The liver is positioned at the interface between two routes traversed by pathogens in disseminating infection. Whereas blood-borne pathogens are efficiently cleared in hepatic sinusoids by Kupffer ...cells (KCs), it is unknown how the liver prevents dissemination of peritoneal pathogens accessing its outer membrane. We report here that the hepatic capsule harbors a contiguous cellular network of liver-resident macrophages phenotypically distinct from KCs. These liver capsular macrophages (LCMs) were replenished in the steady state from blood monocytes, unlike KCs that are embryonically derived and self-renewing. LCM numbers increased after weaning in a microbiota-dependent process. LCMs sensed peritoneal bacteria and promoted neutrophil recruitment to the capsule, and their specific ablation resulted in decreased neutrophil recruitment and increased intrahepatic bacterial burden. Thus, the liver contains two separate and non-overlapping niches occupied by distinct resident macrophage populations mediating immunosurveillance at these two pathogen entry points to the liver.
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•A distinct subset of resident macrophages (LCMs) occupies the hepatic capsule•LCMs are replenished from blood monocytes in the steady state•LCMs recruit neutrophils in response to bacteria reaching the liver capsule•LCM depletion decreases neutrophil recruitment and increases liver pathogen load
The hepatic sinusoids harbor a well-characterized resident macrophage population, Kupffer cells. Sierro et al. report an additional liver-resident macrophage population occupying the hepatic capsule, phenotypically and developmentally distinct from Kupffer cells, which plays a role in immunosurveillance by sensing peritoneal pathogens and recruiting neutrophils to control intrahepatic bacterial dissemination.
Giant lobes of plasma extend approximate55degrees above and below the Galactic center, glowing in emission from gamma rays (the Fermi Bubbles) to microwaves and polarized radio waves. We use ...ultraviolet absorption-line spectra from the Hubble Space Telescope to constrain the velocity of the outflowing gas within these regions, targeting the quasar PDS 456 (scriptl b = 10degrees.4, +11degrees.2). This sightline passes through a clear biconical structure seen in hard X-ray and gamma-ray emission near the base of the northern Fermi Bubble. We report two high-velocity metal absorption components, at upsilon sub(LSR) = -235 and +250 km s super(-1), which cannot be explained by co-rotating gas in the Galactic disk or halo. Their velocities are suggestive of an origin on the front and back side of an expanding biconical outflow emanating from the Galactic center. We develop simple kinematic biconical outflow models that can explain the observed profiles with an outflow velocity of > ~900 km s super(-1) and a full opening angle of approximate110degrees (matching the X-ray bicone). This indicates Galactic center activity over the last approximate2.5-4.0 Myr, in line with age estimates of the Fermi Bubbles. The observations illustrate the use of UV spectroscopy to probe the properties of swept-up gas venting into the Fermi Bubbles.
Abstract
Tungsten ditelluride (WTe
2
) is an atomically layered transition metal dichalcogenide whose physical properties change systematically from monolayer to bilayer and few-layer versions. In ...this report, we use apertureless scattering-type near-field optical microscopy operating at Terahertz (THz) frequencies and cryogenic temperatures to study the distinct THz range electromagnetic responses of mono-, bi- and trilayer WTe
2
in the same multi-terraced micro-crystal. THz nano-images of monolayer terraces uncovered weakly insulating behavior that is consistent with transport measurements. The near-field signal on bilayer regions shows moderate metallicity with negligible temperature dependence. Subdiffractional THz imaging data together with theoretical calculations involving thermally activated carriers favor the semimetal scenario with
$$\Delta \approx -10\,{{{\rm{meV}}}$$
Δ
≈
−
10
meV
over the semiconductor scenario for bilayer WTe
2
. Also, we observed clear metallic behavior of the near-field signal on trilayer regions. Our data are consistent with the existence of surface plasmon polaritons in the THz range confined to trilayer terraces in our specimens. Finally, data for microcrystals up to 12 layers thick reveal how the response of a few-layer WTe
2
asymptotically approaches the bulk limit.
To investigate the association of gestational age and mode of birth with early child development.
Population-based record linkage cohort study was conducted among 153 730 live-born infants of ≥32 ...weeks' gestation with developmental assessments at school age, in New South Wales, Australia, 2002 to 2007. Children were assessed in 5 domains: physical health and well-being, language and cognition, social competence, emotional maturity, and general knowledge and communication. Children scoring in the bottom 10% of national domains were considered developmentally vulnerable, and children developmentally vulnerable for ≥2 domains were classified as developmentally high risk (DHR), the primary outcome. Robust multivariable Poisson models were used to obtain individual and combined adjusted relative risks (aRRs) of gestational age and mode of birth for DHR children.
Overall, 9.6% of children were DHR. The aRR (95% confidence interval) of being DHR increased with decreasing gestational age (referent: 40 weeks); 32 to 33 weeks 1.25 (1.08-1.44), 34 to 36 weeks 1.26 (1.18-1.34), 37 weeks 1.17 (1.10-1.25), 38 weeks 1.06 (1.01-1.10), 39 weeks 0.98 (0.94-1.02), ≥41 weeks 0.99 (0.94-1.03), and for labor induction or prelabor cesarean delivery (planned birth; referent: vaginal birth after spontaneous labor), 1.07 (1.04-1.11). The combined aRR for planned birth was 1.26 (1.18-1.34) at 37 weeks and 1.13 (1.08-1.19) at 38 weeks.
Early (at <39 weeks) planned birth is associated with an elevated risk of poor child development at school age. The timing of planned birth is modifiable, and strategies to inform more judicious decision-making are needed to ensure optimal child health and development.
Immunosuppressed organ-transplant recipients have an increased incidence of, and mortality from, skin cancer. Nicotinamide (vitamin B
) enhances the repair of ultraviolet (UV) radiation-induced DNA ...damage, reduces the cutaneous immunosuppressive effects of UV radiation, and reduces the incidence of keratinocyte cancers (including squamous-cell and basal-cell carcinomas) and actinic keratoses among high-risk immunocompetent patients. Whether oral nicotinamide is useful for skin-cancer chemoprevention in organ-transplant recipients is unclear.
In this phase 3 trial, we randomly assigned, in a 1:1 ratio, organ-transplant recipients who had had at least two keratinocyte cancers in the past 5 years to receive 500 mg of nicotinamide or placebo twice daily for 12 months. Participants were examined for skin lesions by dermatologists at 3-month intervals for 12 months. The primary end point was the number of new keratinocyte cancers during the 12-month intervention period. Secondary end points included the numbers of squamous-cell and basal-cell carcinomas during the 12-month intervention period, the number of actinic keratoses until 6 months after randomization, safety, and quality of life.
A total of 158 participants were enrolled, with 79 assigned to the nicotinamide group and 79 to the placebo group. The trial was stopped early owing to poor recruitment. At 12 months, there were 207 new keratinocyte cancers in the nicotinamide group and 210 in the placebo group (rate ratio, 1.0; 95% confidence interval, 0.8 to 1.3; P = 0.96). No significant between-group differences in squamous-cell and basal-cell carcinoma counts, actinic keratosis counts, or quality-of-life scores were observed. Adverse events and changes in blood or urine laboratory variables were similar in the two groups.
In this 12-month, placebo-controlled trial, oral nicotinamide therapy did not lead to lower numbers of keratinocyte cancers or actinic keratoses in immunosuppressed solid-organ transplant recipients. (Funded by the National Health and Medical Research Council; ONTRANS Australian New Zealand Clinical Trials Registry number, ACTRN12617000599370.).
An Update on Orthobiologics: Cautious Optimism Nelson, Patrick A.; George, Tom; Bowen, Edward ...
The American journal of sports medicine,
01/2024, Letnik:
52, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Orthobiologics are rapidly growing in use given their potential to augment healing for multiple musculoskeletal conditions. Orthobiologics consist of a variety of treatments including platelet-rich ...plasma and stem cells that provide conceptual appeal in providing local delivery of growth factors and inflammation modulation. The lack of standardization in nomenclature and applications within the literature has led to a paucity of high-quality evidence to support their frequent use. The purpose of this review was to describe the current landscape of orthobiologics and the most recent evidence regarding their use.
To evaluate blood-labyrinth barrier permeability using delayed gadolinium enhanced three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) in patients with untreated sporadic vestibular ...schwannoma (VS) to interrogate the etiopathogenesis of progressive sensorineural hearing loss.
Prospective case series.
Single institution tertiary care center.
Patients with previously untreated small to medium-sized unilateral VS undergoing 3D-FLAIR imaging 10 minutes (immediate) and 5 to 8 hours (delayed) after administration of intravenous gadolinium.
Comparison of cochlear and vestibular signal intensity ratios (SIRs) across immediate and delayed images and across the tumor and nontumor ear.
Six of eight (75%) patients demonstrated asymmetric enhancement of inner ear structures on delayed contrast-enhanced imaging. Delayed mean cochlea and vestibule SIRs were significantly greater than immediate SIRs (cochlea: 1.91 versus 1.21 p = 0.02; vestibule 1.74 versus 1.15 p = 0.02). A higher vestibule SIR was statistically significantly associated with poorer pure-tone average and word recognition scores (p = 0.001).
Ears with VS exhibited increased enhancement on delayed 3D FLAIR imaging. These findings suggest that alterations in blood-labyrinth barrier permeability may explain progressive sensorineural hearing loss in a subset of patients with untreated VS.
Idiopathic subglottic stenosis (iSGS) is a localized airway disease that almost exclusively affects females. Understanding the molecular mechanisms involved may provide insights leading to ...therapeutic interventions. Next-generation sequencing was performed on tissue sections from patients with iSGS (n = 22), antineutrophil cytoplasmic antibody–associated vasculitis (AAV; n = 5), and matched controls (n = 9) to explore candidate genes and mechanisms of disease. Gene expression changes were validated, and selected markers were identified by immunofluorescence staining. Epithelial-mesenchymal transition (EMT) and leukocyte extravasation pathways were the biological mechanisms most relevant to iSGS pathogenesis. Alternatively activated macrophages (M2) were abundant in the subepithelium and perisubmucosal glands of the airway in iSGS and AAV. Increased expression of the mesenchymal marker S100A4 and decreased expression of the epithelial marker epithelial cell adhesion molecule (EPCAM) further supported a role for EMT, but to different extents, in iSGS and antineutrophil cytoplasmic antibody–associated subglottic stenosis. In patients with iSGS, high expression of prostate transmembrane protein, androgen induced 1 (PMEPA1), an EMT regulator, was associated with a shorter recurrence interval (25 versus 116 months: hazard ratio = 4.16; P = 0.041; 95% CI, 1.056–15.60). Thus, EMT is a key pathogenetic mechanism of subglottic stenosis in iSGS and AAV. M2 macrophages contribute to the pathogenesis of both diseases, suggesting a shared profibrotic mechanism, and PMEPA1 may be a biomarker for predicting disease recurrence in iSGS.
Gallic acid (GA, 3,4,5-trihydroxybenzoic acid) is a widely used natural food additive of interest to food chemistry researchers, especially regarding its effects on myofibrillar protein (MP) ...oxidation. However, existing studies regarding MP oxidation by GA-combined with Fenton reagents are inconsistent, and the detailed mechanisms have not been fully elucidated. This work validated hydroxyl radical (HO
) as the primary oxidant for MP carbonylation; in addition, it revealed three functions of GA in the Fenton oxidation of MP. By coordination with Fe(III), GA reduces Fe(III) to generate Fe(II), which is the critical reagent for HO
generation; meanwhile, the coordination improves the availability and reactivity of Fe(III) under weakly acidic and near-neutral pH, i.e., pH 4-6. Second, the intermediates formed during GA oxidation, including semiquinone and quinone, promoted Fenton reactivity by accelerating Fe catalytic cycling. Finally, GA can scavenge HO
radicals, thus exhibiting a certain degree of antioxidant property. All three functions contribute to MP oxidation as observed in GA-containing meat.
Aromatic carboxylic anhydrides are ubiquitous building blocks in organic materials chemistry and have received considerable attention in the synthesis of organic semiconductors, pigments, and battery ...electrode materials. Here we extend the family of aromatic carboxylic anhydrides with a unique new member, a conjugated cyclophane with four anhydride groups. The cyclophane is obtained in a three‐step synthesis and can be functionalised efficiently, as shown by the conversion into tetraimides and an octacarboxylate. Crystal structures reveal the high degree of porosity achievable with the new building block. Excellent electrochemical properties and reversible reduction to the tetraanions are shown for the imides; NMR and EPR measurements confirm the global aromaticity of the dianions and evidence the global Baird aromaticity of the tetraanions. Considering the short synthesis and unique properties, we expect widespread use of the new building block in the development of organic materials.
A unique new member of the family of aromatic carboxylic anhydride building blocks—a conjugated square‐shaped cyclophane with four anhydride groups—is presented. The building block can be obtained in a three‐step synthesis and functionalised efficiently to give materials with highly interesting properties ranging from high degrees of porosity to excellent electrochemical properties, as shown by the conversion into imides and carboxylates.
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