Comparative transcriptomic evidence of physiological changes and potential relationships in vertebrates under different dormancy states.

Dormancy represents a fascinating adaptive strategy for organisms to survive in unforgiving environments. After a period of dormancy, organisms often exhibit exceptional resilience. This period is typically divided into hibernation and aestivation based on seasonal patterns. However, the mechanisms by which organisms adapt to their environments during dormancy, as well as the potential relationships between different states of dormancy, deserve further exploration. Here, we selected Perccottus glenii and Protopterus annectens as the primary subjects to study hibernation and aestivation, respectively. Based on histological and transcriptomic analysis of multiple organs, we discovered that dormancy involved a coordinated functional response across organs. Enrichment analyses revealed noteworthy disparities between the two dormant species in their responses to extreme temperatures. Notably, similarities in gene expression patterns pertaining to energy metabolism, neural activity, and biosynthesis were noted during hibernation, suggesting a potential correlation between hibernation and aestivation. To further explore the relationship between these two phenomena, we analyzed other dormancy-capable species using data from publicly available databases. This comparative analysis revealed that most orthologous genes involved in metabolism, cell proliferation, and neural function exhibited consistent expression patterns during dormancy, indicating that the observed similarity between hibernation and aestivation may be attributable to convergent evolution. In conclusion, this study enhances our comprehension of the dormancy phenomenon and offers new insights into the molecular mechanisms underpinning vertebrate dormancy.

Chromosome-level genome provides insight into the evolution and conservation of the threatened goral (Naemorhedus goral).

BACKGROUND: Gorals Naemorhedus resemble both goats and antelopes, which prompts much debate about the intragenus species delimitation and phylogenetic status of the genus Naemorhedus within the subfamily Caprinae. Their evolution is believed to be linked to the uplift of the Qinghai-Tibet Plateau (QTP). To better understand its phylogenetics, the genetic information is worth being resolved. RESULTS: Based on a sample from the eastern margin of QTP, we constructed the first reference genome for Himalayan goral Naemorhedus goral, using PacBio long-read sequencing and Hi-C technology. The 2.59 Gb assembled genome had a contig N50 of 3.70 Mb and scaffold N50 of 106.66 Mb, which anchored onto 28 pseudo chromosomes. A total of 20,145 protein-coding genes were predicted in the assembled genome, of which 99.93% were functionally annotated. Phylogenetically, the goral was closely related to muskox on the mitochondrial genome level and nested into the takin-muskox clade on the genome tree, rather than other so-called goat-antelopes. The cladogenetic event among muskox, takin and goral occurred sequentially during the late Miocene (~ 11 - 5 Mya), when the QTP experienced a third dramatic uplift with consequent profound changes in climate and environment. Several chromosome fusions and translocations were observed between goral and takin/muskox. The expanded gene families in the goral genome were mainly related to the metabolism of drugs and diseases, so as the positive selected genes. The Ne of goral continued to decrease since ~ 1 Mya during the Pleistocene with active glaciations. CONCLUSION: The high-quality goral genome provides insights into the evolution and valuable information for the conservation of this threatened group.

Molecular phylogeny of the genus Muntiacus with special emphasis on the phylogenetic position of Muntiacus gongshanensis.

Muntjac deer (Cervidae: Muntiacus) are often cited as an excellent model for the study of vertebrate evolution due to their fast rate of change in chromosome number among vertebrates. However, the phylogenetic relationships within Muntiacus generally, and the taxonomic status of Muntiacus gongshanensis specifically, remain unclear. Here, the phylogenetic relationships within Muntiacus were studied using mitochondrial genome (mitogenome) and cytochrome b (cyt b) segments. Our results recognize 12 species within Muntiacus and support the controversial species M. gongshanensis, M. putaoensis, and M. malabaricus. Furthermore, Bayesian inference (BI) and maximum-likelihood (ML) approaches revealed M. gongshanensis and M. crinifrons to be closely related species, with M. feae as their sister species, and M. putaoensis and M. truongsonensis to be closely related, with M. rooseveltorum as their sister species. The distribution range of M. gongshanensis was also confirmed in southwest China (Namdapha, Modong, Zayu and Gongshan) and northern Myanmar (Putao). The results of this study provide insight into the evolution of Muntiacus and further provide a molecular basis for the taxonomic evaluation of the genus in the future and fundamental data for the conservation of M. gongshanensis.

A new species of Amolops (Anura: Ranidae) from northern Myanmar.

A new species of the genus Amolops, Amolopsputaoensissp. nov., is described from northern Myanmar. The new species can be distinguished from its congeners by the following characters: (1) dorsolateral fold distinct; (2) upper-lip stripe white; (3) male body size 37.6-40.2 mm; (4) ground color of dorsal surface brown, flank green, small warts on dorsum; (5) two internal subgular vocal sacs present; (6) HL slightly shorter than HW; (7) two palmar tubercles present, supernumerary tubercles and outer metatarsal tubercle absent; (8) tympanum smaller than half of eye diameter; (9) vomerine teeth present; (10) tibiotarsal articulation reaching beyond snout tip; (11) supratympanic fold indistinct; (12) pineal body present; (13) finger webbing absent, presence of circummarginal groove on tip of first finger; (14) nuptial pads present. The population from Myanmar represented a distinct maternal lineage within the Amolops monticola group and was recovered as a sister taxon to Amolops aniqiaoensis with strong support (100) based on concatenated data. Average uncorrected pairwise distances ( P-distances) between the specimens from Myanmar and other species in the genus ranged from 2.69% (vs. A. aniqiaoensis) to 12.24% (vs. A. indoburmanensis) for 16S rRNA, 6.14% (vs. A. aniqiaoensis) to 15.79% (vs. A. panhai) for COI, and 9.66% (vs. A. aniqiaoensis) to 19.52% (vs. A. afghanus) for ND2.

Cognitive impairment and associated risk factors in older adult hemodialysis patients: a cross-sectional survey.

The clinical epidemiological features of cognitive impairment in Chinese older adult patients undergoing hemodialysis are not clear, we aimed to identify the extent and patterns of cognitive impairment among those patients. We conducted a cross-sectional study of 613 hemodialysis patients aged 50 to 80 from 11 centers in Beijing. A neuropsychological battery of 11 tests covering domains of attention/processing speed, executive function, memory, language, and visuospatial function was applied, patients were classified as none, mild, or major cognitive impairment according to the fifth version of the Diagnostic and Statistical Manual of Mental Disorders criteria for cognitive impairment. Compared with Chinese population norms, 37.2% of the participants had mild cognitive impairment, 43.7% had major cognitive impairment. Memory and language were the most severe impaired domains in the mild cognitive impairment group, attention and visuospatial function domains were the most serious impaired domains in the major cognitive impairment group. Concomitant impairment across multiple cognitive domains was common. Factors associated with major cognitive impairment included age, education level, history of stroke and hypertension, dialysis vintage, and single-pool Kt/V. There is a high frequency of cognitive impairment in Chinese older adult hemodialysis patients, with varying severity and concomitant impairment across multiple domains.

New country records for three species of frog from Myanmar including two genera (Nasutixalus and Oreolalax).

Myanmar, a biodiversity hotspot, harbors a striking diversity and endemism of species. Despite this, its herpetofauna remains one of the least explored in continental Asia due to restrictions of crossing political boundaries and infrastructure in remote regions. Many species in adjacent China and India are hypothesized to occur in Myanmar but records are wanting. Recent fieldwork found the frogs Polypedates braueri, Nasutixalus jerdonii and Oreolalax jingdongensis there, and the latter two species represent new generic records for Myanmar. All major morphological characters of these populations match the original descriptions. In addition, our matrilineal genealogy based on DNA barcoding confirms their identities. Overall, these findings confirm that the amphibian diversity is underestimated and this has important implications for conservation. Analyses indicate that northern Myanmar is a biogeographic corridor for the Himalayas, southern China, and northeastern India.

The First Report of Laparoscopic Pancreaticoduodenectomy for Primary Duodenal Carcinoma in a Patient With Situs Inversus Totalis: Report of a Rare Case.

BACKGROUND: Situs inversus (SI) is a rare congenital anomaly characterized by the transposition of thoracic and abdominal viscera. Laparoscopic pancreaticoduodenectomy (LPD) is increasingly used in patients with periampullar and pancreatic carcinomas. For patients with SI, LPD can be more complicated because of reversed anatomy and possible other associated anomalies that have not been expected before surgery. CASE PRESENTATION: A female patient with SI totalis presented with inappetence, vomiting, and weight loss for 2 months. Imaging modalities and angiography revealed a mass in the periampullary region without obvious vascular abnormalities. The mass was successfully resected via LPD based on an elaborate preoperative plan. The surgical pathology report demonstrated adenocarcinoma of the duodenal papilla. The patient has been followed up for 4 months and no tumor recurrence or long-term complications were observed. CONCLUSION: LPD is technically difficult but feasible in patients with SI.

Investigation of non-tuberculous mycobacteria in a primary hospital from southeastern China.

INTRODUCTION: Non-tuberculous mycobacterium (NTM) can colonize the human body, leading to opportunistic infection. This study was conducted to analyze the NTM species composition in a primary hospital and investigate the potential features of the patients with different NTM species. METHODOLOGY: Mycobacterial strains were collected from the patients admitted at the hospital from January 2016 to May 2019. MPB64 assay was used to screen NTM strains and confirmed by Rv0577 amplification. The species were identified by hsp65 sequencing. The clinical records of patients with NTM were retrospectively reviewed. RESULTS: Among the 122 identified NTM isolates, the most common strains were Mycobacterium avium complex (MAC, n = 102, 83.6%), Mycobacterium abscessus (n = 9, 7.4%) and Mycobacterium lentiflavum (n = 5, 4.1%). The predominant species among MAC were Mycobacterium chimaera (n = 57, 46.7%), followed by Mycobacterium intracellulare (n = 25, 20.5%) and Mycobacterium colombiense (n = 17, 13.9%). A significantly lower percentage of positive acid-fast assay was observed in Mycobacterium colombiense positive patients than in those with Mycobacterium intracellulare and Mycobacterium chimaera. Mycobacterium intracellulare was more frequently isolated in patients from the infectious department than in other MAC members. CONCLUSIONS: A predominant prevalence of Mycobacterium chimaera in Dongyang of Zhejiang Province was different from other regions in China, indicating that its prevalence has been likely underestimated. The heterogeneity in clinical features, caused by different MAC members, required an accurate species identification of the NTM isolated in the primary hospitals.

Complete mitochondrial genome of Gongshan muntjac (Muntiacus gongshanensis), a Critically Endangered deer species.

The first complete mitochondrial genome of the Gongshan muntjac (Muntiacus gongshanensis) was determined and annotated (GenBank accession nos. MK882935). The 16,356 bp circular genome contained 13 protein-coding genes (PGCs), 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and 1 control region (D-loop). Phylogenetic analysis revealed that Gongshan muntjac is most closely related to Black muntjac (Muntiacus crinifrons), with Fea's muntjac (Muntiacus feae) as their sister species. These data will be useful for further studies on the genetic diversity and molecular phylogenetic relationship of the genus Muntiacus.

A preoperative nomogram predicts prognosis of up front resectable patients with pancreatic head cancer and suspected venous invasion.

BACKGROUND: Pancreatic head adenocarcinoma is commonly diagnosed at an advanced stage when adjacent vascular invasion is present. This study aimed to establish a preoperative prognostic nomogram for patients who underwent attempted curative resectional surgery for pancreatic head cancer with suspected peripancreatic venous invasion. METHODS: Data on all consecutive patients were retrospectively collected from 2012 to 2016 at four academic institutions. The demographic and radiological parameters were analyzed using univariate and multivariate Cox regression analyses. The final nomogram was established using the concordance Harrell's C-indices and calibration curves from data obtained in three institutions and validated in the cohort of patients coming from the fourth institution. RESULTS: The nomogram was constructed using data from 178 patients while the validation cohort consisted of 61 patients. Age, length of tumor contact, peripancreatic venous abnormalities and lymph node staging were independent factors of overall survival. The nomogram showed good probabilities of survival on calibration curves. The C-index of the model in predicting overall survival (OS) was 0.824 for the validation cohort. CONCLUSIONS: The nomogram accurately predicted OS in patients with pancreatic head cancer with suspected peripancreatic venous invasion after attempted curative pancreatic resectional surgery.

Bird diversity in northern Myanmar and conservation implications.

We conducted four bird biodiversity surveys in the Putao area of northern Myanmar from 2015 to 2017. Combined with anecdotal information collected between 2012 and 2015, we recorded 319 bird species, including two species (Arborophila mandellii and Lanius sphenocercus) previously unrecorded in Myanmar. Bulbuls (Pycnonotidae), babblers (Timaliidae), pigeons and doves (Columbidae), and pheasants and partridges (Phasianidae) were the most abundant groups of birds recorded. Species richness below 1 500 m a. s. l. was higher than species richness at higher elevations. Our results suggest that the current protected areas in this region should be expanded to lower elevations to cover critical conservation gaps.

Complete mitochondrial genome of the leaf muntjac (Muntiacus putaoensis) and phylogenetics of the genus Muntiacus.

The leaf muntjac (Muntiacus putaoensis) is an endemic deer species found in the east trans-Himalayan region. In recent years, population numbers have decreased due to heavy hunting and habitat loss, and little genetic data exists for this species, thus our knowledge of distribution rangs and population sizes likewise remain limited. We obtained mtDNA genes and the complete mitochondrial genome sequence of M. putaoensis using PCR, followed by direct sequencing. The complete mitogenome sequence was determined as a circular 16 349 bp mitochondrial genome, containing 13 protein-coding genes, two rRNA genes, 22 tRNA genes, and one control region, the gene composition and order of which were similar to most other vertebrates so far reported. Most mitochondrial genes, except for ND6 and eight tRNAs, were encoded on the heavy strand. The overall base composition of the heavy strand was 33.1% A, 29.3% T, 24.2% C, and 13.4% G, with a strong AT bias of 62.4%. There were seven regions of gene overlap totaling 95 bp and 11 intergenic spacer regions totaling 74 bp. Phylogenetic analyses (ML and BI) among the Muntiacus genus based on the sequenced of mitogenome and ND4L-ND4 supported M. putaoensis as a member of Muntiacus, most closely related to M. vuquangensis. However, when analyses based on cyt b included two more muntjacs, M. truongsonensis was most closely related to M. putaoensis rather than M. vuquangensis, and together with M. rooseveltorum, likely forming a M. rooseveltorum complex of the species. This study will help in the exploration of the evolutionary history and taxonomic status of the leaf muntjac, as well as its protection as a genetic resource.

Modified-FOLFIRINOX in metastatic pancreatic cancer: A prospective study in Chinese population.

FOLFIRINOX chemotherapy has shown remarkable responses in patients with metastatic pancreatic cancer (MPC), and has significantly improved prognosis. However, FOLFIRINOX is currently not frequently applied in China because of its high incidence of adverse events, and there is no recognized optimization for this therapy in Chinese population. Modification of FOLFIRINOX may be better for its acceptance in China. In this study, we evaluated the efficacy and safety of modified-FOLFIRINOX in patients with MPC. A total of 62 MPC patients were treated with modified-FOLFIRINOX (no Fluorouracil bolus, 85% Oxaliplatin and 75% Irinotecan) between April 2014 and April 2017 in our institute. 40 of them were evaluated, with a response rate of 32.5% (13/40). The frequent grade 3/4 adverse events are neutropenia (29%) and alanine aminotransferase elevation (14.5%). No treatment-related death was observed. The median overall survival and median progression-free survival are 10.3 months and 7.0 months, respectively. In conclusion, modified-FOLFIRINOX had significantly improved tolerance with similar efficacy to FOLFIRINOX. These findings may provide evidence for the use of FOLFIRINOX in Chinese patients with MPC.

Taxonomic status of a population of Gymoncypris waddelli Regan, 1905 (Cypriniformes: Schizothoracinae) distributed in Pengqu River, Tibet, China.

Gymnocypris waddelli, a highland cold-water fish, is distributed among rivers and lakes of the southern Qinghai-Tibet Plateau. Although previously described as G. waddelli, specimens from the Pengqu River are morphologically distinguishable from those from Lake Yamzhog Yumco, which is the type locality of G. waddelli. We investigated morphological variations of G. waddelli specimens from Pengqu River and Lake Yamzhog Yumco using not only traditional morphological methods but also newly-developed geometric morphometric analysis; furthermore, mitochondrial Cytochrome b (Cyt b) gene analysis was employed to explore the phylogenetic position of the Pengqu River population. Our morphological analyses suggested that G. waddelli from the Pengqu River had an obtuse snout, nearly straight oral fissure, shorter lower jaw than upper jaw, broad mouth and sparse inside gill rakers of the first arch relative to the Lake Yamzhog Yumco population. The strongly supported monophyly of Pengqu population according to mitochondrial datasets was obtained, indicating genetic differences between Pengqu River and Lake Yamzhog Yumco populations. Given their substantial genetic and morphological divergence, specimens from Pengqu River warrant recognition as a distinct species, here described and named Gymnocypris pengquensis.

Hypoxia-Induced Epithelial-to-Mesenchymal Transition in Hepatocellular Carcinoma Induces an Immunosuppressive Tumor Microenvironment to Promote Metastasis.

Portal vein tumor thrombosis (PVTT) is a significant risk factor for metastasis in hepatocellular carcinoma (HCC) patients and is therefore associated with poor prognosis. The presence of PVTT frequently accompanies substantial hypoxia within the tumor microenvironment, which is suggested to accelerate tumor metastasis, but it is unclear how this occurs. Recent evidence has shown that the hypoxia-inducible factor HIF-1α induces epithelial-to-mesenchymal transition (EMT) in tumor cells to facilitate metastasis. In this study, we investigated whether hypoxia-induced EMT in cancer cells also affects immune cells in the tumor microenvironment to promote immunosuppression. We found that hypoxia-induced EMT increased the expression of the CCL20 cytokine in hepatoma cells. Furthermore, coculture of monocyte-derived macrophages with hypoxic hepatoma cells revealed that the expression of indoleamine 2, 3-dioxygenase (IDO) was induced in monocyte-derived macrophages in a CCL20-dependent manner. In turn, these IDO-expressing monocyte-derived macrophages suppressed T-cell proliferation and promoted the expansion of immunosuppressive regulatory T cells. Moreover, high CCL20 expression in HCC specimens was associated with PVTT and poor patient survival. Collectively, our findings suggest that the HIF-1α/CCL20/IDO axis in hepatocellular carcinoma is important for accelerating tumor metastasis through both the induction of EMT and the establishment of an immunosuppressive tumor microenvironment, warranting further investigation into the therapeutic effects of blocking specific nodes of this signaling network.

LB-100 sensitizes hepatocellular carcinoma cells to the effects of sorafenib during hypoxia by activation of Smad3 phosphorylation.

Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis. The multikinase inhibitor sorafenib is the only clinically proved systematic treatment for HCC. However, few patients respond to sorafenib. Hypoxic microenvironments contribute to sorafenib resistance. LB-100, a serine/threonine protein phosphatase 2A (PP2A) inhibitor was previously found to be a chemosensitizer in HCC. Here, we tested whether LB-100 could sensitize HCC to the effects of sorafenib. Intriguingly, LB-100 enhanced the effects of sorafenib in HCC cells only during hypoxic environments. LB-100 dramatically increased intracellular p-Smad3 level, which was responsible for the effect of LB-100 as a sensitizer. LB-100 downregulated Bcl-2 expression and enhanced sorafenib-induced apoptosis in HCC cells. We further proved that PP2A mediated LB-100-induced p-Smad3 overexpression. In addition, p38 mitogen-activated protein kinase pathway was activated in hypoxic conditions, and enhanced p-Smad3-dependent Bcl-2 inhibition and consequent apoptosis. In conclusion, LB-100 sensitized HCC cells to sorafenib in hypoxic environments. This effect was mediated by inactivation of PP2A, resulting in enhanced level of p-Smad3. Increased p-Smad3 downregulated Bcl-2, causing increased apoptosis of HCC cells.

CD97 promotes gastric cancer cell proliferation and invasion through exosome-mediated MAPK signaling pathway.

AIM: To investigate the mechanism underlying the promoting role of CD97 in gastric cancer cell proliferation and invasion. METHODS: Two types of exosomes released by gastric cancer cells with high (SGC/wt) or low (SGC/kd) CD97 expression were isolated by ultracentrifugation and identified by electron microscopy and western blot analysis. The influences of the two exosomes on gastric cancer cell proliferation and invasion were investigated by proliferation and Matrigel invasion assays. Exosomal miRNAs were subsequently isolated from the two samples and their miRNA profiles were compared via microarray assay analysis. Reverse transcription-quantitative real-time polymerase chain reaction was used to validate the microarray assay. Target genes of the differently expressed microRNAs were predicted based on five independent algorithms and were then subjected to gene oncology enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. After identifying the pathway that was the most likely altered, tumor cells were treated with the two exosomes at different concentrations, and the pathway activation was identified through western blot analysis. RESULTS: Exosomes isolated from SGC/wt cells significantly promoted tumor cell proliferation in a dose-dependent manner in vitro. SGC/wt exosomes also significantly elevated the invasiveness of both SGC/wt (129.67 ± 8.327 vs 76.00 ± 5.292, P < 0.001) and SGC/kd (114.52 ± 9.814 vs 45.73 ± 4.835, P < 0.001) cells as compared to the exosomes released by SGC/kd cells. Microarray assay of the two exosomes revealed that 62 miRNAs were differently regulated with a signal intensity of > 500 and a false discovery rate < 0.05. The following KEGG analysis defined the MAPK signaling pathway as the most likely candidate pathway that regulated tumor cell proliferation and invasion. Through western blot analysis, significant up-regulations of phosphorylated MAPKs, including extracellular signal-regulated kinase, Jun NH2-terminal kinase, and p38 mitogen-activated protein kinase, were detected in a dose-dependent manner in the SGC/wt exosomes treated groups, confirming activation of the MAPK signaling pathway stimulated by SGC/wt exosomes. CONCLUSION: CD97 promotes gastric cancer cell proliferation and invasion in vitro through exosome-mediated MAPK signaling pathway, and exosomal miRNAs are probably involved in activation of the CD97-associated pathway.

Association between circulating endothelial cells and carotid atherosclerosis in patients receiving maintenance hemodialysis.

Accelerated atherosclerosis is the major cause of mortality in maintenance hemodialysis (MHD) patients, and endothelial injury associated with MHD might contribute strongly to pathogenesis. The current study was designed to explore possible associations between circulating endothelial cells (CECs) and intima-media thickness of common carotid artery (CCA-IMT) as an indicator of carotid atherosclerosis. Sixty-two MHD patients and 26 age- and sex-matched healthy volunteers were recruited. The number of CECs was determined in peripheral blood using multiparametric flow cytometry. CCA-IMT and presence of plaques in the common carotid arteries were assessed with ultrasound. Laboratory tests results and the demographics were recorded. The finding indicated that numbers of CECs were higher in patients before hemodialysis (predialysis) compared with numbers in controls (P = 0.045). CCA-IMT was also significantly higher in patients than in controls (P < 0.01). A positive relationship was observed between predialysis CECs numbers and CCA-IMT (P < 0.01) in MHD patients. In multiple linear regression analysis, the relationship between the predialysis CECs level and CCA-IMT remained the same even if adjusting for confounding effects. Accordingly, the investigation indicates that the CECs level is positively associated with CCA-IMT in our hemodialysis patients. CECs might be an important marker to the severity of carotid atherosclerosis in MHD patients.

[Morphological differentiations of the gills of two Gymnocypris przewa-lskii subspecies in different habitats and their functional adaptations].

Gill morphologies of two subspecies of Gymnocypris przewalskii (Gymnocypris przewalskii przewalskii and Gymnocypris przewalskii ganzihonensis) in different habitats were analyzed under scanning electron microscope. Results indicated that G. p. przewalskii had numerous long and dense-lined gill rakers while G. p. ganzihonensis had few short and scatter-lined gill rakers. There were no significant differences in distance between gill filaments (DBF) and distance gill lamella (DBL) between the two subspecies, but gill filaments of G. p. przewalskii were longer than in G. p. ganzihonensis. The electron microscopic study indicated that the pavement epithelium cells of G. p. przewalskii were well defined as irregular ovals, but were hexagonal in G. p. ganzihonensis. Moreover, G. p. przewalskii had more chloride cells than G. p. ganzihonensis, and mucous cells were only found on the surface of gill filaments of G. p. przewalskii. The morphological differences between the two subspecies of G. przewalskii are adaptations to their corresponding diets and habitats.

Influence of up-regulation of Notch ligand DLL4 on biological behaviors of human gastric cancer cells.

AIM: To investigate the potential roles of Delta-like ligand 4 (DLL4) on the biological behavior of gastric cancer cells and its molecular mechanisms. METHODS: A recombinant eukaryotic expression vector containing human DLL4 gene was constructed and transfected into the human gastric cancer cell line SGC7901. Clones with up-regulated DLL4 were selected and amplified. The effect of DLL4 up-regulation on gastric cancer cell growth was assessed using cell growth assay. The migration and invasion were assessed using a transwell migration assay and matrigel invasion assay. Matrix metalloproteinases were detected using the zymogram technique. Cells were implanted subcutaneously into male BALB/c nu/nu mice. Tumor volumes were then calculated and compared. DLL4 staining in the implanted tumor was performed using immunohistochemistry technique. RESULTS: Growth curves over a six-day time course showed significantly promoted cell proliferation of SGC7901 cells with up-regulated DLL4. DLL4 up-regulation in SGC7901 cells promoted the migration (205.4 ± 15.2 vs 22.3 ± 12.1, P < 0.05) and invasion (68.8 ± 5.3 vs 18.2 ± 6.0, P < 0.05) in vitro and tumorigenicity in vivo (2640.5 ± 923.6 mm(3) vs 1115.1 ± 223.8 mm(3), P < 0.05). Furthermore, significantly increased mRNA level and increased secretion of matrix metalloproteinase-2 (MMP-2) proenzyme were observed in SGC7901 cells with up-regulated DLL4. However, increased MMP-9 mRNA level but decreased extracellular MMP-9 proenzyme level was observed. CONCLUSION: Our observations indicated a mechanism by which activation of DLL4-mediated Notch signaling promotes the expression and secretion of MMP-2 proenzyme and influences the progress of gastric cancer.