Advances in the clinical treatment of multidrug-resistant pathogens using polymyxins.

OBJECTIVES: Polymyxins are a vital class of antibiotics used to combat multidrug-resistant Gram-negative bacteria. However, their use is limited due to potential nephrotoxicity and the availability of alternative antibiotics. This review aims to examine the properties of polymyxins and the clinical advances in their use for treating infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB). METHODS: This review analyses literature on polymyxin properties and various clinical approaches, including intravenous drip infusion, nebulized or dry powder inhalation, and ointment application. Treatment efficacy in terms of bacterial eradication, cure rate and mortality rate are reviewed and evaluated. RESULTS: Polymyxins have been reintroduced to treat critical infections due to the increasing prevalence of CR-GNB. Clinical trials and studies have confirmed that polymyxins can effectively treat CR-GNB infections when the formulation and administration are appropriate, with acceptable levels of nephrotoxicity. CONCLUSIONS: In the future, the development of polymyxin formulations will aim to improve their clinical effectiveness while reducing toxicity and side effects and preventing the emergence of polymyxin-resistant strains. Enhanced efficacy and minimized potential side effects can be achieved by developing new polymyxin-delivery systems that provide a smart and controlled release or customized patient administration.

Target Attainment and Population Pharmacokinetics of Nirmatrelvir/Ritonavir in Critically Ill Adult Patients.

Background: The population pharmacokinetics of nirmatrelvir/ritonavir (NIR/RIT) has not yet been described for critically ill adult patient. Purpose: This was a prospective observational population pharmacokinetic study of nirmatrelvir/ritonavir (NIR/RIT) in critically ill adult patients and identify optimal dosing regimens. Patients and Methods: The prescription of NIR/RIT is determined by the attending physician and ranges from 150mg/100mg to 300mg/100mg twice a day. Two to three serial blood samples were collected for each patient after the second doses. We developed and validated PK model for plasma NIR and plasma RIT. Monte Carlo dosing simulations were performed to assess target attainment. Results: We analyzed 89 plasma samples from 31 adult patients. The data were best described by a one-compartment model. Among the covariates tested on pharmacokinetic parameters, creatinine clearance (CrCL) and area under curve (AUC) of RIT had a significant effect on apparent clearance (CL/F) of NIR. Mean (SD) parameters estimates for the absorption rate constant (Ka), apparent distribution (V/F) and CL/F were 0.42 (0.10) h-1. 36.5 (8.5) L, 3.6 (0.26) L/h, respectively. Dosing simulations showed that the target in vitro 90% effective concentration (EC90) was more likely to be achieved twice a day than once a day at the same daily dose of NIR. High CrCL, low AUC of RIT were associated with a reduced likelihood of NIR reaching the target EC90. Conclusion: Based on our dosing simulations, the initial dosage of NIR/RIT was 300mg/100mg twice a day in critically ill patients with CrCL>45 mL/min; When CrCL in critically ill patients is between 15 and 45 mL/min, NIR/RIT is 150mg/100mg twice a day. The maintenance dose is adjusted according to CrCL and AUC of RIT, with the dosages varying between 75mg/100mg and 300mg/100mg.

Antiviral activity of a polysaccharide from Sargassum fusiforme against respiratory syncytial virus.

This experiment examined the antiviral activity of polysaccharides from Sargassum fusiforme against respiratory syncytial virus (RSV) in vitro, including their mechanism of action and preliminary structural analysis. Four polysaccharides (SFP1, SFP2, SFP3, and SFP4) were purified from Sargassum fusiforme using a DEAE-52 cellulose column and an NW Super 150 gel column. CCK-8 and western blot were utilized to study the antiviral activities and mechanisms of the polysaccharides. Preliminary structural analysis was conducted using HPLC and NMR techniques. The findings suggest that SFP4 (120 kD) is an acidic chemical compound composed of 88.8 % total sugars, 0.13 % proteins, 10.8 % glucuronidic acids, and 21.1 % sulfates. It contains at least ten monosaccharides, primarily mannuronic acid and fucose. Among the four polysaccharides, SFP4 had the highest anti-RSV activity, with a therapeutic index (TI) exceeding 139. SFP4 exhibited noteworthy antiviral efficacy in both upper and lower respiratory cells that were infected, especially when administered as a prophylactic treatment 2 h in advance. Furthermore, SFP4 showed a dose-dependent antiviral effect, with the highest therapeutic index (TI > 320) observed at a concentration of 7.81 µg·mL-1 during the prophylactic phase. It was speculated that SFP4's antiviral effect is due to its ability to inhibit the attachment of G-proteins to cells.

Safety of Traditional Growing Rods in Patients with Early-Onset Congenital Scoliosis Associated with Type-I Split Cord Malformation.

BACKGROUND: Literature regarding the application of traditional growing rod (TGR) instrumentation in patients with early-onset congenital scoliosis with type-I split cord malformation is scarce. The purpose of the present study was to assess the safety and effectiveness of TGR surgery and repeated lengthening procedures in patients with congenital scoliosis with type-I split cord malformation not treated with prophylactic osseous spur excision. METHODS: Thirteen patients with early-onset congenital scoliosis associated with type-I split cord malformation and a stable neurologic status between March 2009 and July 2020 were recruited. All patients underwent primary TGR surgery and subsequent repeated lengthening procedures without osseous spur excision by the same surgical team. Clinical information and radiographic data from the preoperative, postoperative, and latest follow-up periods were collected. RESULTS: The mean preoperative Cobb angle of the major coronal curve was 74.62° ± 25.59°, the mean early postoperative angle was 40.23° ± 17.89°, and the mean latest follow-up angle was 40.62° ± 16.60°. The scoliotic deformity correction percentage was 46.81% ± 12.26% after the initial operation and 45.08% ± 15.53% at the latest follow-up. Compared with the preoperative values, significant improvements were observed in the coronal and sagittal balance early postoperatively and at the latest follow-up (p < 0.05 for all). The average annual amounts of spinal height gained were 15.73 ± 5.95 mm at T1-S1, 8.94 ± 3.94 mm at T1-T12, and 12.02 ± 6.70 mm between the instrumented segments. The total height gained at T1-S1 and T1-T12 was 72.18 ± 28.74 mm and 37.62 ± 12.53 mm, respectively. No intraoperative neurophysiological monitoring events were observed, and no case of neurological deficit was observed postoperatively or during follow-up. CONCLUSIONS: Patients without neurologic deficit and having a stable neurologic exam who have early-onset congenital scoliosis associated with type-I split cord malformation can safely and effectively undergo TGR surgery, followed by repeated lengthening procedures, without prophylactic osseous spur excision. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Identification of the circRNA-miRNA-mRNA network for treating methamphetamine-induced relapse and behavioral sensitization with cannabidiol.

AIMS: This study aims to investigate the pharmacological effects and the underlying mechanism of cannabidiol (CBD) on methamphetamine (METH)-induced relapse and behavioral sensitization in male mice. METHODS: The conditioned place preference (CPP) test with a biased paradigm and open-field test were used to assess the effects of CBD on METH-induced relapse and behavioral sensitization in male mice. RNA sequencing and bioinformatics analysis was employed to identify differential expressed (DE) circRNAs, miRNAs, and mRNAs in the nucleus accumbens (NAc) of mice, and the interaction among them was predicted using competing endogenous RNAs (ceRNAs) network analysis. RESULTS: Chronic administration of CBD (40 mg/kg) during the METH withdrawal phase alleviated METH (2 mg/kg)-induced CPP reinstatement and behavioral sensitization in mice, as well as mood and cognitive impairments following behavioral sensitization. Furthermore, 42 DEcircRNAs, 11 DEmiRNAs, and 40 DEmRNAs were identified in the NAc of mice. The circMeis2-miR-183-5p-Kcnj5 network in the NAc of mice is involved in the effects of CBD on METH-induced CPP reinstatement and behavioral sensitization. CONCLUSIONS: This study constructed the ceRNAs network for the first time, revealing the potential mechanism of CBD in treating METH-induced CPP reinstatement and behavioral sensitization, thus advancing the application of CBD in METH use disorders.

Modification of myofibrillar protein structural characteristics: Effect of ultrasound-assisted first-stage thermal treatment on unwashed Silver Carp surimi gel.

The hardness properties of unwashed surimi gel are considered as the qualities of gelation defect. This research investigated the effect of ultrasound-assisted first-stage thermal treatment (UATT) on the physicochemical properties of unwashed Silver Carp surimi gel, and the enhancement mechanism. UATT could reduce protein particle size, which significantly reduced from 142.22 µm to 106.70 µm after 30 min of UATT compared with the nature protein. This phenomenon can promote the protein crosslinking, resulting in the hardness of surimi gel increased by 15.08 %. Partially unfolded structure of myofibrillar protein and exposures of tryptophan to water, lead to the increase in the zeta potential absolute value, driven by UATT. The reduced SH group level and the conformational conversion of proteins from random coiling to α-helix and ß-sheet, which was in support of intermolecular interaction and gel network construction. The results are valuable for processing protein gels and other food products.

Application of a water-energy-carbon coupling index to evaluate the long-term operational stability of the anaerobic-anoxic-oxic-membrane bioreactor (A2/O-MBR) process under the influence of rainstorms.

In the context of global climate change, sudden rainstorms and typhoons induce fluctuations in hydraulic shocks to wastewater treatment plants (WWTPs) in coastal areas, causing two challenges of stable effluent quality and low-carbon operation. We established a quantitative evaluation method for resistance of wastewater treatment processes to hydraulic shocks based on the water-energy-carbon nexus using operational data from a WWTP in southeast coastal China from July 2018 to December 2022. The effects of hydraulic shocks on the operational stability of the anaerobic-anoxic-oxic-membrane bioreactor (A2/O-MBR) process were analyzed following five steps. The results showed that the gray water footprint (GWF) of the process was 9.3% lower than that of the A2/O process. The energy footprint (ENF) and carbon footprint (CF) were approximately 2.1 times and 1.7 times higher than those of the A2/O process, respectively. The resistance to hydraulic shocks of the A2/O-MBR process is approximately 5.5 times higher than that of the A2/O process. In conclusion, the A2/O-MBR process exhibits higher process operational stability when subjected to hydraulic shocks, which is more conducive to the efficient and stable operation of WWTPs in rainstorm and typhoon-prone areas. The evaluation methodology provides qualitative technical support for selecting upgrading processes for WWTPs in different regions.

Morphological analysis of isolated hemivertebra: radiographic manifestations related to the severity of congenital scoliosis.

PURPOSE: The natural history of congenital scoliosis (CS) caused by hemivertebra varies greatly. This study aimed to explore the association between the morphology of hemivertebra and the severity of CS, since the diagnosis of the hemivertebra. METHODS: Patients with isolated (single fully segmented) hemivertebra were enrolled. The degree and progression of deformity were compared by three morphological parameters of hemivertebra, comprising whether the width of hemivertebra extends across the central vertical line of lower adjacent vertebra (midline); the lateral height ratio (LHR, lateral height of hemivertebra× 2/(lateral height of HV-1 plus HV + 1) with the cut-point being 0.9; and the sagittal position of hemivertebra that was divided into the lateral and posterolateral group. RESULTS: In total, 156 patients (mean age 9.7 ± 6.2 years, 81 males) were enrolled. The number of thoracic, thoracolumbar (T12/13-L1), and lumbar hemivertebrae were 63, 41, and 52, respectively. Hemivertebrae across the midline had larger scoliosis and kyphosis (58.3 ± 20.6° vs. 42.8 ± 15.0°, P <  0.001; 45.1 ± 32.5° vs. 29.5 ± 25.7°, P = 0.013, respectively). Hemivertebrae with LHR ≥0.9 was associated with larger scoliosis (55.7 ± 20.6° vs. 41.4 ± 13.3°, P <  0.001). Larger scoliosis and kyphosis were observed in posterolateral hemivertebrae (54.4 ± 21.0° vs. 44.4 ± 15.6°, P = 0.026; 51.4 ± 31.5° vs. 20.6 ± 17.1°, P <  0.001, respectively). Co-occurrence of more than one of the three positive parameters above indicated higher annual progression (5.0 ± 2.2° vs. 3.3 ± 1.3°, P <  0.001). CONCLUSION: Three positive parameters, width across the midline, LHR ≥0.9, and posterolateral position were associated with a more severe deformity in patients with isolated hemivertebra. Hemivertebrae with more than one positive parameter may cause progressive deformity, and thus need prompt surgery. LEVEL OF EVIDENCE: Prognostic, level IV.

Multi-omics Analysis of Volatile Flavor Components in Pacific Chub and Spanish Mackerel during Freezing using GC-MS-O.

This study employed gas chromatography-mass spectrometry with olfactory (GC-MS-O) and multi-omics methods to investigate the changes in volatile flavor compounds during the freezing process of Pacific chub mackerel (Scomber japonicus) from Japan and China, and Spanish mackerel (Scomberomorus niphonius). A total of 18 volatile flavor compounds were identified, and significant differences in volatile flavor components were observed among samples frozen for 1 week, 1 year, and 2 years. The results of the Partial least squares regression (PLSR) indicated that the fishy odor was correlated with independent variables such as fatty acids (FA 22:4, FA 28:6, FA 24:4), differentially expressed genes (Gene.2425 (NDUFA5), Gene.38 (GPX1), and Gene.2844 (DAD1)). Classification and regression tree (CART) analysis revealed that the peak area values of fatty acids (FA 22:5, FA 20:4) and fatty acid esters of hydroxy fatty acids (FAHFA 18:0/22:3) were the main differentiating factors for fishy odor perception.

High concentrations of nirmatrelvir/ritonavir in critically ill patients receiving continuous renal replacement therapy.

OBJECTIVES: Nirmatrelvir/ritonavir is a highly efficacious agent against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although dose adjustment is recommended in patients with renal impairment according to the package insert for Paxlovid (Pfizer), there is no dose recommendation for patients with severe renal impairment who require continuous renal replacement therapy (CRRT). METHODS: To characterise the features of nirmatrelvir/ritonavir in critically ill Chinese patients undergoing CRRT, therapeutic drug monitoring of nirmatrelvir/ritonavir was performed by high-performance liquid chromatography tandem mass spectrometry assay in eight patients. RESULTS: Nirmatrelvir trough concentrations ranged from 3325.34 ng/mL to 15 625.46 ng/mL. Concentrations were up to 7-fold higher compared with patients with normal renal function and 2-fold higher compared with patients with end-stage renal disease undergoing haemodialysis. CONCLUSIONS: These results suggest that a dose reduction should be implemented in the treatment of patients with CRRT.

Acute kidney injury associated with colistin sulfate vs. polymyxin B sulfate therapy: A real-world, retrospective cohort study.

OBJECTIVE: To compare the incidence of acute kidney injury (AKI) in patients treated with colistin sulfate (CS) and polymyxin B sulfate (PMB). METHODS: Sociodemographic and laboratory measures of adult patients who received intravenous CS or PMB for at least 72 h for the first time at the study hospital from October 2021 to November 2022 were collected retrospectively. The primary outcome was the incidence of AKI, defined by the Kidney Diseases Improving Global Outcomes criteria. The secondary outcome was 30-day mortality. RESULTS: In total, 109 patients were included in the CS cohort and 176 patients were included in the PMB cohort. The incidence of AKI was significantly higher in the PMB cohort compared with the CS cohort (50.6% vs. 18.3%; P<0.001). On multi-variate analysis, CS therapy [hazard ratio (HR) 0.275; P<0.001] was an independent protective factor for AKI, along with higher estimated glomerular filtration rate. Nevertheless, 30-day mortality was similar in the PMB and CS cohorts (21.6% vs. 13.8%; P=0.099). Multi-variate analyses revealed that CS therapy was not associated with 30-day mortality (HR 0.968; P=0.926), while intensive care unit admission, combination with meropenem, Charlson score and stage 3 AKI were independent risk factors for 30-day mortality. After balancing the baseline characteristics of patients using propensity score matching, the main results were unchanged. CONCLUSION: The incidence of AKI was significantly lower in the CS cohort compared with the PMB cohort. However, 30-day mortality was similar in the two cohorts.

Revisiting effects of teacher characteristics on physiological and psychological stress: a virtual reality study.

Identifying personal characteristics associated with teachers' stress is a longstanding research goal with important implications for practice. The present work revisits the effects of individual characteristics in terms of neuroticism, classroom management self-efficacy, and cognitive (reasoning) abilities on stress using virtual reality (VR). Relying on a sample of 56 German pre-service teachers (Mage = 22.73, SDage = 4.93; 50.9% females), we capitalized on a VR classroom environment that allowed the integration of experimental control and authentic teaching situations, where pre-service teachers responded to the disruptive behaviors of the student avatars. We focused on stress responses in terms of psychological stress (self-reported stress) assessed after the VR session, and physiological stress (heart rate) assessed during the VR session. A total of 30 (26) participants was assigned to a condition with higher (lower) levels of disruptive student behavior, referred to as higher and lower complexity condition, respectively. Results from linear mixed-effects models revealed that neuroticism positively predicted psychological and physiological stress responses in pre-service teachers, whereas classroom management self-efficacy and cognitive (reasoning) abilities were not significantly related to stress responses. Level of complexity and the interaction between complexity and individual characteristics did not have an effect. This study underlines the value of VR as a tool for psychological research and contributes to existing knowledge on teacher characteristics and stress.

Cannabidiol protects the liver from α-Amanitin-induced apoptosis and oxidative stress through the regulation of Nrf2.

α-Amanitin, the primary lethal toxin of Amanita, specifically targets the liver, causing oxidative stress, hepatocyte apoptosis, and irreversible liver damage. As little as 0.1 mg/kg of α-amanitin can be lethal for humans, and there is currently no effective antidote for α-amanitin poisoning. Cannabidiol is a non-psychoactive natural compound derived from Cannabis sativa that exhibits a wide range of anti-inflammatory, antioxidant, and anti-apoptotic effects. It may play a protective role in preventing liver damage induced by α-amanitin. To investigate the potential protective effects of cannabidiol on α-amanitin-induced hepatocyte apoptosis and oxidative stress, we established α-amanitin exposure models using C57BL/6J mice and L-02 cells in vitro. Our results showed that α-amanitin exposure led to oxidative stress, apoptosis, and DNA damage in both mouse hepatocytes and L-02 cells, resulting in the death of mice. We also found that cannabidiol upregulated the level of Nrf2 and antioxidant enzymes, alleviating apoptosis, and oxidative stress in mouse hepatocytes and L-02 cells and increasing the survival rate of mice. Our findings suggest that cannabidiol has hepatoprotective effects through the regulation of Nrf2 and antioxidant enzymes and may be a potential therapeutic drug for Amanita poisoning.

Enhanced batch sorting and rapid sensory analysis of Mackerel products using YOLOv5s algorithm and CBAM: Validation through TPA, colorimeter, and PLSR analysis.

This study employed the YOLOv5s algorithm to establish a rapid quality identification model for Pacific chub mackerel (S. japonicus) and Spanish mackerel (S. niphonius). Data augmentation was conducted using the copy-paste augmentation within the YOLOv5s network. Furthermore, a small object detection layer was integrated into the network structure's neck, while the convolutional block attention module (CBAM) was incorporated into the convolutional module to optimize the model. The model's accuracy was assessed through sensory evaluation, texture profile analysis, and colorimeter analysis. The findings indicated that the enhanced model achieved a mAP@0.5 score of 0.966, surpassing the original version's score of 0.953. Moreover, the improved model's params was only 7.848 M, and an average detection time of 115 ms/image (image resolution 2400 × 3200). Furthermore, sensory and physicochemical indicators are reliably distinguished between qualified and unqualified samples. The PLSR model exhibited R2X, R2Y, and Q2 values of 0.977, 0.956, and 0.663, respectively.

α-amanitin induces autophagy through AMPK-mTOR-ULK1 signaling pathway in hepatocytes.

Amanitin poisoning is one of the most life-threatening mushroom poisonings. α-Amanitin plays a key role in Amanita phalloides intoxication. α-Amanitin shows toxic effects on the liver. However, the mechanism by which α-amanitin induces liver injury has not been elucidated. Autophagy plays a crucial role in maintaining cellular homeostasis and is closely related to the occurrence of a variety of diseases. Studies have shown that autophagy may play an important role in the process of α-amanitin-induced liver injury. However, the mechanism of α-amanitin-induced autophagy remains unclear. Thus, this study aimed to explore the mechanisms of α-amanitin in inducing hepatotoxicity in Sprague Dawley (SD) rats and the normal human liver cell line L02 cells. The SD rats and L02 cells exposed to α-amanitin were observed to determine whether α-amanitin could induce the autophagy of rat liver and L02 cells. The regulatory relationship between autophagy and the AMPK-mTOR-ULK pathway by exposing the autophagy agonist (rapamycin (RAPA)), autophagy inhibitor (3-methylademine (3-MA)), and AMPK inhibitor (compound C) was also explored. Autophagy-related proteins and AMPK-mTOR-ULK pathway-related proteins were detected using Western blot. The results of the study indicated that exposure to different concentrations of α-amanitin led to morphological changes in liver cells and significantly elevated levels of ALT and AST in the serum of SD rats. Additionally, the expression levels of LC3-II, Beclin-1, ATG5, ATG7, AMPK, p-AMPK, mTOR, p-mTOR, and ULK1 were significantly increased in the rat liver. And we found that L02 cells exposed to 0.5 µM α-amanitin for 6 h significantly induced autophagy and activated the AMPK-mTOR-ULK1 pathway. Pretreated with RAPA, 3-MA, and compound C for 1 h, the expression levels of autophagy-related proteins and AMPK-mTOR-ULK pathway-related proteins significantly changed. Our results indicates that autophagy and the AMPK-mTOR-ULK pathway are involved in the process of α-amanitin-induced liver injury. This study may foster the identification of actionable therapeutic targets for A. phalloides intoxication.

Rapid screening of sensory attributes of mackerel using big data mining techniques and rapid sensory evaluation methods.

The present study aimed to investigate the potential of big data mining technology in conjunction with rapid sensory evaluation methods for the swift screening of sensory attributes of three kinds of frozen mackerel. Specifically, two rapid sensory evaluation methods, namely ideal profile method (IPM) and check-all-that-apply (CATA), were implemented and compared with the conventional descriptive analysis method. The results revealed that eight sensory attributes based on consumer network evaluations demonstrated significant consistency during the training process (p < .05). Notably, the application of web-based sensory attributes yielded highly comparable results between IPM and traditional descriptive analysis (0.915). Moreover, the results of the IPM preference map were in closer agreement with those of traditional descriptive analysis. While traditional sensory evaluation boasts high accuracy and a greater ability to detect nuances, the evolution of sensory evaluation technology has shifted its focus toward consumers. Rapid sensory evaluation analysis technology supports the collection of information directly from consumers, even by untrained or semi-trained groups, thereby presenting broad prospects for product qualitative analysis.

pH-shift strategy improving the thermal stability and oxidation stability of rice starch/casein-based high internal phase emulsions for the application in fish cake.

The thermal stability of the different pH-shift rice starch/casein-based high internal phase emulsions (SC-HIPE) were evaluated in the present study to verify potential in improving the quality of fish cake. The results showed that the pH-shift treatment improved thermal stability (from 27.23% to 76.33%) and oxidation time (from 5.01 h to 6.86 h) of SC-HIPE, which showed the smaller droplet size (decreased from 15.14 to 1.64 µm) and higher storage module. The breaking force of FC with thermal stable SC-HIPE (average 64.95 g) was higher than that with thermal unstable SC-HIPE (51.05 g). The cohesiveness, adhesiveness and chewiness could be improved by adding thermal stable SC-HIPE, compared with pork fat. Additionally, combining sensory evaluation, the thermal stable SC-HIPE improved the gel quality, thus it could be completely replaced pork fat in the preparation of FC, which provided theoretical guidance for the preparation and application of fat substitutes.

Effects of pork fat and linseed oil as additives on gel quality of fish cake.

Pork fat (PF) is a necessary ingredient in making traditional fish cakes (TFCs), which contains saturated fatty acids with potential health concerns. While linseed oil (LO) containing α-linolenic acid is a potential nutrient-enhancing fat substitute. In this study, the effect of pork fat and linseed oil level on gel quality, sensory characteristics, microstructure, and protein conformation of TFCs were characterized. Results showed that the TFCs with 30% pork fat (wt/wt) had the highest gel strength. Additionally, sensory evaluation determined that TFCs with 30% pork fat scored the best by a sensory panel with high gel strength, water-holding capacity, and fresh and sweet taste. The gel strength, chewiness, and hardness of nutrient-enriched fish cakes with 20% linseed oil replaced for pork fat were higher than that only with pork fat (wt/wt) without changing in tenderness and elasticity. Visual results showed that the network was uniform at a moderate level of linseed oil addition (20% LO/PF replacement ratio). The results of this study provided technical guidelines for standardizing the TFC manufacture processes, and useful insight for the development of fish cakes with reduced animal fat content for additional health benefits for consumers.

Positive Feedback Regulation of Circular RNA Hsa_circ_0000566 and HIF-1α promotes Osteosarcoma Progression and Glycolysis Metabolism.

Hypoxia is an indispensable factor for cancer progression and is closely associated with the Warburg effect. Circular RNAs (CircRNA) have garnered considerable attention in molecular malignancy therapy as they are potentially important modulators. However, the roles of circRNAs and hypoxia in osteosarcoma (OS) progression have not yet been elucidated. This study reveals the hypoxia-sensitive circRNA, Hsa_circ_0000566, that plays a crucial role in OS progression and energy metabolism under hypoxic stress. Hsa_circ_0000566 is regulated by hypoxia-inducible factor-1α (HIF-1α) and directly binds to it as well as to the Von Hippel-Lindau (VHL) E3 ubiquitin ligase protein. Consequentially, binding between VHL and HIF-1α is impeded. Furthermore, Hsa_circ_0000566 contributes to OS progression by binding to HIF-1α (while competing with VHL) and by confers protection against HIF-1α against VHL-mediated ubiquitin degradation. These findings demonstrate the existence of a positive feedback loop formed by HIF-1α and Hsa_circ_0000566 and the key role they play in OS glycolysis. Taken together, these data indicate the significance of Hsa_circ_0000566 in the Warburg effect and suggest that Hsa_circ_0000566 could be a potential therapeutic target to combat OS progression.