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Providing library patrons with seamless linking from database citations to full-text electronic journals (e-journals) is a goal of librarians, database vendors, and patrons. A number of products have been developed with this goal in mind. One important resource that provides such links to full-text publications from PubMed is LinkOut, freely available from the National Library of Medicine. Libraries face three practical issues when trying to implement PubMed's LinkOut: managing e-journals in general, determining which vendors, aggregators, and/or e-journals can work with LinkOut, and guiding patrons to access all of the full text that the library offers. This paper discusses each of these challenges from one library's perspective. [ABSTRACT FROM AUTHOR]

Legg-Calvé-Perthes disease (LCPD) is a childhood hip disorder characterized by ischemic injury to the epiphysis of the femoral head, but changes to the metaphysis have also been implicated in its pathogenesis. Quantitative magnetic resonance imaging (MRI) relaxation time mapping techniques are potentially useful to detect injury in LCPD, but studies to date have focused on the epiphysis. The purpose of this study was to assess whether T2, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation times can detect early metaphyseal changes in an LCPD piglet model. Complete epiphyseal ischemia of one femoral head was surgically induced and confirmed using contrast-enhanced MRI in n = 10 6-week-old piglets; the contralateral side was unoperated. The bilateral hips were imaged 1 week after surgery in vivo at 3T MRI using relaxation time mapping and contrast-enhanced MRI. Relaxation times and thicknesses of the metaphyseal primary and secondary spongiosa were measured and compared between the ischemic and contralateral-control femoral heads using paired t-tests. In the ischemic femoral heads, T2 relaxation times were significantly increased in the primary spongiosa (6.7 ± 9.8 ms, p = 0.029), and T2, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation times were significantly decreased in the secondary spongiosa (respectively: -13.3 ± 9.3 ms, p = 0.013; -32 ± 23 ms, p < 0.001; -43 ± 41 ms, p = 0.009; and -39 ± 13 ms, p < 0.001). The secondary spongiosa thickness was also significantly decreased in the ischemic femoral heads (p < 0.001). In conclusion, T2, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation time mapping techniques can detect early changes in the metaphysis following ischemic injury to the epiphysis of the femoral head in a piglet model of LCPD., (© 2024 The Author(s). Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

EGFR-targeted therapies are efficacious, but toxicity is common and can be severe. Urokinase type plasminogen activator receptor (uPAR)-targeted drugs are only emerging, so neither their efficacy nor toxicity is fully established. Recombinant eBAT was created by combining cytokines EGF and uPA on the same single-chain molecule with truncated Pseudomonas toxin. Its purpose was to simultaneously target tumors and their vasculature in the tumor microenvironment. In prior studies on mice and dogs, the drug proved efficacious. Here, we report the safety of eBAT in normal wildtype, uPAR knockout, and immunoreplete and immunodeficient tumor-bearing mice, as well as in dogs with spontaneous sarcoma that more closely mirror human cancer onset. In immunocompetent mice, tumor-bearing mice, uPAR knockout mice, and mice receiving species-optimized eBAT, toxicities were mild and self-limiting. Likewise, in dogs with life-threatening sarcoma given dosages found to be biologically active, eBAT was well tolerated. In mice receiving higher doses, eBAT was associated with dose-dependent evidence of liver injury, including portal biliary hyperplasia, oval cell proliferation, lymphoplasmacytic inflammation, periportal hepatocellular microvesicular change, hemorrhage, necrosis, and apoptosis. The results support continuing the clinical development of eBAT as a therapeutic agent for individuals with sarcoma and other cancers.

Energy storage and endocrine functions of the Drosophila fat body make it an excellent model for elucidating mechanisms that underlie physiological and pathophysiological organismal metabolism. Combined with Drosophila's robust genetic and immunofluorescence microscopy toolkits, studies of Drosophila fat body function are ripe for cell biological analysis. Unlike the larval fat body, which is easily removed as a single, cohesive sheet of tissue, isolating intact adult fat body proves to be more challenging, thus hindering consistent immunofluorescence labeling even within a single piece of adipose tissue. Here, we describe an improved approach to handling Drosophila abdomens that ensures full access of the adult fat body to solutions generally used in immunofluorescence labeling protocols. In addition, we assess the quality of fluorescence reporter expression and antibody immunoreactivity in response to variations in fixative type, fixation incubation time, and detergent used for cellular permeabilization. Overall, we provide several recommendations for steps in a whole-mount staining protocol that results in consistent and robust immunofluorescence labeling of the adult Drosophila fat body., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Ostechondritis dissecans (OCD) is an orthopaedic disease characterized by formation of osteochondral defects in developing joints. Epiphyseal cartilage necrosis (osteochondrosis [OC]) caused by focal failure of vascular supply is the known precursor lesion of OCD, but it remains to be established how the severity of vascular failure drives lesion healing or progression. In the current study we have implemented a novel piglet model of induced osteochondrosis of the lateral trochlear ridge of the femur to determine the role that the extent of ischemia plays in the development and progression of OC/OCD lesions. Ten 4-week-old Yorkshire piglets underwent surgical interruption of the vascular supply to the entirety (n = 4 pigs) or the distal half (n = 6 pigs) of the lateral trochlear ridge of the femur. At 2, 6, and 12 weeks postoperatively, distal femora were evaluated by magnetic resonance imaging (MRI) to determine the fate of induced OC lesions. At 12 weeks, piglets were euthanized, and the surgical sites were examined histologically. After complete devascularization, lesion size increased between the 6- and 12-week MRI by an average of 24.8 mm2 (95% CI: [-2.2, 51.7]; p = 0.071). During the same period, lesion size decreased by an average of 7.6 mm2 (95% CI: [-24.5, 19.4]; p = 0.83) in piglets receiving partial devascularization. At 12 weeks, average ± SD lesion size was larger (p<0.001) in piglets undergoing complete (73.5 ± 17.6 mm2) vs. partial (16.5 ± 9.8 mm2) devascularization. Our study demonstrates how the degree of vascular interruption determines lesion size and likelihood of healing in a large animal model of trochlear OC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tóth et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

From insects to humans, oogenesis is tightly linked to nutritional input, yet little is known about how whole organism physiology matches dietary changes with oocyte development. Considering that diet-induced adipose tissue dysfunction is associated with an increased risk for fertility problems, and other obesity-associated pathophysiologies, it is critical to decipher the cellular and molecular mechanisms linking adipose nutrient sensing to remote control of the ovary and other tissues. Our previous studies in Drosophila melanogaster have shown that amino acid sensing, via the amino acid response pathway and mTOR-mediated signaling function within adipocytes to control germline stem cell maintenance and ovulation, respectively. Additionally, we demonstrated that insulin/insulin-like growth factor signaling within adipocytes employs distinct effector axes, PI3K/Akt1-dependent and -independent, downstream of insulin receptor activity to mediate fat-to-ovary communication. Here, we report that the Ras/MAPK signaling axis functions in adipocytes to regulate early germline cyst survival and ovulation of mature oocytes but is not important for germline stem cell maintenance or the progression through vitellogenesis. Thus, these studies uncover the complexity of signaling pathway activity that mediates inter-organ communication., Competing Interests: Declaration of competing interest 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Sodium-ion batteries are emerging as a sustainable solution to tackle the growing global energy demands. In this context, organic electrode materials complement such technologies as they are composed of earth-abundant elements. As organic anodes, sodium carboxylates exhibit promising applicability in a wide range of molecules. To harness the advantages of individual systems and to minimise their limitations, in this work, an approach to form binary mixtures of sodium carboxylates using one-pot, microwave-assisted synthesis is presented. The target mixtures were synthesised in 30 min with disodium naphthalene-2,6-dicarboxylate (Na-NDC) as a common constituent in all. Both components in all mixtures were shown to participate in the charge storage and had a considerable effect on the performance characteristics, such as specific capacity and working voltage, in half and full cell formats. This approach opens a new avenue for enabling organic materials to be considered as more competitive candidates in sodium-ion batteries and promote their use in other material classes to overcome their limitations., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Failure of endochondral ossification due to interruption of the vascular supply to the epiphyseal cartilage is a critical step in the development of osteochondritis dissecans (OCD). Herein we describe the vascular architecture of the distal humeral epiphyseal cartilage in pigs and identify characteristic features that have been associated with sites predisposed to OCD development across species. Distal humeral specimens were harvested from pigs (n = 5, ages = 1, 10, 18, 30, and, 42 days old) and imaged at 9.4T magnetic resonance imaging (MRI) using a 3D gradient recalled echo sequence. The MRI data were processed using a quantitative susceptibility mapping (QSM) pipeline to visualize the vascular architecture. Specimens were also evaluated histologically to identify the presence of ischemic epiphyseal cartilage necrosis (osteochondrosis [OC]-latens) and associated failure of endochondral ossification (OC-manifesta). The QSM data enabled visualization of two distinct vascular beds arising from the perichondrium at the lateral and medial aspects of the distal humeral epiphysis. Elongated vessels originating from these beds coursed axially to supply the lateral and medial thirds of epiphyseal cartilage. At 18 days of age and older, a shift from perichondrial to transosseous blood supply was noted axially, which appeared more pronounced on the lateral side. This shift coincided with histologic identification of OC-latens (30- and 42-day-old specimens) and OC-manifesta (18- and 42-day-old specimens) lesions in the corresponding regions. The vascular anatomy and its evolution at the distal humeral epiphysis closely resembles that previously reported at predilection sites of knee OCD, suggesting a shared pathophysiology between the knee and elbow joints., (© 2023 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Organismal macronutrient intake modulates organ and tissue function. Dietary amino acids play essential roles in metabolic processes that support normal tissue growth, repair, and function. For example, in Drosophila melanogaster , protein-deficient diets lead to reduced overall organismal growth during larval development and severely decreased egg production in adult females. Multiple tissues, therefore, must sense and respond to dietary protein input. Amino acid transporter proteins facilitate the movement of amino acids across cellular membranes. Based on high-throughput expression studies, the Drosophila genome is predicted to encode 58 amino acid transporters. We have set out to determine if there are tissue-specific amino acid requirements for proper tissue function by first assessing the complement of amino acid transporters expressed in several adult tissues. Using RT-PCR to assess transcript levels, we find that most of the 24 amino acid transporters examined are expressed in the head, thorax, abdomen, gut, and ovary, while a subset shows differential transcript expression. This work will serve as the foundation for future studies addressing the impact of physiological factors, like nutrition, on amino acid sensing by individual tissues., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2024 by the authors.)

Sin Nombre virus (SNV) is an emerging virus that was first discovered in the Four Corners region of the United States in 1993. The virus causes a disease known as Hantavirus Pulmonary Syndrome (HPS), sometimes called Hantavirus Cardiopulmonary Syndrome (HCPS), a life-threatening illness named for the predominance of infection of pulmonary endothelial cells. SNV is one of several rodent-borne hantaviruses found in the western hemisphere with the capability of causing this disease. The primary reservoir of SNV is the deer mouse ( Peromyscus maniculatus ), and the virus is transmitted primarily through aerosolized rodent excreta and secreta. Here, we review the history of SNV emergence and its virus biology and relationship to other New World hantaviruses, disease, treatment, and prevention options.

Pathways leading to osteoarthritis (OA) are diverse depending on the risk factors involved; thus, developing OA therapeutics has been challenging. Here we report that nuclear protein-1 (Nupr1), a stress-inducible protein/transcription factor, is activated by pathways associated with obesity and aging in chondrocytes. Treatment of human chondrocytes with free fatty acids (palmitate and oleate; a model for high-fat diet/obesity) induced PERK signaling and increased expression of caspase-3, TRB3, and Nupr1. On the other hand, treatment of chondrocytes with menadione (oxidative stress inducer) induced oxidation of IRE1, activated antioxidant response (higher Nrf2 expression), and increased expression of Nupr1 and matrix metalloproteinases. Experimental OA was induced by destabilization of the medial meniscus (DMM) in the knee joints of Nupr1 +/+ and Nupr1 -/- mice. Loss of Nupr1 expression reduced the severity of cartilage lesions in this model. Together, our findings suggest that Nupr1 is a common factor activated by signaling pathways activated by obesity (ER stress) and age (oxidative stress) and a potential drug target for OA resulting from various risk factors., (© 2023 Federation of American Societies for Experimental Biology.)

Objective: To determine the effects of acute (≤7 days) femoral head ischemia on the proximal femoral growth plate and metaphysis in a piglet model of Legg-Calvé-Perthes disease (LCPD). We hypothesized that qualitative and quantitative histological assessment would identify effects of ischemia on endochondral ossification., Design: Unilateral femoral head ischemia was surgically induced in piglets, and femurs were collected for histological assessment at 2 (n = 7) or 7 (n = 5) days post-ischemia. Samples were assessed qualitatively, and histomorphometry of the growth plate zones and primary spongiosa was performed. In a subset of samples at 7 days, hypertrophic chondrocytes were quantitatively assessed and immunohistochemistry for TGFβ1 and Indian hedgehog was performed., Results: By 2 days post-ischemia, there was significant thinning of the proliferative and hypertrophic zones, by 63 μm (95% CI -103, -22) and -19 μm (95% CI -33, -5), respectively. This thinning persisted at 7 days post-ischemia. Likewise, at 7 days post-ischemia, the primary spongiosa was thinned to absent by an average of 311 μm (95% CI -542, -82) in all ischemic samples. TGFβ1 expression was increased in the hypertrophic zone at 7 days post-ischemia., Conclusions: Alterations to the growth plate zones and metaphysis occurred by 2 days post-ischemia and persisted at 7 days post-ischemia. Our findings suggest that endochondral ossification may be disrupted at an earlier time point than previously reported and that growth disruption may occur in the piglet model as occurs in some children with LCPD., (Copyright © 2023 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

The development of multielectron redox-active cathode materials is a top priority for achieving high energy density with long cycle life in the next-generation secondary battery applications. Triggering anion redox activity is regarded as a promising strategy to enhance the energy density of polyanionic cathodes for Li/Na-ion batteries. Herein, K 2 Fe(C 2 O 4 ) 2 is shown to be a promising new cathode material that combines metal redox activity with oxalate anion (C 2 O 4 2- ) redox. This compound reveals specific discharge capacities of 116 and 60 mAh g -1 for sodium-ion batterie (NIB) and lithium-ion batterie (LIB) cathode applications, respectively, at a rate of 10 mA g -1 , with excellent cycling stability. The experimental results are complemented by density functional theory (DFT) calculations of the average atomic charges., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Juvenile osteochondritis dissecans (JOCD) is a pediatric orthopedic disorder that involves the articular-epiphyseal cartilage complex and underlying bone. Clinical disease is often characterized by the presence of radiographically apparent osteochondral flaps and fragments. The existence of early JOCD lesions (osteochondrosis latens [OCL] and osteochondrosis manifesta [OCM]) that precede the development of osteochondral flaps and fragments is also well recognized. However, identification of naturally occurring OCL lesions (confined to cartilage) using noninvasive imaging techniques has not yet been accomplished. We hypothesized that 10.5 T magnetic resonance imaging (MRI) can identify naturally occurring OCL lesions at predilection sites in intact joints of juvenile pigs. Unilateral elbows and knees (stifles) were harvested from three pigs aged 4, 8, and 12 weeks, and scanned in a 10.5 T MRI to obtain morphological 3D DESS images, and quantitative T2 and T1ρ relaxation time maps. Areas with increased T2 and T1ρ relaxation times in the articular-epiphyseal cartilage complex were identified in 1/3 distal femora and 3/3 distal humeri and were considered suspicious for OCL or OCM lesions. Histological assessment confirmed the presence of OCL or OCM lesions at each of these sites and failed to identify additional lesions. Histological findings included necrotic vascular profiles associated with areas of chondronecrosis either confined to the epiphyseal cartilage (OCL, 4- and 8-week-old specimens) or resulting in a delay in endochondral ossification (OCM, 12-week-old specimen). Future studies with clinical MR systems (≤7 T) are needed to determine whether these MRI methods are suitable for the in vivo diagnosis of early JOCD lesions in humans., (© 2022 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Nutritional stress impacts many insect species that have differing reproductive strategies and life histories, yet it is unclear how nutrient-sensing signaling pathways mediate tissue-specific responses to changes in dietary input. In Drosophila melanogaster , insulin/insulin-like growth factor (IIS) and mTOR-mediated signaling within adipocytes regulates oogenesis. To facilitate comparative study of nutrient-sensing pathway activity in the fat body, we developed antibodies to assess IIS (anti-FOXO) and mTOR signaling (anti-TOR) across three nymphalid species (Lepidoptera). By optimizing whole-mount fat body immunostaining, we find FOXO nuclear enrichment in adult adipocytes, like that observed in Drosophila . Additionally, we show a previously uncharacterized TOR localization pattern in the fat body., (Copyright: © 2023 by the authors.)

Since the outbreak of SARS-CoV-2, a multitude of strategies have been explored for the means of protection and shielding against virus particles: filtration equipment (PPE) has been widely used in daily life. In this work, we explore another approach in the form of deactivating coronavirus particles through selective binding onto the surface of metal-organic frameworks (MOFs) to further the fight against the transmission of respiratory viruses. MOFs are attractive materials in this regard, as their rich pore and surface chemistry can easily be modified on demand. The surfaces of three MOFs, UiO-66(Zr), UiO-66-NH 2 (Zr), and UiO-66-NO 2 (Zr), have been functionalized with repurposed antiviral agents, namely, folic acid, nystatin, and tenofovir, to enable specific interactions with the external spike protein of the SARS virus. Protein binding studies revealed that this surface modification significantly improved the binding affinity toward glycosylated and non-glycosylated proteins for all three MOFs. Additionally, the pores for the surface-functionalized MOFs can adsorb water, making them suitable for locally dehydrating microbial aerosols. Our findings highlight the immense potential of MOFs in deactivating respiratory coronaviruses to be better equipped to fight future pandemics.

Sodium-ion batteries (NIBs) are emerging as promising devices for energy storage applications. Porous solids, such as metal-organic frameworks (MOFs), are well suited as electrode materials for technologies involving bulkier charge carriers. However, only limited progress has been made using pristine MOFs, primarily due to lack of redox-active organic groups in the materials. In this work a azo-functional MOF, namely UiO-abdc, is presented as an electrode compound for sodium-ion insertion. The MOF delivers a stable capacity (∼100 mA h g -1 ) over 150 cycles, and post-cycling characterisation validates the stability of the MOF and participation of the azo-group in charge storage. This study can accelerate the realisation of pristine solids, such as MOFs and other porous organic compounds, as battery materials.

Physiological status, particularly dietary input, has major impacts on the Drosophila melanogaster ovarian germline stem cell lineage. Moreover, several studies have shed light on the role that inter-organ communication plays in coordinating whole-organism responses to changes in physiology. For example, nutrient-sensing signaling pathways function within the fat body to regulate germline stem cells and their progeny in the ovary. Together with its incredible genetic and cell biological toolkits, Drosophila serves as an amenable model organism to use for uncovering molecular mechanisms that underlie physiological control of adult stem cells. In this methods chapter, we describe a general dietary manipulation paradigm, genetic manipulation of adult adipocytes, and whole-mount ovary immunofluorescence to investigate physiological control of germline stem cells., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

This brief report provides an overview of lessons learned through evaluation of the first five years of the NIA-funded South Carolina-Advancing Diversity in Aging Research (SC-ADAR) undergraduate program, whose goal is to increase the number of qualified underrepresented minority (URM) students who pursue scientific graduate studies in programs focusing on medicine, science, technology, engineering, and mathematics and aging. Partnering with five Historically Black Colleges and Universities in South Carolina, we implemented a research training approach that included two consecutive summers of research training in a University of South Carolina faculty laboratory, as part of a comprehensive 24-month research education program. In addition to the mentored research experience in a laboratory, students had coursework in the biology of aging and social gerontology, with additional workshops tailored to emergent student needs including basic academic skills development, work-life management skills, reflective social experiences, and enhanced support in the transition from undergraduate to graduate school. We provide an overview of lessons learned throughout the early program period, and a description of the iterative changes we made in the program in response to this learning, all of which have been incorporated into the existing SC-ADAR program.

Objective: To determine if the quantitative MRI techniques T2 and T1ρ mapping are sensitive to ischemic injury to epiphyseal cartilage in vivo in a piglet model of Legg-Calvé-Perthes disease using a clinical 3T MRI scanner. We hypothesized that T2 and T1ρ relaxation times would be increased in the epiphyseal cartilage of operated vs contralateral-control femoral heads 1 week following onset of ischemia., Design: Unilateral femoral head ischemia was surgically induced in eight piglets. Piglets were imaged 1 week post-operatively in vivo at 3T MRI using a magnetization-prepared 3D fast spin echo sequence for T2 and T1ρ mapping and a 3D gradient echo sequence for cartilage segmentation. Ischemia was confirmed in all piglets using gadolinium contrast-enhanced MRI. Median T2 and T1ρ relaxation times were measured in the epiphyseal cartilage of the ischemic and control femoral heads and compared using paired t-tests. Histological assessment was performed on a subset of five piglets., Results: T2 and T1ρ relaxation times were significantly increased in the epiphyseal cartilage of the operated vs control femoral heads (ΔT2 = 11.9 ± 3.7 ms, 95% CI = [8.8, 15.0] ms, P < 0.0001; ΔT1ρ = 12.8 ± 4.1 ms, 95% CI = [9.4, 16.2] ms, P < 0.0001). Histological assessment identified chondronecrosis in the hypertrophic and deep proliferative zones within ischemic epiphyseal cartilage., Conclusions: T2 and T1ρ mapping are sensitive to ischemic injury to the epiphyseal cartilage in vivo at clinical 3T MRI. These techniques may be clinically useful to assess injury and repair to the epiphyseal cartilage to better stage the extent of ischemic damage in Legg-Calvé-Perthes disease., (Copyright © 2022 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

The fundamental understanding of electrochemical reaction kinetics for lithium/sodium-ion batteries (LIBs & NIBs) is a significant criterion for advancing new-generation electrode materials. Herein, we demonstrate a novel lithium-rich perovskite oxalate KLi 3 Fe(C 2 O 4 ) 3 (KLFC) cathode with the combination of cation and anion redox delivering discharge capacities of 86 and 99 mA h g -1 after 100 cycles for a LIB and NIB, respectively, with good cyclability. Experimental Raman spectroscopy analysis combined with DFT calculations of charged/discharged samples illustrate the oxalate anion redox activity. Further, first-principles calculations of the partial density of states and Bader charges analysis have also characterised the redox behaviour and charge transfer during the potassium extraction processes.

In collaboration with the American College of Veterinary Pathologists.

Objective: The study objective was to determine whether overexpression of the mitochondrial antioxidant peroxidase, peroxiredoxin 3 (Prx3), reduces the severity of osteoarthritis (OA) in mice., Methods: Age-related OA (age 18 and 24 months) and OA induced by destabilization of the medial meniscus (DMM at age 6 months) were assessed in male mice that overexpress a human Prdx3 transgene encoding the Prx3 protein. Lox-stop-lox-Prdx3 (iPrdx3) mice were crossed with aggrecan-Cre ERT2 mice to produce iPrdx3AgCre ERT2 or with Col2Cre to produce iPrdx3Col2Cre mice. Germline transgenics (Prdx3Tg) were also evaluated. Prx3 protein level was assessed by immunoblotting and functionally after induction of elevated mitochondrial hydrogen peroxide (H 2 O 2 ) using menadione. Histological sections of stifle joints were scored for cartilage damage (Articular Cartilage Structure score [ACS]), osteophytes, and synovial hyperplasia and were evaluated by histomorphometry., Results: Overexpression of Prx3 maintained mitochondrial membrane integrity and inhibited p38 phosphorylation in the presence of elevated H 2 O 2 . ACS scores of 18-month-old iPrdx3AgCre ERT2 mice (mean ± SD, 4.88 ± 5.05) were significantly lower than age-matched iPrdx3 controls (11.75 ± 6.34, P = 0.002) and trended lower in the 18-month Prdx3Tg group (P = 0.14), whereas no significant differences between experimental and control groups at 24 months of age or in OA induced by DMM surgery were noted. Osteophyte scores trended lower in the 18-month-old Prdx3Tg group (P = 0.09) and at 24 months in the iPrdx3Col2Cre mice (P = 0.05). There were no significant group differences in synovial hyperplasia or histomorphometric measures., Conclusion: Overexpression of the mitochondrial peroxidase Prx3 reduced the severity of age-related OA, but not at advanced ages and not in DMM-induced OA in younger mice., (© 2022 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Conjugated alkali metal dicarboxylates have recently received attention for applications as organic anode materials in lithium- and sodium-ion batteries. In order to understand and optimise these materials, it is important to be able to characterise both the long-range and local aspects of the crystal structure, which may change during battery cycling. Furthermore, some materials can display polymorphism or hydration behaviour. NMR crystallography, which combines long-range crystallographic information from diffraction with local information from solid-state NMR via interpretation aided by DFT calculations, is one such approach, but this has not yet been widely applied to conjugated dicarboxylates. In this work, we evaluate the application of NMR crystallography for a set of model lithium and sodium dicarboxylate salts. We investigate the effect of different DFT geometry optimisation strategies and find that the calculated NMR parameters are not systematically affected by the choice of optimisation method, although the inclusion of dispersion correction schemes is important to accurately reproduce the experimental unit cell parameters. We also observe hydration behaviour for two of the sodium salts and provide insight into the structure of an as-yet uncharacterised structure of sodium naphthalenedicarboxylate. This highlights the importance of sample preparation and characterisation for organic sodium-ion battery anode materials in particular., (© 2022 The Authors. Magnetic Resonance in Chemistry published by John Wiley & Sons Ltd.)

We studied systemic ceftriaxone, and free/local tobramycin and doxycycline in a controlled rat model representing a generic acute exogenous joint infection. We hypothesized that evidence of infection (quantitative colony forming units [CFU], qualitative scanning electron microscopy [SEM], histopathology) (1a) would be reduced with local versus systemic antibiotic, (1b) any antibiotic would be superior to control, (2) there would be a difference among antibiotics, and (3) antibiotic would not be detectable in serum at 4-week euthanasia. Study groups included infected and noninfected (1) control (no treatment), (2) systemic ceftriaxone (daily), (3) local tobramycin, and (4) local doxycycline (10 rats/group; power = 0.8). With IACUC approval, a reliable acute exogenous joint infection was created by slowly injecting 50-μl, 10 4 CFU Staphylococcus aureus, into the distal femoral medullary canal. The antibiotic formulation was introduced locally to the femoral canal and joint space. After 4 weeks, serum, pin, bone, and synovium were obtained. CFU/ml of bone and synovium were quantified using macrotiter method. SEM imaged biofilm on the surface of the pin, histopathology identified tissue response, liquid chromatography/mass spectrometry quantified plasma antibiotic. (1) Groups receiving any antibiotic reported lower CFU/ml in synovium compared with no treatment. (2) In the synovium, free/local tobramycin reduced CFU/ml to a greater extent than free/local doxycycline (p < 0.05). (3) Antibiotic in plasma after the local application was nondetectable in all groups after 4 weeks. SEM revealed no difference in biofilm on pin among all groups., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

This study investigated the sensitivity of T1ρ and T2 relaxation time mapping to detect acute ischemic injury to the secondary ossification center (SOC) and epiphyseal cartilage of the femoral head in a piglet model of Legg-Calvé-Perthes disease. Six piglets underwent surgery to induce global right femoral head ischemia and were euthanized 48 h later. Fresh operated and contralateral-control femoral heads were imaged ex vivo with T1, T2, and T1ρ mapping using a 9.4T magnetic resonance imaging scanner. The specimens were imaged a second time after a freeze/thaw cycle and then processed for histology. T1, T2, and T1ρ measurements in the SOC, epiphyseal cartilage, articular cartilage, and metaphysis were compared between operated and control femoral heads using paired t tests. The effects of freeze/thaw, T1ρ spin-lock frequency, and fat saturation were also investigated. Five piglets with histologically confirmed ischemic injury were quantitatively analyzed. T1ρ was increased in the SOC (101 ± 15 vs. 73 ± 16 ms; p = 0.0026) and epiphyseal cartilage (84.9 ± 9.2 vs. 74.3 ± 3.6 ms; p = 0.031) of the operated versus control femoral heads. T2 was also increased in the SOC (28.7 ± 2.0 vs. 22.7 ± 1.7; p = 0.0037) and epiphyseal cartilage (57.4 ± 4.7 vs. 49.0 ± 2.7; p = 0.0041). No changes in T1 were detected. The sensitivities of T1ρ and T2 mapping in detecting ischemic injury were maintained after a freeze/thaw cycle, and T1ρ sensitivity was maintained after varying spin-lock frequency and applying fat saturation. In conclusion, T1ρ and T2 mapping are sensitive in detecting ischemic injury to the SOC and epiphyseal cartilage of the femoral head as early as 48 h after ischemia induction., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Obesity has repeatedly been linked to reorganization of the gut microbiome, yet to this point obesity therapeutics have been targeted exclusively toward the human host. Here, we show that gut microbe-targeted inhibition of the trimethylamine N-oxide (TMAO) pathway protects mice against the metabolic disturbances associated with diet-induced obesity (DIO) or leptin deficiency ( Lep ob/ob ). Small molecule inhibition of the gut microbial enzyme choline TMA-lyase (CutC) does not reduce food intake but is instead associated with alterations in the gut microbiome, improvement in glucose tolerance, and enhanced energy expenditure. We also show that gut microbial CutC inhibition is associated with reorganization of host circadian control of both phosphatidylcholine and energy metabolism. This study underscores the relationship between microbe and host metabolism and provides evidence that gut microbe-derived trimethylamine (TMA) is a key regulator of the host circadian clock. This work also demonstrates that gut microbe-targeted enzyme inhibitors have potential as anti-obesity therapeutics., Competing Interests: RS, CG, LO, WM, NS, AH, RB, DO, RH, AB, AB, CF, KF, FA, DF, AG, CN, KC, AM, JA, MM, MG, BW, TM, AA, GS, AK, AL, JB No competing interests declared, JB reports being eligible to receive royalty payments for inventions or discoveries related to cardiovascular therapeutics from the Proctor & Gamble Co, JG Employee of Procter & Gamble Company, ZW, SH reports being named as co-inventor on pending and issued patents 20200121615 held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics. Reports being a paid consultant for Procter & Gamble, having received research funds from Procter & Gamble, Roche Diagnostics, and being eligible to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics or therapeutics from Cleveland Heart Lab and Procter & Gamble, (© 2022, Schugar et al.)

Sodium-ion batteries are commanding increasing attention owing to their promising electrochemical performance and sustainability. Organic electrode materials (OEMs) complement such technologies as they can be sourced from biomass and recycling them is environmentally friendly. Organic anodes based on sodium carboxylates have exhibited immense potential, except the limitation of current synthesis methods concerning upscaling and energy costs. In this work, a rapid and energy efficient microwave-assisted synthesis for organic anodes is presented using sodium naphthalene-2,6-dicarboxylate as a model compound. Optimizing the synthesis and electrode composition enables the compound to deliver a reversible initial capacity of ≈250 mAh g -1 at a current density of 25 mA g -1 with a high initial Coulombic efficiency (≈78%). The capacity is stable over 400 cycles and the compound also exhibits good rate performance. The successful demonstration of this rapid synthesis may facilitate the transition to preparing organic battery materials by scalable, efficient methods., (© 2021 The Authors. Small Methods published by Wiley-VCH GmbH.)

The rapid growth in the field of metal-organic frameworks (MOFs) over recent years has highlighted their high potential in a variety of applications. For biological and environmental applications MOFs with low toxicity are vitally important to avoid any harmful effects. For this reason, Ca-based MOFs are highly desirable owing to their low cost and high biocompatibility. Useful Ca MOFs are still rare owing to the ionic character and large size of the Ca 2+ ion tending to produce dense phases. Presented here is a novel Ca-based MOF containing 2,3-dihyrdoxyterephthalate (2,3-dhtp) linkers Ca(2,3-dhtp)(H 2 O) (SIMOF-4). The material undergoes a phase transformation on heating, which can be followed by variable temperature powder X-ray diffraction. The structure of the high temperature form was obtained using single-crystal X-ray diffraction. The electrochemical properties of SIMOF-4 were also investigated for use in a Na ion battery.

Objective: To compare the Osteoarthritis Research Society International (OARSI) and Articular Cartilage Structure (ACS) grading schemes applied to multiple and single sections, along with additional histologic measures, in two mouse models of Osteoarthritis (OA)., Methods: Six coronal histologic stifle joint sections were collected from 40 C57BL/6J mice, including aged mice with spontaneous OA (approximately 18 months of age; n = 15) and young (12-week-old) mice that either underwent destabilization of the medial meniscus (DMM) surgery (n = 15) or sham surgery (n = 10). Sections were evaluated with the standard OARSI (0-6) scheme, a modified OARSI scheme, the ACS (0-12) scheme, histomorphometry of cartilage and bone, and scoring of osteophytes (0-3) and synovial hyperplasia (0-3). Principal components analysis (PCA) was used to determine the features explaining the greatest variability among the sections., Results: The grading schemes performed similarly when applied to a single mid-coronal section or six total coronal sections per joint. OARSI grading produced similar results when applied to hematoxylin and eosin or toluidine blue-stained sections. Aged mice had higher severity scores in the LTP than DMM mice (mid-coronal OARSI grade aged = 2.3 and DMM = 1.1, p = 0.0006; ACS grade aged = 4.1 and DMM = 1.6, p = 0.0024). PCA resulted in retention of four factors that accounted for 78.4% of the total variance. Factor 1 (36.4%) included the OARSI grade, ACS grade, Toluidine blue grade, articular cartilage area and thickness and the osteophyte grade., Conclusions: Grading of a single mid-coronal section using either the OARSI or ACS schemes combined with osteophyte and histomorphometric measures can consistently define OA severity in mice., (Copyright © 2021 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Transition-metal oxalates have wide applications in magnetics, photoemission, electrochemistry, etc. Herein, using hydrothermal reactions, five cobalt(II) oxalates, Na 2 Co 2 (C 2 O 4 ) 3 ·2H 2 O ( I ), Na 2 Co(C 2 O 4 ) 2 ·8H 2 O ( II ), KLi 3 Co(C 2 O 4 ) 3 ( III ), Li 4 Co(C 2 O 4 ) 3 ( IV ), and (NH 4 ) 2 Co 2 (C 2 O 4 )F 4 ( V ) have been synthesized, and their structures are determined from single-crystal X-ray diffraction or Rietveld refinement of powder X-ray diffraction data. Notably, IV and V are identified for the first time. The structures of these cobalt oxalates are versatile, covering 0D, 1D, 2D, and 3D frameworks, while the coordination environments of Co 2+ centers are uniquely distorted octahedra. As representative examples, I and III are investigated as cathode materials for secondary batteries. Both exhibited electrochemical activity despite large cell polarization. The present study enriches the transition-metal oxalate family and provides new options for energy storage materials.

Electrochemical energy storage (EES) devices are gaining ever greater prominence in the quest for global energy security. With increasing applications and widening scope, rechargeable battery technology is gradually finding avenues for more abundant and sustainable systems such as Na-ion (NIB) and K-ion batteries (KIB). Development of suitable electrode materials lies at the core of this transition. Organic redox-active molecules are attractive candidates as negative electrode materials owing to their low redox potentials and the fact that they can be obtained from biomass. Also, the rich structural diversity allows integration into several solid-state polymeric materials. Research in this domain is increasingly focused on deploying molecular engineering to address specific electrochemical limitations that hamper competition with rival materials. This Minireview aims to summarize the advances in both the electrochemical properties and the materials development of organic anode materials., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

Objective: While a role for vitamin K in maintaining joint tissue homeostasis has been proposed based on the presence of vitamin K dependent proteins in cartilage and bone, it is not clear if low vitamin K intake is causally linked to joint tissue degeneration. To address this gap, we manipulated vitamin K status in aging mice to test its effect on age-related changes in articular cartilage and sub-chondral bone., Methods: Eleven-month old male C57BL6 mice were randomly assigned to a low vitamin K diet containing 120 mcg phylloquinone/kg diet (n = 32) or a control diet containing 1.5 mg phylloquinone/kg diet (n = 30) for 6 months. Knees were evaluated histologically using Safranin O and H&E staining, as well as using micro-CT., Results: Eleven mice in the low vitamin K diet group and three mice in the control group died within the first 100 days of the experiment (p = 0.024). Mice fed the low vitamin K diet had higher Safranin-O scores, indicative of more proteoglycan loss, compared to mice fed the control diet (p ≤ 0.026). The articular cartilage structure scores did not differ between the two groups (p ≥ 0.190). The sub-chondral bone parameters measured using micro CT also did not differ between the two groups (all p ≥ 0.174)., Conclusion: Our findings suggest low vitamin K status can promote joint tissue proteoglycan loss in older male mice. Future studies are needed to confirm our findings and obtain a better understanding of the molecular mechanisms underlying the role of vitamin K in joint tissue homeostasis., Competing Interests: The authors have no conflicts to declare., (© 2020 The Authors.)

Introduction: Alcohol increases the risk of colon cancer. Colonic inflammation mediates the effects of alcohol on colon carcinogenesis. Circadian rhythm disruption enhances the alcohol's effect on colonic inflammation and cancer., Objective: Here, we investigate the diurnal variation of lymphocyte infiltration in the colonic mucosa in response to alcohol., Methods: Sixty C57BL6/J mice were fed a chow diet, and gavaged with alcohol at a specific time once per day for 3 consecutive days. Immunohistochemistry and immunofluorescence staining were used to quantify total, effector, and regulatory T cells in the colon. Student's t test, one-way ANOVA, and two-way ANOVA were used to determine significance., Results: Following the alcohol binge, the composition of immune T cell subsets in the mouse colon was time-dependent. Alcohol did not alter the total number of CD3 + T cells. However, upon alcohol treatment, T-bet + T helper 1 (Th1) cells appeared to dominate the T cell population following a reduction in Foxp3 + regulatory T cell (Treg) numbers. Depletion of Tregs was time-dependent, and their numbers were dramatically reduced when alcohol was administered during the rest phase. A reduction in Tregs significantly increased the Th1/Treg ratio, resulting in a more proinflammatory milieu., Conclusions: Alcohol enhanced the proinflammatory profile in the colon mucosa, as demonstrated by a higher T-bet + /Foxp3 + ratio, especially during the rest phase. These findings may partly account for the interaction of circadian rhythm disruption with alcohol in colon inflammation and cancer., Competing Interests: None of the authors has any potential conflicts (financial, professional, or personal) related to the manuscript to disclose., (Copyright © 2020 by S. Karger AG, Basel.)

Hierarchical carbon-rich materials have shown immense potential for various electrochemical applications. Metal-organic frameworks (MOFs) are well suited precursors for obtaining such templated carbon matrices. Usually these conversions are carried out by energy intensive processes and lead to the presence of toxic transition metal residues. Herein, we demonstrate the green, scalable, microwave-assisted synthesis of a three-dimensional s-block metal based MOF and its efficient transformation into a carbonaceous material. The MOF-derived solid functions as a negative electrode for lithium-ion batteries having moderate low-rate capacities and cycling stability., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Observed in a wide variety of organism, from invertebrates to mammals, nutritional status modulates the energetically costly effort of producing female gametes. Despite this long-standing link between nutrition and ovarian function, relatively little is known about the cellular and molecular mechanisms that underlie how dietary components modulate egg production. Drosophila melanogaster, with its powerful and extensive genetic tools as well as its well-characterized ovarian response to diet, has proven to be instrumental in addressing this issue. This review covers what we currently know about the dietary control of oogenesis in Drosophila and the salient features of the fruit fly that make it a model for nutritional control of ovarian function.

Clostridium difficile is a well-documented cause of enterocolitis in several species, including humans, with limited documentation in New World nonhuman primates. We report several cases of C. difficile -associated pseudomembranous enterocolitis, including a case in a Geoffroy's spider monkey ( Ateles geoffroyi ) and several cases in common marmosets ( Callithrix jacchus ). The histologic lesions included a spectrum of severity, with most cases characterized by the classic "volcano" lesions described in humans and several other animal species. C. difficile was isolated from the colon of the spider monkey, while the presence of toxin A or toxin B or of the genes of toxin A or B by polymerase chain reaction served as corroborative evidence in several affected marmosets. C. difficile should be considered a cause of enterocolitis in these species.