Performance evaluation of rural water environment governance based on AHP: a case study of the Beitang River Basin.

Rural water environment governance in China still lacks a systematic and comprehensive assessment protocol to help analyze and improve such governance performance. The Analytic Hierarchy Process (AHP) method was employed in this study to build a governance assessment system that integrates ecological conditions, water pollution control, and public satisfaction. To cover these topics, the assessment system is composed of an indicator layer that is customized to rural water environment governance in China. The Beitang River, located in the rural region of Hangzhou, Zhejiang, China, was presented as a case study. Field investigation provided raw data for this assessment. A questionnaire survey was conducted to interview local residents on the governance performance. An additional survey with executives who played major roles in the governance was performed to reconstruct a water environment assessment on the Beitang River prior to the governance, in order to highlight the effects of the governance through contrast. The results showed consistency in the questionnaire survey and the assessment system. The AHP assessment system was able to reflect the improvement in the water quality, river ecology, and residential welfare after the governance, and suggested limits and future directions in the following upgrade programs for the river basin.

CircRTN4 aggravates mesangial cell dysfunction by activating the miR-513a-5p/FN axis in lupus nephritis.

Circular RNAs (circRNAs) are regulators of gene expression that can regulate cell proliferation and programmed cell death and serve as biomarkers in renal diseases. However, the specific traits and underlying mechanisms of circRNAs in the progression of lupus nephritis (LN) have not been elucidated. In the present study, we clarified that hsa_circ_0054595 (circRTN4) was upregulated in human renal mesangial cells (HRMCs). In cultured HRMCs, circRTN4 could enhance FN expression by directly interacting with miR-513a-5p. High circRTN4 expression in monocytes disseminated into HRMCs in an exosomal manner, thereby accelerating cell proliferation and extracellular matrix deposition. In addition, knockdown of circRTN4 in the kidney or peripheral blood alleviated renal damage in MRL/lpr and BALB/c mice. Clinically, high levels of circRTN4 were found in peripheral blood mononuclear cells and kidney tissues of LN patients, hence serving as an effective biomarker for LN detection and a novel therapeutic target. Our findings indicated that circRTN4 exacerbates mesangial cell dysfunction by activating the miR-513a-5p/FN axis in lupus nephritis.

The pros and cons of cytokines for fowl adenovirus serotype 4 infection.

Hepatitis-hydropericardium syndrome (HHS), caused by fowl adenovirus serotype 4 (FAdV-4), has spread on chicken farms worldwide, causing huge economic losses. Currently, the exact mechanism of pathogenesis of FAdV-4 remains unknown. Despite the severe inflammatory damage observed in chickens infected with pathogenic FAdV-4, few studies have focused on the host immune system-virus interactions and cytokine secretion. Host immunity acts as one of the most robust defense mechanisms against infection by pathogens, and cytokines are important in their elimination. However, excessive inflammatory cytokine secretion could contribute to the pathogenesis of FAdV-4. Understanding of the roles of cytokines produced during FAdV-4 infection is important for the study of pathogenicity and for developing strategies to control FAdV-4. Several previous studies have addressed the immune responses to FAdV-4 infection, but there has not been a systematic review of this work. The present review provides a detailed summary of the current findings on cytokine production induced by FAdV-4 infection to accelerate our understanding of FAdV-4 pathogenesis.

What we bet on is not only tangible money, but also good mood.

A surprisingly large number of lottery prizes go unclaimed every year. This leads us to suspect that what people bet on is not only money, but also good mood. We conducted three studies to explain, from an emotional perspective, why people play lottery games. We first conducted two survey studies to assess mood state reported by online (Study 1a) and offline lottery buyers (Study 1b) at different stages of lottery play. The results revealed that participants' highest mood appeared before knowing whether they had won. In Study 2, we manipulated the means of reward (lottery tickets vs. cash) and compared participants' mood changes at different stages of a rewards game in the laboratory. We found the following: first, lottery group participants were generally in a better mood; second, 42% of lottery group participants did not come to the laboratory to collect scratch cards; and third, lottery group participants took more time to return to the laboratory to check their tickets than participants in the cash group. In Study 3, we examined whether priming good or bad mood could influence participants' preferences for cash versus lottery tickets. The results revealed that participants who were primed for poor mood had a higher preference for lottery tickets compared with their good mood counterparts. These findings suggest that what our participants sought in lottery play was not only money, but improved mood.

The drip loss inhibitory mechanism of nanowarming in jumbo squid (Dosidicus gigas) mantles: protein structure and molecular dynamics simulation.

BACKGROUND: The magnetic nanoparticles plus microwave thawing (MNPMT), a new rewarming technology entitled 'nanowarming', can serve as an effective method to achieve rapid and uniform thawing, thus reducing drip loss. The purpose of this study was to decipher the drip loss inhibitory mechanism of MNPMT in jumbo squid (Dosidicus gigas) from the perspectives of protein structure and ice crystal recrystallization. A number of different techniques such as dynamic rheology, Raman spectra, intrinsic fluorescence measurement, and ultraviolet (UV) absorption spectra were conducted to analyze myofibrillar protein conformation and stability of jumbo squid. Scanning electron microscopy (SEM) and myofibrillar fragmentation index (MFI) were used to observe the growth of ice crystals. The interaction between magnetic nanoparticles (MNPs) and ice crystals was studied by using molecular dynamic (MD) simulation. RESULTS: MNPMT exhibited the highest storage modulus (G') value at 90 °C, suggesting the protein conformation was more stable. The increase in α-helices, fluorescence intensity and characteristic absorption peak of MNPMT illustrated that MNPMT can effectively maintain the secondary and tertiary structure of the protein. Compared with cold storage thawing (CST) and microwave thawing (MT), the MFI value of MNPMT was significantly decreased (P < 0.01). The result of MD simulation showed that MNPs displayed a tendency to gradually approach the surface of ice crystals, and induced a certain degree of damage to the ice crystal surface, thereby markedly inhibiting ice crystal recrystallization. CONCLUSION: MNPMT can reduce the drip loss by keeping the protein conformation stable and inhibiting the recrystallization of ice crystals during the thawing process. © 2022 Society of Chemical Industry.

Influence of additional methanol on both pre- and post-denitrification processes in treating municipal wastewater.

Changes in functional properties of biological denitrification in the long-term use of methanol were explored in both pre- and post-denitrification processes. The two systems employed were sequencing batch reactor (SBR) using post-denitrification in temporal sequence, and Carrousel oxidation ditch, which was equipped with a separate pre-denitrification zone. In the SBR, stable nitrate reduction rates reached after 37 days elapsed with addition of methanol (TOC/N = 1.4-1.8) at the start of anoxic phase, and specific denitrification rate increased from 0.378 mgNOx-N·(gVSS·h)-1 to 2.406 mgNOx-N·(gVSS·h)-1. Besides, by means of nitrogen uptake rate (NUR) batch tests based on methanol-adapted sludge, the appropriate range of TOC/N ratios for complete denitrification was estimated to be 1.10-2.68. By comparison, the Carrousel oxidation ditch that was fed with methanol in the anaerobic zone took fewer days (29 days) to obtain a constant effluent nitrate. Moreover, the denitrification yield in ditch was elevated from an initial value of 0.082 mgTN/mgCOD to 0.123 mgTN/mgCOD, and the nitrogen removal efficiency reached up to a level of 68%. The focus on denitrification potential with external methanol is valuable to provide information for developing carbon dosage control, as well as predict the nitrate effluent quality of the plant.

Vitellogenin from planthopper oral secretion acts as a novel effector to impair plant defenses.

Vitellogenin (Vg) is a well-known nutritious protein involved in reproduction in nearly all oviparous animals, including insects. Recently, Vg has been detected in saliva proteomes of several piercing-sucking herbivorous arthropods, including the small brown planthopper (Laodelphax striatellus, SBPH). Its function, however, remains unexplored. We investigated the molecular mechanism underlying SBPH orally secreted Vg-mediated manipulation of plant-insect interaction by RNA interference, phytohormone and H2 O2 profiling, protein-protein interaction studies and herbivore bioassays. A C-terminal polypeptide of Vg (VgC) in SBPH, when secreted into rice plants, acted as a novel effector to attenuate host rice defenses, which in turn improved insect feeding performance. Silencing Vg reduced insect feeding and survival on rice. Vg-silenced SBPH nymphs consistently elicited higher H2 O2 production, a well-established defense mechanism in rice, whereas expression of VgC in planta significantly hindered hydrogen peroxide (H2 O2 ) accumulation and promoted insect performance. VgC interacted directly with the rice transcription factor OsWRKY71, a protein which is involved in induction of H2 O2 accumulation and plant resistance to SBPH. These findings indicate a novel effector function of Vg: when secreted into host rice plants, this protein effectively weakened H2 O2 -mediated plant defense through its association with a plant immunity regulator.

Expression, purification and functional identification of the modified hEGF protein.

Human epidermal growth factor (hEGF) plays an important role in the growth and division of epithelial cells and has good application prospects in skin-related injuries and diseases. Weak skin penetration and rapid clearance of hEGF in skin via the mononuclear phagocyte system have restricted the application of hEGF. To overcome these shortcomings, the recombinant gene TAT-hEGF-CD47 was constructed in our experiments, and the fusion protein TAT-hEGF-CD47 was expressed, purified and renatured. The cell proliferation-promoting function, skin penetration and concentration of TAT-hEGF-CD47 in skin after its application were determined. The results showed that TAT-hEGF-CD47 effectively promoted human skin fibroblast and skin epithelial cell proliferation, and the proliferation-promoting effect was positively correlated with the TAT-hEGF-CD47 concentration. After administration to the skin, TAT-hEGF-CD47 effectively penetrated the epidermal layer of the skin because of the TAT domain and stayed in the skin for a long time because the CD47 fragment slowed its clearance via the mononuclear phagocytic system. In conclusion, TAT-hEGF-CD47 exhibits high cell proliferation-promoting activity, high skin penetration efficiency and long retention time in skin and has laid the foundation for its wide application in skin repair, ulcer, diabetes and even cancer treatments.

[3 + 2 + 1] Pyridine Skeleton Synthesis Using Acetonitrile as C4N1 Units and Solvent.

The first [3 + 2 + 1] methodology for pyridine skeleton synthesis via cascade carbopalladation/cyclization of acetonitrile, arylboronic acids, and aldehydes was developed. This reaction proceeds via six step tandem reaction sequences involving the carbopalladation reaction of acetonitrile, a nucleophilic addition, a condensation, an intramolecular Michael addition, cyclization, and aromatization. Delightfully, both palladium acetate and supported palladium nanoparticles catalyzed this reaction with similar catalytic performance. The characterization results of the fresh and used supported palladium nanoparticle catalysts indicated that the reaction might be performed via a Pd(0)/Pd(II) catalytic cycle that began with Pd(0). Furthermore, the products showed good fluorescence characteristics. The green homogeneous/heterogenous catalytic methodologies pave a new way for constructing the pyridine skeleton.

Win by Quantity: a Striking Rickettsia-Bias Symbiont Community Revealed by Seasonal Tracking in the Whitefly Bemisia tabaci.

Maintaining an adaptive seasonality is a basic ecological requisite for cold-blooded organism insects which usually harbor various symbionts. However, how coexisting symbionts coordinate in insects during seasonal progress is still unknown. The whitefly Bemisia tabaci in China harbors the obligate symbiont Portiera that infects each individual, as well as various facultative symbionts. In this study, we investigated whitefly populations in cucumber and cotton fields from May to December 2019, aiming to reveal the fluctuations of symbiont infection frequencies, symbiont coordination in multiple infected individuals, and host plants effects on symbiont infections. The results indicated that the facultative symbionts Hamiltonella (H), Rickettsia (R), and Cardinium (C) exist in field whiteflies, with single (H) and double (HC and HR) infections occurring frequently. Infection frequencies of Hamiltonella (always 100%) and Cardinium (29.50-34.38%) remained steady during seasonal progression. Rickettsia infection frequency in the cucumber whitefly population decreased from 64.47% in summer to 35.29% in winter. Significantly lower Rickettsia infection frequency (15.55%) was identified in cotton whitefly populations and was not subject to seasonal fluctuation. Nevertheless, Rickettsia had a significantly quantitative advantage in the symbiont community of whitefly individuals and populations from both cucumber and cotton field all through the seasons. Moreover, higher Portiera and Hamiltonella densities were found in HC and HR whitefly than in H whitefly, suggesting these symbionts may contribute to producing nutrients for their symbiont partners. These results provide ample cues to further explore the interactions between coexisting symbionts, the coevolutionary relationship between symbionts and host symbiont-induced effects on host plant use.

HMGB1 protein promotes glomerular mesangial matrix deposition via TLR2 in lupus nephritis.

Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus. Patients with LN mostly die of sclerosing glomerulonephritis and renal failure. The inhibition of glomerular mesangial matrix deposition is an efficient method to restrict the progress of renal injury. By recognizing and binding extracellular and intracellular ligands, Toll-like receptor 2 (TLR2) contributes to the pathogenesis of most immune diseases. However, the relationship between TLR2 and LN is still unknown. Our previous studies confirmed that high-mobility group box 1 (HMGB1), an important ligand of TLR2, promotes the progression of LN by inducing the proliferation of glomerular mesangial cells. However, whether or not HMGB1 participates in the pathogenesis of glomerular mesangial matrix deposition in LN remains unknown. In this study, we observed the upregulated expression of TLR2 in the glomeruli of LN patients and MRL/lpr mice. The inhibition of either TLR2 or HMGB1 inhibited the release of fibronectin and the activation of the MyD88/NF-κB pathway in mesangial cells cultured with LN plasma. In addition, both TLR2- and HMGB1-deficient mice showed reduced 24 hr urine protein levels and improved glomerular histological changes and sclerosis levels. These results indicate that TLR2 regulates glomerular mesangial matrix deposition in LN through the activation of the MyD88/NF-κB pathway by binding to HMGB1.

Background-dependent Wolbachia-mediated insecticide resistance in Laodelphax striatellus.

Although facultative endosymbionts are now known to protect insect hosts against pathogens and parasitoids, the effects of endosymbionts on insecticide resistance are still unclear. Here we show that Wolbachia are associated with increased resistance to the commonly used insecticide, buprofezin, in the small brown planthopper (Laodelphax striatellus) in some genetic backgrounds while having no effect in other backgrounds. In three Wolbachia-infected lines from experimental buprofezin-resistant strains and one line from a buprofezin-susceptible line established from Chuxiong, Yunnan province, China, susceptibility to buprofezin increased after removal of Wolbachia. An increase in susceptibility was also evident in a Wolbachia-infected line established from a field population in Rugao, Jiangsu province. However, no increase was evident in two field populations from Nanjing and Fengxian, Jiangsu province, China. When Wolbachia was introgressed into different genetic backgrounds, followed by Wolbachia removal, the data pointed to Wolbachia effects that depend on the nuclear background as well as on the Wolbachia strain. However, there was no relationship between Wolbachia density and the component of buprofezin resistance associated with the symbiont. The results suggest that Wolbachia effects associated with chemical resistance are complex and unpredictable, but also that they can be substantial.

Ultra-broadband metamaterial absorber from ultraviolet to long-wave infrared based on CMOS-compatible materials.

Broadband absorption of electromagnetic waves in different wavelength regions is desired for applications ranging from highly efficient solar cells, waste heat harvesting, multi-color infrared (IR) detection to sub-ambient radiative cooling. Taper-shaped structures made up of alternating metal/dielectric multilayers offer the broadest absorption bandwidth so far, but face a trade-off between optical performance and material choice, i.e., those with the broadest bandwidth utilize exclusively CMOS-incompatible materials, hampering their large-scale applications. In this work, through careful examination of the unique material property of aluminum (Al) and zinc sulfide (ZnS), a sawtooth-like and a pyramid-like multilayer absorber is proposed, whose working bandwidth (0.2-15 µm) covers from ultraviolet (UV) all the way to long-wave infrared (LWIR) range, being compatible with CMOS technology at the same time. The working principle of broadband absorption is elucidated with effective hyperbolic metamaterial model plus the excitation of multiple slow-light modes. Absorption performance such as polarization and incidence-angle dependence are also investigated. The proposed Al-ZnS multilayer absorbers with ultra-broadband near-perfect absorption may find potential applications in infrared imaging and spectroscopy, radiative cooling, solar energy conversion, etc.

A novel potent metal-binding NDM-1 inhibitor was identified by fragment virtual, SPR and NMR screening.

NDM-1 can hydrolyze nearly all available ß-lactam antibiotics, including carbapenems. NDM-1 producing bacterial strains are worldwide threats. It is still very challenging to find a potent NDM-1 inhibitor for clinical use. In our study, we used a metal-binding pharmacophore (MBP) enriched virtual fragment library to screen NDM-1 hits. SPR screening helped to verify the MBP virtual hits and identified a new NDM-1 binder and weak inhibitor A1. A solution NMR study of 15N-labeled NDM-1 showed that A1 disturbed all three residues coordinating the second zinc ion (Zn2) in the active pocket of NDM-1. The perturbation only happened in the presence of zinc ion, indicating that A1 bound to Zn2. Based on the scaffold of A1, we designed and synthesized a series of NDM-1 inhibitors. Several compounds showed synergistic antibacterial activity with meropenem against NDM-1 producing K. pneumoniae.

Implementation of a Multiplex and Quantitative Proteomics Platform for Assessing Protein Lysates Using DNA-Barcoded Antibodies.

Molecular analysis of tumors forms the basis for personalized cancer medicine and increasingly guides patient selection for targeted therapy. Future opportunities for personalized medicine are highlighted by the measurement of protein expression levels via immunohistochemistry, protein arrays, and other approaches; however, sample type, sample quantity, batch effects, and "time to result" are limiting factors for clinical application. Here, we present a development pipeline for a novel multiplexed DNA-labeled antibody platform which digitally quantifies protein expression from lysate samples. We implemented a rigorous validation process for each antibody and show that the platform is amenable to multiple protocols covering nitrocellulose and plate-based methods. Results are highly reproducible across technical and biological replicates, and there are no observed "batch effects" which are common for most multiplex molecular assays. Tests from basal and perturbed cancer cell lines indicate that this platform is comparable to orthogonal proteomic assays such as Reverse-Phase Protein Array, and applicable to measuring the pharmacodynamic effects of clinically-relevant cancer therapeutics. Furthermore, we demonstrate the potential clinical utility of the platform with protein profiling from breast cancer patient samples to identify molecular subtypes. Together, these findings highlight the potential of this platform for enhancing our understanding of cancer biology in a clinical translation setting.

Singleton molecular species delimitation based on COI-5P barcode sequences revealed high cryptic/undescribed diversity for Chinese katydids (Orthoptera: Tettigoniidae).

BACKGROUND: DNA barcoding has been developed as a useful tool for species discrimination. Several sequence-based species delimitation methods, such as Barcode Index Number (BIN), REfined Single Linkage (RESL), Automatic Barcode Gap Discovery (ABGD), a Java program uses an explicit, determinate algorithm to define Molecular Operational Taxonomic Unit (jMOTU), Generalized Mixed Yule Coalescent (GMYC), and Bayesian implementation of the Poisson Tree Processes model (bPTP), were used. Our aim was to estimate Chinese katydid biodiversity using standard DNA barcode cytochrome c oxidase subunit I (COI-5P) sequences. RESULTS: Detection of a barcoding gap by similarity-based analyses and clustering-base analyses indicated that 131 identified morphological species (morphospecies) were assigned to 196 BINs and were divided into four categories: (i) MATCH (83/131 = 64.89%), morphospecies were a perfect match between morphospecies and BINs (including 61 concordant BINs and 22 singleton BINs); (ii) MERGE (14/131 = 10.69%), morphospecies shared its unique BIN with other species; (iii) SPLIT (33/131 = 25.19%, when 22 singleton species were excluded, it rose to 33/109 = 30.28%), morphospecies were placed in more than one BIN; (iv) MIXTURE (4/131 = 5.34%), morphospecies showed a more complex partition involving both a merge and a split. Neighbor-joining (NJ) analyses showed that nearly all BINs and most morphospecies formed monophyletic cluster with little variation. The molecular operational taxonomic units (MOTUs) were defined considering only the more inclusive clades found by at least four of seven species delimitation methods. Our results robustly supported 61 of 109 (55.96%) morphospecies represented by more than one specimen, 159 of 213 (74.65%) concordant BINs, and 3 of 8 (37.5%) discordant BINs. CONCLUSIONS: Molecular species delimitation analyses generated a larger number of MOTUs compared with morphospecies. If these MOTU splits are proven to be true, Chinese katydids probably contain a seemingly large proportion of cryptic/undescribed taxa. Future amplification of additional molecular markers, particularly from the nuclear DNA, may be especially useful for specimens that were identified here as problematic taxa.

Rapid and visual detection of Lawsonia intracellularis with an improved recombinase polymerase amplification assay combined with a lateral flow dipstick.

BACKGROUND: Lawsonia intracellularis (L. intracellularis) is the etiologic agent of porcine proliferative enteropathy (PPE), which is reported in many swine breeding countries all over the world, and has caused enormous economic losses in intensive pig production systems. Therefore, the aim of this study was to develop a simple and rapid method for on-site detection of Lawsonia intracellularis (L. intracellularis). As the isothermal recombinase polymerase amplification (RPA) can be performed at a constant temperature and its product is directly observed on a lateral-flow dipstick (LFD) with naked eyes without electrophoresis, the RPA-LFD assay should be useful for field diagnosis of L. intracellularis as well as its detection from clinical samples. RESULTS: The established RPA-LFD assay could be finished in 30 min at a wide temperature range of 25 to 40 °C, and the amplicons could be visualized by naked eyes. The developed RPA-LFD assay was specific to dnaA gene of L. intracellularis, and did not detect nucleic acids extracted from other common gastrointestinal pathogens. The minimum detection of this RPA-LFD method was 400 L. intracellularis per reaction, which was as sensitive as conventional PCR. Further, the RPA-LFD assay was performed with 150 clinical fecal samples and the detection results were compared with conventional PCR. Results showed that the coincidence rate of RPA-LFD and conventional PCR was 100%. CONCLUSIONS: The combined RPA with LFD assay provides a simple, rapid, specific and sensitive alternative for field diagnosis of L. intracellularis infection.

Population Dynamics of Wolbachia in Laodelphax striatellus (Fallén) Under Successive Stress of Antibiotics.

Wolbachia are the most common symbionts in arthropods; antibiotic treatment for eliminating the symbionts from their host is necessary to investigate the functions. Tetracycline antibiotics are widely used to remove endosymbiont Wolbachia from insect hosts. However, very little has been known on the effects of tetracycline on population size of Wolbachia in small brown planthopper (SBPH), Laodelphax striatellus (Fallén), an important insect pest of rice in Asia. Here, we investigated the dynamics of Wolbachia population density in females and males of L. striatellus by real-time fluorescent quantitative PCR method. The Wolbachia density in females and males of L. striatellus all declined sharply after treatment with 2 mg/mL tetracycline for one generation, and continued to decrease to a level which could not be detected by both qPCR and diagnostic PCR after treated for another generation, then maintained at 0 in the following three generations with continuous antibiotic treatment. Wolbachia infection did not recover in L. striatellus after stopping tetracycline treatment for ten generations. This is the first report to precisely monitor the population dynamics of Wolbachia in L. striatellus during successive tetracycline treatment and after that. The results provide a useful method for evaluating the efficiency of artificial operation of endosymbionts.

Upregulated microRNA-485 suppresses apoptosis of renal tubular epithelial cells in mice with lupus nephritis via regulating the TGF-ß-MAPK signaling pathway by inhibiting RhoA expression.

Lupus nephritis (LN) is a common and severe complication of systemic lupus erythematosus. Without intervention, LN may cause acute kidney injury and end-stage renal disease. This study aims to determine whether microRNA-485 (miR-485) affects renal tubular epithelial cells (RTECs) in LN mice via the TGF-ß-MAPK signaling pathway by targeting RhoA. Renal tissue samples were initially extracted from 15 LN and 15 normal mice. RTECs were cultivated in vitro and grouped after transfection of different mimics, inhibitors, or siRNA- RhoA. The target gene of miR-485 was confirmed by dual-luciferase reporter assay. Flow cytometry and MTT assay were applied to detect cell viability and apoptosis. It was determined that RhoA was a target gene of miR-485. We found that urine protein, creatinine, RhoA, interleukin 6 (IL-6), transforming growth factor-ß1 (TGF-ß1), and p38 mitogen-activated protein kinases (p38MAPK) were highly expressed in renal tissues of LN mice, while poor levels of miR-485 were recorded. The overexpression of miR-485 or siRNA- RhoA or the combination of miR-485 and siRNA- RhoA was demonstrated to lead to a reduction of levels of RhoA, IL-6, TGF-ß, and p38MAPK, as well as a promotion of RTECs proliferation and inhibition of RTECs apoptosis. Taken together, these findings indicated that overexpressed miR-485 downregulates RhoA which could promote cell viability and inhibit apoptosis of RTECs by regulating the RhoA-mediated TGF-ß-MAPK signaling pathway in LN mice.

AKT isoform-specific expression and activation across cancer lineages.

BACKGROUND: Aberrant AKT activation is prevalent across human cancer lineages, providing an important therapeutic target. AKT comprises three isoforms that mediate critical non-redundant, even opposing functions in cancer pathophysiology. Therefore, targeting specific AKT isoforms in particular cancers may be more effective than pan-AKT inhibition while avoiding disadvantages of pan-AKT inhibition. Currently, AKT isoform-specific expression and activation in cancer are not clearly characterized. METHODS: We systematically characterized AKT isoform-specific expression and activation in 211 cancer cell lines derived from different lineages and genetic backgrounds using a reverse-phase protein array platform. RESULTS: We found that phosphorylation, but not expression, of AKT1 and AKT2 was coordinated in most but not all cells. Different cancer lineages displayed differential AKT1 and AKT2 expression and phosphorylation. A PIK3CA hotspot mutation H1047R but not E545K was associated with selective activation of AKT2 but not AKT1. CONCLUSIONS: Our study identified and validated AKT isoform-specific expression and phosphorylation in certain cell lines and demonstrated that genetic changes can affect AKT isoform-specific activation. These results provide a more precise understanding of AKT isoform-specific signaling and, in addition, facilitate AKT isoform targeting for personalized cancer therapies.