Transferrin-inspired iron delivery across the cell membrane using [(L2Fe)2(µ-O)] (L = chlorquinaldol) to harness anticancer activity of ferroptosis.

Although iron is a bio-essential metal, dysregulated iron acquisition and metabolism result in production of reactive oxygen species (ROS) due to the Fenton catalytic reaction, which activates ferroptotic cell death pathways. The lipophilic Fe(III)-chelator chlorquinaldol (L; i.e., 5,7-dichloro-8-hydroxy-2-methylquinoline) strongly favors the formation of a highly stable binuclear Fe(III) complex [(L2Fe)2(µ-O)] (1) that can mimic the function of the Fe(III)-transferrin complex in terms of the strong binding to Fe(III) and facile release of Fe(II) when the metal center is reduced. It should be noted that the cellular uptake of 1 is not transferrin receptor-mediated but enhanced by the high lipophilicity of chlorquinaldol. Once 1 is transported across the cell membrane, Fe(III) can be reduced by ferric reductase or other cellular antioxidants to be released as Fe(II), which triggers the Fenton catalytic reaction, thus harnessing the anticancer activity of iron. As the result, this transferrin-inspired iron-delivery strategy significantly reduces the cytotoxicity of 1 in normal human embryonic kidney cells (HEK 293) and the hemolytic activity of 1 in human red blood cells (hRBCs), giving rise to the unique tumor-specific anticancer activity of this Fe(III) complex.

Development of Biocompatible Ga2(HPO4)3 Nanoparticles as an Antimicrobial Agent with Improved Ga Resistance Development Profile against Pseudomonas aeruginosa.

Ga(III) can mimic Fe(III) in the biological system due to its similarities in charge and ionic radius to those of Fe(III) and can exhibit antimicrobial activity by disrupting the acquisition and metabolism of Fe in bacterial cells. For example, Ga(NO3)3 has been proven to be effective in treating chronic lung infections by Pseudomonas aeruginosa (P. aeruginosa) in cystic fibrosis patients in a recent phase II clinical trial. However, Ga(NO3)3 is an ionic compound that can hydrolyze to form insoluble hydroxides at physiological pH, which not only reduces its bioavailability but also causes potential renal toxicity when it is used as a systemic drug. Although complexion with suitable chelating agents has offered a varying degree of success in alleviating the hydrolysis of Ga(III), the use of nanotechnology to deliver this metallic ion should constitute an ultimate solution to all the above-mentioned problems. Thus far, the development of Ga-based nanomaterials as metalloantibiotics is an underexploited area of research. We have developed two different synthetic routes for the preparation of biocompatible Ga2(HPO4)3 NPs and shown that both the PVP- or PEG-coated Ga2(HPO4)3 NPs exhibit potent antimicrobial activity against P. aeruginosa. More importantly, such polymer-coated NPs do not show any sign of Ga-resistant phenotype development after 30 passes, in sharp contrast to Ga(NO3)3, which can rapidly develop Ga-resistant phenotypes of P. aeruginosa, indicating the potential of using Ga2(HPO4)3 NPs a new antimicrobial agent in place of Ga(NO3)3.

Harnessing the dual antimicrobial mode of action with a lipophilic Mn(II) complex using the principle of the Irving-Williams Series to completely eradicate Staphylococcus aurous.

The judicious selection of 5,7-dibromo-2-methy-8-quinolinol (BQ) as a Mn(II) ionophore results in the synthesis of Mn(BQ)2(DMSO)2·DMSO (1), a potent metalloantibiotic with a dual antimicrobial mode of action against four different strains of Staphylococcus aurous (SA) bacteria (MIC = 0.625 µg mL-1). Additionally, 1 can overcome ciprofloxacin-resistance in methicillin-resistant SA bacteria.

Lipophilic Fe(III)-Complex with Potent Broad-Spectrum Anticancer Activity and Ability to Overcome Pt Resistance in A2780cis Cancer Cells.

Although iron is essential for all forms of life, it is also potentially toxic to cells as the increased and unregulated iron uptake can catalyze the Fenton reaction to produce reactive oxygen species (ROS), leading to lipid peroxidation of membranes, oxidation of proteins, cleavage of DNA and even activation of apoptotic cell death pathways. We demonstrate that Fe(hinok)3 (hinok = 2-hydroxy-4-isopropyl-2,4,6-cycloheptatrien-1-one), a neutral Fe(III) complex with high lipophilicity is capable of bypassing the regulation of iron trafficking to disrupt cellular iron homeostasis; thus, harnessing remarkable anticancer activity against a panel of five different cell lines, including Pt-sensitive ovarian cancer cells (A2780; IC50 = 2.05 ± 0.90 µM or 1.20 µg/mL), Pt-resistant ovarian cancer cells (A2780cis; IC50 = 0.92 ± 0.73 µM or 0.50 µg/mL), ovarian cancer cells (SKOV-3; IC50 = 1.23 ± 0.01 µM or 0.67 µg/mL), breast cancer cells (MDA-MB-231; IC50 = 3.83 ± 0.12 µM or 2.0 µg/mL) and lung cancer cells (A549; IC50 = 1.50 ± 0.32 µM or 0.82 µg/mL). Of great significance is that Fe(hinok)3 exhibits unusual selectivity toward the normal HEK293 cells and the ability to overcome the Pt resistance in the Pt-resistant mutant ovarian cancer cells of A2780cis.

Lifestyles and the risk of an asthma attack in adult asthma patients: a cross-sectional study using NHANES database.

BACKGROUND: The influence of physical activity, diet and sleep on asthma has been well documented by recent studies respectively. However, few studies focus on the relationship between asthma attack and the overall lifestyle, which comprises interrelated lifestyle factors. This study aims to investigate the influence of lifestyles on the ratio of asthma attack. Data were extracted from the NHANES database (2017 to May 2020). METHODS: A total of 834 asthmatic patients were enrolled and divided into non-asthma attack (N.=460) and asthma attack (N.=374) groups. The risk factors for asthma attacks were preliminarily identified by univariate logistic analysis, then multivariate logistic analysis was employed to select independent risk factors other than lifestyles and further determine the association between lifestyles and asthma attacks. RESULTS: After multivariate logistic analysis, engagement of vigorous activity (Model 1 P=0.010, Model 2 P=0.016, Model 3 P=0.012), engagement of moderate activity (Model 1 P=0.006, Model 2 P=0.008, Model 3 P=0.003) and sleep disorder (Model1 P=0.001, Model 2 P<0.001, Model 3 P=0.008) were determined as independent risk factors of lifestyles for an asthma attack in the past year. CONCLUSIONS: This research documented that, for asthmatic patients, engagement of vigorous activity, engagement of moderate activity, and sleep disorder will make an asthma attack more likely to happen.

Harnessing the Dual Antimicrobial Mechanism of Action with Fe(8-Hydroxyquinoline)3 to Develop a Topical Ointment for Mupirocin-Resistant MRSA Infections.

8-Hydroxyquinoline (8-hq) exhibits potent antimicrobial activity against Staphylococcus aureus (SA) bacteria with MIC = 16.0-32.0 µM owing to its ability to chelate metal ions such as Mn2+, Zn2+, and Cu2+ to disrupt metal homeostasis in bacterial cells. We demonstrate that Fe(8-hq)3, the 1:3 complex formed between Fe(III) and 8-hq, can readily transport Fe(III) across the bacterial cell membrane and deliver iron into the bacterial cell, thus, harnessing a dual antimicrobial mechanism of action that combines the bactericidal activity of iron with the metal chelating effect of 8-hq to kill bacteria. As a result, the antimicrobial potency of Fe(8-hq)3 is significantly enhanced in comparison with 8-hq. Resistance development by SA toward Fe(8-hq)3 is considerably delayed as compared with ciprofloxacin and 8-hq. Fe(8-hq)3 can also overcome the 8-hq and mupirocin resistance developed in the SA mutant and MRSA mutant bacteria, respectively. Fe(8-hq)3 can stimulate M1-like macrophage polarization of RAW 264.7 cells to kill the SA internalized in such macrophages. Fe(8-hq)3 exhibits a synergistic effect with both ciprofloxacin and imipenem, showing potential for combination therapies with topical and systemic antibiotics for more serious MRSA infections. The in vivo antimicrobial efficacy of a 2% Fe(8-hq)3 topical ointment is confirmed by the use of a murine model with skin wound infection by bioluminescent SA with a reduction of the bacterial burden by 99 ± 0.5%, indicating that this non-antibiotic iron complex has therapeutic potential for skin and soft tissue infections (SSTIs).

Broad-Spectrum Antimicrobial Activity of Ultrafine (BiO)2CO3 NPs Functionalized with PVP That Can Overcome the Resistance to Ciprofloxacin, AgNPs and Meropenem in Pseudomonas aeruginosa.

Although it has no known biochemical role in living organisms, bismuth has been used to treat syphilis, diarrhea, gastritis and colitis for almost a century due to its nontoxic nature to mammalian cells. When prepared via a top-down sonication route from a bulk sample, bismuth subcarbonate (BiO)2CO3 nanoparticles (NPs) with an average size of 5.35 ± 0.82 nm exhibit broad-spectrum potent antibacterial activity against both the gram-positive and gram-negative bacteria including methicillin-susceptible Staphylococcus aureus (DSSA), methicillin-resistant Staphylococcus aureus (MRSA), drug-susceptible Pseudomonas aeruginosa (DSPA) and multidrug-resistant Pseudomonas aeruginosa (DRPA). Specifically, the minimum inhibitory concentrations (MICs) are 2.0 µg/mL against DSSA and MRSA and 0.75 µg/mL against DSPA and DRPA. In sharp contrast to ciprofloxacin, AgNPs and meropenem, (BiO)2CO3 NPs show no sign of developing Bi-resistant phenotypes after 30 consecutive passages. On the other hand, such NPs can readily overcome the resistance to ciprofloxacin, AgNPs and meropenem in DSPA. Finally, the combination of (BiO)2CO3 NPs and meropenem shows a synergistic effect with the fractional inhibitory concentration (FIC) index of 0.45.

Exploring the Multifunctionality of Mechanochemically Synthesized γ-Alumina with Incorporated Selected Metal Oxide Species.

γ-Alumina with incorporated metal oxide species (including Fe, Cu, Zn, Bi, and Ga) was synthesized by liquid-assisted grinding-mechanochemical synthesis, applying boehmite as the alumina precursor and suitable metal salts. Various contents of metal elements (5 wt.%, 10 wt.%, and 20 wt.%) were used to tune the composition of the resulting hybrid materials. The different milling time was tested to find the most suitable procedure that allowed the preparation of porous alumina incorporated with selected metal oxide species. The block copolymer, Pluronic P123, was used as a pore-generating agent. Commercial γ-alumina (SBET = 96 m2·g-1), and the sample fabricated after two hours of initial grinding of boehmite (SBET = 266 m2·g-1), were used as references. Analysis of another sample of γ-alumina prepared within 3 h of one-pot milling revealed a higher surface area (SBET = 320 m2·g-1) that did not increase with a further increase in the milling time. So, three hours of grinding time were set as optimal for this material. The synthesized samples were characterized by low-temperature N2 sorption, TGA/DTG, XRD, TEM, EDX, elemental mapping, and XRF techniques. The higher loading of metal oxide into the alumina structure was confirmed by the higher intensity of the XRF peaks. Samples synthesized with the lowest metal oxide content (5 wt.%) were tested for selective catalytic reduction of NO with NH3 (NH3-SCR). Among all tested samples, besides pristine Al2O3 and alumina incorporated with gallium oxide, the increase in reaction temperature accelerated the NO conversion. The highest NO conversion rate was observed for Fe2O3-incorporated alumina (70%) at 450 °C and CuO-incorporated alumina (71%) at 300 °C. The CO2 capture was also studied for synthesized samples and the sample of alumina with incorporated Bi2O3 (10 wt.%) gave the best result (1.16 mmol·g-1) at 25 °C, while alumina alone could adsorb only 0.85 mmol·g-1 of CO2. Furthermore, the synthesized samples were tested for antimicrobial properties and found to be quite active against Gram-negative bacteria, P. aeruginosa (PA). The measured Minimum Inhibitory Concentration (MIC) values for the alumina samples with incorporated Fe, Cu, and Bi oxide (10 wt.%) were found to be 4 µg·mL-1, while 8 µg·mL-1 was obtained for pure alumina.

Mechanochemical Synthesis of Nanoparticles for Potential Antimicrobial Applications.

There is an increased interest in porous materials due to their unique properties such as high surface area, enhanced catalytic properties, and biological applications. Various solvent-based approaches have been already used to synthesize porous materials. However, the use of large volume of solvents, their toxicity, and time-consuming synthesis make this process less effective, at least in terms of principles of green chemistry. Mechanochemical synthesis is one of the effective eco-friendly alternatives to the conventional synthesis. It adopts the efficient mixing of reactants using ball milling without or with a very small volume of solvents, gives smaller size nanoparticles (NPs) and larger surface area, and facilitates their functionalization, which is highly beneficial for antimicrobial applications. A large variety of nanomaterials for different applications have already been synthesized by this method. This review emphasizes the comparison between the solvent-based and mechanochemical methods for the synthesis of mainly inorganic NPs for potential antimicrobial applications, although some metal-organic framework NPs are briefly presented too.

Europium-151 and iron-57 nuclear resonant vibrational spectroscopy of naturally abundant KEu(III)Fe(II)(CN)6 and Eu(III)Fe(III)(CN)6 complexes.

We have performed and analyzed the first combined 151Eu and 57Fe nuclear resonant vibrational spectroscopy (NRVS) for naturally abundant KEu(III)[Fe(II)(CN)6] and Eu(III)[Fe(III)(CN)6] complexes. Comparison of the observed 151Eu vs.57Fe NRVS spectroscopic features confirms that Eu(III) in both KEu(III)[Fe(II)(CN)6] and Eu(III)[Fe(III)(CN)6] occupies a position outside the [Fe(CN)6] core and coordinates to the N atoms of the CN- ions, whereas Fe(III) or Fe(II) occupies the site inside the [Fe(CN)6]4- core and coordinates to the C atoms of the CN- ions. In addition to the spectroscopic interest, the results from this study provide invaluable insights for the design and evaluation of the nanoparticles of such complexes as potential cellular contrast agents for their use in magnetic resonance imaging. The combined 151Eu and 57Fe NRVS measurements are also among the first few explorations of bi-isotopic NRVS experiments.

Clinical features and prognosis of COVID-19 patients with metabolic syndrome: A multicenter, retrospective study.

Background: Few studies have investigated the impacts of metabolic syndrome (MS) on coronavirus disease 2019 (COVID-19). We described the clinical features and prognosis of confirmed COVID-19 patients with MS during hospitalization and after discharge. Methods: Two hundred and thirty-three COVID-19 patients from the hospitals in 8 cities of Jiangsu, China were retrospectively included. Clinical characteristics of COVID-19 patients were described and risk factors of severe illness were analyzed by logistic regression analysis. Results: Forty-five (19.3%) of 233 COVID-19 patients had MS. The median age of COVID-19 patients with MS was significantly higher than non-MS patients (53.0 years vs. 46.0 years, P = 0.004). There were no significant differences of clinical symptoms, abnormal chest CT images, and treatment drugs between two groups. More patients with MS had severe illness (33.3% vs. 6.4%, P < 0.001) and critical illness (4.4% vs. 0.5%, P = 0.037) than non-MS patients. The proportions of respiratory failure and acute respiratory distress syndrome in MS patients were also higher than non-MS patients during hospitalization. Multivariate analysis showed that concurrent MS (odds ratio [OR] 7.668, 95% confidence interval [CI] 3.062-19.201, P < 0.001) and lymphopenia (OR 3.315, 95% CI 1.306-8.411, P = 0.012) were independent risk factors of severe illness of COVID-19. At a median follow-up of 28 days after discharge, bilateral pneumonia was found in 95.2% of MS patients, while only 54.7% of non-MS patients presented bilateral pneumonia. Conclusions: 19.3% of COVID-19 patients had MS in our study. COVID-19 patients with MS are more likely to develop severe complications and have worse prognosis. More attention should be paid to COVID-19 patients with MS.

Antecedentes: Pocos estudios han investigado el impacto del síndrome metabólico (SM) en la enfermedad por coronavirus 2019 (COVID-19). Describimos las características clínicas y el pronóstico de los pacientes con COVID-19 confirmados con SM durante la hospitalización y después del alta. Métodos: Se incluyó de forma retrospectiva a 233 pacientes con COVID-19 de los hospitales de 8 ciudades de Jiangsu (China). Se describieron sus características clínicas y se analizaron los factores de riesgo de enfermedad grave mediante un análisis de regresión logística. Resultados: De los 233 pacientes, 45 (19,3%) tenían EM. La mediana de edad de estos pacientes con EM fue significativamente mayor que la de los pacientes sin él (53,0 años frente a 46,0 años; p = 0,004). No hubo diferencias significativas en cuanto a los síntomas clínicos, las imágenes de TC torácica anormales y los fármacos de tratamiento entre los 2 grupos. Hubo más pacientes con EM que tuvieron enfermedades graves (33,3% frente a 6,4%; p < 0,001) y críticas (4,4% frente a 0,5%; p = 0,037) que los pacientes sin EM. Las proporciones de insuficiencia respiratoria y síndrome de dificultad respiratoria aguda en los pacientes con EM también fueron mayores que en los pacientes sin EM durante la hospitalización. El análisis multivariante mostró que la EM concurrente (odds ratio [OR] 7,668; intervalo de confianza [IC] del 95%: 3,062-19,201; p < 0,001) y la linfopenia (OR 3,315; IC del 95%: 1,306-8,411; p = 0,012) eran factores de riesgo independientes de COVID-19 grave. En una mediana de seguimiento de 28 días tras el alta, se encontró neumonía bilateral en el 95,2% de los pacientes con EM, mientras que solo la presentaron el 54,7% de los pacientes sin EM. Conclusiones: El 19,3% de los pacientes con COVID-19 tenían EM en nuestro estudio. Los pacientes con COVID-19 y EM son más propensos a desarrollar complicaciones graves y tienen peor pronóstico. Se debe prestar más atención a los pacientes con COVID-19 y EM.

Clinical features and prognosis of COVID-19 patients with metabolic syndrome: A multicenter, retrospective study / Características clínicas y pronóstico de los pacientes con COVID-19 y síndrome metabólico: un estudio multicéntrico y retrospectivo

Background:Few studies have investigated the impacts of metabolic syndrome (MS) on coronavirus disease 2019 (COVID-19). We described the clinical features and prognosis of confirmed COVID-19 patients with MS during hospitalization and after discharge.Methods:Two hundred and thirty-three COVID-19 patients from the hospitals in 8 cities of Jiangsu, China were retrospectively included. Clinical characteristics of COVID-19 patients were described and risk factors of severe illness were analyzed by logistic regression analysis.Results:Forty-five (19.3%) of 233 COVID-19 patients had MS. The median age of COVID-19 patients with MS was significantly higher than non-MS patients (53.0 years vs. 46.0 years, P=0.004). There were no significant differences of clinical symptoms, abnormal chest CT images, and treatment drugs between two groups. More patients with MS had severe illness (33.3% vs. 6.4%, P<0.001) and critical illness (4.4% vs. 0.5%, P=0.037) than non-MS patients. The proportions of respiratory failure and acute respiratory distress syndrome in MS patients were also higher than non-MS patients during hospitalization. Multivariate analysis showed that concurrent MS (odds ratio [OR] 7.668, 95% confidence interval [CI] 3.062–19.201, P<0.001) and lymphopenia (OR 3.315, 95% CI 1.306–8.411, P=0.012) were independent risk factors of severe illness of COVID-19. At a median follow-up of 28 days after discharge, bilateral pneumonia was found in 95.2% of MS patients, while only 54.7% of non-MS patients presented bilateral pneumonia.Conclusions:19.3% of COVID-19 patients had MS in our study. COVID-19 patients with MS are more likely to develop severe complications and have worse prognosis. More attention should be paid to COVID-19 patients with MS. (AU)

Antecedentes:Pocos estudios han investigado el impacto del síndrome metabólico (SM) en la enfermedad por coronavirus 2019 (COVID-19). Describimos las características clínicas y el pronóstico de los pacientes con COVID-19 confirmados con SM durante la hospitalización y después del alta.Métodos:Se incluyó de forma retrospectiva a 233 pacientes con COVID-19 de los hospitales de 8 ciudades de Jiangsu (China). Se describieron sus características clínicas y se analizaron los factores de riesgo de enfermedad grave mediante un análisis de regresión logística.Resultados:De los 233 pacientes, 45 (19,3%) tenían EM. La mediana de edad de estos pacientes con EM fue significativamente mayor que la de los pacientes sin él (53,0 años frente a 46,0 años; p = 0,004). No hubo diferencias significativas en cuanto a los síntomas clínicos, las imágenes de TC torácica anormales y los fármacos de tratamiento entre los 2 grupos. Hubo más pacientes con EM que tuvieron enfermedades graves (33,3% frente a 6,4%; p < 0,001) y críticas (4,4% frente a 0,5%; p = 0,037) que los pacientes sin EM. Las proporciones de insuficiencia respiratoria y síndrome de dificultad respiratoria aguda en los pacientes con EM también fueron mayores que en los pacientes sin EM durante la hospitalización. El análisis multivariante mostró que la EM concurrente (odds ratio [OR] 7,668; intervalo de confianza [IC] del 95%: 3,062-19,201; p < 0,001) y la linfopenia (OR 3,315; IC del 95%: 1,306-8,411; p = 0,012) eran factores de riesgo independientes de COVID-19 grave. En una mediana de seguimiento de 28 días tras el alta, se encontró neumonía bilateral en el 95,2% de los pacientes con EM, mientras que solo la presentaron el 54,7% de los pacientes sin EM.Conclusiones:El 19,3% de los pacientes con COVID-19 tenían EM en nuestro estudio. Los pacientes con COVID-19 y EM son más propensos a desarrollar complicaciones graves y tienen peor pronóstico. Se debe prestar más atención a los pacientes con COVID-19 y EM. (AU)

Bi2O3 nanoparticles exhibit potent broad-spectrum antimicrobial activity and the ability to overcome Ag-, ciprofloxacin- and meropenem-resistance in P. aeruginosa: the next silver bullet of metal antimicrobials?

Antimicrobial resistance is a persistent threat to global public health. In order to combat the spread of pathogenic bacteria, numerous antimicrobial materials have been incorporated into wound dressings and medical devices such as implants and catheters. The most frequently utilized of these materials are Ag-salts and Ag-nanoparticles (AgNPs) due to their low minimum inhibitory concentrations (MICs) against common Gram-negative pathogenic bacteria such as P. aeruginosa. However, such Ag-based materials are limited to treating Gram-negative bacteria and prone to generating Ag-resistant phenotypes after only 7 consecutive exposures to these materials at a sub-inhibitory concentration. Here, we demonstrate α-Bi2O3 NPs as potential replacements for such materials, i.e., α-Bi2O3 NPs that exhibit potent broad-spectrum antibacterial activity (MIC = 0.75 µg mL-1 against P. aeruginosa; MIC = 2.5 µg mL-1 against S. aureus). Furthermore, these NPs are effective against Ag-resistant and carbapenem-resistant bacteria (MICs = 1.0 µg mL-1 and 1.25 µg mL-1, respectively) and also show a synergistic effect with meropenem (mero) in P. aeruginosa bacteria, allowing for the use of meropenem with smaller therapeutic doses (fractional inhibitory concentration = 0.45). Finally, unlike other materials that have been explored as effective antimicrobials, α-Bi2O3 NPs do not contribute to the development of Bi-resistant phenotypes after 30 passages of consecutive exposure to a sub-lethal dose of such NPs. Our results demonstrate that Bi-based materials represent a critical tool against multidrug resistant bacteria and require greater attention within the community. We anticipate this study to inspire broader investigation into the use of other metal oxides as antimicrobial materials, particularly those that limit the development of resistant phenotypes.

Clinical features and prognosis of COVID-19 patients with metabolic syndrome: A multicenter, retrospective study.

BACKGROUND: Few studies have investigated the impacts of metabolic syndrome (MS) on coronavirus disease 2019 (COVID-19). We described the clinical features and prognosis of confirmed COVID-19 patients with MS during hospitalization and after discharge. METHODS: Two hundred and thirty-three COVID-19 patients from the hospitals in 8 cities of Jiangsu, China were retrospectively included. Clinical characteristics of COVID-19 patients were described and risk factors of severe illness were analyzed by logistic regression analysis. RESULTS: Forty-five (19.3%) of 233 COVID-19 patients had MS. The median age of COVID-19 patients with MS was significantly higher than non-MS patients (53.0 years vs. 46.0 years, P=0.004). There were no significant differences of clinical symptoms, abnormal chest CT images, and treatment drugs between two groups. More patients with MS had severe illness (33.3% vs. 6.4%, P<0.001) and critical illness (4.4% vs. 0.5%, P=0.037) than non-MS patients. The proportions of respiratory failure and acute respiratory distress syndrome in MS patients were also higher than non-MS patients during hospitalization. Multivariate analysis showed that concurrent MS (odds ratio [OR] 7.668, 95% confidence interval [CI] 3.062-19.201, P<0.001) and lymphopenia (OR 3.315, 95% CI 1.306-8.411, P=0.012) were independent risk factors of severe illness of COVID-19. At a median follow-up of 28 days after discharge, bilateral pneumonia was found in 95.2% of MS patients, while only 54.7% of non-MS patients presented bilateral pneumonia. CONCLUSIONS: 19.3% of COVID-19 patients had MS in our study. COVID-19 patients with MS are more likely to develop severe complications and have worse prognosis. More attention should be paid to COVID-19 patients with MS.

Harnessing the toxicity of dysregulated iron uptake for killing Staphylococcus aureus: reality or mirage?

Iron is essential for all forms of life including pathogenic bacteria. However, iron is also a double-edged sword in biology, as increase of iron uptake can result in reactive oxygen species (ROS)-triggered cell death from the iron-catalyzed Fenton reaction. In this study, we demonstrate that iron-hinokitiol, Fe(hinok)3, a neutral Fe(III) complex formed with the naturally occurring metal chelator hinokitiol; (2-hydroxy-4-isopropyl-2,4,6-cycloheptatrien-1-one) can harness the clear ability, due to its high lipophilicity and the nonpolar nature, to penetrate the cell membrane of Staphylococcus aureus (SA) and exhibit potent antimicrobial activity that is enhanced by approximately 10 000 times as compared with hinokitiol itself. Additionally, this Fe(III) complex shows a strong ability to inhibit biofilm formation. More importantly, the development of resistance in SA toward this complex is considerably hampered in comparison with that toward ciprofloxacin. The in vivo evaluation of antimicrobial efficacy in the murine model of skin wound infection by SA confirms that the treatment with a single dose of this complex can reduce the bacterial burden by 83%, demonstrating the therapeutic potential of Fe(hinok)3 in treating skin and soft tissue infections.

An aluminum lining to the dark cloud of silver resistance: harnessing the power of potent antimicrobial activity of γ-alumina nanoparticles.

Although a biologically nonessential element in living organisms, aluminum is notably nontoxic to eukaryotic cells and has a venerable history of medicinal use. We demonstrate that polyethylene glycol-coated γ-alumina nanoparticles (Al2O3-NPs) with an average size of 15 nm prepared from a commercial bulk γ-alumina (γ-Al2O3) via the top-down sonication technique exhibit antibacterial activity that is comparable to that of AgNPs against both the Gram-negative drug-susceptible Pseudomonas aeruginosa (DSPA) and multidrug-resistant Pseudomonas aeruginosa (DRPA) bacteria, while the antibacterial activity of such Al2O3-NPs considerably surpasses that of AgNPs against both the Gram-positive methicillin-susceptible Staphylococcus aureus (DSSA) and methicillin-resistant Staphylococcus aureus (MRSA) bacteria. We also demonstrate that the DSPA bacteria sequentially exposed to Al2O3-NPs for 30 days show no indication of resistance development. Furthermore, such Al2O3-NPs can completely overcome the drug resistance developed in the conventional antibiotic ciprofloxacin-resistant and AgNP-resistant mutants without developing Al resistance.

K2 Mn3 [FeII (CN)6 ]2 NPs with High T1 -Relaxivity Attributable to Water Coordination on the Mn(II) Center for Gastrointestinal Tract MR Imaging.

The lack of acid stability in the stomach and of temporal stability when moving through the gastrointestinal (GI) tract has made the development of oral magnetic resonance imaging (MRI) contrast agents based on the platform of Gd3+ -complexes problematic.On the other hand, the negative contrast enhancement produced by the T2 -weighted magnetic metal oxide nanoparticles (NPs) often renders the image readout difficult. Biocompatible NPs of the manganese Prussian blue analog K2 Mn3 [FeII (CN)6 ]2 exhibit extremely high stability under the acidic conditions of the gastric juice. Additionally, the high r1 relaxivity, low toxicity, and high temporal stability of such NPs offer great potential for the development of a true T1 -weighted oral contrast agent for MRI of the entire GI tract.

Clinical and virological course of patients with coronavirus disease 2019 in Jiangsu province, China: a retrospective, multi-center cohort study.

BACKGROUND: The clinical and virological course of patients with coronavirus disease 2019 (COVID-19) are lacking. We aimed to describe the clinical and virological characteristics of COVID-19 patients from 10 designated hospitals in 10 cities of Jiangsu province, China. The factors associated with the clearance of SARS-CoV-2 were investigated. METHODS: A total of 328 hospitalized patients with COVID-19 were retrospectively recruited. The epidemiological, clinical, laboratory, radiology and treatment data were collected. The associated factors of SARS-CoV-2 clearance were analyzed. RESULTS: The median duration of hospitalization was 16.0 days (interquartile range [IQR] 13.0-21.0 days). On multivariate Cox regression analysis, age > 60 years (hazard ratio [HR] 0.643, 95% confidence interval [CI] 0.454-0.911, P = 0.013) was associated with the delayed SARS-CoV-2 clearance, while the atomized inhalation of interferon α-2b could improve the clearance of SARS-CoV-2 (HR, 1.357, 95% CI 1.050-1.755, P = 0.020). Twenty-six (7.9%) patients developed respiratory failure and 4 (1.2%) patients developed ARDS. Twenty (6.1%) patients were admitted to the ICU, while no patient was deceased. CONCLUSIONS: Our study found that age > 60 years was associated with the delayed SARS-CoV-2 clearance, while treated with atomized inhalation of interferon α-2b could promote the clearance of SARS-CoV-2.

Risk of severe illness of COVID-19 patients with NAFLD and increased NAFLD fibrosis scores.

BACKGROUND: There is still little knowledge about the association of liver fibrosis with the clinical outcomes of COVID-19 patients with non-alcoholic fatty liver disease (NAFLD). The aim of the study was to determine the association of NAFLD fibrosis score (NFS)-determined liver fibrosis with clinical outcomes of COVID-19 patients with NAFLD. METHODS: The NAFLD was diagnosed by the Hepatic Steatosis Index (HSI) in the absence of other causes of chronic liver diseases. NFS was used to evaluate the severity of liver fibrosis. RESULTS: A total of 86 COVID-19 patients with NAFLD were included. The median age was 43.5 years, and 58.1% of patients were male. Thirty-eight (44.2%) patients had advanced liver fibrosis according to the NFS. Multivariate analysis indicated that concurrent diabetes (odds ratio [OR] 8.264, 95% confidence interval [CI] 1.202-56.830, p = 0.032) and advanced liver fibrosis (OR 11.057, 95% CI 1.193-102.439, p = 0.034) were independent risk factors of severe illness in COVID-19 patients with NAFLD. CONCLUSION: NAFLD patients with NFS-determined advanced liver fibrosis are at higher risk of severe COVID-19.

Lipophilic Ga Complex with Broad-Spectrum Antimicrobial Activity and the Ability to Overcome Gallium Resistance in both Pseudomonas aeruginosa and Staphylococcus aureus.

Antibiotic resistance (AR) necessitates the discovery of new antimicrobials with alternative mechanisms of action to those employed by conventional antibiotics. One such strategy utilizes Ga3+ to target iron metabolism, a critical process for survival. Still, Ga-based therapies are generally ineffective against Gram-positive bacteria and promote Ga resistance. In response to these drawbacks, we report a lipophilic Ga complex, [Ga2L3(bpy)2] (L = 2,2'-bis(3-hydroxy-1,4-naphthoquinone; bpy = 2,2'-bipyridine)), effective against drug-resistant Pseudomonas aeruginosa (DRPA; minimum inhibitory concentration, MIC = 10 µM = 14.8 µg/mL) and methicillin-resistant Staphylococcus aureus (MRSA, MIC = 100 µM = 148 µg/mL) without iron-limited conditions. Importantly, [Ga2L3(bpy)2] shows noticeably delayed and decreased resistance in both MRSA and DRPA, with only 8× MIC in DRPA and none in MRSA after 30 passages. This is likely due to the dual mode of action afforded by Ga (disruption of iron metabolism) and the ligand (reactive oxygen species production). Overall, [Ga2L3(bpy)2] demonstrates the utility of lipophilic metal complexes with multiple modes of action in combatting AR in Gram-positive and Gram-negative bacteria.