Discrepant diversity patterns and function of bacterial and fungal communities on an earthquake-prone mountain gradient in Northwest Sichuan, China

Patterns of microbial diversity on elevational gradients have been extensively studied, but little is known about those patterns during the restoration of earthquake-fractured alpine ecosystems. In this study, soil properties, soil enzyme activities, abundance and diversity of soil bacterial and fungal communities at four positions along a 2.6-km elevational gradient in the Snow Treasure Summit National Nature Reserve, located in Pingwu County, Southwest China. Although there were no significant changes in the soil chemical environment, bacterial and fungal communities were significantly different at different elevations. The overall fungal community presented an N-shaped diversity pattern with increasing elevation, while bacterial diversity decreased significantly with elevation. Changes in microbial diversity were associated with soil phosphorus, plant litter, and variations in dominant microbial taxa. Differences in enzyme activities among elevations were regulated by microbial communities, with changes in catalase and acid phosphatase activities mainly controlled by Acidobacteria and Planctomycetaceae bacteria, respectively (catalase: p < 0.001; acid phosphatase: p < 0.01), and those in β-glucosidase, sucrase, and urease activities mainly controlled by fungi. The β-glucosidase and sucrase were both positively correlated with Herpotrichiellaceae, and urease was positively correlated with Sebacinaceae (p < 0.05). These findings contribute to the conservation and management of mountain ecosystems in the face of changing environmental conditions. Further research can delve into the specific interactions between microbial communities, soil properties, and vegetation to gain deeper insights into the intricate ecological dynamics within earthquake-prone mountain ecosystems

Topological Supercavity Resonances in the Finite System

Acoustic resonant cavities play a vital role in modern acoustical systems. The ultrahigh quality-factor resonances are highly desired for some applications such as high-resolution acoustic sensors and acoustic lasers. Here, a class of supercavity resonances is theoretically proposed and experimentally demonstrated in a coupled acoustic resonator system, arising from the merged bound states in the continuum (BICs) in geometry space. Their topological origin is demonstrated by explicitly calculating their topological charges before and after BIC merging, accompanied by charges annihilation. Compared with other types of BICs, they are robust to the perturbation brought by fabrication imperfection. Moreover, it is found that such supercavity modes can be linked with the Friedrich-Wintgen BICs supported by an entire rectangular (cuboid) resonator sandwiched between two rectangular (or circular) waveguides and thus more supercavity modes are constructed. Then, these coupled resonators are fabricated and such a unique phenomenon-moving, merging, and vanishing of BICs-is experimentally confirmed by measuring their reflection spectra, which show good agreement with the numerical simulation and theoretical prediction of mode evolution. The results may find exciting applications in acoustic and photonics, such as enhanced acoustic emission, filtering, and sensing

MST4 Phosphorylation of ATG4B Regulates Autophagic Activity, Tumorigenicity, and Radioresistance in Glioblastoma

ATG4B stimulates autophagy by promoting autophagosome formation through reversible modification of ATG8. We identify ATG4B as a substrate of mammalian sterile20-like kinase (STK) 26/MST4. MST4 phosphorylates ATG4B at serine residue 383, which stimulates ATG4B activity and increases autophagic flux. Inhibition of MST4 or ATG4B activities using genetic approaches or an inhibitor of ATG4B suppresses autophagy and the tumorigenicity of glioblastoma (GBM) cells. Furthermore, radiation induces MST4 expression, ATG4B phosphorylation, and autophagy. Inhibiting ATG4B in combination with radiotherapy in treating mice with intracranial GBM xenograft markedly slows tumor growth and provides a significant survival benefit. Our work describes an MST4-ATG4B signaling axis that influences GBM autophagy and malignancy, and whose therapeutic targeting enhances the anti-tumor effects of radiotherapy., • MST4 kinase regulates the growth, sphere formation, and tumorigenicity of GBM cells • MST4 stimulates autophagy by activating ATG4B through phosphorylation of ATG4B S383 • Radiation increases MST4 expression and ATG4B phosphorylation, inducing autophagy • Inhibiting ATG4B enhances the anti-tumor effects of radiotherapy in GBM PDX models , Huang et al. show that radiation induces MST4 expression and that MST4 phosphorylates ATG4B at serine 383, which increases ATG4B activity and autophagic flux. Inhibition of ATG4B reduces autophagy and tumorigenicity of glioblastoma (GBM) cells and improves the impact of radiotherapy on GBM growth in mice

Stemness Analysis Uncovers That The Peroxisome Proliferator-Activated Receptor Signaling Pathway Can Mediate Fatty Acid Homeostasis In Sorafenib-Resistant Hepatocellular Carcinoma Cells

Hepatocellular carcinoma (HCC) stem cells are regarded as an important part of individualized HCC treatment and sorafenib resistance. However, there is lacking systematic assessment of stem-like indices and associations with a response of sorafenib in HCC. Our study thus aimed to evaluate the status of tumor dedifferentiation for HCC and further identify the regulatory mechanisms under the condition of resistance to sorafenib. Datasets of HCC, including messenger RNAs (mRNAs) expression, somatic mutation, and clinical information were collected. The mRNA expression-based stemness index (mRNAsi), which can represent degrees of dedifferentiation of HCC samples, was calculated to predict drug response of sorafenib therapy and prognosis. Next, unsupervised cluster analysis was conducted to distinguish mRNAsi-based subgroups, and gene/geneset functional enrichment analysis was employed to identify key sorafenib resistance-related pathways. In addition, we analyzed and confirmed the regulation of key genes discovered in this study by combining other omics data. Finally, Luciferase reporter assays were performed to validate their regulation. Our study demonstrated that the stemness index obtained from transcriptomic is a promising biomarker to predict the response of sorafenib therapy and the prognosis in HCC. We revealed the peroxisome proliferator-activated receptor signaling pathway (the PPAR signaling pathway), related to fatty acid biosynthesis, that was a potential sorafenib resistance pathway that had not been reported before. By analyzing the core regulatory genes of the PPAR signaling pathway, we identified four candidate target genes, retinoid X receptor beta (RXRB), nuclear receptor subfamily 1 group H member 3 (NR1H3), cytochrome P450 family 8 subfamily B member 1 (CYP8B1) and stearoyl-CoA desaturase (SCD), as a signature to distinguish the response of sorafenib. We proposed and validated that the RXRB and NR1H3 could directly regulate NR1H3 and SCD, respectively. Our results suggest that the combined use of SCD inhibitors and sorafenib may be a promising therapeutic approach

Contribution of the Argonaute-1 Isoforms to Invertebrate Antiviral Defense

<div><p>Argonaute (Ago) protein, the central component of the RNA interference (RNAi) pathway, plays important roles in host innate antiviral immunity. Most organisms harbor a large number of different Ago proteins and isoforms; however, the roles of Ago isoforms in immune defense against pathogens remain unclear. In the present study, three Argonaute-1 (Ago1) isoforms, termed Ago1A, Ago1B, and Ago1C, were found in <em>Marsupenaeus japonicus</em> shrimp. Quantitative real-time PCR (polymerase chain reaction) revealed that isoforms Ago1A and Ago1B containing an insertion sequence in the PIWI domain, were significantly up-regulated in lymphoid organ and hemolymph, and also upon white spot syndrome virus (WSSV) challenge, indicating the involvement of Ago1A and Ago1B in antiviral immunity. The results showed that silencing of Ago1A with a sequence-specific siRNA led to a significant increase of WSSV loads. It was revealed that knockdown of Ago1B mRNA by 37–70% resulted in higher virus loads in shrimp. However, upon silencing Ago1B by more than 85%, a two-fold increase in Ago1A mRNA was observed but viral load was the same as untreated controls challenged with WSSV, suggesting that the simultaneous up-regulation of Ago1A might compensate for the loss of Ago1B. These data indicated that Ago1A played more important roles in the antiviral immune response than Ago1B. The simultaneous inhibition of Ago1A and Ago1B resulted in a greater increase in viral loads than Ago1A or Ago1B alone, indicating that Ago1A and Ago1B isoforms were involved in shrimp antiviral immunity. It was revealed that Ago1C had no effect on virus infection. Therefore, the current study presented the first report on the contribution of Ago isoforms in the invertebrate defense against virus infection.</p> </div

Identification of shrimp Ago1 isoforms.

<p>Schematic diagram of three isoforms (Ago1A, Ago1B, and Ago1C) of shrimp Ago1 gene. The numbers show the sites of Ago1-fragment 1 and Ago1-fragment 2 in Ago1.</p

Amino acid alignments of shrimp Ago1 isoforms and Ago homologs from other species.

<p>The conserved PAZ and PIWI domains were boxed. Amino acid differences between shrimp Ago1 isoforms were highlighted with asterisks. <i>Homo sapiens</i>, Hs Ago1 (GenBank accession no. NP_036331.1); <i>Mus musculus</i>, Mm Ago1 (AAI29916.1); <i>Tribolium castaneum</i>, Tc Ago1 (XP_971295.2); <i>Bombyx mori</i>, Bm Ago1 (NP_001095931.1); <i>Drosophila melanogaster</i>, Dm Ago1 (NP_725341.1); Dm Ago2 (NP_Q9VUQ5); <i>Apis mellifera</i> Am Ago1 (XP_624444.3); <i>Litopenaeus vannamei</i>, Lv Ago1 (NP_ADK25180.1); Lv Ago2 (NP_ADK25181.1); <i>Marsupenaeus japonicus</i>, Mj Ago1.</p

Specificities of siRNAs targeting Ago1 isoforms.

<p>S2 cells were transiently co-transfected with the Flag-tagged Ago1 isoform constructs and the isoform-specific siRNAs. At 48 h after transfection, cell lysates were analyzed using western blot with anti-FLAG antibody. The β-actin was used as a control. Lane headings showed the FLAG-tagged Ago1 isoforms and the isoform-specific siRNAs. The Ago1A/B-siRNA could specifically target both Ago1A and Ago1B. The antibodies used were indicated on the left.</p