The robustness of porin-cytochrome gene clusters from Geobacter metallireducens in extracellular electron transfer.

To investigate their roles in extracellular electron transfer (EET), the porin-cytochrome (pcc) gene clusters Gmet0825-0828, Gmet0908-0910, and Gmet0911-0913 of the Gram-negative bacterium Geobacter metallireducens were deleted. Failure to delete all pcc gene clusters at the same time suggested their essential roles in extracellular reduction of Fe(III)-citrate by G. metallireducens. Deletion of Gmet0825-0828 had no impact on bacterial reduction of Fe(III)-citrate but diminished bacterial reduction of ferrihydrite and abolished anode reduction and direct interspecies electron transfer (DIET) to Methanosarcina barkeri and Geobacter sulfurreducens. Although it had no impact on the bacterial reduction of Fe(III)-citrate, deletion of Gmet0908-0910 delayed ferrihydrite reduction, abolished anode reduction, and diminished DIET. Deletion of Gmet0911-0913 had little impact on DIET but diminished bacterial reductions of Fe(III)-citrate, ferrihydrite, and anodes. Most importantly, deletions of both Gmet0825-0828 and Gmet0908-0910 restored bacterial reduction of ferrihydrite and anodes and DIET. Enhanced expression of Gmet0911-0913 in this double mutant when grown in coculture with G. sulfurreducens ΔhybLΔfdnG suggested that this cluster might compensate for impaired EET functions of deleting Gmet0825-0828 and Gmet0908-0910. Thus, these pcc gene clusters played essential, distinct, overlapping, and compensatory roles in EET of G. metallireducens that are difficult to characterize as deletion of some clusters affected expression of others. The robustness of these pcc gene clusters enabled G. metallireducens to mediate EET to different acceptors for anaerobic growth even when two of its three pcc gene clusters were inactivated by mutation. The results from this investigation provide new insights into the roles of pcc gene clusters in bacterial EET. IMPORTANCE: The Gram-negative bacterium Geobacter metallireducens is of environmental and biotechnological significance. Crucial to the unique physiology of G. metallireducens is its extracellular electron transfer (EET) capability. This investigation sheds new light on the robust roles of the three porin-cytochrome (pcc) gene clusters, which are directly involved in EET across the bacterial outer membrane, in the EET of G. metallireducens. In addition to their essential roles, these gene clusters also play distinct, overlapping, and compensatory roles in the EET of G. metallireducens. The distinct roles of the pcc gene clusters enable G. metallireducens to mediate EET to a diverse group of electron acceptors for anaerobic respirations. The overlapping and compensatory roles of the pcc gene clusters enable G. metallireducens to maintain and restore its EET capability for anaerobic growth when one or two of its three pcc gene clusters are deleted from the genome.

Characterization of the SUF FeS cluster synthesis machinery in the amitochondriate eukaryote Monocercomonoides exilis.

Monocercomonoides exilis is the first known amitochondriate eukaryote. Loss of mitochondria in M. exilis ocurred after the replacement of the essential mitochondrial iron-sulfur cluster (ISC) assembly machinery by a unique, bacteria-derived, cytosolic SUF system. It has been hypothesized that the MeSuf pathway, in cooperation with proteins of the cytosolic iron-sulfur protein assembly (CIA) system, is responsible for the biogenesis of FeS clusters in M. exilis, yet biochemical evidence is pending. Here, we address the M. exilis MeSuf system and show that SUF genes, individually or in tandem, support the loading of iron-sulfur (FeS) clusters into the reporter protein IscR in Escherichia coli. The Suf proteins MeSufB, MeSufC, and MeSufDSU interact in vivo with one another and with Suf proteins of E. coli. In vitro, the M. exilis Suf proteins form large complexes of varying composition and hence may function as a dynamic biosynthetic system in the protist. The putative FeS cluster scaffold MeSufB-MeSufC (MeSufBC) forms multiple oligomeric complexes, some of which bind FeS clusters and form selectively only in the presence of adenosine nucleotides. The multi-domain fusion protein MeSufDSU binds a PLP cofactor and can form higher-order complexes with MeSufB and MeSufC. Our work demonstrates the biochemical property of M. exilis Suf proteins to act as a functional FeS cluster assembly system and provides insights into the molecular mechanism of this unique eukaryotic SUF system.

"Bowling Collision Effect" of CoMo6 Polyoxometalate Units Enables Wide Temperature Range from -20 to 60 °C and Dendrite Mitigation Li-S Batteries.

To improve the performance of Lithium-Sulfur (Li-S) batteries, the reaction catalysts of lithium polysulfides (LiPSs) reactions should have the characteristics of large surface area, efficient atomic utilization, high conductivity, small size, good stability, and strong adjustability. Herein, Anderson-type polyoxometalate ([TMMo6O24]n-, TM = Co, Ni, Fe, represented by TMMo6 POMs) are used as the modified materials for Li-S battery separator. By customizing the central metal atoms, this work gains insights into the layer-by-layer electron transfer mechanism between TMMo6 units and LiPSs, similar to the collision effect of a bowling ball. Theoretical analysis and in situ experimental characterization show that the changes of CoMo6 units with moderate binding energy and lowest Gibbs free energy result in the formation of robust polar bonds and prolonged S─S bonds after adsorption. Hence, the representative Li-S battery with CoMo6 and graphene composite modified separator has a high initial capacity of 1588.6 mA h g-1 at 0.2 C, excellent cycle performance of more than 3000 cycles at 5 C, and uniform Li+ transport over 1900 h. More importantly, this work has revealed the inherent contradiction between the kinetics and thermodynamics, achieving a stable cycle in the temperature range of -20 to 60 °C.

Constructing Co4(SO4)4 Clusters within Metal-Organic Frameworks for Efficient Oxygen Electrocatalysis.

Multinuclear metal clusters are ideal candidates to catalyze small molecule activation reactions involving the transfer of multiple electrons. However, synthesizing active metal clusters is a big challenge. Herein, on constructing an unparalleled Co4(SO4)4 cluster within porphyrin-based metal-organic frameworks (MOFs) and the electrocatalytic features of such Co4(SO4)4 clusters for the oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) is reported. The reaction of CoII sulfate and metal complexes of tetrakis(4-pyridyl)porphyrin under solvothermal conditions afforded Co4-M-MOFs (M═Co, Cu, and Zn). Crystallographic studies revealed that these Co4-M-MOFs have the same framework structure, having the Co4(SO4)4 clusters connected by metalloporphyrin units through Co─Npyridyl bonds. In the Co4(SO4)4 cluster, the four CoII ions are chemically and symmetrically equivalent and are each coordinated with four sulfate O atoms to give a distorted cube-like structure. Electrocatalytic studies showed that these Co4-M-MOFs are all active for electrocatalytic OER and ORR. Importantly, by regulating the activity of the metalloporphyrin units, it is confirmed that the Co4(SO4)4 cluster is active for oxygen electrocatalysis. With the use of Co porphyrins as connecting units, Co4-Co-MOF displays the highest electrocatalytic activity in this series of MOFs by showing a 10 mA cm-2 OER current density at 357 mV overpotential and an ORR half-wave potential at 0.83 V versus reversible hydrogen electrode (RHE). Theoretical studies revealed the synergistic effect of two proximal Co atoms in the Co4(SO4)4 cluster in OER by facilitating the formation of O─O bonds. This work is of fundamental significance to present the construction of Co4(SO4)4 clusters in framework structures for oxygen electrocatalysis and to demonstrate the cooperation between two proximal Co atoms in such clusters during the O─O bond formation process.

Space-time distribution of intestinal infectious diseases and their association with socioeconomic variables in Ecuador.

Background: Intestinal infectious diseases are a global concern in terms of morbidity, and they are closely linked to socioeconomic variables such as quality of life, weather and access to healthcare services. Despite progress in spatial analysis tools and geographic information systems in epidemiology, studies in Ecuador that evaluate temporal trends, specific geographic groups, and their correlation with socioeconomic variables are lacking. The absence of such information makes it challenging to formulate public health policies. This study sought to identify the spatial and temporal patterns of these diseases in Ecuador, along with their correlation with socioeconomic variables. Methods: In Ecuador, the study was carried out in a continental territory, focusing on data related to intestinal infectious diseases collected from the National Institute of Statistics and Census (Instituto Nacional de Estadística y Censos) during the period from 2014 to 2019. This study involved spatial and temporal analyses using tools such as the global Moran's index and Local Indicators of Spatial Association to identify spatial clustering patterns and autocorrelation. Additionally, correlations between morbidity rates and socioeconomic variables were examined. Results: During the investigated period, Ecuador registered 209,668 cases of these diseases. Notable variations in case numbers were identified, with a 9.2% increase in 2019 compared to the previous year. The most impacted group was children under 5 years old, and the highest rates were centered in the southern and southwestern regions of the country, with Limón Indanza and Chunchi being the cantons with the highest rates, notably showing a significant increase in Limón Indanza. Additionally, there were significant correlations between morbidity rates and socioeconomic variables, school dropout rates, low birth weight, and access to water services. Conclusion: This study emphasizes the importance of considering socioeconomic variables when addressing these diseases in Ecuador. Understanding these correlations and geospatial trends can guide the development of health policies and specific intervention programs to reduce the incidence in identified high-risk areas. More specific research is needed to understand the underlying causes of variability in morbidity and develop effective prevention strategies.

Body image, illness uncertainty and symptom clusters in surgically treated breast cancer survivors: An exploratory factor analysis and correlational study.

PURPOSE: To determine the relationship among body image, illness uncertainty, and symptom clusters in surgically treated breast cancer survivors. METHODS: A correlational, descriptive study was conducted in a convenience sample of 60 women surgically treated breast cancer survivors recruited in a private hospital and a survivor center. A questionnaire of sociodemographic characteristics, MUIS-C Scale, and QLQ-C30 and Module BR-23 were used. Variable characteristics and associations were analyzed with descriptive statistics and Pearson correlation coefficient, and exploratory factor analysis using unweighted least squares and Promax rotation was used for symptom clustering. RESULTS: A three-factor structure was found: an anxiety symptom cluster, a breast symptom cluster, and an arm symptoms, depression, and fatigue symptom cluster, explaining 46,47% of the variance. Significant correlations were found among body image and illness uncertainty (r = -0,390, p < 0,01), body image and the anxiety symptom cluster (r = 0,613, p < 0,01), illness uncertainty and the anxiety symptom cluster (r = -0,421, p < 0,01), the breast symptom cluster (r = -0,425, p < 0,01), and the arm symptoms - depression - fatigue symptom cluster (r = -0,443, p < 0,01). CONCLUSION: The relationships among all variables were statistically significant. Nurses providing care to BC survivors need to address the multidimensionality of the symptom experience and its correlates to better assist their patients. Further research is needed to elucidate the biopsychosocial underpinnings of those relationships.

Evaluation of appropriateness of antibiotic prescribing in primary healthcare institutions in China using proxy indicator.

Background: Our objectives were to develop a set of proxy indicators (PIs) suited for assessing antibiotic use appropriateness in China's primary healthcare institutions (PHIs), and assess performance scores of these PIs while exploring factors that influence the antibiotic appropriateness. Methods: We selected potential PIs for the PHIs through a RAND-modified Delphi procedure, and assessed clinimetric properties, focusing on measurability, applicability, and potential for improvement. PIs with favorable clinimetric properties were used to evaluate antibiotic prescription appropriateness by calculating performance scores of each PI. Institutions were categorized into three clusters representing different levels of appropriateness. We used the chi-square test and an ordinal logistic regression model at PHI level to explore factors influencing antibiotic appropriateness. Findings: Eighteen PIs were developed through two rounds of online surveys and one face-to-face meeting involving 20 stakeholders. All PIs met the clinimetric properties criteria and were used to analyze 209,662 antibiotic prescriptions across 269 PHIs. The percentage of PHIs meeting the target ranged from 3.1% to 69.3%, with 6 PIs below 10%. The appropriateness of antibiotic prescriptions was significantly associated with percentages of patients' gender of the PHIs. Interpretation: The varied and suboptimal performance of the PIs indicated the need for diverse efforts to enhance the rational antibiotic use at PHI level. It was necessary to devise distinct sets of PIs for diverse settings in future endeavors. Funding: This work was supported by the National Natural Science Foundation of China (grant numbers 72374009, 81973294).

Nickel atom-clusters nanozyme for boosting ferroptosis tumor therapy.

The translation of Fe-based agents for ferroptosis tumor therapy is restricted by the unstable iron valence state, the harsh catalytic environment, and the complex tumor self-protection mechanism. Herein, we developed a stable nickel-based single-atom-metal-clusters (NSAMCs) biocatalyst for efficient tumor ferroptosis therapy. NSAMCs with a nanowire-like nanostructure and hydrophilic functional groups exhibit good water-solubility, colloidal stability, negligible systemic toxicity, and target specificity. In particular, NSAMCs possess excellent peroxidase-like and glutathione oxidase-like activities through the synergistic influence between metal clusters and single atoms. The dual-enzymatic performance enables NSAMCs to synergistically promote efficient ferroptosis of cancer cells through lipid peroxidization aggregation and glutathione peroxidase 4 inactivation. Importantly, NSAMCs highlight the boost of ferroptosis tumor therapy via the synergistic effect between single-atoms and metal clusters, providing a practical and feasible paradigm for further improving the efficiency of ferroptosis tumor treatment.

Codon usage bias in yeasts and its correlation with gene expression, growth temperature, and protein structure.

Codon usage bias (CUB) has been described in viruses, prokaryotes, and eukaryotes and has been linked to several cellular and environmental factors, such as the organism's growth temperature, gene expression levels, and regulation of protein synthesis and folding. Most of the studies in this area have been conducted in bacteria and higher eukaryotes, in some cases with different results. In this study, a comparative analysis of CUB in yeasts isolated from cold and template environments was performed in order to evaluate the correlation of CUB with yeast optimal temperature of growth (OTG), gene expression levels, cellular function, and structure of encoded proteins. Among the main findings, highly expressed ORFs tend to have a more similar CUB within and between yeasts, and a direct correlation between codons ending in C and expression level was generally found. A low correspondence between CUB and OTG was observed, with an inverse correlation for some codons ending in C. The clustering of yeasts based on their CUB partially aligns with their OTG, being more consistent for yeasts with lower OTG. In most yeasts, the abundance of preferred codons was generally lower at the 5' end of ORFs, higher in segments encoding beta strand, lower in segments encoding extracellular and transmembrane regions, and higher in "translation" and "energy metabolism" pathways, especially in highly expressed ORFs. Based on our findings, it is suggested that the abundance and distribution of preferred and non-preferred codons along mRNAs contribute to proper protein folding and functionality by regulating protein synthesis rates, becoming a more important factor under conditions that require faster protein synthesis in yeasts.

Additive-Assisted Forming High-Quality Thin Films of Sn-Oxo Cluster for Nanopatterning.

Recently, metal-oxo clusters (MOCs) have attracted significant interest in fabricating nanoscale patterns in semiconductors via lithography. However, many MOCs are highly crystalline, making it difficult for them to form films and hindering subsequent nanopatterning processes. In this study, we developed a novel and simple method to enhance the film-forming ability of aromatic tetranuclear Sn-oxo clusters by adding additives. Theoretical calculations and Fourier-transform infrared (FTIR) analysis revealed the formation of intermolecular hydrogen bonds between the Sn-oxo clusters and additives, which induced a crystal-gel phase transition at -20 °C, thereby inhibiting the easy crystallization of the Sn-oxo clusters. High-quality and uniform thin films with surface roughness below 0.3 nm were prepared via spin coating. The obtained thin films exhibited good lithographic performance under deep ultraviolet (DUV), electron beam, and extreme-ultraviolet irradiation without a photo acid generator/photoinitiator, and 13- and 21 nm-wide line patterns were obtained on the films via electron-beam and extreme-ultraviolet lithographies. This study will pave the way for the further investigation of novel MOCs for advanced lithography and other thin-film applications.

Iron­sulfur cluster synthesis in plastids by the SUF system: A mechanistic and structural perspective.

About 50 proteins expressed in plastids of photosynthetic eukaryotes ligate iron­sulfur (Fe-S) clusters and ensure vital functions in photosynthesis, sulfur and nitrogen assimilation, but also in the synthesis of pigments, vitamins and hormones. The synthesis of these Fe-S clusters, which are co- or post-translationally incorporated into these proteins, relies on several proteins belonging to the so-called sulfur mobilization (SUF) machinery. An Fe-S cluster is first de novo synthesized on a scaffold protein complex before additional late-acting maturation factors act in the specific transfer, possible conversion and insertion of this cluster into target recipient proteins. In this review, we will summarize what is known about the molecular mechanisms responsible for both the synthesis and transfer steps, focusing in particular on the structural aspects that allow the formation of the required protein complexes.

Initiation of hnRNPA1 Low-Complexity Domain Condensation Monitored by Dynamic Light Scattering.

Biomolecular condensates (BMCs) exhibit physiological and pathological relevance in biological systems. Both liquid and solid condensates play significant roles in the spatiotemporal regulation and organization of macromolecules and their biological activities. Some pathological solid condensates, such as Lewy Bodies and other fibrillar aggregates, have been hypothesized to originate from liquid condensates. With the prevalence of BMCs having functional and dysfunctional roles, it is imperative to understand the mechanism of biomolecular condensate formation and initiation. Using the low-complexity domain (LCD) of heterogenous ribonuclear protein A1 (hnRNPA1) as our model, we monitored initial assembly events using dynamic light scattering (DLS) while modulating pH and salt conditions to perturb macromolecule and condensate properties. We observed the formation of nanometer-sized BMCs (nano-condensates) distinct from protein monomers and micron-sized condensates. We also observed that conditions that solubilize micron-sized protein condensates do not solubilize nano-condensates, indicating that the balance of forces that stabilize nano-condensates and micron-sized condensates are distinct. These findings provide insight into the forces that drive protein phase separation and potential nucleation structures of macromolecular condensation.

Risk factors for persistent fatal opioid-involved overdose clusters in Massachusetts 2011-2021: a spatial statistical analysis with socio-economic, accessibility, and prescription factors.

BACKGROUND: Fatal opioid-involved overdose rates increased precipitously from 5.0 per 100,000 population to 33.5 in Massachusetts between 1999 and 2022. METHODS: We used spatial rate smoothing techniques to identify persistent opioid overdose-involved fatality clusters at the ZIP Code Tabulation Area (ZCTA) level. Rate smoothing techniques were employed to identify locations of high fatal opioid overdose rates where population counts were low. In Massachusetts, this included areas with both sparse data and low population density. We used Local Indicators of Spatial Association (LISA) cluster analyses with the raw incidence rates, and the Empirical Bayes smoothed rates to identify clusters from 2011 to 2021. We also estimated Empirical Bayes LISA cluster estimates to identify clusters during the same period. We constructed measures of the socio-built environment and potentially inappropriate prescribing using principal components analysis. The resulting measures were used as covariates in Conditional Autoregressive Bayesian models that acknowledge spatial autocorrelation to predict both, if a ZCTA was part of an opioid-involved cluster for fatal overdose rates, as well as the number of times that it was part of a cluster of high incidence rates. RESULTS: LISA clusters for smoothed data were able to identify whether a ZCTA was part of a opioid involved fatality incidence cluster earlier in the study period, when compared to LISA clusters based on raw rates. PCA helped in identifying unique socio-environmental factors, such as minoritized populations and poverty, potentially inappropriate prescribing, access to amenities, and rurality by combining socioeconomic, built environment and prescription variables that were highly correlated with each other. In all models except for those that used raw rates to estimate whether a ZCTA was part of a high fatality cluster, opioid overdose fatality clusters in Massachusetts had high percentages of Black and Hispanic residents, and households experiencing poverty. The models that were fitted on Empirical Bayes LISA identified this phenomenon earlier in the study period than the raw rate LISA. However, all the models identified minoritized populations and poverty as significant factors in predicting the persistence of a ZCTA being part of a high opioid overdose cluster during this time period. CONCLUSION: Conducting spatially robust analyses may help inform policies to identify community-level risks for opioid-involved overdose deaths sooner than depending on raw incidence rates alone. The results can help inform policy makers and planners about locations of persistent risk.

Refining Risk Criteria May Substantially Reduce Unnecessary Additional Surgeries after Local Resection of T1 Colorectal Cancer.

BACKGROUND: The low positive predictive value for lymph node metastases (LNM) of common practice risk criteria (CPRC) in T1 colorectal carcinoma (CRC) leads to manyunnecessary additional surgeries following local resection. This study aimed to identify criteria that may improve on the CPRC. METHODS: Logistic regression analysis was performed to determine the association of diverse variables with LNM or 'poor outcome' (LNM and/or distant metastases and/or recurrence) in a single center T1 CRC cohort. The diagnostic capacity of the set of variables obtained was compared with that of the CPRC. RESULTS: The study comprised 161 cases. Poorly differentiated clusters (PDC) and tumor budding grade > 1 (TB > 1) were the only independent variables associated with LNM. The area under the curve (AUC) for these criteria was 0.808 (CI 95% 0.717-0.880) compared to 0.582 (CI 95% 0.479-0.680) for CPRC. TB > 1 and lymphovascular invasion (LVI) were independently associated with 'poor outcome', with an AUC of 0.801 (CI 95% 0.731-0.859), while the AUC for CPRC was 0.691 (CI 95% 0.603-0.752). TB > 1, combined either with PDC or LVI, would reduce false positives between 41.5% and 45% without significantly increasing false negatives. CONCLUSIONS: Indicating additional surgery in T1 CRC only when either TB > 1, PDC, or LVI are present could reduce unnecessary surgeries significantly.

In-depth understanding the synergisms of Cu atomic clusters on Cu single atoms for highly effective electrocatalytic oxygen reduction reaction and Zn-Air battery.

In this paper, a novel, simple and mild soft template assisted strategy and further carbonization approach has been constructed to the size-tunable preparation of porous Cu-N-C/Surfactant catalysts successfully. Note that the pluronic F127 has a significant influence on the synthesis of porous Cu-N-C/F127 with the atomically dispersed Cu-N4 and adjacent Cu atomic clusters (ACs) than other surfactants owing to their particular non-ionic structure. By combining a series of experimental analysis and density functional theory (DFT) calculations, the synergistic effects between the adjacent Cu ACs and atomically dispersed Cu-N4 are favorable for manipulating the binding energy of O2 adsorption and intermediates desorption at the atomic interface of catalysts, resulting in an excellent electrocatalytic ORR performance with a faster kinetics for Cu-N-C/F127 than those of the Cu-N-C, Cu-N-C/CTAB, Cu-N-C/SDS, and comparable with the commercial Pt/C catalyst. This method not only provides a novel approach for synthesizing highly effective copper based single atom catalysts toward ORR, but also offers an in-depth understanding of the synergisms of adjacent ACs on the Cu single atoms (SAs) for highly effective electrocatalytic ORR and Zn-air Battery.

Iron Homeostatic Regulation in Saccharomyces cerevisiae: Introduction to a Computational Modeling Method.

Over the past 30 years, much has been learned regarding iron homeostatic regulation in budding yeast, S. cerevisiae, including the identity of many of the proteins and molecular-level regulatory mechanisms involved. Most advances have involved inferring such mechanisms based on the analysis of iron-dysregulation phenotypes arising in various genetic mutant strains. Still lacking is a cellular- or system-level understanding of iron homeostasis. These experimental advances are summarized in this review, and a method for developing cellular-level regulatory mechanisms in yeast is presented. The method employs the results of Mössbauer spectroscopy of whole cells and organelles, iron quantification of the same, and ordinary differential equation-based mathematical models. Current models are simplistic when compared to the complexity of iron homeostasis in real cells, yet they hold promise as a useful, perhaps even required, complement to the popular genetics-based approach. The fundamental problem in comprehending cellular regulatory mechanisms is that, given the complexities involved, different molecular-level mechanisms can often give rise to virtually indistinguishable cellular phenotypes. Mathematical models cannot eliminate this problem, but they can minimize it.

High-Throughput Mining of Novel Compounds from Known Microbes: A Boost to Natural Product Screening.

Advanced techniques can accelerate the pace of natural product discovery from microbes, which has been lagging behind the drug discovery era. Therefore, the present review article discusses the various interdisciplinary and cutting-edge techniques to present a concrete strategy that enables the high-throughput screening of novel natural compounds (NCs) from known microbes. Recent bioinformatics methods revealed that the microbial genome contains a huge untapped reservoir of silent biosynthetic gene clusters (BGC). This article describes several methods to identify the microbial strains with hidden mines of silent BGCs. Moreover, antiSMASH 5.0 is a free, accurate, and highly reliable bioinformatics tool discussed in detail to identify silent BGCs in the microbial genome. Further, the latest microbial culture technique, HiTES (high-throughput elicitor screening), has been detailed for the expression of silent BGCs using 500-1000 different growth conditions at a time. Following the expression of silent BGCs, the latest mass spectrometry methods are highlighted to identify the NCs. The recently emerged LAESI-IMS (laser ablation electrospray ionization-imaging mass spectrometry) technique, which enables the rapid identification of novel NCs directly from microtiter plates, is presented in detail. Finally, various trending 'dereplication' strategies are emphasized to increase the effectiveness of NC screening.

Lifestyle Clusters of Diet Quality, Sleep, and Screen Time and Associations with Weight Status in Children from Madrid City: ENPIMAD Study.

BACKGROUND: Childhood overweight and obesity is a global concern and has increased in Spain over the last decades. Combinations of lifestyle behaviors (i.e., diet, sleep, and sedentarism) are highly related to weight status. Therefore, this study aimed to identify lifestyle patterns among children from Madrid City, and analyze associations with the prevalence of overweight, obesity, and abdominal obesity, considering socio-economic factors. METHODS: A cross-sectional analysis was conducted on 4545 children from the ENPIMAD study with data on diet, sleep, anthropometric, and socio-economic variables. K-means cluster analysis was used to identify lifestyle clusters, and logistic regressions were used to examine the associations between socio-economic indicators and cluster membership, and between clusters and weight status. RESULTS: Findings show three lifestyle clusters (healthy, mixed, and unhealthy), with boys and older children more represented in the unhealthy cluster. Food insecurity and low socio-economic status were associated with unhealthier clusters in boys and girls. Children in unhealthier clusters were more likely to have obesity and abdominal obesity. However, these associations disappeared in girls after controlling for food insecurity. CONCLUSION: These results provide insight into the combination of behaviors and socio-economic factors associated with childhood obesity that may aid in the design of future interventions.

A Chemoproteomic Approach to Monitor Native Iron-Sulfur Cluster Binding.

Iron-sulfur (Fe-S) clusters are essential redox-active metallocofactors participating in electron transfer, radical chemistry, primary metabolism, and gene regulation. Successful trafficking and incorporation of Fe-S clusters into target proteins are critical to proper cellular function. While biophysical studies of isolated Fe-S proteins provide insight into the structure and function of these inorganic cofactors, few strategies currently exist to directly interrogate Fe-S cluster binding within a cellular environment. Here, we describe a chemoproteomic platform to report on Fe-S cluster incorporation and occupancy directly within a native proteome, enabling the characterization of Fe-S biogenesis pathways and the identification of undiscovered Fe-S proteins.

Fe/Cu MOFs of Fe2+-rich and Cu-doping via in situ reduction as nanozyme for peroxidase-like catalycity enhancement.

Fe-MOFs of mixed valence was synthesized by a solvothermal method via the in-situ reduction of ethylene glycol (EG) pre-coordination with the proper ratio of Fe2+/Fe3+ between 0.83 and 2.46. Synchronously with copper introduction, the Fe/Cu MOFs of mixed valence (Fe/Cu-MVMOFs) was then one pot acquired to remarkably improve the affinity of Fe2+ and Cu+ to H2O2 and promote the conversion efficiency of Fe2+/Fe3+ via the electron transfer among Fe-Cu bimetal clusters (XPS and XRD). Hence, the maximum reaction rate of H2O2 with Fe/Cu-MVMOFs reached 16.65 M·s-1, along with Km as low as 0.0479 mM. H2O2 and glutathione (GSH) were efficiently detected, ranging from 0.25 to 60 µM and from 0.2 to 40 µM, respectively. The investigation of catalyzation selectivity and practical serum detection by Fe/Cu-MVMOFs illustrated the efficacy and efficiency, denoting Fe/Cu-MVMOFs as the promising peroxidase candidate.