BPR3P0128, a non-nucleoside RNA-dependent RNA polymerase inhibitor, inhibits SARS-CoV-2 variants of concern and exerts synergistic antiviral activity in combination with remdesivir.

Viral RNA-dependent RNA polymerase (RdRp), a highly conserved molecule in RNA viruses, has recently emerged as a promising drug target for broad-acting inhibitors. Through a Vero E6-based anti-cytopathic effect assay, we found that BPR3P0128, which incorporates a quinoline core similar to hydroxychloroquine, outperformed the adenosine analog remdesivir in inhibiting RdRp activity (EC50 = 0.66 µM and 3 µM, respectively). BPR3P0128 demonstrated broad-spectrum activity against various severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern. When introduced after viral adsorption, BPR3P0128 significantly decreased SARS-CoV-2 replication; however, it did not affect the early entry stage, as evidenced by a time-of-drug-addition assay. This suggests that BPR3P0128's primary action takes place during viral replication. We also found that BPR3P0128 effectively reduced the expression of proinflammatory cytokines in human lung epithelial Calu-3 cells infected with SARS-CoV-2. Molecular docking analysis showed that BPR3P0128 targets the RdRp channel, inhibiting substrate entry, which implies it operates differently-but complementary-with remdesivir. Utilizing an optimized cell-based minigenome RdRp reporter assay, we confirmed that BPR3P0128 exhibited potent inhibitory activity. However, an enzyme-based RdRp assay employing purified recombinant nsp12/nsp7/nsp8 failed to corroborate this inhibitory activity. This suggests that BPR3P0128 may inhibit activity by targeting host-related RdRp-associated factors. Moreover, we discovered that a combination of BPR3P0128 and remdesivir had a synergistic effect-a result likely due to both drugs interacting with separate domains of the RdRp. This novel synergy between the two drugs reinforces the potential clinical value of the BPR3P0128-remdesivir combination in combating various SARS-CoV-2 variants of concern.

Effectiveness and evolution of anti-SARS-CoV-2 spike protein titers after three doses of COVID-19 vaccination in people with HIV.

BACKGROUND: Real-world vaccine effectiveness following the third dose of vaccination against SARS-CoV-2 remains less investigated among people with HIV (PWH). METHODS: PWH receiving the third dose of BNT162b2 and mRNA-1273 (either 50- or 100-µg) were enrolled. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, SARS-CoV-2 infection, seroconversion of anti-nucleocapsid IgG, death, or loss to follow-up. Anti-spike IgG was determined every 1-3 months. RESULTS: Of 1427 participants undergoing the third-dose COVID-19 vaccination, 632 (44.3%) received 100-µg mRNA-1273, 467 (32.8%) 50-µg mRNA-1273, and 328 (23.0%) BNT162b2 vaccine and the respective rate of SARS-CoV-2 infection or seroconversion of anti-nucleocapsid IgG was 246.1, 280.8 and 245.2 per 1000 person-months of follow-up (log-rank test, p = 0.28). Factors associated with achieving anti-S IgG titers >1047 BAU/mL included CD4 count <200 cells/mm3 (adjusted odds ratio [aOR], 0.11; 95% CI, 0.04-0.31), plasma HIV RNA >200 copies/mL (aOR, 0.27; 95% CI, 0.09-0.80), having achieved anti-spike IgG >141 BAU/mL within 3 months after primary vaccination (aOR, 3.69; 95% CI, 2.68-5.07), receiving BNT162b2 vaccine as the third dose (aOR, 0.20; 95% CI, 0.10-0.41; reference, 100-µg mRNA-1273), and having previously received two doses of mRNA vaccine in primary vaccination (aOR, 2.46; 95% CI, 1,75-3.45; reference, no exposure to mRNA vaccine). CONCLUSIONS: PWH receiving different types of the third dose of COVID-19 vaccine showed similar vaccine effectiveness against SARS-CoV-2 infection. An additional dose with 100-µg mRNA-1273 could generate a higher antibody response than with 50-µg mRNA-1273 and BNT162b2 vaccine.

Dosimetry and efficiency comparison of knowledge-based and manual planning using volumetric modulated arc therapy for craniospinal irradiation.

BACKGROUND: Craniospinal irradiation (CSI) poses a challenge to treatment planning due to the large target, field junction, and multiple organs at risk (OARs) involved. The aim of this study was to evaluate the performance of knowledge-based planning (KBP) in CSI by comparing original manual plans (MP), KBP RapidPlan initial plans (RPI), and KBP RapidPlan final plans (RPF), which received further re-optimization to meet the dose constraints. PATIENTS AND METHODS: Dose distributions in the target were evaluated in terms of coverage, mean dose, conformity index (CI), and homogeneity index (HI). The dosimetric results of OARs, planning time, and monitor unit (MU) were evaluated. RESULTS: All MP and RPF plans met the plan goals, and 89.36% of RPI plans met the plan goals. The Wilcoxon tests showed comparable target coverage, CI, and HI for the MP and RPF groups; however, worst plan quality was demonstrated in the RPI plans than in MP and RPF. For the OARs, RPF and RPI groups had better dosimetric results than the MP group (P < 0.05 for optic nerves, eyes, parotid glands, and heart). The planning time was significantly reduced by the KBP from an average of 677.80 min in MP to 227.66 min (P < 0.05) and 307.76 min (P < 0.05) in RPI, and RPF, respectively. MU was not significantly different between these three groups. CONCLUSIONS: The KBP can significantly reduce planning time in CSI. Manual re-optimization after the initial KBP is recommended to enhance the plan quality.

Klebsiella pneumoniae K2 capsular polysaccharide degradation by a bacteriophage depolymerase does not require trimer formation.

K2-capsular Klebsiella pneumoniae is a hypervirulent pathogen that causes fatal infections. Here, we describe a phage tailspike protein, named K2-2, that specifically depolymerizes the K2 capsular polysaccharide (CPS) of K. pneumoniae into tetrasaccharide repeating units. Nearly half of the products contained O-acetylation, which was thought crucial to the immunogenicity of CPS. The product-bound structures of this trimeric enzyme revealed intersubunit carbohydrate-binding grooves, each accommodating three tetrasaccharide units of K2 CPS. The catalytic residues and the key interactions responsible for K2 CPS recognition were identified and verified by site-directed mutagenesis. Further biophysical and functional characterization, along with the structure of a tetrameric form of K2-2, demonstrated that the formation of intersubunit catalytic center does not require trimerization, which could be nearly completely disrupted by a single-residue mutation in the C-terminal domain. Our findings regarding the assembly and catalysis of K2-2 provide cues for the development of glycoconjugate vaccines against K. pneumoniae infection. IMPORTANCE: Generating fragments of capsular polysaccharides from pathogenic bacteria with crucial antigenic determinants for vaccine development continues to pose challenges. The significance of the C-terminal region of phage tailspike protein (TSP) in relation to its folding and trimer formation remains largely unexplored. The polysaccharide depolymerase described here demonstrates the ability to depolymerize the K2 CPS of K. pneumoniae into tetrasaccharide fragments while retaining the vital O-acetylation modification crucial for immunogenicity. By carefully characterizing the enzyme, elucidating its three-dimensional structures, conducting site-directed mutagenesis, and assessing the antimicrobial efficacy of the mutant enzymes against K2 K. pneumoniae, we offer valuable insights into the mechanism by which this enzyme recognizes and depolymerizes the K2 CPS. Our findings, particularly the discovery that trimer formation is not required for depolymerizing activity, challenge the current understanding of trimer-dependent TSP activity and highlight the catalytic mechanism of the TSP with an intersubunit catalytic center.

Facile Adaptation of a Fused Deposition Modeling 3D Printer to Motionless Printing through Programmable Electric Relay: Discretized Modeling and Experiments.

In this study, a fused deposition modeling 3D printer is modified into a motionless printer, which has the potential to print patterns in a noiseless manner possibly with improved resolution and in less delay time by eliminating the movement of nozzle or collector. In this motionless 3D printer, both nozzle and collector are fixed, whereas the extruded polymer melt is driven by high-voltage switching points on the collector. By this approach, simple 3D patterns such as multilayer circles, squares, and walls have been printed using two polymer melts with different rheological properties, high-temperature polylactic acid and acrylonitrile butadiene styrene. Furthermore, a discretized, nonisothermal bead and spring model is developed to probe printing patterns. The effect of parameters, such as number of conducting points, switching time, voltage and material properties on the accuracy of the printed simple 3D patterns, are thoroughly studied, and we demonstrated that various fiber collection patterns obtained from the experiments are favorably compared with the simulation results.

The Efficacy of Anthropometric Indicators in Predicting Non-Alcoholic Fatty Liver Disease Using FibroScan® CAP Values among the Taiwanese Population.

The controlled attenuation parameter (CAP) measurement obtained from FibroScan® is a low-risk method of assessing fatty liver. This study investigated the association between the FibroScan® CAP values and nine anthropometric indicators, including the abdominal volume index (AVI), body fat percentage (BFP), body mass index (BMI), conicity index (CI), ponderal index (PI), relative fat mass (RFM), waist circumference (WC), waist-hip ratio (WHR), and waist-to-height ratio (WHtR), and risk of non-alcoholic fatty liver disease (fatty liver). We analyzed the medical records of adult patients who had FibroScan® CAP results. CAP values <238 dB/m were coded as 0 (non- fatty liver) and ≥238 dB/m as 1 (fatty liver). An individual is considered to have class 1 obesity when their body mass index (BMI) ranges from 30 kg/m2 to 34.9 kg/m2. Class 2 obesity is defined by a BMI ranging from 35 kg/m2 to 39.9 kg/m2, while class 3 obesity is designated by a BMI of 40 kg/m2 or higher. Out of 1763 subjects, 908 (51.5%) had fatty liver. The BMI, WHtR, and PI were found to be more strongly correlated with the CAP by the cluster dendrogram with correlation coefficients of 0.58, 0.54, and 0.54, respectively (all p < 0.0001). We found that 28.3% of the individuals without obesity had fatty liver, and 28.2% of the individuals with obesity did not have fatty liver. The BMI, CI, and PI were significant predictors of fatty liver. The BMI, PI, and WHtR demonstrated better predictive ability, indicated by AUC values of 0.72, 0.68, and 0.68, respectively, a finding that was echoed in our cluster group analysis that showed interconnected clustering with the CAP. Therefore, of the nine anthropometric indicators we studied, the BMI, CI, PI, and WHtR were found to be more effective in predicting the CAP score, i.e., fatty liver.

Small-molecule PIK-93 modulates the tumor microenvironment to improve immune checkpoint blockade response.

Immune checkpoint inhibitors (ICIs) targeting PD-L1 immunotherapy are state-of-the-art treatments for advanced non-small cell lung cancer (NSCLC). However, the treatment response of certain patients with NSCLC is unsatisfactory because of an unfavorable tumor microenvironment (TME) and poor permeability of antibody-based ICIs. In this study, we aimed to discover small-molecule drugs that can modulate the TME to enhance ICI treatment efficacy in NSCLC in vitro and in vivo. We identified a PD-L1 protein-modulating small molecule, PIK-93, using a cell-based global protein stability (GPS) screening system. PIK-93 mediated PD-L1 ubiquitination by enhancing the PD-L1-Cullin-4A interaction. PIK-93 reduced PD-L1 levels on M1 macrophages and enhanced M1 antitumor cytotoxicity. Combined PIK-93 and anti-PD-L1 antibody treatment enhanced T cell activation, inhibited tumor growth, and increased tumor-infiltrating lymphocyte (TIL) recruitment in syngeneic and human peripheral blood mononuclear cell (PBMC) line-derived xenograft mouse models. PIK-93 facilitates a treatment-favorable TME when combined with anti-PD-L1 antibodies, thereby enhancing PD-1/PD-L1 blockade cancer immunotherapy.

Epidemiology of Chronic Hepatitis B Infection in the Cohort of College Students with Vaccination in Taiwan.

After the mass vaccination project in Taiwan, the prevalence of the hepatitis B virus (HBV) infection for the college-aged population of 18 to 21 years is uncertain. We aimed to investigate the prevalence of hepatitis B markers in different birth cohorts. A total of 38,075 students in universities in Kaohsiung area undergoing entrance examinations between July 2006 to September 2020 were included. Seroprevalence of the hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) status and laboratory data were collected. The seropositive rate of HBsAg was less than 1% for students born after 1991. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were significantly higher, and body mass index (BMI) was significantly lower in HBV carriers compared to those who were not carriers (all p < 0.001). Multivariate logistic regression showed that age, male, higher BMI, and positive HBsAg were risk factors of abnormal ALT value. A decrease in the positive rate of anti-HBs which was significantly higher in the cohort of plasma-derived vaccines than recombinant vaccines was found. We concluded that there were decreasing trends in seropositive rates of HBsAg and anti-HBs for students of the college-aged population in the Kaohsiung area. The status of HBsAg was a predictive factor of abnormal ALT levels. The period effect on anti-HBs seropositivity for DNA recombinant vaccine somehow existed.

X-linked dystonia parkinsonism: epidemiology, genetics, clinical features, diagnosis, and treatment.

X-linked dystonia parkinsonism (XDP) is a rare X-linked recessive degenerative movement disorder that only affects Filipino descent, predominantly males. Its underlying cause is associated with the genetic alterations in the TAF1/DYT3 multiple transcription system. SINE-VNTR-Alu (SVA) retrotransposon insertion was suggested to be the responsible genetic mutation. Clinically, it initially presents as focal dystonia and generalizes within years. Parkinsonism arises years later and coexists with dystonia. Nonmotor symptoms like cognitive impairment and mood disorders are also common among XDP patients. XDP diagnosis relies on clinical history and physical examination. On imaging, abnormalities of the striatum, such as atrophy, are widely seen and can explain the clinical presentations with a three-model pathway of the striatum. Treatments aim for symptomatic relief of dystonia and parkinsonism and to prevent complications. Oral medications, chemo-denervation, and surgery are used in XDP patients. This review summarizes the currently important information regarding XDP, providing a synoptic overview and understanding of XDP for future studies.

Evolution of anti-SARS-CoV-2 spike protein titers after two-dose of COVID-19 vaccination among people living with HIV.

Background: A community COVID-19 outbreak caused by the B.1.1.7 SARS-CoV-2 variant occurred in Taiwan in May 2021. High-risk populations such as people living with HIV (PLWH) were recommended to receive two doses of COVID-19 vaccines. While SARS-CoV-2 vaccines have demonstrated promising results in general population, real-world information on the serological responses remains limited among PLWH. Methods: PLWH receiving the first dose of SARS-CoV-2 vaccine from 2020 to 2021 were enrolled. Determinations of anti-SARS-CoV-2 spike IgG titers were performed every one to three months, the third dose of the SARS-CoV-2 vaccine or confirmed SARS-CoV-2 infection. All serum samples were tested for anti-nucleocapsid antibody and those tested positive were excluded from analysis. Results: A total of 1189 PLWH were enrolled: 829 (69.7%) receiving two doses of the AZD1222 vaccine, 232 (19.5%) of the mRNA-1273 vaccine, and 128 (10.8%) of the BNT162b2 vaccine. At all time-points, PLWH receiving two doses of mRNA vaccines had consistently higher antibody levels than those receiving the AZD1222 vaccine (p <0.001 for all time-point comparisons). Factors associated with failure to achieve an anti-spike IgG titer >141 BAU/mL within 12 weeks, included type 2 diabetes mellitus (DM) (adjusted odds ratio [aOR], 2.24; 95% CI, 1.25-4), a CD4 T cell count <200 cells/mm3 upon receipt of the first dose of vaccination (aOR, 3.43; 95% CI, 1.31-9) and two homologous AZD1222 vaccinations (aOR, 16.85; 95%CI, 10.13-28). For those receiving two doses of mRNA vaccines, factors associated with failure to achieve an anti-spike IgG titer >899 BAU/mL within 12 weeks were a CD4 T cell count <200 cells/mm3 on first-dose vaccination (aOR, 3.95; 95% CI, 1.08-14.42) and dual BNT162b2 vaccination (aOR, 4.21; 95% CI, 2.57-6.89). Conclusions: Two doses of homologous mRNA vaccination achieved significantly higher serological responses than vaccination with AZD1222 among PLWH. Those with CD4 T cell counts <200 cells/mm3 and DM had consistently lower serological responses.

Delayed Skin Reactions to COVID-19 mRNA-1273 Vaccine: Case Report and Literature Review.

BACKGROUND: The COVID-19 mRNA vaccine was granted emergency use authorization (EUA) on December 18, 2020. Some patients experienced a transient, pruritic rash at the injection site, which was referred to as "COVID arm". It is considered a delayed-type hypersensitivity reaction and occurs mostly in individuals after vaccination with the Moderna vaccine but rarely with other mRNA vaccines. CASE SUMMARY: A healthy 33-year-old woman with no history of disease or long-term medication presented with fever and rash on the left upper arm three days after her first vaccination with the mRNA-1273 vaccine (Moderna). RESULTS: After treatment with antihistamines, all lesions gradually resolved over the following 4 to 5 days. CONCLUSION: We report a case of "COVID arm": a localized erythematous rash surrounding the injection site that arose three days after the first dose of the Moderna COVID-19 vaccine. Delayed injection site reactions occurred in approximately 0.8% of vaccinated people after the first dose and in approximately 0.2% after the second dose. The lesions persisted for several days and then resolved without treatment. Health care providers were not prepared to address these delayed local reactions to the mRNA-1273 vaccine. Given the scale-up of mass vaccination campaigns worldwide, these skin reactions may likely generate concerns among patients and requests for evaluation. Although these skin reactions have not been consistently recognized, guidance regarding the second dose of the vaccine has varied, and many patients have unnecessarily received antibiotic agents.

Mouse hybrid genome mediates diverse brain phenotypes with the specificity of reciprocal crosses.

Hybrid species have more genetic diversity than their parents. However, the impact of the hybrid genome of reciprocal crosses on brain function remains largely unknown. We performed behavioral, molecular, and neuronal analyses on C57BL/6J mice (B6), CAST/EiJ mice (CAST), and hybrid mice resulting from reciprocal crosses of the two strains, B6/CAST F1i and B6/CAST F1r, respectively. Hybrid mice displayed greater motor strength and coordination, food grinding, social dominance, and less sociability compared to their parental strains. Parental origin influenced body weight, locomotor speed, and heat nociception of hybrid mice. Parental origin, cell type, and the interaction of both affected expression patterns of hybrid genomes including imprinted genes. There was a correlation between affected genes and corresponding behavioral phenotypes. Hybrid genomes mediated neuronal activity in the locus coeruleus, a brain region implicated in arousal, adaptive behaviors, and sleep-wake cycle due to its norepinephrine projections throughout the central nervous system. The comprehensive brain phenotypes in these hybrid mice reveal important functional readouts associated with interactions of hybrid genomes and impacts of parental genomes.

Femtosecond Exciton and Carrier Relaxation Dynamics of Two-Dimensional (2D) and Quasi-2D Tin Perovskites.

The dynamics of exciton and free-carrier relaxation of low-dimensional tin iodide perovskites, BA2FAn-1SnnI3n+1, where n = 1 (N1), 2 (N2), 5 (N5), and 10 (N10), were investigated with femtosecond transient absorption spectra (TAS). The absorption and photoluminescence spectra of N1 and N2 show exciton characteristics due to quantum confinement, whereas N5 and N10 display a free-carrier nature, the same as for bulk three-dimensional (3D) films. The TAS profiles were fitted according to a global kinetic model with three time coefficients representing the interactions of biexcitons, trions, and excitons for N1 and N2 and hot carriers, cold carriers, and shallow trap carriers for N5 and N10. The carrier relaxation dynamics of N5 and N10 were similar to those of 3D FASnI3 except for the absence of surface recombination in the deep-trap states due to passivation of the grain surfaces by the long alkyl chain for these quasi-2D samples (N5/N10 vs 3D).

Perilla (Perilla frutescens) leaf extract inhibits SARS-CoV-2 via direct virus inactivation.

BACKGROUND: While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presents with mild or no symptoms in most cases, a significant number of patients become critically ill. Remdesivir has been approved for the treatment of coronavirus disease 2019 (COVID-19) in several countries, but its use as monotherapy has not substantially lowered mortality rates. Because agents from traditional Chinese medicine (TCM) have been successfully utilized to treat pandemic and endemic diseases, we designed the current study to identify novel anti-SARS-CoV-2 agents from TCM. METHODS: We initially used an antivirus-induced cell death assay to screen a panel of herbal extracts. The inhibition of the viral infection step was investigated through a time-of-drug-addition assay, whereas a plaque reduction assay was carried out to validate the antiviral activity. Direct interaction of the candidate TCM compound with viral particles was assessed using a viral inactivation assay. Finally, the potential synergistic efficacy of remdesivir and the TCM compound was examined with a combination assay. RESULTS: The herbal medicine Perilla leaf extract (PLE, approval number 022427 issued by the Ministry of Health and Welfare, Taiwan) had EC50 of 0.12 ± 0.06 mg/mL against SARS-CoV-2 in Vero E6 cells - with a selectivity index of 40.65. Non-cytotoxic PLE concentrations were capable of blocking viral RNA and protein synthesis. In addition, they significantly decreased virus-induced cytokine release and viral protein/RNA levels in the human lung epithelial cell line Calu-3. PLE inhibited viral replication by inactivating the virion and showed additive-to-synergistic efficacy against SARS-CoV-2 when used in combination with remdesivir. CONCLUSION: Our results demonstrate for the first time that PLE is capable of inhibiting SARS-CoV-2 replication by inactivating the virion. Our data may prompt additional investigation on the clinical usefulness of PLE for preventing or treating COVID-19.

Vorinostat combined with brigatinib overcomes acquired resistance in EGFR-C797S-mutated lung cancer.

The development of a new generation of tyrosine kinase inhibitors (TKIs) has improved the treatment response in lung adenocarcinomas. However, acquired resistance often occurs due to new epidermal growth factor receptor (EGFR) mutations. In particular, the C797S mutation confers drug resistance to T790M-targeting EGFR TKIs. To address C797S resistance, a promising therapeutic avenue is combination therapy that targets both total EGFR and acquired mutations to increase drug efficacy. We showed that combining vorinostat, a histone deacetylase inhibitor (HDACi), with brigatinib, a TKI, enhanced antitumor effects in primary culture and cell lines of lung adenocarcinomas harboring EGFR L858R/T790M/C797S mutations (EGFR-3M). While EGFR phosphorylation was decreased by brigatinib, vorinostat reduced total EGFR-3M (L858R/T790M/C797S) proteins through STUB1-mediated ubiquitination and degradation. STUB1 preferably ubiquitinated other EGFR mutants and facilitated protein turnover compared to EGFR-WT. The association between EGFR and STUB1 required the functional chaperone-binding domain of STUB1 and was further enhanced by vorinostat. Finally, STUB1 levels modulated EGFR downstream functions. Low STUB1 expression was associated with significantly poorer overall survival than high STUB1 expression in patients harboring mutant EGFR. Vorinostat combined with brigatinib significantly improved EGFR-TKI sensitivity to EGFR C797S by inducing EGFR-dependent cell death and may be a promising therapy in treating C797S-resistant lung adenocarcinomas.

Clinical validation of an automated reverse transcription-insulated isothermal PCR assay for the detection of severe acute respiratory syndrome coronavirus 2.

To determine clinical performance of the single-target SARS-CoV-2 orf 1 ab reverse transcription-insulated isothermal PCR (RT-iiPCR) assay, the positive percentage agreement between this assay and a laboratory real-time RT-PCR assay was 96.8% (30 of 31; 95% confidence interval [CI], 90.5%-100%) and the negative percentage agreement was 97.1% (67 of 69; 95% CI, 93.1%-100%).

Molecular Chirality Detection with Periodic Arrays of Three-Dimensional Twisted Metamaterials.

Rapid detection of the handiness of chiral molecules is an important topic for pharmaceutical industries because chiral drugs with opposing handiness sometimes exhibit unwanted side effects. In this research, a rapid optical method is proposed to determine the handiness of the chiral drug "Thalidomide". The platform is a large array of three-dimensional (3D) twisted metamaterials fabricated with a novel method by combining nanospherical-lens lithography (NLL) and hole-mask lithography (HML). The fabrication is high-throughput and the twisted metamaterials cover a large area. Strong circular dichroism (CD) response is observed in the near-infrared (NIR) region, which enables the chiral detection to be performed by a low-cost and portable spectroscope system. The proposed nanofabrication method significantly improves the capabilities of NLL and HML, which can be quickly adapted to fabricate various periodic 3D metamaterials. In addition, the results of this research pave the road for the rapid penetration of nanophotonics into the pharmaceutical industries.

Qualitative and Quantitative Analysis of Ukrainian Iris Species: A Fresh Look on Their Antioxidant Content and Biological Activities.

The major groups of antioxidant compounds (isoflavonoids, xanthones, hydroxycinnamic acids) in the rhizome methanol extracts of four Ukrainian Iris sp. (Iris pallida, Iris hungarica, Iris sibirica, and Iris variegata) were qualitatively and quantitatively analyzed using HPLC-DAD and UPLC-MS/MS. Gallic acid, caffeic acid, mangiferin, tectoridin, irigenin, iristectorigenin B, irisolidone, 5,6-dihydroxy-7,8,3',5'-tetramethoxyisoflavone, irisolidone-7-O-ß-d-glucopyranoside, germanaism B, and nigricin were recognized by comparing their UV/MS spectra, chromatographic retention time (tR) with those of standard reference compounds. I. hungarica and I. variegata showed the highest total amount of phenolic compounds. Germanaism B was the most abundant component in the rhizomes of I. variegata (7.089 ± 0.032 mg/g) and I. hungarica (6.285 ± 0.030 mg/g). The compound analyses showed good calibration curve linearity (r2 > 0.999) and low detection and quantifications limit. These results validated the method for its use in the simultaneous quantitative evaluation of phenolic compounds in the studied Iris sp. I. hungarica and I. variegata rhizomes exhibited antioxidant activity, as demonstrated by the HPLC-ABTS system and NRF2 expression assay and anti-inflammatory activity on respiratory burst in human neutrophils. Moreover, the extracts showed anti-allergic and cytotoxic effects against cancer cells. Anti-coronavirus 229E and lipid formation activities were also evaluated. In summary, potent antioxidant marker compounds were identified in the examined Iris sp.