UFPS: A unified framework for partially annotated federated segmentation in heterogeneous data distribution.

Partially supervised segmentation is a label-saving method based on datasets with fractional classes labeled and intersectant. Its practical application in real-world medical scenarios is, however, hindered by privacy concerns and data heterogeneity. To address these issues without compromising privacy, federated partially supervised segmentation (FPSS) is formulated in this work. The primary challenges for FPSS are class heterogeneity and client drift. We propose a unified federated partially labeled segmentation (UFPS) framework to segment pixels within all classes for partially annotated datasets by training a comprehensive global model that avoids class collision. Our framework includes unified label learning (ULL) and sparse unified sharpness aware minimization (sUSAM) for class and feature space unification, respectively. Through empirical studies, we find that traditional methods in partially supervised segmentation and federated learning often struggle with class collision when combined. Our extensive experiments on real medical datasets demonstrate better deconflicting and generalization capabilities of UFPS.

Quinolone Resistance Genes and Their Contribution to Resistance in Vibrio cholerae Serogroup O139.

BACKGROUND: Quinolones are commonly used for reducing the duration of diarrhea, infection severity, and limiting further transmission of disease related to Vibrio cholerae, but V. cholerae susceptibility to quinolone decreases over time. In addition to mutations in the quinolone-resistance determining regions (QRDRs), the presence of qnr and other acquired genes also contributes to quinolone resistance. RESULTS: We determined the prevalence of quinolone resistance related genes among V. cholerae O139 strains isolated in China. We determined that eight strains carried qnrVC, which encodes a pentapeptide repeat protein of the Qnr subfamily, the members of which protect topoisomerases from quinolone action. Four qnrVC alleles were detected: qnrVC1, qnrVC5, qnrVC12, and qnrVC9. However, the strains carrying qnrVC1, qnrVC5, and qnrVC12 were ciprofloxacin (CIP)-sensitive. Contrastingly, the strain carrying qnrVC9 demonstrated high CIP resistance. qnrVC9 was carried by a small plasmid, which was conjugative and contributed to the high CIP resistance to the receptor V. cholerae strain. The same plasmid was also detected in V. vulnificus. The qnrVC1, qnrVC5, and qnrVC12 were cloned into expression plasmids and conferred CIP resistance on the host V. cholerae O139 strain. CONCLUSIONS: Our results revealed the contribution of quinolone resistance mediated by the qnrVC9 carried on the small plasmid and its active horizontal transfer among Vibrio species. The results also suggested the different effects of qnrVC alleles in different V. cholerae strains, which is possibly due to differences in sequences of qnrVC alleles and even the genetic characteristics of the host strains.

Gut Microbiota is the Key to the Antidepressant Effect of Chaihu-Shu-Gan-San.

Accumulating evidence highlights the link between gut microbiota and depression. As an antidepressant herbal drug in clinic, Chaihu-Shu-Gan-San (CSGS) has also been used in China for the treatment of various gastrointestinal disorders. Therefore, we hypothesize that the gut microbiota might be involved in the effect of CSGS. Here, we investigated the antidepressant effects of CSGS against chronic variable stress (CVS)-induced depression rats with and without antibiotic treatment using 16S rRNA gene sequencing and ultra-performance liquid chromatography coupled with time of flight mass spectrometry (UPLC-Q-TOF/MS) based metabolome approaches. As a result, the prominent effects of CSGS against the depression-like behavioral disorder of CVS-induced rats were significantly weakened when the gut microbiota was changed after oral administration of the broad-spectrum antibiotic. The mediation of CSGS on hippocampal levels of serotonin (5-HT) and glutamic acid (Glu) was also receded with the antibiotic treatment. Further investigation on the diversity of microbiome indicated that the improvement effect of CSGS on gut microbiota dysbiosis-especially the phylum level of Firmicutes-was attenuated compared with the CSGS combined antibiotic treated one. Moreover, 3-hydroxypicolinic acid (H4) and inosine (H8) in the hippocampus were considered as important biomarkers for depression and are also associated with gut microbiota mediated CSGS efficacy. Taken together, our current study indicated that gut microbiota is a critical factor in the antidepressant effect of CSGS, and this acts in part through gut microbiota to improve depression-related biomarkers.

New antiproliferative germacranolides from Carpesium divaricatum.

Six new highly oxygenated (2-7) and one known (1) germacranolides were isolated from the whole plant of Carpesium divaricatum. The planar structures and relative configurations of the new compounds were determined by detailed spectroscopic analysis. The absolute configurations of 1 and 3 were established by circular dichroism (CD) and X-ray crystallographic analyses, and the stereochemistry of the new compounds 2 and 4-6 were determined by similar CD data to 1 and 3, respectively. All isolates were evaluated for their antiproliferative activities against three human tumor cell lines, and compounds 3 and 6 show antiproliferative activities against HeLa and Hep G2 cells with IC50 values of 4.13-8.37 µM. Intensive mechanism study showed that 3 caused cell-cycle arrest at the S/G2 phase and induced apoptosis in Hep G2 cells through a mitochondria-related pathway.

Pharmacokinetics of costunolide and dehydrocostuslactone after oral administration of Radix aucklandiae extract in normal and gastric ulcer rats.

Costunolide and dehydrocostuslactone are the main active ingredients of Radix Aucklandiae (RA). An accurate and sensitive LC-MS/MS method was established to simultaneously determine contents of costunolide and dehydrocostuslactone in plasma. There were significant differences in pharmacokinetic parameters (AUC0-t, Cmax,1, Cmax,2, Tmax,1, Vd, and CL) of costunolide and dehydrocostuslactone between RA group and costunolide group or dehydrocostuslactone group. The relative bioavailability of costunolide or dehydrocostuslactone of RA extract was improved. As compared to normal group, the Tmax,2 values of dehydrocostuslactone of RA in gastric ulcer group were prolonged, while the Cmax,1, Cmax,2, and AUC0-t values decreased.

Upregulated microRNA-485 suppresses apoptosis of renal tubular epithelial cells in mice with lupus nephritis via regulating the TGF-ß-MAPK signaling pathway by inhibiting RhoA expression.

Lupus nephritis (LN) is a common and severe complication of systemic lupus erythematosus. Without intervention, LN may cause acute kidney injury and end-stage renal disease. This study aims to determine whether microRNA-485 (miR-485) affects renal tubular epithelial cells (RTECs) in LN mice via the TGF-ß-MAPK signaling pathway by targeting RhoA. Renal tissue samples were initially extracted from 15 LN and 15 normal mice. RTECs were cultivated in vitro and grouped after transfection of different mimics, inhibitors, or siRNA- RhoA. The target gene of miR-485 was confirmed by dual-luciferase reporter assay. Flow cytometry and MTT assay were applied to detect cell viability and apoptosis. It was determined that RhoA was a target gene of miR-485. We found that urine protein, creatinine, RhoA, interleukin 6 (IL-6), transforming growth factor-ß1 (TGF-ß1), and p38 mitogen-activated protein kinases (p38MAPK) were highly expressed in renal tissues of LN mice, while poor levels of miR-485 were recorded. The overexpression of miR-485 or siRNA- RhoA or the combination of miR-485 and siRNA- RhoA was demonstrated to lead to a reduction of levels of RhoA, IL-6, TGF-ß, and p38MAPK, as well as a promotion of RTECs proliferation and inhibition of RTECs apoptosis. Taken together, these findings indicated that overexpressed miR-485 downregulates RhoA which could promote cell viability and inhibit apoptosis of RTECs by regulating the RhoA-mediated TGF-ß-MAPK signaling pathway in LN mice.

Chaihu-Shu-Gan-San regulates phospholipids and bile acid metabolism against hepatic injury induced by chronic unpredictable stress in rat.

Chaihu-Shu-Gan-San (CSGS) is a famous classic traditional Chinese medicines (TCM) formula for treatment of liver stagnancy recorded in a famous book of traditional Chinese medicine, Jing Yue Quan Shu published in 1624. It has been extensively accepted as an antidepressant in China and its mechanism of action is still not clear. Previously we have found that hepatic injury happens in chronic unpredicted mild stress (CUMS). Thus, the protection of CSGS against hepatic injury induced by CUMS treatment was explored by metabonomics study and gene expression of the rat liver tissue. The results indicated that CSGS improved 8 of the 18 perturbed potential biomarkers in liver tissues of rats treated with CUMS, and involved in regulating phospholipids and bile acid metabolism against hepatic injury induced by CUMS in rat. The expressions of two apoptosis associated genes (Bcl-2 and Bax) and four genes (Pnpla6, Pla2g15, Baat and Gad1) related to the perturbed metabolic pathways were further investigated by quantitative real-time polymerase chain reaction (qRT-PCR). Both metabonomics and studies of genetic influences on metabolites demonstrated that CSGS inhibited hepatocyte apoptosis, and regulated phospholipids and bile acid metabolism against hepatic injury induced by CUMS in rat. Exploring the protection of CSGS against hepatic injury related to depression further clarify the relationship between CUMS-induced depression and hepatic injury, and also provide a novel insight to understand the underlying antidepressive mechanism of CSGS.

Novel Function of Extracellular Matrix Protein 1 in Suppressing Th17 Cell Development in Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS characterized by demyelination and axonal damage. Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model for human MS. Although Th17 cells are important for disease induction, Th2 cells are inhibitory in this process. In this article, we report the effect of a Th2 cell product, extracellular matrix protein 1 (ECM1), on the differentiation of Th17 cells and the development of EAE. Our results demonstrated that ECM1 administration from day 1 to day 7 following the EAE induction could ameliorate the Th17 cell responses and EAE development in vivo. Further study of the mechanism revealed that ECM1 could interact with αv integrin on dendritic cells and block the αv integrin-mediated activation of latent TGF-ß, resulting in an inhibition of Th17 cell differentiation at an early stage of EAE induction. Furthermore, overexpression of ECM1 in vivo significantly inhibited the Th17 cell response and EAE induction in ECM1 transgenic mice. Overall, our work has identified a novel function of ECM1 in inhibiting Th17 cell differentiation in the EAE model, suggesting that ECM1 may have the potential to be used in clinical applications for understanding the pathogenesis of MS and its diagnosis.

Cassane-type diterpenes from the seeds of Caesalpinia minax with their antineoplastic activity.

Five new cassane-type diterpenes, neocaesalpin AA (1), neocaesalpin AB (2), neocaesalpin AC (3), neocaesalpin AD (4) and neocaesalpin AE (5), were isolated from Caesalpinia minax together with three known compounds, 12α-methoxyl,5α,14ß-dihydroxy-1α,6α,7ß-triacetoxycass-13(15)-en-16,12-olide (6), spirocaesalmin (7) and magnicaesalpin (8). Their structures were elucidated based on 1D and 2D NMR, MS and CD analyses. Compounds 1-6 were tested against Hela, HCT-8, HepG-2, MCF-7 and A549 cancer cells and showed moderate cytotoxicity with IC50 values from 18.4 to 83.9 µM.

Molecular cloning and expression of gene encoding aromatic amino acid decarboxylase in 'Vidal blanc' grape berries.

The pleasantly fruity and floral 2-phenylethanol are a dominant aroma compound in post-ripening 'Vidal blanc' grapes. However, to date little has been reported about its synthetic pathway in grapevine. In the present study, a full-length cDNA of VvAADC (encoding aromatic amino acid decarboxylase) was firstly cloned from the berries of 'Vidal blanc', an interspecific hybrid variety of Vitis vinifera × Vitis riparia. This sequence encodes a complete open reading frame of 482 amino acids with a calculated molecular mass of 54 kDa and isoelectric point value (pI) of 5.73. The amino acid sequence deduced shared about 79% identity with that of aromatic L: -amino acid decarboxylases (AADCs) from tomato. Real-time PCR analysis indicated that VvAADC transcript abundance presented a small peak at 110 days after full bloom and then a continuous increase at the berry post-ripening stage, which was consistent with the accumulation of 2-phenylethanol, but did not correspond to the trends of two potential intermediates, phenethylamine and 2-phenylacetaldehyde. Furthermore, phenylalanine still exhibited a continuous increase even in post-ripening period. It is thus suggested that 2-phenylethanol biosynthetic pathway mediated by AADC exists in grape berries, but it has possibly little contribution to a considerable accumulation of 2-phenylethanol in post-ripening 'Vidal blanc' grapes.

Oxalate impairs aminophospholipid translocase activity in renal epithelial cells via oxidative stress: implications for calcium oxalate urolithiasis.

PURPOSE: We evaluated the possible involvement of phospholipid transporters and reactive oxygen species in the oxalate induced redistribution of renal epithelial cell phosphatidylserine. MATERIALS AND METHODS: Madin-Darby canine kidney cells were labeled with the fluorescent phospholipid NBD-PS in the inner or outer leaflet of the plasma membrane and then exposed to oxalate in the presence or absence of antioxidant. This probe was tracked using a fluorescent quenching assay to assess the bidirectional transmembrane movement of phosphatidylserine. Surface expressed phosphatidylserine was detected by annexin V binding assay. The cell permeable fluorogenic probe DCFH-DA was used to measure the intracellular reactive oxygen species level. RESULTS: Oxalate produced a time and concentration dependent increase in phosphatidylserine, which may have resulted from impaired aminophospholipid translocase mediated, inward directed phosphatidylserine transport and from enhanced phosphatidylserine outward transport. Adding the antioxidant N-acetyl-L-cysteine significantly attenuated phosphatidylserine externalization by effectively rescuing aminophospholipid translocase activity. CONCLUSIONS: To our knowledge our findings are the first to show that oxalate induced increased reactive oxygen species generation impairs aminophospholipid translocase activity and decreased aminophospholipid translocase activity has a role in hyperoxaluria promoted calcium oxalate urolithiasis by facilitating phosphatidylserine redistribution in renal epithelial cells.

Paeonol pharmacokinetics in the rat following i.m. administration.

The pharmacokinetic behavior and bioavailability of paeonol were determined after a single intramuscular (i.m.) injection of 10 mg/kg to rats. Plasma paeonol concentrations were measured by high performance liquid chromatography (HPLC). The main pharmacokinetic parameters were as follows: mean elimination half-life (t(1/2z)) 59.85 +/- 10.23 min, time to reach peak concentration (Tmax) 7.50 +/- 2.74 min, maximum concentration (Cmax) 0.71 +/- 0.13 mg/l, total body clearance (CLz) 0.24 +/- 0.03 l/min/kg, the area under concentration-time curve from 0 to 4 h (AUC(0-4h)) 39.01 +/- 5.69 mg/l x min, the area under concentration-time curve from 0 to infinity (AUC(0-infinity)) 43.06 < or = 6.10 mg/l x min. The absolute bioavailability of paeonol after i.m. administration amounted to 68.68%.