Spatial evolution of the proton-coupled Mott transition in correlated oxides for neuromorphic computing.

The proton-electron coupling effect induces rich spectrums of electronic states in correlated oxides, opening tempting opportunities for exploring novel devices with multifunctions. Here, via modest Pt-aided hydrogen spillover at room temperature, amounts of protons are introduced into SmNiO3-based devices. In situ structural characterizations together with first-principles calculation reveal that the local Mott transition is reversibly driven by migration and redistribution of the predoped protons. The accompanying giant resistance change results in excellent memristive behaviors under ultralow electric fields. Hierarchical tree-like memory states, an instinct displayed in bio-synapses, are further realized in the devices by spatially varying the proton concentration with electric pulses, showing great promise in artificial neural networks for solving intricate problems. Our research demonstrates the direct and effective control of proton evolution using extremely low electric field, offering an alternative pathway for modifying the functionalities of correlated oxides and constructing low-power consumption intelligent devices and neural network circuits.

2D Janus Polarization Functioned by Mechanical Force.

2D polarization materials have emerged as promising candidates for meeting the demands of device miniaturization, attributed to their unique electronic configurations and transport characteristics. Although the existing inherent and sliding mechanisms are increasingly investigated in recent years, strategies for inducing 2D polarization with innovative mechanisms remain rare. This study introduces a novel 2D Janus state by modulating the puckered structure. Combining scanning probe microscopy, transmission electron microscopy, and density functional theory calculations, this work realizes force-triggered out-of-plane and in-plane dipoles with distorted smaller warping in GeSe. The Janus state is preserved after removing the external mechanical perturbation, which could be switched by modulating the sliding direction. This work offers a versatile method to break the space inversion symmetry in a 2D system to trigger polarization in the atomic scale, which may open an innovative insight into configuring novel 2D polarization materials.

Clinical Effects of Ultrasound-Guided Acupotomy in Knee Osteoarthritis Treatment.

The protocol presented here demonstrates the operation method of ultrasound-guided acupotomy for knee osteoarthritis (KOA), including patient recruitment, preoperative preparation, manual operation, and postoperative care. The purpose of this protocol is to relieve pain and improve knee function in patients with KOA. A total of 60 patients with KOA admitted between June 2022 and June 2023 were treated with ultrasound-guided acupotomy. Pathological changes and knee function scores were compared before and after the treatment. After 1 week of treatment, the synovial thickness of the suprapatellar bursae was significantly lesser than before treatment (p < 0.05), the Hospital for Special Surgery Knee Score (HSS) was significantly higher than before treatment (p < 0.05), the Visual analogue scale (VAS) was significantly lower than those of the control group (p < 0.05) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were significantly lower than those of the control group (p < 0.05). Therefore, ultrasound-guided acupotomy for the treatment of KOA can reduce synovial thickness, relieve pain, improve knee joint function, and have a remarkable curative effect.

Characterization of the active components and bioaccessibility of phenolics in differently colored foxtail millets.

Differently colored foxtail millet (Setaria italica) cultivars were compared regarding their amylose, B-complex vitamin, vitamin E, and phenolic compositions, as well as the bioaccessibility of their phenolics in simulated in vitro digestion. Dark-colored foxtail millets contained more thiamine, pyridoxine, and tocopherols, but less riboflavin, than light-colored ones. Phenolics were more abundant in dark-colored cultivars. Insoluble bound fractions accounted for 75%-83% of the total phenolics, with ferulic acid detected as the most plentiful compound. The major bioaccessible phenolic was free ferulic acid, with 100%-120% bioaccessibility, depending on cultivar, followed by p-coumaric acid and isoferulic acid (50%-80%). These relatively high bioaccessibilities were likely due to the release of soluble conjugated or insoluble bound phenolics during digestion. However, the contents of other free phenolics were largely decreased following in vitro digestion, resulting in low bioaccessibility, which also means that the release from the conjugated and bound fractions was poor.

Occurrence, potential sources, and ecological risks of traditional and novel organophosphate esters in facility agriculture soils: A case study in Beijing, China.

Although traditional organophosphate esters (OPEs) in soils have attracted widespread interest, there is little information on novel OPEs (NOPEs), especially in facility agriculture soils. In this work, we surveyed 11 traditional OPEs, four NOPEs, and four corresponding organophosphite antioxidant precursors (OPAs) for the NOPEs in soil samples collected from facility greenhouses and open fields. The median summed concentrations of traditional OPEs and NOPEs were 14.1 µg/kg (range: 5.38-115 µg/kg) and 702 µg/kg (range: 348-1952 µg/kg), respectively, in film-mulched soils from greenhouses. These concentrations were much higher than those in soils without mulch films, which suggests that OPEs in soils are associated with plastic mulch films. Tris(2,4-di-tert-butylphenyl) phosphate, which is a NOPE produced by oxidation of (2,4-di-tert-butylphenyl) phosphite, was the predominant congener in farmland soils, with concentrations several orders of magnitude greater than those of traditional OPEs. Comparisons of OPEs in different mulch films and the corresponding mulched soils revealed that degradable and black films caused more severe pollution than polyethylene and white films. Traditional OPEs, including tris(2-ethylhexyl) phosphate and tricresyl phosphate, exhibited moderate risks in farmland soils, especially in film-mulched soils. NOPEs, including trisnonylphenol phosphate, posed high ecological risks to the terrestrial ecosystem. Risk evaluations should be conducted for a broad range of NOPEs in the environment.

Proteomic analysis of serum extracellular vesicles from biliary tract infection patients to identify novel biomarkers.

Biliary tract infection (BTI), a commonly occurring abdominal disease, despite being extensively studied for its initiation and underlying mechanisms, continues to pose a challenge in the quest for identifying specific diagnostic biomarkers. Extracellular vesicles (EVs), which emanate from diverse cell types, serve as minute biological entities that mirror unique physiological or pathological conditions. Despite their potential, there has been a relatively restricted exploration of EV-oriented methodologies for diagnosing BTI. To uncover potent protein biomarkers for BTI patients, we applied a label-free quantitative proteomic method known for its unbiased and high-throughput nature. Furthermore, 192 differentially expressed proteins surfaced within EVs isolated from individuals afflicted with BTI. Subsequent GO and KEGG analyses pinpointed Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and Crumbs homolog 3 (CRB3) as noteworthy biomarkers. Validation via data analysis of plasma-derived EV samples confirmed their specificity to BTI. Our study leveraged an unbiased proteomic tool to unveil CEACAM1 and CRB3 as promising protein biomarkers in serum EVs, presenting potential avenues for the advancement of diagnostic systems for BTI detection.

Discovery of N-(phenylsulfonyl)thiazole-2-carboxamides as potent α-glucosidase inhibitors.

In a search for novel nonsugar α-glucosidase inhibitors for diabetes treatment, a series of N-(phenylsulfonyl)thiazole-2-carboxamide derivatives were designed and synthesized, the α-glucosidase inhibitory activities were then evaluated. Several compounds with promising α-glucosidase inhibitory effects were identified. Among these, compound W24 which shows low cytotoxicity and good α-glucosidase inhibitory activity with an IC50 value of 53.0 ± 7.7 µM, is more competitive compared with the commercially available drug acarbose (IC50 = 228.3 ± 9.2 µM). W24 was identified as a promising candidate in the development of α-glucosidase inhibitors. Molecular docking studies and molecular dynamics simulation were also performed to reveal the binding pattern of the active compound to α-glucosidase, and the binding free energy of the best compound W24 was 36.3403 ± 3.91 kcal/mol.

Preliminary comparative genomics analysis among Corynebacterium kroppenstedtii complex necessitates a reassessment of precise species associated with mastitis.

AIMS: This study aimed to characterize the first complete genome of Corynebacterium parakroppenstedtii and clarify the evolutionary relationship in the Corynebacterium kroppenstedtii complex (CKC) by using comparative genomics analysis. METHODS AND RESULTS: The genome of isolate yu01 from a breast specimen was sequenced, and 35 CKC genomes were collected. Analysis of 16S rRNA, rpoB, and fusA suggested ambiguous identification, whereas ANI analysis assigned isolate yu01 as Coryne. parakroppenstedtii. The fourth genospecies "Corynebacterium aliikroppenstedtii" was identified in CKC. Comparative genomics analysis suggested that the genomic arrangement in CKC was highly conserved. A total of 43 potential virulence genes and 79 species-specific genes were detected. Most genome-based phylogenetic analysis were incapable of resolving the interspecific evolutionary relationships among CKCs. A total of 20 core genes were found to be distinguishable in CKC. CONCLUSIONS: This study suggested the limited divergence and unavailability of normal single gene-based identification in CKC and questioned the precise species of strains associated with mastitis, identified as Coryne. kroppenstedtii in previous studies. The 20 genes showed potential to enhance the methods for the identification and epidemiological investigation of CKC.

Livestock wastes from family-operated farms are potential important sources of potentially toxic elements, antibiotics, and estrogens in rural areas in North China.

The open-air storage and disposal of livestock waste from family-operated livestock farms can be a potential health threat to rural residents. In this study, the occurrence and seasonal distribution of 8 potentially toxic elements, 24 antibiotics, and 4 estrogens were investigated in 44 waste samples from 11 rural farms in North China. The results showed that these micropollutants were ubiquitous in livestock waste, with concentration ranges of 238.9-4555 mg/kg for potentially toxic elements, not detected (ND) to 286,672 µg/kg for antibiotics and ND to 229.5 µg/kg for estrogens. The pollutants in animal wastes showed seasonal variation. Since these wastes are directly applicable to nearby farmland without treatment, the risks those wastes pose to farmland soils were also evaluated. Risk assessment results showed that Zn, Cd, Hg, FF and DC in swine manures were at high risk, while total estrogens in chicken and dairy cattle manures were at high risk. The results will provide important data for the regulation of animal wastes produced by small-scale livestock farms in rural areas of China.

In Situ Tyrosinase Monitoring by Wearable Microneedle Patch toward Clinical Melanoma Screening.

Despite the potential indicating role of tyrosinase (TYR) in cutaneous melanoma, how to capture the real changes of TYR in suspicious skin remains a major challenge. Unlike the traditional human serum test, this study reports a sensing platform that incorporates a wearable microneedle (MN) patch and trimetallic Au@Ag-Pt nanoparticles (NPs) for surface-enhanced Raman scattering (SERS) and colorimetric dual-mode detecting TYR in human skin in situ toward potential melanoma screening. In the presence of TYR, catechol immobilized on MN is preferentially oxidized to benzoquinone, which competitively impedes the interaction of MN and Au@Ag-Pt NPs, triggering the SERS-colorimetric signal reciprocal switch. Using a B16F10 mouse melanoma model, our platform is capable of noninvasively piercing the skin surface and detecting TYR levels before and during anti-PD-1 antibody treatment, which would be highly informative for prognostic judgment and illness monitoring of melanoma. Through in situ sensing for capturing the metabolic changes of TYR in advance, this platform was successfully applied to discriminate the melanoma subjects from skin moles and normal ones (p < 0.001), as well as screen potential melanoma from lactate dehydrogenase (LDH)-negative patients. Melanoma growth and prognosis can still be monitored through recording the continuous change of TYR levels. More importantly, the well-defined flexible and stretchable characteristics of the MN patch allow robustly adhering to the skin without inducing chemical or physical irritation. We believe this platform integrating MN-based in situ sensing, TYR responsiveness, and SERS/colorimetric dual-readout strategy will have high clinical importance in early diagnosis and monitoring of cutaneous melanoma.

Novel Coumarin Derivatives Inhibit the Quorum Sensing System and Iron Homeostasis as Antibacterial Synergists against Pseudomonas aeruginosa.

Pseudomonas aeruginosa (P. aeruginosa) is well-known to cause biofilm-associated drug resistance and infections that often lead to treatment failure. Herein, we reported a dual-acting antibiofilm strategy by inhibiting both the bacterial quorum sensing system and the iron uptake system. A series of coumarin derivatives were synthesized and evaluated, and compound 4t was identified as the most effective biofilm inhibitor (IC50 = 3.6 µM). Further mechanistic studies have confirmed that 4t not only inhibits the QS systems but also competes strongly with pyoverdine as an iron chelator, causing an iron deficiency in P. aeruginosa. Additionally, 4t significantly improved the synergistic antibacterial effects of ciprofloxacin and tobramycin by more than 200-1000-fold compared to the single-dose antibiotic treatments. Therefore, our study has shown that 4t is a potentially novel antibacterial synergist candidate to treat bacterial infections.

Enhanced recovery nursing and mental health education on postoperative recovery and mental health of laparoscopic liver resection.

BACKGROUND: Patients undergoing laparoscopic resection of liver metastases of colorectal cancer are prone to negative emotions and decrease of digestive function. Early nursing and psychological intervention are necessary. AIM: To observe the effect of enhanced recovery nursing combined with mental health education on postoperative recovery and mental health of patients undergoing laparoscopic resection of liver metastases of colorectal cancer. METHODS: One hundred and twenty patients who underwent laparoscopic resection of liver metastases of colorectal cancer at our hospital between March 2021 and March 2023, were selected as participants. The patients admitted from March 1, 2021 to February 28, 2022 were set as the control group, and they were given routine nursing combined with mental health education intervention. While the patients admitted from March 1, 2022 to March 31, 2023 were set as the observation group, they were given accelerated rehabilitation surgical nursing combined with mental health education intervention. The differences in postoperative recovery-related indices, complications and pain degrees, and mental health-related scores were compared between groups. The T lymphocyte subset levels of the two groups were also compared. RESULTS: The postoperative exhaust, defecation, eating and drainage time of the observation group were shorter than those of the control group. The pain scores of the observation group were lower than those of the control group at 6, 12, 24, 48, and 72 h after surgery. The cumulative complication rate of the observation group was lower than that of the control group (P < 0.05). The CD4+/CD8+ in the observation group was higher than that in the control group 3 d after surgery (P < 0.05). After intervention, the self-rating depression scale, self-rating anxiety scale, avoidance dimension, and yielding dimension in Medical coping style (MCMQ) scores of the two groups were lower than those prior to intervention, and the scores in the observation group were lower than those in the control group (P < 0.05). The face dimension score in the MCMQ score was higher than that before intervention, and that of the observation group was higher than that of the control group (P < 0.05). After intervention, the total scores of the life function index scale (FLIC) and psychological well-being scores of cancer patients in the two groups, and the physical and social well-being scores in the observation group, were higher than those before intervention. The nursing satisfaction of the observation group was higher than that of the control group (P < 0.05). The physical, psychological, and social well-being, and the total FLIC scores of the observation group were higher than those in the control group after surgery (P < 0.05). CONCLUSION: Enhanced recovery nursing combined with mental health education can promote the recovery of gastrointestinal function, improve the mental health and quality of life of patients after laparoscopic resection of colorectal cancer liver metastases, and reduce the incidence of complications.

Chemoprevention of lotus leaf ethanolic extract through epigenetic activation of the NRF2-mediated pathway in murine skin JB6 P+ cell neoplastic transformation.

Background and aim: Skin is one barrier protecting from environmental risk factors that can make skin cells cancerous through DNA damage and oxidative stress. The nuclear factor erythroid 2-related factor 2 (NRF2) pathway is an anti-stress defense system that can be regulated by DNA methylation and histone modification. Dietary phytochemicals have chemopreventive properties that can inhibit or delay carcinogenesis. The lotus leaf is a traditional medicinal plant containing many polyphenols whose extracts show many biological activities, including antioxidant, anti-obesity, and anti-cancer. This study aim to investigate the effect of lotus leaves on neoplastic transformation in murine skin JB6 P+ cells. Experimental procedure: Lotus leaves were extracted with water (LL-WE) and ethanol (LL-EE), and the LL-WE residues were further extracted with ethanol (LL-WREE). JB6 P+ cells were treated with different extracts. The chemoprotective effect would be evaluated by heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase (NQO1), and UDP glucuronosyltransferase family 1 member A1 (UGT1A1) expression. Results and conclusion: LL-EE contained higher total phenolics and quercetin among extracts. In mouse skin JB6 P+ cells with 12-O-tetradecanoylphorbol-13-acetate treatment, LL-EE showed the greatest potential to suppress skin carcinogenesis. LL-EE activated the NRF2 pathway by upregulating antioxidant and detoxification enzymes upregulates antioxidant and detoxification enzymes, including HO-1, NQO1, and UGT1A1, and downregulates DNA methylation, which might be caused by lower DNA methyltransferase and histone deacetylase levels. Therefore, our results show that LL-EE reduces the neoplastic transformation of skin JB6 P+ cells, potentially by activating the NRF2 pathway and regulating epigenetic DNA methylation and histone acetylation.

Design, synthesis and biological evaluation of novel 3-hydroxypyridin-4(1H)-ones based hybrids as Pseudomonas aeruginosa biofilm inhibitors.

Pseudomonas aeruginosa (P. aeruginosa) is a gram-negative pathogenic bacterium, often causative drug-resistance related human infections, given its great capacity to form bioflm. It uses three major quorum sensing (QS) systems, las, rhl, and pqs, to regulate the expression of genes related to virulence and biofilm formation. Consequently, strategies for inhibiting QS have garnered considerable attention as antimicrobial therapies. In this study, we designed and synthesized several 3-hydroxypyridin-4(1H)-one hybrids and assessed their potential as the inhibitors of P. aeruginosa biofilm formation. The most active compound identified was 12h; it exhibited satisfactory biofilm inhibitory activity (IC50: 10.59 ± 1.17 µM). Mechanistic studies revealed that 12h significantly inhibited the fluorescence of the PAO1-lasB-gfp and PAO1-pqsA-gfp fluorescent reporter strains and the production of Las-regulated (elastase) and Pqs-regulated (pyocyanin) virulence factors. These findings indicate that 12h inhibited biofilm formation by suppressing the expression of lasB and pqsA, thereby inactivating the las and pqs pathways. Furthermore, 12h improved the antibiotic susceptibility of P. aeruginosa and reduced the acute virulence of this bacterium in the African green monkey kidney cell line Vero. In conclusion, 3-hydroxypyridin-4(1H)-one hybrids, such as 12h, represent a promising class of antibacterial agents against P. aeruginosa.

[Determination of 15 halogenated polycyclic aromatic hydrocarbons in aquatic products by stable isotope dilution coupled with gas chromatography-triple quadrupole mass spectrometry].

Halogenated polycyclic aromatic hydrocarbons (H-PAHs), including chlorinated polycyclic aromatic hydrocarbons (Cl-PAHs) and brominated polycyclic aromatic hydrocarbons (Br-PAHs), are compounds in which one or more hydrogen atoms replaced by chlorine or bromine atoms. These compounds are not only difficult to degrade but also highly fat soluble and toxic. They are a new type of high-risk organic pollutants with structures similar to those of dioxins, and their toxicity is even higher than that of the parent polycyclic aromatic hydrocarbons (PAHs). The bioaccumulation of H-PAHs can be predicted by their octanol-water partition coefficient (Kow); in general, higher bioaccumulation capacity and Kow values indicate greater fat solubility. Therefore, animal-derived foods with higher fat contents, such as animal meat, milk, aquatic products, and their processed forms, are more likely to be contaminated with higher contents of H-PAHs than those with lower fat contents. In this work, a gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) method coupled with stable isotope dilution was established to determine 15 H-PAHs in aquatic products. The instrument and pretreatment methods were systematically optimized. The GC-MS/MS used in this method can effectively eliminate matrix interferences and features high sensitivity and low analytical cost; thus, it has good application prospects. The samples were added with an isotope internal standard before extraction to calibrate the loss of the tested substance during the pretreatment process, extracted by accelerated solvent extraction, purified using gel permeation chromatography and PRiME HLB columns, and then analyzed by GC-MS/MS. The use of two DB-5MS chromatographic columns (30 m×0.25 mm×0.25 µm) and microplate fluidics technology to connect chromatographic columns 1 and 2 in series led to better separation effects, good peak shapes, and high target compound responses. The 15 H-PAHs demonstrated good linearities in the range of 1-50 µg/L, with correlation coefficients (r) greater than or equal to 0.993. The relative standard deviation (RSD) values of the relative response factor (RRF) of the H-PAHs were less than 9%, the method detection limit (MDL) was 0.009-0.072 µg/kg, and the method quantification limit (MQL) was 0.031-0.240 µg/kg. Three spiked levels of 0.25, 1.0, 2.5 µg/kg were added to the blank samples to determine the recovery and precision. The recoveries for these spiked levels were 74.6%-116.8%, 77.8%-123.2%, and 71.9%-124.8%, respectively, and the corresponding RSDs were 0.6%-8.2%, 0.6%-9.0%, and 0.4%-10.6%, respectively. The total actual content of H-PAHs in aquatic product samples was 0.60-3.54 µg/kg. Among the H-PAHs investigated, 9-chlorophenanthrene (9-ClPhe) showed the greatest detection rate (100%) and highest content (1.15 µg/kg), indicating that H-PAHs widely exist in aquatic products. Thus, further assessment of the dietary exposure risk of these compounds is necessary. The developed method simplifies the pretreatment step, and has the advantages of simplicity, rapid analysis, high recoveries, and good stability. It is suitable for the qualitative and quantitative analysis of H-PAHs in actual aquatic product samples and provides reliable technical support for the residue status and risk assessment of H-PAHs in aquatic products.

New abietane and tigliane diterpenoids from the roots of Euphorbia fischeriana and their cytotoxic activities.

Three new abietane and two new tigliane diterpenoids were isolated from the roots Euphorbia fischeriana. Their structures were elucidated by spectroscopic methods and quantum chemical calculation. Compounds 4 and 5 exhibited the inhibitory activities against human cancer cells HeLa and HepG2, with IC50 ranging from 3.54 to 11.45 µM.

Giant Superlinear Power Dependence of Photocurrent Based on Layered Ta2 NiS5 Photodetector.

Photodetector based on two-dimensional (2D) materials is an ongoing quest in optoelectronics. 2D photodetectors are generally efficient at low illuminating power but suffer severe recombination processes at high power, which results in the sublinear power-dependent photoresponse and lower optoelectronic efficiency. The desirable superlinear photocurrent is mostly achieved by sophisticated 2D heterostructures or device arrays, while 2D materials rarely show intrinsic superlinear photoresponse. This work reports the giant superlinear power dependence of photocurrent based on multilayer Ta2 NiS5 . While the fabricated photodetector exhibits good sensitivity (3.1 mS W-1 per □) and fast photoresponse (31 µs), the bias-, polarization-, and spatial-resolved measurements point to an intrinsic photoconductive mechanism. By increasing the incident power density from 1.5 to 200 µW µm-2 , the photocurrent power dependence varies from sublinear to superlinear. At higher illuminating conditions, prominent superlinearity is observed with a giant power exponent of γ = 1.5. The unusual photoresponse can be explained by a two-recombination-center model where density of states of the recombination centers (RC) effectively closes all recombination channels. The photodetector is integrated into camera for taking photos with enhanced contrast due to superlinearity. This work provides an effective route to enable higher optoelectronic efficiency at extreme conditions.

Genome Sequence of Cluster BI1 Streptomyces griseus Phage TaidaOne.

Bacteriophage TaidaOne was isolated from soil collected in Taipei, Taiwan, using the host Streptomyces griseus. It is a siphovirus with a 56,183-bp genome that contains 86 protein-coding genes. Based on gene content similarity, it was assigned to actinobacteriophage subcluster BI1, within which only TaidaOne and GirlPower genomes contain an acetyltransferase homolog gene.

Sesquiterpene lactones from Artemisia vulgaris L. as potential NO inhibitors in LPS-induced RAW264.7 macrophage cells.

Twelve new guaianolide sesquiterpene lactones (1-12), along with ten known analogs (13-22) were isolated from an EtOH extract of the dried aerial parts of Artemisia vulgaris L. The new structures were elucidated via abundant spectroscopic data analyses (HRESIMS, IR, 1D, and 2D NMR), and the absolute configurations of these compounds were determined by X-ray crystallography and ECD calculations. The compounds (1-22) were identified as guaiane-type sesquiterpenes with characteristic α-methylene-γ-lactone and α,ß-unsaturated carbonyl moieties. All compounds were tested for their inhibitory activity against NO production in lipopolysaccharide-stimulated RAW264.7 macrophages. The isolated sesquiterpenoids dose-dependently exhibited an NO production inhibitory activity by inhibiting the expression of inducible NO oxidase (iNOS) and cyclooxygenase-2 (COX-2) with IC50 values ranging from 1.0 to 3.6 µM. The inhibitory effect on the NO production of the compounds (1-4 and 6-22) is better than that of the positive control (dexamethasone). The different substitutions of compounds on C-8 influence anti-inflammatory effects, as evidenced by the in silico analysis of related binding interactions of new compounds (1-12) with iNOS.