Search Results (18,674)

Increases in global temperatures, due to the climate change, are generating stress in most plant species. We hypothesize that young plants of Opuntia spp. adjust their Crassulacean acid metabolism (CAM) to the increase in nighttime temperature, allowing them to continue growing. The study was carried out in a greenhouse and laboratory of the Colegio de Postgraduados, Montecillo, Mexico. Three-month-old greenhouse-grown plants remained in a control environment with an average day/night temperature of 19.1/12.3 °C or were maintained in a chamber with increased nighttime temperatures averaging 19.1/18.9 °C day/night for 70 days. The experimental design was completely randomized with two treatments (control and high nighttime temperatures). After 70 days of high nighttime temperatures (HNT), at dawn (end of CAM phase I), plants had a 45% decrease in glucose (2.9 to 1.5 mg/100 mg dry tissue; dt) concentration and doubled and tripled fructose (0.43 to 0.95 mg/100 mg dt) and sucrose (0.47 to 0.09 mg/100 mg dt) concentrations. Glucose consumption may be related to the plant’s metabolic energy expenditure to overcome stress. The significant increase in fructose and sucrose is explainable by their function as signaling molecules among others. In contrast, photosynthetic efficiency, i.e., increased compared to the control, but the difference of acidity (end of phase I less phase III), the concentration of starch (1 mg/100 mg dt), free amino acids and soluble protein (1.2 mg/100 mg dt), wet and dry matter, stem height (60 cm) and width of the stem at dawn were not significantly affected. The adjustments in C and N metabolism and the non-significant effect on growth promoted by 70 HNT days may be related to adjustments in enzyme activities without changes in protein concentration. Young Opuntia spp. plants adjust their metabolism in response to increased nighttime temperatures, allowing them to maintain growth similar to that of the control. The results confirm the great potential of using the Opuntia genus in agriculture and genetic improvement in the face of the challenges posed by climatic change. Full article

This work aims to enhance the stability of the Mg/Al₃Y interface through first-principles investigations of low-cost dopants. Density functional theory calculations were employed to systematically examine the bulk properties of Mg and Al₃Y, as well as the structural stability, electronic characteristics, and alloying element effects at the Mg(0001)/Al₃Y(0001) interface. The calculated lattice parameters, elastic moduli, and phonon spectra demonstrate that both Mg and Al₃Y are dynamically stable. Owing to the similar hexagonal symmetry and a small lattice mismatch (~1.27%), a low-strain semi-coherent Mg(0001)/(2 × 2)Al₃Y(0001) interface can be constructed. Three representative interfacial stacking configurations (OT, MT, and HCP) were examined, among which the MT configuration exhibits significantly higher work of adhesion, indicating superior interfacial stability. Differential charge density and density of states analyses reveal pronounced charge transfer from Mg to Al/Y atoms and strong orbital hybridization, particularly involving Y-d states, which underpins the enhanced interfacial bonding. Furthermore, the segregation behavior and adhesion enhancement effects of typical alloying elements (Si, Ca, Ti, Mn, Cu, Zn, Zr, and Sn) were systematically evaluated. The results show that Mg-side interfacial sites, especially Mg₂ and Mg₃, are thermodynamically favored for segregation, with Zr and Ti exhibiting the strongest segregation tendency and the most significant improvement in interfacial adhesion. These findings provide fundamental insights into interfacial strengthening mechanisms and offer guidance for the alloy design of high-performance Mg-based composites. Full article

Forest restoration programs are increasingly adopted to mitigate climate change-driven ecosystem degradation, yet the plant functional strategies underpinning successful tree establishment are not fully understood. We investigated the effect of vapour pressure deficit and soil conditions on the interplay between leaf gas exchange and carbon metabolism in three-year-old saplings of different species characterised by distinct functional strategies, as well as non-structural carbohydrate (NSC) partitioning at plant desiccation. We performed two complementary experiments to evaluate interspecific functional differences between Fraxinus ornus L., Quercus cerris L., and Quercus pubescens Willd. in a Mediterranean restored woodland and to compare them with fully irrigated nursery conspecifics. Stomatal sensitivity to closure was similar between species, whereas higher leaf gas exchange and reduced leaf shedding increased twig sugars, as in the case of F. ornus, likely contributing to its better establishment. Irrigation augmented gas exchange rates in potted saplings under moderate evaporative demand but overall did not increase NSCs compared with outplanted conspecifics, possibly because of different carbon demand. Desiccated saplings maintained substantial NSCs, but their reduced pools, especially starch, suggested that they were consumed as a response to drought. Overall, findings indicate that NSC allocation can help define proxies of plant performance in restoration programs. Full article

Oral mucosa healing is a complex process that involves the innate wound healing system, including the coagulation cascade, extracellular matrix remodeling, immune cell responses, and fibroblast and epithelial responses, within the context of a dynamic resident microbiome. Unlike cutaneous wounds, oral wounds heal rapidly with minimal scarring despite constant exposure to diverse microbial communities, saliva, and mechanical stress. Emerging evidence highlights the critical interplay between microbiome-mediated signaling and macrophage plasticity in shaping wound outcomes, suggesting that similar mechanisms operate within the oral cavity. Inflammation is an essential component of wound repair, and its resolution is necessary to promote tissue remodeling and functional regeneration. Macrophages play a central role in this transition through phenotype switching from a pro-inflammatory (M1) to a pro-resolving, anti-inflammatory (M2) state. This review synthesizes current understanding of the oral microbiome’s influence on macrophage polarization across distinct stages of oral wound healing and examines microbial-based strategies that modulate the immune response to enhance repair. Significant knowledge gaps remain, including limited clinical translation, inter-individual variability in microbiome composition, and complete mechanistic insight into host–microbe immune interaction. Addressing these challenges enables the development of precision microbiome-based therapeutics that restore microbial balance, direct macrophage-driven regeneration, and improve outcomes in oral wounds and chronic inflammatory conditions. Full article

The pivotal clinical trials, CARTITUDE-1 and KarMMa-3, showed promising response rates in relapsed and refractory multiple myeloma (RRMM) with use of BCMA-directed CAR T-cell therapy; however, a major challenge is determining suitability in patients who do not meet trial inclusion criteria due to suboptimal organ function. In this multicenter retrospective study, we evaluated the safety and efficacy of BCMA CAR-T therapy in patients with RRMM and renal impairment (RI), defined as creatinine clearance (CrCL) of less than 45 mL/min. We evaluated 223 patients treated with idecabtagene vicleucel (ide-cel) or ciltacabtagene autoleucel (cilta-cel) between May 2021 and April 2024. Outcomes were compared between baseline RI (11.2%) and normal renal function (nRF) cohorts. Response rates were similar at 1 month (p = 0.09), 3 months (p > 0.9), and 6 months (p = 0.8). Progression-free survival (PFS) was 21.9 months in the RI group compared to 15 months in the nRF group (p = 0.32), while overall survival (OS) was 27.9 months for patients with RI versus not reached for patients with nRF (p = 0.87). Patients with RI had higher rates of immune effector cell-associated neurotoxicity syndrome (ICANS) (60% vs. 19%, p = 0.04) and infections (44% vs. 20%, p = 0.008). We found that BCMA CAR-T demonstrated comparable efficacy in RRMM patients with baseline RI, although these patients exhibited increased rates of neurotoxicity and infections. Full article

In the present work, three-dimensional (3D) simulations have been performed for the characterization of a rectangular column for a uniform gas distributor with µm-sized holes at a ratio of 5. The model is first validated with experimental data from the literature. Simulations are then performed for a gas distributor with identical pitch but two different hole sizes, namely 600 µm and 200 µm. Three superficial gas velocities, namely 0.002 m/s, 0.004 m/s, and 0.006 m/s, were used for each distributor type. The gas movement in the fluid is found to be a strong function of hole size. For a 600 µm hole size, the operating condition has minimal impact on gas plume movement and moves centrally in a fully aerated regime. However, for a hole size of 200 µm, for all superficial velocities, the gas plume movement is dynamic and partially aerated. The plume moves along the right wall initially and then follows vertically. These characteristics are different from the meandering plume in centrally located spargers. The liquid mixing in the bulk is a function of time. During the plume development flow, different shapes are observed. Based on the analogy with the shapes found in nature, these shapes have been termed as balloon, cap, jet or candle flame, bull horn, mushroom, tree shape, and disintegrated mushroom shapes. Quantitative insights have been obtained in the form of time-averaged radial profiles of both volume fractions and liquid axial velocities. A symmetric parabolic shape for a hole size of 600 µm and skewed asymmetric shapes for a 200 µm hole size for three different axial positions, namely 0.1, 0.25, and 0.4 m, are observed. Correlations for gas holdup and liquid velocity have been proposed for low superficial velocities, which are in good agreement with the CFD simulation data, with a deviation of 15–20%. The deviations are partly due to the use of the k-ε turbulent model. The correlations perform better than the correlations available in the reported literature for similar superficial gas velocities. Full article

Background and Objectives: Interstitial lung diseases (ILDs) have been increasingly linked to neurological manifestations, including cognitive dysfunction and motor impairments, yet the prevalence and severity of these associations remain underexplored. We aimed to (1) compare the frequency of neurological symptoms between patients with and without ILD; (2) evaluate differences in cognitive and motor function scores; (3) perform subgroup analyses based on MoCA (Montreal Cognitive Assessment) scores; and (4) identify potential risk factors for neurological involvement. Methods: In this cross-sectional study, we enrolled 77 patients (40 with ILD and 37 without ILD). We recorded demographic data, smoking status, and body mass index (BMI). Neurological symptoms (tremor, diminished reflexes, paresthesia, etc.) were documented. Cognitive assessments included the MoCA and Symbol Digit Modalities Test (SDMT). Motor function was evaluated via the Berg Balance Scale (BBS), Timed Up and Go (TUG), Single-Leg Stance (SLS), and Grooved Pegboard Test (GPT). Results: Neurological symptoms were more prevalent in ILD (42.5%) than in non-ILD patients (16.2%; p = 0.003). Tremor appeared in 35% of ILD vs. 11% of non-ILD (p = 0.007). ILD patients showed lower mean SLS scores (7.2 ± 3.1 vs. 9.1 ± 3.8 s, p = 0.03) but similar TUG times (10.3 ± 2.1 vs. 9.6 ± 2.3 s, p = 0.20). MoCA scores < 26 were more common in those with ILDs (45% vs. 19%; p = 0.01). Among ILD participants, those with MoCA < 26 had significantly higher rates of tremor (51% vs. 24%, p = 0.04). Logistic regression revealed ILD diagnosis (OR = 3.12, 95% CI: 1.27–7.65, p = 0.013), older age (OR = 1.09 per year, p = 0.02), and smoking history (OR = 2.01, p = 0.05) as independent risk factors for neurological involvement. Conclusions: Our findings suggest that ILD is associated with a higher burden of neurological symptoms and subtle impairments in cognition and motor performance. Recognizing and addressing these manifestations may improve patient management, underscoring the importance of an integrative, multidisciplinary approach. Full article

Background and Objectives: Renin-angiotensin system inhibitors (RASIs) are recommended to preserve residual kidney function (RKF) in patients on peritoneal dialysis (PD); however, evidence of benefit is inconsistent. This study evaluated the effect of RASI on RKF decline among patients undergoing PD. Materials and Methods: We conducted a retrospective cohort study among PD patients at a large metropolitan dialysis centre in Australia. RKF was assessed using residual Kt/V and urine volume from PD adequacy tests. Time zero was PD initiation. RASI exposure was modelled as a time-dependent variable to avoid immortal-time bias. Linear mixed-effects models were fitted for each outcome, including random intercepts and slopes for time (years since PD start) with unstructured covariance. Fixed effects included time, RASI(t), time × RASI(t), age, sex, baseline RKF, PD modality, PD infection episodes, loop diuretic use, and comorbidities. Results: Of 307 PD patients, 231 met the inclusion criteria; 111 (48.1%) received RASI. RASI users were younger than non-users [65 years (IQR 56–74) vs. 72 years (IQR 61–77); p = 0.014]. Residual Kt/V declined by 0.26 units/year; RASI exposure showed no significant effect on urine volume trajectory and a borderline slower Kt/V decline (interaction β = +0.038, p = 0.069). Hospitalisation and PD-related infection rates were similar between groups. Conclusions: RASI therapy was not associated with meaningful RKF preservation in PD patients in this cohort. While earlier studies suggested renoprotective effects of RASI while on PD, our findings align with recent evidence of mixed efficacy. Larger prospective trials are needed to clarify the role of RASI in maintaining RKF and improving long-term outcomes in PD. Full article

Artificial intelligence (AI)-based structure prediction tools have emerged as powerful methods for understanding previously unsolved structures. AI-predicted models are widely used for protein function identification, drug development, and protein engineering. Although AI-predicted structures offer significant opportunities to advance research, their inaccuracies can lead to misinterpretations of molecular mechanisms. Thus, evaluating the structural differences between AI-predicted and experimental structures is crucial for accurately understanding molecular mechanisms and guiding the design of subsequent experiments. In this study, the previously unreported crystal structure of xylanase from Hypocrea virens (HviGH11) was compared with the structures predicted by ESMFold, AlphaFold2, AlphaFold3, and RoseTTAFold. The overall fold of HviGH11 was highly similar between the experimental and AI-predicted models; however, the conformation of the thumb domain of the protein varied across the models. The substrate-binding cleft of experimental HviGH11 was similar to that in the model structures generated by ESMFold, AlphaFold2, and AlphaFold3, but significantly different from those in the model structures generated by RoseTTAFold. The substrate docking study illustrated that the binding mode of xylohexaose in the substrate-binding cleft differed between the experimental and AI-predicted HviGH11 structures. These findings provide insights into the applications of AI-predicted models and offer guidance for appropriate application in structural and functional studies and biotechnology. Full article

Live coral cover is a key indicator of coral reef composition, health, and functioning. Airborne imaging spectroscopy provides verifiably accurate estimates of live coral cover to seawater depths of 25 m, yet satellite-based approaches have not achieved the same level of performance. The new Tanager-1 satellite carries a high-fidelity imaging spectrometer in sun-synchronous Earth orbit, providing an opportunity to transition from airborne to spaceborne imaging of live corals and other benthic constituents. We coordinated overpasses of Tanager-1 and Global Airborne Observatory (GAO) imaging spectrometer measurements of coral reef to a depth of 25 m in Hawaiʻi. Tanager-1 has a spatial resolution of 30 m, while the GAO data were collected at 2 m resolution, requiring detailed modeling to simulate 30 m data for subsequent comparison to the satellite data. At 30 m resolution, the two sensors generated similar geographic patterns of live coral, macroalgal, and sand cover. Field validation indicated similar precision and accuracy of live coral cover estimates, and the ratio of live coral to macroalgal cover proved similar between sensors. Overall results indicate that live coral cover can be mapped with high-fidelity imaging spectroscopy from Earth orbit. With the advent of more spaceborne imaging spectrometers, a new era of live coral monitoring will be possible, filling a critical gap for repeated assessments of reef compositional change at a global level. Full article

Background/Objectives: Nusinersen is a synthetic antisense RNA oligonucleotide employed in the management of spinal muscular atrophy, a rare neuromuscular disorder, by modulating the alternative splicing of the survival motor neuron 2 (SMN2) gene. GNR-100 represents the first generic version of the reference listed drug (RLD), containing nusinersen sodium as the active pharmaceutical ingredient. We performed comprehensive evaluations in accordance with FDA guidelines, including side-by-side comparative analyses of critical quality attributes, to thoroughly characterize the structural and functional properties of both nusinersen products. Results/Methods: GNR-100 was comprehensively demonstrated to be highly similar to RLD in terms of oligonucleotide structure, physicochemical properties, impurity profile, and in vitro cell-based assays for SMN-gene splice-switching and SMN-protein activity. Structural analyses confirmed that the oligonucleotide primary sequences and chemical structures were identical. The diastereomeric composition and higher-order structures were also similar between the proposed generic and the reference product. Comparable resistance to phosphodiesterase degradation and nearly identical melting temperatures of the oligonucleotide duplexes with their complementary strand further substantiated the structural sameness of the nusinersen products. The impurity profile of the proposed therapeutic oligonucleotide was consistent with that of RLD, and the collectively reduced levels of impurities, as assessed by orthogonal analytical methods, indicated no meaningful impact on the safety profile. Moreover, both products exhibited comparable biological activity in enhancing the production of full-length SMN2 mRNA transcripts and functional SMN protein in fibroblasts derived from SMA patients. Conclusions: These quality studies demonstrate that GNR-100 exhibits no significant differences from the licensed drug across structural, physicochemical, biophysical, and biological attributes, establishing its potential as a cost-effective therapeutic alternative for patients with spinal muscular atrophy. Full article

As a dominant typology of urban development and a critical component of public infrastructure, super high-rise buildings have transitioned from a speed-driven expansion model to one that emphasizes a balanced approach between development pace and quality. Within the context of urban stock renewal, numerous super high-rise buildings now face pressing needs for retrofitting to enhance their sustainability and urban integration. This study establishes “urbanity”—defined as the capacity of the built environment to foster vibrant, inclusive, and sustainable urban life—as a core evaluation criterion for assessing the retrofitting and renewal of super high-rise buildings. Based on a comprehensive literature review and field investigations, 21 representative indicators were identified, and the key factors influencing the upgrading of such buildings were determined. Subsequently, 20 super high-rise buildings in Shanghai were selected as case studies, and their urbanity performance was assessed using a fuzzy comprehensive evaluation model (FCEM). The findings reveal common challenges, including architectural homogenization, functional singularity, limited vitality in near-ground spaces, weak integration with surrounding infrastructure, and inefficient utilization of urban landscape resources. Furthermore, the study analyzes urbanity-oriented enhancement strategies implemented in the selected cases and proposes targeted improvement measures across five key dimensions: building morphology, functional configuration, near-ground space, infrastructure, and urban landscape. The research contributes to the body of knowledge on sustainable urban regeneration by providing a practical evaluation framework and actionable strategies for retrofitting super high-rise buildings. The findings aim to support more livable, inclusive, and resilient urban environments, with implications for both Chinese and global cities facing similar challenges in high-density urban contexts. Full article

An adaptive and efficient particle swarm optimization (PSO)-based learning algorithm to determine neuron centers in the hidden layer of a radial basis neural network (RBNN) is developed in the present work for regression problems. The proposed PSO–RBNN algorithm searches the entire input domain space to discover optimal neuron centers by solving an optimization problem and aims to overcome the limitation of center selection from the training data. The network is built in a sequential manner using optimal neuron centers until some specified criterion is met, and therefore, it exploits the concept of neuron significance during the learning process. The Gaussian function with a constant spread (also known as width) is chosen as the radial basis function for each neuron. To illustrate the effectiveness of the PSO–RBNN algorithm over the orthogonal least squares (OLS) method (a popular learning algorithm under a similar category, which selects the neuron center from training data), numerical simulations for different types of nonlinear problems of varying dimensions and complexities are conducted. Finally, a comparison with multiple existing algorithms for network design is made using available data. The results show that the RBNN architecture developed with the proposed learning algorithm exhibits superior convergence, displays good generalization ability, and requires a smaller number of neurons, resulting in an efficient and compact network architecture. Full article

Neuroimmune interactions play a critical role in the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), with microglia acting as key mediators of neuroinflammation. Microglia exhibit dual roles, contributing to both neuroprotection and neurotoxicity depending on their activation state. In AD, amyloid-beta (Aβ) aggregation leads to chronic microglial activation, resulting in excessive pro-inflammatory cytokine release (e.g., TNF-α, IL-1β, IL-6), oxidative stress, and synaptic dysfunction. In PD, α-synuclein aggregation triggers a similar neuroinflammatory cascade, exacerbating dopaminergic neuronal loss in the substantia nigra. Beyond inflammatory responses, microglia regulate synaptic plasticity, phagocytose pathological proteins, and interact with peripheral immune cells, influencing disease progression. Emerging evidence suggests that genetic variants in genes such as TREM2, CD33, and HLA modulate microglial function, thereby altering susceptibility to neurodegeneration. Dysregulated microglial responses, characterized by impaired clearance of protein aggregates and prolonged neuroinflammation, further amplify neuronal damage. Therapeutic strategies targeting microglial activation are under investigation, aiming to balance neuroinflammatory responses and enhance clearance mechanisms. Small-molecule inhibitors, monoclonal antibodies, and modulators of innate immune pathways are being explored to mitigate microglia-driven pathology. Understanding the complex interplay between microglia and neurodegeneration could pave the way for precision medicine approaches, optimizing treatments based on individual immune profiles. Further research is essential to delineate microglial heterogeneity across disease stages and uncover novel targets for therapeutic intervention. Full article

Background: Several studies have attempted to identify the initiating drivers of small intestinal neuroendocrine tumor (SI-NET) development and the molecular mechanisms underlying their progression and metastatic spread. Previous gene expression studies have used bulk microarrays or RNA sequencing to compare tumor tissue with normal intestinal mucosa. However, the intestine comprises multiple distinct cell types, and bulk analyses are limited by this cellular heterogeneity, which can confound tumor-specific signals. Methods: We performed single-cell RNA sequencing on primary SI-NETs and paired normal mucosa from two patients to directly compare tumor cells with their cells of origin, the enterochromaffin (EC) cells. To minimize type I errors, we applied a two-step validation strategy by overlapping differentially expressed genes with an external single-cell dataset and cross-referencing candidate genes for enteroendocrine expression in the Human Protein Atlas. Results: For further distinction and characterization, ECs were subdivided into serotonergic and non-serotonergic clusters. This analysis revealed that the SI-NET cells are transcriptionally more similar to serotonergic ECs, consistent with serum metabolite profiles derived from clinical parameters. Our analyses uncovered a loss-of-expression program characterized by regulators of epithelial differentiation and in parallel, a gain-of-expression program displayed neuronal signaling gene induction, implicating functional reprogramming toward neuronal-like properties. Together, these specific losses and gains suggest that our patient-derived SI-NETs undergo adaptation through both loss of enteroendocrine functions and acquisition of neurobiological-promoting signaling pathways. Conclusions: These findings nominate candidate drivers for further functional validation and highlight potential therapeutic strategies in our patient cohort, including restoring suppressed Notch signaling and targeting aberrant neuronal signaling networks. However, even with a two-step validation procedure, the modest cohort size limits statistical power and generalizability, particularly for the proposed association to a serotonergic phenotype. Larger, multi-patient single-cell studies are required to confirm these mechanisms and establish their clinical relevance. Full article