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Hepatocellular carcinoma (HCC) is a highly lethal cancer characterized by dominant driver mutations, including p53. Consequently, there is an urgent need to search for novel therapeutic agents to treat HCC. Andrographolide (Andro), a clinically available anti-inflammatory phytochemical agent, has shown inhibitory effects against various types of cancer, including HCC. However, the underlying molecular mechanisms of its action remain poorly understood. This study aims to investigate the molecular mechanisms by which p53 and p62 collectively affect Andro-induced HCC cell death, using both in vitro and in vivo models. In vitro cellular experiments were conducted to examine the effects of Andro on cell viability and elucidate its mechanisms of action. In vivo xenograft experiments further validated the anti-cancer effects of Andro. Andro induced dose- and time-dependent HCC cell death while sparing normal HL-7702 hepatocytes. Furthermore, Andro caused DNA damage through the generation of reactive oxygen species (ROS), a critical event leading to cell death. Notably, HCC cells expressing p53 exhibited greater resistance to Andro-induced cell death compared to p53-deficient cells, likely due to the ability of p53 to induce G2/M cell cycle arrest. Additionally, Andro-induced p62 aggregation led to the proteasomal degradation of RAD51 and 53BP1, two key proteins involved in DNA damage repair. Consequently, silencing or knocking out p62 facilitated DNA damage repair and protected HCC cells. Importantly, disruption of either p53 or p62 did not affect the expression of the other protein. These findings were further supported by the observation that xenograft tumors formed by p62-knockout HCC cells displayed increased resistance to Andro treatment. This study elucidates the mechanistic basis of Andro-induced HCC cell death. It provides valuable insights for repurposing Andro for the treatment of HCC, regardless of the presence of functional p53. [Display omitted] [ABSTRACT FROM AUTHOR]

The traditional biological wastewater treatment process faces issues of inefficiency and high greenhouse gas emissions. This study firstly established a symbiotic system between Tribonema sp. and Pseudomonas sp. (an aerobic denitrifying phosphorus accumulation bacteria). Results showed that co-culture systems significantly increased the removal rates of nutrients from wastewater and the biomass and lipid content of both microorganisms. The optimal inoculation ratio was 25:1, resulting in the removal rates of PO 4 3--P, NH 4 +-N, NO 3 --N, TN and TOC increased by up to 31.47%, 133.12%, 39.84%, 206.54%, 31.92%, and an increase of 6.72% and 80.11% in the biomass of Tribonema sp. and Pseudomonas sp., respectively, compared to single cultures. CO 2 release from respiration exceeded CO 2 fixation by microalgae. The CH 4 concentration in co-culture systems was lower than that in single cultures, with low levels of N 2 O detected. This symbiotic system effectively transforms wastewater nutrients into biomass resources while minimizing greenhouse gas emission. [Display omitted] • Symbiosis between Tribonema sp. and ADPA bacteria firstly constructed. • The optimal Tribonema sp. and Pseudomonas sp. inoculation ratio was 25:1. • The symbiosis achieved the highest nutrients removal and microorganism biomass. • Tribonema sp. and Pseudomonas sp. co-culture has the potential of GHG reduction. [ABSTRACT FROM AUTHOR]

Solid Te-doped Li 1.5 Al 0.5 Te x Ge 1.5- x (PO 4) 3 (LATGP) electrolyte materials are successfully prepared by the sol-gel method. The structure, morphology, and ionic and electronic conductivities of samples with different doping concentrations are analyzed by X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, electrochemical impedance spectroscopy, and DC polarization. The results reveal that Te doping can effectively promote the ionic conductivity of LAGP material, reaching a value of 6.33 × 10−4 S cm−1 at room temperature for Li 1.5 Al 0.5 Te 0.06 Ge 1.44 (PO 4) 3. Then, LATGP sheets are coated with graphite (G) by the magnetron sputtering method to improve the interfacial characteristics between the Li metal and LAGP electrolyte at high current densities. The polarization voltage curves of the symmetric graphite-modified Li/G@LATGP@G/Li cells remain stable after 800 h at high current densities of 0.5 mA cm−2 and 1 mA cm−2. The solid-state Li/G@LATGP/LiFePO 4 full cell presents an initial specific discharge capacity of 154.4 mAh·g−1 at a current density of 0.1 mA cm−2 as well as a capacity retention of 87.8% after 100 cycles. These results indicate that Te doping combined with graphite surface coating can effectively improve the ion transport and interfacial characteristics of solid LAGP electrolyte. • Te-doped Li 1.5 Al 0.5 Ge 1.5 (PO 4) 3 solid electrolyte materials. • High ionic conductivity of Li 1.5 Al 0.5 Te 0.06 Ge 1.44 (PO 4) 3 solid electrolyte. • Graphite modified interface between Li and LAGP. [ABSTRACT FROM AUTHOR]

• Moral goodness judgment and moral beauty judgment recruited the common brain activity in the left inferior OFC. • Moral goodness judgment mainly relied on the emotional facet of moral cognition, but moral beauty judgment relied on both the rational and emotional components of moral cognition. • Moral beauty judgment induced greater brain activity implicated in theory of mind (ToM), suggesting that it needs to understand the others' mental states but moral goodness judgment does not. • Moral beauty judgment also activated a cortical network that is considered mainly responsible for the processing of empathy, indicating that it involves empathic concerns for others. • The brain harbors neural systems for common and for domain-specific evaluations for moral goodness and moral beauty judgments. The objects of moral goodness and moral beauty judgments both generally refer to the positive moral acts or virtues of humans, and goodness must precede moral beauty. The main difference is that moral beauty, but not moral goodness, triggers emotional elevation. However, little is known about the neural mechanisms involved in both judgments. In the current study, 28 healthy female participants were scanned when they rated the good and beautiful extent of positive moral acts in daily life depicted in scene drawings to investigate the neural systems supporting moral goodness and moral beauty, specifically to test whether neural activity associated with moral beauty is same or different than moral goodness. The conjunction analysis of the contrasts between moral goodness judgment and moral beauty judgment identified the involvement of the left inferior orbitofrontal cortex (OFC), suggesting that the two judgments recruited the activity of a common brain region. Importantly, compared with the moral goodness judgment, the moral beauty judgment induced greater activity in more advanced cortical regions implicated in elevated emotions, including the anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC), superior frontal gyrus (SFG) and the left temporo-parietal junction (TPJ). These regions have been strongly correlated with the cognitive aspects of moral cognition, including theory of mind (ToM). In addition, moral beauty judgment also activated brain regions implicated in empathy including the midline structures and the anterior insula. Based on these results, the brain harbors neural systems for common and for domain-specific evaluations of moral goodness and moral beauty judgments. Our study thus provides novel and compelling neural evidence for the essence of moral beauty and advances the current knowledge of the neural mechanisms underlying the beauty-is-good stereotype. [ABSTRACT FROM AUTHOR]

The microecology of endophytic fungi in special habitats, such as the interior of different tissues from a medicinal plant, and its effects on the formation of metabolites with different biological activities are of great importance. However, the factors affecting fungal community formation are unclear. This study is the first to utilize "mini-community" remodeling to understand the above phenomena. First, high-throughput sequencing technology was applied to explore the community composition and diversity of endophytic fungi in the above-ground tissues (Ea) and below-ground tissues (Eb) of Ephedra sinica. Second, fungi were obtained through culture-dependent technology and used for "mini-community" remodeling in vitro. Then, the effects of environmental factors, partner fungi, and plant tissue fluid (internal environment) on endophytic fungal community formation were discussed. Results showed that environmental factors played a decisive role in the selection of endophytic fungi, that is, in Ea and Eb, 93.8% and 25.3% of endophytic fungi were halophilic, respectively, and 10.6% and 60.2% fungi were sensitive to high temperature (33 °C), respectively. Meanwhile, pH had little effect on fungal communities. The internal environment of the plant host further promoted the formation of endophytic fungal communities. [ABSTRACT FROM AUTHOR]

Abstract Chronic diabetic foot ulcer (DFU) is a major cause of disability and mortality in patients with diabetes. Dysfunctional endothelial progenitor cells (EPCs) play important roles in preventing vascular complications in these patients. Our results determined the elevated expression of histone deacetylase 2 (HDAC2) both in patients with DFU and in high glucose (HG) induced EPCs. In this study, HDAC2 siRNA (si-HDAC2) was transfected to investigate the effects of HDAC2 on EPCs. Cell proliferation decreased in HG-induced EPCs, but it was upregulated after si-HDAC2 transfection. Tube formation of EPCs also decreased with HG, which was reversed by si-HDAC2 transfection. Furthermore, inflammatory factors and reactive oxygen species (ROS) in EPCs were detected, showing that HG increased TNF-α, IL-1β, IL-6, and ROS production in EPCs. However, si-HDAC2 reversed these effects. These results indicate that HDAC2 inhibitor may resist HG-induced EPC injury. Finally, reduced expression of HO-1-Sirt1 signaling in HG-induced EPCs also was reversed by HDAC2 siRNA. In conclusion, these findings indicate that HDAC2 inhibitor may prevent impaired cell proliferation, tube formation, inflammation, and ROS production in high-glucose EPCs. Highlights • HDAC2 expression in patients with DFU and in HG-induced EPC • HDAC2 loss promoted cell proliferation and tube formation of EPC induced by HG. • HDAC2 loss attenuated inflammatory and oxidative stress of EPC induced by HG. • HDAC2 loss reduced injury in EPCs due to HG by activating the HO-1/Sirt1 pathway. [ABSTRACT FROM AUTHOR]

Purpose To develop a universal gene therapy to overcome the genetic heterogeneity in retinitis pigmentosa (RP) resulting from mutations in rhodopsin ( RHO ). Design Experimental study for a combination gene therapy that uses both gene ablation and gene replacement. Participants This study included 2 kinds of human RHO mutation knock-in mouse models: Rho P23H and Rho D190N . In total, 23 Rho P23H/P23H , 43 Rho P23H/+ , and 31 Rho D190N/+ mice were used for analysis. Methods This study involved gene therapy using dual adeno-associated viruses (AAVs) that (1) destroy expression of the endogenous Rho gene in a mutation-independent manner via an improved clustered regularly interspaced short palindromic repeats-based gene deletion and (2) enable expression of wild-type protein via exogenous cDNA. Main Outcome Measures Electroretinographic and histologic analysis. Results The thickness of the outer nuclear layer (ONL) after the subretinal injection of combination ablate-and-replace gene therapy was approximately 17% to 36% more than the ONL thickness resulting from gene replacement-only therapy at 3 months after AAV injection. Furthermore, electroretinography results demonstrated that the a and b waves of both Rho P23H and Rho D190N disease models were preserved more significantly using ablate-and-replace gene therapy ( P < 0.001), but not by gene replacement monotherapy. Conclusions As a proof of concept, our results suggest that the ablate-and-replace strategy can ameliorate disease progression as measured by photoreceptor structure and function for both of the human mutation knock-in models. These results demonstrate the potency of the ablate-and-replace strategy to treat RP caused by different Rho mutations. Furthermore, because ablate-and-replace treatment is mutation independent, this strategy may be used to treat a wide array of dominant diseases in ophthalmology and other fields. Clinical trials using ablate-and-replace gene therapy would allow researchers to determine if this strategy provides any benefits for patients with diseases of interest. [ABSTRACT FROM AUTHOR]

The discrete element method (DEM) is used to simulate two types of mixing processes (radial mixing and axial mixing) of particles with and without cohesive interparticle forces in a two-dimensional (2D) fluidized bed. By using the Ashton index, the mixing degree is quantified and the differences between the mixing characteristics of particles with and without cohesive interparticle forces are compared. The cohesive interparticle forces, which impair bubble behaviors, can apparently weaken the mixing process and prolong the mixing time. This effect increases with increasing cohesive interparticle force. Radial mixing, which is mainly dependent on the convective mixing caused by bubbles, is relatively sensitive to cohesive interparticle force and shows a long mixing time, while axial mixing, which is mainly induced by the bubble wake, is less sensitive to cohesive interparticle force and presents a fast mixing process. Finally, to weaken the effect of cohesive interparticle force, an uneven air distribution is introduced, which greatly improves the mixing process by changing the bubble movement. This method may be helpful for the reduction of particle agglomeration in high-temperature fluidized beds. [ABSTRACT FROM AUTHOR]

A graphene surface coating strategy (G@LATP), to modify and improve the interfacial characteristics between the Lithium Aluminum Titanium Phosphate (LATP) electrolyte and different anodes, such as Li metal and Si film has been proposed. As a result, the Li/Li symmetric cell with graphene coating modified LATP electrolyte exhibits excellent cyclic stability, even at large current densities of 0.5 mA·cm−2 and 1 mA·cm−2. The modified Li/G@LATP/LiFePO 4 solid-state full cell is delivering a discharge specific capacity of 136 mAh· g −1 after 200 cycles at a current density of 0.1 mA·cm−2, corresponding to a capacity retention of 86.1%. The graphene coating technique also led to improved cyclic stability in the Si/Si symmetric cell with modified LATP electrolyte at current densities of 0.1 mA·cm−2 and 0.3 mA·cm−2, with polarization voltages of 0.063 V and 0.27 V after cycling for 1000 h, respectively. Moreover, the Si/G@LATP/LiFePO 4 full cell shows an outstanding discharge specific capacity of 161 mAh· g −1 at its 2nd cycle, with a capacity retention of 92.9% after 200 cycles. These results show that graphene coating of the LATP electrolyte is a facile and effective method to improve the interfacial characteristics of Li/LATP and Si/LATP. [ABSTRACT FROM AUTHOR]

Antinomy(III) selenide (Sb 2 Se 3) nanorods were successfully prepared using a simple solvothermal method and then carbon-coated employing an ex-situ coating process with glucose as the carbon source. The composition and morphology of the prepared samples were characterized by X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, and transmission electron microscopy. In electrochemical investigations, Sb 2 Se 3 @C nanorods presented initial specific discharge capacities of 626.0 mAh·g−1 and 319.9 mAh·g−1 at 0.1 C and 1 C in a half-cell structure, respectively, with capacity retentions of 66.4 and 81.8% after 100 cycles. Electrochemical impedance spectroscopy analysis and galvanostatic intermittent titration technique tests revealed that carbon coating effectively promotes both the electronic and ionic conductivities of the Sb 2 Se 3 @C material, which is beneficial for its electrochemical performance. A Sb 2 Se 3 @C/Li 1.3 Al 0.3 Ti 1.7 (PO 4) 3 /LiFePO 4 quasi-solid-state battery was also assembled and delivered a specific discharge capacity of 332.4 mAh·g−1 at 0.2 C with a capacity retention of 60.1% after 100 cycles. In this work, Sb 2 Se 3 @C nanorods were successfully explored as anode material for quasi-solid-state lithium batteries. [Display omitted] [ABSTRACT FROM AUTHOR]

The discrete element method (DEM) is used to simulate three particle ejection mechanisms in a two-dimensional (2D) bubbling fluidized bed. The aim of the study is to analyze the particle ejection mechanisms and to investigate the effects of externally imposed interparticle forces on particle ejection. The ejection mechanisms are observed to be highly dependent on the extent of bubble coalescence. Bulge burst, which is induced by an isolated bubble eruption at the free bed surface, exhibits a regular dome contour with a lower initial velocity; wake spike, which is caused by the coalescence of two bubbles, shows a form of a spike with a higher initial velocity; jet spray, which is induced by the coalescence of more bubbles, presents continuous and violent clouds of particles. The induction of cohesive interparticle force not only delays the onset of particle ejection but also weakens its strength. The effect increases with increasing cohesive force. When cohesive force is increased to a high value, the occurrence of particle agglomeration further weakens particle ejection. For three different mechanisms, bulge burst is most sensitive to cohesive interparticle force, followed by wake spike and jet spray. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ferric hydroxide-polyphosphate nanoparticles were prepared in a wet chemical way. • Colloidal stability was good under spray/freeze-drying/gastrointestinal conditions. • Weak pro-oxidant activity was observed in glyceryl trilinoleate emulsion. • High relative iron bioavailability (∼170% relative to FeSO 4) was observed in rats. • Cellular iron uptake invoked a DMT1-independent/macropinocytosis-dependent pathway. Polyphosphates are widely used food additives with the potential to increase iron bioavailability but chemical nature of their soluble complexes with iron remains largely unknown. Here, pyrophosphate, tripolyphosphate, hexametaphosphate and ∼25-chain-length polyphosphate solubilized 896, 896, 1120 and 1344 mg Fe(III) per g, respectively, at neutral pH by mediating the formation of highly-negatively-charged ferric hydroxide-polyphosphate nanoparticles (PolyP-FeONPs). PolyP-FeONPs displayed fading yellow color with increasing initial dissolved P/Fe ratio ((P/Fe) init) and decreasing polyphosphate length due to rising proportion of Fe(III)-phosphate bonds, and specifically, pyrophosphate resulted colorless PolyP-FeONPs at (P/Fe) init ≥ 4. PolyP-FeONPs had weak pro-oxidant activity in glyceryl trilinoleate emulsion and good colloidal stability under spray/freeze-drying and gastrointestinal conditions. Serum iron kinetics in rats revealed sustained iron release and ∼170% iron bioavailability of oral PolyP-FeONPs relative to FeSO 4. Calcein-fluorescence-quenching assay in polarized Caco-2 cells unveiled divalent-metal-transporter-1-independent and macropinocytosis-dependent iron uptake from PolyP-FeONPs. This study helps develop food-compatible, highly-bioavailable and sustained-release iron preparations. [ABSTRACT FROM AUTHOR]