Electrolyte Engineering via Fluorinated Siloxane Solvent for Achieving High-Performance Lithium-Metal Batteries.

Advanced solvent is of important significance to develop an excellent electrolyte that simultaneously maintains a high ionic conductivity, wide electrochemical window, and good compatibility with electrodes for high-performance lithium-metal batteries (LMBs). To realize a stable electrode/electrolyte interface and a uniform lithium (Li) deposition process, an optimal fluorinated siloxane (3,3,3-trifluoropropyltrimethoxysilane, TFTMS) is proposed as a cosolvent with 1,2-dimethoxyethane (DME) and highly antioxidative fluoroethylene carbonate (FEC) to formulate a Li-metal compatibility electrolyte. The TFTMS-based electrolyte presents high oxidization stability, high Li+ conductivity, and high Li+ transfer number, contributing to the accelerated reaction kinetics, homogeneous Li deposition behavior, and stable interfacial chemistry. Therefore, high Li stripping/plating reversibility (∼99%) and stable cycling (1400 h) are achieved in the TFTMS-based electrolyte, giving rise to the excellent electrochemical performance of practical Li-metal full cells. Moreover, an industrial 4 Ah NCM811|Gr pouch cell with the TFTMS-based electrolyte is demonstrated to display similar cycling performance with the commercial carbonate electrolyte in 120 cycles at 1 C. This work offers an approach toward high-performance LMBs through rational electrolyte design with fluorinated siloxane solvent.

Functional characteristics of DNA N6-methyladenine modification based on long-read sequencing in pancreatic cancer.

Abnormalities of DNA modifications are closely related to the pathogenesis and prognosis of pancreatic cancer. The development of third-generation sequencing technology has brought opportunities for the study of new epigenetic modification in cancer. Here, we screened the N6-methyladenine (6mA) and 5-methylcytosine (5mC) modification in pancreatic cancer based on Oxford Nanopore Technologies sequencing. The 6mA levels were lower compared with 5mC and upregulated in pancreatic cancer. We developed a novel method to define differentially methylated deficient region (DMDR), which overlapped 1319 protein-coding genes in pancreatic cancer. Genes screened by DMDRs were more significantly enriched in the cancer genes compared with the traditional differential methylation method (P < 0.001 versus P = 0.21, hypergeometric test). We then identified a survival-related signature based on DMDRs (DMDRSig) that stratified patients into high- and low-risk groups. Functional enrichment analysis indicated that 891 genes were closely related to alternative splicing. Multi-omics data from the cancer genome atlas showed that these genes were frequently altered in cancer samples. Survival analysis indicated that seven genes with high expression (ADAM9, ADAM10, EPS8, FAM83A, FAM111B, LAMA3 and TES) were significantly associated with poor prognosis. In addition, the distinction for pancreatic cancer subtypes was determined using 46 subtype-specific genes and unsupervised clustering. Overall, our study is the first to explore the molecular characteristics of 6mA modifications in pancreatic cancer, indicating that 6mA has the potential to be a target for future clinical treatment.

Unraveling temporal and spatial biomarkers of epithelial-mesenchymal transition in colorectal cancer: insights into the crucial role of immunosuppressive cells.

The occurrence and progression of tumors can be established through a complex interplay among tumor cells undergoing epithelial-mesenchymal transition (EMT), invasive factors and immune cells. In this study, we employed single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (ST) to evaluate the pseudotime trajectory and spatial interactive relationship between EMT-invasive malignant tumors and immune cells in primary colorectal cancer (CRC) tissues at different stages (stage I/II and stage III with tumor deposit). Our research characterized the spatiotemporal relationship among different invasive tumor programs by constructing pseudotime endpoint-EMT-invasion tumor programs (EMTPs) located at the edge of ST, utilizing evolution trajectory analysis integrated with EMT-invasion genes. Strikingly, the invasive and expansive process of tumors undergoes remarkable spatial reprogramming of regulatory and immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), regulatory T cells (Treg), and exhausted T cells (Tex). These EMTP-adjacent cell are linked to EMT-related invasion genes, especially the C-X-C motif ligand 1 (CXCL1) and CXCL8 genes that are important for CRC prognosis. Interestingly, the EMTPs in stage I mainly produce an inflammatory margin invasive niche, while the EMTPs in stage III tissues likely produce a hypoxic pre-invasive niche. Our data demonstrate the crucial role of regulatory and immunosuppressive cells in tumor formation and progression of CRC. This study provides a framework to delineate the spatiotemporal invasive niche in CRC samples.

Fluorinated Nonflammable In Situ Gel Polymer Electrolyte for High-Voltage Lithium Metal Batteries.

Rechargeable lithium metal batteries (LMBs) offer excellent opportunities for applications requiring high-energy-density battery systems. So far, it has received a lot of interest in pairing higher-energy-density high-voltage nickel-rich cathodes. Here, fluorinated solvents were used instead of the usual carbonate solvents to prepare gel polymer electrolytes (FGPE) by in situ polymerization of polymers introducing the fluorine-containing groups. Theoretically and experimentally, FGPE has proven to be ultra-compatible with the lithium metal anode and LiNi0.8Co0.1Mn0.1O2 cathode. A stable plating/stripping process of over 2000 h can be achieved for symmetrical lithium cells using FGPE. The Li||FGPE||NCM811 cell has a longer cycle life at a high voltage (4.5 V). In addition, the zero self-extinguishing time indicates that the FGPE has sufficient safety. In summary, the design of this electrolyte provides ideas to improve the safety and energy density of LMBs.

Developing CuS for Predicting Aggressiveness and Prognosis in Lung Adenocarcinoma.

Cuproptosis is a newfound cell death form that depends on copper (Cu) ionophores to transport Cu into cancer cells. Studies on the relationship have covered most common cancer types and analyzed the links between cuproptosis-related genes (CRGs) and various aspects of tumor characteristics. In this study, we evaluated the role of cuproptosis in lung adenocarcinoma (LUAD) and constructed the cuproptosis-related score (CuS) to predict aggressiveness and prognosis in LUAD, so as to achieve precise treatment for patients. CuS had a better predictive performance than cuproptosis genes, possibly due to the synergy of SLC family genes, and patients with a high CuS had a poor prognosis. Functional enrichment analysis revealed the correlation between CuS and immune and mitochondrial pathways in multiple datasets. Furthermore, we predicted six potential drugs targeting high-CuS patients, including AZD3759, which is a targeted drug for LUAD. In conclusion, cuproptosis is involved in LUAD aggressiveness, and CuS can accurately predict the prognosis of patients. These findings provide a basis for precise treatment of patients with high CuS in LUAD.

Time-Varying Functional Connectivity of Rat Brain during Bipedal Walking on Unexpected Terrain.

The cerebral cortex plays an important role in human and other animal adaptation to unpredictable terrain changes, but little was known about the functional network among the cortical areas during this process. To address the question, we trained 6 rats with blocked vision to walk bipedally on a treadmill with a random uneven area. Whole-brain electroencephalography signals were recorded by 32-channel implanted electrodes. Afterward, we scan the signals from all rats using time windows and quantify the functional connectivity within each window using the phase-lag index. Finally, machine learning algorithms were used to verify the possibility of dynamic network analysis in detecting the locomotion state of rats. We found that the functional connectivity level was higher in the preparation phase compared to the walking phase. In addition, the cortex pays more attention to the control of hind limbs with higher requirements for muscle activity. The level of functional connectivity was lower where the terrain ahead can be predicted. Functional connectivity bursts after the rat accidentally made contact with uneven terrain, while in subsequent movement, it was significantly lower than normal walking. In addition, the classification results show that using the phase-lag index of multiple gait phases as a feature can effectively detect the locomotion states of rat during walking. These results highlight the role of the cortex in the adaptation of animals to unexpected terrain and may help advance motor control studies and the design of neuroprostheses.

Feature extraction of 3D Chinese rose model based on color and shape features.

Flower classification is of great importance to the research fields of plants, food, and medicine. Due to more abundant information on three-dimensional (3D) flower models than two-dimensional 2D images, it makes the 3D models more suitable for flower classification tasks. In this study, a feature extraction and classification method were proposed based on the 3D models of Chinese roses. Firstly, the shape distribution method was used to extract the sharpness and contour features of 3D flower models, and the color features were obtained from the Red-Green-Blue (RGB) color space. Then, the RF-OOB method was employed to rank the extracted flower features. A shape descriptor based on the unique attributes of Chinese roses was constructed, χ2 distance was adopted to measure the similarity between different Chinese roses. Experimental results show that the proposed method was effective for the retrieval and classification tasks of Chinese roses, and the average classification accuracy was approximately 87%, which can meet the basic retrieval requirements of 3D flower models. The proposed method promotes the classification of Chinese roses from 2D space to 3D space, which broadens the research method of flower classification.

Revealing the Potential Markers of N(4)-Acetylcytidine through acRIP-seq in Triple-Negative Breast Cancer.

Understanding the causes of tumorigenesis and progression in triple-receptor negative breast cancer (TNBC) can help the design of novel and personalized therapies and prognostic assessments. Abnormal RNA modification is a recently discovered process in TNBC development. TNBC samples from The Cancer Genome Atlas database were categorized according to the expression level of NAT10, which drives acetylation of cytidine in RNA to N(4)-acetylcytidine (ac4C) and affects mRNA stability. A total of 703 differentially expressed long non-coding RNAs (lncRNAs) were found between high- and low-expressed NAT10 groups in TNBC. Twenty of these lncRNAs were significantly associated with prognosis. Two breast cancer tissues and their paired normal tissues were sequenced at the whole genome level using acetylated RNA immunoprecipitation sequencing (acRIP-seq) technology to identify acetylation features in TNBC, and 180 genes were significantly differentially ac4c acetylated in patients. We also analyzed the genome-wide lncRNA expression profile and constructed a co-expression network, containing 116 ac4C genes and 1080 lncRNAs. Three of these lncRNAs were prognostic risk lncRNAs affected by NAT10 and contained in the network. The corresponding reciprocal pairs were "LINC01614-COL3A1", "OIP5-AS1-USP8", and "RP5-908M14.9-TRIR". These results indicate that RNA ac4c acetylation involves lncRNAs and affects the tumor process and prognosis of TNBC. This will aid the prediction of drug targets and drug sensitivity.

Classification of Subgroups with Immune Characteristics Based on DNA Methylation in Luminal Breast Cancer.

Luminal breast cancer (BC) accounts for a large proportion of patients in BC, with high heterogeneity. Determining the precise subtype and optimal selection of treatment options for luminal BC is a challenge. In this study, we proposed an MSBR framework that integrate DNA methylation profiles and transcriptomes to identify immune subgroups of luminal BC. MSBR was implemented both on a key module scoring algorithm and "Boruta" feature selection method by DNA methylation. Luminal A was divided into two subgroups and luminal B was divided into three subgroups using the MSBR. Furthermore, these subgroups were defined as different immune subgroups in luminal A and B respectively. The subgroups showed significant differences in DNA methylation levels, immune microenvironment (immune cell infiltration, immune checkpoint PD1/PD-L1 expression, immune cell cracking activity (CYT)) and pathology features (texture, eccentricity, intensity and tumor-infiltrating lymphocytes (TILs)). The results also showed that there is a subgroup in both luminal A and B that has the benefit from immunotherapy. This study proposed a classification of luminal BC from the perspective of epigenetics and immune characteristics, which provided individualized treatment decisions.

Effect of neuromorphic transcutaneous electrical nerve stimulation (nTENS) of cortical functional networks on tactile perceptions: an event-related electroencephalogram study.

Background.Transcutaneous electrical nerve stimulation (TENS) is generally applied for tactile feedback in the field of prosthetics. The distinct mechanisms of evoked tactile perception between stimulus patterns in conventional TENS (cTENS) and neuromorphic TENS (nTENS) are relatively unknown. This is the first study to investigate the neurobiological effect of nTENS for cortical functional mechanism in evoked tactile perception.Methods.Twenty-one healthy participants were recruited in this study. Electroencephalogram (EEG) was recorded while the participants underwent a tactile discrimination task. One cTENS pattern (square pattern) and two nTENS patterns (electromyography and single motor unit patterns) were applied to evoke tactile perception in four fingers, including the right and left index and little fingers. EEG was preprocessed and somatosensory-evoked potentials (SEPs) were determined. Then, source-level functional networks based on graph theory were evaluated, including clustering coefficient, path length, global efficiency, and local efficiency in six frequency bands.Main results.Behavioral results suggested that the single motor units (SMUs) pattern of nTENS was the most natural tactile perception. SEPs results revealed that SMU pattern exhibited significant shorter latency in P1 and N1 components than the other patterns, while nTENS patterns have significantly longer latency in P3 component than cTENS pattern. Cortical functional networks showed that the SMU pattern had the lowest short path and highest efficiency in beta and gamma bands.Conclusion.This study highlighted that distinct TENS patterns could affect brain activities. The new characteristics in tactile manifestation of nTENS would provide insights for the application of tactile perception restoration.

Sex-Specific Difference in Outcomes after Transcatheter Mitral Valve Repair with MitraClip Implantation: A Systematic Review and Meta-Analysis.

Background: Implantation of the MitraClip is a safe and effective therapy for mitral valve repair in patients ineligible for surgery or at high risk of adverse surgical outcomes. However, only limited information is available concerning sex differences in transcatheter mitral valve repair. We therefore sought to conduct a comprehensive meta-analysis of studies that investigated differences between men and women in outcomes following MitraClip implantation. Methods: The PubMed and Embase databases were searched until November 2019 for studies reporting outcomes after MitraClip implantation in women versus men. Outcomes included all-cause mortality and major complications at 30 days and one year of follow-up. Results: Six studies (n = 1,109 women; n = 1,743 men) were analyzed. At 30 days, women had a similar risk of postoperative complications, such as stroke, major bleeding, and pericardium effusion, without differences in all-cause mortality, procedure success, or MitraClip usage. At one year, the all-cause mortality, the reduction of mitral regurgitation, and the risk of rehospitalization for heart failure were also comparable between male and female patients. Conclusion: Gender disparity was not found in complications or prognosis of patients undergoing MitraClip implantation. This study suggests that gender should not be considered as a critical factor in the selection of patients as candidates for MitraClip implantation of concern during follow-up.

DiseaseMeth version 3.0: a major expansion and update of the human disease methylation database.

DNA methylation has a growing potential for use as a biomarker because of its involvement in disease. DNA methylation data have also substantially grown in volume during the past 5 years. To facilitate access to these fragmented data, we proposed DiseaseMeth version 3.0 based on DiseaseMeth version 2.0, in which the number of diseases including increased from 88 to 162 and High-throughput profiles samples increased from 32 701 to 49 949. Experimentally confirmed associations added 448 pairs obtained by manual literature mining from 1472 papers in PubMed. The search, analyze and tools sections were updated to increase performance. In particular, the FunctionSearch now provides for the functional enrichment of genes from localized GO and KEGG annotation. We have also developed a unified analysis pipeline for identifying differentially DNA methylated genes (DMGs) from the original data stored in the database. 22 718 DMGs were found in 99 diseases. These DMGs offer application in disease evaluation using two self-developed online tools, Methylation Disease Correlation and Cancer Prognosis & Co-Methylation. All query results can be downloaded and can also be displayed through a box plot, heatmap or network module according to whichever search section is used. DiseaseMeth version 3.0 is freely available at http://diseasemeth.edbc.org/.

Multisite Simultaneous Neural Recording of Motor Pathway in Free-Moving Rats.

Neural interfaces typically focus on one or two sites in the motoneuron system simultaneously due to the limitation of the recording technique, which restricts the scope of observation and discovery of this system. Herein, we built a system with various electrodes capable of recording a large spectrum of electrophysiological signals from the cortex, spinal cord, peripheral nerves, and muscles of freely moving animals. The system integrates adjustable microarrays, floating microarrays, and microwires to a commercial connector and cuff electrode on a wireless transmitter. To illustrate the versatility of the system, we investigated its performance for the behavior of rodents during tethered treadmill walking, untethered wheel running, and open field exploration. The results indicate that the system is stable and applicable for multiple behavior conditions and can provide data to support previously inaccessible research of neural injury, rehabilitation, brain-inspired computing, and fundamental neuroscience.

Spinal Cord Injury-Induced Changes in Encoding and Decoding of Bipedal Walking by Motor Cortical Ensembles.

Recent studies have shown that motor recovery following spinal cord injury (SCI) is task-specific. However, most consequential conclusions about locomotor functional recovery from SCI have been derived from quadrupedal locomotion paradigms. In this study, two monkeys were trained to perform a bipedal walking task, mimicking human walking, before and after T8 spinal cord hemisection. Importantly, there is no pharmacological therapy with nerve growth factor for monkeys after SCI; thus, in this study, the changes that occurred in the brain were spontaneous. The impairment of locomotion on the ipsilateral side was more severe than that on the contralateral side. We used information theory to analyze single-cell activity from the left primary motor cortex (M1), and results show that neuronal populations in the unilateral primary motor cortex gradually conveyed more information about the bilateral hindlimb muscle activities during the training of bipedal walking after SCI. We further demonstrated that, after SCI, progressively expanded information from the neuronal population reconstructed more accurate control of muscle activity. These results suggest that, after SCI, the unilateral primary motor cortex could gradually regain control of bilateral coordination and motor recovery and in turn enhance the performance of brain-machine interfaces.

Preparation of Si-Mn/biochar composite and discussions about characterizations, advances in application and adsorption mechanisms.

A novel Si-Mn binary modified biochar composite material (SMBC) was prepared after being sintered 450 °C for 2 h. The crystal structure, surface functional groups, surface morphology and element composition, specific surface area and pore structure were characterized by XRD, FTIR, XPS, SEM + EDS and BET etc. The results showed that the surface of SMBC was rough and loose, and the specific surface area increased to 35.4284 m2/g. Si and Mn were uniformly attached to the surface of biochar in the form of SiO2, MnOx, MnSiO3. Batch adsorption experiments showed that SMBC had a higher removal efficiency (139.06 mg/g, above 98%) for Cu(II) when the dosage was 2 g/L and pH = 6. The cycle experiments showed that SMBC had good reusability, and its regeneration efficiency still reached 80.24%. The leaching amount of Mn (0.65 mg/L) was greatly reduced and avoid second-pollution resulted from ion exchange, which was attributed to the existence of Si-O-Mn bonds, and they could help Mn adhere to the surface of biochar more stable. The adsorption process was dominated by single-layer chemical adsorption and mainly occurred in the membrane diffusion stage. Cu(II) mainly formed -COOCu, -OCu, Cu(OH)2, Cu(OH)2CO3, Si-O-Cu, Mn-O-Cu by the mechanisms such as precipitation (4.74%), ion exchange (13.81%), complexation and physical adsorption (total 81.45% of the two mechanisms). Among them, complexation was dominant in the adsorption process.

Mixed biochar obtained by the co-pyrolysis of shrimp shell with corn straw: Co-pyrolysis characteristics and its adsorption capability.

The co-pyrolysis characteristics of shrimp shell (SS) with corn straw (CS) were investigated by comprehensive characterization to reveal the synergistic effects and further discuss the adsorption capability. TGA results showed that pyrolysis behavior and reactivity were improved with the increase of heating rate and doping ratio of CS. Flynn-Wall-Ozawa (FWO) and distributed activation energy model (DAEM) indicated that co-pyrolysis can effectively reduce energy consumption and promote the decomposition of CaCO3. TG-FTIR and Py-GC/MS analysis indicated that the release of CH4, CO2, CO and NH3 at the doping ratio of 25% CS (75SS+25CS) was higher than that at other doping ratios, and the relative proportions of N-heterocyclics and oxygenates were lower, which was conducive to the development of pore structure for mixed biochar and effectively alleviated the pollution during co-pyrolysis process. The structure of mixed biochar was improved, confirmed by the characterizations of BET, SEM, FTIR and XRD. The mixed biochar prepared at 800 °C (75SS+25CS800) exhibited optimal porosity, aromatization and the most thorough CaCO3 decomposition. Batch adsorption experiment showed that the removal rate of 50 mg/L Cu(II) by 75SS+25CS800 was close to 100% under the dosage of 1 g/L and pH = 3-6. The adsorption process was well described by Langmuir, pseudo-second-order and Webber-Morris model, illustrating diffusion monolayer chemisorption was the main adsorption mechanism of Cu(II) on 75SS+25CS800. The maximum adsorption capacity of 75SS+25CS800 for Cu(II) was 79.77 mg/g at 35 °C. In short, this study provided a reference in optimizing the preparation process and improving the adsorption performance of mixed biochar.

Unexpected Terrain Induced Changes in Cortical Activity in Bipedal-Walking Rats.

Humans and other animals can quickly respond to unexpected terrains during walking, but little is known about the cortical dynamics in this process. To study the impact of unexpected terrains on brain activity, we allowed rats with blocked vision to walk on a treadmill in a bipedal posture and then walk on an uneven area at a random position on the treadmill belt. Whole brain EEG signals and hind limb kinematics of bipedal-walking rats were recorded. After encountering unexpected terrain, the θ band power of the bilateral M1, the γ band power of the left S1, and the θ to γ band power of the RSP significantly decreased compared with normal walking. Furthermore, when the rats left uneven terrain, the ß band power of the bilateral M1 and the α band power of the right M1 decreased, while the γ band power of the left M1 significantly increased compared with normal walking. Compared with the flat terrain, the θ to low ß (3-20 Hz) band power of the bilateral S1 increased after the rats contacted the uneven terrain and then decreased in the single- or double- support phase. These results support the hypothesis that unexpected terrains induced changes in cortical activity.

Impact of atrial fibrillation on outcomes of patients treated by transcatheter mitral valve repair: A systematic review and meta-analysis.

BACKGROUND: Conflicting data have been reported related to the impact of atrial fibrillation (AF) on outcomes after transcatheter mitral valve repair with MitraClip (MC) implantation. In this study, we assessed the prognosis of MC-treated patients according to the presence of pre-existing AF. METHODS: Randomized and observational studies reporting outcomes of pre-existing AF or sinus rhythm in patients undergoing MC treatment were identified with an electronic search. Outcomes of interest were short-and long-term mortality, stroke, bleeding, rehospitalization, myocardial infarction (MI), cardiogenic shock, acute procedure success, the hospital stay, and the number of Clips implanted. RESULTS: Eight studies (8466 individuals) were eligible. Compared to sinus rhythm, long-term mortality, the risk of bleeding, rehospitalization, and longer hospital stay were significantly higher in AF groups, whereas similar correlations were found in the analysis of other outcomes. CONCLUSION: AF may be related with worse outcomes in patients undergoing MC implantation, including long-term mortality, major bleeding, and rehospitalization. AF should be taken into account when referring a patient for MC treatment.

Paracrine Interactions Involved in Human Induced Pluripotent Stem Cells Differentiation into Chondrocytes.

Osteoarthritis (OA), as a degenerative joint disease, is the most common form of joint disorder that causes pain, stiffness, and other symptoms associated with OA. Various genetic, biomechanical, and environmental factors have a relevant role in the development of OA. To date, extensive efforts are currently being made to overcome the poor self-healing capacity of articular cartilage. Despite the pivotal role of chondrocytes, their proliferation and repair capacity after tissue injury are limited. Therefore, the development of new strategies to overcome these constraints is urgently needed. Recent advances in regenerative medicine suggest that pluripotent stem cells are promising stem cell sources for cartilage repair. Pluripotent stem cells are undifferentiated cells that have the capacity to differentiate into different types of cells and can self-renew indefinitely. In the past few decades, numerous attempts have been made to regenerate articular cartilage by using induced pluripotent stem cells (iPSCs). The potential applications of patient-specific iPSCs hold great promise for regenerative medicine and OA treatment. However, there are different culture conditions for the preparation and characterization of human iPSCs-derived chondrocytes (hiChondrocytes). Recent biochemical analyses reported that several paracrine factors such as TGFb, BMPs, WNT, Ihh, and Runx have been shown to be involved in cartilage cell proliferation and differentiation from human iPSCs. In this review, we summarize and discuss the paracrine interactions involved in human iPSCs differentiation into chondrocytes in different cell culture media.

Alternative treatment strategies to sorafenib in patients with advanced hepatocellular carcinoma: a meta-analysis of randomized Phase III trials.

INTRODUCTION: This meta-analysis was conducted to evaluate efficacy and safety in patients treated with sorafenib vs other tyrosine-kinase inhibitors (TKIs) or selective internal radiotherapy (SIRT) for advanced hepatocellular carcinoma (HCC). METHODS: Electronic databases were systematically reviewed for randomized Phase III trials comparing sorafenib with other TKIs or SIRT in advanced HCC. Sorafenib was defined as the control arm. Other TKIs or SIRT was defined as the experimental arm. Overall survival (OS), time to progression (TTP), objective response rate (ORR), disease-control rate (DCR), and adverse events (AEs) were reviewed. Four trials in the other-TKI group (n=4,218) and two in the SIRT group (n=819) were eligible. RESULTS: Compared with sorafenib, other TKIs showed similar benefit on OS (HR 1.08, 95% CI 0.93-1.24; P=0.31) and TTP (HR 0.86, 95% CI 0.66-1.12; P=0.26) for advanced HCC. A significant increase in ORR (RR 1.67, 95% CI 1.15-2.43; P=0.008) was found with other TKIs, but no increase in DCR (RR 1.11, 95% CI 0.98-1.26; P=0.11) was observed. Other TKIs were associated with more frequent grade 3/4 AEs than sorafenib, including hypertension (P<0.00001), thrombocytopenia (P=0.002), fatigue (P<0.00001), decreased appetite (P<0.00001), and vomiting (P<0.0001). For locally advanced HCC, neither OS (HR 1.14, 95% CI 0.98-1.32; P=0.09) nor TTP (HR 0.87, 95% CI 0.74-1.02; P=0.10) differed significantly in SIRT and sorafenib. There was an increase in ORR (RR 2.60, 95% CI 1.69-4.00; P<0.0001), but no improvement in DCR (RR 0.91, 95% CI 0.81-1.02; P=0.11) in the SIRT group. Fewer patients treated with SIRT had grade 3/4 AEs than those treated with sorafenib, including diarrhea (P<0.0001), fatigue (P=0.0006), and hand-foot syndrome (P=0.0002). Other TKIs were noninferior to sorafenib in OS and TTP in advanced HCC, but with increased risk of toxicities. CONCLUSION: Patients with locally advanced HCC treated with SIRT got similar efficacy with less toxicity to those treated with sorafenib.