Dissection of the Genetic Basis of Genotype by Environment Interactions for Morphological Traits and Protein Content in Winter Wheat Panel Grown in Morocco and Spain.

To fulfill the growing demand for wheat consumption, it is important to focus on enhancement breeding strategies targeting key parameters such as yield, thousand kernel weight (TKW), quality characteristics including morphological traits, and protein content. These elements are key to the ongoing and future objectives of wheat breeding programs. Prioritizing these factors will effectively help meet the rising demand for wheat, especially given the challenges posed by unpredictable weather patterns. This study evaluated the morphological traits and protein content of 249 winter wheat varieties and advanced lines grown in eleven different environments in Morocco and Spain incorporating three varied sowing dates. The results showed considerable variability in morphological traits and protein content. Significant correlations were observed among various grain traits, with most grain morphological parameters exhibiting negative correlations with protein content. Differences across environments (p ≤ 0.01) in all traits, genotypes, and genotype by environment interaction were significant. A factorial regression analysis revealed significant impacts of environmental conditions on all grain morphological parameters, protein content, and TKW during the three growth stages. The study identified several high-performing and stable genotypes across diverse environments, providing valuable insights for wheat breeding programs such as genotypes 129, 234, 241, and 243. Genome-Wide Association Studies pinpointed 603 significant markers across 11 environments, spread across chromosomes. Among these, 400 markers were linked with at least two traits or observed in at least two different environments. Moreover, twelve marker-trait associations were detected that surpassed the Bonferroni correction threshold. These findings highlight the importance of targeted breeding efforts to enhance wheat quality and adaptability to different environmental conditions.

Acclimation to warmer temperatures can protect host populations from both further heat stress and the potential invasion of pathogens.

Thermal acclimation can provide an essential buffer against heat stress for host populations, while acting simultaneously on various life-history traits that determine population growth. In turn, the ability of a pathogen to invade a host population is intimately linked to these changes via the supply of new susceptible hosts, as well as the impact of warming on its immediate infection dynamics. Acclimation therefore has consequences for hosts and pathogens that extend beyond simply coping with heat stress-governing both population growth trajectories and, as a result, an inherent propensity for a disease outbreak to occur. The impact of thermal acclimation on heat tolerances, however, is rarely considered simultaneously with metrics of both host and pathogen population growth, and ultimately fitness. Using the host Daphnia magna and its bacterial pathogen, we investigated how thermal acclimation impacts host and pathogen performance at both the individual and population scales. We first tested the effect of maternal and direct thermal acclimation on the life-history traits of infected and uninfected individuals, such as heat tolerance, fecundity, and lifespan, as well as pathogen infection success and spore production. We then predicted the effects of each acclimation treatment on rates of host and pathogen population increase by deriving a host's intrinsic growth rate (rm) and a pathogen's basic reproductive number (R0). We found that direct acclimation to warming enhanced a host's heat tolerance and rate of population growth, despite a decline in life-history traits such as lifetime fecundity and lifespan. In contrast, pathogen performance was consistently worse under warming, with within-host pathogen success, and ultimately the potential for disease spread, severely hampered at higher temperatures. Our results suggest that hosts could benefit more from warming than their pathogens, but only by linking multiple individual traits to population processes can the full impact of higher temperatures on host and pathogen population dynamics be realised.

Situational analysis of hypertension management at primary health care level in São Paulo, Brazil: population, healthcare professional and health system perspectives.

BACKGROUND: Government-led, population-wide initiatives are crucial for advancing the management of hypertension - a leading cause of cardiovascular disease (CVD) morbidity and mortality. An urban population health initiative was conducted against this backdrop, focussing on hypertension in the primary health system in São Paulo, Brazil. Within the frame of the initiative and under the supervision and leadership of the municipal health authorities, a situational analysis was conducted on the needs in hypertension management, marking the first phase of a Design Thinking process. This article describes the situational analysis process and presents the identified elements to be strengthened considering hypertension diagnosis, treatment and control. METHODS: First, a mixed-methods approach was used, starting with a literature review of municipal hypertension data followed by meetings (N = 20) with the local public health administration to assess health system level components. To investigate activities on hypertension diagnosis, treatment and control, nine primary healthcare units were selected from two districts of São Paulo city- Itaquera and Penha- which received an online form addressed to managers, participated in conversation circles of staff and patients, and underwent shadowing of community health agents. RESULTS: Data gave rise to two main outputs: (i) a patient care journey map; and (ii) a matrix summarizing the identified needs at patient, healthcare professional and health system level for diagnosis, treatment and control of hypertension. Patient awareness and knowledge of hypertension was found to be insufficient and its management needs to be improved. For health professionals, disease awareness, technical training, more time dedicated to patients, and simplified guidelines and clinical decision-making tools for hypertension management were identified as principal needs. The situational analysis found that the healthcare systems efficiency might be improved by establishing defined treatment and care delivery goals with a focus on outcomes and implemented through action plans. CONCLUSIONS: This situational analysis identified several needs related to hypertension control in São Paulo that are in line with global challenges to improve the control of CVD risk factors. Findings were also confirmed locally in an expansion phase of this situational analysis to additional primary care facilities. As a consequence, solutions were designed, promptly taken up and implemented by the municipal health secretariat.

Duration of Morning Hyperinsulinemia is Key to the Enhancement of Hepatic Glucose Uptake and Glycogen Storage Later in the Day.

The second meal phenomenon refers to the improvement in glucose tolerance seen following a second identical meal. We previously showed that 4 hours of morning (AM) hyperinsulinemia, but not hyperglycemia, enhanced hepatic glucose uptake (HGU) and glycogen storage during an afternoon (PM) hyperinsulinemic hyperglycemic clamp (HIHG). Our current aim was to determine if the duration or pattern of morning hyperinsulinemia is important for the PM response to a HIHG clamp. To determine this, we administered the same total amount of insulin either over 2h in the first half of the morning (Ins2h-A), over 2h in the 2nd half of the morning (Ins2h-B), or over the entire 4h (Ins4h) of the morning. In the 4h PM period, all three groups had 4x basal insulin, 2x basal glycemia, and portal glucose infusion to simulate a meal. During the PM clamp, there was a marked increase in the mean hepatic glucose uptake and hepatic glycogen synthesis in the Ins4h group compared to the Ins2h-A and Ins2h-B groups, despite matched hepatic glucose and insulin loads. Thus, the longer duration (Ins4h) of mild hyperinsulinemia in the morning seems to be the key to much greater liver glucose uptake during the PM clamp.

Estimating Prevalence and Infection Intensity of Soil-Transmitted Helminths Using Quantitative Polymerase Chain Reaction and Kato-Katz in School-Age Children in Angola.

Quantitative polymerase chain reaction (qPCR) is gaining recognition in soil-transmitted helminth (STH) diagnostics, especially for Strongyloides stercoralis and differentiating hookworm species. However, sample preservation and DNA extraction may influence qPCR performance. We estimated STH prevalence and infection intensity by using qPCR in schoolchildren from Huambo, Uige, and Zaire, Angola, and compared its performance with that of the Kato-Katz technique (here termed Kato-Katz). Stool samples from 3,063 children (219 schools) were preserved in 96% ethanol and analyzed by qPCR, of which 2,974 children (215 schools) had corresponding Kato-Katz results. Cluster-adjusted prevalence and infection intensity estimates were calculated by qPCR and Kato-Katz, with cycle threshold values converted to eggs per gram for qPCR. Cohen's kappa statistic evaluated agreement between qPCR and Kato-Katz. DNA extraction and qPCR were repeated on 191 (of 278) samples that were initially qPCR negative but Kato-Katz positive, of which 112 (58.6%) became positive. Similar prevalence for Ascaris lumbricoides (37.5% versus 34.6%) and Trichuris trichiura (6.5% versus 6.1%) were found by qPCR and Kato-Katz, respectively, while qPCR detected a higher hookworm prevalence (11.9% versus 2.9%). The prevalence of moderate- or high-intensity infections was higher by Kato-Katz than by qPCR. Agreement between qPCR and Kato-Katz was very good for A. lumbricoides, moderate for T. trichiura, and fair for hookworm. Strongyloides stercoralis prevalence was 4.7% (municipality range, 0-14.3%), and no Ancylostoma ceylanicum was detected by qPCR. Despite suboptimal performance, presumably due to fixative choice, qPCR was fundamental in detecting S. stercoralis and excluding zoonotic A. ceylanicum. Further evaluations on sample fixatives and DNA extraction methods are needed to optimize and standardize the performance of qPCR.

The secretome of macrophages has a differential impact on spinal cord injury recovery according to the polarization protocol.

Introduction: The inflammatory response after spinal cord injury (SCI) is an important contributor to secondary damage. Infiltrating macrophages can acquire a spectrum of activation states, however, the microenvironment at the SCI site favors macrophage polarization into a pro-inflammatory phenotype, which is one of the reasons why macrophage transplantation has failed. Methods: In this study, we investigated the therapeutic potential of the macrophage secretome for SCI recovery. We investigated the effect of the secretome in vitro using peripheral and CNS-derived neurons and human neural stem cells. Moreover, we perform a pre-clinical trial using a SCI compression mice model and analyzed the recovery of motor, sensory and autonomic functions. Instead of transplanting the cells, we injected the paracrine factors and extracellular vesicles that they secrete, avoiding the loss of the phenotype of the transplanted cells due to local environmental cues. Results: We demonstrated that different macrophage phenotypes have a distinct effect on neuronal growth and survival, namely, the alternative activation with IL-10 and TGF-ß1 (M(IL-10+TGF-ß1)) promotes significant axonal regeneration. We also observed that systemic injection of soluble factors and extracellular vesicles derived from M(IL-10+TGF-ß1) macrophages promotes significant functional recovery after compressive SCI and leads to higher survival of spinal cord neurons. Additionally, the M(IL-10+TGF-ß1) secretome supported the recovery of bladder function and decreased microglial activation, astrogliosis and fibrotic scar in the spinal cord. Proteomic analysis of the M(IL-10+TGF-ß1)-derived secretome identified clusters of proteins involved in axon extension, dendritic spine maintenance, cell polarity establishment, and regulation of astrocytic activation. Discussion: Overall, our results demonstrated that macrophages-derived soluble factors and extracellular vesicles might be a promising therapy for SCI with possible clinical applications.

Ternary (molybdenum disulfide/graphene)/carbon nanotube nanocomposites assembled via a facile colloidal electrostatic path as electrocatalysts for the oxygen reduction reaction: Composition and nitrogen-doping play a key role in their performance.

Nanocomposites have garnered attention for their potential as catalysts in electrochemical reactions vital for technologies like fuel cells, water splitting, and metal-air batteries. This work focuses on developing three-dimensional (3D) nanocomposites through aqueous phase exfoliation, non-covalent functionalization of building blocks with surfactants and polymers, and electrostatic interactions in solution leading to the nanocomposites assembly and organization. By combining molybdenum disulfide (MoS2) layers with graphene nanoplatelets (GnPs) to form a binary 2D composite (MoS2/GnP), and subsequently incorporating multiwalled carbon nanotubes (MWNTs) to create ternary 3D composites, we explore their potential as catalysts for the oxygen reduction reaction (ORR) critical in fuel cells. Characterization techniques such as X-ray photoelectron spectroscopy, scanning electron microscopy, and X-ray diffraction elucidate material composition and structure. Our electrochemical studies reveal insights into the kinetics of the reactions and structure-activity relationships. Both the (MoS2/GnP)-to-MWNT mass ratio and nitrogen-doping of GnPs (N-GnPs) play a key role on the electrocatalytic ORR performance. Notably, the (MoS2/N-GnP)/MWNT material, with a 3:1 mass ratio, exhibits the most effective ORR activity. All catalysts demonstrate good long-term stability and methanol crossover tolerance. This facile fabrication method and observed trends offer avenues for optimizing composite electrocatalysts further.

Phacoemulsification with implantation of a trifocal intraocular lens in eyes with asteroid hyalosis and synchysis scintillans.

PURPOSE: To compare the visual outcomes in both eyes of patients who undergo phacoemulsification and trifocal intraocular lens (IOL) implantation and have asteroid hyalosis (AH) or synchysis scintillans (SS) in only one eye. METHODS: A retrospective comparative case series was performed. We evaluated uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), predictability, safety, efficacy, and satisfaction after implantation of the same model of trifocal IOL in both eyes (PhysIOL FineVision Pod-F and Micro-F and Rayner RayOne Trifocal). RESULTS: A total of 164 eyes of 82 patients (41 females, 50%) met the inclusion criteria. There were no statistically significant differences in sphere, cylinder, spherical equivalent, UDVA, UIVA, or UNVA between the groups. Postoperative CDVA was slightly better in the control group (logMAR 0.03) than in the AH/SS group (logMAR 0.04) (P: 0.014). There were no statistically significant differences in predictability, safety index, or efficacy index between the groups. Overall subjective satisfaction was good (98.2%). CONCLUSIONS: Visual outcomes and satisfaction are good after implantation of trifocal IOLs in eyes with AH or SS. Therefore, trifocal IOLs should not be ruled out in these patients when no other vitreoretinal disorder is present.

European soybean to benefit people and the environment.

Europe imports large amounts of soybean that are predominantly used for livestock feed, mainly sourced from Brazil, USA and Argentina. In addition, the demand for GM-free soybean for human consumption is project to increase. Soybean has higher protein quality and digestibility than other legumes, along with high concentrations of isoflavones, phytosterols and minerals that enhance the nutritional value as a human food ingredient. Here, we examine the potential to increase soybean production across Europe for livestock feed and direct human consumption, and review possible effects on the environment and human health. Simulations and field data indicate rainfed soybean yields of 3.1 ± 1.2 t ha-1 from southern UK through to southern Europe (compared to a 3.5 t ha-1 average from North America). Drought-prone southern regions and cooler northern regions require breeding to incorporate stress-tolerance traits. Literature synthesized in this work evidenced soybean properties important to human nutrition, health, and traits related to food processing compared to alternative protein sources. While acknowledging the uncertainties inherent in any modelling exercise, our findings suggest that further integrating soybean into European agriculture could reduce GHG emissions by 37-291 Mt CO2e year-1 and fertiliser N use by 0.6-1.2 Mt year-1, concurrently improving human health and nutrition.

Efficient 2D Neck Model for Simulation of the Whiplash Injury Mechanism.

Whiplash injuries, mainly located in the neck, are one of the most common injuries resulting from road collisions. These injuries can be particularly challenging to detect, compromising the ability to monitor patients adequately. This work presents the development and validation of a computationally efficient model, called Efficient Neck Model-2D (ENM-2D), capable of simulating the whiplash injury mechanism. ENM-2D is a planar multibody model consisting of several bodies that model the head and neck with the same mass and inertia properties of a male occupant model in the 50th percentile. The damping and non-linear spring parameters of the kinematic joints were identified through a multiobjective optimization process, solved sequentially. The TNO-Human Body Model (TNO-HBM), a validated occupant model for rear impact, was simulated, and its responses were used as a reference for validation purposes. The root mean square (RMS) of the deviations of angular positions of the bodies were used as objective functions, starting from the bottom vertebra to the top, and ending in the head. The sequence was repeated until it converged, ending the optimization process. The identified ENM-2D model could simulate the whiplash injury mechanism kinematics and accurately determine the injury criteria associated with head and neck injuries. It had a relative deviation of 8.3% for the head injury criteria and was 12.5 times faster than the reference model.

Neutrophil-mediated type IV collagen degradation is elevated in patients with mild endoscopic ulcerative colitis reflecting early mucosal destruction.

Neutrophils play a significant role in sustaining chronic inflammation in Inflammatory Bowel Disease. The intestinal basement membrane acts as a barrier for immunological homeostasis, where the α3 and α4 chains of type IV collagen are expressed on the mucosal surface. We wanted to develop a biomarker reflecting early tissue injury, providing an opportunity for intervention. Two competitive enzyme-linked immunosorbent assays (ELISAs) quantifying human neutrophil elastase (HNE) degraded neo-epitopes of COL4A3 and COL4A4 were developed and investigated in two observational cohorts (n = 161, n = 100). A biomarker of MMP-mediated degradation of COL4A1 (C4M) was used for comparison. In Cohort 1, patients with mild endoscopic ulcerative colitis showed elevated levels of C4A3-HNE compared to those with severe disease. C4M had a strong positive correlation with disease activity. C4A3-HNE/C4M provided superior discrimination between mild and severe endoscopic disease and negatively correlated to disease activity. In Cohort 2, C4A4-HNE and C4A4-HNE/C4M showed similar trends. C4A3-HNE and C4A4-HNE possibly reflect early intestinal tissue injury. Combining the markers with a biomarker of another α-chain of the same collagen provides information on two distinct stages of mucosal damage. These biomarkers may be used to monitor disease flare-up in patients in remission, reducing the need for frequent endoscopic procedures.

Phenotypic adaptation to temperature in the mosquito vector, Aedes aegypti.

Most models exploring the effects of climate change on mosquito-borne disease ignore thermal adaptation. However, if local adaptation leads to changes in mosquito thermal responses, "one size fits all" models could fail to capture current variation between populations and future adaptive responses to changes in temperature. Here, we assess phenotypic adaptation to temperature in Aedes aegypti, the primary vector of dengue, Zika, and chikungunya viruses. First, to explore whether there is any difference in existing thermal response of mosquitoes between populations, we used a thermal knockdown assay to examine five populations of Ae. aegypti collected from climatically diverse locations in Mexico, together with a long-standing laboratory strain. We identified significant phenotypic variation in thermal tolerance between populations. Next, to explore whether such variation can be generated by differences in temperature, we conducted an experimental passage study by establishing six replicate lines from a single field-derived population of Ae. aegypti from Mexico, maintaining half at 27°C and the other half at 31°C. After 10 generations, we found a significant difference in mosquito performance, with the lines maintained under elevated temperatures showing greater thermal tolerance. Moreover, these differences in thermal tolerance translated to shifts in the thermal performance curves for multiple life-history traits, leading to differences in overall fitness. Together, these novel findings provide compelling evidence that Ae. aegypti populations can and do differ in thermal response, suggesting that simplified thermal performance models might be insufficient for predicting the effects of climate on vector-borne disease transmission.

Variation in temperature of peak trait performance constrains adaptation of arthropod populations to climatic warming.

The capacity of arthropod populations to adapt to long-term climatic warming is currently uncertain. Here we combine theory and extensive data to show that the rate of their thermal adaptation to climatic warming will be constrained in two fundamental ways. First, the rate of thermal adaptation of an arthropod population is predicted to be limited by changes in the temperatures at which the performance of four key life-history traits can peak, in a specific order of declining importance: juvenile development, adult fecundity, juvenile mortality and adult mortality. Second, directional thermal adaptation is constrained due to differences in the temperature of the peak performance of these four traits, with these differences expected to persist because of energetic allocation and life-history trade-offs. We compile a new global dataset of 61 diverse arthropod species which provides strong empirical evidence to support these predictions, demonstrating that contemporary populations have indeed evolved under these constraints. Our results provide a basis for using relatively feasible trait measurements to predict the adaptive capacity of diverse arthropod populations to geographic temperature gradients, as well as ongoing and future climatic warming.

New Inoculation Strategy for Legume Based on Rhizobium-Metabolite Co-encapsulation.

The new strategies that are trying to be developed to protect microorganisms for a successful application have generated various types of granulated, powdered, or liquid formulations. In this work, we have developed a rhizobial encapsulation system for legumes accompanied by metabolites to enhance microorganism-plant communication. This novel way of producing a biofertilizer for legumes was developed based on alginate, a degradable compound that allows environmentally friendly use. This way of generating an inoculant allows it designing by making different molecular combinations for different purposes, being a double inoculant, biological and molecular.

Pathways linking nutrient enrichment, habitat structure, and parasitism to host-resource interactions.

Human activities simultaneously alter nutrient levels, habitat structure, and levels of parasitism. These activities likely have individual and joint impacts on food webs. Furthermore, there is particular concern that nutrient additions and changes to habitat structure might exacerbate the size of epidemics and impacts on host density. We used a well-studied zooplankton-fungus host-parasite system and experimental whole water column enclosures to factorially manipulate nutrient levels, habitat structure (specifically: mixing), and presence of parasites. Nutrient addition increased infection prevalence, density of infected hosts, and total host density. We hypothesized that nutrients, mixing, and parasitism were linked in multiple ways, including via their combined effects on phytoplankton (resource) abundance, and we used structural equation modeling to disentangle these pathways. In the absence of the parasite, both nutrients and mixing increased abundance of phytoplankton, whereas host density was negatively related to phytoplankton abundance, suggesting a mixture of bottom-up and top-down control of phytoplankton. In the presence of the parasite, nutrients still increased phytoplankton abundance but mixing no longer did, and there was no longer a significant relationship between host density and phytoplankton. This decoupling of host-resource dynamics may have resulted from reduced grazing due to illness-mediated changes in feeding behavior. Overall, our results show that the impact of one human activity (e.g., altered habitat structure) might depend on other human impacts (e.g., parasite introduction). Fortunately, carefully designed experiments and analyses can help tease apart these multifaceted relationships, allowing us to understand how human activities alter food webs, including interactions between hosts and their parasites and resources.

Macular Neovascularization Type Influence on Anti-VEGF Intravitreal Therapy Outcomes in Age-Related Macular Degeneration.

PURPOSE: To evaluate the influence of macular neovascularization (MNV) lesion type on 12-month clinical outcomes in treatment-naive eyes with neovascular age-related macular degeneration (nAMD) treated with anti-VEGF drugs nationwide. DESIGN: Multicenter national nAMD database observational study. SUBJECTS: One thousand six hundred six treatment-naive nAMD eyes (1330 patients) undergoing anti-VEGF therapy for 12 months nationwide. METHODS: Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution letters, number of injections and visits were was collected using a validated web-based tool. Neovascular lesion phenotype was classified as type 1 (T1, n = 711), type 2 (T2, n = 505), type 3 (T3, n = 315), and aneurysmal type 1 (A-T1, n = 75), according to the new proposed consensus classification. MAIN OUTCOME MEASURES: Mean VA change at 12 months, final VA at 12 months, number of injections, time to lesion inactivation. RESULTS: A total of 1606 treatment-naive nAMD eyes (1330 patients) received a median of 7 injections over 12 months. Mean (± standard deviation) baseline VA was significantly lower for T2 (49.4 ± 23.5 letters) compared with T1 (57.8 ± 20.8) and T3 (58.2 ± 19.4) (both P < 0.05) lesions. Mean VA change at 12 months was significantly greater for A-T1 (+9.5 letters) compared with T3 (+3.1 letters, P < 0.05). Patients with T3 lesions had fewer active visits (24.9%) than those with other lesion types (T1, 30.5%; T2, 32.6%; A-T1, 27.5%; all P < 0.05). Aflibercept was the most used drug in A-T1 lesions (70.1%) and ranibizumab in T1 (40.7%), T2 (57.7%), and T3 (47.6%) lesions. CONCLUSIONS: This study highlights the relevance of MNV type on clinical outcomes in nAMD and reports significant differences in baseline VA, VA change, and lesion activity at 12 months. This report provides data about lesion-specific clinical features, which may guide the management of nAMD cases and potentially support personalized clinical decision making for these patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Natural History and Surgical Outcomes of Lamellar Macular Holes.

PURPOSE: To assess the natural history and surgical outcomes of lamellar macular holes (LMHs). DESIGN: Retrospective and consecutive case series. SUBJECTS: Patients with LMHs from multiple tertiary care centers. METHODS: Clinical charts and OCT scans were reviewed. MAIN OUTCOME MEASURES: The visual acuity (VA) changes and the occurrence rate of full-thickness macular hole (FTMH) were studied in both groups. Within the operated group, factors associated with 6-month VA and development of FTMH were explored. RESULTS: One hundred seventy-eight eyes were included, of which 89 were monitored and 89 underwent surgery. In the observation group, the mean VA decreased from 0.25 ± 0.18 to 0.28 ± 0.18 logarithm of the minimum angle of resolution (logMAR; P = 0.13), with 14 eyes (15.7%) that lost ≥ 0.2 logMAR VA, after 45.7 ± 33.3 months. Nine eyes (10.1%) spontaneously developed an FTMH. In the operated group, the mean VA increased from 0.47 ± 0.23 to 0.35 ± 0.25 logMAR at 6 months (P < 0.001) and 0.36 ± 0.28 logMAR (P = 0.001) after 24.1 ± 30.1 months. By multivariate analysis, better baseline VA (P < 0.001), the presence of an epiretinal membrane (P = 0.03), and the peeling of the internal limiting membrane (ILM; P = 0.02), with a greater effect of ILM perihole sparing, were associated with a greater 6-month VA. Perihole epiretinal proliferation sparing was associated with a better postoperative VA by univariate analysis (P = 0.03), but this was not significant by multivariate analysis. Eight eyes (9.0%) developed a postoperative FTMH. Using Cox proportional hazard ratios [HRs], pseudophakia at baseline (HR, 0.06; 95% confidence interval [CI], 0.00-0.75; P = 0.03) and peeling of the ILM (HR, 0.05; 95% CI, 0.01-0.39; P = 0.004) were protective factors, while ellipsoid zone disruption (HR, 10.5; 95% CI, 1.04-105; P = 0.05) was associated with an increased risk of FTMH. CONCLUSION: Observed eyes with LMH experienced, on average, progressive VA loss. Patients with LMH and altered vision may benefit from surgery. Internal limiting membrane peeling, with perihole ILM sparing, represents a crucial step of the surgery associated with a greater VA and a lower risk of postoperative FTMH. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Cemtirestat dimerization in liposomes and erythrocytes exposed to peroxyl radicals was reverted by thiol-disulfide exchange with GSH.

In the model system of DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) liposomes exposed to peroxyl radicals generated by the azoinitiator AAPH, cemtirestat (CMTI-SH) inhibited lipid peroxidation more efficiently than the natural antioxidant glutathione. In the concentrations 100 to 500 µM, both CMTI-SH and GSH induced distinct lag phases in the initial stages of lipid peroxidation yet GSH produced consistently shorter induction periods (about twice) than equimolar CMTI-SH. Moreover, concentration dependence of lipid peroxidation inhibition measured at the 80th minute, revealed about three times higher IC50 value for GSH compared to CMTI-SH. When the incubations prolonged till 180 min no further absorbance changes at 270 and 302 nm, respectively, occurred. After addition of the reducing agent tris(2-carboxyethyl)phosphine, the absorbance peak at 270 nm shifted back to 302 nm. These findings pointed to the presence of reducible CMTI-SH disulfide whose definite structure was confirmed by proving identity of TLC retention and spectral data with those of the synthesized CMTI disulfide. When CMTI-SH and GSH were present simultaneously in the liposomal incubations, the mixing effect on the induction period was synergistic rather than additive. This was explained by ability of GSH to reduce CMTI disulfide which was proved in separate experiments with an authentic CMTI disulfide prepared synthetically. This finding was also demonstrated by experiment with CMTI-disulfide to protect the erythrocytes against oxidative damage induced by peroxyl radicals. To conclude, CMTI-SH scavenges reactive oxygen species yielding CMTI disulfide while GSH maintains CMTI-SH in the reduced state. This finding was also demonstrated by experiment with CMTI-disulfide to protect the erythrocytes against oxidative damage induced by peroxyl radicals. CMTI-SH would thus represent the first line of the cellular defense against peroxyl radical mediated oxidative stress.

Cemtirestat inhibited lipid peroxidation more efficiently than GSHCemtirestat disulfide was proved as the main oxidation productCemtirestat disulfide protected erythrocytes against oxidative damageCemtirestat disulfide was readily reduced by GSHMechanism of thiol-disulfide exchange reaction was suggested.

Genetic Diversity and Genome-Wide Association Study for the Phenology Response of Winter Wheats of North America, Western Asia, and Europe.

Wheat is a staple food in many areas around the World. In the 20th century, breeders and scientists were able to boost wheat yield considerably. However, a yield plateau has become a concern and is threatening food security. Investments in cutting-edge technologies, including genomics and precision phenology measurements, can provide valuable tools to drive crop improvement. The objectives of this study were to (i) investigate the genetic diversity in a set of winter wheat lines, (ii) characterize their phenological response under different vernalization and photoperiod conditions, and (iii) identify effective markers associated with the phenological traits. A total of 249 adapted genotypes of different geographical origin were genotyped using the 35K Axiom® Wheat Breeder's Array. A total of 11,476 SNPs were used for genetic analysis. The set showed an average polymorphism information content of 0.37 and a genetic diversity of 0.43. A population structure analysis revealed three distinct subpopulations mainly related to their geographical origin (Europe, North America, and Western Asia). The lines of CGIAR origin showed the largest diversity and the lowest genetic distance to all other subpopulations. The phenology of the set was studied under controlled conditions using four combinations of long (19 h light) and short photoperiod (13 h light) and long vernalization (49 days at 5 °C) and no vernalization. With this, phenological traits such as earliness per se (Eps), relative response to vernalization (RRV), and relative response to photoperiod (RRP) were calculated. The phenotypic variation of growing degree days was significant in all phenology combinations. RRV ranged from 0 to 0.56, while RRP was higher with an overall average of 0.25. The GWAS analysis detected 30 marker-trait associations linked to five phenological traits. The highest significant marker was detected on chromosome 2D with a value of -log10(p) = 11.69. Only four loci known to regulate flowering exceeded the Bonferroni correction threshold of -log10(p) > 5.1. These results outline a solid foundation to address global food security and offer tremendous opportunities for advancing crop improvement strategies.

New Insights in Hydrogels for Periodontal Regeneration.

Periodontitis is a destructive inflammatory disease characterized by microbial infection that damages the tissues supporting the tooth (alveolar bone, gingiva, periodontal ligament, and cementum), ultimately resulting in the loss of teeth. The ultimate goal of periodontal therapy is to achieve the regeneration of all of the periodontal tissues. Thus, tissue engineering approaches have been evolving from simple membranes or grafts to more complex constructs. Hydrogels are highly hydrophilic polymeric networks with the ability to simulate the natural microenvironment of cells. In particular, hydrogels offer several advantages when compared to other forms of scaffolds, such as tissue mimicry and sustained drug delivery. Moreover, hydrogels can maintain a moist environment similar to the oral cavity. Hydrogels allow for precise placement and retention of regenerative materials at the defect site, minimizing the potential for off-target effects and ensuring that the treatment is focused on the specific defect site. As a mechanism of action, the sustained release of drugs presented by hydrogels allows for control of the disease by reducing the inflammation and attracting host cells to the defect site. Several therapeutic agents, such as antibiotics, anti-inflammatory and osteogenic drugs, have been loaded into hydrogels, presenting effective benefits in periodontal health and allowing for sustained drug release. This review discusses the causes and consequences of periodontal disease, as well as the advantages and limitations of current treatments applied in clinics. The main components of hydrogels for periodontal regeneration are discussed focusing on their different characteristics, outcomes, and strategies for drug delivery. Novel methods for the fabrication of hydrogels are highlighted, and clinical studies regarding the periodontal applications of hydrogels are reviewed. Finally, limitations in current research are discussed, and potential future directions are proposed.