Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 330
Filtrar
1.
Insect Biochem Mol Biol ; : 103312, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31904488

RESUMO

Various insect species including moths have shown significant foraging preference to acetic acid. However, the olfactory reception and behavioral outputs of acetic acid in moths remain unsolved. The female adults of Oriental armyworm, Mythimna separata, exhibit high preference to acetic acid enriched sweet vinegar solutions, making them good targets for exploration of acid reception and performance. We first proved that acetic acid is an essential component which elicited electrophysiological responses from volatiles of the sweet vinegar solution. Successive single sensillum recording tests showed that at least 4 types (as1, as2, as3, and as4) of sensilla were involved in acetic acid reception in the antennae. The low dosages of acetic acid elicited upwind flight and close search, and pre-contact proboscis extension responses of the fasted females, indicating it serves as a food related olfactory cue. In vivo optical imaging data showed that low dosages of acetic acid activated one ordinary glomerulus (DC3), and high dosages evoked additional two glomeruli (DC1 and AC1) in the antennal lobe. A systematic survey on olfaction related receptors in three related transcriptomes has yielded 67 olfactory receptors (ORs) and 19 ionotropic receptors (IRs). Among, MsepIR8a, MsepIR64a, MsepIR75q1, and MsepIR75q2 were chosen as putative acid receptors by blasting against known acid IRs in Drosophila and comparing essential amino acid residues which related to acid sensing. Later in situ hybridization revealed that MsepIr8a was co-expressed with each of the other 3 Irs, suggesting its putative co-receptor role. This study reveals olfactory reception of acetic acid as an attractant in M. separata, and provides the solid basis for later deorphanization of relevant receptors.

2.
Chin Med J (Engl) ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31809322

RESUMO

OBJECTIVE: Endometriosis is a common gynecologic disease that frequently leading to chronic pelvic pain, severe dysmenorrhea, and subfertility. As first-line hormonal treatment can interfere with ovulation and may cause recurrent pelvic pain, exploration of new non-hormonal therapeutic approaches becomes increasingly necessary. This review aimed to evaluate the pre-clinical and clinical efficacy and safety of non-hormonal treatment for endometriosis DATA SOURCES:: Databases including PubMed, Embase, Cochrane Library, SINOMED, ClinicalTrials.gov, and Google Scholar were searched up to October 2019, using search terms "endometriosis" and "non-hormonal therapy." STUDY SELECTION: Twenty-four articles were reviewed for analysis, including nine animal studies and 15 human trials; all were published in English. RESULTS: Twenty-four articles were identified, including 15 human trials with 861 patients and nine animal studies. Some agents have been evaluated clinically with significant efficacy in endometriosis-related pelvic pain and subfertility, such as rofecoxib, etanercept, pentoxifylline, N-palmitoylethanolamine, resveratrol, everolimus, cabergoline (Cb2), and simvastatin. Other drugs with similar pharmacological properties, like parecoxib, celecoxib, endostatin, rapamycin, quinagolide, and atorvastatin, have only been tested in animal studies. CONCLUSIONS: Clinical data about most of the non-hormonal agents are not sufficient to support them as options for replacement therapy for endometriosis. In spite of this, a few drugs like pentoxifylline showed strong potential for real clinical application.

3.
Int Immunopharmacol ; 78: 106050, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31812724

RESUMO

BACKGROUND: Advanced melanoma, one of the most lethal forms of skin cancer, remains a difficult condition to treat, despite the substantial scientific progression in cancer treatment. Oncolytic virotherapy (OV), either alone or combined with immune checkpoint inhibitors (ICIs), has often been administrated in an attempt to cure this malignancy. However, the clinical outcomes dramatically vary among different reports. METHODS: In this study, we performed a meta-analysis to evaluate the clinical efficacy and safety profile of OV, combined with ICIs in some cases, in advanced melanoma patients. The original clinical studies were identified based on the online query in PubMed, Cochrane, and Web of Science before December 30, 2018. RESULTS: A total of 18 publications involving 1472 patients were included for the final meta-analysis. The data concerning objective response rate (ORR) and incidence rate of severe immune-related adverse events (irAEs) were extracted accordingly from the text or supplementary materials. The results illustrated that a single treatment of OV could generate a 25% ORR for advanced melanoma, and the ORR could be improved to 45% if combined with ICIs. Further analysis demonstrated that the introduction of ICIs in OV could increase the incidence rate of severe irAEs (AE ≥ 3) from 12% to 39%. However, the rate attributed to OV remains at 12% in the combination group. CONCLUSION: The clinical efficacy of OV can be significantly improved by ICIs even though more onerous burden will be exerted simultaneously on the safety profile.

4.
Sci Total Environ ; : 135123, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31818587

RESUMO

The extensive use of roxarsone (ROX) in livestock and poultry husbandry causes the production of arylarsenic-contaminated manure/wastewater. Anaerobic digestion is a conventional technique for livestock manure/wastewater treatment. However, the factors affecting arsenic volatilization are poorly understood in arylarsenic-loaded anaerobic reactors. The main factors such as ROX loading, exposure time of anaerobic granular sludge (AGS) to ROX, and volatile fatty acid (VFA) levels, affecting arsenic volatilization were investigated in this study. The results indicated that ROX loading of 5.70 mg-As·L-1 triggered the maximum volatile arsenic yield of 6.78 ng-As·g-1-VSS·d-1, which was 4.95 times higher compared to the ROX-free assay. The conversion of ROX into inorganic arsenic was an essential step for arsenic volatilization. The 160-day and 270-day exposure of AGS to ROX caused 6-fold and 8-fold increase in volatile arsenic yield, respectively, compared to the 0-day exposure. With the longer-time exposure to ROX, AGS provided more available arsenic for volatilization and its arsenic-volatilizing capacity was significantly enhanced. VFA level was positively associated with arsenic volatilization (r = 0.832-0.950; p < 0.05). The abundance of arsM genes in AGS increased by 34.62-129.05% after the 100-day incubation, and was strongly correlated to arsenic volatilization. Based on these results, possible pathway of arsenic volatilization in ROX-loaded digesters were proposed. The result from this study improves a better understanding of the potential of arsenic volatilization in arylarsenic-contaminated environments.

5.
Regen Med ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31829095

RESUMO

Aim: To determine the efficacy and safety of intracoronary infusion of autologous bone marrow mesenchymal stem cells (MSCINJ) in combination with intensive atorvastatin (ATV) treatment for patients with anterior ST-segment elevation myocardial infarction-elevation myocardial infarction. Patients & methods: The trial enrolls a total of 100 patients with anterior ST-elevation myocardial infarction. The subjects are randomly assigned (1:1:1:1) to receive routine ATV (20 mg/d) with placebo or MSCsINJ and intensive ATV (80 mg/d) with placebo or MSCsINJ. The primary end point is the absolute change of left ventricular ejection fraction within 12 months. The secondary end points include parameters in cardiac function, remodeling and regeneration, quality of life, biomarkers and clinical outcomes. Results & conclusion: The trial will implicate the essential of cardiac micro-environment improvement ('fertilizing') for cell-based therapy. Clinical Trial Registration: NCT03047772.

6.
Int J Biol Sci ; 15(13): 2885-2896, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31853225

RESUMO

It is universally acknowledged that long non-coding RNAs (lncRNAs) involved in tumorigenesis in human cancers. However, the function and mechanism of many lncRNAs in colorectal cancer (CRC) remain unclear. By analyzing the two sets of CRC-related gene microarrays data, downloaded from the Gene Expression Omnibus (GEO) database and the lncRNA expression in a set of RNA sequencing data, we found that lncRNA SLCO4A1-AS1 was significantly upregulated in CRC tissues. We then collected CRC tissue samples and verified that SLCO4A1-AS1 is highly expressed in CRC tissues. Furthermore, SLCO4A1-AS1 was also upregulated in the CRC cell line. In situ hybridization results showed that high expression of SLCO4A1-AS1 was associated with poor prognosis in patients with CRC. Next, we found that SLCO4A1-AS1 promoted CRC cell proliferation, migration, and invasion. Results of western blotting assays show that its mechanism may relate to the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) pathway. Therefore, SLCO4A1-AS1 may be a potential biomarker for CRC prognosis and a new target for colorectal cancer therapy.

8.
Mikrochim Acta ; 186(12): 831, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31758272

RESUMO

Lateral flow assays, as a low-cost, simple, portable and disposable product of vitro diagnostic, are being widely used for point-of-care testing. However, the poor sensitivity of LFAs is the main challenge for commercialization. In order to enhance the sensitivity of LFAs, cellulose nanofibers (CNFs) have been integrated into LFAs to enhance the sensitivity of protein LFAs. A simple method is also presented to modify the properties of paper substrate by incorporating CNFs into a nitrocellulose membrane to enhance the sensitivity of nucleic acid LFAs. This method changes the pore size, porosity, surface groups and surface area of paper substrate and then increases the adsorption ability of biomolecules on paper substrate. The results indicate that the sensitivity of nucleic acid LFAs in Staphylococcus aureus testing achieves a 20-fold enhancement. Hence, we anticipate that this simple method has the potential for other paper-based devices to improve the performance. Graphical abstractA simple method is used to modify the properties of paper substrate by incorporating cellulose nanofibers (CNFs) into nitrocellulose (NC) membrane to enhance the sensitivity of nucleic acid LFAs.

9.
Sci Rep ; 9(1): 17162, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31748581

RESUMO

Ultra-low-loss and large-effective-area fiber has been successfully applied in transoceanic transmission, which is considered as a promising candidate for 100 Gbit/s and beyond 100 Gbit/s coherent long-haul terrestrial optical networks. Several theoretical and experimental investigations have been reported, including provincial terrestrial field trial. To support long-haul terrestrial application, it is urgent to prove that the ultra-low-loss and large-effective-area fiber after terrestrial deployment can significantly enhance the performance of long-haul transmission over 1000 km compared with the conventional single mode fiber. In this paper, we extended our previous work and summarized design methods for complex terrestrial environment. To verify the fiber characteristics in long-haul terrestrial transmission, we installed the longest terrestrial ultra-low-loss and large-effective-area fiber link in the world with a total length of 1539.6 km. The results show that the transmission performances of wavelength-division-multiplexed signals with per-channel data rates of 100 Gbit/s, 200 Gbit/s, and 400 Gbit/s over the ultra-low-loss and large-effective-area fiber are all obviously improved, demonstrating that this fiber is more suitable for ultrahigh-speed long-haul terrestrial transmission.

10.
J Insect Sci ; 19(6)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31725878

RESUMO

Armyworm feeding in large, destructive groups is hugely difficult to control and the oriental armyworm, Mythimna separata (Walk), is one such pest. In this study, we reported a semisynthetic artificial diet for the oriental armyworm. This diet is based on Ritter's diet, a formula developed for Heliothis zea. The survival of M. separata was extremely low and only around 2% insects can reach the adult stage on Ritter's diet. But, it can reach up to 100% if corn leaf powder (CLP) was mixed, and insects grew faster and gained more mass. After testing a set of mixtures of Ritter's diet and CLP, we found that 14.3% was the optimal proportion of CLP for making the artificial diet. We then used chloroform to extract CLP. Insect performance was still much better on Ch-extracted CLP diets than that on Ritter's diet, but it was poorer than that on the diets containing unprocessed CLP, suggesting that the essential factor(s) was only partially extracted from corn leaf. We then used methanol and dichloromethane, two solvents differing in their polarity, to process the extractions and analyzed the extracted chemicals using gas chromatography-mass spectrometry (GC-MS). Insects had a better performance on dichloromethane-extracted CLP diet in comparison to methanol-extracted one, indicating that the important factor(s) is more prone to methanol extraction. The reported recipe here is useful for the research on M. separata and possibly other grain-crop eating armyworms. The functions of the chemicals extracted from corn leaf tissue can be investigated in the future studies.

11.
J Proteome Res ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31647243

RESUMO

The major protein in Chinese yam (Dioscorea opposita Thunb.) glycoprotein, 30CYGP, exhibits strong immunomodulatory activities. Research has identified the sequence and structure of 30CYGP; however, 30CYGP N-glycoform composition and immunoactivity remain unknown. We isolated and purified 30CYGP from Chinese yam and used that material to release the N-glycans contained within. The N-glycans were labeled with 1-phenyl-3-methyl-5-pyrazolone and analyzed via ESI-MS and online LC-MS. Additionally, the immunoactivities of 30CYGP and de-glycosylated 30CYGP in the RAW264.7 cell line were investigated. Six 30CYGP N-glycans were observed in total, in which three were modified with xylose (XM: 40%) and three with xylose and fucose (XFM: 60%). Furthermore, de-glycosylated 30CYGP had significantly weaker immunoactivity than 30CYGP. This study demonstrated that novel N-glycoforms may enhance 30CYGP immunoactivity. Further research on the role of varied glycosylation patterns in immunoactivity is needed.

12.
Nat Commun ; 10(1): 3978, 2019 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484936

RESUMO

The pH in atherosclerotic lesions varies between individuals. IgE activates macrophage Na+-H+ exchanger (Nhe1) and induces extracellular acidification and cell apoptosis. Here, we show that the pH-sensitive pHrodo probe localizes the acidic regions in atherosclerotic lesions to macrophages, IgE, and cell apoptosis. In Apoe-/- mice, Nhe1-deficiency or anti-IgE antibody reduces atherosclerosis and blocks lesion acidification. Reduced atherosclerosis in Apoe-/- mice receiving bone marrow from Nhe1- or IgE receptor FcεR1-deficient mice, blunted foam cell formation and signaling in IgE-activated macrophages from Nhe1-deficient mice, immunocomplex formation of Nhe1 and FcεR1 in IgE-activated macrophages, and Nhe1-FcεR1 colocalization in atherosclerotic lesion macrophages support a role of IgE-mediated macrophage Nhe1 activation in atherosclerosis. Intravenous administration of a near-infrared fluorescent pH-sensitive probe LS662, followed by coregistered fluorescent molecular tomography-computed tomography imaging, identifies acidic regions in atherosclerotic lesions in live mice, ushering a non-invasive and radiation-free imaging approach to monitor atherosclerotic lesions in live subjects.

13.
Nat Commun ; 10(1): 4237, 2019 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-31530873

RESUMO

The codling moth Cydia pomonella, a major invasive pest of pome fruit, has spread around the globe in the last half century. We generated a chromosome-level scaffold assembly including the Z chromosome and a portion of the W chromosome. This assembly reveals the duplication of an olfactory receptor gene (OR3), which we demonstrate enhances the ability of C. pomonella to exploit kairomones and pheromones in locating both host plants and mates. Genome-wide association studies contrasting insecticide-resistant and susceptible strains identify hundreds of single nucleotide polymorphisms (SNPs) potentially associated with insecticide resistance, including three SNPs found in the promoter of CYP6B2. RNAi knockdown of CYP6B2 increases C. pomonella sensitivity to two insecticides, deltamethrin and azinphos methyl. The high-quality genome assembly of C. pomonella informs the genetic basis of its invasiveness, suggesting the codling moth has distinctive capabilities and adaptive potential that may explain its worldwide expansion.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31512996

RESUMO

BACKGROUND: Forkhead box C1 (FOXC1) is an important cancer associated gene in tumor. PPAR-γ and C/EBPα are both transcriptional regulators involved in tumor development. OBJECTIVE: We aimed to clarify the function of PPAR-γ, C/EBPα in hepatocellular carcinoma (HCC) and relationship of PPAR-γ, C/EBPα and FOXC1 in HCC. METHOD: Western blotting, immunofluorescent staining and immunohistochemistry were used to evaluate protein expression. qRT-PCR was used to assess mRNA expression. Co-IP was performed to detect the protein interaction. And ChIP and fluorescent reporter detection were used to determine the binding between protein and FOXC1 promoter. RESULTS: C/EBPα could bind to FOXC1 promoter and PPAR-γ could strengthen C/EBPα's function. Expressions of C/EBPα and PPAR-γ were both negatively related with FOXC1 in human HCC tissue. Confocal displayed that C/EBPα was co-located with FOXC1 in HepG2 cells. C/EBPα could bind to FOXC1 promoter by ChIP. Luciferase activity detection exhibited that C/EBPα could inhibit FOXC1 promoter activity, especially FOXC1 promoter from -600 to -300 was the critical binding site. Only PPAR-γ couldn't influence luciferase activity but strengthen inhibited effect of C/EBPα. Further, the Co-IP displayed that PPAR-γ could bind to C/EBPα. When C/EBPα and PPAR-γ was both high expressed, cell proliferation, migration, invasion and colony information were inhibited enormously. C/EBPα plasmid combined with or without PPAR-γ agonist MDG548 treatment exhibited a strong tumor inhibition and FOXC1 suppression in mice. CONCLUSION: Our data establish C/EBPα targeting FOXC1 as potential determinant in the HCC, which supplies a new pathway to treat HCC. However, PPAR-γ has no effect on FOXC1 expression.

15.
J Nat Med ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31435860

RESUMO

The core of solid tumors is characterized by hypoxia and a nutrient-starved microenvironment and has gained much attention as targets of anti-cancer drugs. In the course of search for selective growth inhibitors against the cancer cells adapted to nutrient starvation, epidithiodiketopiperazine DC1149B (1) together with structurally related compounds, trichodermamide A (2) and aspergillazine A (3), were isolated from culture extract of marine-derived Trichoderma lixii. Compounds 1 exhibited potent selective cytotoxic activity against human pancreatic carcinoma PANC-1 cells cultured under glucose-starved conditions with IC50 values of 0.02 µM. The selective index of the compound 1 was found to be 35,500-fold higher for cells cultured under glucose-starved conditions than those under the general culture conditions. The mechanistic analysis indicated that compound 1 inhibited the response of the ER stress signaling. In addition, these effects of compound 1 could be mediated by inhibiting complex II in the mitochondrial electron transport chain.

16.
Front Immunol ; 10: 1612, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31402909

RESUMO

Sepsis-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) remains the leading complication for mortality caused by bacterial infection. The regulatory T (Treg) cells appear to be an important modulator in resolving lung injury. Despite the extensive studies, little is known about the role of macrophage HMGB1/PTEN/ß-catenin signaling in Treg development during ALI. Objectives: This study was designed to determine the roles and molecular mechanisms of HMGB1/PTEN/ß-catenin signaling in mediating CD4+CD25+Foxp3+ Treg development in sepsis-induced lung injury in mice. Setting: University laboratory research of First Affiliated Hospital of Anhui Medical University. Subjects: PTEN/ß-catenin Loxp and myeloid-specific knockout mice. Interventions: Groups of PTENloxp/ß-cateninloxp and myeloid-specific PTEN/ß-catenin knockout (PTENM-KO/ß-cateninM-KO) mice were treated with LPS or recombinant HMGB1 (rHMGB1) to induce ALI. The effects of HMGB1-PTEN axis were further analyzed by in vitro co-cultures. Measures and Main Results: In a mouse model of ALI, blocking HMGB1 or myeloid-specific PTEN knockout (PTENM-KO) increased animal survival/body weight, reduced lung damage, increased TGF-ß production, inhibited the expression of RORγt and IL-17, while promoting ß-catenin signaling and increasing CD4+CD25+Foxp3+ Tregs in LPS- or rHMGB-induced lung injury. Notably, myeloid-specific ß-catenin ablation (ß-cateninM-KO) resulted in reduced animal survival and increased lung injury, accompanied by reduced CD4+CD25+Foxp3+ Tregs in rHMGB-induced ALI. Furthermore, disruption of macrophage HMGB1/PTEN or activation of ß-catenin significantly increased CD4+CD25+Foxp3+ Tregs in vitro. Conclusions: HMGB1/PTEN/ß-catenin signaling is a novel pathway that regulates Treg development and provides a potential therapeutic target in sepsis-induced lung injury.

17.
Front Neurosci ; 13: 776, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396046

RESUMO

There is a pressing need to further our understanding of the mechanisms underlying the depression symptoms in patients with post-stroke depression (PSD) in order to inform targeted therapeutic approaches. While previous research has demonstrated a reorganization in the functional brain network of PSD, it remains uncertain whether, or not it also occurs in the structural brain network. We therefore aim to investigate the structural brain network of patients with PSD as compared to post-stroke non-depression (PSND) patients. In addition, our research considers the relationship between network metrics and functional measurements. Thirty-one PSD patients and twenty-three PSND patients were recruited. All patients underwent MRI and functional assessments, including the Barthel index, mini-mental state examination (MMSE), and Hamilton depression rating scale (HAMD). Diffusion tensor imaging was used to construct the structural brain network and to conduct the subsequent graph theoretical analysis. Network measures were computed and compared between PSD and PSND patients. Associations between functional assessments and network measures were studied as well. We successfully detected increased global and local efficiency in patients with PSD. Regions with disrupted local connections were located primarily in the cognitive and limbic systems. More importantly, PSD patients' global and regional network measures were associated with depression severity, as measured by HAMD. These findings suggest that disrupted global and local network topologies might contribute to PSD patients' depression symptoms. Therefore, connectome-based network measures could be potential bio-markers for evaluating stroke patients' depression levels.

18.
Chin Med J (Engl) ; 132(16): 1959-1964, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31373908

RESUMO

BACKGROUND: Nickel-induced allergic contact dermatitis (Ni-ACD) is a global health problem. More detailed knowledge on the skin uptake of haptens is required. This study aimed to investigate the penetration process and distribution of nickel in skin tissues with late phase and early phase of Ni-ACD to understand the mechanisms of metal allergy. METHODS: Forty Hartley guinea pigs were divided into four groups according to the NiSO4 sensitizing concentration and the NiSO4 challenged concentration: the 5% NiSO4-group, 5% to 10% (sensitization-challenge; late phase group); 10% NiSO4-group, 10% to 10% (sensitization-challenge; early-phase group); and the positive and negative controls. Pathological biopsies were performed on each group. The depth profile of nickel element concentration in the skin of guinea pigs was detected by synchrotron radiation micro X-ray fluorescence spectroscopy (SR-µ-XRF) and micro X-ray absorption near-edge spectroscopy (µ-XANES). RESULTS: In each section, the nickel element concentration in both the 5% NiSO4-group and 10% NiSO4-group was significantly higher than that in the negative control group. In the upper 300-µm section of skin for the early phase group, the nickel element concentration was significantly higher than that in the lower section of skin. In deeper sections (>200 µm) of skin, the concentration of nickel in the early phase group was approximately equal to that in the late phase group. The curve of the late phase group was flat, which means that the nickel element concentration was distributed uniformly by SR-µ-XRF. According to the XANES data for the 10% NiSO4 metal salt solution, structural changes occurred in the skin model sample, indicating that nickel was not present in the Ni aqueous ionic state but in the nickel-binding protein. CONCLUSIONS: This study showed that the distribution of the nickel element concentration in ACD skin tissue was different between the early phase and late phase groups. The nickel element was not present in the Ni aqueous ionic state but bound with certain proteins to form a complex in the stratum corneum in ACD model tissue.

19.
Insects ; 10(8)2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31366119

RESUMO

The impact and sustainability of two interventions that have been formulated to introduce integrated pest management (IPM) into rice and maize crops in Southwestern China, Laos, and Myanmar between 2011 and 2016, and were assessed at the end of 2017. From 22 Trichogramma rearing facilities established during the interventions, 11 were still producing substantial quantities of biocontrol agents 1.5 years after project support had ended, while seven had stopped operations completely, and four were doing stock rearing only. Through the implementation of biological control-based IPM, slightly higher yields were achieved in maize and rice (4-10%), when compared to control farmers, but the difference was not statistically significant. However, the use of pesticides nearly halved when farmers started using Trichogramma egg-cards as a biological control agent. Support from either public or private institutions was found to be important for ensuring the sustainability of Trichogramma rearing facilities. Many of the suggested IPM measures were not adopted by smallholder farmers, indicating that the positive impacts of the interventions mostly resulted from the application of Trichogramma biological control agents. The following assessment suggests that further promotion of IPM adoption among farmers is needed to upscale the already positive effects of interventions that facilitate reductions in synthetic pesticide use, and the effects on sustainable agricultural production of rice and maize in the target area more generally.

20.
Cancer Discov ; 9(11): 1590-1605, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31350327

RESUMO

The kinase LKB1 is a critical tumor suppressor in sporadic and familial human cancers, yet the mechanisms by which it suppresses tumor growth remain poorly understood. To investigate the tumor-suppressive capacity of four canonical families of LKB1 substrates in vivo, we used CRISPR/Cas9-mediated combinatorial genome editing in a mouse model of oncogenic KRAS-driven lung adenocarcinoma. We demonstrate that members of the SIK family are critical for constraining tumor development. Histologic and gene-expression similarities between LKB1- and SIK-deficient tumors suggest that SIKs and LKB1 operate within the same axis. Furthermore, a gene-expression signature reflecting SIK deficiency is enriched in LKB1-mutant human lung adenocarcinomas and is regulated by LKB1 in human cancer cell lines. Together, these findings reveal a key LKB1-SIK tumor-suppressive axis and underscore the need to redirect efforts to elucidate the mechanisms through which LKB1 mediates tumor suppression. SIGNIFICANCE: Uncovering the effectors of frequently altered tumor suppressor genes is critical for understanding the fundamental driving forces of cancer growth. Our identification of the SIK family of kinases as effectors of LKB1-mediated tumor suppression will refocus future mechanistic studies and may lead to new avenues for genotype-specific therapeutic interventions.This article is highlighted in the In This Issue feature, p. 1469.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA