SH-U-454

Hypoxia-Induced ADAM23 Drives Neuron-Tumor Crosstalk and Therapeutic Resistance in Hepatocellular Carcinoma.

Park Taehyun T, Kim Soeun S, Cho Hyunjung H, Nam Johyeon J et al.

Hypoxia and nutrient deprivation are fundamental drivers of tumor aggressiveness and therapeutic resistance in hepatocellular carcinoma (HCC). While the involvement of neural components in the tumor microenvironment (TME) is increasingly recognized, the molecular transducers linking metabolic stress to neuron-tumor crosstalk remain elusive. Here, we identify ADAM23 (A disintegrin and metalloproteinase 23) as a hypoxia-responsive mediator that mediates communication between HCC cells and neuronal cells. ADAM23 expression was markedly upregulated in HCC cells under both chemical (CoCl2) and physical hypoxia (1% O2), a process further amplified by glucose deprivation and directly modulated by HIF-1α. Functional assays revealed that ADAM23 overexpression promotes epithelial-mesenchymal transition (EMT) and enhances cell viability under metabolic stress. Notably, sorafenib-resistant HCC cells (Huh7SR) exhibited high levels of ADAM23 secretion, which triggered proliferative and metabolic activation in neuronal SH-SY5Y cells. In 3D co-culture spheroid models, Huh7SR cells mixed with SH-SY5Y cells displayed significantly larger spheroid volumes and enhanced neuronal fluorescence compared with parental controls, suggesting that ADAM23-mediated interactions facilitate a supportive neural niche. Analysis of The Cancer Genome Atlas (TCGA) datasets and patient microarrays confirmed that ADAM23 is significantly overexpressed in HCC and positively correlates with HIF-1α expression. Moreover, elevated expression of ADAM23 was significantly correlated with poor overall survival. Collectively, our findings underscore ADAM23 as a critical metabolic-neural linker that promotes HCC progression and drug resistance. These findings suggest that the ADAM23-mediated neuron-tumor axis may represent a potential therapeutic target in aggressive HCC.

Author Correction - with Update (U+C): Miniature and versatile genome regulation TnpB-ωRNA toolkits facilitate cancer immunotherapy.

Lu Junlin J, Lai Jiajian J, Cheng Liang L, Zhan Hengji H et al.

Severe PTSD symptoms magnify episodic memory-encoding deficits and amygdala-ACC attenuation during unpredictable threat in male combat veterans.

Aberg Kristoffer C KC, Efrati Shai S, Idan Sagi S, Merzbach Rachel R et al.

PTSD is marked by atypical coupling between emotion and learning, yet it remains unclear how threat that is situational (the presence of potential danger) shapes episodic memory. We investigated whether unpredictability-driven threat alters incidental memory formation as a function of PTSD symptom severity (PTSDss). Sixty male combat veterans underwent fMRI scanning during incidental encoding of everyday objects presented under unpredictable threat (U), predictable threat (P), or no threat (N). Threat was operationalized as potential exposure to a highly aversive sound. An unexpected recognition test followed 90 min later. We related memory (hit rates), subjective anxiety, and encoding-related BOLD activity to PTSDss assessed with CAPS-5. Greater PTSDss predicted heightened anxiety and poorer memory for items specifically presented under unpredictable threat. While amygdala and dorsal anterior cingulate activity during encoding tracked overall memory success, these responses were attenuated with increasing PTSDss in the U condition. By linking unpredictable threat to both behavioral and neural markers of disrupted episodic memory encoding, the study helps explain how memory-related symptoms may develop and persist in PTSD.

Comparative chloroplast genomics of six Bupleurum (Apiaceae) accessions: candidate barcodes, phylogeny based on available plastomes, and candidate RNA-editing sites.

He Yujie Y, Wu Mingxuan M, Wang Aohan A, Gao Chengwen C

Bupleurum L. (Apiaceae), a taxonomically intricate genus of about 190 species and a source of Radix Bupleuri (Chai Hu), is difficult to discriminate because of convergent morphology, infraspecific variation, and limited genomic sampling. This study aimed to characterize plastome variation, identify and validate candidate molecular markers, reconstruct plastid phylogenetic relationships, and assess candidate plastid RNA-editing sites in Bupleurum. We assembled six plastomes from subgenus Bupleurum, screened 51 Bupleurum plastomes for diagnostic loci, reconstructed whole-plastome and partitioned protein-coding-sequence phylogenies, and predicted plastid C-to-U RNA-editing candidates across the six newly assembled plastomes using a PREP-Cp-compatible workflow. Candidate barcode performance was evaluated against the reference plastome phylogenies, and codon-based models were used to test for positive selection. The plastomes were 154,496-155,778 bp with the canonical quadripartite structure and GC contents of 37.67-37.73%. Gene content was stable (131-132 genes; 86-87 protein-coding genes); B. falcatum subsp. cernuum lacked ycf15 but contained an additional inverted-repeat-associated ycf1 annotation. A/U-ending synonymous codons were favoured. Finite pairwise Ka/Ks estimates were below 1 for most genes, and site-specific codon models detected no positive selection. Each plastome contained 55-61 pure microsatellites, dominated by A/T mononucleotide motifs. MarkerSeek ranked 265 features and identified atpF-atpH, petA-psbJ, rpl32-trnL-UAG, and ycf1 as leading candidate barcodes. ycf1 recovered 38 of 41 nodes strongly supported by both reference trees, whereas a partitioned four-locus analysis recovered 40 of 41 and distinguished all 51 accession sequences. However, only one of seven multi-accession operational binomial groups was monophyletic, and only one showed a positive local barcode gap. The whole-plastome phylogeny recovered Bupleurum as monophyletic relative to Chamaesium. The two sampled Penninervia accessions occupied early-diverging positions without forming an exclusive clade. B. falcatum subsp. cernuum was sister to B. ranunculoides, with B. ranunculoides subsp. telonense sister to that pair. A partitioned 74-CDS analysis recovered the same key relationships and 45 of 50 internal bipartitions. Across the six newly assembled plastomes, 57-63 nonsynonymous C-to-U candidates were predicted per accession (367 total) in 21-22 genes; 269 affected the second codon position and 98 the first. Bupleurum plastomes are structurally conservative but retain localised divergence useful for marker development. Concordant whole-plastome and CDS genealogies support genus monophyly, whereas sparse Penninervia sampling and maternal plastid inheritance preclude rejecting traditional subgeneric classification. The predicted RNA-editing sites represent candidates for future experimental validation rather than an established Bupleurum editome. These genomic resources support authentication, conservation, and evolutionary research in Bupleurum.