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1.
Phys Rev Lett ; 133(3): 033201, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39094141

ABSTRACT

Excess "micromotion" of trapped ions due to the residual radio-frequency (rf) trapping field at their location is often undesirable and is usually carefully minimized. Here, we induce precise amounts of excess micromotion on individual ions by adjusting the local static electric field they experience. Micromotion modulates the coupling of an ion to laser fields, ideally tuning it from its maximum value to zero as the ion is moved away from the trap's rf null. We use tunable micromotion to vary the Rabi frequency of stimulated Raman transitions over two orders of magnitude, and to individually control the rates of resonant fluorescence from three ions under global laser illumination without any changes to the driving light fields. The technique is amenable to situations where addressing individual ions with focused laser beams is challenging, such as tightly packed linear ion strings or two-dimensional ion arrays illuminated from the side.

2.
Parkinsonism Relat Disord ; 127: 107082, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39106762

ABSTRACT

BACKGROUND: Up to 10 % of Parkinson's disease (PD) populations carry a genetic risk variant, which may not only increase one's chance of developing PD but also affect disease presentation and progression. We hypothesize motor impairment in genetic carriers of PD correlate to different patterns of microstructural changes over time. DESIGN/METHODS: Data were accessed from the Parkinson's Progression Markers Initiative (PPMI) project. Connectometry analyses were performed for GBA1+ PD, LRRK2+ PD, and sporadic PD correlating white matter structural changes, as measured by quantitative anisotropy (QA), with motor impairment, as measured by MDS-UPDRS III. RESULTS: There was a negative correlation between QA and MDS-UPDRS III in all 3 cohorts at 48 months. In GBA1+ PD (n = 12), the white matter tracts identified were cortical and subcortical, while in the LRRK2+ PD (n = 18) and sporadic PD (n = 45) cohorts white tracts identified were primarily subcortical and within the brainstem. CONCLUSIONS: Our findings highlight the association between motor symptom progrerssion and structural connectivity in individuals with GBA1+ PD, LRRK2+ PD, and sporadic PD. Due to the small sample size, larger studies are needed in the future to confirm the findings.

3.
Abdom Radiol (NY) ; 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39088019

ABSTRACT

PURPOSE: To assess the accuracy, reliability, and readability of publicly available large language models in answering fundamental questions on hepatocellular carcinoma diagnosis and management. METHODS: Twenty questions on liver cancer diagnosis and management were asked in triplicate to ChatGPT-3.5 (OpenAI), Gemini (Google), and Bing (Microsoft). Responses were assessed by six fellowship-trained physicians from three academic liver transplant centers who actively diagnose and/or treat liver cancer. Responses were categorized as accurate (score 1; all information is true and relevant), inadequate (score 0; all information is true, but does not fully answer the question or provides irrelevant information), or inaccurate (score - 1; any information is false). Means with standard deviations were recorded. Responses were considered as a whole accurate if mean score was > 0 and reliable if mean score was > 0 across all responses for the single question. Responses were also quantified for readability using the Flesch Reading Ease Score and Flesch-Kincaid Grade Level. Readability and accuracy across 60 responses were compared using one-way ANOVAs with Tukey's multiple comparison tests. RESULTS: Of the twenty questions, ChatGPT answered nine (45%), Gemini answered 12 (60%), and Bing answered six (30%) questions accurately; however, only six (30%), eight (40%), and three (15%), respectively, were both accurate and reliable. There were no significant differences in accuracy between any chatbot. ChatGPT responses were the least readable (mean Flesch Reading Ease Score 29; college graduate), followed by Gemini (30; college) and Bing (40; college; p < 0.001). CONCLUSION: Large language models provide complex responses to basic questions on hepatocellular carcinoma diagnosis and management that are seldomly accurate, reliable, or readable.

4.
J Rheumatol ; 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39089841

ABSTRACT

Imagine you are an ambitious technology innovator keen on advancing health care in the digital era. You could have chosen another industry, but you select health care because you want to make a difference in people's lives.

5.
J Autoimmun ; 148: 103299, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39096716

ABSTRACT

OBJECTIVE: Autoantibodies and autoimmune diseases after SARS-CoV-2 infection are widely reported. Given evolving variants, milder infections, and increasing population vaccination, we hypothesized that SARS-CoV-2 infection earlier in the pandemic would be associated with more autoimmune connective tissue disease (CTD) symptoms and immunologic abnormalities. METHODS: Patients ≥18 years old with COVID-19 3/1/2020-8/15/2022 completed the CTD Screening Questionnaire and were tested for 27 autoimmune serologies, SARS-CoV-2 serologies, cell-bound complement activation products (CB-CAPs), and T and B lymphocyte immunophenotypes by flow cytometry. We assessed relationships between symptoms, serologies, and immunophenotypes in earlier (3/1/2020-1/31/2021) vs. later (2/1/2021-8/15/2022) periods, with different predominating SARS-CoV-2 viruses. RESULTS: 57 subjects had earlier and 23 had later pandemic COVID-19. 35 % of earlier vs. 17 % of later pandemic patients had CTD symptoms (p 0.18). More patients were antinuclear antibody (ANA) positive (44 % vs. 13 %, p 0.01) and had lupus anticoagulant (11 % vs. 4 %, p 0.67). After adjustment for age, race, and sex, earlier (vs. later) COVID-19 was associated with increased ANA positivity (OR 4.60, 95%CI 1.17, 18.15). No subjects had positive CB-CAPs. T and B cell immunophenotypes and SARS-CoV-2 serologies did not differ by group. In heatmap analyses, higher autoantibody variety was seen among those with infection in the early pandemic. CONCLUSION: In this sample, having COVID-19 infection in the earlier (pre-2/1/2021) vs. later pandemic was associated with more CTD symptoms, ANA positivity, and autoantibody reactivities. Earlier SARS-CoV-2 variants circulating in a less vaccinated population with less natural immunity may have been more immunogenic.

7.
medRxiv ; 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39132493

ABSTRACT

There is growing recognition that earliest signs of autism need not clearly manifest in the first three years of life. To what extent is this variation in developmental trajectories associated with age at autism diagnosis? Does the genetic profile of autism vary with age at autism diagnosis? Using longitudinal data from four birth cohorts, we demonstrate that two different trajectories of socio-emotional behaviours are associated with age at diagnosis. We further demonstrate that the age at autism diagnosis is partly heritable (h 2 SNP = 0.12, s.e.m = 0.01), and is associated with two moderately correlated (r g = 0.38, s.e.m = 0.07) autism polygenic factors. One of these factors is associated with earlier diagnosis of autism, lower social and communication abilities in early childhood. The second factor is associated with later autism diagnosis, increased socio-emotional difficulties in adolescence, and has moderate to high positive genetic correlations with Attention-Deficit/Hyperactivity Disorder, mental health conditions, and trauma. Overall, our research identifies an axis of heterogeneity in autism, indexed by age at diagnosis, which partly explains heterogeneity in autism and the profiles of co-occurring neurodevelopmental and mental health profiles. Our findings have important implications for how we conceptualise autism and provide one model to explain some of the diversity within autism.

8.
Environ Sci Technol ; 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39133145

ABSTRACT

In the pursuit of carbon neutrality, China's 2060 targets have been largely anchored in reducing greenhouse gas emissions, with less emphasis on the consequential benefits for air quality and public health. This study pivots to this critical nexus, exploring how China's carbon neutrality aligns with the World Health Organization's air quality guidelines (WHO AQG) regarding fine particulate matter (PM2.5) exposure. Coupling a technology-rich integrated assessment model, an emission-concentration response surface model, and exposure and health assessment, we find that decarbonization reduces sulfur dioxide (SO2), nitrogen oxides (NOx), and PM2.5 emissions by more than 90%; reduces nonmethane volatile organic compounds (NMVOCs) by more than 50%; and simultaneously reduces the disparities across regions. Critically, our analysis reveals that further targeted reductions in air pollutants, notably NH3 and non-energy-related NMVOCs, could bring most Chinese cities into attainment of WHO AQG for PM2.5 5 to 10 years earlier than the pathway focused solely on carbon neutrality. Thus, the integration of air pollution control measures into carbon neutrality strategies will present a significant opportunity for China to attain health and environmental equality.

9.
Anal Chem ; 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39116295

ABSTRACT

The excellent versatility of 5-axis computer numerical control (CNC) micromilling has led to its application for prototyping NMR microcoils tailored to mass-limited samples (reducing development time and cost). However, vibrations during 5-axis milling can hinder the creation of complex 3D volume microcoils (i.e., solenoids and saddle coils). To address these limitations, a high-resolution NSCNC ELARA 4-axis milling machine was developed with the extra precision required for making complex 3D volume microcoils. Upon investigating the performance of resonators made with various copper-coated dielectrics, resonators with poly(methyl methacrylate) (PMMA) provided the best SNR/line shape. Thus, complex 1.7 mm microcoil designs were machined from Cu-coated PMMA. A milled 6.4 mm solenoid also provided 6.6× the total carbon signal for a 13C-labeled broccoli seed compared to a commercial inverse 5 mm NMR probe (demonstrating potential for larger coil designs). However, the manufacture of coils <1.7 mm with copper-coated PMMA rods was challenging as ∼0.5 mm of remaining PMMA was needed to retain their structural integrity. To manufacture smaller microcoils, both a solenoid and saddle coil (both with 1 mm O.D., 0.1 mm thick walls) were etched from Cu-coated glass capillaries using a UV picosecond laser that was mounted onto an NSCNC 5-axis MiRA7L. Both resonators showed excellent signal and identified a wide range of metabolites in a 13C-labeled algae extract, while the solenoid was further tested on two copepod egg sacs (∼4 µg of total sample). In summary, the flexibility to prototype complex microcoils in-house allows laboratories to tailor microcoils to specific mass-limited samples while avoiding the costs of cleanrooms.

10.
J Viral Hepat ; 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39136176

ABSTRACT

It is critical to address hepatitis C virus (HCV) in carceral settings to achieve worldwide elimination of the virus. We describe New Mexico's (NM) experience expanding HCV treatment in state prisons, supplemented with Project ECHO (ECHO; virtual mentorship through guided practice) and the NM Peer Education Program (NMPEP). We describe how using these programs may be a model for expanding treatment in prisons globally. ECHO, NM Corrections Department (NMCD) and Wexford Health Services (WHS) collaborate to treat HCV in state prisons and increase HCV knowledge among incarcerated persons using NMPEP. Each person arriving in prison is tested for HCV and those with active infection receive baseline labs, which are reviewed. Patients not meeting criteria for simplified treatment are presented to ECHO for expert guidance. Otherwise, patients are treated by WHS without consultation. NMPEP provides patient-to-patient education in prisons, addressing HCV myths and exploring treatment refusals. From December 2020 to June 2023, 3603 people had HCV viremia. In this study, 1685 people started treatment: 1280 were treated using the simplified algorithm and 405 were presented to ECHO. Of the 988 people who completed treatment and had sustained virologic response (SVR) labs drawn, 89.2% achieved SVR (i.e., cure). Most of the 107 people who did not achieve SVR had presumed reinfection. NMPEP trained 148 peer educators who educated 3832 peers about HCV prevention and treatment. HCV treatment in prisons can be expanded by implementing simplified treatment algorithms, use of the ECHO model for patients with advanced disease and peer education.

11.
Article in English | MEDLINE | ID: mdl-39136551

ABSTRACT

Physical activity plays a fundamental role in human health and disease. Exercise has been shown to improve a wide variety of disease states, and the scientific community is committed to understanding the precise molecular mechanisms that underlie the exquisite benefits. This review provides an overview of molecular responses to acute exercise and chronic training, particularly energy mobilization and generation, structural adaptation, inflammation, and immune regulation. Further it offers a detailed discussion on known molecular signals and systemic regulators activated during various forms of exercise and their role in orchestrating health benefits. Critically, the increasing use of multi-omic technologies is explored with an emphasis on how multi-omic and multi-tissue studies contribute to a more profound understanding of exercise biology. These data inform anticipated future advancement in the field and highlight the prospect of integrating exercise with pharmacology for personalized disease prevention and treatment.

12.
BMC Gastroenterol ; 24(1): 255, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39123126

ABSTRACT

BACKGROUND: Particulate matter exposure (PM) is a cause of aerodigestive disease globally. The destruction of the World Trade Center (WTC) exposed first responders and inhabitants of New York City to WTC-PM and caused obstructive airways disease (OAD), gastroesophageal reflux disease (GERD) and Barrett's Esophagus (BE). GERD not only diminishes health-related quality of life but also gives rise to complications that extend beyond the scope of BE. GERD can incite or exacerbate allergies, sinusitis, bronchitis, and asthma. Disease features of the aerodigestive axis can overlap, often necessitating more invasive diagnostic testing and treatment modalities. This presents a need to develop novel non-invasive biomarkers of GERD, BE, airway hyperreactivity (AHR), treatment efficacy, and severity of symptoms. METHODS: Our observational case-cohort study will leverage the longitudinally phenotyped Fire Department of New York (FDNY)-WTC exposed cohort to identify Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BAD-BURN). Our study population consists of n = 4,192 individuals from which we have randomly selected a sub-cohort control group (n = 837). We will then recruit subgroups of i. AHR only ii. GERD only iii. BE iv. GERD/BE and AHR overlap or v. No GERD or AHR, from the sub-cohort control group. We will then phenotype and examine non-invasive biomarkers of these subgroups to identify under-diagnosis and/or treatment efficacy. The findings may further contribute to the development of future biologically plausible therapies, ultimately enhance patient care and quality of life. DISCUSSION: Although many studies have suggested interdependence between airway and digestive diseases, the causative factors and specific mechanisms remain unclear. The detection of the disease is further complicated by the invasiveness of conventional GERD diagnosis procedures and the limited availability of disease-specific biomarkers. The management of reflux is important, as it directly increases risk of cancer and negatively impacts quality of life. Therefore, it is vital to develop novel noninvasive disease markers that can effectively phenotype, facilitate early diagnosis of premalignant disease and identify potential therapeutic targets to improve patient care. TRIAL REGISTRATION: Name of Primary Registry: "Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BADBURN)". Trial Identifying Number: NCT05216133 . Date of Registration: January 31, 2022.


Subject(s)
Barrett Esophagus , Biomarkers , Firefighters , Gastroesophageal Reflux , September 11 Terrorist Attacks , Humans , Barrett Esophagus/diagnosis , Barrett Esophagus/etiology , Gastroesophageal Reflux/diagnosis , Biomarkers/blood , Case-Control Studies , Firefighters/statistics & numerical data , New York City , Occupational Exposure/adverse effects , Particulate Matter/adverse effects , Particulate Matter/analysis , Observational Studies as Topic , Male
13.
Ear Nose Throat J ; : 1455613241266467, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-39126318

ABSTRACT

Objectives: To analyze trends in error publication in the top Otolaryngology-Head and Neck Surgery (OHNS) journals. Methods: A retrospective bibliometric analysis utilizing journal-specific search engines of the top 30 OHNS journals (by impact factor) were queried for "errata OR erratum OR corrigenda OR corrigendum OR correction OR corrections," utilizing errors published between 2000 and 2023. Corrections were classified into "erratum" for errors originating from the journal and "corrigendum" for errors originating from the author. Error severity was categorized as trivial, minor, or major, based on the magnitude of their impact on outcomes or their interpretation by the reader. Results: Of the 739 analyzed errors, 62.5% (n = 462) were errata and 37.5% (n = 277) corrigenda, averaging 26.39 (±27.5) errors per journal. There was no correlation between impact factor and error occurrence (P = .979). Trends demonstrated growing numbers of errors published over the years. Mean duration between the publication date of the original article and the error was 10.8 months (±19.4 months), but there was no significant correlation between impact factor and this duration (P = .953). Most corrected articles were original research articles (n = 568, 76.9%), predominantly with the first author from the United States (n = 262, 36.1%). Most errors involved authorship (n = 273, 36.9%) and were "Trivial" in severity (n = 544, 73.6%). However, 72 (9.7%) errors were "Major" and altered the article's findings or interpretation significantly. Conclusion: A multitude of errors exist in the otolaryngology field. Despite most being insignificant and affecting authorship, roughly 10% significantly affect an article's conclusions/outcomes.Level of Evidence: 4.

14.
J Vasc Interv Radiol ; 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39111618

ABSTRACT

PURPOSE: To investigate the effect of patient and tumor-specific characteristics on the size of immediate phase lung microwave ablation (MWA) zone and establish a prediction model. METHODS AND MATERIALS: This IRB-approved, HIPAA compliant cohort included 164 lesions from 99 patients who underwent CT-guided lung MWA and the two-dimensional elliptical ground-glass opacity ablation zone was measured. Duration, maximum temperature, tumor depth, presence of emphysema, history of ipsilateral lung ablation, surgery, and radiation were recorded. K-fold cross validation with k=5 and Least Absolute Shrinkage and Selection Operator were used to build prediction models for the major and minor axes, and area of the ablation zone. RESULTS: The median of immediate phase ablation duration was 2 minutes (IQR: 1.5 - 4.25) with 65W of power for all ablations. The mean major, minor axes, and area of ablation zone were 3.1±0.6cm, 2.0±0.5cm, and 5.1±2.1cm2. The major axis, minor axis, and area of immediate phase ablation zone dimensions were significantly associated with duration (p<0.001, p<0.001, p<0.001), maximum temperature (p<0.001, p<0.001, p<0.001), tumor depth (p=0.387, p<0.001, p<0.001), history of ipsilateral lung ablation (p=0.008, p=0.286, p=0.076), and lung radiation (p=0.001, p=0.042, p=0.015). The prediction model showed R2 values for major and minor axes and area of the ablation zone to be 0.50, 0.45, and 0.53, respectively. CONCLUSION: Duration, maximum temperature, tumor depth, history of ipsilateral lung ablation, surgery, and radiation were significantly associated with the ablation zone dimensions and size and can be used to build the prediction model to approximate the immediate phase lung MWA zone.

15.
Radiat Oncol ; 19(1): 104, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39095864

ABSTRACT

BACKGROUND: Radiotherapy (RT) in head and neck squamous cell cancer (HNSCC) often leads to sticky saliva and xerostomia (SSX). Dose sparing of salivary glands (SG) reduces occurrence of SSX but few studies investigated the relationship between RT dose to SG substructures and SSX. We therefore investigated this hypothesis, focusing on the parotid duct (PD). METHODS: Retrospective data was collected from 99 HNSCC patients treated at our center with (chemo-)radiotherapy (CRT). PD and other organs-at-risk (OAR) were (re-)contoured and DVHs were generated without re-planning. SSX was graded according to CTCAE v.4.03 and evaluated at acute, subacute, and two late timepoints. RESULTS: Most patients presented with loco-regionally advanced disease. In 47% of patients, up-front neck dissection preceded CRT. Weighted mean dose was 28.6 Gy for bilateral parotid glands (PG), and 32.0 Gy for PD. Acute SSX presented as grades 0 (35.3%), I (41.4%), II (21.2%) and III (2.0%). There was no association of OARs and SSX ≥ grade 2 in univariable logistic regression (LR). Multivariable LR showed statistically significant relationship of acute SSX with: PG weighted mean dose (OR 0.84, p = 0.004), contralateral PG mean dose (OR 1.14, p = 0.02) and contralateral PD planning OAR (PD PRV) mean dose (OR 1.84, p = 0.03). CONCLUSIONS: There was an association of acute SSX with dose exposure of PD PRV in multivariable regression, only. Due to statistical uncertainties and the retrospective nature of this analysis, further studies are required to confirm or reject the hypothesis.


Subject(s)
Head and Neck Neoplasms , Organs at Risk , Parotid Gland , Radiotherapy Dosage , Squamous Cell Carcinoma of Head and Neck , Xerostomia , Humans , Xerostomia/etiology , Retrospective Studies , Male , Female , Middle Aged , Parotid Gland/radiation effects , Aged , Head and Neck Neoplasms/radiotherapy , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Organs at Risk/radiation effects , Adult , Aged, 80 and over , Saliva/radiation effects , Radiation Injuries/etiology , Carcinoma, Squamous Cell/radiotherapy , Radiotherapy, Intensity-Modulated/adverse effects , Radiotherapy, Intensity-Modulated/methods , Radiotherapy Planning, Computer-Assisted/methods
16.
Nat Immunol ; 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39112630

ABSTRACT

The thymus is essential for establishing adaptive immunity yet undergoes age-related involution that leads to compromised immune responsiveness. The thymus is also extremely sensitive to acute insult and although capable of regeneration, this capacity declines with age for unknown reasons. We applied single-cell and spatial transcriptomics, lineage-tracing and advanced imaging to define age-related changes in nonhematopoietic stromal cells and discovered the emergence of two atypical thymic epithelial cell (TEC) states. These age-associated TECs (aaTECs) formed high-density peri-medullary epithelial clusters that were devoid of thymocytes; an accretion of nonproductive thymic tissue that worsened with age, exhibited features of epithelial-to-mesenchymal transition and was associated with downregulation of FOXN1. Interaction analysis revealed that the emergence of aaTECs drew tonic signals from other functional TEC populations at baseline acting as a sink for TEC growth factors. Following acute injury, aaTECs expanded substantially, further perturbing trophic regeneration pathways and correlating with defective repair of the involuted thymus. These findings therefore define a unique feature of thymic involution linked to immune aging and could have implications for developing immune-boosting therapies in older individuals.

17.
Pediatr Pulmonol ; 59 Suppl 1: S115-S122, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39105344

ABSTRACT

Up to 90% of people with CF (pwCF) will have some form of hepatobiliary involvement. This manuscript aims to explore the different endovascular, endoscopic, radiological and surgical procedures available to diagnose and manage the most severe form of CF hepatobiliary involvement (CFHBI) known as advanced cystic fibrosis liver disease (aCFLD), seen in 10% of pwCF. These procedures and interventions include liver biopsy, hepatic venous pressure gradient measurement, gastrostomy tube placement to optimize nutrition, paracentesis, endoscopic variceal control of bleeding and portosystemic shunting before liver transplantation. By utilizing advanced diagnostic or surgical techniques, healthcare professionals of pwCF can more effectively manage patients with CFHBI and aCFLD and potentially improve patient outcomes.


Subject(s)
Cystic Fibrosis , Humans , Cystic Fibrosis/surgery , Cystic Fibrosis/complications , Cystic Fibrosis/diagnostic imaging , Liver Diseases/diagnostic imaging , Liver Diseases/surgery , Liver Transplantation , Endovascular Procedures/methods , Gastrostomy/methods , Portasystemic Shunt, Surgical/methods , Paracentesis/methods
18.
Biochem Pharmacol ; : 116480, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39128587

ABSTRACT

Alamandine (ALA) exerts protective effects similar to angiotensin (Ang) (1-7) through Mas-related G protein-coupled receptor type D receptor (MrgDR) activation, distinct from Mas receptor (MasR). ALA induces anti-inflammatory effects in mice but its impact in human macrophages remains unclear. We aimed to investigate the anti-inflammatory effects of ALA in human macrophages. Interleukin (IL)-6 and IL-1ß were measured by ELISA in human THP-1 macrophages and human monocyte-derived macrophages exposed to lipopolysaccharide (LPS). Consequences of MasR-MrgDR heteromerization were investigated in transfected HEK293T cells. ALA decreased IL-6 and IL-1ß secretion in LPS-activated THP-1 macrophages. The ALA-induced decrease in IL-6 but not in IL-1ß was prevented by MasR blockade and MasR downregulation, suggesting MasR-MrgDR interaction. In human monocyte-derived M1 macrophages, ALA decreased IL-1ß secretion independently of MasR. MasR-MrgDR interaction was confirmed in THP-1 macrophages, human monocyte-derived macrophages, and transfected HEK293T cells. MasR and MrgDR formed a constitutive heteromer that was not influenced by ALA. ALA promoted Akt and ERK1/2 activation only in cells expressing MasR-MrgDR heteromers, and this effect was prevented by MasR blockade. While Ang-(1-7) reduced cellular proliferation in MasR -but not MrgDR- expressing cells, ALA antiproliferative effect was elicited in cells expressing MasR-MrgDR heteromers. ALA also induced an antiproliferative response in THP-1 cells and this effect was abolished by MasR blockade, reinforcing MasR-MrgDR interaction. MasR-MrgDR heteromerization is crucial for ALA-induced anti-inflammatory and antiproliferative responses in human macrophages. This study broaden our knowledge of the protective axis of the RAS, thus enabling novel therapeutic approaches in inflammatory-associated diseases.

19.
ACS Sustain Chem Eng ; 12(26): 9822-9832, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38966239

ABSTRACT

Oxalate esters and isosorbide serve as intriguing polymer building blocks, as they can be sourced from renewable resources, such as CO2 and glucose, and the resulting polyesters offer outstanding material properties. However, the low reactivity of the secondary hydroxyl groups makes it difficult to generate high-molecular-weight polymers from isosorbide. Combining diaryl oxalates with isosorbide appears to be a promising approach to produce high-molecular-weight isosorbide-based polyoxalates (PISOX). This strategy seems to be scalable, has a short polymerization time (<5 h), and uniquely, there is no need for a catalyst. PISOX demonstrates outstanding thermal, mechanical, and barrier properties; its barrier to oxygen is 35 times better than PLA, it possesses mechanical properties comparable to high-performance thermoplastics, and the glass transition temperature of 167 °C can be modified by comonomer incorporation. What makes this high-performance material truly exceptional is that it decomposes into CO2 and biomass in just a few months in soil under home-composting conditions and it hydrolyzes without enzymes present in less than a year in 20 °C water. This unique combination of properties has the potential to be utilized in a range of applications, such as biomedical uses, water-resistant coatings, compostable plastic bags for gardening and agriculture, and packaging plastics with diminished environmental impact.

20.
mSystems ; : e0041624, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38990071

ABSTRACT

Medium-chain carboxylates (MCCs) are used in various industrial applications. These chemicals are typically extracted from palm oil, which is deemed not sustainable. Recent research has focused on microbial chain elongation using reactors to produce MCCs, such as n-caproate (C6) and n-caprylate (C8), from organic substrates such as wastes. Even though the production of n-caproate is relatively well-characterized, bacteria and metabolic pathways that are responsible for n-caprylate production are not. Here, three 5 L reactors with continuous membrane-based liquid-liquid extraction (i.e., pertraction) were fed ethanol and acetate and operated for an operating period of 234 days with different operating conditions. Metagenomic and metaproteomic analyses were employed. n-Caprylate production rates and reactor microbiomes differed between reactors even when operated similarly due to differences in H2 and O2 between the reactors. The complete reverse ß-oxidation (RBOX) pathway was present and expressed by several bacterial species in the Clostridia class. Several Oscillibacter spp., including Oscillibacter valericigenes, were positively correlated with n-caprylate production rates, while Clostridium kluyveri was positively correlated with n-caproate production. Pseudoclavibacter caeni, which is a strictly aerobic bacterium, was abundant across all the operating periods, regardless of n-caprylate production rates. This study provides insight into microbiota that are associated with n-caprylate production in open-culture reactors and provides ideas for further work.IMPORTANCEMicrobial chain elongation pathways in open-culture biotechnology systems can be utilized to convert organic waste and industrial side streams into valuable industrial chemicals. Here, we investigated the microbiota and metabolic pathways that produce medium-chain carboxylates (MCCs), including n-caproate (C6) and n-caprylate (C8), in reactors with in-line product extraction. Although the reactors in this study were operated similarly, different microbial communities dominated and were responsible for chain elongation. We found that different microbiota were responsible for n-caproate or n-caprylate production, and this can inform engineers on how to operate the systems better. We also observed which changes in operating conditions steered the production toward and away from n-caprylate, but more work is necessary to ascertain a mechanistic understanding that could be predictive. This study provides pertinent research questions for future work.

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