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Tuberous sclerosis complex (TSC) is an incurable multisystem disease associated with hamartomatous tumors of brain, heart, skin, kidney and lung. The TSC proteins (TSC1 and TSC2) inhibit the mechanistic/mammalian target of rapamycin complex 1 (mTORC1), an exquisitely sensitive molecular sensor that regulates cell growth, cell metabolism and autophagy. mTORC1 is hyperactive in many malignancies, including TSC. Treatment of TSC-associated tumors with mTOR inhibitors leads to partial responses, with prompt regrowth upon treatment cessation, highlighting the unmet clinical need for cytocidal therapies. We previously discovered that miR-29b expression is strongly upregulated following rapamycin treatment. However, the functional significance and therapeutic impact of miR-29b induction by rapamycin in the therapy of TSC is unknown. We found that miR-29b expression is induced by rapamycin in vitro in 4 different TSC2-deficient cells and in vivo TSC-2 deficient tumors. Inhibition of miR-29b significantly decreased anchorage-independent cell growth by 40% (p < 0.01), and combined rapamycin treatment and miR-29b inhibition further suppressed growth by 73% (p < 0.0001). In addition, miR-29b knockdown inhibited cell migration and invasion by 68% (p < 0.05) and 50% (p < 0.01), respectively. miR-29b inhibition combined with rapamycin further decreased cell migration and invasion by 77% (p < 0.001) and 74% (p < 0.001), respectively. These findings suggest that miR-29b acts as an “onco-miR” in this context. Importantly, miR-29b knockdown in TSC2-deficient cells significantly suppressed tumorigenesis in vivo by 52% (p < 0.0001). Furthermore, the combination of rapamycin and miR-29b inhibition resulted in a more robust inhibition of tumor volume compared with miR control (47% vs. 24% inhibition) (p < 0.01). To gain insight into the molecular mechanisms by which miR-29b promotes tumorigenesis, we performed RNA-sequencing on miR-29b knockdown and control cells treated with rapamycin. 236 genes were upregulated in miR-29b knockdown cells by at least 2.0-fold and p < 0.05. Retinoid receptor beta (RARβ), one of the candidates, was increased in miR-29b knockdown cells at the mRNA level by 2.25-fold (p < 0.01) and protein expression by 2-fold (p < 0.05). RARβ is a tumor suppressor in many types of tumors. Interestingly, RARβ expression is downregulated by rapamycin (67% (p < 0.001)) and upregulated 4-fold following miR-29b inhibition (p < 0.05). Lastly, we found the 3'UTR activity of RARβ was upregulated in miR-29b knockdown cells by 4-fold (p < 0.001) using a luciferase reporter assay, supporting a model in which RARβ is a direct target of miR-29b. These studies demonstrate that miR-29b induction by rapamycin promotes TSC2-deficient tumorigenesis. miR-29b is a potential therapeutic target for TSC-associated tumors and possibly other mTORC-1 hyperactive tumors. Citation Format: Heng-Jia Liu, Hilaire C. Lam, Christian V. Baglini, Alex K. Conttrill, Stephen Y. Chan, Elizabeth P. Henske. Rapamycin-upregulated miR-29b promotes mTORC1-hyperactivative cell growth by downregulating retinoic acid receptor β (RARβ) [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr A28.

Renal angiomyolipoma (AML) and cysts are seen in 70-80% of patients with the human tumor suppressor gene syndrome tuberous sclerosis complex (TSC). Renal cell carcinoma (RCC) also is relatively common in TSC. Although two-hit loss of TSC1/2 is established in AML and TSC-RCC, the mechanisms and signaling pathways underlying TSC tumor development are not well understood. TSC-related tumor models were generated through i.p. tamoxifen (TM) injection (10mg/kg) at embryonic day 17.5 in Tsc2f/fROSA26-CreERT2 (n=24), Tsc2f/f CAG-CreERT2 mice (n=2) and Tsc1f/f CAG-CreERT2 mice (n=19). Extensive TSC-associated kidney papillary RCC (PRCC) and hybrid oncocytic/chromophobe tumors (HOCT) were seen in every kidney of these mice at age of 6 months, confirmed by IHC. A phospho-RTK immunoblot screen was performed using lysates from kidney tumors in comparison to normal kidneys. pAXL levels were ~2.8-fold higher versus normal kidney, whereas other pRTKs showed no apparent change. Immunoblotting confirmed the upregulated levels of both p-AXL (Tyr 702) and total AXL in kidney tumor lysates vs. normal kidneys. Q-RT-PCR of mRNA also showed 2-fold increase in AXL mRNA. Bioinformatic analysis suggested that AXL is a probable target of the transcription factor JUN. RNA-seq data showed that AMLs had the highest level of JUN expression in comparison to 28 different kinds of cancer (from TCGA). JUN was highly expressed in the mouse kidney tumors compared to normal kidneys in both protein and mRNA levels. JUN levels were also assessed using TSC-null cell lines (TSC2-/- angiomyolipoma cells (h), Tsc2-/- renal cell carcinoma cells (m), TSC1-/- bladder cancer cells (h), Tsc1-/- lung cancer cells (m)) versus their TSC add-back counterparts. All TSC-null cells showed a higher level of JUN and AXL compared to their TSC add-back counterparts. Both rapamycin (20nM) and Torin (500nM) treatment of these cell lines for 24h led to a reduction in JUN expression, with a stronger effect from Torin than rapamycin. To identify connections between JUN and AXL, JUN and AXL CRISPR KO were performed in 2 Tsc2-/- renal cell carcinoma cell lines. JUN KO led to a major decrease in AXL expression, and AXL KO led to a decrease of JNK, ERK and JUN. A positive feedback loop may exist between JUN and AXL through JNK and ERK pathway. R428, an inhibitor of AXL, was used to treat our Tsc2f/f ROSA26-CreERT2 mice and Tsc2+/- AJ mice (12.5mg/kg, twice daily, oral gavage, 3 weeks). Kidney tumor volume decreased dramatically compared with vehicle-treated mice in both cohorts (31.38 vs 4.11 mm³, p=0.001; 1.84 vs 0.05 mm³, p=0.02). These findings suggest that JUN and AXL are both upregulated in response to TSC1/TSC2 loss and mTORC1 activation and contribute to tumorigenesis, and that there is potential therapeutic value to targeting these events. Citation Format: Heng Du, Heng-jia Liu, Damir Khabibullin, Mahsa Zarei, John Dreier, Chin-Lee Wu, Elizabeth Henske, David Kwiatkowski. Targeting mTOR/JUN/AXL pathway in TSC-related tumors [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr B13.

Purpose: To investigate the anti-arthritic activity of arglabin in Freund’s complete adjuvant- induced arthritis in rats, and the likely underlying mechanism.Methods: A total of 40 male albino Wistar rats weighing between 120 and 150 g were used for this study. The rats were divided into four groups of ten rats each: control group, arthritis group, arglabintreated group, and standard (STD) group. Chronic arthritis was induced by injecting Freund's complete adjuvant in the plantar region of the rats. Rats in the arglabin-treated group received 5 ng/g arglabin intraperitoneally (i.p.), while those in the STD group received 1.5 mg/kg indomethacin, p.o. for 4 weeks. The development of arthritis was assessed at 0, 7, 14, 21 and 28th day of protocol by measuring thermal hyperalgesia, mechanical nociceptive threshold, arthritic score and paw volume. Activities of liver alkaline phosphatase (ALP), alanine amino-transaminase (ALT) and aspartate amino-transaminase (AST), and the levels of inflammatory cytokines -tumor necrosis factor-α (TNF-α), interferon gamma (IFN-γ), interleukin (IL)-6 and interleukin (IL)-1β were measured in the synovial fluid, while those of inflammatory mediators - thromboxane B2 (TXB2), prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) were determined in serum. The expressions of mRNAs of nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were also determined in rat synovial tissues.Results: Arglabin significantly decreased the paw swelling and arthritic scores, but significantly increased the paw withdrawal latency, when compared to the arthritis group (p < 0.05). It also attenuated the altered levels of inflammatory cytokines in arthritic rats, and significantly reduced the levels of inflammatory mediators, when compared to the arthritis group (p < 0.05). The expressions of mRNAs of NFkB, COX-2 and iNOS also significantly decreased in arglabin-treated group, relative to the arthritis group (p < 0.05).Conclusion: The anti-arthritic activity of arglabin is due to its effect on inflammatory pathway via decreases in the levels of inflammatory mediators and cytokines, and decrease in the expressions of NFkB, COX-2 and iNOS in the synovial tissues of arthritic rats.Keywords: Arglabin, Arthritis, Freund’s complete adjuvant, Inflammatory cytokines

Mesoporous g-C3N4is prepared by a hard template method and is then decorated by carbon quantum dots (CQDs) and TiO2nanoparticles through an impregnation route followed by a hydrothermal method. The synthesized hybrids possess higher specific surface area up to 131[Formula: see text]cm2/g and show effective absorption of visible light range and improved instantaneous photocurrent response, which reveals the enhanced photo-generated carrier separation efficiency. The first-order kinetic reaction rate constant of photocatalytic degradation of gaseous benzene by TCPCN-2 is 5.5 times of the bulk g-C3N4. Its degradation rate is up to 96.08% with good photocatalytic stability. Thus, the TiO2nanoparticles and CQDs co-decorated g-C3N4hybrids are promising photocatalysts.

Tuberous sclerosis complex (TSC) is an incurable multisystem disease characterized by mTORC1-hyperactive tumors. TSC1/2 mutations also occur in other neoplastic disorders, including lymphangioleiomyomatosis (LAM) and bladder cancer. Whether TSC-associated tumors will respond to immunotherapy is unknown. We report here that the programmed death 1 coinhibitory receptor (PD-1) is upregulated on T cells in renal angiomyolipomas (AML) and pulmonary lymphangioleiomyomatosis (LAM). In C57BL/6J mice injected with syngeneic TSC2-deficient cells, anti-PD-1 alone decreased 105K tumor growth by 67% (P < 0.0001); the combination of PD-1 and CTLA-4 blockade was even more effective in suppressing tumor growth. Anti-PD-1 induced complete rejection of TSC2-deficient 105K tumors in 37% of mice (P < 0.05). Double blockade of PD-1 and CTLA-4 induced rejection in 62% of mice (P < 0.01). TSC2 reexpression in TSC2-deficient TMKOC cells enhanced antitumor immunity by increasing T cell infiltration and production of IFN-γ/TNF-α by T cells, suggesting that TSC2 and mTORC1 play specific roles in the induction of antitumor immunity. Finally, 1 month of anti-PD-1 blockade reduced renal tumor burden by 53% (P < 0.01) in genetically engineered Tsc2+/- mice. Taken together, these data demonstrate for the first time to our knowledge that checkpoint blockade may have clinical efficacy for TSC and LAM, and possibly other benign tumor syndromes, potentially yielding complete and durable clinical responses.

We demonstrate that two interferometric autocorrelation traces obtained by sampling two second-harmonic tones around the carrier would be sufficient to algebraically retrieve the spectral phase of a 3.5 fs pulse.

Gentiana apiata N. E. Brown (Gentianaceae) is a perennial herb plant and only grows in Qinba Mountains in China. Here, we first characterized the complete nucleotide sequence of chloroplast (cp) genome of G. apiata via Illumina next generation sequencing platform. The complete chloroplast genome of G. apiata was 144,274 bp in length, comprising of a large single copy (LSC) region of 77,353 bp, a small single copy (SSC) region of 17,009 bp, and two inverted repeat regions (IRs) of 24,956 bp. The cp genome contains 127 genes, including 82 protein-coding genes, 35 tRNA, eight rRNA genes, and two pseudogenes. Phylogenetic analysis based on 18 cp genome sequences showed that G. apiata closely related to congeneric species.

The P-Rex (phosphatidylinositol (3,4,5)-trisphosphate (PIP3)-dependent Rac exchanger) family (P-Rex1 and P-Rex2) of the Rho guanine nucleotide exchange factors (Rho GEFs) activate Rac GTPases to regulate cell migration, invasion, and metastasis in several human cancers. The family is unique among Rho GEFs, as their activity is regulated by the synergistic binding of PIP3 and Gβγ at the plasma membrane. However, the molecular mechanism of this family of multi-domain proteins remains unclear. We report the 1.95 Å crystal structure of the catalytic P-Rex1 DH-PH tandem domain in complex with its cognate GTPase, Rac1 (Ras-related C3 botulinum toxin substrate-1). Mutations in the P-Rex1·Rac1 interface revealed a critical role for this complex in signaling downstream of receptor tyrosine kinases and G protein-coupled receptors. The structural data indicated that the PIP3/Gβγ binding sites are on the opposite surface and markedly removed from the Rac1 interface, supporting a model whereby P-Rex1 binding to PIP3 and/or Gβγ releases inhibitory C-terminal domains to expose the Rac1 binding site.

The dhole (Cuon alpinus), a canid, is categorized as Endangered (EN) on the IUCN Red List and is listed as a category II protected species in China. Presence-absence data are extremely rare in western China, and possible existence of remnant populations of dholes is not clear. Here, we document new records of dhole in a protected area in an arid region of the Altun Mountains in Xinjiang Autonomous Region in western China. From a total of 4517 camera-trap days at ten water sites between 2011 and 2013, we obtained seven independent records of dhole at three sites. Additionally, another reserve in Gansu Province which is located near Altun Mountains also recorded the species through camera-trap surveys. Our results indicate that dhole populations exist in the vast arid region of the Altun Mountains, and the current distribution of the dhole might be widespread in western China. We suggest that conservation efforts in this region should focus on minimizing the persecution and poaching of both dholes and their prey.

There are significant gaps in our knowledge of wild camel ecology; especially the activity patterns that allow them to adapt to desert environments. The wild Bactrian camel (Camelus bactrianus) is a critically endangered species that survives in the extreme desert conditions of Central Asia. We conducted camera trapping surveys at seven watering sites in the northern piedmont of the Altun Mountains from 2010 to 2012. We analyzed the frequency of photo-captures to elucidate the wild camels’ diel activity patterns, and the seasonal variation in their activity at watering sites. We found that these wild camels were predominantly diurnal at watering sites, with an increase in relative activity from sunrise, reaching a peak toward midday, and then gradually decreasing in activity until sunset. The camels visited watering sites more often in winter than in summer. These results provide a guide for water development in the conservation of ungulates in arid areas.

Phosphoinositide 3-kinase (PI3K) signalling is aberrantly activated in many human cancers, including breast cancer. PI3K is activated downstream of receptor tyrosine kinases (RTKs) to generate the lipid second messengers, PtdIns(3,4,5)P₃ and PtdIns(3,4)P₂, which activate numerous downstream signalling effectors including Akt and Rac-GEFs to promote cell proliferation, survival and motility. P-Rex1 (PtdIns(3,4,5)P₃-dependent Rac exchanger factor 1), a Rac-GEF, is highly expressed in a significant proportion of human breast cancers,and P-Rex1 overexpression may be oncogenic. In breast cancer cells, P-Rex1 promotes oncogenic signalling by integrating signals from HER2/3 and CXCR4 membrane surface receptors, however, P-Rex1 downstream signalling effectors are poorly characterised. This thesis examines the downstream effectors of P-Rex1 in breast cancer. Overexpression of P-Rex1 in ER-negative human breast cancer MDA-MB-231-luc-D3H1 cells enhanced oncogenic EGF-stimulated ERK1/2 activation, anchorage-independent cell growth, cell proliferation, migration, survival and xenograft tumour growth. In addition, PRex1 knockdown studies in ER-positive MCF-7-luc-F5 breast cancer cells supported the contention that P-Rex1 enhances oncogenic signalling in breast cancer via ERK1/2. In conclusion, studies presented in this thesis suggest that P-Rex1 is an important regulator of oncogenic ERK1/2 signalling in breast cancer.

A trial was conducted to investigate water sensitivity index (WSI) and water production function (WPF) of processing tomato subjected to water deficits in an arid environment. The WSI at various growth stages of processing tomato were maintained and a periodical WPF was established based on Blank model. The maximum WSI of processing tomato was marked at flowering with 0.7108 while the minimum was maintained at seedling with-0.0854. In addition, WSI was extremely lower at full fruiting compared to at flowering but notably higher than at seedling. Therefore, processing tomato was extremely sensitive to water deficit at flowering and high levels of soil moisture contents should be maintained while was not sensitive to water deficit at seedling and high levels of water deficits could be controlled without causing yield reduction.

An experiment was conducted to determine the effect of regulated deficit irrigation (RDI) on water use and economic benefit of processing tomato in an arid environment. The results indicated that seasonal total irrigation water applied to processing tomato was significantly (p0.05) occurred between fully irrigated crops and RDI plants subjected to water deficits at full fruiting as well as low deficit at late fruiting. However, in comparison with fully irrigated crops IWUE was significantly reduced with 20.5% and 22.2% in RDI plants both subjected to water deficits at flowering. Compared to full irrigation, the net income was significantly reduced with 11.3% to 45.3% in RDI plots except that subjected to low water deficit at seedling. Therefore, low water deficit RDI at seedling while full irrigation during flowering to late fruiting could be used to effectively reduce irrigation water application and improve IWUE of processing tomato without causing economic benefit reduction in arid areas.

This study constitutes an empirical fleet with electric vehicles (EV) and conventional vehicles (CV) which used by a large number of test participants who have different travel mileage to research the fuel-saving efficiency of EVs under daily travel mode within six months. Experimental results show that there is a great difference in energy consumption when EV running under different average temperatures and seasons. During summer (high temperature) and winter (low temperature) the energy consumption is bigger and the average electric consumption of 100-kilometer is 12.3 kWh/100km. The fuel-saving efficiency of EV in Tianjin empirical test is 66.7% and which is 74.8% in ten typical cities in China. EV has better fuel-saving effect in the whole country. The fuel-saving efficiency in working-days and rest-days is 80.3% and 42.2% respectively. EV has the best fuel-saving effect in working-days.

An experiment was conducted to determine the water sensitivity index (WSI) and water production function (WPF) of processing tomato under regulated deficit irrigation (RDI) in an arid environment. The WSI at different growth periods of processing tomato was maintained and a periodical WPF was established based on Jensen model. The maximum WSI was maintained at flowering with 0.8122 while the minimum was marked at seedling with 0.0589. In addition, WSI at full fruiting was much lower than at flowering but higher than at late fruiting. Therefore, processing tomato was extremely sensitive to water deficit at flowering and enough water should be applied to crops to maintain a high yield, while processing tomato was not sensitive to water deficit at seedling and a high level of water deficit could be reasonably controlled at this period through RDI without causing yield reduction.

An experiment was conducted to investigate the effect of regulated deficit irrigation (RDI) on yield and water use efficiency (WUE) of processing tomato in an arid climate. The results showed that crop yields of processing tomato were significantly (p0.05) existed between fully irrigated crops and RDI plants subject to water deficit at seedling or late fruiting. However, in comparison with fully irrigated crops WUE was significantly reduced by 16.3%~23.3% in RDI plants subject to water deficits respectively at flowering and full fruiting as well as subject to high water deficit at late fruiting. Therefore, low level of RDI at seedling while full irrigation during flowering to late fruiting could be applied to effectively improve yield and WUE of processing tomato in arid areas.

A trial was conducted to determine the effect of water deficit at tuber initiation of potato regulated with mulched drip irrigation on tuber yield and efficiency of water use in an arid environment. The results indicated that tuber yield of potato was significantly (p0.05) was found both in water use efficiency and irrigation water use efficiency between water deficit treatments. Therefore, soil water deficit at tuber initiation regulated with mulched drip irrigation could be used to effectively improve potato water use efficiency and irrigation water use efficiency in an arid environment.

An experiment was conducted to determine the effect of water deficit regulated with mulched drip irrigation on photosynthetic physiology characteristics at potato tuber initiation in an arid environment. The results indicated that potato leaf photosynthetic rate (PR), transpiration rate (TR) and stomatal conductance (SC) at tuber initiation were greatly affected by water deficit regulated with mulched drip irrigation. Daily PR varied with a double-peak curve within a day at tuber initiation. The TR increased sharply after 7:00 and the maximum was marked at 13:00 in all the treatments and CK at tuber initiation, then started to decrease, and TR also decreased with soil water deficit level increase, so was SC performance. Significant positive relations (p

An experiment was carried out to determine the effect of water deficit regulated with mulched drip irrigation on plant growth of processing tomato in an arid environment. The results indicated that Water deficit had little effect on plant height of processing tomato at full fruiting and late fruiting except that at seedling and flowering. Still, no effect of water deficit regulation on stem diameter was found at all measured growth stages. However, leaf area index and dry matter was significantly (p

The soil water contents in spring maize field were monitored continuously using soil neutron probe combined with drying-weighing method. Meanwhile, the effect of limited irrigation on crop periodic water consumption and its percentage in total water use, leaf area index, and grain yield of spring maize were explored. The results indicated that both the periodic water consumption and its percentage in total water use varied from low to high then to low within maize growing season, with the maximum valued both at silking to middle grain filling. In addition, leaf area indexes were greatly improved by full irrigation before maize filling, and grain yield was not reduced by efficient limited irrigation management, contrarily, yield increase and 31.1% of significant irrigation water saving were achieved, which was beneficial to the optimization of soil water ecological processing and limited irrigation management.

An experiment was conducted to determine the effect of mulched drip irrigation under water deficit on soil water content (SWC), stored soil water (SSW), daily water consumption (DWC) and ratio of water consumption in total water use (RWC) of potato in an arid area. Five water deficit treatments designed to subject potato to various levels of soil water deficit at different crop growth stages and a full irrigation control were established. The result indicated that the maximum SWC was at 20 cm depth in soil profile and that in 10 to 40 cm increment varied sharply during potato growing season. The SWC, SSW, DWC and RWC were significantly affected by mulched drip irrigation at water deficit regulation stages except at starch accumulation. Therefore, proper levels of soil water deficit regulated with mulched drip irrigation at proper plant growth stages could be used to regulate soil water status, stored soil water and crop water consumption effectively.

A field trial was conducted in 2007 and 2008 to investigate the difference in soil nutrients and grain yield of spring wheat (Triticum aestivum) as influenced by regulated deficit irrigation (RDI) in an arid area. Three RDI treatments and a no-water-deficit control (CK) were designed to subject wheat to various degrees of soil water deficit at different crop developmental stages. Significant differences (p0.05) occurred among the RDI treatments. Meanwhile, no differences were found in soil total nitrogen (STN) and soil total phosphorus (STP) contents among the treatments and CK. SOM content was improved by 6.2% to 7.2% in RDI treatments than in the CK over the two growing seasons, while the STN, STP, and SAK contents were increased by 1.2% to 2.5%, 1.4% to 5.6%, and 9.0% to 11.2%, respectiely. The STP (t=10.900, p2=1, p

A field experiment was carried out in 2007 and 2008 growing seasons to explore the comprehensive evaluation of soil nutrients in spring wheat field under regulated deficit irrigation (RDI) in an arid environment. The soil organic matter, soil total and available nitrogen, phosphorus, and potassium in 0~40 cm layer after two years of RDI management were selected as the evaluating factors to determine both the weighing coefficient of each soil nutrient component and the comprehensive evaluation index for soil nutrients (CEISN) using the membership function in fuzzy mathematics. The results showed that the CEISN was higher in all the RDI management than that in the no water deficit control except 3.5% lower in RDI2 over CK. The CEISN improvement was respectively 6.3%, 6.1%, 6.1%, 5.3%, 4.9%, and 3.8% higher in RDI7, RDI4, RDI5, RDI1, RDI3, RDI6 than in CK sequentially. Consequently, after two years of experiment, the optimal water management and sustainable soil nutrient use pattern was maintained in RDI7 due to its maximum CEISN in all the water deficit regulation regimes.

An experiment was carried out to determine the effect of mulched drip irrigation under water deficit on leaf area index (LAI), leaf area duration (LAD), dry matter (DM) and relative growth rate (RGR) of potato in an arid environment. Five water deficit treatments and a full irrigation control were established to subject potato to various levels of soil water deficit at different crop growth stages. The result indicated that potato LAI and LAD at all the determined growth stages were not reduced under water deficit regulation. Additionally, the DM and RGR at starch accumulation were not significantly decreased under water deficit either. Therefore, medium soil water deficit regulated at 55%~65% of field capacity with mulched drip irrigation at potato tuber initiation could be used to effectively improve leaf area index, leaf area duration, dry matter and relative growth rate of plants.

A trial was carried out to investigate the effect of limited water supply on leaf area duration (LAD), relative growth rate (RGR), crop growth rate (CGR), and above-ground biomass (AB) of spring maize. The results indicated that the LAD was significantly (p1, MI3, MI4, MI5, CK than MI2 during both 12-leaf stage to heading and heading to silking. There was no significant difference (p>0.05) in RGR among all the treatments and check during 6-leaf to 12-leaf stage and silking to middle grain filling, but significant difference occurred during other measured stages. Also, significant difference was found in CGR among some treatments and check during all the measured growth stages. The maximum AB of maize was maintained in CK with 23.0 t ha-1, significantly improved by 16.2%, 16.2%, 22.3% and 41.1%, 35.3% respectively than in MI1, MI4, MI5 and MI2, MI3, and the minimum AB was recorded in MI2 with 16.3 t ha-1.

An experiment was conducted to determine the effect of limited water supply on plant height, leaf area, dry matter and net assimilation rate (NAR) of spring maize. The results indicated that limited water supply had little effect on plant height of maize at six-leaf, twelve-leaf, heading and early grain filling except the end of filling. Leaf growth and leaf area expansion were effectively increased at middle and late maize growth stages under limited water supply and the maximum leaf area was maintained at early grain filling to middle filling. In addition, dry matter accumulation of maize in reproductive organs may be promoted by limited water supply. Finally, limited water supply also had great effect on net assimilation rate of maize and the maximum was maintained at six-leaf to twelve-leaf, followed by heading to silking.

An experiment was conducted to explore the integrated evaluation on soil nutrients in spring maize field subjected to limited irrigation (LI) in oasis region. The soil organic matter (SOM), soil total and available nitrogen (STN and SAN) and phosphorus (STP and SAP), and soil available potassium (SAK) in 0~40 cm increment at harvest of maize subjected to LI were selected as the evaluation factors to calculate the weighing coefficient of each soil nutrient and the IEI for soil nutrients using the membership function in fuzzy mathematics. At maize harvest, differences were not significant (p>0.05) in SOM, STN, STP, SAP, and SAK within 0~40 cm increment among treatments and CK, but significant difference (p5, which was respectively 187.3%, 96.8%, and 41.2% higher over MI2 valued the minimum, MI1, and CK. The IEI was improved by 12.4% to 22.3% in all the other treatments and CK compared to the minimum marked in MI4, with the maximum valued in MI3 treatments. Therefore, after one year experiment, the optimized irrigation management was maintained in MI3 treatment due to its maximum IEI in all the LI regimes.

An experiment was carried out to optimize limited irrigation (LI) schedules for spring maize in a desert oasis region. The grain yield, water use efficiency (WUE), irrigation water use efficiency (IWUE), and integrated evaluation index for soil nutrients (IEISN) in 0~40 cm soil depth of maize field subject to LI were selected as the synthetical factors in evaluating and optimizing the LI schedules. The unifactor matrix and weighing coefficient matrixes of evaluating factors were formed for fuzzy judgement and the synthetical evaluation index (SEI) determination. Compared to the minimum in MI4, the SEI for spring maize was respectively improved by 46.5%, 20.9%, 38.9%, 27.8%, and 23.8% in MI1, MI2, MI3, MI5, and CK. Therefore, the MI1 irrigation regime was recommended as the optimized LI schedule for spring maize in the desert oasis region due to its maximum SEI caused by the least water application, maximum grain yield, WUE, and IWUE, and 95.2% of the maximum IEISN.

PtdIns(3,4,5)P3-dependent Rac exchanger 1 (PREX1) is a Rac-guanine nucleotide exchange factor (GEF) overexpressed in a significant proportion of human breast cancers that integrates signals from upstream ErbB2/3 and CXCR4 membrane surface receptors. However, the PREX1 domains that facilitate its oncogenic activity and downstream signaling are not completely understood. We identify that ERK1/2 MAPK acts downstream of PREX1 and contributes to PREX1-mediated anchorage-independent cell growth. PREX1 overexpression increased but its shRNA knockdown decreased ERK1/2 phosphorylation in response to EGF/IGF-1 stimulation, resulting in induction of the cell cycle regulators cyclin D1 and p21(WAF1/CIP1) PREX1-mediated ERK1/2 phosphorylation, anchorage-independent cell growth, and cell migration were suppressed by inhibition of MEK1/2/ERK1/2 signaling. PREX1 overexpression reduced staurosporine-induced apoptosis whereas its shRNA knockdown promoted apoptosis in response to staurosporine or the anti-estrogen drug tamoxifen. Expression of wild-type but not GEF-inactive PREX1 increased anchorage-independent cell growth. In addition, mouse xenograft studies revealed that expression of wild-type but not GEF-dead PREX1 resulted in the formation of larger tumors that displayed increased phosphorylation of ERK1/2 but not AKT. The impaired anchorage-independent cell growth, apoptosis, and ERK1/2 signaling observed in stable PREX1 knockdown cells was restored by expression of wild-type but not GEF-dead-PREX1. Therefore, PREX1-Rac-GEF activity is critical for PREX1-dependent anchorage-independent cell growth and xenograft tumor growth and may represent a possible therapeutic target for breast cancers that exhibit PREX1 overexpression.

AIM: To investigate the effects of posterior scleral reinforcement (PSR) in the treatment of pathological myopia. METHODS: The study included 52 eyes in 43 patients with pathological myopia who underwent PSR (PSR group), and 52 eyes in 36 age- and myopia-matched patients who did not undergo such treatment as control group. Axial length, refraction error, best corrected visual acuity (BCVA), and macular scans by optical coherence tomography (OCT) were recorded at baseline, 6mo, 1, 3 and 5y after the surgery, and the complications were noted. RESULTS: There were no statistical differences in axial length, refractive error, or BCVA between the PSR group and the control group at baseline. At the end of the follow-up, the mean axial length was 29.79±1.26 mm in the PSR group, which was significantly shorter than that in the control group (30.78±1.30 mm) (P＜0.01), and the mean refractive error was -16.86±2.53 D in the PSR group, which was significantly lower than that in the control group (-19.18±2.12 D) (P＜0.01). A statistically significant difference in BCVA was found between the PSR group (0.51 ±0.25 logMAR) and the control group (0.62 ±0.26 logMAR) at the postoperative 5-year follow-up (P＜0.01). There were no serious complications during the 5-year follow-up period. CONCLUSION: PSR can prevent axial elongation and myopia progression in eyes with pathological myopia.

AIM: To investigate the effects of posterior scleral reinforcement (PSR) combined with vitrectomy for myopic foveoschisis. METHODS: Thirty-nine highly myopic eyes of 39 patients with myopic foveoschisis underwent PSR combined with vitrectomy. Best corrected visual acuity (BCVA), refraction error, and the foveal thickness by optical coherence tomography (OCT) were recorded before and after the surgery, and complications were noted. RESULTS: The follow-up period was 12mo, and the main focus was on the results of the 12-month follow-up visit. The mean preoperative BCVA was 0.96±0.43 logMAR. At the final follow-up visit, the mean BCVA was 0.46±0.28 logMAR, which significantly improved compared with the preoperative one (P=0.003). The BCVA improved in 33 eyes (84.62%), and unchanged in 6 eyes (15.38%). At the end of follow-up, the mean refractive error was -15.13±2.55 D, and the improvement was significantly compared with the preoperative one (-17.53±4.51 D) (P=0.002). Twelve months after surgery, OCT showed complete resolution of the myopic foveoschisis and a reat¬tachment of the fovea in 37 eyes (94.87%) and partial resolution in the remained two eyes (5.13%). The foveal thickness was obviously reduced at 12-month follow-up visit (196.45±36.35 μm) compared with the preoperative one (389.32±75.56 μm) (P=0.002). There were no serious complications during the 12mo follow-up period. CONCLUSION: PSR combined with vitrectomy is a safe and effective procedure for myopic foveoschisis with both visual and anatomic improvement.