Early-phase pandemic in Italy: Covid-19 spread determinant factors.

Although the Covid-19 pandemic is still ongoing, the environmental factors beyond virus transmission are only partially known. This statistical study has the aim to identify the key factors that have affected the virus spread during the early phase of pandemic in Italy, among a wide set of potential determinants concerning demographics, environmental pollution and climate. Because of its heterogeneity in pollution levels and climate conditions, Italy provides an ideal scenario for an ecological study. Moreover, the selected period excludes important confounding factors, as different virus variants, restriction policies or vaccines. The short-term relationship between the infection maximum increase and demographic, pollution and meteo-climatic parameters was investigated, including both winter-spring and summer 2020 data, also focusing separately on the two seasonal periods and on North vs Centre-South. Among main results, the importance of population size confirmed social distancing as a key management option. The pollution hazardous role undoubtedly emerged, as NO2 affected infection increase in all the studied scenarios, PM2.5 manifested its impact in North of Italy, while O3 always showed a protective action. Whereas higher temperatures were beneficial, especially in the cold season with also wind and relative humidity, solar irradiance was always relevant, revealing several significant interactions with other co-factors. Presented findings address the importance of the environment in Sars-CoV-2 spread and indicated that special carefulness should be taken in crowded areas, especially if they are highly polluted and weakly exposed to sun. The results suggest that containment of future epidemics similar to Covid-19 could be supported by reducing environmental pollution, achieving safer social habits and promoting preventive health care for better immune system response, as an only comprehensive strategy.

Molecular characterization of homo- and heterodimeric mercury(II)-bis-thiolates of some biologically relevant thiols by electrospray ionization and triple quadrupole tandem mass spectrometry.

A series of 24 compounds of general formula R(1)S-Hg-SR(2), R(1) and R(2) being biologically relevant thiol-containing amino acids and peptides (cysteine, homo-cysteine, penicillamine, N-acetyl-cysteine, N-acetyl-penicillamine, cysteinyl-glycine, gamma-glutamyl-cysteine and glutathione) were prepared by direct reaction of mercury(II) ions and thiols in water at millimolar concentration. The obtained products were characterized by electrospray ionization and triple quadrupole tandem mass spectrometry. The source spectra of equimolar mixtures of two different thiols reacting with a stoichiometric amount of mercury(II) show the peak clusters of the three theoretically expected bis-thiolato-mercury(II) complexes with relative intensities close to the theoretically expected 1:2:1 ratio, thus pointing at lack of substantial discrimination between the different thiols, the only observed exception being homo-cysteine, which is less reactive than cysteine and penicillamine. The fragment spectra are structure-specific for the different ligands bound to the metal ion and allow a stand-alone discrimination of some constitutional isomer pairs. Among the peculiar fragmentation processes observed, loss of neutral ammonia from protonated symmetrical and unsymmetrical mercury(II)-bis-thiolates with free, protonizable amino groups leads to the formation of thiirane-carboxylic bound species; this process is suppressed when the protonated amino group is in the gamma-position with respect to the sulfur atom, as in the case of compounds with homo-cysteine. This unusual behavior may hint at unforeseen mechanisms for the interaction of mercury(II) with biological structures, ultimately leading to cellular and organ toxicity. Compounds with N-acetylated amino acids show distinctive fragment ions to which the connectivity of a protonated 2-methyl-oxazoline-5-carboxylic acid may be proposed on the basis of the loss of water and of the elements of formic acid. Finally, the adducts of mercury(II) with glutathione and gamma-glutamyl-cysteine feature a distinctive decomposition channel by loss of a pyroglutamic unit, much the same as protonated glutathione, glutathione disulfide, the S-glutathionyl adducts of biologically occurring electrophiles and other (pseudo)-peptides with gamma-glutamyl bonds.

Characterization of the disulfides of bio-thiols by electrospray ionization and triple-quadrupole tandem mass spectrometry.

Glutathione and other intracellular low molecular mass thiols act both as the major endogenous antioxidant and redox buffer system and, as recently highlighted, as an important regulator of cellular homeostasis. Such cellular functions are mediated by protein thiolation, a newly recognized post-translational modification which involves the formation of mixed disulfides between GSH and key disulfide-linked Cys residues in the native protein structure. It is also well known that thiol-seeking heavy metals, such as mercury, cadmium and lead, may interfere in this regulatory system, thus disrupting the cellular functioning. To identify such mixed disulfides in order to investigate their biological role, 15 homo- and heterodimeric disulfides were prepared by air oxidation of binary mixtures containing cysteine, homocysteine, penicillamine, N-acetylcysteine, N-acetylpenicillamine and glutathione and their protonated molecules were characterized by mass spectrometry. Collisionally activated unimolecular decomposition of protonated homo- and heterodimeric disulfides generated by electrospray ionization gives rise to fission of the disulfide system both between the two sulfur atoms and across the C--S bonds, to yield structurally specific fragments which allow one to define the structure of the compounds and to discriminate between isomeric compounds. Fission between the sulfur atoms yields a pair of R--S(+) ions and, in some cases, also the complementary fragments corresponding to the protonated amino acids. Fission across the C--S bonds mainly occurs in the disulfides of N-acetylcysteine and N-acetylpenicillamine and gives rise to non-S-containing fragments formally similar to those obtained from some mercapturic acids. The complementary fragments, formally connected as R--S--S(+) ions are also observed. Fragmentation of glutathione disulfides mainly shows the characteristic loss of the terminal gamma-linked glutamic acid and little, if any, fragmentation of the disulfide system.