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Biobanking of tissue from clinically obtained kidney biopsies for later analysis with multiomic approaches, such as single-cell technologies, proteomics, metabolomics, and the different types of imaging, is an inevitable step to overcome the need of disease model systems and toward translational medicine. Hence, collection protocols that ensure integration into daily clinical routines by the usage of preservation media that do not require liquid nitrogen but instantly preserve kidney tissue for both clinical and scientific analyses are necessary. Thus, we modified a robust single-nucleus dissociation protocol for kidney tissue stored snap-frozen or in the preservation media RNAlater and CellCover. Using at first porcine kidney tissue as a surrogate for human kidney tissue, we conducted single-nucleus RNA sequencing with the widely recognized Chromium 10X Genomics platform. The resulting datasets from each storage condition were analyzed to identify any potential variations in transcriptomic profiles. Furthermore, we assessed the suitability of the preservation media for additional analysis techniques such as proteomics, metabolomics, and the preservation of tissue architecture for histopathological examination including immunofluorescence staining. In this study, we show that in daily clinical routines, the preservation medium RNAlater facilitates the collection of highly preserved human kidney biopsies and enables further analysis with cutting-edge techniques like single-nucleus RNA sequencing, proteomics, and histopathological evaluation. Only metabolome analysis is currently restricted to snap-frozen tissue. This work will contribute to build tissue biobanks with well-defined cohorts of the respective kidney disease that can be deeply molecularly characterized, opening up new horizons for the identification of unique cells, pathways and biomarkers for the prevention, early identification, and targeted therapy of kidney diseases. NEW & NOTEWORTHY In this study, we addressed challenges in integrating clinically obtained kidney biopsies into everyday clinical routines. Using porcine kidneys, we evaluated preservation media (RNAlater and CellCover) versus snap freezing for multi-omics processing. Our analyses highlighted RNAlater's suitability for single-nucleus RNA sequencing, proteome analysis and histopathological evaluation. Only metabolomics are currently restricted to snap-frozen biopsies. Our research established a cryopreservation protocol that facilitates tissue biobanking for advancing precision medicine in nephrology.

Th17 cells play crucial roles in host defense and the pathogenesis of autoimmune diseases in the skin. While their differentiation mechanisms have been extensively studied, the origin of skin Th17 cells remains unclear. In this study, we analyzed single-cell RNA-sequencing data and identify the presence of Th17 cells in the human thymus. Thymic Th17 cells were characterized by high expression levels of Sphingosine-1-Phosphate Receptor 1 (S1PR1), a receptor crucial for T cell egress from lymphoid tissues. In mice, Th17 cell-specific knockout of S1pr1 resulted in the accumulation of Th17 cells in the thymus and a corresponding decrease in their numbers in the skin. Th17 cells that accumulated in the thymus exhibited a lower IL-17A production capacity compared to those in the skin, indicating that the local environment in the skin is important for maintaining the Th17 cell phenotype. Additionally, using a murine psoriasis model, we demonstrated that Th17 cell-specific knockout of S1pr1 reduced their migration to the inflamed skin, thereby ameliorating disease progression. Collectively, our data suggest that S1PR1 mediates Th17 cell migration from the thymus to the skin, thereby modulating their functional engagement in both homeostatic and inflammatory conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Engesser, Wang, Kapffer, Kaffke, Peters, Paust, Geissen, Krebs, Panzer and Asada.)

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a life-threatening autoimmune disease that often results in kidney failure caused by crescentic glomerulonephritis (GN). To date, treatment of most patients with ANCA-GN relies on non-specific immunosuppressive agents, which may have serious adverse effects and be only partially effective. Here, using spatial and single-cell transcriptome analysis, we characterize inflammatory niches in kidney samples from 34 patients with ANCA-GN and identify proinflammatory, cytokine-producing CD4 + and CD8 + T cells as a pathogenic signature. We then utilize these transcriptomic profiles for digital pharmacology and identify ustekinumab, a monoclonal antibody targeting IL-12 and IL-23, as the strongest therapeutic drug to use. Moreover, four patients with relapsing ANCA-GN are treated with ustekinumab in combination with low-dose cyclophosphamide and steroids, with ustekinumab given subcutaneously (90 mg) at weeks 0, 4, 12, and 24. Patients are followed up for 26 weeks to find this treatment well-tolerated and inducing clinical responses, including improved kidney function and Birmingham Vasculitis Activity Score, in all ANCA-GN patients. Our findings thus suggest that targeting of pathogenic T cells in ANCA-GN patients with ustekinumab might represent a potential approach and warrants further investigation in clinical trials., (© 2024. The Author(s).)

Background: Most patients with chronic kidney disease (CKD) are old, comorbid, and subjected to polypharmacy. This study describes prevalence and predictors of potentially inappropriate medication (PIM) in CKD patients., Materials and Methods: Medication plans of CKD patients of the "Greifswald Approach to Individualized Medicine" cross-sectional study (GANI_MED) were checked for PIM based on kidney function (PIM-K) and PIM for elderly patients (PIM-E). PIM-K were defined by prescription instructions of product labeling. PIM-E were defined by BEERS, -PRISCUS, and FORTA criteria. Predictors for PIM were identified through multiple stepwise regression., Results: 375 patients were included (age: 67.9 ± 13.5 years; estimated glomerular filtration rate (eGFR): 23.3 ± 18.6 mL/min/1.73m 2 ; prescriptions: 11.1 ± 4.7). 44.5% of all CKD patients had PIM-K, and 43.2 to 79.0% of all elderly patients had PIM-E. Polypharmacy and reduced eGFR were predictors for PIM. The risk for PIM-K was increased by 3.8 (95% confidence interval (CI): 1.5 - 9.6) with 10 or more prescriptions and by 8.7 (95% CI: 1.3 - 58.5) with an eGFR below 30 mL/min/1.73m 2 . On average, elderly patients with 10 or more prescriptions had 3.0 ± 1.7 PIM-E., Conclusion: Polypharmacy, PIM-K, and PIM-E affect many CKD patients and can lead to adverse events. Deprescribing and targeted prescribing may improve the outcome of CKD patients and elderly patients.

Pathogenic mucormycetes induce diseases with considerable morbidity and mortality in immunocompromised patients. Virulence data comparing different Mucorales species and various underlying risk factors are limited. We therefore compared the pathogenesis of inhalative infection by Rhizopus (R.) arrhizus and Lichtheimia (L.) corymbifera in murine models for predominant risk factors for onset of infection. Mice with diabetes or treated with cyclophosphamide or cortisone acetate were challenged via the intranasal route with an isolate of R. arrhizus or L. corymbifera, respectively. Clinical, immunological and inflammation parameters as well as efficacy of posaconazole prophylaxis were monitored over 14 days. Whereas immunocompetent mice showed no clinical symptoms after mucormycete infection, mice treated with either cyclophosphamide (CP) or cortisone acetate (CA) were highly susceptible. Animals infected with the isolate of R. arrhizus showed prolonged survival and lower mortality, compared to those exposed to the L. corymbifera isolate. This lower virulence of R. arrhizus was risk factor-dependent, since diabetic mice died only after infection with Rhizopus, whereas all Lichtheimia-infected diabetic animals survived. Under posaconazole prophylaxis, both mucormycetes were able to establish breakthrough infections in CA- and CP-treated mice, but the course of infection was significantly delayed. Detailed analysis revealed that susceptibility of CA- and CP-treated mice could not be mimicked by exclusive lack or downmodulation of neutrophils, platelets or complement, but can be supposed to be the consequence of a broad immunosuppressive effect induced by the drugs. Both Lichtheimia corymbifera and Rhizopus arrhizus induce invasive mycoses in immunocompromised hosts after inhalative infection. Key parameters such as virulence and immunopathogenesis vary strongly according to fungal species and underlying risk group. Selected neutropenia is no sufficient risk factor for onset of inhalative mucormycosis., Competing Interests: The authors have declared that no competing interests exist. As mentioned in the Funding Statement, the “INNPATH GmbH” is a diagnostic institute for clinical pathology and molecular pathology and is a 100% affiliate of the “Tirol Kliniken” (Tyrol Clinics). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Dialysis patients are frequently exposed to Staphylococcus aureus due to stays in dialysis centers, hospitals or rest homes. The hemodialysis vascular access is a potential entry site for S. aureus, in particular when using a central venous catheter (CVC) which increases the risk of sepsis compared to arteriovenous (AV) fistula. We prospectively followed a cohort of 86 hemodialysis patients from an outpatient dialysis center over 25 months analyzing S. aureus carrier status, S. aureus infection rates and mortality., Methods: Demographic data and patients´ medical histories were collected and followed from all hemodialysis patients. Blood samples, nasal swabs and swabs from the hemodialysis vascular access site were taken every six months for a period of 25 months and tested for S. aureus. Strains were cultured and further characterized by spa PCR and microarray-based genotyping. Resulting data were compared with those from the general population., Results: In cross-sectional analyses, an average of 40% of hemodialysis patients were S. aureus carriers compared to 27% in the general population. Longitudinally, a total of 65% were S. aureus carriers: 16% were persistent carriers, 43% were intermittently colonized. The most common S. aureus lineage in the dialysis patient cohort was the clonal complex (CC) 8 and the spa type t008, while in the general population, the clonal complex CC30 dominates. During the study period, we observed six S. aureus-associated blood stream infections with one S. aureus attributable death. S. aureus carriers with an AV fistula were more densely colonized in the nasal mucosa compared to patients with a CVC. Overall mortality was lower for hemodialysis patients with a positive S. aureus carrier status compared to non-carriers (hazard ratio of 0.19)., Conclusions: Compared to the general population, hemodialysis patients were more frequently colonized with S. aureus and displayed both different S. aureus colonization densities as well as lineages, possibly explained by more frequent exposure to health care environments. The lower overall mortality in carriers compared to non-carriers is intriguing and will be investigated in detail in the future., Trial Registration: ISRCTN 14385893 , 2. October 2018, retrospectively registered.

Objective: Potentially Inappropriate Medications (PIMs) in older patients are prevalent and possess the potential for modification. It is linked to several detrimental health outcomes. The extent of research pertaining to PIMs in Thailand remains restricted. The primary aim of the present study was to determine the prevalence of PIMs, employing the Beers criteria from 2023. The secondary objective focused on the identification of factors correlated with PIMs within this population. Materials and Methods: A retrospective electronic medical record of older patients at outpatient clinics of Srinagarind Hospital during November 2021 and November 2022 was reviewed. Patient demographic data were collected and analyzed. The Beers criteria (version 2023) were employed for identifying PIMs. Logistic regression analysis was used to determine contributing to the occurrence of PIMs. Results: Of the 23,758 patients enrolled, 49.03% were found to have at least one PIM. The factors that exhibited associations were age (odds ratio [OR] 1.01), polypharmacy (=5 medications) (OR 6.29), dementia (OR 1.84), osteoarthritis (OR 1.40), chronic kidney disease (OR 1.29), hypertension (OR 1.15), dyslipidemia (OR 0.87), diabetes mellitus (OR 0.84), gastritis/gastrointestinal reflux disease/peptic ulcer disease (OR 0.59), and peripheral vascular disease (OR 0.29). Conclusion: The present study highlights the high prevalence of PIMs among elderly outpatients. Factors associated with PIMs were identified, it is possible to develop and implement targeted strategies aimed at reducing the use of PIMs in order to mitigate the negative clinical consequences associated with PIMs in these populations. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to compare the prevalence of potentially inappropriately prescribed drugs in hemodialysis patients and patients with chronic kidney disease who did not require renal replacement therapy, as well as to identify risk factors associated with potentially inappropriate prescribing. Methods: The study was designed as a cross‐sectional study conducted at the Department of Nephrology, Clinical Center in Nis, Serbia. The patients were divided into two groups: (1) patients on hemodialysis treatment and (2) patients with various degrees of chronic kidney disease without renal replacement therapy. The presence or absence of potentially inappropriate prescribing was determined using the 2015 AGS Beers criteria. Findings: The study included a total of 218 patients aged 65 years and over. The number of patients with potentially inappropriate prescribed drugs did not differ significantly (chi‐square = 0.000, p = 1.000) between patients on hemodialysis (27 of 83, i.e., 32.5%) and patients with various degrees of chronic kidney disease without renal replacement therapy (44 of 135, i.e., 32.6%). Factors associated with potentially inappropriate prescribing in hemodialysis patients were the number of drugs (hazard ratio [HR] = 1.919, 95% confidence interval [CI]: 1.325–2.780) and number of comorbidities (HR = 1.743, 95% CI: 1.109–2.740). The number of drugs (HR = 1.438, 95% CI: 1.191–1.736) was the only independent factor associated with increased risk of potentially inappropriate prescribing in patients without renal replacement therapy. Discussion: Our study showed that potentially inappropriate prescribing is a relatively frequent phenomenon present in about a third of patients in both study groups. The number of prescribed drugs was the main factor associated with the increased risk of potentially inappropriate prescribing in both groups. [ABSTRACT FROM AUTHOR]

Molybdenum dinitrogen complexes have played a major role as catalytic model systems of nitrogenase. In comparison, analogous tungsten complexes have in most cases found to be catalytically inactive. Herein, a tungsten complex was shown to be supported by a pentadentate tetrapodal (pentaPod) phosphine ligand, under conditions of N 2 fixation, primarily catalyzes the hydrogen evolution reaction (HER), in contrast to its Mo analogue, which catalytically mediates the nitrogen-reduction reaction (N 2 RR). DFT calculations were employed to evaluate possible mechanisms and identify the most likely pathways of N 2 RR and HER activities exhibited by Mo- and W-pentaPod complexes. Two mechanisms for N 2 RR by PCET are considered, starting from neutral (M(0) cycle) and cationic (M(I) cycle) dinitrogen complexes (M=Mo, W). The latter was found to be energetically more favorable. For HER three scenarios are treated; that is, through bimolecular reactions of early M-N x H y intermediates, pure hydride intermediates or mixed M(H)(N x H y ) species., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Mucormycosis presents a formidable challenge to clinicians and researchers. Animal models are an essential part of the effort to decipher the pathogenesis of mucormycosis and to develop novel pharmacotherapeutics against it. Diverse model systems have been established, using a range of animal hosts, immune and metabolic perturbations, and infection routes. An understanding of the characteristics, strengths, and drawbacks of these models is needed to optimize their use for specific research aims. [ABSTRACT FROM AUTHOR]

It has been observed in literature that the stability of tyrosinase‐mimicked μ‐η2:η2‐peroxo‐dicopper(II) (P) can be perturbed in presence of counter‐anions (CAs) such as PhCO2−, CF3SO3−, TsO− and SbF6−. In this work, we unravel computational indicators using density functional theory to screen and study the stability of P in experimentally‐reported cases. These indicators are Gibbs energies, geometrical parameters such as distances and angles, independent gradient model based on Hirshfeld partition (IGMH) generated data, orbitals' overlap, and distortion‐interaction (DI) energies. Our DFT computed Gibbs energies indicate that P is stable in case of PhCO2− and TsO−. CF3SO3− allows P and its isoelectronic species bis‐μ‐oxo‐dicopper (O) to coexist. SbF6− shows that O is in excess. Our indicators reveal that the stability of P in case of PhCO2− and TsO− is due to the better placing of P and its CA, thus leading to better interactions and overlap of orbitals. Other indicator displays that the plane of Cu2O2 core in P is more bend in PhCO2− and TsO− cases as compared to the plane in the other two cases. In addition, the IGMH‐based indicator displays higher values in the case of PhCO2− and TsO− than the other CAs. [ABSTRACT FROM AUTHOR]

A novel dinucleating bis(pyrazolyl)methane ligand was developed for tyrosinase model systems. After ligand synthesis, the corresponding Cu(I) complex was synthesized and upon oxygenation, formation of a µ-η2:η2 peroxido complex could be observed and monitored using UV/Vis-spectroscopy. Due to the high stability of this species even at room temperature, a molecular structure of the complex could be characterized via single-crystal XRD. Additional to its promising stability, the peroxido complex showed catalytic tyrosinase activity which was investigated via UV/Vis-spectroscopy. Products of the catalytic conversion could be isolated and characterized and the ligand could be successfully recycled after catalysis experiments. Furthermore, the peroxido complex was reduced by reductants with different reduction potentials. The characteristics of the electron transfer reactions were investigated with the help of the Marcus relation. The combination of the high stability and catalytic activity of the peroxido complex with the new dinucleating ligand, enables the shift of oxygenation reactions for selected substrates towards green chemistry, which is furthered by the efficient ligand recycling capability. [ABSTRACT FROM AUTHOR]

Molybdenum dinitrogen complexes have played a major role as catalytic model systems of nitrogenase. In comparison, analogous tungsten complexes have in most cases found to be catalytically inactive. Herein, a tungsten complex was shown to be supported by a pentadentate tetrapodal (pentaPod) phosphine ligand, under conditions of N2 fixation, primarily catalyzes the hydrogen evolution reaction (HER), in contrast to its Mo analogue, which catalytically mediates the nitrogen‐reduction reaction (N2RR). DFT calculations were employed to evaluate possible mechanisms and identify the most likely pathways of N2RR and HER activities exhibited by Mo‐ and W‐pentaPod complexes. Two mechanisms for N2RR by PCET are considered, starting from neutral (M(0) cycle) and cationic (M(I) cycle) dinitrogen complexes (M=Mo, W). The latter was found to be energetically more favorable. For HER three scenarios are treated; that is, through bimolecular reactions of early M‐NxHy intermediates, pure hydride intermediates or mixed M(H)(NxHy) species. [ABSTRACT FROM AUTHOR]

Synthetic biology applies concepts from electrical engineering and information processing to endow cells with computational functionality. Transferring the underlying molecular components into materials and wiring them according to topologies inspired by electronic circuit boards has yielded materials systems that perform selected computational operations. However, the limited functionality of available building blocks is restricting the implementation of advanced information-processing circuits into materials. Here, a set of protease-based biohybrid modules the bioactivity of which can either be induced or inhibited is engineered. Guided by a quantitative mathematical model and following a design-build-test-learn (DBTL) cycle, the modules are wired according to circuit topologies inspired by electronic signal decoders, a fundamental motif in information processing. A 2-input/4-output binary decoder for the detection of two small molecules in a material framework that can perform regulated outputs in form of distinct protease activities is designed. The here demonstrated smart material system is strongly modular and can be used for biomolecular information processing for example in advanced biosensing or drug delivery applications., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Background: Mucormycetes, a heterogeneous group of fungi, induce a life-threatening disease called mucormycosis. Immune deficiencies represent a major risk factor; hence, we wanted to illuminate the role of complement and platelets in the defense against mucormycetes. Methods: Rhizopus arrhizus (Ra), Rhizopus microsporus (Rm), Lichtheimia ramosa (Lr), Lichtheimia corymbifera (Lc), Rhizomucor pusillus (Rmp), and Mucor circinelloides (Mc) spores were opsonized with human and mouse serum, and C1q, C3c, and terminal complement complex (C5b-9) deposition was measured. Additionally, thrombocytopenic, C3-deficient, or C6-deficient mice were intravenously infected with selected isolates. Survival and immunological parameters were monitored, and fungal burden was determined and compared to that of immunocompetent and neutropenic mice. Results: In vitro experiments showed significant differences in complement deposition between mucormycetes. Mc isolates bound up to threefold more human C5b-9 than other mucormycetes. Lr, Lc, and Mc bound high levels of murine C3c, whereas human C3c deposition was reduced on Mc compared to Lr and Lc. Murine C3c deposition negatively correlated with virulence. Complement deficiencies and neutropenia, but not thrombocytopenia, were shown to be a risk factor for a lethal outcome. Conclusion: Complement deposition varies between mucormycetes. Additionally, we demonstrated that complement and neutrophilic granulocytes, but not platelets, play an important role in a murine model of disseminated mucormycosis. [ABSTRACT FROM AUTHOR]

Iron ore pellets not only have excellent metallurgical and mechanical properties but are also essential raw materials for improving iron and steel smelting in the context of the increasing global depletion of high-grade iron ore resources. Organic polymers, as important additive components for the production of high-quality pellets, have a significant impact on the formation as well as the properties of pellets. In this review, the mechanisms of organic polymers on the pelletizing properties, bursting temperature, and pellet strength at low and high temperatures, as well as the existing measures and mechanisms to improve the high-temperature strength of the organic binder pellets are systematically summarized. Compared with traditional bentonite additives, the organic polymers greatly improve the pelletizing rate and pellet strength at low temperatures, and significantly reduces metallurgical pollution. However, organic binders often lead to a decrease in pellet bursting temperature and pellet strength at high temperatures, which can be significantly improved by compounding with a small amount of low-cost inorganic minerals, such as bentonite, boron-containing compounds, sodium salts, and copper slag. At the same time, some industrial solid wastes can be rationally used to reduce the cost of pellet binders. [ABSTRACT FROM AUTHOR]

Pellet ore not only has excellent metallurgical and mechanical properties, but is also an important metallurgical raw material used to solve the problem of increasing depletion of global high-grade iron ore resources. Bentonite has long been widely used in pellet ore production, which is not only expensive but also causes serious metallurgical pollution. Organic binders can form stronger adhesion and cohesion with mineral particles inside the green pellets than capillary forces, which greatly improves the pelletizing rate and significantly increases the strength of green and dry pellets, and it becomes an indispensable alternative to bentonite because it volatilizes pyrolytically at high temperatures, leaving almost no inorganic contaminants inside the pellet ore. In order to let more pellet researchers fully understand the research status and pelletizing theory of organic binders, this review systematically summarizes seven common organic binders, and elaborates on their adhesion mechanism and process characteristics, so as to provide references for pellet researchers and readers to further prepare cost-effective pellet binders and improve advanced pelletizing technology. [ABSTRACT FROM AUTHOR]

Objective: Staphylococcus aureus nasal carriage screening among hemodialysis patients is not standard practice in Thailand, because of data lacking regarding prevalence and correlation with subsequent infection. We aimed to investigate the prevalence of S. aureus nasal carriage and its association with bloodstream infection among hemodialysis patients. In this prospective multicenter cohort study, participants were screened for S. aureus nasal carriage over 2 consecutive weeks. Incidence of S. aureus bloodstream infection over the next 12 months was observed. Results: The prevalence of S. aureus nasal carriage was 11.67%. Incidence of S. aureus bacteremia among participants with and without S. aureus nasal carriage were 7.1% and 3.8%, respectively. The odds ratio for nasal carriage and subsequent bacteremia was 1.96 (95% CI 0.04–21.79; p = 0.553). Survival analysis showed that time to bacteremia among participants in the two groups did not significantly differ (p = 0.531). Prevalence of S. aureus nasal carriage among hemodialysis patients in Thailand was low. Patients presenting with S. aureus nasal carriage did not have increased risk of S. aureus bacteremia after 12-month follow-up. Nasal S. aureus screening and decolonization should not be encouraged in this setting. [ABSTRACT FROM AUTHOR]

This study explores the rhetoric, discourse, visual representation, and news narratives regarding asylum seekers (AS) in the European Union in Israeli media. Integrating cultural representation theory and foreign news proximity-distance approaches, this research focuses on differences in media coverage of AS in the EU between mainstream, community, and social media, and then suggests a model and theoretical implications. The sample included 340 Hebrew language news items from television, print and online newspapers, radio broadcasts, and social media posts from 2011 to 2019. A thematic analysis was conducted. Based on theory of representation, this study found that AS are presented as Others in two different ways based on media type. Community and social media seek to productively compare the Other (AS) to Israelis to encourage concern over Israeli identity and values. In contrast, mainstream media promote narratives that do not invite comparisons—either tacit or explicit—to Israel. Based on proximity-distance approaches, we found that mainstream media content is appropriated by social and community media for different rhetorical ends using a scale of proximity ranging from hostile to hospitable. Community and social media used mainly domestication rhetoric in contrast to mainstream media, which distance the issue, covering it as newsworthy. [ABSTRACT FROM AUTHOR]

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N-chlorotaurine (NCT) can be used topically as a well-tolerated anti-infective at different body sites. The aim of this study was to investigate the efficacy of inhaled NCT in a mouse model of fungal pneumonia. Specific pathogen-free female C57BL/6JRj seven-week-old mice were immune-suppressed with cyclophosphamide. After 4 days, the mice were inoculated intranasally with 1.5 × 10E7 spores of Lichtheimia corymbifera or 1.0 × 10E7 spores of Aspergillus fumigatus. They were randomized and treated three times daily for 10 min with aerosolized 1% NCT or 0.9% sodium chloride starting 1 h after the inoculation. The mice were observed for survival for two weeks, and fungal load, blood inflammation parameters, bronchoalveolar lavage, and histology of organs were evaluated upon their death or at the end of this period. Inhalations were well-tolerated. After challenge with L. corymbifera, seven out of the nine mice (77.8%) survived for 15 days in the test group, which was in strong contrast to one out of the nine mice (11.1%) in the control group (p = 0.0049). The count of colony-forming units in the homogenized lung tissues came to 1.60 (1.30; 1.99; median, quartiles) log10 in the test group and to 4.26 (2.17; 4.53) log10 in the control group (p = 0.0032). Body weight and temperature, white blood count, and haptoglobin significantly improved with NCT treatment. With A. fumigatus, all the mice except for one in the test group died within 4 days without a significant difference from the control group. Inhaled NCT applied early demonstrated a highly significant curative effect in L. corymbifera pneumonia, while this could not be shown in A. fumigatus pneumonia, probably due to a too high inoculum. Nevertheless, this study for the first time disclosed efficacy of NCT in pneumonia in vivo. [ABSTRACT FROM AUTHOR]

Introduction: Staphylococcus aureus is a successful pathogen in hospital and community. Hemodialysis patients have high colonization rates. Interactions between them and their household contacts, are an opportunity to understand the S. aureus colonization between hospitals and community. This study aims to determine the clinical and epidemiological characteristics of S. aureus colonization in hemodialysis patients and their household contacts, as well as the genetic relationship between their isolates. Methods: A cross-sectional study was conducted on hemodialysis patients from hospital-associated dialysis center in Medellín-Colombia, and their household contacts between 2019 and 2020. Colonization was assessed in the nostrils for household contacts and nostrils and skin around the catheter insertion for hemodialysis patients. Epidemiological information was obtained, and colonization was evaluated in their pets' oral cavities. Bacterial identification and susceptibility were assessed using phenotypic and molecular methods. Molecular typing included SCCmec typing, pulsed-field gel electrophoresis (PFGE), spa typing, and virulence factor detection. Results: Colonization frequency was 35.6% (n = 16/45) in patients (87.5% MSSA– 12.5% MRSA) and 43.1% (n = 53/123) in household contacts (88.7% MSSA—11.3% MRSA). Of 45 homes, 77.8% presented colonized people. Colonization was detected in at least two household members in 46.7% of homes, of which 52.4% had a genetic relationship. Colonization was 16% (n = 4/25) in pets (75% MRSA—25% MSSA). The most frequent clonal complex was CC8 (15.6%), and the spa typing revealed high diversity. Conclusion: This study shows a high frequency of colonization by S. aureus in both hemodialysis patients and their household contacts and a significant genetic relationship between their isolates. This demonstrates an exchange of this bacterium and that homes are an important source of colonization to patients, highlighting the need for prevention strategies outside the hospital to avoid future infections, and the importance of the populations with permanent transit between the two environments. [ABSTRACT FROM AUTHOR]

It has been observed in literature that the stability of tyrosinase-mimicked μ-η 2 :η 2 -peroxo-dicopper(II) (P) can be perturbed in presence of counter-anions (CAs) such as PhCO 2 - , CF 3 SO 3 - , TsO - and SbF 6 - . In this work, we unravel computational indicators using density functional theory to screen and study the stability of P in experimentally-reported cases. These indicators are Gibbs energies, geometrical parameters such as distances and angles, independent gradient model based on Hirshfeld partition (IGMH) generated data, orbitals' overlap, and distortion-interaction (DI) energies. Our DFT computed Gibbs energies indicate that P is stable in case of PhCO 2 - and TsO - . CF 3 SO 3 - allows P and its isoelectronic species bis-μ-oxo-dicopper (O) to coexist. SbF 6 - shows that O is in excess. Our indicators reveal that the stability of P in case of PhCO 2 - and TsO - is due to the better placing of P and its CA, thus leading to better interactions and overlap of orbitals. Other indicator displays that the plane of Cu 2 O 2 core in P is more bend in PhCO 2 - and TsO - cases as compared to the plane in the other two cases. In addition, the IGMH-based indicator displays higher values in the case of PhCO 2 - and TsO - than the other CAs., (© 2023 Wiley-VCH GmbH.)

Tripod ligands with a neopentyl backbone and one (trpd‐1 pln), two (trpd‐2 pln) or three (trpd‐3 pln) phospholane end groups are synthesized and used for the synthesis of MoX3 (X=Cl, Br, I) complexes supported by these ligands. NaxHg reduction of [MoBr3(trpd‐3 pln)], in the presence of N2 and the bidentate coligand dppm leads to the molybdenum(0) mono(dinitrogen) complex [Mo(N2)(trpd‐3 pln)(dppm)] with a moderately activated N2 ligand. An attempt to further increase the activation by using dmpm as coligand leads to a mixture containing desired [Mo(N2)(trpd‐3 pln)(dmpm)], but also the bis(dinitrogen) complex [Mo(N2)2(κ2‐trpd‐3 pln)2] and the homoleptic complex [Mo(trpd‐3 pln)2]. Protonation of [Mo(N2)(trpd‐3 pln)(dppm)] with [H(OEt2)2][Al{OC(CF3)3}4] generates the hydrazido(2‐) complex [Mo(NNH2)(trpd‐3 pln)(dppm)][Al{OC(CF3)3}4]2. [ABSTRACT FROM AUTHOR]

Coronavirus disease (COVID-19)-associated mucormycosis (CAM) is an emerging threat globally, especially in India. More than 40,000 CAM cases have been reported in India. The emergence of CAM cases in India has been attributed to environmental, host, and iatrogenic factors. Mucorales spore burden has been reported globally; however, their presence is higher in tropical countries such as India, contributing to the emergence of CAM. Before the COVID-19 pandemic, patients with diabetes mellitus, haematological malignancies, solid organ transplants, corticosteroid therapy and neutropenia were more prone to mucormycosis, whereas in COVID-19 patients, virus-induced endothelial dysfunction, hyperglycaemia, and immune dysfunction following corticosteroid use increase the risk of acquiring mucormycosis. The interaction of Mucorales spores with the epithelial cells, followed by endothelial invasion, is a crucial step in the pathogenesis of mucormycosis. Endothelial damage and increased endothelial receptor expression induced by COVID-19 infection may predispose patients to CAM. COVID-19 infection may directly induce hyperglycaemia by damaging beta cells of the pancreas or by corticosteroid therapy, which may contribute to CAM pathogenesis. Iron acquisition from the host, especially in diabetic ketoacidosis (DKA) or deferoxamine therapy, is an important virulence trait of Mucorales. Similarly, the hyperferritinaemia caused by COVID-19 may act as a source of iron for Mucorales growth and invasion. In addition, corticosteroid treatment reduces or abolishes the innate immune functions of phagocytic cells contributing to the pathogenesis of CAM. This review aims to discuss primarily the host and iatrogenic factors shared between COVID-19 and mucormycosis that could explain the emergence of CAM. [ABSTRACT FROM AUTHOR]

Rhodium(III) and ruthenium(II) complexes supported by a pentadentate tetrapodal (pentaPod) phosphine ligand are synthesized through abstraction of one chloride ligand from initially obtained κ4‐pentaPod coordinated dichloro complexes [MCl2(κ4‐P2MePP2Ph)]+/0 (M=Rh(III), Ru(II)) with alkali salts of weakly coordinating anions. While for the rhodium κ5‐pentaPod complex the remaining, axial chloride ligand could not be replaced by di‐ or triatomic ligands, in case of ruthenium the complexes [Ru(CN)(κ5‐P2MePP2Ph]Al(pftb)4 (5) and [Ru(N3)(κ5‐P2MePP2Ph]Al(pftb)4 (6) could be generated through ligand exchange. By comparison of NMR parameters and employing DFT calculations, additional insights into the electronic influence of different ligands (i. e. Cl−, CN−, N3−) could be gained. [ABSTRACT FROM AUTHOR]

Populists are often described as using a more aggressive, offensive, and anxiety-fuelled rhetoric than non-populists. Yet, little systematic evidence exists that this is the case. This article presents the first large-scale systematic study comparing the communication style of populists and non-populists worldwide, and introduces an original dataset based on expert ratings. The dataset contains systematic information for 195 candidates having competed in 40 national elections worldwide between June 2016 and June 2017. Results highlight that, controlling for "usual suspects" that drive negativity and emotional campaigns, populist campaigns are 15% more negative and contain 11% more character attacks and 8% more fear messages than campaigns of non-populist candidates. [ABSTRACT FROM AUTHOR]

Tissue engineering approaches, with the goals of replacing or recovering damaged or diseased tissues, or of reconstituting tissues in vitro for disease modeling and drug development, have the potential to make significant contributions to medicine. Advances in stem cell biology, biomaterial synthesis and characterization, and microscale technologies have made engineered tissues a reality. However, the classic tools used to build tissues in the lab do not allow for complete control of cell behaviors. More recently, synthetic biology principles have developed robust and versatile approaches to program cells with artificial genetic circuits, where cell behavior and function can be manipulated. At the interface between synthetic biology and tissue engineering, there is space for a new area of investigation where material engineering and cellular engineering complement and sustain each other. In this progress report, synthetic biology principles and how they have been used to engineer cells with potential to dictate cell behavior and function in tissue constructs of the future are briefly described. It is believed that this research area still needs further exploration to fully exploit synthetic biology to make smart and functional cellular constructs for therapeutic and in vitro applications. [ABSTRACT FROM AUTHOR]

On the basis of plasma technology, the progress of the volatile organic compounds' (VOCs') degradation by low‐temperature plasma alone is discussed first, including reactor types, influencing factors of plasma degradation of VOCs and the reaction mechanism between plasma and VOCs. Then, the research status of three VOC degradation technologies (catalysis, adsorption, and biotechnology) and their synergistic degradation of VOCs with plasma are reviewed, including the effect of catalyst position on VOC degradation, the interaction mechanism between plasma and catalyst; the factors affecting the adsorption of VOCs by carbon‐based adsorbents and zeolite, the degradation of VOCs by plasma‐assisted adsorbent; the features of different biological systems, the influencing factors of VOC degradation by the biotrickling system, and the degradation of VOCs by plasma‐assisted biotreatment. Finally, the prospects of developments in high‐tech based on plasma are discussed. [ABSTRACT FROM AUTHOR]

In this paper, a high-temperature test experimental system is built to investigate the dependence of the strength of a C/SiC composite material on temperature. Unintuitively, the strength increases with temperature. To investigate the microscopic mechanism, scanning electron microscopy (SEM) of an in situ bending test experiment is performed. Our hypothesis is that due to significant residual tensile stress in inter-fibre matrix, external loads reach the ultimate stress first. As the temperature increases, the matrix residual tensile stress decreases, a larger external load needs to be applied for matrix failure, which is exhibited macroscopically as increased strength. To prove this hypothesis, the inter-fibre matrix residual stress and its dependence on temperature are calculated via a finite element method. Next, using a SiC wrapper layer around a single C fibre as an experiment object, the finite element calculation is verified directly via micro-Raman spectroscopy. [ABSTRACT FROM AUTHOR]

Late‐stage functionalization of lead compounds is of high interest in drug discovery since it offers an easy access to metabolites and derivatives of a lead compound without the need to redesign an often long multistep synthesis. Owing to their high degree of chemoselectivity, biocatalytic transformations, enzymatic oxidations in particular, are potentially very powerful because they could allow the synthesis of less lipophilic derivatives of a lead compound. In the majority of cases, enzymatic oxidations have been used in an empirical way as their regioselectivity is difficult to predict. In this publication, the concept of using docking/protecting groups in a biomimetic fashion was investigated, which could help steer the regioselectivity of a P450BM3‐mediated oxidation. A novel set of docking/protecting groups was designed that can be cleaved under very mild conditions and address the often problematic aqueous solubility of the substrates. Vabicaserin was used as tool compound containing typical groups such as basic, aliphatic, and aromatic moieties. The results were rationalized with the help of in silico docking and molecular dynamic studies. Novel solubilizing docking‐protecting groups enable the regioselective P450BM3‐mutant mediated late‐stage oxidation of lead compounds by binding the substrate (orange) in a biomimetic fashion (e.g. palmitic acid, green). Enzymatic oxidation, mild deprotection and purification yields hydroxylated derivatives that are difficult to obtain by classical chemical synthesis. [ABSTRACT FROM AUTHOR]

Cells are crowded microenvironments filled with macromolecules undergoing constant physical and chemical interactions. The physicochemical makeup of the cells affects various cellular responses, determines cell-cell interactions and influences cell decisions. Chemical and physical properties differ between cells and within cells. Moreover, these properties are subject to dynamic changes in response to environmental signals, which often demand adjustments in the chemical or physical states of intracellular molecules. Indeed, cellular responses such as gene expression rely on the faithful relay of information from the outside to the inside of the cell, a process termed signal transduction. The signal often traverses a complex path across subcellular spaces with variable physical chemistry, sometimes even influencing it. Understanding the molecular states of such signaling molecules and their intracellular environments is vital to our understanding of the cell. Exploring such intricate spaces is possible today largely because of experimental and theoretical tools. Here, we focus on one tool that is commonly used in chemical physics studies — light. We summarize recent work which uses light to both visualize the cellular environment and also control intracellular processes along the axis of signal transduction. We highlight recent accomplishments in optical microscopy and optogenetics, an emerging experimental strategy which utilizes light to control the molecular processes in live cells. We believe that optogenetics lends unprecedented spatiotemporal precision to the manipulation of physicochemical properties in biological contexts. We hope to use this work to demonstrate new opportunities for chemical physicists who are interested in pursuing biological and biomedical questions. [ABSTRACT FROM AUTHOR]

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