Altered gut microbiota and metabolites in untreated myasthenia gravis patients.

Objective: The homeostasis of the immune system is influenced by the gut microbiota. Previous studies have reported dysbiosis in the gut microbiota of myasthenia gravis (MG) patients. To investigate potential alterations in gut microbiota and metabolites in newly diagnosed and untreated MG patients, we conducted a case-control study. Methods: Fecal samples were collected from 11 newly diagnosed and untreated MG patients as well as 11 age-and sex-matched healthy controls. These samples underwent analysis for gut microbiota using 16S ribosomal RNA (rRNA) gene sequencing, while fecal metabolome was analyzed using liquid chromatography-electrospray tandem mass spectrometry system (LC-ESI-MS/MS). Results: The microbial community richness (observed species) and diversity (Shannon and Simpson indices) were significantly lower in the MG group compared to the control group. Microbiota composition analysis revealed significant differences between the MG and control groups at phylum, family, and genus levels. Linear discriminant analysis effect size (LEfSe) analysis showed a substantial decrease in abundance of the genus Faecalibacterium within the MG group. Fecal metabolome analysis identified three up-regulated metabolites involved in amino acid metabolism (taurine, creatinine, L-carnitine), one up-regulated metabolite involved in lipid metabolism (oleic acid), with correlation analysis indicating a positive association between Faecalibacterium abundance and creatinine levels. Conclusion: Our findings suggest that dysbiosis already exists in newly diagnosed and untreated MG patients, implying that dysbiosis within the gut microbiota may be an initiating factor contributing to MG pathogenesis. Furthermore, F. prausnitzii may hold promise as a probiotic for treating MG.

Counting-loss correction method based on window pulse shaping.

In order to obtain a precise X-ray counting rate, a window shaping algorithm is proposed and is applied. The proposed algorithm shapes original pulses into window pulses with sharp edge and stable width. In the experiment, the measured counting rate at 3.9uA tube current is used to estimate the incoming counting rate. The dead time and corrected counting rate are estimated by the paralyzable dead-time model. The experimental results show that the mean dead time of radiation events is 260ns and the relative mean deviation is 3.44% in the newly designed counting system. While the incoming counting rate is in the range of 100kcps to 2Mcps, the relative error of the corrected counting rate compared with the incoming counting rate is less than 1.78%. The proposed algorithm suppresses the dead time swing and improves the accuracy of the total counting rate of X-ray fluorescence spectrum.

Peak tailing cancellation techniques for digital CR-(RC)n filter.

The CR-(RC)n filter is used for Semi-Gaussian pulse shaping in analog spectroscopy. A new digital CR-(RC)n filter is presented based on the recursive models of the CR filter and RC filter. The spectroscopic signal reconstruction technique is proposed. This technique is applied to digital exponential decay signals obtained by the digitization of analog signals that represent the combined response of a FAST-SDD detector and the associated front-end circuit. Compared with the direct application of the digital CR-(RC)n filter, the technique eliminates the undershoot of the Semi-Gaussian pulse which is the primary cause of the low-energy peak tailing. And, the digital pole-zero cancellation filter follows digital CR-(RC)n filter to reduce the long tail of the shaped Semi-Gaussian pulse which leads to the high-energy peak tailing. Experimental results based on XRF signals of manganese sample show that the proposed techniques can cancel peak tailing due to the shaped Semi-Gaussian pulse improving FWTM/FWHM ratio and throughput capability.

Characterization of the complete mitochondrial genome of the lung fluke, Paragonimus heterotremus.

In this study, the complete mitochondrial genome of human lung fluke, Paragonimus heterotremus, was recovered through Illumina sequencing data. This complete mitochondrial genome of P. heterotremus is 13,927 bp in length and has a base composition of A (16.6%), T (41.8%), C (13.%), G (28.4%), demonstrating an obvious bias of high AT content (58.4%). The mitochondrial genome contains a typically conserved structure, encoding 12 protein-coding genes (PCGs), 22 transfer RNA genes (tRNA), 2 ribosomal RNA genes (12S rRNA and 16S rRNA) and a control region (D-loop region). All PCGs were located on the H-strand. ND4 gene and ND4L gene were overlapped by 39 bp. The nucleotide sequence of 12 PCGs of P. heterotremus and other 10 parasite species were used for phylogenetic analysis. The result indicated P. heterotremus a relative close relationship with species Paragonimus westermani (AF219379.2).

Characterization of the complete chloroplast genome of sorrel (Rumex acetosa).

Rumex acetosa, known as sheep's sorrel, red sorrel, sour weed, and field sorrel, is a species of flowering plant in the buckwheat family Polygonaceae. In this study, the complete chloroplast (cp) genome of R. acetosa (Rumiceae) was determined through Illumina sequencing method. The complete chloroplast genome of R. acetosa was 160,269 bp in length and contained a pair of IR regions (30,503 bp) separated by a small single copy region (13,128 bp) and a large single copy region (86,135 bp). This cp genome is encoded with 129 genes including 83 protein-coding genes, 36 tRNA genes, and 8 ribosomal RNA genes. The overall GC content of R. acetosa cp genome is 37.2%. By phylogenetic analysis using Bayesian method, R. acetosa showed the closest relationship with other 2 Rumiceae species, Rheum palmatum and Oxyria sinensis.

Sodium Hydroxide Pinpoint Pressing Permeation Method for the Animal Modeling of Sick Sinus Syndrome.

Sodium hydroxide pinpoint pressing permeation (SHPPP) was investigated in order to build a rat model of sick sinus syndrome (SSS), which is easy to operate and control the degree of damage, with fewer complications and applicable for large and small animals.Thirty healthy Wistar rats (15 males and 15 females, weighing 250-350 g) were randomly divided into 3 groups, namely a formaldehyde thoracotomy wet compressing group (FTWC), formaldehyde pinpoint pressing permeation group (FPPP) group, and SHPPP group. The number of surviving rats, heart rate (HR), sinoatrial node recovery time (SNRT), corrected SNRT (CSNRT), and sinoatrial conduction time (SACT) were recorded 3 days, one week, and two weeks after modeling.The achievement ratio of modeling was 10% in the FTWC group, 40% in the FPPP group, and 70% in the SHPPP group, and the differences were statistically significant (χ(2) = 7.250, P = 0.007). Meanwhile, the HR was reduced by about 37% in these 3 groups 3 days after modeling, while the reduction was maintained only in SHPPP (P > 0.05) and the HR was re-elevated in the FTWC and FPPP groups 2 weeks after modeling (P < 0.05). Additionally, the SNRT, cS-NRT, and SACT were significantly prolonged compared with pre-modeling in all 3 groups (P < 0.01).SHPPP was the best method with which to build an SSS model with stable and lasting low HR and high success rate of modeling, which might be helpful for further studies on the SSS mechanisms and drugs.

Transcriptional modulation of BCRP gene to reverse multidrug resistance by toremifene in breast adenocarcinoma cells.

Breast cancer resistance protein (BCRP/ABCG2), an ATP-binding cassette half transporter, confers multidrug resistance (MDR) to a series of antitumor agents such as mitoxantrone, daunorubicin, SN-38, and topotecan, and often limits the efficacy of chemotherapy. Recent studies have indicated that a putative estrogen response element (ERE) is located in the promoter region of the BCRP gene. However, whether and how BCRP is regulated transcriptionally by toremifene (TOR) remains unknown. In the present study, two plasmid vectors have been designed to express the wild-type full-length BCRP cDNA enforced driven by its endogenous promoter containing a functional ERE and a constitutive cytomegalovirus (CMV) promoter as control, respectively, which were transfected into estrogen-responsive MCF-7 and estrogen-independent MDA-MB-231 human breast adenocarcinoma cell lines. We showed that toremifene alone significantly downregulated BCRP mRNA and protein levels in estrogen receptor α (ERα)-positive MCF-7 cells in a dose-dependent manner, and the inhibitory effect was partially reversed by estrone (E(1)). Furthermore, gel shift assays demonstrated that specific binding of ERα to the ERE in the BCRP promoter is essential for transcriptional inhibition of BCRP by toremifene. Interestingly, toremifene alone increased the cellular accumulation of mitoxantrone in BCRP-transfected cells, suggesting that TOR indeed inhibits BCRP-mediated drug efflux and overcome drug resistance. To the best of our knowledge, this is the first report describing a direct effect of toremifene on BCRP. Our results thus indicate that toremifene by itself downregulates BCRP expression to reverse BCRP-mediated atypical multidrug resistance via a novel transcriptionally mechanism, which might be involved in TOR-ER complexes binding to the ERE of BCRP promoter to repress transcription of BCRP gene.

Transcriptional upregulation of breast cancer resistance protein by 17beta-estradiol in ERalpha-positive MCF-7 breast cancer cells.

OBJECTIVES: Breast cancer resistance protein (BCRP) confers resistance to certain anticancer drugs such as mitoxantrone, topotecan and SN-38. A putative estrogen response element (ERE) was located in the promoter region of the BCRP gene. The present study aimed to investigate whether human BCRP expression is regulated pretranscriptionally by 17beta-estradiol. METHODS: Two recombinant plasmids (pcDNA3-promoter-BCRP and pcDNA3-CMV-BCRP) were designed to express the full-length BCRP cDNA enforced driven by its endogenous promoter containing a functional ERE and a control constitutive cytomegalovirus (CMV) promoter, respectively, which were transfected into estrogen receptor alpha (ERalpha)-positive MCF-7 and ERalpha-negative MDA-MB-231 breast cancer cell lines. RESULTS: 17beta-estradiol significantly upregulated BCRP mRNA and protein expression in a dose-dependent manner, and the effect was abolished by the antiestrogen tamoxifen. Furthermore, electrophoretic mobility shift assays demonstrated that the putative ERE in the promoter region of the BCRP gene and ERalpha are essential for transcriptional activation of BCRP by 17beta-estradiol. CONCLUSIONS: Taken together, our findings indicate that BCRP expression is upregulated by 17beta-estradiol via a novel pretranscriptional mechanism which might be involved in 17beta-estradiol-ER complexes binding to the ERE of BCRP promoter via the classical pathway to activate transcription of the BCRP gene.