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Microbial Biotechnology Jun 2022Aspergillus niger, an important industrial workhorse for citric acid production, is characterized by polar hyphal growth with complex pelleted, clumped or dispersed...
Aspergillus niger, an important industrial workhorse for citric acid production, is characterized by polar hyphal growth with complex pelleted, clumped or dispersed macromorphologies in submerged culture. Although organic acid titres are dramatically impacted by these growth types, studies that assess productivity and macromorphological changes are limited. Herein, we functionally analysed the role of the protein kinase A (PKA)/cyclic adenosine monophosphate (cAMP) signalling cascade during fermentation by disrupting and conditionally expressing the pkaC gene. pkaC played multiple roles during hyphal, colony and conidiophore growth. By overexpressing pkaC, we could concomitantly modify hyphal growth at the pellet surface and improve citric acid titres up to 1.87-fold. By quantitatively analysing hundreds of pellets during pilot fermentation experiments, we provide the first comprehensive correlation between A. niger pellet surface morphology and citric acid production. Finally, by intracellular metabolomics analysis and weighted gene coexpression network analysis (WGCNA) following titration of pkaC expression, we unveil the metabolomic and transcriptomic basis underpin hyperproductivity and pellet growth. Taken together, this study confirms pkaC as hub regulator linking submerged macromorphology and citric acid production and provides high-priority genetic leads for future strain engineering programmes.
Topics: Aspergillus niger; Citric Acid; Fermentation
PubMed: 35213792
DOI: 10.1111/1751-7915.14020 -
Animals : An Open Access Journal From... Nov 2022Physical pellet quality and AMEN concentration are strongly related to each other in broiler feeding. A study was conducted to evaluate the relationship between dietary...
Physical pellet quality and AMEN concentration are strongly related to each other in broiler feeding. A study was conducted to evaluate the relationship between dietary AMEN concentration and feed processing on pellet quality, nutrient digestibility, broiler performance, serum markers, and yield of commercial cuts. Six diets were formulated. The first diet had the recommended AMEN concentration, each further diet was calculated with 40 kcal/kg less, from 0 to −200 kcal/kg, resulting in six levels for each feed phase: starter (1−14 d), grower (15−28 d), and finisher (29−35 d). These diets were processed with and without expander conditioning prior to pelleting, using an average corn particle size of 1.6 mm, ground with a roller mill. A total of 1008 one-day-old male Ross 308 broiler chickens were placed in a 6 × 2 (6 energy levels and 2 conditionings) factorial trial with six boxes as replications, with three in each broiler performance trial period. Excreta were collected 2 days before the end of each feed phase for apparent total tract digestibility measurement. On day 36, four broilers from each replication (pen) were weighed and then euthanized for blood collection, following which the gastrointestinal organs were weighed, and the ileal and gizzard contents were collected. On day 37, all remaining broilers were slaughtered after fasting to measure commercial cuts and abdominal fat. The results show that the pellet durability index (PDI) was most affected by energy reducing and expander conditioning prior to pelleting, and it was better when diets had energy reduced by 40 to 200 kcal/kg (p > 0.001), as when expander conditioning was used. Digestibility of nutrients was slightly affected by treatments, as was the broiler performance; however, feed efficiency was improved in broiler-fed diets without AMEN reduction and when an expander was used, with p = 0.050 and p = 0.031, respectively. No effects were observed on the weight of gastrointestinal tract organs and serum markers, except for liver (p = 0.037) and α-amylase (p = 0.047). The lowest liver weight and lowest serum protein, cholesterol, triglyceride, gamma-glutamyl, and lipase concentrations were obtained when diets were formulated without energy reduction (Ross-0). There was no effect on commercial cuts relative to live weight at slaughter. The energy reduction was well reflected in the proportion of abdominal fat, which decreased when AMEN was reduced (p = 0.001). The present study shows it is possible to use diets with up to 200 kcal/kg reduction in AMEN without losses in performance, and the use of expander conditioning prior to pelleting promotes higher pellet quality and broiler feed efficiency.
PubMed: 36428353
DOI: 10.3390/ani12223126 -
PloS One 2022This study was carried out to produce low-emitting biomass pellets biofuel from selected forest trees such as (Cedrus deodara and Pinus wallichiana) and agricultural...
This study was carried out to produce low-emitting biomass pellets biofuel from selected forest trees such as (Cedrus deodara and Pinus wallichiana) and agricultural crop residues such as (Zea mays and Triticum aestivum) in Gilgit-Baltistan, Pakistan using indigenously developed technology called pelletizer machine. Characterization, environmental life cycle impact assessment, and cumulative energy demand of biomass pellets biofuel produced from selected agriculture crops and forest tree residues were conducted. The primary data for biomass pellets production was collected by visiting various wood processing factories, sawmills, and agricultural crop fields in the study area. Biomass pellets are a type of biofuel that is often made by compressing sawdust and crushing biomass material into a powdery form. The particles are agglomerated as the raw material is extensively compressed and pelletized. Biomass pellets have lower moisture content, often less than 12%. Physically, the produced pellets were characterized to determine moisture content, pellet dimensions, bulk density, higher heating value, ash content, lower heating value, and element analysis. A functional unit of one kilogram (kg) biomass pellets production was followed in this study.The life cycle impact assessment of one kg biomass pellets biofuel produced from selected agro-forest species revealed environmental impact categories such as acidification (0.006 kg SO2 eq/kg pellets), abiotic depletion (0.018 kg Sb eq/kg pellets), marine aquatic ecotoxicity (417.803 kg 1,4-DB eq/kg pellets), human toxicity (1.107 kg 1,4-DB eq/kg pellets), freshwater aquatic ecotoxicity (0.191 kg 1,4-DB eq/kg pellets), eutrophication (0.001 kg PO4 eq/kg pellets), global warming (0.802 kg CO2 eq/kg pellets), and terrestrial ecotoxicity (0.008 kg 1,4-DB eq/kg pellets). Fossil fuel consumption was the hotspot source to all environmental impacts investigated. To measure the cumulative energy demand of biomass pellets made from different agroforestry species leftovers showed that the maximum cumulative energy was from wheat straw pellets (13.737 MJ), followed by corncob pellets (11.754 MJ), deodar sawdust pellets (10.905 MJ) and blue pine sawdust pellets (10.877 MJ). Among the various production activities, collection and transportation of primary raw material, crushing, screening, adding adhesives, pelletizing, cooling, final screening, and packing have the maximum contribution to the water scarcity index, followed by lubricating oil (0.00147m3). In contrast, the minimum contribution to water footprint was from electricity (0.00008m3) and wheat starch (0.00005m3). The highest contribution to the ecological footprint impact categories such as carbon dioxide, nuclear, and land occupation was lubricating oil and less contribution of wheat starch and electricity for manufacturing one kg pellets biofuel. It is concluded that physico-mechanical and combustion properties of the biomass pellets biofuel developed in the present study were following the Italian recommended standards. Therefore, it is strongly recommended that the Government of Pakistan should introduce the renewable biomass pellets industry in the country to reduce dependency on fossil fuels for cooking and heating purposes.
Topics: Animals; Biofuels; Biomass; Carbon Dioxide; Crops, Agricultural; Fossil Fuels; Humans; Life Cycle Stages; Starch; Water
PubMed: 36206274
DOI: 10.1371/journal.pone.0275005 -
Obstetrics and Gynecology Apr 2022To evaluate topiramate and etonogestrel pharmacokinetic interactions in contraceptive implant users.
OBJECTIVE
To evaluate topiramate and etonogestrel pharmacokinetic interactions in contraceptive implant users.
METHODS
We conducted a prospective, noninferiority study with healthy women using etonogestrel implants continuously for 12-36 months. We measured baseline serum etonogestrel concentrations and then began a 6-week titrated topiramate regimen to standard migraine (100 mg/day) and epilepsy (400 mg/day) dosages. We repeated serum etonogestrel concentrations at 3 weeks (100 mg/day), 4 weeks (200 mg/day), and 6 weeks (400 mg/day) of topiramate therapy. We measured etonogestrel using a validated liquid chromatography-tandem, mass-spectrometry assay and tested for noninferiority (less than 30% decrease) in serum etonogestrel concentrations from baseline.
RESULTS
We enrolled 48 total participants; 32 completed 3 weeks, 31 completed 4 weeks, and 27 completed all follow-up visits. Participants' median age was 25.3 years (range 18.3-37.2), median body mass index (BMI) was 25.5 kg/m2 (range 18.7-42.2), and median duration of implant use was 24 months (range 12-36). Median etonogestrel concentrations were 142 pg/mL (range 76.2-771) at baseline, 126 pg/mL (range 72.4-585) at 3 weeks, 119 pg/mL (range 65.6-542) at 4 weeks, and 105 pg/mL (46.2-859) at 6 weeks. The 95% CIs for mean percent change in serum etonogestrel concentrations from baseline were [-37.3%+16.9%], [-45.4%+5.2%], and [-66.8%+24.8%] at 3 weeks, 4 weeks, and 6 weeks, respectively. Excluding one participant who had a serum etonogestrel concentration less than 90 pg/mL at baseline, 30.8% of participants (8/26, 95% CI 14.3-51.8%) had a serum etonogestrel concentration less than 90 pg/mL at 6 weeks.
CONCLUSION
Though only a mild enzyme-inducing antiepileptic drug, concomitant topiramate use led to inferior serum etonogestrel concentrations among implant users, with a significant proportion reaching etonogestrel concentrations below the threshold for ovulatory suppression when taking antiepileptic dosages of topiramate.
FUNDING SOURCE
This study was primarily funded through an Investigator-Initiated Study grant from Merck Sharp & Dohme Corp [MISP#57073]. This work was also supported by NIH/NCATS CTSA Grant Number UL1 TR001082 and NICHD K12 Women's Reproductive Health Research Scholar Program (grant number 5K12HD001271-18).
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, NCT03335163.
Topics: Adolescent; Adult; Contraceptive Agents, Female; Desogestrel; Drug Implants; Female; Humans; Prospective Studies; Topiramate; Young Adult
PubMed: 35594123
DOI: 10.1097/AOG.0000000000004697 -
International Journal of Molecular... Sep 2022The preparation of amorphous and co-amorphous systems (CAMs) effectively addresses the solubility and bioavailability issues of poorly water-soluble chemical entities....
The preparation of amorphous and co-amorphous systems (CAMs) effectively addresses the solubility and bioavailability issues of poorly water-soluble chemical entities. However, stress conditions imposed during common pharmaceutical processing (e.g., tableting) may cause the recrystallization of the systems, warranting close stability monitoring throughout production. This work aimed at assessing the water and heat stability of amorphous olanzapine (OLZ) and OLZ-CAMs when subject to wet granulation and pelletization. Starting materials and products were characterized using calorimetry, diffractometry and spectroscopy, and their performance behavior was evaluated by dissolution testing. The results indicated that amorphous OLZ was reconverted back to a crystalline state after exposure to water and heat; conversely, OLZ-CAMs stabilized with saccharin (SAC), a sulfonic acid, did not show any significant loss of the amorphous content, confirming the higher stability of OLZ in the CAM. Besides resistance under the processing conditions of the dosage forms considered, OLZ-CAMs presented a higher solubility and dissolution rate than the respective crystalline counterpart. Furthermore, in situ co-amorphization of OLZ and SAC during granule production with high fractions of water unveils the possibility of reducing production steps and associated costs.
Topics: Crystallization; Drug Stability; Olanzapine; Saccharin; Solubility; Sulfonic Acids; Tablets; Water; X-Ray Diffraction
PubMed: 36142179
DOI: 10.3390/ijms231810234 -
Microorganisms Dec 2022Soil microbes play important roles in plant health and ecosystem functioning, however, they can often be disturbed or depleted in degraded lands. During seed-based...
Soil microbes play important roles in plant health and ecosystem functioning, however, they can often be disturbed or depleted in degraded lands. During seed-based revegetation of such sites there is often very low germination and seedling establishment success, with recruitment of beneficial microbes to the rhizosphere one potential contributor to this problem. Here we investigated whether Australian native plant species may benefit from planting seed encapsulated within extruded seed pellets amended with one of two microbe-rich products: a commercial vermicast extract biostimulant or a whole-soil inoculum from a healthy reference site of native vegetation. Two manipulative glasshouse trials assessing the performance of two Australian native plant species ( and ) were carried out in both unmodified field-collected soil (trial 1) and in the same soil reduced in nutrients and microbes (trial 2). Seedling emergence and growth were compared between pelleted and bare-seeded controls and analyzed alongside soil nutrient concentrations and culturable microbial community assessments. The addition of microbial amendments maintained, but did not improve upon, high levels of emergence in both plant species relative to unamended pellets. In trial 1, mean time to emergence of seedlings was slightly shorter in both amended pellet types relative to the standard pellets, and in trial 2, whole-soil inoculum pellets showed significantly improved growth metrics. This work shows that there is potential for microbial amendments to positively affect native plant emergence and growth, however exact effects are dependent on the type of amendment, the plant species, and the characteristics of the planting site soil.
PubMed: 36677347
DOI: 10.3390/microorganisms11010055 -
Graefe's Archive For Clinical and... May 2023The purpose of this study is to evaluate clinical outcomes of autoimmune retinopathy (AIR) in the patients treated with intravitreal dexamethasone implant (IDI).
PURPOSE
The purpose of this study is to evaluate clinical outcomes of autoimmune retinopathy (AIR) in the patients treated with intravitreal dexamethasone implant (IDI).
METHOD
Twenty-one eyes of 11 AIR patients treated with at least 1 injection of IDI were retrospectively reviewed. Clinical outcomes before and after treatment, including best corrected visual acuity (BCVA), optic coherence tomography (OCT), fundus autofluorescence (FAF), full-field electroretinography (ff-ERG), and visual field (VF) at last visit within 6 and/or 12 months, were recorded.
RESULTS
Among all the patients, 3 had cancer-associated retinopathy (CAR) and 8 had non-paraneoplastic-AIR (npAIR) with mean followed up of 8.52 ± 3.03 months (range 4-12 months). All patients achieved improved or stable BCVA within 6 and/or 12 months after the treatment. Cystoid macular edema (CME) in 2 eyes and significant retinal inflammation in 4 eyes were markedly resolved after single injection. Central retinal thickness (CFT) in all eyes without CME, ellipsoid zone (EZ) on OCT in 71.4% of eyes, ERG response in 55% of eyes, and VF in 50% of eyes were stable or improved within 6 months after treatment. At last visit within 12 months, both BCVA and CFT remained stable in the eyes treated with either single or repeated IDI; however, progression of EZ loss and damage of ERG response occurred in some patients with single IDI.
CONCLUSION
Clinical outcomes, including BCVA and parameters of OCT, ERG, and VF, were stable or improved after IDI in a majority of AIR patients. Local treatment of AIR with IDI was a good option to initiate the management or an alternative for the patients' refractory to the systemic therapy but with limited side effect.
Topics: Humans; Dexamethasone; Glucocorticoids; Autoimmune Diseases; Retinal Diseases; Retrospective Studies; Tomography, Optical Coherence; Macular Edema; Retina; Intravitreal Injections; Drug Implants; Diabetic Retinopathy
PubMed: 36565329
DOI: 10.1007/s00417-022-05941-x -
Journal of Glaucoma Sep 2019There is a limit beyond which increasing either the concentration of a prostaglandin analog (PGA) or its dosing frequency fails to produce increases in ocular... (Review)
Review
There is a limit beyond which increasing either the concentration of a prostaglandin analog (PGA) or its dosing frequency fails to produce increases in ocular hypotensive efficacy with topical dosing. Intracameral PGA dosing with a bimatoprost implant, however, does not exhibit the same intraocular pressure (IOP)-lowering plateau at studied concentrations, and the maximum-achievable ocular hypotensive effects are not yet known. This suggests that the bimatoprost intracameral implant may activate another mechanism of action in addition to the mechanism(s) activated by topical application. Episcleral venous pressure (EVP) is a key determinant of IOP, and experimental manipulation of the episcleral vasculature can change both EVP and IOP. The recent observation that topical and intracameral PGA drug delivery routes produce different patterns of conjunctival hyperemia suggested that the differences in the IOP-lowering profiles may be caused by differing effects on the episcleral vasculature. Recent experiments in animals have shown that topical PGAs increase EVP, while the bimatoprost intracameral implant causes a smaller, transient increase in EVP, followed by a sustained decrease. The increase in EVP could be limiting the IOP-lowering efficacy of topical PGAs. In contrast, the decrease in EVP associated with the bimatoprost implant could explain its enhanced IOP-lowering effects. Further research on EVP as a target for IOP lowering is indicated to improve our understanding of this potentially important pathway for treating patients with glaucoma.
Topics: Administration, Ophthalmic; Animals; Antihypertensive Agents; Bimatoprost; Drug Implants; Glaucoma; Humans; Intraocular Pressure; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins, Synthetic; Sclera; Venous Pressure
PubMed: 31261285
DOI: 10.1097/IJG.0000000000001307 -
Computational and Experimental Studies of Selected Types of Biomass Combustion in a Domestic Boiler.Materials (Basel, Switzerland) Jul 2022The paper analyzes the suitability of four types of biomass pellets as a fuel for heating purposes. Three types of waste biomass (sunflower husks, rapeseed cake, and...
The paper analyzes the suitability of four types of biomass pellets as a fuel for heating purposes. Three types of waste biomass (sunflower husks, rapeseed cake, and corn straw) and one type of biomass grown for energy purposes (willow) were selected. After appropriate preparation, the selected starting materials were subjected to the pelletization process. Selected physical and chemical properties of the studied biomass pellets were determined. All four types of the analyzed pellets met the EN-ISO-17225-2:2014 standard in terms of bulk density, dimensions, as well as nitrogen and moisture content. The highest calorific value was pellets made of sunflower husk (17.27 MJ/m) and willow (16.81 MJ/m), while the calorific value of pellets made of corn straw and rapeseed cake did not exceed 16.5 MJ/m and did not meet the standard. In addition, the ash content for these two types of pellets was well above the standard. A 10 kW domestic biomass boiler was employed for burning the tested pellets. The consumption of analyzed fuels during boiler operation was determined. The concentration of CO, CO, and NO in exhaust gases was also examined. The obtained experimental results were compared with the numerical calculations with the use of ANSYS Chemkin-Pro using two mechanisms. The highest concentrations of CO and CO were observed during the combustion of sunflower and willow husk pellets, which probably resulted from the highest carbon content and, thus, the highest calorific value when compared to cake and straw pellets. For all analyzed pellets, the value of NO and NO concentration was similar and did not exceed 368 ppm and 18 ppm, respectively. The results closest to the experiment were obtained for calculations using the mechanism developed by Glarborg et al. The research carried out in the article shows that out of the four analyzed types of pellets, only sunflower and willow husk pellets can be burned in a domestic boiler adapted to burning wood pellets, which is a cheap alternative to wood pellets.
PubMed: 35888294
DOI: 10.3390/ma15144826 -
Journal of Animal Science Nov 2019Predominately Angus steers (n = 24; initial BW = 435 ± 28.3 kg) were used to evaluate non-coated (NC) and coated implants (CI) containing equal amounts of trenbolone...
Feedlot performance and biological responses to coated and non-coated steroidal implants containing trenbolone acetate and estradiol benzoate in finishing beef steers1,2,3.
Predominately Angus steers (n = 24; initial BW = 435 ± 28.3 kg) were used to evaluate non-coated (NC) and coated implants (CI) containing equal amounts of trenbolone acetate (TBA; 200 mg) and estradiol benzoate (EB; 28 mg) in finishing steers on sera metabolite responses, gene expression, and immunohistochemical analyses of the Longissimus muscle (LM). Performance data were analyzed as a randomized complete block design, and all other data were analyzed as repeated measures for a completely randomized design. Treatments were no implant (NI), NC (Synovex-PLUS; Zoetis, Parsippany, NJ), and CI (Synovex-One Feedlot) implant. There were 2 pen replicates per treatment (n = 4 steers/pen). LM biopsies, blood, and BW were collected before feeding on days 0, 14, 28, 56, 84, 112, and 133, with final BW being captured on day 140. Genes of interest were determined by RT-qPCR using two housekeeping genes. Sera was analyzed for estradiol-17β (E2),17β-trenbolone (TbOH), insulin-like growth factor 1 (IGF-I), NEFA, and urea-N (SUN). An α of 0.10 determined significance for performance and sera data; α of 0.05 was used for gene and histology data. No performance differences (P ≥ 0.10) were detected. An implant × day interaction (P ≤ 0.10) for E2, IGF-I, and SUN was detected; implants elevated (P ≤ 0.10) E2, 17β-TbOH, and IGF-I; and decreased SUN across day of the study, meaning sera metabolites are not altered with time on feed. An implant × day interaction was detected for myogenic factor 5 (MYF-5) positive cells and proportions of MHCIIX. In LM, CI had greater (P < 0.10) IGF-I in LM over NI. CI increased (P < 0.05) G protein-coupled estrogen receptor 1 (GPER1) expression, as well as, GPER1 semi-quantitative scores over NI and NC. An implant × day interaction (P ≤ 0.05) for estrogen and androgen receptor-positive nuclei was detected; implants had increased (P ≤ 0.05) estrogen and androgen receptor-positive nuclei compared to NI. CIs increase genes associated with muscle tissue growth.
Topics: Anabolic Agents; Animal Feed; Animals; Cattle; Diet; Drug Implants; Eating; Estradiol; Immunohistochemistry; Insulin-Like Growth Factor I; Male; Muscle, Skeletal; Random Allocation; Red Meat; Steroids; Trenbolone Acetate
PubMed: 31541251
DOI: 10.1093/jas/skz298