Two types of generalized integrable decompositions and new solitary-wave solutions for the modified Kadomtsev-Petviashvili equation with symbolic computation

The modified Kadomtsev-Petviashvili (mKP) equation is shown in this paper to be decomposable into the first two soliton equations of the 2N-coupled Chen-Lee-Liu and Kaup-Newell hierarchies by respectively nonlinearizing two sets of symmetry Lax pairs. In these two cases, the decomposed (1+1)-dimensional nonlinear systems both have a couple of different Lax representations, which means that there are two linear systems associated with the mKP equation under the same constraint between the potential and eigenfunctions. For each Lax representation of the decomposed (1+1)-dimensional nonlinear systems, the corresponding Darboux transformation is further constructed such that a series of explicit solutions of the mKP equation can be recursively generated with the assistance of symbolic computation. In illustration, four new families of solitary-wave solutions are presented and the relevant stability is analyzed.Comment: 23 page

Effects of Yulin Tong Bu formula on modulating gut microbiota and fecal metabolite interactions in mice with polycystic ovary syndrome

BackgroundPolycystic ovarian syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism, ovarian dysfunction and polycystic ovarian morphology. Gut microbiota dysbiosis and metabolite are associated with PCOS clinical parameters. Yulin Tong Bu formula (YLTB), a traditional Chinese medicine formula, has been recently indicated to be capable of ameliorating polycystic ovary symptoms and correcting abnormal glucose metabolism. However, the therapeutic mechanism of YLTB on PCOS has not been fully elucidated.MethodsA pseudo sterile mouse model was established during this four-day acclimatization phase by giving the animals an antibiotic cocktail to remove the gut microbiota. Here, the therapeutic effects of YLTB on PCOS were investigated using dehydroepiandrosterone plus high-fat diet-induced PCOS mice model. Female prepuberal mice were randomly divided into three groups; namely, the control group, PCOS group and YLTB (38.68 g·kg-1·day-1) group. To test whether this effect is associated with the gut microbiota, we performed 16S rRNA sequencing studies to analyze the fecal microbiota of mice. The relationships among metabolites, gut microbiota, and PCOS phenotypes were further explored by using Spearman correlation analysis. Then, the effect of metabolite ferulic acid was then validated in PCOS mice.ResultsOur results showed that YLTB treatment ameliorated PCOS features (ovarian dysfunction, delayed glucose clearance, decreased insulin sensitivity, deregulation of glucolipid metabolism and hormones, etc.) and significantly attenuated PCOS gut microbiota dysbiosis. Spearman correlation analysis showed that metabolites such as ferulic acid and folic acid are negatively correlated with PCOS clinical parameters. The effect of ferulic acid was similar to that of YLTB. In addition, the bacterial species such as Bacteroides dorei and Bacteroides fragilis were found to be positively related to PCOS clinical parameters, using the association study analysis.ConclusionThese results suggest that YLTB treatment systematically regulates the interaction between the gut microbiota and the associated metabolites to ameliorate PCOS, providing a solid theoretical basis for further validation of YLTB effect on human PCOS trials

Assessing the Effect of Simultaneous Combining of Transcranial Direct Current Stimulation and Transcutaneous Auricular Vagus Nerve Stimulation on the Improvement of Working Memory Performance in Healthy Individuals

A previous study found that combining transcranial direct current stimulation (tDCS) and transcutaneous auricular vagus nerve stimulation (taVNS) could evoke significantly larger activation on a range of cortical and subcortical brain regions than the numerical summation of tDCS and taVNS effects. In this study, two within-subject experiments were employed to investigate its effects on working memory (WM). In experiment 1, the WM modulatory effects of tDCS over the left dorsolateral prefrontal cortex (DLPFC), taVNS, and simultaneous joint simulation of tDCS over the left DLPFC and taVNS (SJS-L) were compared among 60 healthy subjects. They received these three interventions between the baseline test and post-test in a random manner three times. In spatial 3-back task, there was a significant interaction between time and stimulations in the accuracy rate of matching trials (mACC, p=0.018). MACCs were significantly improved by SJS (p = 0.001) and taVNS (p = 0.045), but not by tDCS (p = 0.495). Moreover, 41 subjects in the SJS group showed improvement, which was significantly larger than that in the taVNS group (29 subjects) and tDCS group (26 subjects). To further investigate the generalization effects of SJS, 72 students were recruited in experiment 2. They received tDCS over the right DLPFC, taVNS, simultaneous joint simulation of tDCS over the right DLPFC and taVNS (SJS-R), and sham stimulation in a random manner four times. No significant results were found, but there was a tendency similar to experiment 1 in the spatial 3-back task. In conclusion, combining tDCS and taVNS might be a potential non-invasive neuromodulation technique which is worthy of study in future

KLF2 is a clinical diagnostic and treatment biomarker of breast cancer

Background: As a highly prevalent malignancy among women worldwide, breast cancer, remains a critical public health issue necessitating the development of novel therapeutics and biomarkers. Kruppel Like Factor 2 (KLF2), a member of the Kruppel family of transcription factors, has been implicated in various types of cancer due to its diminished expression; however, the potential implications of KLF2 expression in relation to breast cancer progression, prognosis, and therapy remain unclear.Methods: The present study employed the Tumor Immune Estimation Resource (TIMER) and The Human Protein Atlas databases to investigate the expression pattern of KLF2 in pan-cancer. The relationship between KLF2 expression and clinical features or immune infiltration of The Cancer Genome Atlas (TCGA) breast cancer samples was evaluated using Breast Cancer Integrative Platform (BCIP) and TIMER. The expression levels of KLF2 in breast cancer were validated via immunohistochemical staining analysis. Gene Set Enrichment Analysis (GSEA) to study the KLF2-related gene ontology. STRING database was employed to construct a protein-protein interaction (PPI) network of KLF2 in relation to vascular endothelial growth factor A (VEGFA) and hypoxia-inducible factor 1α (HIF1α). The expression of KLF2 following diverse breast cancer therapies was analyzed in the Gene Expression Omnibus (GEO) databases. The expression of KLF2 following treatment with simvastatin was validated via immunofluorescence and western blotting.Results: Our study reveals that KLF2 displays significantly reduced expression in cancerous tissues compared to non-cancerous controls. Patients with low KLF2 expression levels exhibited poor prognosis across multiple cancer types. KLF2 expression levels were found to be reduced in advanced cancer stages and grades, while positively correlated with the expression of estrogen receptor (ER), progesterone receptor (PR), and tumor size in breast cancer. KLF2 expression is associated with diverse immune infiltration cells, and may impact the breast tumor immune microenvironment by regulating dendritic cell activation. Additionally, we observed a negative correlation between KLF2 expression levels and angiogenesis, as well as the expression of VEGFA and HIF1α. Notably, the anticancer drug simvastatin could induce KLF2 expression in both breast cancer.Conclusion: Based on our observations, KLF2 has potential as a diagnostic, prognostic, and therapeutic biomarker for breast cancer

Design, synthesis, cytotoxic activity and molecular docking studies of new 20(S)-sulfonylamidine camptothecin derivatives

20(S)-Sulfonylamidine CPT-derivatives were prepared and tested for cytotoxicity.Several analogs showed superior cytotoxic activity compared to irinotecan.Key structural features related to cytotoxicity were identified by SAR analysis.Compounds 9 and 15c interacted with Topo I-DNA by a different binding mode from CPT.These compounds are new generation CPT-derived antitumor agents.In an ongoing investigation of 20-sulfonylamidine derivatives (9, YQL-9a) of camptothecin (1) as potential anticancer agents directly and selectively inhibiting topoisomerase (Topo) I, the sulfonylamidine pharmacophore was held constant, and a camptothecin derivatives with various substitution patterns were synthesized. The new compounds were evaluated for antiproliferative activity against three human tumor cell lines, A-549, KB, and multidrug resistant (MDR) KB subline (KBvin). Several analogs showed comparable or superior antiproliferative activity compared to the clinically prescribed 1 and irinotecan (3). Significantly, the 20-sulfonylamidine derivatives exhibited comparable cytotoxicity against KBvin, while 1 and 3 were less active against this cell line. Among them, compound 15c displayed much better cytotoxic activity than the controls 1, 3, and 9. Novel key structural features related to the antiproliferative activities were identified by structure–activity relationship (SAR) analysis. In a molecular docking model, compounds 9 and 15c interacted with Topo I-DNA through a different binding mode from 1 and 3. The sulfonylamidine side chains of 9 and 15c could likely form direct hydrogen bonds with Topo I, while hydrophobic interaction with Topo I and π–π stacking with double strand DNA were also confirmed as binding driving forces. The results from docking models were consistent with the SAR conclusions. The introduction of bulky substituents at the 20-position contributed to the altered binding mode of the compound by allowing them to form new interactions with Topo I residues. The information obtained in this study will be helpful for the design of new derivatives of 1 with most promising anticancer activity.CPT (green), 9 (magenta), and 15c (blue) in the binding site of DNA-Topo-I

Synthesis of novel spin-labeled derivatives of 5-FU as potential antineoplastic agents

Chemotherapy is a general treatment option for various cancers, including lung cancer. In order to find compounds with superior bioactivity and less toxicity against lung cancer, novel spin-labeled 5-fluorouracil (5-FU) derivatives (3a–f) were synthesized and evaluated against four human tumor cell lines (A-549, DU-145, KB, and KBvin). Two promising compounds 3d and 3f exhibited IC50 values of 2.76 and 2.38 μM, respectively, against non-small cell lung carcinoma cell line A-549. These compounds were twofold more cytotoxic than 5-FU and less toxic against other tested cell lines. Compound 3f exhibited seven times more selective cytotoxicity against A-549 than 5-FU. Our results suggest that compounds 3d and 3f merit further investigation for development into clinical trial candidates for non-small cell lung cancer

Most Lithium-rich Low-mass Evolved Stars Revealed as Red Clump stars by Asteroseismology and Spectroscopy

Lithium has confused scientists for decades at almost each scale of the universe. Lithium-rich giants are peculiar stars with lithium abundances over model prediction. A large fraction of lithium-rich low-mass evolved stars are traditionally supposed to be red giant branch (RGB) stars. Recent studies, however, report that red clump (RC) stars are more frequent than RGB. Here, we present a uniquely large systematic study combining the direct asteroseismic analysis with the spectroscopy on the lithium-rich stars. The majority of lithium-rich stars are confirmed to be RCs, whereas RGBs are minor. We reveal that the distribution of lithium-rich RGBs steeply decline with the increasing lithium abundance, showing an upper limit around 2.6 dex, whereas the Li abundances of RCs extend to much higher values. We also find that the distributions of mass and nitrogen abundance are notably different between RC and RGB stars. These findings indicate that there is still unknown process that significantly affects surface chemical composition in low-mass stellar evolution.Comment: 27 pages, 10 figures, 3 table

Several Polymorphisms of KCNQ1 Gene Are Associated with Plasma Lipid Levels in General Chinese Populations

BACKGROUND: Potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) is thought to be an important candidate gene of diabetes. Several single nucleotide polymorphisms (SNPs) in a 40-kb linkage disequilibrium (LD) block in its intron 15 have been identified to be associated with diabetes in East Asian populations in recent genome-wide association studies. The aim of this study was to investigate whether KCNQ1 polymorphisms influence the levels of the metabolic phenotypes in general Chinese populations. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the associations of two SNPs (rs2237892 and rs2237895) in the aforementioned 40-kb LD block, a missense variant rs12720449 (P448R) in exon 10, and a synonymous variant rs1057128 (S546S) in exon 13 with metabolic phenotypes in a Uyghur population (n = 478) and replicated these associations in a Han population (n = 2,485). We found that rs2237892-T allele was significantly associated with decreased triglyceride levels (p(combined) = 0.001). The minor G allele of the rs12720449, with sharp difference of the allelic frequency between European and East Asian populations (0.2% versus 14%, respectively), was associated with a lower triglyceride levels than G allele in Uyghur subjects (p = 0.004), in Han subjects (p = 0.052), and in subjects of meta-analysis (p(combined) = 0.001). Moreover, the minor A allele of the rs1057128 was also associated with decreased triglyceride levels in meta-analysis (p(combined) = 0.010). CONCLUSIONS: To the best of our knowledge, this is the first report associating a missense mutation of KCNQ1, rs12720449, with triglyceride levels. Rs2237892, representing the 40-kb LD block, is also associated with triglyceride levels in Han population. Further studies are required to replicate these findings in other East Asian populations