A semi-automated cell tracking protocol for quantitative analyses of neutrophil swarming to sterile and S. aureus contaminated bone implants in a mouse femur model.

Implant-associated osteomyelitis remains a major orthopaedic problem. As neutrophil swarming to the surgical site is a critical host response to prevent infection, visualization and quantification of this dynamic behavior at the native microenvironment of infection will elucidate previously unrecognized mechanisms central to understanding the host response. We recently developed longitudinal intravital imaging of the bone marrow (LIMB) to visualize host cells and fluorescent S. aureus on a contaminated transfemoral implant in live mice, which allows for direct visualization of bacteria colonization of the implant and host cellular responses using two-photon laser scanning microscopy. To the end of rigorous and reproducible quantitative outcomes of neutrophil swarming kinetics in this model, we developed a protocol for robust segmentation, tracking, and quantifications of neutrophil dynamics adapted from Trainable Weka Segmentation and TrackMate, two readily available Fiji/ImageJ plugins. In this work, Catchup mice with tdTomato expressing neutrophils received a transfemoral pin with or without ECFP/EGFP-expressing USA300 methicillin-resistant Staphylococcus aureus (MRSA) to obtain 30-minute LIMB videos at 2-, 4-, and 6-hours post-implantation. The developed semi-automated neutrophil tracking protocol was executed independently by two users to quantify the distance, displacement, speed, velocity, and directionality of the target cells. The results revealed high inter-user reliability for all outcomes (ICC > 0.96; p > 0.05). Consistent with the established paradigm on increased neutrophil swarming during active infection, the results also demonstrated increased neutrophil speed and velocity at all measured time points, and increased displacement at later time points (6 hours) in infected versus uninfected mice (p < 0.05). Neutrophils and bacteria also exhibit directionality during migration in the infected mice. The semi-automated cell tracking protocol provides a streamlined approach to robustly identify and track individual cells across diverse experimental settings and eliminates inter-observer variability.

Simulation of Radiation-Induced DNA Damage and Protection by Histones Using the Code RITRACKS.

(1) Background: DNA damage is of great importance in the understanding of the effects of ionizing radiation. Various types of DNA damage can result from exposure to ionizing radiation, with clustered types considered the most important for radiobiological effects. (2) Methods: The code RITRACKS (Relativistic Ion Tracks), a program that simulates stochastic radiation track structures, was used to simulate DNA damage by photons and ions spanning a broad range of linear energy transfer (LET) values. To perform these simulations, the transport code was modified to include cross sections for the interactions of ions or electrons with DNA and amino acids for ionizations, dissociative electron attachment, and elastic collisions. The radiochemistry simulations were performed using a step-by-step algorithm that follows the evolution of all particles in time, including reactions between radicals and DNA structures and amino acids. Furthermore, detailed DNA damage events, such as base pair positions, DNA fragment lengths, and fragment yields, were recorded. (3) Results: We report simulation results using photons and the ions 1H+, 4He2+, 12C6+, 16O8+, and 56Fe26+ at various energies, covering LET values from 0.3 to 164 keV/µm, and performed a comparison with other codes and experimental results. The results show evidence of DNA protection from damage at its points of contacts with histone proteins. (4) Conclusions: RITRACKS can provide a framework for studying DNA damage from a variety of ionizing radiation sources with detailed representations of DNA at the atomic scale, DNA-associated proteins, and resulting DNA damage events and statistics, enabling a broader range of future comparisons with experiments such as those based on DNA sequencing.

Binary Solvent Induced Stable Interphase Layer for Ultra-Long Life Sodium Metal Batteries.

Sodium foil, promising for high-energy-density batteries, faces reversibility challenges due to its inherent reactivity and unstable solid electrolyte interphase (SEI) layer. In this study, a stable sodium metal battery (SMB) is achieved by tuning the electrolyte solvation structure through the addition of co-solvent 2-methyl tetrahydrofuran (MTHF) to diglyme (Dig). The introduction of cyclic ether-based MTHF results in increased anion incorporation in the solvation structure, even at lower salt concentrations. Specifically, the anion stabilization capabilities of the environmentally sustainable MTHF co-solvent lead to a contact-ion pair-based solvation structure. Time-of-flight mass spectroscopy analysis reveals that a shift toward an anion-dominated solvation structure promotes the formation of a thin and uniform SEI layer. Consequently, employing a NaPF6-based electrolyte with a Dig:MTHF ratio of 50% (v/v) binary solvent yields an average Coulombic efficiency of 99.72% for 300 cycles in Cu||Na cell cycling. Remarkably, at a C/2 cycling rate, Na||Na symmetric cell cycling demonstrates ultra-long-term stability exceeding 7000 h, and full cells with Na0.44MnO2 as a cathode retain 80% of their capacity after 500 cycles. This study systematically examines solvation structure, SEI layer composition, and electrochemical cycling, emphasizing the significance of MTHF-based binary solvent mixtures for high-performance SMBs.

In Situ Engineering of Inorganic-Rich Solid Electrolyte Interphases via Anion Choice Enables Stable, Lithium Anodes.

The discovery of liquid battery electrolytes that facilitate the formation of stable solid electrolyte interphases (SEIs) to mitigate dendrite formation is imperative to enable lithium anodes in next-generation energy-dense batteries. Compared to traditional electrolyte solvents, tetrahydrofuran (THF)-based electrolyte systems have demonstrated great success in enabling high-stability lithium anodes by encouraging the decomposition of anions (instead of organic solvent) and thus generating inorganic-rich SEIs. Herein, by employing a variety of different lithium salts (i.e., LiPF6, LiTFSI, LiFSI, and LiDFOB), it is demonstrated that electrolyte anions modulate the inorganic composition and resulting properties of the SEI. Through novel analytical time-of-flight secondary-ion mass spectrometry methods, such as hierarchical clustering of depth profiles and compositional analysis using integrated yields, the chemical composition and morphology of the SEIs generated from each electrolyte system are examined. Notably, the LiDFOB electrolyte provides an exceptionally stable system to enable lithium anodes, delivering >1500 cycles at a current density of 0.5 mAh g-1 and a capacity of 0.5 mAh g-1 in symmetrical cells. Furthermore, Li//LFP cells using this electrolyte demonstrate high-rate, reversible lithium storage, supplying 139 mAh g(LFP) -1 at C/2 (≈0.991 mAh cm-2 , @ 0.61 mA cm-2 ) with 87.5% capacity retention over 300 cycles (average Coulombic efficiency >99.86%).

2023 International Consensus Meeting on musculoskeletal infection: Summary from the treatment workgroup and consensus on treatment in preclinical models.

In vitro and in vivo studies are critical for the preclinical efficacy assessment of novel therapies targeting musculoskeletal infections (MSKI). Many preclinical models have been developed and applied as a prelude to evaluating safety and efficacy in human clinical trials. In performing these studies, there is both a requirement for a robust assessment of efficacy, as well as a parallel responsibility to consider the burden on experimental animals used in such studies. Since MSKI is a broad term encompassing infections varying in pathogen, anatomical location, and implants used, there are also a wide range of animal models described modeling these disparate infections. Although some of these variations are required to adequately evaluate specific interventions, there would be enormous value in creating a unified and standardized criteria to animal testing in the treatment of MSKI. The Treatment Workgroup of the 2023 International Consensus Meeting on Musculoskeletal Infection was responsible for questions related to preclinical models for treatment of MSKI. The main objective was to review the literature related to priority questions and estimate consensus opinion after voting. This document presents that process and results for preclinical models related to (1) animal model considerations, (2) outcome measurements, and (3) imaging.

Longitudinal intravital imaging of the bone marrow for analysis of the race for the surface in a murine osteomyelitis model.

Critical knowledge gaps of orthopedic infections pertain to bacterial colonization. The established dogma termed the Race for the Surface posits that contaminating bacteria compete with host cells for the implant post-op, which remains unproven without real-time in vivo evidence. Thus, we modified the murine longitudinal intravital imaging of the bone marrow (LIMB) system to allow real-time quantification of green fluorescent protein (GFP+) host cells and enhanced cyan fluorescent protein (ECFP+) or red fluorescent protein (RFP+) methicillin-resistant Staphylococcus aureus (MRSA) proximal to a transfemoral implant. Following inoculation with ~105 CFU, an L-shaped metal implant was press-fit through the lateral cortex at a 90° angle ~0.150 mm below a gradient refractive index (GRIN) lens. We empirically derived a volume of interest (VOI) = 0.0161 ± 0.000675 mm3 during each imaging session by aggregating the Z-stacks between the first (superior) and last (inferior) in-focus LIMB slice. LIMB postimplantation revealed very limited bacteria detection at 1 h, but by 3 h, 56.8% of the implant surface was covered by ECFP+ bacteria, and the rest were covered by GFP+ host cells. 3D volumetric rendering of the GFP+ and ECFP+ or RFP+ voxels demonstrated exponential MRSA growth between 3 and 6 h in the Z-plane, which was validated with cross-sectional ex vivo bacterial burden analyses demonstrating significant growth by ~2 × 104 CFU/h on the implant from 2 to 12 h post-op (p < 0.05; r2 > 0.98). Collectively, these results show the competition at the surface is completed by 3 h in this model and demonstrate the potential of LIMB to elucidate mechanisms of bacterial colonization, the host immune response, and the efficacy of antimicrobials.

A semi-automated cell tracking protocol for quantitative analyses of neutrophil swarming to sterile and S. aureus contaminated bone implants in a mouse femur model.

Implant-associated osteomyelitis remains a major orthopaedic problem. As neutrophil swarming to the surgical site is a critical host response to prevent infection, visualization and quantification of this dynamic behavior at the native microenvironment of infection will elucidate previously unrecognized mechanisms central to understanding the host response. We recently developed longitudinal intravital imaging of the bone marrow (LIMB) to visualize fluorescent S. aureus on a contaminated transfemoral implant and host cells in live mice, which allows for direct visualization of bacteria colonization of the implant and host cellular responses using two-photon laser scanning microscopy. To the end of rigorous and reproducible quantitative outcomes of neutrophil swarming kinetics in this model, we developed a protocol for robust segmentation, tracking, and quantifications of neutrophil dynamics adapted from Trainable Weka Segmentation and TrackMate, two readily available Fiji/ImageJ plugins. In this work, Catchup mice with tdTomato expressing neutrophils received a transfemoral pin with or without ECFP-expressing USA300 methicillin-resistant Staphylococcus aureus (MRSA) to obtain 30-minute LIMB videos at 2-, 4-, and 6-hours post-implantation. The developed semi-automated neutrophil tracking protocol was executed independently by two users to quantify the distance, displacement, speed, velocity, and directionality of the target cells. The results revealed high inter-reader reliability for all outcomes (ICC > 0.98; p > 0.05). Consistent with the established paradigm on increased neutrophil swarming during active infection, the results also demonstrated increased neutrophil speed and velocity at all measured time points, and increased displacement at later time points (6 hours) in infected versus uninfected mice (p < 0.05). Neutrophils and bacteria also exhibit directionality during migration in the infected mice. The semi-automated cell tracking protocol provides a streamlined approach to robustly identify and track individual cells across diverse experimental settings and eliminates inter-observer variability.

Evidence of bisphosphonate-conjugated sitafloxacin eradication of established methicillin-resistant S. aureus infection with osseointegration in murine models of implant-associated osteomyelitis.

Eradication of MRSA osteomyelitis requires elimination of distinct biofilms. To overcome this, we developed bisphosphonate-conjugated sitafloxacin (BCS, BV600072) and hydroxybisphosphonate-conjugate sitafloxacin (HBCS, BV63072), which achieve "target-and-release" drug delivery proximal to the bone infection and have prophylactic efficacy against MRSA static biofilm in vitro and in vivo. Here we evaluated their therapeutic efficacy in a murine 1-stage exchange femoral plate model with bioluminescent MRSA (USA300LAC::lux). Osteomyelitis was confirmed by CFU on the explants and longitudinal bioluminescent imaging (BLI) after debridement and implant exchange surgery on day 7, and mice were randomized into seven groups: 1) Baseline (harvested at day 7, no treatment); 2) HPBP (bisphosphonate control for BCS) + vancomycin; 3) HPHBP (hydroxybisphosphonate control for HBCS) + vancomycin; 4) vancomycin; 5) sitafloxacin; 6) BCS + vancomycin; and 7) HBCS + vancomycin. BLI confirmed infection persisted in all groups except for mice treated with BCS or HBCS + vancomycin. Radiology revealed catastrophic femur fractures in all groups except mice treated with BCS or HBCS + vancomycin, which also displayed decreases in peri-implant bone loss, osteoclast numbers, and biofilm. To confirm this, we assessed the efficacy of vancomycin, sitafloxacin, and HBCS monotherapy in a transtibial implant model. The results showed complete lack of vancomycin efficacy while all mice treated with HBCS had evidence of infection control, and some had evidence of osseous integrated septic implants, suggestive of biofilm eradication. Taken together these studies demonstrate that HBCS adjuvant with standard of care debridement and vancomycin therapy has the potential to eradicate MRSA osteomyelitis.

Epidemiological updates of post-traumatic related limb osteomyelitis in china: a 10 years multicentre cohort study.

BACKGROUND: Post-traumatic related limb osteomyelitis (PTRLO) is a complex bone infection. Currently, there are no available microbial data on a national scale that can guide appropriate antibiotic selection, and explore the dynamic changes in dominant pathogens over time. This study aimed to conduct a comprehensive epidemiological analysis of PTRLO in China. METHODS: The study was approved by the Institutional Research Board (IRB), and 3526 PTRLO patients were identified from 212 394 traumatic limb fracture patients at 21 hospitals between 1 January 2008 and 31 December 2017. A retrospective analysis was conducted to investigate the epidemiology of PTRLO, including changes in infection rate (IR), pathogens, infection risk factors and antibiotic resistance and sensitivity. RESULTS: The IR of PTRLO increased gradually from 0.93 to 2.16% (Z=14.392, P <0.001). Monomicrobial infection (82.6%) was significantly higher than polymicrobial infection (17.4%) ( P <0.001). The IR of Gram-positive (GP) and Gram-negative (GN) pathogens showed a significant increase from the lowest 0.41% to the highest 1.15% (GP) or 1.62% (GN), respectively. However, the longitudinal trend of GP vs. GN's composition did not show any significance (Z=±1.1918, P >0.05). The most prevalent GP strains were Methicillin-sensitive Staphylococcus aureus (MSSA) (17.03%), Methicillin-resistant Staphylococcus aureus (MRSA) (10.46%), E. faecalis (5.19%) and S. epidermidis (4.87%). In contrast, the dominant strains GN strains were Pseudomonas Aeruginosa (10.92%), E. cloacae (10.34%), E. coli (9.47%), Acinetobacter Baumannii (7.92%) and Klebsiella Pneumoniae (3.33%). In general, the high-risk factors for polymicrobial infection include opened-fracture (odds ratio, 2.223), hypoproteinemia (odds ratio, 2.328), and multiple fractures (odds ratio, 1.465). It is important to note that the antibiotics resistance and sensitivity analysis of the pathogens may be influenced by complications or comorbidities. CONCLUSIONS: This study provides the latest data of PTRLO in China and offers trustworthy guidelines for clinical practice. (China Clinical Trials.gov number, ChiCTR1800017597).

Evidence of Bisphosphonate-Conjugated Sitafloxacin Eradication of Established Methicillin-Resistant S. aureus Infection with Osseointegration in Murine Models of Implant-Associated Osteomyelitis.

Eradication of MRSA osteomyelitis requires elimination of distinct biofilms. To overcome this, we developed bisphosphonate-conjugated sitafloxacin (BCS, BV600072) and hydroxybisphosphonate-conjugate sitafloxacin (HBCS, BV63072), which achieve "target-and-release" drug delivery proximal to the bone infection and have prophylactic efficacy against MRSA static biofilm in vitro and in vivo. Here we evaluated their therapeutic efficacy in a murine 1-stage exchange femoral plate model with bioluminescent MRSA (USA300LAC::lux). Osteomyelitis was confirmed by CFU on the explants and longitudinal bioluminescent imaging (BLI) after debridement and implant exchange surgery on day 7, and mice were randomized into seven groups: 1) Baseline (harvested at day 7, no treatment); 2) HPBP (bisphosphonate control for BCS) + vancomycin; 3) HPHBP (bisphosphonate control for HBCS) + vancomycin; 4) vancomycin; 5) sitafloxacin; 6) BCS + vancomycin; and 7) HBCS + vancomycin. BLI confirmed infection persisted in all groups except for mice treated with BCS or HBCS + vancomycin. Radiology revealed catastrophic femur fractures in all groups except mice treated with BCS or HBCS + vancomycin, which also displayed decreases in peri-implant bone loss, osteoclast numbers, and biofilm. To confirm this, we assessed the efficacy of vancomycin, sitafloxacin, and HBCS monotherapy in a transtibial implant model. The results showed complete lack of vancomycin efficacy, while all mice treated with HBCS had evidence of infection control, and some had evidence of osseous integrated septic implants, suggestive of biofilm eradication. Taken together these studies demonstrate that HBCS adjuvant with standard of care debridement and vancomycin therapy has the potential to eradicate MRSA osteomyelitis.

Reduced angiogenesis and delayed endochondral ossification in CD163-/- mice highlights a role of M2 macrophages during bone fracture repair.

While recent studies showed that macrophages are critical for bone fracture healing, and lack of M2 macrophages have been implicated in models of delayed union, functional roles for specific M2 receptors have yet to be defined. Moreover, the M2 scavenger receptor CD163 has been identified as a target to inhibit sepsis following implant-associated osteomyelitis, but potential adverse effects on bone healing during blockage therapy have yet to be explored. Thus, we investigated fracture healing in C57BL/6 versus CD163-/- mice using a well-established closed, stabilized, mid-diaphyseal femur fracture model. While gross fracture healing in CD163-/- mice was similar to that of C57BL/6, plain radiographs revealed persistent fracture gaps in the mutant mice on Day 14, which resolved by Day 21. Consistently, 3D vascular micro-CT demonstrated delayed union on Day 21, with reduced bone volume (74%, 61%, and 49%) and vasculature (40%, 40%, and 18%) compared to C57BL/6 on Days 10, 14, and 21 postfracture, respectively (p < 0.01). Histology confirmed large amounts of persistent cartilage in CD163-/- versus C57BL/6 fracture callus on Days 7 and 10 that resolves over time, and immunohistochemistry demonstrated deficiencies in CD206+ M2 macrophages. Torsion testing of the fractures confirmed the delayed early union in CD163-/- femurs, which display decreased yield torque on Day 21, and a decreased rigidity with a commensurate increase in rotation at yield on Day 28 (p < 0.01). Collectively, these results demonstrate that CD163 is required for normal angiogenesis, callus formation, and bone remodeling during fracture healing, and raise potential concerns about CD163 blockade therapy.

Camphene-Assisted Fabrication of Free-Standing Lithium-Ion Battery Electrode Composites.

Free-standing electrode (FSE) architectures hold the potential to dramatically increase the gravimetric and volumetric energy density of lithium-ion batteries (LIBs) by eliminating the parasitic dead weight and volume associated with traditional metal foil current collectors. However, current FSE fabrication methods suffer from insufficient mechanical stability, electrochemical performance, or industrial adoptability. Here, we demonstrate a scalable camphene-assisted fabrication method that allows simultaneous casting and templating of FSEs comprising common LIB materials with a performance superior to their foil-cast counterparts. These porous, lightweight, and robust electrodes simultaneously enable enhanced rate performance by improving the mass and ion transport within the percolating conductive carbon pore network and eliminating current collectors for efficient and stable Li+ storage (>1000 cycles in half-cells) at increased gravimetric and areal energy densities. Compared to conventional foil-cast counterparts, the camphene-derived electrodes exhibit ∼1.5× enhanced gravimetric energy density, increased rate capability, and improved capacity retention in coin-cell configurations. A full cell containing both a free-standing anode and cathode was cycled for over 250 cycles with greater than 80% capacity retention at an areal capacity of 0.73 mA h/cm2. This active-material-agnostic electrode fabrication method holds potential to tailor the morphology of flexible, current-collector-free electrodes, thus enabling LIBs to be optimized for high power or high energy density Li+ storage. Furthermore, this platform provides an electrode fabrication method that is applicable to other electrochemical technologies and advanced manufacturing methods.

Assessment of community-wide antimicrobials usage in Eastern China using wastewater-based epidemiology.

Wastewater-based epidemiology (WBE) has potential to identify the epidemiological links between people, animals, and the environment, as part of antimicrobial resistance (AMR) surveillance. In this study, we investigated six wastewater treatment plants (WWTPs) serving six communities located in two regions in Eastern China: Site A in Zhejiang and site B in Jiangsu province to assess the public use of antimicrobial agents (AA). Fifty antimicrobials and 24 of their metabolites were quantified using ultraperformance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-MS/MS). Spatiotemporal trends were established for measured concentrations, daily loads, and population-normalised daily loads. Daily AA mass loads varied between 1.6 g/day and 324.6 g/day reflecting the WWTP scales, with macrolides and ß-lactams showing the highest overall environmental burden at 223.7 g/day and 173.7 g/day, respectively. Emissions of antibiotic residues from manufacturing have been observed, with the peak daily load 12-fold higher than the overall load from a community serving a population of over 600,000. Community exposure levels of 225.2 ± 156.2 mg/day/1000 inhabitant and 351.9 ± 133.5 mg/day/1000 inhabitant were recorded in site A and B, respectively. Paired parent-metabolites analysis identified a large proportion (64-78%) of un-metabolised metronidazole and clindamycin at site B, indicating improper disposal of unused drugs either in the community or in livestock production. Consumption levels, calculated via WBE, suggested relatively low antimicrobial usage in Eastern China compared to other areas in China. This first application of WBE in Eastern China to assess the community-wide exposure to AAs has potential to inform regional antimicrobial stewardship.

Impacts of Antibiotic Residues in the Environment on Bacterial Resistance and Human Health in Eastern China: An Interdisciplinary Mixed-Methods Study Protocol.

Antibiotic resistance is a global health challenge that threatens human and animal lives, especially among low-income and vulnerable populations in less-developed countries. Its multi-factorial nature requires integrated studies on antibiotics and resistant bacteria in humans, animals, and the environment. To achieve a comprehensive understanding of the situation and management of antibiotic use and environmental transmission, this paper describes a study protocol to document human exposure to antibiotics from major direct and indirect sources, and its potential health outcomes. Our mixed-methods approach addresses both microbiological and pathogen genomics, and epidemiological, geospatial, anthropological, and sociological aspects. Implemented in two rural residential areas in two provinces in Eastern China, linked sub-studies assess antibiotic exposure in population cohorts through household surveys, medicine diaries, and biological sampling; identify the types and frequencies of antibiotic resistance genes in humans and food-stock animals; quantify the presence of antibiotic residues and antibiotic resistance genes in the aquatic environment, including wastewater; investigate the drivers and behaviours associated with human and livestock antibiotic use; and analyse the national and local policy context, to propose strategies and systematic measurements for optimising and monitoring antibiotic use. As a multidisciplinary collaboration between institutions in the UK and China, this study will provide an in-depth understanding of the influencing factors and allow comprehensive awareness of the complexity of AMR and antibiotic use in rural Eastern China.

Spectroscopic investigation of the electronic and excited state properties of para-substituted tetraphenyl porphyrins and their electrochemically generated ions.

Porphyrins play pivotal roles in many crucial biological processes including photosynthesis. However, there is still a knowledge gap in understanding electronic and excited state implications associated with functionalization of the porphyrin ring system. These effects can have electrochemical and spectroscopic signatures that reveal the complex nature of these somewhat minor substitutions, beyond simple inductive or electronic effect correlations. To obtain a deeper insight into the influences of porphyrin functionalization, four free-base, meso-substituted porphyrins: tetraphenyl porphyrin (TPP), tetra(4-hydroxyphenyl) porphyrin (THPP), tetra(4-carboxyphenyl) porphyrin (TCPP), and tetra(4-nitrophenyl) porphyrin (TNPP), were synthesized, characterized, and investigated. The influence of various substituents, (-hydroxy,-carboxy, and -nitro) in the para position of the meso-substituted phenyl moieties were evaluated by spectroelectrochemical techniques (absorption and fluorescence), femtosecond transient absorption spectroscopy, cyclic and differential pulse voltammetry, ultraviolet photoelectron spectroscopy (UPS), and time-dependent density functional theory (TD-DFT). Spectral features were evaluated for the neutral porphyrins and differences observed among the various porphyrins were further explained using rendered frontier molecular orbitals pertaining to the relevant transitions. Electrochemically generated anionic and cationic porphyrin species indicate similar absorbance spectroscopic signatures attributed to a red-shift in the Soret band. Emissive behavior reveals the emergence of one new fluorescence decay pathway for the ionic porphyrin, distinct from the neutral macrocycle. Femtosecond transient absorption spectroscopy analysis provided further analysis of the implications on the excited-state as a function of the para substituent of the free-base meso-substituted tetraphenyl porphyrins. Herein, we provide an in-depth and comprehensive analysis of the electronic and excited state effects associated with systematically varying the induced dipole at the methine bridge of the free-base porphyrin macrocycle and the spectroscopic signatures related to the neutral, anionic, and cationic species of these porphyrins.

Development of Bisphosphonate-Conjugated Antibiotics to Overcome Pharmacodynamic Limitations of Local Therapy: Initial Results with Carbamate Linked Sitafloxacin and Tedizolid.

The use of local antibiotics to treat bone infections has been questioned due to a lack of clinical efficacy and emerging information about Staphylococcus aureus colonization of the osteocyte-lacuno canalicular network (OLCN). Here we propose bisphosphonate-conjugated antibiotics (BCA) using a "target and release" approach to deliver antibiotics to bone infection sites. A fluorescent bisphosphonate probe was used to demonstrate bone surface labeling adjacent to bacteria in a S. aureus infected mouse tibiae model. Bisphosphonate and hydroxybisphosphonate conjugates of sitafloxacin and tedizolid (BCA) were synthesized using hydroxyphenyl and aminophenyl carbamate linkers, respectively. The conjugates were adequately stable in serum. Their cytolytic activity versus parent drug on MSSA and MRSA static biofilms grown on hydroxyapatite discs was established by scanning electron microscopy. Sitafloxacin O-phenyl carbamate BCA was effective in eradicating static biofilm: no colony formation units (CFU) were recovered following treatment with 800 mg/L of either the bisphosphonate or α-hydroxybisphosphonate conjugated drug (p < 0.001). In contrast, the less labile tedizolid N-phenyl carbamate linked BCA had limited efficacy against MSSA, and MRSA. CFU were recovered from all tedizolid BCA treatments. These results demonstrate the feasibility of BCA eradication of S. aureus biofilm on OLCN bone surfaces and support in vivo drug development of a sitafloxacin BCA.

Li-Zn Overlayer to Facilitate Uniform Lithium Deposition for Lithium Metal Batteries.

The highly reactive nature and rough surface of Li foil can lead to the uncontrollable formation of Li dendrites when employed as an anode in a lithium metal battery. Thus, it could be of great practical utility to create uniform, electrochemically stable, and "lithiophilic" surfaces to realize homogeneous deposition of Li. Herein, a LiZn alloy layer is deposited on the surface of Li foil by e-beam evaporation. The idea is to introduce a uniform alloy surface to increase the active area and make use of the Zn sites to induce homogeneous nucleation of Li. The results show that the alloy film protected the Li metal anode, allowing for a longer cycling life with a lower deposition overpotential over a pure-Li metal anode in symmetric Li cells. Furthermore, full cells pairing the modified lithium anode with a LiFePO4 cathode showed an incremental increase in Coulombic efficiency compared with pure-Li. The concept of using only an alloy modifying layer by an in-situ e-beam deposition synthesis method offers a potential method for enabling lithium metal anodes for next-generation lithium batteries.

In-Situ Characterization of Dynamic Morphological and Phase Changes of Selenium-doped Germanium Using a Single Particle Cell and Synchrotron Transmission X-ray Microscopy.

The dynamic information of lithium-ion battery active materials obtained from coin cell-based in-situ characterizations might not represent the properties of the active material itself because many other factors in the cell could have impacts on the cell performance. To address this problem, a single particle cell was developed to perform the in-situ characterization without the interference of inactive materials in the battery electrode as well as the X-ray-induced damage. In this study, the dynamic morphological and phase changes of selenium-doped germanium (Ge0.9 Se0.1 ) at the single particle level were investigated via synchrotron-based in-situ transmission X-ray microscopy. The results demonstrate the good reversibility of Ge0.9 Se0.1 at high cycling rate that helps understand its good cycling performance and rate capability. This in-situ and operando technique based on a single particle battery cell provides an approach to understanding the dynamic electrochemical processes of battery materials during charging and discharging at the particle level.

Stabilization of a Highly Ni-Rich Layered Oxide Cathode through Flower-Petal Grain Arrays.

Nickel adds to the capacity of layered oxide cathodes of lithium-ion batteries but comprises their stability. We report a petal-grained Li[Ni0.89Co0.10Sb0.01]O2 cathode that is, nevertheless, stable. The stability originates from the ordering of the nanosized grains in a dense, flower-petal-like array, where the elongated and nearly parallel grains radiate from the center to the surface. The ordering of the grains prevents microcrack generation from abrupt lattice changes of the stressful H2-H3 phase transition. The tight packing of the nanograins is conserved upon cycling, preventing destructive seepage of the electrolytic solution into the particles. The half-cell, cycling between 2.7-4.3 V versus Li/Li+ at a 0.5 C rate retains 95.0% of its initial capacity of 220 mAh g-1 after 100 cycles. The full-cell, cycling with a graphite anode and between 3.0-4.2 V at a 1 C rate, retains 83.9% of its initial capacity after 1000 cycles.