TRIM21 induces selective autophagic degradation of c-Myc and sensitizes regorafenib therapy in colorectal cancer.

Kirsten rat sarcoma virus (KRAS) mutation is associated with malignant tumor transformation and drug resistance. However, the development of clinically effective targeted therapies for KRAS-mutant cancer has proven to be a formidable challenge. Here, we report that tripartite motif-containing protein 21 (TRIM21) functions as a target of extracellular signal-regulated kinase 2 (ERK2) in KRAS-mutant colorectal cancer (CRC), contributing to regorafenib therapy resistance. Mechanistically, TRIM21 directly interacts with and ubiquitinates v-myc avian myelocytomatosis viral oncogene homolog (c-Myc) at lysine 148 (K148) via K63-linkage, enabling c-Myc to be targeted to the autophagy machinery for degradation, ultimately resulting in the downregulation of enolase 2 expression and inhibition of glycolysis. However, mutant KRAS (KRAS/MT)-driven mitogen-activated protein kinase (MAPK) signaling leads to the phosphorylation of TRIM21 (p-TRIM21) at Threonine 396 (T396) by ERK2, disrupting the interaction between TRIM21 and c-Myc and thereby preventing c-Myc from targeting autophagy for degradation. This enhances glycolysis and contributes to regorafenib resistance. Clinically, high p-TRIM21 (T396) is associated with an unfavorable prognosis. Targeting TRIM21 to disrupt KRAS/MT-driven phosphorylation using the antidepressant vilazodone shows potential for enhancing the efficacy of regorafenib in treating KRAS-mutant CRC in preclinical models. These findings are instrumental for KRAS-mutant CRC treatment aiming at activating TRIM21-mediated selective autophagic degradation of c-Myc.

Progress in using cross-linking technologies to increase the thermal stability of colloidal delivery systems.

In recent years, crosslinking technology has been found and widely used in food, textile, pharmaceutical, bioengineering and other fields. Crosslinking is a reaction in which two or more molecules bond to each other to form a stable three-dimensional network structure to improve the strength, heat resistance and other properties of substances. The researchers found that the cross-linking technology has a significant effect on improving the thermal stability of the colloidal delivery system. In this paper, crosslinking techniques that can be used to improve the thermal stability of colloidal delivery systems are reviewed, including enzyme-, ion-, chemical-, and combined cross-linking. Initially, the underlying mechanisms of these crosslinking technologies is reviewed. Then, the impacts of crosslinking on the heat-stability of colloidal delivery systems are discussed. Finally, the application of crosslinked delivery systems in improving the thermal stability of probiotics, polyphenols, pigments, and nutrients in foods and food packaging materials is introduced. The ability of proteins and polysaccharides to form heat-stable colloidal delivery systems can be improved by crosslinking. Nevertheless, more research is required to establish the impact of different crosslinking on the thermal stability of a broader range of different delivery systems, as well as to ensure their safety and efficacy.

Recent advances in enzymatic modification techniques to improve the quality of flour-based fried foods.

Flour-based fried foods are among the most commonly consumed foods worldwide. However, the sensory attributes and nutritional value of fried foods are inconsistent and unstable. Therefore, the creation of fried foods with desirable sensory attributes and good nutritional value remains a major challenge for the development of the fried food industry. The quality of flour-based fried foods can sometimes be improved by physical methods and the addition of chemical modifiers. However, enzyme modification is widely accepted by consumers due to its unique advantages of specificity, mild processing conditions and high safety. Therefore, it is important to elucidate the effects of enzyme treatments on the sensory attributes (color, flavor and texture), oil absorption and digestibility of flour-based fried foods. This paper reviews recent research progress in utilizing enzyme modification to improve the quality of flour-based fried foods. This paper begins with the effects of common enzymes on the physicochemical properties (rheological property, retrogradation property and specific volume) of dough. Based on the analysis of the mechanism of formation of sensory attributes and nutritional properties, it focuses on the application of amylase, protease, transglutaminase, and lipase in the regulation of sensory attributes and nutritional properties of flour-based fried foods.

The Rechargeable Aluminum Battery: Opportunities and Challenges.

Aluminum battery systems are considered as a system that could supplement current lithium batteries due to the low cost and high volumetric capacity of aluminum metal, and the high safety of the whole battery system. However, first the use of ionic liquid electrolytes leading to AlCl4 - instead of Al3+ , the different intercalation reagents, the sluggish solid diffusion process and the fast capacity fading during cycling in aluminum batteries all need to be thoroughly explored. To provide a good understanding of the opportunities and challenges of the newly emerging aluminum batteries, this Review discusses the reaction mechanisms and the difficulties caused by the trivalent reaction medium in electrolytes, electrodes, and electrode-electrolyte interfaces. It is hoped that the Review will stimulate scientists and engineers to develop more reliable aluminum batteries.

An Aluminum-Sulfur Battery with a Fast Kinetic Response.

The electrochemical performance of the aluminum-sulfur (Al-S) battery has very poor reversibility and a low charge/discharge current density owing to slow kinetic processes determined by an inevitable dissociation reaction from Al2 Cl7- to free Al3+ . Al2 Cl6 Br- was used instead of Al2 Cl7- as the dissociation reaction reagent. A 15-fold faster reaction rate of Al2 Cl6 Br- dissociation than that of Al2 Cl7- was confirmed by density function theory calculations and the Arrhenius equation. This accelerated dissociation reaction was experimentally verified by the increase of exchange current density during Al electro-deposition. Using Al2 Cl6 Br- instead of Al2 Cl7- , a kinetically accelerated Al-S battery has a sulfur utilization of more than 80 %, with at least four times the sulfur content and five times the current density than that of previous work.

Constant Flux of Spatial Niche Partitioning through High-Resolution Sampling of Magnetotactic Bacteria.

Magnetotactic bacteria (MTB) swim along magnetic field lines in water. They are found in aquatic habitats throughout the world, yet knowledge of their spatial and temporal distribution remains limited. To help remedy this, we took MTB-bearing sediment from a natural pond, mixed the thoroughly homogenized sediment into two replicate aquaria, and then counted three dominant MTB morphotypes (coccus, spirillum, and rod-shaped MTB cells) at a high spatiotemporal sampling resolution: 36 discrete points in replicate aquaria were sampled every ∼30 days over 198 days. Population centers of the MTB coccus and MTB spirillum morphotypes moved in continual flux, yet they consistently inhabited separate locations, displaying significant anticorrelation. Rod-shaped MTB were initially concentrated toward the northern end of the aquaria, but at the end of the experiment, they were most densely populated toward the south. The finding that the total number of MTB cells increased over time during the experiment argues that population reorganization arose from relative changes in cell division and death and not from migration. The maximum net growth rates were 10, 3, and 1 doublings day-1 and average net growth rates were 0.24, 0.11, and 0.02 doublings day-1 for MTB cocci, MTB spirilla, and rod-shaped MTB, respectively; minimum growth rates for all three morphotypes were -0.03 doublings day-1 Our results suggest that MTB cocci and MTB spirilla occupy distinctly different niches: their horizontal positioning in sediment is anticorrelated and under constant flux.IMPORTANCE Little is known about the horizontal distribution of magnetotactic bacteria in sediment or how the distribution changes over time. We therefore measured three dominant magnetotactic bacterium morphotypes at 36 places in two replicate aquaria each month for 7 months. We found that the spatial positioning of population centers changed over time and that the two most abundant morphotypes (MTB cocci and MTB spirilla) occupied distinctly different niches in the aquaria. Maximum and average growth and death rates were quantified for each of the three morphotypes based on 72 sites that were measured six times. The findings provided novel insight into the differential behavior of noncultured magnetotactic bacteria.

Phosphate flow between hybrid histidine kinases CheA3 and CheS3 controls Rhodospirillum centenum cyst formation.

Genomic and genetic analyses have demonstrated that many species contain multiple chemotaxis-like signal transduction cascades that likely control processes other than chemotaxis. The Che3 signal transduction cascade from Rhodospirillum centenum is one such example that regulates development of dormant cysts. This Che-like cascade contains two hybrid response regulator-histidine kinases, CheA3 and CheS3, and a single-domain response regulator CheY3. We demonstrate that cheS3 is epistatic to cheA3 and that only CheS3∼P can phosphorylate CheY3. We further show that CheA3 derepresses cyst formation by phosphorylating a CheS3 receiver domain. These results demonstrate that the flow of phosphate as defined by the paradigm E. coli chemotaxis cascade does not necessarily hold true for non-chemotactic Che-like signal transduction cascades.

Partial Dislocations in Graphene and Their Atomic Level Migration Dynamics.

We demonstrate the formation of partial dislocations in graphene at elevated temperatures of ≥500 °C with single atom resolution aberration corrected transmission electron microscopy. The partial dislocations spatially redistribute strain in the lattice, providing an energetically more favorable configuration to the perfect dislocation. Low-energy migration paths mediated by partial dislocation formation have been observed, providing insights into the atomistic dynamics of graphene during annealing. These results are important for understanding the high temperature plasticity of graphene and partial dislocation behavior in related crystal systems, such as diamond cubic materials.

Atomic level spatial variations of energy states along graphene edges.

The local atomic bonding of carbon atoms around the edge of graphene is examined by aberration-corrected scanning transmission electron microscopy (STEM) combined with electron energy loss spectroscopy (EELS). High-resolution 2D maps of the EELS combined with atomic resolution annular dark field STEM images enables correlations between the carbon K-edge EELS and the atomic structure. We show that energy states of graphene edges vary across individual atoms along the edge according to their specific C-C bonding, as well as perpendicular to the edge. Unique spectroscopic peaks from the EELS are assigned to specific C atoms, which enables unambiguous spectroscopic fingerprint identification for the atomic structure of graphene edges with unprecedented detail.

Inflating graphene with atomic scale blisters.

Using 80 kV electron beam irradiation we have created graphene blister defects of additional carbon atoms incorporated into a graphene lattice. These structures are the antithesis of the vacancy defect with blister defects observed to contain up to six additional carbon atoms. We present aberration-corrected transmission electron microscopy data demonstrating the formation of a blister from an existing divacancy, together with further examples that undergo reconfiguration and annihilation under the electron beam. The relative stability of the observed variations of blister are discussed and considered in the context of previous calculations. It is shown that the blister defect is seldom found in isolation and is more commonly coupled with dislocations where it can act as an intermediate state, permitting dislocation core climb without the atom ejection from the graphene lattice required for nonconservative motion.

Stability and dynamics of the tetravacancy in graphene.

The relative prevalence of various configurations of the tetravacancy defect in monolayer graphene has been examined using aberration corrected transmission electron microscopy (TEM). It was found that the two most common structures are extended linear defect structures, with the 3-fold symmetric Y-tetravacancy seldom imaged, in spite of this being a low energy state. Using density functional theory and tight-binding molecular dynamics calculations, we have determined that our TEM observations support a dynamic model of the tetravacancy under electron irradiation, with Stone-Wales bond rotations providing a mechanism for defect relaxation into lowest energy configurations. The most prevalent tetravacancy structures, while not necessarily having the lowest formation energy, are found to have a local energy minimum in the overall energy landscape for tetravacancies, explaining their relatively high occurrence.

The role of the bridging atom in stabilizing odd numbered graphene vacancies.

Vacancy defects in graphene with an odd number of missing atoms, such as the trivacancy, have been imaged at atomic resolution using aberration corrected transmission electron microscopy. These defects are not just stabilized by simple bond reconstructions between under-coordinated carbon atoms, as exhibited by even vacancies such as the divacancy. Instead we have observed reconstructions consisting of under-coordinated bridging carbon atoms spanning the vacancy to saturate edge atoms. We report detailed studies of the effect of this bridging atom on the configuration of the trivacancy and higher order odd number vacancies, as well as its role in defect stabilization in amorphous systems. Theoretical analysis using density functional theory and tight-binding molecular dynamics calculations demonstrate that the bridging atom enables the low energy reconfiguration of these defect structures.

Atomic structure and dynamics of metal dopant pairs in graphene.

We present an atomic resolution structural study of covalently bonded dopant pairs in the lattice of monolayer graphene. Two iron (Fe) metal atoms that are covalently bonded within the graphene lattice are observed and their interaction with each other is investigated. The two metal atom dopants can form small paired clusters of varied geometry within graphene vacancy defects. The two Fe atoms are created within a 10 nm diameter predefined location in graphene by manipulating a focused electron beam (80 kV) on the surface of graphene containing an intentionally deposited Fe precursor reservoir. Aberration-corrected transmission electron microscopy at 80 kV has been used to investigate the atomic structure and real time dynamics of Fe dimers embedded in graphene vacancies. Four different stable structures have been observed; two variants of an Fe dimer in a graphene trivacancy, an Fe dimer embedded in two adjacent monovacancies and an Fe dimer trapped by a quadvacancy. According to spin-sensitive DFT calculations, these dimer structures all possess magnetic moments of either 2.00 or 4.00 µB. The dimer structures were found to evolve from an initial single Fe atom dopant trapped in a graphene vacancy.

Optimized determination of polybrominated diphenyl ethers by ultrasound-assisted liquid-liquid extraction and high-performance liquid chromatography.

A method based on ultrasound-assisted liquid-liquid extraction and high-performance liquid chromatography has been optimized for the determination of six polybrominated diphenyl ether congeners. The optimal condition relevant to the extraction was first investigated, more than 98.7 ± 0.7% recovery was achieved with dichloromethane as extractant, 5 min extraction time, and three cycles of ultrasound-assisted liquid-liquid extraction. Then multiple function was employed to optimize polybrominated diphenyl ether detection conditions with overall resolution and chromatography signal area as the responses. The condition chosen in this experiment was methanol/water 93:7 v/v, flow rate 0.80 mL/min, column temperature 30.0°C. The optimized technique revealed good linearity (R(2) > 0.9962 over a concentration range of 1-100 µg/L) and repeatability (relative standard deviation < 6.3%). Furthermore, the detection limit (S/N = 3) of the method were ranged from 0.02 to 0.13 µg/L and the quantification limit (S/N = 10) ranged from 0.07 to 0.35 µg/L. Finally, the proposed method was applied to spiked samples and satisfactory results were achieved. These results indicate that ultrasound-assisted liquid-liquid extraction coupled with high-performance liquid chromatography was effective to identify and quantify the complex polybrominated diphenyl ethers in effluent samples.

Sensitivity of graphene edge states to surface adatom interactions.

Electron beam irradiation at 60 kV is used to open holes in graphene and expose fresh clean edges for further examination by electron energy loss spectroscopy (EELS) at the single atom level combined with scanning transmission electron microscopy (STEM). We show that light element surface adatoms attached on top of the edges of graphene influence the carbon K-edge EELS. A single nitrogen adatom on graphene was imaged by STEM and chemically identified by EELS. We also extend this study to small graphene nanoribbons, termed nanoconstrictions. The arrival of surface adatoms disrupt the detection of unique carbon edge states present in both single edges and in the nanoconstrictions. The spatial distribution of the EELS signals is also examined. These results show that edge states in graphene are highly sensitive to single atom functionalization and sheds light on their long-term stability.

Rippling graphene at the nanoscale through dislocation addition.

Ripples in graphene are an out-of-plane distortion that help stabilize suspended monolayer graphene. The introduction of disclinations and dislocations into the lattice of graphene is predicted to extensively ripple graphene to form "hillocks" to accommodate the strain in the system. Here, we confirm this theoretical prediction by intentionally introducing large numbers of dislocations into a predefined area of pristine monolayer graphene by scanning focused electron beam irradiation and imaging the rippled atomic lattice structure with aberration-corrected transmission electron microscopy. Hillocks are observed and analyzed using geometric phase analysis to determine heights of ~0.5 nm. Time-dependent imaging shows the rippling is dynamic under the electron beam and can fluctuate between different structural configurations. This demonstrates a means of perturbing the structure of graphene in all three spatial dimensions with nanoscale precision.

Dynamics of single Fe atoms in graphene vacancies.

Focused electron beam irradiation has been used to create mono and divacancies in graphene within a defined area, which then act as trap sites for mobile Fe atoms initially resident on the graphene surface. Aberration-corrected transmission electron microscopy at 80 kV has been used to study the real time dynamics of Fe atoms filling the vacancy sites in graphene with atomic resolution. We find that the incorporation of a dopant atom results in pronounced displacements of the surrounding carbon atoms of up to 0.5 Å, which is in good agreement with density functional theory calculations. Once incorporated into the graphene lattice, Fe atoms can transition to adjacent lattice positions and reversibly switch their bonding between four and three nearest neighbors. The C atoms adjacent to the Fe atoms are found to be more susceptible to Stone-Wales type bond rotations with these bond rotations associated with changes in the dopant bonding configuration. These results demonstrate the use of controlled electron beam irradiation to incorporate dopants into the graphene lattice with nanoscale spatial control.

Clear cell hepatocellular carcinoma: Gd-EOB-DTPA-enhanced MR imaging features and prognosis.

PURPOSE: To investigate imaging findings on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) and prognosis of clear cell hepatocellular carcinoma (CCHCC) comparing with non-otherwise specified hepatocellular carcinoma (NOS-HCC). METHODS: The clinical, pathological and MR imaging features of 42 patients with CCHCC and 84 age-matched patients with NOS-HCC were retrospectively analyzed from January 2015 to October 2021. Univariate and multivariate logistic regression and Cox regression analyses were performed to identify independent diagnostic and prognostic factors for CCHCC. Disease-free survival (DFS) and overall survival (OS) were determined by Kaplan-Meier analysis. RESULTS: CCHCC showed fat content more frequently (P < 0.001) and relatively higher Edmondson tumor grade (P = 0.001) compared with NOS-HCC. The lesion-to-muscle ratio (LMR) and lesion-to-liver ratio (LLR) of CCHCC on pre-enhancement T1-weighted imaging (pre-T1WI) (P = 0.001, P = 0.003) and hepatobiliary phase (HBP) (P = 0.007, P = 0.048) were significantly higher than those of NOS-HCC. The area under the curve (AUC) for fat content, LLR on pre-T1WI and their combination with better diagnostic performance in predicting CCHCC were 0.678, 0.666, and 0.750, respectively. There was no statistically significant difference in clinical outcomes between CCHCC and NOS-HCC. Multivariate Cox analysis confirmed that tumor size > 2 cm and enhancing capsule were independent prognostic factors for DFS and OS among CCHCC patients. CONCLUSION: Fat content and adjusted lesion signal intensity on pre-T1WI and HBP could be used to differentiate CCHCC from NOS-HCC. CCHCC had similar prognosis with NOS-HCC.

Utilization of diverse probiotics to create human health promoting fatty acids: A review.

Many probiotics produce functional lipids with health-promoting properties, such as short-chain fatty acids, linoleic acid and omega-3 fatty acids. They have been shown to maintain gut health, strengthen the intestinal barrier, and have anti-inflammatory and antioxidant effects. In this article, we provide an up-to-date review of the various functional lipids produced by probiotics. These probiotics can be incorporated into foods, supplements, or pharmaceuticals to produce these functional lipids in the human colon, or they can be used in industrial biotechnology processes to generate functional lipids, which are then isolated and used as ingredients. We then highlight the different physiological functions for which they may be beneficial to human health, in addition to discussing some of the challenges of incorporating probiotics into commercial products and some potential solutions to address these challenges. Finally, we highlight the importance of testing the efficacy and safety of the new generation of probiotic-enhanced products, as well as the great potential for the marketization of related products.

Safety risk assessment of subway shield construction under-crossing a river using CFA and FER.

Numerous subway projects are planned by China's city governments, and more subways can hardly avoid under-crossing rivers. While often being located in complex natural and social environments, subway shield construction under-crossing a river (SSCUR) is more susceptible to safety accidents, causing substantial casualties, and monetary losses. Therefore, there is an urgent need to investigate safety risks during SSCUR. The paper identified the safety risks during SSCUR by using a literature review and experts' evaluation, proposed a new safety risk assessment model by integrating confirmatory factor analysis (CFA) and fuzzy evidence reasoning (FER), and then selected a project to validate the feasibility of the proposed model. Research results show that (a) a safety risk list of SSCUR was identified, including 5 first-level safety risks and 38 second-level safety risks; (b) the proposed safety risk assessment model can be used to assess the safety risk of SSCUR; (c) safety inspection, safety organization and duty, quicksand layer, and high-pressure phreatic water were the high-level risks, and the onsite total safety risk was at the medium level; (d) management-type safety risks, environment-type safety risks, and personnel-type safety risks have higher expected utility values, and manager-type safety risks were expected have higher risk-utility values when compared to worker-type safety risks. The research can enrich the theoretical knowledge of SSCUR safety risk assessment and provide references to safety managers for conducting scientific and effective safety management on the construction site when a subway crosses under a river.