Precision and Robust Models on Healthcare Institution Federated Learning for Predicting HCC on Portal Venous CT Images.

Hepatocellular carcinoma (HCC), the most common type of liver cancer, poses significant challenges in detection and diagnosis. Medical imaging, especially computed tomography (CT), is pivotal in non-invasively identifying this disease, requiring substantial expertise for interpretation. This research introduces an innovative strategy that integrates two-dimensional (2D) and three-dimensional (3D) deep learning models within a federated learning (FL) framework for precise segmentation of liver and tumor regions in medical images. The study utilized 131 CT scans from the Liver Tumor Segmentation (LiTS) challenge and demonstrated the superior efficiency and accuracy of the proposed Hybrid-ResUNet model with a Dice score of 0.9433 and an AUC of 0.9965 compared to ResNet and EfficientNet models. This FL approach is beneficial for conducting large-scale clinical trials while safeguarding patient privacy across healthcare settings. It facilitates active engagement in problem-solving, data collection, model development, and refinement. The study also addresses data imbalances in the FL context, showing resilience and highlighting local models' robust performance. Future research will concentrate on refining federated learning algorithms and their incorporation into the continuous implementation and deployment (CI/CD) processes in AI system operations, emphasizing the dynamic involvement of clients. We recommend a collaborative human-AI endeavor to enhance feature extraction and knowledge transfer. These improvements are intended to boost equitable and efficient data collaboration across various sectors in practical scenarios, offering a crucial guide for forthcoming research in medical AI.

Design, synthesis, and evaluation of VHL-based EZH2 degraders for breast cancer.

EZH2 (enhancer of zeste homolog 2) is one of the most important histone methyltransferases (HMTs), and overexpression of EZH2 can lead to proliferation, migration and angiogenesis of tumor cells. But most of EZH2 inhibitors are only effective against some hematologic malignancies and have poor efficacy against solid tumors. Here, we report the design, synthesis, and evaluation of highly potent proteolysis targeting chimeric (PROTACs) small molecules targeting EZH2. We developed a potent and effective EZH2 degrader P4, which effectively induced EZH2 protein degradation and inhibited breast cancer cell growth. Further studies showed that P4 can significantly decrease the degree of H3K27me3 in MDA-MB-231 cell line, induce apoptosis and G0/G1 phase arrest in Pfeiffer and MDA-MB-231 cell lines. Therefore, P4 is a potential anticancer molecule for breast cancer treatment.

Design, synthesis and biological evaluation of pyrimidine base hydroxamic acid derivatives as dual JMJD3 and HDAC inhibitors.

The Jumonji domain-containing protein demethylase 3 (JMJD3) and histone deacetylase (HADC) are related to various cancers and regard as antitumor targets for drug discovery. In this study, based on rational drug design strategy, we designed and synthesized a series of pyrimidine derivatives with hydroxamic acid as novel dual JMJD3 and HDAC inhibitors for synergistic cancer treatment. Compound A5b exhibited inhibitory potency against JMJD3 and HDAC1/6 simultaneously and favorable cytotoxicity against human cancer cells such as A549 and U937. Furthermore, mechanistic studies showed that A5b treatment in A549 cells increased the hypermethylation of histone H3K27 and hyperacetylation of H3K9, suppressed clonogenicity, migration and invasion of cancer cells. Besides, A5b induced apoptosis via the cleavage of caspase-7 and PARP, and G1 cell cycle arrest via upregulated p21 expression. All these results suggested that A5b was the first dual inhibitor against JMJD3 and HDAC and can be a potential compound for cancer therapy.

Decontamination of mustard sulfur and VX by sodium percarbonate complexed with 1-acetylguanidine as a novel activator.

The peroxide-based decontaminants had attracted great attention for degradation of chemical warfare agents (CWAs) because of their high performance, non-corrosive and environmental-friendly merits. Hydrogen peroxide can be activated by some organic activators to enhance the oxidation ability. In this work, a novel formula based on sodium percarbonate (SPC) complexed with 1-acetylguanidine (ACG) was investigated for decontamination of sulfur mustard (HD) and VX as CWAs. In the experimental results, the active species acetyl peroxide imide acid in the formula aqueous solution was detected in situ by Raman and 13C NMR spectroscopy. The optimized conditions of the decontamination formula (SPC/ACG) were suggested that, the molar ratio of active oxygen and activator ([O]/[ACG]) was 1:1 while the pH value of the formula aqueous solution was about 9. To achieve the decontamination percentage over 99%, the molar ratio of active oxygen to CWA ((O)/(CWA)) needed to be at least 3 for HD and 7 for VX. Meanwhile, the degradation products detected by gas chromatography/mass spectrometry (GC/MS), liquid chromatography/mass spectrometry (LC/MS) and ion chromatography (IC) indicated that the oxidation and elimination reactions should have occurred on HD molecule, while the degradation of VX mainly originate from the nucleophilic substitution and oxidation reactions.

Discovery of triazolo [1,5-a] pyridine derivatives as novel JAK1/2 inhibitors.

Small molecule JAK inhibitors have been demonstrated efficacy in rheumatoid arthritis, inflammatory bowel disease, and psoriasis with the approval of several drugs. Aiming to develop potent JAK1/2 inhibitors, two series of triazolo [1,5-a] pyridine derivatives were designed and synthesized by various strategies. The pharmacological results identified the optimized compounds J-4 and J-6, which exerted high potency against JAK1/2, and selectivity over JAK3 in enzyme assays. Furthermore, J-4 and J-6 effectively suppressed proliferation of JAK1/2 high-expression BaF3 cells accompanied with acceptable metabolic stability in liver microsomes. Therefore, J-4 and J-6 might serve as promising JAK1/2 inhibitors for further investigation.

Identification of new defective interfering RNA species associated with porcine reproductive and respiratory syndrome virus infection.

In the present study, seven new defective interfering (DI) RNA species of porcine reproductive and respiratory syndrome virus (PRRSV) were identified. RT-PCR, Northern blot and sequence analyses indicated that these DI RNA specie have deletions of 8513-9176 nucleotides located between Nsp1/Nsp2 and Nsp10. Compared with the previous DI RNAs of PRRSV reported, they have three distinct characteristics: much smaller deletion sizes; different nucleotide repeats (2-12nt) used in the junction sites and in-frame deletions. The results further suggested that the similarity-assisted RNA recombination may be the main cause of generation of DI RNAs in PRRSV and probably in other arteriviruses.

Successful medical treatment of spinal epidural abscess.

Spinal epidural abscess is a rare but potentially fatal disease. A 67-year-old female suffered fever and painful swelling of the right knee and lower leg for one week. Both synovial fluid and blood cultures yielded methicillin-sensitive Staphylococcus aureus. Low back pain developed and fever was sustained despite the administration of intravenous oxacillin. Magnetic resonance imaging (MRI) of the thoracolumbar spine revealed spinal epidural abscess from T12 to S1. Because of severe hypoalbuminemia and general anasarca and followed by exploratory laparotomy for massive duodenal bleeding, she did not receive surgical intervention for the spinal epidural abscess. After intravenous administration of oxacillin 2 g 4-hourly for 12 weeks, she recovered and follow-up MRI confirmed the efficacy of the medical treatment. She remained well at 1-year follow-up. In a patient with minimal neurological deficit or surgical contraindication, spinal epidural abscess can be successfully treated with a medical regimen.