Association Between Dietary Factors and Chronic Sinusitis Among Korean Individuals: Insights From a Large Population-Based Study in Asia.

Objective: Population-based studies on chronic sinusitis have predominantly focused on Europe and the Americas, but research on chronic sinusitis within large Asian populations remains scarce. This study aims to explore the link between dietary factors and chronic sinusitis among ethnic Koreans in Asia. Design: A cross-sectional study. Setting: Data were collected from the Korean National Health and Nutrition Examination Survey (KNHANES) in 2012. Participants: Participants in the study were included based on a doctor's diagnosis of chronic sinusitis, as determined through the ear, nose, and throat examination questionnaires. Results: Adolescents [adjusted P value (aP) < .001, adjusted odds ratio (aOR) = 1.881, 95% confidence interval (CI) = 1.380-2.564] and individuals with college and higher education (aP = .042, aOR = 1.298, 95% CI = 1.009-1.669) were more likely to develop chronic rhinosinusitis. In addition, levels of dietary fat [P = .001, interquartile range (IQR) = 34.085] and energy intake (P = .004, IQR = 981.106) were associated with an increased risk of chronic sinusitis. Moreover, high dietary inflammatory index (aP < .001, aOR = 0.547, 95% CI = 0.415-0.721), and high intake of fried pork chops (aP = .028, aOR = 1.335, 95% CI = 1.033-1.777), bread (aP = .024, aOR = 1.364, 95% CI = 1.042-1.786), and rice (aP = .021, aOR = 1.382, 95% CI = 1.051-1.818) were risk factors for chronic sinusitis, while cucumber consumption (aP < .001, aOR = 0.547, 95% CI = 0.415-0.721) was a protective factor for chronic sinusitis. Conclusion: This study revealed a significant correlation between diet and development of chronic sinusitis. These findings suggest that promoting an anti-inflammatory dietary pattern and providing guidance on healthy eating habits could help reduce the incidence of chronic sinusitis and enhance its management.

New ε-N-thioglutaryl-lysine derivatives as SIRT5 inhibitors: Chemical synthesis, kinetic and crystallographic studies.

SIRT5 has been implicated in various physiological processes and human diseases, including cancer. Development of new highly potent, selective SIRT5 inhibitors is still needed to investigate disease-related mechanisms and therapeutic potentials. We here report new ε-N-thioglutaryllysine derivatives, which were designed according to SIRT5-catalysed deacylation reactions. These ε-N-thioglutaryllysine derivatives displayed potent SIRT5 inhibition, of which the potential photo-crosslinking derivative 8 manifested most potent inhibition with an IC50 value of 120 nM to SIRT5, and low inhibition to SIRT1-3 and SIRT6. The enzyme kinetic assays revealed that the ε-N-thioglutaryllysine derivatives inhibit SIRT5 by lysine-substrate competitive manner. Co-crystallographic analyses demonstrated that 8 binds to occupy the lysine-substate binding site by making hydrogen-bonding and electrostatic interactions with SIRT5-specific residues, and is likely positioned to react with NAD+ and form stable thio-intermediates. Compound 8 was observed to have low photo-crosslinking probability to SIRT5, possibly due to inappropriate position of the diazirine group as observed in SIRT5:8 crystal structure. This study provides useful information for developing drug-like inhibitors and cross-linking chemical probes for SIRT5-related studies.

Knowledge mapping of interleukin-33: a bibliometric study.

Interleukin-33 (IL-33) is a member of the IL-1 family of cytokines. IL-33 is associated with the expression of tissue damage or necrosis after increasing and being released into the cell, it influences the suppression of tumorigenicity 2 (ST2) receptor expression of a variety of immune cells (including mast cells and type 2 congenital lymphocytes). Furthermore, during type 2 innate immune reactions and allergic inflammation IL-33 plays a central role in immune amplification and "alarming"; thus, regulating immune responeses. IL-33 is closely related to inflammation-related diseases such as allergic diseases, autoimmune diseases, infectious diseases, and tumors. It is essential in maintaining tissue homeostasis, eliminating inflammation, and repairing tissue damage. We searched the Web of Science Core Collection (WoSCC) database for relevant publications on IL-33 from 2005 to 2021 and screened them according to specific inclusion criteria. A total of 2626 articles were included in our analysis. Using Microsoft Excel 2019 (Redmond, WA), VOSviewer 1.6.11 (The Centre for Science and Technology Studies, CWTS), and Citespace5.8. R2 (Drexel University, Philadelphia, PA) were used for data processing and visualization. Countries/regions, journals, authors, co-cited references, and keywords were analyzed. We discovered that IL-33 plays an important role as a cytokine in numerous diseases, especially allergic diseases. Studying its mechanism of action is of great importance for developing novel drugs and therapeutics.

Analysis of drug factors in 5-aminolevulinic acid photodynamic therapy for oral potentially malignant disorder.

OBJECTIVES: This study aimed to analyze the influence of drug factors on the efficacy of 5-aminolevulinic acid (ALA) photodynamic therapy for oral potentially malignant disorder to improve clinical efficacy and promote clinical rational drug use. METHODS: Literature on the treatment of oral potentially malignant disorder by using ALA photodynamic therapy was collected and analyzed from PubMed, ISI Web of Knowledge database, CNKI, VIP, and Wanfang database. RESULTS: A total of 690 cases were collected, with an average complete response rate of 65.94%. The groups treated with 16.8% methyl aminolevulinate cream, local topical, once a week, and pre-activation time of 2-4 hours were better than the other subgroups, with average complete response rates of 100%, 66.91%, 78.28%, and 77.54%, respectively. CONCLUSIONS: Drug factors have direct influence on the curative effect. The development of novel oral ALA formulations from the perspective of drug improvement is an important strategy to improve efficacy.

Chinese University Students' Awareness and Acceptance of the COVID-19 Vaccine: A Cross-Sectional Study.

Purpose: The emergence of the mutant virus has exacerbated the COVID-19 epidemic, and vaccines remain an effective and viable means of resistance. As a socially influential young group, university students' awareness and acceptance of the COVID-19 vaccine are crucial to achieving herd immunity. This study aimed to assess the awareness and acceptance of the COVID-19 vaccine among Chinese university students and identify possible factors associated with their awareness level and vaccine hesitancy. Patients and Methods: An anonymous cross-sectional survey was conducted among Chinese university students between 10 and 28 June 2021. We collected information on the demographic characteristics, awareness and acceptance of the COVID-19 vaccine, and influencing factors. Sleep disturbances and anxiety disorders were also evaluated. Multinomial logistic regression analyses were performed. Results: Among the 721 participants (aged 18 to 23 years) with a female predominance (68.9%), 40.4% of cases exhibited moderate awareness the COVID-19 vaccine, and 87.4% of cases expressed high acceptance of the vaccine. Participants' awareness of the COVID-19 vaccine was associated with gender, ethnicity, region of residence, grade level, satisfaction with current state of pandemic control, the perceived likelihood of a COVID-19 pandemic rebound, the source number of COVID-19 information, concerns about differences in vaccine manufacturers, acceptance of current state-approved vaccines and insomnia level. Furthermore, age, preferred channels for vaccination and the acceptance of current state-approved vaccines were significantly associated with their acceptance of the vaccine. Conclusion: This study reflected Chinese university students' high acceptance, but insufficient awareness of the COVID-19 vaccine, some students have insomnia and anxiety problems. These require the government to take measures such as individualized publicity and education, adding professional psychological counseling courses to improve the university students' awareness of vaccines and public health events, and comprehensively promote vaccination to cope with the ever-changing situation of the COVID-19 epidemic.

Marine volatile organic compounds and their impacts on marine aerosol-A review.

Volatile organic compounds (VOCs) play a vital role in the global carbon budget and in the regional formation of ozone in the troposphere, and are emitted from both natural and anthropogenic activities. They can also serve as a source of secondary organic aerosol (SOA). Field and model studies showed evidences of a strong marine biogenic influence on marine aerosols. Although knowledge of terrestrial VOC emissions and SOA formation mechanisms has been advanced considerably over the last decades, processes constraining marine VOC emissions and marine SOA formation remain poorly understood. Seawater contains an extremely complex, diverse, and largely unidentified mixture of VOCs. Despite the fact that the ocean covers 70% of the Earth's surface, the role of the ocean in the global budget of VOCs is still unclear. The distribution and emission of sea surface VOCs exhibit considerable spatial-temporal variation, with higher concentrations often, but not always, correlated with biological activities. VOCs in surface seawater have been measured in various geographic regions, however, knowledge of the distribution of marine VOCs and the role of the oceans in the global atmospheric chemistry is still insufficient due to the paucity of measurements. This study reviews marine VOCs in terms of current analytical methods, global marine VOCs measurements, their effects on SOA, and future needs for understanding the role of marine VOCs in the chemistry of the atmosphere.

Real time analysis of trace volatile organic compounds in ambient air: a comparison between membrane inlet single photon ionization mass spectrometry and proton transfer reaction mass spectrometry.

Real-time monitoring of volatile organic compounds (VOCs) is critical for a better understanding of chemical processes in ambient air or making minute-by-minute decisions in emergency situations. Proton transfer reaction mass spectrometry (PTR-MS) is nowadays the most commonly used technique for real-time monitoring of VOCs while membrane single photon ionization mass spectrometry (MI-SPI-MS) is a promising MS technique for online detection of trace VOCs. Here, to evaluate the potential of MI-SPI-MS as a complementary tool to PTR-MS, a comprehensive comparison has been performed between MI-SPI-MS and PTR-MS. By using two sets of standard gas mixtures TO15 and PAMS, SPI-MS shows advantages in the detection of ≥C5 alkanes, aromatics and halogens; especially for aromatics, the LODs can reach the ppt level. PTR-MS has performed better in the detection of alkenes, ketones and aldehydes. For outdoor measurements, a number of VOCs have been detected while using MI-SPI-MS and PTR-MS in parallel. Consistent temporal variations have been observed for toluene, C8-aromatics and C9-aromatics by the two instruments, with a more sensitive response from the MI-SPI-MS. Thus by measuring both standard gas mixture and complex ambient air samples, we have successfully demonstrated that MI-SPI-MS will be a helpful tool to provide important complementary information on aromatics and alkanes in air, and proper application of MI-SPI-MS will benefit the real-time monitoring of trace VOCs in relative fields.

Sensitive fluorogenic substrates for sirtuin deacylase inhibitor discovery.

Sirtuins (SIRTs) are NAD+-dependent lysine deacylases, regulating many important biological processes such as metabolism and stress responses. SIRT inhibitors may provide potential benefits against SIRT-driven human diseases. Development of efficient assay platforms based on fluorogenic substrates will facilitate the discovery of high-quality SIRT inhibitors. We here report 16 new fluorogenic peptide substrates (P1-P16) designed with structurally diverse tetrapeptides and acyl modifications. Tests of P1-P16 against SIRT isoforms identified several sensitive substrates for SIRT1, SIRT2, SIRT3 and SIRT5, which manifested lower KM values and higher catalytic efficiency, and particularly had less signal interference in inhibitor screening compared with our previously reported internally quenched fluorescent substrates. Co-crystallization of sensitive substrates P13 and P15 with SIRT5 revealed an unexpected binding mode, involving interactions with residues from active site bordering surfaces, different from that observed for other peptides derived from natural protein substrates. By using SIRT5 sensitive substrates, we found that TW-37, a Bcl-2 inhibitor, displayed low micromolar inhibition to SIRT5, which was further validated by isothermal titration calorimetry analyses, offering a new point to develop dual-action SIRT5/Bcl-2 inhibitors against cancers. This work provides assay platform and structural basis for developing new substrates and inhibitors targeting human SIRTs.

Discovery of mercaptopropanamide-substituted aryl tetrazoles as new broad-spectrum metallo-ß-lactamase inhibitors.

ß-Lactam antibiotic resistance mediated by metallo-ß-lactamases (MBL) has threatened global public health. There are currently no available inhibitors of MBLs for clinical use. We previously reported the ruthenium-catalyzed meta-selective C-H nitration synthesis method, leading to some meta-mercaptopropanamide substituted aryl tetrazoles as new potent MBL inhibitors. Here, we described the structure-activity relationship of meta- and ortho-mercaptopropanamide substituted aryl tetrazoles with clinically relevant MBLs. The resulting most potent compound 13a showed IC50 values of 0.044 µM, 0.396 µM and 0.71 µM against VIM-2, NDM-1 and IMP-1 MBL, respectively. Crystallographic analysis revealed that 13a chelated to active site zinc ions via the thiol group and interacted with the catalytically important residues Asn233 and Tyr67, providing further structural information for the development of thiol based MBL inhibitors.

Assessing indoor gas phase oxidation capacity through real-time measurements of HONO and NOx in Guangzhou, China.

The hydroxyl radical (OH) is one of the most important oxidants controlling the oxidation capacity of the indoor atmosphere. One of the main OH sources indoors is the photolysis of nitrous acid (HONO). In this study, real-time measurements of HONO, nitrogen oxides (NOx) and ozone (O3) in an indoor environment in Guangzhou, China, were performed under two different conditions: (1) in the absence of any human activity and (2) in the presence of cooking. The maximum NOx and HONO levels drastically increased from 15 and 4 ppb in the absence of human activity to 135 and 40 ppb during the cooking event, respectively. The photon flux was determined for the sunlit room, which has a closed south-east oriented window. The photon flux was used to estimate the photolysis rate constants of NO2, J(NO2), and HONO, J(HONO), which span the range between 8 × 10-5 and 1.5 × 10-5 s-1 in the morning from 9:30 to 11:45, and 8.5 × 10-4 and 1.5 × 10-4 s-1 at noon, respectively. The OH concentrations calculated by photostationary state (PSS) approach, observed around noon, are very similar, i.e., 2.4 × 106 and 3.1 × 106 cm-3 in the absence of human activity and during cooking, respectively. These results suggest that under "high NOx" conditions (NOx higher than a few ppb) and with direct sunlight in the room, the NOx and HONO chemistry would be similar, independent of the geographic location of the indoor environment, which facilitates future modeling studies focused on indoor gas phase oxidation capacity.

Structure-Based Development of (1-(3'-Mercaptopropanamido)methyl)boronic Acid Derived Broad-Spectrum, Dual-Action Inhibitors of Metallo- and Serine-ß-lactamases.

The emergence and spread of bacterial pathogens acquired metallo-ß-lactamase (MBL) and serine-ß-lactamase (SBL) medicated ß-lactam resistance gives rise to an urgent need for the development of new dual-action MBL/SBL inhibitors. Application of a pharmacophore fusion strategy led to the identification of (2'S)-(1-(3'-mercapto-2'-methylpropanamido)methyl)boronic acid (MS01) as a new dual-action inhibitor, which manifests broad-spectrum inhibition to representative MBL/SBL enzymes, including the widespread VIM-2 and KPC-2. Guided by the VIM-2:MS01 and KPC-2:MS01 complex structures, further structural optimization yielded new, more potent dual-action inhibitors. Selectivity studies indicated that the inhibitors had no apparent inhibition to human angiotensin-converting enzyme-2 and showed selectivity across serine hydrolyases in E. coli and human HEK293T cells labeled by the activity-based probe TAMRA-FP. Moreover, the inhibitors displayed potentiation of meropenem efficacy against MBL- or SBL-positive clinical isolates without apparent cytotoxicity. This work will aid efforts to develop new types of clinically useful dual-action inhibitors targeting MBL/SBL enzymes.

Crystallographic and SAR analyses reveal the high requirements needed to selectively and potently inhibit SIRT2 deacetylase and decanoylase.

A high-quality X-ray crystal structure reveals the mechanism of compound 1a inhibiting SIRT2 deacetylase and decanoylase. Structure-activity relationship (SAR) analysis of the synthesized derivatives of 1a reveals the high requirements needed for selective inhibitors to bind with the induced hydrophobic pocket and potently inhibit sirtuin 2 deacetylase.

X-ray crystal structure guided discovery of new selective, substrate-mimicking sirtuin 2 inhibitors that exhibit activities against non-small cell lung cancer cells.

Human sirtuin 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase, and is implicated in human diseases including cancer. Selective small-molecule inhibitors for SIRT2 are sought as chemical tools and potential therapeutics. Here we report the X-ray crystal structure guided structure-activity relationship studies of new N-(3-(phenoxymethyl)phenyl)acetamide derivatives with SIRT2, which led to the identification of potent, selective SIRT2 inhibitors. Crystallographic analyses reveal that the new inhibitors act via inducing the formation of an enlarged hydrophobic pocket and particularly mimicking the interactions made by myristoylated-lysine substrates. The most potent inhibitor 24a could dose-dependently elevate the acetylation level of α-tubulin in the non-small cell lung cancer H441 cells, which have a high expression level of SIRT2 as determinated by Western blotting analyses. Further cellular assays reveal that 24a restrains cell growth mainly through inhibiting cellular proliferation rather than inducing apoptosis. Moreover, 24a could suppress the migration and invasion of H441 cells. These results provide an excellent basis for further development of new potent, selective, and cell active SIRT2 inhibitors as chemical tools and potential therapeutics for SIRT2-driven non-small cell lung cancers.

Virtual target screening reveals rosmarinic acid and salvianolic acid A inhibiting metallo- and serine-ß-lactamases.

Rosmarinic acid (RA), a polyphenolic phytochemical, has broad-spectrum biological and pharmacological activity. A virtual target screening method termed IFPTarget combined with enzyme inhibition assays led to the identification of the clinically relevant metallo-ß-lactamase (MBL) VIM-2 as one of unexploited targets of RA. The enzyme kinetic studies indicated that RA is a fully reversible, substrate-competitive VIM-2 inhibitor. The isothermal titration calorimetry (ITC) analyses revealed that the initial binding of RA to VIM-2 is mainly due to enthalpy contribution. Further inhibition assays with RA related compounds revealed that salvianolic acid A, a derivative of RA, manifests potent inhibition to VIM-2, more interestingly, which shows inhibitory activity against the NDM-1, another clinically relevant MBL subtype, and the serine-ß-lactamase TEM-1 that is structurally and mechanistically distinct from the VIM-2 and NDM-1.

((S)-3-Mercapto-2-methylpropanamido)acetic acid derivatives as metallo-ß-lactamase inhibitors: Synthesis, kinetic and crystallographic studies.

The emergence and global spread of metallo-ß-lactamase (MBL) mediated resistance to almost all ß-lactam antibacterials poses a serious threat to public health. Since no clinically useful MBL inhibitors have been reported, there is an urgent need to develop new potent broad-spectrum MBL inhibitors effective against antibacterial resistance. Herein, we synthesized a set of 2-substituted ((S)-3-mercapto-2-methylpropanamido) acetic acid derivatives, some of which displayed potent inhibition with high ligand efficiency to the clinically relevant MBL subtypes, Verona Integron-encoded MBL (VIM)-2 and New Delhi MBL (NDM)-1. Kinetic studies revealed that the inhibitors are not strong zinc chelators in solution, and they bind reversibly to VIM-2 but dissociate very slowly. Crystallographic analyses revealed that they inhibit VIM-2 via chelating the active site zinc ions and interacting with catalytically important residues. Further cell- and zebrafish-based assays revealed that the inhibitors slightly increase susceptibility of E. coli cells expressing VIM-2 to meropenem, and they have no apparent toxicity to the viability of HEK293T cells and the zebrafish embryogenesis.

Structure-based discovery of new selective small-molecule sirtuin 5 inhibitors.

Human sirtuin 5 (SIRT5) is a protein deacylase regulating metabolic pathways and stress responses and is implicated in metabolism-related diseases. Small-molecule inhibitors for SIRT5 are sought as chemical tools and potential therapeutics. Herein, we proposed a customized virtual screening approach targeting catalytically important and unique residues Tyr102 and Arg105 of SIRT5. Of the 20 tested virtual screening hits, six compounds displayed marked inhibitory activities against SIRT5. For the hit compound 19, a series of newly synthesized (E)-2-cyano-N-phenyl-3-(5-phenylfuran-2-yl)acrylamide derivatives/analogues were carried out structure-activity relationship analyses, resulting in new more potent inhibitors, among which 37 displayed the most potent inhibition to SIRT5 with an IC50 value of 5.59 ± 0.75 µM. The biochemical studies revealed that 37 likely acts via competitive inhibition with the succinyl-lysine substrate, rather than the NAD+ cofactor, and it manifested substantial selectivity for SIRT5 over SIRT2 and SIRT6. This study will aid further efforts to develop new selective SIRT5 inhibitors as tools and therapeutics.

IFPTarget: A Customized Virtual Target Identification Method Based on Protein-Ligand Interaction Fingerprinting Analyses.

Small-molecule target identification is an important and challenging task for chemical biology and drug discovery. Structure-based virtual target identification has been widely used, which infers and prioritizes potential protein targets for the molecule of interest (MOI) principally via a scoring function. However, current "universal" scoring functions may not always accurately identify targets to which the MOI binds from the retrieved target database, in part due to a lack of consideration of the important binding features for an individual target. Here, we present IFPTarget, a customized virtual target identification method, which uses an interaction fingerprinting (IFP) method for target-specific interaction analyses and a comprehensive index (Cvalue) for target ranking. Evaluation results indicate that the IFP method enables substantially improved binding pose prediction, and Cvalue has an excellent performance in target ranking for the test set. When applied to screen against our established target library that contains 11,863 protein structures covering 2842 unique targets, IFPTarget could retrieve known targets within the top-ranked list and identified new potential targets for chemically diverse drugs. IFPTarget prediction led to the identification of the metallo-ß-lactamase VIM-2 as a target for quercetin as validated by enzymatic inhibition assays. This study provides a new in silico target identification tool and will aid future efforts to develop new target-customized methods for target identification.