The detection of renal cell carcinoma (RCC) has been rising due to the enhanced utilization of cross-sectional imaging and incidentally discovered lesions with adverse pathology demonstrate potential ...for metastasis. The purpose of our study was to determine the clinical and multiparametric dynamic contrast-enhanced magnetic resonance imaging (CEMRI) associated independent predictors of adverse pathology for cT1/2 RCC and develop the predictive model.
We recruited 105 cT1/2 RCC patients between 2018 and 2022, all of whom underwent preoperative CEMRI and had complete clinicopathological data. Adverse pathology was defined as RCC patients with nuclear grade III-IV; pT3a upstage; type II papillary RCC, collecting duct or renal medullary carcinoma, unclassified RCC; sarcomatoid/rhabdoid features. The qualitative and quantitative CEMRI parameters were independently reviewed by two radiologists. Univariate and multivariate binary logistic regression analyses were utilized to determine the independent predictors of adverse pathology for cT1/2 RCC and construct the predictive model. The receiver operating characteristic (ROC) curve, confusion matrix, calibration plot, and decision curve analysis (DCA) were conducted to compare the diagnostic performance of different predictive models. The individual risk scores and linear predicted probabilities were calculated for risk stratification, and the Kaplan-Meier curve and log-rank tests were used for survival analysis.
Overall, 45 patients were pathologically confirmed as RCC with adverse pathology. Clinical characteristics, including gender, and CEMRI parameters, including RENAL score, tumor margin irregularity, necrosis, and tumor apparent diffusion coefficient (ADC) value were identified as independent predictors of adverse pathology for cT1/2 RCC. The clinical-CEMRI predictive model yielded an area under the curve (AUC) of the ROC curve of 0.907, which outperformed the clinical model or CEMRI signature model alone. Good calibration, better clinical usefulness, excellent risk stratification ability of adverse pathology and prognosis were also achieved for the clinical-CEMRI predictive model.
The proposed clinical-CEMRI predictive model offers the potential for preoperative prediction of adverse pathology for cT1/2 RCC. With the ability to forecast adverse pathology, the predictive model could significantly benefit patients and clinicians alike by providing enhanced guidance for treatment planning and decision-making.
During Gram-negative bacterial infections, excessive LPS induces inflammation and sepsis via action on immune cells. However, the bulk of LPS can be cleared from circulation by the liver. Liver ...clearance is thought to be a slow process mediated exclusively by phagocytic resident macrophages, Kupffer cells (KC). However, we discovered that LPS disappears rapidly from the circulation, with a half-life of 2-4 min in mice, and liver eliminates about three quarters of LPS from blood circulation. Using microscopic techniques, we found that ∼75% of fluor-tagged LPS in liver became associated with liver sinusoidal endothelial cells (LSEC) and only ∼25% with KC. Notably, the ratio of LSEC-KC-associated LPS remained unchanged 45 min after infusion, indicating that LSEC independently processes the LPS. Most interestingly, results of kinetic analysis of LPS bioactivity, using modified limulus amebocyte lysate assay, suggest that recombinant factor C, an LPS binding protein, competitively inhibits high-density lipoprotein (HDL)-mediated LPS association with LSEC early in the process. Supporting the previous notion, 3 min postinfusion, 75% of infused fluorescently tagged LPS-HDL complex associates with LSEC, suggesting that HDL facilitates LPS clearance. These results lead us to propose a new paradigm of LSEC and HDL in clearing LPS with a potential to avoid inflammation during sepsis.
A novel sequential catalysis by combining gold catalysis with early transition metal catalysis was developed. Biologically important bicyclo4.n.0 aminals were obtained under very mild conditions.
The existing integrated energy station (IES) planning does not consider the lifecycle of the energy conversion equipment and the growth modes of various loads at the same time, which will inevitably ...affect the economics of the IES planning. This paper proposes a planning and design of regional IESs that takes the load growth mode into account, aiming at the lowest total cost of regional IESs in the planning lifecycle. Based on the operation mode about of the IES coupled with the three-networks involving the natural gas network (NGN), power distribution network (PDN) and transportation network (TN), the selection and capacity configuration of the equipment in the IES are optimized. The solution process of staged planning for IESs is proposed based on load calculation, power distribution and economic checking computations. The optimization calculation is carried out by reasonably dividing the time interval and setting the calculation criteria for the power distribution module. Finally, four MW-level IESs coupled with IEEE 33-node PDN, 20-node NGN and 12-node TN are simulated on the basis of MATLAB. The results show that the equipment investment and operation costs of the regional IESs can be decreased by about 7.1%, and the accumulated waste of various equipment capacity is decreased by nearly 16.51 MW, which verifies the effectiveness of the proposed model and strategy. Furthermore, the results show that it is more practical and economical to consider the equipment lifecycle and load growth mode for the medium and long-term planning of IESs.
Cholesterol from peripheral tissue, carried by HDL, is metabolized in the liver after uptake by the HDL receptor, SR-B1. Hepatocytes have long been considered the only liver cells expressing SR-B1; ...however, in this study we describe two disparate immunofluorescence (IF) experiments that suggest otherwise. Using high-resolution confocal microscopy employing ultrathin (120 nm) sections of mouse liver, improving z-axis resolution, we identified the liver sinusoidal endothelial cells (LSEC), marked by FcγRIIb, as the cell within the liver expressing abundant SR-B1. In contrast, the hepatocyte, identified with β-catenin, expressed considerably weaker levels, although optical resolution of SR-B1 was inadequate. Thus, we moved to a different IF strategy, first separating dissociated liver cells by gradient centrifugation into two portions, hepatocytes (parenchymal cells) and LSEC (non-parenchymal cells). Characterizing both portions for the cellular expression of SR-B1 by flow cytometry, we found that LSEC expressed considerable amounts of SR-B1 while in hepatocytes SR-B1 expression was barely perceptible. Assessing mRNA of SR-B1 by real time PCR we found messenger expression in LSEC to be about 5 times higher than in hepatocytes.
Renal cell carcinoma (RCC) is a frequent urological malignancy characterized by a high rate of metastasis and lethality. The treatment strategy for advanced RCC has moved through multiple iterations ...over the past three decades. Initially, cytokine treatment was the only systemic treatment option for patients with RCC. With the development of medicine, antiangiogenic agents targeting vascular endothelial growth factor and mammalian target of rapamycin and immunotherapy, immune checkpoint inhibitors (ICIs) have emerged and received several achievements in the therapeutics of advanced RCC. However, ICIs have still not brought completely satisfactory results due to drug resistance and undesirable side effects. For the past years, the interests form researchers have been attracted by the combination of ICIs and targeted therapy for advanced RCC and the angiogenesis and immunogenic tumor microenvironmental variations in RCC. Therefore, we emphasize the potential principle and the clinical progress of ICIs combined with targeted treatment of advanced RCC, and summarize the future direction.
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We reported the base-promoted cyclization of N-Boc arylimidrazone toward 1,2-dihydro 3H-1,2,4-triazol-3-one. This procedure tolerated methyl, methoxy, chloro, bromo, fluoro, cyano, ...methylcarbonyl groups well. Thus, it represents a facile and high efficient pathway leading to 1,2-dihydro 3H-1,2,4-triazol-3-one. Mechanism study revealed this procedure proceeded with the intramolecular nucleophilic cyclization rather than N-isocyanate intermediate.
Sertoli cells are vital to maintain spermatogenesis and their function decline during aging. Epimedium has the effects of tonifying kidney-yang, strengthening bones and muscles, and expelling wind ...and dampness, and is commonly used in the treatment of kidney-yang deficiency, impotence and spermatorrhea. Icariin is the main active ingredients from Epimedium exhibiting delaying aging effects and improving male reproductive dysfunction. Whereas, it remains poorly understood how icariin alleviates age-associated decline in testicular function by protecting against the damage of junction function of Sertoli cells.
This study aimed to evaluate the improvement effect of icariin on Sertoli cell junction function damage and explore the underlying mechanisms.
Male C57BL/6 mice and mouse Sertoli cell line TM4 cells were utilized to assess the improvement effect of icariin on aging-associated Sertoli cell junction function injury. H&E staining, transmission electron microscopy, qPCR, Western blot, molecular docking, siRNA transfection, and immunofluorescence were performed in this study.
Dietary administration of icariin remarkly attenuated age-associated deterioration in spermatogenic function as evidenced by elevated testicular weight and index, sperm concentration and sperm viability. In addition, icariin protected Sertoli cell junction function from age-associated damage as proven by increased Sertoli cell numbers, improved tight junction ultrastructure, and upregulated junction-related proteins (ZO-1, Occludin and β-Catenin). Moreover, icariin significantly upregulated ERα/c-fos signaling and PKR pathway in testicular Sertoli cells. Similarly, in vitro studies revealed that deletion of ERα, c-fos or PKR abolished the improvement effects of icariin on Sertoli cell junction function damage.
Icariin effectively mitigates age-associated decline in testicular function by diminished Sertoli cell junction function damage through upregulating PKR pathway via ERα/c-fos signaling. Therefore, attenuating Sertoli cell junction function injury by the upregulation of PKR pathway via ERα/c-fos signaling probably indicates an effective target for the prevention and treatment of testicular spermatogenic function with aging.
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•Icariin alleviates the injury of Sertoli cell junction function with aging.•Icariin attenuates junction function injury by upregulating ERα/c-fos signaling.•Icariin activates PKR pathway via upregulation of ERα/c-fos signaling in Sertoli cells.•Icariin may be a candidate agent for prevention of age-related testicular dysfunction.
A novel tandem metal relay catalytic system was developed by combining gold-catalyzed cycloisomerization with an early transition-metal-catalyzed inverse-electron-demand hetero-Diels-Alder (IED-HDA) ...reaction. Various biologically important spiroaminals and spiroketals were obtained with very high efficiency under mild conditions.
•The Monte Carlo method is used to construct the charging load of EV in the planning area divided into four different vehicles type.•The Prim algorithm is adopted to search for the optimal network ...layout of energy transmission pipelines.•Proposed collaborative planning modeling promotes the time-of-use electricity price scheme to change the temporal and spatial characteristics of EV charging load.•The growth of EV charging load in the planning area has not increased the investment and operation-maintenance costs of DES equipment, and reduced carbon transaction costs as well as improved economic of system operation.•Simulations are conducted to verify the effeteness of proposed method.
Under the dual-carbon goal, the number of electric vehicle (EV) has surged, and the uncertainty of the temporal and spatial characteristics of the load has become prominent, which brings the challenge for higher requirements to the equipment composition of distributed energy station (DES) and performance of station-network. This paper proposes a collaborative planning method for low-carbon DES with networks, which is focusing on the characteristics of EV charging behavior. First of all, based on the quantitative analysis of the temporal and spatial distribution of charging load of four typical types of EV, including private vehicle, public vehicle, taxi and bus, the Monte Carlo method is used to construct the charging load modeling of EV in the region area. In addition, the low-carbon DES is modeled equipped with photovoltaic (PV) and power to gas (P2G) devices, and the Prim algorithm is adopted to search for the optimal network layout of energy transmission pipelines in the region area. Under carbon trading mechanism, aiming at the lowest annualized total cost of the regional station-network, a station-network collaborative planning modeling strategy for the capacity allocation of low-carbon DES with networks is established. Finally, the case study for a project in Beijing China is implemented on MATLAB, to prove the effectiveness of the method proposed in the paper. The time-of-use electricity price scheme changes the temporal and spatial characteristics of EV load. For example, more than 2 MW the EV load can be brought into the valley price range, which reduces the carbon transaction cost and energy purchase cost of DES by 50 thousand yuan almost when peak-valley electricity price difference is close to 1.2 yuan. At the same time, the growth of EV charging load(the penetration rate of EV can reach up to 20%) in the planning area has not increased the investment and operation-maintenance costs of DES equipment.
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