The oxidized phospholipid PGPC impairs endothelial function by promoting endothelial cell ferroptosis via FABP3.

Ferroptosis is a novel cell death mechanism that is mediated by iron-dependent lipid peroxidation. It may be involved in atherosclerosis development. Products of phospholipid oxidation play a key role in atherosclerosis. 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) is a phospholipid oxidation product present in atherosclerotic lesions. It remains unclear whether PGPC causes atherosclerosis by inducing endothelial cell ferroptosis. In this study, human umbilical vein endothelial cells (HUVECs) were treated with PGPC. Intracellular levels of ferrous iron, lipid peroxidation, superoxide anions (O2•-), and glutathione were detected, and expression of fatty acid binding protein-3 (FABP3), glutathione peroxidase 4 (GPX4), and CD36 were measured. Additionally, the mitochondrial membrane potential (MMP) was determined. Aortas from C57BL6 mice were isolated for vasodilation testing. Results showed that PGPC increased ferrous iron levels, the production of lipid peroxidation and O2•-, and FABP3 expression. However, PGPC inhibited the expression of GPX4 and glutathione production and destroyed normal MMP. These effects were also blocked by ferrostatin-1, an inhibitor of ferroptosis. FABP3 silencing significantly reversed the effect of PGPC. Furthermore, PGPC stimulated CD36 expression. Conversely, CD36 silencing reversed the effects of PGPC, including PGPC-induced FABP3 expression. Importantly, E06, a direct inhibitor of the oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine IgM natural antibody, inhibited the effects of PGPC. Finally, PGPC impaired endothelium-dependent vasodilation, ferrostatin-1 or FABP3 inhibitors inhibited this impairment. Our data demonstrate that PGPC impairs endothelial function by inducing endothelial cell ferroptosis through the CD36 receptor to increase FABP3 expression. Our findings provide new insights into the mechanisms of atherosclerosis and a therapeutic target for atherosclerosis.

Endothelial extracellular vesicles induce acute lung injury via follistatin-like protein 1.

Cardiopulmonary bypass has been speculated to elicit systemic inflammation to initiate acute lung injury (ALI), including acute respiratory distress syndrome (ARDS), in patients after cardiac surgery. We previously found that post-operative patients showed an increase in endothelial cell-derived extracellular vesicles (eEVs) with components of coagulation and acute inflammatory responses. However, the mechanism underlying the onset of ALI owing to the release of eEVs after cardiopulmonary bypass, remains unclear. Plasma plasminogen-activated inhibitor-1 (PAI-1) and eEV levels were measured in patients with cardiopulmonary bypass. Endothelial cells and mice (C57BL/6, Toll-like receptor 4 knockout (TLR4-/-) and inducible nitric oxide synthase knockout (iNOS-/-)) were challenged with eEVs isolated from PAI-1-stimulated endothelial cells. Plasma PAI-1 and eEVs were remarkably enhanced after cardiopulmonary bypass. Plasma PAI-1 elevation was positively correlated with the increase in eEVs. The increase in plasma PAI-1 and eEV levels was associated with post-operative ARDS. The eEVs derived from PAI-1-stimulated endothelial cells could recognize TLR4 to stimulate a downstream signaling cascade identified as the Janus kinase 2/3 (JAK2/3)-signal transducer and activator of transcription 3 (STAT3)-interferon regulatory factor 1 (IRF-1) pathway, along with iNOS induction, and cytokine/chemokine production in vascular endothelial cells and C57BL/6 mice, ultimately contributing to ALI. ALI could be attenuated by JAK2/3 or STAT3 inhibitors (AG490 or S3I-201, respectively), and was relieved in TLR4-/- and iNOS-/- mice. eEVs activate the TLR4/JAK3/STAT3/IRF-1 signaling pathway to induce ALI/ARDS by delivering follistatin-like protein 1 (FSTL1), and FSTL1 knockdown in eEVs alleviates eEV-induced ALI/ARDS. Our data thus demonstrate that cardiopulmonary bypass may increase plasma PAI-1 levels to induce FSTL1-enriched eEVs, which target the TLR4-mediated JAK2/3/STAT3/IRF-1 signaling cascade and form a positive feedback loop, leading to ALI/ARDS after cardiac surgery. Our findings provide new insight into the molecular mechanisms and therapeutic targets for ALI/ARDS after cardiac surgery.

High-density lipoprotein regulates angiogenesis by affecting autophagy via miRNA-181a-5p.

We previously demonstrated that normal high-density lipoprotein (nHDL) can promote angiogenesis, whereas HDL from patients with coronary artery disease (dHDL) is dysfunctional and impairs angiogenesis. Autophagy plays a critical role in angiogenesis, and HDL regulates autophagy. However, it is unclear whether nHDL and dHDL regulate angiogenesis by affecting autophagy. Endothelial cells (ECs) were treated with nHDL and dHDL with or without an autophagy inhibitor. Autophagy, endothelial nitric oxide synthase (eNOS) expression, miRNA expression, nitric oxide (NO) production, superoxide anion (O2•-) generation, EC migration, and tube formation were evaluated. nHDL suppressed the expression of miR-181a-5p, which promotes autophagy and the expression of eNOS, resulting in NO production and the inhibition of O2•- generation, and ultimately increasing in EC migration and tube formation. dHDL showed opposite effects compared to nHDL and ultimately inhibited EC migration and tube formation. We found that autophagy-related protein 5 (ATG5) was a direct target of miR-181a-5p. ATG5 silencing or miR-181a-5p mimic inhibited nHDL-induced autophagy, eNOS expression, NO production, EC migration, tube formation, and enhanced O2•- generation, whereas overexpression of ATG5 or miR-181a-5p inhibitor reversed the above effects of dHDL. ATG5 expression and angiogenesis were decreased in the ischemic lower limbs of hypercholesterolemic low-density lipoprotein receptor null (LDLr-/-) mice when compared to C57BL/6 mice. ATG5 overexpression improved angiogenesis in ischemic hypercholesterolemic LDLr-/- mice. Taken together, nHDL was able to stimulate autophagy by suppressing miR-181a-5p, subsequently increasing eNOS expression, which generated NO and promoted angiogenesis. In contrast, dHDL inhibited angiogenesis, at least partially, by increasing miR-181a-5p expression, which decreased autophagy and eNOS expression, resulting in a decrease in NO production and an increase in O2•- generation. Our findings reveal a novel mechanism by which HDL affects angiogenesis by regulating autophagy and provide a therapeutic target for dHDL-impaired angiogenesis.

High-density lipoprotein regulates angiogenesis by long non-coding RNA HDRACA.

Normal high-density lipoprotein (nHDL) can induce angiogenesis in healthy individuals. However, HDL from patients with coronary artery disease undergoes various modifications, becomes dysfunctional (dHDL), and loses its ability to promote angiogenesis. Here, we identified a long non-coding RNA, HDRACA, that is involved in the regulation of angiogenesis by HDL. In this study, we showed that nHDL downregulates the expression of HDRACA in endothelial cells by activating WW domain-containing E3 ubiquitin protein ligase 2, which catalyzes the ubiquitination and subsequent degradation of its transcription factor, Kruppel-like factor 5, via sphingosine 1-phosphate (S1P) receptor 1. In contrast, dHDL with lower levels of S1P than nHDL were much less effective in decreasing the expression of HDRACA. HDRACA was able to bind to Ras-interacting protein 1 (RAIN) to hinder the interaction between RAIN and vigilin, which led to an increase in the binding between the vigilin protein and proliferating cell nuclear antigen (PCNA) mRNA, resulting in a decrease in the expression of PCNA and inhibition of angiogenesis. The expression of human HDRACA in a hindlimb ischemia mouse model inhibited the recovery of angiogenesis. Taken together, these findings suggest that HDRACA is involved in the HDL regulation of angiogenesis, which nHDL inhibits the expression of HDRACA to induce angiogenesis, and that dHDL is much less effective in inhibiting HDRACA expression, which provides an explanation for the decreased ability of dHDL to stimulate angiogenesis.

Phylogenetic classification and palm-inflorescence anthophily of the Colocasiomyia zeylanica species group (Diptera: Drosophilidae), with descriptions of five new species.

The zeylanica group is one of the six species groups of the anthophilic genus Colocasiomyia de Meijere in the family Drosophilidae. In addition to two known species, five morphospecies have been recognized as members of this species group but left undescribed formally. In this study, species delimitation of these putatively new species was determined by barcoding of the mitochondrial COI (cytochrome c oxydase subunit I) gene and morphological comparison. Phylogenetic relationships within the genus Colocasiomyia were inferred by a cladistic analysis of 89 morphological characters. Based on the results of these analyses, we redefined the zeylanica species group and established two subgroups within it: the zeylanica subgroup comprised of C. zeylanica, C. nepalensis, C. pinangae sp. nov., C. besaris sp. nov. and C. luciphila sp. nov., and the oligochaeta subgroup of C. oligochaeta sp. nov. and C. grimaldii sp. nov. In addition, we briefly address the anthophilic habits of drosophilid flies using palm (Arecaceae) inflorescences, especially of the zeylanica group, compiling scattered collection records from the Oriental and Papuan regions.

Secondary reversion to sexual monomorphism associated with tissue-specific loss of doublesex expression.

Animal evolution is characterized by frequent turnover of sexually dimorphic traits-new sex-specific characters are gained, and some ancestral sex-specific characters are lost, in many lineages. In insects, sexual differentiation is predominantly cell autonomous and depends on the expression of the doublesex (dsx) transcription factor. In most cases, cells that transcribe dsx have the potential to undergo sex-specific differentiation, while those that lack dsx expression do not. Consistent with this mode of development, comparative research has shown that the origin of new sex-specific traits can be associated with the origin of new spatial domains of dsx expression. In this report, we examine the opposite situation-a secondary loss of the sex comb, a male-specific grasping structure that develops on the front legs of some drosophilid species. We show that while the origin of the sex comb is linked to an evolutionary gain of dsx expression in the leg, sex comb loss in a newly identified species of Lordiphosa (Drosophilidae) is associated with a secondary loss of dsx expression. We discuss how the developmental control of sexual dimorphism affects the mechanisms by which sex-specific traits can evolve.

Evolution of the Colocasiomyia gigantea Species Group (Diptera: Drosophilidae): Phylogeny, Biogeography and Shift of Host Use.

The gigantea species group of the genus Colocasiomyia de Meijere (Diptera: Drosophilidae) is among the four aroid-breeding species groups in this genus; however, it differs from the remaining three groups in the host use: all the flies in this group use plants from the subfamily Monsteroideae instead of from the subfamily Aroideae. So far, we have not resolved the phylogenetic relationship within this group, making it difficult to trace its geographical origin, pattern of species diversification and history of host plant use. In this study, we reconstructed the phylogenetic relationships within the C. gigantea group using DNA sequences of eight (two mitochondrial and six nuclear) gene markers, and we inferred the ancestral areas and host plants of the group based on the resulting phylogeny. According to the results, the C. gigantea group may have diverged from its sister group (i.e., the C. cristata group) through vicariance between the northeastern Oriental region and Sundaland + Wallacea, and the subsequent diversification of the C. gigantea group occurred mostly in the northeastern Oriental region, although an Oriental-to-Sundaland dispersal was followed by vicariance between these two areas, which finally gave rise to the C. gigantea-C. scindapsae lineage in the latter area. We inferred the most likely ancestral host plant of the C. gigantea group to be of the genus Rhaphidophora Hassk, with possible subsequent shifts to Scindapsus Schott and/or Epipremnum Schott plants. We discuss the potential for the egg filaments in the C. gigantea group to be used as a model system for comparative studies in pollination mutualism and developmental genetics concerning tubulogenesis.

A new species of the Colocasiomyia gigantea species group (Diptera, Drosophilidae) breeding on inflorescences of Scindapsus maclurei (Araceae).

The gigantea group is one of the six species groups of the genus Colocasiomyia Meijere, 1914 (Diptera, Drosophilidae). All the nine known species of this group breed on inflorescence/infructescence of host plants of the subfamily Monsteroideae (Araceae) and are geographically restricted to the Oriental region: seven species found exclusively from Rhaphidophora spp. in southern China, and the remaining two from Sabah (host plant: Scindapsus coriaceus) in Borneo or from West Java (host plant: Epipremnum pinnatum). In the present paper, a new member of the gigantea group, C. daiae sp. nov., is described, with adult specimens and eggs collected from inflorescences of Scindapsus maclurei in Hainan, China and larvae and pupae reared from field-collected eggs in the laboratory.

The genus Dettopsomyia Lamb, 1914 (Diptera, Drosophilidae) from southern China.

The genus Dettopsomyia was established by Lamb in 1914 for a single species, De.formosa described therein. It contains 13 known species recorded from the Old World (the Oriental, Australasian, Palearctic and Afrotropical regions). In the present paper, five new species discovered from southern China are described as members of Dettopsomyia: De.acutipenis Wang & Gao, sp. nov., De.serripenis Wang & Gao, sp. nov., De.discontinua Wang & Gao, sp. nov., De.camelonota Wang, Li & Gao, sp. nov. and De.paranigrovittata Wang, Li & Gao, sp. nov. The new species were delimitated, based on not only morphological characters but also molecular data.

Highly contiguous assemblies of 101 drosophilid genomes.

Over 100 years of studies in Drosophila melanogaster and related species in the genus Drosophila have facilitated key discoveries in genetics, genomics, and evolution. While high-quality genome assemblies exist for several species in this group, they only encompass a small fraction of the genus. Recent advances in long-read sequencing allow high-quality genome assemblies for tens or even hundreds of species to be efficiently generated. Here, we utilize Oxford Nanopore sequencing to build an open community resource of genome assemblies for 101 lines of 93 drosophilid species encompassing 14 species groups and 35 sub-groups. The genomes are highly contiguous and complete, with an average contig N50 of 10.5 Mb and greater than 97% BUSCO completeness in 97/101 assemblies. We show that Nanopore-based assemblies are highly accurate in coding regions, particularly with respect to coding insertions and deletions. These assemblies, along with a detailed laboratory protocol and assembly pipelines, are released as a public resource and will serve as a starting point for addressing broad questions of genetics, ecology, and evolution at the scale of hundreds of species.

Simvastatin inhibits POVPC-mediated induction of endothelial-to-mesenchymal cell transition.

Endothelial-to-mesenchymal transition (EndMT), the process by which an endothelial cell (EC) undergoes a series of molecular events that result in a mesenchymal cell phenotype, plays an important role in atherosclerosis. 1-Palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC), derived from the oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine, is a proinflammatory lipid found in atherosclerotic lesions. Whether POVPC promotes EndMT and how simvastatin influences POVPC-mediated EndMT remains unclear. Here, we treated human umbilical vein ECs with POVPC, simvastatin, or both, and determined their effect on EC viability, morphology, tube formation, proliferation, and generation of NO and superoxide anion (O2•-). Expression of specific endothelial and mesenchymal markers was detected by immunofluorescence and immunoblotting. POVPC did not affect EC viability but altered cellular morphology from cobblestone-like ECs to a spindle-like mesenchymal cell morphology. POVPC increased O2- generation and expression of alpha-smooth muscle actin, vimentin, Snail-1, Twist-1, transforming growth factor-beta (TGF-ß), TGF-ß receptor II, p-Smad2/3, and Smad2/3. POVPC also decreased NO production and expression of CD31 and endothelial NO synthase. Simvastatin inhibited POVPC-mediated effects on cellular morphology, production of O2•- and NO, and expression of specific endothelial and mesenchymal markers. These data demonstrate that POVPC induces EndMT by increasing oxidative stress, which stimulates TGF-ß/Smad signaling, leading to Snail-1 and Twist-1 activation. Simvastatin inhibited POVPC-induced EndMT by decreasing oxidative stress, suppressing TGF-ß/Smad signaling, and inactivating Snail-1 and Twist-1. Our findings reveal a novel mechanism of atherosclerosis that can be inhibited by simvastatin.

Phylogeny, taxonomy and flower-breeding ecology of the Colocasiomyia cristata species group (Diptera: Drosophilidae), with descriptions of ten new species.

The phylogeny of the Colocasiomyia cristata species group is reconstructed as a hypothesis, based on DNA sequences of two mitochondrial and six nuclear genes and 51 morphological characters. The resulting tree splits this species group into two clades, one of which corresponds to the colocasiae subgroup. Therefore, a new species subgroup named as the cristata subgroup is established for the other clade. Within the cristata subgroup, three subclades are recognized and each of them is defined as a species complex: the cristata complex composed of five species (including three new ones: C. kinabaluana sp. nov., C. kotana sp. nov. and C. matthewsi sp. nov.), the sabahana complex of two species (C. sabahana sp. nov. and C. sarawakana sp. nov.), and the xenalocasiae complex of five species (including C. sumatrana sp. nov. and C. leucocasiae sp. nov.). There are, however, three new species (C. ecornuta sp. nov., C. grandis sp. nov. and C. vieti sp. nov.) not assigned to any species complex. In addition, breeding habits are described for four cristata-subgroup species, each of which monopolizes its specific host plant. And, data of host-plant use are compiled for all species of the cristata group from records at various localities in the Oriental and Papuan regions. The evolution of host-plant selection and sharing modes is considered by mapping host-plant genera of each species on the phylogenetic tree resulting from the present study.

Associations of coenzyme Q10 with endothelial function in hemodialysis patients.

BACKGROUND: Endothelial dysfunction is common in patients undergoing hemodialysis (HD). However, little is known about the relationship between endothelial dysfunction and coenzyme Q10 (CoQ10) levels in HD patients. METHODS: Eligible HD patients were enrolled in this study according to prespecified inclusion and exclusion criteria. Endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Plasma CoQ10, serum malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. The potential confounders identified by univariate analyses (P < 0.15) were selected in a stepwise multiple regression model. RESULTS: In total, 111 HD patients were enrolled in this study. The mean CoQ10 level was 633.53 ± 168.66 ng/mL, and endothelial dysfunction was prevalent (91.0%) using a cut-off value of 10% FMD. A significant correlation was observed between FMD and plasma CoQ10 level (r = 0.727, P < 0.001). After adjusting for potential parameters, a stepwise multivariate linear regression analysis revealed that CoQ10 level was an independent predictor of FMD (ß = 0.018, P < 0.001). When CoQ10 was dichotomized using the median value (639.74 ng/mL), the conclusion remained unchanged (ß = 0.584, P < 0.001). Pearson's correlation analyses revealed that plasma CoQ10 level was negatively correlated with MDA (r = -0.48, P < 0.001) and 8-OHdG (r = -0.43, P < 0.001) levels. CONCLUSION: Our data demonstrate that impaired brachial artery FMD was common in HD patients. CoQ10 level was independently associated with FMD, and oxidative stress may constitute a link between CoQ10 level and endothelial dysfunction in these patients.

Descriptions of two new species of the genus Colocasiomyia (Diptera, Drosophilidae) breeding on Rhaphidophora host plants in Yunnan, China.

The genus Colocasiomyia de Meijere (Diptera, Drosophilidae) is known to include 30 described and nearly 60 undescribed species classified into six species groups. Among these, the C. gigantea group of seven known species (two Southeast Asian and five Chinese) proved to be peculiar for its specificity on monsteroid (subfamily Monsteroideae, family Araceae) host plants. In this paper, two new species, C. todai Jiao & Gao, sp. nov. and C. liae Jiao & Gao, sp. nov., are described as members of the C. gigantea group with specimens collected from inflorescences of the monsteroid host species Rhaphidophora peepla (Roxb.) Schott and R. crassicaulis Engl. & Krause, respectively, in Yunnan, China. The two new species are delimitated, in comparison with all known species, based on not only morphological but also DNA barcode (partial sequence of the mitochondrial COI, i.e., cytochrome c oxydase subunit I, gene) data. A revised key to all the nine species of the C. gigantea species group is provided.

Synergistic antitumor activity of sorafenib and artesunate in hepatocellular carcinoma cells.

Sorafenib is currently the standard chemotherapy drug for treatment of advanced hepatocellular carcinoma (HCC). But its efficacy requires improvement, it is imperative to seek therapeutic strategies that combine sorafenib with other anticancer agents. In this study we investigated the synergistic anticancer effect of combining sorafenib and artesunate, an anti-malaria drug derivative, against HCC in vitro and in vivo. We first showed that artesunate (1-100 µM) alone dose-dependently inhibited the proliferation of five HCC cell lines tested with IC50 values of around 100 µM. Artesunate treatment dose-dependently increased the ROS level in both HuH7 and Hep3B cells; addition of NAC significantly ameliorated the antiproliferation effect of artesunate against HuH7 and Hep3B cells. Then we demonstrated that combination of sorafenib and artesunate exerted synergistic antiproliferation effect and induced synergistic apoptosis in HCC cell lines. In nude mice bearing Hep3B xenografts, combined administration of sorafenib and artesunate significantly enhanced the suppression on tumor growth. We further revealed that sorafenib dose-dependently decreased the levels of p-ERK and p-STAT3, whereas artesunate markedly increased the levels of p-ERK and p-STAT3 in HuH7 and Hep3B cells. When used in combination, sorafenib abolished artesunate-elevated levels of p-STAT3 and p-ERK. Moreover, pharmacological inhibition of ERK by inhibitor PD0325901 or STAT3 by inhibitor Stattic markedly enhanced the anticancer activity of artesunate, suggesting that suppression of ERK and STAT3 signaling by sorafenib contributes to the synergistic anticancer activity against HCC caused by combination of sorafenib and artesunate. Taken together, our results provide an evidence for possible use of sorafenib plus artesunate or artemisinin analogs for treatment of HCC in the future.

The Hirtodrosophila melanderi species group (Diptera: Drosophilidae) from the Huanglong National Nature Reserve, Sichuan, China.

The Hirtodrosophila melanderi species group is currently known for thirteen described species, most of which were thought to be fungivorous. More than half known species of this species group were recorded exclusively from high altitude zone to the southeast of the Qinghai-Tibet Plateau in China. In our recent field survey in the Huanglong National Nature Reserve (located to the east of the Qinghai-Tibet Plateau) in Sichuan Province, China, we collected dozens of specimens of the H. melanderi group there. In the present study, these specimens are subjected to species delimitation based on data of not only morphology, but also DNA barcodes (nucleotide sequences of a 658-bp fragment of the mitochondrial cytochrome c oxidase subunit I gene). The five new species thus recognized are described: Hirtodrosophila minshanensis sp. nov., H. lambda sp. nov., H. zhangae sp. nov., H. zouae sp. nov., and H. nigrispina sp. nov. In addition, an updated key to all species of the H. melanderi species group is provided.

Downregulated miR-383-5p contributes to the proliferation and migration of gastric cancer cells and is associated with poor prognosis.

AIM: The study aims to identify differentially expressed microRNAs (DEMs) in gastric cancer (GC) and explore the expression, prognosis and downstream regulation role of miR-383-5p in GC. METHODS: The GC miRNA-Seq and clinical information were downloaded from Firebrowse which stores integrated data sourced from The Cancer Genome Atlas database. The DEMs were identified with limma package in R software at the cut-off criteria of P < 0.05 and |log2 fold change| > 1.0 (|log2FC| > 1.0). The expression of miR-383-5p in GC cell lines and 54 paired GC tissues was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The overall survival curve of miR-383-5p and the association between its expression and clinicopathological features were explored. Wound healing and cell counting kit-8 assays were performed to investigate the capacity of miR-383-5p in cell proliferation and migration. The downstream target genes were predicted by bioinformatics tools (miRDB, TargetScan and starBase). The consensus target genes were selected for gene functional enrichment analysis by FunRich v3.0 software. The luciferase reporter assay was performed to verify the potential targeting sites of miR-383-5p on lactate dehydrogenase A (LDHA). RESULTS: A total of 21 down-regulated miRNAs (including miR-383-5p) and 202 up-regulated miRNAs were identified by analyzing GC miRNA-Seq data. Survival analysis found that patients with low miR-383-5p expression had a shorter survival time (median survival time 21.1 months) than those with high expression (46.9 months). The results of qRT-PCR indicated that miR-383-5p was downregulated in GC cell lines and tissues, which was consistent with miRNA-Seq data. The expression of miR-383-5p was significantly associated with tumor size and differentiation grade. Besides, overexpression of miR-383-5p suppressed GC cells proliferation and migration. A total of 49 common target genes of miR-383-5p were obtained by bioinformatics tools and gene functional enrichment analysis showed that these predicted genes participated in PI3K, mTOR, c-MYC, TGF-beta receptor, VEGF/VEGFR and E-cadherin signaling pathways. The data showed that expression of miR-383-5p was negatively correlated with target LDHA (r = -0.203). Luciferase reporter assay suggested that LDHA was a target of miR-383-5p. CONCLUSION: The present study concluded that miR-383-5p was downregulated and may act as a tumor suppressor in GC. Furthermore, its target genes were involved in important signaling pathways. It could be a prognostic biomarker and play a vital role in exploring the molecular mechanism of GC.

The Lordiphosa denticeps species group (Diptera: Drosophilidae) in China, with redescriptions of four known species and descriptions of nine new species.

Based on specimens collected from Yunnan, Xizang, and Taiwan in China, nine new species of the Lordiphosa denticeps species group, L. mikioides sp. nov., L. kimurai sp. nov., L. anthophilia sp. nov., L. yangi sp. nov., L. tibetica sp. nov., L. medogensis sp. nov., L. hamatispina sp. nov., L. secula sp. nov., and L. spatulata sp. nov., were described and four known species, L. denticeps (Okada Sasakawa), L. neokurokawai (Singh Gupta), L. ramula Zhang, and L. tripartita (Okada), were redescribed. In addition, we provided a key to all species of this species group. Males of three new species, L. mikioides, L. kimurai, and L. anthophilia, have distinct sex-combs consisting of black, stout teeth on the 1st and 2nd tarsomeres of foreleg; the large, longitudinal sex-comb on the 1st tarsomere is similar to those seen in the L. miki species group and the subgenus Sophophora Sturtevant of the genus Drosophila Fallén. Two of these and another new species were collected at flowering Impatiens L. (Balsaminaceae) stands: all specimens of L. anthophilia and L. medogensis directly from flowers, and some specimens of L. kimurai by net sweeping. The presence of large, longitudinal sex-combs and the flower-visiting habit were reported for the first time in the L. denticeps group.

Taxonomy of the Hirtodrosophila melanderi species group (Diptera: Drosophilidae), with descriptions of four new species from southwestern China.

The Hirtodrosophila melanderi species group contains nine known species recorded from either the Old or the New World. All these species were thought to be strict fungivorous drosophilids. In the present study, we give supplementary descriptions for three of these known species, all recorded from Yunnan, southwestern China, H. furcapenis, H. furcapenisoides, and H. longifurcapenis, by examining respective type specimen(s). We then describe four new species of the same group, H. seticlasper Katoh Gao, sp. nov., H. spinicerca Katoh Gao, sp. nov., H. serratifurcapenis Katoh Gao, sp. nov., and H. truncifurca Katoh Gao, sp. nov., all discovered recently from high altitudes (ca. 3,500 to 3,800 m a.s.l.) in Tibet (Xizang), southwestern China. The delimitation of these new species is firstly performed in light of morphology and further with the aid of DNA sequences of the mitochondrial COI (cytochrome c oxydase, subunits I) gene. In addition, a key to all the species of the species group is provided.