Insights into the response mechanisms of Tetradesmus obliquus to aged polylactic acid and tetracycline exposure via transcriptome analysis and physiological evaluations.

Microplastics (MPs) and antibiotics, identified as emerging pollutants, are extensively prevalent in aquatic environments and display prolonged durability. Unlike conventional plastics, biodegradable plastics are more susceptible to decomposition in the environment, resulting in the generation of microplastics and posing potential risks to the aquatic ecosystems. In this study, we assessed growth inhibition, chlorophyll a content, malondialdehyde content (MDA), and antioxidant enzyme activities. These measurements were integrated with transcriptome analysis to explore the response mechanisms of virgin and aged polylactic acid (vPLA and aPLA) and tetracycline (TC) following 14-day exposure to Tetradesmus obliquus, either individually or in combination. The findings indicated that exposure to vPLA did not significantly impact the growth of T. obliquus. Conversely, aPLA demonstrated growth-promoting effects on T. obliquus, particularly in the latter incubation stages. Moreover, a 14-day exposure significantly increased the chlorophyll a content and the activities of superoxide dismutase (SOD), catalase glutathione (CAT) and glutathione S-transferase (GST) within the algal cells. Apart from 1 mg L-1, the TC concentrations of 2.5, 5.0, and 10 mg L-1 exhibited significant toxic effects on T. obliquus, including growth inhibition, decreased chlorophyll a content, elevated activities of SOD, CAT, and GST, and increased MDA levels. Exposure to a combination of 300 mg L-1 aPLA and 5.0 mg L-1 TC, compared to solely 5 mg L-1 TC, demonstrated a notable reduction in TC toxicity to T. obliquus in the presence of aPLA. This was indicated by elevated algal cell density and chlorophyll a content, as well as a decrease in MDA content. Transcriptome analysis indicated an enrichment of differentially expressed genes (DEGs) in pathways linked to porphyrin metabolism, photosynthesis, carbon fixation, and metabolism within the aPLA+TC combined exposure. The study aid in expanding our knowledge of the potential ecological risks posed by biodegradable plastics and accompanying pollutants in aquatic environments.

Olig2-enriched exosomes: A novel therapeutic approach for cuprizone-induced demyelination.

The research aims to study the therapeutic impact of HEK293-XPack-Olig2 cell-derived exosomes on remyelination of the corpus callosum in a cuprizone-induced demyelinating disease model. A lentiviral vector expressing Olig2 was constructed using XPack technology. The highly abundant Olig2 exosomes (ExoOs) were isolated by centrifugation for subsequent experiments. Western blot, nanoparticle tracking analysis (NTA), and electron microscopy showed no significant difference in particle size and morphology between Exos and ExoOs, and a high level of Olig2 expression could be detected in ExoOs, indicating that exosome modification by XPack technology was successful. The Black Gold/Fluromyelin staining analysis showed that the ExoOs group significantly reduced the demyelination area in the corpus callosum compared to the PBS and Exos groups. Additionally, the PDGFRα/APC staining of the demyelinating region revealed an increase in APC+ oligodendrocytes and a decrease in PDGFRα+ oligodendrocyte progenitor cells (OPCs) in the ExoOs group. Furthermore, there was evident myelin regeneration in the demyelinated areas after ExoOs treatment, with better g-ratio and a higher number of intact myelin compared to the other treatment groups. The level of Sox10 expression in the brain tissue of the ExoOs group were higher compared to those of the PBS and Exos groups. The demyelination process can be significantly slowed down by the XPack-modified exosomes, the differentiation of OPCs promoted, and myelin regeneration accelerated under pathological conditions. This process is presumed to be achieved by changing the expression level of intracellular differentiation-related genes after exosomes transport Olig2 enriched into oligodendrocyte progenitors.

Firefly toxin lucibufagins evolved after the origin of bioluminescence.

Fireflies were believed to originally evolve their novel bioluminescence as warning signals to advertise their toxicity to predators, which was later adopted in adult mating. Although the evolution of bioluminescence has been investigated extensively, the warning signal hypothesis of its origin has not been tested. In this study, we test this hypothesis by systematically determining the presence or absence of firefly toxin lucibufagins (LBGs) across firefly species and inferring the time of origin of LBGs. We confirm the presence of LBGs in the subfamily Lampyrinae, but more importantly, we reveal the absence of LBGs in other lineages, including the subfamilies of Luciolinae, Ototretinae, and Psilocladinae, two incertae sedis lineages, and the Rhagophthalmidae family. Ancestral state reconstructions for LBGs based on firefly phylogeny constructed using genomic data suggest that the presence of LBGs in the common ancestor of the Lampyrinae subfamily is highly supported but unsupported in more ancient nodes, including firefly common ancestors. Our results suggest that firefly LBGs probably evolved much later than the evolution of bioluminescence. We thus conclude that firefly bioluminescence did not originally evolve as direct warning signals for toxic LBGs and advise that future studies should focus on other hypotheses. Moreover, LBG toxins are known to directly target and inhibit the α subunit of Na+, K+-ATPase (ATPα). We further examine the effects of amino acid substitutions in firefly ATPα on its interactions with LBGs. We find that ATPα in LBG-containing fireflies is relatively insensitive to LBGs, which suggests that target-site insensitivity contributes to LBG-containing fireflies' ability to deal with their own toxins.

Different microbial functional traits drive bulk and rhizosphere soil phosphorus mobilization in an alpine meadow after nitrogen input.

Enhanced nitrogen (N) input is expected to influence the soil phosphorus (P) cycling through biotic and abiotic factors. Among these factors, soil microorganisms play a vital role in regulating soil P availability. However, the divergent contribution of functional microorganisms to soil P availability in the rhizosphere and bulk soil under N addition remains unclear. We conducted an N addition experiment with four N input rates (0, 5, 10, and 15 g N m-2 year-1) in an alpine meadow over three years. Metagenomics was employed to investigate the functional microbial traits in the rhizosphere and bulk soil. We showed that N addition had positive effects on microbial functional traits related to P-cycling in the bulk and rhizosphere soil. Specifically, high N addition significantly increased the abundance of most microbial genes in the bulk soil but only enhanced the abundance of five genes in the rhizosphere soil. The soil compartment, rather than the N addition treatment, was the dominant factor explaining the changes in the diversity and network of functional microorganisms. Furthermore, the abundance of functional microbial genes had a profound effect on soil available P, particularly in bulk soil P availability driven by the ppa and ppx genes, as well as rhizosphere soil P availability driven by the ugpE gene. Our results highlight that N addition stimulates the microbial potential for soil P mobilization in alpine meadows. Distinct microbial genes play vital roles in soil P availability in bulk and rhizosphere soil respectively. This indicates the necessity for models to further our knowledge of P mobilization processes from the bulk soil to the rhizosphere soil, allowing for more precise predictions of the effects of N enrichment on soil P cycling.

Lrp13a and Lrp13b serve as vitellogenin receptors in the ovary of zebrafish†.

In oviparous animals, egg yolk is largely derived from vitellogenin, which is taken up from the maternal circulation by the growing oocytes via the vitellogenin receptor. Recently, a novel member of the lipoprotein receptor superfamily termed low-density lipoprotein receptor-related protein 13 was identified and proposed as a candidate of vitellogenin receptor in oviparous animals. However, the roles of low-density lipoprotein receptor-related protein 13 in vitellogenesis are still poorly defined. Here, we investigated the expression, vitellogenin-binding properties, and function of low-density lipoprotein receptor-related protein 13 in zebrafish. Two different lrp13 genes termed lrp13a and lrp13b were found in zebrafish. Reverse transcription polymerase chain reaction and quantitative polymerase chain reaction revealed both lrp13s to be predominantly expressed in zebrafish ovary, and in situ hybridization detected both lrp13s transcripts in the ooplasm of early stage oocytes. Two yeast hybrid studies showed that among eight vitellogenins of zebrafish, Vtg1, 2, and 3 bind to Lrp13a, while Vtg1, 2, and 5 bind to Lrp13b. We created zebrafish lrp13a and lrp13b mutant lines using CRISPR/Cas9. Knockout of lrp13a leads to a male-biased sex ratio and decreased diameter of embryo yolk, while knockout of lrp13b and double knockout of lrp13a and lrp13b leads to the delay of vitellogenesis, followed by follicular atresia. These phenotypes of mutants can be explained by the disruption of vitellogenesis in the absence of Lrp13s. Taken together, our results indicate that both Lrp13a and Lrp13b can serve as vitellogenin receptors in zebrafish among other vitellogenin receptors that are not yet described.

Soil properties and fungal community jointly explain N2O emissions following N and P enrichment in an alpine meadow.

Nutrient enrichment, such as nitrogen (N) and phosphorus (P), typically affects nitrous oxide (N2O) emissions in terrestrial ecosystems, predominantly via microbial nitrification and denitrification processes in the soil. However, the specific impact of soil property and microbial community alterations under N and P enrichment on grassland N2O emissions remains unclear. To address this, a field experiment was conducted in an alpine meadow of the northeastern Qinghai-Tibetan Plateau. This study aimed to unravel the mechanisms underlying N and P enrichment effects on N2O emissions by monitoring N2O fluxes, along with analyzing associated microbial communities and soil physicochemical properties. We observed that N enrichment individually or in combination with P enrichment, escalated N2O emissions. P enrichment dampened the stimulatory effect of N enrichment on N2O emissions, indicative of an antagonistic effect. Structural equation modeling (SEM) revealed that N enrichment enhanced N2O emissions through alterations in fungal community composition and key soil physicochemical properties such as pH, ammonium nitrogen (NH4+-N), available phosphorus (AP), microbial biomass carbon (MBC), and microbial biomass nitrogen (MBN)). Notably, our findings demonstrated that N2O emissions were significantly more influenced by fungal activities, particularly genera like Fusarium, rather than bacterial processes in response to N enrichment. Overall, the study highlights that N enrichment intensifies the role of fungal attributes and soil properties in driving N2O emissions. In contrast, P enrichment exhibited a non-significant effect on N2O emissions, which highlights the critical role of the fungal community in N2O emissions responses to nutrient enrichments in alpine grassland ecosystems.

Low-threshold lasing from bound states in the continuum with dielectric metasurfaces.

Bound states in the continuum (BICs) with extremely large quality factors (Q factors) can enhance the light-matter interaction and thus achieve low-threshold lasing. Here, we theoretically propose and experimentally demonstrate the low-threshold lasing at room temperature based on BICs. A threshold of approximately 306.7 W/cm2 (peak intensity) under a 7.5 ns-pulsed optical excitation is presented in an all-dielectric metasurface system consisting of titanium dioxide (TiO2) nanopillars with a dye film. Also, the multimode lasing can be excited by the higher pumping. Our results may find exciting applications in on-chip coherent light sources, filtering, and sensing.

Mechanism of Salt Tolerance and Plant Growth Promotion in Priestia megaterium ZS-3 Revealed by Cellular Metabolism and Whole-Genome Studies.

Approximately one-third of agricultural land worldwide is affected by salinity, which limits the productivity and sustainability of crop ecosystems. Plant-growth-promoting rhizobacteria (PGPR) are a potential solution to this problem, as PGPR increases crop yield through improving soil fertility and stress resistance. Previous studies have shown that Priestia megaterium ZS-3(ZS-3) can effectively help plants tolerate salinity stress. However, how ZS-3 regulates its metabolic adaptations in saline environments remains unclear. In this study, we monitored the metabolic rearrangement of compatibilisers in ZS-3 and combined the findings with genomic data to reveal how ZS-3 survives in stressful environments, induces plant growth, and tolerates stress. The results showed that ZS-3 tolerated salinity levels up to 9%. In addition, glutamate and trehalose help ZS-3 adapt to osmotic stress under low NaCl stress, whereas proline, K+, and extracellular polysaccharides regulate the osmotic responses of ZS-3 exposed to high salt stress. Potting experiments showed that applying the ZS-3 strain in saline and neutral soils could effectively increase the activities of soil acid phosphatase, urease, and invertase in both soils, thus improving soil fertility and promoting plant growth. In addition, strain ZS-3-GFP colonised the rhizosphere and leaves of Cinnamomum camphora well, as confirmed by confocal microscopy and resistance plate count analysis. Genomic studies and in vitro experiments have shown that ZS-3 exhibits a variety of beneficial traits, including plant-promoting, antagonistic, and other related traits (such as resistance to saline and heavy metal stress/tolerance, amino acid synthesis and transport, volatile compound synthesis, micronutrient utilisation, and phytohormone biosynthesis/regulatory potential). The results support that ZS-3 can induce plant tolerance to abiotic stresses. These data provide important clues to further reveal the interactions between plants and microbiomes, as well as the mechanisms by which micro-organisms control plant health.

PD-1 blockade combined with ICE regimen in relapsed/refractory diffuse large B-cell lymphoma.

The prognosis of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is poor. The efficacy of salvage therapy with ICE (ifosfamide, carboplatin, and etoposide) is limited. DLBCL can evade immune surveillance by upregulating programmed cell death ligand 1 (PD-L1). The purpose of this study was to explore the efficacy and safety of programmed cell death 1 (PD-1) blockade combined with ICE regimen (P-ICE) in the treatment of R/R DLBCL patients. In this study, we retrospectively explored efficacy and toxicity in R/R DLBCL patients treated with P-ICE. Prognostic biomarkers, including clinical features and molecular markers related to efficacy, were explored. From February 2019 to May 2020, a total of 67 patients treated with the P-ICE regimen were analyzed. The median follow-up time was 24.7 months (range: 1.4-39.6 months), with an objective response rate (ORR) of 62.7% and a complete response rate (CRR) of 43.3%. The 2-year progression-free survival (PFS) and overall survival (OS) rates were 41.1% (95% CI: 35.0-47.2%) and 65.6% (95% CI: 59.5-71.7%), respectively. Age, Ann Arbor stage, international prognostic index (IPI) score, and response to first-line chemotherapy were correlated with the ORR. Grade 3 and 4 adverse events (AEs) related to the P-ICE regimen were reported in 21.5% of patients. The most common AE was thrombocytopenia (9.0%). No treatment-related deaths occurred. In patients with R/R DLBCL, the P-ICE regimen has promising efficacy and mild toxicity.

Soluble CD4 effectively prevents excessive TLR activation of resident macrophages in the onset of sepsis.

T lymphopenia, occurring in the early phase of sepsis in response to systemic inflammation, is commonly associated with morbidity and mortality of septic infections. We have previously shown that a sufficient number of T cells is required to constrain Toll-like receptors (TLRs) mediated hyperinflammation. However, the underlying mechanisms remains unsolved. Herein, we unveil that CD4+ T cells engage with MHC II of macrophages to downregulate TLR pro-inflammatory signaling. We show further that the direct contact between CD4 molecule of CD4+ T cells or the ectodomain of CD4 (soluble CD4, sCD4), and MHC II of resident macrophages is necessary and sufficient to prevent TLR4 overactivation in LPS and cecal ligation puncture (CLP) sepsis. sCD4 serum concentrations increase after the onset of LPS sepsis, suggesting its compensatory inhibitive effects on hyperinflammation. sCD4 engagement enables the cytoplasmic domain of MHC II to recruit and activate STING and SHP2, which inhibits IRAK1/Erk and TRAF6/NF-κB activation required for TLR4 inflammation. Furthermore, sCD4 subverts pro-inflammatory plasma membrane anchorage of TLR4 by disruption of MHC II-TLR4 raft domains that promotes MHC II endocytosis. Finally, sCD4/MHCII reversal signaling specifically interferes with TLR4 but not TNFR hyperinflammation, and independent of the inhibitive signaling of CD40 ligand of CD4+ cells on macrophages. Therefore, a sufficient amount of soluble CD4 protein can prevent excessive inflammatory activation of macrophages via alternation of MHC II-TLR signaling complex, that might benefit for a new paradigm of preventive treatment of sepsis.

Droplet microarray platforms for high-throughput drug screening.

High-throughput screening platforms are fundamental for the rapid and efficient processing of large amounts of experimental data. Parallelization and miniaturization of experiments are important for improving their cost-effectiveness. The development of miniaturized high-throughput screening platforms is essential in the fields of biotechnology, medicine, and pharmacology. Currently, most laboratories use 96- or 384-well microtiter plates for screening; however, they have disadvantages, such as high reagent and cell consumption, low throughput, and inability to avoid cross-contamination, which need to be further optimized. Droplet microarrays, as novel screening platforms, can effectively avoid these shortcomings. Here, the preparation method of the droplet microarray, method of adding compounds in parallel, and means to read the results are briefly described. Next, the latest research on droplet microarray platforms in biomedicine is presented, including their application in high-throughput culture, cell screening, high-throughput nucleic acid screening, drug development, and individualized medicine. Finally, the challenges and future trends in droplet microarray technology are summarized.

Geometrical Theory of Electromagnetic Nonreciprocity.

Recent advances in electromagnetic nonreciprocity raise the question of how to engineer the nonreciprocal electromagnetic response with geometrical approaches. In this Letter, we examine this problem by introducing generalized electromagnetic continua consisting structured points, which carry extra degrees of freedom over coordinate transformation. We show that general nonreciprocal media have a unique time-varying Riemannian metric structure with local spinning components. It is demonstrated that the nonreciprocity can be alternatively identified as the torsion tensor of a Riemann-Cartan space, which could provide analytic expressions for the magneto-optical effect and the axionic magnetoelectric coupling. Our theory not only gives a deeper insight into the fundamental understanding of electromagnetic nonreciprocity but also provides a practical principle to geometrically design nonreciprocal devices through frame transformation.

Case Report: The effective treatment of patients in advanced no-small cell lung cancer patients with EGFR G719X/S768I/L861Q and acquired MET amplification: A case series and literature review.

Preclinical cases suggest that EGFR tyrosine kinase inhibitors (TKIs) plus MET TKIs are a potential therapy for non-classical EGFR mutant lung cancers with MET amplification acquired resistance. Herein, we report for the first time the effectiveness of novel combination treatment regimens for patients with EGFR G719X/S768I/L861Q. Until the last follow-up assessment, two patients demonstrated improved survival after they switched to afatinib combined with savolitinib (PFS: 10 months) and furmonertinib combined with crizotinib (PFS: 6 months), respectively, that did not observed increased incidence and severity of adverse events. According to the findings of this study and literature review, various responses were observed from the combined therapy in NSCLC patients who harbored uncommon EGFR mutations and MET amplification. Furthermore, Next generation sequencing (NGS) leads to the discovery of uncommon of EGFR and reveals the co-mutations in NSCLC.

Surface modification of cellulose via photo-induced click reaction.

To pursue highly functional ecologically friendly materials, functionalized cellulose has gained increasing number of research interests within the last decades. Compared with other cellulose modification approaches, surface modification of cellulose via photo-induced click reaction is a particular attractive cellulose modification strategy as it integrates the advantages of photochemistry, click reaction and surface modification. High efficiency, quantitative conversion and spatial temporal control are achieved. The physical and chemical properties of various cellulose surfaces are also effectively regulated by using this strategy, which significantly expands their applications. In this mini-review, we summarized the recent progress in cellulose surface modification via photo-induced click reactions. The principles and the merits of photo-induced thiol-X and cycloaddition reactions were compared and highlighted. Photo-induced thiol-ene reaction, thiol-yne reaction, tetrazole-ene cycloaddition, Diels-Alder cycloaddition, and azide-alkyne cycloaddition applied in modification of various cellulose surfaces were introduced in order. At last, the challenges and outlook of photo-induced click reaction in cellulose surface modification were discussed. We hope this review will provide insights into photo-induced click chemistry, cellulose surface modification and novel sustainable materials.

NSCLC patients with rare EGFR Ex19del/G724S mutation showed good response to afatinib combined with chemotherapy treatment: A two-case report.

EGFR G724S mutation in exon 18 has been shown to be resistant to both first- and third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, we found a rare mutation of EGFR Ex19del/G724S in two patients with lung cancer who demonstrated a favorable response to the combination of afatinib and chemotherapy. Identified by next-generation sequencing (NGS), EGFR G724S was found from a primary and a secondary tumor biopsy, respectively. Treated with afatinib combined with chemotherapy, both patients responded well and achieved progression-free survival. Analysis of acquired mutations developed during treatment using afatinib revealed that the emergence of EGFR T790M or ALK fusion was the potential mechanism of afatinib resistance. Our study lends credence to treatment using afatinib combined with chemotherapy as a viable option for patients with Ex19del/G724S.

Model Emulsions Stabilized with Nonionic Surfactants: Structure and Rheology Across Catastrophic Phase Inversion.

The catastrophic phase inversion process of model emulsions (water/Span 80-Tween 80/heptane) from oil-in-water to water-in-oil emulsion was investigated. During this process, the phase inversion of the emulsion was monitored through Fourier transform infrared spectroscopy (FT-IR). In emulsions without NaCl, oil-in-water gel emulsions are formed prior to phase inversion. As the HLB value increases, the oil volume fraction required for phase inversion becomes higher. Polydisperse distribution of the gel emulsion is observed from microscope optical images. The Turbiscan Lab stability analyzer indicates that O/W gel emulsions before the phase inversion has good stability at 50 °C. Rheological measurements reveal that emulsions exhibit non-Newtonian behavior. The viscosity of the gel emulsions increases significantly prior to phase inversion. As the oil volume fraction increases, the storage modulus and loss modulus of the gel emulsion increase to a maximum, at which catastrophic phase inversion occurs. In emulsions with NaCl, there is no oil-in-water gel emulsion formed before phase inversion. The physicochemical properties of the emulsion play a crucial role in whether gel emulsions are produced during catastrophic phase inversion. These gel emulsions have the potential to diversify the applications in crude oil extraction, drug delivery systems, packaging materials, and other fields.

Gut-specific cardenolide-resistant sodium pump primed an omnivore to feed on toxic oleander.

Apocynaceae plants produce toxic cardenolides to defend against their herbivores. Cardenolides could inhibit the α subunit of Na+/K+-ATPase (ATPα), which plays critical roles in biological processes such as muscle contraction, neural function, and osmoregulation. Numerous herbivores that specialized on cardenolides-producing milkweeds carry parallel molecular changes in ATPα that confer resistance. We found that Pacific Ducetia (Ducetia japonica), an omnivorous katydid, could feed on cardenolides-rich oleander leaves. ATPα in D. japonica has undergone parallel molecular changes just like milkweed specialists. These changes evolved at the common ancestors of the leaf katydids before the diversification of Apocynaceae and may prime species in this lineage to feed on cardenolides-rich food. In summary, we reported the first case of cardenolide resistance in katydid, with convergent molecular evolution in ATPα, also an unusual case of cardenolides resistance in nonspecialist species that evolved earlier than the currently known cardenolide-producing plants.

Mie Resonances Enabled Subtractive Structural Colors with Low-Index-Contrast Silicon Metasurfaces.

All-dielectric structural colors are attracting increasing attention due to their great potential for various applications in display devices, imaging security certification, optical data storage, and so on. However, it remains a great challenge to achieve vivid structural colors with low-aspect-ratio silicon nanostructures directly on a silicon substrate, which is highly desirable for future integrated optoelectronic devices. The main obstacle comes from the difficulty in achieving strong Mie resonances by Si nanostructures on low-index-contrast substrates. Here, we demonstrate a generic principle to create vivid bright field structural colors by using silicon nanopillars directly on top of the silicon substrate. Complementary colors across the full visible spectrum are achieved as a result of the enhanced absorption due to Mie resonances. It is shown that the color saturation increases with the increasing of the nanopillar height. Remarkably, blue and black colors are generated by trapezoid nanopillar arrays as a result of the absorption at long wavelengths or all visible wavelengths. Our strategy provides a powerful scheme for accelerating the integrated optoelectronic applications in nanoscale color printing, imaging, and displays.

Effectiveness and tolerability of adjunctive perampanel in the treatment of pediatric patients with uncontrolled epilepsy: A retrospective, single-center, real-world study.

OBJECTIVE: The main aim of this study was to assess the efficacy, safety, and tolerability of adjunctive perampanel (PER) in the treatment of children and adolescents with epilepsy. METHODS: Pediatric patients who visited the pediatric epilepsy clinic of Henan Provincial People's Hospital between May 2020 and December 2021 were recruited. All participants were treated with PER as adjunctive therapy and were seen routinely (minimum: a baseline and 12-week visit). The efficacy and tolerability of adjunctive PER for the treatment of epilepsy were investigated. RESULTS: One hundred and fourteen patients were enrolled, among whom 7 (6.1%) were lost to follow-up. At 12 weeks, the responder rate and the seizure-free rate were 56.1% (60/107) and 32.7% (35/107), respectively. The responder rate increased with the duration of PER administration and was significantly higher when PER was used as an early add-on (after ≤2 prior antiseizure medications (ASMs)) than a late add-on (after >2 prior ASMs). However, there was no significant difference in the treatment efficacy of adjunctive PER in patients with different epilepsy etiologies or types. Adverse events, including irritability, dizziness, somnolence, ataxic gait, weight gain, and tinnitus, were reported in thirty-two patients (29.9%). CONCLUSIONS: In a routine clinical setting of pediatric patients with epilepsy, good effectiveness and tolerability of adjunctive PER were demonstrated. Notably, patients initiating PER as an early add-on showed a better seizure outcome than those initiating PER as a late add-on.

Precipitation increase counteracts warming effects on plant and soil C:N:P stoichiometry in an alpine meadow.

Temperature and precipitation are expected to increase in the forthcoming decades in the northeastern Qinghai-Tibetan Plateau, with uncertain effects of their interaction on plant and soil carbon:nitrogen:phosphorus (C:N:P) stoichiometry in alpine ecosystems. A two-year field experiment was conducted to examine the effects of warming, precipitation increase, and their interaction on soil and plant C:N:P stoichiometry at functional groups and community level in an alpine meadow. Warming increased aboveground biomass of legumes and N:P ratios of grasses and community, but did not affect soil C:N:P stoichiometry. The piecewise structural equation model (SEM) indicated that the positive effect of warming on community N:P ratio was mainly resulted from its positive influence on the aboveground biomass of functional groups. Precipitation increase reduced C:N ratios of soil, grasses, and community, indicating the alleviation in soil N-limitation and the reduction in N use efficiency of plant. SEM also demonstrated the decisive role of grasses C:N:P stoichiometry on the response of community C:N:P stoichiometry to precipitation increase. The interaction of warming and precipitation increase did not alter plant community and soil, N:P and C:P ratios, which was resulting from their antagonistic effects. The stable soil and plant community C:N:P stoichiometry raised important implications that the effect of warming was offset by precipitation increase. Our study highlights the importance of considering the interaction between warming and precipitation increase when predicting the impacts of climate change on biogeochemical cycles in alpine meadow ecosystems.