Dissolved trace elements in the Ganges-Brahmaputra-Meghna River Basin: A new approach for estimating trace element flux inputs from rivers into the world's oceans.

Understanding the changes in the chemical compositions of dissolved trace elements from source to sink is important for determining their spatiotemporal variations and the contributions from each sub-catchment in the Ganges, Brahmaputra, and Meghna Rivers. To estimate weathering and matter transfer in these Rivers and the Ganges-Brahmaputra-Meghna (G-B-M) Estuary, we measured 15 dissolved trace element concentrations from surface and bottom water samples and exchangeable trace metals from suspended particulate matter (SPM). From December 2019 to January 2020, post-monsoon samples were collected from the upstream of the three rivers and the G-B-M Estuary. Dissolved trace elements in the Ganges and Meghna Rivers exhibited remarkable spatial variations, whereas those in the Brahmaputra River and the G-B-M Estuary were uniform. The dissolved trace elements, basic information (river length and drainage area), and physicochemical parameters (pH, dissolved oxygen, and conductivity) of the three rivers were inconsistent. The sample sites near urban areas and industrial centers had high concentrations of dissolved trace elements. In the G-B-M Estuary, iron and lead concentrations decreased along the salinity gradient, whereas selenium levels gradually increased, which may have been released by the SPM owing to its highly exchangeable trace metals. Compared with historical concentrations, trace elements that entered the G-B Estuary from the Ganges and Brahmaputra Rivers exhibited either decreased or increased metal fluxes due to additional terrigenous sources, suggesting that the inputs of trace element flux from the Ganges and Brahmaputra Rivers into the oceans may need to be re-evaluated. Furthermore, Fe and Pb concentrations and river fluxes in the Ganges and Changjiang have decreased in recent years. Hence, the fluxes of certain trace elements that enter the oceans from large rivers may require re-evaluation.

Fabrication of a magnetic functionalized chitosan hydrogel for effective extraction of aflatoxins from cereals.

A magnetic adsorbent was synthesized by coupling magnetic nanoparticles, UiO-66-NH2 and 1-butyl-trimethylimidazole bromide ([BMIM][Br]) to chitosan (CS)-based composite conveniently. A series of modern characterizations were employed to assess its properties. The results showed that UiO-66-NH2 was uniformly distributed within the composite via in-situ growth, which can enhance the porosity obviously. The introduction of various ligands enables the composite to exhibit excellent extraction performance for four aflatoxins (AFs) through multiple interactions. The adsorption mechanism was elucidated and the main factors affecting extraction efficiency were evaluated. Under optimal conditions, the limits of detection (LODs) ranged from 0.08 to 0.56 µg/kg. The established method was successfully utilized to determine AFs from cereal samples (rice, glutinous rice, wheat, soybean, paddy, and corn) with satisfactory recovery of 77% âˆ¼ 119% with relative standard deviations (RSDs) of 1.0% âˆ¼ 11.7% (n = 5). The adsorbent demonstrated sufficient robustness for repeated use at least six times without obvious damage of extraction property.

Personal, external, and psychological factors influencing adherence to nutrition and diet in patients undergoing metabolic/bariatric surgery: a systematic synthesis of mixed methods research.

AIMS: To offer a holistic view of the personal, external, and psychological factors influencing adherence to nutrition and diet in patients undergoing metabolic/bariatric surgery. METHODS: This systematic synthesis of mixed methods research involved a comprehensive search for articles in English databases, including PubMed, Cochrane Library, Web of Science, EBSCO, Scopus, and Embase, as well as Chinese databases. The search encompassed articles published from the inception of the database up to June 2023. Following the evaluation of literature quality and extraction of relevant information from the selected studies, data from both quantitative and qualitative studies were integrated. The extracted data were analyzed separately, and themes were identified and summarized to elucidate the factors influencing adherence to nutritional and dietary guidelines. The methodology adhered to the guidelines recommended by the Joanna Briggs Institute (JBI) for mixed methods systematic evaluations. RESULTS: Three themes and their corresponding descriptive elements were identified, including: (1) Personal factors: subjective factors (attitude, capability, awareness, behaviors), objective factors (age, sex, work status, economic level, physical activity, dietary habits, weight change); (2) External factors: medication (quantity of pills, complexity of intake times, side effects, unpleasant smell or taste), surgery factor, social influences (family members, dietitians, and peers); (3) Psychological factors: self-efficacy, attachment anxiety, and mental health problems. CONCLUSIONS: The synthesis provided a comprehensive overview of the factors influencing postoperative compliance of nutrition and diet among patients undergoing metabolic and bariatric surgery. It emphasizes the necessity for clinical staff to tailor interventions based on these diverse factors, as well as to attach importance to patients' mental health, giving multidimensional dietary guidance and health care.

Ionic liquid-functionalized mesoporous multipod silica for simultaneously effective extraction of aflatoxin B1 and its two precursors from grain.

BACKGROUND: Aflatoxin B1 (AFB1) and its precursors contaminate food and agricultural products, posing a significant risk to food safety and human health, but simultaneous and effective extraction and determination of AFB1 and its precursors with varied structures is still a challenging task. RESULTS: In this study, a bisimidazolium-type ionic liquid functionalized mesoporous multipod silica (SiO2@mPMO-IL(im)2) was fabricated to extract AFB1 and its two precursors, i.e., averantin and sterigmatocystin. The SiO2@mPMO-IL(im)2 could simultaneously extract three targets with varied structures based on the multipods, mesopores, and multifunctional groups. The density functional theory calculations further verified the multiple interactions between SiO2@mPMO-IL(im)2 and targets. The fabricated SiO2@mPMO-IL(im)2 could effectively extract and determine three targets in grains by combing with dispersive solid-phase extraction and high-performance liquid chromatography. Good linearity (r2 > 0.9978), low LODs (0.9-1.5 µg kg-1) and LOQs (3.0-4.5 µg kg-1), satisfactory spiked recoveries (92.5%-106.8%) and high precisions (RSD<6.4%) were observed. SIGNIFICANCE AND NOVELTY: This work demonstrates the feasibility of SiO2@mPMO-IL(im)2 for simultaneous and effective extraction of toxins with varied structures and provides a promising sample preparation for the analysis of AFB1 and its precursors in grain samples.

Anti-Cancer Potency of Copper-Doped Carbon Quantum Dots Against Breast Cancer Progression.

Introduction: The anti-cancer potency of copper-doped carbon quantum dots (Cu-CDs) against breast cancer progression needs more detailed investigations. Methods: With urea and ethylene glycol applied as carbon sources and copper sulfate used as a reactive dopant, Cu-CDs were synthesized in the current study by a one-step hydrothermal synthesis method, followed by the characterization and biocompatibility evaluations of Cu-CDs. Subsequently, the anti-cancer potency of Cu-CDs against breast cancer progression was confirmed by these biochemical, molecular, and transcriptomic assessments, including viability, proliferation, migration, invasion, adhesion, clonogenicity, cell cycle distribution, apoptosis, redox homeostasis, and transcriptomic assays of MDA-MB-231 cells. Results: The biocompatibility of Cu-CDs was confirmed based on the non-significant changes in the pathological and physiological parameters in the Cu-CDs treated mice, as well as the noncytotoxic effect of Cu-CDs on normal cells. Moreover, the Cu-CDs treatments not only decreased the viability, proliferation, migration, invasion, adhesion, and clonogenicity of MDA-MB-231 cells but also induced the redox imbalance, cell cycle arrest, and apoptosis of MDA-MB-231 cells via ameliorating the mitochondrial dysfunctions and regulating the MAPK signaling pathway. Conclusion: Our findings confirmed the biosafety and excellent anti-cancer potency of Cu-CDs against breast cancer progression by tapping into mechanisms that disrupt malignant behaviors and oxidative homeostasis of breast cancer cells.

Scalable Production of Highly Conductive 2D NbSe2 Monolayers with Superior Electromagnetic Interference Shielding Performance.

Thin, flexible, and electrically conductive films are in demand for electromagnetic interference (EMI) shielding. Two-dimensional NbSe2 monolayers have an electrical conductivity comparable to those of metals (106-107 S m-1) but are challenging for high-quality and scalable production. Here, we show that electrochemical exfoliation of flake NbSe2 powder produces monolayers on a large scale (tens of grams), at a high yield (>75%, monolayer), and with a large average lateral size (>20 µm). The as-exfoliated NbSe2 monolayer flakes are easily dispersed in diverse organic solvents and solution-processed into various macroscopic structures (e.g., free-standing films, coatings, patterns, etc.). Thermal annealing of the free-standing NbSe2 films reduces the interlayer distance of restacked NbSe2 from 1.18 to 0.65 nm and consequently enhances the electrical conductivity to 1.16 × 106 S m-1, which is superior to those of MXenes and reduced graphene oxide. The optimized NbSe2 film shows an EMI shielding effectiveness (SE) of 65 dB at a thickness of 5 µm (>110 dB for a 48-µm-thick film), among the highest in materials of similar thicknesses. Moreover, a laminate of two layers of the NbSe2 film (2 µm thick) with an insulating interlayer shows a high SE of 85 dB, surpassing that of the 20-µm-thick NbSe2 film (83 dB). A two-layer theoretical model is proposed, and it agrees with the experimental EMI SE of the laminated NbSe2 films. The ability to produce NbSe2 monolayers on a tens of grams scale will enable their diverse applications beyond EMI shielding.

Construction of MOFs@COFs composite material as stationary phase for efficient separation of diverse organic compounds.

BACKGROUND: The development of efficent chromatographic stationary phases (SP) with mixed-mode or multiple interactions in high-performance liquid chromatography (HPLC) for the separation of complex samples is a challenging task. Metal organic frameworks (MOFs)-based SP can provide desired multiple interactions and enable the separation of a diverse range of solutes, but have limitations of low column efficiency and poor stability. RESULTS: Herein, the hybrid MOFs@Covalent organic frameworks (COFs) materials were used as SP in HPLC due to their synergistic structural features. The SiO2@NH2-UiO-66@CTF SP was synthesized by integration of NH2-UiO-66 and covalent triazine framework (CTF) onto silica surface. Due to the unique structure of SiO2@NH2-UiO-66@CTF with hierarchical-pores, this column showed higher column efficiency (up to 49,369 plates m-1 for alkylbenzenes) than the reported columns packed with MOFs-based SP. Owing to the Zr4+-N coordination bonding between CTF and NH2-UiO-66, the structural stability of SiO2@NH2-UiO-66@CTF can be improved. Furthermore, this new column exhibited remarkable column stability with relative standard deviation of retention time of <0.40% after 400 injections. With the combined advantages of multifunctional properties, high column efficiency, and good stability, SiO2@NH2-UiO-66@CTF SP showed excellent selectivity for the separation of a variety of hydrophobic, aromatic, heteroatomic, and hydrophilic analytes. SIGNIFICANCE AND NOVELTY: This work not only offers a promising SP with multiple retention mechanisms for HPLC, but also provides an efficient strategy for development of high column efficiency MOFs-based SP with good stability. Moreover, the MOFs@COFs hybrid materials were expanded in application area through this study, and the research results can also afford the foundation for further explore its structural characteristics.

A Novel and Highly Efficient Microextraction Method for the Determination of Aflatoxin Precursor Averantin in Fatty Grain Samples.

Averantin (AVN) is an important aflatoxin biosynthetic precursor and has been listed in the screening range of mycotoxins. Herein, a novel ionic liquid-based one-, two-, and three-phase transition microextraction (IL-OTTPTME) method was combined with high-performance liquid chromatography for the extraction and determination of AVN in fatty grain samples. The formation of a homogeneous solution and three-phase system during the IL-OTTPTME process allowed both efficient extraction and coextracted lipid cleanup. Density functional theory calculations and distribution coefficient determination results demonstrated that AVN extraction by IL mainly occurred through hydrogen-bond and π-π interactions. Under optimized conditions, the LOD and LOQ of the proposed method were 0.5 and 1.5 ng/g, respectively. Finally, the method was used to determine AVN in several grains with different fat contents, achieving satisfactory relative recoveries (86.0-107.8%) and RSDs (1.2-6.2%, n = 3).

Simple and rapid ionic liquid-based one-, two-, three-phase transition microextraction for efficient extraction of trace organic pollutants and elimination of lipid co-extractives from fatty food matrices.

Extraction of trace contaminants from fatty food matrices is challenging in food analysis. Herein, a new ionic liquid-based one-, two-, three-phase transition microextraction (IL-OTTPTME) was proposed to efficiently extract trace targets while simultaneously eliminating lipid co-extractives. The method performance was illustrated through the determination of chrysoidine in fatty soybean products using high-performance liquid chromatography-ultraviolet/visible detection. The strong interactions and infinite contact between IL and chrysoidine in the one-phase system ensured ultra-high extraction efficiency (∼100 %). Density functional theoretical calculations confirmed the presence of strong hydrogen bonding and π-π interactions. The formation of the three-phase system during extraction could completely eliminate lipid co-extractives. The IL-OTTPTME integrated extraction, enrichment and cleanup steps into one step, making it rapid and extremely easy to operate. The method had a wide linear range of 0.5-5000 µg/kg and low limit of detection (0.15 µg/kg). It also had satisfactory relative recoveries (95.1 %-104.0 %) and low RSDs (≤5.0 %, n = 5).

Transcriptomics and metabolomics profiling reveals involvement of flavonoids in early nodulation of Caucasian clover (Trifolium ambiguum).

Caucasian clover (Trifolium ambiguum) is a perennial rooted and tillering leguminous forage with strong adaptability, outstanding stress tolerance and other preferable traits. However, the specificity with rhizobia limits the extended application of Caucasian clover. Therefore, it is important to study the changes of genes and metabolites in the early process of nodulation in Caucasian clover to improve its nodulation and nitrogen fixation ability. In this study, we used Caucasian clover as the experimental material to investigate its nodulation mechanism using transcriptomic and metabolomic approaches, such that to break the nitrogen fixation barrier for the promotion of Caucasian clover. Metabolomic and transcriptomic profiling revealed that both DAMs and DEGs were significantly enriched in the phenylpropanoid and flavonoid biosynthetic pathways, with DEGs showing up-regulation at 3 days and 6 days post inoculation (dpi) with rhizobia, and some DEGs showing down-regulation at 9 dpi. Accumulation of flavonoids was significantly increased at both 3 dpi and 6 dpi, and some compounds were significantly decreased at 9 dpi. A total of 35 DEGs were involved in flavonoid synthesis by WGCNA analysis, among which HCT, CCR, COMT and F3H played an important role. This study provides insights in understanding the molecular mechanism of nodulation and nitrogen fixation in Caucasian clover.

Environment-Aware Rate Adaptation Based on Occasional Request and Robust Adjustment in 802.11 Networks.

The IEEE 802.11 standard provides multi-rate support for different versions. As there is no specification on the dynamic strategy to adjust the rate, different rate adaptation algorithms are applied according to different manufacturers. Therefore, it is often hard to interpret the performance discrepancy of various devices. Moreover, the ever-changing channels always challenge the rate adaptation, especially in the scenario with scarce spectrum and low SNR. As a result, it is important to sense the radio environment cognitively and reduce the unnecessary oscillation of the transmission rate. In this paper, we propose an environment-aware robust (EAR) algorithm. This algorithm employs an occasional small packet, designs a rate scheme adaptive to the environment, and enhances the robustness. We verify the throughput of EAR using network simulator NS-3 in terms of station number, motion speed and node distance. We also compare the proposed algorithm with three benchmark methods: AARF, RBAR and CHARM. Simulation results demonstrate that EAR outperforms other algorithms in several wireless environments, greatly improving the system robustness and throughput.

Improving the safety and efficacy of phage therapy from the perspective of phage-mammal interactions.

Phage therapy has re-emerged as a promising solution for combating antimicrobial-resistant bacterial infections. Increasingly, studies have revealed that phages possess therapeutic potential beyond their antimicrobial properties, including regulating the gut microbiome and maintain intestinal homeostasis, as a novel nanocarrier for targeted drug delivery. However, the complexity and unpredictability of phage behavior during treatment pose a significant challenge in clinical practice. The intricate interactions established between phages, humans, and bacteria throughout their long coexistence in the natural ecosystem contribute to the complexity of phage behavior in therapy, raising concerns about their efficacy and safety as therapeutic agents. Revealing the mechanisms by which phages interact with the human body will provide a theoretical basis for increased application of promising phage therapy. In this review, we provide a comprehensive summary of phage-mammal interactions, including signaling pathways, adaptive immunity responses, and phage-mediated anti-inflammatory responses. Then, from the perspective of phage-mammalian immune system interactions, we present the first systematic overview of the factors affecting phage therapy, such as the mode of administration, the physiological status of the patient, and the biological properties of the phage, to offer new insights into phage therapy for various human diseases.

Nitrogen accumulation and attenuation in the Ganges-Brahmaputra-Meghna river system: An evaluation with multiple stable isotopes and microbiota.

We examined dissolved inorganic nitrogen (DIN) accumulation and attenuation in the lower stream and estuary of the Ganges-Brahmaputra-Meghna River system. In the lower stream of Ganges, Meghna and Brahmaputra rivers, nitrate (NO3-) was the dominant component in the DIN pool apart from the site near an industrial center. Concentrations of NO3- displayed minor differences between surface and bottom water, accounting for >90 % of the riverine DIN pool. Sources of NO3- were likely to be municipal wastewater and fertilizer based on signals of 15N-NO3- and 18O-NO3-. In the Meghna River, ammonium concentration in river water increased due to sewage discharge from local industrial centers. In the estuary, likely due to the high-abundance nitrifiers, nitrification rates overwhelmed removal rates and led to NO3- accumulation. Towards coastal ocean, DIN concentrations decreased due to seawater dilution and biological assimilation, indicating a tight linkage between the riverine input and ecological stability in the receiving water.

Mechanistic investigation of the influence of defects on armchair unburned carbon for PbCl2 adsorption.

As the largest consumer of coal energy, coal-fired power plants emit large amounts of PbCl2 each year, which is of wide concern due to its high toxicity, global migration, and accumulation. Unburned carbon is considered a promising adsorbent for effective PbCl2 removal. However, there is a problem that the current unburned carbon model cannot show the structure of carbon defects on the actual unburned carbon surface. Therefore, it is important to construct defective unburned carbon models with practical significance. In addition, the adsorption mechanism of PbCl2 by an unburned model is not studied deeply enough and the reaction mechanism is not clear yet. This has seriously affected the development of effective adsorbents. To reveal the adsorption mechanism of PbCl2 on unburned carbon, the adsorption mechanism of PbCl2 on defective unburned carbon surfaces was analyzed by using the density flooding theory to investigate the adsorption process of PbCl2 on different unburned carbon models. This will provide theoretical guidance for the design and development of adsorbents for the removal of PbCl2 from coal-fired power plants.

Potential differentiation of successive SARS-CoV-2 mutations by RNA: DNA hybrid analyses.

The constant mutation of SARS-CoV-2 has triggered a new round of public health crises and has had a huge impact on existing vaccines and diagnostic tools. It is essential to develop a new flexible method to distinguish mutations to prevent the spread of the virus. In this work, we used the combination of density functional theory (DFT) and non-equilibrium Green's function formulation with decoherence, to theoretically study the effect of viral mutation on charge transport properties of viral nucleic acid molecules. We found that all mutation of SARS-CoV-2 on spike protein was accompanied by the change of gene sequence conductance, this is attributed to the change of nucleic acid molecular energy level caused by mutation. Among them, the mutations L18F, P26S, and T1027I caused the largest conductance change after mutation. This provides a theoretical possibility for detecting virus mutation based on the change of molecular conductance of virus nucleic acid.

Association of Perceived Stress With Depression Among Vaccinated Healthcare Workers During the SARS-CoV-2 Variant Outbreak: The Mediating Role of Compassion Fatigue.

OBJECTIVE: Depression was common during coronavirus disease-2019 (COVID-19) pandemic, while the association of perceived stress with depression among vaccinated healthcare workers has not been investigated. This study aimed to address this issue. METHODS: We included a total of 898 fully vaccinated healthcare workers during the outbreak of severe acute respiratory syndrome coronavirus 2 Delta variant in Nanjing, 2021. Depression was ascertained by Patient Health Questionnaire-9, with a cut-off score of ≥5 indicative of mild-to-severe depression. Perceived stress, resilience, and compassion fatigue were assessed by Perceived Stress Scale-10, Resilience Scale-25, and Professional Quality of Life Scale version-5, respectively. Logistic regression analyses were used to estimate the odds ratio (OR) and 95% confidence interval (CI), along with subgroup and mediation analyses. RESULTS: The prevalence of mild-to-severe depression was 41.1% in vaccinated healthcare workers. The odd of mild-to-severe depression was increased with higher perceived stress. Compared with vaccinated healthcare workers with the lowest tertile of perceived stress, those with the highest tertile had increased odds of mild-to-severe depression by 120% (OR 2.20, 95% CI 1.46 to 3.31) after multivariable-adjustment. However, perceived stress was not associated with mild-to-severe depression in vaccinated healthcare workers with strong resilience, but was in those with weak resilience (pinteraction=0.004). Further analysis showed that compassion fatigue mediated the relationship between perceived stress and mild-to-severe depression, with a mediating effect of 49.7%. CONCLUSION: Perceived stress was related to an increased odd of mild-to-severe depression in vaccinated healthcare workers during COVID-19 pandemic, and this relationship might be explained by compassion fatigue.

Fe3O4/ZIFs-based magnetic solid-phase extraction for the effective extraction of two precursors with diverse structures in aflatoxin B1 biosynthetic pathway.

The aflatoxin B1 (AFB1) early warning technique based on precursors is an effective strategy for the prevention of AFB1 contamination risk. The determination of precursors is imperative to ensure the efficiency of the early warning technique. Herein, a controllable magnetic adsorbent Fe3O4/ZIFs was first introduced for the effective extraction and determination of averantin (AVN) and sterigmatocystin (ST) precursors in cereal by combining magnetic solid-phase extraction (MSPE) and high-performance liquid chromatography (HPLC). Benefiting from the abundant adsorption sites and multifunctional groups matching the analytes, Fe3O4/ZIFs effectively and simultaneously extracted AVN and ST with great differences in polarity and structure via multiple interactions. AVN was extracted by Fe3O4/ZIFs mainly through π-π and hydrophobic interactions, while ST was extracted predominantly by electrostatic interactions and surface complexation. The limits of detection were 0.08 µg kg-1 (AVN) and 0.36 µg kg-1 (ST). The developed method exhibited satisfactory spiked recoveries (79.1%-105.4%) in the determination of AVN and ST in rice. This work provides a novel analytical strategy for further studying AFB1 early warning technique and the formation and transformation of aflatoxins.

Remarkable enhancement of photocatalytic performance in LaCrO3 through a controlled chemical reduction process.

A controlled chemical reduction process was performed on LaCrO3 assisted by CaH2 at a relatively low temperature (773 K), and the impact on the photocatalytic and magnetic properties is discussed. The reduction process leads to the formation of oxygen vacancies that enhance photocatalytic properties by acting as traps that retard the hole/electron recombination processes. In addition, the existence of oxygen defects induces some subtle structural modifications, resulting in Cr-O-Cr angle variation that influences the magnetic behavior of the material. Therefore, the use of a controlled chemical reduction process is an effective method for tunning the physical-chemical properties of transition-metal oxide-based materials, even in cases with high chemical stability.

Preparation and characterization of glucose-based covalent organic polymer coated silica as stationary phase for high-performance liquid chromatography.

Carbohydrate is a renewable, sustainable, hydrophilic, and biodegradable natural product, which is widely used in the field of adsorption. In this study, a glucose-based covalent organic polymer (COP) coated silica was fabricated by facile solvent knitting reaction between tetrabenzylglucose and silica-phenyl with anhydrous aluminum trichloride as catalyst, forming a core-shell stationary phase (donated as SiO2@COPBn-glu) for high performance liquid chromatography. The prepared SiO2@COPBn-glu was characterized by scanning electron microscopy, transmission electron microscopy, Fourier-transform infrared spectrometry, solid-state 13C nuclear magnetic resonance spectrometry, X-ray photoelectron spectroscopy, and N2 adsorption-desorption experiments. Owing to the coexistence of benzene units and alkyl, hydroxyl and ether groups in the skeleton of COPBn-glu shell, the developed chromatographic packing exhibited reversed-phase/hydrophilic interaction mixed-mode with multiple retention mechanisms, such as hydrophobic, π-π, hydrogen bonding, and electron donor-acceptor interactions. The results revealed that the SiO2@COPBn-glu column demonstrated excellent selectivity and retention behavior for both hydrophilic and hydrophobic compounds with good repeatability and stability. Meanwhile, the chromatographic performance of the prepared SiO2@COPBn-glu column was compared with a C18 column to assess the role of the coating COPBn-glu shell. Therefore, the development of the SiO2@COPBn-glu stationary phase expands the potential application of COPs in separation field.

Cardiac glycoside neriifolin exerts anti-cancer activity in prostate cancer cells by attenuating DNA damage repair through endoplasmic reticulum stress.

Prostate cancer (PCa) is one of the most common cancers in men. Patients with recurrent disease initially respond to androgen-deprivation therapy, but the tumor eventually progresses into castration-resistant PCa. Thus, new therapeutic approaches for PCa resistance to current treatments are urgently needed. Here, we report that cardiac glycoside neriifolin suppresses the malignancy of cancer cells via increasing DNA damage and apoptosis through activation of endoplasmic reticulum stress (ERS) in prostate cancers. We found that cardiac glycoside neriifolin markedly inhibited the cell growth and induced apoptosis in prostate cancer cells. Transcriptome sequence analysis revealed that neriifolin significantly induced DNA damage and double strand breaks (DSBs), validated with attenuation expression of genes in DSBs repair and increasing phosphorylated histone H2AX (γ-H2AX) foci formation, a quantitative marker of DSBs. Moreover, we found that neriifolin also activated ERS, evidenced by upregulation and activation of ERS related proteins, including eukaryotic initiation factor 2α (eIF2α), protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) and C/EBP homologous protein (CHOP) as well as downregulation of CCAATenhancerbinding protein alpha (C/EBP-α), a transcriptional factor that forms heterodimers with CHOP. In addition, neriifolin treatment dramatically inhibited the by tumor growth, which were reversed by CHOP loss or overexpression of C/EBP-α in nude mice. Mechanistically, neriifolin suppressed the tumor growth by increasing DNA damage and apoptosis through CHOP-C/EBP-α signaling axis of ERS in prostate cancers. Taken together, these results suggest that cardiac glycoside neriifolin may be a potential tumor-specific chemotherapeutic agent in prostate cancer treatment.