Characteristics of plastid genomes in the genus Ceratostigma inhabiting arid habitats in China and their phylogenomic implications.

BACKGROUND: Ceratostigma, a genus in the Plumbaginaceae, is an ecologically dominant group of shrubs, subshrub and herb mainly distributed in Qinghai-Tibet Plateau and North China. Ceratostigma has been the focal group in several studies, owing to their importance in economic and ecological value and unique breeding styles. Despite this, the genome information is limited and interspecific relationships within the genus Cerotastigma remains unexplored. Here we sequenced, assembled and characterized the 14 plastomes of five species, and conducted phylogenetic analyses of Cerotastigma using plastomes and nuclear ribosomal DNA (nrDNA) data. RESULTS: Fourteen Cerotastigma plastomes possess typical quadripartite structures with lengths from 164,076 to 168,355 bp that consist of a large single copy, a small single copy and a pair of inverted repeats, and contain 127-128 genes, including 82-83 protein coding genes, 37 transfer RNAs and eight ribosomal RNAs. All plastomes are highly conservative and similar in gene order, simple sequence repeats (SSRs), long repeat repeats and codon usage patterns, but some structural variations in the border of single copy and inverted repeats. Mutation hotspots in coding (Pi values > 0.01: matK, ycf3, rps11, rps3, rpl22 and ndhF) and non-coding regions (Pi values > 0.02: trnH-psbA, rps16-trnQ, ndhF-rpl32 and rpl32-trnL) were identified among plastid genomes that could be served as potential molecular markers for species delimitation and genetic variation studies in Cerotastigma. Gene selective pressure analysis showed that most protein-coding genes have been under purifying selection except two genes. Phylogenetic analyses based on whole plastomes and nrDNA strongly support that the five species formed a monophyletic clade. Moreover, interspecific delimitation was well resolved except C. minus, individuals of which clustered into two main clades corresponding to their geographic distributions. The topology inferred from the nrDNA dataset was not congruent with the tree derived from the analyses of the plastid dataset. CONCLUSION: These findings represent the first important step in elucidating plastome evolution in this widespread distribution genus Cerotastigma in the Qinghai-Tibet Plateau. The detailed information could provide a valuable resource for understanding the molecular dynamics and phylogenetic relationship in the family Plumbaginaceae. Lineage genetic divergence within C. minus was perhaps promoted by geographic barriers in the Himalaya and Hengduan Mountains region, but introgression or hybridization could not be completely excluded.

Ultrasensitive Sub-monolayer Palladium Induced Chirality Switching and Topological Evolution of Skyrmions.

Chiral spin textures are fundamentally interesting, with promise for device applications. Stabilizing chirality is conventionally achieved by introducing Dzyaloshinskii-Moriya interaction (DMI) in asymmetric multilayers, where the thickness of each layer is at least a few monolayers. Here we report an ultrasensitive chirality switching in (Ni/Co)n multilayer induced by capping with only 0.22 monolayer of Pd. Using spin-polarized low-energy electron microscopy, we monitor the gradual evolution of domain walls from left-handed to right-handed Néel walls and quantify the DMI induced by the Pd capping layer. We also observe the chiral evolution of a skyrmion during the DMI switching, where no significant topological protection is found as the skyrmion winding number varies. This corresponds to a minimum energy cost of <1 attojoule during the skyrmion chirality switching. Our results demonstrate the detailed chirality evolution within skyrmions during the DMI sign switching, which is relevant to practical applications of skyrmionic devices.

3D Interconnected Magnetic Nanowire Networks as Potential Integrated Multistate Memristors.

Interconnected magnetic nanowire (NW) networks offer a promising platform for three-dimensional (3D) information storage and integrated neuromorphic computing. Here we report discrete propagation of magnetic states in interconnected Co nanowire networks driven by magnetic field and current, manifested in distinct magnetoresistance (MR) features. In these networks, when only a few interconnected NWs were measured, multiple MR kinks and local minima were observed, including a significant minimum at a positive field during the descending field sweep. Micromagnetic simulations showed that this unusual feature was due to domain wall (DW) pinning at the NW intersections, which was confirmed by off-axis electron holography imaging. In a complex network with many intersections, sequential switching of nanowire sections separated by interconnects was observed, along with stochastic characteristics. The pinning/depinning of the DWs can be further controlled by the driving current density. These results illustrate the promise of such interconnected networks as integrated multistate memristors.

3D Nanomagnetism in Low Density Interconnected Nanowire Networks.

Free-standing, interconnected metallic nanowire networks with densities as low as 40 mg/cm3 have been achieved over centimeter-scale areas, using electrodeposition into polycarbonate membranes that have been ion-tracked at multiple angles. Networks of interconnected magnetic nanowires further provide an exciting platform to explore 3-dimensional nanomagnetism, where their structure, topology, and frustration may be used as additional degrees of freedom to tailor the materials properties. New magnetization reversal mechanisms in cobalt networks are captured by the first-order reversal curve method, which demonstrate the evolution from strong demagnetizing dipolar interactions to intersection-mediated domain wall pinning and propagation, and eventually to shape-anisotropy dominated magnetization reversal. These findings open up new possibilities for 3-dimensional integrated magnetic devices for memory, complex computation, and neuromorphics.

[Comparison of Clinical Efficacy of Thermal Ablation vs. Surgical Resection of Metachronous Colorectal Liver Metastasis].

Objective: To compare the treatment efficacy of thermal ablation versus surgical resection of metachronous colorectal liver metastasis (CRLM) and to explore the potential candidates suited for thermal ablation. Methods: The data of 319 patients with CRLM who underwent radical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences between November 2007 and January 2021 were retrospectively collected. The patients were divided into two groups, the thermal ablation group and the surgical resection group, according to the actual treatments they received. Propensity score matching (PSM) was applied to balance the baseline characteristics between the two groups. Cox regression analysis was conducted to identify the risk factors for recurrence and survival. Survival analysis was performed for intergroup comparison. Results: Using PSM at 1∶1 ratio, 92 patients were included in the thermal ablation group and 92 patients were included in the surgical resection group.The median overall survival (OS) in the thermal ablation group was 49 (95% confidence interval, 37-76) months, which was shorter than that of the surgical resection group ( P<0.01). Multivariate Cox regression analysis indicated that the T staging of primary tumor, number of metastatic tumor, maximum diameter of metastatic tumor, preoperative serum carcinoembryonic antigen (CEA) level, and treatment method were independent risk factors affecting OS. Compared with the surgical resection group, the thermal ablation group demonstrated higher hepatic recurrence rate (59.8% vs. 23.9%, P<0.01), shorter disease-free survival (DFS) (10 months vs. 33 months, P<0.01), and shorter length of hospital stay (7 days vs. 14 days, P<0.01). Subgroup analysis, conducted with the data of the 319 patients before PSM, showed that early recurrence patients who underwent thermal ablation or surgical resection had comparable median OS (29 months vs. 42 months, P=0.35). For the non-early recurrence patients, the median OS of the thermal ablation group was shorter than that of the surgical resection group ( P<0.01). Conclusion: For the treatment of CRLM, the efficacy of surgical resection was better than that of thermal ablation. However, the efficacy was comparable between the two treatments for early recurrence patients of CRLM.

Two novel mutations in TCIRG1 induced infantile malignant osteopetrosis: a case report.

BACKGROUND: Infantile malignant osteopetrosis (IMO) is a rare autosomal recessive disease characterized by a higher bone density in bone marrow caused by the dysfunction of bone resorption. Clinically, IMO can be diagnosed with medical examination, bone mineral density test and whole genome sequencing. CASE PRESENTATION: We present the case of a 4-month-old male infant with abnormal skull development, hypocalcemia and premature closure of the cranial sutures. Due to the hyper bone density showed by his radiographic examination, which are characteristic patterns of IMO, we speculated that he might be an IMO patient. In order to confirm this diagnosis, a high-precision whole exome sequencing of the infant and his parents was performed. The analysis of high-precision whole exome sequencing results lead to the identification of two novel heterozygous mutations c.504-1G > C (a splicing site mutation) and c.1371delC (p.G458Afs*70, a frameshift mutation) in gene TCIRG1 derived from his parents. Therefore, we propose that there is a close association between these two mutations and the onset of IMO. CONCLUSIONS: To date, these two novel mutations in gene TCIRG1 have not been reported in the reference gene database of Chinese population. These variants have likewise not been reported outside of China in the Genome Aggregation Database (gnomAD). Our case suggests that the use of whole exome sequencing to detect these two mutations will improve the identification and early diagnosis of IMO, and more specifically, the identification of homozygous individuals with TCIRG1 gene mutation. We propose that these mutations in gene TCIRG1 could be a novel therapeutic target for the IMO in the future.

Switch from Polymorphic to Homogenous Self-Assembly of Virus-Like Particles of Simian Virus 40 through Double-Cysteine Substitution.

Self-assembled virus-like particles (VLPs) hold great potential as natural nanomaterials for applications in many fields. For such purposes, monodisperse size distribution is a desirable property. However, the VLPs of simian virus 40 (SV40), a representative VLP platform, are characterized by polymorphism. In an attempt to eliminate the polymorphism, 15 mutants of the VLP subunit (VP1) are constructed through the substitution of double cysteines at the VP1 pentamer interfaces, generating a group of VLPs with altered size distributions. One of the mutants, SS2 (L102C/P300C), specifically forms homogenous T = 1-like tiny VLPs of 24 ± 3 nm in diameter. Moreover, the stability of the SS2 VLPs is markedly enhanced compared with that of wild-type VLPs. The homogeneous self-assembly and stability enhancement of SS2 VLPs can be attributed to the new disulfide bonds contributed by Cys102 and Cys300, which are identified by mass spectrometry and explored by molecular dynamics simulations. Endocytosis inhibition assays indicate that SS2 VLPs, like the polymorphic wild-type VLPs, preserve the multipathway feature of cellular uptake. SS2 VLPs may serve as an evolved version of SV40 VLPs in future studies and applications. The findings of this work would be useful for the design and fabrication of VLP-based materials and devices.

Unidirectional Magneto-Resistance in Modulation-Doped Magnetic Topological Insulators.

Nonlinear unidirectional spin Hall magnetoresistance (USMR) has been reported in heavy metal/ferromagnet bilayers, which could be employed as an effective method in detecting the magnetization orientation in spintronic devices with two-terminal geometry. Recently, another unidirectional magnetoresistance (UMR) was reported in magnetic topological insulator (TI)-based heterostructures at cryogenic temperature, whose amplitude is orders of magnitude larger than the USMR measured in heavy metal-based magnetic heterostructures at room temperature. Here, we report the UMR effect in the modulation-doped magnetic TI structures. This UMR arises due to the interplay between the magnetic dopant's magnetization and the current-induced surface spin polarization, when they are parallel or antiparallel to each other in the TI material. By varying the dopant's position in the structure, we reveal that the UMR is mainly originating from the interaction between the magnetization and the surface spin-polarized carriers (not bulk carriers). Furthermore, from the magnetic field-, the angular rotation-, and the temperature-dependence, we highlight the correlation between the UMR effect and the magnetism in the structures. The large UMR versus current ratio in TI-based magnetic bilayers promises the easy readout in TI-based spintronic devices with two-terminal geometry.

Interfacial States and Fano-Feshbach Resonance in Graphene-Silicon Vertical Junction.

Interfacial quantum states are drawing tremendous attention recently because of their importance in design of low-dimensional quantum heterostructures with desired charge, spin, or topological properties. Although most studies of the interfacial exchange interactions were mainly performed across the interface vertically, the lateral transport nowadays is still a major experimental method to probe these interactions indirectly. In this Letter, we fabricated a graphene and hydrogen passivated silicon interface to study the interfacial exchange processes. For the first time we found and confirmed a novel interfacial quantum state, which is specific to the 2D-3D interface. The vertically propagating electrons from silicon to graphene result in electron oscillation states at the 2D-3D interface. A harmonic oscillator model is used to explain this interfacial state. In addition, the interaction between this interfacial state (discrete energy spectrum) and the lateral band structure of graphene (continuous energy spectrum) results in Fano-Feshbach resonance. Our results show that the conventional description of the interfacial interaction in low-dimensional systems is valid only in considering the lateral band structure and its density-of-states and is incomplete for the ease of vertical transport. Our experimental observation and theoretical explanation provide more insightful understanding of various interfacial effects in low-dimensional materials, such as proximity effect, quantum tunneling, etc. More important, the Fano-Feshbach resonance may be used to realize all solid-state and scalable quantum interferometers.

Planar Hall Effect in Antiferromagnetic MnTe Thin Films.

We show that the spin-orbit coupling (SOC) in α-MnTe impacts the transport behavior by generating an anisotropic valence-band splitting, resulting in four spin-polarized pockets near Γ. A minimal k·p model is constructed to capture this splitting by group theory analysis, a tight-binding model, and ab initio calculations. The model is shown to describe the rotation symmetry of the zero-field planer Hall effect (PHE). The PHE originates from the band anisotropy given by SOC, and is quantitatively estimated to be 25%-31% for an ideal thin film with a single antiferromagnetic domain.

Effect of balloon dilation eustachian tuboplasty combined with tympanic tube insertion in the treatment of chronic recurrent secretory otitis media.

PURPOSE: To investigate the long-term clinical effect of balloon dilation eustachian tuboplasty (BET) combined with tympanic tube insertion (TTI) in the treatment of chronic recurrent secretory otitis media (CRSOM). MATERIALS AND METHODS: A retrospective study of 30 cases of CRSOM treated with BET combined with TTI under general anesthesia between August 2014 and September 2016. Thirty cases of CRSOM treated with TTI in the same period were taken as the control group. All cases were followed over 24 months. The scores of eustachian tube (ET) function preoperation, 1 month, 6 months, 12 months, and 24 months postoperation were collected and analyzed, respectively. A satisfaction questionnaire was used to evaluate the therapy at 24-months postoperation. RESULTS: The symptoms were significantly improved and the ET score was obviously increased postsurgery in most cases treated with BET plus TTI compared with those treated with TTI alone. The highest ET score was obtained at 6 months post BET. Five (14%) cases (6 ears) of CRSOM recurred. The 24-month postoperation follow-up questionnaire showed that 84.6% of the patients were satisfied with the treatment, while ten cases (25%) in the TTI group recurred. CONCLUSION: BET combined with TTI surgery is an effective therapy for patients with CRSOM.

Room-Temperature Skyrmions in an Antiferromagnet-Based Heterostructure.

Magnetic skyrmions as swirling spin textures with a nontrivial topology have potential applications as magnetic memory and storage devices. Since the initial discovery of skyrmions in non-centrosymmetric B20 materials, the recent effort has focused on exploring room-temperature skyrmions in heavy metal and ferromagnetic heterostructures, a material platform compatible with existing spintronic manufacturing technology. Here, we report the surprising observation that a room-temperature skyrmion phase can be stabilized in an entirely different class of systems based on antiferromagnetic (AFM) metal and ferromagnetic (FM) metal IrMn/CoFeB heterostructures. There are a number of distinct advantages of exploring skyrmions in such heterostructures including zero-field stabilization, tunable antiferromagnetic order, and sizable spin-orbit torque (SOT) for energy-efficient current manipulation. Through direct spatial imaging of individual skyrmions, quantitative evaluation of the interfacial Dzyaloshinskii-Moriya interaction, and demonstration of current-driven skyrmion motion, our findings firmly establish the AFM/FM heterostructures as a promising material platform for exploring skyrmion physics and device applications.

A Study of Vertical Transport through Graphene toward Control of Quantum Tunneling.

Vertical integration of van der Waals (vdW) materials with atomic precision is an intriguing possibility brought forward by these two-dimensional (2D) materials. Essential to the design and analysis of these structures is a fundamental understanding of the vertical transport of charge carriers into and across vdW materials, yet little has been done in this area. In this report, we explore the important roles of single layer graphene in the vertical tunneling process as a tunneling barrier. Although a semimetal in the lateral lattice plane, graphene together with the vdW gap act as a tunneling barrier that is nearly transparent to the vertically tunneling electrons due to its atomic thickness and the transverse momenta mismatch between the injected electrons and the graphene band structure. This is accentuated using electron tunneling spectroscopy (ETS) showing a lack of features corresponding to the Dirac cone band structure. Meanwhile, the graphene acts as a lateral conductor through which the potential and charge distribution across the tunneling barrier can be tuned. These unique properties make graphene an excellent 2D atomic grid, transparent to charge carriers, and yet can control the carrier flux via the electrical potential. A new model on the quantum capacitance's effect on vertical tunneling is developed to further elucidate the role of graphene in modulating the tunneling process. This work may serve as a general guideline for the design and analysis of vdW vertical tunneling devices and heterostructures, as well as the study of electron/spin injection through and into vdW materials.

Tailoring exchange couplings in magnetic topological-insulator/antiferromagnet heterostructures.

Magnetic topological insulators such as Cr-doped (Bi,Sb)2Te3 provide a platform for the realization of versatile time-reversal symmetry-breaking physics. By constructing heterostructures exhibiting Néel order in an antiferromagnetic CrSb and ferromagnetic order in Cr-doped (Bi,Sb)2Te3, we realize emergent interfacial magnetic phenomena which can be tailored through artificial structural engineering. Through deliberate geometrical design of heterostructures and superlattices, we demonstrate the use of antiferromagnetic exchange coupling in manipulating the magnetic properties of magnetic topological insulators. Proximity effects are shown to induce an interfacial spin texture modulation and establish an effective long-range exchange coupling mediated by antiferromagnetism, which significantly enhances the magnetic ordering temperature in the superlattice. This work provides a new framework on integrating topological insulators with antiferromagnetic materials and unveils new avenues towards dissipationless topological antiferromagnetic spintronics.

Topological Transitions Induced by Antiferromagnetism in a Thin-Film Topological Insulator.

Magnetism in topological insulators (TIs) opens a topologically nontrivial exchange band gap, providing an exciting platform for manipulating the topological order through an external magnetic field. Here, we show that the surface of an antiferromagnetic thin film can magnetize the top and the bottom TI surface states through interfacial couplings. During the magnetization reversal, intermediate spin configurations are ascribed from unsynchronized magnetic switchings. This unsynchronized switching develops antisymmetric magnetoresistance spikes during magnetization reversals, which might originate from a series of topological transitions. With the high Néel ordering temperature provided by the antiferromagnetic layers, the signature of the induced topological transition persists up to ∼90 K.

Population Genetics of the Endangered and Wild Edible Plant Ottelia acuminata in Southwestern China Using Novel SSR Markers.

Ottelia acuminata is an edible aquatic plant species that is endemic to southwestern China. This plant has experienced habitat degradation resulting from environmental change and extensive human disturbance. Determining the genetic variation and genetic structure of O. acuminata populations could help develop strategies to collect, evaluate, utilize and conserve the species. To this end, we genotyped 183 individuals sampled throughout the species distribution using twelve novel nuclear microsatellite loci (nSSRs). Eight of these nSSRs exhibited low average levels of genetic diversity (HE = 0.351, Ho = 0.376) and showed evidence of significant inbreeding across several populations. A high degree of genetic differentiation was identified among populations (FST = 0.457), probably resulting from limited pollen and seed-mediated gene flow. Only 17.8% of variation existed between O. acuminata var. acuminata and other O. acuminata varieties. Bayesian analysis and a UPGMA dendrogram based on Nei's genetic distance also revealed notably low genetic differentiation among the varieties. This low genetic differentiation is possibly attributed to shared ancestral polymorphisms since their divergence. Additional taxonomic and phylogenetic studies with additional molecular markers are needed to determine the population genetic relationship between O. acuminata varieties. Conservation of this species depends on in situ and ex situ actions, such as controlling habitat water pollution and overexploitation and creating a germplasm bank based on the population genetic differences. To the best of our knowledge, this study represents the first attempt to understand the population genetics of O. acuminata in China using novel nSSR markers developed from transcriptome sequencing and could contribute to the conservation management of this economic plant.

Room-Temperature Skyrmion Shift Device for Memory Application.

Magnetic skyrmions are intensively explored for potential applications in ultralow-energy data storage and computing. To create practical skyrmionic memory devices, it is necessary to electrically create and manipulate these topologically protected information carriers in thin films, thus realizing both writing and addressing functions. Although room-temperature skyrmions have been previously observed, fully electrically controllable skyrmionic memory devices, integrating both of these functions, have not been developed to date. Here, we demonstrate a room-temperature skyrmion shift memory device, where individual skyrmions are controllably generated and shifted using current-induced spin-orbit torques. Particularly, it is shown that one can select the device operation mode in between (i) writing new single skyrmions or (ii) shifting existing skyrmions by controlling the magnitude and duration of current pulses. Thus, we electrically realize both writing and addressing of a stream of skyrmions in the device. This prototype demonstration brings skyrmions closer to real-world computing applications.

MicroRNA expression profile in exosome discriminates extremely severe infections from mild infections for hand, foot and mouth disease.

BACKGROUND: Changes of miRNAs in exosome have been reported in different disease diagnosis and provided as potential biomarkers. In this study, we compared microRNA profile in exosomes in 5 MHFMD and 5 ESHFMD as well as in 5 healthy children. METHODS: Different expression of miRNAs in exosomes across all the three groups were screened using miRNA microarray method. Further validated test was conducted through quantitative real-time PCR assays with 54 exosome samples (18 ESHFMD, 18 MHFMD, and 18 healthy control). The judgment accuracy was then estimated by the receiver operating characteristic (ROC) curve analysis; and the specificity and sensitivity were evaluated by the multiple logistic regression analysis. RESULTS: There were 11 different miRNAs in exosomes of MHFMD and ESHFMD compared to healthy children, of which 4 were up-regulated and 7 were down-regulated. Further validation indicated that the 4 significant differentially expressed candidate miRNAs (miR-671-5p, miR-16-5p, miR-150-3p, and miR-4281) in exosome showed the same changes as in the microarray analysis, and the expression level of three miRNAs (miR-671-5p, miR-16-5p, and miR-150-3p) were significantly different between MHFMD or ESHFMD and the healthy controls. The accuracy of the test results were high with the under curve (AUC) value range from 0.79 to 1.00. They also provided a specificity of 72%-100% and a sensitivity of 78%-100%, which possessed ability to discriminate ESHFMD from MHFMD with the AUC value of 0.76-0.82. CONCLUSIONS: This study indicated that the exosomal miRNA from patients with different condition of HFMD express unique miRNA profiles. Exosomal miRNA expression profiles may provide supplemental biomarkers for diagnosing and subtyping HFMD infections.

Single-Phase L10-Ordered High Entropy Thin Films with High Magnetic Anisotropy.

The vast high entropy alloy (HEA) composition space is promising for discovery of new material phases with unique properties. This study explores the potential to achieve rare-earth-free high magnetic anisotropy materials in single-phase HEA thin films. Thin films of FeCoNiMnCu sputtered on thermally oxidized Si/SiO2 substrates at room temperature are magnetically soft, with a coercivity on the order of 10 Oe. After post-deposition rapid thermal annealing (RTA), the films exhibit a single face-centered-cubic phase, with an almost 40-fold increase in coercivity. Inclusion of 50 at.% Pt in the film leads to ordering of a single L10 high entropy intermetallic phase after RTA, along with high magnetic anisotropy and 3 orders of magnitude coercivity increase. These results demonstrate a promising HEA approach to achieve high magnetic anisotropy materials using RTA.

Predicting Survival Using Whole-Liver MRI Radiomics in Patients with Hepatocellular Carcinoma After TACE Refractoriness.

PURPOSE: To develop a model based on whole-liver radiomics features of pre-treatment enhanced MRI for predicting the prognosis of hepatocellular carcinoma (HCC) patients undergoing continued transarterial chemoembolization (TACE) after TACE-resistance. MATERIALS AND METHODS: Data from 111 TACE-resistant HCC patients between January 2014 and March 2018 were retrospectively collected. At a ratio of 7:3, patients were randomly assigned to developing and validation cohorts. The whole-liver were manually segmented, and the radiomics signature was extracted. The tumor and liver radiomics score (TLrad-score) was calculated. Models were trained by machine learning algorithms and their predictive efficacies were compared. RESULTS: Tumor stage, tumor burden, body mass index, alpha-fetoprotein, and vascular invasion were revealed as independent risk factors for survival. The model trained by Random Forest algorithms based on tumor burden, whole-liver radiomics signature, and clinical features had the highest predictive efficacy, with c-index values of 0.85 and 0.80 and areas under the ROC curve of 0.96 and 0.83 in the developing cohort and validation cohort, respectively. In the high-rad-score group (TLrad-score > - 0.34), the median overall survival (mOS) was significantly shorter than in the low-rad-score group (17 m vs. 37 m, p < 0.001). A shorter mOS was observed in patients with high tumor burden compared to those with low tumor burden (14 m vs. 29 m, p = 0.007). CONCLUSION: The combined radiomics model from whole-liver signatures may effectively predict survival for HCC patients continuing TACE after TACE refractoriness. The TLrad-score and tumor burden are potential prognostic markers for TACE therapy following TACE-resistance.