In vitro and in vivo anti-tumor effect of Trichobakin fused with urokinase-type plasminogen activator ATF-TBK.

BACKGROUND: Trichobakin (TBK), a member of type I ribosome-inactivating proteins (RIPs), was first successfully cloned from Trichosanthes sp Bac Kan 8-98 in Vietnam. Previous study has shown that TBK acts as a potential protein synthesis inhibitor; however, the inhibition efficiency and specificity of TBK on cancer cells remain to be fully elucidated. METHODS AND RESULTS: In this work, we employed TBK and TBK conjugated with a part of the amino-terminal fragment (ATF) of the urokinase-type plasminogen activator (uPA), which contains the Ω-loop that primarily interacts with urokinase-type plasminogen activator receptor, and can be a powerful carrier in the drug delivery to cancer cells. Four different human tumor cell lines and BALB/c mice bearing Lewis lung carcinoma cells (LLC) were used to evaluate the role of TBK and ATF-TBK in the inhibition of tumor growth. Here we showed that the obtained ligand fused RIP (ATF-TBK) reduced the growth of four human cancer cell lines in vitro in the uPA receptor level-dependent manner, including the breast adenocarcinoma MDA-MB 231 cells and MCF7 cells, the prostate carcinoma LNCaP cells and the hepatocellular carcinoma HepG2 cells. Furthermore, the conjugate showed anti-tumor activity and prolonged the survival time of tumor-bearing mice. The ATF-TBK also did not cause the death of mice with doses up to 48 mg/kg, and they were not significantly distinct on parameters of hematology and serum biochemistry between the control and experiment groups. CONCLUSIONS: In conclusion, ATF-TBK reduced the growth of four different human tumor cell lines and inhibited lung tumor growth in a mouse model with little side effects. Hence, the ATF-TBK may be a target to consider as an anti-cancer agent for clinical trials.

Four Steroidal Saponins from the Trunks of Dracaena cambodiana with Inhibition of NO Production in LPS Activated RAW264.7 Cells.

Dracaena cambodiana Pierre ex Gagnep. is well known as a medicinal plant and widely distributed in Vietnam. Phytochemical investigation on the trunks of D. cambodiana lead to the isolation of four undescribed compounds (1-4) together with seven known ones (5-11). Their structures were determined to be pennogenin-24-yl-O-ß-D-glucopyranoside (1), 17α-hydroxycambodianoside C (2), (25R)-27-hydroxypenogenin 3-O-α-L-rhamnopyranosyl-(1→3)-[α-L-rhamnopyranosyl-(1→2)]-ß-D-glucopyranoside (3), (3ß,25R)-17α,22α-dihydroxy-furost-5-en-3-yl-O-α-L-rhamnopyranosyl-(1→3)-[α-L-rhamnopyranosyl-(1→2)]-ß-D-glucopyranoside (4), dracagenin A (5), 1-O-ß-D-glucopyranosyl-2-hydroxy-4-allylbenzene (6), 1-O-α-L-rhamnopyranosyl-(1→6)-ß-D-glucopyranosyl-2-hydroxy-allylbenzene (7), 2-O-α-L-rhamnopyranosyl-(1→6)-ß-D-glucopyranosyl-1-hydroxy-allylbenzene (8), cinnamrutinoside A (9), icariside D1 (10), and seco-isolariciresinol 9-O-ß-glucopyranoside (11) by extensive spectroscopic investigation, HR-ESI-MS, 1D and 2D NMR spectra. The anti-inflammatory activity of the isolated compounds was evaluated on macrophages. Compounds 1-6 significantly inhibited nitric oxide production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Among them, compound 1 showed the best inhibitory activity with an IC50 value of 8.90±0.56 µM.

Alkaloids and Lignans from the Aerial Parts of Rauvolfia tetraphylla Inhibit NO Production in LPS-activated RAW 264.7 Cells.

Three previously undescribed compounds named rauvolphyllas A-C (1-3), along with thirteen known compounds, 18ß-hydroxy-3-epi-α-yohimbine (4), yohimbine (5), α-yohimbine (6), 17-epi-α-yohimbine (7), (E)-vallesiachotamine (8), (Z)-vallesiachotamine (9), 16S-E-isositsirikine (10), Nb -methylisoajimaline (11), Nb -methylajimaline (12), ajimaline (13), (+)-lyoniresinol 3α-O-ß-D-glucopyranoside (14), (+)-isolarisiresinol 3α-O-ß-D-glucopyranoside (15), and (-)-lyoniresinol 3α-O-ß-D-glucopyranoside (16) were isolated from the aerial parts of Rauvolfia tetraphylla L. Their chemical structures were elucidated based on the extensive spectroscopic interpretation of HR-ESI-MS, 1D and 2D NMR spectra. The absolute configurations of 2 and 3 were determined by experimental ECD spectra. Compounds 5, 6, 7, and 11-13 exhibited nitric oxide production inhibition activity in LPS-activated RAW 264.7 cells with the IC50 values of 79.10, 44.34, 51.28, 33.54, 37.67, and 28.56 µM, respectively, compared to that of the positive control, dexamethasone, which showed IC50 value of 13.66 µM. The other isolates were inactive with IC50 values over 100 µM.

Four Undescribed compounds Isolated from the Aerial Parts of Phyllanthus cochinchinensis with Antimicrobial Activity and NO Production Inhibitory Activity in LPS Activated RAW 264.7 Cells.

Four previously undescribed compounds named phyllancosides A and B (1 and 2), and phyllancochines A and B (3 and 4) together with ten known compounds (5-14) were isolated from the aerial parts of Phyllanthus cochinchinensis Spreng. Their chemical structures were elucidated on the basis of comprehensive analysis of IR, HR-ESI-MS, 1D and 2D NMR spectra. The absolute configurations of 1 and 2 were determined by electronic circular dichroism (ECD) spectra. Compounds 3, 4, and 10 showed antimicrobial activity against E. faecalis, S. aureus, and B. cereus with the MIC values in range of 32-256 µg/mL. Compound 11 inhibited E. faecalis and B. cereus, and 7 inhibited S. aureus with the MIC values in range of 64-128 µg/mL. In addition, compounds 1, 3, 4, 8, and 9 showed significantly NO production inhibitory activity in LPS activated RAW 264.7 cells with IC50 values ranging from 36.57 to 56.34 µM.

Undescribed Lignanamide and Flavone C-Glucoside Isolated from the Aerial Parts of Piper Samentosum with NO Production Inhibitory Activity in LPS Activated RAW 264.7†Cells.

In this study, two undescribed compounds (1 and 2), together with eight known compounds (3-10) were isolated from the aerial parts of Piper samentosum by various chromatography methods. Their chemical structures were determined to be 7'''-oxolyciumamide N (1), vitexin 2''-O-ß-D-(6'''-feruloyl)-glucopyranoside (2), 1,2-dihydro-6,8-dimethoxy-7-hydroxy-1-(3,4-dihydroxyphenyl)-N1,N2-bis-[2-(-hydroxyphenyl)ethyl]-2,3-napthalene dicarboamide (3), vitexin 6''-O-ß-D-glucopyranoside (4), vitexin 2''-O-α-L-rhamnopyranoside (5), methyl 2-hydroxybenzoate-2-O-ß-D-apiofuranosyl-(1→2)-O-ß-D-glucopyranoside (6), ficuside G (7), methyl 2-O-ß-D-glucopyranosylbenzoate (8), methyl 2,5-dihydroxybenzoate-5-O-ß-D-glucopyranoside (9), and 3,7-dimethyloct-1-ene-3,6,7-triol 6-O-ß-D-glucopyranoside (10) by spectroscopic data analysis including HR-ESI-MS, 1D-, and 2D-NMR spectra. Compounds 1-5 inhibited nitric oxide production in LPS-stimulated RAW264.7 macrophages with the IC50 values of 27.62, 74.03, 38.54, 70.39, and 44.95 µM, respectively. The NMR data of 9 were firstly reported herein.

Five New Furostanol Glycosides from the Fruits of Tribulus terrestris with NO Production Inhibitory Activity.

Eight furostanol glycosides including five undescribed compounds, named tribufurostanosides A-E (1-5), and three known ones (6-8) were isolated from the fruits of Tribulus terrestris L. Their chemical structures were determined by the IR, HR-ESI-MS, 1D-, and 2D-NMR spectra. Furostanols 1-8 significantly inhibited nitric oxide production in LPS activated RAW 264.7 cells with IC50 values ranging from 14.2 to 64.7 µM, compared to that of the positive control compound, dexamethazone (IC50 13.6 µM).

Undescribed Triterpenes from the Leaves of Syzygium myrsinifolium with Their α-Glucosidase and α-Amylase Inhibition Activity.

Two undescribed triterpenes, syzyfolium A (1) and syzyfolium B (2), together with twelve known compounds, terminolic acid (3), actinidic acid (4), piscidinol A (5), threo-dihydroxydehydrodiconiferyl alcohol (6), lariciresinol-4-O-ß-D-glucoside (7), icariol A2 (8), 14ß,15ß-dihydroxyklaineanone (9), garcimangosone D (10), (+)-catechin (11), myricetin-3-O-α-L-rhamnopyranoside (12), quercitrin (13), and 3, 4, 5-trimethoxyphenyl-(6'-O-galloyl)-O-ß-D-glucopyranoside (14) were isolated from the leaves of Syzygium myrsinifolium. Their chemical structures were determined by IR, HR-ESI-MS, 1D and 2D NMR spectra. Compounds 3 and 4 inhibited significantly α-glucosidase with IC50 values of 23.99 and 36.84, respectively, and compounds 1 and 2 inhibited significantly α-amylase with IC50 values of 35.48 and 43.65 µM, respectively.

Four New Steroidal Saponins from the Roots of Dracaena cambodiana with NO Production Inhibition Activity in LPS Activated RAW 264.7 Cells.

Seven steroidal saponins including three new 16,23-cyclocholestanes (1-3) and one new pregane (4) were isolated from the roots of Dracaena cambodiana Pierre ex Gagnep. Their chemical structures were elucidated to be (23R,25R)-26-O-ß-D-glucopyranosyl-16,23-cyclocholesta-5,17(20)-dien-22-one-3ß,16α,26-triol-3-O-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→3)]-ß-D-glucopyranoside (1), (23R,25R)-26-O-ß-D-glucopyranosyl-16,23-cyclocholesta-5,17,20(22)-trien-3ß,22,26-triol-3-O-α-L-rhamnopyranosyl-(1→3)-ß-D-glucopyranoside (2), (23R,25R)-16,23-cyclocholesta-5,16,20(22)-trien-3ß,22,26-triol-3-O-α-L-rhamnopyranosyl-(1→3)-ß-D-glucopyranoside (3), 3ß-[(O-α-L-rhamnopyranosyl-(1→3)-[α-L-rhamnopyranosyl-(1→2)]-ß-D-gluco-pyranosyl)oxy]-pregna-5,17(20)-diene-16-one-20-carboxylic acid 4''''-O-ß-D-glucopyranosylisopentyl ester (4), cambodianoside A (5), diosbulbiside C (6), and diosbulbiside D (7), by IR, HR-ESI-MS, 1D and 2D NMR spectra. Compounds 1 and 4-7 inhibited nitric oxide (NO) production in lipopolysaccharide activated RAW 264.7 cells with IC50 values ranging from 19.03±1.84 to 67.92±3.81 µM, whereas compounds 2 and 3 were inactive with IC50 values over 100 µM.

Hericium VN, an undescribed compound isolated from Hericium erinaceus and its cytotoxic activity on human brain astrocytoma.

Hericium erinaceus is a species of mushroom with high nutritional value that is used mainly as food in tropical countries. Phytochemical study of H. erinaceus led to the isolation of an undescribed compound, named as hericium VN (1), together with nine known compounds, 1-(2-formyl-1-pyrrolyl)butanoic acid (2), herierin III (3), 5'-(methylthio)adenosine (4), adenosine (5), nicotinic acid (6), (22E,24R)-5α,8α-epidioxyergosta-6,9(11),22-trien-3ß-ol (7), 5α,8α-peroxycerevisterol (8), (22E,24R)-5α,8α-epidioxy-egosta-6,22-diene 3-O-ß-D-glucopyranoside (9), and cerevisterol (10) based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. The absolute configuration of compound 1 was determined by experimental combined with calculated electronic circular dichroism spectra. Compound 7 exhibited cytotoxic effects against brain tumor cell line CCF-STTG1 with the IC50 value of 15.50 µM, compared to that of the positive control compound, doxorubicin, which showed IC50 value of 15.84 µM.

Bithiophene and coumestan derivatives from Eclipta prostrata (L.) L. and their hepatoprotective activity.

One new bithiophene derivative, 5-(but-3-en-1-yn-1-yl)-5'-(methoxymethyl)-2,2'-bithiophene (1), along with twelve known compounds, senecioester (2), tiglinsaureester (3), 5-acetoxymethyl-2'-(but-3-en-1-yn-1-yl)-2,5'-bithiophene (4), 5-(4-isovaleroyloxybut-1-ynyl)-2,2'-bithiophene (5), 5-hydroxymethyl-(2,5':2',5'')-terthienyl tiglate (6), 5-hydroxymethyl-(2,5':2',5'')-terthienyl agelate (7), 5- hydroxymethyl-2,5':2',5''-terthiophene dimethylacrylate (8), 5-methoxymethyl-2,2':5',2''-terthiophene (9), α-terthiophene (10), 1,3,8,9-tetrahydroxycoumestan 3-sulfate (11), demethylwedelolactone (12), and wedelolactone (13) were isolated from the methanol extract of aerial parts of Eclipta prostrata (L.) L. All isolated compounds were evaluated for the protective ability on the HepG2 cells. At the concentration of 100 µM, compounds 11-13 showed the highest hepatoprotective effects, with HepG2 cell viability ranging from 38.68% to 48.54%. Bithiophenes showed higher hepatoprotective cell viability than terthiophenes.

The influence of attributes on community preferences regarding antibiotic treatment: evidence from a discrete choice model.

Antibiotic resistance (AR) rates in Vietnam are among the highest in Asia, and recent infections due to multi-drug resistance in the country have caused thousands of deaths each year. This study investigated a Vietnamese community's preferences for antibiotic treatment and its knowledge and attitudes regarding antibiotics. A discrete choice experiment-based survey was developed and administered to the population of interest. The respondents were given sociodemographic-, knowledge- and attitude-related items and 17 pairs of choice tasks. Two hypothetical options were included in each choice task. Latent class analysis was conducted to determine the differences among the respondents' preferences. Among 1,014 respondents, 805 (79.4%) gave valid questionnaires. A three-latent-class model with four covariates (age, healthcare-related education or career, occupation, and attitude classifications) was used in the analysis. All five attributes significantly influenced the respondents' decisions. The majority, including young employed respondents with non-healthcare-related work or education, found treatment failure more important. Older respondents who had healthcare-related education/careers and/or appropriate antibiotic use- and antibiotics resistance-related attitudes, regarded contribution to antibiotic resistance as an important attribute in selecting antibiotic treatments. Unemployed individuals with correct knowledge identified the cost of antibiotic treatment as the most essential decision-making factor. Findings suggest minimal antibiotic impact on resistance; only 7.83% view it as amajor concern. The respondents exhibited substantial preference heterogeneity, and the general Vietnamese public had poor knowledge of and attitudes toward antibiotic use and antibiotic resistance. This study emphasizes the need for individual responsibility for antibiotic resistance and appropriate antibiotic use.

Efficiency of freeze- and spray-dried microbial preparation as active dried starter culture in kombucha fermentation.

BACKGROUND: Kombucha is a widely consumed fermented beverage produced by fermenting sweet tea with a symbiotic culture of bacteria and yeast (SCOBY). The dynamic nature of microbial communities in SCOBY may pose challenges to production scale-up due to unpredictable variations in microbial composition. Using identified starter strains is a novel strategy to control microorganism composition, thereby ensuring uniform fermentation quality across diverse batches. However, challenges persist in the cultivation and maintenance of these microbial strains. This study examined the potential of microencapsulated kombucha fermentation starter cultures, specifically Komagataeibacter saccharivorans, Levilactobacillus brevis and Saccharomyces cerevisiae, through spray-drying and freeze-drying. RESULTS: Maltodextrin and gum arabic-maltodextrin were employed as carrier agents. Our results revealed that both spray-dried and freeze-dried samples adhered to physicochemical criteria, with low moisture content (2.18-7.75%) and relatively high solubility (65.75-87.03%) which are appropriate for food application. Freeze-drying demonstrated greater effectiveness in preserving bacterial strain viability (88.30-90.21%) compared to spray drying (74.92-78.66%). Additionally, the freeze-dried starter strains demonstrated similar efficacy in facilitating kombucha fermentation, compared to the SCOBY group. The observations included pH reduction, acetic acid production, α-amylase inhibition and elevated total polyphenol and flavonoid content. Moreover, the biological activity, including antioxidant potential and in vitro tyrosinase inhibition activity, was enhanced in the same pattern. The freeze-dried strains exhibited consistent kombucha fermentation capabilities over a three-month preservation, regardless of storage temperature at 30 or 4 °C. CONCLUSION: These findings highlight the suitability of freeze-dried starter cultures for kombucha production, enable microbial composition control, mitigate contamination risks and ensure consistent product quality. © 2024 Society of Chemical Industry.

Clinical validation of a ctDNA-Based Assay for Multi-Cancer Detection: An Interim Report from a Vietnamese Longitudinal Prospective Cohort Study of 2795 Participants.

The SPOT-MAS assay "Screening for the Presence Of Tumor by Methylation And Size" detects the five most common cancers in Vietnam by evaluating circulating tumor DNA in the blood. Here, we validated its performance in a prospective multi-center clinical trial, K-DETEK. Our analysis of 2795 participants from 14 sites across Vietnam demonstrates its ability to detect cancers in asymptomatic individuals with a positive predictive value of 60%, with 83.3% accuracy in detecting tumor location. We present a case report to support further using SPOT-MAS as a complementary method to achieve early cancer detection and provide the opportunity for early treatment.

Discovery of Four New Compounds from Macropanax membranifolius and Their Cytotoxic Activity.

A phytochemical investigation of the methanolic extract of the Macropanax membranifolius C.B. Shang leaves led to the isolation of three new flavans, (2R,3R)-4'-O-methylcatechin 5-O-ß-D-glucopyranoside (1), (2S,3S)-4'-O-methylcatechin 5-O-ß-D-glucopyranoside (2), (2S,3R)-4'-O-methylcatechin 5-O-ß-D-glucopyranoside (3), one new triterpene glycoside 3-O-ß-D-xylopyranosyl-(1→6)-[ß-D-xylopyranosyl-(1→2)]-ß-D-glucopyranosyl-oleanolic acid 28-O-ß-D-glucopyranoside (4), together with nine known compounds (5-13). Their chemical structures were elucidated based on HR-ESI-MS, NMR spectroscopic data. The absolute configurations of compounds 1-3 were established by electronic circular dichroism (ECD) spectra. At concentration of 20 µM, compounds 1-13 showed the percentages of dead cell in the range of 2.14 % to 33.61 % against KB, HepG2, HL60, P388, HT29, and MCF7 cancerous cell lines by SRB assay.

Dimethylbutyrylated Dibenzocyclooctadiene Lignans from the Fruits of Schisandra cauliflora Inhibit NO Production in LPS-Activated RAW264.7 Cells.

From the fruits of Schisandra cauliflora, five new dimethylbutyrylated dibenzocyclooctadiene lignans, named schisandracaurins A-E, were isolated using separation and chromatographic techniques. Their structures were determined by extensive analyses of HR-ESI-MS, NMR, and ECD spectra. The schisandracaurins A-E potentially inhibited NO production in LPS-activated RAW264.7 cells with their IC50 values from 21.4 to 30.3 µM.

A Pair of Undescribed Alkaloid Enantiomers from Marine Sponge-Derived Fungus Hamigera avellanea and Their Antimicrobial and Cytotoxic Activities.

From marine sponge-associated fungus Hamigera avellanea, thirteen secondary metabolites including a pair of undescribed alkaloid enantiomers (+)-hamiavemin A (4S) (+)-1 and (-)-hamiavemin A (4R) (-)-1. Compound 1 was enantiomers resolved by the Chiralpak AS-3 column, using a hexane/isopropanol mobile phase. Their structures were determined based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. The absolute configuration of (+)-1 and (-)-1 were assigned tentatively by ECD calculations. Among the isolates, compound 6 showed strongest antibacterial activity against Enterococcus faecalis, Staphylococcus aureus, Bacillus cereus, Escherichia coli, Salmonella enterica, and Candida albicans with the MIC values of 2, 2, 16, 32, 64, and 16 µg/mL, respectively, which were stronger than that of the positive control compound, kanamycin (MIC values ranging from 4 to 128 µg/mL). In addition, compounds 1, 2, and 9 showed moderate cytotoxic activity against three cancer cell lines, HepG2, A549, and MCF-7 with the IC50 values ranging from 55.35±1.70 to 83.02±2.85 µg/mL.

Four New Stilbene Derivatives Isolated from Gnetum latifolium var. funiculare Markgr. and Their Inhibition of NO Production in LPS-activated RAW264.7 Cells.

Gnetum latifolium var. funiculare Markgr. is a medicinal plant and widely distributed in mountainous areas of Vietnam. Phytochemical investigation on the trunks of this plant afforded eight stilbene derivatives (1-8) including for new compounds (1-4). Their structures were determined based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. Among the isolates, compounds 1-3 showed moderate NO production inhibition in LPS-activated RAW264.7 cells with the IC50 values ranging from 46.81 to 68.10 µM, compounds 4 and 6 showed weak effects with the IC50 values of 96.57 and 79.46 µM, respectively, compared to that of the positive control compound, dexamethasone (IC50 14.20 µM).

Three Undescribed Iridoid Derivatives Isolated from the Fruits of Vitex trifolia with Their Cytotoxic and Antimicrobial Activities.

Vitex trifolia L. is a medicinal plant and widely distributed in the northern mountainous areas of Vietnam. Phytochemical study on the fruits of this plant led to the isolation of nine iridoid derivatives (1-9) including three undescribed compounds (1-3). Their structures were elucidated to be 3''-hydroxyscrophuloside A1 (1), 3''-hydroxycallicoside D (2), 2'-p-hydroxybenzoylaucubin (3), 6'-p-hydroxybenzoylmussaenosidic acid (4), nishindaside (5), agnuside (6), 10-O-vanilloylaucubin (7), 6'-O-p-hydroxybenzoyl-gardoside (8), and buddlejoside B (9) based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. Compounds 1, 2, 4, and 8 significantly posessed anti-barterial activity against Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa strains with MIC values in range of 16-64 µg/mL. At concentration of 20 µM, compounds 1-9 did not show cytotoxic effects against human lung cancer cells (PC9).

Robust Adaptive Control Strategy for a Bidirectional DC-DC Converter Based on Extremum Seeking and Sliding Mode Control.

This paper presents a new control strategy that combines classical control and an optimization scheme to regulate the output voltage of the bidirectional converter under the presence of matched and mismatched disturbances. In detail, a control-oriented modeling method is presented first to capture the system dynamics in a common canonical form, allowing different disturbances to be considered. To estimate and compensate for unknown disturbances, an extended state observer (ESO)-based continuous sliding mode control is then proposed, which can guarantee high tracking precision, fast disturbance rejection, and chattering reduction. Next, an extremum seeking (ES)-based adaptive scheme is introduced to ensure system robustness as well as optimal control effort under different working scenarios. Finally, comparative simulations with classical proportional-integral-derivative (PID) control and constant switching gains are conducted to verify the effectiveness of the proposed adaptive control methodology through three case studies of load resistance variations, buck/boost mode switching, and input voltage variation.

Performance Analysis of Multihop Full-Duplex NOMA Systems with Imperfect Interference Cancellation and Near-Field Path-Loss.

Outage probability (OP) and potential throughput (PT) of multihop full-duplex (FD) nonorthogonal multiple access (NOMA) systems are addressed in the present paper. More precisely, two metrics are derived in the closed-form expressions under the impact of both imperfect successive interference cancellation (SIC) and imperfect self-interference cancellation. Moreover, to model short transmission distance from the transmit and receive antennae at relays, the near-field path-loss is taken into consideration. Additionally, the impact of the total transmit power on the performance of these metrics is rigorously derived. Furthermore, the mathematical framework of the baseline systems is provided too. Computer-based simulations via the Monte Carlo method are given to verify the accuracy of the proposed framework, confirm our findings, and highlight the benefits of the proposed systems compared with the baseline one.