Spectrum of variants in a large Chinese Gitelman syndrome cohort.

Gitelman syndrome (GS) is caused by SLC12A3 biallelic variants. A previous study showed that large rearrangements (LRGs) of SLC12A3 accounted for the low sensitivity of genetic testing. However, a systematic screening for LRGs in Chinese GS patients is lacking. Massively parallel sequencing (MPS) and multiplex ligation-dependent probe amplification (MLPA) were performed to sequence the genomic DNA of patients with clinically diagnosed GS. Of 165 index cases, MPS identified 151 cases with two or more affected alleles and 14 cases with one variant allele. LRGs were detected by MLPA in 20 out of 27 cases, including 15 cases with suspected LRGs by MPS. Among these 20 cases with LRGs, the results of MPS and MLPA were identical in only 8 cases. Additional LRGs in 6 cases were detected by MLPA alone. In 6 cases, E4_E6del was identified by MPS, while E4_E5del and Intron6del were identified by MLPA. Among the 102 distinct variants, 30 are novel. LRGs were found in 20 cases (12.1%). LRGs were found in 12.1% of our Chinese GS patients cohort. We show that MPS and MLPA are two complementary techniques with the ability to improve the diagnostic yield of GS.

New Cytotoxic Cytochalasans from a Plant-Associated Fungus Chaetomium globosum kz-19.

Four new cytochalasans, phychaetoglobins A-D (1-4), together with twelve known cytochalasans (5-16), were isolated from a mangrove-associated fungus Chaetomium globosum kz-19. The new structures were elucidated on the basis of extensive 1D and 2D NMR, HR ESIMS spectroscopic analyses, and electronic circular dichroism (ECD) calculations. The absolute configuration of 2 was established by application of Mosher's method. Compounds 4-8 exhibited moderate cytotoxicities against A549 and HeLa cell lines with the IC50 values less than 20 µM.

[Secondary metabolites of Streptomyces sp. A1693].

By means of various chromatographic methods such as Sephadex LH-20，ODS，and semi-preparative HPLC，ten compounds were isolated from Streptomyces sp. A1693 and their structures were elucidated on the basis of spectroscopic data and physico-chemical methods. The compounds comprised 5 butenolides，2 diketopiperazines，and 3 antimycin antibiotics. The structures were identified as (5S)-5-(11-hydroxymethyloctyl)furan-2(5H)-one (1), (5S)-5-(11-hydroxy-11-methylheptyl)furan-2(5H)-one (2), (5S)-5-(11-methyl-12-oxooctyl) furan-2(5H)-one (3), (5S)-5-(11-hydroxy-11-methyloctyl)furan-2(5H)-one (4), (5S)-5-(11-hydroxy-12-methyloctyl)furan-2(5H)-one（5），cyclo-Phe-Val (6)，cyclo-Phe-Ile (7)，uranchimycin A (8)，uranchimycin B (9)，and deisovalerylblastomycin (10). Among them，1 was defined as a new compound. All the compounds didn't show the cytotoxic activity against A549 cell line (IC50>50 mg·L⁻¹).

Triterpenoids from Euphorbia maculata and Their Anti-Inflammatory Effects.

Euphorbia maculata is a medicinal plant of the Euphorbiaceae family, which can produce anti-inflammatory and cancer chemopreventive agents of triterpenoids. The present study reports on the bioactive triterpenoids of this plant. Two new lanostane-type triterpenoids, named (3S,4S,7S,9R)-4-methyl-3,7-dihydroxy-7(8→9) abeo-lanost-24(28)-en-8-one (1) and 24-hydroperoxylanost-7,25-dien-3ß-ol (2), together with 15 known triterpene derivatives, were isolated from Euphorbia maculata. The structures of the new compounds were determined on the basis of extensive spectroscopic data (UV, MS, ¹H and 13C-NMR, and 2D NMR) analysis. All tetracyclic triterpenoids (1⁻11) were evaluated for their anti-inflammatory effects in the test of TPA-induced inflammation (1 µg/ear) in mice. The triterpenes exhibited significant anti-inflammatory activities.

The function of Eriocheir sinensis transferrin and iron in Spiroplasma eriocheiris infection.

Transferrin, a member of the iron binding superfamily protein, plays an extremely important role in the transport of iron in the biological process of cells. The result of preliminary proteomic study on E. sinensis hemocytes infected Spiroplasma eriocheiris showed the expression of transferrin (EsTF) and ferrin (EsFe) significantly changed. In addition, other reports have confirmed that transferrin, ferritin and iron are involved in the immune response of hosts. In order to validate the immune function of EsTF, the whole length of EsTF was successfully amplified by the gene cloning and RACE technique. The results showed that the full-length cDNA of the EsTF gene was 2748 bp, including a 2193 bp open reading frame which encodes 730 amino acids. The result of bioinformatics analysis showed EsTF contains two highly conserved TR_FER domains. Evolutionary analysis showed that EsTF has a close genetic relationship with other TFs of invertebrates. In addition, EsTF mRNA was highly transcripted in nerve and intestine tissues, followed by hemocytes. The expression of EsTF, EsFe1 and EsFe2 increased after exogenous supplemental of iron under the concentration of 100 nmol/L in water. After exogenous supplement of iron and injection with S. eriocheiris, these three gene transcription of mRNA levels were higher than that of PBS group, while lower than the S. eriocheiris group and the iron group. Besides, the copy number of S. eriocheiris in the experimental group was significantly reduced, and the death rate decreased. As can be seen, iron made transferrin and ferritin return to normal levels during the infection of S. eriocheiris and help the host maintain normal immunity levels to resist S. eriocheiris. These results further demonstrated that EsTF, EsFe1, EsFe2 and iron play a role in the immune defense mechanism of the crabs to resist S. eriocheiris infection.