Low-Cytotoxic Core-Sheath ZnO NWs@TiO2-xNy Triggered Piezo-photocatalytic Antibacterial Activity.

Sonophotodynamic antimicrobial therapy (SPDAT) is recognized as a highly efficient biomedical treatment option, known for its versatility and remarkable healing outcomes. Nevertheless, there is a scarcity of sonophotosensitizers that demonstrate both low cytotoxicity and exceptional antibacterial effectiveness in clinical applications. In this paper, a novel ZnO nanowires (NWs)@TiO2-xNy core-sheath composite was developed, which integrates the piezoelectric effect and heterojunction to build dual built-in electric fields. Remarkably, it showed superb antibacterial effectiveness (achieving 95% within 60 min against S. aureus and ∼100% within 40 min against E. coli, respectively) when exposed to visible light and ultrasound. Due to the continuous interference caused by light and ultrasound, the material's electrostatic equilibrium gets disrupted. The modification in electrical properties facilitates the composite's ability to attract bacterial cells through electrostatic forces. Moreover, Zn-O-Ti and Zn-N-Ti bonds formed at the interface of ZnO NWs@TiO2-xNy, further enhancing the dual internal electric fields to accelerate the excited carrier separation to generate more reactive oxygen species (ROS), and thereby boosting the antimicrobial performance. In addition, the TiO2 layer limited Zn2+ dissolution into solution, leading to good biocompatibility and low cytotoxicity. Lastly, we suggest a mechanistic model to offer practical direction for the future development of antibacterial agents that are both low in toxicity and high in efficacy. In comparison to the traditional photodynamic therapy systems, ZnO NWs@TiO2-xNy composites exhibit super piezo-photocatalytic antibacterial activity with low toxicity, which shows great potential for clinical application as an antibacterial nanomaterial.

Endoplasmic reticulum stress and death receptor-mediated apoptosis in the neuronal differentiation of adult adipose-derived stromal cells.

Apoptosis is the primary cause of cell death in the differentiation of Adipose-derived stromal cells (ADSCs) into neurons. However, the relationship between endoplasmic reticulum stress (ERS) and death receptor-mediated apoptosis in ADSC-induced neuronal differentiation is not clear. ADSCs were isolated and induced to differentiate into neurons using ß-mercaptoethanol. The expression of neuron-specific enolase (NSE), GRP94, CHOP, Fas/FasL, TNFR1/TNF-α, DR5/TRAIL, Caspase8, and Caspase3 in ADSCs was examined using immunocytochemistry and Western blotting before induction, during pre-induction, and after induction. Transmission electron microscopy (TEM) was used to observe changes in the morphology of the endoplasmic reticulum (ER), and the MTT assay was employed to measure cell viability in the uninduced and induced groups. Additionally, the number of apoptotic cells during the induction process was measured using flow cytometry with Annexin V/PI. With increasing induction time, the positive expression rates of CHOP, Fas/FasL, Caspase8, Caspase-3, and NSE gradually increased, while the positive expression rate of GRP94 decreased. TNFR1/TNF-α and DR5/TRAIL peaked at 5 h post-induction and then decreased at 8 h. TEM revealed swelling and expansion of the ER, vacuolar changes, and degranulation in cells. The MTT assay showed a gradual decrease in the absorbance of surviving cells in all groups. Flow cytometry indicated an increasing rate of apoptosis in cells. Therefore, ERS in the normal culture and growth of ADSCs, manifesting as enhanced unfolded protein response (UPR), maintains the normal survival of ADSCs. However, in the process of ADSC-induced differentiation into neurons, ERS and death receptor-mediated apoptosis are significant causes of cell death.

Effects of Dietary Fish Meal Replaced by Fish Steak Meal on Growth Performance, Antioxidant Capacity, Intestinal Health and Microflora, Inflammatory Response, and Protein Metabolism of Large Yellow Croaker Larimichthys crocea.

Although fish steak meal (FSM) is a potentially available protein source, its efficiency as a fish meal (FM) substitute remains unclear to date. To this end, this study was carried out to determine the effects of dietary FM replaced by FSM on growth performance, antioxidant capacity, intestinal health and microflora, inflammatory response, and protein metabolism of large yellow croaker. Five isolipidic and isonitrogenous diets were formulated by substituting FM with FSM at levels of 0% (FSM0, control diet), 25% (FSM25), 50% (FSM50), 75% (FSM75), and 100% (FSM100), and were fed to juvenile large yellow croaker for 8 weeks. Compared with the control diet, the replacement of 25% dietary FM with FSM did not markedly alter the weight gain (WG) and specific growth rate (SGR). When the FM substitution level was over 25%, WG and SGR markedly reduced. The intestinal structure observation found that the FSM75 and FSM100 diets markedly decreased villus height, villus width, and muscle thickness of the anterior intestine. The FSM75 and FSM100 diets significantly decreased enzyme activities of amylase (AMS), lipase (LPS), trypsin, catalase (CAT), and total superoxide dismutase (T-SOD) and the total antioxidant capacity (T-AOC), and increased the malondialdehyde (MDA) content in the liver of large yellow croaker. The mRNA expression levels of intestinal barrier and inflammatory response-related genes suggested that the FSM50, FSM75, and FSM100 diets significantly decreased the mRNA abundances of intestinal barrier-related genes and anti-inflammatory response-related genes, and increased the mRNA abundances of proinflammatory gene il-6 in the anterior intestine. The compositions of intestinal microflora displayed that the FSM50, FSM75, and FSM100 diets decreased relative abundances of Firmicutes phylum and increased relative abundances of Proteobacteria phylum. In addition, the results of protein expression levels showed that the phosphorylation level of mammalian target of rapamycin (mTOR) and 4E-binding protein 1 (4E-BP1) in FSM75 and FSM100 groups were markedly reduced. In conclusion, FSM can replace up to 25% dietary FM without compromising the growth performance, intestinal health, and protein metabolism of the large yellow croaker.

Metabolic Profile of Alzheimer's Disease: Is 10-Hydroxy-2-decenoic Acid a Pertinent Metabolic Adjuster?

Alzheimer's disease (AD) represents a significant public health concern in modern society. Metabolic syndrome (MetS), which includes diabetes mellitus (DM) and obesity, represents a modifiable risk factor for AD. MetS and AD are interconnected through various mechanisms, such as mitochondrial dysfunction, oxidative stress, insulin resistance (IR), vascular impairment, inflammation, and endoplasmic reticulum (ER) stress. Therefore, it is necessary to seek a multi-targeted and safer approach to intervention. Thus, 10-hydroxy-2-decenoic acid (10-HDA), a unique hydroxy fatty acid in royal jelly, has shown promising anti-neuroinflammatory, blood-brain barrier (BBB)-preserving, and neurogenesis-promoting properties. In this paper, we provide a summary of the relationship between MetS and AD, together with an introduction to 10-HDA as a potential intervention nutrient. In addition, molecular docking is performed to explore the metabolic tuning properties of 10-HDA with associated macromolecules such as GLP-1R, PPARs, GSK-3, and TREM2. In conclusion, there is a close relationship between AD and MetS, and 10-HDA shows potential as a beneficial nutritional intervention for both AD and MetS.

Rheological studies of cellulose nanocrystal/dimethyl sulfoxide organogels.

Cellulose nanocrystals (CNCs)/H2O gels have received significant interest in various applications for the past decades. And yet CNCs organogels, which are important to their wider application, are less explored. In this work, CNCs/Dimethyl sulfoxide (DMSO) organogels are carefully investigated by rheological methods. It is found that metal ions also can facilitate the organogel formation as in hydrogel. Charge screening and coordination effects play vital roles in the organogel formation and their mechanical strength. CNCs/DMSO gels with different cations display similar mechanical strength, while CNCs/H2O gels show increasing mechanical strength with the increasing valence of cations. It seems that the coordination between cations and DMSO alleviate the influence of valence on gel mechanical strength. Due to weak, fast and reversible electrostatic interactions among CNCs particles, both CNCs/DMSO and CNCs/H2O gels show instant thixotropic behavior, which may find some interesting applications in the field of drug delivery. The morphological changes observed in polarized optical microscope appear to be consistent with rheological results.

Partial Substitution of Fish Meal with Soy Protein Concentrate on Growth, Liver Health, Intestinal Morphology, and Microbiota in Juvenile Large Yellow Croaker (Larimichthys crocea).

The present study investigated the growth performance, feed utilization, intestinal morphology, and microbiota communities of juvenile large yellow croaker (Larimichthys crocea) fed diets containing different proportions of soy protein concentrate (SPC) (0, 15%, 30%, and 45%, namely FM, SPC15, SPC30, and SPC45) as a substitute for fish meal (FM) for 8 weeks. The weight gain (WG) and specific growth rate (SGR) in fish fed SPC45 were significantly lower than those fed FM and SPC15 but not differ with these fed SPC30. The feed efficiency (FE) and protein efficiency ratio (PER) decreased sharply when the dietary SPC inclusion level was higher than 15%. The activity of alanine aminotransferase (ALT) and expression of alt and aspartate aminotransferase (ast) were significantly higher in fish fed SPC45 than those fed FM. The activity and mRNA expression of acid phosphatase were opposite. The villi height (VH) in distal intestine (DI) showed a significant quadratic response to increasing dietary SPC inclusion levels and was highest in SPC15. The VH in proximal intestine, middle intestine decreased significantly with increasing dietary SPC levels. The 16S rRNA sequences in intestine revealed that fish fed SPC15 had higher bacterial diversity and abundance of Phylum Firmicutes such as order Lactobacillales and order Rhizobiaceae than those fed other diets. Genus vibrio, family Vibrionaceae and order Vibrionales within phylum Proteobacteria were enriched in fish fed FM and SPC30 diets. Tyzzerella and Shewanella that belongs to phylum Firmicutes and Proteobacteria, respectively, were enriched in fish fed SPC45 diet. Our results indicated that SPC replacing more than 30% FM could lead to lower quality diet, retard growth performance, ill health, disordered intestine structure, and microbiota communities. Tyzzerella could be the bacteria indicator of intestinal in large yellow croaker fed low quality diet due to high SPC content. Based on the quadratic regression analysis of WG, the best growth performance could be observed when the replacement of FM with SPC was 9.75%.

Correction to "Research on MgSO4 Whiskers Grown on the Surface of Porous Materials".

[This corrects the article DOI: 10.1021/acsomega.2c06533.].

Research on MgSO4 Whiskers Grown on the Surface of Porous Materials.

The wooden sluice site of the Nanyue Kingdom in Guangzhou, China, is covered with white magnesium sulfate salt whiskers continuously growing from the surface. In this paper, polarizing microscopy, scanning electron microscopy, infrared thermography, Fourier transform infrared spectrometry, and surface tension analysis were utilized to comprehensively analyze the micromorphology of whiskers grown on the surfaces of porous materials collected at the site of Nanyue Kingdom, as well as the change laws of magnesium sulfate solution droplets on the porous hydrophilic matrix, and the migration and crystallization of magnesium sulfate solution in the capillary tube. The diameters of magnesium sulfate salt whiskers grown on the surfaces of porous samples range from 30 to 110 µm. For the first time, it is clear to see that the whisker's structure is hollow and nodular. There are solid crystalline salts in hollow tubes, and some of them are aqueous. The top sections of whiskers are approximately circular and are composed of particles with a size of about 0.4-4.0 µm. Their growth conditions are mainly characterized by the high humidity environment where the porous material is located or locally located, the formation of an annular whisker base, and the pressure difference generated during the formation progress of water-bearing crystals in the capillary of the whisker. The research results expound on the circumstances and mechanism of magnesium sulfate solution-induced whisker development on the surface of porous materials, providing a reference for the study of the whisker growth mechanism.

Thermal vacuum de-oxygen fabrication of new catalytic pigments: SiO2@TiO2-x amorphous photonic crystals for formaldehyde removal.

Eliminating benzene and formaldehyde pollution is indispensable after the popularity of colorful home decoration in current society. The possibility and advantages of vividly colorful amorphous photonic crystals (APCs) as catalytic pigments were established. Biomimetic synthesis of APCs is an effective approach to obtaining angle-independent structural colors. Herein, we introduce oxygen vacancies through thermal vacuum de-oxygenation to synthesize SiO2@TiO2-x APCs for angle-independent structural colors and enhanced photocatalytic performance in one step. Core-shell nanospheres with controllable particle size were synthesized using a mixed-solvent method as the structural unit of APCs to prepare seven structural colors: red, orange, yellow, green, cyan, blue, and purple. The photocatalytic activity of in situ fabricated SiO2@TiO2-x APCs was conspicuously enhanced by thermal vacuum deoxidation. An amorphous layer formed on the TiO2 nanocrystals provides TiO2-x with excellent spectral response to visible light, transient photocurrent, and surface photovoltage up to 38.44 µA cm-2 and 28.8 mV, respectively. Black TiO2-x absorbs incoherent scattering, causing APCs to generate vividly angle-independent structural colors. The existence of oxygen vacancies in TiO2-x promotes electron activation and a synergistic effect with the photonic local effect of APCs in improving the degradation of formaldehyde by catalytic pigments, effectively protecting the beautiful living environment of human beings.

HERC3 promotes YAP/TAZ stability and tumorigenesis independently of its ubiquitin ligase activity.

YAP/TAZ transcriptional co-activators play pivotal roles in tumorigenesis. In the Hippo pathway, diverse signals activate the MST-LATS kinase cascade that leads to YAP/TAZ phosphorylation, and subsequent ubiquitination and proteasomal degradation by SCFß-TrCP . When the MST-LATS kinase cascade is inactive, unphosphorylated or dephosphorylated YAP/TAZ translocate into the nucleus to mediate TEAD-dependent gene transcription. Hippo signaling-independent YAP/TAZ activation in human malignancies has also been observed, yet the mechanism remains largely elusive. Here, we report that the ubiquitin E3 ligase HERC3 can promote YAP/TAZ activation independently of its enzymatic activity. HERC3 directly binds to ß-TrCP, blocks its interaction with YAP/TAZ, and thus prevents YAP/TAZ ubiquitination and degradation. Expression levels of HERC3 correlate with YAP/TAZ protein levels and expression of YAP/TAZ target genes in breast tumor cells and tissues. Accordingly, knockdown of HERC3 expression ameliorates tumorigenesis of breast cancer cells. Our results establish HERC3 as a critical regulator of the YAP/TAZ stability and a potential therapeutic target for breast cancer.

Effect of Mg Powder's Particle Size on Structure and Mechanical Properties of Ti Foam Synthesized by Space Holder Technique.

Titanium foam has been the focus of special attention for its specific structure and potential applications in purification, catalyst substrate, heat exchanger, biomaterial, aerospace and naval industries. However, the liquid-state foaming techniques are difficult to use in fabricating Ti foam because of its high melting temperature and strong chemical reactivity with atmospheric gases. Here, the fabrication of Ti foams via the powder metallurgy route was carried out by utilizing both magnesium powders and magnesium particles as spacer holders, and Ti powders as matrix metal. The green compacts containing Ti powder, Mg powder and Mg particles were heated to a certain temperature to remove the magnesium and obtain the Ti foam. The results show that the porosities of the obtained Ti foam are about 35-65%, and Young's modulus and yield strength are found to be in the ranges of 22-126 MPa and 0.063-1.18 GPa, respectively. It is found that the magnesium powders play a more important role than the magnesium particles in the deformation and the densification of the green compact during the pressing, and the pore structure of Ti foam depends on the amount and the size of the magnesium spacer holders after sintering.

Effects of an Isobutylene-Maleic Anhydride Copolymer on the Rheological Behavior and Early Hydration of Natural Hydraulic Lime.

Natural hydraulic lime (NHL) is a cementitious material widely used in the restoration of stone cultural relics and maintenance of historic buildings, the practical use of which is mainly hindered by its poor fluidity. Due to the multilayer (double-layer) adsorption that isobutylene-maleic anhydride (IBMA) has on the surface of NHL, the effects that IBMA copolymer have on the fluidity and hydration of NHL were thus investigated. Moreover, the yield stress and plastic viscosity of NHL pastes were found to be reduced significantly by the incorporation of IBMA. Combined with the effects of electrostatic repulsion and steric hindrance, the flocculated structures in NHL pastes were gradually dismantled, releasing the trapped water and leading to a significant enhancement in the fluidity of NHL. IBMA was found to postpone the early hydration of NHL. In particular, it showed that adding specific content of IBMA can significantly improve the early strength of NHL.

The Development of New Catalytic Pigments Based on SiO2 Amorphous Photonic Crystals via Adding of Dual-Functional Black TiO2-x Nanoparticles.

Biomimetic synthesis of amorphous photonic crystals (APCs) is an effective approach to obtaining non-iridescent structural colors. However, the structural colors of artificially prepared APCs are dim or even white due to the influence of incoherent scattering. In this paper, we present a novel method to combine APCs with black TiO2-x to construct a noniridescent structural color pigments with high visibility and photocatalytic activity. Due to the absorption of incoherently scattered light by black TiO2-x , the color saturation of structural colors has been significantly increased. In addition, the utilization rate of photogenic carriers was effectively enhanced by the slow light effect generated from the pseudoband gap of SiO2 APCs with TiO2-x absorbed full spectrum. The tone and color saturation of catalytic pigments is controlled by the diameter of SiO2 nanospheres and the ratio of TiO2-x nanoparticles, which provides a controllable application study in color-related fields as artwork, environmental coatings, and textiles.

The Aptamer Ob2, a novel AChE inhibitor, restores cognitive deficits and alleviates amyloidogenesis in 5×FAD transgenic mice.

Loss of cerebral cholinergic neurons and decreased levels of acetylcholine (ACh) are considered to be major factors causing cognitive dysfunction in Alzheimer's disease (AD). Abnormally elevated levels of acetylcholinesterase (AChE) resulting in decreased levels of ACh are common in AD patients; thus, AChE inhibitors (AChEIs) are widely used for the treatment of AD. In our previous work, we acquired DNA aptamers Ob1, Ob2, and Ob3 against human brain AChE from systematic evolution of ligands by exponential enrichment (SELEX). In this study, we investigated the effect of these aptamers on learning and memory abilities, as well as the underlying mechanism in a 5×FAD transgenic AD mouse model. Here, we showed that only aptamer Ob2 exhibits a good inhibitory effect on both mouse and human AChE activity. In addition, chronic treatment with aptamer Ob2 significantly improved cognitive ability of 5×FAD mice in the Morris water maze. Moreover, the mechanism of aptamer Ob2 in 5×FAD mice may be associated with its inhibition of AChE activity, alleviation of the levels of Aß by lowering the expression of ß-secretase (BACE1), and activation of astrocytes in the brains of 5×FAD mice. These results indicate that aptamer Ob2 exhibits potential as an effective AChEI for the treatment of AD.

AMBRA1 Promotes TGFß Signaling via Nonproteolytic Polyubiquitylation of Smad4.

Transforming growth factor ß (TGFß) is prometastatic in advanced cancers and its biological activities are mainly mediated by the Smad family of proteins. Smad4 is the central signal transducer and transcription factor in the TGFß pathway, yet the underlying mechanisms that govern transcriptional activities of Smad4 are not fully understood. Here, we show that AMBRA1, a member of the DDB1 and CUL4-associated factor (DCAF) family of proteins, serves as the substrate receptor for Smad4 in the CUL4-RING (CRL4) ubiquitin ligase complex. The CRL4-AMBRA1 ubiquitin ligase mediates nonproteolytic polyubiquitylation of Smad4 to enhance its transcriptional functions. Consequently, AMBRA1 potentiated TGFß signaling and critically promoted TGFß-induced epithelial-to-mesenchymal transition, migration, and invasion of breast cancer cells. Mouse models of breast cancer demonstrated that AMBRA1 promotes metastasis. Collectively, these results show that CRL4-AMBRA1 facilitates TGFß-driven metastasis by increasing Smad4 polyubiquitylation, suggesting AMBRA1 may serve as a new therapeutic target in metastatic breast cancer. SIGNIFICANCE: This study identifies AMBRA1 as a novel regulator of TGFß signaling and breast cancer metastasis, supporting further exploration of AMBRA1 as a target for cancer therapy.

Establishing High-Performance Quasi-Solid Zn/I2 Batteries with Alginate-Based Hydrogel Electrolytes.

Zinc-iodine (Zn/I2) batteries are recognized as a kind of leading candidate for large-scale energy storage systems, owing to the high-capacity dissolution-deposition reactions on both electrodes. Nevertheless, the lifespan of Zn/I2 batteries is severely limited by the uncontrolled shuttling of triiodide ions (I3-) and unfavorable side reactions on Zn anodes. Herein, an alginate-based polyanionic hydrogel electrolyte is designed and synthesized by ion exchange and Zn2+-induced cross-linking. The immobile, negatively charged polyanionic chains on the hydrogel skeleton effectively block I3- from shuttling, while simultaneously transporting cations that are indispensable for battery chemistry. Moreover, this hydrogel can also enhance the cycling durability of Zn anodes by alleviating Zn's dendritic growth and corrosion reactions, due to the homogenized Zn2+ flux and reduced interfacial contact between free water and metallic Zn. Consequently, this alginate-based hydrogel electrolyte enables stable Zn plating/stripping for over 600 h at 2 mA cm-2 and 2 mAh cm-2 (corresponding to 10% depth of discharge). Serving as an electrolyte for Zn/I2 full batteries, this hydrogel helps the battery to achieve a high capacity of 183.4 mAh g-1 (capacity retention = 97.6%) after even 200 cycles at 0.2 A g-1, 77.4% higher than that of the traditional ZnSO4 aqueous counterpart (residual capacity = 41.5 mAh g-1). This work indicates the promising potential of electrolyte design on the performance improvement of aqueous Zn/I2 batteries.

Effects of Time-Dependent Protein Restriction on Growth Performance, Digestibility, and mTOR Signaling Pathways in Juvenile White Shrimp Litopenaeus vannamei.

A 6-week feeding strategy experiment was conducted to investigate the effects of time-dependent protein restriction and subsequent recovery on shrimp. Diets with protein levels of 43 and 36% were used as adequate and restricted diets, respectively. Shrimp with an initial body weight of 6.52 ± 0.46 g were given four feeding strategies: feeding on an adequate diet for six weeks (T1, the control), having protein-restricted diet in weeks 1 and 4 (T2), being given a protein-restricted diet in weeks 1, 3, and 5 (T3), and having protein-restricted diet in weeks 1, 2, 4, and 5 (T4). WG, SGR, FE, and PER of shrimp in T1-T3 showed no significant difference (P > 0.05), these indicators of T4 were significantly reduced (P < 0.05). No significant differences were found in digestive enzyme activities of shrimp among all treatments (P > 0.05). Crude protein content of shrimp muscle in T4 was lower than that of T1-T3. The expression level of tor in T4 was lower than that in other treatments, while 4e-bp was higher than that of other treatments. To balance saving on feeding cost and growth performance, giving the shrimp a protein-restricted diet for 1 week with subsequent refeeding (T2 and T3) is suitable for shrimp under high-density conditions.

Migration, Crystallization and Dissolution Changes of Salt Solution with Color Rendering Property in Porous Quartz Materials.

In order to visually display the migration and crystallization process of salt solution in porous cultural relics, copper sulfate solution with color rendering property was selected to record the migration, crystallization and resolution of salt solution in simulated SiO2 samples under different environmental conditions in real time through high-resolution recording system, scanning electron microscope system, salt phase X-ray diffraction system, and so on. The results showed the migration of salt solution in porous samples was related to the structural characteristics of the porous samples, the migration rate of salt solution, the evaporation rate and the change frequency of crystallization-resolution, etc., in which the large pore size of the sample, the higher the concentration and the faster migration and evaporation rate of salt solution, the greater the change rate of the brine accumulation zone or salt crystallization zone in the different porous samples. During the humidification-drying cycles of rainfall, the higher the cycle frequency of humidification-drying was, the higher the drying temperature was, the more frequent the crystallization-analysis change of salt in the salt-bearing sample was, and the more extensive the distribution of salt crystal zone was. This is the first time to visualize the salt belt by simulating the changing process of a salt solution with a color rendering property in porous samples. This has scientific theoretical guidance for the study of the migration-crystallization changes of soluble salts contained in porous silicate cultural relics. The visibility analysis results of multilayer salt crystal belts can also provide the preliminary basis for further effective desalination of salt bearing cultural relics.

Ten-Year Outcomes of Percutaneous Radiofrequency Ablation for Colorectal Cancer Liver Metastases in Perivascular vs. Non-Perivascular Locations: A Propensity-Score Matched Study.

PURPOSE: To compare long-term outcomes of percutaneous radiofrequency ablation for colorectal liver metastases in perivascular versus non-perivascular locations. METHODS: This retrospective study included 388 consecutive patients with colorectal liver metastases (246 men, 142 women; age range 27-86 years) who underwent percutaneous radiofrequency ablation between January 2006 and December 2018. Propensity-score matching was performed for groups with perivascular and non-perivascular colorectal liver metastases. Rates of accumulative local tumor progression, overall survival, intra/extrahepatic recurrence, and complications were compared between the two groups. RESULTS: We successfully matched 104 patients each in the perivascular and non-perivascular groups (mean age: 60.1 ± 11.5 and 60.1 ± 11.3 years, respectively). Cumulative local tumor progression rates at 6 months, 1 years, 3 years, and 5 years, respectively, were 8.8%,14.8%, 18.9%, and 18.9% in the perivascular group and 8.8%, 13.1%, 15.5%, and 15.5% in the non-perivascular group. The 1-, 3-, 5-, and 10-year overall survival rates, respectively, were 91.3%, 45.6%, 23.9%, and 18.7% in the perivascular group and 88.0%, 47.2%, 27.2%, and 22.6% in the non-perivascular group. No significant between-group differences were detected in cumulative local tumor progression (p=0.567, hazard ratio: 1.224) or overall survival (p = 0.801, hazard ratio: 1.047). The major complication rate was 1.0% (1/104, p > 0.999) in both groups. Tumor size was the only independent prognostic factor for local tumor progression (hazard ratio: 2.314; p = 0.002). On multivariate analysis for overall colorectal liver metastases, tumor diameter >3 cm, tumor location in the right colon, multiple tumors, and extrahepatic metastases before radiofrequency ablation (hazard ratios: 2.046, 1.920, 1.706, and 1.892, respectively; all p < 0.001) and intrahepatic recurrence (hazard ratio: 1.564; p = 0.002) were associated with poor overall survival. CONCLUSION: Cumulative local tumor progression, overall survival, and major complications rates did not differ significantly between perivascular and non-perivascular colorectal liver metastases after percutaneous radiofrequency ablation. For perivascular colorectal liver metastases, percutaneous radiofrequency ablation is a safe and effective treatment option.

Targeting SKA3 suppresses the proliferation and chemoresistance of laryngeal squamous cell carcinoma via impairing PLK1-AKT axis-mediated glycolysis.

Spindle and kinetochore-associated complex subunit 3 (SKA3) is a well-known regulator of chromosome separation and cell division, which plays an important role in cell proliferation. However, the mechanism of SKA3 regulating tumor proliferation via reprogramming metabolism is unknown. Here, SKA3 is identified as an oncogene in laryngeal squamous cell carcinoma (LSCC), and high levels of SKA3 are closely associated with malignant progression and poor prognosis. In vitro and in vivo experiments demonstrate that SKA3 promotes LSCC cell proliferation and chemoresistance through a novel role of reprogramming glycolytic metabolism. Further studies reveal the downstream mechanisms of SKA3, which can bind and stabilize polo-like kinase 1 (PLK1) protein via suppressing ubiquitin-mediated degradation. The accumulation of PLK1 activates AKT and thus upregulates glycolytic enzymes HK2, PFKFB3, and PDK1, resulting in enhancement of glycolysis. Furthermore, our data reveal that phosphorylation at Thr360 of SKA3 is critical for its binding to PLK1 and the increase in glycolysis. Collectively, the novel oncogenic signal axis "SKA3-PLK1-AKT" plays a critical role in the glycolysis of LSCC. SKA3 may serve as a prognostic biomarker and therapeutic target, providing a potential strategy for proliferation inhibition and chemosensitization in tumors, especially for LSCC patients with PLK1 inhibitor resistance.