Microelectrochemical Sensor Reveals Tunneling Nanotube-Mediated Intercellular Communication of Endothelial Mechanotransduction.

The intercellular communication of mechanotransduction has a significant impact on various cellular processes. Tunneling nanotubes (TNTs) have been documented to possess the capability of transmitting mechanical stimulation between cells, thereby triggering an influx of Ca2+ ions. However, the related kinetic information on the TNT-mediated intercellular mechanotransduction communication is still poorly explored. Herein, we developed a classic and sensitive Pt-functionalized carbon fiber microelectrochemical sensor (Pt/CF) to study the intercellular communication of endothelial mechanotransduction through TNTs. The experimental findings demonstrate that the transmission of mechanical stimulation from stimulated human umbilical vein endothelial cells (HUVECs) to recipient HUVECs connected by TNTs occurred quickly (<100 ms) and effectively promoted nitric oxide (NO) production in the recipient HUVECs. The kinetic profile of NO release exhibited remarkable similarity in stimulated and recipient HUVECs. But the production of NO in the recipient cell is significantly attenuated (16.3%) compared to that in the stimulated cell, indicating a transfer efficiency of approximately 16.3% for TNTs. This study unveils insights into the TNT-mediated intercellular communication of mechanotransduction.

Template-Assisted Synthesis of 2D Perovskite Grating Single Crystal Films at Low Temperatures for UV Polarization-Sensitive Photodetectors.

2D perovskites have attracted tremendous attention due to their superior optoelectronic properties and potential applications in optoelectronic devices. Especially, the larger bandgap of 2D perovskite means that they are suitable for UV photodetection. However, the layered structure of 2D perovskites hinders the interlayer carrier transport, which limits the improvement of device performance. Therefore, nanoscale structures are normally used to enhance the light absorption ability, which is an effective strategy to improve the photocurrent in 2D perovskite-based photodetectors. Herein, a template-assisted low-temperature method is proposed to fabricate 2D perovskite ((C6H5C2H4NH3)2PbBr4, (PEA)2PbBr4) grating single crystal films (GSCFs). The crystallinity of the (PEA)2PbBr4 GSCFs is significantly improved due to the slow evaporation of the precursor solution under low temperatures. Based on this high crystalline quality and extremely ordered microstructures, the metal-semiconductor-metal photodetectors are assembled. Finite-different time-domain (FDTD) simulation and experiment indicate that the GSCF-based photodetectors exhibit significantly improved performance in comparison with the plane devices. The optimized 2D perovskite photodetectors are sensitive to UV light and demonstrate a responsivity and detectivity of 28.6 mA W-1 and 2.4 × 1011 Jones, respectively. Interestingly, the photocurrent of this photodetector varies as the angle of the incident polarized light, resulting in a high polarization ratio of 1.12.

Examining dynamic developmental trends: the interrelationship between age-friendly environments and healthy aging in the Chinese population-evidence from China Health and Retirement Longitudinal Study, 2011-2018.

BACKGROUND: The objective of this research is to investigate the dynamic developmental trends between Age-Friendly Environments (AFE) and healthy aging in the Chinese population. METHODS: This study focused on a sample of 11,770 participants from the CHARLS and utilized the ATHLOS Healthy Aging Index to assess the level of healthy aging among the Chinese population. Linear mixed model (LMM) was used to explore the relationship between AFE and healthy aging. Furthermore, a cross-lagged panel model (CLPM) and a random-intercept cross-lagged panel model (RI-CLPM) were used to examine the dynamic developmental trends of healthy aging, taking into account both Between-Person effects and Within-Person effects. RESULTS: The results from LMM showed a positive correlation between AFE and healthy aging (ß = 0.087, p < 0.001). There was a positive interaction between the geographic distribution and AFE (central region * AFE: ß = 0.031, p = 0.038; eastern region * AFE: ß = 0.048, p = 0.003). In CLPM and RI-CLPM, the positive effect of healthy aging on AFE is a type of Between-Person effects (ß ranges from 0.147 to 0.159, p < 0.001), while the positive effect of AFE on healthy aging is Within-Person effects (ß ranges from 0.021 to 0.024, p = 0.004). CONCLUSION: Firstly, individuals with high levels of healthy aging are more inclined to actively participate in the development of appropriate AFE compared to those with low levels of healthy aging. Furthermore, by encouraging and guiding individuals to engage in activities that contribute to building appropriate AFE, can elevate their AFE levels beyond the previous average level, thereby improving their future healthy aging levels. Lastly, addressing vulnerable groups by reducing disparities and meeting their health needs effectively is crucial for fostering healthy aging in these populations.

Uptake, subcellular distribution, and fate of tetracycline in two wetland plants supplemented with microbial agents: Effect and mechanism.

The use of wetland plants in the context of phytoremediation is effective in the removal of antibiotics from contaminated water. However, the effectiveness and efficiency of many of these plants in the removal of antibiotics remain undetermined. In this study, the effectiveness of two plants-Phragmites australis and Iris pseudacorus-in the removal of tetracycline (TC) in hydroponic systems was investigated. The uptake of TC at the roots of I. pseudacorus and P. australis occurred at concentrations of 588.78 and 106.70 µg/g, respectively, after 7-day exposure. The higher uptake of TC in the root of I. pseudacorus may be attributed to its higher secretion of root exudates, which facilitate conditions conducive to the reproduction of microorganisms. These rhizosphere-linked microorganisms then drove the TC uptake, which was higher than that in the roots of P. australis. By elucidating the mechanisms underlying these uptake-linked outcomes, we found that the uptake of TC for both plants was significantly suppressed by metabolic and aquaporin inhibition, suggesting uptake and transport of TC were active (energy-dependent) and passive (aquaporin-dominated) processes, respectively. The subcellular distribution patterns of I. pseudacorus and P. australis in the roots were different, as expressed by differences in organelles, cell wall concentration levels, and transport-related dynamics. Additionally, the microbe-driven enhancement of the remediation capacities of the plants was studied comprehensively via a combined microbial-phytoremediation hydroponic system. We confirmed that the microbial agents increased the secretion of root exudates, promoting the variation of TC chemical speciation and thus enhancing the active transport of TC. These results contribute toward the improved application of wetland plants in the context of antibiotic phytoremediation.

Nanoscale and ultra-high extinction ratio optical memristive switch based on plasmonic waveguide with square cavity.

A resistive switch effect-based optical memristive switch with an ultra-high extinction ratio and ultra-compact size working at 1550 nm is proposed. The device is composed of a metal-insulator-metal waveguide and a square resonator with active electrodes. The formation and rupture of conductive filaments in the resonant cavity can alter the resonant wavelength, which triggers the state of the optical switch ON or OFF. The numerical results demonstrate that the structure has an ultra-compact size (less than 1 µm) and ultra-high extinction ratio (37 dB). The proposed device is expected to address the problems of high-power consumption and large-scale optical switches and can be adopted in optical switches, optical modulation, optical storage and computing, and large-scale photonic integrated devices.

Silicon facilitated the physical barrier and adsorption of cadmium of iron plaque by changing the biochemical composition to reduce cadmium absorption of rice roots.

Silicon effectively inhibits cadmium (Cd) uptake in rice, iron plaque on root surface was the primary link and first interface of Cd entering into rice root. To elucidate the mechanism of iron plaque under silicon treatment on root Cd uptake, the morphological characteristics of iron plaque, mechanisms of Cd adsorption of iron plaque and effect of iron plaque on Cd uptake by rice roots of Yuzhenxiang (YZX) and Xiangwanxian (XWX) rice varieties were studied by employing energy spectrum analysis technique, non-invasive micro-test technique, and isothermal-kinetic adsorption method. Scanning electron microscopy-X-ray energy dispersive (SEM-EDX) analysis showed that denser crystal structure of iron plaque was observed at Si treatment, silicon promoted the thickening of iron plaque and strengthened the isolation of iron plaque to Cd, which reduced the Cd content of white roots of YZX and XWX varieties by 30.2% and 20.9% respectively. However, the blocking effect of iron plaque on Cd was weakened under silicon treatment with iron plaque removed, Cd content in iron plaque of YZX and XWX cultivars was significantly decreased by 36.3% and 18.4%, Cd concentrations in white root and shoot was significantly increased, and the influxes of Cd2+ at elongation and maturation zone of root were increased in multiples. The results of adsorption test showed that the adsorption process of iron plaque was mainly a monolayer adsorption completed by boundary diffusion. The X-ray photoelectron spectroscopy (XPS) results demonstrated that silicon changed the biochemical composition of iron plaque and increased the density of the carbon-oxygen bound groups on iron plaque, which is the most likely reasons for the higher affinity of Cd adsorption ability of iron plaque observed in the silicon treated iron plaque. This study suggested the silicon-facilitated iron plaque have played critical effects in controlling the Cd accumulation in rice roots by changing the morphology and chemical composition of iron plaque.

Impacts of wet-dry alternations on cadmium and zinc immobilisation in soil remediated with iron oxides.

Chemical immobilisation is extensively used for in-situ remediation of heavy metals contaminated soil. Immobilised heavy metals could be reactivated by multiple factors such as pH, moisture, temperature, rainfall, etc., among which rainfall is very important, especially acid rain in southern China. Wet-dry alternations were used to simulate the leaching of metals by rainwater. The variation of cadmium (Cd) and zinc (Zn) speciation distribution in soil immobilised with iron oxides (goethite (GE) and 2-line ferrihydrite (GLS)) was investigated. The impacts of wet-dry alternations on the properties of the soil and amendments were also assessed. In the soil without amendments (OS) and amended with GE (GS), the stable fractions were reactivated and transformed into labile fractions under wet-dry alternations. In the soil amended with GLS (LS), the exchangeable and carbonate-bound Cd decreased while the soluble, Fe-Mn oxide bound and organic bound Cd increased. The carbonate-bound Zn was transformed into the Fe-Mn oxide-bound Zn. Transformation from the amorphous iron oxide into crystalline iron oxide in GS and LS were 4.9% and 5.3%. The Pearson correlation analysis showed that the soil pH and the iron-oxide speciation were strongly correlated with Cd/Zn fractions in the soil. The specific surface area, pore volume and adsorption capacity of the iron oxides decreased by 9.26%, 38.89% and 62-73% (for GE), 1.88%, 22.22% and 26-55% (for GLS). The altered soil properties and morphological differences between the two iron oxides under wet-dry alternations were important reasons for Cd/Zn reactivation.

A meta-analysis of the effect of different body mass index on surgical wound infection after colorectal surgery.

We conducted a meta-analysis to assess the effect of different body mass index on surgical wound infection after colorectal surgery. A systematic literature search up to November 2022 was performed and 2349 related studies were evaluated. The chosen studies comprised 15 595 colorectal surgery subjects participated in the selected studies' baseline trials; 4390 of them were obese according to the selected body mass index cut-off used to measure obesity in the selected studies, while 11 205 were nonobese. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated to assess the effect of different body mass index on wound infection after colorectal surgery by the dichotomous methods with a random or fixed effect model. The body mass index ≥30 kg/m2 resulted in significantly higher surgical wound infection after colorectal surgery (OR, 1.76; 95% CI, 1.46-2.11, P < .001) compared with the body mass index <30 kg/m2 . The body mass index ≥25 kg/m2 resulted in significantly higher surgical wound infection after colorectal surgery (OR, 1.64; 95% CI, 1.40-1.92, P < .001) compared with the body mass index <25 kg/m2 . The subjects with higher body mass index had a significantly higher surgical wound infection after colorectal surgery compared with the subjects with normal body mass index.

Perineal wound complications after vertical rectus abdominis myocutaneous flap and mesh closure following abdominoperineal surgery and pelvic exenteration of anal and rectal cancers: A meta-analysis.

A meta-analysis research was implemented to appraise the perineal wound complications (PWCs) after vertical rectus abdominis myocutaneous (VRAM) flap and mesh closure (MC) following abdominoperineal surgery (AS) and pelvic exenteration (PE) of anal and rectal cancers. Inclusive literature research till April 2023 was done and 2008 interconnected researches were revised. Of the 20 picked researches, enclosed 2972 AS and PE of anal and rectal cancers persons were in the utilized researchers' starting point, 1216 of them were utilizing VRAM flap, and 1756 were primary closure (PC). Odds ratio (OR) and 95% confidence intervals (CIs) were utilized to appraise the consequence of VRAM flap in treating AS and PE of anal and rectal cancers by the dichotomous approach and a fixed or random model. VRAM flap had significantly lower PWCs (OR, 0.64; 95% CI, 0.42-0.98, p < 0.001), and major PWCs (OR, 0.50; 95% CI, 0.32-0.80, p = 0.004) compared to PC in AS and PE of anal and rectal cancers persons. However, VRAM flap and PC had no significant difference in minor PWCs (OR, 1; 95% CI, 0.54-1.85, p = 1.00) in AS and PE of anal and rectal cancer persons. VRAM flap had significantly lower PWCs, and major PWCs, however, no significant difference was found in minor PWCs compared to PC in AS and PE of anal and rectal cancers persons. However, caution needs to be taken when interacting with its values since there was a low sample size of most of the chosen research found for the comparisons in the meta-analysis.

Three-dimensional heterogeneous electro-Fenton system with reduced graphene oxide based particle electrode for Acyclovir removal.

New pollutant pharmaceutical and personal care products (PPCPs), especially antiviral drugs, have received increasing attention not only due to their increase in usage after the outbreak of COVID-19 epidemics but also due to their adverse impacts on water ecological environment. Electro-Fenton technology is an effective method to remove PPCPs from water. Novel particle electrodes (MMT/rGO/Fe3O4) were synthesized by depositing Fe3O4 nanoparticles on reduced graphene oxide modified montmorillonite and acted as catalysts to promote oxidation performance in a three-dimensional Electro-Fenton (3D-EF) system. The electrodes combined the catalytic property of Fe3O4, hydrophilicity of montmorillonite and electrical conductivity of graphene oxides, and applied for the degradation of Acyclovir (ACV) with high efficiency and ease of operation. At optimal condition, the degradation rate of ACV reached 100% within 120 min, and the applicable pH range could be 3 to 11 in the 3D-EF system. The stability and reusability of MMT/rGO/Fe3O4 particle electrodes were also studied, the removal rate of ACV remained at 92% after 10 cycles, which was just slightly lower than that of the first cycle. Potential degradation mechanisms were also proposed by methanol quenching tests and FT-ICR-MS.

Immobilization of AgCl/Pd Heterojunctions on Nitrogen-Doped Carbon Nanotubes: Interfacial Design-Induced Electronic Regulation Enhances Photocatalytic Activity.

Rationally designing interface structure to modulate the electronic structure of a photocatalyst is an efficient strategy to facilitate the separation and migration of photogenerated charge carriers and improve photocatalytic activity. In this work, a AgCl/Pd heterostructure encapsulated by N-doped carbon nanotubes (AgCl/Pd@N-C) with a fan-like morphology assembled hollow tubes was synthesized by pyrolysis of a AgCl/Pd@Bim precursor. The unique interface structure not only increases the number of photogenerated charge carriers, but also provides an effective channel for the separation of electrons and holes, which have been proved by density functional theory (DFT) calculations. As expected, the obtained AgCl/Pd-3@N-C exhibited greatly enhanced conversion efficiency and recyclability toward the photocatalytic oxidative coupling of amine under blue-light irradiation.

Porous Pure MXene Fibrous Network for Highly Sensitive Pressure Sensors.

Wearable and elastic pressure sensors have caused widespread concern due to the popularity of smart terminals and human health monitoring. To obtain a flexible pressure sensor with a wide detection region and outstanding sensitivity, exploring new materials and novel structures has become the first choice for the research. Here, a wearable and flexible MXene fibrous network pressure sensor (MFNS) with a high sensitivity and wide detection region is reported. The holistic fiber network is composed of pure MXene fibers; among them, MXene fibers were prepared by wet-spinning of MXene nanosheets. The MFNS exhibits a high sensitivity in a wide detection region (51 kPa-1 for 14.7 kPa and 427 kPa-1 within the 14.7-19.9 kPa range), a low detection limit (8 Pa), a robust durability (10,000 cycles), and a prompt response (95 ms). Due to the superior performance of MFNS, it also proves prospective applications for human motion signal detection (such as swallowing, pulse beat, and joint motion) and measuring pressure distribution. This work provides an effective way to fabricate a high-performance pressure sensor for human-machine interactions, personal healthcare monitoring, and multitouch devices.

Highly Transparent and Flexible Zn-Ti3C2Tx MXene Hybrid Capacitors.

With the development of transparent and wearable electronic devices, energy supply units with high transmittance and flexibility, long cycle life, and high power and energy density are urgently needed. Zinc ion hybrid capacitors (ZIHCs) combined with the advantages of both supercapacitors and zinc ion batteries are promising energy supply components in the abovementioned devices. In addition, the preparation of multifunctional devices has become a trend for the need of space- and resource-saving. Therefore, obtaining ZIHCs with high transmittance and exploring their potential applications are meaningful challenges. Herein, a transparent and flexible ZIHC composed of a patterned zinc foil anode, transparent MXene cathode, and ZnSO4-polyacrylamide (PAM) hydrogel electrolyte is designed and realized. The ZIHC exhibits a superior capacitance of 318 µF cm-2 (5 mV s-1) with 94% transmittance and retains 76% of the initial capacitance after 10,000 charge-discharge cycles. It also shows excellent flexibility, i.e., its capacitance has no obvious attenuation under different bending states. Interestingly, the leakage current of the ZIHC is highly sensitive to electric fields, which shows potential application in electric field detection. This work presents a method to realize the multifunctional ZIHC with electric field sensing function for transparent and flexible wearable devices in the future.

Selective Degradation of Electron-Rich Organic Pollutants Induced by CuO@Biochar: The Key Role of Outer-Sphere Interaction and Singlet Oxygen.

Efficient degradation of organic pollutants by oxidative radicals is challenging in the complex soil environment because of the invalid consumption of radicals by nontarget background substances and the generation of secondary halogenated organic pollutants. Nonradical-based oxidation is a promising pollutant removal method due to its high selectivity and environmental adaptability. Herein, a biochar-supported sheetlike CuO (e-CuO@BC) was developed, which exhibited efficient activation of peroxydisulfate (PDS) via nonradical pathways. The activation mechanisms were identified as (i) formation of surface-bonding active complexes via an outer-sphere interaction between e-CuO@BC and PDS and (ii) the continuous generation of 1O2 by the cycling of the Cu(I)/Cu(II) redox couple. In addition, the activation of PDS primarily occurred at the crystal facet (001) of e-CuO occupied by Cu atoms and was well facilitated by the Cu-O-C bond, which induced electron-rich centers around CuO. Two oxidative species from PDS activation, including surface-bonding active complexes and 1O2, showed a highly selective degradation toward electron-rich pollutants. Moreover, a highly efficient mineralization of organic pollutants and an effective inhibition on the generation of toxic byproducts (i.e., halogenated organics) was indicated by the intermediate and final degradation products. This study provides a comprehensive understanding of the heterogeneous activation process of PS by the e-CuO@BC catalyst for electron-rich organic pollutant removal.

LIMD2 promotes tumor proliferation, invasion, and epithelial-mesenchymal transition in clear cell renal cell carcinoma.

LIMD2 was found upregulated in various tumors and metastatic samples and associated with a poor prognosis. But the role of LIMD2 in clear cell renal cell carcinoma (ccRCC) remains elusive. The expression of LIMD2 in ccRCC was analyzed using cohort data downloaded from TCGA and ICGC databases. In vitro and in vivo experiments were then conducted to study the biological role of LIMD2 in ccRCC and explore the possible mechanism. The results indicated that LIMD2 was overexpressed and correlated with a poor outcome in ccRCC. LIMD2 promoted the malignancy of ccRCC both in vitro and in vivo. LIMD2 induced epithelial-mesenchymal transition (EMT) via activating the ILK/Akt pathway in ccRCC. In conclusion, LIMD2 is overexpressed and promotes proliferation, invasion, and EMT in ccRCC, which may serve as a potential novel therapeutic target for ccRCC.

[Effect of Pien Tze Huang against EV71].

This study aims to investigate the inhibitory effect of Pien Tze Huang(PZH) on enterovirus 71(EV71). To be speci-fic, chemiluminescence method was adopted to evaluate the toxicity of PZH to African green monkey kidney(Vero) cells and human rhabdomyosarcoma(RD) cells, and cytopathic effect(CPE) method to assess the inhibition on EV71-GFP reporter virus and EV71 C4 wild-type virus. The results showed that PZH had low cytotoxicity to Vero cells and RD cells, with the half-maximal cytotoxic concentration(CC_(50)) of about 0.691 3-0.879 2 mg·mL~(-1) for the two. In addition, PZH can effectively inhibit the replication of EV71 within the non-cytotoxic concentration range, and dose-dependently alleviate the cytopathic changes caused by virus infection, with the half-maximal effective concentration(EC_(50)) of 0.009 2-0.106 3 mg·mL~(-1). On the basis of the above results, the green fluorescent protein(GFP), indirect immunofluorescence assay(IFA), and median tissue culture infective dose(TCID_(50)) were employed to assess and verify the anti-EV71-GFP and anti-EV71 C4 activity of PZH. The results demonstrated that PZH can dose-dependently lower the expression of GFP by EV71-GFP and structural protein VP-1 by EV71 C4 and decrease the production of progeny infectious viruses. The EC_(50) of PZH for EV71-GFP and EV71 C4 was about 0.006 0-0.006 2 mg·mL~(-1) and 0.006 6-0.025 6 mg·mL~(-1), respectively. This study suggested that PZH may exert antiviral activity by acting on EV71 and interfering with the expression of VP-1. At the moment, there is still a lack of specific anti-EV71 drugs. This study proposed a new idea for the symptomatic treatment of EV71 infections such as hand-foot-mouth disease and verified an effective drug for the treatment of EV71 infections.

CircPVT1 promotes progression in clear cell renal cell carcinoma by sponging miR-145-5p and regulating TBX15 expression.

Emerging evidence revealed that circular RNAs (circRNAs) play significant roles in regulating tumorigenesis and cancer progression. However, few circRNAs were well characterized in clear cell renal cell carcinoma (ccRCC). We found that circPVT1 was significantly upregulated in ccRCC tissues and positively associated with the clinical stage. The Area Under Curve of tissue and serum circPVT1 expression in ccRCC were 0.93 and 0.86, respectively. Importantly, we demonstrated that circPVT1 promoted ccRCC growth and metastasis in vitro and in vivo. We also found that circPVT1 directly binds to miRNA-145-5p via the Biotin-labelled miRNA pulldown assay and dual-luciferase reporter assay, and miR-145-5p inhibitor significantly attenuated the effect of circPVT1 knockdown on ccRCC cells. Moreover, through RNA sequencing and bioinformatics analysis, we demonstrated that TBX15 was regulated by the circPVT1/miR-145-5p axis and predicted poor prognosis in ccRCC. These findings suggest that circPVT1 promotes ccRCC growth and metastasis through sponging miR-145-5p and regulating downstream target TBX15 expression. The circPVT1/miR-145-5p/TBX15 axis might be a potential diagnostic marker and therapeutic target in ccRCC.

Pien Tze Huang (PZH) as a Multifunction Medicinal Agent in Traditional Chinese Medicine (TCM): a review on cellular, molecular and physiological mechanisms.

RELEVANCE: Pien Tze Huang (PZH) is a well-known Traditional Chinese Medicine (TCM), characterized by a multitude of pharmacological effects, such as hepatoprotection and inhibition of inflammation and cell proliferative conditions. Many of these effects have been validated at the cellular, molecular and physiological levels but, to date, most of these findings have not been comprehensively disclosed. OBJECTIVES: This review aims to provide a critical summary of recent studies focusing on PZH and its multiple pharmacological effects. As a result, we further discuss some novel perspectives related to PZH's mechanisms of action and a holistic view of its therapeutic activities. METHODS: A systematic review was performed focusing on PZH studies originated from original scientific resources. The scientific literature retrieved for this work was obtained from International repositories including NCBI/PubMed, Web of Science, Science Direct and China National Knowledge Infrastructure (CNKI) databases. RESULTS: The major active componentes and their potential functions, including hepatoprotective and neuroprotective effects, as well as anti-cancer and anti-inflammatory activities, were summarized and categorized accordingly. As indicated, most of the pharmacological effects were validated in vitro and in vivo. The identification of complex bioactive components in PZH may provide the basis for further therapeutic initiatives. CONCLUSION: Here we have collectively discussed the recent evidences covering most, if not all, pharmacological effects driven by PZH. This review provides novel perspectives on understanding the modes of action and the holistic view of TCM. The rational development of future clinical trials will certainly provide evidence-based medical evidences that will also confirm the therapeutic advantages of PZH, based on the current information available.

M2 macrophages secrete CXCL13 to promote renal cell carcinoma migration, invasion, and EMT.

OBJECTIVE: M2 macrophages are associated with a poor prognosis in a variety of malignancies. There are, however, few relevant investigations in clear cell renal cell carcinoma (ccRCC). METHODS: The expression of M2 macrophages in ccRCC tissues was first discovered using immunohistochemistry in this study. Then, M2 macrophages were created in vitro to see how they affected the proliferation, migration, invasion, and EMT of ccRCC cells. Using qPCR and prognostic analysis identifies important chemokine. Antibody neutralization tests confirmed the chemokine's involvement and function. Pathway inhibitors confirmed the main pathway of M2 macrophages in ccRCC. Finally, qPCR and IHC were used to confirm the expression of chemokine receptors in ccRCC tissues. RESULTS: The presence of M2 macrophages was linked to a poor outcome in ccRCC. M2 macrophages enhanced the proliferation, migration, invasion, and EMT of ccRCC lines in vitro. CXCL13 was identified as the main chemokine by prognostic analysis and qPCR tests. CXCL13 neutralizing antibodies can inhibit the stimulation of M2 macrophages in ccRCC lines' proliferation, migration, invasion, and EMT. M2 macrophages and CXCL13 may activate the Akt pathway in ccRCC lines, and Akt inhibitors decrease ccRCC lines proliferation, migration, invasion, and EMT. CXCR5 expression is a poor prognostic factor for renal cell carcinoma, according to qPCR and immunohistochemistry. In vivo experiments further proved that CXCL13 secreted by M2 macrophages can promote tumor proliferation. CONCLUSIONS: M2 macrophages in the immunological milieu secrete CXCL13, which promotes ccRCC proliferation, migration, invasion, and EMT. Our findings contribute to a better understanding of the function of the tumor microenvironment in the incidence and progression of ccRCC, and they may point to novel therapeutic targets for ccRCC.

Development and validation of a CT-based nomogram for preoperative prediction of clear cell renal cell carcinoma grades.

OBJECTIVES: Nuclear grades are proved to be one of the most significant prognostic factors for clear cell renal cell carcinoma (ccRCC). Radiomics nomogram is a widely used noninvasive tool that could predict tumor phenotypes. In this study, we performed radiomics analysis to develop and validate a CT-based nomogram for the preoperative prediction of nuclear grades in ccRCC. METHOD: CT images and clinical data of 258 ccRCC patients were retrieved from the Cancer Imaging Archive (TCIA). Radiomics features were extracted from arterial-phase CT images using 3D Slicer software. LASSO regression model was performed to develop a radiomics signature in the training set (n = 143). A radiomics nomogram was constructed combining radiomics signature and selected clinical predictors. Receiver operating characteristic (ROC) curve and calibration curve were used to determine the performance of the radiomics nomogram in the training and validation set (n = 115). Decision curve analysis was used to assess the clinical usefulness of the CT-based nomogram. RESULTS: One thousand three hundred sixteen radiomics features were extracted from arterial-phase CT images. A radiomics signature, consisting of 20 features, was developed and showed a favorable performance in discriminating nuclear grades with an area under the curve (AUC) of 0.914 and 0.846 in the training and validation set, respectively. The CT-based nomogram, including the radiomics signature and the CT-determined T stage, achieved good calibration and discrimination in the training set (AUC, 0.929; 95% CI, 0.886-0.972) and validation set (AUC, 0.876; 95% CI, 0.812-0.939). Decision curve analysis demonstrated the clinical usefulness of the CT-based nomogram. CONCLUSION: The noninvasive CT-based nomogram, including radiomics signature and CT-determined T stage, could improve the accuracy of preoperative grading of ccRCC and provide individualized treatment for ccRCC patients. KEY POINTS: • Contrast-enhanced CT may help in preoperative grading of ccRCC. • The CT-based nomogram incorporated a radiomics signature and CT-determined T stage could preoperatively predict ccRCC grades. • The CT-based nomogram has the potential to improve individualized treatment and assist clinical decision making of ccRCC patients.