Integrating CdIn2S4 semiconductors with S-vacancy MoS2 nanosheets to fabricate a multi-channel aptasensing chip for photoelectrochemical detection of multiple mycotoxins.

BACKGROUND: The importance of multi-target simultaneous detection lies in its ability to significantly boost detection efficiency, making it invaluable for rapid and cost-effective testing. Photoelectrochemical (PEC) sensors have emerged as promising candidates for detecting harmful substances and biomarkers, attributable to their unparalleled sensitivity, minimal background signal, cost-effectiveness, equipment simplicity, and outstanding repeatability. However, designing an effective multi-target detection strategy remains a challenging task in the PEC sensing field. Consequently, there is a pressing need to address the development of PEC sensors capable of simultaneously detecting multiple targets. RESULTS: CdIn2S4/V-MoS2 heterojunctions were successfully prepared via a hydrothermal method. These heterojunctions exhibited a high photocurrent intensity, representing a 1.53-fold enhancement compared to CdIn2S4 alone. Next, we designed a multi-channel aptasensing chip using ITO as the substrate. Three working electrodes were created via laser etching and subsequently modified with CdIn2S4/V-MoS2 heterojunctions. Thiolated aptamers were then self-assembled onto the CdIn2S4/V-MoS2 heterojunctions via covalent bonds, serving as recognition tool. By empolying the CdIn2S4/V-MoS2 heterojunctions as the sensing platform and aptamers as recognition tool, we successfully developed a disposable aptasensing chip for the simultaneous PEC detection of three typical mycotoxins (aflatoxin B1 (AFB1), ochratoxin A (OTA), and zearalenone (ZEN)). This aptasensing chip exhibited wide detection range for AFB1 (0.05-50 ng/mL), OTA (0.05-500 ng/mL), and ZEN (0.1-250 ng/mL). Furthermore, it demonstrated ultra-low detection limits of 0.017 ng/mL for AFB1, 0.016 ng/mL for OTA, and 0.033 ng/mL for ZEN. SIGNIFICANCE AND NOVELTY: The aptasensing chip stands out for its cost-effectiveness, simplicity of fabrication, and multi-channel capabilities. The versatility and practicality enable it to serve as a powerful platform for designing multi-channel PEC aptasensors. With its ability to detect multiple targets with high sensitivity and specificity, the aptasensing chip holds immense potential for applications across diverse fields, such as environmental monitoring, clinical diagnostics, and food safety monitoring, where multi-target detection is crucial.

Unveiling the therapeutic potential of Taxifolin in Cancer: From molecular mechanisms to immune modulation and synergistic combinations.

BACKGROUND: Taxifolin (TAX), a flavonoid abundant in various medicinal plants, has gained attention for its multifaceted role in cancer therapy and cytoprotection against chemotherapy-induced toxicities. TAX modulates key signaling pathways to regulate several processes within tumors, thus potentially playing an important role in tumor suppression. PURPOSE: This review aims to explore the current understanding of TAX's role in cancer therapy including its antitumor mechanisms, synergistic combinations, and cytoprotective effects. The review also addresses the safety profile of TAX, highlights its pharmacokinetic (PK) properties limiting its use, and summarizes the suggested pharmaceutical and chemical solutions to overcome these limitations. METHODOLOGY: A literature review was conducted through searching online databases such as PubMed and Google Scholar using several combinations of relevant keywords related to TAX's potential in anticancer therapy. A total of 84 articles published within the last 15 years were included in this review and analyzed following the PRISMA guidelines. RESULTS: TAX inhibits tumor proliferation, migration, and invasion via the cGMP-PKG pathway, inducing G1-phase arrest and apoptosis. TAX's anti-angiogenic and pro-apoptotic effects are mediated by downregulating Hif1-α, VEGF, and AKT. Additionally, it can synergize the conventional chemotherapeutic agents, enhancing their efficacy and mitigating drug resistance by inhibiting P-glycoprotein expression. Additionally, TAX demonstrates cytoprotective effects against cisplatin-induced nephrotoxicity and neurotoxicity, cyclophosphamide/pazopanib-induced hepatotoxicity, methotrexate-induced oral mucositis, and doxorubicin-induced cardiotoxicity by inhibiting ferroptosis. TAX further has immunomodulatory effects in the tumor microenvironment, enhancing immune responses and sensitizing tumors to immune checkpoint inhibitors. Advancements in TAX's anticancer effects include introducing novel drug delivery systems and chemical modifications to generate derivatives with improved pharmacological effects. CONCLUSION: Clinical trials are needed to confirm TAX's safety and effectiveness in cancer therapy, optimize formulations, and investigate synergistic combinations. Overall, TAX holds promise as a versatile anticancer agent, offering direct anticancer effects and protective benefits against chemotherapy-induced toxicities.

Safety and efficacy of fruquintinib-based therapy in patients with advanced or metastatic sarcoma.

BACKGROUND: The purpose of this study was to evaluate the efficacy and safety of fruquintinib-based therapy as a salvage therapy for patients with advanced or metastatic sarcoma, including soft tissue sarcoma (STS) and bone sarcoma. METHODS: Patients with advanced or metastatic sarcoma were divided into two groups. One group received fruquintinib monotherapy, while the other received fruquintinib combined therapy. Safety and efficacy of fruquintinib-based therapy were recorded and reviewed retrospectively, including progression-free survival (PFS), overall response rate (ORR), and adverse events (AEs). RESULTS: Between August 2021 and December 2022, 38 sarcoma patients were retrospectively included. A total of 14 patients received fruquintinib alone (including 6 STS and 8 bone sarcoma), while 24 were treated with fruquintinib combined therapy (including 2 STS and 22 bone sarcoma). The median follow-up was 10.2 months (95% CI, 6.4-11.5). For the entire population, the median PFS was 8.0 months (95% CI, 5.5-13.0). The ORR was 13.1%, while the disease control rate (DCR) was 86.8%. The univariate analysis showed that radiotherapy history (HR, 4.56; 95% CI, 1.70-12.24; p = 0.003), bone sarcoma (HR, 0.34; 95% CI, 0.14-0.87; p = 0.024), and treatment method of fruquintinib (HR, 0.36; 95% CI, 0.15-0.85; p = 0.021) were significantly associated with PFS. The multivariate analysis showed that patients without radiotherapy history were associated with a better PFS (HR, 3.71; 95% CI: 1.31-10.55; p = 0.014) than patients with radiotherapy history. Patients in combination group reported pneumothorax (8.3%), leukopenia (33.3%), thrombocytopenia (12.5%), diarrhea (4.2%), and anemia (4.2%) as the most frequent grade 3 or higher treatment-emergent AEs (TEAEs), while there was no severe TEAEs occurred in the monotherapy group. CONCLUSIONS: Fruquintinib-based therapy displayed an optimal tumor control and an acceptable safety profile in patients with advanced or metastatic sarcoma.

Design of Multi-Target drugs of HDACs and other Anti-Alzheimer related Targets: Current strategies and future prospects in Alzheimer's diseases therapy.

Alzheimer disease (AD) is the most prevalent form of dementia that develops spontaneously in the elderly. It's worth mentioning that as people age, the epigenetic profile of the central nervous system cells changes, which may speed up the development of various neurodegenerative disorders including AD. Histone deacetylases (HDACs) are a class of epigenetic enzymes that can control gene expression without altering the gene sequence. Moreover, a promising strategy for multi-target hybrid design was proposed to potentially improve drug efficacy and reduce side effects. These hybrids are monocular drugs that contain various pharmacophore components and have the ability to bind to different targets at the same time. The HDACs ability to synergistically boost the performance of other anti-AD drugs, as well as the ease with which HDACs inhibitor cap group, can be modified. This has prompted numerous medicinal chemists to design a novel generation of HDACs multi-target inhibitors. Different HDACs inhibitors and other ones such as acetylcholinesterase, butyryl-cholinesterase, phosphodiesterase 9, phosphodiesterase 5 or glycogen synthase kinase 3ß inhibitors were merged into hybrids for treatment of AD. This review goes over the scientific rationale for targeting HDACs along with several other crucial targets in AD therapy. This review presents the latest hybrids of HDACs and other AD target pharmacophores.

Helmet Radio Frequency Phased Array Applicators Enhance Thermal Magnetic Resonance of Brain Tumors.

Thermal Magnetic Resonance (ThermalMR) integrates Magnetic Resonance Imaging (MRI) diagnostics and targeted radio-frequency (RF) heating in a single theranostic device. The requirements for MRI (magnetic field) and targeted RF heating (electric field) govern the design of ThermalMR applicators. We hypothesize that helmet RF applicators (HPA) improve the efficacy of ThermalMR of brain tumors versus an annular phased RF array (APA). An HPA was designed using eight broadband self-grounded bow-tie (SGBT) antennae plus two SGBTs placed on top of the head. An APA of 10 equally spaced SGBTs was used as a reference. Electromagnetic field (EMF) simulations were performed for a test object (phantom) and a human head model. For a clinical scenario, the head model was modified with a tumor volume obtained from a patient with glioblastoma multiforme. To assess performance, we introduced multi-target evaluation (MTE) to ensure whole-brain slice accessibility. We implemented time multiplexed vector field shaping to optimize RF excitation. Our EMF and temperature simulations demonstrate that the HPA improves performance criteria critical to MRI and enhances targeted RF and temperature focusing versus the APA. Our findings are a foundation for the experimental implementation and application of a HPA en route to ThermalMR of brain tumors.

Research progress of multi-target HDAC inhibitors blocking the BRD4-LIFR-JAK1-STAT3 signaling pathway in the treatment of cancer.

Histone deacetylase inhibitors (HDACis) show beneficial effects on different hematological malignancy subtypes. However, their impacts on treating solid tumors are still limited due to diverse resistance mechanisms. Recent studies have found that the feedback activation of BRD4-LIFR-JAK1-STAT3 pathway after HDACi incubation is a vital mechanism inducing resistance of specific solid tumor cells to HDACis. This review summarizes the recent development of multi-target HDACis that can concurrently block BRD4-LIFR-JAK1-STAT3 pathway. Moreover, our findings hope to shed novel lights on developing novel multi-target HDACis with reduced BRD4-LIFR-JAK1-STAT3-mediated drug resistance in some tumors.

Pills of Multi-Target H2S Donating Molecules for Complex Diseases.

Among the various drug discovery methods, a very promising modern approach consists in designing multi-target-directed ligands (MTDLs) able to modulate multiple targets of interest, including the pathways where hydrogen sulfide (H2S) is involved. By incorporating an H2S donor moiety into a native drug, researchers have been able to simultaneously target multiple therapeutic pathways, resulting in improved treatment outcomes. This review gives the reader some pills of successful multi-target H2S-donating molecules as worthwhile tools to combat the multifactorial nature of complex disorders, such as inflammatory-based diseases and cancer, as well as cardiovascular, metabolic, and neurodegenerative disorders.

Improved Particle Filter Algorithm for Multi-Target Detection and Tracking.

In modern radar detection systems, the particle filter technique has become one of the core algorithms for real-time target detection and tracking due to its good nonlinear and non-Gaussian system state estimation capability. However, when dealing with complex dynamic scenes, the traditional particle filter algorithm exposes obvious deficiencies. The main expression is that the sample degradation is serious, which leads to a decrease in estimation accuracy. In multi-target states, the algorithm is difficult to effectively distinguish and stably track each target, which increases the difficulty of state estimation. These problems limit the application potential of particle filter technology in multi-target complex environments, and there is an urgent need to develop a more advanced algorithmic framework to enhance its robustness and accuracy in complex scenes. Therefore, this paper proposes an improved particle filter algorithm for multi-target detection and tracking. Firstly, the particles are divided into tracking particles and searching particles. The tracking particles are used to maintain and update the trajectory information of the target, and the searching particles are used to identify and screen out multiple potential targets in the environment, to sufficiently improve the diversity of the particles. Secondly, the density-based spatial clustering of applications with noise is integrated into the resampling phase to improve the efficiency and accuracy of particle replication, so that the algorithm can effectively track multiple targets. Experimental result shows that the proposed algorithm can effectively improve the detection probability, and it has a lower root mean square error (RMSE) and a stronger adaptability to multi-target situation.

Sporadic Parathyroid Carcinoma Treated With Lenvatinib, Exhibiting a Novel Somatic MEN1 Mutation.

Parathyroid carcinoma (PC) is extremely rare and is primarily treated surgically. Chemotherapy is an option for advanced stages, but no standard regimen exists. Emerging research suggests the efficacy of multitarget tyrosine kinase inhibitors (MTKIs) for PC, targeting vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR). A 61-year-old Japanese woman presented with a neck mass, diagnosed as PC with pleural and lumbar metastases. After parathyroidectomy and radiation for lumbar metastasis, immunohistochemistry showed VEGFR overexpression, leading to targeted therapy with MTKIs. Despite no actionable mutations on cancer genomic panel test, a novel MEN1 somatic mutation (NM_130801: exon2: c.332delG: p.G111fs*8) was identified, which may affect VEGFR2 expression and tumor epigenetics. Although severe hand-foot syndrome necessitated dose reductions and treatment interruptions, sorafenib treatment managed hypercalcemia with evocalcet and denosumab. Lenvatinib, as second-line therapy, was effective against pleural metastases but caused thrombocytopenia and hematuria, leading to discontinuation and uncontrolled recurrence and metastasis progression. Our case highlights the need for further research on genomic profiling, molecular targets, and therapy response in PC.

Exploring the potential of cryptochlorogenic acid as a dietary adjuvant for multi-target combined lung cancer treatment.

BACKGROUND: Lung cancer is a highly malignant disease with limited treatment options and significant adverse effects. It is urgent to develop novel treatment strategies for lung cancer. In recent years, TMEM16A has been confirmed as a specific drug target for lung cancer. The development of TMEM16A-targeting drugs and combined administration for the treatment of lung cancer has become a research hotspot. METHODS: Fluorescence screening and electrophysiological experiments were conducted to confirm the inhibitory effect of CCA on TMEM16A. Molecular dynamics simulation and site-directed mutagenesis were employed to analyze the binding mode of CCA and TMEM16A. CCK-8, colony formation, wound healing, transwell, and annexin-V experiments were conducted to explore the regulatory effects and mechanisms of CCA on the proliferation, migration, and apoptosis of lung cancer cells. Tumor model mice and pharmacokinetic experiments were used to examine the efficacy and safety of CCA and cisplatin in vivo. RESULTS: This study firstly confirmed that CCA effectively inhibits TMEM16A to exert anticancer effects and analyzed the pharmacological mechanism. CCA bound to S517/N546/E623/E633/Q637 of TMEM16A through hydrogen bonding and electrostatic interactions. It inhibited the proliferation and migration, and induced apoptosis of lung cancer cells by targeting TMEM16A. In addition, the combined administration of CCA and cisplatin exhibited a synergistic effect, enhancing the efficacy of lung cancer treatment while reducing side effects. CONCLUSION: CCA is an effective novel inhibitor of TMEM16A, and it synergizes with cisplatin in anticancer treatment. These findings will provide new research ideas and lead compound for the combination therapy of lung cancer.

Patient-Provider Communication and Colorectal Cancer Screening Completion Using Multi-target Stool DNA Testing.

Colorectal cancer (CRC) screening continues to be underutilized in the USA despite the availability of multiple effective, guideline-recommended screening options. Provider recommendation has been consistently shown to improve screening completion. Understanding how patient-provider communication influences CRC screening can inform interventions to improve screening completion. We developed a behavioral theory-informed survey to identify patient-provider communication factors associated with multi-target stool DNA (mt-sDNA) screening completion. The survey was administered by RTI International between 03/2022 and 06/2022 to a sample of US adults ages 45-75 who received a valid order for mt-sDNA screening with a shipping date between 5/2021 and 9/2021. Respondents completed an electronic or paper survey. Multivariable logistic regression was used to identify patient-provider communication factors associated with mt-sDNA test completion. A total of 2973 participants completed the survey (response rate, 21.7%) and 81.6% of them (n = 2427) reported having had a conversation with provider about mt-sDNA testing before the test was ordered. Having a conversation with the provider about the test, including discussions about costs, the need for follow-up testing and test instructions were associated with higher odds of test completion and being "very likely" to use the test in the future. Lack of discussion about advantages and disadvantages of available CRC screening options and lack of patient involvement in CRC screening decision-making were associated with reduced odds of test completion and likelihood of future use. Healthcare providers play a key role in patient adherence to CRC screening and must be appropriately prepared and resourced to educate and to engage patients in shared decision-making about CRC screening.

Design of a multi-carrier X-ray source for communication with energy modulation information.

X-ray communication is a kind of space communication technology which uses X-ray as information carrier. In order to improve the information transmission capacity, communication rate and anti-interference ability of X-ray communication, we proposes to design a novel multi-target X-ray source. The source is composed of a fast switching module of light channels based on FPGA technology and four photoelectric X-ray tubes with different target materials: Cr, Fe, Ni, and Cu. Using Geant4 software, we determined the optimal target thickness for each material, which enabled us to fully leverage the characteristic X-rays for multi-channel signal modulation transmission. Moreover, using CST software for particle trajectory simulation and optimization of the electron beam revealed that at a tube voltage of 20 kV, the focus area measures approximately 1.2 mm×1.2 mm. The simulations show that four kinds of spectra with high distinctiveness can be generated from the Cr, Fe, Ni, and Cu targets. Within a single modulation period, these spectra can be combined in various ways to create 16 different X-ray spectra signals, thereby increasing the number of communication elements and enhancing the information transmission rate.

Quaternized antimicrobial peptide mimics based on harmane as potent anti-MRSA agents by multi-target mechanism covering cell wall, cell membrane and intracellular targets.

Infectious disease caused by methicillin-resistant Staphylococcus aureus (MRSA) seriously threatens public health. The design of antimicrobial peptide mimics (AMPMs) based on natural products (NPs) is a new strategy to kill MRSA and slow the development of drug resistance recently. Here, we reported the design and synthesis of novel AMPMs based on harmane skeleton. Notably, compound 9b exhibited comparable or even better anti-MRSA activity in vitro and in vivo with minimum inhibitory concentration (MIC) of 0.5-2 µg/mL than the positive drug vancomycin. The highly active compound 9b not only showed low cytotoxicity, no obvious hemolysis and good plasma stability, but also presented low tendency of developing resistance. Anti-MRSA mechanism revealed that compound 9b could destroy cell wall structure by interacting with lipoteichoic acid and peptidoglycan, cause membrane damage by depolarization, increased permeability and destructed integrity, reduce cell metabolic activity by binding to lactate dehydrogenase (LDH), interfere cellular redox homeostasis, and bind to DNA. Overall, compound 9b killed the MRSA by multi-target mechanism, which provide a promising light for combating the growing MRSA resistance.

Proteasome and PARP1 dual-target inhibitor for multiple myeloma: Fluzoparib.

One of the current mainstream treatments for multiple myeloma (MM) is chemotherapy. However, due to the high clonal heterogeneity and genomic complexity of MM, single-target drugs have limited efficacy and are prone to drug resistance. Therefore, there is an urgent need to develop multi-target drugs against MM. We screened drugs that simultaneously inhibit poly(ADP-ribose) polymerase 1 (PARP1) and 20S proteasome through computer-aided drug discovery (CADD) techniques, and explored the binding mode and dynamic stability of selected inhibitor to proteasome through Molecular biology (MD) simulation method. Thus, the dual-target inhibition effect of fluzoparib was proposed for the first time, and the ability of dual-target inhibition and tumor killing was explored at the enzyme, cell and animal level, respectively. This provides a theoretical and experimental basis for exploring multi-target inhibitory drugs for cancers.

Multi-Target In-Silico modeling strategies to discover novel angiotensin converting enzyme and neprilysin dual inhibitors.

Cardiovascular diseases, including heart failure, stroke, and hypertension, affect 608 million people worldwide and cause 32% of deaths. Combination therapy is required in 60% of patients, involving concurrent Renin-Angiotensin-Aldosterone-System (RAAS) and Neprilysin inhibition. This study introduces a novel multi-target in-silico modeling technique (mt-QSAR) to evaluate the inhibitory potential against Neprilysin and Angiotensin-converting enzymes. Using both linear (GA-LDA) and non-linear (RF) algorithms, mt-QSAR classification models were developed using 983 chemicals to predict inhibitory effects on Neprilysin and Angiotensin-converting enzymes. The Box-Jenkins method, feature selection method, and machine learning algorithms were employed to obtain the most predictive model with ~ 90% overall accuracy. Additionally, the study employed virtual screening of designed scaffolds (Chalcone and its analogues, 1,3-Thiazole, 1,3,4-Thiadiazole) applying developed mt-QSAR models and molecular docking. The identified virtual hits underwent successive filtration steps, incorporating assessments of drug-likeness, ADMET profiles, and synthetic accessibility tools. Finally, Molecular dynamic simulations were then used to identify and rank the most favourable compounds. The data acquired from this study may provide crucial direction for the identification of new multi-targeted cardiovascular inhibitors.

Multi-target Compounds against Trypanosomatid Parasites and Mycobacterium tuberculosis.

Multi-target drug treatment has become popular as a substitute for traditional monotherapy. Monotherapy can lead to resistance and side effects. Multi-target drug discovery is gaining importance as data on bioactivity becomes more abundant. The design of multi-target drugs is expected to be an important development in the pharmaceutical industry in the near future. This review presents multi-target compounds against trypanosomatid parasites (Trypanosoma cruzi, T. brucei, and Leishmania sp.) and tuberculosis (Mycobacterium tuberculosis), which mainly affect populations in socioeconomically unfavorable conditions. The article analyzes the studies, including their chemical structures, viral strains, and molecular docking studies, when available. The objective of this review is to establish a foundation for designing new multi-target inhibitors for these diseases.

Occurrence of emerging contaminants in three river basins impacted by wastewater treatment plant effluents: Spatio-seasonal patterns and environmental risk assessment.

The concern on the fate and distribution of contaminants of emerging concern (CECs) is a burning topic due to their widespread occurrence and potential harmful effects. Particularly, antibiotics have received great attention due to their implications in antimicrobial resistance occurrence. The impact of wastewater treatment plants (WWTP) is remarkable, being one of the main pathways for the introduction of CECs into aquatic systems. The combination of novel analytical methodologies and risk assessment strategies is a promising tool to find out environmentally relevant compounds posing major concerns in freshwater ecosystems impacted by those wastewater effluents. Within this context, a multi-target approach was applied in three Spanish river basins affected by different WWTP treated effluents for spatio-temporal monitoring of their chemical status. Solid phase extraction followed by ultra-high-performance liquid chromatography were used for the quantification of a large panel of compounds (n = 270), including pharmaceuticals and other consumer products, pesticides and industrial chemicals. To this end, water samples were collected in four sampling campaigns at three locations in each basin: (i) upstream from the WWTPs; (ii) WWTP effluent discharge points (effluent outfall); and (iii) downstream from the WWTPs (500 m downriver from the effluent outfall). Likewise, 24-h composite effluent samples from each of the WWTPs were provided in all sampling periods. First the occurrence and distribution of these compounds were assessed. Diverse seasonal trends were observed depending on the group of emerging compounds, though COVID-19 outbreak affected variations of certain pharmaceuticals. Detection frequencies and concentrations in effluents generally exceeded those in river samples and concentrations measured upstream WWTPs were generally low or non-quantifiable. Finally, risks associated with maximum contamination levels were evaluated using two different approaches to account for antibiotic resistance selection as well. From all studied compounds, 89 evidenced environmental risk on at least one occasion in this study.

An Integrative Network Pharmacology and Bioinformatics Approach for Deciphering the Multi-target Effect of Nyctanthes arbortristis L. against COVID-19.

INTRODUCTION: The COVID-19 pandemic represents a significant challenge across scientific, medical, and societal dimensions. The unpredictability of the disease progression, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), underscores the urgent need for identifying compounds that target multiple aspects of the virus to ensure swift and effective treatment. Nyctanthes arbortristis L., a delicate, perennial, deciduous shrub found across various Asian regions, has been recognized for its wide range of pharmacological benefits, including hepatoprotective, antimalarial, antibacterial, anti-inflammatory, antioxidant, and antiviral properties. METHODS: Various in vitro studies revealed the therapeutic significance of Nyctanthes arbortristis against COVID-19. However, the exact molecular mechanism remains unclarified. In the present study, a network pharmacology approach was employed to uncover the active ingredients, their potential targets, and signaling pathways in Nyctanthes arbortristis for the treatment of COVID-19. In the framework of this study, we explored the active ingredient-target-pathway network and figured out that naringetol, ursolic acid, betasitosterol, and daucosterol decisively contributed to the development of COVID-19 by affecting IL6, MAPK3, and MDM2 genes. RESULTS: The results of molecular docking analysis indicated that Nyctanthes arbortristis exerted effective binding capacity in COVID-19. Further, we disclosed the targets, biological functions, and signaling pathways of Nyctanthes arbortristis in COVID-19. The analysis indicated that Nyctanthes arbortristis could help treat COVID-19 through the enhancement of immunologic functions, inhibition of inflammatory reactions and regulation of the cellular microenvironment. In short, the current study used a series of network pharmacologybased and computational analyses to understand and characterize the binding capacity, biological functions, pharmacological targets and therapeutic mechanisms of Nyctanthes arbortristis in COVID-19. CONCLUSION: However, the findings were not validated in actual COVID-19 patients, so further investigation is needed to confirm the potential use of Nyctanthes arbortristis for treating COVID-19.

Design and thermal-hydraulic analysis of multi-target system with 100 MeV proton linear accelerator for the production of 67Cu and 68Ge radioisotopes.

Radioisotopes are widely used in the fields of medicine, science, and industry. The growing demand for medical radioisotopes has driven research on alternative production methods. In particular, both isotopes of 67Cu and 68Ge play vital roles in the medical environment in many countries to be used in the radio-immunotherapy and the positron emission tomography imaging, respectively. This study designed a multi-target system consisting of two Zn and one Ga2O3 plates to enable simultaneous production of the medical radioisotopes 67Cu and 68Ge using 100 MeV proton beams. To understand the thermal effect on the multi-targets, we examined the distribution of energy absorbed in each solid plate target when exposed to an accelerated proton beam through the thermal-fluid analysis based on ANSYS simulation. For confirming thermal stability for two Zn targets and one Ga2O3 target, the modified water flow path inside the multi-target system was designed effectively with the controlled distribution of multiple sub-holes between main inlet and the following four channels. It was confirmed that the newly designed multi-target system of Zn and Ga2O3 solid plates shows higher thermal stability than the case of uniform distribution of water inlet, which means it could be exposed to a higher current beam of 7.57% to decrease the processing time.