Gene loci of highly expressed genes provide ideal sites for transgene expression. Casein genes are highly expressed in mammals leading to the synthesis of substantial amounts of casein proteins in milk. We have assessed the α-casein (CSN1S1) gene as a site of transgene expression in transgenic mice and a mammary gland cell line. A transgene encoding an antibody light chain gene (A1L) was inserted into the α-casein gene using sequential homologous and site-specific recombination. Expression of the inserted transgene is directed by the α-casein promoter, is responsive to lactogenic hormone activation, leads to the synthesis of a chimeric α-casein/A1L transgene mRNA and secretion of the recombinant A1L protein into milk. Transgene expression is highly consistent in all transgenic lines, but much lower than that of the α-casein gene (4%). Recombinant A1L protein accounted for 0.5% and 1.6% of total milk protein in heterozygous and homozygous transgenic mice, respectively. The absence of the α-casein protein in homozygous A1L transgenic mice leads to a reduction of total milk protein and delayed growth of the pups nursed by these mice. Overall, the data demonstrate that the insertion of a transgene into a highly expressed endogenous gene is insufficient to guarantee its abundant expression.

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The main challenge faced by many mechanical engineering educators is the implementation of real solutions during their courses. One alternative can be a project-based learning, where the students can be engaged in the development and analysis process currently applied in the industry. This kind of teaching process not only can be used to improve the quality of teaching-learning process but also the students can have opportunities to solve real engineering problem. This paper therefore reports a project-based learning implemented in mechanical engineering courses given in bachelor´s and master’s degree. The component under evaluation has been selected considering the student’s interest, this criterion was also taken to involve several students into a real project process to their learning development. During the semester have been delivered activities to solve the same problem using different approaches based on student´s skills. This procedure can be replicated for students and teachers by following steps. To begin this process, the first step is present the theoretical basis for modal analysis. The second step is to apply theorical knowledge to structure a numerical finite element model. Then, it is used Hypermesh, Optistruct and HyperView software to solve and simulate. The final step was to perform experimental using a three-dimensional scanning vibrometer on 60 samples. It is well noted that the implementation of engineering software commonly used at the industry would increase students’ confidence. This allows students to perform real problem-solving activities to develop outcomes as establish goals, plan task, meet deadlines. Therefore, this paper shows an engineering solution process to provide a learning alternative to teach the modal finite method solutions correlation with experimental solutions.

Background: While intravenous fluid (IVF) therapy in patients with sickle cell disease (SCD) admitted for a vaso-occlusive episodes (VOE) can help reduce red blood cell sickling, clinical practice varies across institutions. We examined the relationship between IVF therapy and hospital length of stay (HLOS), as well as adverse events, such as acute chest syndrome (ACS), pediatric intensive care unit (PICU) transfer and 28-day readmission. Methods: This is a single-center retrospective analysis of SCD VOE hospitalizations between January 2015 and April 2020. Patients with SCD, age 0-30, with consecutive hospitalizations for VOE were included. For the first 3 days of each admission, an “IVF ratio” was calculated by dividing actual IVF rate administered by weight-based maintenance IVF (mIVF) rate. Results: A total of 617 hospitalizations for 161 patients were included. Mean HLOS was 5.7 days, (SD 3.9), and mean IVF volume over the first 3 days of admission was 139.6 ml/kg/day (SD 57.8). Multivariate analysis showed that for each additional 0.5 times the mIVF rate, HLOS increased by 0.53 days (P<0.001; 95% CI: 0.609–0.989), but there was no significant association between IVF therapy and adverse events. History of chronic pain was associated with increased odds of readmission (OR, 6.4; 95% CI: 3.93 – 10.52). Conclusions: Despite the theoretical potential for IVF therapy to slow down the sickling process, our findings suggest that increased IVF therapy was associated with prolonged HLOS, which places a burden on patients, families, and the health system.

Children with transfusion dependent thalassemia have an impaired ability to synthesize alpha or beta globin which results in anemia. Packed red blood cell (PRBC) transfusions are required to increase hemoglobin which supports appropriate growth and development. PRBC transfusions must be completed with 4 hours however infusion rates vary across institutions. Our institution infuses PRBC’s up to 10mL/kg/hr. A descriptive study of 21 children who received a total of 276 transfusions during 2021 demonstrated that this rate is safe and well tolerated. Shorter transfusion times support patients’ and families’ time, resources, and quality of life and aptly utilize institutional resources.

This study provides a new perspective on understanding the intricacies of water-mediated connectivity in ecosystems, bridging landscape ecology and geomorphology through network science. We highlight dryland and river floodplain ecosystems as distinct examples of contrasting water-controlled systems. We (1) discuss central considerations in developing Structural Connectivity (SC) and Functional Connectivity (FC) networks of water-mediated connectivity; (2) quantify the emergent patterns in these networks; and (3) evaluate the capacity of network science tools for investigating connectivity characteristics. Connectivity is quantified using seven parameters at both network and node levels. We find that Link Density, Betweenness Centrality, and Page Rank Centrality are highly sensitive to directionality; Global Efficiency and Degree Centrality are particularly sensitive to weights; while Relative Node Efficiency remains unaffected by weights and directions. Our study underscores the potential to transform how we quantify and understand water-mediated connectivity, especially in consideration of the role(s) of weights and directionality. This interdisciplinary review has implications for both theoretical insights and practical applications in environmental management and conservation efforts.

Background Fetal growth restriction (FGR) is defined differently by the American College of Obstetrics and Gynecology (ACOG), Society for Maternal-Fetal Medicine (SMFM), and the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG). Objective The purpose of this study was to investigate the predictive effect of three different diagnostic criteria of FGR on small-for-gestational-age (SGA) and adverse neonatal outcome (ANO), so as to find a better FGR-definition for Chinese population. Study Design The clinical data of singleton pregnancy who received regular pregnancy care and gave birth at the Department of Obstetrics and Gynecology of Peking University First Hospital from January 1, 2021, to June 30, 2021 were collected. FGR cases were determined according to three different diagnostic criteria by ACOG, SMFM, or ISUOG. The primary outcome was the prediction of SGA and a composite ANO. SGA was defined as neonatal birth weight less than 10 th percentile. An ANO included one of these adverse outcomes: neonatal umbilical arterial blood pH < 7.1, 5-minute Apgar score<7, acute respiratory distress syndrome (ARDS), intraventricular hemorrhage, and neonatal convulsion, and transfer to the neonatal intensive care unit (NICU). The specificity, sensitivity, negative predictive value (NPV) and positive predictive value (PPV) of the different diagnostic criteria for SGA and ANO were compared. The discriminatory capacities of the three FGR-definitions were compared using the area under receiver-operating-characteristics curves (AUC). Results A total of 2340 cases were included in this study, and 115 (4.9%), 63 (2.7%), and 48 (2.1%) cases of FGR were diagnosed using the diagnostic criteria issued by the SMFM, ACOG, and ISUOG respectively. There were 147 (6.28%) cases of SGA neonates. The SMFM criteria had higher sensitivity (40.82% vs 24.49%, 20.41%) for SGA compared to the ACOG and ISUOG criteria. On the contrary, the ISUOG criteria had a higher specificity (99.18% vs 97.49%, 98.77%) than the SMFM and ACOG criteria for predicting SGA. A total of 127 (5.43%) cases were complicated with ANO. All three definitions had low sensitivity for ANO (17.32%, 12.6%, 11.81%) and high specificity of 95.8%, 97.88% and 98.51%. The AUCs of SMFM for predicting SGA (0.692) and ANO (0.566) were slightly higher than those of ACOG (0.616, 0.552) and ISUOG (0.598, 0.552). Conclusion The predictive value of the SMFM and ISUOG definition for SGA and ANO was better than that of the ACOG criteria. In Chinese population, the discriminatory capacities of SMFM FGR definition were superior compared to the other two definitions.

Chromosomal inversions have been identified in many natural populations and can be responsible for novel traits and fast adaptation. In zebra finch, an inversion in the Z chromosome has a pleiotropic effect on multiple traits but especially on sperm. Males heterokaryotypic for the inversion have sperm with a longer midpiece and higher velocity. They have higher fertility and siring success than homokaryotypic males. To understand the effect the Z inversion on these traits, we examined young males at different stages of testis development using two homokaryotypic lines and heterokaryotypes. We sampled both testis and liver tissue to identify gene expression differences. In testis, 520 differentially expressed genes were found and most of them were located on chromosome Z. They were functionally enriched for sperm-related traits. In liver, 420 differentially expressed genes were not enriched for any specific functions but showed also an overrepresentation on chromosome Z. In both tissues, this overrepresentation was located near the distal end of Z but also in the middle of the chromosome. For the heterokaryotype, we observed several genes with expression patterns more similar to one or the other karyotype, based on similarity to homokaryotype invidividuals. This was confirmed with SNPs for three genes, and interestingly one gene, dmgdh, had allele-specific expression originating from only one inversion-allele in the testis, yet both inversion alleles were expressed in the liver. This allele-specific difference in tissue-specific expression demonstrates a pleiotropic effect of the inversion and thus suggests a mechanism for divergent phenotypic effects resulting from an inversion.

There is ongoing debate concerning whether there exists a generalizable effect of land-use change on biodiversity and consequently zoonotic disease risk. Strong data informing this debate is sparse because ecological and sampling complexities make it challenging to establish direct links between vertebrate hosts (and non-hosts), vectors, and pathogens across landscapes. However, emerging molecular methods using invertebrate-derived DNA (iDNA) can now measure species diversity and interactions from vector bloodmeals, which has the potential to improve mechanistic understanding of the effects of land-use change on zoonotic disease risk. Here, we used iDNA metabarcoding of vectors and their bloodmeals to disentangle the complex relationships between Leishmania parasites, known sandfly vectors, and potential wildlife hosts. We collected 56,775 sandflies during 3,159 trap nights at 39 forested sites across the southern Amazon ‘Arc of Deforestation’, which exemplifies global patterns of deforestation and fragmentation at the borders of tropical forest ecosystems due to agricultural expansion. We found that vector community composition was influenced by forest cover and pasture cover, and the most common vector, Nyssomia spp., was encountered less frequently in forests surrounded by pasture. Sandflies fed on a diversity of vertebrates, but the edge-loving nine-banded armadillo, Dasypus novemcinctus, was overwhelmingly the most prevalent host, followed by the greater long-nosed armadillo, Dasypus kappleri. The probability of a host being detected in sandfly bloodmeals was lower at sites with higher forest cover, which was overwhelmingly due to reduced bloodmeals arising from D. novemcinctus. Armadillos were also the most prevalent sylvatic vertebrate taxon in sandfly pools that were positive for Leishmania, further suggesting that these xenarthrans are a key host pathway for zoonotic disease transmission.

Objective: To examine whether women with a history of hysteroscopic adhesiolysis (HA)-treated intrauterine adhesions (IUAs) were at higher risk of adverse obstetrical outcomes in subsequent pregnancies. Design: Retrospective cohort study. Setting: A tertiary-care hospital in Shanghai, China. Population: 114,142 pregnant women who were issued an antenatal card and received routine antenatal care in Shanghai First Maternity and Infant Hospital between January 2016 and October 2021. Methods: From the cohort of 114,142 pregnant women, women with history of HA-treated IUAs before this pregnancy (N=780) were compared with 4 women with no history of IUAs (N=3010) matched on propensity score, maternal age and parity, mode of conception, pre-pregnancy BMI and prior history of abortion. Main outcome measures: Pregnancy complications, placental abnormalities, postpartum hemorrhage and adverse birth outcomes. Results : Compared with women with no history of IUAs, women with a history of HA-treated IUAs were at higher risks of preeclampsia (RR=1.69, 95% CI, 1.23, 2.33), placenta accreta spectrum (RR=4.72, 95% CI, 3.9, 5.73) and previa (RR=4.23, 95% CI, 2.85, 6.30), postpartum hemorrhage (RR=2.86, 95% CI, 1.94, 4.23), preterm premature rupture of membranes (RR=3.02, 95% CI, 1.97, 4.64) and iatrogenic preterm birth (RR=2.86, 95% CI, 2.14, 3.81) . Those women were also more likely to receive cervical cerclage (RR=5.63, 95% CI, 3.95, 8.02) during pregnancy and hemostatic therapies after delivery (RR=2.17, 95% CI, 1.75, 2.69). Moreover, we observed that the RRs of those adverse obstetrical outcomes increased with the increasing number of hysteroscopic surgeries. Conclusion: Our findings suggest that pregnant women with a history of HA-treated IUAs, especially those with a history of repeat HAs, are at higher risk of adverse obstetrical outcomes. Key words: hysteroscopic adhesiolysis, obstetrical outcomes, propensity score matching, cohort study

Geographic isolation and chromosome evolution are two of the major drivers of diversification in eukaryotes in general, and specifically, in plants. On one hand, range shifts induced by Pleistocene glacial oscillations deeply shaped the evolutionary trajectories of species in the Northern Hemisphere. On the other hand, karyotype variability within species or species complexes may have adaptive potential as different karyotypes may represent different recombination rates and linkage groups that may be associated with locally adapted genes or supergenes. Organisms with holocentric chromosomes are ideal to study the link between local adaptation and chromosome evolution, due to their high cytogenetic variability, especially when it seems to be related to environmental variation. Here, we integrate the study of the phylogeography, chromosomal evolution and ecological requirements of a plant species complex distributed in the Western Euro-Mediterranean region (Carex gr. laevigata, Cyperaceae). We aim to clarify the relative influence of these factors on population differentiation and ultimately on speciation. We obtained a well-resolved RADseq phylogeny that sheds light on the phylogeographic patterns of molecular and chromosome number variation, which are compatible with south-to-north postglacial migration. In addition, landscape genomics analyses identified candidate loci for local adaptation, and also strong significant associations between the karyotype and the environment. We conclude that karyotype distribution in C. gr. laevigata has been constrained by both range shift dynamics and local adaptation. Our study demonstrates that chromosome evolution may be responsible, at least partially, for microevolutionary patterns of population differentiation and adaptation in Carex.

Seedling establishment under natural conditions is often limited by numerous interacting factors. We tested the combined effects of drought, herbaceous competition, and ectomycorrhizal fungi (EMF) on the growth and shape of Aleppo pine seedlings and their associated EMF community. EMF inoculum significantly increased seedlings’ height, biomass, and the number of side branches. However, under either competition or drought, the effect of EMF on seedling biomass and height was greatly reduced, while the effect on shoot branching was maintained. All plants were strongly dominated by Geopora, a fungal genus known to inoculate seedlings in dry habitats. Under a combination of drought and competition, EMF had no influence on plant growth and shape. This discrepancy highlights the complexity of the benefits provided to seedlings by EMF under ecologically relevant conditions.

Organic solar cells (OSCs) have already been a popular topic of research for a long time. As a well-known electron transport layer (ETL) material for the inverted device architecture, sol-gel-derived ZnO displays certain defective surfaces that cause excessive charge recombination and lower device performance. While UV-light soaking is a requirement for the ZnO layer to function properly, the same can also be caused by the photodegradation of conjugated organic semiconductors. The photostability of OSCs has always been a hot research topic, as the radiation of UV light may cause changes in the material’s properties, and that, in turn, may cause rapid attenuation of the devices. Herein, ZnO is modified by inserting the commonly used sunscreen ingredient benzophenone-3 (BP-3) between the photoactive layer, consisting of a PM6:Y6 blend, and ZnO to reduce the impact of UV radiation on the photosensitive layer. The addition of BP-3 successfully enhances the photovoltaic parameters, and a remarkable open-circuit voltage (Voc) value of 0.887 V is obtained for PM6:Y6-based inverted solar cells, corresponding to a Voc loss as small as 0.547 V. Finally, the application of this strategy raises the device’s power conversion efficiency from 12.44 to 13.71% and provides improved UV stability.

This paper delves into the intricate relation between the terms social dissonance, necropolitics, and Sophocles’ tragedy, Antigone. By attempting an interdisciplinary analysis and by bringing together elements of contemporary art, political theory, and classical literature, I will explore the complex dynamics between social dissonance, necropolitics, and the quest for human dignity. While examining Antigone’s defiance in the face of oppressive power, we are reminded of the enduring importance of dissent and the indomitable spirit of individuals striving for justice and autonomy in the face of oppressive systems. Drawing parallels between the socio-political context in which Sophocles wrote Antigone and contemporary manifestations of necropolitics, this paper illuminates the enduring relevance of the play. Moreover, it emphasizes the contemporary significance of social dissonance, as proposed by Mattin (2022), in understanding power struggles and forms of resistance. The collision of these concepts and ideas occurs in their shared focus on power dynamics and the resistance against oppressive systems: they explore the ways in which power operates, so as to control and manipulate individuals and communities, creating conditions of discord and subjugation. They emphasize the potential for resistance, challenging dominant narratives and asserting the agency and dignity of marginalized voices. When examining the intersection of necropolitics and social dissonance, one can analyse how the exercise of necropolitical power leads to social dissonance by silencing dissent, suppressing alternative narratives, and perpetuating oppressive structures. The clash between the dominant necropolitical regime and the underlying social dissonance exposes the tension and contradictions within society, laying the foundation for resistance movements and the pursuit of justice and autonomy.

The management objectives of many protected areas must meet the dual mandates of protecting biodiversity while providing recreational opportunities. Balancing these mandates is made difficult by constraints on monitoring trends in the status of biodiversity and impacts of recreation. Using detections from 45 camera traps deployed between July 2019 and September 2021, we assessed the potential impacts of recreation on spatial and temporal habitat use for 8 medium- and large-bodied terrestrial mammals in an isolated alpine protected area: Cathedral Provincial Park, Canada. We hypothesized that some wildlife perceive a level of threat from people, such that they avoid ‘risky times’ or ‘risky places’ associated with human activity. Other species may benefit from associating with people, be it through access to anthropogenic resource subsidies or filtering of competitors/predators that are more human-averse (i.e., human shield hypothesis). Specifically, we predicted that large carnivores would show the greatest segregation from people while mesocarnivores and ungulates would associate spatially with people. We found spatial co-occurrence between ungulates and recreation, consistent with the human shield hypothesis, but did not see the predicted negative relationship between larger carnivores and humans, except for coyotes (Canis latrans). Temporally, all species other than cougars (Puma concolor) had activity patterns significantly different from that of recreationists, suggesting potential displacement in the temporal niche. Wolves (Canis lupus) and mountain goats (Oreamnos americanus) showed shifts in temporal activity away from people on recreation trails relative to off-trail areas, providing further evidence of potential displacement. Our results highlight the importance of monitoring spatial and temporal interactions between recreation activities and wildlife communities, in order to ensure the effectiveness of protected areas in an era of increasing human impacts.

1.- There is a strong decrease in liana diversity along latitudinal and altitudinal gradients at global scale, and there is a marked difference in liana diversity between tropical and temperate ecosystems. From these observations it has been proposed that cold temperatures would restrict the liana ecological patterns, because of the vulnerability of their vascular system to freezing-thaw embolism. 2.- Our aim was to establish the functional mechanism behind the loss of liana diversity along a latitudinal temperature gradient. We evaluate the ecological liana performance as the apical growth rate in ten liana species, and functional traits associated with efficiency (maximum hydraulic conductivity and percentage of lost conductivity) and the safety (vessel diameter, vessel density, wood density and root pressure) of water transport. 4.- We found that in the southern site (colder) of the latitudinal gradient lianas species the have low performance, with a 5-fold decrease in their apical growth rate compared to the northern sites (warmer). These would be consequence of a much lower water transport efficiency (26.1-fold decrease) respect to liana species that inhabit northern (warmer) sites, as an outcome of a higher freezing-thaw embolism (37.5% of PLC) and reduction of vessel diameter (3 times narrower). 5.- These results are unmistakable evidence that cold temperature restricts liana performance, in cold environment liana species exhibit a strong decrease in performance, a low efficiency and higher safety of water transport. On the other hand, in warmer sites, we found that liana species exhibit functional strategies associated with higher performance, higher efficiency and low safety of water transport capacity. This trade-off between efficiency and safety of water transport and their effect over performance would explain the latitudinal pattern of liana diversity

The extensive utilization of plastics in modern human society has resulted in severe environmental pollution caused by microplastics (MP/MPs). The escalating consumption of plastics has led to pervasive presence of microplastics in aquatic environments, which not only carry toxic organic matter, transport toxic chemicals, but also spread through the food chain, seriously threatening marine life and human health. Therefore, various advanced strategies have been developed for separating and degrading MPs from water. Using magnetic materials and their nanostructures for targeting, adsorbing, transporting, and degrading MPs is a promising strategy. However, a comprehensive review of MP remediation using magnetic materials and their nanostructures is currently lacking. The present work aims to fill in the gap by providing a critical review of the recent advances in MP removal/degradation using magnetic materials. The primary focus is to compare and analyze MP’s removal efficiencies of different magnetic materials, including iron/ferrite nanoparticles, magnetic nanocomposites, and micromotors, aiming to unravel the underlying roles of magnetic materials in different types of MP degradation and present the general strategies for designing them to achieve optimal performance. Finally, the review outlines the forthcoming challenges and perspectives in the development of magnetic nanomaterials for MP remediation.

Ecological interactions between parasites and their hosts play a fundamental role in evolutionary processes. Selection pressures are exerted on parasites and their hosts, usually resulting in high levels of specificity. Such is the case of ectoparasitic bat-flies, but how large-scale spatial gradients affect the dynamics of their interactions with their bat hosts is still unknown. In the present study, we investigated interaction patterns between bats and their ectoparasitic flies (Streblidae and Nycteribiidae), both presenting their peak of diversity in the Neotropical region, along a latitudinal gradient. Using network analyses and parasitic indices, grounded on the latitudinal diversity gradient theory, we evaluated how spatial gradients affect species interactions and parasitic indices at the macroscale level, predicting that interaction networks should become richer in species, leading to increases in network modularity, size, and specialization, and to a decrease in nestedness and connectance. We conducted a literature review, focusing on studies done in the Neotropical region, and data of our own authorship. We obtained a richness of 97 species of bats parasitized by 128 species of ectoparasitic flies, distributed into 57 interaction networks between latitudes 29ºS and 19ºN in the Neotropic. Network metrics and parasitic indices varied along the latitudinal gradient, with changes in richness of bats and their ectoparasitic flies and in the structure of their interactions; network specialization, modularity and connectance increase with latitude, while network size decreases with latitude. Regions closer to the equator had higher parasite loads. Our results show that interaction networks metrics present a latitudinal gradient and that such interactions, when observed at a local scale, hide variations that only become perceptible at larger scales. In this way, ectoparasites such as bat flies are not only influenced by the ecology and biology of their hosts, but by other environmental factors acting directly on their distribution and survival.

IntroductionDegenerative aneurysms of deep femoral arteries are extremely rare, accounting for 1-2.6% of all femoral artery aneurysms(1). They are difficult to diagnose in the early stage and found in large size at presentation because they are located deeply and covered by several muscles(2). Deep femoral artery aneurysm (DFAA) can cause complicated conditions such as rapid expansion, rupture, and acute lower limb ischemia due to distal embolism of thrombus. Repair is always recommended for DFAA because of the possibility of those complications(3). We herein report either surgical or endovascular treatment of three cases of DFAA.

Background: Irreversible electroporation technology is an emerging tissue ablation technique that offers advantages over traditional catheter ablation techniques, such as minimal thermal damage and less treatment time. However, as this technique also involves delivering energy through a catheter to target tissue, there is a challenge with regards to the contact between the catheter and the targeted tissue, and there is a lack of related research on this issue. Further study is therefore necessary. Method: This study aims to examine this issue using potato models, with three experimental groups. First, the relationship between the effect of biphasic and monophasic output modes and contact force was studied. Next, the effect of different voltages on the response relationship at biphasic output mode was examined. Finally, impedance analysis was used to test the contact impedance under different contact forces. Results: The irreversible electroporation ablation efficacy increases with the increase of contact force for both monophasic and biphasic output modes, and there is a strong correlation between the ablation efficacy and the contact force. Under a fixed biphasic output mode, the irreversible electroporation ablation efficacy increases with increasing contact force, and there is a strong correlation between the ablation efficacy and the contact force. Conclusion: The results indicate that, under common IRE electrical parameter configuration, the effect of IRE on the tissue has a positive response to the contact force of the electrode in the potato model. This finding has important implications for the design of electrodes used in IRE for the treatment of atrial fibrillation.

Aims: To analyze and compare the adverse events (AEs) and adverse drug reaction (ADRs) associated with pirfenidone and nintedanib, two antifibrotic drugs commonly used in the treatment of idiopathic pulmonary fibrosis (IPF), based on real-world data. Methods: We collected reports from the FD Adverse Event Reporting System (FAERS) and VigiAccess databases. Two main disproportional analysis, including reporting odds ratio (ROR) and proportional reporting ratio (PRR), were conducted to determine the association of these drugs with signals at both the preferred term (PT) and system organ class (SOC) levels. Results: A total of 55,949 reports for pirfenidone and 35,884 reports for nintedanib were obtained from the FAERS database. Correspondingly, the VigiAccess database provided 37,187 reports for pirfenidone and 23,134 reports for nintedanib. Male patients and individuals over the age of 65 were more likely to report AEs for both drugs. Gastrointestinal disorders emerged as the most significant signal at SOC level for both pirfenidone and nintedanib. Additionally, signals such as nausea, diarrhoea and decreased appetite were notable at PT level. Furthermore, we also identified signals, including hemiplegic migraine for pirfenidone and asthenia, constipation, as well as flatulence for nintedanib, which were previously unknown or underestimated risks. Conclusion: This study identified AEs and ADRs of pirfenidone and nintedanib in the treatment of IPF, confirming the most of the corresponding label information is relatively safe. However, some unexpected risk signals should be taken seriously, and further research is needed to manage the safety profiles of these drugs in IPF patients.

Widespread species of Phragmites australis has a high degree of intraspecific variation in functional traits along external climatic and environmental gradients. However, the underlying mechanisms of the environmental gradient at regional scale on intraspecific variation and adaptation strategies of species functional traits are still not well understood. The leaf, stem and root traits of P. australis in lakeshore wetlands of semi-arid and arid regions in the Inner Mongolia Plateau were measured to reveal the variability of functional traits at regional scales and the influencing factors, and to reveal the ecological adaptation strategies of P. australis in different regions through plant economic spectrum. The results showed that variation of functional traits of P. australis had a significant latitudinal pattern. Temperature determined the intraspecific variation of the functional traits of P. australis, and the influence of soil properties was small. Plant economic spectrum theory was also applicable to the functional traits of various organs and whole plants of P. australis, and different ecological adaptation strategies were confirmed across arid and semi-arid regions. This study provides a new understanding of intraspecific variation of functional traits of P. australis originates from temperature-mediated climatic differences brought about by sampling geographic locations, rather than the soil properties of the sampling locations and the joint of climate and soil. The utilization and assimilation of resources of P. australis were conservative in arid regions, while in semi-arid regions it was an acquisition strategy.

In present work, we investigated preview saturated control (PSC) regarding constrained discrete-time delayed systems (CD-TDS). First, using an input-output approach, discrete time-varying delay system was eliminated formally. Discrete-time system with constant time delay was gained. Then, an augmented error system (AES) was constructed through an auxiliary signal related to state variables, which changed the problem of PSC transform into a problem of robust stability for the interconnected subsystem. Afterwards, using linear matrix inequality (LMI) as well as Lyapunov function, sufficient robust stability conditions regarding closed-loop system and design of PSC laws were given. Finally, numerical simulations were performed, and they demonstrated our result validity that presented.

CASE REPORT