MIA3 promotes the degradation of GSH (glutathione) by binding to CHAC1, thereby promoting the progression of hepatocellular carcinoma.

MIA3 (melanoma inhibitory active protein 3)/TANGO1 (Golgi transporter component protein) plays an important role in the initiation, development, and metabolism of cancer. We aimed to explore the role and underlying molecular mechanisms of MIA3/TANGO1 in the growth and migration of hepatoma cells. According to the analysis of The Cancer Genome Atlas (TCGA) database, MIA3 is expressed at higher levels in hepatocellular carcinoma (HCC) tissues than in normal tissues. Real-time quantitative polymerase chain reaction (qRT-PCR), immunohistochemistry, and western blotting were used to detect mRNA and protein expression in HCC tissues and cells. The in vitro function of MIA3 in HCC cells was evaluated using Cell Counting Kit-8 (CCK-8), colony formation, cell migration and invasion, and flow cytometry assays. Hep-G2 cells with MIA3 overexpression were subjected to RNA-seq, and the downstream target gene CHAC1 (glutathione-specific γ-glutamyl cyclotransferase 1) was selected according to the results of the volcano map of gene enrichment. The relationship between MIA3 and CHAC1 was revealed by coimmunoprecipitation and confocal microscopy. MIA3 expression was upregulated in HCC organizations and HCC samples in the TCGA dataset. Knocking out MIA3 inhibited the proliferation, migration, and invasion of Hep-G2 cells and promoted the apoptosis of Hep-G2 cells. Overexpression of MIA3 in Huh7 cells promoted the proliferation, migration, and invasion and suppressed the apoptosis of Huh7 cells. Overexpression of MIA3 promoted the expression of CHAC1 and the degradation of glutathione (GSH), thereby promoting the growth and metastasis of HCC cells. Knocking out MIA3 inhibited the expression of CHAC1 and slowed the degradation of glutathione, thereby inhibiting the growth and metastasis of HCC cells. MIA3 further promotes the growth, metastasis, and invasion of hepatoma cells by binding to the CHAC1 protein and promoting GSH degradation.

Comprehensive Effects of Suppression of MicroRNA-383 in Human Bone-Marrow-Derived Mesenchymal Stem Cells on Treating Spinal Cord Injury.

BACKGROUND/AIMS: Transplantation of bone-marrow-derived mesenchymal stem cells (MSCs) promotes neural cell regeneration after spinal cord injury (SCI). Recently, we showed that suppression of microRNA-383 (miR-383) in MSCs increased the protein levels of glial cell line derived neurotrophic factor (GDNF), resulting in improved therapeutic effects on SCI. However, the overall effects of miR-383 suppression in MSCs on SCI therapy were not determined yet. Here, we addressed this question. METHODS: We used bioinformatics tools to predict all miR-383-targeting genes, confirmed the functional bindings in a dual luciferase reporter assay. The effects of alteration of candidate genes in MSCs on cell proliferation were analyzed by MTT assay and by Western blotting for PCNA. The effects on angiogenesis were assessed by HUVEC assay. The effects on SCI in vivo were analyzed by transplantation of the modified MSCs into nude rats that underwent SCI. RESULTS: Suppression of miR-383 in MSCs not only upregulated GDNF protein, but also increased vascular endothelial growth factor A (VEGF-A) and cyclin-dependent kinase 19 (CDK19), two other miR-383 targets. MiR-383-suppression-induced increases in CDK19 resulted in a slight but significant increase in MSC proliferation, while miR-383-suppression-induced increases in VEGF-A resulted in a slight but significant increase in MSC-mediated angiogenesis. CONCLUSIONS: Upregulation of CDK19 and VEGF-A by miR-383 suppression in MSCs further improve the therapeutic potential of MSCs in treating SCI in rats.

Suppression of MicroRNA-383 Enhances Therapeutic Potential of Human Bone-Marrow-Derived Mesenchymal Stem Cells in Treating Spinal Cord Injury via GDNF.

BACKGROUND/AIMS: Transplantation of bone-marrow-derived mesenchymal stem cells (MSCs) has been used to treat spinal cord injury (SCI) to enhance tissue repair and neural cell regeneration. Glial cell line derived neurotrophic factor (GDNF) is an identified neural growth and survival factor. Here, we examined whether modification of GDNF levels in MSCs may further increase the potential of MSCs in promoting neural cell regeneration and subsequently the therapeutic outcome. METHODS: We examined the mRNA and protein levels of GDNF in human MSCs by RT-qPCR and Western blot, respectively. Bioinformatics analyses were done to predict microRNAs (miRNAs) that target GDNF in MSCs. The functional binding of miRNAs to GDNF mRNA was examined by a dual luciferase reporter assay. MSCs were transduced with adeno-associated virus (AAV) carrying null or antisense for miR-383 (as-miR-383), which were transplanted into nude rats that underwent SCI. The intact tissue, cavity volume, and recovery of locomotor activity were assessed. RESULTS: MSCs expressed very low GDNF protein, but surprisingly high levels of GDNF mRNA. Bioinformatics analyses showed that miR-383 inhibited protein translation of GDNF, through binding to the 3'-UTR of the GDNF mRNA. MSCs transduced with AAV-as-miR-383 further increased the intact tissue percentage, decreased cavity volume, and enhanced the recovery of locomotor activity in nude rats that underwent SCI, compared to MSCs. CONCLUSIONS: Suppression of miR-383 may increase the therapeutic potential of human bone-marrow-derived MSCs in treating SCI via augmentation of GDNF protein levels.

Surgical treatment of giant aneurysm of hepatic artery: report of three cases.

BACKGROUND/AIMS: To explore the surgical way of treating giant hepatic artery aneurysm(HAA). METHODOLOGY: Three hepatic artery aneurysm patients who were performed aneurysm resection without revascularization of the hepatic artery were reviewed. After surgery, the values of liver function and enhanced CT scan of the patients were followed. RESULTS: All the three patients were recovered well postoperatively and only several values of biochemistry marks of liver function as ALT, AST, TBIL and DB in one case with liver cirrhosis were elevated and decreased to normal ranges in a few days postoperatively. The values of biochemistry marks of liver function in other two cases were within normal limits. The enhanced CT scan also showed arteries in the liver after hepatic artery aneurysm resection. CONCLUSIONS: Giant HAA may be safely removed without revascularization of the hepatic artery.

[Build of focal cerebral ischemia model in different varieties of mice with modification monofilament].

OBJECTIVE: To establish a general method of focal cerebral ischemia model in different varieties of mice. METHOD: Each group of healthy adult KM and C57BL/6 mice were randomly divided into control group (n = 10) and MCAO group (n = 10). The mice in MCAO group were applied in the preparation of the MCAO model by intraluminal occlusion using monofilament. Twenty-four hours after operation,the neurologic function was evaluated,middle cerebral artery blood flow was monitored and the infarction volume was calculated by TTC staining, to evaluate the reliability of the model. RESULT: In the MCAO group, the base value of the cerebral blood flow down of KM and C57BL/6 mice respectively was (81.65 ± 4.59)%, (83.68 ± 6.25)%. The neurological deficit score respectively was (2.30 ± 0.82), (2.50 ± 0.80). TTC staining can clearly show the infarction area, and relatively stable, 24 hours of the survival rate of KM and C57BL/6 mice were 100% and 80% respectively. CONCLUSION: The key link is the optimization and improvement of monofilament, temperature, anesthesia and so on. The modified intraluminal occlusion of MCAO using monofilament is a kind of reliable and simple method to establish experimental cerebral ischemia model in mice.

[Analysis on prescription rules of treating senile dementia based on traditional Chinese medicine inheritance auxiliary systems].

This is designed to analyze and summarize medication rules for treating senile dementia with Chinese medicine in CNKI according to the traditional Chinese medicine (TCM) inheritance auxiliary system. Collect documents in CNKI that account treating senile dementia with Chinese formula; filter and establish a formula database, and then to search for medication rules on the TCM inheritance auxiliary system. It is filtered that 104 formulas are used for treating senile dementia screening treat senile dementia, involving 147 kinds of Chinese medicine. Tonic medicine are most frequently used, followed by the medicine of activating blood circulation and resuscitating; medicine pair most used is Ligusticum chuanxiong Hort-Acorus tatarinowii, accounting for 27.9% of all formula. And then 8 core pairs and 4 new formulas are evolved. Analysis on formulas for treating senile dementia filtered form CNKI by TCM inheritance auxiliary system shows prescription is mainly tonifying, activating blood circulation and resuscitating, that reveals prescription rules, to provide a reference for clinical treatment.

[Differences and drivers of leaf stable carbon and nitrogen isotope in herbs under different vegetation types on the eastern Qinghai-Tibet Plateau]. / é’è—é«˜åŽŸä¸œç¼˜ä¸åŒæ¤è¢«ç±»åž‹ä¸‹è‰æœ¬æ¤ç‰©å¶ç‰‡ç¢³æ°®ç¨³å®šåŒä½ç´ å·®å¼‚åŠå ¶é©±åŠ¨å› ç´ .

The natural abundance of stable carbon and nitrogen isotopes (δ13C and δ15N) in leaves can provide comprehensive information on the physiological and ecological processes of plants and has been widely used in ecological research. However, recent studies on leaf δ13C and δ15N have focused mainly on woody species, few studies have been conducted on herbs in different vegetation types, and their differences and driving factors are still unclear. In this study, we focused on the herbs in subalpine coniferous forests, alpine shrublands, and alpine mea-dows on the eastern Qinghai-Tibet Plateau, and investigated the differences in leaf δ13C and δ15N of herbs and the driving factors. The results showed that there were significant differences in leaf δ13C and δ15N values of herbs among different vegetation types, with the highest δ13C and δ15N values in alpine meadows, followed by alpine shrublands, and the lowest in subalpine coniferous forests. Using variation partitioning analysis, we revealed that differences in leaf δ13C and δ15N of herbs among various vegetation types were driven by both leaf functional traits and climate factors, with the contribution of leaf functional traits being relatively higher than that of climate factors. Hierarchical partitioning results indicated that mean annual temperature (MAT), chlorophyll content index, leaf nitrogen content per unit area (Narea), and leaf mass per area were the main drivers of leaf δ13C variations of herbs across different vegetation types, while the relative importance of Narea and MAT for variation in leaf δ15N of herbs was much higher than those other variables. There was a strong coupling relationship between leaf δ13C and δ15N as indicated by the result of the ordinary least squares regression. Our findings could provide new insights into understanding the key drivers of leaf δ13C and δ15N variations in herbs across different vegetation types.

[Multidimensional biodiversity of subalpine forest communities on the eastern edge of the Qinghai-Tibet Plateau, China]. / é’è—é«˜åŽŸä¸œç¼˜äºšé«˜å±±æ£®æž—ç¾¤è½çš„å¤šç»´åº¦ç”Ÿç‰©å¤šæ ·æ€§.

We analyzed multidimensional biodiversity (including species diversity, functional diversity, and phylogenetic diversity) of needle-broadleaf mixed forests of Abies fargesii var. faxoniana-Betula spp. and needleleaf forests of A. fargesii var. faxoniana in the subalpine regions of eastern edge of Qinghai-Tibet Plateau. We measured leaf functional traits including leaf area, leaf thickness, leaf dry matter content, and specific leaf area. The results showed that leaf thickness (0.28 mm) and leaf dry matter content (319.86 mg·g-1) in the needle-broadleaf mixed forests were significantly lower than in the needleleaf forest (0.39 mm and 371.33 mg·g-1, respectively), while specific leaf area (192.74 cm2·g-1) was significantly higher (100.91 cm2·g-1). Leaf area showed no significant difference between the two forest communities (27.88 and 26.63 cm2, respectively). The phylogenetic signals of all leaf functional traits were significant, except for leaf thickness. The phylogenetic structure of the needle-broadleaf mixed forests and needleleaf forest communities tended toward divergence. Shannon diversity index, Simpson diversity index, species richness, functional richness, functional dispersion, Rao's quadratic entropy, and phylogenetic diversity in the needle-broadleaf mixed forests were all significantly higher than in the needleleaf forest, and these indices were significantly positively correlated. Competitive exclusion played a major role in the assembly of subalpine forest communities, and species diversity, functional diversity, and phylogenetic diversity exhibited synchrony.

Responses of leaf traits to altitude in Quercus aquifolioides and Sorbus rehderiana on the eastern edge of the Qinghai-Tibet Plateau, China.

As the most senstitive plant organs to environmental changes, leaves serve as crucial indicators of plant survival strategies. We measured the morphology, anatomical traits, gas exchange parameters, and chlorophyll fluorescence parameters of Quercus aquifolioides (evergreen broad-leaved) and Sorbus rehderiana (deciduous broad-leaved) at altitudes of 2600, 2800, 3000, 3200 and 3400 m on the eastern edge of the Qinghai-Tibet Plateau, China. We explored the similarity and difference in their responses to altitude change and the ecological adaptation strategy. The results showed that as the altitude increased, leaf dry matter content of Q. aquifolioides decreased, that of S. rehderiana increased, leaf size for both species gradually decreased, and the palisade coefficient of Q. aquifolioides showed a decreasing trend, contrasting with the increasing trend in S. rehderiana. As the altitude increased, the thickness of leaves, palisade tissue, spongy tissue, upper epidermis, and lower epidermis of both species increased significantly, with the increment of 22.4%, 4.9%, 45.1%, 23.3%, 19.6%, and 28.2%, 46.9%, 8.9%, 25.9%, 20.8% at altitude of 3400 m, respectively, compared with the altitude of 2600 m. The gas exchange and chlorophyll fluorescence parameters of S. rehderiana significantly increased with increasing altitude, while Q. aquifolioides showed the opposite trend. Leaf anatomical traits, gas exchange, and chlorophyll fluorescence parameters of both species displayed considerable plasticity. There were significant correlations among most leaf traits and between leaf traits and altitude. The survival strategy of Q. aquifolioides was more conservative in response to altitude changes, while that of S. rehderiana was more active. Both species adapted to different altitudes by adjusting their own traits.

Effects of slope aspect on soil enzyme activity and microbial nutrient limitation in subalpine region of wes-tern Sichuan, China.

Exploring the resource limitation of soil microbial metabolism is essential to understand ecosystem functions and processes. However, the spatially divergent patterns and drivers of soil microbial nutrient limitation cha-racteristics in montane ecosystems at small scales, especially at the slope aspect scale, are still unclear. In this study, we measured soil enzyme activities involved in carbon (C), nitrogen (N) and phosphorus (P) cycle and quantified the microbial nutrient limitations by enzyme stoichiometry in two representative mountain sites in subalpine region of western Sichuan, including the sunny and shady slopes with different vegetation types (shrubland and forest, respectively) in Miyaluo of Lixian County, and with the same vegetation type (shrubland) in Yakexia of Heishui County. The results showed that soil enzyme activities and their stoichiometric ratios were significantly different between slope aspects in Miyaluo, while the differences were not significant in Yakexia. The stoichiometry ratio of C-, N- and P-acquiring enzymes on the sunny slope of Miyaluo was 1:0.96:0.92, approaching the 1:1:1 ratio at the global scale, but deviated from 1:1:1 on the shady slope of Miyaluo (1:1.39:0.75) and the different slopes of Yakexia (1:1.09:1.35). There was no significant difference in vector length between slope aspects at both sites, indicating no significant effect of slope aspect on the microbial C limitation. The vector angle was significantly higher on the sunny slope (43.6°) than that on the shady slope (28.7°) in Miyaluo, suggesting that the microorganisms were mainly N-limited. Partial least squares path model showed that the vector angle was mainly directly influenced by the soil nutrient ratios. The vector angle ranged from 50.3° to 51.4°, and did not differ between slope aspects in Yakexia. Therefore, differences in vegetation types between slope aspects drove variations in soil enzyme activity and microbial nutrient limitation through soil properties. It would provide a scientific basis for predicting the spatial pattern of soil enzyme activity and microbial nutrient limitation.

[Vertical distribution of natural abundance of stable carbon and nitrogen isotopes along the soil profile and the underlying mechanisms]. / åœŸå£¤å‰–é¢ç¢³æ°®ç¨³å®šåŒä½ç´ è‡ªç„¶ä¸°åº¦çš„åž‚ç›´åˆ†å¸ƒæ¨¡å¼åŠå ¶å½±å“æœºåˆ¶.

Understanding the changes of natural abundance of stable carbon and nitrogen isotopes (δ13C and δ15N) along soil profile is of great importance in revealing the mechanisms of soil carbon and nitrogen cycling in terrestrial ecosystems. Based on a comprehensive review on the distribution of δ13C and δ15N along soil profile, the mechanisms underlying their vertical distribution were mainly introduced here. There were three mechanisms driving the δ13C vertical distribution in soil profile: 1) historical changes of vegetation δ13C value, 2) changes of C3-C4 species dominance in plant communities, 3) accumulation of 13C-enriched microbial-derived carbon during decomposition. The effects of 13C Suess effect on the vertical distribution of δ13C in soil profile were also discussed. There were four mechanisms underlying the vertical distribution of δ15N in soil profile: 1) 15N-depletion gas loss during denitrification, 2) accumulation of 15N-enriched microbial-derived nitrogen during decomposition, 3) accumulation of 15N-encriched mycorrhizal fungi residues in deep soil as a result of transferring 15N-depleted nitrogen compounds to plants by mycorrhizae, 4) intera-ction between soil organic matter and mineral substance. We proposed important concerning points for the future study on vertical distribution of natural abundance of stable carbon and nitrogen isotopes in soil profile.

CircATRNL1 protects against osteoarthritis by targeting miR-153-3p and KLF5.

BACKGROUND: Osteoarthritis (OA) is characterized by chondrocyte injury. Circular RNAs (circRNAs) are involved in the pathogenesis of various diseases, including OA. The purpose of this study was to determine the potential role of circATRNL1 in OA pathology in vitro. METHODS: Human chondrocytes were isolated and treated with interleukin-1 beta (IL-1ß) to mimic OA in vitro. High-throughput RNA sequencing was performed to identify differentially expressed circRNAs, miRNAs and mRNAs between IL and 1ß-treated chondrocytes and normal chondrocytes. The expression of circATRNL1, miR-153-3p and KLF5 was measured using quantitative real-time polymerase chain reaction (qRT-PCR). For functional analyses, cell apoptosis was assessed using a flow cytometry assay. Extracellular matrix (ECM) degradation was monitored by measuring the levels of ECM-associated proteins by Western blot. The potential target miRNAs of circATRNL1 were screened by bioinformatics analysis and verified by dual-luciferase reporter assay. RESULTS: The expression of circATRNL1 was decreased in IL-1ß-treated chondrocytes. CircATRNL1 overexpression ameliorated cell apoptosis and ECM degradation, which were promoted by IL-1ß treatment. Mechanistic analysis revealed that circATRNL1 directly targeted miR-153-3p and that miR-153-3p could reverse the inhibitory effects of circATRNL1 overexpression on inflammatory responses, cell apoptosis and ECM degradation. KLF5 is a target of miR-153-3p. CONCLUSION: Taken together, the results in this study suggested that circATRNL1 might ameliorate the development and progression of OA through regulating miR-153-3p/KLF5 axis. Our study increased the understanding of circRNAs as therapeutic targets in the treatment of OA.

Juvenile Hormone-Sensitive Ribosomal Activity Enhances Viral Replication in Aedes aegypti.

Zika virus (ZIKV; Flaviviridae) is a devastating virus transmitted to humans by the mosquito Aedes aegypti. The interaction of the virus with the mosquito vector is poorly known. The double-stranded RNA (dsRNA)-mediated interruption or activation of immunity-related genes in the Toll, IMD, JAK-STAT, and short interfering RNA (siRNA) pathways did not affect ZIKV infection in A. aegypti. Transcriptome-based analysis indicated that most immunity-related genes were upregulated in response to ZIKV infection, including leucine-rich immune protein (LRIM) genes. Further, there was a significant increment in the ZIKV load in LRIM9-, LRIM10A-, and LIRM10B-silenced A. aegypti, suggesting their function in modulating viral infection. Further, gene function enrichment analysis revealed that viral infection increased global ribosomal activity. Silencing of RpL23 and RpL27, two ribosomal large subunit genes, increased mosquito resistance to ZIKV infection. In vitro fat body culture assay revealed that the expression of RpL23 and RpL27 was responsive to the Juvenile hormone (JH) signaling pathway. These two genes were transcriptionally regulated by JH and its receptor methoprene-tolerant (Met) complex. Silencing of Met also inhibited ZIKV infection in A. aegypti. This suggests that ZIKV enhances ribosomal activity through JH regulation to promote infection in mosquitoes. Together, these data reveal A. aegypti immune responses to ZIKV and suggest a control strategy that reduces ZIKV transmission by modulating host factors. IMPORTANCE Most flaviviruses are transmitted between hosts by arthropod vectors such as mosquitoes. Since therapeutics or vaccines are lacking for most mosquito-borne diseases, reducing the mosquito vector competence is an effective way to decrease disease burden. We used high-throughput sequencing technology to study the interaction between mosquito Aedes aegypti and ZIKV. Leucine-rich immune protein (LRIM) genes were involved in the defense in response to viral infection. In addition, RNA interference (RNAi) silencing of RpL23 and RpL27, two JH-regulated ribosomal large subunit genes, suppressed ZIKV infection in A. aegypti. These results suggest a novel control strategy that could block the transmission of ZIKV.

Imaging of dermatofibrosarcoma protuberans of breast.

Dermatofibrosarcoma protuberans (DFSP) is a rare superficial soft tissue malignancy. We report a 45-year-old woman diagnosed with DFSP involving the breast. Ultrasound of DFSP revealed a heteroechogenetic breast mass, which showed normal adjacent dermis. Mammography disclosed a high-density mass without microcalcification. MRI showed an enhancing lobulated lesion with small area of cystic change and hemorrhage. The patient underwent excision biopsy and pathology revealed DFSP of the breast. DFSP involving the breast is rare and preoperative diagnosis by imaging could be a challenge for clinicians. A solitary mixed echogenicity and ill-defined soft tissue with no microcalcification located in the subdermal region could indicate the presence of DFSP.

Three novel trehalase genes from Harmonia axyridis (Coleoptera: Coccinellidae): cloning and regulation in response to rapid cold and re-warming.

Trehalose is the main blood sugar in insects. To study the function of trehalase during exposure to low temperatures, three other novel cDNAs of trehalase were cloned from Harmonia axyridis by transcriptome sequencing and rapid amplification of cDNA ends. One of the cloned cDNAs encoded a soluble trehalase, the second trehalase cDNA encoded a transmembrane-like domain, and the third cDNA encoded a membrane-bound protein. Therefore, these cDNAs were, respectively, named HaTreh1-5, HaTreh2-like, and HaTreh2. HaTreh1-5, HaTreh2-like, and HaTreh2 cDNAs encoded proteins containing 586, 553, and 633 amino acids with predicted masses of approximately 69.47, 63.46, and 73.66 kDa, and pIs of 9.20, 5.52, and 6.31, respectively. All three novel trehalases contained signal motifs "PGGINKESYYLDSY", "QWDYPNAWPP", and a highly conserved glycine-rich (GGGGEY) region. The expression levels of HaTreh1-5 and HaTreh2 mRNAs were high during adult stages, whereas HaTreh2-like was expressed in low amounts in the fourth larval stage. The results showed that the activity of membrane-bound trehalases decreased from 25 to 10 °C and from 5 to - 5 °C during cooling. The results also revealed a decreasing trend in expression of the three HaTreh mRNAs during the cooling treatment, and an initial decrease followed by an increase during the process of re-warming.

Response of photosynthetic nitrogen use efficiency in Betula utilis to altitudinal variation along Balang Mountain, Sichuan, China.

To better understand the response and adaptation of plants to altitudinal changes, four sites at the altitude of 2200 m, 2500 m, 3100 m and 3400 m on Balang Mountain were selected to test and calculate the eco-physiological parameters in leaves of Betula utilis, including photosynthetic nitrogen use efficiency (PNUE), CO2 diffusion conductance (stomatal conductance gs and mesophyll conductance gm) and nitrogen allocation in each component (fractions of leaf nitrogen allocated to Rubisco PR, to bioenergetics PB, to light-harvesting components PL, and to cell wall PCW). Their changes with altitudinal variations and the relationships between leaf PNUE and the other parameters were analyzed. The results showed that PNUE, PR, and PB of the leaves were relatively higher at 2500 m and 3100 m. With the increases of altitude, gs and gm increased and PL decreased. The correlations between PR, PB and PNUE were significant, indicating that PR and PB were the main factors driving the changes in leaf PNUE in response to altitudinal variations. Besides, the fraction of leaf nitrogen allocated to photosynthetic apparatus (PP) was relatively higher at 2500 m and 3100 m. With increasing altitude, PCW decreased and the fraction of leaf nitrogen allocated to the other components (Pother) increased, which suggested that B. utilis leaves tended to allocate more nitrogen to the other components instead of the photosynthetic apparatus and cell wall with the increasing altitude to well adapt environmental changes.

Aedes aegypti HPX8C modulates immune responses against viral infection.

Mosquitoes act as vectors of numerous pathogens that cause human diseases. Dengue virus (DENV) transmitted by mosquito, Aedes aegypti, is responsible for dengue fever epidemics worldwide with a serious impact on human health. Currently, disease control mainly relies on vector targeted intervention strategies. Therefore, it is imperative to understand the molecular mechanisms underlying the innate immune response of mosquitoes against pathogens. In the present study, the expression profiles of immunity-related genes in the midgut responding to DENV infection by feeding were analyzed by transcriptome and quantitative real-time PCR. The level of Antimicrobial peptides (AMPs) increased seven days post-infection (d.p.i.), which could be induced by the Toll immune pathway. The expression of reactive oxygen species (ROS) genes, including antioxidant genes, such as HPX7, HPX8A, HPX8B, HPX8C were induced at one d.p.i. and peaked again at ten d.p.i. in the midgut. Interestingly, down-regulation of the antioxidant gene HPX8C by RNA interference led to reduction in the virus titer in the mosquito, probably due to the elevated levels of ROS. Application of a ROS inhibitor and scavenger molecules further established the role of oxygen free radicals in the modulation of the immune response to DENV infection. Overall, our comparative transcriptome analyses provide valuable information about the regulation of immunity related genes in the transmission vector in response to DENV infection. It further allows us to identify novel molecular mechanisms underlying the host-virus interaction, which might aid in the development of novel strategies to control mosquito-borne diseases.

Homocysteine inhibits the viability and migration ability of human umbilical vein endothelial cells by downregulating the expression of vascular endothelial growth factor.

The current study aimed to explore the effect of homocysteine (Hcy) on the viability and migration ability of human umbilical vein endothelial cells (HUVECs), as well as to examine the underlying mechanism. The association between the expression level of Hcy and lower extremity deep vein thrombosis (DVT) was detected in clinical samples collected from patients. In addition, the effect of Hcy on the viability and migration ability of HUVECs was detected by cell counting kit-8 and Transwell assays, respectively, while vascular endothelial growth factor (VEGF) expression was measured in order to verify the effect of Hcy on VEGF. The results indicated that the serum Hcy levels in DVT patients were significantly increased. In vitro experiments also confirmed that Hcy was able to significantly inhibit the viability and migration ability of HUVECs, and downregulate the expression of VEGF in these cells. Furthermore, the inhibitory effect of Hcy on HUVEC viability and migration ability was achieved by downregulating the expression of VEGF using small interfering RNA transfection. In conclusion, Hcy inhibited the viability and migration ability of HUVECs by downregulating the expression of VEGF. This may underlie the high incidence of DVT in patients with hyperhomocysteinemia.

Nitrogen and carbon source-sink relationships in trees at the Himalayan treelines compared with lower elevations.

No single hypothesis or theory has been widely accepted for explaining the functional mechanism of global alpine/arctic treeline formation. The present study tested whether the alpine treeline is determined by (1) the needle nitrogen content associated with photosynthesis (carbon gain); (2) a sufficient source-sink ratio of carbon; or (3) a sufficient C-N ratio. Nitrogen does not limit the growth and development of trees studied at the Himalayan treelines. Levels of non-structural carbohydrates (NSC) in trees were species-specific and site-dependent; therefore, the treeline cases studied did not show consistent evidence of source/carbon limitation or sink/growth limitation in treeline trees. However, results of the combined three treelines showed that the treeline trees may suffer from a winter carbon shortage. The source capacity and the sink capacity of a tree influence its tissue NSC concentrations and the carbon balance; therefore, we suggest that the persistence and development of treeline trees in a harsh alpine environment may require a minimum level of the total NSC concentration, a sufficiently high sugar:starch ratio, and a balanced carbon source-sink relationship.