Search

Abstract Certain immune-checkpoint inhibitors have a narrow therapeutic window (TW) as cancer therapeutics, and engineered dual-/multi-targeting agents could potentially widen the TW to bring true clinical benefits. We report a new rationally-designed bispecific-antibody (BsAb), HX009, simultaneously targeting PD1 and CD47 to improve both the efficacy and safety over the respective single-targeting agents by grafting the extracellular domain of SIRPα onto the parental anti-PD1-monoclonal antibody, HX008. This resulted in an IgG4-based “2 × 2” symmetric structure but with an intentionally-reduced CD47-binding affinity, suggesting a novel candidate cancer immunotherapy. Specifically, HX009 has binding affinity constant of 8.951 × 10–9 M for human PD1 and 2.557 × 10–8 M for human CD47, respectively, where the CD47 binding is significantly weaker as compared to the binding affinity of HX008 to PD1 as well as the binding affinity of SIRPα-Fc to CD47, leading to little binding to RBCs and platelets and is contrasting to many CD47-agents in development. However, HX009 effectively and simultaneously binds to the PD1 and CD47 on PD1+CD47+ T-cells via cis-binding and elicits enhanced T cell activation compared to the parental HX008. HX009 caused little cytokine-release in human peripheral blood mononuclear cells. HX009 cross-species binds to cynomolgus monkey PD1/CD47 but not to rodents, making cynomolgus monkeys the choice of species to investigate the pharmacokinetics (PK) and toxicology of HX009. HX009’s anti-tumor activities were confirmed in several humanized preclinical mouse models by determining either its anti-PD1 (humanized hu-CD47-MC38 models) or anti-CD47 (HuT-102 lymphoma CDX and three PDX-AML models) functions, although limited available humanized models have hindered broadly demonstration of enhanced anti-tumor activities contributed from the dual targeting of the BsAb. The expanded DLBCL-PDX trial data suggested that both EBV-status and OX40 expression could potentially be two positive predictors for response to HX009. An intravenous (IV) infusion PK study in cynomolgus monkey revealed its largely vasculature distribution, terminal half-life (T1/2) of ~ 50 h, and dose-proportional exposure without accumulation. The anti-drug antibody (ADA) was observed in all monkeys as expected, affecting the PK parameters of repeated administration. The IV single-dose toxicology study with a 14-day observation revealed a maximum tolerated dose of 150 mg/kg, while the repeated-dose (once weekly for 4 weeks, 5 doses in total) study showed a highest non-severely toxic dose (HNSTD) of 15 mg/kg. The desired preclinical PK and safety profiles, along with its antitumor activity, support HX009’s candidacy for its clinical development.

Societal Impact Statement Unraveling the genetic intricacies and evolutionary history of Asian Hickories through advanced genome sequencing gives valuable insights into their ecological adaptations. Understanding the impact of historical dynamics, climate fluctuations, and geographical barriers on Asian hickories not only contributes to scientific knowledge but also empowers policymakers with evidence‐based decisions and guides conservationists in their efforts to protect vulnerable species. The identification of potential habitats, especially for the endangered Carya kweichowensis, offers a promising avenue for targeted conservation efforts, aligning with global initiatives to preserve Earth's precious biodiversity, but also ensures the conservation of a vital genetic reservoir for nut‐bearing economic tree species. Summary Biogeographic characteristics of disjunct distribution play a vital role in plant geography and the endangered mechanism. The whole genome resequencing provides an opportunity to study the genetic relationship, population diffusion, and floristic evolution of disjunctive‐distribution flora. Based on the SNPs (single nucleotide polymorphisms) data generated by the whole genome deep resequencing of five EA (Eastern Asian) Carya species, we constructed the phylogenetic tree, genetic structure, and species distribution modeling to clarify the phylogenetic relationships and to predict the potential distribution area of EA Carya. Phylogenetic analysis of Carya revealed two distinct clades, separating EA Carya from NA (North America) Carya. C. kweichowensis, an endangered species, showed the lowest nucleotide diversity and the earliest divergence among studied EA Carya species. Species distribution modeling predicted suitable habitats for five EA Carya species, revealing the potential distribution of endangered C. kweichowensis. Importantly, minimal spatial overlap was observed among distribution regions of EA Carya species during different time periods. The uneven regional distribution of EA Carya is believed to be a consequence of Quaternary climate fluctuations, mountain barriers hindering species dispersal, and the limited cold tolerance of these trees. EA Carya highlights the significant role of climate and geological changes in their regional distribution and migration routes in Asia. Furthermore, the discovery of potential habitats offers a promising avenue for the conservation of C. kweichowensis.

Abstract Retinol is widely used to treat skin ageing because of its effect on cell differentiation, proliferation and apoptosis. However, its potential benefits appear to be limited by its skin permeability. Herein, we investigated the transcutaneous behavior of retinol in semisolid cosmetics, in both in vitro and in vivo experiments. In vitro experiments used the modified Franz diffusion cell combined with Raman spectroscopy. In in vivo experiments, the content of retinol in rat skin and plasma was detected with HPLC. Retinol in semisolid cosmetics was mainly concentrated in the stratum corneum in the skin of the three animal models tested, and in any case did not cross the skin barrier after a 24 h dermatologic topical treatment in Franz diffusion cells tests. Similar results were obtained in live mice and rats, where retinol did not cross the skin barrier and did not enter the blood circulation. Raman spectroscopy was used to test the penetration depth of retinol in skin, which reached 16 μm out of 34 μm in pig skin, whereas the skin of mouse and rat showed too strong bakground interference. To explore epidermal transport mechanism and intradermal residence, skin transcriptomics was performed in rats, which identified 126 genes upregulated related to retinol transport and metabolism, relevant to the search terms “retinoid metabolic process” and “transporter activity”. The identity of these upregulated genes suggests that the mechanism of retinol action is linked to epidermis, skin, tissue and epithelium development.

The natural gas pipeline system (NGPS) is complex with a diverse network topology. This study elucidates the network characteristics of the NGPS, revealing that it shares commonalities with small-world networks, but with differences caused by its structural and operational characteristics. The combination of the low aggregation effect caused by branching structure and the offsetting effect caused by economic and geographical constraints results in a network with small world characteristics. NGPS has longer mean path than common small world network, but the aggregation factor is close to that of a standard small world network. With respect to its small-world characteristics and correlation with self-organized criticality (SOC), an in-depth study of the SOC characteristics of the NGPS was conducted utilizing a combination of traditional logarithm analysis and R/S analysis. The findings establish that there are atypical SOC characteristics, characterized by a weakened power law within a specific functional range, thereby encouraging the advancement of SCADA and other safety technologies. Because of the line-pack, which induces time lags in the NGPS, NGPS can prevent the cascade failures. The reasons for the periodicity and centrality of NGPS data are analyzed by the affecting components, with the R/S analysis verifying a weak positive correlation of the function data across different time series. The interlinking of the SOC and R/S analysis illustrates the connection between critical status, accident type, and operation index. The results prove the reasonability and importance of insurance measures, such as regular internal detection, higher grade steel pipes change and staff training et al., in a novel view of SOC. The future works in building accidents database and human factors study are proposed.

Abstract CSF1R is a receptor tyrosine kinase responsible for the growth/survival/polarization of macrophages and overexpressed in some AML patients. We hypothesized that a novel multi-kinase inhibitor (TKi), narazaciclib (HX301/ON123300), with high potency against CSF1R (IC50 ~ 0.285 nM), would have anti-AML effects. We tested this by confirming HX301’s high potency against CSF1R (IC50 ~ 0.285 nM), as well as other kinases, e.g. FLT3 (IC50 of ~ 19.77 nM) and CDK6 (0.53 nM). An in vitro proliferation assay showed that narazaciclib has a high growth inhibitory effect in cell cultures where CSF1R or mutant FLT3-ITD variants that may be proliferation drivers, including primary macrophages (IC50 of 72.5 nM) and a subset of AML lines (IC50

Flexible pressure sensors are lightweight and highly sensitive, making them suitable for use in small portable devices to achieve precise measurements of tiny forces. This article introduces a low-cost and easy-fabrication strategy for piezoresistive flexible pressure sensors. By embedding silver nanowires into a polydimethylsiloxane layer with micro-pyramids on its surface, a flexible pressure sensor is created that can detect low pressure (17.3 Pa) with fast response (

Abstract Axially chiral thioethers and sulfoxides emerge as two pivotal classes of ligands and organocatalysts, which have remarkable features in the stereoinduction of various asymmetric transformations. However, the lack of easy methods to access such molecules with diverse structures has hampered their broader utilization. Herein, an oxidative kinetic resolution for sulfides using a chiral bifunctional squaramide as the catalyst with cumene hydroperoxide as the terminal oxidant is established. This asymmetric approach provides a variety of axially chiral thioethers as well as sulfoxides bearing both axial and central chirality, with excellent diastereo‐ and enantioselectivities. This catalytic system also successfully extends to the kinetic resolution of benzothiophene‐based sulfides. Preliminary mechanism investigation indicates that the multiple hydrogen bonding interactions between the bifunctional squaramide catalyst and substrates play a crucial role in determining the enantioselectivity and reactivity.

Bohai Sea is China's inland sea, its complex marine and atmospheric optical properties pose a challenge to the application of satellite data to retrieve chlorophyll-a (CHLA) concentration with high accuracy. The high accuracy retrieval results of CHLA require simultaneous consideration of the adaptability of atmospheric correction algorithms and CHLA retrieval models. In this study, four atmospheric correction methods [the standard atmospheric correction algorithms of GDPS1.4.1 and GDPS2.0, the standard near-infrared atmospheric correction algorithm of NASA (Seadas_Default), and management unit of the North Sea mathematical models (Seadas_MUMM)] and four CHLA retrieval models (OC2, YOC, OC3G, and OC2M-HI) were selected in the process of applying geostationary ocean color imager (GOCI) data to retrieve CHLA in Bohai Sea. Based on the in situ data, the adaptability of their pairwise combinations in retrieval of CHLA in Bohai Sea was evaluated. The results indicate that the OC2 and OC3G models significantly overestimated the CHLA. The combination of the Seadas_Default atmospheric correction algorithm with the YOC CHLA retrieval model, or the combination of the Seadas_MUMM atmospheric correction algorithm with the YOC CHLA retrieval model, is more suitable for the retrieval of CHLA using GOCI data in Bohai Sea. In addition, this study shows that the CHLA obtained based on the data from eight-scene GOCI data were different to the data obtained based on single-scene GOCI data (approximating traditional polar-orbiting satellite sensor data) in daily, monthly, and yearly average results. The monthly mean difference between the two is the most significant, ranging from -0.66 to 1.49 μg/l.

Rose is a highly significant ornamental plant with substantial edible and medicinal value, cultivated worldwide primarily for perfume production. Recently, Rosa yangii, a new species found in northwestern Yunnan, China, has drawn attention due to its strong sweet scented flowers. In this study, the floral components of R. yangii were extracted at different flowering stages using solid phase micro extraction (SPME) and analyzed through gas chromatography–mass spectrometry (GC–MS). A total of 131 volatile organic compounds (VOCs) were detected from R. yangii, including 69 odor compounds. The production and release of floral VOCs were the highest during the initial-open stage, making it the most suitable time for harvesting as a significant number of floral components were synthesized and preserved. The analysis of the odor activity values (OAV) highlighted several key aromatic ingredients of R. yangii, such as eugenol, methyleugenol, benzeneacetaldehyde and phenylethylalcohol, heptanal, decanal, (E)-2-hexen-1-yl acetate, caryophyllene, and others. Metabolome and time-order gene co-expression networks (TO-GCN) revealed that VOCs and benzenoids/phenylpropanoids, along with associated genes, played a pivotal role in the overall floral regulatory network of R. yangii. MYB and bHLH were identified as the essential regulatory factors governing the regulation of eugenol synthase (EGS) and isoeugenol synthase (IGS), consequently influencing the sweet scent of R. yangii. The findings of this study provide a scientific foundation for enhancing fragrance through molecular breeding of ornamental plants. Furthermore, the study facilitated the development and utilization of this new plant’s essential oil material in various industries, including food storage, aromatherapy, cosmetic, and perfumery.

A new species Rosa funingensis and its variant R. funingensis f. rosea, both collected from Yunnan Province, China, are, for the first time, documented and illustrated in this study. Morphological analysis in comparison with two related species in the wild, R. gigantea and R. rubus, presents distinguishable features through leaf surfaces, inflorescences and the shape of styles. R. funingensis leaf surfaces are abaxially villous, purple-red, pale green when mature, adaxially glabrous, dark green; inflorescences solitary or 2–5(7) in corymbose cyme; and styles connate into a column or not, exserted.

Background: Since 2019, Perampanel (PER) has been endorsed in China as an adjunctive treatment for focal seizures, both with and without impaired awareness, and for the transition from focal to bilateral tonic-clonic seizures. Limited research exists regarding the efficacy of PER in treating post-stroke epilepsy (PSE) in China. Empirical studies are essential to guide treatment protocols. We conducted a retrospective study to assess the efficacy and tolerability of PER in 58 PSE patients treated between October 2019 and July 2023. Method: This study encompassed 58 patients with PSE, treated with PER either as monotherapy or as part of adjunctive therapy, and underwent follow-up for a minimum duration of 6 months. The study assessed changes in seizure frequency, adverse events (AEs), drug retention rate, maintenance dose, and adverse reactions following PER treatment. Results: The study included 58 PSE patients, with 60.3% males and 39.7% females, ranging in age from 18 to 89, mostly within the 61–70 age group. Ischemic strokes constituted 58.6% of cases, while hemorrhagic strokes accounted for 41.4%. Focal seizures, either with or without impaired awareness, were noted in 62.1% of patients, and a transition from focal to bilateral tonic-clonic seizures was seen in 32.8%. The retention rates for PER at 3 and 6 months stood at 94.8% and 84.5% respectively, and the most commonly administered maintenance dose was 4 mg/day (41.28%). In the adjunctive therapy group, efficacy rates were 66.7% at 3 months and 78.6% at 6 months, compared to 80.0% at 3 months and 85.7% at 6 months in the monotherapy group. In the efficacy analysis, with a criterion of ≥50% reduction in seizure frequency, the overall efficacy rates at 3 and 6 months were 69.1% and 79.6%, respectively. Adverse reactions occurred in 46.6% of patients, primarily involving irritability and somnolence (both 27.6%), with no marked difference in incidence between the adjunctive and monotherapy groups (P > 0.05). Conclusion: PER exhibits favorable efficacy and tolerability in Chinese PSE patients, possibly at lower doses.

Tumor microenvironment (TME) is a complex dynamic system with many tumor-interacting components including tumor-infiltrating leukocytes (TILs), cancer associated fibroblasts, blood vessels, and other stromal constituents. It intrinsically affects tumor development and pharmacology of oncology therapeutics, particularly immune-oncology (IO) treatments. Accurate measurement of TME is therefore of great importance for understanding the tumor immunity, identifying IO treatment mechanisms, developing predictive biomarkers, and ultimately, improving the treatment of cancer. Here, we introduce a mouse-IO NGS-based (NGSmIO) assay for accurately detecting and quantifying the mRNA expression of 1080 TME related genes in mouse tumor models. The NGSmIO panel was shown to be superior to the commonly used microarray approach by hosting 300 more relevant genes to better characterize various lineage of immune cells, exhibits improved mRNA and protein expression correlation to flow cytometry, shows stronger correlation with mRNA expression than RNAseq with 10x higher sequencing depth, and demonstrates higher sensitivity in measuring low-expressed genes. We describe two studies; firstly, detecting the pharmacodynamic change of interferon-γ expression levels upon anti-PD-1: anti-CD4 combination treatment in MC38 and Hepa 1-6 tumors; and secondly, benchmarking baseline TILs in 14 syngeneic tumors using transcript level expression of lineage specific genes, which demonstrate effective and robust applications of the NGSmIO panel.

Abstract Viral infection in respiratory tract usually leads to cell death, impairing respiratory function to cause severe disease. However, the diversity of clinical manifestations of SARS-CoV-2 infection increases the complexity and difficulty of viral infection prevention, and especially the high-frequency asymptomatic infection increases the risk of virus transmission. Studying how SARS-CoV-2 affects apoptotic pathway may help to understand the pathological process of its infection. Here, we uncovered SARS-CoV-2 imployed a distinct anti-apoptotic mechanism via its N protein. We found SARS-CoV-2 virus-like particles (trVLP) suppressed cell apoptosis, but the trVLP lacking N protein didn’t. Further study verified that N protein repressed cell apoptosis in cultured cells, human lung organoids and mice. Mechanistically, N protein specifically interacted with anti-apoptotic protein MCL-1, and recruited a deubiquitinating enzyme USP15 to remove the K63-linked ubiquitination of MCL-1, which stabilized this protein and promoted it to hijack Bak in mitochondria. Importantly, N protein promoted the replications of IAV, DENV and ZIKV, and exacerbated death of IAV-infected mice, all of which could be blocked by a MCL-1 specific inhibitor, S63845. Altogether, we identifed a distinct anti-apoptotic function of the N protein, through which it promoted viral replication. These may explain how SARS-CoV-2 effectively replicates in asymptomatic individuals without cuasing respiratory dysfunction, and indicate a risk of enhanced coinfection with other viruses. We anticipate that abrogating the N/MCL-1-dominated apoptosis repression is conducive to the treatments of SARS-CoV-2 infection as well as coinfections with other viruses.

Abstract Both PD1/PD-L1 and CD47 blockades have demonstrated limited activity in most subtypes of NHL save NK/T-cell lymphoma. The hemotoxicity with anti-CD47 agents in the clinic has been speculated to account for their limitations. Herein we describe a first-in-class and rationally designed bispecific antibody (BsAb), HX009, targeting PD1 and CD47 but with weakened CD47 binding, which selectively hones the BsAb for tumor microenvironment through PD1 interaction, potentially reducing toxicity. In vitro characterization confirmed: (1) Both receptor binding/ligand blockade, with lowered CD47 affinity; (2) functional PD1/CD47 blockades by reporter assays; (3) T-cell activation in Staphylococcal-enterotoxin-B-pretreated PBMC and mixed-lymphocyte-reaction. In vivo modeling demonstrated antitumor activity in Raji-B and Karpass-229-T xenograft lymphomas. In the humanized mouse syngeneic A20 B-lymphoma (huCD47-A20) HuGEMM model, which has quadruple knocked-in hPD1xhPD-L1xhCD47xhSIRPα genes and an intact autologous immune-system, a contribution of effect is demonstrated for each targeted biologic (HX008 targeting PD1 and SIRPα-Fc targeting CD47), which is clearly augmented by the dual targeting with HX009. Lastly, the expression of the immune-checkpoints PD-L1/L2 and CD47 seemed co-regulated among a panel of lymphoma-derived-xenografts, where HX009 maybe more effective in those with upregulated CD47. Our data warrants HX009’s further clinical development for treating NHLs.

Infectious diseases pose a huge threat to human health. Human infectious diseases, especially infections originating from zoonotic or vector-borne sources, are an important global challenge. With the rising number of humans that engage in international travel, infectious disease outbreaks can spread rapidly across continents and borders worldwide. It is therefore important to monitor the transmission of infectious disease efficiently to prevent epidemics. We obtained surveillance data from the Shusi Tech Global Epidemic Information Monitoring System and comprehensively analyzed the timing and location of outbreaks in infected populations from April-June 2024.

A critical comprehension of the impact of snow cover on urban bidirectional reflectance is pivotal for precise assessments of energy budgets, radiative forcing, and urban climate change. This study develops a numerical model that employs the Monte Carlo ray-tracing technique and a snow anisotropic reflectance model (ART) to simulate spectral albedo and bidirectional reflectance, accounting for urban structure and snow anisotropy. Validation using three flat surfaces and MODIS data (snow-free, fresh snow, and melting snow scenarios) revealed minimal errors: the maximum domain-averaged BRDF bias was 0.01% for flat surfaces, and the overall model-MODIS deviation was less than 0.05. The model’s performance confirmed its accuracy in reproducing the reflectance spectrum. A thorough investigation of key factors affecting bidirectional reflectance in snow-covered urban canyons ensued, with snow coverage found to be the dominant influence. Urban coverage, building height, and soot pollutant concentration significantly impact visible and infrared reflectance, while snow grain size has the greatest effect on shortwave infrared. The bidirectional reflectance at backward scattering angles (0.5–0.6) at 645 nm is lower than forward scattering (around 0.8) in the principal plane as snow grain size increases. These findings contribute to a deeper understanding of snow-covered urban canyons’ reflectance characteristics and facilitate the quantification of radiation interactions, cloud-snow discrimination, and satellite-based retrieval of aerosol and snow parameters.

Advanced glycation end product (AGE) accumulation due to diabetes causes vascular and neurological lesions, delaying healing. The use of stem cells could overcome these problems. Although many studies have shown the potential beneficial effects of stem cell therapies in the treatment of chronic and refractory skin ulcers, their delivery methods are still under investigation. Human periodontal ligament stem cells (hPDLSCs) can spontaneously differentiate into myofibroblasts in specific cultures; therefore, they have the potential to effectively treat diabetic wounds and may also have applications in the field of medical cosmetics. The myofibroblastic differentiation ability of hPDLSCs in the presence of AGEs was evaluated by the expression of α-SMA and COL1A1 using RT-qPCR and WB technology. Wound healing in diabetic mice, induced by streptozotocin (STZ) and assessed using H&E staining, Masson staining, and immunohistochemical (IHC) and immunofluorescence (IF) staining, was used to validate the effects of hPDLSCs. In the wound tissues, the expression of α-SMA, COL1A1, CD31, CD206, iNOS, and vimentin was detected. The findings indicated that in H-DMEM, the expression of COL1A1 exhibited a significant decrease, while α-SMA demonstrated an increase in P7 cells, ignoring the damage from AGEs (p < 0.05). In an STZ-induced diabetic C57BL/6J mice whole-skin defect model, the healing rate of the hPDLSCs treatment group was significantly higher than that in the models (on the 7th day, the rate was 65.247% vs. 48.938%, p < 0.05). hPDLSCs have been shown to spontaneously differentiate into myofibroblasts in H-DMEM and resist damage from AGEs in both in vivo and in vitro models, suggesting their potential in the field of cosmetic dermatology.

The purpose of this study is to develop a smart training and assessment system called SmartCPR, for teaching and training cardiopulmonary resuscitation (CPR), based on human posture estimation techniques. In this system, trainees can automatically recognize and evaluate whether chest compressions during CPR meet the standard of high-quality CPR by simply using a device such as a smart phone. Through the system, trainees are able to obtain real-time feedback on the quality of compressions so that they can adjust the cycle, depth, frequency, and posture of compressions to meet the standard of high-quality CPR. In addition, the SmartCPR system is convenient for CPR trainers. Trainers can instantly and accurately assess whether the trainee’s compressions meet the standard of high-quality CPR, which reduces the risk of manual assessment errors and also reduces the trainer’s teaching pressures. Therefore, the SmartCPR system developed in this study can be an important tool for CPR teaching and training for physicians, which can provide training and guidance for high-quality CPR maneuvers and enable trainees to become more proficient in CPR and self-training.

Atopic dermatitis (AD), a prevalent chronic inflammatory skin disorder, is marked by impaired skin barrier function and persistent pruritus. It significantly deteriorates patients’ quality of life, making it one of the most burdensome non-lethal skin disorders. Filaggrin plays a crucial role in the pathophysiology of barrier disruption in AD, interacting with inflammatory mediators. It is an integral part of the extracellular matrix architecture, serving to protect the skin barrier and attenuate the inflammatory cascade. In this study, we engineered a novel recombinant human filaggrin (rhFLA-10) expression vector, which was subsequently synthesized and purified. In vitro and ex vivo efficacy experiments were conducted for AD. rhFLA-10, at low concentrations (5 to 20 μg/mL), was non-toxic to HACaT cells, significantly inhibited the degranulation of P815 mast cells, and was readily absorbed by cells, thereby exerting a soothing therapeutic effect. Furthermore, rhFLA-10 demonstrated anti-inflammatory properties (p < 0.05). In vivo, efficacy experiments further substantiated that rhFLA-10 could effectively ameliorate AD in mice and facilitate the repair of damaged skin (p < 0.001). These findings underscore the considerable potential of rhFLA-10 in the treatment of AD.

Objective: The Fas-activated serine/threonine kinase (FASTK) family of proteins has been recently found to be able to regulate mitochondrial gene expression post-transcriptionally. Nonetheless, there is a paucity of study about the role of the FASTK family in kidney renal clear cell carcinoma (KIRC). This study was conducted to explore the correlation of FASTK family genes with expression, prognosis, and immune infiltration in KIRC. Methods: We collected the data from the UALCAN, GeneMANIA, STRING, CancerSEA, cBioPortal, Kaplan-Meier plotter, GEPIA, TISIDB and TIMER databases to evaluate the genetic alterations, differential expression, prognostic significance, and immune cell infiltration of FASTKs in patients with KIRC. Results: In tumor tissues of KIRC, the mRNA expression level of FASTK and TBRG4 was elevated, whereas that of FASTKD1, FASTKD2, and FASTKD5 was lowered compared with normal tissues ( P