Cellulose synthesis from germinated tiger nut residue and its application in the production of a functional cookie.

In this study, cellulose was synthesized from the residue obtained after germinating tiger nuts for 0, 48, 72 or 96 h. The influence of the synthesized cellulose (0%, 2%, or 5%) on the quality of clove extract laden-cookies was evaluated. The optimum structure, morphology, and thermal properties of cellulose were obtained after geminating tiger nuts for 72 h. Adding cellulose to the dough stabilized the total phenolic, flavonoid, and protein contents and radical scavenging activity during the baking operation. The addition of 2% cellulose generally enhanced the hydration, pasting, and viscoelastic properties of the dough. However, 5% cellulose negatively affected the highlighted properties, culminating in poorer textural and sensory properties of the cookies produced therefrom. Germination could be effective in modifying the properties of cellulose from tiger nuts; thus, enhancing its application in the production of a functional cookie. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-024-05972-8.

Effect of dorsoplantar miniscrew fixation of the second metatarsal base fracture on residual diastases in acute lisfranc fracture-dislocation.

PURPOSE: This study aimed to evaluate and compare the clinico-radiographic outcomes between two techniques for acute Lisfranc fracture-dislocation with a large, displaced second metatarsal base plantar fracture: isolated Lisfranc screw fixation versus Lisfranc joint fixation with dorsoplantar miniscrew fixation of the second metatarsal base. METHODS: We retrospectively compared the clinico-radiographic outcome between patients who underwent isolated Lisfranc screw fixation (Group 1, 26 patients) and those who underwent Lisfranc joint fixation with dorsoplantar miniscrew fixation of the second metatarsal base (Group 2, 23 patients). The main outcome measurements were the postoperative distance between the medial cuneiform and second metatarsal base on standing anteroposterior foot radiographs, known as the C1-M2 distance. Residual diastasis was defined as C1-M2 distance ≥ 2 mm on the affected side compared with that on the contralateral side. We also assessed the Foot and Ankle Ability Measure (FAAM)-activities of daily living (ADL) and sports subscale scores at three, six and ≥ 18 months postoperatively. RESULTS: At the final follow-up, the mean C1-M2 distance on the affected side compared with that on the contralateral side was significantly greater in Group 1 than in Group 2 (3.9 versus 0.7 mm, P = 0.027). Furthermore, Group 1 showed a higher incidence of residual diastases at the final follow-up (69.2%) than the Group 2 (13.0%, P < 0.001). The FAAM-ADL scores at the final follow-up did not differ significantly between the groups (P = 0.518), but the FAAM Sports score was significantly higher in Group 2 than in Group 1 (P = 0.001). CONCLUSIONS: The postoperative C1-M2 distance was better maintained with Lisfranc joint fixation with dorsoplantar miniscrew fixation of the second metatarsal base than with isolated Lisfranc screw fixation. We recommend that surgeons exercise caution when dealing with a second metatarsal plantar fracture and consider performing secure fixation using the dorsoplantar miniscrew technique for improved clinical outcomes.

Convolutional Neural Network-Based Drone Detection and Classification Using Overlaid Frequency-Modulated Continuous-Wave (FMCW) Range-Doppler Images.

This paper proposes a novel drone detection method based on a convolutional neural network (CNN) utilizing range-Doppler map images from a frequency-modulated continuous-wave (FMCW) radar. The existing drone detection and identification techniques, which rely on the micro-Doppler signature (MDS), face challenges when a drone is small or located far away, leading to performance degradation due to signal attenuation and faint (MDS). In order to address these issues, this paper suggests a method where multiple time-series range-Doppler images from an FMCW radar are overlaid onto a single image and fed to a CNN. The experimental results, using actual data for three different drone sizes, show significant performance improvements in drone detection accuracy compared to conventional methods.

Efficacy of RCI001 as a Therapeutic Candidate in a Primary Sjögren Syndrome Mouse Model.

PURPOSE: The aim of this study was to investigate the efficacy of RCI001 (RCI) in a mouse model of primary Sjögren syndrome. METHODS: Eight 12-week-old NOD.B10-H2b mice were used in this study. All experimental animals were randomly divided into phosphate-buffered saline (PBS) and RCI groups in NOD.B10-H2b mice. The eyes of mice were topically treated with PBS or RCI twice a day for a week. Ocular surface staining (OSS) and tear secretion were compared between before and after treatment. The transcript levels of inflammatory cytokines and nicotinamide adenine dinucleotide phosphate oxidase (NOX) in the conjunctiva and cornea (CC) and lacrimal gland were assayed. In addition, immunofluorescence staining of the conjunctiva was assessed. RESULTS: The RCI group showed significant clinical improvement in OSS and tear secretion after 1 week of treatment compared with the baseline (both P < 0.001) and showed better improvement in OSS and tear secretion than the PBS group after 1 week of treatment (both P < 0.05). The levels of IL-1ß and IL-17 in CC and IL-6 in the lacrimal gland were also significantly reduced in the RCI group compared with the PBS group (each P < 0.05). Transcript levels of NOX2 and NOX4 were also significantly reduced in CC of the RCI group compared with those of the PBS group (P < 0.05). The RCI group also resulted in lower conjunctival expression of oxidative stress markers (4-hydroxy-2-nonenal, hexanoyl-lysine, and NOX4) than the PBS group. CONCLUSIONS: Topical RCI001 demonstrated excellent therapeutic efficacy in a mouse model of primary Sjögren syndrome by inhibiting inflammation and oxidative stress.

Senoinflammation as the underlying mechanism of aging and its modulation by calorie restriction.

Senoinflammation is characterized by an unresolved low-grade inflammatory process that affects multiple organs and systemic functions. This review begins with a brief overview of the fundamental concepts and frameworks of senoinflammation. It is widely involved in the aging of various organs and ultimately leads to progressive systemic degeneration. Senoinflammation underlying age-related inflammation, is causally related to metabolic dysregulation and the formation of senescence-associated secretory phenotype (SASP) during aging and age-related diseases. This review discusses the biochemical evidence and molecular biology data supporting the concept of senoinflammation and its regulatory processes, highlighting the anti-aging and anti-inflammatory effects of calorie restriction (CR). Experimental data from CR studies demonstrated effective suppression of various pro-inflammatory cytokines and chemokines, lipid accumulation, and SASP during aging. In conclusion, senoinflammation represents the basic mechanism that creates a microenvironment conducive to aging and age-related diseases. Furthermore, it serves as a potential therapeutic target for mitigating aging and age-related diseases.

Hemp sprout-derived exosome-like nanovesicles as hepatoprotective agents attenuate liver fibrosis.

Non-alcoholic fatty liver disease (NAFLD) is a form of hepatic steatosis in which more than 5% of the liver's weight is fat, primarily due to the overconsumption of soft drinks and a Western diet. In this study, we investigate the potential of plant-derived exosome-like nanovesicles (PENs) to prevent liver fibrosis and leaky gut resulting from NAFLD. Specifically, we examine whether hemp sprout-derived exosome-like nanovesicles (HSNVs) grown on smart farms could exert protective effects against NAFLD by inhibiting liver fibrosis. HSNVs ranging from 100-200 nm were measured using nanoparticle tracking analysis (NTA). HSNVs (1 mg kg-1) were orally administered for 5 weeks to mice with NAFLD induced by feeding them a Western diet (WD; a fat- and cholesterol-rich diet) and fat-, fructose-, and cholesterol-rich (FFC) diet for 8 weeks. Importantly, the administration of HSNVs markedly reduced oxidative stress and fibrosis marker proteins in NAFLD mouse models and LX2 cells. Furthermore, treatment with HSNVs prevented a significant decrease in the quantity of gut barrier proteins and endotoxin levels in NAFLD mouse models. For the first time, these results demonstrate that HSNVs can exhibit a hepatoprotective effect against gut leakiness and WD/FFC-induced liver fibrosis by inhibiting oxidative stress and reducing fibrosis marker proteins.

Comparing Knowledge and Perceptions of Palliative Care Among Neuro-Oncology Patients, Caregivers, and Providers to a Representative U.S. Sample.

BACKGROUND: Primary brain tumors (PBTs) pose a significant health challenge, affecting patients and their caregivers. While early integration of palliative care (PC) has shown benefits in advanced cancer, its integration for PBT patients, particularly glioblastoma (GBM) patients, remains complex. We hypothesized that our previous PC integration efforts may have failed due to knowledge-gaps and misconceptions among patients, caregivers, and providers. OBJECTIVE: This study aimed to identify knowledge gaps and misconceptions about PC among patients with primary brain tumors (PBTs), their caregivers, and their medical providers. METHOD: An electronic survey was distributed to PBT patients, caregivers, and medical providers, that included questions regarding PC from the Health Information National Trends Survey (HINTS). Survey responses were analyzed; comparisons were made between the 3 groups as well as the general population. RESULTS: Of 141 respondents (59 patients, 57 caregivers, and 25 providers), each group held perspectives on PC differing from the general population. While all groups had an improved understanding of PC's role in symptom management, uncertainty persisted among patients and caregivers regarding life-prolonging treatment and certain PC goals like caregiver support or end-of-life care. CONCLUSION: Understanding gaps in knowledge and perceptions of PC among PBT patients and caregivers is crucial for effective intervention, with caregivers playing a vital role in advocating for PC. Future research should explore factors influencing these perceptions and development of targeted education to improve early PC referrals for patients with PBTs.

Additional injection laryngoplasty as a salvage treatment for unilateral vocal fold paralysis.

OBJECTIVES: Injection laryngoplasty (IL) has been widely used as an initial treatment option for unilateral vocal fold paralysis (UVFP). An additional (second) IL is considered a salvage treatment for unsatisfactory outcomes of initial IL resulting from inadequate injection or early resorption of the injection material. This study aims to evaluate the efficacy of additional IL, distinguishing between "salvage" (within 4 months) and "repeated" injections (beyond 4 months), and to analyze prognostic factors for successful outcomes. METHODS: This retrospective study involved patients who received IL at Asan Medical Center from January 2014 to December 2020. Voice parameters were collected after each procedure, and those who conducted the statistical analysis were blinded to the study subjects. Among the 65 patients who underwent additional IL, 51 patients were enrolled in this study. Postinjection grade, roughness, breathiness, asthenia, strain (GRBAS) scales were used to determine satisfactory treatment outcomes. Success of the additional IL was defined as a postinjection grade of dysphonia score of 0 or 1, with a reduction in grade compared with the preinjection grade. RESULTS: The mean age of the patients was 61.6 years. Out of a total of 51 patients, 37 were men participating in the study. The odds ratio represents the likelihood of success in the second IL. Improved voice outcome after the additional IL was maintained in 23 (45%) patients. Compared with the failure group, the success group had a longer injection time interval between the initial and additional injection (9.1 vs. 7.4 months, respectively, p = 0.010). The success group had a higher proportion of patients with injection intervals >6 months (73.9% vs. 42.9%, p = 0.026). Logistic regression analysis revealed an injection interval >6 months had an odds ratio of 0.265 (confidence interval: 0.080-0.874, p = 0.029). CONCLUSIONS: Additional injections would benefit the patients whose voice outcomes are maintained for a longer period (>6 months) after the first injection.

Functional connectivity of the amygdala in relation to high stress and low mindfulness.

BACKGROUND: High psychological stress has been associated with several brain functional changes, including functional connectivity (FC) alterations in regions such as the prefrontal cortex and the amygdala. This study explored FC alterations associated with high perceived stress, and also investigated whether these neuroimaging features were correlated with low levels of mindfulness. METHODS: This study included 29 adults (12 males and 17 females; mean age: 27.6 ± 3.2) who complained of moderate or higher perceived stress and 31 adults (17 males and 14 females; mean age: 29.2 ± 7.2) who complained of low-level stress on the questionnaire scale. Seed-based resting-state FC analysis was conducted to compare between high and low stress groups. The dorsolateral prefrontal cortex (DLPFC), the ventromedial prefrontal cortex (VMPFC) and the amygdala were selected as seeds. RESULTS: High stress group showed weaker left amygdala-based FC in the left cerebellum crus II and the left orbitofrontal cortex compared with low stress group. High stress group had weaker FC between the left DLPFC and the left inferior parietal lobule. On the contrary, high stress group had stronger FC between the left VMPFC and the left caudate compared with low stress group. Weaker FC between the amygdala and the cerebellum crus II was correlated with lower level of awareness facet of mindfulness. CONCLUSIONS: Those with high perceived stress showed low levels of mindfulness and several FC alterations centered on the prefrontal cortex and amygdala. Our findings also suggest that weak amygdala-based FC alterations associated with high psychological stress are related to low-level awareness facet of mindfulness.

Integrated Structural Modulation Inducing Fast Charge Transfer in Aqueous Zinc-Ion Batteries.

Aqueous Zn-ion batteries (AZIBs) are promising energy-storage devices owing to their exceptional safety, long cycle life, simple production, and high storage capacity. Manganese oxides are considered potential cathode materials for AZIBs, primarily because of their safety, low cost, simple synthesis, and high storage capacity. However, MnO2-based cathodes tend to deteriorate structurally during long-term cycling, which reduces their reversible capacity. In this study, an advanced α-MnO2@SnO2 nanocomposite via facile hydrothermal synthesis is developed. The synergistic effects of lattice disorder and increased electron conductivity in the α-MnO2@SnO2 nanocomposite mitigate structural degradation and enhance the overall electrochemical performance. The nanocomposite exhibits a high reversible capacity of 347 mAh g-1 at a current density of 100 mA g-1 after 50 cycles. Furthermore, it exhibits excellent rate performance and stable capacity even after 1000 cycles, maintaining a capacity of 78 mAh g-1 at a high current density of 5 A g-1. This excellent electrochemical performance is attributed to the reversible Zn intercalation in α-MnO2@SnO2 nanocomposites due to the increased structural stability and fast ion/electron exchange caused by the distortion of the tunnel structure, on the basis of various ex situ experiments, density functional theory calculations, and electrochemical characterizations.

A microbiome-biochar composite synergistically eliminates the environmental risks of antibiotic mixtures and their toxic byproducts.

This study developed a continuous reactor system employing a hybrid hydrogel composite synthesized using a complex sludge microbiome and an adsorbent (HSA). This HSA-based system effectively eliminated the environmental risks associated with a mixture of the antibiotics ciprofloxacin and sulfamethoxazole, which exhibited higher toxicity in combination than individually at environmentally relevant levels. Analytical chemistry experiments revealed the in-situ generation of various byproducts (BPs) within the bioreactor system, with two of these BPs recording toxicity levels that surpassed those of their parent compound. The HSA approach successfully prevented the functional microbiome from being washed out of the reactor, while HSA efficiently removed antibiotic residues in their original and BP forms through synergistic adsorptive and biotransformation mechanisms, ultimately reducing the overall ecotoxicity. The use of HSA thus demonstrates promise not only as a mean to reduce the threat posed by toxic antibiotic residues to aquatic ecosystems but also as a practical solution to operational challenges, such as biomass loss/washout, that are frequently encountered in various environmental bioprocesses.

Molecular protocol to develop ß-carotene-biofortified rice events via molecular optimization.

Providing food with nutrition and functionality is crucial for sustaining human life. Rice (Oryza sativa L.) is a representative staple crop with high carbohydrate content but low amounts of essential amino acids, micronutrients, and carotenoids such as provitamin A. To improve the nutritional quality, rice endosperm was biofortified to accumulate carotenoids such as ß-carotene through genetic engineering (i.e., using synthetic carotenoid biosynthetic genes, a nonmammalian viral polycistronic sequence, and an optimized promoter and transit peptide) and high-throughput rice transformation (approximately 300 transgenic plants per construct). To facilitate the safety assessment of genetically modified food, molecular characterization was performed to select elite lines equipped with a single intergenic insertion of T-DNA, high transgene expression, in this case leading to high carotenoid content, and with phenotypic and compositional substantial equivalence. In this study, we present ß-carotene-biofortified rice event candidate lines eligible for commercial use and a disclosed molecular protocol for the development of biotech rice crops.

Cocaine-derived hippuric acid activates mtDNA-STING signaling in alcoholic liver disease: Implications for alcohol and cocaine co-abuse.

The simultaneous abuse of alcohol-cocaine is known to cause stronger and more unpredictable cellular damage in the liver, heart, and brain. However, the mechanistic crosstalk between cocaine and alcohol in liver injury remains unclear. The findings revealed cocaine-induced liver injury and inflammation in both marmosets and mice. Of note, co-administration of cocaine and ethanol in mice causes more severe liver damage than individual treatment. The metabolomic analysis confirmed that hippuric acid (HA) is the most abundant metabolite in marmoset serum after cocaine consumption and that is formed in primary marmoset hepatocytes. HA, a metabolite of cocaine, increases mitochondrial DNA leakage and subsequently increases the production of proinflammatory factors via STING signaling in Kupffer cells (KCs). In addition, conditioned media of cocaine-treated KC induced hepatocellular necrosis via alcohol-induced TNFR1. Finally, disruption of STING signaling in vivo ameliorated co-administration of alcohol- and cocaine-induced liver damage and inflammation. These findings postulate intervention of HA-STING-TNFR1 axis as a novel strategy for treatment of alcohol- and cocaine-induced excessive liver damage.

Prediction for Perioperative Stroke Using Intraoperative Parameters.

BACKGROUND: Perioperative stroke is a severe complication following surgery. To identify patients at risk for perioperative stroke, several prediction models based on the preoperative factors were suggested. Prediction models often focus on preoperative patient characteristics to assess stroke risk. However, most existing models primarily base their predictions on the patient's baseline characteristics before surgery. We aimed to develop a machine-learning model incorporating both pre- and intraoperative variables to predict perioperative stroke. METHODS AND RESULTS: This study included patients who underwent noncardiac surgery at 2 hospitals with the data of 15 752 patients from Seoul National University Hospital used for development and temporal internal validation, and the data of 449 patients from Boramae Medical Center used for external validation. Perioperative stroke was defined as a newly developed ischemic lesion on diffusion-weighted imaging within 30 days of surgery. We developed a prediction model composed of pre- and intraoperative factors (integrated model) and compared it with a model consisting of preoperative features alone (preoperative model). Perioperative stroke developed in 109 (0.69%) patients in the Seoul National University Hospital group and 11 patients (2.45%) in the Boramae Medical Center group. The integrated model demonstrated superior predictive performance with area under the curve values of 0.824 (95% CI, 0.762-0.880) versus 0.584 (95% CI, 0.499-0.667; P<0.001) in the internal validation; and 0.716 (95% CI, 0.560-0.859) versus 0.505 (95% CI, 0.343-0.654; P=0.018) in the external validation, compared to the preoperative model. CONCLUSIONS: We suggest that incorporating intraoperative factors into perioperative stroke prediction models can improve their accuracy.

Functionalized Congeners of 2H-Chromene P2Y6 Receptor Antagonists.

The P2Y6 receptor (P2Y6R), a Gq-coupled receptor, is a potential drug discovery target for various inflammatory and degenerative conditions. Antagonists have been shown to attenuate colitis, acute lung injury, etc. In the search for competitive antagonists, we have investigated the SAR of 3-nitro-2-(trifluoromethyl)-2H-chromene derivatives, although high affinity is lacking. We now reveal that long-chain amino-functionalized congeners display greatly enhanced affinity in the antagonism of UDP-induced Ca2+ mobilization in human (h) P2Y6R-transfected 1321N1 astrocytoma cells. A 6-(Boc-amino-n-heptylethynyl) analogue 30 (MRS4940) had an IC50 of 162 nM, which was a 123-fold greater affinity than the corresponding unprotected primary alkylamine, 107-fold greater than the corresponding pivaloyl derivative 30, and 132-fold selective compared to the P2Y14R. However, similar Boc-amino chains attached at the 8-position produced weak µM affinity. Thus, the P2Y6R affinity depended on the chain length, attachment point, and terminal functionality. Off-target activities, at 45 sites, were tested for acylamino derivatives 20, 24, 26, 30, 31, and 37, which showed multiple interactions, particularly at the biogenic amine receptors. The more potent analogues may be suitable for evaluation in inflammation and cancer models, which will be performed in future studies.

The Comparative Metabolism of a Novel Hepatocellular Carcinoma Therapeutic Agent, 2,3-Diamino-N-(4-(benzo[d]thiazol-2-yl)phenyl)propanamide, in Human and Animal Hepatocytes.

[2,3-diamino-N-(4-(benzo[d]thiazol-2-yl)phenyl)propanamide], named as ETN101, is a novel therapeutic agent for hepatocellular carcinoma. In vitro studies examined ETN101 metabolites in human, mouse, rat, dog, and monkey hepatocytes and identified the drug-metabolizing enzymes involved using cDNA-expressed human recombinant cytochrome P450s (CYPs), carboxylesterases (CESs), N-acetyltransferase (NAT) 1, and human liver cytosol. ETN101 showed similar metabolic stability across hepatocytes from five species, with particularly comparable stability in humans, rats, and monkeys. Its half-life was 75.0 min in humans, 68.9 in rats, 73.1 in monkeys, 120.4 in mice, and 112.7 in dogs. Thirty-four ETN101 metabolites, including the major metabolite M1, were identified using liquid chromatography-high-resolution mass spectrometry. ETN101 was primarily metabolized to M1 and CYP1A2 is exclusively responsible for M1 metabolism. Both NAT1 and NAT2 were responsible for the N-acetylation of M1 to M2. ETN101 remained stable in human CESs. In conclusion, this study provides comprehensive insights into the metabolic characteristics of ETN101, valuable for its toxicological and clinical development.

Battery-Free, Wireless Multi-Modal Sensor, and Actuator Array System for Pressure Injury Prevention.

Simultaneous monitoring of critical parameters (e.g., pressure, shear, and temperature) at bony prominences is essential for the prevention of pressure injuries in a systematic manner. However, the development of wireless sensor array for accurate mapping of risk factors has been limited due to the challenges in the convergence of wireless technologies and wearable sensor arrays with a thin and small form factor. Herein, a battery-free, wireless, miniaturized multi-modal sensor array is introduced for continuous mapping of pressure, shear, and temperature at skin interfaces. The sensor array includes an integrated pressure and shear sensor consisting of 3D strain gauges and micromachined components. The mechanically decoupled design of the integrated sensor enables reliable data acquisition of pressure and shear at skin interfaces without the need for additional data processing. The sensor platform enables the analysis of interplay among localized pressure, shear, and temperature in response to changes in the patient's movement, posture, and bed inclination. The validation trials using a novel combination of wireless sensor arrays and customized pneumatic actuator demonstrate the efficacy of the platform in continuous monitoring and efficient redistribution of pressure and shear without repositioning, thereby improving the patient's quality of life.

The Impact of a Twice-daily vs Once-daily Proton Pump Inhibitor Dosing Regimen on Laryngopharyngeal Reflux Symptoms: A Prospective Randomized Controlled Trial.

Background/Aims: Proton pump inhibitors (PPIs) play a crucial role in managing laryngopharyngeal reflux (LPR), but the optimal dosing regimen remains unclear. We aim to compare the effectiveness of the same total PPI dose administered twice daily versus once daily in LPR patients. Methods: We conducted a prospective randomized controlled trial at a tertiary referral hospital, enrolling a total of 132 patients aged 19-79 with LPR. These patients were randomly assigned to receive either a 10 mg twice daily (BID) or a 20 mg once daily (QD) dose of ilaprazole for 12 weeks. The Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) were assessed at 8 weeks and 16 weeks. The primary endpoint was the RSI response, defined as a reduction of 50% or more in the total RSI score from the baseline. We also analyzed the efficacy of the dosing regimens and the impact of dosing and duration on treatment outcomes. Results: The BID group did not display a higher response rate for RSI than the QD group. The changes in total RSI scores at the 8-week and 16-week visits showed no significant differences between the 2 groups. Total RFS alterations were also comparable between both groups. Each dosing regimen demonstrated significant decreases in RSI and RFS. Conclusions: Both BID and QD PPI dosing regimens improved subjective symptom scores and objective laryngoscopic findings. There was no significant difference in RSI improvement between the 2 dosing regimens, indicating that either dosing regimen could be considered a viable treatment option.

KCTD17-mediated Ras stabilization promotes hepatocellular carcinoma progression.

Background/Aims: Potassium channel tetramerization domain containing 17 (KCTD17) protein, an adaptor for the cullin3 (Cul3) ubiquitin ligase complex, has been implicated in various human diseases; however, its role in hepatocellular carcinoma (HCC) remains elusive. Here, we aimed to elucidate the clinical features of KCTD17, and investigate the mechanisms by which KCTD17 affects HCC progression. Methods: We analyzed transcriptomic data from patients with HCC. Hepatocyte-specific KCTD17 deficient mice were treated with diethylnitrosamine (DEN) to assess its effect on HCC progression. Additionally, we tested KCTD17-directed antisense oligonucleotides for their therapeutic potential in vivo. Results: Our investigation revealed the upregulation of KCTD17 expression in both tumors from patients with HCC and mouse models of HCC, in comparison to non-tumor controls. We identified the leucine zipper-like transcriptional regulator 1 (Lztr1) protein, a previously identified Ras destabilizer, as a substrate for KCTD17-Cul3 complex. KCTD17-mediated Lztr1 degradation led to Ras stabilization, resulting in increased proliferation, migration, and wound healing in liver cancer cells. Hepatocyte-specific KCTD17 deficient mice or liver cancer xenograft models were less susceptible to carcinogenesis or tumor growth. Similarly, treatment with KCTD17-directed antisense oligonucleotides (ASO) in a mouse model of HCC markedly lowered tumor volume as well as Ras protein levels, compared to those in control ASO-treated mice. Conclusions: KCTD17 induces the stabilization of Ras and downstream signaling pathways and HCC progression and may represent a novel therapeutic target for HCC.

Covalent organic framework-hybridized Ag nanoparticles as SERS substrate for highly sensitive detection of DNA bases.

Currently, research in the development of high-performance sensing platforms has increased to fulfill the needs of analysis and detection. In this study, we developed a novel type of surface-enhanced Raman scattering (SERS) chip composed of a covalent organic framework (COF)-silver nanoparticles (AgNPs) nanocomposite, and this nanocomposite was fabricated by a one-step method of ultrasonically mixing the obtained COF and AgNPs. The fabricated chip exhibited high sensitivity and repeatable SERS effects. Practical application results showed that the chip was highly sensitive and reliable and capable of detecting DNA bases (adenine) to fit an equation in the range from 0.01 pM to 1 nM, with an R-square of 0.97253 and a detection limit of ~0.026 pM (signal-to-noise ratio (S/N) = 3). Therefore, the proposed SERS system has potential applications in biological assays.