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CoSPlay: Cooperative Self-Play at Test-Time with Self-Generated Code and Unit Test
Machine learning-based identification of key genes underlying sex differences in hepatocellular carcinoma and targeted drug screening
Biomed Rep. 2026 Apr 24;24(6):74. doi: 10.3892/br.2026.2147. eCollection 2026 Jun.
ABSTRACT
Hepatocellular carcinoma (HCC) shows a marked predominance in men, yet the molecular basis for this sex disparity remains unclear. The present study leveraged multi-omics data and machine learning algorithms to identify key genes associated with sex-specific differences in HCC and to screen for putative candidate compounds, aiming to provide new insights for sex-specific therapy. The mRNA expression data of male and female patients with HCC and paracancerous tissues were obtained from the GEO and TCGA databases. To mitigate overfitting, data were partitioned into independent training and testing sets. Candidate genes were screened by differential expression analysis and weighted gene co-expression network analysis. A total of four complementary algorithms, random forest, support vector machines, generalized linear models and extreme gradient boosting were used to identify key genes with high predictive capability. CYP17A1 and IRX3 were identified as the top differentially expressed core genes associated with HCC in men. Pan-cancer analysis showed that CYP17A1 was lowly expressed in the majority of tumors, but significantly highly expressed in HCC, rectal adenocarcinoma and gastric cancer (P<0.001). Functional cell-based assays showed that knockout of CYP17A1 inhibited the proliferation, migration and invasion ability of HCC cells (P<0.001). Immunohistochemistry showed that CYP17A1 protein expression was significantly increased in HCC tissues from male patients when compared with that in paracancerous tissues (P<0.001), whereas there was no significant difference in female patient tissues (P>0.05). Notably, while IRX3 was identified computationally, its functional role remains to be experimentally validated. Molecular docking predicted a potential interaction between the natural compound Saikosaponin A and the CYP17A1 protein, and cellular assays revealed that it dose-dependently inhibits HCC cell malignant phenotypes. The present study suggests that CYP17A1 is associated with sex differences in HCC, potentially via the androgen signaling axis. Furthermore, IRX3 emerges as a novel hypothesis-generating candidate gene. Finally, the findings of the present study highlight Saikosaponin A as a putative therapeutic candidate for male patients with HCC, warranting further target-dependency investigations.
PMID:42125766 | PMC:PMC13158723 | DOI:10.3892/br.2026.2147
Effect of the Maxing Huoqiao granule on nonsevere community-acquired pneumonia: A multicenter, double-blind, placebo-controlled randomized trial
Pharmacol Res. 2026 Apr 9:108186. doi: 10.1016/j.phrs.2026.108186. Online ahead of print.
ABSTRACT
Community-acquired pneumonia (CAP) remains a major global public health challenge with substantial morbidity and mortality. Although preclinical studies suggest that Maxing Huoqiao (MXHQ) granule may have therapeutic potential for pneumonia, high-quality clinical evidence is still limited. We conducted a multicenter, double-blind, randomized, placebo-controlled trial at two tertiary hospitals in China to evaluate the clinical efficacy of MXHQ as adjunctive therapy and to explore its potential mechanisms in adults with nonsevere CAP receiving standard moxifloxacin treatment. A total of 96 patients were enrolled and randomized (1:1:1) to receive standard-dose MXHQ, low-dose MXHQ, or placebo in addition to moxifloxacin for 7 days, with a 14-day follow-up. The primary endpoint was clinical cure, defined as composite recovery of major respiratory symptoms, lung rales, and fever; secondary endpoints included symptom relief, radiographic improvement, and safety. Compared with placebo, standard-dose MXHQ was associated with a higher day-14 clinical cure rate (30.78% vs. 68.97%; RR = 0.45, 95% CI = 0.24-0.83; P < 0.01). Furthermore, the standard-dose intervention was correlated with a shorter time to relief and recovery of cough and sputum (P < 0.05), as well as improvements in symptom scores (P < 0.05) and promoting lesion absorption on chest CT (P < 0.05). Low-dose MXHQ showed no significant clinical benefit, whereas safety profiles were comparable across all groups. Transcriptomic analyses of peripheral blood mononuclear cells, complemented by a Streptococcus pneumonia animal model, indicated that the clinical benefits of MXHQ are linked to the modulation of inflammation and innate immunity. These omics and in vivo observations suggest a potential mechanism underlying the protective effects of MXHQ against inflammatory injury and promotion of tissue repair, involving the regulation of anti-inflammatory mediators and tissue repair-related factors. (Chictr.org.cn, ID Number: ChiCTR2400082095).
PMID:41966499 | DOI:10.1016/j.phrs.2026.108186
Beyond Retrieval: Modeling Confidence Decay and Deterministic Agentic Platforms in Generative Engine Optimization
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Lightweight liquid neural networks decipher salivary metabolic fingerprinting for high-risk periodontitis screening in diabetes
npj Digital Medicine, Published online: 07 April 2026; doi:10.1038/s41746-026-02593-7
Lightweight liquid neural networks decipher salivary metabolic fingerprinting for high-risk periodontitis screening in diabetesHoloTrauma 3X Triadic AI Co reasoning for robot assisted emergency maxillofacial reconstruction
npj Digital Medicine, Published online: 04 April 2026; doi:10.1038/s41746-026-02573-x
HoloTrauma 3X Triadic AI Co reasoning for robot assisted emergency maxillofacial reconstructionStrand-asymmetric G-runs and G4s downstream of TSS modulate tumor suppressor gene transcription
Oncogene, Published online: 02 April 2026; doi:10.1038/s41388-026-03761-5
Strand-asymmetric G-runs and G4s downstream of TSS modulate tumor suppressor gene transcriptionXuanwu: Evolving General Multimodal Models into an Industrial-Grade Foundation for Content Ecosystems
Incorporating LLM Embeddings for Variation Across the Human Genome
DNA damage burden causes selective CUX2 neuron loss in neuroinflammation
Nature, Published online: 01 April 2026; doi:10.1038/s41586-026-10310-3
DNA damage burden and inadequate repair in CUX2+ cortical layer 2/3 excitatory neurons contributes to selective vulnerability in neuroinflammatory injury.MKA: Memory-Keyed Attention for Efficient Long-Context Reasoning
tRF-3005a regulates exon skipping of SPAG4 by interacting with RALY to drive gastric cancer progression
Cell Death Discovery, Published online: 24 March 2026; doi:10.1038/s41420-026-03049-3
tRF-3005a regulates exon skipping of SPAG4 by interacting with RALY to drive gastric cancer progressionThinking in Streaming Video
CoCo: Code as CoT for Text-to-Image Preview and Rare Concept Generation
Dial: A Knowledge-Grounded Dialect-Specific NL2SQL System
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Effects of daily multivitamin–multimineral and cocoa extract supplementation on epigenetic aging clocks in the COSMOS randomized clinical trial
Nature Medicine, Published online: 09 March 2026; doi:10.1038/s41591-026-04239-3
In a prespecified ancillary analysis of the COSMOS randomized trial, supplementation with daily multivitamins, but not with cocoa extract, over the course of 2 years decreased biological aging, as measured by epigenetic aging clocks.