Enhanced CO2 Electroreduction to Multi-Carbon Products on Copper via Plasma Fluorination.

The electroreduction of carbon dioxide (CO2) to multi-carbon (C2+) compounds offers a viable approach for the up-conversion of greenhouse gases into valuable fuels and feedstocks. Nevertheless, current industrial applications face limitations due to unsatisfactory conversion efficiency and high overpotential. Herein, a facile and scalable plasma fluorination method is reported. Concurrently, self-evolution during CO2 electroreduction is employed to control the active sites of Cu catalysts. The copper catalyst modified with fluorine exhibits an impressive C2+ Faradaic efficiency (FE) of 81.8% at a low potential of -0.56 V (vs a reversible hydrogen electrode) in an alkaline flow cell. The presence of modified fluorine leads to the exposure and stabilization of high-activity Cu+ species, enhancing the adsorption of *CO intermediates and the generation of *CHO, facilitating the subsequent dimerization. This results in a notably improved conversion efficiency of 13.1% and a significant reduction in the overpotential (≈100 mV) for the C2+ products. Furthermore, a superior C2+ FE of 81.6% at 250 mA cm-2, coupled with an energy efficiency of 31.0%, can be achieved in a two-electrode membrane electrode assembly electrolyzer utilizing the fluorine-modified copper catalyst. The strategy provides novel insights into the controllable electronic modification and surface reconstruction of electrocatalysts with practical potential.

Positive effect of microvascular proliferation on functional recovery in experimental cervical spondylotic myelopathy.

Background and purpose: Cervical Spondylotic Myelopathy (CSM), the most common cause of spinal cord dysfunction globally, is a degenerative disease that results in non-violent, gradual, and long-lasting compression of the cervical spinal cord. The objective of this study was to investigate whether microvascular proliferation could positively affect neural function recovery in experimental cervical spondylotic myelopathy (CSM). Methods: A total of 60 male adult Sprague-Dawley (SD) were randomly divided into four groups: Control (CON), Compression (COM), Angiostasis (AS), and Angiogenesis (A G),with 15 rats in each group. Rats in the AS group received SU5416 to inhibit angiogenesis, while rats in the AG group received Deferoxamine (DFO) to promote angiogenesis. Motor and sensory functions were assessed using the Basso Beattie Bresnahan (BBB) scale and somatosensory evoked potential (SEP) examination. Neuropathological degeneration was evaluated by the number of neurons, Nissl bodies (NB), and the de-myelination of white matter detected by Hematoxylin & Eosin(HE), Toluidine Blue (TB), and Luxol Fast Blue (LFB) staining. Immunohistochemical (IHC) staining was used to observe the Neurovascular Unit (NVU). Results: Rats in the CON group exhibited normal locomotor function with full BBB score, normal SEP latency and amplitude. Among the other three groups, the AG group had the highest BBB score and the shortest SEP latency, while the AS group had the lowest BBB score and the most prolonged SEP latency. The SEP amplitude showed an opposite performance to the latency. Compared to the COM and AS groups, the AG group demonstrated significant neuronal restoration in gray matter and axonal remyelination in white matter. DFO promoted microvascular proliferation, especially in gray matter, and improved the survival of neuroglial cells. In contrast, SU-5416 inhibited the viability of neuroglial cells by reducing micro vessels. Conclusion: The microvascular status was closely related to NVU remodeling an-d functional recovery. Therefore, proliferation of micro vessels contributed to function -al recovery in experimental CSM, which may be associated with NVU remodeling.

Bioactive Components of Areca Nut: An Overview of Their Positive Impacts Targeting Different Organs.

Areca catechu L. is a widely cultivated tropical crop in Southeast Asia, and its fruit, areca nut, has been consumed as a traditional Chinese medicinal material for more than 10,000 years, although it has recently attracted widespread attention due to potential hazards. Areca nut holds a significant position in traditional medicine in many areas and ranks first among the four southern medicines in China. Numerous bioactive compounds have been identified in areca nuts, including alkaloids, polyphenols, polysaccharides, and fatty acids, which exhibit diverse bioactive functions, such as anti-bacterial, deworming, anti-viral, anti-oxidant, anti-inflammatory, and anti-tumor effects. Furthermore, they also display beneficial impacts targeting the nervous, digestive, and endocrine systems. This review summarizes the pharmacological functions and underlying mechanisms of the bioactive ingredients in areca nut. This helps to ascertain the beneficial components of areca nut, discover its medicinal potential, and guide the utilization of the areca nut.

Gut Microbiome and Metabolome Modulation by High-Hydrostatic-Pressure-Processed Tomato Juice.

High hydrostatic pressure (HHP) is a non-thermal pasteurization technology for the enhancement of food products' safety and quality. The components of tomato juice can be affected by HHP processing. Little is known about the effects of HHP-processed tomato juice on the gut microbiome and metabolism. Here, we performed high-throughput sequencing and metabolomics profiling to determine the critical differences in gut microbiota structure and metabolic profiles in mice administered with HHP-processed tomato juice. Tomato juice administration significantly increased the gut bacterial alpha diversity and the relative abundance of Bacteroides. The mice administered with HHP-processed tomato juice were characterized by the enrichment of Bacteroidetes, Alistieps, and Faecalibaculum compared with those administered with HTST-processed tomato juice. Moreover, HHP-processed tomato juice promoted SCFA levels, which were positively correlated with the enriched Alistieps. Our results show that HHP-processed tomato juice may drive healthy gut microbes and metabolites.

High hydrostatic pressure induced gastrointestinal digestion behaviors of quercetin-loaded casein delivery systems under different calcium concentration.

Casein micelle has a structure of outer hydrophilicity and inner hydrophobicity, its typical digestion characteristic is gastric coagulation. Based on calcium content as the key factor to control this process, high hydrostatic pressure (HHP) was firstly used to modify the micelle structure by mediating the tight connection between casein molecules themselves and with colloidal calcium, then the quercetin-loaded delivery systems were prepared. And in order to investigate the effect of exogenous calcium, calcium chloride was added for digestion. The results indicated that HHP broke the limitation of casein micelles as delivery carriers for hydrophobic components and increased the EE from 51.18 ± 3.07 % to 76.17 ± 3.41 %. During gastric digestion, higher pressure and exogenous calcium synergistically increased the clotting ability and inhibited the release of quercetin. In the small intestine, curds decomposed more slowly under higher pressure and calcium concentration, so the degradation of quercetin was effectively inhibited.

OTUD4 promotes the progression of glioblastoma by deubiquitinating CDK1 and activating MAPK signaling pathway.

Glioblastoma, IDH-Wild type (GBM, CNS WHO Grade 4) is a highly heterogeneous and aggressive primary malignant brain tumor with high morbidity, high mortality, and poor patient prognosis. The global burden of GBM is increasing notably due to limited treatment options, drug delivery problems, and the lack of characteristic molecular targets. OTU deubiquitinase 4 (OTUD4) is a potential predictive factor for several cancers such as breast cancer, liver cancer, and lung cancer. However, its function in GBM remains unknown. In this study, we found that high expression of OTUD4 is positively associated with poor prognosis in GBM patients. Moreover, we provided in vitro and in vivo evidence that OTUD4 promotes the proliferation and invasion of GBM cells. Mechanism studies showed that, on the one hand, OTUD4 directly interacts with cyclin-dependent kinase 1 (CDK1) and stabilizes CDK1 by removing its K11, K29, and K33-linked polyubiquitination. On the other hand, OTUD4 binds to fibroblast growth factor receptor 1 (FGFR1) and reduces FGFR1's K6 and K27-linked polyubiquitination, thereby indirectly stabilizing CDK1, ultimately influencing the activation of the downstream MAPK signaling pathway. Collectively, our results revealed that OTUD4 promotes GBM progression via OTUD4-CDK1-MAPK axis, and may be a prospective therapeutic target for GBM treatment.

Lycopene Ameliorated DSS-Induced Colitis by Improving Epithelial Barrier Functions and Inhibiting the Escherichia coli Adhesion in Mice.

Adherent-invasive Escherichia coli plays an important role in the pathogenesis of inflammatory bowel disease. Blocking the adhesion of E. coli to intestinal epithelial cells appears to be useful for attenuating inflammatory bowel disease. Lycopene has been reported to have anti-inflammatory and antimicrobial activities. The aim of this study was to test the intervention effect of lycopene on colitis in mice and to investigate the possible mechanism through which lycopene affects the adhesion of E. coli to intestinal epithelial cells. Lycopene (12 mg/kg BW) attenuated dextran sulfate sodium (DSS)-induced colitis, decreased the proportion of E. coli, and activated the NLR family pyrin domain containing 12 and inactivated nuclear factor kappa B pathways. Furthermore, lycopene inhibited the adhesion of E. coli O157:H7 to Caco-2 cells by blocking the interaction between E. coli O157:H7 and integrin ß1. Lycopene ameliorated DSS-induced colitis by improving epithelial barrier functions and inhibiting E. coli adhesion. Overall, these results show that lycopene may be a promising component for the prevention and treatment of colitis.

Inactivation mechanisms on pectin methylesterase by high pressure processing combined with its recombinant inhibitor.

High pressure processing (HPP) juice often experiences cloud loss during storage, caused by the activity of pectin methylesterase (PME). The combination of HPP with natural pectin methylesterase inhibitor (PMEI) could improve juice stability. However, extracting natural PMEI is challenging. Gene recombination technology offers a solution by efficiently expressing recombinant PMEI from Escherichia coli and Pichia pastoris. Experimental and molecular dynamics simulation were conducted to investigate changes in activity, structure, and interaction of PME and recombinant PMEI during HPP. The results showed PME retained high residual activity, while PMEI demonstrated superior pressure resistance. Under HPP, PMEI's structure remained stable, while the N-terminus of PME's α-helix became unstable. Additionally, the helix at the junction with the PME/PMEI complex changed, thereby affecting its binding. Furthermore, PMEI competed with pectin for active sites on PME, elucidating. The potential mechanism of PME inactivation through the synergistic effects of HPP and PMEI.

Transcription factors WOX11 and LBD16 function with histone demethylase JMJ706 to control crown root development in rice.

Crown roots are the main components of root systems in cereals. Elucidating the mechanisms of crown root formation is instrumental for improving nutrient absorption, stress tolerance, and yield in cereal crops. Several members of the WUSCHEL-related homeobox (WOX) and lateral organ boundaries domain (LBD) transcription factor families play essential roles in controlling crown root development in rice (Oryza sativa). However, the functional relationships among these transcription factors in regulating genes involved in crown root development remain unclear. Here, we identified LBD16 as an additional regulator of rice crown root development. We showed that LBD16 is a direct downstream target of WOX11, a key crown root development regulator in rice. Our results indicated that WOX11 enhances LBD16 transcription by binding to its promoter and recruiting its interaction partner JMJ706, a demethylase that removes histone H3 lysine 9 dimethylation (H3K9me2) from the LBD16 locus. In addition, we established that LBD16 interacts with WOX11, thereby impairing JMJ706-WOX11 complex formation and repressing its own transcriptional activity. Together, our results reveal a feedback system regulating genes that orchestrate crown root development in rice, in which LBD16 acts as a molecular rheostat.

The aggregation of casein micelles induced by Ca2+ during in vitro digestion: effects on the release of loaded anthocyanins.

Colloidal calcium phosphate (CCP) confers a modifiable structure to micellar casein (MC), which endows it with potential advantages as a delivery carrier. However, it is difficult to achieve multipattern release of the core material in the intestine with MC as a single wall. In this study, we prepared an anthocyanin-casein-based delivery system utilizing MC with different freezing degrees as the wall material with the objective of achieving the controlled release of anthocyanin as the model core in the intestine. The results showed that freezing could significantly reduce the CCP level up to 50%. Static in vitro simulated digestion with the addition of exogenous Ca2+ showed that the designed delivery system exhibited low anthocyanin release (15%-35%) in the gastric tract. The pattern of release in the intestine depended on the CCP dissociation degree. High and low dissociation degrees corresponded to slow release (from 15% to 65% within 2 h) and burst release (from 35% to 90% within 5 min), respectively. WAXS/SAXS analysis revealed that exogenous serum Ca2+ inherent in simulated gastric fluid and endogenous serum Ca2+ induced by CCP dissociation was synergistically involved in the reconstitution of CCP-mediated nanoclusters and large aggregates. The freezing degree of MC determined the endogenous serum Ca2+ level, which influenced the gastric aggregation behavior of wall MC and ultimately led to a fairly different gastrointestinal release behavior of anthocyanins.

Online legal driving behavior monitoring for self-driving vehicles.

Defined traffic laws must be respected by all vehicles when driving on the road, including self-driving vehicles without human drivers. Nevertheless, the ambiguity of human-oriented traffic laws, particularly compliance thresholds, poses a significant challenge to the implementation of regulations on self-driving vehicles, especially in detecting illegal driving behaviors. To address these challenges, here we present a trigger-based hierarchical online monitor for self-assessment of driving behavior, which aims to improve the rationality and real-time performance of the monitoring results. Furthermore, the general principle to determine the ambiguous compliance threshold based on real driving behaviors is proposed, and the specific outcomes and sensitivity of the compliance threshold selection are analyzed. In this work, the effectiveness and real-time capability of the online monitor were verified using both Chinese human driving behavior datasets and real vehicle field tests, indicating the potential for implementing regulations in self-driving vehicles for online monitoring.

The synergistic effect of κ-carrageenan and l-lysine on the 3D printability of yellow flesh peach gels: The importance of material elasticity in the printing process.

This study investigated the effect of κ-carrageenan and l-lysine on the physical, chemical and textural properties of yellow flesh peaches and their suitability for 3D printing. The addition of κ-carrageenan and l-lysine was found to improve the apparent viscosity, elasticity, gel strength, and Young's modulus of the yellow flesh peach with κ-carrageenan and l-lysine gels (PCLG) and increase the minimum piston pressure required for 3D printing, thereby improving the printing performance. Optimum levels of κ-carrageenan and l-lysine (0.1 mmol/mL and 3.42 × 10-2 mmol/mL, respectively) were found to enhance mechanical strength, viscoelasticity and print fidelity. On the other hand, when the addition of κ-carrageenan is 0.1 mmol/mL, the addition of l-lysine causes an increase in the G0 value and a decrease in the η0 value of the PCLG according to Burger's model, indicating a transition from viscosity to elasticity and an increase in maximum extrusion force, while the apparent viscosity does not change significantly. The results of 3D printing showed that when the addition of κ-carrageenan and l-lysine reached 0.1 mmol/mL and 6.84 × 10-2 mmol/mL, respectively, the PCLG could not be smoothly extruded, indicating that elasticity also plays an important role during the extrusion process of the mixed gel.

A Review of Healthy Dietary Choices for Cardiovascular Disease: From Individual Nutrients and Foods to Dietary Patterns.

Cardiovascular disease (CVD) remains the first cause of mortality globally. Diet plays a fundamental role in cardiovascular health and is closely linked to the development of CVD. Numerous human studies have provided evidence on the relationship between diet and CVD. By discussing the available findings on the dietary components that potentially influence CVD progression and prevention, this review attempted to provide the current state of evidence on healthy dietary choices for CVD. We focus on the effects of individual macronutrients, whole food products, and dietary patterns on the risks of CVD, and the data from population-based trials, observational studies, and meta-analyses are summarized. Unhealthy dietary habits, such as high intake of saturated fatty acids, sugar-sweetened beverages, red meat, and processed meat as well as high salt intake are associated with the increased risk of CVD. Conversely, increased consumption of plant-based components such as dietary fiber, nuts, fruits, and vegetables is shown to be effective in reducing CVD risk factors. The Mediterranean diet appears to be one of the most evidence-based dietary patterns beneficial for CVD prevention. However, there is still great debate regarding whether the supplementation of vitamins and minerals confers cardioprotective benefits. This review provides new insights into the role of dietary factors that are harmful or protective in CVD, which can be adopted for improved cardiovascular health.

Identification of peptides from honeybee gut symbionts as potential antimicrobial agents against Melissococcus plutonius.

Eusocial pollinators are crucial elements in global agriculture. The honeybees and bumblebees are associated with a simple yet host-restricted gut community, which protect the hosts against pathogen infections. Recent genome mining has led to the discovery of biosynthesis pathways of bioactive natural products mediating microbe-microbe interactions from the gut microbiota. Here, we investigate the diversity of biosynthetic gene clusters in the bee gut microbiota by analyzing 477 genomes from cultivated bacteria and metagenome-assembled genomes. We identify 744 biosynthetic gene clusters (BGCs) covering multiple chemical classes. While gene clusters for the post-translationally modified peptides are widely distributed in the bee guts, the distribution of the BGC classes varies significantly in different bee species among geographic locations, which is attributed to the strain-level variation of bee gut members in the chemical repertoire. Interestingly, we find that Gilliamella strains possessing a thiopeptide-like BGC show potent activity against the pathogenic Melissococcus plutonius. The spectrometry-guided genome mining reveals a RiPP-encoding BGC from Gilliamella with a 10 amino acid-long core peptide exhibiting antibacterial potentials. This study illustrates the widespread small-molecule-encoding BGCs in the bee gut symbionts and provides insights into the bacteria-derived natural products as potential antimicrobial agents against pathogenic infections.

Gastric aggregation of micellar casein powders induced by high hydrostatic pressure: Effect of serum Ca2+ level.

Micellar casein (MC) has a unique gastric colloidal behavior in response to Ca2+ cross-linking, and its aggregation properties are closely related to pepsin and gastric acid. In this study, MC with different levels of colloidal calcium phosphate (CCP) was obtained by high hydrostatic pressure (HHP) at different pressures, followed by spray drying to obtain the powders. Different amounts of calcium chloride (exogenous Ca2+) were added to MC powders prior to in vitro simulated digestion to investigate the effect of exogenous serum Ca2+ levels on the aggregation behavior and the structure change of curds generated in gastric tract. The results revealed that HHP induced the emergence of more Ca2+-binding sites, thus Ca2+ was more likely to bind to MC matrix with low CCP levels. Meanwhile, high serum Ca2+ level provided more opportunities to form aggregates. The Highest pressure (500 MPa) with the highest Ca2+ level (5 mM) caused the lowest solubility aggregates, which were only 30% at the end of gastric digestion (120 min), half of the control sample (0 MPa with 0.15 mM Ca2+). The results of wide-angle X-ray scattering / small-angle X-ray scattering suggested that both pepsin and gastric acid-induced aggregation via Ca2+ as a bridge. For pepsin, Ca2+ cross-linked between para-κ-casein; For gastric acid, Ca2+ recombined phosphorylation sites and caused cross-linking of casein subunits.

Safety, immunogenicity and immune-persistence of heterologous prime-boost immunization with BBIBP-CorV and ZF2001 against SARS-CoV-2 in healthy adults aged 18 years or older.

BACKGROUND: Because SARS-CoV-2 mutations and immunity wane over time, a third dose of heterologous COVID-19 vaccine is proposed for individuals primed with inactivated COVID-19 vaccine. RESEARCH DESIGN AND METHODS: We conducted a single-center, open-label trial to assess the safety, immunogenicity, and immune-persistence of a heterologous BBIBP-CorV/ZF2001 prime-boost vaccination in Chinese adults. 480 participants who had been primed with two doses of BBIBP-CorV, received a third dose of ZF2001 after an interval of 3-4, 5-6, or 7-9 months. RESULTS: The overall incidence of adverse reactions within 30 days after vaccination was 5.83%. No serious adverse reactions were reported. The respective geometric mean titers (GMTs) of neutralizing antibodies for 3-4, 5-6, and 7-9 months groups at baseline were 2.06, 2.02, and 2.10; which increased to 55.42, 63.45, and 62.06 on day 14; then decreased to 17.53, 23.79, and 26.73 on day 30; before finally waning to 8.29, 9.24, and 9.51 on day 180. After the booster, the three groups showed no significant differences in GMTs. GMTs were lower in older participants than younger participants. CONCLUSIONS: A heterologous BBIBP-CorV/ZF2001 prime-boost vaccination was safe and immunogenic. Prime-boost intervals did not affect the immune response. The immune response was weaker in older adults than younger adults. CLINICAL TRIAL IDENTIFIER: NCT05205083.

Effect of inoculating Pichia spp. starters on flavor formation of fermented chili pepper: Metabolomics and genomics approaches.

The influence of Pichia spp. on flavor formation and metabolic pathways during chili pepper fermentation was investigated in this study. Multiple omics approaches were employed, including metabolomics analysis to identify volatile and non-volatile flavor compounds, and genomic analysis to gain insights into the underlying molecular mechanism driving flavor formation of chili peppers inoculated with Pichia spp. The results showed that inoculation with Pichia spp. accelerated fermentation process of chili peppers compared to spontaneous fermentation. Metabolomics analysis showed P. fermentans promoted characteristic terpenes [e.g., (Z)-ß-ocimene and linalool], L-glutamate, gamma-aminobutyric acid, and succinate production, while P. manshurica produced more alcohols (e.g., isoamyl alcohol and phenylethyl alcohol) and phenols (e.g., 4-ethylguaiacol and 2-methoxy-4-methylphenol). Genomics analysis revealed that a substantial portion of the genes in Pichia spp. were associated with amino acid and carbohydrate metabolism. Specifically, the pathways involved in amino acid metabolism and the release of glycoside-bound aromatic compounds were identified as the primary drivers behind the unique flavor of fermented chili peppers, facilitated by Pichia spp.

Effect of pasteurization processing and storage conditions on softening of acidified chili pepper: Pectin and it related enzymes.

The softening of acidified chili peppers induced by processing and storage has become a major challenge for the food industry. This study aims to explore the impact of pasteurization techniques, thermal processing (TP), high-pressure processing (HPP), addition of sodium metabisulfite (SMS), and storage conditions (25 °C, 37 °C, and 42 °C for 30 days) on the texture-related properties of acidified chili pepper. The results showed that the textural properties of samples were destructed by TP (the hardness of samples decreased by 19.43 %) but were less affected by HPP and SMS. Compared with processing, storage temperature had a more dominant impact on texture and pectin characteristics. With increased storage temperature, water-solubilized pectin fraction content increased (increased by 160.99 %, 136.74 %, and 13.01 % in TP, HPP, and SMS-stored groups, respectively), but sodium carbonate-solubilized pectin fraction content decreased (decreased by 29.84 %, 26.81 %, and 8.60 % in TP-, HPP-, and SMS-stored groups, respectively), especially in TP-stored groups. Multivariate data analysis showed that softening was more closely related to pectin conversion induced by acid hydrolysis and pectinase depolymerization. This finding offers new perspectives for the production of acidified chili pepper.

Arecoline alleviated loperamide induced constipation by regulating gut microbes and the expression of colonic genome.

This study aimed to investigate the effects of arecoline on constipation by intervening at different times to explore its preventive and therapeutic effects. Symptoms related to constipation, gut microbes, short-chain fatty acid (SCFA) content in the cecum, and gene expression in the colon were measured to examine the effect of arecoline on relieving constipation. The results showed that arecoline intervention alleviated loperamide-induced constipation, as evidenced by significantly shortened intestinal transit time, increased fecal water content, improved small bowel propulsion, and increased defecation frequency. In addition, arecoline significantly reduced the levels of gastrointestinal regulatory peptides such as somatostatin and vasoactive intestinal peptide in the serum, thereby regulating intestinal peristalsis. Histopathological analysis showed that arecoline ameliorated intestinal injury caused by constipation. Gut microbial analysis indicated that arecoline altered the taxonomic composition and levels of its metabolite SCFAs in the gut microbiota. Furthermore, the colonic transcriptome results indicated that genes expression related to intestinal diseases were significantly down-regulated by arecoline intervention. In conclusion, the results of the correlation analysis propose a possible mechanism of arecoline in alleviating constipation by modulating the gut microbes and their metabolites and regulating the gut genome.

Kuwanon H Inhibits Melanoma Growth through Cytotoxic Endoplasmic Reticulum Stress and Impaired Autophagy Flux.

Although great progress has been made recently in targeted and immune-based therapies, additional treatments are needed for most melanoma patients due to acquired chemoresistance, recurrence, or metastasis. Elevated autophagy is required for the pathogenesis of melanoma to attenuate metabolic stress, protecting cancer cells from chemotherapeutics or radiation. Thus, intervention with autophagy is a promising strategy for melanoma treatment. Here, we examined a novel antimelanoma natural compound named kuwanon H (KuH), which significantly inhibited melanoma cell growth in vitro/vivo. Mechanistically, KuH induced cytotoxic endoplasmic reticulum (ER) stress, which inhibited cell viability and induced apoptosis. Meanwhile, KuH-induced ER stress mediated autophagysome formation through the ATF4-DDIT3-TRIB3-AKT-MTOR axis. Importantly, KuH impaired autophagy flux, which contributed to the anticancer effects of KuH. Finally, our results showed that KuH enhanced the sensitivity of melanoma cells to cisplatin, both in vitro and in vivo, by impairing autophagy degradation of reactive oxygen species and damaged mitochondria. Our findings indicate that KuH is a promising candidate anticancer natural product for melanoma therapy.