Initial Lag Research Articles

Multigenerational hybridisation results in heterosis and facilitates adaptive introgression, with no evidence of outbreeding depression in a pair of marine gastropods.

Anthropogenic environmental changes continue to threaten species globally. For example, translocation of species has caused unintentional hybridisation, which has contributed to species declines. On the other hand, hybridisation can be used to increase the evolutionary potential of species vulnerable to rapid environmental change, although the benefits of mixing genetically divergent lineages do not come without risks to individual fitness and the long-term viability of populations. Here, we use a combination of genome-wide Single Nucleotide Polymorphism (SNP) markers, mitochondrial DNA sequencing and measurements of growth rate to determine the genetic consequences of hybridisation between two congeneric marine gastropods across 27 years (~18 generations). Multigeneration hybridisation resulted from the introduction of the intertidal periwinkle Bembicium vittatum (a direct developer) into the native range of its congener Bembicium auratum (a species with planktotrophic larval dispersal). Despite significant genetic divergence between the species, we found no direct evidence of outbreeding depression in the admixed population. Instead, we found evidence for heterosis, which dissipated over time. After an initial lag, the frequency of introduced B. vittatum alleles declined dramatically in the hybrid population. However, a few B. vittatum alleles (3.18%) increased significantly in frequency against the overall trend, providing evidence of adaptive introgression. In the context of hybridisation as a conservation management tool, our results provide some evidence of the potential benefits that can be gained, and suggest that the costs due to outbreeding depression can be small.

Moisture uptake during storage of coffee packed into compostable capsules decreases the quality of coffee brew

Compostable bioplastics for coffee capsule production should satisfy compostability requirements while providing a moisture barrier able to guarantee the espresso coffee quality. The present study aimed at exploring the time required for coffee packed in biobased PBS capsules and stored under different temperature and relative humidity to reach critical moisture levels triggering quality decay. Samples were stored in plastic boxes containing supersaturated solutions of Mg(NO3)2, NaNO2 or NaCl guaranteeing 54, 65 or 75 % RH, placed at 20, 30 and 45 °C in thermostatic incubators. During storage, the coffee powder was analysed for moisture uptake and water activity, and the coffee brew was extracted to measure the pH, selected as the quality indicator. Over 18 months, moisture uptake rapidly increased, reaching critical levels within 3 weeks in the worst-case scenario (i.e., 45 °C and 75 % RH). The evolution of pH presented an initial lag phase and a subsequent linear decay, which were respectively shorter (< 15 days) and faster (pH < 5.1 within 1 month) in the worst-case scenario. The findings highlight the role of T and RH in affecting coffee quality decay and emphasize the potential drawbacks of adopting biopolymer-based packaging. These outcomes could help food manufacturers in scouting new packaging materials for coffee capsule applications, evidencing the potential drawbacks of replacing conventional packaging materials with biobased ones. In this regard, it is recommended that a thorough cost-benefit analysis is carried out before transitioning from conventional to compostable packaging to ensure sustainability goals are effectively met while maintaining product quality.

Evolution of Azerbaijani Science Fiction and Emin Mahmudov

The evolution of science fiction literature in Azerbaijan has been characterized by a delayed emergence compared to European, American, and Russian counterparts. Despite this initial lag, Azerbaijani science fiction writers have made commendable strides, drawing influence from both global and local literary traditions. This article explores the historical context and thematic concerns of Azerbaijani science fiction literature, analyzing the impact of influential global authors on Azerbaijani writers and examining the stylistic elements present in their works. Additionally, the article delves into the life and career of Emin Mahmudov (1925-2010), a prominent Azerbaijani writer celebrated for his contributions to the genre. Mahmudov’s vivid imagination, intellectual depth, and exploration of cosmic themes have left an indelible mark on Azerbaijani literature. Through an exploration of Mahmudov’s works, such as “Prisoners of Neptune” and “Turbulence,” which delve into existential questions amidst rapid cosmic voyages, this article sheds light on the unique trajectory of science fiction literature in Azerbaijan and its broader significance within the global literary landscape.

Methylisothiazolinone modulates community assembly and improves syntrophic cooperation via adaptive evolution during sludge anaerobic digestion

Various antimicrobials could pose multifaced threats to anaerobic digestion (AD) of waste-activated sludge (WAS), yet it is still unclear how antimicrobials would affect the metabolic activity and assembly process of anaerobic microbiome. In this study, a typical antimicrobial, methylisothiazolinone (MIT), was introduced in AD and induced an initial lag effect on methane production that was eventually recovered. Although MIT disintegrated WAS to promote the release of bioavailable substrates from extracellular polymeric substances (EPS), it also caused adverse stress to the microbiome. The initial microbial metabolic activities and syntrophic relationships associated with methane generation were distinctly inhibited. Because the self-adaptive systems of two-component systems (e.g., ddpF, and ddpD) and quorum sensing (e.g., cheR, and cydB) were activated to restore the syntrophic interaction among functional anaerobes, metabolic activities were gradually recovered for methane generation. Ultimately, the methane-generation species (e.g., Methanobacterium, and Methanomassiliicoccus) were driven as core species by deterministic processes, while non-functional species (e.g., Nitrospirota) were marginalized by stochastic processes under MIT stress. Overall, this finding indicated the intrinsic drive of evolutionary adaptation, unraveled the community assembly process at phylogenetic level under antimicrobial stress, and gave direction on the assessment and mitigation of external contaminant-related ecological risks in WAS treatment.

5-year valve academic research consortium-3 outcomes and predictors of mortality in a 10-year Asian transcatheter aortic valve implantation registry

Abstract Background Transaortic valvular implantation (TAVI) has revolutionised the management of aortic stenosis (AS). Uptake in Asia has caught up in recent years, after an initial lag due to expensive cost, limited subsidies, and scarce accessibility. Hence, longitudinal outcomes of TAVI remain largely unknown in Asian patients. Purpose This study aims to present the 5-year mortality endpoints in an Asian cohort followed up over a decade. Methods 253 patients with symptomatic severe aortic stenosis status post TAVI were retrospectively enrolled at a tertiary academic hospital from 2010-2021. The main outcomes were defined as short-term (30-day), mid-term (1-year) and long-term (5-year) all-cause mortality. Baseline demographics, procedural findings and clinical outcomes were analysed. Kaplan-Meier curves and multiple Cox regression analyses were constructed. Results The mean age was 75.2 + 10.2 years. 120 (47.4%) patients were female and 167 (66%) were Chinese. 168 patients (66.7%) received balloon-expandable valves, 80 patients (31.7%) underwent self-expandable valves, and 4 patients (1.6%) had mechanical-expandable valves. Malignancy was associated with worse short-term mortality at 30-days (HR 3.65, p = 0.054), while pulmonary disease and previous stroke were associated with worse long-term mortality at 5-years (HR 2.27, p = 0.012 and HR 2.02, p = 0.064). Worse all-cause mortality at 30-days, 1-year and 5-years were associated with high NT-Pro BNP levels (HR 1.04, p = 0.046; HR 1.05, p = 0.002 and HR 1.04, p &amp;lt; 0.001), the presence of peripheral arterial disease (PAD) (HR 4.32, p = 0.056; HR 4.48, p = 0.006 and HR 2.43, p = 0.023) and chronic kidney disease (CKD) (HR 6.19, p = 0.006; HR 6.77, p &amp;lt; 0.001 and HR 2.09, p = 0.008). Society of Thoracic Surgery (STS) score (HR 1.11, p = 0.001; HR 1.13, p &amp;lt; 0.001 and HR 1.12, p &amp;lt; 0.001) and Valve Academic Research Consortium (VARC) III endpoints of acute kidney injury (AKI) (HR 6.68, p = 0.047, HR 10.8, p &amp;lt; 0.001 and HR 6.99, p &amp;lt; 0.001), cardiogenic shock (HR 26.3, p &amp;lt; 0.001, HR 12.0, p &amp;lt; 0.001 and HR 4.29, p = 0.011) and structural complications (HR 40.3, p &amp;lt; 0.001, HR 18.1, p &amp;lt; 0.001 and HR 5.18, p = 0.008) were associated with worse all –cause mortality at time-points of 30-days, 1-year and 5-years respectively. On multivariate analyses adjusted for comorbidities and outcomes, STS score and structural complications were independent predictors of 30-day, 1-year, and 5-year all-cause mortality (HR 1.16; p = 0.003, HR 1.09, p = 0.003 and HR 1.10, p &amp;lt; 0.001) and (HR 62.7, p &amp;lt; 0.007; HR 18.9, p &amp;lt; 0.001 and HR 10.6, p = 0.001) respectively. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) use was protective of survival within 1-year (HR 0.37, p = 0.022). Conclusions STS score and VARC III endpoints of structural complications were reliable predictors of all-cause mortality in Asian patients with TAVI. ACE inhibitor and ARB use was protective against mortality at 1-year.Cox regression analysesKaplan-Meier curves

Synergistic impact of tank mixing pendimethalin and pyroxasulfone on soil enzymatic and microbial dynamics.

A field experiment was carried out during the Rabi 2022-23 at Punjab Agricultural University, Ludhiana to evaluate the effect of pyroxasulfone and pendimethalin on soil enzymatic and microbial activities when applied individually or as a tank mix combination. The experiment employed a factorial randomized complete block design in triplicate encompassing 16 treatments. Control soils exhibited a continuous increase in enzymatic and microbial activities over time. In herbicide-treated plots, a highly dose-dependent lag phase was observed in all enzymatic and microbial activities which gets shorter or disappear at higher application rates. Following the initial lag phase, inhibition in enzymatic and microbial activities was observed with higher inhibition in tank mix combination (90.7 to 99.1% up to 90days after herbicide application (DAA) followed by pendimethalin (77.3 to 92.9% up to 90 DAA) and pyroxasulfone (30.3 to 76.2% up to 45 DAA). After initial inhibition, enzymatic and microbial activities increased at harvest. Principal component analysis (PCA) revealed that dehydrogenase activity among soil enzymes and bacteria among microbial populations were more sensitive to studied herbicides. Based on the values of the Integrated Biomarker Response (IBRv2), pendimethalin had a greater impact on soil activities than pyroxasulfone, and their combined application exhibited a synergistic effect.

Catch the Cyber Thief: A Multi-Dimensional Asymmetric Network Attack–Defense Game

This paper presents a novel multi-dimensional asymmetric game model for network attack–defense decision-making, called “Catch the Cyber Thief”. The model is built upon the concept of partially observable stochastic games (POSG) and is designed to systematically incorporate multi-dimensional asymmetry into network attack–defense problems. The attack agent is called a “thief” who wants to control a key host by exploring the unfamiliar network environment, and the defense agent is called a “police” who needs to catch the opponent before its goal is accomplished. The results indicate that the asymmetry of network attack and defense is not only influenced by attack and defense strategies but also by spatio-temporal factors such as the attacker’s initial position, network topology, and defense lag time. In addition, we have found that there may exist the “attack rhythm,” which makes “how to maintain a good attack rhythm” and “how to generate a robust defense strategy against different attackers” worth exploring. Compared with existing attack–defense game models, our game model can better generate a direct mapping relationship with real elements, enabling us to understand network attack and defense interactions better, recognize security risks, and design defense strategies that can directly serve real-world decision-making.

A 3D micro-computed tomography study comparing embryonic skeletal development in layer versus broiler strains of the domestic chicken

Our objective was to analyze the effect of selection for divergent traits in the domestic chicken on embryonic skeletal development, which could affect postnatal bird welfare. Development was compared between the Ross 308 broiler line (fast growth and muscle mass accrual) and Novoponte layers (high laying rate and egg quality). In Study 1 (Initial Conditions), we characterized egg composition prior to incubation and identified the onset of embryonic skeletal mineralization in the 2 strains. In Study 2 (Developmental Dynamics), we used 3D X-ray tomographic imaging (µCT) on incubation days ED11, ED13, ED15 and ED17 to track skeletal maturation trajectories as a pseudo-time series. Results showed that Ross 308 embryos, which are heavier than Novoponte embryos, possess higher levels of yolk nutrients including phosphorus and calcium, but lower eggshell mineral content, than Novoponte embryos. Skeletal mineralization started synchronously in both strains, on ED11. The higher mineral ion content in the larger yolk of Ross 308 eggs compared to Novoponte eggs may partly explain why skeletal mineralization in Ross 308 embryos advances faster: using µCT, we show that the mandible and tibiotarsi in Ross 308 embryos are larger at ED11 and ED13 compared with Novoponte embryos. However, Novoponte embryos catch up from this initial lag in mineralization by ED15. The timing of the Novoponte acceleration coincides with the functional activation of the chorioallantoic membrane in releasing calcium from the inner eggshell. This correlates with a decrease in eggshell thickness from ED11 to ED17 in Novoponte eggs, which was not observed during Ross 308 incubation. To conclude, while some temporal discrepancies exist in early skeletal development between the embryos of Ross 308 and Novoponte strains, overall prenatal skeletal maturation seems to be robustly regulated. Despite selection for antagonist production traits, layer and broiler prehatch skeletal morphology ultimately synchronizes. Practically, since the extent of skeletal maturity equalizes between strains towards the end of incubation, refinements of farming practices, postnatal environment, and diet should be considered for improving domestic fowl welfare.

Operando monitoring of gelation kinetics of polyacrylamide hydrogel using in-fiber dual-MZI

Operando monitoring of gelation kinetics and exploring the gelation law are crucial for optimizing the performance of hydrogels. In this paper, we propose a novel superposition sensing structure based on an integrated dual-Mach–Zehnder interferometer (MZI), which can simultaneously sense temperature and refractive index (RI), with an RI sensitivity of −10,173 nm/RIU and a temperature sensitivity of 8.14 nm/ °C. For the first time, its application for the operando monitoring of gelation kinetics of polyacrylamide hydrogel (PAH) is demonstrated. By establishing the kinetic curves of temperature and RI information in the gelation process, it is confirmed that the gelation process can be divided into three stages: initial lag, rapid gelation, and final saturation. In addition, two gelation laws are verified through experiments: (1) As the concentration of monomers and crosslinkers increases, RI changes, and the amount of heat released gradually increases. (2) As the concentration of catalysts increases, the gelation time decreases significantly. This superposition sensing technique based on dual-MZI can be further applied to monitor other complex dynamic biochemical processes, thereby providing insights into the laws and mechanisms of reaction processes.

Novel long-acting treatment for schizophrenia based on paliperidone dissolving and implantable microarray patches

Schizophrenia is a severe mental disorder that affects millions of people worldwide. Several atypical antipsychotic medications, including paliperidone (PPD), has been developed and proven effective in treating it. To date, four PPD extended-release products have been launched commercially, providing up to six months of therapeutic effect with a single administration. However, the need for hospital injections by professional healthcare workers not only lead to poor patients’ adherence, but also put additional pressure on the healthcare system. Therefore, three PPD microarray patch (PPD MAP) systems based on dissolving microneedle technology and implantable microneedle technology were developed in this work. The two dissolving microarray patch systems contained either PPD crude drug (PPD DMAP-CD) or PPD nanocrystal (PPD DMAP-NC) and the implantable MAP contained PPD crude drug (PPD IMAP). All three types of PPD MAPs showed excellent mechanical and insertion properties as they achieved over 256 µm insertion depth in skin model. In vitro release study showed that PPD released from IMAP in a much more sustained manner (up to 14 days) than PPD did from DMAPs (7 days), with only 20 % initial burst release from IMAP compared with 43–71 % from DMAPs. The MAP dissolution study showed that both DMAPs can be immediately dissolved within less than 3 min once inserted into the skin, indicating a faster action potential compared with IMAP. Ex vivo delivery study showed that 1.68 ± 0.23 mg, 1.39 ± 0.07 mg, and 1.18 ± 0.12 mg were delivered from DMAP-CD, DMAP-NC and IMAP, respectively, demonstrating that over 50 % and up to 70 % of PPD in the MAPs can be delivered into the skin. The IMAP offers most sustained release of PPD whereas DMAP-NC exhibits fastest PPD release (11.19 % vs 20.01 % into Franz cell receiver compartment over 24 h). This work presents a promising alternative for the sustained delivery of antipsychotic drugs, allowing for patient self-administration and extended release concurrently. Patients may potentially use both DMAP and IMAP to achieve a sustained release of PPD while also avoid having an initial therapeutic lag.

The effect of arginine on the growth of probiotics

Objective(s)The study objective was to examine the effect of arginine (Arg) supplementation on the growth of probiotics. MethodsLacticaseibacillus rhamnosus GG, Lactiplantibacillus plantarum, and Lactobacillus acidophilus were identified as potential probiotics. L. rhamnosus GG and L. plantarum were selected for further experimentation. The probiotics were co-treated with 0.9 % NaCl (negative control), 0.5 % Arg, and 1.0 % Arg in a 1:1 ratio for 24 h at 5 % CO2, 37 °C. The probiotics were tested for growth profiles, spectroscopic turbidity assay, metabolic assays (XTT and WST-8), live/dead cell assessment using confocal laser scanning microscopy (CLSM), and colony forming units (CFU). ResultsThe growth profiles of L. rhamnosus GG and L. plantarum were found to be similar, whereas L. acidophilus showed minimal or no transition from the initial lag phase. In the turbidity assay, the end-point absorbance for L. rhamnosus GG with 1.0 % Arg was significantly lower than 0.9 % NaCl and 0.5 % Arg (p < 0.05). For metabolic assays and CFU, increasing concentrations of Arg increased the viable cells for L. rhamnosus GG (p < 0.05), but decreased viability for L. plantarum (p < 0.05). Metabolic assays with dual-species bacterial suspensions indicated that Arg co-treatment inhibited viable proportions compared to control (p < 0.05). The dead cell proportion was significantly lower than live cell proportion for all tested interventions and probiotics (p < 0.05). ConclusionIncreasing concentrations of Arg promote the growth of L. rhamnosus GG, while conversely inhibiting the growth of L. plantarum. Therefore, the effect of prebiotic Arg on probiotics is concentration-dependent, leading to a selective promotion or inhibition of growth. Clinical significanceThe present study results show that Arg supplementation can selectively enhance the growth of L. rhamnosus GG while inhibit the growth of L. plantarum. This underscores the need to consider strain-specific responses in probiotic formulations when developing Arg-based synbiotics for modulating biofilms and creating ecologically homeostatic biofilm microenvironments.

A detailed study on the cooking kinetics of fresh and hard to cook common beans (Phaseolus vulgaris L.): A case study on bean accessions of different market classes

A large-scale study was conducted to obtain a more holistic understanding of the cooking behavior for different bean accessions in terms of cooking kinetics and time to cook. Fresh and aged soaked beans from twenty-four accessions were assessed for texture evolution during cooking at 95 °C using the most informative objective compression texture analysis method. Texture evolution was modelled by the conventional fractional conversion model as well as modified three-parameter models to capture the lag phase. The initial texture varied across bean accessions and is significantly positively related to bean size. Significant but limited differences in initial texture on ageing were observed, the difference being accession dependent. The texture evolution during cooking, cooking kinetics and time to cook varied across bean accessions and storage conditions and all bean accessions developed the hard to cook defect. The softening rate constants for fresh beans were significantly higher (0.026–0.053) and more variable than for aged beans (0.008–0.014, almost similar values). Fresh and aged beans of a given accession softened to similar levels of final relative hardness. The lag phase was more prominent in aged beans (up to ≈25 min) than non-aged beans (0–7 min). Therefore, the difference in time to cook for fresh beans across accessions is mainly determined by the difference in initial hardness and cooking rate constant, while for aged beans these differences depend on initial hardness and lag time and to a lesser extent on the cooking rate constant.

SERS characterization of biochemical changes associated with biodesulfurization of dibenzothiophene using Gordonia sp. HS126-4N

In this study, Gordonia sp. HS126-4N was employed for dibenzothiophene (DBT) biodesulfurization, tracked over 9 days using SERS. During the initial lag phase, no significant spectral changes were observed, but after 48 h, elevated metabolic activity was evident. At 72 h, maximal bacterial population correlated with peak spectrum variance, followed by stable spectral patterns. Despite 2-hydroxybiphenyl (2-HBP) induced enzyme suppression, DBT biodesulfurization persisted. PCA and PLS-DA analysis of the SERS spectra revealed distinctive features linked to both bacteria and DBT, showcasing successful desulfurization and bacterial growth stimulation. PLS-DA achieved a specificity of 95.5 %, sensitivity of 94.3 %, and AUC of 74 %, indicating excellent classification of bacteria exposed to DBT. SERS effectively tracked DBT biodesulfurization and bacterial metabolic changes, offering insights into biodesulfurization mechanisms and bacterial development phases. This study highlights SERS' utility in biodesulfurization research, including its use in promising advancements in the field.

Microbial abundances and carbon use under ambient temperature or experimental warming in a southern boreal peatland

Organic peat soils occupy relatively little of the global land surface area but store vast amounts of soil carbon in northern latitudes where climate is warming at a rapid pace. Warming may result in strong positive feedbacks of carbon loss and global climate change driven by microbial processes if warming alters the balance between primary productivity and decomposition. To elucidate effects of warming on the microbial communities mediating peat carbon dynamics, we explored the abundance of broad microbial groups and their source of carbon (i.e. old carbon versus more recently fixed photosynthate) using microbial lipid analysis (δ13C PLFA) of peat samples under ambient temperatures and before/after initiation of experimental peat warming (+ 2.25, + 4.5, + 6.75, and + 9 °C). This analysis occurred over a profile to 2 m depth in an undrained, ombrotrophic peat bog in northern Minnesota. We found that the total microbial biomass and individual indicator lipid abundances were stratified by depth and strongly correlated to temperature under ambient conditions. However, under experimental warming, statistically significant effects of temperature on the microbial community were sporadic and inconsistent. For example, 3 months after experimental warming the relative abundance of Gram-negative bacterial indicators across depth combined and > 50 cm depth and Gram-positive bacterial indicators at 20–50 cm depth showed significant positive relationships to temperature. At that same timepoint, however, the relative abundance of Actinobacterial indicators across depth showed a significant negative relationship to temperature. After 10 months of experimental warming, the relative abundance of fungal biomarkers was positively related to temperature in all depths combined, and the absolute abundance of anaerobic bacteria declined with increasing temperature in the 20–50 cm depth interval. The lack of observed response in the broader microbial community may suggest that at least initially, microbial community structure with peat depth in these peatlands is driven more by bulk density and soil water content than temperature. Alternatively, the lack of broad microbial community response may simply represent a lag period, with more change to come in the future. The long-term trajectory of microbial response to warming in this ecosystem then could either be direct, after this initial lag time, or indirect through other physical or biogeochemical changes in the peat profile. These initial results provide an important baseline against which to measure long-term microbial community and carbon-cycling responses to warming and elevated CO2.

Resveratrol-Loaded Polydimethylsiloxane-Silica Hybrid Materials: Synthesis, Characterization, and Antitumoral Activity.

In this work, hybrid materials within the polydimethylsiloxane-silica (PDMS-SiO2) system, synthesized via the sol-gel method, were developed and characterized for their potential to incorporate and release the bioactive compound resveratrol (RES). RES was incorporated into the materials with a high loading efficiency (>75%) using the rotary evaporator technique. This incorporation induced the amorphization of RES, resulting in enhanced solubility and in vitro release when compared to the free polyphenolic compound. The release profiles displayed pH dependence, exhibiting notably faster release at pH 5.2 compared to pH 7.4. The gradual release of RES over time demonstrated an initial time lag of approximately 4 h, being well described by the Weibull model. In vitro cytotoxicity studies were conducted on human osteosarcoma cells (MG-63), revealing a concentration-dependent decrease in cell viability for RES-loaded samples (for concentrations >50 µg mL-1).

Preparation of tofacitinib sustained-release tablets using hot melt extrusion technology

This study aimed to develop a tablet that shows a drug release profile similar to the tofacitinib sustained-release tablet (Xeljanz XR®; OROS™) using hot melt extrusion technology. Tofacitinib citrate was selected as the drug. HPMCAS, HPMCP, and Kollidon VA64 were used as thermoplastic polymers to prepare a hot-melt extrudate. The extrudate was obtained from a twin screw extruder and pelletizer. The granules were compressed using a single punch press machine and then coated. TGA, DSC, XRD, FT-IR, and SEM were performed on the hot melt extrudate to understand its physicochemical properties. Dissolution tests were performed using the paddle method (USP Apparatus II). The results showed that the crystallinity state of tofacitinib changed to amorphous after the hot melt extrusion process; however, no chemical change was observed. The drug release profile was similar to that of Xeljanz XR®, which has an initial lag time owing to its OROS™ formulation; a coating process was performed to obtain a similar drug release profile. The lag time was controlled by adjusting the thickness of the coating layer. Moreover, the extrudate size and compression force during tableting did not significantly affect drug release. In conclusion, the new tofacitinib sustained-release tablet prepared using hot melt extrusion showed a drug release behavior similar to that of Xeljanz XR®.

Correlation of salivary cytokine IL-17A and 1,25 dihydroxycholecalciferol in patients undergoing orthodontic treatment.

The management of malocclusion has developed greatly in terms of treatment simulation and biomechanics, but treatment duration has been a great concern to the clinician as well as the patient. 1-25dihydroxycholecalciferol (biologically active form of Vitamin D) stimulates both osteoclasts and osteoblasts and was found to be the most significant in Orthodontic Tooth Movement acceleration. Inflammatory cytokines like IL-17A also play an important role in osteoclastogenesis and can enhance the rate of Orthodontic Tooth Movement.To perform a simultaneous evaluation of pro-inflammatory salivary cytokine IL-17A and salivary 1-25dihydroxycholecalciferol and to correlate their role on orthodontic tooth movement.A prospective cohort study was conducted among n = 97 patients. Saliva samples were collected from the patients at three phases of the orthodontic treatment, centrifuged and stored at 4℃ for evaluation of salivary 1-25dihydroxycholecalciferol levels and Pro-inflammatory cytokine IL-17A using ELISA.The mean salivary 1-25dihydoxycholecalciferol levels were 41.250ng/ml, 33.246ng/ml and 35.043ng/ml during the initial phase, lag phase and post lag phase of orthodontic treatment. The mean pro-inflammatory cytokine IL-17 A levels were 107.79pg/ml, 102.98pg/ml and 66.156pg/ml during the initial phase, lag phase and post lag phase of orthodontic treatment. There was a correlation between the salivary 1-25dihydroxycholecalciferol level and salivary cytokine IL-17A levels during the various phases of orthodontic treatment using Spearman's correlation rho test and linear regression analysis. There was no significant difference (p > 0.05) between 1-25dihydroxycholecalciferol levels and gender during the various phases (initial phase, lag phase and post lag phase) of Orthodontic treatment.There was a negative correlation between salivary 1-25dihydroxycholecalciferol level and salivary cytokine IL-17A levels during the various phases of orthodontic treatment. The level of 1-25dihydroxycholecalciferol and salivary cytokine IL-17A have been quantified during the various phases of Orthodontic treatment and this can be used clinically for the supplementation of Vitamin D in patients with low vitamin D levels and can enhance the treatment duration for the patient with less damaging effects to the surrounding tissues.

UV-detoxification of spent sulfite liquor for polymerization of lignosulfonates and succinic acid fermentation with Actinobacillus succinogenes

Spent Sulfite Liquor (SSL), a byproduct of sulfite pulp production, contains lignosulfonates (LS) dissolved in a liquid phase rich in sugars, and phenolic substances. This study investigates the effects of UV-irradiation on SSL as a microbial substrate. UV-irradiation of SSL resulted in the polymerization of LS. The molecular weight of LS increased from 1949 Da to 5637 Da (at 3 days of irradiation). FTIR spectroscopy revealed structural changes, including an increase in phenolic OH groups and the formation of β-O-4 ether linkages. Batch fermentations with Actinobacillus succinogenes demonstrated that UV-irradiated SSL led to higher succinic acid production and reduced by-product formation. By product formation was reduced from 0.90 g byproduct per g succinic acid to only 0.62 g in irradiated media. Although the initial lag phase was longer for irradiated SSL, acid production eventually exceeded that of non-irradiated SSL and standard medium. Ultimately, a concentration of 14.40 g L-1 with a yield of 0.56 g of succinic acid per gram of consumed sugar was attained. This represented an increase of 3.01 g L-1 compared to standard media. In conclusion, UV-irradiation upgraded SSL by a higher specificity of succinic acid and allowing better utilization of LS in various applications through polymerization, aligning with sustainable production goals.

On methodological errors in estimating the initial velocities of enzyme-catalyzed reactions and on approaches to their correction(a case study with lactate dehydrogenase)

A universal algorithm is proposed to compute the initial velocities of enzyme-catalyzed reactions at “zero time” from the kinetic curve for substrate consumption or product accumulation determined by direct measurements of changes in enzyme activities. The research is illustrated with a commercial lactate dehydrogenase sample and a standard biochemical test kit. The proposed approach makes it possible to virtually eliminate systematic errors in measurements, determine the initial velocity with the same accuracy regardless of the levels of enzyme activities, reduce time spent on analysis to one minute, and expand the scope of application of standard test kits for studying enzymes isolated from different sources when solving a wide range of problems. The algorithm cannot be applied to analyses of coupled enzyme reactions because there is a long initial lag phase in respective kinetic curves.

Pan msr gene deleted strain of Salmonella Typhimurium suffers oxidative stress, depicts macromolecular damage and attenuated virulence

Salmonella encounters but survives host inflammatory response. To defend host-generated oxidants, Salmonella encodes primary antioxidants and protein repair enzymes. Methionine (Met) residues are highly prone to oxidation and convert into methionine sulfoxide (Met-SO) which compromises protein functions and subsequently cellular survival. However, by reducing Met-SO to Met, methionine sulfoxide reductases (Msrs) enhance cellular survival under stress conditions. Salmonella encodes five Msrs which are specific for particular Met-SO (free/protein bound), and ‘R’/‘S’ types. Earlier studies assessed the effect of deletions of one or two msrs on the stress physiology of S. Typhimurium. We generated a pan msr gene deletion (Δ5msr) strain in S. Typhimurium. The Δ5msr mutant strain shows an initial lag in in vitro growth. However, the Δ5msr mutant strain depicts very high sensitivity (p < 0.0001) to hypochlorous acid (HOCl), chloramine T (ChT) and superoxide-generating oxidant paraquat. Further, the Δ5msr mutant strain shows high levels of malondialdehyde (MDA), protein carbonyls, and protein aggregation. On the other side, the Δ5msr mutant strain exhibits lower levels of free amines. Further, the Δ5msr mutant strain is highly susceptible to neutrophils and shows defective fitness in the spleen and liver of mice. The results of the current study suggest that the deletions of all msrs render S. Typhimurium highly prone to oxidative stress and attenuate its virulence.