Review of the genus Qinshuiacris (Orthoptera: Acrididae) from China with proposal of Caryanda viridis-species group and description of a new species.

Based on an examination of type and additional material, Qinshuiacris viridis Zheng & Mao, 1996 and some allied species in the genus Caryanda are reviewed. Q. viridis Zheng & Mao, 1996 is transferred to Caryanda as a new combination: C. viridis (Zheng & Mao, 1996) comb. nov.. The female of C. viridis is described for the first time and sixty-two topotypes are designated. The genus Qinshuiacris Zheng & Mao, 1996 is synonymized with Caryanda Stål, 1878 because of the transfer of the type species. C. yini Mao & Ren, 2006 is proposed as a new junior synonym of C. dehongensis Mao, Xu & Yang, 2003. A new species, C. eshana Mao sp. nov., is also described and illustrated. Additionally, the conception of the Caryanda viridis-species group is proposed to contain the four allied species with falciform cerci: C. albomaculata Mao, Ren & Ou, 2007, C. dehongensis Mao, Xu & Yang, 2003, C. eshana Mao sp. nov., and C. viridis (Zheng & Mao, 1996) comb. nov.. A key to the species of C. viridis-species group is provided. Type specimens are deposited in the Biological Science Museum, Dali University (BMDU), Yunnan Province, China, in the Institute of Zoology, Shaanxi Normal University (IZSNU), Shaanxi Province, China and in the Institute of Zoology, Chinese Academy of Sciences, Beijing, China (IZCAS).

A review of Caryanda viridis- species group (Orthoptera: Acrididae) with a new species.

A new species of Caryanda viridis- species group, i.e. Caryanda biserrata Mao et Yin sp. nov. is described and illustrated. C. xinpingensis Mao, 2017 is included into C. viridis- species group, and C. viridoides Mao, Ren & Ou, 2011 is removed from it. C. viridis- species group presently contains six species: C. viridis (Zheng & Mao, 1996), C. dehongensis Mao, Xu & Yang, 2003, C. albomaculata Mao, Ren & Ou, 2007, C. eshana Mao, 2015, C. xinpingensis Mao, 2017 and C. biserrata Mao et Yin sp. nov.. The key to the six species of C. viridis- species group is updatad.

Taxonomy on three allied genera within Arcypterini (Orthoptera: Acrididae) from Qinghai-Xizang Plateau, China.

The generic diagnosis of three allied genera, Leuconemacris Zheng, 1988, Asulconotoides Liu, 1984 and Asulconotus Ying, 1974, are compared and redescribed. Four new species, Leuconemacris acuminata, sp. nov., L. xinlongensis, sp. nov., L. muliensis, sp. nov. and Asulconotus acarinatus, sp. nov. are described and illustrated. Two new combinations are established: Asulconotoides asulcata (Zheng, 1988) comb. nov. = Leuconemacris asulcata Zheng, 1988 and Asulconotoides microptera (Zheng, 1988), comb. nov. = Leuconemacris microptera Zheng, 1988. All updated keys to genera and species are given.

Descriptions on two new species of the genus Macromotettixoides (Orthoptera: Tetrigidae: Metrodorinae ) from China.

Two new species Macromotettixoides amplifronta sp. nov. and M. yingjiangensis sp. nov. from Yunnan, are described and illustrated with photographs. An updated key to species of the genus Macromotettixoides is provided.

Deletion of peroxiredoxin 6 potentiates lipopolysaccharide-induced acute lung injury in mice.

OBJECTIVE: To investigate the role and signaling pathway of peroxiredoxin 6, a newly identified peroxidase, in lipopolysaccharide-induced acute lung injury. DESIGN: Prospective, randomized, controlled study. SETTING: Research laboratory. SUBJECTS: Peroxiredoxin 6 (-/-) and wild-type C57BL/6 mice. INTERVENTIONS: Wild-type or peroxiredoxin 6 (-/-) mice were challenged by intratracheal instillation of lipopolysaccharide (5 mg/kg) for 4 hrs or 24 hrs for lung injury measurement. In other studies, peritoneal macrophages, isolated from wild-type and peroxiredoxin 6 (-/-) mice, were preincubated in presence or absence of mitogen-activated protein kinases inhibitors for 30 mins before being stimulated with lipopolysaccharide (1 µg/mL) for 4 hrs. MEASUREMENTS AND MAIN RESULTS: Bronchoalveolar lavage myeloperoxidase activity and the lung injury score were significantly increased in peroxiredoxin 6 (-/-) mice compared with wild-type mice after lipopolysaccharide instillation at both 4 hrs and 24 hrs. Hydrogen peroxide and malondialdehyde levels, as well as nuclear factor-κB activities, tumor necrosis factor-α, interleukin-1ß, and matrix metalloproteinase-9 messenger RNA, protein concentration, and activities were significantly increased whereas total antioxidative capability was markedly decreased in lungs of peroxiredoxin 6 (-/-) mice compared with wild-type mice. In vitro studies showed intracellular reactive oxygen species levels and release of tumor necrosis factor-α, interleukin-1, and matrix metalloproteinase-9 were significantly increased in macrophages from peroxiredoxin 6 (-/-) mice compared with that from wild-type mice after lipopolysaccharide stimulation. Cytokines release was partially suppressed by extracellular signal-regulated kinase and c-Jun N-terminal kinase inhibitors, but not by the p38 mitogen-activated protein kinase inhibitor. CONCLUSIONS: Deletion of peroxiredoxin 6 exaggerates lipopolysaccharide-induced acute lung injury and inflammation with increased oxidative stress, inflammatory responses, and matrix degradation, all of which were partially dependent on nuclear factor-κB, extracellular signal-regulated kinase, and c-Jun N-terminal kinase pathways.

Taxonomic review of the genus Assamacris (Orthoptera: Acrididae: Catantopinae) with a new species and a newly discovered female.

Taxonomic review of the genus Assamacris Uvarov, 1942 is given. The genus Traulitonkinacris You Bi, 1983 is synonymized with Assamacris. Traulitonkinacris bifurcatus You Bi, 1983 is transferred to Assamacris as a new combination. Assamacris splendida sp. nov. is described as new species. A newly discovered female of A. curticerca (Huang, 1981) is introduced. A key to the species is updated.

Taxonomic revision of Phaesticus Uvarov and synonymy with Flatocerus Liang amp; Zheng syn. nov. (Orthoptera: Tetrigidae).

The genus Phaesticus Uvarov, 1940 is revised here with updated generic characteristics and a key to the species. New synonyms and a new combination are proposed: 1) Phaesticus Uvarov, 1940 = Flatocerus Liang Zheng, 1984 syn. nov.; 2) P. mellerborgi (Stål, 1855) = P. insularis (Hancock, 1907) syn. nov., = P. carinatus Zheng, 1998 syn. nov., = P. azemii Mahmood, Idris Salmah, 2007 syn. nov., = F. brachynotus Liang, Chen Chen, 2008 syn. nov., = P. uvarovi Storozhenko Dawwrueng, 2015 syn. nov.; 3) P. moniliantennatus (Günther, 1940) = F. nankunshanensis Liang Zheng, 1984 syn. nov., = F. wuyishanensis Zheng, 1991 syn. nov., = F. guizhouensis Wang, 1992 syn. nov., = F. daqingshanensis Zheng Jiang, 1998 syn. nov., = F. dentifemura Zheng, 2003 syn. nov.; 4) P. hainanensis (Liang, 1988) comb. nov. = F. hainanensis Liang, 1988. Intraspecific variation in the lengths of the hind pronotal processes and hind wings in the family Tetrigidae are discussed in detail.

A new species of the genus Tuberfemurus (Orthoptera: Tetrigoidea: Cladonotinae) with comments on the characters of mitochondrial genome.

A new species, Tuberfemurus viridulus sp. nov. is described and illustrated with photographs. The new species is similar to T. torulisinotus Deng, 2019, but differs from the latter by broader vertex, invisible frontal costa in profile, distinctly truncate apex of hind pronotal process, and two large triangular projections on lower outer carinae of hind femur. An updated key to species of Tuberfemurus is provided. Simultaneously, the complete mitochondrial genome of Tuberfemurus viridulus sp. nov. is sequenced and analyzed. The total length of the assembled mitogenome is 15,060 bp with 37 typical mitochondrial genes and a non-coding region (A + T-rich region). The order and orientation of the gene arrangement pattern are identical to that of most Tetrigoidea species. All PCGs initiate with the standard start codon of ATN, except ATP6 with GAC and ND1 with TTG; and terminate with the complete stop codon (TAA/TAG) or with an incomplete T- codon. This data could provide the genome information available for Tetrigoidea and facilitate phylogenetic studies of related insects.

Osteogenic differentiation characteristics of hip joint capsule fibroblasts obtained from patients with ankylosing spondylitis.

BACKGROUND: Autoimmune disease are fairly common and one that has an excessive degree of disability is Ankylosing spondylitis (AS). As the main cells in connective tissues, fibroblasts may play important roles in AS ossification. The conducted research aims to establish the osteogenic disparity characteristics of fibroblasts cultured in vitro, obtained via AS patients hip joint capsule, as well as investigating the pathological osteogenic molecular workings of AS. METHODS: AS patients hip joint capsules were acquired and fracture patients as the control with the finite fibroblast line were established by using tissue culture method. AS fibroblast proliferation, cycle and apoptosis, expression of osteogenic marker genes, osteogenic phenotypes, and the activation degree of the bone morphogenetic protein (BMP)/Smads signalling pathway were detected by flow cytometry, western blotting and real-time fluorescent quantitative polymerase chain reaction. RESULTS: Proliferative activity in AS fibroblasts were abnormally high, and the apoptotic rate decreased. Compared with normal fibroblasts, the mRNA expression of osteogenic marker genes, expression of osteogenic phenotypes, protein expression of core-binding factor a1 (Cbfa1), Smad1, Smad4, Smad5, phosphorylated (p) Smad1, and pSmad5 in AS fibroblasts were higher; however, the expression of Smad6 was lower. Moreover, recombinant human bone morphogenetic protein-2(rhBMP-2) stimulated Cbfa1 expression by normal and AS fibroblasts through the BMP/Smads signalling pathway. CONCLUSIONS: The fibroblasts of hip joint capsules in patients with AS cultured in vitro have biologic characteristics of osteogenic differentiation and may be important target cells of AS ossification. The Activated BMP/Smads signalling pathway could potentially be a mechanism relating to fibroblasts differentiating into osteoblasts and an ossification mechanism for AS.

A taxonomic study of the genus Macromotettixoides (Tetrigidae, Metrodorinae) with descriptions of two new species and two newly discovered males.

Fifteen species of Macromotettixoides are systematically researched in this paper. Two new species (M. tuberculata Mao, Li Han, sp. n. and M. truncata Mao, Li Han, sp. n.) and two newly discovered males (M. curvimarginus (Zheng Xu) and M. longling Deng) are introduced with descriptions and illustrations. An updated identification key to all known species of the genus is given.

Optimal PD-L1-high cutoff for association with overall survival in patients with urothelial cancer treated with durvalumab monotherapy.

BACKGROUND: Studies have indicated that programmed death ligand 1 (PD-L1) expression may have utility as a predictive biomarker in patients with advanced/metastatic urothelial carcinoma (UC). Different immunohistochemical (IHC) assays are in development to assess PD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (ICs). METHODS: In this post hoc analysis of the single-arm, phase 1/2 Study 1108 (NCT01693562), PD-L1 expression was evaluated from tumor samples obtained prior to second-line treatment with durvalumab in patients with advanced/metastatic UC using the VENTANA (SP263) IHC Assay. The primary objective was to determine whether the TC ≥ 25%/IC ≥ 25% algorithm (i.e., cutoff of ≥ 25% TC or ≥ 25% IC with PD-L1 staining at any intensity above background) was optimal for predicting response to durvalumab. PD-L1 expression data were available from 188 patients. RESULTS: After a median follow-up of 15.8 and 14.6 months, higher PD-L1 expression was associated with longer overall survival (OS) and progression-free survival (PFS), respectively, with significant separation in survival curves for PD-L1-high and-low expressing patients for the TC ≥ 25%/IC ≥ 25% cutoff (median OS: 19.8 vs 4.8 months; hazard ratio: 0.46; 90% confidence interval: 0.33, 0.639). OS was also prolonged for PD-L1-high compared with-low patients when samples were categorized using TC/IC combined positive score ≥ 10 and IC≥ 5% cutoffs. In multivariate analysis, IC but not TC PD-L1 expression was significantly associated with OS, PFS, and objective response rate (P < 0.001 for each), although interaction analysis showed similar directionality of benefit for ICs and TCs. CONCLUSIONS: These findings support the utility of a combined TC/IC algorithm for predicting response to durvalumab in patients with UC, with the TC≥ 25%/IC≥ 25% cutoff optimal when used with the VENTANA (SP263) IHC Assay.

Analytical Validation and Clinical Utility of an Immunohistochemical Programmed Death Ligand-1 Diagnostic Assay and Combined Tumor and Immune Cell Scoring Algorithm for Durvalumab in Urothelial Carcinoma.

CONTEXT.­: Clinical responses to anti-programmed death receptor-1 and anti-programmed death ligand-1 (PD-L1) agents are generally improved in patients with high PD-L1 expression compared with those with low/negative expression across several tumor types, including urothelial carcinoma. OBJECTIVE.­: To validate a PD-L1 immunohistochemical diagnostic test in urothelial carcinoma patients treated with the anti-PD-L1 monoclonal antibody durvalumab. DESIGN.­: The Ventana PD-L1 (SP263) assay was validated for intended use in urothelial carcinoma formalin-fixed, paraffin-embedded samples in studies addressing sensitivity, specificity, robustness, and precision, and implemented in study CD-ON-MEDI4736-1108 (NCT01693562). Efficacy was analyzed in patients classified according to prespecified PD-L1 expression cutoffs: PD-L1 high (if >1% of the tumor area contained tumor-associated immune cells, ≥25% of tumor cells or ≥25% of immune cells stained for PD-L1; if ≤1% of the tumor area contained immune cells, ≥25% of tumor cells or 100% of immune cells stained for PD-L1) and PD-L1 low/negative (did not meet criteria for PD-L1 high). RESULTS.­: The assay met all predefined acceptance criteria for sensitivity, specificity, and precision. Interreader and intrareader precision overall agreement were 93.0% and 92.4%, respectively. For intraday reproducibility and interday precision, overall agreement was 99.2% and 100%, respectively. Interlaboratory overall agreement was 92.6%. In study CD-ON-MEDI4736-1108, durvalumab demonstrated clinical activity and durable responses in both PD-L1-high and PD-L1-low/negative subgroups, although objective response rates tended to be higher in the PD-L1-high subgroup than in the PD-L1-low/negative subgroup. CONCLUSIONS.­: Determination of PD-L1 expression in urothelial carcinoma patients using the Ventana PD-L1 (SP263) assay was precise, highly reproducible, and clinically relevant.

Preventive effects of curcumin and dexamethasone on lung transplantation-associated lung injury in rats.

OBJECTIVE: To investigate potential effects of curcumin or dexamethasone on lung transplantation-associated lung injury. DESIGN: Prospective, randomized, controlled study. SETTING: Research laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Sham-operated rats were used as time-matched controls. Experimental rats were subjected to unilateral orthotopic lung transplantation with 4 hrs of cold ischemia followed by 2 hrs (or 24 hrs) of reperfusion. Animals were randomly assigned to vehicle-, curcumin-, or dexamethasone-treated groups. MEASUREMENTS AND MAIN RESULTS: Transplantation-associated lung injury was characterized by an increased alveolar-capillary permeability and myeloperoxidase activity and decreased levels of arterial oxygen tension/inspired oxygen concentration ratio. Pretreatment with curcumin and dexamethasone significantly prevented barrier disruption, lung edema, tissue inflammation, and decreased PaO2 at the early stage of posttransplantation. Nuclear factor-kappaB in transplanted lungs was activated, accompanied by an increase in messenger RNA levels and protein content of tumor necrosis factor-alpha, interleukin-6, and matrix metalloproteinase-9 in lung graft. Those changes were prevented by pretreatment with curcumin and dexamethasone. CONCLUSIONS: Curcumin can be an alternative therapy for protecting lung transplantation-associated injury by suppressing nuclear factor-kappaB-mediated expression of inflammatory genes.

Upregulation of AQP3 and AQP5 induced by dexamethasone and ambroxol in A549 cells.

Aquaporins (AQPs) are membrane channel proteins that play roles in the regulation of water permeability in many tissues. AQP1 and AQP5 expressed in lung provide the principal route for osmotically driven water transport. In the airways, AQP3 and AQP4 facilitate water transport. Dexamethasone and ambroxol are often used to treat patients with pulmonary diseases accompanied by airway hypersecretion. The role of AQPs in these effective treatments has not been addressed. In this study, we analyzed the expression of AQPs in a human airway epithelial cell line (A549 cells) and showed that AQP3 and 5, but not AQP1 and 4, were expressed in A549 cells. Both dexamethasone and ambroxol stimulated the expression of AQP3 and 5 at the mRNA and protein levels. The data suggest potential roles of AQP3 and 5 in the regulation of airway hypersecretion, perhaps ultimately providing a target for treating such diseases.

µ-4,4'-Bipyridine-κN:N'-bis-[aqua-(4,4'-bi-pyridine-κN)(l-valinato-κN,O)copper(II)] dinitrate dihydrate.

In the title dinuclear complex, [Cu(2)(C(5)H(10)NO(2))(2)(C(10)H(8)N(2))(3)(H(2)O)(2)](NO(3))(2)·2H(2)O, each of the two l-valinate anions chelates a Cu(II) center through the amino N and carboxyl-ate O atom, forming a five-membered ring. A 4,4'-bipyridine mol-ecule bridges two water-coordinated Cu atoms, each of which is connected to another 4,4'-bipyridine, giving rise to a square-pyramidal coordination geometry for the Cu(II) centers. The dinuclear dications, nitrate anions and uncoord-inated water mol-ecules are linked into a two-dimensional structure.

2-Methoxy-phenyl 2-{2-[1-methyl-5-(4-methyl-benzo-yl)pyrrol-2-yl]acetamido}acetate.

The title compound, amtolmetin guacil, C(24)H(24)N(2)O(5), is a new gastroprotective non-steroidal anti-inflammatory drug. In the crystal structure, the drug mol-ecule is linked into a one-dimensional structure along the c axis by weak N-H⋯O inter-actions between the amide groups. C-H⋯O and C-H⋯π inter-actions influence the packing.

Characterization of the complete mitochondrial genome of the Yunnan endemic grasshopper Longchuanacris curvifurculus (Insecta: Orthoptera: Catantopidae).

Longchuanacris curvifurculus (L. curvifurculus) was once a dominating grasshopper in the Yunnan province (People's Republic of China) that occupy important ecological niche. However, its population has severely declined because of the deterioration of ecological environment. Identifying the species and source of L. curvifurculus is important for biodiversity conservation and ecological/environmental preservation. In the study, the complete mitochondrial genome of L. curvifurculus was assembled from high-coverage (36.8×) Illumina MiSeq sequencing data. The circular genome is 15,450 bp in length, harboring 37 typical mitochondrial genes and one control region. The nucleotide composition is asymmetric (43.0% A, 14.3% C, 10.5% G, and 32.2% T), with an overall A + T content of 75.2%. All the protein-coding genes (PCGs) are initiated with typical ATN start codons and terminated by the typical TAA codons or the incomplete T(aa) codon. The control region has a remarkably high A + T content (84.9%) and is located between genes rrnS and trnV.

Population Modeling of Tumor Kinetics and Overall Survival to Identify Prognostic and Predictive Biomarkers of Efficacy for Durvalumab in Patients With Urothelial Carcinoma.

Durvalumab is an anti-PD-L1 monoclonal antibody approved for patients with locally advanced or metastatic urothelial carcinoma (UC) that has progressed after platinum-containing chemotherapy. A population tumor kinetic model, coupled with dropout and survival models, was developed to describe longitudinal tumor size data and predict overall survival in UC patients treated with durvalumab (NCT01693562) and to identify prognostic and predictive biomarkers of clinical outcomes. Model-based covariate analysis identified liver metastasis as the most influential factor for tumor growth and immune-cell PD-L1 expression and baseline tumor burden as predictive factors for tumor killing. Tumor or immune-cell PD-L1 expression, liver metastasis, baseline hemoglobin, and albumin levels were identified as significant covariates for overall survival. These model simulations provided further insights into the impact of PD-L1 cutoff values on treatment outcomes. The modeling framework can be a useful tool to guide patient selection and enrichment strategies for immunotherapies across various cancer indications.

Population Pharmacokinetics of Durvalumab in Cancer Patients and Association With Longitudinal Biomarkers of Disease Status.

The objectives of this analysis were to develop a population pharmacokinetics (PK) model of durvalumab, an anti-PD-L1 antibody, and quantify the impact of baseline and time-varying patient/disease characteristics on PK. Pooled data from two studies (1,409 patients providing 7,407 PK samples) were analyzed with nonlinear mixed effects modeling. Durvalumab PK was best described by a two-compartment model with both linear and nonlinear clearances. Three candidate models were evaluated: a time-invariant clearance (CL) model, an empirical time-varying CL model, and a semimechanistic time-varying CL model incorporating longitudinal covariates related to disease status (tumor shrinkage and albumin). The data supported a slight decrease in durvalumab clearance with time and suggested that it may be associated with a decrease in nonspecific protein catabolic rate among cancer patients who benefit from therapy. No covariates were clinically relevant, indicating no need for dose adjustment. Simulations indicated similar overall PK exposures following weight-based and flat-dosing regimens.

Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study.

IMPORTANCE: The data reported herein were accepted for assessment by the US Food and Drug Administration for Biologics License Application under priority review to establish the clinical benefit of durvalumab as second-line therapy for locally advanced or metastatic urothelial carcinoma (UC), resulting in its recent US approval. OBJECTIVE: To report a planned update of the safety and efficacy of durvalumab in patients with locally advanced/metastatic UC. DESIGN, SETTING, AND PARTICIPANTS: This is an ongoing phase 1/2 open-label study of 191 adult patients with histologically or cytologically confirmed locally advanced/metastatic UC whose disease had progressed on, were ineligible for, or refused prior chemotherapy from 60 sites in 9 countries as reported herein. INTERVENTION: Patients were administered durvalumab intravenous infusion, 10 mg/kg every 2 weeks, for up to 12 months or until progression, starting another anticancer therapy, or unacceptable toxic effects. MAIN OUTCOMES AND MEASURES: Primary end points were safety and confirmed objective response rate (ORR) per blinded independent central review (Response Evaluation Criteria In Solid Tumors [RECIST], version 1.1). RESULTS: A total of 191 patients with UC had received treatment. As of October 24, 2016 (90-day update), the median follow-up was 5.78 months (range, 0.4-25.9 months). The median age of patients was 67.0 years and most were male (136 [71.2%]) and white (123 [71.1%]). All patients had stage 4 disease, and 190 (99.5%) had prior anticancer therapy (182 [95.3%] postplatinum). The ORR was 17.8% (34 of 191; 95% CI, 12.7%-24.0%), including 7 complete responses. Responses were early (median time to response, 1.41 months), durable (median duration of response not reached), and observed regardless of programmed cell death ligand-1 (PD-L1) expression (ORR, 27.6% [n = 27; 95% CI, 19.0%-37.5%] and 5.1% [n = 4; 95% CI, 1.4%-12.5%] in patients with high and low or negative expression of PD-L1, respectively). Median progression-free survival and overall survival were 1.5 months (95% CI, 1.4-1.9 months) and 18.2 months (95% CI, 8.1 months to not estimable), respectively; the 1-year overall survival rate was 55% (95% CI, 44%-65%), as estimated by Kaplan-Meier method. Grade 3/4 treatment-related adverse events (AEs) occurred in 13 patients (6.8%); grade 3/4 immune-mediated AEs occurred in 4 patients (2.1%); and treatment-related AEs led to discontinuation of 3 patients (1.6%), 2 of whom had immune-mediated AEs that led to death (autoimmune hepatitis and pneumonitis). CONCLUSIONS AND RELEVANCE: Durvalumab, 10 mg/kg every 2 weeks, demonstrates favorable clinical activity and an encouraging and manageable safety profile in patients with locally advanced/metastatic UC. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01693562.