Two new huntsman spiders from Xiaolong Mountains in Gansu Province, China (Araneae, Sparassidae).

Two new species of the sparassid genera Pseudopoda Jäger, 2000 and Sinopoda Jäger, 1999 are described from Xiaolong Mountains, Gansu, China: Pseudopoda tricuspidata sp. n. (♂♀) and Sinopoda subcampanacea sp. n. (♂♀). Photos of habitus and genitalia are provided.

Two new species of the genus Pseudopoda Jäger, 2000 and first description of the male of Pseudopoda physematosa (Araneae, Sparassidae) from Yunnan Province, China.

Two new species of the genus Pseudopoda Jäger, 2000 are reported from Yunnan Province, China: Pseudopoda mingshengi sp. nov. (male, female) and P. uncata sp. nov. (male, female). The male of P. physematosa Zhang, Jäger & Liu, 2019 is described for the first time.

Acquired multiple mutations ALK I1171N, L1196M and G1202R mediate lorlatinib resistance in EML4-ALK-rearranged malignant pleural mesothelioma: a case report.

EML4-ALK rearranged malignant pleural mesothelioma (MPM) is rare and its responses to anaplastic lymphoma kinase (ALK) inhibitors, including alectinib and lorlatinib, remain unexplored. In this case report, we describe a patient with EML4-ALK-rearranged stage IIIB MPM who was administered with alectinib and lorlatinib as first-line and fourth-line therapy, respectively. He had remarkable response evaluated as partial response on both regimens lasting approximately 3.5 months on each regimen. His plasma samples were collected during the treatment course and submitted for targeted sequencing to understand the molecular mechanisms of his therapeutic resistance. Sequencing analysis revealed the emergence of ALK I1171N and L1196M at alectinib progression. Meanwhile, ALK I1171N, L1196M, and G1202R mutations were identified at lorlatinib progression, wherein L1196M is confirmed to be in cis to G1202R. We speculate that these multiple mutations synergistically mediated his resistance to both alectinib and lorlatinib. Our report describes the detection of EML4-ALK rearrangement in a patient with MPM who had remarkable therapeutic response with ALK inhibitors. Moreover, our case also revealed acquired mechanisms of lorlatinib resistance mediated by multiple mutations ALK I1171N, L1196M, and G1202R, contributing an incremental step to our understanding of the complexity of acquired resistance mechanisms in sequential ALK inhibitor therapy. The reviews of this paper are available via the supplemental material section.

Four new species of the genus Mallinella (Araneae: Zodariidae) from Malaysia.

Four new species of the genus Mallinella Strand, 1906, from the natural forests of Malaysia, are described as Mallinella bicanaliculata sp. n. (♂♀), M. calautica sp. n. (♂♀), M. laxa sp. n. (♂♀), and M. obliqua sp. n. (♂♀). The four new species belong to four species groups and were collected from the forest litter in Sabah state by sieving.

Three new species of the genus Zodarion (Araneae, Zodariidae) from China.

Three new species of the genus Zodarion Walckenaer, 1826, from China, are described as Zodarionapertum sp. n. (♂♀, from Xinjiang), Z.planum sp. n. (♂, from Shaanxi), and Z.ovatum sp. n. (♂♀, from Yunnan).

Three new species of the spider genus Asceua from Malaysia (Araneae, Zodariidae).

Three new species of the genus Asceua Thorell, 1887, from the natural forests of Malaysia, are described as Asceuabifurca sp. n. (♂♀), A.curva sp. n. (♂), and A.trimaculata sp. n. (♀). The genus Asceua is reported from Malaysia for the first time.

Two new species of the spider Family Zodariidae from Laos.

Two new Zodariidae species, collected from the natural forest of Pakse City, Champasak Province, Laos, are described as Asceua adunca sp. nov. (male, female) and Mallinella renaria sp. nov. (male, female). Asceua torquata (Simon, 1909) and A. piperata Ono, 2004 are newly recorded from Laos, and the male of A. piperata is described and illustrated for the first time.

miR-21 modulates the effect of EZH2 on the biological behavior of human lung cancer stem cells in vitro.

Non-small-cell lung cancer has a high mortality rate and poor prognosis. Therefore, novel therapeutic approaches are urgently needed to enhance patient survival rates. In this study, we investigated the effects of miR-21 and EZH2 on the biological behavior of human lung cancer stem cells in vitro. We found increased expression of EZH2 and miR-21 in LCSCs, and miR-21 overexpression increased EZH2 levels in LCSCs. In addition, EZH2 and miR-21 knockdown increased the sensitivity of LCSCs to chemo- and radiation therapy, and exogenous EZH2 expression rescued the effects of anti-miR-21. Cell proliferation was reduced by 39.2% and 69.7% in the presence of radio- or chemotherapy combined with anti-miR-21 transfection, respectively. The downstream molecules included Cdc2, cyclin B1, and Bcl-2, which are involved in the regulation of cell cycle and apoptosis and which could themselves be reduced or enhanced by changes in miR-21 and EZH2 levels in LCSCs. This study demonstrates the direct relationship between miR-21 and EZH2 which was increased by 43% after the application of the miR-21 mimic. Above data indicates that these two molecules can influence the biological behavior of LCSCs by altering their corresponding targets. Our findings support the potential roles of miR-21 and EZH2 in improving the therapeutic efficacy of clinical lung cancer treatments.

miR-218 suppresses epithelial-to-mesenchymal transition by targeting Robo1 and Ecop in lung adenocarcinoma cells.

AIM: Although, miR-218 has been implicated in epithelial-to-mesenchymal transition process, the detailed mechanisms of miR-218 involvement in epithelial-to-mesenchymal transition in human lung adenocarcinoma cell are still unclear. MATERIALS & METHODS: miR-218 function assays and its target gene analysis were performed. RESULTS: miR-218 suppresses human lung adenocarcinoma cell migration and invasion and inhibits its target gene, Ecop and Robo1 expression, which subsequently suppresses NF-κB activity and its downstream targets. CONCLUSION: miR-218 inhibits human lung adenocarcinoma cell migration and invasion via the suppression of Ecop and Robo1 expression, thus suggesting that miR-218 could serve as a potential therapeutic target.

Three new spider species of the genus Pholcus from the Taihang Mountains of China (Araneae, Pholcidae).

In this study, three new species belonging to the genus Pholcus, collected from a forest of the Taihang Mountains, P. R. China, are described under the names of Pholcus papillatus sp. n. (male, female), Pholcus curvus sp. n. (male, female) and Pholcus auricularis sp. n. (male, female).

Genome-Wide Transcriptional Profiling Reveals Two Distinct Outcomes in Central Nervous System Infections of Rabies Virus.

Rabies remains a major public health concern in many developing countries. The precise neuropathogenesis of rabies is unknown, though it is hypothesized to be due to neuronal death or dysfunction. Mice that received intranasal inoculation of an attenuated rabies virus (RABV) strain HEP-Flury exhibited subtle clinical signs, and eventually recovered, which is different from the fatal encephalitis caused by the virulent RABV strain CVS-11. To understand the neuropathogenesis of rabies and the mechanisms of viral clearance, we applied RNA sequencing (RNA-Seq) to compare the brain transcriptomes of normal mice vs. HEP-Flury or CVS-11 intranasally inoculated mice. Our results revealed that both RABV strains altered positively and negatively the expression levels of many host genes, including genes associated with innate and adaptive immunity, inflammation and cell death. It is found that HEP-Flury infection can activate the innate immunity earlier through the RIG-I/MDA-5 signaling, and the innate immunity pre-activated by HEP-Flury or Newcastle disease virus (NDV) infection can effectively prevent the CVS-11 to invade central nervous system (CNS), but fails to clear the CVS-11 after its entry into the CNS. In addition, following CVS-11 infection, genes implicated in cell adhesion, blood vessel morphogenesis and coagulation were mainly up-regulated, while the genes involved in synaptic transmission and ion transport were significantly down-regulated. On the other hand, several genes involved in the MHC class II-mediated antigen presentation pathway were activated to a greater extent after the HEP-Flury infection as compared with the CVS-11 infection suggesting that the collaboration of CD4(+) T cells and MHC class II-mediated antigen presentation is critical for the clearance of attenuated RABV from the CNS. The differentially regulated genes reported here are likely to include potential therapeutic targets for expanding the post-exposure treatment window for RABV infection.

[Development of New Molecular EZH2 on Lung Cancer Invasion and Metastasis].

Lung cancer is a serious threat to human health malignancies upward trend in morbidity and mortality. It is hot topic to investigate the molecular mechanisms of lung cancer development and explore the new therapeutic targets. The underlying mechanism of EZH2 on lung cancer development will demonstrate the new pathway of lung cancer development, invasion and metastasis. The exploration and application of new targeted molecular will improve the survival rate and living quality of lung cancer patients in future.

EGFR and K-RAS mutations and ERCC1, TUBB3, TYMS, RRM1 and EGFR mRNA expression in non-small cell lung cancer: Correlation with clinical response to gefitinib or chemotherapy.

Personalizing medicines has refined the traditional treatments for non-small-cell lung cancer (NSCLC). In the present study, efforts towards personalizing delivery of care based on the status of EGFR and K-RAS mutations, and mRNA expression levels of ERCC1, TUBB3, TYMS, RRM1 and EGFR by choosing appropriate treatments for 52 patients with NSCLC were discussed. Among these 52 NSCLC patients, there were 14 patients treated with gefitinib. Ten patients with EGFR exon 21 point mutations or exon 19 deletions had better treatment outcomes following gefitinib treatment (71.4%). There were 38 patients treated with platinum-based chemotherapy. Docetaxel-platinum based chemotherapy was chosen as the first-line treatment when the patients had low or median ERCC1/TUBB3 expression and gemcitabine-platinum based chemotherapy was chosen when the patients had low or median ERCC1/RRM1 expression. In total, 26 cases had mRNA expression levels of ERCC1/TUBB3 or ERCC1/RRM1 that could be used to predict the treatment outcomes of chemotherapy (68.4%). The present results indicated that the mutation status of EGFR, as well as the mRNA expression levels of ERCC1, TUBB3 and RRM1, could be used as predictors of the response to gefitinib or chemotherapy.

Three new Sinopoda species (Araneae: Sparassidae) from southern China.

Three new species of the huntsman spider genus Sinopoda Jäger, 1999, collected from Sichuan Province and Chongqing Municipality, P. R. China, are described: Sinopoda cochlearia sp. nov. (male, female), S. globosa sp. nov. (male, female) and S. longiducta sp. nov. (male, female). All three new species were collected from native forest by hand.

Pharmacokinetic profile of paclitaxel in the plasma, lung, and diaphragm following intravenous or intrapleural administration in rats.

BACKGROUND: The optimal chemotherapy route for non-small cell lung cancers involving the phrenic nerve and diaphragm is unclear. The pharmacokinetic properties of paclitaxel following intravenous (IV) or intrapleural (IP) administration were analyzed in the plasma, lung, and diaphragm in a rat model. The purpose of this study was to determine whether IP injection increased paclitaxel concentration in the diaphragm. METHODS: Paclitaxel was administered by IV or IP to male Sprague-Dawley rats. The concentration of drug in the plasma, lung, and diaphragm was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters area under the curve (AUC), mean residence time (MRT), peak plasma concentration (Cmax), and half-life (t1/2) were analyzed. RESULTS: Paclitaxel concentration in the plasma, lung, and diaphragm decreased quickly following IV administration. However, after IP injection, paclitaxel reached a high concentration in the plasma, lung, and diaphragm that declined gradually. Significant differences in all parameters, except Cmax in the lung, were observed between the two routes of administration (all P < 0.05). Plasma exposure to paclitaxel IP was 41.1% of that observed after IV in the first 24 hours (P < 0.05). IP also significantly increased exposure of paclitaxel in comparison with IV administration to 267.3% and 905.7% of IV administration in the lung and diaphragm, respectively (P < 0.05). CONCLUSION: These results suggest that IP administration may reduce systemic distribution of paclitaxel and increase the concentration in the lung and diaphragm. This could increase therapeutic efficacy by increasing the available drug and reduce systemic toxicity.

Production of monoclonal antibody against EP0 protein of pseudorabies virus and determination of its recognized epitope.

Early protein 0 (EP0) is especially important for modulating PRV gene expression and reactivation from the latent state, but the mechanisms have not been elucidated. In this study, six monoclonal antibodies (MAbs) against EP0 protein of PRV were generated and their characterizations were investigated. Western blot analysis showed all six MAbs could react with immunizing antigen, but only 2B12 and 2C6 could react with native EP0 protein from PRV-infected cells. ELISA additivity tests revealed that at least three epitopes in EP0 were defined by six MAbs. The epitope recognized by MAb 2B12 was further identified in 287-292 aa of EP0 protein using a series of expressed overlapping peptides. These MAbs may provide valuable tools for further research of the functions of EP0 in PRV infection.

New species of Pseudopoda Jäger, 2000 from Southern China (Araneae, Sparassidae).

Four new species of the huntsman spider genus Pseudopoda Jäger, 2000 are described from Southern China: Pseudopoda acuminata sp. n. from Suiyang County, Guizhou Province, P. emei sp. n. from Emei Mountain, Sichuan Province, P. lacrimosa sp. n. from Fugong County and Tengchong County, Yunnan Province, and P. robusta sp. n. fromJinyun Mountain, Chongqing Municipality.

[Identification and isolation of cancer stem cells from A549 cells].

BACKGROUND AND OBJECTIVE: Lung cancer stem cells are the root causes of lung cancer malignant phenotype and potential therapeutic target, the aim of this study is to isolate and characterize the cancer stem cells in the lung adenoearcinomas cell line A549, so as to provide an experimental basis for further stem cell research. METHODS: The cancer stem cells were isolated from the lung adenoearcinomas cell line A549 using FACS. And the difference of colony formation, cell proliferation and tumorigenicity in vitro were also tested. The expression of CD133 and ABCG2 were evaluated by RT-PCR and Western blot. RESULTS: The percentage of SP cells was 5.93% of A549 and 0.32% of A549 after incubation with verapamil. The results showed that there were significantly higher expression of CD133 and ABCG2 on SP cells than that of non-SP cells. And the ability of colony formation, cell proliferation and tumorigenicity in SP cell group were remarkably higher than that in non-SP cell group. CONCLUSIONS: Our results suggested that the cancer stem cells with higher expression of CD133 and ABCG2 can be isolated from the lung adenoearcinomas cell line A549 using FACS and be used in the further research experiments.

Four new species of the genus Pseudopoda Jäger, 2000 (Araneae, Sparassidae) from Yunnan Province, China.

Four new species of the huntsman spider genus Pseudopoda Jäger, 2000 are reported from Yunnan Province, China: Pseudopoda gibberosa sp. nov. (male, female), P. semiannulata sp. nov. (male, female), P. breviducta sp. nov. (male, female) and P. triangula sp. nov. (male, female).

EZH2 silencing with RNAi enhances irradiation-induced inhibition of human lung cancer growth in vitro and in vivo.

Non-small cell lung cancer (NSCLC) has a high mortality rate and poor prognosis. The aim of the present study was to silence EZH2 and explore the antitumor effect of small interfering RNA (siRNA)-EZH2 in combination with radiotherapy, which is a main treatment for NSCLC. The results showed that irradiation in the presence of siRNA-EZH2 arrested A549 cells in the G(0) and G(1) phases, delayed cell cycle progression and effectively inhibited cell proliferation, compared with cells that received radiotherapy alone. The combined therapy enhanced the percentage of apoptotic A549 cells in vitro and reduced the tumor size, in addition to increasing the survival rate in tumor xenograft experiments. This study demonstrates the antitumor activity of ionizing radiation therapy in combination with siRNA-EZH2 in NSCLC, both in vitro and in vivo, as well as providing a scientific rationale for targeting EZH2 to enhance the sensitivity of cancer to radiotherapy in NSCLC patients.