OsMPK12 positively regulates rice blast resistance via OsEDC4-mediated transcriptional regulation of immune-related genes.

Mitogen-activated protein kinase (MAPK) signalling cascades are functionally important signalling modules in eukaryotes. Transcriptome reprogramming of immune-related genes is a key process in plant immunity. Emerging evidence shows that plant MAPK cascade is associated with processing (P)-body components and contributes to transcriptome reprogramming of immune-related genes. However, it remains largely unknown how this process is regulated. Here, we show that OsMPK12, which is induced by Magnaporthe oryzae infection, positively regulates rice blast resistance. Further analysis revealed that OsMPK12 directly interacts with enhancer of mRNA decapping protein 4 (OsEDC4), a P-body-located protein, and recruits OsEDC4 to where OsMPK12 is enriched. Importantly, OsEDC4 directly interacts with two decapping complex members OsDCP1 and OsDCP2, indicating that OsEDC4 is a subunit of the mRNA decapping complex. Additionally, we found that OsEDC4 positively regulates rice blast resistance by regulating expression of immune-related genes and maintaining proper mRNA levels of some negatively-regulated genes. And OsMPK12 and OsEDC4 are also involved in rice growth and development regulation. Taken together, our data demonstrate that OsMPK12 positively regulates rice blast resistance via OsEDC4-mediated mRNA decay of immune-related genes, providing new insight into not only the new role of the MAPK signalling cascade, but also posttranscriptional regulation of immune-related genes.

Cognitive status and its risk factors in patients with hypertension and diabetes in a low-income rural area of China: A cross-sectional study.

OBJECTIVES: The proportion of older people with dementia in China is gradually increasing with the increase in the aging population over recent years. Hypertension and diabetes are common non-communicable diseases among rural populations in China. However, it remains unclear whether these conditions affect the occurrence and development of cognitive impairment as there is limited research on cognitive status and its risk factors among residents of rural areas. METHODS: A multi-stage stratified cluster random sampling method was used to select 5400 participants from rural permanent residents. A self-designed structured questionnaire was used to investigate demographic data of the participants. Cognitive function was assessed using the Montreal Cognitive Function Assessment Scale (MoCA). The results were analyzed using chi-square test, ANOVA and multiple linear regression analysis. RESULTS: A total of 5028 participants returned the survey, giving a response rate of 93.1%. Higher education (odds ratio (OR) = 3.2, 95% confidence interval (CI) 2.87-3.54, p < 0.001), higher income (OR = 1.61, 95% CI 1.16-2.07, p < 0.001), and dietary control (OR = 0.66, 95%CI 0.34-0.98, p < 0.001) were protective factors. A visual representation of the relationship between annual income and MoCA score showed an inverted U-curve, the group with an annual income of 6000-7999 RMB had a maximum OR of 1.93 (95%CI 0.12-2.74, p < 0.001). While difficulty in maintaining sleep were risk factors for cognitive impairment (OR = -2.28, 95% CI-4.18-0.39, p = 0.018). CONCLUSIONS: Participants with middle incomes had better cognitive status than those with the highest incomes. Higher education, proper diet control and good sleep are beneficial to the cognitive status of residents in rural areas.

Client-counselor behavioral and inter-brain synchronization among dismissing and secure clients and its association with alliance quality and outcome.

Objective This study aimed to explore whether behavioral synchrony (BS) and inter-brain synchrony (IBS) could serve as potential biomarkers for alliance quality or outcomes among clients with different adult attachment styles. Method: We assessed the clients' self-report working alliance and clinical outcomes as well as simultaneously measured BS using motion energy analysis (MEA) and IBS with functional near-infrared spectroscopy (fNIRS) among 37 secure (N = 21) or dismissing (N = 16) clients with their counselors during the first psychological counseling meeting. Results: Dismissing dyads manifested significantly higher late-stage counselor-led and client-led IBS (p = .018) than secure dyads. Adult attachment style served as the moderators in the correlation of both whole-stage client-led BS with bond dimension of alliance (p = .015) as well as in the correlation of both whole-stage no-lag IBS with CORE-10 score changes (p = .022). Moreover, increases in the whole-stage client-led BS were significantly associated with decreases in early-stage, late-stage and whole-stage no-lag IBS (all ps ≤ 0.01). Conclusion: These findings revealed the potentially impeding role of interpersonal synchrony in alliance quality for dismissing clients, at least during the first psychological counseling meetings. They also might partially validate the relationship between different modalities of interpersonal synchrony.

Aluminum maltolate triggers ferroptosis in neurons: mechanism of action.

Aluminum (Al), a neurotoxic element, can induce Alzheimer's disease (AD) via triggering neuronal death. Ferroptosis is a new type of programmed cell death related to neurological diseases. Unfortunately, its role in aluminum-induced neuronal death remains completely unclear. This study aimed to investigate whether ferroptosis is involved in neuronal death in response to aluminum exposure as well as its underlying mechanism. In this study, rat adrenal pheochromocytoma (PC12) cells were treated with 200 µM aluminum maltolate (Al(mal)3) for 24 h, and related biochemical indicators were assessed to determine whether ferroptosis was induced by aluminum in neurons. Then, the potential mechanism was explored by detecting of these genes and proteins associated with ferroptosis after adding ferroptosis-specific agonist Erastin (5 µM) and antagonist Ferrostatin-1 (Fer-1) (5 µM). The experimental results demonstrated that aluminum exposure significantly increased the death of PC12 cells and caused specific mitochondrial pathological changes of ferroptosis in PC12 cells. Further research confirmed that ferroptosis was triggered by aluminum in PC12 cells by means of activating the oxidative damage signaling pathway, which was displayed as inhibition of the cysteine/glutamate antiporter system (system Xc-), causing the depletion of cellular glutathione (GSH) and inactivation of glutathione peroxidase (GSH-PX) eventually lead to accumulation of reactive oxygen species (ROS). Taken together, ferroptosis was a means of neuronal death induced by aluminum and oxidative damage may be its underlying mechanism, which also provided some new clues to potential target for the intervention and therapy of AD.

Dual-Functional Supernanoparticles with Microwave Dynamic Therapy and Microwave Thermal Therapy.

The cytotoxic reactive oxygen species (ROS) generated by photoactivated sensitizers have been well explored in tumor therapy for nearly half a century, which is known as photodynamic therapy (PDT). The poor light penetration depth severely hinders PDT as a primary or adjuvant therapy for clinical indication. Whereas microwaves (MWs) are advantageous for deep penetration depth, the MW energy is considerably lower than that required for the activation of any species to induce ROS generation. Herein we find that liquid metal (LM) supernanoparticles activated by MW irradiation can generate ROS, such as ·OH and ·O2. On this basis, we design dual-functional supernanoparticles by loading LMs and an MW heating sensitizer ionic liquid (IL) into mesoporous ZrO2 nanoparticles, which can be activated by MW as the sole energy source for dynamic and thermal therapy concomitantly. The microwave sensitizer opens the door to an entirely novel dynamic treatment for tumors.

[Study on composition, antibiotic activity and antioxidant activity of volatile oils from uyghur medicine Althaea rosea].

Althaea rosea is a type of mallow plant. Its dry flowers are one of common herb in Uyghur medicines and recorded to have several efficacies such as external application for detumescence, moistening lung and arresting cough, sweating and relieving asthma, diminishing swelling and promoting eruption, soothing the nerves and strengthening heart. However, there are only fewer studies on effective components of A. rosea and no literature about its volatile oil and pharmacological activity. In this paper, the volatile oil of A. rosea was obtained by using the chemical distillation and extraction method. The individual chemical components were separated from the volatile oil and identified by the Gas Chromatograph-Mass Spectrometer technique (GC-MS). The antioxidant activity against free radicals was detected by the'ultraviolet and visible spectrophotometer method. The antibiotic activity was detected by the filter paper diffusion method. The experimental results showed nearly 70 compounds in the volatile oil, with complex chemical components. With a low content, most of the compounds were aromatic and aliphatic compounds and their derivatives. A. rosea had a better antibiotic activity for common microorganisms, with a wide antibacterial spectrum. According to the results, the volatile oil of A. rosea will have a good application value in medicine, food and cosmetic industries, which provided a scientific basis for the development of natural A. rosea resources.

Modification of Fatty acids in membranes of bacteria: implication for an adaptive mechanism to the toxicity of carbon nanotubes.

We explored whether bacteria could respond adaptively to the presence of carbon nanotubes (CNTs) by investigating the influence of CNTs on the viability, composition of fatty acids, and cytoplasmic membrane fluidity of bacteria in aqueous medium for 24 h exposure. The CNTs included long single-walled carbon nanotubes (L-SWCNTs), short single-walled carbon nanotubes (S-SWCNTs), short carboxyl single-walled carbon nanotubes (S-SWCNT-COOH), and aligned multiwalled carbon nanotubes (A-MWCNTs). The bacteria included three common model bacteria, Staphyloccocus aureus (Gram-positive), Bacillus subtilis (Gram-positive), and Escherichia coli (Gram-negative), and one polybrominated diphenyl ether degrading strain, Ochrobactrum sp. (Gram-negative). Generally, L-SWCNTs were the most toxic to bacteria, whereas S-SWCNT-COOH showed the mildest bacterial toxicity. Ochrobactrum sp. was more susceptible to the toxic effect of CNTs than E. coli. Compared to the control in the absence of CNTs, the viability of Ochrobactrum sp. decreased from 71.6-81.4% to 41.8-70.2%, and E. coli from 93.7-104.0% to 67.7-91.0% when CNT concentration increased from 10 to 50 mg L(-1). The cytoplasmic membrane fluidity of bacteria increased with CNT concentration, and a significant negative correlation existed between the bacterial viabilities and membrane fluidity for E. coli and Ochrobactrum sp. (p < 0.05), indicating that the increase in membrane fluidity induced by CNTs was an important factor causing the inactivation of bacteria. In the presence of CNTs, E. coli and Ochrobactrum sp. showed elevation in the level of saturated fatty acids accompanied with reduction in unsaturated fatty acids, compensating for the fluidizing effect of CNTs. This demonstrated that bacteria could modify their composition of fatty acids to adapt to the toxicity of CNTs. In contrast, S. aureus and B. subtilis exposed to CNTs increased the proportion of branched-chain fatty acids and decreased the level of straight-chain fatty acids, which was also favorable to counteract the toxic effect of CNTs. This study suggests that the bacterial tolerances to CNTs are associated with both the adaptive modification of fatty acids in the membrane and the physicochemical properties of CNTs. This is the first report about the physiologically adaptive response of bacteria to CNTs, and may help to further understand the ecotoxicological effects of CNTs.

Particle swarm inspired underwater sensor self-deployment.

Underwater sensor networks (UWSNs) can be applied in sea resource reconnaissance, pollution monitoring and assistant navigation, etc., and have become a hot research field in wireless sensor networks. In open and complicated underwater environments, targets (events) tend to be highly dynamic and uncertain. It is important to deploy sensors to cover potential events in an optimal manner. In this paper, the underwater sensor deployment problem and its performance evaluation metrics are introduced. Furthermore, a particle swarm inspired sensor self-deployment algorithm is presented. By simulating the flying behavior of particles and introducing crowd control, the proposed algorithm can drive sensors to cover almost all the events, and make the distribution of sensors match that of events. Through extensive simulations, we demonstrate that it can solve the underwater sensor deployment problem effectively, with fast convergence rate, and amiable to distributed implementation.

TCDformer: A transformer framework for non-stationary time series forecasting based on trend and change-point detection.

Although time series prediction models based on Transformer architecture have achieved significant advances, concerns have arisen regarding their performance with non-stationary real-world data. Traditional methods often use stabilization techniques to boost predictability, but this often results in the loss of non-stationarity, notably underperforming when tackling major events in practical applications. To address this challenge, this research introduces an innovative method named TCDformer (Trend and Change-point Detection Transformer). TCDformer employs a unique strategy, initially encoding abrupt changes in non-stationary time series using the local linear scaling approximation (LLSA) module. The reconstructed contextual time series is then decomposed into trend and seasonal components. The final prediction results are derived from the additive combination of a multilayer perceptron (MLP) for predicting trend components and wavelet attention mechanisms for seasonal components. Comprehensive experimental results show that on standard time series prediction datasets, TCDformer significantly surpasses existing benchmark models in terms of performance, reducing MSE by 47.36% and MAE by 31.12%. This approach offers an effective framework for managing non-stationary time series, achieving a balance between performance and interpretability, making it especially suitable for addressing non-stationarity challenges in real-world scenarios.

Sleep deprivation from mid-gestation leads to impaired of motor coordination in young offspring mice with microglia activation in the cerebellar vermis.

OBJECTIVE: To investigate the effects of mid-pregnancy sleep deprivation (SD) in C57BL/6 J mice on the motor coordination of the offspring and to explore the potential mechanism of microglia activation in the cerebellar vermis of the offspring involved in the induction of impaired motor coordination development. METHODS: C57BL/6 J pregnant mice were randomly divided into the SD and control groups. SD was implemented by the multi-platform method from first day of the middle pregnancy (gestation day 8, GD8). At postnatal day 21 (PND21), we measured the development of motor behavior and collected cerebellar vermis tissues to observe the activation of microglia by H&E staining, the expression of microglia-specific markers ionized calcium-binding adaptor molecule-1 (Iba-1) and cluster of differentiation 68 (CD68) by immunohistochemical, and interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor -α (TNF-α) by real-time quantitative PCR (RT-qPCR). RESULTS: In the offspring of SD group, comparing to the control group, the total time of passage and the reverse crawl distance in the balance beam test, and the frequency of falls from the suspension cord was increased; with lower max rotational speed and shorter duration in the rotarod experiment. Further, we found that the microglia of cerebellar vermis tissues emerged an amoeba-like activation. The mean gray value of Iba-1 was lower, the density of positive cells of CD68 and the expression levels of IL-6 and TNF-α were increased. CONCLUSIONS: The motor coordination of offspring is impaired, accompanying a SD from mid-pregnancy, and the cerebellar vermis showed microglia activation and pro-inflammatory response. It suggested the adverse effects of SD from mid-gestation on the development of motor coordination through the inflammatory response in the cerebellar vermis of the offspring.

Metformin alleviates the cognitive impairment induced by benzo[a]pyrene via glucolipid metabolism regulated by FTO/FoxO6 pathway in mice.

Benzo[a]pyrene (B[a]P) is neurotoxic; however, the mechanism and prevention are still unclear. In this study, we assessed the intervention effect of metformin (MET) on cognitive dysfunction in mice induced by B[a]P from the perspective of glucolipid metabolism. Forty-two male healthy ICR mice were randomly categorized into 6 groups and were gavaged with B[a]P (0, 2.5, 5, or 10 mg/kg), 45 times for 90 days. The controls were gavaged with edible peanut oil, and the intervention groups were co-treated with B[a]P (10 mg/kg) and MET (200 or 300 mg/kg). We assessed the cognitive function of mice, observed the pathomorphological and ultrastructural changes, and detected neuronal apoptosis and glucolipid metabolism. Results showed that B[a]P dose-dependently induced cognitive impairment, neuronal damage, glucolipid metabolism disorder in mice, and enhanced proteins of fat mass and obesity-associated protein (FTO) and forkhead box protein O6 (FoxO6) in the cerebral cortex and liver, which were alleviated by the MET intervention. The findings indicated the critical role of glucolipid metabolism disorder in the cognitive impairment in mice caused by B[a]P and the prevention of MET against B[a]P neurotoxicity by regulating glucolipid metabolism via restraining FTO/FoxO6 pathway. The finding provides a scientific basis for the neurotoxicity and prevention strategies of B[a]P.

Aspirin ameliorates the neurotoxicity of benzo[a]pyrene in mice and HT22 cells: Possible role of miRNA-mRNA network.

Benzo[a]pyrene (B[a]P) is neurotoxic, however, the mechanism and potential prevention are yet not clear. This study explored the miRNA-mRNA network in the B[a]P-induced neurotoxicity in mice and HT22 cells and the intervention of aspirin (ASP). HT22 cells were treated for 48 h with DMSO, B[a]P (20 µM), or both B[a]P (20 µM) and ASP (4 µM). Following B[a]P treatment, compared to the DMSO controls, HT22 cells showed injured cell morphology, reduced cell viability and neurotrophic factor concentrations, and increased LDH leakage, Aß1-42, and inflammatory factor concentrations, which were improved by ASP. RNA sequencing and qPCR verified the significant differences of miRNA and mRNA profiles following B[a]P treatment, which were rescued by ASP. Bioinformatics analysis suggested the miRNA-mRNA network could be involved in the neurotoxicity of B[a]P and the intervention of ASP. The neurotoxicity and neuroinflammation were induced in mice's brains by B[a]P, and the target miRNA and mRNA were proved to be consistent with in vitro, which were ameliorated by ASP. The findings demonstrate a possible role of miRNA-mRNA network in the B[a]P-induced neurotoxicity. If this is confirmed by additional experiments, it will provide a promising pathway of intervention against B[a]P, using ASP or other agents with fewer toxic effects.

BPDE-DNA adduct formation and alterations of mRNA, protein, and DNA methylation of CYP1A1, GSTP1, and GSTM1 induced by benzo[a]pyrene and the intervention of aspirin in mice.

Benzo[a]pyrene (B[a]P), one typical environmental pollutant, the toxicity mechanisms, and potential prevention remain perplexing. Available evidence suggests cytochrome P450 1A1 (CYP1A1) and glutathione S-transferases (GSTs) metabolize B[a]P, resulting in metabolic activation and detoxification of B[a]P. This study aimed to reveal the impact of B[a]P exposure on trans-7,8-diol-anti-9,10-epoxide DNA (BPDE-DNA) adduct formation, level of CYP1A1, glutathione S-transferase pi (GSTP1) and glutathione S-transferase mu1 (GSTM1) mRNA, protein and DNA methylation in mice, and the potential prevention of aspirin (ASP). This study firstly determined the BPDE-DNA adduct formation in an acute toxicity test of a large dose in mice induced by B[a]P, which subsequently detected CYP1A1, GSTP1, and GSTM1 at levels of mRNA, protein, and DNA methylation in the organs of mice in a subacute toxicity test at appropriate doses and the potential prevention of ASP, using the methods of real-time quantitative PCR (QPCR), western blotting, and real-time methylation-specific PCR (MSP), respectively. The results verified that B[a]P induced the formation of BPDE-DNA adduct in all the organs of mice in an acute toxicity test, and the order of concentration of which was lung > kidney > liver > brain. In a subacute toxicity test, following B[a]P treatment, mice showed a dose-dependent slowdown in body weight gain and abnormalities in behavioral and cognitive function and which were alleviated by ASP co-treatment. Compared to the controls, following B[a]P treatment, CYP1A1 was significantly induced in all organs in mice at mRNA level (P < 0.05), was suppressed in the lung and cerebrum of mice at protein level, and inhibited at DNA methylation level in the liver, lung, and cerebrum, whereas GSTP1 and GSTM1 at mRNA, protein, and DNA methylation levels showed organ-specific changes in mice following B[a]P treatment, which was generally alleviated by ASP intervention. In conclusion, B[a]P induced BPDE-DNA adduct formation in all organs in mice and altered the mRNA, protein, and DNA methylation levels in CYP1A1, GSTP1, and GSTM1 in an organ-dependent pattern, which could be related to the organ toxicity and mechanism of B[a]P. ASP intervention may be an effective measure to prevent B[a]P toxicity. The findings provide scientific evidence for further study on the organ toxicity and mechanisms of B[a]P.

Interaction between pH-shifted ovalbumin and insoluble neohesperidin: Experimental and binding mechanism studies.

In this study, ovalbumin (OVA) formed a complex with neohesperidin (NH) via a pH-shifting method. The NH-OVA complex self-assembled into NH-OVA nano-particles, which were then characterized and whose binding mechanism was evaluated by using multi-spectroscopic, thermodynamics, and molecular docking simulation methods. Fluorescence intensity decreased after OVA was complexed with NH. The binding constant of the OVA-NH complex was in the order of 6.32 × 105 M-1 suggesting that the complex is stable. Circular dichroism (CD) analysis showed that α -helix content increased, ß-folding, ß -turning, and irregular crimp content decreased after OVA and NH binding. Isothermal titration calorimetry results showed that hydrophobic interactions and hydrogen bonds made an important impact in the complex formation. The molecular docking results revealed that Van der Waals forces and hydrogen bonds contributed to the free binding energy of the complex. There were multiple possible surface binding sites between OVA with NH. The obtained results provide new insights into the interaction mechanism of OVA and NH, and as a vehicle for NH, the OVA has shown promising applications in functional foods.

Aspirin ameliorates the cognition impairment in mice following benzo[a]pyrene treatment via down-regulating BDNF IV methylation.

Benzo[a]pyrene (B[a]P) is neurotoxic, however, the mechanisms remain unclear and there is no effective prevention. Available evidence suggests a role of DNA methylation in B[a]P-induced neurotoxicity. This study investigated the brain-derived neurotrophic factor (BDNF) IV methylation in the development of and aspirin intervention against B[a]P's neurotoxicity in mice and HT22 cells. Mice were intraperitoneally treated with solvent or B[a]P (0.5, 2, and 10 mg/kg b.w.) for 60 days. An intervention group was treated simultaneously with B[a]P (10 mg/kg, i.p.) and aspirin (10 mg/kg, daily water-drinking). The treated mice showed a dose-dependent cognitive and behavioral impairment, and cerebral cell apoptosis, which were alleviated by aspirin co-treatment. Following B[a]P treatment, DNA methyltransferase (DNMTs) and BDNF IV hypermethylation were increased in the cerebral cortex of mice compared to controls, while significant decreases were found in BDNF IV and BDNF mRNA, and BDNF protein levels. Aspirin co-treatment rescued DNMTs activation and BDNF IV hypermethylation, and mitigated the recession in BDNF mRNA and protein induced by B[a]P treatment. Similar results were shown in HT22 cells. These findings reveal a critical role of BDNF IV methylation in the neurotoxicity of B[a]P, and demonstrate a promising prevention of aspirin against B[a]P-induced cognitive impairment via inhibiting BDNF IV hypermethylation.

Selective capture of toxic anionic dyes of a novel prepared DMDAAC-grafted chitosan/genipin/cellulose hydrogel beads with antibacterial activity.

Novel eco-friendly and green dimethyldiallylammonium chloride (DMDAAC) grafted chitosan/genipin/cellulose hydrogel beads (CCBG-g-PDMDAAC), were fabricated as selective adsorbents for anionic dyes. The physical and chemical structural changes of the prepared hydrogels were evaluated by FTIR, XRD, SEM and TG-DSC analysis. Results showed CCBG-g-PDMDAAC efficiently and selectively adsorb anionic dyes (Reactive Red 195-RR195 and Methyl orange-MO) from mixture of dye solutions. Endowed chitosan-based hydrogels the advantage of acid insolubility and good adsorption. RR195 and MO adsorption process were described better with pseudo-second-order kinetic model and Langmuir isotherm model with a maximum adsorption capacity of 1333.52 and 190.48 mg/g, respectively, indicating that monolayer chemisorption controlled the sorption process. Moreover, the hydrogels exhibited nice reusability and against S. aureus and E. coli. The hydrogels are promising for the potential application in wastewater treatment and antibacterial simultaneously.

LncRNA DCST1-AS1 Sponges miR-107 to Upregulate CDK6 in Cervical Squamous Cell Carcinoma.

INTRODUCTION: LncRNAs have been reported to play critical roles in liver cancer, while its role in other cancers remains unclear. The aim of this study was to investigate the role of DCST1-AS1 in cervical squamous cell carcinoma (CSCC). METHODS: Expression of DCST1-AS1 in CSCC tissues and non-tumor tissues from 68 CSCC patients was determined by RT-qPCR. A 5-year follow-up study was carried out to explore the prognostic value of DCST1-AS1 for CSCC. Overexpression of DCST1-AS1 and miR-107 was achieved in CSCC tissues to explore the interaction between them. The roles of DCST1-AS1, miR-107 and CDK6 in regulating the proliferation and viability of CSCC cells were assessed by cell proliferation and viability assays, respectively. RESULTS: We found that DCST1-AS1 was upregulated in CSCC and predicted poor survival. RNA interaction prediction showed potential interaction between DCST1-AS1 and miR-107. However, overexpression experiments revealed no significant interaction between them. Moreover, overexpression of DCST1-AS1 led to upregulate CDK6 and increase cell proliferation rate, while overexpression of miR-107 played an opposite role and attenuate the effects of overexpression of DCST1-AS1. CONCLUSION: DCST1-AS1 may sponge miR-107 to upregulate CDK6 in CSCC.

Synthesis of Hydrophobic Propionyl Neohesperidin Ester Using an Immobilied Enzyme and Description of Its Anti-proliferative and Pro-apoptotic Effects on MCF-7 Human Breast Cancer Cells.

Neohesperidin (NH) is a natural flavonoid glycoside compound with considerable physiological and pharmacological activities. However, its bioavailability is limited due to poor solubility, and few studies have so far attempted improve the solubility and bioavailability of NH. In this study, we structurally modified NH using an immobilized lipase to improve lipophilicity and therefore expand its applicability in lipophilic media as well as enhance its bioavailability in vivo. In addition, we aimed investigated the pro-apoptoptotic activity of this new compound (propionyl neohesperidin ester, PNHE) in MCF-7 breast cancer cells using a variety of cellular assays, including the MTT (3-(4, 5-dimethyl- 2-thiazolyl)-2, 5-diphenyl-2-h-tetrazolium bromide assay, assessment of intracellular reactive oxygen species (ROS) levels, and flow cytometry. We successfully synthesized PNHE using immobilized lipases, and the esterification of NH was confirmed by Fourier transform-infrared spectroscopy (FT-IR). Compared to NH, HNPE showed higher anti-proliferative and pro-apoptotic in MCF-7 breast cancer cells, which may be explained by its increased lipophilicity compared to neohesperidin, benefiting to the action of NH on the cancer cell wall. The IC50 of PNHE for inducing apoptosis of MCF-7 cells was 185.52 µg/mL. PNHE increased both the proportion of cells in Sub-G1 phase and the cellular ROS content, indicating a certain therapeutic effect of HNPE on breast cancer.

Preparation of crystalline nanocellulose/hydroxypropyl ß cyclodextrin/carboxymethyl cellulose polyelectrolyte complexes and their controlled release of neohesperidin-copper (II) in vitro.

A natural hydrogel film was prepared using carboxymethyl cellulose (CMC), cellulose nanocrystals (CNC), and hydroxypropyl ß cyclodextrin (HP-ß-CD) as reactants and citric acid as the cross-linking agent and used for the controlled release of neohesperidin-copper(II)(NH-Cu (II)). The hydrogel film was characterized by ATR-FTIR, XRD, TGA and DSC. The film showed controlled swelling behavior; the release behavior of NH-Cu(II) from the hydrogel film was also investigated in different solutions including distilled water, various salt solutions including 0.9% NaCl, and solutions having different pH values. Thiazolyl blue tetrazolium bromide assay and relative growth rates were adopted to evaluate the biocompatibility and cytotoxicity of the prepared hydrogel films. The results indicated that the expansion kinetics followed Fickian diffusion and Schott's second-order kinetics model. The hydrogel film exhibited enhanced mechanical properties and improved thermal stability at high temperatures due to the addition of CNC, with the amount of added CNC affecting the swelling ratio, salt sensitivity, and pH sensitivity of the hydrogel film in different solutions. Additionally, the CNC largely improved the loading and encapsulation efficiency of the hydrogel films, with the optimal CNC addition amount being 4% which yielded a loading amount of 753.75 mg/g and an accumulated release rate of 85.08%. The hydrogel film with proven cell compatibility and non-cytotoxicity can potentially be used as a drug delivery and controlled release material.

A Novel and High-Effective Biosynthesis Pathway of Hesperetin-7-O-Glucoside Based on the Construction of Immobilized Rhamnosidase Reaction Platform.

Hesperetin-7-O-glucoside (HMG) is a precursor for synthesizing a sweetener named neohesperidin dihydrochalcone, and the coordination toward flavonoids of metal ions tends to increase the water solubility of flavonoids. In order to achieve effective synthesis of HMG, an immobilized enzyme catalysis platform was constructed using an immobilized rhamnosidase on Fe3O4@graphene oxide (Fe3O4@GO), a novel reaction pathway based on the platform was designed for preparing a hesperidin complex as a soluble substrate, and ammonium hydroxide as a ligand dissociation agent to obtain HMG. The Fe3O4@GO was characterized by Fourier transform infrared (FT-IR), X-ray diffraction (XRD), scanning electron microscope (SEM), and thermal methods (TG/DSC) analysis to evaluate the immobilization matrix properties. The enzyme activity in free and immobilized form at different pH and temperature was optimized. The reusability of immobilized enzyme was also determined. In addition, the kinetic parameters (K m and V max) were computed after experiment. Results indicated that rhamnosidase immobilized on Fe3O4@GO using a green cross-linker of genipin hydrolyzed successfully and selectively the soluble hesperidin-Cu (II) complex into HMG-Cu (II), a permanent magnet helped the separation of immobilized enzyme and hydrolytes, and ammonium hydroxide was an effective ligand dissociation agent of translating HMG-Cu (II) into HMG with high purity determined by ultraviolet-visible (UV-Vis) spectra analysis and time-of-flight mass spectrometry (TOF-MS). As a result, a novel and high-effective biosynthesis pathway of HMG based on a selectively catalytic reaction platform were constructed successfully. The pathway based on the platform has great potential to produce valuable citrus monoglycoside flavonoid HMG, and the designed reaction route are feasible using the hesperidin-Cu (II) complex with good solubility as a reaction substrate and using ammonium water as a dissociation agent.