Clinicopathological characteristics and typing of multilocular cystic renal neoplasm of low malignant potential.

BACKGROUND: Up until now, no research has been reported on the association between the clinical growth rate of multilocular cystic renal neoplasm of low malignant potential (MCRNLMP) and computed tomography (CT) imaging characteristics. Our study sought to examine the correlation between them, with the objective of distinguishing unique features of MCRNLMP from renal cysts and exploring effective management strategies. AIM: To investigate optimal management strategies of MCRNLMP. METHODS: We retrospectively collected and analyzed data from 1520 patients, comprising 1444 with renal cysts and 76 with MCRNLMP, who underwent renal cyst decompression, radical nephrectomy, or nephron-sparing surgery for renal cystic disease between January 2013 and December 2021 at our institution. Detection of MCRNLMP utilized the Bosniak classification for imaging and the 2016 World Health Organization criteria for clinical pathology. RESULTS: Our meticulous exploration has revealed compelling findings on the occurrence of MCRNLMP. Precisely, it comprises 1.48% of all cases involving simple renal cysts, 5.26% of those with complex renal cysts, and a noteworthy 12.11% of renal tumors coexisting with renal cysts, indicating a statistically significant difference (P = 0.001). Moreover, MCRNLMP constituted a significant 22.37% of the patient population whose cysts demonstrated a rapid growth rate of ≥ 2.0 cm/year, whereas it only represented 0.66% among those with a growth rate below 2.0 cm/year. Of the 76 MCRNLMP cases studied, none of the nine patients who underwent subsequent nephron-sparing surgery or radical nephrectomy following renal cyst decompression experienced recurrence or metastasis. In the remaining 67 patients, who were actively monitored over a 3-year postoperative period, only one showed suspicious recurrence on CT scans. CONCLUSION: MCRNLMP can be tentatively identified and categorized into three types based on CT scanning and growth rate indicators. In treating MCRNLMP, partial nephrectomy is preferred, while radical nephrectomy should be minimized. After surgery, active monitoring is advisable to prevent unnecessary nephrectomy.

Time alignment quantum illumination based on single real-time coincidence counting.

We propose and demonstrate an improved quantum illumination protocol based on the time correlation of twin photons, for the high signal-to-noise ratio (SNR) of target detection and signal reconstruction in the strong noise environment. The Hong-Ou-Mandel (HOM) interferometer is applied after the spontaneous parametric down-conversion (SPDC) process to construct a probing twin-beam in which the photon times are precisely aligned between the beams. At the radar receiver, we put forward a single real-time coincidence counting (SRCC) method on a series of time slices to reconstruct the probe signals of pulse radar and calculate the SNR advantages against the conventional pulse radar, as well as the quantum illumination (QI) protocol. Our main achievements in this research are the realization of real-time detection of quantum information while acquiring a higher SNR than QI and classical illumination (CI) protocols, as well as its demonstration of strong robustness to noise and losses, which also proposes what we believe to be a novel way for quantum target detection.

Evaluating the ecological vulnerability of Chongqing using deep learning.

This study used deep learning to evaluate the ecological vulnerability of Chongqing, China, discuss the deep learning evaluations of ecological vulnerability, and generate vulnerability maps that support local ecological environment protection and governance decisions and provide reference for future studies. The information gain ratio was used to screen the influencing factors, selecting 16 factors that influence ecological vulnerability. Deep neural network (DNN) and convolutional neural network (CNN) methods were used for modeling, and two ecological vulnerability maps of the study area were generated. The results showed that the mean absolute error and root mean square error of the DNN and CNN models were relatively small, and the fitting accuracy was high. The area under the receiver operating characteristic curve of the CNN model was 0.926, which was better than that of the DNN model (0.888). Random forest was applied to calculate the importance of the influencing factors in the two models. Because the main factor was geological features, the relative ecological vulnerability was mainly affected by karst topography. Through the analysis of the ecological vulnerability map, the areas with higher vulnerability are the karst mountains of Dabashan, Wushan, and Qiyaoshan in the northeast and southeast, as well as the valley between mountains and cities in the center and west of the study area. According to the investigation of these areas, the primary ecological problems are low forest quality, structural irregularities caused by self-geological factors, severe desertification, and soil erosion. Human activity is also an important factor that causes ecological vulnerability in the study area. In conclusion, deep learning, particularly CNN models, can be used for ecological vulnerability assessments. The ecological vulnerability maps conformed to the basic cognition of field surveys and can provide references for other deep learning vulnerability studies. While the overall vulnerability of the study area is not high, ecological problems that lead to its vulnerability should be addressed by future ecological protection and management measures.

Design of potent B-RafV600E inhibitors by multiple copy simulation search strategy.

B-Raf kinase is a vital intermedium in the mitogen-activated protein kinase (MAPK) signaling pathway, which transforms extracellular signals into cellular mechanisms. Mutations in this kinase, for instance, the most common V600E mutation, can lead to the ERK signaling pathologically activated and hence cause severe diseases such as somatic tumors. So far, the development of B-Raf inhibitors has made remarkable progress. However, the resistance and relapse of approved Raf drugs have been widely reported, and the optimization for old drugs and the discovery for new inhibitors still remain a significant task. In this study, we designed and evaluated a series of novel B-RafV600E inhibitors. A fragment library has been established before the docking simulation carried out using the MCSS strategy (multicopy simulation search). The appropriate fragments were reassembled to provide new candidate compounds, which were further screened by iterative docking simulations and molecular dynamics. Bioassays were carried out to evaluate the pharmacological profile of the compounds identified and synthesized. The result showed that compound 5n had an impressive enzyme inhibitory and antiproliferation activity, suggesting a promising potential in the future study.

[Short-term responses of foliar multi-element stoichiometry and nutrient resorption of slash pine to N addition in subtropical China]. / äºšçƒ­å¸¦æ¹¿åœ°æ¾å¶ç‰‡å¤šå ƒç´ åŒ–å­¦è®¡é‡ä¸Žå »åˆ†å›žæ”¶å¯¹æ°®æ·»åŠ çš„çŸ­æœŸå“åº”.

We conducted a field experiment with three levels of N addition (0, 40 and 120 kg N·hm-2·a-1) in a Pinus elliottii plantation in subtropical China and collected green and senesced needles of P. elliottii at the peak (July) and the end (October) of each growing season in 2014 and 2015 for clarifying effects of nitrogen additions on concentrations of nine elements (C, N, P, K, Ca, Mg, Al, Fe and Mn) in the green and senesced needles and their corresponding resorption efficiency and resorption proficiency. Our results showed that N addition had positive effects on concentrations of N, Al and Mn, negative effects on the P concentration and the Ca concentration in 2014, and neutral effects on concentrations of C, K, Mg and Fe in green needles. N addition signifi-cantly increased foliar N/P. These stoichiometric responses were N level-dependent (stronger at high N rate). N addition significantly decreased N resorption efficiency in 2015 and increased that of K in 2014. Compared with the resorption efficiency, resorption proficiency responded more strongly to increased available N. N addition significantly decreased resorption proficiency of N, and increased that of P, K, and the concentration of Fe in senesced needles, however, there were no significant effects on the concentrations of Ca, Mg, Al and Mn in senesced needles. We concluded that responses of foliar stoichiometry to N addition were element-specific, and plants might cope with changing environments via adjusting internal nutrient cycle (resorption). The elevated foliar N/P and K/P suggested a shift from N and P co-limitation to P limitation with N additions, and increased concentrations of Al and Mn might imply potential toxicity of metal ions to P. elliottii.

[Effects of nitrogen addition on available nitrogen content and acidification in cold-temperate coniferous forest soil in the growing season].

Based on a low-level and multi-form N addition control experiment, this study took cold-temperate coniferous forest in Daxing'an Ling as the research object. After long-term and continuous nitrogen addition in situ, the available nitrogen (NH4(+) -N & NO3(-) -N) contents and pH values of the soil (0-10 cm) were measured in the early growing season (May) and the peak growing season (August) in 2010, 2012 and 2013. The results showed that, the available nitrogen in the early and peak growing seasons was mainly NH4(+) -N which accounted for over 96% of the inorganic nitrogen content, while the content of NO3(-) -N was very low. With the time extension of nitrogen addition, the effects of nitrogen addition on the NH4(+) -N content in 0-10 cm soil were more obvious in the early growing season than that in the peak growing season, and the NH4(+) -N content was mainly affected by the type of nitrogen addition. On the contrary, the NO3(-) -N content in 0-10 cm soil was higher in the peak growing season than that in the early growing season. The effect of N input was obvious on NO3(-) -N content in both early and peak growing seasons, and low nitrogen treatment tended to promote the enrichment of NO3(-) -N. As time went on, the response of NH4(+) -N and NO3(-) -N content to N addition was changed from insignificant in the early stage to significant in the late stage. N addition had a significant impact on the pH value of the 0-10 cm soil in the early and peak growing seasons. The pH values of the soil with low nitrogen treatment and the soil in the peak growing season were relatively lower. With the extension of the nitrogen addition time, the response of pH value also turned from insignificant in the early stage to significant in the late stage. Because of the long-term and continuous nitrogen addition, the 0 - 10 cm soil in this cold-temperate coniferous forest was obviously acidified.

The imprinted H19 gene regulates human placental trophoblast cell proliferation via encoding miR-675 that targets Nodal Modulator 1 (NOMO1).

Preeclampsia is a pregnancy-specific syndrome mainly characterized by hypertensive disorder and proteinuria after gestational weeks 20. So far the etiology of preeclampsia remains unclear. We previously reported that preeclamptic placentas exhibited decreased mRNA expression and hypermethylation in promoter region of the paternally imprinted H19 gene compared with normal placentas. H19 has recently been identified to encode the precursor of miR-675, indicating a possible novel functional pathway of the imprinting gene. The aim of the present study was to identify the roles of H19 gene via miR-675 pathway in human trophoblast cells, and to figure out the involvement of this pathway in pathogenesis of preeclampsia. Knockdown of H19 gene or inhibition of miR-675 exhibited similar proliferation-promoting effect in human trophoblastic JEG-3 cells. Target gene prediction in combination with luciferase assay revealed that miR-675 could directly downregulate Nodal Modulator 1 (NOMO1) protein expression by binding to 3'-UTR sequence of NOMO1. Overexpression of NOMO1 in JEG-3 cells could rescue miR-675-surppressed cell proliferation and phosphorylation of Smad2, while Nodal had additive effect with miR-675 in suppression cell proliferation and activation of Smad2. In early-onset preeclamptic placentas, expression levels of H19 gene and miR-675 were appreciably lower, while NOMO1 protein level was higher than those in normal placentas. Taken together, our data suggested that H19 gene could inhibit human trophoblast cell proliferation via encoding miR-675 that targeted NOMO1, and aberrantly lowered expression of H19 in placenta may participate in the excessive proliferation of trophoblast cells observed in early-onset severe preeclampsia by downregulating miR-675 which targets NOMO1 and interferes with Nodal signaling.

Detection of global DNA methylation and paternally imprinted H19 gene methylation in preeclamptic placentas.

Preeclampsia (PE) is a severe hypertensive disorder associated with pregnancy; despite substantial research effort in the past several years, the etiology of PE is still unclear. The role of epigenetic factors in the etiology of PE, including DNA methylation, has been poorly characterized. In the present study, we investigated global DNA methylation as well as DNA methylation of the paternally imprinted H19 gene in preeclamptic placentas. Using 5-methylcytosine immunohistochemistry and Alu and LINE-1 repeat pyrosequencing, we found that the global DNA methylation level and the DNA (cytosine-5) methyltransferase 1 mRNA level were significantly higher in the early-onset preeclamptic placentas when compared with the normal controls. Data from methylation-sensitive high resolution melting demonstrated hypermethylation of the promoter region of the H19 gene, and results of real-time PCR showed decreased mRNA expression of H19 gene in the early-onset preeclamptic placentas as compared with the normal controls. Our results suggest that abnormal DNA methylation during placentation might be involved in the pathophysiology of PE, especially early-onset preeclampsia.

Prostasin regulates human placental trophoblast cell proliferation via the epidermal growth factor receptor signaling pathway.

BACKGROUND: Prostasin is a glycosylphosphatidylinositol-anchored extracellular serine protease with a role in epidermal growth factor receptor (EGFR) signal modulation. EGFR signaling has been shown to be important for regulating cytotrophoblast (CT) cell proliferation in human placenta. We investigated the impact of prostasin expression regulation on this cellular function as well as the molecular mechanisms involved in human cytotrophoblastic cells. METHODS: An immortalized normal human CT cell line (B6Tert-1) was used as an in vitro cell model. Prostasin expression in B6Tert-1 cells was knocked down by transfection of a short interfering RNA. Lentivirus-mediated expression of recombinant human prostasin under tetracycline regulation was performed to obtain stable B6Tert-1 cell sublines that over-expressed prostasin. Changes in cell proliferation and EGFR signaling were evaluated by immunocytochemistry for Ki67 and western blot analysis, respectively, in B6Tert-1 cells with knocked-down or increased prostasin expression. RESULTS: Prostasin knock-down in B6Tert-1 cells resulted in inhibition of cell proliferation, in association with down-regulated EGFR protein expression (both P < 0.05 versus control) as well as reduced phosphorylation of c-raf, mitogen-activated protein kinase (MAPK) kinases (MEK1/2) and extracellular signal-regulated kinases (Erk1/2) (all P < 0.05 versus control). Over-expression of prostasin led to up-regulation of the EGFR protein, but had no effect on cell proliferation or phosphorylation of MAPK signaling molecules in the B6Tert-1 cells. CONCLUSIONS: Prostasin may regulate trophoblast cell proliferation via modulating the EGFR-MAPK signaling pathway.

[DOT1: a distinct class of histone lysine methyltransferase].

Lysine methylation is an important covalent modification of histone and has fundamental and divers roles in biological processes including regulation of chromatin structure dynamics and gene expression. Recently, a distinct class of histone lysine methyltransferase DOT1 was found to methylate histone H3 lysine79 (H3K79) residue, which is located on the accessible face of the core nucleosome. The DOT1 proteins do not contain a SET domain, a conserved sequence motif found in all previously characterized histone H3 lysine methyltransferases that act on the histone N-termianl tail. The characteristics of DOT1 proteins and H3K79 methylation suggest that they may have important and characteristic functions. Here, we summarize recent advances in specific structure of DOT1 protein, biological functions of DOT1 proteins and H3K79 methylation and trans-histone regulatory1 between histone H2B ubiquitination and H3K79 methylation.