Bifunctionality and Antitumor Efficacy of ZG-126, a Vitamin D Receptor Agonist/Histone Deacetylase Inhibitor Hybrid Molecule.

Analogues of hormonal vitamin D, 1,25-dihydroxyvitamin D (1,25D), signal through the nuclear vitamin D receptor (VDR). They have potential in combination therapies with other anticancer agents such as histone deacetylase inhibitors (HDACi's). Here, we characterize the ZG series of hybrid compounds that combine HDACi within the backbone of a VDR agonist. All display improved solubility, with ZG-126 being the most robustly bifunctional molecule in multiple cell lines. ZG-126 is well tolerated and strongly induces VDR target gene expression in vivo at therapeutic doses. Its antitumor efficacy is superior to 1,25D and the HDACi SAHA, separately or together, in mouse models of melanoma and triple-negative breast cancer (TNBC). Notably, ZG-126 treatment reduces metastases almost 4-fold in an aggressive TNBC model. ZG-126 also reduces total macrophage infiltration and the proportion of immunosuppressive M2-polarized macrophages in TNBC tumors by 2-fold. ZG-126 thus represents a bifunctional and efficacious anticancer agent with improved physicochemical properties.

First report of the family Ideoroncidae (Arachnida, Pseudoscorpiones) from China, with description of a new species.

Background: The pseudoscorpion genus Shravana Chamberlin, 1930, belonging to the family Ideoroncidae Chamberlin, 1930, currently contains 13 species. To date, no ideoroncid species has been recorded from China. New information: The family Ideoroncidae Chamberlin, 1930 is reported from China for the first time. A new species of the genus Shravana Chamberlin, 1930, collected from Xizang Autonomous Region, China, is described under the name of Shravanazhui Gao & Zhang, sp. nov. on the basis of both sexes. The finding of this new species expands the distribution range of this family in Asia.

Four new species of cave-adapted pseudoscorpions (Pseudoscorpiones, Pseudotyrannochthoniidae) from Guizhou, China.

Four new troglomorphic pseudotyrannochthoniid pseudoscorpion species collected from karst caves in Guizhou Province are described with detailed diagnoses and illustrations: Allochthoniusbainiensis sp. nov. from Liangfeng Cave (Xishui County), Allochthoniuspandus sp. nov. from Daozuo Cave (Xishui County), Allochthoniusxinqiaoensis sp. nov. from Sanjie Cave (Fenggang County), and Spelaeochthoniuswulibeiensis sp. nov. from Wulibei Cave (Weining County). Spelaeochthoniuswulibeiensis sp. nov. represents the first record of the genus in China. The diagnostic features of these four new cave-adapted (troglomorphic) species are presented and discussed, as well as compared with closely related species. The data on their distribution, habitat and ecology of the species are also given.

Two new species of cave-adapted pseudoscorpions (Pseudoscorpiones, Chthoniidae) from Yunnan, China.

Two new cave-adapted pseudoscorpion species belonging to the family Chthoniidae are described: Tyrannochthoniuspandus sp. nov. from Biyu Cave (Yunnan: Luxi) and Lagynochthoniuslaoxueyanensis sp. nov. from Laoxueyan Cave (Yunnan: Yanshan). Both of them, collected from the dark zone of caves, are highly troglomorphic species.

Two new species of the pseudoscorpion subfamily Lamprochernetinae Beier, 1932 from Guizhou, China (Pseudoscorpiones: Chernetidae).

Two new species of the pseudoscorpion subfamily Lamprochernetinae Beier, 1932 are described from Guizhou Province, China, Nudochernes pseudotroglobius sp. nov. and Megachernes biyunensis sp. nov., with detailed diagnoses, descriptions and illustrations.

Diversity of cave-dwelling pseudoscorpions from eastern Yunnan in China, with the description of eleven new species of the genus Lagynochthonius (Pseudoscorpiones, Chthoniidae).

Eleven new Lagynochthonius species from twelve karst caves of eastern Yunnan are described, including detailed diagnosis and illustrations: L. crassus sp. nov. from Unnamed Cave 1 (Maguan County), L. fengi sp. nov. from Unnamed Cave 2 (Yanjin County), L. magnidentatus sp. nov. from Xiao Cave (Fuyuan County), L. minimus sp. nov. from Yanfen Cave and Cizhu Cave (Xichou County), L. retrorsus sp. nov. from Qinglong Cave (Daguan County), L. serratus sp. nov. from Unnamed Cave 3 (Malipo County), L. spinulentus sp. nov. from Yingshan Cave (Zhenxiong County), L. xiaolinensis sp. nov. from Dayan Cave (Zhenxiong County), L. xibaiensis sp. nov. from Hama Cave (Zhenxiong County), L. xinjiaoensis sp. nov. from Yueliang Cave (Fuyuan County), L. yaowangguensis sp. nov. from Unnamed Cave 4 (Malipo County). An identification key to all known Lagynochthonius species from China is also provided.

Two new Atemnus species (Pseudoscorpiones: Atemnidae) from Xinjiang, China.

Two new species of the genus Atemnus Canestrini, 1884 are reported from China: A. hamiensis sp. nov. and A. niger sp. nov. A key to all known species of Atemnus is provided.

Two new cave-dwelling species of Tyrannochthonius Chamberlin 1929 (Pseudoscorpiones: Chthoniidae) from the Guizhou karst, China.

Two new troglomorphic pseudoscorpion species, Tyrannochthonius harveyi, sp. nov. and Tyrannochthonius zhai, sp. nov., are described from the dark zone of caves in the tower karst of the Guizhou Province in China. Both species are presently known only from single caves and are likely to have very restricted distribution ranges.

First record of the genus Orochernes (Pseudoscorpiones: Chernetidae) from China, with description of a new species.

The chernetid genus Orochernes Beier, 1968 is reported from China for the first time. Orochernes ganziensis sp. n. is described from the Sichuan Province and characterized through illustrations and genetic data. The spermathecae of the genus Orochernes are illustrated for the first time.

Complete mitochondrial genome sequence and phylogenetic implications of Chorosoma macilentum (Heteroptera: Rhopalidae).

The complete mitogenome of Chorosoma macilentum Stål, 1858 was obtained using a next-generation sequencing approach, which is the first report in genus Chorosoma. The genome is 16,330 bp long with high A + T content. The phylogenetic analyses based on 13 protein-coding genes (PCGs) provide strong support for monophyly of each family within Pentatomomorpha. Chorosoma Macilentum was clustered together with other species within Rhopalidae, and grouped sibling species with Aeschyntelus notatus.

Two-year observation of a randomized trial on tacrolimus-based therapy with withdrawal of steroids or mycophenolate mofetil after renal transplantation.

OBJECTIVE: To evaluate the safety and feasibility of steroid or mycophenolate mofetil (MMF) withdrawal from tacrolimus-based immunosuppressant regimen in renal allograft recipients. METHODS: A cohort of 45 patients following cadaveric renal allograft transplantation were randomly divided into 3 groups based on the regimen of combination of tacrolimus, steroid, and MMF: triple therapy group, steroid withdrawal group, and MMF withdrawal group. During 2 years, survival of patients and allografts, clinical acute rejection, adverse events, hepatic and renal allograft function, and blood lipids were monitored to evaluate the safety and feasibility of steroid or MMF withdrawal after renal transplantation. RESULTS: During two-year observation, steroid or MMF was successfully withdrawn from immunosuppressant regimen based on tacrolimus without any clinical acute rejection. Patient and graft survival rates were 100% and all the renal allografts kept excellent function. Some adverse events occurred and there were no significant differences among groups. CONCLUSION: Withdrawal of steroid or MMF in low-immunological-risk renal allografts treated with tacrolimus-based immunosuppressant regimen can be achieved with no increased risk of acute rejection.