Photodynamic activity rather than drilling causes membrane damage by a light-powered molecular nanomotor.

The chase toward endowing chemical compounds with machine-like functions mimicking those of biological molecular machineries has yielded a variety of artificial molecular motors (AMMs). Pharmaceutical applications of photoexcited monomolecular unidirectionally-rotating AMMs have been envisioned in view of their ability to permeabilize biological membranes. Nonetheless, the mechanical properties of lipid membranes render the proposed drilling activity of AMMs doubtful. Here, we show that singlet oxygen released by a photoexcited "molecular drill" oxidized unsaturated lipids composing giant unilamellar vesicles. In contrast, giant liposomes built of saturated lipids were inert to AMM photoactuation. The AMM did not mechanically destroy gramicidin A ion channels in planar bilayer lipid membranes but instead photoinactivated them. Sodium azide, a singlet oxygen quencher, reduced both AMM-mediated light-induced dye release from unsaturated large unilamellar vesicles and protected gramicidin A from photoinactivation. Upon additional consideration of the underlying bilayer mechanics, we conclude that AMMs' envisioned therapeutic and pharmaceutical applications rely on their photodynamic activity rather than their nanomechanical drilling abilities.

Analysis of Avian Influenza (H5N5) Viruses Isolated in the Southwestern European Part of the Russian Federation in 2020-2021.

In 2021, several isolates of the H5N5 avian influenza virus (AIV) were detected in Europe and the Russian Federation, which differed from those detected in 2020. Genetic analysis revealed a relationship between the highly pathogenic avian influenza H5N5 subtype, detected in Europe, and some isolates detected in the Russian Federation territory in 2020-2021: it was shown that both originated in the Caspian Sea regions around the autumn of 2020. The appearance of H5N5 subtype viruses in the spring of 2021 in Europe and the Russian Federation was not associated with the mass migration of birds from Africa. The results of the analysis revealed the presence of a deletion in the stem of a neuraminidase between bp 139 and 204 (open reading frame). It has been shown that AIVs of the H5N5 subtype are capable of long-term circulation in wild bird populations with the possibility of reassortment. The results also highlighted the need for careful monitoring of the circulation of AIVs in the Caspian Sea region, the role of which, in the preservation and emergence of new antigenic variants of such viruses in Eurasia, is currently underestimated.

Chlorin Endogenous to the North Pacific Brittle Star Ophiura sarsii for Photodynamic Therapy Applications in Breast Cancer and Glioblastoma Models.

Photodynamic therapy (PDT) represents a powerful avenue for anticancer treatment. PDT relies on the use of photosensitizers-compounds accumulating in the tumor and converted from benign to cytotoxic upon targeted photoactivation. We here describe (3S,4S)-14-Ethyl-9-(hydroxymethyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid (ETPA) as a major metabolite of the North Pacific brittle stars Ophiura sarsii. As a chlorin, ETPA efficiently produces singlet oxygen upon red-light photoactivation and exerts powerful sub-micromolar phototoxicity against a panel of cancer cell lines in vitro. In a mouse model of glioblastoma, intravenous ETPA injection combined with targeted red laser irradiation induced strong necrotic ablation of the brain tumor. Along with the straightforward ETPA purification protocol and abundance of O. sarsii, these studies pave the way for the development of ETPA as a novel natural product-based photodynamic therapeutic.

Inflammatory parameters and pulmonary biomarkers in smokers with and without chronic obstructive pulmonary disease (COPD).

BACKGROUND: We organized this study in order to investigate differences in serum inflammatory profiles and circulating serum pneumoproteins between smokers with and without chronic obstructive pulmonary disease (COPD). METHODS: Patients aged 35-70 years with COPD and a smoking history ≥10 pack-years (cases, n=38) and 38 participants with the same smoking history without COPD (controls) were included in a comparative study conducted as part of a population-based cross-sectional study with 2,388 individuals in northwestern Russia. Cases and controls were matched for age and smoking history. Airflow obstruction (AO) was defined using forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) <0.70 and/or FEV1/FVC < lower limit of the normal cut-off values. Patients at risk for COPD were reassessed using a standardized diagnostic work-up protocol. Several parameters, among which four inflammatory biomarkers [the high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) levels] and two pneumoproteins [surfactant protein D (SP-D) and Clara cell secretory protein 16 (CC16)], were measured in the peripheral blood. Systemic inflammation was defined as at least 2 or more elevated biomarker levels. RESULTS: Out of all smokers, 57.9% with normal spirometry and 36.8% with COPD did not have systemic inflammation, whereas 44.7% of the patients with COPD and 5.3% of the patients without AO demonstrated at least two elevated biomarker levels. No difference in age, gender, and smoking history, environmental and occupational exposure was found between the non-inflamed and the inflamed smokers. Of all risk factors studied, only COPD was associated with systemic inflammation [odds ratio (OR) 11.42, 95% confidence interval (CI): 2.13-58.84]. CONCLUSIONS: Our study describes the systemic inflammatory network pattern associated with COPD and how it differs from the pattern in smokers with normal lung function. Systemic inflammation is not present in all smokers with COPD; in contrast, some non-obstructed smokers are characterized by systemic inflammation. From this perspective, smoking itself could be seen as a disease and studied accordingly. TRIAL REGISTRATION: NCT02307799.

The megadiverse fauna of Neotropical Cerambycidae (Coleoptera): Notes, descriptions, new records, new species, and revalidations.

Holonotus latithorax Thomson, 1861 (Prioninae, Solenopterini), and Periestola Breuning, 1943 (Lamiinae, Acanthocinini) are revalidated. A lectotype is designated for Holonotus latithorax. The following new synonyms are proposed: Lagocheirus plantaris indistinctus Dillon, 1957 = Lagocheirus plantaris plantaris Erichson, 1847 (Lamiinae, Acanthocinini); Paracobelura curiosa Monné Martins, 1976 = Periestola strandi Breuning, 1943 (Lamiinae, Acanthocinini), with a new country record for Panama; Anisopodus humeralis Bates, 1863 = Anisopodus lignicola Bates, 1863, with a new Brazilian state record. New species are described from Colombia: Lepturges (Lepturges) brechlini; Pseudosparna antonkozlovi; Hyperplatys ushveridzei; Blabia antonkozlovi; and Cycnidolon antonkozlovi. The female of Nealcidion napoensis Nascimento McClarin, 2018 is described, and the species is reported for Colombia for the first time. Additionally, the following new records are reported: Amniscites pictipes (Bates, 1863) from Colombia; two new department records in Colombia for Onalcidion tavakiliani Audureau, 2013; new department record in Colombia for Trypanidius irroratus Monné Delfino, 1980; Icublabia multispinosa Galileo Martins, 2003 for Colombia including additional notes; new department record in Colombia for Blabia intricata Martins Galileo, 1995; Obrium costaricum Hovore Chemsak, 1980 for Panama; Pantonyssus nigriceps Bates, 1870 for Colombia; Stizocera geniculata (Pascoe, 1866) for Colombia; and Pygmodeon obtusum (Bates, 1874) for Panama. Stizocera geniculata is also excluded from the fauna of the Brazilian state of Rondônia.

Regio-isomeric effects in tandem mass spectra of sulfonium cations generated from thiacyclane based sulfonium salts under soft ionization conditions.

The influence of regio-isomerism of even-electron sulfonium ions on tandem electrospray and matrix-assisted laser desorption/ionization mass spectra recorded by using collision-induced dissociation was investigated. The initial organic sulfides belonged to isomeric thiabicyclane series (substituted 7- and 8-thiabicyclo[4.3.0]nonanes, 2- and 3-thiabicyclo[4.4.0]decanes) and phenylthiolanes. To investigate by the abovementioned mass spectrometry methods, the sulfides were preliminary S-alkylated by methyl, ethyl iodides, their deuterated analogs and trialkoxonium tetrafluoroborates to form corresponding sulfonium salts. The latter salts readily gave off corresponding sulfonium cations under abovementioned desorption/ionization conditions and these cations were precursor ions in collision-induced dissociation experiments. The main quantitative and frequently qualitative differences between collision-induced dissociation spectra of isomers were manifested in mass numbers and relative intensities of the ions Alk-S+ = CHR (formal structure) that originated from the destruction of sulfur-containing ring. Corresponding peaks are particularly abundant for cations Alk-S+ = CH2 and their intensities are usually greater than for other C-substituted homologues. Qualitative difference between fragmentation features of 2- and 3-phenylthiolanium cations is that only the latter can eliminate neutral C2H4S molecule.

The RESPECT study: RESearch on the PrEvalence and the diagnosis of COPD and its Tobacco-related etiology: a study protocol.

BACKGROUND: Smoking remains a leading health risk factor among Europeans. Tobacco, together with other factors, will lead to an expansive epidemic of chronic diseases, including COPD, among the working population in Russia. The general aim of the RESearch on the PrEvalence and the diagnosis of COPD and its Tobacco-related etiology (RESPECT) study is to gain a better understanding of the prevalence, pathogenesis and symptoms of COPD. METHODS/DESIGN: The RESPECT study is a prospective, population-based cohort study of subjects aged 35-70 years in two north-west regions of the Russian Federation (Saint Petersburg and Arkhangelsk). The study includes three components: a cross-sectional study (prevalence), a case-control study and a cohort study (diagnostic). An investigator who interviewed the patient completed three questionnaires. Spirometry, including a reversibility test, was offered to all participants. Individuals displaying forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 0.7 and/or FEV1/FVC < the lower limit of normal before and/or after bronchodilation were included in a follow-up study and were examined by a pulmonologist using a standardized comprehensive examination protocol. A future case-control study of two matched groups of patients (heavy smokers with COPD versus heavy smokers without COPD) will provide information on which factors (biomarkers, including pneumoproteins, in serum and induced sputum) are related to tobacco-induced COPD. DISCUSSION: In total, 3133 individuals (2122 from St. Petersburg and 1012 from Arkhangelsk) aged 35-70 years agreed to participate in this study and met the inclusion criteria. In total, 2974 participants met the quality criteria for spirometry, and 2388 reversibility tests were performed. A cohort of newly defined obstructive pulmonary disease patients (247 persons) was established for follow-up investigation. The RESPECT study will provide information regarding the prevalence of COPD in the north-west region of the Russian Federation. Moreover, the comprehensive RESPECT database will enable us to explore new research questions, provide novel insight into the risk factors and different phenotypes of COPD, and contribute to an improved understanding of the reasons why some heavy smokers develop the disease whereas others do not. CLINICAL TRIAL REGISTRATION: NCT02307799 (the release date: 12/01/2014).