Wiley最新文献

Disproportionality analyses suggested a cardiovascular risk signal for romosozumab, while statistically significant associations were not found in the real-world database studies. Therefore, a larger comparative study was necessary to examine this signal. This study aimed to compare the cardiovascular risks of romosozumab with those of teriparatide in the overall population and in groups with a history of major adverse cardiovascular events (MACE). A new user cohort study was conducted using Japan's national claims database. Patients aged ≥ 40 years who initiated romosozumab or teriparatide between March 2019 and March 2023 were analyzed. A multivariable Cox proportional hazards model was used to estimate the adjusted hazard ratio (aHR) for MACE. Subgroup analyses were conducted based on MACE history. A total of 251,219 romosozumab and 500,445 teriparatide users were analyzed (most common age group was 80-89 years for both drugs; men: 9.33% for romosozumab and 14.14% for teriparatide). MACE occurred in 1853 romosozumab and 3427 teriparatide users, with incidence rates of 1.09 and 1.22 per 100 person-years, respectively. The aHR (95% confidence interval [CI]) for romosozumab compared with teriparatide was 1.00 (0.94-1.06). In subgroup analyses based on MACE history, the aHRs (95% CI) for no history, for the one-year period leading up to t₀, and for more than 1 year before t₀ were 1.01 (0.95-1.08), 0.93 (0.72-1.21), and 1.00 (0.85-1.18), respectively. In conclusion, no statistically significant difference in MACE risk was observed between romosozumab and teriparatide in Japan's national claims database, regardless of MACE history.

The continuous fragmentation of tropical forests is a major threat to biodiversity and ecosystem functioning. This process creates extensive forest edges, alters microclimates, and promotes shifts in species composition. Functional traits are key to understanding how species respond to these disturbances and to predicting future vegetation dynamics. This study investigates the ecological strategies of species located at the edges and interiors of forest fragments in the Eastern Amazon. We sampled abundant tree species in seven forest fragments distributed across three municipalities in Pará, Brazil. We analysed 16 morphological and anatomical traits related to leaf economics and xylem function. Comparisons were made between edge and interior environments, and traits were correlated with edaphic variables. Species at forest edges had traits associated with hydraulic efficiency, including higher hydraulic conductivity and a greater fiber fraction. In contrast, interior species displayed a range of strategies, from resource-acquisitive to conservative. We found evidence of a decoupling between leaf and wood trait axes, with wood traits varying independently from leaf traits. Soil conditions influenced trait patterns only at fragment edges. Our study enhances understanding of the mechanisms regulating species survival, as evidenced by the different strategies adopted by plants in the interior and at the edges of forest fragments, reflecting contrasting responses to resource availability. These findings also provide support for conservation and forest management strategies and contribute to policy development aimed at mitigating the impacts of fragmentation on Amazonian biodiversity.

Non-structural carbohydrates (NSC), including soluble sugars (SS) and starch (ST), are vital for plant metabolism and stress resilience. However, how the allocation of NSC and their components varies diurnally between C3 trees and shrubs in arid regions, and their respective roles in drought response, has received limited attention. This study examines the diurnal dynamics of NSC in leaves of woody species to elucidate growth-form-specific carbon storage strategies. In August 2023, we measured SS and ST concentrations in leaves of 16 C3 common species (11 trees, 5 shrubs) in Xinjiang, comparing daytime and nighttime levels. We used a two-way ANOVA to assess the effects of life form (tree/shrub) and time (day/night) on NSC, SS, ST, and SS:ST. Trees had significantly higher NSC and SS concentrations than shrubs. Life form and time jointly influenced NSC, ST, and SS:ST ratios, while SS concentration varied only with life form. Starch accumulates during the day and decreases at night, indicating it is a temporary carbon reserve that is converted to sugars for nighttime metabolism. The findings highlight divergent carbon allocation strategies between the studied C3 trees and shrubs, with trees maintaining higher NSC pools. Diurnal starch turnover underscores its importance in balancing carbon supply under arid conditions. These insights advance our understanding of growth-form-specific adaptations in carbon allocation within water-limited ecosystems.

Space is considered one of the harshest environments for living organisms, where ionizing radiation poses a significant threat to biological systems. Although plants exhibit higher resistance to radiation than animals, their photosynthetic machinery remains highly vulnerable. Given the role of plants in Controlled Ecological Life Support Systems (CELSSs), understanding how environment influences plant performance is critical for space missions. This study investigated the combined effects of X-ray irradiation (0.3, 10, or 20 Gy) and light quality (white, red, or red-blue LEDs) on young Vigna radiata L. plants. To assess plant potential acclimation strategies to radiation, we evaluated key functional traits, focusing on growth and photosynthetic performance. Specifically, we quantified in vivo chlorophyll fluorescence, photosynthetic pigments (chlorophylls, carotenoids), and expression of two major photosynthetic proteins: D1 (PSII core) and Rubisco. To our knowledge, no previous studies have explored how specific light wavelengths modulate plant responses to ionizing radiation during early development stages. Our results showed that red light enhances biomass allocation to shoots, promotes pigment accumulation, specifically at 0.3 and 10 Gy, and maintains higher photochemical efficiency and protein expression even at the highest radiation dose, compared to other light wavelengths. Maintaining an appropriate light environment during initial phases of growth enhances photosynthetic performance, reducing the harmful effects of X-rays, thus enabling plants to fulfil their ecological role in CELSSs.

Monosaccharides play a central role in metabolic networks and in the biosynthesis of glycomolecules, which perform essential functions across all domains of life. Thus, identifying and quantifying these building blocks is crucial in both research and industry. Routine methods have been established to facilitate the analysis of common monosaccharides. However, despite the presence of common metabolites, most organisms utilize distinct sets of monosaccharides and derivatives. These molecules therefore display a large diversity, potentially numbering in the hundreds or thousands, with many still unknown. This complexity presents significant challenges in the study of glycomolecules, particularly in microbes, including pathogens and those with the potential to serve as novel model organisms. This review discusses mass spectrometric techniques for the isomer-sensitive analysis of monosaccharides, their derivatives, and activated forms. Although mass spectrometry allows for untargeted analysis and sensitive detection in complex matrices, the presence of stereoisomers and extensive modifications necessitates the integration of advanced chromatographic, electrophoretic, ion mobility, or ion spectroscopic methods. Furthermore, stable-isotope incorporation studies are critical in elucidating biosynthetic routes in novel organisms.

Caves present unique ecological conditions that influence the distribution and adaptation of species, yet studies on cave-associated vegetation remain limited. This study investigated how cave conditions affect the functional traits of Miconia sellowiana Naudin (Melastomataceae), comparing individuals from the cave interior with those from the adjacent understory. Our objective was to understand how these environments influence the species' morpho-functional characteristics and ecological relevance, aiming to identify physiological responses to the constraints of each habitat. Based on this, we hypothesize that caves act as distinct environmental filters compared to the understory, selecting for unique morphological and physiological variations. Leaf morpho-functional traits were evaluated, including macroscopic dimensions (length, width, and leaf area) and microscopic characteristics, such as the anatomy of the central vein, mesophyll, and epidermis. Samples were fixed, processed for histological sections, and analysed by optical and electron microscopy. Statistical analysis included PCA to identify morpho-functional patterns and Student's t-tests/Wilcoxon tests to compare variables between habitats. Cave individuals had thinner leaves, with fewer layers of photosynthetic parenchyma, smaller relative phloem area in the central vein, lower stomatal density, and reduced leaf area and length compared to understory individuals. Low light availability, high humidity, shallow soils, and nutrient scarcity in caves likely limit the development of thicker leaves and affect stomatal density, vascular tissue, and leaf size. These results suggest that cave environments drive morpho-functional and physiological variations in surrounding plants. This study fills gaps in the literature and highlights ecological mechanisms that sustain life in subterranean ecosystems.

A considerable number of oral antitumor therapeutics (OAT) has the potential for causing pseudo-worsening of kidney function (PW) due to inhibition of renal creatinine secretion, i.e., kidney function is unaffected, while creatinine-based calculation of glomerular filtration rate (eGFR) erroneously indicates an impaired kidney function. Nonrecognition of PW can lead to dose reductions, interruptions, or discontinuations of OAT. The extent and incidence of PW has so far not been studied for a broad set of OAT in clinical routine. In this retrospective, multicenter cohort study, 694 AMBORA patients newly started on OAT were assessed for eligibility. eGFR values were compared between baseline and within 30 days of treatment. OAT were separated into the groups unlikely causing and likely causing/with proven PW. The usage of cystatin C measurements as an alternative method for assessing kidney function was evaluated. A total of 238 patients received 38 OAT likely causing PW/with proven PW. In this group, eGFR decreased significantly (-6.8 ml/min, p < 0.001). In 17.2% of these patients, eGFR decreased by ≥20 ml/min. Significant decreases in eGFR were observed for patients receiving, for example, abemaciclib, ribociclib, and osimertinib. Cystatin C measurements were not performed in 95.8% of the patients. In the group of 67 patients receiving OAT unlikely causing PW, there was no significant change in eGFR. In clinical routine, multiple OAT associated with PW are prescribed. A very low rate of usage of creatinine-independent methods for assessing kidney function (cystatin C) indicates that further training of oncologists is required on OAT-induced PW to further improve patient safety.

The bud bank of perennial grasses is a key aspect of their reproduction and longevity in frequently burned ecosystems. We investigated how fire intensity and time since fire affected fire-stimulated flowering and bud activity of wiregrass (Aristida beyrichiana), a foundational bunchgrass in south-eastern US pine savannas. We manipulated fuels and monitored fire temperatures in plants during an experimental fire. We tested effects of plant size and fire intensity on flowering stem production and proportions of active and dead buds. We compared active, dead and total buds from plants in the experimental burn with those in stands burned one and 2 years ago, and described the species' bud morphology and anatomy. The duration above 60 °C had a marginally significant negative effect on the number of flowering stems per plant. This effect was less than the significant positive correlation of flowering stem number with plant size. Fire intensity did not affect the proportions of dead and active buds 5 months after fire. There were significant differences in proportions of active, dead and dormant buds 1 year after fire, and the total number of buds decreased with time since fire. Plants had an average of one bud per tiller, and mean bud depth was 3 cm. Perennial bud banks are a substantial source of regenerative biomass for plants in fire-prone savannas. For fire-stimulated flowering species, frequent fires are likely important for maintaining large bud banks that supply both vegetative and flowering structures. A focus on belowground structures should shed light on long-term ecosystem dynamics in fire-prone ecosystems.

Verekitug, a novel, high-affinity, fully human monoclonal antibody targeting thymic stromal lymphopoietin receptor (TSLPR), is in development as a potential treatment for severe asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and chronic obstructive pulmonary disease (COPD). This phase 1b, double-blind, randomized, placebo-controlled, multiple ascending-dose trial assessed the safety, tolerability, immunogenicity, pharmacokinetics, and pharmacodynamics of verekitug administered subcutaneously in patients with mild-moderate asthma. Thirty-two participants were randomized in 4 placebo-controlled dosing cohorts (3 × 100-mg or 200-mg doses, once every 4 weeks; 2 × 300-mg doses, once every 12 weeks; single 25-mg dose) and observed for 32 weeks. The primary endpoint was safety; secondary endpoints were pharmacokinetics and immunogenicity. Exploratory endpoints included TSLPR occupancy and biomarker effects. Treatment-emergent adverse events were mild or moderate. Complete TSLPR occupancy was observed at the first timepoint (2 weeks post dose) and maintained for 24 weeks (doses ≥100 mg). Rapid mean reductions in fractional exhaled nitric oxide, eosinophils, and interleukin-5 (up to -54%, -65%, and -64%, respectively) were sustained up to 24 weeks (doses ≥100 mg). The mean verekitug half-life was ~20 days. Low-titer antidrug antibody response was observed in some participants, without clinically meaningful impact on pharmacokinetics, pharmacodynamics, or safety. Verekitug was generally well tolerated, with rapid, substantial, and sustained effects on asthma biomarkers. These findings support further development of verekitug for treating severe asthma, CRSwNP, and COPD.