Production Profile Research Articles

Characterization of Wormhole Growth and Propagation Dynamics during CHOPS Processes by Integrating Rate Transient Analysis and a Pressure-Gradient-Based Sand Failure Criterion in the Presence of Foamy Oil Behavior

Summary Characterization of wormhole growth and propagation dynamics has been made possible with the semi-analytical models developed in this work by integrating both rate transient analysis (RTA) and a pressure-gradient-based (PGB) sand failure criterion in the presence of foamy oil behavior. The nonlinearity caused by the foamy oil properties is linearized using pseudofunctions, while the source function and finite difference methods are applied to obtain the solutions for the linearized models in the matrix and wormhole subsystems, respectively. A sequential method is adopted to solve the coupling fluid-solid problem, where new wormhole segments can be generated once the PGB sand failure criterion has been achieved, while their updated petrophysical properties can be sent back to obtain the solutions for the fluid flow in the next time interval. Furthermore, the influence of sand failure/fluidizing and foamy oil properties on the dynamic wormhole network can be investigated with the generated type curves. Both wormhole growth and foamy oil flow dictate an upward fluid production at the early times, while the production-induced pressure depletion dominates the declining production at the late times. The fractal wormhole networks can be dynamically characterized by history matching the field fluid and sand production profiles. Both the sand failure degree and foamy oil properties dictate the effective wormhole coverage and intensity. Sand production is found to be influenced by both the breakdown pressure gradient and wormhole conductivities, while oil production rate can be dominated by the wormhole coverage and intensity. Foamy oil flow can increase the oil production rate and increase the wormhole coverage compared with the conventional oil. The newly developed method in this work has been validated and then applied at field scale to dynamically characterize the wormhole growth and propagation by considering both the sand failure phenomenon and foamy oil properties within a unified, consistent, and accurate framework. Compared to the conventional numerical simulations, the novelty of such a semi-analytical method can not only allow us to characterize the growth and propagation dynamics of the fractal-like wormholes without the need for grid refinement near the wormhole grids but also take the complex sand failure and foamy oil behavior into account. In addition, it can minimize the impact of grid orientation effects in numerical simulations, enabling the growth and propagation of the wormholes in arbitrary directions rather than orthogonal directions conditioned to the largest pressure gradient.

Fermented Fish Products: Balancing Tradition and Innovation for Improved Quality.

The flavor profile of fermented fish products is influenced by the complex interplay of microbial and enzymatic actions on the raw materials. This review summarizes the various factors contributing to the unique taste and aroma of these traditional foods. Key ingredients include locally sourced fish species and a variety of spices and seasonings that enhance flavor while serving as cultural markers. Starter cultures also play a critical role in standardizing quality and accelerating fermentation. Flavor compounds in fermented fish are primarily derived from the metabolism of carbohydrates, lipids, and proteins, producing a diverse array of free amino acids, peptides, and volatile compounds such as aldehydes, ketones, alcohols, and esters. The fermentation process can be shortened by certain methods to reduce production time and costs, allowing for faster product turnover and increased profitability in the fermented fish market. Fermented fish products also show potent beneficial effects. This review highlights the importance of integrating traditional practices with modern scientific approaches. Future research directions to enhance the quality of fermented fish products are suggested.

The Effects of Hemp Hay (Canapa sativa L.) in the Diets of Grazing Goats on Milk Production and Fatty Acid Profile.

Hemp (Cannabis sativa L.) is a cosmopolitan annual herbaceous plant used in the past as a source of textile fiber. Currently, hemp is receiving great interest as animal feed due to its chemical and nutritional properties. The aim of this study was to explore the effects of supplementing goats' diets with hemp hay on the milk yield, chemical composition, and fatty acid profile. Twenty multiparous goats, immediately after kidding, were divided into two homogenous groups (C: control vs. H: hemp); the goats had free access to the pasture, and both groups received a supplement of 500 g/head/day of a barley and corn meal mixture (50/50). In addition, group H was given 250 g/head/day of hemp hay while group C received the same amount of alfalfa hay. The milk yield was measured daily, and milk samples were collected monthly 4 times to evaluate the milk composition and fatty acid profile. The milk yield was significantly (p < 0.05) higher in the experimental group, while no differences were found in the milk chemical composition. Concerning the fatty acid profile, the milk from group H was characterized by significantly lower concentrations of C11:0, C12:0, C13:0, C14:0, C15:0, and C17:0 and higher C16:0 and C18:0. Among the polyunsaturated FA, C18:2 n6 and C20:4 were significantly (p < 0.001) lower, and C20:5 n3 was significantly (p < 0.05) higher in the milk from group H than that from group C. The n6/n3, LA/ALA and AA/EPA ratios were significantly (p < 0.001) lower in the milk from group H, while the CLAs were unaffected by the treatment.

Quality by design steered approach for co-encapsulation of timolol maleate and dorzolamide hydrochloride in injectable liposomes

Glaucoma is caused by high intraocular pressure, which can causes blindness. Combinations of timolol and dorzolamide are used for its treatment with a requirement of multiple dosing with dosing being twice or four times a day. Conventional eye drops have poor pre-corneal retention and is thus less available for action. This study utilizes principles of Quality by Design for formulation of injectable liposomes coloaded with timolol maleate and dorzolamide HCl, which overcomes limitations of conventional eye drops. For implementation of Quality by Design principles a systematic approach involving defining Quality Target Product Profile, identification of Critical Quality Attributes, mapping Critical Quality Attributes to Critical Process Parameters and Critical Material Attributes, Failure Mode and Effect Analysis based risk assessment, Taguchi screening, and 32 full factorial Design of Experiments design were utilized. A robust model for formulation of coloaded liposomes was successfully developed. Design of Experiments approach allowed to obtain optimized batch having particle size of 116.1 nm, encapsulation efficiency of dorzolamide HCl of 72.12 % and encapsulation efficiency of timolol maleate of 71.94 %. In-vitro drug release showed a sustained release for 4 days. The prepared formulation was in the desired osmolarity range. Biosafety was proved using histopathological characterization. In-vivo studies for assessing the Intra Ocular Pressure reduction showed that there was no significant difference in Intra Ocular Pressure reduction between prepared liposomes and marketed formulation but were superior than marketed formulation because of less fluctuations in Intra Ocular Pressure. Prepared coloaded injectable liposomes lays the foundation for further research in the area and can be translated from to bench side for commercial clinical use.

Evaluation of extended-spectrum β-lactamase production and plasmid-mediated quinolone resistance in Escherichia coli isolated from raw milk

This study aimed to determine the antibiotic resistance and extended-spectrum β-lactamase production profiles of Escherichia coli isolates obtained from raw milk samples. To this end, the study used a chromogenic-based culture method, MALDI-TOF-MS, 16S rRNA gene sequencing, disc diffusion, and combined disc techniques. PCR was also performed to detect ESBL (blaSHV, blaTEM, and blaCTX-M), quinolone (qnrA, qnrB, and qnrS) genes, and the presence of class I integrons. A total of 47 (78.33%) E. coli isolates were identified by morphological, biochemical, and molecular tests. All isolates exhibited susceptibility to gentamicin and tobramycin. Resistance rates to different antibiotics were observed as follows: ampicillin, 51.06%; nalidixic acid, 23.40%; trimethoprim/sulfamethoxazole, 17.02%; meropenem, 14.89%; ceftazidime, 8.51%; cefotaxime, 8.51%; piperacillin-tazobactam, 4.25%; aztreonam, 4.25%; imipenem, 4.25%; and levofloxacin, 2.12%. ESBL production was positive in 3 (6.38%) of the isolates. Bla genes were detected in 11 isolates (blaSHV = 9 [19.14%], blaTEM = 4 [8.5%], and blaCTX = 3 [6.38%]). The qnrB, qnrS, and qnrA genes were found in 5 (10.63%), 4 (8.51%), and 1 (2.12%) isolates, respectively. The intI1 gene was detected in 14 (29.78%) isolates.

Chemical Profile and Potential Application of Agri-food Waste Products for Counteracting Diabetes Induced Neuropathy in Rats.

This study aimed to prepare defatted ethanol extract of Abelmoschus esculentus leaves, Morus nigra leaves and Punica granatum peel, to identify the chemical composition of these extracts and to explore their efficacy in counteracting diabetic neuropathy. LC-ESI-MS spectrometry was the hyphenated tool for component identification of these extracts. Behavioral, biochemical, and histopathological investigations were carried out after treatments of diabetic rats. The phenolic contents in the extracts are 16.38, 34.75 and 40.57 mg GAE/g extract regarding A. esculentus leaves, M. nigra leaves and P. granatum peel respectively. Chemodiversity of the phenolic contents was observed from the LC/Mass, where A. esculentus extract contained isoflavonoids and flavanones, M. nigra extract consisted of benzofurans, prenylated flavonoids, stilbenes, and xanthones, and P. granatum extract was rich in ellagitanins, condensed tannins, and anthocyanins. The extracts normalize of blood glucose levels, enhance the explorative behavior of the rats and their response time to thermal pain, restore the oxidant/antioxidant balance, attenuate inflammation, augment brain monoamines levels and modulate MAO-A and Ache enzyme activity. Furthermore, they recovered brain histopathological alterations. Conclusively, this study offers experimental evidence for the neuroprotective impact of studied defatted ethanol extracts against diabetic neuropathy via their hypoglycemic effect, antioxidant activity, and anti-inflammatory potential.

1,3-Disubstituted thiourea derivatives: Promising candidates for medicinal applications with enhanced cytotoxic effects on cancer cells

The distinct chemical structure of thiourea derivatives provides them with an advantage in selectively targeting cancer cells. In our previous study, we selected the most potent compounds, 2 and 8, with 3,4-dichloro- and 3-trifluoromethylphenyl substituents, respectively, across colorectal (SW480 and SW620), prostate (PC3), and leukemia (K-562) cancer cell lines, as well as non-tumor HaCaT cells. Our research has demonstrated their anticancer potential by targeting key molecular pathways involved in cancer progression, including caspase 3/7 activation, NF-κB (Nuclear Factor Kappa-light-chain-enhancer of activated B cells) activation decrease, VEGF (Vascular Endothelial Growth Factor) secretion, ROS (Reactive Oxygen Species) production, and metabolite profile alterations. Notably, these processes exhibited no significant alterations in HaCaT cells. The effectiveness of the studied compounds was also tested on spheroids (3D culture). Both derivatives 2 and 8 increased caspase activity, decreased ROS production and NF-κB activation, and suppressed the release of VEGF in cancer cells. Metabolomic analysis revealed intriguing shifts in cancer cell metabolic profiles, particularly in lipids and pyrimidines metabolism. Assessment of cell viability in 3D spheroids showed that SW620 cells exhibited better sensitivity to compound 2 than 8. In summary, structural modifications of the thiourea terminal components, particularly dihalogenophenyl derivative 2 and para-substituted analog 8, demonstrate their potential as anticancer agents while preserving safety for normal cells.

Evaluation of an electricity-independent method for IS2404 Loop-mediated isothermal amplification (LAMP) diagnosis of Buruli ulcer in resource-limited settings.

Buruli ulcer (BU) caused by Mycobacterium ulcerans (MU) is a devastating necrotic skin disease. PCR, recommended for confirmation of BU by WHO, requires an adequately equipped laboratory, therefore often delaying timely diagnosis and treatment of BU patients in remote settings. Loop-mediated isothermal amplification (LAMP) is a PCR-based protocol for isothermal amplification of DNA that has been suggested for diagnosis of BU in low-resource settings. This is an exploratory diagnostic test evaluation study, with an embedded qualitative sub-study. Its aims are two-fold: First, to evaluate a simple rapid syringe-based DNA extraction method (SM) in comparison with a more elaborate conventional DNA extraction method (CM), followed by a LAMP assay targeting IS2404 for the detection of MU, either using a commercially available pocket warmer (pw) or a heat block (hb) for incubation. Second, to complement this by exploring the diagnostic workflow for BU at a community-based health centre in an endemic area in rural Ghana as an example of a potential target setting, using interviews with researchers and health care workers (HCWs). Diagnostic test evaluation results are discussed in relation to the requirements of a target product profile (TPP) for BU diagnosis and the target setting. A protocol using SM for DNA extraction followed by IS2404 PCR (IS2404 PCRSM) was able to identify MU DNA in 73 out of 83 BU clinical specimens submitted for diagnosis. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of IS2404 PCRSM were 90.12%, 100%, 100% and 65.21% respectively, as compared to the reference standard IS2404 PCR in combination with a standard extraction protocol for mycobacterial DNA. Evaluation of the LAMP assay on 64 SM DNA extracts showed a sensitivity, specificity, PPV and NPV of 83.6%, 100%, 100% and 50%, respectively, using either pocket warmer (pwLAMPSM) or heat block (hbLAMPSM) for incubation of the reaction, as compared to the same reference standard. The limit of detection of pwLAMPSM was found to be 30 copies of the IS2404 target. Interview findings explored barriers to BU diagnosis and treatment, including perceptions of the disease, costs, and availability of transport. Participants confirmed that a diagnosis at the PoC, in addition to screening based on clinical criteria, would be advantageous in order to prevent delays and loss to follow-up. The high diagnostic and analytic accuracy of the pwLAMP, evaluated by us in combination with a syringe-based DNA extraction method, supports its potential use for the rapid detection of MU in suspected BU samples at the community or primary health care level without reliable electricity supply. Further optimization needs include a lysis buffer, evaluation directly at the PoC and/or other sites, assessing staff training requirements and quality control.

Performance evaluation of the Xpert MTB/XDR test for the detection of drug resistance to Mycobacterium tuberculosis among people diagnosed with tuberculosis in South Africa.

Drug-resistant tuberculosis (TB) poses a significant public health concern in South Africa due to its complexity in diagnosis, treatment, and management. This study assessed the diagnostic performance of the Xpert MTB/XDR test for detecting drug resistance in patients with TB by using archived sputum sediments. This study analyzed 322 samples collected from patients diagnosed with TB between 2016 and 2019 across South Africa, previously characterized by phenotypic and genotypic methods. The Xpert MTB/XDR test was evaluated for its ability to detect resistance to isoniazid (INH), ethionamide (ETH), fluoroquinolones (FLQ), and second-line injectable drugs (SLIDs) compared with phenotypic drug susceptibility testing (pDST) and whole-genome sequencing (WGS). Culture, Xpert MTB/RIF Ultra, and Xpert MTB/RIF (G4) tests were performed to determine sensitivity and agreement with this test for TB detection. The sensitivities using a composite reference standard, pDST, and sequencing were >90% for INH, FLQ, amikacin (AMK), kanamycin (KAN), and capreomycin (CAP) resistance, meeting the WHO target product profile criteria for this class. A lower sensitivity of 65.9% (95% CI: 57.1-73.6) for ETH resistance was observed. The Xpert MTB/XDR showed a sensitivity of 98.3% (95% CI: 96.1-99.3) and specificity of 100% (95% CI: 86.7-100) compared with culture, a positive percent agreement (PPA) of 98.8% (95% CI: 93.7-99.8) and negative percent agreement (NPA) of 100.0% (95% CI: 78.5-100.0) compared with G4, and a PPA of 99.5% (95% CI: 97.3-99.9) and NPA of 100.0% (95% CI: 78.5-100.0) compared with Xpert MTB/RIF Ultra for detecting Mycobacterium tuberculosis. The test offers a promising solution for the rapid detection of drug-resistant TB and could significantly enhance control efforts in this setting.

PEGylation in Pharmaceutical Development: Current Status and Emerging Trends in Macromolecular and Immunotherapeutic Drugs.

The purpose of the research is to examine the advantages and difficulties of target-site drug delivery methods, with an emphasis on the application of polyethylene glycol (PEG) to enhance drug solubility, bioavailability, and immune response characteristics. It has been demonstrated that this method lowers immunogenicity, enhances pharmacokinetics, and helps drugs pass the blood-brain barrier while reducing reticuloendothelial system clearance. PEG and its derivatives are being used more and more to alter therapeutic substances, offering an escape from some of the drawbacks of conventional medication formulations. In the review, different PEGylation tactics are examined, including cutting-edge methods for reversing multi-drug resistance in nanocarriers. PEGylation has a number of benefits, but there are still drawbacks, including the immunogenic reaction to PEG, which is sometimes referred to as "anti-PEG antibodies," and stability problems that call for the creation of countermeasures. The study devotes a large amount of its space to listing FDA-approved PEGylated medications, emphasizing their therapeutic advantages and clinical uses in a range of medical specialties. The research also explores the regulatory environment that surrounds PEG, closely examining its effectiveness and safety in medication compositions. The review goes beyond PEGylation and includes lipid-based nanocarriers, including liposomes, nanostructured lipid carriers (NLCs), and solid lipid nanoparticles (SLNs). Because these nanocarriers can target specific tissues or cells, improve bioavailability, and encapsulate pharmaceuticals, they are becoming more and more significant in drug delivery systems. The Target Product Profile (TPP) and Quality by Design (QbD) principles serve as the foundation for the creation and characterization of these lipid-based systems. These tools direct the methodical assessment of material properties and risk assessments during the formulation phase. This method guarantees that the finished product satisfies the appropriate requirements for efficacy, safety, and quality. The regulatory status and safety profile of nano lipid carriers are covered in the paper's conclusion, which emphasizes the importance of careful examination and oversight in bringing these cutting-edge products to market. Overall, this thorough analysis highlights the revolutionary potential of lipid-based nanocarriers and PEGylation in improving drug delivery and therapeutic efficacy, but it also draws attention to the continued difficulties and legal issues that need to be resolved in order to fully reap the benefits of these technologies in biomedicine.

(Invited) Single-Atom Cu Catalysts for Electrochemical CO2 Reduction – Combining Theory, Synthesis and Electrochemical Characterization

Electrochemical CO2 reduction (CO2RR) is a leading sustainable approach for transforming atmospheric CO2 into valuable chemicals. This electrocatalytic process relies on a delicate balance of electron and proton transfer steps, resulting in the formation of diverse 1-carbon and some 2-carbon products, contingent on the surface properties. Extensive exploration of various transition metals for CO2RR has revealed that the binding strength of reaction intermediates on these metals significantly influences product selectivity. Notably, metals such as Au, Ag, Pd, Zn, Cd, Bi, Sn, and In, recognized for their activity in CO2RR, exhibit lower binding strengths for CO2 intermediates, leading to the predominant production of either HCOOH or CO as sole products. In contrast, Cu, with its moderate ability to bind CO2RR intermediates, yields multiple products during CO2RR, albeit with reduced selectivity [1]. Moreover, the overall efficiency of CO2 conversion is hampered by the simultaneous occurrence of the competing hydrogen evolution reaction (HER) at the potentials required for producing desired products. Thus, it is imperative to develop new, effective catalysts. Catalysts capable of suppressing HER while enhancing selectivity are essential for advancing the overall efficiency of CO2 conversion [2].Single-atom catalysts (SACs) are a relatively new class of materials that hold great promise due to their high specific activity and maximum atom utilization [3]. These catalysts often provide singular types of active sites, enhancing selectivity in reactions. However, the vast array of possible SACs, deployable on various supports, makes it impractical, if not possible, to use the traditional trial-and-error studies to yield high performing catalysts within reasonable timeframes. To navigate this complexity, theoretical investigations, especially DFT computations and machine learning techniques, have emerged as powerful tools. They can facilitate the identification of suitable catalyst structures and enable the precise engineering of atomic arrangement, therefore achieving targeted product formation from CO2 with enhanced conversion efficiency. Additionally, conventional synthesis methods suffer from various drawbacks, involving multiple steps, harsh conditions, and a lack of control over the metal site distribution in the carbon matrix, limiting the desired coordination structure [4, 5].Therefore, the work presented in this talk represents our combined experimental-theoretical effort. Specifically, Cu single atoms were strategically deposited onto defective carbon supports and systematically investigated for their performance as CO2RR electrocatalysts. These catalysts were inspired by DFT results showing how the product profile could be manipulated on catalyst surfaces, along with a prediction of the most likely products that would arise from the reaction.These catalysts were synthesized using a novel method denoted as switched solvent synthesis. This approach involves initially impregnating metals onto a carbon support, followed by switching the solvent from aqueous to an organic solvent with a higher dipole moment, and subsequently reducing the resulting mixture under an H2 environment. This innovative method offers notable advantages, enabling the efficient production of SACs in less time, at lower temperatures (~100-500 °C), and with high yields. In this study, Cu SACs were synthesized, and the influence of reaction parameters on the distribution of Cu metal atoms was systematically examined. The confirmation of SAC formation was achieved through various characterization techniques, including aberration-corrected STEM, XRD, and XPS.To assess the electrochemical activity and CO2 reduction abilities of the Cu SACs, electrochemical characterization techniques were employed under both He and CO2-saturated 0.1 M KHCO3 electrolytes. Furthermore, the product distribution and CO2 conversion efficiencies, including activity, stability, selectivity, and faradaic efficiency, of the Cu SACs were rigorously evaluated through electrolysis in a flow cell setup. Quantification of the results was performed using an integrated GC/MS instrument.

Fennel (Foeniculum vulgare Mill.) essential oil: The chemical profile, biological activity, and utilization of the commercial products

Laboratory-isolated essential oils are commonly used in experiments regarding their utilization as natural antioxidant and antimicrobial agents. This study analyzed commercially available essential oils (Serbian-FSR and Russian-FRU) of fennel (Foeniculum vulgare Mill.) and added to the pork patties to investigate their possible role as natural antioxidant and antimicrobial agents. Chemical analysis of the samples showed significant differences in profiles caused by geographical origin and other environmental factors. The main compound in both samples was trans-Anethole, but it had a much higher content in Serbian oils. On the contrary, Russian oil had a high portion of anisaldehyde and linalool. These diversities are the main reason for thermal behavior and biological activity differences. The thermal analysis has shown that FSR had a crystalline form in the solid state, while FRU had an amorphous form. During heating, in FSR, a single-step weight loss was detected, while in FRU, a two-step weight loss was observed, indicating that, in addition to evaporation, components in FRU interacted with each other, forming lesser volatile molecules. After adding pork patties, Russian oil showed higher potency and better protective behavior than Serbian oil. Moreover, mixtures of these oils were added to the patties samples, and results showed higher potency when compared to individual oil samples. This indicated that minor compounds from both oils interacted and synergistically acted to prolong the shelf life of the meat samples. Commercial essential oils could be successfully utilized to prolong shelf life and provide additional intake of natural compounds significant for the human diet.

Extended-spectrum beta-lactamase (ESBL) production and virulence genes profile of avian pathogenic Escherichia coli (APEC) isolated from broiler chickens in eastern Thailand

Avian pathogenic Escherichia coli (APEC) causes colibacillosis, resulting in extensive economic losses for the broiler industry. To date, there is little information in Thailand about virulence-associated genes and antibiotic resistance of APEC strains. Here, this study aimed to investigate the virulence genes and extended-spectrum beta-lactamase (ESBL) characteristics of APEC isolated from broilers. This study used multiplex polymerase chain reaction (PCR) to determine the presence of virulence genes and resistance genes in APEC. Furthermore, the disc diffusion method examined ESBL phenotypes of APEC and antibiotic resistance profiles against 17 antimicrobials. In this study, E. coli was isolated 11 (6.32%) of 174 broiler visceral organs. All E. coli isolates were tested for five APEC-virulence-associated genes (iroN, ompT, hlyF, iutA, and iss). Eight E. coli isolates from broilers with colibacillosis-associated lesions carried two (iroN and ompT) of the APEC virulence genes. One APEC virulence gene (hlyF) was found in E. coli isolates from broilers without lesions. Possibly no individual virulence gene was specific to the APEC strain. Interestingly, the papC, previously detected in humans with uropathogenic E. coli, was found in an APEC isolate. All APEC isolates were ESBL-producing E. coli, and then they were tested for four beta-lactamase-encoding genes (blaTEM, blaCTX-M, blaOXA, and blaSHV). The blaTEM and blaCTX-M were identified in 81.81% (9/11) of the isolates, whereas blaOXA or blaSHV were not detected in any isolate. All APEC showed multi-drug resistance (MDR) phenotypes, especially chloramphenicol, erythromycin, and sulfamethoxazole-trimethoprim. Although antibiotics were not recently used, MDR might be encouraged by horizontally transferring antibiotic-resistance genes. In addition, fluoroquinolone resistances were found in APEC isolates which could transfer resistance genes to humans via the food chain. This study indicates that APEC isolates contain several virulence and bla genes and should be surveillance to prevent the transmission of those genes to humans.

Pet Owners' Preferences for Quality of Life Improvements and Costs Related to Innovative Therapies in Feline Pain Associated with Osteoarthritis-A Quantitative Survey.

This research aimed to explore UK cat owners' preferences for treatments for feline osteoarthritis (OA) by exploring preferences around quality of life (QoL) improvements, safety considerations, and costs associated with hypothetical innovative pain therapies. Aspects identified in an existing conceptual framework were extracted for inclusion in exploratory interviews with cat owners (n = 3) to identify key domains that contribute to the QoL of cats. QoL descriptions for cats with OA and hypothetical product attributes were developed and validated through interviews with veterinarians (n = 3). An online survey was subsequently shared with 255 pet owners in the UK. Pet owners were presented with QoL descriptions and hypothetical product attributes to gather their preferences for QoL improvements and their willingness to pay (WTP) for (unbranded) pain therapies at various price points. Pet owners were motivated to improve their cats' QoL, which translated into WTP for therapies; specifically, pet owners valued QoL improvements in mobility, pain expression, and well-being. When presented with a product profile of the hypothetical novel monoclonal antibody (mAb) and cost, 50% of cat owners were willing to pay more for a mAb that is expected to have improved efficacy and safety when compared to a hypothetical standard of care (SoC). Significantly more pet owners preferred the mAb than the SoC when price was not presented (p < 0.01), with product efficacy and safety driving pet owners' decision-making. The majority of pet owners did not agree that taking their cats to the veterinarian once a month for their treatment would be burdensome. Cat owners in the UK are motivated to improve their cats' QoL, which translates into WTP for the efficacious treatment of pain associated with osteoarthritis. Veterinarians should offer cat owners the pain treatment they feel is best suited for improving the cat's QoL and to ensure subsequent owner-pet bond is preserved.

Heterogeneously deacetylated chitosans possess an unexpected regular pattern favoring acetylation at every third position

Chitosans are promising biopolymers for diverse applications, with material properties and bioactivities depending i.a. on their pattern of acetylation (PA). Commercial chitosans are typically produced by heterogeneous deacetylation of chitin, but whether this process yields chitosans with a random or block-wise PA has been debated for decades. Using a combination of recently developed in vitro assays and in silico modeling surprisingly revealed that both hypotheses are wrong; instead, we found a more regular PA in heterogeneously deacetylated chitosans, with acetylated units overrepresented at every third position in the polymer chain. Compared to random-PA chitosans produced by homogeneous deacetylation of chitin or chemical N-acetylation of polyglucosamine, this regular PA increases the elicitation activity in plants, and generates different product profiles and distributions after enzymatic and chemical cleavage. A regular PA may be beneficial for some applications but detrimental for others, stressing the relevance of the production process for product development.

Characterization of biofilm-forming ability and antibiotic resistance profiles of clinical Pseudomonas aeruginosa isolates from patients with cystic fibrosis

Background: Pseudomonas aeruginosa is a key pathogen in cystic fibrosis (CF) associated infections, known for its biofilm-forming ability and resistance to multiple antibiotics. Understanding the relationship between biofilm production and antibiotic resistance profiles in clinical isolates can guide treatment strategies. Aims and Objectives: The aims of this study were to investigate the biofilm-forming abilities and antibiotic resistance profiles of clinical P. aeruginosa isolates from patients with CF and to determine the relationship between these two factors and their impact on treatment efficacy. Materials and Methods: A cross-sectional study was conducted on 100 clinical isolates of P. aeruginosa from CF patients. Biofilm-forming capacity was categorized as strong, moderate, or weak based on quantitative assays. Antibiotic resistance was assessed for ciprofloxacin, tobramycin, ceftazidime, meropenem, and piperacillin/tazobactam. Multi-drug resistance was defined as resistance to three or more antibiotic classes. Statistical correlations between biofilm-forming capacity and resistance levels were evaluated using the Chi-square tests. Results: Fifty-six percentages of isolates were strong biofilm producers, while 34% and 10% were moderate and weak producers, respectively. The highest antibiotic resistance was observed against ciprofloxacin (60%), followed by tobramycin (50%) and ceftazidime (45%). Forty percentages of the isolates were classified as multi-drug resistant. Strong biofilm producers demonstrated a significantly high correlation with antibiotic resistance (P&lt;0.05). Two predominant clonal groups were identified among the isolates, suggesting a possible clonal spread of resistance traits. Conclusion: The study confirms a strong association between robust biofilm production and heightened antibiotic resistance in P. aeruginosa isolates from CF patients. These findings highlight the need for targeted therapeutic strategies to disrupt biofilm formation and curb resistance spread.

Genetic diversity analysis of tropical and sub-tropical maize germplasm for Striga resistance and agronomic traits with SNP markers.

Striga hermonthica (Sh) and S. asiatica (Sa) are major parasitic weeds limiting cereal crop production and productivity in sub-Saharan Africa (SSA). Under severe infestation, Striga causes yield losses of up to 100%. Breeding for Striga-resistant maize varieties is the most effective and economical approach to controlling the parasite. Well-characterized and genetically differentiated maize germplasm is vital to developing inbred lines, hybrids, and synthetic varieties with Striga resistance and desirable product profiles. The objective of this study was to determine the genetic diversity of 130 tropical and sub-tropical maize inbred lines, hybrids, and open-pollinated varieties germplasm using phenotypic traits and single nucleotide polymorphism (SNP) markers to select Striga-resistant and complementary genotypes for breeding. The test genotypes were phenotyped with Sh and Sa infestations using a 13x10 alpha lattice design with two replications. Agro-morphological traits and Striga-resistance damage parameters were recorded under a controlled environment. Further, high-density Diversity Array Technology Sequencing-derived SNP markers were used to profile the test genotypes. Significant phenotypic differences (P<0.001) were detected among the assessed genotypes for the assessed traits. The SNP markers revealed mean gene diversity and polymorphic information content of 0.34 and 0.44, respectively, supporting the phenotypic variation of the test genotypes. Higher significant variation was recorded within populations (85%) than between populations using the analysis of molecular variance. The Structure analysis allocated the test genotypes into eight major clusters (K = 8) in concordance with the principal coordinate analysis (PCoA). The following genetically distant inbred lines were selected, displaying good agronomic performance and Sa and Sh resistance: CML540, TZISTR25, TZISTR1248, CLHP0303, TZISTR1174, TZSTRI113, TZDEEI50, TZSTRI115, CML539, TZISTR1015, CZL99017, CML451, CML566, CLHP0343 and CML440. Genetically diverse and complementary lines were selected among the tropical and sub-tropical maize populations that will facilitate the breeding of maize varieties with Striga resistance and market-preferred traits.

Quantitative drug susceptibility testing for Mycobacterium tuberculosis using unassembled sequencing data and machine learning.

There remains a clinical need for better approaches to rapid drug susceptibility testing in view of the increasing burden of multidrug resistant tuberculosis. Binary susceptibility phenotypes only capture changes in minimum inhibitory concentration when these cross the critical concentration, even though other changes may be clinically relevant. We developed a machine learning system to predict minimum inhibitory concentration from unassembled whole-genome sequencing data for 13 anti-tuberculosis drugs. We trained, validated and tested the system on 10,859 isolates from the CRyPTIC dataset. Essential agreement rates (predicted MIC within one doubling dilution of observed MIC) were above 92% for first-line drugs, 91% for fluoroquinolones and aminoglycosides, and 90% for new and repurposed drugs, albeit with a significant drop in performance for the very few phenotypically resistant isolates in the latter group. To further validate the model in the absence of external MIC datasets, we predicted MIC and converted values to binary for an external set of 15,239 isolates with binary phenotypes, and compare their performance against a previously validated mutation catalogue, the expected performance of existing molecular assays, and World Health Organization Target Product Profiles. The sensitivity of the model on the external dataset was greater than 90% for all drugs except ethionamide, clofazimine and linezolid. Specificity was greater than 95% for all drugs except ethambutol, ethionamide, bedaquiline, delamanid and clofazimine. The proposed system can provide quantitative susceptibility phenotyping to help guide antimicrobial therapy, although further data collection and validation are required before machine learning can be used clinically for all drugs.

The novel thromboxane prostanoid receptor mediates CTGF production to drive human nasal fibroblast self-migration through NF-κB and PKCδ-CREB signaling pathways.

Chronic rhinosinusitis without nasal polyp (CRSsNP) is characterized by tissue repair/remodeling and the subepithelial stroma region in whose nasal mucosa has been reported by us to have thromboxane A2 (TXA2) prostanoid (TP) receptor and overexpress connective tissue growth factor (CTGF). Therefore, this study aimed to investigate the relationship between TP receptor activation and CTGF production/function in human CRSsNP nasal mucosa stromal fibroblasts. We found that TP agonists including U46619 and IBOP ([1S-[1α,2α(Z),3β(1E,3 S*),4α]]-7-[3-[3-hydroxy-4-(4-iodophenoxy)-1-butenyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid) could promote CTGF protein/messenger RNA expression and secretion. The pharmacological intervention and TP activation assay with U46619 identified the possible participation of PKCμ, PKCδ, nuclear factor-κB (NF-κB), and cyclic AMP response element-binding protein (CREB) phosphorylation/activation in the CTGF induction. Moreover, a phorbol ester-phorbol-12-myristate 13-acetate (PMA) exhibited a similar cellular signaling and CTGF production profile to that elicited by TP activation. However, further small interfering RNA interference analysis revealed that only NF-κB and PKCδ-CREB pathways were necessarily required for TP-mediated CTGF production, which could not be completely supported by those findings from PMA. Finally, in a functional assay, although CTGF did not affect fibroblast proliferation, TP-mediated CTGF could drive novel self-migration in fibroblasts both in the scratch/wound healing and transwell apparatus assays. Meanwhile, the overall staining for stress fibers and formation of the lamellipodia and filopodia-like structures was concomitantly increased in the treated migrating cells. Collectively, we provided here that novel TP mediates CTGF production and self-migration in human nasal fibroblasts through NF-κB and PKCδ-CREB signaling pathways. More importantly, we also demonstrated that thromboxane, TP receptor, CTGF, and stromal fibroblasts may act in concert in the tissue remodeling/repair process during CRSsNP development and progression.

Statistical optimization, kinetic modeling, and techno-economic analysis for the production of high molecular mass dextran using sugarcane industrial waste-molasses

This study focuses on the transformation of industrial wastes to wealth by utilizing treated sugarcane molasses (TCM) to produce dextran. The fermentation conditions for maximum dextran production were initially optimized using central-composite design in shake-flasks. The highest titer of dextran (60.0 ± 2.0 g/L) was obtained with optimized variables of 150 g/L substrate (TCM), 12.8 g/L yeast extract, 39.8 g/L K2HPO4, and 48 h fermentation time. Then, the profiles of dextran production, TCM consumption, and microbial growth were fitted by kinetic models to obtain the following kinetic parameters: 0.35 h−1 maximum specific growth rate (μmax), 0.48 g dextran/g substrate yield coefficient (Yps), 0.07 maintenance coefficient (ms), and 10.73 g product/g cell growth-associated constant (α). For determining the scale-up factors, the fermentation conditions were replicated in a 3 L fermenter at various stirring speeds (50–250 rpm), and a scale-up strategy based on constant P/V was used to predict the power consumption (1.88–285.51 W) for a pilot-scale of 2000 L working volume fermenter at various stirring speeds (10.8–54 rpm). The dextran produced was characterized using gel permeation chromatography to determine the molecular mass variations (3–4000 kDa) with fermentation conditions. The rheological variations of fermentation broth at different stirring speeds were also studied and related to the molecular mass of the dextran produced. Techno-economic analysis for dextran production explored a gross margin of 22.65 %, a return on investment of 16.80 %, and a pay-back time of 5.95 years.