Structure-Based Optimization of Coumestan Derivatives as Polyketide Synthase 13-Thioesterase(Pks13-TE) Inhibitors with Improved hERG Profiles for Mycobacterium tuberculosis Treatment.

Pks13 was identified as a key enzyme involved in the final step of mycolic acid biosynthesis. We previously identified antitubercular coumestans that targeted Pks13-TE, and these compounds exhibited high potency both in vitro and in vivo. However, lead compound 8 presented potential safety concerns because it inhibits the hERG potassium channel in electrophysiology patch-clamp assays (IC50 = 0.52 µM). By comparing the Pks13-TE-compound 8 complex and the ligand-binding pocket of the hERG ion channel, fluoro-substituted and oxazine-containing coumestans were designed and synthesized. Fluoro-substituted compound 23 and oxazine-containing coumestan 32 showed excellent antitubercular activity against both drug-susceptible and drug-resistant Mtb strains (MIC = 0.0039-0.0078 µg/mL) and exhibited limited hERG inhibition (IC50 ≥ 25 µM). Moreover, 32 exhibited improved metabolic stability relative to parent compound 8 while showing favorable bioavailability in mouse models via serum inhibition titration assays.

Microbial nitrification, denitrification and respiration in the leached cinnamon soil of the upper basin of Miyun Reservoir.

Leached cinnamon soil is the main agricultural soil distributed in the North China Plain. In this research, leached cinnamon soil samples were collected in the upper basin of Miyun Reservoir (northeast of Beijing, China). The BaPS method (Barometric Process Separation) was applied to measure nitrification, denitrification and respiration rates. The rates of nitrification, denitrification and respiration were 0-120.35 µg N/kg SDW h, 0-246.86 µg N/kg SDW h and 0.17-225.85 µg C/kg SDW h (Soil Dry Weight, SDW), respectively. The emission rates of CO2 and NxOy through nitrification, denitrification and respiration were 1.00-547.80 and 6.00-4850.65 µmol/h, respectively. The analysis of relationships between nitrification, denitrification and respiration rates indicated that these three microbial processes were interacted, which posed impacts on soil nitrogen availability. As indicated by the results, C:N ratio coupled with content could be taken as the indicators of content, which is usually the predominant form of N available to plants growing in soil. Results showed that content was the highest (i.e., >62.4 mg/kg) when C:N ratio was 5.30-8.40, meanwhile content was 3.71-4.39 mg/kg. Nevertheless, content was the lowest (i.e., <6.40 mg/kg) when C:N ratio was 9.2-12.10, meanwhile content was 3.41-4.35 mg/kg.

Taxonomy of the Quedius mukuensis group (Coleoptera: Staphylinidae: Staphylinini: Quediina) with descriptions of four new species from China.

Four new species of the subgenus Microsaurus Dejean, 1833 of the genus Quedius Stephens, 1829 are described based on specimens collected from China: Q. (Microsaurus) indigestus sp. nov., Q. (Microsaurus) purus sp. nov. and Q. (Microsaurus) rectus sp. nov. from Sichuan, and Q. (Microsaurus) medius sp. nov. from Hubei. The new species all belong to the Quedius mukuensis group, which is now increased to a total of 16 species. Line drawings and color illustrations of the adults, and the genitalia of the new species and some other ones are given. A key to all the species of this group is provided.

Three new species of the genus Quedius (subgenus Microsaurus) from China (Coleoptera: Staphylinidae: Staphylinini: Quediina).

Three new species of the subgenus Microsaurus Dejean, 1833 of the genus Quedius Stephens, 1829 are described based on specimens collected from China: Q. (Microsaurus) bilobus sp. nov. and Q. (Microsaurus) varius sp. nov. from Sichuan, and Q. (Microsaurus) cornutus sp. nov. from Yunnan. Line drawings and color illustrations of adults and genitalia of the new species are provided.

Taxonomy of the subgenus Quedius (Raphirus) Stephens (Coleoptera: Staphylinidae: Staphylinini: Quediina) with descriptions of four new species from China.

Four new species of the subgenus Raphirus Stephens, 1829 of the genus Quedius Stephens, 1829 (Coleoptera: Staphylinidae: Staphylinini: Quediina) are described based on specimens collected from China: Q. (Raphirus) hubeiensis sp. nov. from Hubei, Q. (Raphirus) ningxiaensis sp. nov. from Ningxia, Q. (Raphirus) spissus sp. nov. from Sichuan, and Q. (Raphirus) tenuiculus sp. nov. from Fujian. The females of Q. (Raphirus) oros Smetana, 2011 and Q. (Raphirus) shunichii Smetana, 2010 are described for the first time. Q. (Raphirus) kuiro Smetana, 1988 is recorded for the first time from China. Line drawings and color illustrations of adults and genitalia of all these species and some other ones are provided.

Taxonomy on Quedius euryalus group (Coleoptera: Staphylinidae: Staphylinini: Quediina) from China with description of eight new species.

Eight new species of the subgenus Microsaurus Dejean, 1833 of the genus Quedius Stephens, 1829 are described based on specimens collected in China, namely Q. aculeatus sp. nov., Q. acutulus sp. nov., Q. altus sp. nov., Q. capillus sp. nov., Q. perlucidus sp. nov., Q. postangulus sp. nov., Q. subwrasei sp. nov. from Sichuan and Q. arcus sp. nov. from Ningxia. The female of Q. songpanoides Smetana, 2009 is described for the first time. These new species belong to the Quedius euryalus group and the fauna of this species group is thus increased to 53 species. In addition, this paper reviews the taxonomic history of the Quedius euryalus group and reports the sexual dimorphism in the hind wing length, i.e. male with longer hind wings in many species of the Quedius euryalus group. Line drawings and color illustrations of adults and genitalia of the new species and some other ones are provided, along with a key to all the known species of the euryalus group.

Three new species of Quedius elpenor group (Coleoptera: Staphylinidae: Staphylinini: Quediina) from China.

Three new species of the subgenus Distichalius Casey, 1915 of the genus Quedius Stephens, 1829 are described based on specimens collected in China: Q. (Distichalius) biprominulus sp. nov., Yunnan; Q. (Distichalius) fusus sp. nov., Beijing; and Q. (Distichalius) paululus sp. nov., Sichuan. The new species belong to the Quedius elpenor group and increase the number of species of this group to 10. Line drawings and color illustrations of adults and genitalia of the new species are given. A key to all species of this group is provided and their geographical distribution is mapped.

Taxonomy of the genus Bolitogyrus Chevrolat (Coleoptera: Staphylinidae: Staphylinini: Quediina) from China with description of seven new species.

Seven new species of the genus Bolitogyrus Chevrolat, 1842 are described based on specimens collected in China, namely B. depressus sp. nov. from Guangdong, B. hainanensis sp. nov. and B. magnimaculosus sp. nov. from Hainan, B. metallicus sp. nov. from Hubei, and B. loculus sp. nov., B. profundus sp. nov. and B. uncus sp. nov. from Yunnan. The number of Bolitogyrus species is thus increased to 59. Line drawings and color illustrations of adults and genitalia of the new species and some others are given. A key to species known from China is provided, with the exception of B. fukienensis Scheerpeltz, 1974, which is only known from females. A geographical distribution map of all Chinese species is also compiled.