in the bamboo roots. Intensive management significantly increased (p < 0.05) the bacterial observed species and Chao1 (except 5a) indices associated with bamboo roots. The relative abundances of Firmicutes, Bacteroidetes, and Actinobacteria (except 15a) in the intensively managed bamboo roots significantly increased (p < 0.05) compared with those in Con, while the relative abundance of Proteobacteria significantly decreased in intensively managed bamboo roots (p < 0.05). The phyla Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes were the biomarkers in Con, 5a, 15a, and 20a, respectively. Redundancy analysis (RDA) showed that soil alkali-hydrolysable N (AN), available phosphorus (AP), available K (AK), and total organic carbon (TOC) were significantly correlated (p < 0.05) with the bacterial community compositions. Our results suggest that the root endophytic microbiome of Lei bamboo was markedly influenced by intensive management practices, and the available nutrient status could be the main driving factor for such shifts. Although heavy fertilization in the intensive management system increased the diversity indices, the rapid changes in root endophyte communities and their relevant functions might indicate a high risk for sustainable management.

[Snail control by using soil pasting mixed with niclosamide].

OBJECTIVE: To evaluate the effect of snail control through soil pasting mixed with niclosamide. METHODS: Four sites were selected in different epidemic areas in Sichuan province. Soil pasting mixed with niclosamide was carried on, and the dosage was 0 g/m2, 4 g/m2, 6 g/m2, 8 g/m2 and 10 g/m2 respectively. The mortality rate of snail and the density of snail were observed after 7, 15, 30, 90 and 180 days. RESULTS: The mortality rate of snail was more than 43.3% in blank group after 30 days. The mortality rate of snail was from 75.3% to 100.0% at 4 g/m2 group after 30 days. The mortality rate of snail in 4 g/m2 group was significantly higher than that in the blank group (chi2 = 31.27, P < 0.05). There was no significant difference in the mortality rate of snail among all study groups (chi2 = 1.07, P > 0.05). The decrease rate of snail density was more than 90%. The mortality rate of snail was about 30% higher in Chantu group than Qutu group. The unit cost of Pasting-Mixing Drug with Soil was from 5 to 7 times of spray method, but the total cost was similar for the. two methods at the endpoint of the snail control. CONCLUSION: The effect of soil pasting mixed with niclosamide is good, and the dosage of 4-6 g/m2 is suggested in snail control.