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Microorganisms May 2024Metagenomic sequencing analysis is central to investigating microbial communities in clinical and environmental studies. Short-read sequencing remains the primary...
Metagenomic sequencing analysis is central to investigating microbial communities in clinical and environmental studies. Short-read sequencing remains the primary approach for metagenomic research; however, long-read sequencing may offer advantages of improved metagenomic assembly and resolved taxonomic identification. To compare the relative performance for metagenomic studies, we simulated short- and long-read datasets using increasingly complex metagenomes comprising 10, 20, and 50 microbial taxa. Additionally, we used an empirical dataset of paired short- and long-read data generated from mouse fecal pellets to assess real-world performance. We compared metagenomic assembly quality, taxonomic classification, and metagenome-assembled genome (MAG) recovery rates. We show that long-read sequencing data significantly improve taxonomic classification and assembly quality. Metagenomic assemblies using simulated long reads were more complete and more contiguous with higher rates of MAG recovery. This resulted in more precise taxonomic classifications. Principal component analysis of empirical data demonstrated that sequencing technology affects compositional results as samples clustered by sequence type, not sample type. Overall, we highlight strengths of long-read metagenomic sequencing for microbiome studies, including improving the accuracy of classification and relative abundance estimates. These results will aid researchers when considering which sequencing approaches to use for metagenomic projects.
PubMed: 38792764
DOI: 10.3390/microorganisms12050935 -
Analytical Chemistry Jun 2024The health hazards of micro- and nanoplastic contaminants in drinking water has recently emerged as an area of concern to policy makers and industry. Plastic...
The health hazards of micro- and nanoplastic contaminants in drinking water has recently emerged as an area of concern to policy makers and industry. Plastic contaminants range in size from micro- (5 mm to 1 μm) to nanoplastics (<1 μm). Microfluidics provides many tools for particle manipulation at the microscale, particularly in diagnostics and biomedicine, but has in general a limited capacity to process large volumes. Drinking water and environmental samples with low-level contamination of microplastics require processing of deciliter to liter sample volumes to achieve statistically relevant particle counts. Here, we introduce the EchoGrid, an acoustofluidics device for high throughput continuous flow particle enrichment into a robust array of particle clusters. The EchoGrid takes advantage of highly efficient particle capture through the integration of a micropatterned transducer for surface displacement-based acoustic trapping in a glass and polymer microchannel. Silica seed particles were used as anchor particles to improve capture performance at low particle concentrations and high flow rates. The device was able to maintain the silica grids at a flow rate of 50 mL/min. In terms of enrichment, the device is able to double the final pellet's microplastic concentration every 78 s for 23 μm particles and every 51 s for 10 μm particles at a flow rate of 5 mL/min. In conclusion, we demonstrate the usefulness of the EchoGrid by capturing microplastics in challenging conditions, such as large sample volumes with low microparticle concentrations, without sacrificing the potential of integration with downstream analysis for environmental monitoring.
PubMed: 38790145
DOI: 10.1021/acs.analchem.4c00933 -
Biosensors May 2024Whole-cell biosensors could serve as eco-friendly and cost-effective alternatives for detecting potentially toxic bioavailable heavy metals in aquatic environments....
Whole-cell biosensors could serve as eco-friendly and cost-effective alternatives for detecting potentially toxic bioavailable heavy metals in aquatic environments. However, they often fail to meet practical requirements due to an insufficient limit of detection (LOD) and high background noise. In this study, we designed a synthetic genetic circuit specifically tailored for detecting ionic mercury, which we applied to environmental samples collected from artisanal gold mining sites in Peru. We developed two distinct versions of the biosensor, each utilizing a different reporter protein: a fluorescent biosensor (Mer-RFP) and a colorimetric biosensor (Mer-Blue). Mer-RFP enabled real-time monitoring of the culture's response to mercury samples using a plate reader, whereas Mer-Blue was analysed for colour accumulation at the endpoint using a specially designed, low-cost camera setup for harvested cell pellets. Both biosensors exhibited negligible baseline expression of their respective reporter proteins and responded specifically to HgBr in pure water. Mer-RFP demonstrated a linear detection range from 1 nM to 1 μM, whereas Mer-Blue showed a linear range from 2 nM to 125 nM. Our biosensors successfully detected a high concentration of ionic mercury in the reaction bucket where artisanal miners produce a mercury-gold amalgam. However, they did not detect ionic mercury in the water from active mining ponds, indicating a concentration lower than 3.2 nM Hg-a result consistent with chemical analysis quantitation. Furthermore, we discuss the potential of Mer-Blue as a practical and affordable monitoring tool, highlighting its stability, reliance on simple visual colorimetry, and the possibility of sensitivity expansion to organic mercury.
Topics: Biosensing Techniques; Mercury; Environmental Monitoring; Colorimetry; Water Pollutants, Chemical; Limit of Detection; Gold
PubMed: 38785720
DOI: 10.3390/bios14050246 -
Frontiers in Microbiology 2024The establishment of the rumen microbiota plays an important role in the rumen development. However, little is known about the effects of alfalfa supplementation time on...
The establishment of the rumen microbiota plays an important role in the rumen development. However, little is known about the effects of alfalfa supplementation time on rumen microbiota establishment. Here, a total of 42 Hu lambs, seven-day-old, were chosen for the study. After a week of adjustment, six lambs were sacrificed to establish a baseline. The remaining 36 lambs were randomly split into two groups: one receiving alfalfa hay at 14 days (EAF), the other at 42 days (LAF), both groups received milk replacer and starter pellets. Introducing alfalfa at 14 days of age significantly improved total dry matter intake between 28 and 42 days ( = 0.04) and average daily gain from both 14 to 28 days ( = 0.04) and 28 to 42 days ( < 0.01), but this effect disappears from 56 to 70 days ( > 0.05). At 42 days, the abundances of , , and in the EAF group were significantly higher ( < 0.05) than those in the LAF group (17.8% vs. 3.97, 10.89% vs. 1.77, and 1.27% vs. 0.09%, respectively). At 56 days, the abundances of , , and in the EAF group were significantly lower ( < 0.05) than in the LAF group (3.53% vs. 16.40, 8.78% vs. 18.89, and 2.14% vs. 4.69%). At 70 days, abundance in the EAF group was significantly higher ( < 0.05) than in the LAF group (2.69% vs. 0.85%). The LEfSe analysis showed that was the archaeal biomarker at 14 days in both groups. was enriched at 56 days in the LAF group. Compared to the LAF group, the specific fungal biomarkers in the EAF group included and at 14 days, and at 42 days, , and at 70 days. Correlation analysis results showed strong patterns of association both within and between archaea and fungi, which were influenced by alfalfa supplementation time. In summary, alfalfa supplementation at 14 days of age promotes the growth performance of lambs before weaning, and alfalfa supplementation timing significantly affects rumen archaeal and fungal communities and dynamical changes.
PubMed: 38784814
DOI: 10.3389/fmicb.2024.1380322 -
Chemical Science May 2024A right-side-out orientated self-assembly of cell membrane-camouflaged nanotherapeutics is crucial for ensuring their biological functionality inherited from the source...
A right-side-out orientated self-assembly of cell membrane-camouflaged nanotherapeutics is crucial for ensuring their biological functionality inherited from the source cells. In this study, a universal and spontaneous right-side-out coupling-driven ROS-responsive nanotherapeutic approach, based on the intrinsic affinity between phosphatidylserine (PS) on the inner leaflet and PS-targeted peptide modified nanoparticles, has been developed to target foam cells in atherosclerotic plaques. Considering the increased osteopontin (OPN) secretion from foam cells in plaques, a bioengineered cell membrane (OEM) with an overexpression of integrin α9β1 is integrated with ROS-cleavable prodrugs, OEM-coated ETBNPs (OEM-ETBNPs), to enhance targeted drug delivery and on-demand drug release in the local lesion of atherosclerosis. Both and experimental results confirm that OEM-ETBNPs are able to inhibit cellular lipid uptake and simultaneously promote intracellular lipid efflux, regulating the positive cellular phenotypic conversion. This finding offers a versatile platform for the biomedical applications of universal cell membrane camouflaging biomimetic nanotechnology.
PubMed: 38784734
DOI: 10.1039/d4sc00761a -
Scientific Reports May 2024Microplastics, particles under 5 mm, pervade aquatic environments, notably in Tarragona's coastal region (NE Iberian Peninsula), hosting a major plastic production...
Microplastics, particles under 5 mm, pervade aquatic environments, notably in Tarragona's coastal region (NE Iberian Peninsula), hosting a major plastic production complex. To investigate weathering and yellowness impact on plastic pellets toxicity, sea-urchin embryo tests were conducted with pellets from three locations-near the source and at increasing distances. Strikingly, distant samples showed toxicity to invertebrate early stages, contrasting with innocuous results near the production site. Follow-up experiments highlighted the significance of weathering and yellowing in elevated pellet toxicity, with more weathered and colored pellets exhibiting toxicity. This research underscores the overlooked realm of plastic leachate impact on marine organisms while proposes that prolonged exposure of plastic pellets in the environment may lead to toxicity. Despite shedding light on potential chemical sorption as a toxicity source, further investigations are imperative to comprehend weathering, yellowing, and chemical accumulation in plastic particles.
Topics: Animals; Microplastics; Water Pollutants, Chemical; Larva; Sea Urchins; Plastics; Environmental Monitoring
PubMed: 38782918
DOI: 10.1038/s41598-024-60886-x -
JAMA Network Open May 2024Teratogenic outcomes associated with valproic acid use represent a substantial concern for persons of childbearing age. Regulatory agencies worldwide have enhanced...
IMPORTANCE
Teratogenic outcomes associated with valproic acid use represent a substantial concern for persons of childbearing age. Regulatory agencies worldwide have enhanced warnings or implemented risk minimization programs to reduce exposure during pregnancy.
OBJECTIVES
To determine pregnancy rates during valproic acid use and concomitant contraception use across indications.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study used data from the Merative MarketScan commercial claims databases from January 1, 2005, to December 31, 2020, to identify female patients aged 12 to 44 years who initiated valproic acid treatment and had continuous insurance enrollment 6 months before initiation and 9 months after treatment end. A treatment episode included consecutive prescription fills that occurred within 7 days from the end of the days' supply of the previous dispensing. Data were analyzed from March 1 to September 10, 2023.
MAIN OUTCOMES AND MEASURES
Treatment episodes were categorized by inferred indication using diagnoses preceding treatment initiation, including epilepsy, migraine or headache, mood disorders, and unknown or off-label uses. Pregnancy incidence rate ratios (IRRs) were calculated and were adjusted for age and calendar year. Contraceptive use (prescription contraceptives, intrauterine devices, and implants) during treatment was examined.
RESULTS
The cohort included 165 772 valproic acid treatment episodes among 69 390 women (mean [SD] age, 29.8 [10.0] years). Mood disorders (42.5%) were the most common indication, followed by migraine or headache (20.1%), with epilepsy playing a minor role (14.9%). Pregnancy incidence rates during valproic acid use remained unchanged, with a rate of 1.74 (95% CI, 1.14-2.53) per 100 person-years in 2005 and a rate of 1.90 (95% CI, 1.16-3.12) per 100 person-years in 2019. Compared with epilepsy, pregnancy rates were more than double for mood disorder (IRR, 2.16 [95% CI, 1.93-2.42]) and migraine or headache (IRR, 2.01 [95% CI, 1.92-2.09]). Few treatment episodes coincided with contraceptive use (37 012 [22.3%]), and oral dosage forms were the most common (27 069 [73.1%]).
CONCLUSIONS AND RELEVANCE
In this cohort study of patients of childbearing age who used valproic acid, pregnancy rates during valproic acid use did not decrease despite enhanced US Food and Drug Administration safety communications, and contraception use remained low. Patients with migraine and mood disorders accounted for the largest proportion of valproic acid use and had the highest pregnancy rates, while patients with epilepsy had the lowest. These findings suggest a need to enhance efforts to mitigate prenatal exposure to valproic acid, especially for indications where the risk of use during pregnancy outweighs the benefit.
Topics: Humans; Female; Valproic Acid; Pregnancy; Adult; Retrospective Studies; Adolescent; Prenatal Exposure Delayed Effects; Epilepsy; Young Adult; Anticonvulsants; Child; Pregnancy Rate; Mood Disorders; Migraine Disorders; United States
PubMed: 38776082
DOI: 10.1001/jamanetworkopen.2024.12680 -
International Journal of Medical... 2024To examine time-dependent functional and structural changes of the lower urinary tract in streptozotocin-induced diabetic rats with or without low-dose insulin...
To examine time-dependent functional and structural changes of the lower urinary tract in streptozotocin-induced diabetic rats with or without low-dose insulin treatment and explore the pathophysiological characteristics of insulin therapy on lower urinary tract dysfunction (LUTD) caused by diabetes mellitus (DM). Female Sprague-Dawley rats were divided into five groups: normal control (NC) group, 4 weeks insulin-treated DM (4-DI) group, 4 weeks DM (4-DM) group, 8 weeks insulin-treated DM (8-DI) group and 8 weeks DM (8-DM) group. DM was initially induced by i.p. injection of streptozotocin (65 mg/kg), and then the DI groups received subcutaneous implantation of insulin pellets under the mid dorsal skin. Voiding behavior was evaluated in metabolic cages. The function of bladder and urethra were evaluated by simultaneous recordings of the cystometrogram and urethral perfusion pressure (UPP) under urethane anesthesia. The function of bladder and urethra were tested by organ bath techniques. The morphologic changes of the bladder and urethra were investigated using Hematoxylin-Eosin and Masson's staining. Both 4-and 8-weeks diabetic rats have altered micturition patterns, including increased 12-h urine volume, urinary frequency/12 hours and voided volume. urodynamics showed the EUS bursting activity duration is longer in 4-DM group and shorter in 8-DM group compared to NC group. UPP change in 8-DM were significantly lower than NC group. While none of these changes were found between DI and NC groups. Organ bath showed the response to Carbachol and EFS in bladder smooth muscle per tissue weights was decreased significantly in 4- and 8-weeks DM groups compared with insulin-treated DM or NC groups. In contrast, the contraction of urethral muscle and maximum urethral muscle contraction per gram of the tissue to EFS stimulation were significantly increased in 4- and 8-weeks DM groups. The thickness of bladder smooth muscle was time-dependently increased, but the thickness of the urethral muscle had no difference. DM-induced LUTD is characterized by time-dependent functional and structural remodeling in the bladder and urethra, which shows the hypertrophy of the bladder smooth muscle, reduced urethral smooth muscle relaxation and EUS dysfunction. Low-dose insulin can protect against diuresis-induced bladder over-distention, preserve urethral relaxation and protect EUS bursting activity, which would be helpful to study the slow-onset, time-dependent progress of DM-induced LUTD.
Topics: Animals; Female; Rats; Diabetes Mellitus, Experimental; Insulin; Lower Urinary Tract Symptoms; Rats, Sprague-Dawley; Streptozocin; Time Factors; Urethra; Urinary Bladder; Urination
PubMed: 38774757
DOI: 10.7150/ijms.95461 -
Heliyon May 2024Malaysia is the second largest producer and exporter of palm oil. Though several works have explored achieving emissions reduction in the palm oil sector, there existing...
Malaysia is the second largest producer and exporter of palm oil. Though several works have explored achieving emissions reduction in the palm oil sector, there existing gaps in analysing pathways for achieving net-zero emissions. Moreover, there are limited studies that evaluate the potential of palm oil biomass utilisation pathways based on emissions reduction capabilities, the cost of emissions reduction, and the technology readiness for implementation. Therefore, this study analysed decarbonisation pathways for the upstream and midstream segments of the palm oil sector in Malaysia, encompassing oil palm plantations and palm oil mills. Various sources of greenhouse gas emissions in oil palm plantations and palm oil mills were identified and estimates of emissions were determined as theoretical emissions. The current emissions were established based on the current best practice in the plantation and mill. Several biomass conversion technologies for the recovery of palm-based by-products and conversion into value-added products to decarbonise the palm oil sector and evaluated strategies to attain net-zero status are considered. In this work, the analysis considered both the existing technologies that are adopted by plantations and mills as well as the emerging technologies that have scope for implementation. With the proposed approach, the current emissions level for crude palm oil (CPO) production in Malaysia is estimated as 1121.49 kg CO-eq/t CPO. In current industry practice, empty fruit bunch (EFB) is underutilised as mills are typically located at rural areas with lack of suitable transportation. Besides, the lack of accessibility to the grid also limits the potential of converting EFB into electricity as supply for national grid. This work examined various pathways for EFB utilisation under different scenarios evaluating their contribution potential towards net-zero target in an energy self-sustained CPO production. As shown in the results, converting EFB to briquettes and pellets are able to achieve the net-zero objective. Furthermore, EFB-biochar and EFB-syngas pathways also exhibit the potential to accomplish the net-zero target. Note that this work also assessed the technologies' readiness levels, identified challenges in implementation, and proposed several recommendations.
PubMed: 38774313
DOI: 10.1016/j.heliyon.2024.e30768 -
Scientific Reports May 2024GSK2838232 (GSK8232) is a second-generation maturation inhibitor (MI) developed for the treatment of HIV with excellent broad-spectrum virological profiles. The compound...
GSK2838232 (GSK8232) is a second-generation maturation inhibitor (MI) developed for the treatment of HIV with excellent broad-spectrum virological profiles. The compound has demonstrated promising clinical results as an orally administered agent. Additionally, the compound's physical and pharmacological properties present opportunities for exploitation as long-acting parenteral formulations. Despite unique design constraints including solubility and dose of GSK8232, we report on three effective tunable drug delivery strategies: active pharmaceutical ingredient (API) suspensions, ionic liquids, and subdermal implants. Promising sustained drug release profiles were achieved in rats with each approach. Additionally, we were able to tune drug release rates through a combination of passive and active strategies, broadening applicability of these formulation approaches beyond GSK8232. Taken together, this report is an important first step to advance long-acting formulation development for critical HIV medicines that do not fit the traditional profile of suitable long-acting candidates.
Topics: Animals; Rats; Drug Liberation; Hydrophobic and Hydrophilic Interactions; Delayed-Action Preparations; Anti-HIV Agents; Drug Delivery Systems; Ionic Liquids; Rats, Sprague-Dawley; Male; Solubility; HIV Infections; Anti-Retroviral Agents
PubMed: 38773172
DOI: 10.1038/s41598-024-58583-w