Optimization of the Form Factors of Advanced Li-S Pouch Cells.

Lithium-sulfur (Li-S) batteries hold immense promise as next-generation energy storage due to their high theoretical energy density (2600 Wh kg⁻¹), low cost, and non-toxic nature. However, practical implementation faces challenges, primarily from Li polysulfide (LiPS) shuttling within the cathode and Li dendrite growth at the anode. Optimized electrodes/electrolytes design effectively confines LiPS to the cathode, boosting cycling performance in coin cells to up to hundreds of cycles. Scaling up to larger pouch cells presents new obstacles, requiring further research for long-term stability. A 1.45 Ah pouch cell, with optimized sulfur loading and electrolyte/sulfur ratio is developed, which delivers an energy density of 151 Wh kg-1 with 70% capacity retention up to 100 cycles. Targeting higher energy density (180 Wh kg-1), the developed 1Ah pouch cell exhibits 68% capacity retention after 50 cycles. Morphological analysis reveals that pouch cell failure is primarily from Li metal powdering and resulting polarization, rather than LiPS shuttling. This occurs for continuous Li ion stripping/plating during cycling, leading to dendrite growth and formation of non-reactive Li powder, especially under high currents. These issues increase ion diffusion resistance and reduce coulombic efficiency over time. Therefore, the study highlights the importance of a protected Li metal anode for achieving high-energy-dense batteries.

Mitoribosome Biogenesis.

Mitoribosome biogenesis is a complex and energetically costly process that involves RNA elements encoded in the mitochondrial genome and mitoribosomal proteins most frequently encoded in the nuclear genome. The process is catalyzed by extra-ribosomal proteins, nucleus-encoded assembly factors that act in all stages of the assembly process to coordinate the processing and maturation of ribosomal RNAs with the hierarchical association of ribosomal proteins. Biochemical studies and recent cryo-EM structures of mammalian mitoribosomes have provided hints regarding their assembly. In this general concept chapter, we will briefly describe the current knowledge, mainly regarding the mammalian mitoribosome biogenesis pathway and factors involved, and will emphasize the biological sources and approaches that have been applied to advance the field.

A Comprehensive Study of Historical Detection Data for Pathogen Isolates from U.S. Cattle.

Foodborne pathogens pose substantial health hazards and result in considerable economic losses in the U.S. Fortunately, the National Center for Biotechnology Information Pathogen Detection Isolates Browser (NPDIB) provides valuable access to antimicrobial resistance (AMR) genes and antimicrobial assay data. This study aimed to conduct the first comprehensive investigation of AMR genes in pathogens isolated from U.S. cattle over the past decade, driven by the urgent need to address the dangers of AMR specifically originating in pathogens isolated from U.S. cattle. In this study, around 28,000 pathogen isolate samples were extracted from the NPDIB and then analyzed using multivariate statistical methods, mainly principal component analysis (PCA) and hierarchical clustering (H-clustering). These approaches were necessary due to the high dimensions of the raw data. Specifically, PCA was utilized to reduce the dimensions of the data, converting it to a two-dimensional space, and H-clustering was used to better identify the differences among data points. The findings from this work highlighted Salmonella enterica and Escherichia coli as the predominant pathogens among the isolates, with E. coli being the more concerning pathogen due to its increasing prevalence in recent years. Moreover, tetracycline was observed as the most commonly resistant antimicrobial, with the resistance genes mdsA, mdsB, mdtM, blaEC, and acrF being the most prevalent in pathogen isolates from U.S. cattle. The occurrence of mdtM, blaEC, acrF, and glpT_E448k showed an increase in pathogens isolated from U.S. cattle in recent years. Furthermore, based on the data collected for the locations of AMR cases, Texas, California, and Nebraska were the major areas carrying major AMR genes or antimicrobials with detected resistance. The results from this study provide potential directions for targeted interventions to mitigate pathogens' antimicrobial resistance in U.S. cattle.

Sucrose Gradient Sedimentation Analysis of Mitochondrial Ribosomes.

Mitochondria contain ribosomes (mitoribosomes) specialized in the synthesis of a handful of proteins essential for oxidative phosphorylation. Therefore, mitoribosome integrity and function are essential for the life of eukaryotic cells and lesions that affect them result in devastating human disorders. To broadly analyze the integrity and assembly state of mitoribosomes it is useful to start by determining the sedimentation profile of these structures by sucrose gradient centrifugation of mitochondrial extracts. During centrifugation, mitoribosome subunits, monosomes and polysomes, and potentially accumulated assembly intermediates will sediment through the gradient at different rates. Sedimentation will depend on the centrifugal force applied and the density and viscosity of the gradient. Importantly, it will also depend on the size, shape, and density of the mitoribosome particles present in the samples under study. Variations of this technique, often coupled with additional downstream approaches, have been used to analyze the process of mitoribosome biogenesis, the composition of assembly intermediates, or to monitor the interaction of extraribosomal proteins with individual mitoribosome subunits or monosomes.

Mechanism of membrane-tethered mitochondrial protein synthesis.

Mitochondrial ribosomes (mitoribosomes) are tethered to the mitochondrial inner membrane to facilitate the cotranslational membrane insertion of the synthesized proteins. We report cryo-electron microscopy structures of human mitoribosomes with nascent polypeptide, bound to the insertase oxidase assembly 1-like (OXA1L) through three distinct contact sites. OXA1L binding is correlated with a series of conformational changes in the mitoribosomal large subunit that catalyze the delivery of newly synthesized polypeptides. The mechanism relies on the folding of mL45 inside the exit tunnel, forming two specific constriction sites that would limit helix formation of the nascent chain. A gap is formed between the exit and the membrane, making the newly synthesized proteins accessible. Our data elucidate the basis by which mitoribosomes interact with the OXA1L insertase to couple protein synthesis and membrane delivery.

Real-World Adherence and Persistence to Direct Oral Anticoagulants in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis.

BACKGROUND: Stroke reduction with direct oral anticoagulants (DOACs) in atrial fibrillation (AF) is dependent on adherence and persistence in the real-world setting. Individual study estimates of DOAC adherence/persistence rates have been discordant. Our aims were to characterize real-world observational evidence for DOAC adherence/persistence and evaluate associated clinical outcomes in patients with AF. METHODS AND RESULTS: PubMed, EMBASE, and CINAHL were searched from inception to June 2018. Observational studies that reported real-world DOAC adherence/persistence in patients with AF were included. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analyses for pooled estimates were performed using DerSimonian and Laird random-effects models. Outcomes included DOAC mean proportion of days covered or medication possession ratio, proportion of good adherence (proportion of days covered/medication possession ratio ≥80%), persistence, DOAC versus vitamin K antagonists persistence, and clinical outcomes associated with nonadherence/nonpersistence. Forty-eight observational studies with 594 784 unique patients with AF (59% male; mean age 71 years) were included. The overall pooled mean proportion of days covered/medication possession ratio was 77% (95% CI, 75%-80%), proportion of patients with good adherence was 66% (95% CI, 63%-70%), and proportion persistent was 69% (95% CI, 65%-72%). The pooled proportion of patients with good adherence was 71% (95% CI, 64%-78%) for apixaban, 60% (95% CI, 52%-68%) for dabigatran, and 70% (95% CI, 64%-75%) for rivaroxaban. Similar patterns were found for pooled persistence by agent. The pooled persistence was higher with DOACs than vitamin K antagonists (odds ratio, 1.44 [95% CI, 1.12-.86]). DOAC nonadherence was associated with an increased risk of stroke (hazard ratio, 1.39 [95% CI, 1.06-1.81]). CONCLUSIONS: Suboptimal adherence and persistence to DOACs was common in patients with AF, with 1 in 3 patients adhering to their DOAC <80% of the time, which was associated with poor clinical outcomes in nonadherent patients. Although it is convenient that DOACs do not require laboratory monitoring, greater effort in monitoring for and interventions to prevent nonadherence may be necessary to optimize stroke prevention. Increased clinician awareness of DOAC nonadherence may help identify at-risk patients.

Human COX7A2L Regulates Complex III Biogenesis and Promotes Supercomplex Organization Remodeling without Affecting Mitochondrial Bioenergetics.

The mitochondrial respiratory chain is organized in a dynamic set of supercomplexes (SCs). The COX7A2L protein is essential for mammalian SC III2+IV assembly. However, its function in respirasome (SCs I+III2+IVn) biogenesis remains controversial. To unambiguously determine the COX7A2L role, we generated COX7A2L-knockout (COX7A2L-KO) HEK293T and U87 cells. COX7A2L-KO cells lack SC III2+IV but have enhanced complex III steady-state levels, activity, and assembly rate, normal de novo complex IV biogenesis, and delayed respirasome formation. Nonetheless, the KOs have normal respirasome steady-state levels, and only larger structures (SCs I1-2+III2+IV2-n or megacomplexes) were undetected. Functional substrate-driven competition assays showed normal mitochondrial respiration in COX7A2L-KO cells in standard and nutritional-, environmental-, and oxidative-stress-challenging conditions. We conclude that COX7A2L establishes a regulatory checkpoint for the biogenesis of CIII2 and specific SCs, but the COX7A2L-dependent MRC remodeling is essential neither to maintain mitochondrial bioenergetics nor to cope with acute cellular stresses.