Radiofrequency ablation for papillary thyroid microcarcinoma close to the thyroid capsule versus far from the thyroid capsule: a retrospective study

Introduction: The aim of this study was to evaluate the safety and efficacy of ultrasound-guided radiofrequency ablation (RFA) for the management of papillary thyroid microcarcinoma (PTMC) close to the thyroid capsule. Material and methods: This was a retrospective study of 202 patients with PTMC who underwent RFA close to the thyroid capsule and 80 patients with PTMC who underwent RFA far from the thyroid capsule between June 2015 and December 2022. The follow-up time after RFA, change in size of tumour, location, thyroid function, the rates of PTMC disappearance, and complications were evaluated. Results: A total of 202 patients with PTMC close to the thyroid capsule and 80 patients with PTMC far from the thyroid capsule successfully treated with RFA were studied. The thyroid function including free triiodothyronine (fT3), free thyroxine (fT4), triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) showed no changes after RFA for one months in both groups. The tumour size was increased at 1, 3, and 6 months after RFA compared with pre-operative RFA in both groups. The tumour size was decreased at 12 and 24 months after RFA compared with pre-operative RFA both in both group. Seventy-nine PTMC close to the thyroid capsule and 30 PTMC far from the thyroid capsule completely disappeared as assessed by ultrasound examination. Eighty-four PTMC patients close to the thyroid capsule and 34 PTMC patients far from the thyroid capsule had minor complications after RFA treatment. The complication rates between the 2 groups were similar. Conclusion: Ultrasound-guided RFA seems to be an effective and safe method for patients with PTMC close to the thyroid capsule

Widely Targeted Metabolomics Analysis Reveals Key Quality-Related Metabolites in Kernels of Sweet Corn

Sweet corn (Zea mays convar. saccharata var. rugosa) is a major economic vegetable crop. Different sweet corn cultivars vary largely in flavor, texture, and nutrition. The present study performed widely targeted metabolomics analysis based on the HPLC-MS/MS technology to analyze the metabolic profiles in three sweet corn cultivars widely grown in China. A total of 568 metabolites in the three sweet corn cultivars were detected, of which 262 differential metabolites significantly changed among cultivars. Carbohydrates, organic acids, and amino acids were the majority detected primary metabolites. Organic acids were mainly concentrated on shikimate, benzoic acids, and quinic acid with aromatic groups. And the essential amino acids for the human body, methionine and threonine, were highly accumulated in the high-quality cultivar. In addition, phenylpropanoids and alkaloids were the most enriched secondary metabolites while terpenes were low-detected in sweet corn kernels. We found that the flavonoids exist in both free form and glycosylated form in sweet corn kernels. PCA and HCA revealed clear separations among the three sweet corn cultivars, suggesting distinctive metabolome profiles among three cultivars. The differential metabolites were mapped into flavonoid biosynthesis, phenylpropanoid biosynthesis, biosynthesis of amino acids, and other pathways according to the KEGG classification. Furthermore, we identified skimmin, N′,N″-diferuloylspermidine, and 3-hydroxyanthranilic acid as the key quality-related metabolites related to grain quality traits in sweet corn. The results suggested variations of metabolic composition among the three cultivars, providing the reference quality-related metabolites for sweet corn breeding

PBDEs disrupt homeostasis maintenance and regeneration of planarians due to DNA damage, proliferation and apoptosis anomaly

Polybrominated diphenyl ethers (PBDEs) are widely used as brominated flame retardants in the manufacturing industry, belonging to persistent organic pollutants in the environment. Planarians are the freshwater worms, with strong regenerative ability and extreme sensitivity to environmental toxicants. This study aimed to evaluate the potential acute comprehensive effects of PBDE-47/-209 on freshwater planarians. Methods to detect the effects include: detection of oxidative stress, observation of morphology and histology, detection of DNA fragmentation, and detection of cell proliferation and apoptosis. In the PBDE-47 treatment group, planarians showed increased oxidative stress intensity, severe tissue damage, increased DNA fragmentation level, and increased cell proliferation and apoptosis. In the PBDE-209 treatment group, planarians showed decreased oxidative stress intensity, slight tissue damage, almost unchanged DNA fragmentation level and apoptosis, proliferation increased only on the first day after treatment. In conclusion, both PBDE-47 and PBDE-209 are dangerous environmental hazardous material that can disrupt planarians homeostasis, while the toxicity of PBDE-47 is sever than PBDE-209 that PBDE-47 can lead to the death of planarians

Responses of Vaginal Microbiota to Dietary Supplementation with Lysozyme and its Relationship with Rectal Microbiota and Sow Performance from Late Gestation to Early Lactation

This study was conducted to evaluate the effects of dietary lysozyme (LZM) supplementation on the vaginal microbiota, as well as the relationship between vaginal microbiota and the fecal microbiota of rectum and the reproductive performance of the sow. A total of 60 Yorkshire × Landrace sows (3–6 of parity) were arranged from day 85 of gestation to the end of lactation in a completely randomized design with three treatments (control diet, control diet + lysozyme 150 mg/kg, control diet + lysozyme 300 mg/kg). The results showed that sows fed with lysozyme increased serum interleukin-10 (IL-10, p < 0.05) on day 7 of lactation. The vaginal microbiota varied at different taxonomic levels with LZM supplementation by 16S rRNA gene sequencing. The most representative changes included a decrease in Tenericutes, Streptococcus, Bacillus and increase in Bacteroidetes, Actinobacteria, Enterococcus, and Lactobacillus (p < 0.05). There were 777 OTUs existing in both, vaginal and fecal microbiota. The addition of LZM also decreased the abundance of Tenericutes (p < 0.05) in the vagina and feces. The changes in the microbiota were correlated in some cases positively with the performance of the sow, for example, Bacillus in feces was positively correlated with the neonatal weight (p < 0.05). These results indicate that the addition of lysozyme to the diet of sow during perinatal period promote the change of vaginal bacterial community after farrowing. The variations in vaginal microbiota are also associated with the changes in the fecal microbiology of the rectum and the reproductive performance of the sow. Therefore, it is concluded that dietary supplementation with lysozyme in sows in late gestation stage until early lactation, is beneficial to establish vaginal microbiota that seems to promote maternal health and reproductive performance

KinomeMETA: meta-learning enhanced kinome-wide polypharmacology profiling

Kinase inhibitors are crucial in cancer treatment, but drug resistance and side effects hinder the development of effective drugs. To address these challenges, it is essential to analyze the polypharmacology of kinase inhibitor and identify compound with high selectivity profile. This study presents KinomeMETA, a framework for profiling the activity of small molecule kinase inhibitors across a panel of 661 kinases. By training a meta-learner based on a graph neural network and fine-tuning it to create kinase-specific learners, KinomeMETA outperforms benchmark multi-task models and other kinase profiling models. It provides higher accuracy for understudied kinases with limited known data and broader coverage of kinase types, including important mutant kinases. Case studies on the discovery of new scaffold inhibitors for PKMYT1 and selective inhibitors for drug-resistant mutants of FGFRs demonstrate the role of KinomeMETA in virtual screening and kinome-wide activity profiling. Overall, KinomeMETA has the potential to accelerate kinase drug discovery by more effectively exploring the kinase polypharmacology landscape

Research Resource: Genome-Wide Mapping of in Vivo Androgen Receptor Binding Sites in Mouse Epididymis

Epididymal function depends on androgen signaling through the androgen receptor (AR), although most of the direct AR target genes in epididymis remain unknown. Here we globally mapped the AR binding regions in mouse caput epididymis in which AR is highly expressed. Chromatin immunoprecipitation sequencing indicated that AR bound selectively to 19,377 DNA regions, the majority of which were intergenic and intronic. Motif analysis showed that 94% of the AR binding regions harbored consensus androgen response elements enriched with multiple binding motifs that included nuclear factor 1 and activator protein 2 sites consistent with combinatorial regulation. Unexpectedly, AR binding regions showed limited conservation across species, regardless of whether the metric for conservation was based on local sequence similarity or the presence of consensus androgen response elements. Further analysis suggested the AR target genes are involved in diverse biological themes that include lipid metabolism and sperm maturation. Potential novel mechanisms of AR regulation were revealed at individual genes such as cysteine-rich secretory protein 1. The composite studies provide new insights into AR regulation under physiological conditions and a global resource of AR binding sites in a normal androgen-responsive tissue