The association between gout flares and monosodium urate burden assessed using musculoskeletal ultrasound in patients with gout.

Background: Ultrasound (US) has a high sensitivity in detecting monosodium urate (MSU) deposition in gout patients. However, the value of US in predicting gout flares has been reported only in a few monocentric studies. Objective: To investigate the association between gout flares in the previous year and US-detected MSU burden using two different US scores. Design: A retrospective study. Methods: Patients with gout were consecutively recruited to undergo musculoskeletal US examinations of their knees, ankles, and feet. The score derived from Outcome Measure in Rheumatology (hereinafter referred to as MSU score) and musculoskeletal US features-based (hereinafter referred to as MSKF score) were used to quantify the MSU burden of gout. Odds ratios for frequent gout flares were calculated. Results: We enrolled 1894 patients with gout (mean age: 45 years; gout duration: 5 years; males: 96.1%), experiencing a median of three flares over the past year. Of these, 428 (22.6%) patients reported frequent (⩾7) gout flares. The MSU and MSKF median scores were 6 and 9, respectively. For each five-point increase in MSU and MSKF score, the odds ratio of frequent gout flares increased 1.13-fold and 1.24-fold, respectively. The area under the curve (AUC) for the MSU and MSKF score was 0.635 [95% confidence interval (CI): 0.604-0.665] and 0.688 (95% CI: 0.659-0.718), respectively, (AUC difference 0.054, p value for AUC difference < 0.001). Conclusion: The MSU and MSKF scores were significantly associated with the number of gout flares in the previous year. The MSKF score outperformed the MSU score in terms of frequent gout flare discrimination.

Orphan Nuclear Receptor NR4A3 Promotes Vascular Calcification via Histone Lactylation.

BACKGROUND: Medial arterial calcification is a chronic systemic vascular disorder distinct from atherosclerosis and is commonly observed in patients with chronic kidney disease, diabetes, and aging individuals. We previously showed that NR4A3 (nuclear receptor subfamily 4 group A member 3), an orphan nuclear receptor, is a key regulator in apo (apolipoprotein) A-IV-induced atherosclerosis progression; however, its role in vascular calcification is poorly understood. METHODS: We generated NR4A3-/- mice and 2 different types of medial arterial calcification models to investigate the biological roles of NR4A3 in vascular calcification. RNA-seq was performed to determine the transcriptional profile of NR4A3-/- vascular smooth muscle cells under ß-glycerophosphate treatment. We integrated CUT&Tag analysis and RNA-seq data to further investigate the gene regulatory mechanisms of NR4A3 in arterial calcification and target genes regulated by histone lactylation. RESULTS: NR4A3 expression was upregulated in calcified aortic tissues from chronic kidney disease mice, 1,25(OH)2VitD3 overload-induced mice, and human calcified aorta. NR4A3 deficiency preserved the vascular smooth muscle cell contractile phenotype, inhibited osteoblast differentiation-related gene expression, and reduced calcium deposition in the vasculature. Further, NR4A3 deficiency lowered the glycolytic rate and lactate production during the calcification process and decreased histone lactylation. Mechanistic studies further showed that NR4A3 enhanced glycolysis activity by directly binding to the promoter regions of the 2 glycolysis genes ALDOA and PFKL and driving their transcriptional initiation. Furthermore, histone lactylation promoted medial calcification both in vivo and in vitro. NR4A3 deficiency inhibited the transcription activation and expression of Phospho1 (phosphatase orphan 1). Consistently, pharmacological inhibition of Phospho1-attenuated calcium deposition in NR4A3-overexpressed vascular smooth muscle cells, whereas overexpression of Phospho1 reversed the anticalcific effect of NR4A3 deficiency in vascular smooth muscle cells. CONCLUSIONS: Taken together, our findings reveal that NR4A3-mediated histone lactylation is a novel metabolome-epigenome signaling cascade mechanism that participates in the pathogenesis of medial arterial calcification.

Nanomodulators targeting endothelial WNT and pericytes to reversibly open the blood-tumor barrier for boosted brain tumor therapy.

The blood-brain barrier (BBB)/blood-tumor barrier (BTB) impedes brain entry of most brain-targeted drugs, whether they are water-soluble or hydrophobic. Endothelial WNT signaling and neoplastic pericytes maintain BTB low permeability by regulating tight junctions. Here, we proposed nitazoxanide (NTZ) and ibrutinib (IBR) co-loaded ICAM-1-targeting nanoparticles (NI@I-NPs) to disrupt the BTB in a time-dependent, reversible, and size-selective manner by targeting specific ICAM-1, inactivating WNT signaling and depleting pericytes in tumor-associated blood vessels in breast cancer brain metastases. At the optimal NTZ/IBR mass ratio (1:2), BTB opening reached the optimum effect at 48-72 h without any sign of intracranial edema and cognitive impairment. The combination of NI@I-NPs and chemotherapeutic drugs (doxorubicin and etoposide) extended the median survival of mice with breast cancer brain metastases. Targeting BTB endothelial WNT signaling and tumor pericytes via NI@I-NPs could open the BTB to improve chemotherapeutic efficiency against brain metastases.

Pleistocene glaciation advances the cryptic speciation of Stellera chamaejasme L. in a major biodiversity hotspot.

The mountains of Southwest China comprise a significant large mountain range and biodiversity hotspot imperiled by global climate change. The high species diversity in this mountain system has long been attributed to a complex set of factors, and recent large-scale macroevolutionary investigations have placed a broad timeline on plant diversification that stretches from 10 million years ago (Mya) to the present. Despite our increasing understanding of the temporal mode of speciation, finer-scale population-level investigations are lacking to better refine these temporal trends and illuminate the abiotic and biotic influences of cryptic speciation. This is largely due to the dearth of organismal sampling among closely related species and populations, spanning the incredible size and topological heterogeneity of this region. Our study dives into these evolutionary dynamics of speciation using genomic and eco-morphological data of Stellera chamaejasme L. We identified four previously unrecognized cryptic species having indistinct morphological traits and large metapopulation of evolving lineages, suggesting a more recent diversification (~2.67-0.90 Mya), largely influenced by Pleistocene glaciation and biotic factors. These factors likely influenced allopatric speciation and advocated cyclical warming-cooling episodes along elevational gradients during the Pleistocene. The study refines the evolutionary timeline to be much younger than previously implicated and raises the concern that projected future warming may influence the alpine species diversity, necessitating increased conservation efforts.

Arming Amorphous NiMoO4 on Nickel Phosphide Enables Highly Stable Alkaline Seawater Oxidation.

Seawater electrolysis holds tremendous promise for the generation of green hydrogen (H2 ). However, the system of seawater-to-H2 faces significant hurdles, primarily due to the corrosive effects of chlorine compounds, which can cause severe anodic deterioration. Here, a nickel phosphide nanosheet array with amorphous NiMoO4 layer on Ni foam (Ni2 P@NiMoO4 /NF) is reported as a highly efficient and stable electrocatalyst for oxygen evolution reaction (OER) in alkaline seawater. Such Ni2 P@NiMoO4 /NF requires overpotentials of just 343 and 370 mV to achieve industrial-level current densities of 500 and 1000 mA cm-2 , respectively, surpassing that of Ni2 P/NF (470 and 555 mV). Furthermore, it maintains consistent electrolysis for over 500 h, a significant improvement compared to that of Ni2 P/NF (120 h) and Ni(OH)2 /NF (65 h). Electrochemical in situ Raman spectroscopy, stability testing, and chloride extraction analysis reveal that is situ formed MoO4 2- /PO4 3- from Ni2 P@NiMoO4 during the OER test to the electrode surface, thus effectively repelling Cl- and hindering the formation of harmful ClO- .

Efficacy and safety of orlistat in male patients with overweight/obesity and hyperuricemia: results of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Obesity is associated with elevated serum uric acid (SUA) levels and frequent gout flares. Losing weight can reduce the SUA level and gout flares. The effect of orlistat on SUA levels and gout flares in patients with overweight/obesity and hyperuricemia (HUA) has not been extensively studied. This study investigated the effects of orlistat on SUA levels and gout flares compared to placebo in overweight and obese patients with HUA. METHODS: A total of 72 Chinese patients with overweight/obesity and HUA were randomly divided into a placebo group (35, 48.6%) and an orlistat group (37, 51.4%); the trial lasted 12 weeks. The primary endpoints were the relative changes in body weight, the SUA level, and gout flares in the per-protocol population. RESULTS: Orlistat reduced the proportion of patients with gout flares (log-rank P = 0.023, hazard ratio = 0.31, 95% confidence interval 0.11-0.85). There was no significant difference in SUA level between the two groups. The average weight loss of the orlistat group was 2.85 kg, and the average weight loss of the placebo group was 0.76 kg. The weight loss in the orlistat group was significantly greater than that in the control group (P < 0.05). CONCLUSIONS: This study is the first to demonstrate that orlistat has no significant effect on SUA levels in patients with overweight/obesity and HUA. The utility of orlistat as an adjunct therapy to prevent gout flares during weight loss in patients with HUA was emphasized. TRIAL REGISTRATION: Clinicaltrials.gov NCT05496075.

Multifunctional Polyoxometalates-Based Ionohydrogels toward Flexible Electronics.

Multifunctional flexible electronics present tremendous opportunities in the rapidly evolving digital age. One potential avenue to realize this goal is the integration of polyoxometalates (POMs) and ionic liquid-based gels (ILGs), but the challenge of macrophase separation due to poor compatibility, especially caused by repulsion between like-charged units, poses a significant hurdle. Herein, the possibilities of producing diverse and homogenous POMs-containing ionohydrogels by nanoconfining POMs and ionic liquids (ILs) within an elastomer-like polyzwitterionic hydrogel using a simple one-step random copolymerization method, are expanded vastly. The incorporation of polyzwitterions provides a nanoconfined microenvironment and effectively modulates excessive electrostatic interactions in POMs/ILs/H2 O blending system, facilitating a phase transition from macrophase separation to a submillimeter scale worm-like microphase-separation system. Moreover, combining POMs-reinforced ionohydrogels with a developed integrated self-powered sensing system utilizing strain sensors and Zn-ion hybrid supercapacitors has enabled efficient energy storage and detection of external strain changes with high precision. This work not only provides guidelines for manipulating morphology within phase-separation gelation systems, but also paves the way for developing versatile POMs-based ionohydrogels for state-of-the-art smart flexible electronics.

Correlation Between Impaired Sensitivity to Thyroid Hormones and Serum Uric Acid in Female Patients with Obesity and After Laparoscopic Sleeve Gastrectomy.

OBJECTIVE: An alterable risk factor for hyperuricemia is obesity. Additionally, obese persons may have a moderate form of acquired resistance to thyroid hormones. Thyrotropin (TSH), thyroid hormones, and obesity all interact subtly. However, the connection between thyroid hormone sensitivity and hyperuricaemia in obese patients both before and after laparoscopic sleeve gastrectomy (LSG) has not yet been clarified. The objective of our study was to investigate the connection between impaired thyroid hormone sensitivity and elevated uric acid (UA) levels before and after LSG. METHODS: In total, 1,054 euthyroid patients with obesity (481 males, 573 females), 248 (143 females) of whom underwent subsequent LSG, were enrolled in this retrospective study. Anthropometric measurements and thyroid hormone and UA levels were taken before and 3 months after LSG. RESULTS: Female patients with obesity with impaired sensitivity to thyroid hormones had higher UA levels (P for trend < 0.01). The odds ratio of the fourth versus first quartile of TFQI, TSHI, and TT4RI were 4.285 [confidence interval (CI): 1.360-13.507], 3.700 [CI: 1.276-10.729], and 2.839 [CI: 1.014-7.948], respectively, with robust relationships with female hyperuricemia (all P < 0.05). However, there was only a positive correlation between the decline in UA levels and TFQI, TSHI, and TT4RI in females following LSG. CONCLUSION: Female hyperuricemia is correlated with higher thyroid hormone resistance index scores. Resistance to thyroid hormones was greatly improved by LSG. The decrease in UA levels after surgery is correlated with the improvement of thyroid hormone resistance after LSG.

Oral exposure of polystyrene microplastics and doxycycline affects mice neurological function via gut microbiota disruption: The orchestrating role of fecal microbiota transplantation.

The debris of plastics with a size < 5 mm, called microplastics, possess long-lived legacies of plastic pollution and a growing threat to human beings. The adverse effects and corresponding molecular mechanisms of microplastics are still largely unknown and must be prioritized. Antibiotics commonly co-existed with microplastics; the current study investigated the syngenetic toxic effect of doxycycline (Dox) and polystyrene microplastics (PS). Specifically, we found that Dox combined with PS exposure perturbed gut microbiota homeostasis in mice, which mediated brain lesions and inflammation with a concomitant decline in learning and memory behaviors through the gut-brain axis. Of note, PS exposure resulted in intestinal damage and structural change, but Dox did not accelerate the disruption of intestinal barrier integrity in PS-treated mice. Interestingly, fecal microbiota transplantation (FMT) can reverse neurological impairment caused by combined PS and Dox exposure via compensating gut microbes; therefore, the learning and memory abilities of mice were also recovered. This work not only provides insights into the syngenetic effect of microplastics and antibiotics and highlights their distal neurotoxicity through the gut-brain axis but also offers a promising strategy against their combined toxicity.

Separation of lignin derivatives from hemp fiber using supercritical CO2, ethanol, and water at different temperatures.

The process of lignin extraction often involves intricate chemical transformations, influencing its potential for high-value utilization. By investigating the process of lignin derivatives extraction from hemp fibers using supercritical CO2, ethanol, and water, we identified the relationship between the chemical structure of lignin derivatives and temperature. This discovery contributes to controlling the chemical structure of lignin derivatives through temperature modulation. We observed that lignin derivatives extracted within the temperature range of 100-120 °C exhibited the lowest average molecular weight and polydispersity index, presenting a disordered microstructure with the highest hydroxyl content. Lignin derivatives extracted between 140 and 160 °C showed an increase in average molecular weight and polydispersity index, decreased hydroxyl content, and a gradual transformation of microstructure into spherical particles. At 180 °C, the average molecular weight and polydispersity index of lignin derivatives decreased, the microstructure of lignin derivatives showed fewer spherical particles, while its hydroxyl content exhibited a partial recovery. Chemical analysis revealed a lower degree of condensation in lignin derivatives at 100-120 °C. Between 120 and 160 °C, the degree of condensation increased. At 180 °C, extensive degradation occurred in lignin derivatives. This research advances innovative techniques for lignin derivative separation, contributing to their utilization in higher-value applications.

Exosome Heterogeneity Affects the Distal "Barrier-Crossing" Trafficking of Exosome Encapsulated Quantum Dots.

The biological activities of nanoparticles (NPs), which include endocytosis by macrophages and subsequent intracellular degradation and/or release, transfer to other cells, or translocation across tissue barriers, highly depend on their fate in living organisms. Yet, translocation across barriers, especially the distal "barrier-crossing" trafficking of NPs, is still unclear. The exosome (Exo) plays a crucial role in intercellular communication and biological barrier trafficking. Here, we report that ZnCdSe@ZnS quantum dots (QDs), as a representation of NPs in biomedical applications, could cross the blood-brain barrier and approach the mouse brain via active Exo encapsulation. By employing multiple techniques, we demonstrated that QDs were internalized by macrophages (J774A.1) and tumor cells (HeLa) and then released to the extracellular environment along with Exo. Exo encapsulation facilitates the distal barrier-crossing trafficking of QDs in vivo, while Exo biogenesis inhibitor GW4869 suppressed the QDs enriched in the brains of mice with a 4T1-Luc breast cancer xenograft. Interestingly, Exo heterogeneity affects the distal trafficking of enveloped QDs. Exo derived from tumorous HeLa cells, not macrophages, that were enriched in functional proteins with cell adhesion, cell migration, axon guidance, and cell motility, showed a better capacity for the remote trafficking of QDs. This study proposes Exo as a vehicle to deliver exogenous NPs to translocate across the distal barrier and provides further information for biomedical application and the risk assessment of NPs.

Long-term polystyrene nanoplastic exposure disrupt hepatic lipid metabolism and cause atherosclerosis in ApoE-/- mice.

Nanoplastics (NPs) exposure is usually linked with abnormal inflammation and oxidative stress, which are high-risk triggers of atherosclerosis; however, whether this exposure causes the development of atherosclerosis is vague. Here, we found that PS NPs co-exposure with ox-LDL induces significant accumulation of lipid, as well as oxidative stress and inflammation in RAW264.7 macrophages. Using an ultrasound biomicroscope (UBM), we observed the emergence of atherosclerotic plaques at the aortic arch of apolipoprotein knockout (ApoE-/-) mice after being exposed to PS NPs for three months. Oil-red O and hematoxylin-eosin (H&E) staining at the mice's aortic root also observed the deposition of lipids with plaque formation. Moreover, the development of atherosclerotic disease is associated with disturbances in lipid metabolism and oxidative stress damage in the mice liver. In conclusion, this study provides additional evidence to further understand the possible cardiovascular damage caused by NPs exposure.

Coexistence of Ferroelectricity and Ferromagnetism in Atomically Thin Two-Dimensional Cr2S3/WS2 Vertical Heterostructures.

Two-dimensional (2D) heterostructures with ferromagnetism and ferroelectricity provide a promising avenue to miniaturize the device size, increase computational power, and reduce energy consumption. However, the direct synthesis of such eye-catching heterostructures has yet to be realized up to now. Here, we design a two-step chemical vapor deposition strategy to growth of Cr2S3/WS2 vertical heterostructures with atomically sharp and clean interfaces on sapphire. The interlayer charge transfer and periodic moiré superlattice result in the emergence of room-temperature ferroelectricity in atomically thin Cr2S3/WS2 vertical heterostructures. In parallel, long-range ferromagnetic order is discovered in 2D Cr2S3 via the magneto-optical Kerr effect technique with the Curie temperature approaching 170 K. The charge distribution variation induced by the moiré superlattice changes the ferromagnetic coupling strength and enhances the Curie temperature. The coexistence of ferroelectricity and ferromagnetism in 2D Cr2S3/WS2 vertical heterostructures provides a cornerstone for the further design of logic-in-memory devices to build new computing architectures.

Coronal ApoE Protein Combines with LRP1 to Inactivate GSK3ß That Mitigates Silica Nanoparticle-Induced Brain Lesion.

Silica nanoparticles (SiO2 NPs) are widely used engineered materials that warrant their obvious environmental exposure risk. Our previous study has shown that different routes of SiO2 NP exposure on the glycogen synthase kinase 3 beta (GSK3ß) activity were related to the serum proteins enriched on the surface of SiO2 NPs, which implied that a particular protein in the serum changed the inherent toxic behavior of SiO2 NPs and inhibited the activation of GSK3ß by SiO2 NPs. Here, we identified that the SiO2 NP surface enriched a large amount of apolipoprotein E (ApoE), and the ApoE protein corona bound to the lipoprotein receptor-related protein 1 (LRP1) to inactivate GSK3ß, thereby reducing the damage of SiO2 NPs to the brain. This work presented the first evidence that specific biocorona reduced the toxicity of SiO2 NPs at the molecular level, which helped to elucidate the role of specific corona components on nanotoxicity.

Oxalate anions-intercalated NiFe layered double hydroxide as a highly active and stable electrocatalyst for alkaline seawater oxidation.

Seawater electrolysis is gaining recognition as a promising method for hydrogen production. However, severe anode corrosion caused by the high concentration of chloride ions (Cl-) poses a challenge for the long-term oxygen evolution reaction. Herein, an anti-corrosion strategy of oxalate anions intercalation in NiFe layered double hydroxide on nickel foam (NiFe-C2O42- LDH/NF) is proposed. The intercalation of these highly negatively charged C2O42- serves to establish electrostatic repulsion and impede Cl- adsorption. In alkaline seawater, NiFe-C2O42- LDH/NF requires an overpotential of 337 mV to gain the large current density of 1000 mA cm-2 and operates continuously for 500 h. The intercalation of C2O42- is demonstrated to significantly boost the activity and stability of NiFe LDH-based materials during alkaline seawater oxidation.

High-efficiency electrocatalytic nitrite-to-ammonia conversion on molybdenum doped cobalt oxide nanoarray at ambient conditions.

Electrochemical conversion of nitrite (NO2-) contaminant to green ammonia (NH3) is a promising approach to achieve the nitrogen cycle. The slow kinetics of the complex multi-reaction process remains a serious issue, and there is still a need to design highly effective and selective catalysts. Herein, we report that molybdenum doped cobalt oxide nanoarray on titanium mesh (Mo-Co3O4/TM) acts as a catalyst to facilitate electroreduction of NO2- to NH3. Such a catalyst delivers an extremely high Faradaic efficiency of 96.9 % and a corresponding NH3 yield of 651.5 µmol h-1 cm-2 at -0.5 V with strong stability. Density functional theory calculations reveal that the introduction of Mo can induce the redistribution of electrons around Co atoms and further strengthen the adsorption of NO2-, which is the key to facilitating the catalytic performance. Furthermore, the assembled battery based on Mo-Co3O4/TM suggests its practical application value.

Single-cell disulfidptosis regulator patterns guide intercellular communication of tumor microenvironment that contribute to kidney renal clear cell carcinoma progression and immunotherapy.

Background: Disulfidptosis, an emerging type of programmed cell death, plays a pivotal role in various cancer types, notably impacting the progression of kidney renal clear cell carcinoma (KIRC) through the tumor microenvironment (TME). However, the specific involvement of disulfidptosis within the TME remains elusive. Methods: Analyzing 41,784 single cells obtained from seven samples of KIRC through single-cell RNA sequencing (scRNA-seq), this study employed nonnegative matrix factorization (NMF) to assess 24 disulfidptosis regulators. Pseudotime analysis, intercellular communication mapping, determination of transcription factor activities (TFs), and metabolic profiling of the TME subgroup in KIRC were conducted using Monocle, CellChat, SCENIC, and scMetabolism. Additionally, public cohorts were utilized to predict prognosis and immune responses within the TME subgroup of KIRC. Results: Through NMF clustering and differential expression marker genes, fibroblasts, macrophages, monocytes, T cells, and B cells were categorized into four to six distinct subgroups. Furthermore, this investigation revealed the correlation between disulfidptosis regulatory factors and the biological traits, as well as the pseudotime trajectories of TME subgroups. Notably, disulfidptosis-mediated TME subgroups (DSTN+CD4T-C1 and FLNA+CD4T-C2) demonstrated significant prognostic value and immune responses in patients with KIRC. Multiple immunohistochemistry (mIHC) assays identified marker expression within both cell clusters. Moreover, CellChat analysis unveiled diverse and extensive interactions between disulfidptosis-mediated TME subgroups and tumor epithelial cells, highlighting the TNFSF12-TNFRSF12A ligand-receptor pair as mediators between DSTN+CD4T-C1, FLNA+CD4T-C2, and epithelial cells. Conclusion: Our study sheds light on the role of disulfidptosis-mediated intercellular communication in regulating the biological characteristics of the TME. These findings offer valuable insights for patients with KIRC, potentially guiding personalized immunotherapy approaches.

Cellular nucleus image-based smarter microscope system for single cell analysis.

Cell imaging technology is undoubtedly a powerful tool for studying single-cell heterogeneity due to its non-invasive and visual advantages. It covers microscope hardware, software, and image analysis techniques, which are hindered by low throughput owing to abundant hands-on time and expertise. Herein, a cellular nucleus image-based smarter microscope system for single-cell analysis is reported to achieve high-throughput analysis and high-content detection of cells. By combining the hardware of an automatic fluorescence microscope and multi-object recognition/acquisition software, we have achieved more advanced process automation with the assistance of Robotic Process Automation (RPA), which realizes a high-throughput collection of single-cell images. Automated acquisition of single-cell images has benefits beyond ease and throughout and can lead to uniform standard and higher quality images. We further constructed a single-cell image database-based convolutional neural network (Efficient Convolutional Neural Network, E-CNN) exceeding 20618 single-cell nucleus images. Computational analysis of large and complex data sets enhances the content and efficiency of single-cell analysis with the assistance of Artificial Intelligence (AI), which breaks through the super-resolution microscope's hardware limitation, such as specialized light sources with specific wavelengths, advanced optical components, and high-performance graphics cards. Our system can identify single-cell nucleus images that cannot be artificially distinguished with an accuracy of 95.3%. Overall, we build an ordinary microscope into a high-throughput analysis and high-content smarter microscope system, making it a candidate tool for Imaging cytology.

Effects of UV-B radiation on pollen germination and tube growth: A global meta-analysis.

Despite widespread recognition of pollen's potential sensitivity to ultraviolet-B (UV-B) radiation (280-315 nm), there remains ongoing debate surrounding the extent and mechanisms of this effect. In this study, using published data on pollen germination and tube growth including 377 pair-wise comparisons from 77 species in 30 families, we present the first global quantification of the effects of UV-B radiation on pollen germination and tube growth, along with its underlying mechanisms. Our results showed a substantial reduction in both pollen germination and tube growth in response to UV-B radiation, affecting 90.9 % and 84.2 % of species, respectively. Notably, these reductions exhibited phylogenetic constraints, highlighting the role of evolutionary history in shaping the sensitivity of pollen germination and tube growth to UV-B radiation. A negative correlation between elevation and the sensitivity of pollen tube growth was detected, suggesting that pollens from plants at higher elevations exhibit greater resistance to UV-B radiation. Our investigation also revealed that the effects of UV-B radiation on pollen germination and tube growth were influenced by a range of abiotic and biotic factors. Nevertheless, the intensity and duration of UV-B radiation exposure exhibited the highest explanatory power for the effects on both pollen germination and tube growth. This suggests that the responses of pollens to UV-B radiation are profoundly influenced by its dose, a critical consideration within the context of global change. In conclusion, our study provides valuable insights into the diverse responses of pollen germination and tube growth to UV-B radiation, highlighting the environment and species-dependent nature of pollen's susceptibility to UV-B radiation, with substantial implications for our understanding of the ecological and agricultural consequences of ongoing changes in UV-B radiation.

Silica Nanoparticle Exposure Implicates ß-Amyloid (1-42) Inbound and the Accelerating Alzheimer's Disease Progression in Mice Overexpressing Mutated Forms of Human Amyloid Precursor Protein and Presenilin 1 Genes.

The increasing nanoparticle (NP) applications in the biomedical field have become an emerging concern regarding human health. NP exposure may play a role in the accelerating Alzheimer's disease (AD) progression; however, the etiology of this disorder is complex and remains largely unclear. Here, we identified that intravenous injection of silica NPs (SiNPs) caused the blood-brain barrier breakdown via downregulating tight junction-related gene expressions. Meanwhile, SiNPs upregulate the transport receptor for advanced glycation end products (RAGE) that govern the ß-amyloid (Aß) influx to the brain; however, low-density lipoprotein receptor-related protein 1 (LRP1) that controls the efflux of Aß from the brain was not affected. Consequently, an increase in Aß burden in the brain of SiNP-challenged APP/PS1 mice was found. Intriguingly, plasma apolipoprotein E (ApoE) adsorbed on the surface of SiNPs partially relieves this effect. Using ApoE knockout (ApoE-/-) mice, we confirmed that SiNPs covered with serum without ApoE showed further elevated AD symptoms. Together, this study offered a compilation of data to support the potential risk factors of NP exposure and AD pathology.