Morphological diversity of single neurons in molecularly defined cell types.

Dendritic and axonal morphology reflects the input and output of neurons and is a defining feature of neuronal types1,2, yet our knowledge of its diversity remains limited. Here, to systematically examine complete single-neuron morphologies on a brain-wide scale, we established a pipeline encompassing sparse labelling, whole-brain imaging, reconstruction, registration and analysis. We fully reconstructed 1,741 neurons from cortex, claustrum, thalamus, striatum and other brain regions in mice. We identified 11 major projection neuron types with distinct morphological features and corresponding transcriptomic identities. Extensive projectional diversity was found within each of these major types, on the basis of which some types were clustered into more refined subtypes. This diversity follows a set of generalizable principles that govern long-range axonal projections at different levels, including molecular correspondence, divergent or convergent projection, axon termination pattern, regional specificity, topography, and individual cell variability. Although clear concordance with transcriptomic profiles is evident at the level of major projection type, fine-grained morphological diversity often does not readily correlate with transcriptomic subtypes derived from unsupervised clustering, highlighting the need for single-cell cross-modality studies. Overall, our study demonstrates the crucial need for quantitative description of complete single-cell anatomy in cell-type classification, as single-cell morphological diversity reveals a plethora of ways in which different cell types and their individual members may contribute to the configuration and function of their respective circuits.

Phosphocholine-induced energy source shift alleviates mitochondrial dysfunction in lung cells caused by geospecific PM2.5 components.

Fine particulate matter (PM2.5) is globally recognized for its adverse implications on human health. Yet, remain limited the individual contribution of particular PM2.5 components to its toxicity, especially considering regional disparities. Moreover, prevention solutions for PM2.5-associated health effects are scarce. In the present study, we comprehensively characterized and compared the primary PM2.5 constituents and their altered metabolites from two locations: Taiyuan and Guangzhou. Analysis of year-long PM2.5 samples revealed 84 major components, encompassing organic carbon, elemental carbon, ions, metals, and organic chemicals. PM2.5 from Taiyuan exhibited higher contamination, associated health risks, dithiothreitol activity, and cytotoxicities than Guangzhou's counterpart. Applying metabolomics, BEAS-2B lung cells exposed to PM2.5 from both cities were screened for significant alterations. A correlation analysis revealed the metabolites altered by PM2.5 and the critical toxic PM2.5 components in both regions. Among the PM2.5-down-regulated metabolites, phosphocholine emerged as a promising intervention for PM2.5 cytotoxicities. Its supplementation effectively attenuated PM2.5-induced energy metabolism disorder and cell death via activating fatty acid oxidation and inhibiting Phospho1 expression. The highlighted toxic chemicals displayed combined toxicities, potentially counteracted by phosphocholine. Our study offered a promising functional metabolite to alleviate PM2.5-induced cellular disorder and provided insights into the geo-based variability in toxic PM2.5 components.

Ageing induces tissue-specific transcriptomic changes in Caenorhabditis elegans.

Ageing is a complex process with common and distinct features across tissues. Unveiling the underlying processes driving ageing in individual tissues is indispensable to decipher the mechanisms of organismal longevity. Caenorhabditis elegans is a well-established model organism that has spearheaded ageing research with the discovery of numerous genetic pathways controlling its lifespan. However, it remains challenging to dissect the ageing of worm tissues due to the limited description of tissue pathology and access to tissue-specific molecular changes during ageing. In this study, we isolated cells from five major tissues in young and old worms and profiled the age-induced transcriptomic changes within these tissues. We observed a striking diversity of ageing across tissues and identified different sets of longevity regulators therein. In addition, we found novel tissue-specific factors, including irx-1 and myrf-2, which control the integrity of the intestinal barrier and sarcomere structure during ageing respectively. This study demonstrates the complexity of ageing across worm tissues and highlights the power of tissue-specific transcriptomic profiling during ageing, which can serve as a resource to the field.

MicroRNA-encoded regulatory peptides modulate cadmium tolerance and accumulation in rice.

MicroRNAs (miRNAs) are small noncoding RNAs that play a vital role in plant responses to abiotic and biotic stresses. Recently, it has been discovered that some primary miRNAs (pri-miRNAs) encode regulatory short peptides called miPEPs. However, the presence of miPEPs in rice, and their functions in response to abiotic stresses, particularly stress induced by heavy metals, remain poorly understood. Here, we identified a functional small peptide (miPEP156e) encoded by pri-miR156e that regulates the expression of miR156 and its target SPL genes, thereby affecting miR156-mediated cadmium (Cd) tolerance in rice. Overexpression of miPEP156e led to decreased uptake and accumulation of Cd and reactive oxygen species (ROS) levels in plants under Cd stress, resulting in improved rice Cd tolerance, as observed in miR156-overexpressing lines. Conversely, miPEP156e mutants displayed sensitivity to Cd stress due to the elevated accumulation of Cd and ROS. Transcriptome analysis further revealed that miPEP156e improved rice Cd tolerance by modulating Cd transporter genes and ROS scavenging genes. Our study provides insights into the regulatory mechanism of miPEP156e in rice response to Cd stress and demonstrates the potential of miPEPs as an effective tool for improving crop abiotic stress tolerance.

Pentapeptide PYRAE triggers ER stress-mediated apoptosis of breast cancer cells in mice by targeting RHBDF1-BiP interaction.

Reinforced cellular responses to endoplasmic reticulum (ER) stress are caused by a variety of pathological conditions including cancers. Human rhomboid family-1 protein (RHBDF1), a multiple transmembrane protein located mainly on the ER, has been shown to promote cancer development, while the binding immunoglobulin protein (BiP) is a key regulator of cellular unfolded protein response (UPR) for the maintenance of ER protein homeostasis. In this study, we investigated the role of RHBDF1 in maintaining ER protein homeostasis in breast cancer cells. We showed that deleting or silencing RHBDF1 in breast cancer cell lines MCF-7 and MDA-MB-231 caused marked aggregation of unfolded proteins in proximity to the ER. We demonstrated that RHBDF1 directly interacted with BiP, and this interaction had a stabilizing effect on the BiP protein. Based on the primary structural motifs of RHBDF1 involved in BiP binding, we found a pentapeptide (PE5) targeted BiP and inhibited BiP ATPase activity. SPR assay revealed a binding affinity of PE5 toward BiP (Kd = 57.7 µM). PE5 (50, 100, 200 µM) dose-dependently promoted ER protein aggregation and ER stress-mediated cell apoptosis in MCF-7 and MDA-MB-231 cells. In mouse 4T1 breast cancer xenograft model, injection of PE5 (10 mg/kg, s.c., every 2 days for 2 weeks) significantly inhibited the tumor growth with markedly increased ER stress and apoptosis-related proteins in tumor tissues. Our results suggest that the ability of RHBDF1 to maintain BiP protein stability is critical to ER protein homeostasis in breast cancer cells, and that the pentapeptide PE5 may serve as a scaffold for the development of a new class of anti-BiP inhibitors.

Rice responds to Spodoptera frugiperda infestation via epigenetic regulation of H3K9ac in the jasmonic acid signaling and phenylpropanoid biosynthesis pathways.

KEY MESSAGE: This study provided important insights into the complex epigenetic regulatory of H3K9ac-modified genes involved in the jasmonic acid signaling and phenylpropanoid biosynthesis pathways of rice in response to Spodoptera frugiperda infestation. Physiological and molecular mechanisms underlying plant responses to insect herbivores have been well studied, while epigenetic modifications such as histone acetylation and their potential regulation at the genomic level of hidden genes remain largely unknown. Histone 3 lysine 9 acetylation (H3K9ac) is an epigenetic marker widely distributed in plants that can activate gene transcription. In this study, we provided the genome-wide profiles of H3K9ac in rice (Oryza sativa) infested by fall armyworm (Spodoptera frugiperda, FAW) using CUT&Tag-seq and RNA-seq. There were 3269 and 4609 up-regulated genes identified in plants infested by FAW larvae for 3 h and 12 h, respectively, which were mainly enriched in alpha-linolenic acid and phenylpropanoid pathways according to transcriptomic analysis. In addition, CUT&Tag-seq analysis revealed increased H3K9ac in FAW-infested plants, and there were 422 and 543 up-regulated genes enriched with H3K9ac observed at 3 h and 12 h after FAW feeding, respectively. Genes with increased H3K9ac were mainly enriched in the transcription start site (TSS), suggesting that H3K9ac is related to gene transcription. Integrative analysis of both RNA-seq and CUT&Tag-seq data showed that up-expressed genes with H3K9ac enrichment were mainly involved in the jasmonic acid (JA) and phenylpropanoid pathways. Particularly, two spermidine hydroxycinnamoyl transferase genes SHT1 and SHT2 involved in phenolamide biosynthesis were highly modified by H3K9ac in FAW-infested plants. Furthermore, the Ossht1 and Ossht2 transgenic lines exhibited decreased resistance against FAW larvae. Our findings suggest that rice responds to insect herbivory via H3K9ac epigenetic regulation in the JA signaling and phenolamide biosynthesis pathways.

Lead exposure induced transgenerational developmental neurotoxicity by altering genome methylation in Drosophila melanogaster.

Heavy metal toxicity is a significant global health concern, with particular attention given to lead (Pb) exposure due to its adverse effects on cognitive development, especially in children exposed to low concentrations. While Pb neurotoxicity has been extensively studied, the analysis and molecular mechanisms underlying the transgenerational effects of Pb exposure-induced neurotoxicity remain poorly understood. In this study, we utilized Drosophila, a powerful developmental animal model, to investigate this phenomenon. Our findings demonstrated that Pb exposure during the developmental stage had a profound effect on the neurodevelopment of F0 fruit flies. Specifically, we observed a loss of correlation between the terminal motor area and muscle fiber area, along with an increased frequency of the ß-lobe midline crossing phenotype in mushroom bodies. Western blot analysis indicated altered expression levels of synaptic vesicle proteins, with a decrease in Synapsin (SYN) and an increase in Bruchpilot (BRP) expression, suggesting changes in synaptic vesicle release sites. These findings were corroborated by electrophysiological data, showing an increase in the amplitude of evoked excitatory junctional potential (EJP) and an increase in the frequency of spontaneous excitatory junctional potential (mEJP) following Pb exposure. Importantly, our results further confirmed that the developmental neurotoxicity resulting from grandparental Pb exposure exhibited a transgenerational effect. The F3 offspring displayed neurodevelopmental defects, synaptic function abnormalities, and repetitive behavior despite lacking direct Pb exposure. Our MeDIP-seq analysis further revealed significant alterations in DNA methylation levels in several neurodevelopmental associated genes (eagle, happyhour, neuroglian, bazooka, and spinophilin) in the F3 offspring exposed to Pb. These findings suggest that DNA methylation modifications may underlie the inheritance of acquired phenotypic traits resulting from environmental Pb exposure.

Metabolomic Profiling Reveals the Anti-Herbivore Mechanisms of Rice (Oryza sativa).

The use of secondary metabolites of rice to control pests has become a research hotspot, but little is known about the mechanism of rice self-resistance. In this study, metabolomics analysis was performed on two groups of rice (T1, with insect pests; T2, without pests), indicating that fatty acids, alkaloids, and phenolic acids were significantly up-regulated in T1. The up-regulated metabolites (p-value < 0.1) were enriched in linoleic acid metabolism, terpene, piperidine, and pyridine alkaloid biosynthesis, α-linolenic acid metabolism, and tryptophan metabolism. Six significantly up-regulated differential metabolites in T1 were screened out: N-trans-feruloyl-3-methoxytyramine (1), N-trans-feruloyltyramine (2), N-trans-p-coumaroyltyramine (3), N-cis-feruloyltyramine (4), N-phenylacetyl-L-glutamine (5), and benzamide (6). The insect growth inhibitory activities of these six different metabolites were determined, and the results show that compound 1 had the highest activity, which significantly inhibited the growth of Chilo suppressalis by 59.63%. Compounds 2-4 also showed a good inhibitory effect on the growth of Chilo suppressalis, while the other compounds had no significant effect. RNA-seq analyses showed that larval exposure to compound 1 up-regulated the genes that were significantly enriched in ribosome biogenesis in eukaryotes, the cell cycle, ribosomes, and other pathways. The down-regulated genes were significantly enriched in metabolic pathways, oxidative phosphorylation, the citrate cycle (TCA cycle), and other pathways. Eighteen up-regulated genes and fifteen down-regulated genes from the above significantly enriched pathways were screened out and verified by real-time quantitative PCR. The activities of detoxification enzymes (glutathione S-transferase (GST); UDP-glucuronosyltransferase (UGT); and carboxylesterase (CarE)) under larval exposure to compound 1 were measured, which indicated that the activity of GST was significantly inhibited by compound 1, while the activities of the UGT and CarE enzymes did not significantly change. As determined by UPLC-MS, the contents of compound 1 in the T1 and T2 groups were 8.55 ng/g and 0.53 ng/g, respectively, which indicated that pest insects significantly induced the synthesis of compound 1. Compound 1 may enhance rice insect resistance by inhibiting the detoxification enzyme activity and metabolism of Chilo suppressalis, as well as promoting cell proliferation to affect its normal growth and development process. The chemical-ecological mechanism of the insect resistance of rice is preliminarily clarified in this paper.

HOXC8/TGF-ß1 positive feedback loop promotes liver fibrosis and hepatic stellate cell activation via activating Smad2/Smad3 signaling.

Liver fibrosis occurs in any chronic liver disease, where extraordinary increase of extracellular matrix components is caused by the hepatic stellate cell (HSC) activation. HOXC8 has been disclosed to participate inregulating cell proliferation and fibrosis in tumors. However, the role of HOXC8 in liver fibrosis and the underlying molecular mechanisms has not yet been investigated. In this study, we founded that HOXC8 mRNA and protein was elevated in a carbon tetrachloride (CCl4)-induced liver fibrosis mouse model and transforming growth factor-ß (TGF-ß)-treated human (LX-2) HSC cells. Importantly, we observed that downregulating HOXC8 alleviates liver fibrosis and suppressed the fibrogenic gene induction induced by CCl4 in vivo. In addition, inhibition of HOXC8 suppressed the HSC activation and the expression of fibrosis-associated genes (α-SMA and COL1a1) induced by TGF-ß1 in LX-2 cells in vitro, while HOXC8 overexpression had the opposite effects. Mechanistically, we demonstrated HOXC8 activates TGFß1 transcription and enhanced the phosphorylated Smad2/Smad3 levels, suggesting a positive feedback loop between HOXC8 and TGF-ß1 that facilitates TGF-ß signaling and subsequent HSCs activation. Collectively, our data strongly indicated that a HOXC8/TGF-ß1 positive feedback loop plays as a critical role in controlling the HSC activation and in the liver fibrosis process, suggesting that inhibition of HOXC8 may serve as a promoting therapeutic strategy for diseases characterized by liver fibrosis.

Defect-Rich Single Atom Catalyst Enhanced Polysulfide Conversion Kinetics to Upgrade Performance of Li-S Batteries.

Lithium-sulfur (Li-S) batteries have attracted considerable attention owing to their extremely high energy densities. However, the application of Li-S batteries has been limited by low sulfur utilization, poor cycle stability, and low rate capability. Accelerating the rapid transformation of polysulfides is an effective approach for addressing these obstacles. In this study, a defect-rich single-atom catalytic material (Fe-N4/DCS) is designed. The abundantly defective environment is favorable for the uniform dispersion and stable existence of single-atom Fe, which not only improves the utilization of single-atom Fe but also efficiently adsorbs polysulfides and catalyzes the rapid transformation of polysulfides. To fully exploit the catalytic activity, catalytic materials are used to modify the routine separator (Fe-N4 /DCS/PP). Density functional theory and in situ Raman spectroscopy are used to demonstrate that Fe-N4 /DCS can effectively inhibit the shuttling of polysulfides and accelerate the redox reaction. Consequently, the Li-S battery with the modified separator achieves an ultralong cycle life (a capacity decay rate of only 0.03% per cycle at a current of 2 C after 800 cycles), and an excellent rate capability (894 mAh g-1 at 3 C). Even at a high sulfur loading of 5.51 mg cm-2 at 0.2 C, the reversible areal capacity still reaches 5.4 mAh cm-2 .

Beauvericin exerts an anti-tumor effect on hepatocellular carcinoma by inducing PI3K/AKT-mediated apoptosis.

Beauvericin is a world-spread mycotoxin isolated from the traditional Chinese medicine, Bombyx batryticatus (BB), which has been widely used to treat various neoplastic diseases. This study investigated the anti-hepatocellular carcinoma (HCC) activity of beauvericin and its potential mechanism. In this study, H22-bearing mice were intraperitoneally injected with 3, 5, 7 mg/kg of beauvericin once per-week over a three-week period. TUNEL staining determined the extent of tumor apoptosis induced by beauvericin. ELISA kits detected the level of IL-2, Perforin, and TNF-α, IFN-γ level in the serum. H22 hepatoma cells were exposed to beauvericin (5, 10, and 20 µmol/L) to investigate the underlying pathway. CCK-8 assay was used to observe the influence of beauvericin on the growth of H22 cells. Flow cytometry was used to detect the cell apoptosis and ROS level. Western blotting was performed to detect apoptotic and PI3K/AKT pathway protein production. The results showed that beauvericin could remarkably inhibit the growth of HCC in mice, combined with elevated TNF-α and IL-2. In vitro, beauvericin significantly promoted the generation of ROS, up-regulated Bax/Bcl-2 ratio and cleaved caspase-9, cleaved caspase-3 levels, down-regulated p-PI3K/PI3K ratio, p-AKT/AKT ratio, promoted the apoptosis of H22 cells, and inhibited the growth of H22 cells. Remarkably, treatment with PI3K/AKT activator (740Y-P and SC79) could prevent beauvericin-induced H22 cell apoptosis. These findings collectively indicate that beauvericin inhibits HCC growth by inducing apoptosis via the PI3K/AKT pathway.

RHBDF1 deficiency suppresses melanoma glycolysis and enhances efficacy of immunotherapy by facilitating glucose-6-phosphate isomerase degradation via TRIM32.

Melanoma is a dangerous form of skin cancer, making it important to investigate new mechanisms and approaches to enhance the effectiveness of treatment. Here, we establish a positive correlation between the human rhomboid family-1 (RHBDF1) protein and melanoma malignancy. We demonstrate that the melanoma RHBDF1 decrease dramatically inhibits tumor growth and the development of lung metastases, which may be related to the impaired glycolysis. We show that RHBDF1 function is essential to the maintenance of high levels of glycolytic enzymes, especially glucose-6-phosphate isomerase (GPI). Additionally, we discover that the E3 ubiquitin ligase tripartite motif-containing 32 (TRIM32) mediates the K27/K63-linked ubiquitination of GPI and the ensuing lysosomal degradation process. We prove that the multi-transmembrane domain of RHBDF1 is in competition with GPI, preventing the latter from interacting with NCL1-HT2A-LIN41 (NHL) domain of TRIM32. We also note that the mouse RHBDF1's R747 and Y799 are crucial for competitive binding and GPI protection. Artificially silencing the Rhbdf1 gene in a mouse melanoma model results in declined lactic acid levels, elevated cytotoxic lymphocyte infiltration, and improved tumor responsiveness to immunotherapy. These results provide credence to the hypothesis that RHBDF1 plays a significant role in melanoma regulation and suggest that blocking RHBDF1 may be an efficient technique for reestablishing the tumor immune microenvironment (TIME) in melanoma and halting its progression.

Contribution and Effects of PM2.5-Bound Lead to the Cardiovascular Risk of Workers in a Non-Ferrous Metal Smelting Area Considering Chemical Speciation and Bioavailability.

Lead is known to have toxic effects on the cardiovascular system. Owing to its high concentration, transmission range, and absorption efficiency in organisms, inhalation of fine particulate matter (PM2.5)-bound lead (PM2.5-Pb) may cause significant cardiovascular damage. However, the contribution and adverse effects of PM2.5-Pb on workers and residents in non-ferrous metal smelting areas are not fully understood. In this work, the concentration and chemical speciation of PM2.5-Pb were analyzed to determine its pollution characteristics at a typical non-ferrous metal smelting site. A panel study conducted among factory workers revealed that PM2.5-Pb exposure makes an important contribution to the human absorption of Pb. Although the chemical speciation of PM2.5-Pb suggested poor water solubility, a high bioavailability was observed in mice (tissue average value: 50.1%, range: 31.1-71.1%) subjected to inhalation exposure for 8 weeks. Based on the bioavailability data, the relationship between PM2.5-Pb exposure and cardiovascular damage was evaluated in animal simulation experiments. Finally, a damage threshold and cardiovascular-specific risk assessment model were established for the non-ferrous metal smelting area. Our project not only accurately estimates the risk of PM2.5-bound heavy metals on the cardiovascular system but also offers a scientific basis for future prevention and therapy of PM2.5-Pb-related diseases.

Effect of ibuprofen (IBU) on the sulfur-based and calcined pyrite-based autotrophic denitrification (SCPAD) systems with two filling modes: Performance and toxic response mechanism.

To investigate the effect of ibuprofen (IBU) on the sulfur-based and calcined pyrite-based autotrophic denitrification (SCPAD) systems, two individual reactors with the layered filling (L-SCPAD) and mixed filling (M-SCPAD) systems were established via sulfur and calcined pyrite. Effluent NO3--N concentration of the L-SCPAD and M-SCPAD systems was first increased to 6.44, 0.93 mg/L under 0.5 mg/L IBU exposure and gradually decreased to 1.66 mg/L, 0 mg/L under 4.0 mg/L IBU exposure, indicating that NO3--N removal performance of the M-SCPAD system was better than that of the L-SCPAD system. The variation of extracellular polymeric substances (EPS) characteristics demonstrated that more EPS was secreted in the M-SCPAD system compared to the L-SCPAD system, which contributed to forming a more stable biofilm structure and protecting microorganisms against the toxicity of IBU in the M-SCPAD system. Moreover, the increased electron transfer impedance and decreased cytochrome c implied that IBU inhibited the electron transfer efficiency of the L-SCPAD and M-SCPAD systems. The decreased adenosine triphosphate (ATP) and electron transfer system activity (ETSA) content showed that IBU inhibited metabolic activity, but the M-SCPAD system exhibited higher metabolic activity compared to the L-SCPAD system. In addition, the analysis of the bacterial community indicated a more stable abundance of nitrogen removal function bacteria (Bacillus) in the M-SCPAD system compared to the L-SCPAD system, which was conducive to maintaining a stable denitrification performance. The toxic response mechanism based on the biogeobattery effect was proposed in the SCPAD systems under IBU exposure. This study provided an important reference for the long-term toxic effect of IBU on the SCPAD systems.

Integration of transcriptome and metabolome analyses reveals the role of OsSPL10 in rice defense against brown planthopper.

KEY MESSAGE: OsSPL10 is a negative regulator of rice defense against BPH, knockout of OsSPL10 enhances BPH resistance through upregulation of defense-related genes and accumulation of secondary metabolites. Rice (Oryza sativa L.), one of the most important staple foods worldwide, is frequently attacked by various herbivores, including brown planthopper (BPH, Nilaparvata lugens). BPH is a typical monophagous, phloem-sucking herbivore that has been a substantial threat to rice production and global food security. Understanding the regulatory mechanism of defense responses to BPH is essential for improving BPH resistance in rice. In this study, a SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE 10 (OsSPL10) transcription factor was found to play a negative role in the defenses of rice against BPH. To gain insights into the molecular and biochemical mechanisms of OsSPL10, we performed combined analyses of transcriptome and metabolome, and revealed that knockout of OsSPL10 gene improved rice resistance against BPH by enhancing the direct and indirect defenses. Genes involved in plant hormone signal transduction, MAPK signaling pathway, phenylpropanoid biosynthesis, and plant-pathogen interaction pathway were significantly upregulated in spl10 mutant. Moreover, spl10 mutant exhibited increased accumulation of defense-related secondary metabolites in the phenylpropanoid and terpenoid pathways. Our findings reveal a novel role for OsSPL10 gene in regulating the rice defense responses, which can be used as a potential target for genetic improvement of BPH resistance in rice.

Developmental neurotoxic effects of bisphenol A and its derivatives in Drosophila melanogaster.

As a result of the ban on bisphenol A (BPA), a hormone disruptor with developmental neurotoxicity, several BPA derivatives (BPs) have been widely used in industrial production. However, there are no effective methods for assessing the neurodevelopmental toxic effects of BPs. To address this, a Drosophila exposure model was established, and W1118 was reared in food containing these BPs. Results showed that each BPs displayed different semi-lethal doses ranging from 1.76 to 19.43 mM. Exposure to BPs delayed larval development and affected axonal growth, resulting in the abnormal crossing of the midline of axons in the ß lobules of mushroom bodies, but the damage caused by BPE and BPF was relatively minor. BPC, BPAF, and BPAP have the most significant effects on locomotor behavior, whereas BPC exhibited the most affected social interactions. Furthermore, exposure to high-dose BPA, BPC, BPS, BPAF, and BPAP also significantly increased the expression of Drosophila estrogen-related receptors. These demonstrated that different kinds of BPs had different levels of neurodevelopmental toxicity, and the severity was BPZ > BPC and BPAF > BPB > BPS > BPAP ≈ BPAl ≈ BPF > BPE. Therefore, BPZ, BPC, BPS, BPAF, and BPAP should be evaluated as potential alternatives to BPA.

Bridge Model Updating Based on Wavelet Neural Network and Wind-Driven Optimization.

Aging, corrosive environments, and inadequate maintenance may result in performance deterioration of civil infrastructures, and finite element model updating is a commonly employed structural health monitoring procedure in civil engineering to reflect the current situation and to ensure the safety and serviceability of structures. Using the finite element model updating process to obtain the relationship between the structural responses and updating parameters, this paper proposes a method of using the wavelet neural network (WNN) as the surrogate model combined with the wind-driven optimization (WDO) algorithm to update the structural finite element model. The method was applied to finite element model updating of a continuous beam structure of three equal spans to verify its feasibility, the results show that the WNN can reflect the nonlinear relationship between structural responses and the parameters and has an outstanding simulation performance; the WDO has an excellent ability for optimization and can effectively improve the efficiency of model updating. Finally, the method was applied to update a real bridge model, and the results show that the finite element model update based on WDO and WNN is applicable to the updating of a multi-parameter bridge model, which has practical significance in engineering and high efficiency in finite element model updating. The differences between the updated values and measured values are all within the range of 5%, while the maximum difference was reduced from -10.9% to -3.6%. The proposed finite element model updating method is applicable and practical for multi-parameter bridge model updating and has the advantages of high updating efficiency, reliability, and practical significance.

Effects of multicomponent exercise on quality of life, depression and anxiety among stroke survivors: A systematic review and meta-analysis.

BACKGROUND: Current guidelines stress the importance of exercise, especially multicomponent exercise to older adults with chronic conditions. AIM: To critically synthesise evidence that evaluates the effects of multicomponent exercise on quality of life, depression and anxiety after stroke. DESIGN: Systematic review and meta-analysis followed the PRISMA 2020 statement. METHODS: A systematic search of PubMed, Embase, Web of Science, Cochrane Library, CINAHL and PsycINFO from inception to 12 June 2023 was performed. Risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomised trials (RoB 2). Meta-analyses were conducted using Review Manager 5.4 and narrative syntheses were adopted whenever meta-analysis was inappropriate. The overall certainty of the evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Of 15,351 records identified, nine were eligible and data were available for seven randomised controlled trials, three of which were identified as having a high risk of bias, one as low risk, and five as having some concerns. Subgroup pooled analyses indicated that multicomponent exercise engaged in longer exercise sessions (>60 min) was effective in improving quality of life immediately post-intervention and through 3-6 months post-intervention. However, multicomponent exercise did not significantly affect depression and anxiety. CONCLUSIONS: Multicomponent exercise with longer duration of exercise sessions has promising effects on both short- to medium-term quality of life among stroke survivors. PATIENT OR PUBLIC CONTRIBUTION: This does not apply to our work as it is a review paper. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers could consider encouraging the patients to participate in multicomponent exercise sessions for more than 60 min. It is important to note that stroke survivors should be supervised by trained personnel at the beginning of the training. REGISTRATION: The protocol was registered on PROSPERO.

Responses of anammox and sulfur/pyrite autotrophic denitrification in one-stage system to high nitrogen load: Performance, metabolic and bacterial community.

To remove residual nitrate from anammox process and achieve efficient nitrogen removal, a two-stage system (TAS) with the two individual reactors and a one-stage system (OAS) with the spatial functional areas in one reactor were established via anammox coupling sulfur autotrophic denitrification. The total nitrogen removal efficiency (TNRE) of OAS system (97.85 ± 1.92%) was higher than that of TAS system (93.63 ± 1.87%) under the influent NH4+-N and NO2--N of 227 and 300 mg/L. Meanwhile, the responses of microbial metabolism to high nitrogen load were investigated in term of microbial metabolites, electron transfer and metabolic activity. Microbial metabolites characteristics demonstrated that the OAS system secreted more EPS with lower protein (PN)/polysaccharide (PS) ratio than that in the TAS system, which was beneficial to protect bacteria from high nitrogen load. Electrochemical analysis suggested that the secretion of electron conductive substance (such as PN, PS) and redox active substances (such as flavin mononucleotide, the binding of flavins and cytochrome c on the outer membrane) were increased in the OAS system, which promoted the electron transfer efficiency. Moreover, the electron transport system activity (ETSA) values and ATP contents in OAS system were higher than that in the TAS system, which indicated that metabolic activity was improved in OAS system under the stimulation of high nitrogen load. Additionally, the bacterial community analysis indicated that the functional bacteria of Candidatus_Kuenenia and Armatimonadetes_gp5 had higher abundance in the OAS system than that in the TAS system, which was beneficial to realize the stable nitrogen removal performance. Overall, the responses mechanism of the OAS system was established to explain the resistant to high nitrogen load.

Early mobilisation practice in intensive care units: A large-scale cross-sectional survey in China.

BACKGROUND: The field of early rehabilitation has developed slowly in mainland China and there are limited data on the implementation of early mobilisation (EM) practice in intensive care unit (ICUs) in China. AIMS: To investigate the implementation of EM in ICUs in mainland China and to analyse its influencing factors. STUDY DESIGN: A cross-sectional electronic survey was conducted in 444 ICUs across 11 provinces in China. Head nurses provided data on institutional characteristics and EM practice in ICUs. Logistic regression models were used to identify factors associated with the implementation of EM. RESULTS: In all, 56.98% (253/444) of ICUs implemented EM with comprehensive or complete implementation in 86 ICUs. Of the 191 ICUs that did not use EM, 136 planned to implement EM in the near future. Of the 253 ICUs that used EM, 21.34% of ICUs implemented EM for all eligible patients, while 24.90% would evaluate and carry out EM within 48 h after ICU admission, 39.13% had collaborative EM teams, 34.39% reported the use of EM protocols, 14.63% reported multidisciplinary rounds and 17.39% had medical orders and charging standards for all EM activities. Only 18.18% of ICUs conducted frequent professional training for EM, and abnormal events occurred in 15.41% of ICUs during EM practice. Multivariate logistic regression analysis revealed that an economically strong province, the presence of a dedicated therapist team, more ICU beds and a higher staff-to-bed ratio favoured the implementation of EM. Furthermore, multidisciplinary rounds, well-established medical orders and charging standards, and a high frequency of professional training can lead to the comprehensive promotion and development of EM practice in ICUs. CONCLUSIONS: Both the implementation rate and quality of EM practice for critically ill patients require improvement. EM practice in Chinese ICUs is still nascent and requires development in a variety of domains. RELEVANCE TO CLINICAL PRACTICE: To facilitate the implementation of EM in ICUs, more human resources, especially the involvement of a professional therapist team, should be deployed. In addition, health providers should actively organize multidisciplinary rounds and professional training and formulate appropriate EM medical orders and charging standards.