Atomically dispersed asymmetric cobalt electrocatalyst for efficient hydrogen peroxide production in neutral media.

Electrochemical hydrogen peroxide (H2O2) production (EHPP) via a two-electron oxygen reduction reaction (2e- ORR) provides a promising alternative to replace the energy-intensive anthraquinone process. M-N-C electrocatalysts, which consist of atomically dispersed transition metals and nitrogen-doped carbon, have demonstrated considerable EHPP efficiency. However, their full potential, particularly regarding the correlation between structural configurations and performances in neutral media, remains underexplored. Herein, a series of ultralow metal-loading M-N-C electrocatalysts are synthesized and investigated for the EHPP process in the neutral electrolyte. CoNCB material with the asymmetric Co-C/N/O configuration exhibits the highest EHPP activity and selectivity among various as-prepared M-N-C electrocatalyst, with an outstanding mass activity (6.1 × 105 A gCo-1 at 0.5 V vs. RHE), and a high practical H2O2 production rate (4.72 mol gcatalyst-1 h-1 cm-2). Compared with the popularly recognized square-planar symmetric Co-N4 configuration, the superiority of asymmetric Co-C/N/O configurations is elucidated by X-ray absorption fine structure spectroscopy analysis and computational studies.

Rational Design of Organic Electrocatalysts for Hydrogen and Oxygen Electrocatalytic Applications.

Efficient electrocatalysts are pivotal for advancing green energy conversion technologies. Organic electrocatalysts, as cost-effective alternatives to noble-metal benchmarks, have garnered attention. However, the understanding of the relationships between their properties and electrocatalytic activities remains ambiguous. Plenty of research articles regarding low-cost organic electrocatalysts started to gain momentum in 2010 and have been flourishing recently though, a review article for both entry-level and experienced researchers in this field is still lacking. This review underscores the urgent need to elucidate the structure-activity relationship and design suitable electrode structures, leveraging the unique features of organic electrocatalysts like controllability and compatibility for real-world applications. Organic electrocatalysts are classified into four groups: small molecules, oligomers, polymers, and frameworks, with specific structural and physicochemical properties serving as activity indicators. To unlock the full potential of organic electrocatalysts, five strategies are discussed: integrated structures, surface property modulation, membrane technologies, electrolyte affinity regulation, and addition of anticorrosion species, all aimed at enhancing charge efficiency, mass transfer, and long-term stability during electrocatalytic reactions. The review offers a comprehensive overview of the current state of organic electrocatalysts and their practical applications, bridging the understanding gap and paving the way for future developments of more efficient green energy conversion technologies.

Lithocholic Acid Alleviates Deoxynivalenol-Induced Inflammation and Oxidative Stress via PPARγ-Mediated Epigenetically Transcriptional Reprogramming in Porcine Intestinal Epithelial Cells.

Deoxynivalenol (DON) is a common mycotoxin that induces intestinal inflammation and oxidative damage in humans and animals. Given that lithocholic acid (LCA) has been suggested to inhibit intestinal inflammation, we aimed to investigate the protective effects of LCA on DON-exposed porcine intestinal epithelial IPI-2I cells and the underlying mechanisms. Indeed, LCA rescued DON-induced cell death in IPI-2I cells and reduced DON-stimulated inflammatory cytokine levels and oxidative stress. Importantly, the nuclear receptor PPARγ was identified as a key transcriptional factor involved in the DON-induced inflammation and oxidative stress processes in IPI-2I cells. The PPARγ function was found compromised, likely due to the hyperphosphorylation of the p38 and ERK signaling pathways. In contrast, the DON-induced inflammatory responses and oxidative stress were restrained by LCA via PPARγ-mediated reprogramming of the core inflammatory and antioxidant genes. Notably, the PPARγ-modulated transcriptional regulations could be attributed to the altered recruitments of coactivator SRC-1/3 and corepressor NCOR1/2, along with the modified histone marks H3K27ac and H3K18la. This study emphasizes the protective actions of LCA on DON-induced inflammatory damage and oxidative stress in intestinal epithelial cells via PPARγ-mediated epigenetically transcriptional reprogramming, including histone acetylation and lactylation.

Nuclear Receptor PPARα as a Therapeutic Target in Diseases Associated with Lipid Metabolism Disorders.

Lipid metabolic diseases have substantial morbidity and mortality rates, posing a significant threat to human health. PPARα, a member of the peroxisome proliferator-activated receptors (PPARs), plays a crucial role in lipid metabolism and immune regulation. Recent studies have increasingly recognized the pivotal involvement of PPARα in diverse pathological conditions. This comprehensive review aims to elucidate the multifaceted role of PPARα in metabolic diseases including liver diseases, diabetes-related diseases, age-related diseases, and cancers, shedding light on the underlying molecular mechanisms and some regulatory effects of natural/synthetic ligands of PPARα. By summarizing the latest research findings on PPARα, we aim to provide a foundation for the possible therapeutic exploitation of PPARα in lipid metabolic diseases.

Antibiotic-Induced Recruitment of Specific Algae-Associated Microbiome Enhances the Adaptability of Chlorella vulgaris to Antibiotic Stress and Incidence of Antibiotic Resistance.

Insights into the symbiotic relation between eukaryotic hosts and their microbiome lift the curtain on the crucial roles of microbes in host fitness, behavior, and ecology. However, it remains unclear whether and how abiotic stress shapes the microbiome and further affects host adaptability. This study first investigated the effect of antibiotic exposure on behavior across varying algae taxa at the community level. Chlorophyta, in particular Chlorella vulgaris, exhibited remarkable adaptability to antibiotic stress, leading to their dominance in phytoplankton communities. Accordingly, we isolated C. vulgaris strains and compared the growth of axenic and nonaxenic ones under antibiotic conditions. The positive roles of antibiotics in algal growth were apparent only in the presence of bacteria. Results of 16S rRNA sequencing further revealed that antibiotic challenges resulted in the recruitment of specific bacterial consortia in the phycosphere, whose functions were tightly linked to the host growth promotion and adaptability enhancement. In addition, the algal phycosphere was characterized with 47-fold higher enrichment capability of antibiotic resistance genes (ARGs) than the surrounding water. Under antibiotic stress, specific ARG profiles were recruited in C. vulgaris phycosphere, presumably driven by the specific assembly of bacterial consortia and mobile genetic elements induced by antibiotics. Moreover, the antibiotics even enhanced the dissemination potential of the bacteria carrying ARGs from the algal phycosphere to broader environmental niches. Overall, this study provides an in-depth understanding into the potential functional significance of antibiotic-mediated recruitment of specific algae-associated bacteria for algae adaptability and ARG proliferation in antibiotic-polluted waters.

Curcumin derived from medicinal homologous foods: its main signals in immunoregulation of oxidative stress, inflammation, and apoptosis.

It has been for thousands of years in China known medicinal homologous foods that can be employed both as foods and medicines to benefit human and animal health. These edible herbal materials perform divert roles in the regulation of metabolic disorders, cancers, and immune-related diseases. Curcumin, the primary component derived from medicinal homologous foods like curcuma longa rhizome, is reported to play vital actions in organic activities, such as the numerous pharmacological functions including anti-oxidative stress, anti-inflammation and anti/pro-apoptosis in treating various diseases. However, the potential mechanisms of curcumin-derived modulation still need to be developed and attract more attention worldwide. Given that these signal pathways are enrolled in important bioactive reactions, we collected curcumin's last achievements predominantly on the immune-regulation signals with the underlying targetable strategies in the last 10 years. This mini-review will be helpful to accelerate curcumin and other extracts from medicinal homologous foods use in future human clinical applications.

Sodium Butyrate Ameliorates Deoxynivalenol-Induced Oxidative Stress and Inflammation in the Porcine Liver via NR4A2-Mediated Histone Acetylation.

Mycotoxin-induced liver injury is often accompanied by oxidative stress (OS) and inflammation. This research aimed to explore the potential mechanism of sodium butyrate (NaBu) in modulating hepatic anti-oxidation and anti-inflammation pathways in deoxynivalenol (DON)-exposed piglets. The results show that DON induced liver injury, increased mononuclear cell infiltration, and decreased serum total protein and albumin concentrations. Transcriptomic analysis revealed that reactive oxygen species (ROS) and TNF-α pathways were highly activated upon DON exposure. This is associated with disturbed antioxidant enzymes and increased inflammatory cytokines secretion. Importantly, NaBu effectively reversed the alterations caused by DON. Mechanistically, the ChIP-seq result revealed that NaBu strongly depressed DON-increased enrichment of histone mark H3K27ac at the genes involved in ROS and TNF-α-mediated pathways. Notably, we demonstrated that nuclear receptor NR4A2 was activated by DON and remarkably recovered with the treatment of NaBu. In addition, the enhanced NR4A2 transcriptional binding enrichments at the promoter regions of OS and inflammatory genes were hindered by NaBu in DON-exposed livers. Consistently, elevated H3K9ac and H3K27ac occupancies were also observed at the NR4A2 binding regions. Taken together, our results indicated that a natural antimycotic additive, NaBu, could mitigate hepatic OS and inflammatory responses, possibly via NR4A2-mediated histone acetylation.

Accelerating the Discovery of Transition Metal Borides by Machine Learning on Small Data Sets.

Accurate and efficient prediction of the stability and structure-stability relationship is important to discover materials; however, it requires tremendous efforts via traditional trial-and-error schemes. Here, we presented a small-data set machine learning (ML) method to accelerate the discovery of promising ternary transition metal boride (MAB) candidates. Based on data sets obtained by ab initio calculations, we developed three robust neural networks to predict the decomposition energy (ΔHd) and assess the thermodynamic stability of 212-typed MABs (M2AB2). The quantitative relation between ΔHd and stability was unraveled by several composition-and-structure descriptors. Three hexagonal M2AB2, i.e., Nb2PB2, Nb2AsB2, and Zr2SB2, were discovered to be stable with negative ΔHd, and 75 metastable MABs were identified with ΔHd less than 70 meV/atom. Finally, the dynamical stability and mechanical properties of MABs were investigated by ab initio calculations, whose results further verified the reliability of our ML models. This work provided a ML approach on small data sets to accelerate the discovery of compounds and expanded the MAB phase family to VA and VIA groups.

Construction of a Co/MnO Mott-Schottky Heterostructure to Achieve Interfacial Synergy in the Oxygen Reduction Reaction for Aluminum-Air Batteries.

The rational design of non-noble metal-based electrocatalysts for an efficient oxygen reduction reaction (ORR) is an important research topic to promote the advancement of aluminum-air batteries. In this work, heterostructural Co/MnO nanoparticles encapsulated in a N-doped carbon electrocatalyst were prepared via one-step pyrolysis utilizing different reduction potentials of Co and Mn ions, and the heterointerface between the two phases was confirmed. The prepared catalyst displays Pt/C competitive ORR performance because of the interfacial synergy of a Co/MnO Mott-Schottky (M-S) heterostructure, which leads to boosted conductivity, formation of an M-S barrier, and a reduced oxygen reduction energy barrier for excited electrons. Furthermore, the Co/MnO-based aluminum-air battery displays good discharge performance, demonstrating good feasibility for practical application.

Preventive effect of surface charge on encrustation of biodegradable ureteral stents.

Prevention of encrustation on the surface has always been the biggest challenge for urological implants. In the field of ureteral stent design, biodegradability has attracted much attention in recent years, because biodegradable ureteral stents not only avoid secondary intervention, but also prevent encrustation due to surface renewal by degradation process. Furthermore, researches have focus on some surface parameters to provide guidance for the development of stent materials, such as hydrophilicity or surface charge. In this work, we synthesized two types of poly(ester-carbonate)s, poly(L-lactide-co-5-amino-1,3-dioxan-2-one) (P(LA-co-AC)) containing amino, and poly (L-lactide-co-5-methyl-5-carboxyl-1,3-dioxan-2-one) (P(LA-co-MCC)) containing carboxyl. Blending P(LA-co-AC) and P(LA-co-MCC) with poly(L-lactide-co-Ɛ-caprolactone) (PLACL) respectively, two types of ureteral stent materials were prepared. Due to the influence of ions formed by the dissociation of amino and carboxyl, two types of materials show differences in surface charge analyses. We further developed a dynamic urinary extracorporeal circulation (DUEC) system to assess in vitro encrustation of materials with different surface charges. The results of this comparative study identified that the materials with strong negative surface charge were most favorable for use as ureteral stent, and provided a new approach to surmount the problems faced by urological surgery which complied with the future trend of biodegradable ureteral stent design.

Zinc intake ameliorates intestinal morphology and oxidative stress of broiler chickens under heat stress.

Zinc (Zn), an essential trace element for poultry, plays a crucial role in promoting growth, improving feed conversion efficiency, enhancing antioxidant activity, and preventing disease. This study investigated the impact of different levels and sources of dietary Zn supplementation on the growth performance, intestinal morphology and antioxidant activity of broiler chickens under heat stress conditions. In this experiment, 1024 Xueshan chickens were divided into eight groups and subjected to heat stress conditions with different levels of Zn supplementation (30 mg/kg, 60 mg/kg, and 90 mg/kg) using organic or inorganic sources. Our findings indicated that dietary Zn supplementation significantly increased the feed-to-weight ratio of broilers during the experimental period under heat stress. Moreover, Zn supplementation positively increased the villus height and villus width in the jejunum and ileum at 74 and 88 days old, with the 60 and 90 mg/kg groups outperforming other groups, and organic Zn was more effective than inorganic Zn. Furthermore, Zn supplementation significantly increased serum antioxidant levels, with higher superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-px) activities, and organic Zn was more effective than inorganic Zn. This study concludes that Zn supplementation is beneficial in mitigating the detrimental impacts of heat stress on broilers. The findings suggest that employing Zn as a strategy can enhance productivity in the poultry industry by positively influencing intestinal morphology and bolstering antioxidant activity to counteract potential stress.

Berberine a traditional Chinese drug repurposing: Its actions in inflammation-associated ulcerative colitis and cancer therapy.

Berberine (BBR), an isoquinoline alkaloid extracted from Coptidis Rhizoma, has a long history of treating dysentery in the clinic. Over the past two decades, the polytrophic, pharmacological, and biochemical properties of BBR have been intensively studied. The key functions of BBR, including anti-inflammation, antibacterial, antioxidant, anti-obesity, and even antitumor, have been discovered. However, the underlying mechanisms of BBR-mediated regulation still need to be explored. Given that BBR is also a natural nutrition supplement, the modulatory effects of BBR on nutritional immune responses have attracted more attention from investigators. In this mini-review, we summarized the latest achievements of BBR on inflammation, gut microbes, macrophage polarization, and immune responses associated with their possible tools in the pathogenesis and therapy of ulcerative colitis and cancer in recent 5 years. We also discuss the therapeutic efficacy and anti-inflammatory actions of BBR to benefit future clinical applications.

Anthropogenic impacts on antibiotic resistance genes and their hosts from pristine to urban river using metagenomic and binning approaches.

Driven by anthropogenic pressure, Antibiotic resistance genes (ARGs) could transfer from the environmental resistome into human commensals or even pathogens. The transport of ARGs through aquatic ecosystems is crucial and has attracted attention. Here, we employed metagenomic and binning to compare ARGs profiles, their co-occurrence with metal resistance genes (MRGs) and mobile genetic elements (MGEs), and their hosts between pristine and anthropogenic influenced rivers and explore the ecological mechanisms underlying the dissemination of ARGs induced by anthropogenic activities. The significantly increased relative abundance of macrolide-lincosamide-streptogramins, vancomycin, ß-lactam and sulfonamide resistance genes along the environmental gradient from pristine to polluted sediments implied that anthropogenic impact aided the emergence and dissemination of certain ARGs. At the lower reach of the Ba River, the higher ratios for contigs carrying more than one ARG suggested that anthropogenic pollution favored the co-occurrence of multiple ARGs. Anthropogenic pressures also increased the relative abundance of advantaged hosts, including Chloroflexi, Firmicutes and Euryarchaeota. At the lower reach of Ba River, Romboutsia timonensis carrying multiple ARGs and ICEs were successfully recovered, posing a serious threat to human health by affecting the metabolism of gut microbiomes. And Methanothrix soehngenii affiliated to archaea carrying multiple ARGs, MRGs and ICEs were also recovered from the lower Ba River. The partial least squares path modeling revealed that MGEs were the most predominant factors inducing the ARG profiles, and the antibiotic resistance could be enriched by co-transfer with MRGs. Furthermore, environmental factors could impact the ARG profiles indirectly by first influencing the ARGs' hosts.

BPA disrupted the testis testosterone levels by interfering ER enrichments within StAR 5' flanking region in rare minnow Gobiocypris rarus.

Bisphenol A (BPA) is a widely used endocrine disruptor, which has attracted much attention due to its harmful effects on male reproduction. To investigate the interference of BPA on steroid synthesis in males, male rare minnows (Gobiocypris rarus) were exposed to 15 µg L-1 BPA for 7, 14 and 21 d. Meanwhile, a positive control group was performed with 25 ng L-1 17α-ethynyl estradiol (EE2). Results showed that BPA exposure induced lower testosterone (T) levels, while affecting the transcripts of steroidogenic gene StAR. Moreover, BPA induced abnormal germ cells proliferation in the testis in rare minnow. Transcriptome analysis showed that 354 transcripts significantly differentially expressed after BPA exposure for 14 d, several of them were enriched in the signaling pathways of cell cycle process, PPAR signaling pathway, the steroid synthesis pathway and estrogen signaling pathway. BPA significantly increased estrogen receptor (ER) levels and induced abnormal protein levels of PPARγ. BPA disrupted the StAR expression by interfering ER enrichments within StAR 5' flanking region. Additionally, our study also revealed that BPA and EE2 might have different mechanisms for interfering with steroid hormone levels and germ cells proliferation in the testis.

Dietary Conjugated Linoleic Acid Modulates the Hepatic Circadian Clock Program via PPARα/REV-ERBα-Mediated Chromatin Modification in Mice.

Scope: Disruptions of circadian rhythm cause metabolic disorders and are closely related to dietary factors. In this study, we investigated the interplays between the dietary conjugated linoleic acid (CLA)-induced hepatic steatosis and the circadian clock regulation, in association with lipid homeostasis. Methods and Results: Exposure of mice to 1.5% dietary CLA for 28 days caused insulin resistance, enlarged livers, caused hepatic steatosis, and increased triglyceride levels. Transcriptional profiling showed that hepatic circadian clock genes were significantly downregulated with increased expression of the negative transcription factor, REV-ERBα. We uncovered that the nuclear receptor (NR) PPARα, as a major target of dietary CLA, drives REV-ERBα expression via its binding to key genes of the circadian clock, including Cry1 and Clock, and the recruitment of histone marks and cofactors. The PPARα or REV-ERBα inhibition blocked the physical connection of this NR pair, reduced the cobinding of PPARα and REV-ERBα to the genomic DNA response element, and abolished histone modifications in the CLA-hepatocytes. In addition, we demonstrated that CLA promotes PPARα driving REV-ERBα transcriptional activity by directly binding to the PPAR response element (PPRE) at the Nr1d1 gene. Conclusions: Our results add a layer to the understanding of the peripheral clock feedback loop, which involves the PPARα-REV-ERBα, and provide guidance for nutrients optimization in circadian physiology.

Heterostructural Interface in Fe3C-TiN Quantum Dots Boosts Oxygen Reduction Reaction for Al-Air Batteries.

Oxygen reduction electrocatalysts play important roles in metal-air batteries. Herein, Fe3C-TiN heterostructural quantum dots loaded on carbon nanotubes (FCTN@CNTs) are prepared as electrocatalysts for the oxygen reduction reaction (ORR) through a one-pot pyrolysis. The Fe3C-TiN quantum dots with a diameter of 2-5 nm show the unique characteristic of heterostructural interface. The as-prepared FCTN@CNTs display Pt/C comparable ORR performance (Eonset 1.06 and E1/2 0.95 V) in alkaline medium, which is ascribed to the heterostructural interface between TiN and Fe3C. Furthermore, the Al-air batteries with the FCTN@CNT catalyst display superior discharge performance, demonstrating good feasibility for practical application. This work provides an effective new method to synthesize affordable and efficient oxygen reduction reaction catalysts.

Plasma-Assisted Synthesis of Defect-Rich O and N Codoped Carbon Nanofibers Loaded with Manganese Oxides as an Efficient Oxygen Reduction Electrocatalyst for Aluminum-Air Batteries.

The oxygen reduction reaction (ORR) with sluggish kinetics on the cathode of aluminum-air (Al-air) batteries greatly limits their further development. Here, a new strategy is proposed to synthesize oxygen and nitrogen codoped carbon nanofibers loaded with manganese oxides (MnO/Mn2O3/ONCNF-n) as an efficient electrocatalyst for ORR by using oxygen plasma surface etching. The MnO/Mn2O3/ONCNF-3 exhibit superior ORR performance in an alkaline electrolyte, which is attributed to various active sites including N and O heteroatoms, vacancies, and manganese oxides. Additionally, the fabricated homemade Al-air battery (AAB) with MnO/Mn2O3/ONCNF-3 exhibits a maximum power density of 129.7 mW cm-2, demonstrating comparable performance to AABs based on the commercial Pt/C catalyst. This work provides a new approach of using O2 plasma for enhancing the ORR catalytic activities of carbon materials.

Orphan Nuclear Receptor RORγ Modulates the Genome-Wide Binding of the Cholesterol Metabolic Genes during Mycotoxin-Induced Liver Injury.

Maintaining lipid homeostasis is crucial to liver function, the key organ that governs the whole-body energy metabolism. In contrast, lipid dysregulation has been implicated in mycotoxin-induced liver injury, by which the pathophysiological regulation and the molecular components involved remain elusive. Here we focused on the potential roles of orphan nuclear receptor (NR) RORγ in lipid programming, and aimed to explore its action on cholesterol regulation in the liver of mycotoxin-exposed piglets. We found that liver tissues were damaged in the mycotoxin-exposed piglets compared to the healthy controls, revealed by histological analysis, elevated seral ALT, AST and ALP levels, and increased caspase 3/7 activities. Consistent with the transcriptomic finding of down-regulated cholesterol metabolism, we demonstrated that both cholesterol contents and cholesterol biosynthesis/transformation gene expressions in the mycotoxin-exposed livers were reduced, including HMGCS1, FDPS, SQLE, EBP, FDFT1 and VLDLR. Furthermore, we reported that RORγ binds to the cholesterol metabolic genes in porcine hepatocytes using a genome-wide ChIP-seq analysis, whereas mycotoxin decreased the RORγ binding occupancies genome-wide, especially at the cholesterol metabolic pathway. In addition, we revealed the enrichment of co-factors p300 and SRC, the histone marks H3K27ac and H3K4me2, together with RNA Polymerase II (Pol-II) at the locus of HMGCS1 in hepatocytes, which were reduced by mycotoxin-exposure. Our results provide a deep insight into the cholesterol metabolism regulation during mycotoxin-induced liver injury, and propose NRs as therapeutic targets for anti-mycotoxin treatments.

The Circadian Physiology: Implications in Livestock Health.

Circadian rhythms exist in almost all types of cells in mammals. Thousands of genes exhibit approximately 24 h oscillations in their expression levels, making the circadian clock a crucial regulator of their normal functioning. In this regard, environmental factors to which internal physiological processes are synchronized (e.g., nutrition, feeding/eating patterns, timing and light exposure), become critical to optimize animal physiology, both by managing energy use and by realigning the incompatible processes. Once the circadian clock is disrupted, animals will face the increased risks of diseases, especially metabolic phenotypes. However, little is known about the molecular components of these clocks in domestic species and by which they respond to external stimuli. Here we review evidence for rhythmic control of livestock production and summarize the associated physiological functions, and the molecular mechanisms of the circadian regulation in pig, sheep and cattle. Identification of environmental and physiological inputs that affect circadian gene expressions will help development of novel targets and the corresponding approaches to optimize production efficiency in farm animals.

Multi-level phase-change memory with ultralow power consumption and resistance drift.

By controlling the amorphous-to-crystalline relative volume, chalcogenide phase-change memory materials can provide multi-level data storage (MLS), which offers great potential for high-density storage-class memory and neuro-inspired computing. However, this type of MLS system suffers from high power consumption and a severe time-dependent resistance increase ("drift") in the amorphous phase, which limits the number of attainable storage levels. Here, we report a new type of MLS system in yttrium-doped antimony telluride, utilizing reversible multi-level phase transitions between three states, i.e., amorphous, metastable cubic and stable hexagonal crystalline phases, with ultralow power consumption (0.6-4.3 pJ) and ultralow resistance drift for the lower two states (power-law exponent < 0.007). The metastable cubic phase is stabilized by yttrium, while the evident reversible cubic-to-hexagonal transition is attributed to the sequential and directional migration of Sb atoms. Finally, the decreased heat dissipation of the material and the increase in crystallinity contribute to the overall high performance. This study opens a new way to achieve advanced multi-level phase-change memory without the need for complicated manufacturing procedures or iterative programming operations.