Search

Abstract Polycomb repressive complex 2 (PRC2) catalyzes the writing of the tri-methylated histone H3 at Lys27 (H3K27me3) epigenetic marker and suppresses the expression of genes, including tumor suppressors. The function of the complex can be partially antagonized by the SWI/SNF chromatin-remodeling complex. Previous studies have suggested that PRC2 is important for the proliferation of tumors with SWI/SNF loss-of-function mutations. In the present study, we have developed an EED-directed allosteric inhibitor of PRC2 termed BR0063, which exhibits anti-proliferative properties in a subset of solid tumor cell lines harboring mutations of the SWI/SNF subunits, SMARCA4 or ARID1A. Tumor cells sensitive to BR0063 exhibited several distinct phenotypes, including cell senescence, which was mediated by the up-regulation of CDKN2A/p16. Further experiments revealed that the expression of p16 was suppressed in the BR0063-resistant cells via DNA hypermethylation in the CpG island (CGI) promoter region, rather than via PRC2 occupancy. The expression of TET1, which is required for DNA demethylation, was found to be inversely correlated with p16 CGI methylation, and this may serve as a biomarker for the prediction of resistance to PRC2 inhibitors in SWI/SNF LOF tumors.

Abstract Background Evidence shows that full mycoheterotrophs and holoparasites often have reduced plastid genomes with rampant gene loss, elevated substitution rates, and deeply altered to conventional evolution in mitochondrial genomes, but mechanisms of cytonuclear evolution is unknown. Endoparasitic Sapria himalayana and mycoheterotrophic Gastrodia and Platanthera guangdongensis represent different heterotrophic types, providing a basis to illustrate cytonuclear evolution. Here, we focused on nuclear-encoded plastid / mitochondrial (N-pt / mt) -targeting protein complexes, including caseinolytic protease (ClpP), ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCo), oxidative phosphorylation system (OXPHOS), DNA recombination, replication, and repair (DNA-RRR) system, and pentatricopeptide repeat (PPR) proteins, to identify evolutionary drivers for cytonuclear interaction. Results The severity of gene loss of N-pt PPR and pt-RRR genes was positively associated with increased degree of heterotrophy in full mycoheterotrophs and S. himalayana, while N-mt PPR and mt-RRR genes were retained. Substitution rates of organellar and nuclear genes encoding N-pt/mt subunits in protein complexes were evaluated, cytonuclear coevolution was identified in S. himalayana, whereas disproportionate rates of evolution were observed in the OXPHOS complex in full mycoheterotrophs, only slight accelerations in substitution rates were identified in N-mt genes of full mycoheterotrophs. Conclusions Nuclear compensatory evolution was identified in protein complexes encoded by plastid and N-pt genes. Selection shaping codon preferences, functional constraint, mt-RRR gene regulation, and post-transcriptional regulation of PPR genes all facilitate mito-nuclear evolution. Our study enriches our understanding of genomic coevolution scenarios in fully heterotrophic plants.

Abstract Ankyrin repeat domain 1 (Ankrd1) is an acute response protein that belongs to the muscle ankyrin repeat protein (MARP) family. Accumulating evidence has revealed that Ankrd1 plays a crucial role in a wide range of biological processes and diseases. This review consolidates current knowledge on Ankrd1’s functions in myocardium and skeletal muscle development, neurogenesis, cancer, bone formation, angiogenesis, wound healing, fibrosis, apoptosis, inflammation, and infection. The comprehensive profile of Ankrd1 in cardiovascular diseases, myopathy, and its potential as a candidate prognostic and diagnostic biomarker are also discussed. In the future, more studies of Ankrd1 are warranted to clarify its role in diseases and assess its potential as a therapeutic target.

Abstract Pampus argenteus is a highly commercial marine fish whose population is declining sharply. Here, we generated a female P. argenteus genome, spanning 536.33 Mb with contig N50 of 1.79 Mb; 24070 genes (99.50% of 24,182) were functionally annotated. To improve quality of it, we assembled a 553.79 Mb genome of male fish with contig N50 of 24.75 Mb through HiFi and ultra-long ONT sequence technologies; 550.82 Mb were anchored onto 24 gap-free chromosomes; 22,892 genes (98.1% of 23,346) were functionally annotated; the QV value was 51.55 with 98.9% of BUSCO and 99.39% coverage of Illumina reads. Finally, we compared this genome with previous published one, revealing 37,301 SVs. 52.82 Mb and 18.05 Mb SDs were characterized in our and published assemblies, respectively, and 48.96 Mb PURs were constructed. Thus, this genome assembly exhibits excellent completeness, continuity and accuracy comparing to the published one, which can be current preferred reference genome. Overall, these works help aquaculture and wild resources recovery of P. argenteus and provide a valuable genetic resource for study.

The global food crisis has intensified with climate change, and hybrid rice (Oryza sativa L.) is expected to play a crucial role in ensuring world food security. This study analyzed the parental origins and variety characteristics of 930 hybrid rice varieties bred in Sichuan Province, a typical low-light region and one of the main production areas for hybrid rice, from 2002 to 2022. The results indicate that these varieties were hybridized using 329 direct female and 539 direct male parents. Notably, the female parent Peiai 64 and the male parents Yuehesimiao and Fenghuazhan demonstrated a higher probability of breeding rice varieties with high yield and good quality. An ideal panicle type should possess more grains, a lower 1000-grain weight, a higher seed setting percentage, and greater grain density. It is recommended to increase the utilization of excellent parents in Sichuan Province, such as parents with ideal panicle type to improve resistance to climate change, particularly global dimming.

Abstract Background Metabolic syndrome (MetS) is a precursor to the development of many diseases (atherosclerosis, diabetes, etc.). It is marked by disruptions in glucose and lipid metabolism, along with hypertension. Numerous types of risk factors contribute to the development of the MetS, inflammation and insulin resistance are present throughout the metabolic abnormalities. Chrysanthemum indicum L. is a traditional Chinese plant used for both tea and medicine, known for its high content of total flavonoids, which are important secondary metabolites. Our research led to the extraction of a Buddleoside-Rich Chrysanthemum indicum L. extract (BUDE) which has demonstrated anti-inflammatory properties. Nonetheless, the specific role and mechanism of BUDE in preventing MetS remain unclear. Methods The study initially evaluated the role of BUDE in preventing MetS. Subsequently, it investigated the anti-inflammatory properties of BUDE in the liver and pancreas in response to unhealthy diets. It then examined the level of insulin resistance and pancreatic β-cell function induced by inflammation. Additionally, an lipopolysaccharide (LPS)-induced macrophage inflammation model was used to further investigate the ameliorative effects of BUDE in inflammation. Results BUDE has hypotensive, hypoglycemic and hypolipidemic effects. It can also resolve the imbalance between macrophage subpopulations, impede the triggering of the NF-κB signaling pathway, reduce the secretion of inflammatory mediators, ameliorate insulin resistance, and safeguard organs such as the liver and pancreas from inflammatory damage. These effects collectively contribute to preventing the development of MetS. Discussion BUDE has the ability to modulate macrophage-mediated inflammation, leading to improved insulin resistance. Additionally, it delivers antihypertensive, hypoglycemic, and hypolipidemic effects, offering a potential for preventing MetS.

Abstract Despite the well-established significance of transcription factors (TFs) in pathogenesis, their utilization as pharmacological targets has been limited by the inherent challenges in modulating their protein interactions. The lack of defined small-molecule binding pockets and the nuclear localization of TFs do not favor the use of traditional tools. Aptamers possess large molecular weights, expansive blocking surfaces and efficient cellular internalization, making them compelling tools for modulating TF interactions. Here, we report a structure-guided design strategy called Blocker-SELEX to develop inhibitory aptamers (iAptamers) that selectively block TF interactions. Our approach leads to the discovery of iAptamers that cooperatively disrupt SCAF4/SCAF8-RNAP2 interactions, dysregulating RNAP2-dependent gene expression, which impairs cell proliferation. This approach is further applied to develop iAptamers blocking WDR5-MYC interactions. Overall, our study highlights the potential of iAptamers in disrupting pathogenic TF interactions, implicating their potential utility in studying the biological functions of TF interactions and in nucleic acids drug discovery.

Abstract Many disease resistance genes have been introgressed into wheat from its wild relatives. However, reduced recombination within the introgressed segments hinders the cloning of the introgressed genes. Here, we have cloned the powdery mildew resistance gene Pm13, which is introgressed into wheat from Aegilops longissima, using a method that combines physical mapping with radiation-induced chromosomal aberrations and transcriptome sequencing analysis of ethyl methanesulfonate (EMS)-induced loss-of-function mutants. Pm13 encodes a kinase fusion protein, designated MLKL-K, with an N-terminal domain of mixed lineage kinase domain-like protein (MLKL_NTD domain) and a C-terminal serine/threonine kinase domain bridged by a brace. The resistance function of Pm13 is validated through transient and stable transgenic complementation assays. Transient over-expression analyses in Nicotiana benthamiana leaves and wheat protoplasts reveal that the fragment Brace-Kinase122-476 of MLKL-K is capable of inducing cell death, which is dependent on a functional kinase domain and the three α-helices in the brace region close to the N-terminus of the kinase domain.

Orchidaceae are one of the largest families of angiosperms in terms of species richness. In the last decade, numerous studies have delved into reconstructing the phylogenetic framework of Orchidaceae, leveraging data from plastid, mitochondrial and nuclear sources. These studies have provided new insights into the systematics, diversification and biogeography of Orchidaceae, establishing a robust foundation for future research. Nevertheless, pronounced controversies persist regarding the precise placement of certain lineages within these phylogenetic frameworks. To address these discrepancies and deepen our understanding of the phylogenetic structure of Orchidaceae, we provide a comprehensive overview and analysis of phylogenetic studies focusing on contentious groups within Orchidaceae since 2015, delving into discussions on the underlying reasons for observed topological conflicts. We also provide a novel phylogenetic framework at the subtribal level. Furthermore, we examine the tempo and mode underlying orchid species diversity from the perspective of historical biogeography, highlighting factors contributing to extensive speciation. Ultimately, we delineate avenues for future research aimed at enhancing our understanding of Orchidaceae phylogeny and diversity.

Abstract Background Persistent pain is a prominent symptom of knee osteoarthritis (KOA) and has been associated with cognitive decline in individuals with KOA. The amygdala, a complex structure consisting of nine subnuclei, and programmed cell death protein‐1 (PD‐1) levels play crucial roles in pain regulation and cognitive processing. This study aims to investigate the relationships among amygdala subregion volumes, cognitive function, and PD‐1 levels to elucidate the underlying mechanism of cognitive decline in KOA. Methods In this cross‐sectional study, we recruited 36 patients with KOA and 25 age/gender‐matched healthy controls for neuropsychological tests, structural magnetic resonance imaging scanning, and measurement of serum PD‐1 levels. We used the atlas provided by FreeSurfer software to automatically segment the amygdala subnuclei. Subsequently, we compared the volumes of amygdala subregions between groups and explored their correlation with clinical scores and PD‐1 levels. Results Compared to healthy controls, individuals with KOA exhibited significantly lower scores on global cognition tasks, such as long‐delay free recall, short‐delay free recall, and immediate recall tasks. Moreover, they displayed decreased volumes in lateral nucleus basal nucleus paralaminar nucleus while showing increased volumes in accessory basal nucleus, central nucleus, medial nucleus, and cortical nucleus. Within the KOA group specifically, paralaminar volume was negatively correlated with immediate recall scores; pain scores were negatively correlated with global cognition; basal volume was negatively correlated with PD‐1 levels. Conclusion Our findings highlight those alterations in amygdala subregion volumes along with changes in serum PD‐1 levels may contribute to observe cognitive decline among individuals suffering from KOA.

ABSTRACT: Myocyte enhancer factor 2A (MEF2A) is a transcription factor that plays a critical role in cell proliferation, differentiation and apoptosis. In contrast to the wide characterization of its regulation mechanism in mammalian skeletal muscle, its role in chickens is limited. Especially, its wide target genes remain to be identified. Therefore, we utilized Cleavage Under Targets and Tagmentation (CUT&Tag) technology to reveal the genome-wide binding profile of MEF2A in chicken primary myoblasts thus gaining insights into its potential role in muscle development. Our results revealed that MEF2A binding sites were primarily distributed in intergenic and intronic regions. Within the promoter region, although only 8.87% of MEF2A binding sites were found, these binding sites were concentrated around the transcription start site (TSS). Following peak annotation, a total of 1903 genes were identified as potential targets of MEF2A. Gene Ontology (GO) enrichment analysis further revealed that MEF2A target genes may be involved in the regulation of embryonic development in multiple organ systems, including muscle development, gland development, and visual system development. Moreover, a comparison of the MEF2A target genes identified in chicken primary myoblasts with those in mouse C2C12 cells revealed 388 target genes are conserved across species, 1515 target genes are chicken specific. Among these conserved genes, ankyrin repeat and SOCS box containing 5 (ASB5), transmembrane protein 182 (TMEM182), myomesin 2 (MYOM2), leucyl and cystinyl aminopeptidase (LNPEP), actinin alpha 2 (ACTN2), sorbin and SH3 domain containing 1 (SORBS1), ankyrin 3 (ANK3), sarcoglycan delta (SGCD), and ORAI calcium release-activated calcium modulator 1 (ORAI1) exhibited consistent expression patterns with MEF2A during embryonic muscle development. Finally, TMEM182, as an important negative regulator of muscle development, has been validated to be regulated by MEF2A by dual-luciferase and quantitative real-time PCR (qPCR) assays. In summary, our study for the first time provides a wide landscape of MEF2A target genes in chicken primary myoblasts, which supports the active role of MEF2A in chicken muscle development.

ABSTRACT: The laying hen is the spontaneous model of ovarian tumor. A comprehensive comparison based on RNA-seq from hens and women may shed light on the molecular mechanisms of ovarian cancer. We performed next-generation sequencing of microRNA and mRNA expression profiles in 9 chicken ovarian cancers and 4 normal ovaries, which has been deposited in GSE246604. Together with 6 public datasets (GSE21706, GSE40376, GSE18520, GSE27651, GSE66957, TCGA-OV), we conducted a comparative transcriptomics study between chicken and human. In the present study, miR-451, miR-2188-5p, and miR-10b-5p were differentially expressed in normal ovaries, early- and late-stage ovarian cancers. We also disclosed 499 up-regulated genes and 1,061 down-regulated genes in chicken ovarian cancer. The molecular signals from 9 cancer hallmarks, 25 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and 369 Gene Ontology (GO) pathways exhibited abnormalities in ovarian cancer compared to normal ovaries via Gene Set Enrichment Analysis (GSEA). In the comparative analysis across species, we have uncovered the conservation of 5 KEGG and 76 GO pathways between chicken and human including the mismatch repair and ECM receptor interaction pathways. Moreover, a total of 174 genes contributed to the core enrichment for these KEGG and GO pathways were identified. Among these genes, the 22 genes were found to be associated with overall survival in patients with ovarian cancer. In general, we revealed the microRNA profiles of ovarian cancers in hens and updated the mRNA profiles previously derived from microarrays. And we also disclosed the molecular pathways and core genes of ovarian cancer shared between hens and women, which informs model animal studies and gene-targeted drug development.

Abstract High precision is a very important index in target tracking. In order to improve the prediction accuracy of target tracking, an optimized Kalman filter approach based on improved Gray Wolf algorithm (IGWO-OKF) is proposed in this paper. Since the convergence speed of traditional Gray Wolf algorithm is slow, meanwhile, the number of gray wolves and the choice of the maximum number of iterations has a great influence on the algorithm, a nonlinear control parameter combination adjustment strategy is proposed. An improved Grey Wolf Optimization algorithm (IGWO) is formed by determining the best combination of adjustment parameters through the fastest iteration speed of the algorithm. The improved Grey Wolf Optimization algorithm (IGWO) is formed, and the process noise covariance matrix and observation noise covariance matrix in Kalman filter are optimized by IGWO. The proposed approach is applied into. The experiment results show that the proposed IGWO-OKF approach has low error, high accuracy and good prediction effect.

Defect-free SLM-IN 738LC superalloy samples were fabricated using selective laser melting (SLM). The as-built samples exhibit a cellular structure with fine carbides, γ′ phases, and high-density dislocations at the cell boundary and nano-size γ′ phases in the interior, resulting in excellent deformation resistance and favorable mechanical properties at room temperature, with a yield strength (YS) of 970 MPa, an ultimate tensile strength (UTS) of 1263 MPa, and an elongation (EL) of 33%. This study investigates the evolution behavior of the γ′ phase at different solid solution treatment (SHT) temperatures and its impact on alloy strength and toughness. The 1020 + AHT sample exhibits a uniform distribution of coarse γ′ phases. The samples subjected to 1070 + AHT and 1120 + AHT display a bimodal distribution of γ′ phases. When the SHT temperature was further increased, fine spherical γ′ phases are evenly distributed in the 1160 + AHT and 1200 + AHT samples. Moreover, the γ/γ′ eutectics at the grain boundaries gradually dissolve with increasing SHT temperature, whereas the size and fraction of carbides increase. The room temperature tensile test of the 1070 + AHT sample demonstrated a favorable balance between strength and plasticity (YS = 1217 MPa, UTS = 1472 MPa, EL = 9.25%). This is attributed to the synergistic strengthening effect of the bimodal distribution of the γ′ phase. The temperature-dependent deformation behavior of the 1070 + AHT sample was analyzed at 23 °C, 800 °C, 900 °C, and 1000 °C. At 23 °C, numerous dislocations accumulated around the γ/γ′ interfaces. When the temperature increased to 800–900 °C, the dislocations shearing γ′ phases is activated and the alloy remained high strength. At 1000 °C, both the dislocation shearing and dislocation bypassing mechanisms coexist, resulting in a decrease in the strength of the alloy and an increase in its plasticity. This work provides scientific and theoretical support for SLM-IN 738LC parts with favorable properties.

Abstract Silent information regulator 1 (SIRT1) is a NAD+-dependent class III deacetylase that plays important roles in the pathogenesis of numerous diseases, positioning it as a prime candidate for therapeutic intervention. Among its modulators, SRT2104 emerges as the most specific small molecule activator of SIRT1, currently advancing into the clinical translation phase. The primary objective of this review is to evaluate the emerging roles of SRT2104, and to explore its potential as a therapeutic agent in various diseases. In the present review, we systematically summarized the findings from an extensive array of literature sources including the progress of its application in disease treatment and its potential molecular mechanisms by reviewing the literature published in databases such as PubMed, Web of Science, and the World Health Organization International Clinical Trials Registry Platform. We focuses on the strides made in employing SRT2104 for disease treatment, elucidating its potential molecular underpinnings based on preclinical and clinical research data. The findings reveal that SRT2104, as a potent SIRT1 activator, holds considerable therapeutic potential, particularly in modulating metabolic and longevity-related pathways. This review establishes SRT2104 as a leading SIRT1 activator with significant therapeutic promise.

Abstract There is substantial evidence demonstrating the crucial role of inflammation in oncogenesis. ANKRD1 has been identified as an anti-inflammatory factor and is related to tumor drug resistance. However, there have been no studies investigating the prognostic value and molecular function of ANKRD1 in pan-cancer. In this study, we utilized the TCGA, GTEx, GSCALite, ENCORI, CTRP, DAVID, AmiGO 2, and KEGG databases as well as R language, to explore and visualize the role of ANKRD1 in tumors. We employed the ROC curve to explore its diagnostic significance, while the Kaplan–Meier survival curve and Cox regression analysis were used to investigate its prognostic value. Additionally, we performed Pearson correlation analysis to evaluate the association between ANKRD1 expression and DNA methylation, immune cell infiltration, immune checkpoints, TMB, MSI, MMR, and GSVA. Our findings indicate that ANKRD1 expression is dysregulated in pan-cancer. The ROC curve revealed that ANKRD1 expression is highly sensitive and specific in diagnosing CHOL, LUAD, LUSC, PAAD, SKCM, and UCS (AUC > 85.0%, P

The silver pomfret (Pampus argenteus) is a commercially valuable marine fish species in China. Photobacterium damselae subsp. damselae (PDD) is an opportunistic pathogen in aquaculture environments and has become a serious bacterial pathogen of the aquacultural industry in recent years. In this study, two functional fragments originated from histone-derived peptides (H2A and H4) of the silver pomfret, and were identified and designated as spH2A.2 and spH4. In addition, the full-length cDNA of H2A from silver pomfret (SPH2A) consists of 387 base pairs (bp) coding sequence (CDS) that encodes 128 amino acids (aa), while the full-length cDNA of SPH4 consists of 312 bp CDS and encodes 103 aa. Tissue distribution analysis showed that SPH2A had a higher expression pattern in the head kidney and intestine, while SPH4 was mainly expressed in the spleen. After PDD infection, both histone gene expression levels were significant upregulated at 1 day post-infection (dpi) (P < 0.01) in the liver. Furthermore, spH4 and spH2A.2 peptides had potent antimicrobial activity against Gram-negative bacteria, with the MIC value ranging from 24 to 95 µM and 66–133 µM, respectively. Cytotoxicity of spH4 and spH2A.2 was tested in silver pomfret primary cells (liver, spleen and head kidney), and the results showed that spH4 had no cytotoxicity, while spH2A.2 displayed cytotoxic activity on silver pomfret cells. Additionally, scanning electronic microscope (SEM) analysis revealed that spH4 and spH2A.2 could destroy the PDD cell wall structure. Overall, the spH4 and spH2A.2 peptides were likely prone to exert the antimicrobial activity and may be useful to defend against PDD in silver pomfret aquaculture.

Congenital disorder of glycosylation type Ia (CDG-Ia) is an autosomal recessive genetic disease caused by a mutation in the phosphomannomutase 2 (PMM2) gene. We have identified a 13-month-old boy who has been diagnosed with CDG-Ia. He displays several characteristic symptoms, including cerebellar hypoplasia, severe developmental retardation, hypothyroidism, impaired liver function, and abnormal serum ferritin levels. Through whole-exome sequencing, we discovered novel complex heterozygous mutations in the PMM2 gene, specifically the c.663C > G (p.F221L) mutation and loss of exon 2. Further analysis revealed that the enzymatic activity of the mutant PMM2 protein was significantly reduced by 44.97% (p

To investigate the effect of void defects on the shock response of hexanitrohexaazaisowurtzitane (CL-20) co-crystals, shock responses of CL-20 co-crystals with energetic materials ligands trinitrotoluene (TNT), 1,3-dinitrobenzene (DNB), solvents ligands dimethyl carbonate (DMC) and gamma-butyrolactone (GBL) with void were simulated, using molecular dynamics method and reactive force field. It is found that the CL-20 co-crystals with void defects will form hot spots when impacted, significantly affecting the decomposition of molecules around the void. The degree of molecular fragmentation is relatively low under the reflection velocity of 2 km/s, and the main reactions are the formation of dimer and the shedding of nitro groups. The existence of voids reduces the safety of CL-20 co-crystals, which induced the sensitivity of energetic co-crystals CL-20/TNT and CL-20/DNB to increase more significantly. Detonation has occurred under the reflection velocity of 4 km/s, energetic co-crystals are easier to polymerize than solvent co-crystals, and are not obviously affected by voids. The results show that the energy of the wave decreases after sweeping over the void, which reduces the chemical reaction frequency downstream of the void and affects the detonation performance, especially the solvent co-crystals.

A new species of Orchidaceae, Phalaenopsis zhanhuoensis, from Xichou County, Yunnan, China, is described and illustrated. The novelty is close to P. taenialis, P. wilsonii, and P. stobartiana, but differs from them by having a distinct, fleshy anterior callus with a deeply lobed apex at the base of the labellum and lateral lobes of labellum reflexed and facing outward.

Optics, renowned for its non-contact measurement capabilities, versatility, and high sensitivity, is recognized as a powerful tool driving the technological evolution of precision metrology [...]

Sprite halos are diffuse glow discharges in the D-region ionosphere triggered by the quasi-electrostatic (QES) fields of lightning discharges. A three-dimensional (3D) QES model is adopted to investigate the effect of ionospheric electron density on sprite halos. The electron density is described by an exponential formula, parameterized by reference height (h’) and sharpness (β), and the local inhomogeneity has a Gaussian density distribution. Simulation results indicate that the reference height and steepness of the nighttime electron density affect the penetration altitudes and amplitudes of normalized electric fields, as well as the altitudes and intensities of the corresponding sprite halos optical emissions. A comparison of the daytime and nighttime conditions demonstrates that the daytime electron density profile is not favorable for generating sprite halos emissions. Furthermore, the pre-existing electron density inhomogeneities lead to enhanced local electric fields and optical emissions, potentially offering a plausible explanation for the horizontal displacement between sprites and their parent lightning, as well as their clustering.

Abstract Background Dioscin has many pharmacological effects; however, its role in sepsis‐induced cardiomyopathy (SIC) is unknown. Accordingly, we concentrate on elucidating the mechanism of Dioscin in SIC rat model. Methods The SIC rat and H9c2 cell models were established by lipopolysaccharide (LPS) induction. The heart rate (HR), left ventricle ejection fraction (LVEF), mean arterial blood pressure (MAP), and heart weight index (HWI) of rats were evaluated. The myocardial tissue was observed by hematoxylin and eosin staining. 4‐Hydroxy‐2‐nonenal (4‐HNE) level in myocardial tissue was detected by immunohistochemistry. Superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activities in serum samples of rats and H9c2 cells were determined by colorimetric assay. Bax, B‐cell lymphoma‐2 (Bcl‐2), toll‐like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), phosphorylated‐p65 (p‐p65), and p65 levels in myocardial tissues of rats and treated H9c2 cells were measured by quantitative real‐time PCR and Western blot. Viability and reactive oxygen species (ROS) accumulation of treated H9c2 cells were assayed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide and dihydroethidium staining assays. Results Dioscin decreased HR and HWI, increased LVEF and MAP, alleviated the myocardial tissue damage, and reduced 4‐HNE level in SIC rats. Dioscin reversed LPS‐induced reduction on SOD, CAT, GSH, and Bcl‐2 levels, and increment on Bax and TLR4 levels in rats and H9c2 cells. Overexpressed TLR4 attenuated the effects of Dioscin on promoting viability, as well as dwindling TLR4, ROS and MyD88 levels, and p‐p65/p65 value in LPS‐induced H9c2 cells. Conclusion Protective effects of Dioscin against LPS‐induced SIC are achieved via regulation of TLR4/MyD88/p65 signal pathway.

The stability of the surrounding rock in the inclined coal seam stope is crucial for the safety of the gob-side entry. In this article, we systematically analyze the surrounding rock stability of the gob-side entry formed by roof-cutting (GEFR) in an inclined coal seam. We identify three forms of roof structure evolution in the formation process of GEFR and analyze the two main modules affecting the deformation of the surrounding rock structure. We determine the critical elements of surrounding rock deformation in different stages of the GEFR retaining process. Further, we propose a classification of the deformation of the surrounding rock structure of GEFR into stress and structural types during stabilization. We analyze the length of the gangue side's bearing area and calculate the lateral gangue's impact energy. We establish three instability modes of the roof based on the fractured state of the roof structure of the GEFR and provide a mechanical criterion of instability. Finally, based on the results of our theoretical analysis, we propose a control principle for the surrounding rock deformation of GEFR and establish countermeasures for controlling the roof-cutting angle and an asymmetric coupling support system. A field case study was conducted under conditions involving an inclined thick coal seam to investigate the surrounding rock deformation and overburden stress evolution using field monitoring data. The field test results confirm that the control measures of the control roof-cutting angle and the asymmetric coupling support system positively impact the stability of the surrounding rock of the roof-cutting entry in an inclined coal seam.

Dynamic analysis is a key problem of flywheel energy storage system (FESS). In this paper, a one-dimensional finite element model of anisotropic composite flywheel energy storage rotor is established for the composite FESS, and the dynamic characteristics such as natural frequency and critical speed are calculated. Through the analysis of acceleration transient response, it is found that the flywheel rotor have two critical speeds during acceleration or deceleration process, which are prone to resonance and damage the bearing. Therefore, in order to avoid resonance or reduce resonance peak, the influence of bearing support stiffness, damping and speed-up rate on the critical speed and resonance peak is studied. The calculation results show that the first two order critical speed are affected by the support stiffness. When the stiffness increases, the critical speed of the flywheel rotor increases, but the growth rate decreases. When the damping increases, the critical speed is basically not affected, and the vibration amplitude decreases rapidly. In addition, the resonance peak value of transient response can be effectively reduced by increasing the speed-up rate.

Roxithromycin (ROX), a commonly used macrolide antibiotic, is extensively employed in human medicine and livestock industries. Due to its structural stability and resistance to biological degradation, ROX persists as a resilient environmental contaminant, detectable in aquatic ecosystems and food products. However, our understanding of the potential health risks to humans from continuous ROX exposure remains limited. In this study, we used the zebrafish as a vertebrate model to explore the potential developmental toxicity of early ROX exposure, particularly focusing on its effects on locomotor functionality and CaP motoneuron development. Early exposure to ROX induces marked developmental toxicity in zebrafish embryos, significantly reducing hatching rates (n=100), body lengths (n=100), and increased malformation rates (n=100). The zebrafish embryos treated with a corresponding volume of DMSO (0.1%, v/v) served as vehicle controls (veh). Moreover, ROX exposure adversely affected the locomotive capacity of zebrafish embryos, and observations in transgenic zebrafish Tg(hb9:eGFP) revealed axonal loss in motor neurons, evident through reduced or irregular axonal lengths (n=80). Concurrently, abnormal apoptosis in ROX-exposed zebrafish embryos intensified alongside the upregulation of apoptosis-related genes (bax, bcl2, caspase-3a). Single-cell sequencing further disclosed substantial effects of ROX on genes involved in the differentiation of motor neuron progenitor cells (ngn1, olig2), axon development (cd82a, mbpa, plp1b, sema5a), and neuroimmunity (aplnrb, aplnra) in zebrafish larvae (n=30). Furthermore, the CaP motor neuron defects and behavioral deficits induced by ROX can be rescued by administering ngn1 agonist (n=80). In summary, ROX exposure leads to early-life abnormalities in zebrafish motor neurons and locomotor behavior by hindering the differentiation of motor neuron progenitor cells and inducing abnormal apoptosis.

The hydroxyl groups generated by hydrolysis are grafted onto the surface of BiPO4, and a stable surface hydroxylation structure is formed during the subsequent calcination process. This would facilitate the formation of a new hydroxyl functional structure on the surface of the parent photocatalyst without damaging its intrinsic structure. Synchronous illumination X‐Ray photoelectron spectroscopy shows that the hydroxyl functional ultrafine BiPO4 can realize the conversion of defective oxygen to lattice oxygen, which is more conducive in improving the photocatalytic efficiency. The process of filling hydroxyl oxygen vacancies and forming a stable structure is explored using in‐ situ infrared spectroscopy. The induced dipole moment promotes the separation of photogenerated electron–hole pairs, which is beneficial for the enhancement of photocatalytic activity. The dipole moment of the hydroxyl functional‐modified ultrafine BiPO4 is −1.409 D compared to −1.385 D for ordinary BiPO4. The results of this study indicate that hydroxyl functional structure and reduced sample granularity are effective strategies to improve the photocatalytic performance of BiPO4.

Abstract During the process of coal mining, there is a violent appearance of mining stress when the initial weighting occurs. To guarantee the safety of the gob-side entry formed automatically by roof-cutting (EFARC) in an inclined coal seam, a study was conducted on the initial weighting mechanism and appearance characteristics through field monitoring and theoretical analysis. The findings reveal that, upon the initial breaking of the main roof in the non-pillar mining stope of an inclined coal seam, the deflection of the thin plate structure exhibits asymmetric distribution, with the maximum position situated in the middle-upper part of the thin plate. As the main roof thin plate reaches its limit interval, the tensile fracture first occurs in the middle-upper part of the coal wall in front and back of the stope. Once broken, the thin plate changes to a simply supported state. The analysis of field data reveals that the mine pressure in the non-pillar stope of EFARC shows an asymmetric weighting phenomenon. The periodic weighting interval at the ends of the working face increases, and the weighting intensity decreases. These results can serve as theoretical support for controlling mine pressure in non-pillar mining through EFARC in inclined coal seams and can serve as a basis for further investigations in this area.

This study explored the influence of Cr interfacial segregation on the precipitation mechanism and mechanical properties of MC carbides in high-carbon chromium bearing steels. The precipitation of Cr-doped MC carbides at different concentrations was investigated using microscopic morphological characterization (SEM, EDS and HR-TEM) alongside first principles calculations. The results indicated that both the austenite matrix and MC carbides exhibited, FCC structures, and the following orientation relationships of crystal planes in high-carbon chromium bearing steels were as follows: MC (010)//FCC-Fe (100) and MC (111)//FCC-Fe (111). Initially, Cr atoms adsorbed on the Fe-top site of the MC carbide (010) crystal plane, maintaining a distance of 2.5 Å from the Fe atom. Notably, when the Cr atom doping amount was 0.5, the Cr–Fe metallic bond exhibited a long bond length, large bond angle and low bond strength in the MC transition state (TS), resulting in a reduced, reaction barrier (908.08 kcal/mol), thus promoting the precipitation of MC carbide in bearing steel. However, at a Cr atom doping amount level of 1, the shorter bond length, small bond angle, and higher bonding strength of the Cr–Fe metallic bond in the MC TS, elevated the reaction barrier (49709.72 kcal/mol), inhibiting the precipitation of MC carbide in bearing steel. Additionally, this study quantitatively analyzed the effect of Cr atom content on the brittle plastic properties and hardness of MC carbides. At Cr atom contents of 0.23 and 1, the MC carbide hardness reached a minimum value of 3.0 GPa and a maximum value of 17.1 GPa, respectively. This investigation not only elucidated the atomic scale effects of Cr interfacial segregation on the precipitation mechanism and mechanical properties of MC carbides but also provided new ideas for controlling carbide precipitation in high-carbon chromium bearing steels.

Abstract Wild wheat relatives have been explored in plant breeding to increase the genetic diversity of bread wheat, one of the most important food crops. Aegilops umbellulata is a diploid U genome-containing grass species that serves as a genetic reservoir for wheat improvement. In this study, we report the construction of a chromosome-scale reference assembly of Ae. umbellulata accession TA1851 based on corrected PacBio HiFi reads and chromosome conformation capture. The total assembly size was 4.25 Gb with a contig N50 of 17.7 Mb. In total, 36,268 gene models were predicted. We benchmarked the performance of hifiasm and LJA, two of the most widely used assemblers using standard and corrected HiFi reads, revealing a positive effect of corrected input reads. Comparative genome analysis confirmed substantial chromosome rearrangements in Ae. umbellulata compared to bread wheat. In summary, the Ae. umbellulata assembly provides a resource for comparative genomics in Triticeae and for the discovery of agriculturally important genes.

In this paper, we investigate the extent to which precious metals can be used as a hedge from the perspective of global supply chain uncertainty (GSCU), which is significant for obtaining higher investment returns. This exploration uses the wavelet-based quantile-on-quantile regression (QQR) technique to identify the complex connection between GSCU and the price of precious metals (PMP). We find that GSCU has both positive and negative effects on PMP, which indicates that precious metals do not always hedge against global supply chain uncertainty, in contrast to the predictions of the theoretical model. This analysis considers multiple time scales, showing that severe GSCU can lead to a bull market in precious metals, but moderate GSCU may cause PMP to decline in the short term. However, extremely low GSCU might result in a bear market in precious metals, whereas moderate GSCU could also decrease PMP in the medium run. PMP could also be positively affected by moderate GSCU and it turns negative in the long term due to severe GSCU. A test of these results using the wavelet-based QQR technique reveals that they are robust. Because the global supply chain is strained and faces a potential crisis, our results have important implications for investment by individual investors, firms, countries, and regions.

In warehouses with vast quantities of heavy goods, heavy-duty forklift Automated Guided Vehicles (AGVs) play a key role in facilitating efficient warehouse automation. Due to their large load capacity and high inertia, heavy-duty forklift AGVs struggle to automatically navigate optimized routes. Additionally, rapid acceleration and deceleration can pose safety hazards. This paper proposes a velocity-adaptive model predictive control (MPC)-based path tracking method for heavy-duty forklift AGVs. The movement of heavy-duty forklift-type AGVs is categorized into straight-line and curve-turning motions, corresponding to the straight and curved sections of the reference path, respectively. These sections are segmented based on their curvature. The best driving speeds for straight and curved sections were 1.5 m/s and 0.3 m/s, respectively, while the optimal acceleration rates were 0.2 m/s2 for acceleration and −0.2 m/s2 for deceleration in straight paths and 0.3 m/s2 for acceleration with −0.15 m/s2 for deceleration in curves. Moreover, preferred sampling times, prediction domain, and control domain were determined through simulations at various speeds. Four path tracking methods, including pure tracking, Linear Quadratic Regulator (LQR), MPC, and the velocity-adaptive MPC, were simulated and evaluated under straight-line, turning, and complex double lane change conditions. Field experiments conducted in a warehouse environment demonstrated the effectiveness of the proposed path tracking method. Findings have implications for advancing path tracking control in narrow aisles.

Contamination with cadmium (Cd) is a prominent issue in agricultural non-point source pollution in China. With the deposition and activation of numerous Cd metal elements in farmland, the problem of excessive pollution of agricultural produce can no longer be disregarded. Considering the issue of Cd pollution in farmland, this study proposes the utilization of cross-linked modified biochar (prepared from pine wood) and calcium alginate hydrogels to fabricate a composite material which is called MB-CA for short. The aim is to investigate the adsorption and passivation mechanism of soil Cd by this innovative composite. The MB-CA exhibits a higher heavy metal adsorption capacity compared to traditional biochar and hydrogel due to its increased oxygen-containing functional groups and heavy metal adsorption sites. In the Cd solution adsorption experiment, the highest Cd2+ removal rate reached 85.48%. In addition, it was found that the material also has an excellent pH improvement effect. Through the adsorption kinetics experiment and the soil culture experiments, it was determined that MB-CA adheres to the quasi-second-order kinetic model and is capable of adsorbing 35.94% of Cd2+ in soil. This study validates the efficacy of MB-CA in the adsorption and passivation of Cd in soil, offering a novel approach for managing Cd-contaminated cultivated land.

Abstract Our previous study data suggested that the synapse-associated protein 97 (SAP97) rs3915512 polymorphism is significantly related to clinical performance in schizophrenia. The cerebellum exhibits abundant expression of SAP97, which is involved with negative symptoms, cognition and emotion in schizophrenia. As functional dysconnectivity with the cortical-subcortical-cerebellar circuitry has been widely shown in patients with schizophrenia, cortical-subcortical-cerebellar dysconnectivity can therefore be considered a possible intermediate phenotype that connects risk genes with schizophrenia. In this study, resting-state functional magnetic resonance imaging (fMRI) was applied to evaluate whether the SAP97 rs3915512 polymorphism changes cortical/subcortical-cerebellar resting-state functional connectivity (RSFC) in 104 Han Chinese subjects (52 first-episode schizophrenia (FES) patients and 52 matched healthy controls (HCs)). To examine RSFC between cortical/subcortical regions and the cerebellum, a ROI (region of interest)-wise functional connectivity analysis was conducted. The association between abnormal cortical/subcortical-cerebellar connectivity and clinical manifestation was further assessed in FES patients with different genotypes. The interactive effect of disease and genotype on RSFC was found between the frontal gyrus (rectus) and cerebellum. A positive correlation was suggested between RSFC in the cerebellum and the hostility scores in FES patients with the A allele, and no correlation was found in FES patients with the TT genotype. The current findings identified that SAP97 may be involved in the process of mental symptoms in FES patients via cerebellar connectivity depending on the rs3915512 polymorphism genotype.

Abstract Cancer remains a highly lethal disease in the world. Currently, either conventional cancer therapies or modern immunotherapies are non-tumor-targeted therapeutic approaches that cannot accurately distinguish malignant cells from healthy ones, giving rise to multiple undesired side effects. Recent advances in nanotechnology, accompanied by our growing understanding of cancer biology and nano-bio interactions, have led to the development of a series of nanocarriers, which aim to improve the therapeutic efficacy while reducing off-target toxicity of the encapsulated anticancer agents through tumor tissue-, cell-, or organelle-specific targeting. However, the vast majority of nanocarriers do not possess hierarchical targeting capability, and their therapeutic indices are often compromised by either poor tumor accumulation, inefficient cellular internalization, or inaccurate subcellular localization. This Review outlines current and prospective strategies in the design of tumor tissue-, cell-, and organelle-targeted cancer nanomedicines, and highlights the latest progress in hierarchical targeting technologies that can dynamically integrate these three different stages of static tumor targeting to maximize therapeutic outcomes. Finally, we briefly discuss the current challenges and future opportunities for the clinical translation of cancer nanomedicines.

Abstract Frequent fluctuations in microclimate inevitably cause serious irreversible damage to cultural heritage (such as high risks of cracking, flaking, salt efflorescence, swelling, disaggregation, surface layer detachment, and even microbe diseases). For the caves closed to the visitors, specifying a more rational schedule to minimize human influences on the microclimate is urgent and significant for daily maintenance of the Mogao Grottoes. Interior microclimate fluctuations are caused by air convection between the inside and outside environments, which is highly related to internal and external microclimate differences. Therefore, the occurrence times of the extreme values of temperature (T), relative humidity (RH), T difference (inside T minus outside T), and RH difference (inside RH minus outside RH) between the inside and outside environments of Cave 87 were analysed. The results indicated that the times of the extreme T/RH and T/RH differences showed obvious seasonal characteristics. From April to September, both the daily minimum T and RH differences mainly occurred from 8 am ~ 11 am, and the maximum differences were observed from 16 pm ~ 21 pm. This indicates that door openings for daily investigation and maintenance should be arranged in the morning rather than in the afternoon. The times of the daily extreme T and RH differences occurred from 16 pm ~ 19 pm (minimum) and 8 am ~ 11 am (maximum) from January ~ March and October ~ December, and the door opening time should be accordingly optimized. The analysis results provide more reasonable and specific door opening times for Cave 87 and a scientific reference for preventive conservation of the Mogao Grottoes.

Abstract Background Severe community‐acquired pneumonia (SCAP) is one of the world's most common diseases and a major etiology of acute respiratory distress syndrome (ARDS). Cuproptosis is a novel form of regulated cell death that can occur in various diseases. Methods Our study explored the degree of immune cell infiltration during the onset of severe CAP and identified potential biomarkers related to cuproptosis. Gene expression matrix was obtained from GEO database indexed GSE196399. Three machine learning algorithms were applied: The least absolute shrinkage and selection operator (LASSO), the random forest, and the support vector machine‐recursive feature elimination (SVM‐RFE). Immune cell infiltration was quantified by single‐sample gene set enrichment analysis (ssGSEA) scoring. Nomogram was constructed to verify the applicability of using cuproptosis‐related genes to predict the onset of severe CAP and its deterioration toward ARDS. Results Nine cuproptosis‐related genes were differentially expressed between the severe CAP group and the control group: ATP7B, DBT, DLAT, DLD, FDX1, GCSH, LIAS, LIPT1, and SLC31A1. All 13 cuproptosis‐related genes were involved in immune cell infiltration. A three‐gene diagnostic model was constructed to predict the onset of severe CAP: GCSH, DLD, and LIPT1. Conclusion Our study confirmed the involvement of the newly discovered cuproptosis‐related genes in the progression of SCAP.

Abstract Background Sapria himalayana (Rafflesiaceae) is an endoparasitic plant characterized by a greatly reduced vegetative body and giant flowers; however, the mechanisms underlying its special lifestyle and greatly altered plant form remain unknown. To illustrate the evolution and adaptation of S. himalayasna, we report its de novo assembled genome and key insights into the molecular basis of its floral development, flowering time, fatty acid biosynthesis, and defense responses. Results The genome of S. himalayana is ~ 1.92 Gb with 13,670 protein-coding genes, indicating remarkable gene loss (~ 54%), especially genes involved in photosynthesis, plant body, nutrients, and defense response. Genes specifying floral organ identity and controlling organ size were identified in S. himalayana and Rafflesia cantleyi, and showed analogous spatiotemporal expression patterns in both plant species. Although the plastid genome had been lost, plastids likely biosynthesize essential fatty acids and amino acids (aromatic amino acids and lysine). A set of credible and functional horizontal gene transfer (HGT) events (involving genes and mRNAs) were identified in the nuclear and mitochondrial genomes of S. himalayana, most of which were under purifying selection. Convergent HGTs in Cuscuta, Orobanchaceae, and S. himalayana were mainly expressed at the parasite–host interface. Together, these results suggest that HGTs act as a bridge between the parasite and host, assisting the parasite in acquiring nutrients from the host. Conclusions Our results provide new insights into the flower development process and endoparasitic lifestyle of Rafflesiaceae plants. The amount of gene loss in S. himalayana is consistent with the degree of reduction in its body plan. HGT events are common among endoparasites and play an important role in their lifestyle adaptation.

Lead-based reactor is a new type of reactor using liquid lead or lead-bismuth alloy as a coolant. As the core working element of the main pump, the impeller is subjected to a huge load when conveying heavy metal liquids and is highly susceptible to damage. In this study, we used ANSYS and FLUENT software to investigate the stress, deformation, and creep deformation of the nuclear main pump impeller under a liquid lead-bismuth environment by the fluid-solid coupling method. The maximum equivalent force of the impeller was located at the junction of the blade and hub, which was prone to fatigue damage under the action of alternating load. The stress, deformation, and creep characteristics of the impeller blade were observed to generally increase with rotational speed. Particularly, the junction of the blade root and hub exhibited high susceptibility to stress concentration and fatigue damage. At a flow rate of 0.64 m/s and a speed of 690 r/min, the maximum equivalent force was 16.7 MPa, which was lower than the yield strength of 316L stainless steel. Additionally, the maximum deformation was less than 0.63 mm. Over a five-year period, the creep of the impeller ranged from a minimum of 0.228% to a maximum of 0.447%, indicating that the impeller can reliably operate in a liquid lead-bismuth environment for at least five years.

ObjectiveIt remains unclear whether low-molecular-weight heparin (LMWH) is effective and safe for intracerebral hemorrhage (ICH) patients. This study presents a meta-analysis for elucidating effect of LMWH on preventing venous thromboembolism (VTE) among ICH patients.MethodsArticles were located by systematically searching PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), WANFANG DATA, VIP, and SinoMed databases. The literature was independently screened by two authors, who also extracted data and conducted a qualitative evaluation. With regard to outcomes, their risk ratios (RRs) and 95% confidence intervals (CIs) were computed, and the findings were combined using the random effects model by using Mantel-Haenszel approach.Results30 studies involving 2904 patients were analyzed and compared to control group. According to our findings, early low-dose LMWH, prophylaxis for VTE, was related to the markedly reduced deep vein thrombosis (DVT) (3.6% vs. 17.5%; RR, 0.25; 95% CI, 0.18-0.35; p-valueConclusionsOur meta-analysis suggested that early low-dose of LMWH are safe and effective in ICH patients. More extensive, multicenter, high-quality randomized clinical trials (RCTs) should be conducted to validate the findings and inform clinical practice.

BackgroundNumerous observational studies have reported an association between frailty and atherosclerosis. However, the causal relationship between frailty and the occurrence of atherosclerosis in different anatomical sites remains unclear. we conducted a bidirectional Mendelian randomization (MR) study to evaluate the causal relationship between the frailty index (FI), and both systemic atherosclerosis and lipids.MethodsWe obtained summary statistics from large-scale genome-wide association studies (GWAS) of various phenotypes, including frailty (n = 175,226), coronary atherosclerosis (n = 56,685), cerebral atherosclerosis (n = 150,765), peripheral arterial disease (PAD) (n = 361,194), atherosclerosis at other sites (n = 17,832), LDL-C (n = 201,678), HDL-C (n = 77,409), and triglycerides (n = 78,700). The primary MR analysis employed the inverse variance weighted (IVW) method. Furthermore, to assess reverse causality, we employed inverse MR and multivariate MR analysis.ResultsGenetically predicted FI showed positive associations with the risk of coronary atherosclerosis (OR = 1.47, 95% CI 1.12-1.93) and cerebral atherosclerosis (OR = 1.99, 95% CI 1.05-3.78), with no significant association (p >0.05) applied to peripheral arterial disease and atherosclerosis at other sites. Genetically predicted FI was positively associated with the risk of triglycerides (OR = 1.31, 95% CI 1.08-1.59), negatively associated with the risk of LDL-C (OR = 0.87, 95% CI 0.78-0.97), and showed no significant association with the risk of HDL-C (p >0.05). Furthermore, both reverse MR and multivariate MR analyses demonstrated a correlation between systemic atherosclerosis, lipids, and increased FI.ConclusionOur study elucidated that genetically predicted FI is associated with the risk of coronary atherosclerosis and cerebral atherosclerosis by the MR analysis method, and they have a bidirectional causal relationship. Moreover, genetically predicted FI was causally associated with triglyceride and LDL-C levels. Further understanding of this association is crucial for optimizing medical practice and care models specifically tailored to frail populations.

Our research addresses the critical environmental issue of a fine particulate matter (PM2.5), focusing on its association with the increased infection risks. We explored the influence of PM2.5 on human beta-defensin 1 (HBD1), an essential peptide in mucosal immunity found in the airway epithelium. Using C57BL/6J mice and human bronchial epithelial cells (HBE), we examined the effects of PM2.5 exposure followed by Pseudomonas aeruginosa (P. aeruginosa) infection on HBD1 expression at both mRNA and protein levels. The study revealed that PM2.5’s toxicity to epithelial cells and animals varies with time and concentration. Notably, HBE cells exposed to PM2.5 and P. aeruginosa showed increased bacterial invasion and decreased HBD1 expression compared to the cells exposed to P. aeruginosa alone. Similarly, mice studies indicated that combined exposure to PM2.5 and P. aeruginosa significantly reduced survival rates and increased bacterial invasion. These harmful effects, however, were alleviated by administering exogenous HBD1. Furthermore, our findings highlight the activation of MAPK and NF-κB pathways following PM2.5 exposure. Inhibiting these pathways effectively increased HBD1 expression and diminished bacterial invasion. In summary, our study establishes that PM2.5 exposure intensifies P. aeruginosa invasion in both HBE cells and mouse models, primarily by suppressing HBD1 expression. This effect can be counteracted with exogenous HBD1, with the downregulation mechanism involving the MAPK and NF-κB pathways. Our study endeavors to elucidate the pathogenesis of lung infections associated with PM2.5 exposure, providing a novel theoretical basis for the development of prevention and treatment strategies, with substantial clinical significance.

Extracting vanadium (V) from vanadium slag (VS) by the traditional roasting-leaching process has disadvantages of high energy consumption and high poisonous gases emission. In this work, a green and efficient route was developed to extract V from VS without roasting by electro-oxidation combined with ultrasound cavitation (EOUC) intensification in sulfuric acid solution. The leaching parameters (e.g., leaching temperature, sulfuric acid concentration, anodic current density, ultrasound power, liquid to solid ratio, leaching time and particle size) were optimized. The leaching mechanism was explored by comparing the leaching behavior and mineralogical evolution of the direct sulfuric acidic leaching (DSL), electro-oxidation-assisted sulfuric acidic leaching (EOSL), ultrasound cavitation-assisted sulfuric acidic leaching (UCSL) and EOUC methods. The results show that introducing electric field strengthens the ultrasound cavitation effect on slag particles in sulfuric acid solution. Under the optimum parameter of EOUC method, the leaching rate of V from VS is as high as 94.64 %. Using EOUC method can open the silicate-wrapped structure of the spinel, increase pore volume of VS from 0.00127 cm3 g−1 to 0.01124 cm3 g−1, decrease slag particle size from 26.8 μm to 16.4 μm and improve specific surface area from 0.508 m2 g−1 to 10.855 m2 g−1, which significantly accelerate V leaching process. The exposed spinel was oxidized by both electrochemical route and chemical route, forming a mixture of V3+ ion and VO2+ ion after leaching.

In recent decades, climate change has significantly affected water quality and algal blooms in lakes worldwide. Studying the temporal dynamics patterns of algal production efficiency and its drivers in individual lakes is useful for analyzing the evolutionary trajectory of Chla-TP changes, and identifying the main controlling factors of eutrophication to guide lake management. In this study, we used a dataset for the Lake Gehu (1986–2020) to analyze the drivers of the ETP variability on interannual and seasonal time scales and to quantify the relative impacts and contributions of nutrient and climatic factors on the ETP. The results showed a negative correlation of the Chla-TP relationship appeared in years with very high ETP. The effects of nutritional and climatic factors on the ETP at different time scales were quantified using a generalized additive model. The results showed that the total phosphorus (TP) concentration had a significant effect on the interannual ETP variation, explaining up to 28.9 %. At the intra-annual scale, climatic variables had a much greater effect on the ETP than the nutrient concentration, and the explanatory effect was ranked as temperature > wind speed > rainfall > total nitrogen (TN). Based on the characteristics of seasonal ETP variations, the TPa of Lake Gehu were 50 μg/L, 33 μg/L, 20 μg/L with ETP levels of 0.2, 0.3, 0.5, respectively. This research highlights the significance of nutrient and climatic factors in interannual and seasonal scale, respectively. In addition, ETP influenced by the coupling of nutrient and climate provides a criterion for establishing the seasonal nutrient threshold of lakes.

Membrane capacitive deionization (MCDI) is a cost-effective desalination technique known for its low energy consumption. The performance of MCDI cells relies on the properties of electrode materials. Activated carbon is the most widely used electrode material. However, the capacitive carbon available on the market is often expensive. Here, we developed hierarchically porous biochar by combining carbonization and activation processes, using easily acquired aerobic granular sludge (AGS) from biological sewage treatment plants as a precursor. The biochar had a specific surface area of 1822.07 m2 g−1, with a micropore area ratio of 58.65% and a micropore volume of 0.576 cm3 g−1. The MCDI cell employing the biochar as electrodes demonstrated a specific adsorption capacity of 34.35 mg g−1, comparable to commercially available activated carbon electrodes. Our study presents a green and sustainable approach for preparing highly efficient, hierarchically porous biochar from AGS, offering great potential for enhanced performance in MCDI applications.