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Xu-Hua Duan,1,2 Teng-Fei Li,2 Guo-Feng Zhou,1,* Xin-Wei Han,2,* Chuan-Sheng Zheng,1 Peng-fei Chen,2 Gan-Sheng Feng11Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 2Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, Henan Province, Zhengzhou, People’s Republic of China*These authors contributed equally to this work Purpose: To evaluate the effect of transcatheter arterial embolization (TAE) combined with radiofrequency ablation (RFA) treatment (TAE + RFA) on the expression of heat shock protein 70 (HSP70) in residual tumors and explore the relationship between the HSP70 and CD8+ T-cell infiltrate surrounding residual tumors in the rabbit VX2 liver tumor model.Materials and methods: Animals with VX2 liver tumors were randomized into four groups (control, TAE, RFA, and TAE + RFA) with 15 rabbits in each group. Five rabbits in each group were sacrificed on days 1, 3, and 7 after treatment. HSP70 expression and infiltration of CD8+ T-cells in the liver and residual tumors surrounding the necrosis zone were detected by immunohistochemistry staining. The maximal diameters of tumor necrosis, numbers of metastases, and tumor growth rate were compared on day 7 after treatment.Results: TAE + RFA achieved larger maximal diameter of tumor necrosis, lower tumor growth rate, and fewer metastatic lesions, compared with other treatments on day 7. The number of CD8+ T-cells in the TAE + RFA group was significantly higher than in other groups on days 1, 3, and 7. There was a positive correlation between HSP70 expression level and infiltration of CD8+ T-cells surrounding the residual tumor on day 1 (r=0.9782, P=0.012), day 3 (r=0.93, P=0.021), and day 7 (r=0.8934, P=0.034).Conclusion: In the rabbit VX2 liver tumor model, TAE + RFA activated the highest number of CD8+ T-cells surrounding residual tumors. TAE + RFA appears to be a beneficial therapeutic modality for tumor control and antitumor immune response in this model.Keywords: transcatheter arterial embolization, radiofrequency ablation, heat shock protein 70, CD8+ T-cells, liver tumor

Lighting Research & Technology (LRT) is an influential journal in the field of light and lighting dating back to 1969. To celebrate its 50th birthday, the current study explored its bibliometric characteristics and mapped the bibliographic information graphically through VOSviewer software. This analysis found that the number of papers has steadily increased during recent years. The most productive and cited country was the United Kingdom. The most productive and cited institution was Rensselaer Polytechnic Institute. The most prolific author was Steve Fotios and the most cited author was Mark Rea. The journal most cited together with LRT was Leukos. LRT has become more and more international and interdisciplinary over the last five decades. Suggestions for the development of LRT are provided. Develpoments over the last 50 years have turned LRT into one of leading journals in the light and lighting field, one which has a bright future. [ABSTRACT FROM AUTHOR]

Staufen-1 (STAU1) is a double-stranded RNA-binding protein (RBP) involved in a variety of pathological conditions. In this study, we investigated the potential role of STAU1 in Alzheimer's disease (AD), in which two hallmarks are well-established as cerebral β-amyloid protein (Aβ) deposition and Tau-centered neurofibrillary tangles. We found that STAU1 protein level was significantly increased in cells that stably express full-length APP and the brain of APP/PS1 mice, an animal model of AD. STAU1 knockdown, as opposed to overexpression, significantly decreased the protein levels of β-amyloid converting enzyme 1 (BACE1) and Aβ. We further found that STAU1 extended the half-life of the BACE1 mRNA through binding to the 3' untranslated region (3'UTR). Transcriptome analysis revealed that STAU1 enhanced the expression of growth arrest and DNA damage 45 β (GADD45B) upstream of P38 MAPK signaling, which contributed to STAU1-induced regulation of Tau phosphorylation at Ser396 and Thr181. Together, STAU1 promoted amyloidogenesis by inhibiting BACE1 mRNA decay, and augmented Tau phosphorylation through activating GADD45B in relation to P38 MAPK. Targeting STAU1 that acts on both amyloidogenesis and tauopathy may serve as an optimistic approach for AD treatment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Guo-Jun Chen reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Mitochondrial Ts translation elongation factor (TSFM) is an enzyme that catalyzes exchange of guanine nucleotides. By forming a complex with mitochondrial Tu translation elongation factor (TUFM), TSFM participates in mitochondrial protein translation. We have previously reported that TUFM regulates translation of beta-site APP cleaving enzyme 1 (BACE1) via ROS (reactive oxygen species)-dependent mechanism, suggesting a potential role in amyloid precursor protein (APP) processing associated with Alzheimer's disease (AD), which led to the speculation that TSFM may regulate APP processing in a similar way to TUFM., Methods and Results: Here, we report that in cultured cells, knockdown or overexpression TSFM did not change protein levels in BACE1 and APP. Besides, the levels of cytoplasmic ROS and mitochondrial superoxide, in addition to ATP level, cell viability and mitochondrial membrane potential were not significantly altered by TSFM knockdown in the short term. Further transcriptome analysis revealed that expression of majority of mitochondrial genes were not remarkably changed by TSFM silencing. The possibility of TSFM involved in cardiomyopathy and cancer development was uncovered using bioinformatics analysis., Conclusions: Collectively, short-term regulation of TSFM level in cultured cells does not cause a significant change in proteins involved in APP processing, levels in ROS and ATP associated with mitochondrial function. Whereas our study could contribute to comprehend certain clinical features of TSFM mutations, the roles of TSFM in cardiomyopathy and cancer development might deserve further investigation., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

It is long been suggested that one-carbon metabolism (OCM) is associated with Alzheimer's disease (AD), whereas the potential mechanisms remain poorly understood. Taking advantage of chemical biology, that mitochondrial serine hydroxymethyltransferase (SHMT2) directly regulated the translation of ADAM metallopeptidase domain 10 (ADAM10), a therapeutic target for AD is reported. That the small-molecule kenpaullone (KEN) promoted ADAM10 translation via the 5' untranslated region (5'UTR) and improved cognitive functions in APP/PS1 mice is found. SHMT2, which is identified as a target gene of KEN and the 5'UTR-interacting RNA binding protein (RBP), mediated KEN-induced ADAM10 translation in vitro and in vivo. SHMT2 controls AD signaling pathways through binding to a large number of RNAs and enhances the 5'UTR activity of ADAM10 by direct interaction with GAGGG motif, whereas this motif affected ribosomal scanning of eukaryotic initiation factor 2 (eIF2) in the 5'UTR. Together, KEN exhibits therapeutic potential for AD by linking OCM with RNA processing, in which the metabolic enzyme SHMT2 "moonlighted" as RBP by binding to GAGGG motif and promoting the 5'UTR-dependent ADAM10 translation initiation., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Parasitoid wasps control pests via a precise attack leading to the death of the pest. However, parasitoid larvae exhibit self-protection strategies against bracovirus-induced reactive oxygen species impairment. This has a detrimental effect on pest control. Here, we report a strategy for simulating Microplitis bicoloratus bracovirus using Mix-T dsRNA targeting 14 genes associated with transcription, translation, cell-cell communication, and humoral signaling pathways in the host, and from wasp extracellular superoxide dismutases. We implemented either one-time feeding to the younger instar larvae or spraying once on the corn leaves, to effectively control the invading pest Spodoptera frugiperda . This highlights the conserved principle of "biological pest control," as elucidated by the triple interaction of parasitoid-bracovirus-host in a cooperation strategy of bracovirus against its pest host., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Ma, Long, Yan, Peng, Cai, Zhong, Huang, Qiao, Zhou, Cai, Cheng, Zhou, Han, Liu, Zhang, Tang, Meng and Luo.)

TNFAIP3-interacting protein 2 (TNIP2) is known as a negative regulator of NF-κB signaling and inhibit inflammatory response and apoptosis, and is also involved in RNA metabolism. In this study, we investigated the potential role of TNIP2 in amyloidogenesis critically associated with Alzheimer's disease (AD). We found a significant decline of TNIP2 protein level in both mouse and cell model of AD. In SH-SY5Y and HEK cells that stably express human full-length APP695 (SY5Y-APP and HEK-APP), TNIP2 overexpression decreased the protein levels of β-secretase (BACE1) and C99, as well as Aβ peptides (including Aβ40 and Aβ42), while those of α-secretase (ADAM10) and the related C83 remained unchanged. We further found that TNIP2 promoted the degradation of BACE1 mRNA and was able to bound to the 3' untranslated region (3'UTR) with the reduced luciferase activity. These results indicated that TNIP2 effectively inhibited amyloidogenic processing by regulating the 3'UTR-associated mRNA decay of BACE1., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Zika virus (ZIKV) infection is associated with the birth defect microcephaly and Guillain-Barré syndrome in adults. There is no approved vaccine or specific antiviral agent against ZIKV. ZFD-10, a novel structural skeleton of 1H-pyridazino[4,5-b]indol-4(5H)-one, was firstly synthesized and discovered to be a potent anti-ZIKV inhibitor with very low cytotoxicity. ZFD-10's anti-ZIKV potency is independent of cell lines and ZFD-10 mainly targets the post-entry stages of ZIKV life cycle. Time-of-addition and time-of-withdrawal assays showed that 10 μM ZFD-10 displayed the ability to decrease mainly at the RNA level and weakly the viral progeny particle load. Furthermore, ZFD-10 could protect ZIKV NS5 from thermal unfolding and aggregation and increase the Tagg value of ZIKV NS5 protein from 44.6 to 49.3 °C, while ZFD-10 dose-dependently inhibits ZIKV NS5 RdRp activity using in vitro RNA polymerase assays. Molecular docking study suggests that ZFD-10 affects RdRp enzymatic function through interfering with the fingers and thumb subdomains. These results supported that ZFD-10's cell-based anti-ZIKV activity is related to its anti-RdRp activity of ZIKV NS5. The in vivo anti-ZIKV study shows that the middle-dose (4.77 mg/kg/d) of ZFD-10 protected mice from ZIKV infection and the viral loads of the blood, liver, kidney and brain in the middle-dose and high-dose (9.54 mg/kg/d) were significantly reduced compared to those of the ZIKV control. These results confirm that ZFD-10 has a certain antiviral effect against ZIKV infection in vivo., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Exploring the potential lead compounds for Alzheimer's disease (AD) remains one of the challenging tasks. Here, we report that the plant extract conophylline (CNP) impeded amyloidogenesis by preferentially inhibiting BACE1 translation via the 5' untranslated region (5'UTR) and rescued cognitive decline in an animal model of APP/PS1 mice. ADP-ribosylation factor-like protein 6-interacting protein 1 (ARL6IP1) was then found to mediate the effect of CNP on BACE1 translation, amyloidogenesis, glial activation, and cognitive function. Through analysis of the 5'UTR-targetd RNA-binding proteins by RNA pulldown combined with LC-MS/MS, we found that FMR1 autosomal homolog 1 (FXR1) interacted with ARL6IP1 and mediated CNP-induced reduction of BACE1 by regulating the 5'UTR activity. Without altering the protein levels of ARL6IP1 and FXR1, CNP treatment promoted ARL6IP1 interaction with FXR1 and inhibited FXR1 binding to the 5'UTR both in vitro and in vivo. Collectively, CNP exhibited a therapeutic potential for AD via ARL6IP1. Through pharmacological manipulation, we uncovered a dynamic interaction between FXR1 and the 5'UTR in translational control of BACE1, adding to the understanding of the pathophysiology of AD.

Aims: Amyloid beta (Aβ) is an important pathological feature of Alzheimer's disease (AD). A disintegrin and metalloproteinase 10 (ADAM10) can reduce the production of toxic Aβ by activating the nonamyloidogenic pathway of amyloid precursor protein (APP). We previously found that apicidin, which is a histone deacetylase (HDAC) inhibitor, can promote the expression of ADAM10 and reduce the production of Aβ in vitro. This study was designed to determine the potential of apicidin treatment to reverse learning and memory impairments in an AD mouse model and the possible correlation of these effects with ADAM10., Methods: Nine-month-old APP/PS1 mice and C57 mice received intraperitoneal injections of apicidin or vehicle for 2 months. At 11 months of age, we evaluated the memory performance of mice with Morris water maze (MWM) and context fear conditioning tests. The Aβ levels were assessed in mouse brain using the immunohistochemical method and ELISA. The expression of corresponding protein involved in proteolytic processing of APP and the phosphorylation of tau were assessed by Western blotting., Results: Apicidin reversed the deficits of spatial reference memory and contextual fear memory, attenuated the formation of Aβ-enriched plaques, and decreased the levels of soluble and insoluble Aβ40/42 in APP/PS1 mice. Moreover, apicidin significantly increased the expression of ADAM10, improved the level of sAPPα, and reduced the production of sAPPβ, but did not affect the levels of phosphorylated tau in APP/PS1 mice., Conclusion: Apicidin significantly improves the AD symptoms of APP/PS1 mice by regulating the expression of ADAM10, which may contribute to decreasing the levels of Aβ rather than decreasing the phosphorylation of tau., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Objective: To explore the surgical methods and clinical outcomes of severe angular kyphosis with the length of the spinal cord constant in the osteotomy area. Methods: Clinical data from 20 patients with severe angular kyphosis who underwent surgical treatment from January 2017 to December 2020 in the Department of Spinal Surgery,Hangzhou Xiaoshan District Hospital of Traditional Chinese Medicine were retrospectively analyzed. There were 11 males and 9 females, aged (28.5±8.9) years (range:17 to 46 years).There were 15 cases with congenital angular kyphosis,5 cases with tuberculous angular kyphosis.The angle of kyphosis was (107.1±12.9)° (range:93.2° to 131.4°).Frankel classification:2 cases with grade B,4 cases with grade C,3 cases with grade D.The kyphotic vertex is located at the T 9 to T 12 segments.Pedicle screws were placed in 3 or 4 adjacent segments at the proximal and distal kyphosis apex of the patients using a surgical navigation system.Piezosurgery combined with a grinding drill was used to complete the osteotomy in the apical vertebral region.Titanium mesh or artificial vertebral body was implanted,and the osteotomy surface was closed using this as the fulcrum to complete osteotomy.Spinal X-ray examination was performed before surgery,immediately after surgery and at the last follow-up,and sagittal and coronal Cobb angle,sagittal and coronary balance parameters,anterior vertebral height,posterior vertebral height,and spinal cord length were measured.Pulmonary function,visual analogue scale (VAS),and Oswestry's disability index (ODI) were collected and estimated before and after treatment.The analysis of variance of repeated measurement data was used for each evaluation index before and after treatment,and the t test was used for pairwise comparison. Results: All patients successfully completed surgery,with artificial vertebral body in 11 cases and double titanium mesh in 9 cases.The follow-up time was (28.2±2.3) months (range:26 to 31 months).Sagittal vertical axis improved from (46.9±13.7)mm(range:21.7 to 75.7 mm) before surgery to (10.7±5.5)mm (range:3.6 to 28.1 mm) after surgery,and (11.0±5.7)mm(range:3.6 to 29.3 mm) at the last follow-up,the differences were statistically significant compared to before surgery (all P <0.01).The mean kyphotic Cobb angle was corrected from (107.1±12.9) ° (range:93.2 ° to 131.4°) before surgery to (30.6±8.5) ° (range:20.0 ° to 47.8 °) after surgery (all P <0.01),and (32.1±8.7) ° (range:18.2 ° to 50.8°) at the last follow-up,the differences were statistically significant compared to before surgery(all P <0.01).The anterior vertebral height improved from (14.2±2.9)mm(range:11.04 to 23.6 mm) before surgery to (45.3±7.5)mm(range:29.4 to 56.5 mm) after surgery,and (44.3±6.8)mm(range:29.6 to 56.0 mm) at the last follow-up,the differences were statistically significant compared to before surgery (all P <0.01).The posterior vertebral height was improved from (51.8±5.3)mm (range:43.1 to 61.4 mm)before surgery to (57.6±4.7)mm (range:45.7 to 64.1 mm)after surgery,and (56.3±5.0) mm (range:49.7 to 68.5 mm) at the last follow-up,the differences were statistically significant compared to before surgery (all P <0.01).The spinal cord length of the osteotomy segment was (73.1±12.0)mm (range:56.8 to 98.4 mm) before surgery and (74.8±12.8)mm (range:53.5 to 100.2 mm) after surgery and (75.2±13.7)mm (range:53.9 to 102.4 mm) at the last follow-up,the difference was not statistically significant among them( F =0.144, P =0.866).The ODI and VAS scores improved significantly after surgery and at the last follow-up,and the differences were statistically significant (all P <0.01). Conclusion: The posterior vertebral column resection technique combined with titanium mesh or an artificial vertebral body implant for the treatment of severe angular kyphosis can significantly improve the kyphosis,neurological function,and life quality of patients without affecting the length of the spinal cord.

The prevalence and ravages of Zika virus (ZIKV) seriously endanger human health, especially causing significant neurological defects in both neonates as pediatric microcephaly and adults as Guillain-Barré syndrome. In this work, we studied anti-ZIKV effects of the fused tricyclic derivatives of indoline and imidazolidinone and discovered that some of them are valuable leads for drug discovery of anti-ZIKV agents. The current results show that certain compounds are broad-spectrum inhibitors of ZIKV- and dengue virus (DENV)-infection while distinctive compounds are selective ZIKV inhibitors or selective DENV inhibitors. Compounds of 12, 17 and 28 are more active against Asian ZIKV SZ-VIV01 strain than African ZIKV MR766 strain. It is valued that silylation makes six TBS compounds of 4-nitrophenyl hydrazine series and phenyl hydrazine series more active against ZIKV infection than their phenols. Time-of-addition and withdrawal studies indicate that compound 12 majorly acts on post-infection of RNA synthesis stage of ZIKV life cycle. Moreover, compounds of 12, 17 and 18 are anti-ZIKV agents with the inhibitory activities to ZIKV NS5 RdRp while 12 doesn't inhibit DENV infection even though it is a DENV RdRp inhibitor, 17 is an active agent against DENV infection but is only a weak DENV NS5 RdRp inhibitor, and 28 is inactive against DENV infection and not a DENV NS5 RdRp inhibitor. As a result, a compound's antiviral difference between ZIKV and DENV is not always related to anti-RdRp difference between ZIKV RdRp and DENV RdRp, and structural features of a compound play important roles in executing antiviral and anti-RdRp functions. Further discovery of highly potent broad-spectrum or selective agents against infection by ZIKV and DENV will be facilitated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Zika Virus (ZIKV) infection is a global threat. Other than the congenital neurological disorders it causes, ZIKV infection has been reported to induce cardiac complications. However, the precise treatment plans are unclear. Thus, illustrating the pathogenic mechanism of ZIKV in the heart is critical to providing effective prevention and treatment of ZIKV infection. The mechanism of autophagy has been reported recently in Dengue virus infection. Whether or not autophagy participates in ZIKV infection and its role remains unrevealed. This study successfully established the in vitro cardiomyocytes and in vivo mouse models of ZIKV infection to investigate the involvement of autophagy in ZIKV infection. The results showed that ZIKV infection is both time and gradient-dependent. The key autophagy protein, LC3B, increased remarkably after ZIKV infection. Meanwhile, autophagic flux was detected by immunofluorescence. Applying autophagy inhibitors decreased the LC3B levels. Furthermore, the number of viral copies was quantified to evaluate the influence of autophagy during infection. We found that autophagy was actively involved in the ZIKV infection and the inhibition of autophagy could effectively reduce the viral copies, suggesting a potential intervention strategy for reducing ZIKV infection and the undesired complications caused by ZIKV., (© 2023 Wiley Periodicals LLC.)

Background: Accumulation of hyperphosphorylated Tau (pTau) contributes to the formation of neurofibrillary tangles in Alzheimer's disease (AD), and targeting Tau/pTau metabolism has emerged as a therapeutic approach. We have previously reported that mitochondrial 3-hydroxy-3-methylglutaryl-COA synthase 2 (HMGCS2) is involved in AD by promoting autophagic clearance of amyloid-β protein precursor via ketone body-associated mechanism, whether HMGCS2 may also regulate Tau metabolism remains elusive., Objective: The present study was to investigate the role of HMGCS2 in Tau/p degradation., Methods: The protein levels of Tau and pTau including pT217 and pT181, as well as autophagic markers LAMP1 and LC3-II were assessed by western blotting. The differentially regulated genes by HMGCS2 were analyzed by RNA sequencing. Autophagosomes were assessed by transmission electron microscopy., Results: HMGCS2 significantly decreased Tau/pTau levels, which was paralleled by enhanced formation of autophagic vacuoles and prevented by autophagic regulators chloroquine, bafilomycin A1, 3-methyladenine, and rapamycin. Moreover, HMGCS2-induced alterations of LAMP1/LC3-II and Tau/pTau levels were mimicked by ketone body acetoacetate or β-hydroxybutyrate. Further RNA-sequencing identified ankyrin repeat domain 24 (ANKRD24) as a target gene of HMGCS2, and silencing of ANKRD24 reduced LAMP1/LC3-II levels, which was accompanied by the altered formation of autophagic vacuoles, and diminished the effect of HMGCS2 on Tau/pTau., Conclusion: HMGCS2 promoted autophagic clearance of Tau/pTau, in which ketone body and ANKRD24 played an important role.

AP2S1 is the sigma 2 subunit of adaptor protein 2 (AP2) that is essential for endocytosis. In this study, we investigated the potential role of AP2S1 in intracellular processing of amyloid precursor protein (APP), which contributes to the pathogenesis of Alzheimer disease (AD) by generating the toxic β-amyloid peptide (Aβ). We found that knockdown or overexpression of AP2S1 decreased or increased the protein levels of APP and Aβ in cells stably expressing human full-length APP695, respectively. This effect was unrelated to endocytosis but involved lysosomal degradation. Morphological studies revealed that silencing of AP2S1 promoted the translocalization of APP from RAB9-positive late endosomes (LE) to LAMP1-positive lysosomes, which was paralleled by the enhanced LE-lysosome fusion. In support, silencing of vacuolar protein sorting-associated protein 41 (VPS41) that is implicated in LE-lyso fusion prevented AP2S1-mediated regulation of APP degradation and translocalization. In APP/PS1 mice, an animal model of AD, AAV-mediated delivery of AP2S1 shRNA in the hippocampus significantly reduced the protein levels of APP and Aβ, with the concomitant APP translocalization, LE-lyso fusion and the improved cognitive functions. Taken together, these data uncover a LE-lyso fusion mechanism in APP degradation and suggest a novel role for AP2S1 in the pathophysiology of AD., (© 2022 The Authors. Traffic published by John Wiley & Sons Ltd.)

Infection by Zika virus (ZIKV), a mosquito-transmitted arbovirus and a member of Flavivirus, could make pediatric microcephaly and Guillain-Barré syndrome, which remains an ongoing global threat. The efficient antivirals to ZIKV infection are of great medical need. Andrographolide and its analogues were discovered to be active against flaviviral infection. In this study, we discovered some dehydroandrographolide derivatives of 3-oximido- or 3-alcohol-19-hindered ether to be potent anti-ZIKV agents with low cytotoxicities (CC 50  > 200 μM). Time of addition assay suggests that compound 5a and its analogues act on inhibition of post-entry stage of ZIKV life cycle. It is discovered by experimental and molecular docking studies that active anti-ZIKV compounds of 3a, 5a, 5b and 5c possess inhibitory activities of ZIKV NS5 MTase (methyl transferase) enzymatic activity. Preliminary SAR reveals that C19-modification with bulky groups is necessary for anti-ZIKV infection and replication, anti-ZIKV activity of 5a comes from itself bearing hindered trityl ether but not from its instability, the backbone of dehydroandrographolide is more effective against ZIKV infection than that of andrographolide, and 3-oxime derivatives are more active against ZIKV infection than 3-alcohol derivatives. To our knowledge, 5a is the first reported MTase inhibitor of andrographolide derivatives. More importantly, discovery of active compound 5b with acid-stable 19-OCHPh 2 against ZIKV infection is valued and gives us a clue to design and discover generally acid-stable anti-ZIKV agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Zika virus (ZIKV), a mosquito-borne flavivirus, is a global health concern because of its association with severe neurological disorders such as neonatal microcephaly and adult Guillain-Barre syndrome. Although many efforts have been made to combat ZIKV infection, there is currently no approved vaccines or antiviral drugs available and there is an urgent need to develop effective anti-ZIKV agents. In this study, 26 acetylarylamine- S -DACOs derivatives were prepared, and eight of them were found to have inhibitory activity against Zika virus. Among these substances, 2-[(4-cyclohexyl-5-ethyl-6-oxo-1,6-dihydropyrimidin-2-yl)thio]-N-(3,5-difluorophenyl)acetamide ( 4w ) with the best anti-ZIKV activity was selected for in-depth study of antiviral activity and mechanism of action. Here, we discovered 4w targeted on the ZIKV NS5 RNA -dependent RNA polymerase (RdRp), which exhibited good in vitro antiviral activity without cell species specificity, both at the protein level and at the RNA level can significantly inhibit ZIKV replication. Preliminary molecular docking studies showed that 4w preferentially binds to the palm region of NS5A RdRp through hydrogen bonding with residues such as LYS468, PHE466, GLU465, and GLY467. ZIKV NS5 RdRp enzyme activity experiment showed that 4w could directly inhibit ZIKV RdRp activity with EC 50 = 11.38 ± 0.51 μM. In antiviral activity studies, 4w was found to inhibit ZIKV RNA replication with EC 50 = 6.87 ± 1.21 μM. ZIKV-induced plaque formation was inhibited with EC 50 = 7.65 ± 0.31 μM. In conclusion, our study disclosed that acetylarylamine- S -DACOs is a new active scaffolds against ZIKV, among which compound 4w was proved to be a potent novel anti-ZIKV compound target ZIKV RdRp protein. These promising results provide a future prospective for the development of ZIKV RdRp inhibitors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Xie, Xue, Wang, Yang, Zheng, Luo, Yang, Chen, Yang, Wang, Zhang, He and Zheng.)

A new iso-C 14 [Val 2 , Val 7 ] surfactin isoform ( 1 ) together with eight known ones ( 2 - 9 ), was isolated from the culture of a mushroom derived bacterium, Bacillus halotolerans DMG-7-2. The structures of them were mainly elucidated by NMR and MS data, and the NMR data of 5 also was reported for the first time. The absolute configuration of 1 was determined by Marfey's analysis (for amino acid residues) and the 13 C NMR calculation of the two plausible epimers of 1 (for fatty acid). Compounds 1 - 9 showed moderate cytotoxicity against two human cancer cell lines (A549, MCF-7) and mice microglial BV2 cells, the IC 50 values ranged from 8.91 to 33.00  µ M, and the IC 50 values of the positive control 5-FU were 99.94, 71.49 and 0.12  µ M, respectively.[Formula: see text].

Objective: Apatinib is a novel inhibitor of vascular endothelial growth factor receptor-2. The goal of this study was to evaluate overall survival (OS) after a combination of transarterial chemoembolization (TACE) and apatinib in patients with advanced hepatocellular carcinoma (HCC) and to identify the factors affecting patient survival., Methods: Fifty-one patients with advanced HCC who received TACE in combination with apatinib in our hospital from June 2015 to May 2017 were enrolled. The OS and progression-free survival (PFS) were calculated using the Kaplan-Meier method. The log-rank test and Cox regression model were used to determine the factors affecting OS., Results: The median OS and PFS of the patients were 15 months and 10 months, respectively. The 1-, 2-, and 3-year survival rates were 64.7%, 23.5%, and 1.8%, respectively. Univariate survival analysis showed that patients with Child-Pugh A (P=0.006), reduction rate of proper hepatic artery (P=0.016), hand-foot syndrome (P=0.005), secondary hypertension (P=0.050), and without ascites (P=0.010) had a better OS. Multivariate analysis showed that hand-foot syndrome (P=0.014), secondary hypertension (P=0.017), and reduction rate of proper hepatic artery (P=0.025) were independent predictors of better OS., Conclusion: TACE combined with apatinib is a promising treatment for advanced HCC. Hand-foot syndrome, secondary hypertension, and the reduction rate of proper hepatic artery were associated with a better OS., (© 2022. Huazhong University of Science and Technology.)

Spinocerebellar ataxias (SCAs) are a large group of hereditary neurodegenerative diseases characterized by ataxia and dysarthria. Due to high clinical and genetic heterogeneity, many SCA families are undiagnosed. Herein, using linkage analysis, WES, and RP-PCR, we identified the largest SCA36 pedigree in Asia. This pedigree showed some distinct clinical characteristics. Cognitive impairment and gaze palsy are common and severe in SCA36 patients, especially long-course patients. Although no patients complained of hearing loss, most of them presented with hearing impairment in objective auxiliary examination. Voxel-based morphometry (VBM) demonstrated a reduction of volumes in cerebellum, brainstem, and thalamus (corrected P < 0.05). Reduced volumes in cerebellum were also found in presymptomatic carriers. Resting-state functional MRI (R-fMRI) found reduced ReHo values in left cerebellar posterior lobule (corrected P < 0.05). Diffusion tensor imaging (DTI) demonstrated a reduction of FA values in cerebellum, midbrain, superior and inferior cerebellar peduncle (corrected P < 0.05). MRS found reduced NAA/Cr values in cerebellar vermis and hemisphere (corrected P < 0.05). Our findings could provide new insights into management of SCA36 patients. Detailed auxiliary examination are recommended to assess hearing or peripheral nerve impairment, and we should pay more attention to eye movement and cognitive changes in patients. Furthermore, for the first time, our multimodel neuroimaging evaluation generate a full perspective of brain function and structure in SCA36 patients., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A typical characteristics of polydnavirus (PDV) infection is a persistent immunosuppression, governed by the viral integration and expression of virulence genes. Recently, activation of caspase-3 by Microplitis bicoloratus bracovirus (MbBV) to cleave Innexins, gap junction proteins, has been highlighted, further promoting apoptotic cell disassembly and apoptotic body (AB) formation. However, whether ABs play a role in immune suppression remains to be determined. Herein, we show that ABs transmitted immunosuppressive signaling, causing recipient cells to undergo apoptosis and dismigration. Furthermore, the insertion of viral-host integrated motif sites damaged the host genome, stimulating eIF5A nucleocytoplasmic transport and activating the eIF5A-hypusination translation pathway. This pathway specifically translates apoptosis-related host proteins, such as P53, CypA, CypD, and CypJ, to drive cellular apoptosis owing to broken dsDNA. Furthermore, translated viral proteins, such Vank86, 92, and 101, known to complex with transcription factor Dip3, positively regulated DHYS and DOHH transcription maintaining the activation of the eIF5A-hypusination. Mechanistically, MbBV-mediated extracellular vesicles contained inserted viral fragments that re-integrated into recipients, potentially via the homologous recombinant repair system. Meanwhile, this stimulation regulated activated caspase-3 levels via PI3K/AKT 308 and 473 dephosphorylation to promote apoptosis of granulocyte-like recipients Sf9 cell; maintaining PI3K/AKT 473 phosphorylation and 308 dephosphorylation inhibited caspase-3 activation leading to dismigration of plasmatocyte-like recipient High Five cells. Together, our results suggest that integration-mediated eIF5A hypusination drives extracellular vesicles for continuous immunosuppression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Chen, Cai, Yan, Peng, Li, Cui, Han, Zhang, Meng, Tang, Cai, Long and Luo.)

Dengue virus, belonging to a genus Flavivirus, caused public health problem in recent years. One controversial vaccine of DENV was approved and there is no antiviral for the clinic treatment of DENV, therefore, efficient antivirals to DENV are of great medical significance. In this study, we conducted the design, synthesis, cell-based and target-based activity evaluation of 28 compounds based on indoline structural skeleton against DENV infection. Among them, 13 active compounds against DENV infection were discovered and their structure-activity relationship (SAR) was summarized. In this study, indoline carbohydrazine has derived more active compounds than indoline carboamide. It is discovered that TBS group exhibits a good pharmacophore to enhance anti-DENV activity. Further exploration indicated that post-treatment acts as effective time of addition and compound 15 targeting the post-entry stages of DENV2 viral life cycle. SPR imaging results support there are strong interaction of 13 and 15 with RdRp and compounds 13 and 15 reduce RdRp enzymatic activity, revealing that RdRp of DENV NS5 is the drug target for these series of compounds. Molecular docking deciphered the relationship of the structural feature with the putative binding mode by 13 and 15 with RdRp domain of DENV2 NS5 by hydrogen bonds and hydrophobic interactions to establish the fitted low energy conformation. Future studies will focus on designing more potent inhibitors for the treatment and prevention of dengue virus replication and infection, and understanding the more profound underlying structural features of inhibitors and drug action of the mechanism., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The levels and ratios of sugar and acid are important contributors to fruit taste. Kumquat is one of the most economically important citrus crops, but information on the soluble sugar and organic acid metabolism in kumquat is limited. Here, two kumquat varieties - 'Rongan' (RA) and its mutant 'Huapi' (HP) - were used to assess soluble sugar and organic acid accumulation and the related genes., Results: Soluble sugars include sucrose, glucose and fructose, while malate, quinic acid and citrate are the dominant organic acids in the fruits of both kumquat varieties. HP accumulated more sugars but fewer organic acids than did RA. Transcriptome analysis revealed 63 and 40 differentially expressed genes involved in soluble sugar and organic acid accumulation, respectively. The genes associated with sugar synthesis and transport, including SUS, SPS, TST, STP and ERD6L, were up-regulated, whereas INVs, FRK and HXK genes related to sugar degradation were down-regulated in HP kumquat. For organic acids, the up-regulation of PEPC and NAD-MDH could accelerate malate accumulation. In contrast, high expression of NAD-IDH and GS resulted in citric acid degradation during HP fruit development. Additionally, the PK, PDH, PEPCK and FBPase genes responsible for the interconversion of soluble sugars and organic acids were also significantly altered in the early development stages in HP., Conclusion: The high sugar accumulation in HP fruit was associated with up-regulation of SUS, SPS, TST, STP and ERD6L genes. The PEPCK, PEPC, NAD-MDH, NADP-IDH, GS and FBPase genes played important roles in acid synthesis and degradation in HP kumquat. These findings provide further insight into understanding the mechanisms underlying metabolism of sugars and organic acids in citrus. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Objectives: Response evaluation criteria in solid tumors (RECIST) often fail to identify clinically meaningful response to bevacizumab-containing therapy in colorectal liver metastasis (CRLM). This study aimed to develop RECIST by combining contrast-enhanced and diffusion-weighted magnetic resonance imaging (MRI)., Methods: A total of 126 patients with CRLM who underwent hepatic resection after bevacizumab-containing chemotherapy were split into initial analyses cohort (N = 42, with 76 indexed liver metastases) and validation cohort (N = 84). In lesion-based analyses, percentage decrease of arterial enhancement area and percentage increase of apparent diffusion coefficient (ADC) value from baseline to post-chemotherapy were measured. Their optimal cutoff values for distinguishing pathology-confirmed major and minor response were determined. Then, the developed RECIST (D-RECIST) was established by combining functional and size-based items. Survival relevance of D-RECIST and RECIST was examined in the validation cohort., Results: Percentage decrease of arterial enhancement area and increase of ADC value significantly differed between lesions of pathologic major or minor response, with optimal cutoffs of approximately 33% and 19%, respectively. Patients defined as responders by D-RECIST had a significantly longer median disease-free survival (DFS) than non-responders (p = 0.021; 12.9 versus 8.6 months). No significant difference was observed with RECIST (p = 0.524). In a Cox regression model, D-RECIST- but not RECIST-defined responses independently predicted the DFS (p = 0.034 and 0.811)., Conclusions: D-RECIST-defined responses provided significant prognostic information, and thus may serve as a better response evaluation approach than RECIST in CRLM treated with bevacizumab-containing therapy., Key Points: • Changes in arterial enhancement area and apparent diffusion coefficient value are associated with pathological response in colorectal liver metastases treated with bevacizumab. • The MRI-based response criteria developed by combining size-based and functional features can provide significant prognostic information., (© 2021. European Society of Radiology.)

Thermal ablation in combination with transarterial chemoembolization (TACE) has been reported to exert a more powerful antitumor effect than thermal ablation alone in hepatocellular carcinoma patients. However, the underlying mechanisms remain unclear. The purpose of the present study was to evaluate whether sublethal hyperthermia encountered in the periablation zone during thermal ablation enhances the anticancer activity of doxorubicin in chronically hypoxic (encountered in the tumor area after TACE) liver cancer cells and to explore the underlying mechanisms. In the present study, HepG2 cells precultured under chronic hypoxic conditions (1% oxygen) were treated in a 42°C water bath for 15 or 30 min, followed by incubation with doxorubicin. Assays were then performed to determine intracellular uptake of doxorubicin, cell viability, apoptosis, cell cycle, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and total antioxidant capacity. The results confirmed that sublethal hyperthermia enhanced the intracellular uptake of doxorubicin into hypoxic HepG2 cells. Hyperthermia combined with doxorubicin led to a greater inhibition of cell viability and increased apoptosis in hypoxic HepG2 cells as compared with hyperthermia or doxorubicin alone. In addition, the combination induced apoptosis by increasing ROS and causing disruption of MMP. Pretreatment with the ROS scavenger N-acetyl cysteine significantly inhibited the apoptotic response, suggesting that cell death is ROS-dependent. These findings suggested that sublethal hyperthermia enhances the anticancer activity of doxorubicin in hypoxic HepG2 cells via a ROS-dependent mechanism., (© 2021 The Author(s).)

Rationale: Cervical spondylotic radiculopathy (CSR) is a common sensory, motor, and reflex disorder. Numbness, a common subjective symptom of CSR, lacks objective quantitative indicators and recognized effective treatments, but is also difficult to recover from. We present a case report describing a traditional acupuncture treatment for CSR, utilizing a special acupuncture method and point, namely the Yunmen point., Patient Concerns: A 40-year-old woman presented with unilateral arm numbness caused by CSR., Diagnoses: A diagnosis of CSR was made in the orthopedic department of a local hospital., Interventions: We attempted acupuncture at the Yunmen (LU 2) acupoint combined with neck-seven-acupoint under computed tomographic guidance., Outcomes: After 10 times treatment sessions, the patient no longer experienced weakness, coldness, or numbness in the affected upper limb. In addition, the stiffness in the neck and shoulders was reduced. On physical examination, the patient's left brachial plexus traction test was negative; reassessment of the CSR-20-point score scale showed a perfect score, and the visual analog scale score was 0., Lessons: Our report indicates that acupuncture at the LU 2 acupoint combined with neck-seven-acupoint is effective in treating numbness and coldness of the arm, and other neurological symptoms caused by cervical spondylosis. Moreover, with the appropriate acupuncture technique, the risk of acupuncture at the LU 2 acupoint can be minimized., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Thioredoxin-2 (TXN2) is a mitochondrial protein and represents one of the intrinsic antioxidant enzymes. It has long been recognized that mitochondrial dysfunction and oxidative stress contribute to the pathogenesis of Alzheimer's disease (AD). We hypothesized that mitochondrial TXN2 might play a role in AD-like pathology. In this study, we found that in SH-SY5Y and HEK cells stably express full-length human amyloid-β precursor protein (HEK-APP), TXN2 silencing or over-expression selectively increased or decreased the transcription of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), respectively, without altering the protein levels of others enzymes involved in the catalytic processing of APP. As a result, β-amyloid protein (Aβ) levels were significantly decreased by TXN2. In addition, in cells treated with 3-nitropropionic acid (3-NP) that is known to increase reactive oxygen species (ROS) and promote mitochondrial dysfunction, TXN2 silencing resulted in further enhancement of BACE1 protein levels, suggesting a role of TXN2 in ROS removal. The downstream signaling might involve NFκB, as TXN2 reduced the phosphorylation of p65 and IκBα; and p65 knockdown significantly attenuated TXN2-mediated regulation of BACE1. Concomitantly, the levels of cellular ROS, apoptosis-related proteins and cell viability were altered by TXN2 silencing or over-expression. In APPswe/PS1E9 mice, an animal model of AD, the cortical and hippocampal TXN2 protein levels were decreased at 12 months but not at 6 months, suggesting an age-dependent decline. Collectively, TXN2 regulated BACE1 expression and amyloidogenesis via cellular ROS and NFκB signaling. TXN2 might serve as a potential target especially for early intervention of AD., (© 2020 International Society for Neurochemistry.)

Microplitis bicoloratus bracovirus (MbBV) inhibits the immune response of the host Spodoptera litura by disrupting nuclear factor (NF)-κB signaling and downstream gene expression. However, the underlying molecular mechanisms are not well understood. Herein, we report that viral ankyrin (Vank) proteins interacted with host dorsal-interacting protein 3 (Dip3) to selectively inhibit the transcription of eukaryotic translation initiation factor 4 E (eIF4E). Dip3 and Vank proteins were co-expressed and colocalized in the nucleus. Furthermore, ectopic expression of Dip3 rescued the transcription of some NF-κB-dependent genes suppressed by Vank proteins, including eIF4E. Co-immunoprecipitation and pull-down assays confirmed that Vank proteins interacted with and bound to full-length Dip3, which including MADF, DNA-binding protein, BESS, and protein-protein interaction motifs as well as non-motif sequences. In vivo, RNAi-mediated dip3 silencing decreased eIF4E levels and was accompanied by an immunosuppressive phenotype in S. litura. Our results provided novel insights into the regulation of host transcription during immune suppression by viral proteins that modulate nuclear NF-κB signaling., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Mitochondrial Tu translation elongation factor (TUFM or EF-Tu) is part of the mitochondrial translation machinery. It is reported that TUFM expression is reduced in the brain of Alzheimer's disease (AD), suggesting that TUFM might play a role in the pathophysiology. In this study, we found that TUFM protein level was decreased in the hippocampus and cortex especially in the aged APP/PS1 mice, an animal model of AD. In HEK cells that stably express full-length human amyloid-β precursor protein (HEK-APP), TUFM knockdown or overexpression increased or reduced the protein levels of β-amyloid protein (Aβ) and β-amyloid converting enzyme 1 (BACE1), respectively. TUFM-mediated reduction of BACE1 was attenuated by translation inhibitor cycloheximide (CHX) or α-[2-[4-(3,4-Dichlorophenyl)-2-thiazolyl]hydrazinylidene]-2-nitro-benzenepropanoic acid (4EGI1), and in cells overexpressing BACE1 constructs deleting the 5' untranslated region (5'UTR). TUFM silencing increased the half-life of BACE1 mRNA, suggesting that RNA stability was affected by TUFM. In support, transcription inhibitor Actinomycin D (ActD) and silencing of nuclear factor κB (NFκB) failed to abolish TUFM-mediated regulation of BACE1 protein and mRNA. We further found that the mitochondria-targeted antioxidant TEMPO diminished the effects of TUFM on BACE1, suggesting that reactive oxygen species (ROS) played an important role. Indeed, cellular ROS levels were affected by TUFM knockdown or overexpression, and TUFM-mediated regulation of apoptosis and Tau phosphorylation at selective sites was attenuated by TEMPO. Collectively, TUFM protein levels were decreased in APP/PS1 mice. TUFM is involved in AD pathology by regulating BACE1 translation, apoptosis, and Tau phosphorylation, in which ROS plays an important role., (© 2021 Federation of American Societies for Experimental Biology.)

Five new peptaibols, longibramides A-E (1-5) with 11 amino acid residues, were isolated from a fungus Trichoderma longibrachiatum Rifai DMG-3-1-1, which was isolated from a mushroom Clitocybe nebularis (Batsch) P. Kumm collected from coniferous forest in the subboreal area of northeast China. The structures of longibramides A-E were determined by their spectroscopic data (NMR and MS-MS spectra), their absolute configurations were determined by X-ray diffractions and Marfey's analyses. The X-ray diffractions of longibramides A, B, and the similar CD spectra of A-E showed that they all had α-helix conformations. Longibramides B and E showed moderate cytotoxicities against BV2 and MCF-7 cells and also showed some inhibitory effects against methicillin-resistant Staphylococcus aureus MRSA T144. L-trans-Hyp was not commonly found in natural peptaibols, which was the 6 th or 10 th amino acid residue in longibramides C-E. The X-ray diffractions of longibramides A and B afforded the accuracy conformations of their secondary structures, which maybe help to interpret the structure-activity relationships of the family of peptaibols in the future., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

Objective: Accuracy of preoperative T-staging for colon cancer remains disappointing and may potentially influenced by patients' individual characteristics including visceral adipose tissue (VAT). We sought to clarify the impact of VAT on the accuracy of T-staging by CT., Methods: This study of 216 consecutive patients who underwent elective surgery was conducted in a single cancer center, to control other potentially confounding factors. Patients were divided into accurate- and mis-staging groups according to the comparison between preoperative CT-defined (cT) and postoperative pathologic T-stages (pT). Patients' individual characteristics, including CT-based VAT at L2/L3 level, age, sex, body mass index (BMI), tumor location, present of bowel obstruction and pathologic subtype, were compared between the two groups. Association between VAT and mis-staging was assessed using multivariate logistic regression to adjust for confounders., Results: Of the 216 patients, 84 (39%) were mis-staged by CT. The mean VAT in accurate-staging group was significantly higher than that in mis-staging group (146.8 ± 66.1 cm 2 vs 98.1 ± 44.7 cm 2 , P < 0.001), with an optimal cutoff point of 122 cm 2 for predicting mis-staging. After partial adjustment, a lower VAT (< 122 cm 2 , P < 0.001) and proximal location of tumor (P = 0.004) were independent factors associated with higher probability of mis-staging. Compared to VAT ≥ 122 cm 2 as the reference, VAT < 122 cm 2 exhibited an odds ratio of 2.701 (95% confidence intervals [CI], 1.618-3.907) for the probability of mis-staging., Conclusion: A lower-VAT is associated with an increased probability of inaccurate clinical T-staging in colon cancer., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Sulfuretin is a flavonoid that protects cell from damage induced by reactive oxygen species and inflammation. In this study, we investigated the role of sulfuretin in the processing of amyloid precursor protein (APP), in association with the two catalytic enzymes the α-secretase a disintegrin and metalloproteinase (ADAM10), and the beta-site APP cleaving enzyme 1 (BACE1) that play important roles in the generation of β amyloid protein (Aβ) in Alzheimer's disease (AD). We found that sulfuretin increased the levels of the immature but not the mature form of ADAM10 protein. The enhanced ADAM10 transcription by sulfuretin was mediated by the nucleotides -444 to -300 in the promoter region, and was attenuated by silencing or mutation of transcription factor retinoid X receptor (RXR) and by GW6471, a specific inhibitor of peroxisome proliferator-activated receptor α (PPAR-α). We further found that sulfuretin preferentially increased protein levels of the immature form of APP (im-APP) but significantly reduced those of BACE1, sAPPβ and β-CTF, whereas Aβ1-42 levels were slightly increased. Finally, the effect of sulfuretin on BACE1 and im-APP was selectively attenuated by the translation inhibitor cycloheximide and by lysosomal inhibitor chloroquine, respectively. Taken together, (1) RXR/PPAR-α signaling was involved in sulfuretin-mediated ADAM10 transcription. (2) Alteration of Aβ protein level by sulfuretin was not consistent with that of ADAM10 and BACE1 protein levels, but was consistent with the elevated level of im-APP protein, suggesting that im-APP, an isoform mainly localized to trans-Golgi network, plays an important role in Aβ generation., Competing Interests: The authors declare no competing interests., (© 2020 Chongqing Medical University. Production and hosting by Elsevier B.V.)

Objective: To observe the imbalance of anatomical and functional innervation factors of sympathetic nerves, nerve growth factor (NGF) and leukemia inhibitory factor (LIF), in salt-sensitive hypertensive heart failure rats and to explore the effects of treatment with Guizhi Decoction () on sympathetic remodeling by inhibiting cholinergic transdifferentiation., Methods: SS-13 BN and Dahl salt-sensitive (DS) rats were divided into 3 groups: SS-13 BN group (control group, n=9), DS group (model group, n=9) and GS group (Guizhi Decoction, n=9). After 10 weeks of a high-salt diet, the GS group rats were given Guizhi Decoction and other two groups were given saline at an equal volume as a vehicle. After 4 weeks' intragastric administration, rats were executed to detect the relevant indicators. Echocardiography and plasma n-terminal pro-B type natriuretic peptide (NT-proBNP) levels were used to assess cardiac function. Noradrenaline (NA) levels in the plasma and myocardium were detected to evaluate the sympathetic function. NGF and LIF expression were detected in the myocardium by Western blot or quantitative real-time PCR. Double immunofluorescence or Western blot was used to detect tyrosine hydroxylase (TH), choline acetyltransferase (CHAT) and growth associated protein 43 (GAP43) in order to reflect anatomical and functional changes of sympathetic nerves., Results: DS group had anatomical and functional deterioration of sympathetic nerves in the decompensation period of heart failure compared with SS-13 BN group. Compared with the DS group, Guizhi Decoction significantly decreased the expression of LIF mRNA/protein (P<0.01), increased the expression of NGF (P<0.05 or P<0.01), enhanced the levels of TH+/GAP43+ and TH+/CHAT+ positive nerve fibers (P<0.01), and improved the protein expression of TH and GAP43 in left ventricle, but had no effect on CHAT (P>0.05). Guizhi Decoction inhibited inflammatory infiltration and collagen deposition of myocardial injury, increased the content of myocardial NA (P<0.05), reduced the plasma NA level (P<0.01), improved cardiac function (P<0.01), and improved weight and blood pressure to some extent (P<0.05), compared with DS group., Conclusions: Guizhi Decoction could inhibit cholinergic transdifferentiation of sympathetic nerves, improve the anatomical and functional denervation of sympathetic nerves, and delay the progression of decompensated heart failure. The mechanism may be associated with the correction of the imbalance of NGF and LIF.

Long non-coding RNAs (lncRNAs) play important roles in plant growth and stress responses. As a dominant abiotic stress factor in soil, boron (B) deficiency stress has impacted the growth and development of citrus in the red soil region of southern China. In the present work, we performed a genome-wide identification and characterization of lncRNAs in response to B deficiency stress in the leaves of trifoliate orange ( Poncirus trifoliata ), an important rootstock of citrus. A total of 2101 unique lncRNAs and 24,534 mRNAs were predicted. Quantitative real-time polymerase chain reaction (qRT-PCR) experiments were performed for a total of 16 random mRNAs and lncRNAs to validate their existence and expression patterns. Expression profiling of the leaves of trifoliate orange under B deficiency stress identified 729 up-regulated and 721 down-regulated lncRNAs, and 8419 up-regulated and 8395 down-regulated mRNAs. Further analysis showed that a total of 84 differentially expressed lncRNAs (DELs) were up-regulated and 31 were down-regulated, where the number of up-regulated DELs was 2.71-fold that of down-regulated. A similar trend was also observed in differentially expressed mRNAs (DEMs, 4.21-fold). Functional annotation of these DEMs was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, and the results demonstrated an enrichment of the categories of the biosynthesis of secondary metabolites (including phenylpropanoid biosynthesis/lignin biosynthesis), plant hormone signal transduction and the calcium signaling pathway. LncRNA target gene enrichment identified several target genes that were involved in plant hormones, and the expression of lncRNAs and their target genes was significantly influenced. Therefore, our results suggest that lncRNAs can regulate the metabolism and signal transduction of plant hormones, which play an important role in the responses of citrus plants to B deficiency stress. Co-expression network analysis indicated that 468 significantly differentially expressed genes may be potential targets of 90 lncRNAs, and a total of 838 matched lncRNA-mRNA pairs were identified. In summary, our data provides a rich resource of candidate lncRNAs and mRNAs, as well as their related pathways, thereby improving our understanding of the role of lncRNAs in response to B deficiency stress, and in symptom formation caused by B deficiency in the leaves of trifoliate orange.

The bursa of Fabricius (BF) is the acknowledged central humoural immune organ unique to birds and plays a vital role in B lymphocyte development. In addition, the unique molecular immune features of bursal-derived biological peptides involved in B cell development are rarely reported. In this paper, a novel bursal heptapeptide (BP7) with the sequence GGCDGAA was isolated from the BF and was shown to enhance the monoclonal antibody production of a hybridoma. A mouse immunization experiment showed that mice immunized with an AIV antigen and BP7 produced strong antibody responses and cell-mediated immune responses. Additionally, BP7 stimulated increased mRNA levels of sIgM in immature mouse WEHI-231 B cells. Gene microarray results confirmed that BP7 regulated 2465 differentially expressed genes in BP7-treated WEHI-231 cells and induced 13 signalling pathways and various immune-related functional processes. Furthermore, we found that BP7 stimulated WEHI-231 cell autophagy and AMPK-ULK1 phosphorylation and regulated Bcl-2 protein expression. Finally, chicken immunization showed that BP7 enhanced the potential antibody and cytokine responses to the AIV antigen. These results suggested that BP7 might be an active biological factor that functions as a potential immunopotentiator, which provided some novel insights into the molecular mechanisms of the effects of bursal peptides on immune functions and B cell differentiation.

Background: Changes in the gut microbiota are associated with cardiovascular disease progression. Xiao-Qing-Long Tang (XQLT), a traditional herbal formula, has an anti-inflammatory effect and regulates the steady state of the immune system, which is also associated with the progression of heart failure with preserved ejection faction (HFpEF). In this study, we investigated whether XQLT could contribute to prevent the development of HFpEF and whether the modulation of the gut microbiota by this herbal formula could be involved in such effect., Methods: The gut microbiota, SCFAs, the histology/function of the heart, and systolic blood pressure were examined to evaluate the effect of XQLT on the gut microbiota and the progression of HFpEF after oral administration of XQLT to model rats. Furthermore, we evaluated, through fecal microbiota transplantation experiments, whether the favorable effects of XQLT could be mediated by the gut microbiota., Results: Oral administration of XQLT contributed to the reduction of elevated blood pressure, inflammation, and compensatory hypertrophy, features that are associated with the progression of HFpEF. The gut microbiota composition, SCFA levels, and intestinal mucosal histology were improved after treatment with XQLT. Moreover, fecal transfer from XQLT-treated rats was sufficient to prevent the progression of HFpEF., Conclusions: These data suggested that XQLT prevented the development of HFpEF in model rats by regulating the composition of the gut microbiota., Competing Interests: The authors declare no conflicts of interest.

In ultrasonography, ultrasound contrast agents (UCAs) that possess high acoustic impedance mismatch with the bulk medium are frequently employed to highlight the borders between tissues by enhanced ultrasound scattering in a clinic. Typically, the most common UCA, microbubble, is generally close in size to a red blood cell (<∼10 μm). These microscale UCAs cannot be directly entrapped into the target cells but generate several orders of magnitude stronger echo signals than the nanoscale ones. And their large containment and high ultrasound responsiveness also greatly facilitate to perform combined treatments, e.g., drug delivery and other imaging techniques. So multifunctionalized microscale UCAs appear on this scene and keep growing toward a promising direction for precise theranostics. In this review, we systematically summarize the new advances in the principles and preparations of multifunctionalized microscale UCAs and their medical applications for malignant tumors.

The bursa of Fabricius is an acknowledged central humoral immune organ unique to birds, which is vital to B cell differentiation and antibody production. However, the function and mechanism of the biological active peptide isolated from bursa on B cell development and autophagy were less reported. In this study, we isolated a new oligopeptide with nine amino acids Leu-Met-Thr-Phe-Arg-Asn-Glu-Gly-Thr from avian bursa following RP-HPLC, MODIL-TOP-MS, and MS/MS, which was named after BP9. The results of immunization experiments showed that mice injected with 0.01 and 0.05 mg/mL BP9 plus JEV vaccine generated the significant increased antibody levels, compared to those injected with JEV vaccine only. The microarray analysis on the molecular basis of BP9-treated immature B cell showed that vast genes were involved in various immune-related biological processes in BP9-treated WEHI-231 cells, among which the regulation of cytokine production and T cell activation were both major immune-related processes in WEHI-231 cells with BP9 treatment following network analysis. Also, the differentially regulated genes were found to be involved in four significantly enriched pathways in BP9-treated WEHI-231 cells. Finally, we proved that BP9 induced the autophagy formation, regulated the gene and protein expressions related to autophagy in immature B cell, and stimulated AMPK-ULK1 phosphorylation expression. These results suggested that BP9 might be a strong bursal-derived active peptide on antibody response, B cell differentiation, and autophagy in immature B cells, which provided the linking among humoral immunity, B cell differentiation, and autophagy and offered the important reference for the effective immunotherapeutic strategies and immune improvement.

Background: Bursa of Fabricius plays the vital functions on B cell development and antibody production in poultry. The bursal-derived peptide plays the essential roles on avian immature B cell development., Objectives: Here we explored the functions of the recently reported bursal nonapeptide (BP9) on the antibody production and the molecular basis of BP9 on avian immature B cell., Methods: Chicken were twice immunized with Avian Influenza Virus (AIV) inactivated vaccine plus with BP9 at three dosages, respectively. On two weeks after the second immunization, sera samples were collected from all experimental groups to measure AIV-specific Agglutination Inhibition (HI) antibody titers. Also, on 7th day after the second immunization, spleen lymphocytes were isolated from the immunized chicken to detect the lymphocyte viabilities. DT40 cells were treated with BP9 from 0.02 to 2 μg/mL for 4 and 20h to detect sIgM mRNA levels, and total RNAs from BP9-treated DT40 cells were collected to investigate the gene expression profiles of DT40 cells, and to analyze the enriched pathways and functional biological processes. Finally, nine gene expressions were validated with quantitative PCR (qPCR)., Results: Our investigation proved the strong regulatory roles of BP9 on AIV-specific HI antibody titers and lymphocyte viabilities. BP9 promoted sIgM mRNA levels in DT40 cells, and upregulated 598 gene expressions and downregulated 395 gene expressions in DT40 cells with 0.2μg/mL BP9 treatment. Moreover, our findings verified the significantly enriched six pathways and various the biological functional processes of BP9 on avian immature B cell. Also, we found eight signaling pathways in the enriched biological processes of BP9-treated DT40 cells, and the expressions of nine selected genes with qPCR were identical to that of microarray data., Conclusion: BP9 promoted the antibody production in the 21-old-day chicken immunization, and stimulated the sIgM expression in DT40 cells. Furthermore, we analyzed the gene expression profile and immune-related biological processes of DT40 cells treated with BP9, which provided some new insights into the mechanism on immature B cell development, and provided important references for adjuvant development on vaccine improvement and clinical application., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The Bursa of Fabricius is an acknowledged central humoral immune organ unique to birds, which provides an ideal research model on the immature B cell development., Objective: In this article, our motivation is to study the role on sIgM and establish the molecular basis and functional processes of Bursal Hexapeptide (BHP) in avian immature B cells DT40 cell lines., Methods: In this article, we detected the expressions of sIgM mRNA with qPCR in DT40 cells with BHP treatment, and investigated the gene expression profiles of BHP-treated DT40 cells, employing microarray analyses. Also, to validate the differentially expressed genes, we performed KEGG pathway and Gene Ontology analysis in the BHP-treated DT40 cells. Finally, we comparatively analyzed the similar regulated genes and their involved immune functional processes between DT40 cell and mouse immature B cell line WEHI231 cell with BHP treatment., Results: Following the proposed framework, we proved that the BHP enhanced the mRNA expression levels of IgM in DT40 cells, and induced 460 upregulated genes and 460 downregulated genes in BHP-treated DT40 cells. The pathway analysis showed that the differentially regulated genes in DT40 cell line with BHP treatment were involved in 12 enrichment pathways, in which Toll-like receptor signaling pathway was the vital pathways, and cytokine-cytokine receptor interaction and Jak-STAT signaling pathway were another two important pathways in BHP-treated DT40 cells. Moreover, BHP induced the immune related biological processes in BHP-treated DT40 cells, including T cell related, cytokine related, lymphocyte related, and innate immune response GO terms. Finally, the comparatively analysis showed that there were two downregulated genes GATA3 and IFNG to be found co-existed among the differentially expressed genes in BHP-treated DT40 cell and WEHI231 cells, which shared some same immune related functional processes in both cell lines., Conclusion: After the applying the framework, we proved the inducing roles and the gene expression profiles of BHP on avian immature B cells, and verified some molecular basis from the KEGG and GO analysis. These results provided the insight for mechanism on immature B cell differentiation, and offer the essential direction for the vaccine improvement., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Ethiopia is one of the African countries where Plasmodium falciparum and P. vivax co-exist. Monitoring and evaluation of current malaria transmission status is an important component of malaria control as it is a measure of the success of ongoing interventions and guides the planning of future control and elimination efforts., Main Text: We evaluated changes in malaria control policy in Ethiopia, and reviewed dynamics of country-wide confirmed and clinical malaria cases by Plasmodium species and reported deaths for all ages and less than five years from 2001 to 2016. Districts level annual parasite incidence was analysed to characterize the malaria transmission stratification as implemented by the Ministry of Health. We found that Ethiopia has experienced major changes from 2003 to 2005 and subsequent adjustment in malaria diagnosis, treatment and vector control policy. Malaria interventions have been intensified represented by the increased insecticide treated net (ITN) and indoor residual spraying (IRS) coverage, improved health services and improved malaria diagnosis. However, countrywide ITN and IRS coverages were low, with 64% ITN coverage in 2016 and IRS coverage of 92.5% in 2016 and only implemented in epidemic-prone areas of > 2500 m elevation. Clinical malaria incidence rate dropped from an average of 43.1 cases per 1000 population annually between 2001 and 2010 to 29.0 cases per 1000 population annually between 2011 and 2016. Malaria deaths decreased from 2.1 deaths per 100 000 people annually between 2001 and 2010 to 1.1 deaths per 100 000 people annually between 2011 to 2016. There was shrinkage in the malaria transmission map and high transmission is limited mainly to the western international border area. Proportion of P. falciparum malaria remained nearly unchanged from 2000 to 2016 indicating further efforts are needed to suppress transmission., Conclusions: Malaria morbidity and mortality have been significantly reduced in Ethiopia since 2001, however, malaria case incidence is still high, and there were major gaps between ITN ownership and compliance in malarious areas. Additional efforts are needed to target the high transmission area of western Ethiopia to sustain the achievements made to date.

The red stigmas of saffron are one of the most expensive spices in the world and serve as a traditional Chinese medicine. More saffron has been cultivated in China, and different drying technologies have been studied. However, a comprehensive and comparative analysis of different drying approaches has not been well studied. In this study, we compared electric oven and vacuum oven drying approaches on saffron. We found saffron was dried quicker under high vacuum drying mode with high temperature and the quicker drying rate provided, the more open microstructural interstices on the saffron surface. Both methods were best fit to Midilli and Kucuk model. Besides, the coloring, aroma and bitterness strength after drying showed the similar results. In sum, our data suggested the optimal drying temperature was 100 °C for 20 min for two evaluated methods, however considering the machine cost, the electric oven drying would be the first choice., Competing Interests: Compliance with ethical standardsThe authors declare that they have no conflict of interest.

Objective To analyze the routine and functional magnetic resonance imaging(MRI) features and their potential pathological mechanisms of Hashimoto's encephalopathy(HE). Methods The clinical data and routine and functional MRI images of 30 HE patients who were treated in our center from January 2010 to April 2017 were retrospectively reviewed. Among them,15 patients were examined with contrast-enhanced MRI,16 with diffusion-weighed imaging(DWI),8 with magnetic resonance angiography,2 with magnetic resonance spectroscopy,and 1 with both arterial spin labeled perfusion imaging and diffusion tensor imaging. Seven patients had consecutive clinical and imaging data. The distribution,MRI signals,and functional MRI features of HE were analyzed. Results Among 30 HE patients,routine MRI showed negative results in 8 cases and abnormal findings in 22 cases. Among 22 abnormal cases,9 were characterized by small cerebral vascular disease and 13 had non-specific abnormalities;of these 13 cases,12 had lesions mainly located at the supratentorial white matter,11 had multiple lesions,and 2 had lesions complicated with cerebellum atrophy. The lesions were focal or confluent,punctate or small patchy,showing abnormal signal intensity with iso-or hypo-intensity on T1-weighed imaging,hyper-intensity on both T2-weighed imaging and fluid-attenuated inversion recovery. Most of the lesions had no enhancement(12/15). Among 7 cases with abnormalities on DWI,hyper-intensity on DWI and hypo-intensity on apparent diffusion coefficient were seen in 3 sudden acute cases and hyper-intensity on DWI and increased apparent diffusion coefficient value in 4 sub-acute or slow onset cases. Three cases showed localized intracranial artery stenosis. In 2 cases,magnetic resonance spectroscopy revealed significant lower N-acetylaspartate peak,higher choline peak,and visible lactate peak or lipid peak. Of 7 cases with follow-up data,3 cases had no change,4 cases had changes including softening lesions(2/4),remitted and relapsed lesions(1/4),and rapid progression of brain atrophy with negative finding on the initial MRI(1/4). Conclusion Routine MRI combined with functional imaging can show the features of HE from different perspectives. Routine MRI shows multifocal or confluent lesions in the white matter,mostly without enhancement,while functional imaging may reveal pathological characteristics of different phases of acute or chronic ischemia and demyelinating changes of HE. Combined with clinical data,MRI can differentiate HE from other diseases based on routine and functional MRI appearances.

Background: Autophagy induction is a common mechanism for antitumor chemicals in induction of cancer cell death. However, the role of autophagy in crocin-induced apoptosis is barely studied in hepatocellular carcinoma (HCC)., Materials and Methods: The influence of crocin on growth, apoptosis, and autophagy and its mutual relations were analyzed by Cell Counting Kit-8 assay, flow cytometer, EGFP-LC3 puncta analysis, and Western blot in HCC cells. The activities of Akt/mTOR axis and its roles in autophagy regulation were also detected by Western blot in HCC cells treated with crocin. Finally, the roles of Akt/mTOR axis in crocin-induced autophagic apoptosis were analyzed by Western blot and flow cytometer in HCC cells., Results: The results showed that crocin can induce growth inhibition in a does- and time-dependent pattern by apoptosis. Increased LC3 puncta and upregulated LC3-II accumulation was observed as early as at 6 hours in HepG2 and HCCLM3 cells treated with 3 mg/mL crocin. Moreover, apoptosis analysis using flow cytometer and cleaved poly (ADP-ribose) polymerase detection revealed that autophagy initiation was prior to apoptosis activation in HCC cells treated with crocin. When autophagy was blocked with 3-methyladenine, crocin-induced apoptosis was inhibited in HCC cells. Furthermore, crocin treatment constrained the activities of key proteins in Akt/mTOR signaling, such as p-Akt (S473), p-mTOR (S2448), and p-p70S6K (T389), suggesting that crocin could induce autophagic apoptosis in HCC cells in an Akt/mTOR-dependent mechanism. Indeed, when autophagy was suppressed by forced expression of Akt, the crocin-induced apoptosis was also impaired in HCC cells., Conclusion: The results suggested that crocin could induce autophagic apoptosis in HCC cells by inhibiting Akt/mTOR activity. This study originally revealed that autophagic apoptosis is a novel cytotoxic function of crocin, which lays the theoretical foundation for clinical application of crocin in HCC., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: The bursa of Fabricius (BF) is an acknowledged central immune organ, and is important to B cell differentiation. Bursal hexapeptide (BHP) is the recently reported bursalderived peptide, while its inducing function on immune response is uncertain., Objectives: The main objective of this study was to analyze the immune responses to JEV vaccine in mice induced by BHP plus JEV vaccine, and to detect the signal and biological functions of BHP on immature B cells., Methods: Mice were immunized with Japanese encephalitis virus (JEV) vaccine and BHP from 0.01 mg/mL to 0.25 mg/mL to detect antibody response and cellular immune response, respectively. The production of IgG, IgG1 and IgG2a specific to JEV in serum from immunized mice were measured by ELISA, and T cell subpopulation from immunized mice were detected with using fluorochrome conjugated mAbs of the corresponding PE-Cys/FITC/PE by flow cytometry. Spleen cells from all immunized mice were harvested after one week of second immunization for lymphocyte proliferation assay. Mouse immature B cell WEHI-231 cell was treated with 0.01μg/mL BHP for 4h, and analyzed the involved biological function and pathway of differentially expressed genes with gene microarray., Results: BHP co-immunization with JEV vaccine generated significant increased antibody levels, neutralizing antibody titers and spleen lymphocyte viability, compared to that of vaccine control. The subpopulations of T cells in spleen lymphocytes were significantly modified in the mice coimmunized with JEV vaccine and BHP. The analysis results of gene expression profiles of WEHI- 231 mouse immature B cells with BHP treatment showed that the regulated genes with BHP treatment were involved various immune related biological functions, including proliferation and activation of lymphocyte and T cell, T cell mediated immunity and regulation of adaptive immune response. Furthermore, BHP stimulated three significant enriched pathways, including amphetamine addiction, long-term potentiation, and RIG-I-like receptor signaling pathway., Conclusion: Our results indicated BHP induced significant humoral and cellular immunity to JEV vaccine, and regulated various biological processes and signalling related to immune activation in immature B cells. These results proposed the immunomodulatory function and mechanism of BHP on immune induction, which provided the novel insight on the candidate reagent for immune improvement., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objective: To investigate the features and duration of viral nucleic acid shedding in children with influenza A., Methods: The clinical data of 90 children with influenza A with positive influenza A virus nucleic acid in nasopharyngeal swab detected by PCR were collected, and these children were divided into simple influenza A group (n=10), influenza A-pneumonia group (n=61), influenza A-nervous system damage group (n=10), and influenza A-underlying disease group (n=9). A retrospective analysis was performed for clinical features, treatment process, duration of viral nucleic acid shedding, and prognosis., Results: The most common symptoms in these children were fever (89/90, 99%), cough (89/90, 99%), running nose (69/90, 77%), shortness of breath (26/90, 29%), and myalgia (23/90, 26%). The mean duration of viral nucleic acid shedding in 90 children was 9.4±2.9 days. The simple influenza A group had a significantly shorter duration of viral nucleic acid shedding than the influenza A-pneumonia, influenza A-nervous system damage, and influenza A-underlying disease groups (p<0.05), while there were no significant differences between the influenza A-pneumonia, influenza A-nervous system damage, and influenza A-underlying disease groups (p>0.05). The children who received antiviral therapy within 48 hours after disease onset had significantly shorter duration of viral nucleic acid shedding and time to body temperature recovery than those who received antiviral therapy more than 48 hours after disease onset (p<0.05). Of all the children with body temperature recovery, 83% still tested positive for viral nucleic acid., Conclusions: Complications, underlying diseases, and timing of antiviral therapy are influencing factors for the duration of influenza A virus nucleic acid shedding, and whether body temperature returns to normal cannot be used to decide whether to continue antiviral therapy.

Transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) has been reported to be effective for local control of different-sized hepatocellular carcinomas. However, it is unclear if these benefits could also be applicable to different-sized liver metastases from gastrointestinal cancers. The aim of this study was to evaluate the outcomes of TACE combined with RFA for liver metastases from gastrointestinal cancers. In this study, we retrospectively analyzed clinical data of 19 consecutive patients who had a total of 26 liver metastatic lesions from gastrointestinal cancers and underwent RFA followed by first-time TACE treatment. The tumor recurrence, overall survival rate and procedure-related complications were evaluated. Moreover, patients' demographics and tumor characteristics were analyzed to determine their impact on the outcomes. The technical success of TACE plus RFA was achieved with 2 major procedure-related complications found. The mean follow-up was 21.3 months. The total 1-, 2-, and 3-year survival rate was 89.4%, 52.6%, and 35.1%, respectively. It was found that the tumor size and the ratio of enhancement area were significant factors that influenced the overall survival. In conclusion, patients with gastrointestinal cancer-derived liver metastatic lesions of smaller size and larger enhancement area are considered appropriate candidates for TACE plus RFA.