[Effects of litter thickness on natural regeneration of Larix principis-rupprechtii plantations]. / 枯落物厚度对华北落叶松人工林天然更新的影响.

In this study, we explored the thickness influence of undecomposed litter layer and semi-decomposed litter layer on the natural regeneration in an artificial pure forest of Larix principis-rupprechtii in the forest area of Guandi Mountain. We divided the litter into an undecomposed layer and a semi-decomposed layer, which was further divided into eight groups based on the thickness. The results showed that when the thickness of undecomposed layer was 0.32-0.83 cm, and that of semi-decomposed layer was 0.18-0.89 cm, the regeneration index was larger (≥0.15), and the regeneration was better. When the thickness of undecomposed layer was more than 1.1 cm and that of semi-decomposed layer was more than 0.5 cm, the regeneration index was smaller (≤0.07), and the rege-neration of understory was worse. Results of redundancy analysis showed that the undecomposed layer thickness of litter had a high and stable explanatory ability for natural regeneration, with a contribution rate of 38.7%, while the semi-decomposed layer thickness had no significant effect on natural regeneration. Structural equation modeling revealed that the thickness of undecomposed layer of litter increased the mechanical resistance to seed germination which had a negative direct effect on natural regeneration (-0.617), and a positive indirect effect on natural rege-neration by influencing the content of alkali-hydrolyzed nitrogen and available phosphorus (+0.178). The combined effects (-0.439) showed an inhibitory effect on the natural regeneration. In conclusion, the thickness of undecomposed layer of litter under L. principis-rupprechtii was most closely related to natural regeneration, and the thickness of semi-decomposed layer had a minimal effect on natural regeneration.

Targeted sequencing of DNA/RNA combined with radiomics predicts lymph node metastasis of papillary thyroid carcinoma.

OBJECTIVE: The aim of our study is to find a better way to identify a group of papillary thyroid carcinoma (PTC) with more aggressive behaviors and to provide a prediction model for lymph node metastasis to assist in clinic practice. METHODS: Targeted sequencing of DNA/RNA was used to detect genetic alterations. Gene expression level was measured by quantitative real-time PCR, western blotting or immunohistochemistry. CCK8, transwell assay and flow cytometry were used to investigate the effects of concomitant gene alterations in PTC. LASSO-logistics regression algorithm was used to construct a nomogram model integrating radiomic features, mutated genes and clinical characteristics. RESULTS: 172 high-risk variants and 7 fusion types were detected. The mutation frequencies in BRAF, TERT, RET, ATM and GGT1 were significantly higher in cancer tissues than benign nodules. Gene fusions were detected in 16 samples (2 at the DNA level and 14 at the RNA level). ATM mutation (ATMMUT) was frequently accompanied by BRAFMUT, TERTMUT or gene fusions. ATMMUT alone or ATM co-mutations were significantly positively correlated with lymph node metastasis. Accordingly, ATM knock-down PTC cells bearing BRAFV600E, KRASG12R or CCDC6-RET had higher proliferative ability and more aggressive potency than cells without ATM knock-down in vitro. Furthermore, combining gene alterations and clinical features significantly improved the predictive efficacy for lymph node metastasis of radiomic features, from 71.5 to 87.0%. CONCLUSIONS: Targeted sequencing of comprehensive genetic alterations in PTC has high prognostic value. These alterations, in combination with clinical and radiomic features, may aid in predicting invasive PTC with higher accuracy.

Real-time detection of gastrointestinal leaks via bismuth chelate-enhanced X-ray gastroenterography.

Anastomotic leaks are among the most dreaded complications following gastrointestinal (GI) surgery, and contrast-enhanced X-ray gastroenterography is considered the preferred initial diagnostic method for GI leaks. However, from fundamental research to clinical practice, the only oral iodinated contrast agents currently available for GI leaks detection are facing several challenges, including low sensitivity, iodine allergy, and contraindications in patients with thyroid diseases. Herein, we propose a cinematic contrast-enhanced X-ray gastroenterography for the real-time detection of GI leaks with an iodine-free bismuth chelate (Bi-DTPA) for the first time. The Bi-DTPA, synthesized through a straightforward one-pot method, offers distinct advantages such as no need for purification, a nearly 100 % yield, large-scale production capability, and good biocompatibility. The remarkable X-ray attenuation properties of Bi-DTPA enable real-time dynamic visualization of whole GI tract under both X-ray gastroenterography and computed tomography (CT) imaging. More importantly, the leaky site and severity can be both clearly displayed during Bi-DTPA-enhanced gastroenterography in a rat model with esophageal leakage. The proposed movie-like Bi-DTPA-enhanced X-ray imaging approach presents a promising alternative to traditional GI radiography based on iodinated molecules. It demonstrates significant potential in addressing concerns related to iodine-associated adverse effects and offers an alternative method for visually detecting gastrointestinal leaks.

Expert consensus on endodontic therapy for patients with systemic conditions.

The overall health condition of patients significantly affects the diagnosis, treatment, and prognosis of endodontic diseases. A systemic consideration of the patient's overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy, as well as selecting appropriate therapeutic approaches. This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence, aiming to provide general guidance on clinical procedures, improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health.

Evaluation of image-pro plus assisted superb microvascular imaging for differential diagnosis of renal masses.

OBJECTIVE: Previous research on diagnostic assessment by superb microvascular imaging (SMI) were based on qualitative or semi-quantitative assessments of vascularity, which may be subjective and unrepeatable by different sonographers. This study aimed to evaluate diagnostic performance of SMI Image-pro Plus (IPP) based vascular index (VI) for malignant renal masses. METHOD: We retrospectively reviewed 222 masses in 214 patients who underwent SMI between August 2019 and August 2022 in our study. We evaluated the diagnostic performance of blood flow via Alder grade, VI based on both IPP and SMI. RESULTS: The kappa consistency of the Adler grade and VI for renal masses was classified among different observers were 0.765 and 0.824. The intra-observers correlation ecoefficiency (ICC) were 0.727 and 0.874. Benign renal masses were mainly Adler grade 0, grade I, and grade II, VI was 4.30 ± 4.27 (Range 0.98-16.42); while malignant masses were mainly Adler grade III, VI was 14.95 ± 10.94 (Range 0.79-56.89). VI was higher in malignant than benign masses (t = 15.638, P < 0.01). Among the malignant masses, the mean VI in clear cell renal cell carcinoma was higher than that in papillary renal cell carcinoma and chromophobe renal cell carcinoma (F = 30.659, P < 0.01). The sensitivity, specificity and accuracy of SMI were 80.00%, 71.15%, and 78.64%, respectively. The sensitivity, specificity, and accuracy were 60.59%, 88.46%, and 80.18% by using a VI of 7.95 as the cutoff value to identify malignant lesions from benign masses yielded. VI had better diagnostic efficiency than ultrasonic characteristics and Adler grade in benign and malignant differential diagnosis (Z = 4.851, P < 0.01; Z = 2.732, P < 0.01). CONCLUSION: VI was higher in malignant than benign in renal masses. In malignant masses, VI in CCRCC was higher than that in papillary renal cell carcinoma and ChRCC. As a noninvasive examination, it had important clinical significance in the differential diagnosis of renal masses. VI from IPP may assist sonographer in distinguish renal malignances as a quantitative tool for vascularity.

Screening, identification and evaluation of an acidophilic strain of Bacillus velezensis B4-7 for the biocontrol of tobacco bacterial wilt.

Tobacco (Nicotiana tabacum L.) bacterial wilt, caused by Ralstonia solanacearum, is indeed a highly destructive plant disease, leading to substantial damage in tobacco production. While biological control is considered an effective measure for managing bacterial wilt, related research in this area has been relatively limited compared to other control methods. In order to discover new potential antagonistic bacteria with high biocontrol efficacy against tobacco bacterial wilt, we conducted an analysis of the microbial composition differences between disease-suppressive and disease-conducive soils using Illumina sequencing. As a result, we successfully isolated six strains from the disease-suppressive soil that exhibited antibacterial activity against Ralstonia solanacearum. Among these strains, B4-7 showed the strongest antibacterial activity, even at acidic conditions with a pH of 4.0. Based on genome analysis using Average Nucleotide Identity (ANI), B4-7 was identified as Bacillus velezensis. In greenhouse and field trials, strain B4-7 significantly reduced the disease index of tobacco bacterial wilt, with control efficiencies reaching 74.03% and 46.88% respectively. Additionally, B4-7 exhibited plant-promoting abilities that led to a 35.27% increase in tobacco production in field conditions. Quantitative real-time (qPCR) analysis demonstrated that strain B4-7 effectively reduced the abundance of R. solanacearum in the rhizosphere. Genome sequencing and Liquid Chromatography-Mass Spectrometry (LC-MS) analysis revealed that strain B4-7 potentially produces various lipopeptide metabolites, such as microlactin, bacillaene, difficidin, bacilysin, and surfactin. Furthermore, B4-7 influenced the structure of the rhizosphere soil microbial community, increasing bacterial abundance and fungal diversity, while also promoting the growth of different beneficial microorganisms. In addition, B4-7 enhanced tobacco's resistance to R. solanacearum by increasing the activities of defense enzymes, including superoxide dismutase (SOD), phenylalanine ammonia-lyase (PAL), peroxidase (POD), catalase (CAT), and polyphenol oxidase (PPO). Collectively, these findings suggest that B. velezensis B4-7 holds significant biocontrol potential and can be considered a promising candidate strain for eco-friendly management of tobacco bacterial wilt.

A functional study reveals CsNAC086 regulated the biosynthesis of flavonols in Camellia sinensis.

MAIN CONCLUSION: CsNAC086 was found to promote the expression of CsFLS, thus promoting the accumulation of flavonols in Camellia sinensis. Flavonols, the main flavonoids in tea plants, play an important role in the taste and quality of tea. In this study, a NAC TF gene CsNAC086 was isolated from tea plants and confirmed its regulatory role in the expression of flavonol synthase which is a key gene involved in the biosynthesis of flavonols in tea plant. Yeast transcription-activity assays showed that CsNAC086 has self-activation activity. The transcriptional activator domain of CsNAC086 is located in the non-conserved C-terminal region (positions 171-550), while the conserved NAC domain (positions 1-170) does not have self-activation activity. Silencing the CsNAC086 gene using antisense oligonucleotides significantly decreased the expression of CsFLS. As a result, the concentration of flavonols decreased significantly. In overexpressing CsNAC086 tobacco leaves, the expression of NtFLS was significantly increased. Compared with wild-type tobacco, the flavonols concentration increased. Yeast one-hybrid assays showed CsNAC086 did not directly regulate the gene expression of CsFLS. These findings indicate that CsNAC086 plays a role in regulating flavonols biosynthesis in tea plants, which has important implications for selecting and breeding of high-flavonols-concentration containing tea-plant cultivars.

Potential of melatonin and Trichoderma harzianum inoculation in ameliorating salt toxicity in watermelon: Insights into antioxidant system, leaf ultrastructure, and gene regulation.

Melatonin (MT) is an extensively studied biomolecule with dual functions, serving as an antioxidant and a signaling molecule. Trichoderma Harzianum (TH) is widely recognized for its effectiveness as a biocontrol agent against many plant pathogens. However, the interplay between seed priming and MT (150 µm) in response to NaCl (100 mM) and its interaction with TH have rarely been investigated. This study aimed to evaluate the potential of MT and TH, alone and in combination, to mitigate salt stress (SS) in watermelon plants. The findings of this study revealed a significant decline in the morphological, physiological, and biochemical indices of watermelon seedlings exposed to SS. However, MT and TH treatments reduced the negative impact of salt stress. The combined application of MT and TH exerted a remarkable positive effect by increasing the growth, photosynthetic and gas exchange parameters, chlorophyll fluorescence indices, and ion balance (decreasing Na+ and enhancing K+). MT and TH effectively alleviated oxidative injury by inhibiting hydrogen peroxide formation in saline and non-saline environments, as established by reduced lipid peroxidation and electrolyte leakage. Moreover, oxidative injury induced by SS on the cells was significantly mitigated by regulation of the antioxidant system, AsA-GSH-related enzymes, the glyoxalase system, augmentation of osmolytes, and activation of several genes involved in the defense system. Additionally, the reduction in oxidative damage was examined by chloroplast integrity via transmission electron microscopy (TEM). Overall, the results of this study provide a promising contribution of MT and TH in safeguarding the watermelon crop from oxidative damage induced by salt stress.

LIFU/MMP-2 dual-responsive release of repurposed drug disulfiram from nanodroplets for inhibiting vasculogenic mimicry and lung metastasis in triple-negative breast cancer.

BACKGROUND: Vasculogenic mimicry (VM), when microvascular channels are formed by cancer cells independent of endothelial cells, often occurs in deep hypoxic areas of tumors and contributes to the aggressiveness and metastasis of triple-negative breast cancer (TNBC) cells. However, well-developed VM inhibitors exhibit inadequate efficacy due to their low drug utilization rate and limited deep penetration. Thus, a cost-effective VM inhibition strategy needs to be designed for TNBC treatment. RESULTS: Herein, we designed a low-intensity focused ultrasound (LIFU) and matrix metalloproteinase-2 (MMP-2) dual-responsive nanoplatform termed PFP@PDM-PEG for the cost-effective and efficient utilization of the drug disulfiram (DSF) as a VM inhibitor. The PFP@PDM-PEG nanodroplets effectively penetrated tumors and exhibited substantial accumulation facilitated by PEG deshielding in a LIFU-mediated and MMP-2-sensitive manner. Furthermore, upon exposure to LIFU irradiation, DSF was released controllably under ultrasound imaging guidance. This secure and controllable dual-response DSF delivery platform reduced VM formation by inhibiting COL1/pro-MMP-2 activity, thereby significantly inhibiting tumor progression and metastasis. CONCLUSIONS: Considering the safety of the raw materials, controlled treatment process, and reliable repurposing of DSF, this dual-responsive nanoplatform represents a novel and effective VM-based therapeutic strategy for TNBC in clinical settings.

Expert consensus on difficulty assessment of endodontic therapy.

Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy (RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Expert consensus on irrigation and intracanal medication in root canal therapy.

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment. However, irrigant selection or irrigation procedures are far from clear. The vapor lock effect in the apical region has yet to be solved, impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes. Additionally, ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified. Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes. Indeed, clinicians have been aware of these concerns for years. Based on the current evidence of studies, this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions. The evolution of different kinetic irrigation methods, their effects, limitations, the paradigm shift, current indications, and effective operational procedures regarding intracanal medication are also discussed. This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication, thus facilitating a better understanding of infection control, standardizing clinical practice, and ultimately improving the success of endodontic therapy.

Predictors of portal vein thrombosis after splenectomy in patients with cirrhosis.

BACKGROUND: Portal vein thrombosis (PVT) is a commonthsn complication after splenectomy in patients with cirrhosis. However, the predictors of postoperative PVT are not known. AIM: To investigate the predictors of PVT after splenectomy in patient with cirrhosis. METHODS: A total of 45 patients with cirrhosis who underwent splenectomy were consecutively enrolled from January 2017 to December 2018. The incidence of PVT at 1 months, 3 months, and 12 months after splenectomy in patients with cirrhosis was observed. The hematological indicators, biochemical and coagulation parameters, and imaging features were recorded at baseline and at each observation point. The univariable, multivariable, receiver operating characteristic curve and time-dependent curve analyses were performed. RESULTS: The cumulative incidence of PVT was 40.0%, 46.6%, and 48.9% at 1 months, 3 months, and 12 months after splenectomy. Multivariable analysis showed that portal vein diameter (PVD) ≥ 14.5 mm and monthsdel end-stage liver disease (MELD) score > 10 were independent predictors of PVT at 1 months, 3 months, and 12 months after splenectomy (P < 0.05). Time-dependent curve showed that the cumulative incidence of PVT was significantly different between patients with MELD score ≤ 10 and > 10 (P < 0.05). In addition, the cumulative incidence of PVT in the PVD ≥ 14.5 mm group was significantly higher than that in the PVD < 14.5 mm group (P < 0.05). CONCLUSION: Wider PVD and MELD score > 10 were independent predictors of PVT at 1 months, 3 months, and 12 months after splenectomy in patient with cirrhosis.

Construction and characterization of a reverse genetics system of bovine parainfluenza virus type 3c as a tool for rapid screening of antivirals in vitro.

Bovine parainfluenza virus type 3 (BPIV3) is a key pathogen associated with bovine respiratory disease complex (BRDC). However, its specific pathogenesis mechanisms have not been fully elucidated. Reverse genetics provides a useful method for understanding the pathogenic mechanism of BPIV3. To ensure the functionality of the rescue platforms, we first constructed a minigenome (MG) system of BPIV3 utilizing a 5-plasmid system in this investigation. Then, a full-length infection clone of BPIV3 was obtained from the SX-2021 strain, and different methods were employed to identify the rescued virus. Additionally, we recovered a recombinant BPIV3 using the reverse genetics system that could express enhanced green fluorescence protein (eGFP). Through the growth curve assays, the replicate capability of rBPIV3-SX-EGFP was found to be similar to that of the parental virus. Subsequently, the rBPIV3-SX-EGFP was used to determine the antiviral activity of ribavirin. The results showed that ribavirin had an anti-BPIV3 effect in MDBK cells. In conclusion, the successful development of a reverse genetic system for the SX-2021 strain establishes a foundation for future studies on BPIV3, including investigations into its pathogenic mechanism, gene function, and antiviral screening properties.

A high-current hydrogel generator with engineered mechanoionic asymmetry.

Mechanoelectrical energy conversion is a potential solution for the power supply of miniaturized wearable and implantable systems; yet it remains challenging due to limited current output when exploiting low-frequency motions with soft devices. We report a design of a hydrogel generator with mechanoionic current generation amplified by orders of magnitudes with engineered structural and chemical asymmetry. Under compressive loading, relief structures in the hydrogel intensify net ion fluxes induced by deformation gradient, which synergize with asymmetric ion adsorption characteristics of the electrodes and distinct diffusivity of cations and anions in the hydrogel matrix. This engineered mechanoionic process can yield 4 mA (5.5 A m-2) of peak current under cyclic compression of 80 kPa applied at 0.1 Hz, with the transferred charge reaching up to 916 mC m-2 per cycle. The high current output of this miniaturized hydrogel generator is beneficial for the powering of wearable devices, as exemplified by a controlled drug-releasing system for wound healing. The demonstrated mechanisms for amplifying mechanoionic effect will enable further designs for a variety of self-powered biomedical systems.

Nonmetallic graphite for tumor magnetic hyperthermia therapy.

Magnetic hyperthermia therapy (MHT) has garnered immense interest due to its exceptional spatiotemporal specificity, minimal invasiveness and remarkable tissue penetration depth. Nevertheless, the limited magnetothermal heating capability and the potential toxicity of metal ions in magnetic materials based on metallic elements significantly impede the advancement of MHT. Herein, we introduce the concept of nonmetallic materials, with graphite (Gra) as a proof of concept, as a highly efficient and biocompatible option for MHT of tumors in vivo for the first time. The Gra exhibits outstanding magnetothermal heating efficacy owing to the robust eddy thermal effect driven by its excellent electrical conductivity. Furthermore, being composed of carbon, Gra offers superior biocompatibility as carbon is an essential element for all living organisms. Additionally, the Gra boasts customizable shapes and sizes, low cost, and large-scale production capability, facilitating reproducible and straightforward manufacturing of various Gra implants. In a mouse tumor model, Gra-based MHT successfully eliminates the tumors at an extremely low magnetic field intensity, which is less than one-third of the established biosafety threshold. This study paves the way for the development of high-performance magnetocaloric materials by utilizing nonmetallic materials in place of metallic ones burdened with inherent limitations.

GhRCD1 promotes cotton tolerance to cadmium by regulating the GhbHLH12-GhMYB44-GhHMA1 transcriptional cascade.

Heavy metal pollution poses a significant risk to human health and wreaks havoc on agricultural productivity. Phytoremediation, a plant-based, environmentally benign, and cost-effective method, is employed to remove heavy metals from contaminated soil, particularly in agricultural or heavy metal-sensitive lands. However, the phytoremediation capacity of various plant species and germplasm resources display significant genetic diversity, and the mechanisms underlying these differences remain hitherto obscure. Given its potential benefits, genetic improvement of plants is essential for enhancing their uptake of heavy metals, tolerance to harmful levels, as well as overall growth and development in contaminated soil. In this study, we uncover a molecular cascade that regulates cadmium (Cd2+) tolerance in cotton, involving GhRCD1, GhbHLH12, GhMYB44, and GhHMA1. We identified a Cd2+-sensitive cotton T-DNA insertion mutant with disrupted GhRCD1 expression. Genetic knockout of GhRCD1 by CRISPR/Cas9 technology resulted in reduced Cd2+ tolerance in cotton seedlings, while GhRCD1 overexpression enhanced Cd2+ tolerance. Through molecular interaction studies, we demonstrated that, in response to Cd2+ presence, GhRCD1 directly interacts with GhbHLH12. This interaction activates GhMYB44, which subsequently activates a heavy metal transporter, GhHMA1, by directly binding to a G-box cis-element in its promoter. These findings provide critical insights into a novel GhRCD1-GhbHLH12-GhMYB44-GhHMA1 regulatory module responsible for Cd2+ tolerance in cotton. Furthermore, our study paves the way for the development of elite Cd2+-tolerant cultivars by elucidating the molecular mechanisms governing the genetic control of Cd2+ tolerance in cotton.

A Novel KIF4A-Related Model for Predicting Immunotherapy Response and Prognosis in Kidney Renal Clear Cell Carcinoma.

BACKGROUND: The efficacy of chemotherapy in treating Kidney Renal Clear Cell Carcinoma (KIRC) is limited, whereas immunotherapy has shown some promising clinical outcomes. In this context, KIF4A is considered a potential therapeutic target for various cancers. Therefore, identifying the mechanism of KIF4A that can predict the prognosis and immunotherapy response of KIRC would be of significant importance. METHODS: Based on the TCGA Pan-Cancer dataset, the prognostic significance of the KIF4A expression across 33 cancer types was analyzed by univariate Cox algorithm. Furthermore, overlapping differentially expressed genes (DEGs1) between the KIF4A high- and lowexpression groups and DEGs2 between the KIRC and normal groups were also analyzed. Machine learning and Cox regression algorithms were performed to obtain biomarkers and construct a prognostic model. Finally, the role of KIF4A in KIRC was analyzed using quantitative real-time PCR, transwell assay, and EdU experiment. RESULTS: Our analysis revealed that KIF4A was significant for the prognosis of 13 cancer types. The highest correlation with KIF4A was found for KICH among the tumour mutation burden (TMB) indicators. Subsequently, a prognostic model developed with UBE2C, OTX1, PPP2R2C, and RFLNA was obtained and verified with the Renal Cell Cancer-EU/FR dataset. There was a positive correlation between risk score and immunotherapy. Furthermore, the experiment results indicated that KIF4A expression was considerably increased in the KIRC group. Besides, the proliferation, migration, and invasion abilities of KIRC tumor cells were significantly weakened after KIF4A was knocked out. CONCLUSION: We identified four KIF4A-related biomarkers that hold potential for prognostic assessment in KIRC. Specifically, early implementation of immunotherapy targeting these biomarkers may yield improved outcomes for patients with KIRC.