Revealing operando surface defect-dependent electrocatalytic performance of Pt at the subparticle level.

Understanding the operando defect-tuning performance of catalysts is critical to establish an accurate structure-activity relationship of a catalyst. Here, with the tool of single-molecule super-resolution fluorescence microscopy, by imaging intermediate CO formation/oxidation during the methanol oxidation reaction process on individual defective Pt nanotubes, we reveal that the fresh Pt ends with more defects are more active and anti-CO poisoning than fresh center areas with less defects, while such difference could be reversed after catalysis-induced step-by-step creation of more defects on the Pt surface. Further experimental results reveal an operando volcano relationship between the catalytic performance (activity and anti-CO ability) and the fine-tuned defect density. Systematic DFT calculations indicate that such an operando volcano relationship could be attributed to the defect-dependent transition state free energy and the accelerated surface reconstructing of defects or Pt-atom moving driven by the adsorption of the CO intermediate. These insights deepen our understanding to the operando defect-driven catalysis at single-molecule and subparticle level, which is able to help the design of highly efficient defect-based catalysts.

An immunogenic cell death-related gene expression signature in predicting prognosis of pancreatic ductal adenocarcinoma.

BACKGROUND: Immunogenic cell death (ICD) has been identified as regulated cell death, which is sufficient to activate the adaptive immune response. This study aimed to research ICD-related genes and create a gene model to predict pancreatic ductal adenocarcinoma (PAAD) patients' prognosis. METHODS: The RNA sequencing and clinical data were downloaded from the TGCA and GEO databases. The PAAD samples were classified into two subtypes based on the expression levels of ICD-related genes using consensus clustering. Based on the differentially expressed genes (DEGs), a prognostic scoring model was constructed using LASSO regression and Cox regression, and the scoring model was used to predict the prognosis of PAAD patients. Moreover, colony formation assay was performed to confirm the prognostic value of those genes. RESULTS: We identified two ICD cluster by consensus clustering, and found that the the ICD-high group was closely associated with immune-hot phenotype, favorable clinical outcomes. We established an ICD-related prognostic model which can predict the prognosis of pancreatic ductal adenocarcinoma. Moreover, depletion of NT5E, ATG5, FOXP3, and IFNG inhibited the colony formation ability of pancreatic cancer cell. CONCLUSION: We identified a novel classification for PAAD based on the expression of ICD-related genes, which may provide a potential strategy for therapeutics against PAAD.

Tethered Helical Ladder-Type Aromatic Lactams.

Tethered nonplanar aromatics (TNAs) make up an important class of nonplanar aromatic compounds showing unique features. However, the knowledge on the synthesis, structures, and properties of TNAs remains insufficient. In this work, a new type of TNAs, the tethered aromatic lactams, is synthesized via Pd-catalyzed consecutive intramolecular direct arylations. These molecules possess a helical ladder-type conjugated system of up to 13 fused rings. The overall yields ranged from 3.4 to 4.3%. The largest of the tethered aromatic lactams, 6L-Bu-C14, demonstrates a guest-adaptive hosting capability of TNAs for the first time. When binding fullerene guests, the cavity of 6L-Bu-C14 became more circular to better accommodate spherical fullerene molecules. The host-guest interaction is thoroughly studied by X-ray crystallography, theoretical calculations, fluorescence titration, and nuclear magnetic resonance (NMR) titration experiments. 6L-Bu-C14 shows stronger binding with C70 than with C60 due to the better convex-concave π-π interaction. P and M enantiomers of all tethered aromatic lactams show distinct and persistent chiroptical properties and demonstrate the potential of chiral TNAs as circularly polarized luminescence (CPL) emitters.

Prognostic value of baseline neutrophil/lymphocyte ratio in HER2-positive metastatic breast cancer: exploratory analysis of data from the CLEOPATRA trial.

PURPOSE: This study aimed to evaluate the prognostic role of the baseline neutrophil/lymphocyte ratio (NLR) in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab/pertuzumab. EXPERIMENTAL DESIGN: Data from 780 patients from the CLEOPATRA trial and 248 local patients were collected. Patients were divided into the low and high NLR subgroups by the NLR cutoff value. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) methods were used to control bias. Associations between the NLR and progression-free survival (PFS) and overall survival (OS) were analyzed. RESULTS: The baseline characteristics of the subgroups were well balanced after PSM and IPTW. A low baseline NLR was associated with better PFS and OS in the trastuzumab and docetaxel (TH) group in the unadjusted, PSM and IPTW models. After IPTW, a low NLR, versus a high NLR, was associated with improved PFS (HR 1.35, 95% CI 1.07-1.70, P = 0.012) and OS (HR 1.47, 95% CI 1.12-1.94, P = 0.006) in the TH group. In patients undergoing treatment with trastuzumab and pertuzumab and docetaxel (THP), a low baseline NLR was also correlated with better PFS but not OS across the three models. After IPTW, a low NLR was associated with better PFS (HR 1.52, 95% CI 1.20-1.93, P = 0.001) than a high NLR in the THP group. Multivariate analyses showed that a low baseline NLR was a predictor for PFS and OS in the TH group and for PFS in the THP group in all three models. In the real-world setting, a low baseline NLR was a predictor of better PFS among patients treated with docetaxel plus trastuzumab without or with pertuzumab in the multivariate model (P = 0.015 and 0.008, respectively). CONCLUSIONS: A low baseline NLR is associated with better survival outcomes among HER2-positive MBC patients receiving docetaxel plus trastuzumab/pertuzumab as first-line therapy.

Decreased NMIIA heavy chain phosphorylation at S1943 promotes mitoxantrone resistance by upregulating BCRP and N-cadherin expression in breast cancer cells.

Mitoxantrone (MX) is an effective treatment for breast cancer; however, high efflux of MX that is accomplished by breast cancer resistance protein (BCRP) leads to acquired multidrug resistance (MDR), reducing MX's therapeutic efficacy in breast cancer. Non-muscle myosin IIA (NMIIA) and its heavy phosphorylation at S1943 have been revealed to play key roles in tumor metastasis and progression, including in breast cancer; however, their molecular function in BCRP-mediated MDR in breast cancer remains unknown. In this study, we revealed that the expression of NMIIA heavy chain phosphorylation at S1943 was downregulated in BCRP-overexpressing breast cancer MCF-7/MX cells, and stable expression of NMIIA-S1943A mutant increased BCRP expression and promoted the resistance of MCF-7/MX cells to MX. Meanwhile, NMIIA S1943 phosphorylation induced by epidermal growth factor (EGF) was accompanied by the downregulation of BCRP in MCF-7/MX cells. Furthermore, stable expression of NMIIA-S1943A in MCF-7/MX cells resulted in upregulation of N-cadherin and the accumulation of ß-catenin on the cell surface, which inhibited the nucleus translocation of ß-catenin and Wnt/ß-catenin-based proliferative signaling. EGF stimulation of MCF-7/MX cells showed the downregulation of N-cadherin and ß-catenin. Our results suggest that decreased NMIIA heavy phosphorylation at S1943 increases BCRP expression and promotes MX resistance in breast cancer cells via upregulating N-cadherin expression.

A Sequentially Activated Probe for Imaging of Superoxide Anion and Peroxynitrite in PC12 Cells under Oxidative Stress.

Superoxide anion (O2·-) and peroxynitrite (ONOO-), two important oxidants under oxidative stress, coexist in complex cell and organism systems, playing crucial roles in various physiological and pathological processes, particularly in neurodegenerative diseases. Despite the absence of robust molecular tools capable of simultaneously visualizing O2·- and ONOO- in biosystems, the relationship between these two species remains understudied. Herein, we present sequentially activated fluorescent probe, DHX-SP, which exhibits exceptional selectivity and sensitivity toward O2·- and ONOO-. This probe enables precise imaging of these species in living PC12 cells under oxidative stress conditions using distinct fluorescence signal combinations. Furthermore, the probe DHX-SP has the ability to visualize changes in O2·- and ONOO- levels during ferroptosis of PC12 cells and in the Parkinson's disease model. These findings establish a connection between the crosstalk of the phosphorus group of O2·- and ONOO- in PC12 cells under oxidative stress.

Twin Boundaries-Induced Centrosymmetric Breaking of Hollow CaTiO3 Nanocuboids for Piezocatalytic Hydrogen Evolution.

Piezocatalysis, a transformative mechanochemical energy conversion technique, has received considerable attention over the past decade for its role in processes such as hydrogen evolution from water. Despite notable progress in the field, challenges remain, particularly in the areas of limited piezocatalysis efficiency and limited availability of materials requiring a non-centrosymmetric structure. Here, a pioneering contribution is presented by elucidating the piezocatalytic properties of hollow CaTiO3 nanocuboids, a centrosymmetric material with a nominally nonpolar state. Remarkably, CaTiO3 nanocuboids exhibit an impressive hydrogen production rate of 3.44 mmol g-1 h-1 under ultrasonic vibrations, surpassing the performance of the well-established piezocatalyst BaTiO3 (2.23 mmol g-1 h-1). In contrast, commercial CaTiO3 nanoparticles do not exhibit piezocatalytic performance. The exceptional performance of hollow CaTiO3 nanocuboids is attributed to the abundance presence of twin boundaries on the {110} facet within its crystal structure, which can impart significant polarization strength to CaTiO3. Extending the investigation to other centrosymmetric materials, such as SrZrO3 and BaZrO3, the experimental results also demonstrate their commendable properties for piezocatalytic hydrogen production from water. This research underscores the significant potential of centrosymmetric materials in piezocatalysis.

Integrated physiological, transcriptomic and metabolomic analyses reveal the mechanism of peanut kernel weight reduction under waterlogging stress.

Waterlogging stress (WS) hinders kernel development and directly reduces peanut yield; however, the mechanism of kernel filling in response to WS remains unknown. The waterlogging-sensitive variety Huayu 39 was subjected to WS for 3 days at 7 days after the gynophores touched the ground (DAG). We found that WS affected kernel filling at 14, 21, and 28 DAG. WS decreased the average filling rate and kernel dry weight, while transcriptome sequencing and widely targeted metabolomic analysis revealed that WS inhibited the gene expression in starch and sucrose metabolism, which reduced sucrose input and transformation ability. Additionally, genes related to ethylene and melatonin synthesis and the accumulation of tryptophan and methionine were upregulated in response to WS. WS upregulated the expression of the gene encoding tryptophan decarboxylase (AhTDC), and overexpression of AhTDC in Arabidopsis significantly reduced the seed length, width, and weight. Therefore, WS reduced the kernel-filling rate, leading to a reduction in the 100-kernel weight. This survey informs the development of measures that alleviate the negative impact of WS on peanut yield and quality and provides a basis for exploring high-yield and high-quality cultivation, molecular-assisted breeding, and waterlogging prevention in peanut farming.

Mapping dynamic molecular changes in hippocampal subregions after traumatic brain injury through spatial proteomics.

BACKGROUND: Traumatic brain injury (TBI) often results in diverse molecular responses, challenging traditional proteomic studies that measure average changes at tissue levels and fail to capture the complexity and heterogeneity of the affected tissues. Spatial proteomics offers a solution by providing insights into sub-region-specific alterations within tissues. This study focuses on the hippocampal sub-regions, analyzing proteomic expression profiles in mice at the acute (1 day) and subacute (7 days) phases of post-TBI to understand subregion-specific vulnerabilities and long-term consequences. METHODS: Three mice brains were collected from each group, including Sham, 1-day post-TBI and 7-day post-TBI. Hippocampal subregions were extracted using Laser Microdissection (LMD) and subsequently analyzed by label-free quantitative proteomics. RESULTS: The spatial analysis reveals region-specific protein abundance changes, highlighting the elevation of FN1, LGALS3BP, HP, and MUG-1 in the stratum moleculare (SM), suggesting potential immune cell enrichment post-TBI. Notably, established markers of chronic traumatic encephalopathy, IGHM and B2M, exhibit specific upregulation in the dentate gyrus bottom (DG2) independent of direct mechanical injury. Metabolic pathway analysis identifies disturbances in glucose and lipid metabolism, coupled with activated cholesterol synthesis pathways enriched in SM at 7-Day post-TBI and subsequently in deeper DG1 and DG2 suggesting a role in neurogenesis and the onset of recovery. Coordinated activation of neuroglia and microtubule dynamics in DG2 suggest recovery mechanisms in less affected regions. Cluster analysis revealed spatial variations post-TBI, indicative of dysregulated neuronal plasticity and neurogenesis and further predisposition to neurological disorders. TBI-induced protein upregulation (MUG-1, PZP, GFAP, TJP, STAT-1, and CD44) across hippocampal sub-regions indicates shared molecular responses and links to neurological disorders. Spatial variations were demonstrated by proteins dysregulated in both or either of the time-points exclusively in each subregion (ELAVL2, CLIC1 in PL, CD44 and MUG-1 in SM, and SHOC2, LGALS3 in DG). CONCLUSIONS: Utilizing advanced spatial proteomics techniques, the study unveils the dynamic molecular responses in distinct hippocampal subregions post-TBI. It uncovers region-specific vulnerabilities and dysregulated neuronal processes, and potential recovery-related pathways that contribute to our understanding of TBI's neurological consequences and provides valuable insights for biomarker discovery and therapeutic targets.

Extracellular vesicles of Bacteroides fragilis regulated macrophage polarization through promoted Sema7a expression.

Abnormal activation of macrophage and gut Bacteroides fragilis (BF) are the important induction factors in the occurrence of type 2 diabetes (T2D) and vascular complications. However, it remains unknown whether BF involves in macrophage polarization. In this study, we found that BF extracellular vesicles (EV) can be uptaken by macrophage. BF-EV promote macrophage M1/M2 polarization significantly, and increase Sting expression significantly. Bioinformatics analysis found that Sema7a is an important gene involving in macrophage polarization. The expression of Sema7a can be induced by BF-EV and can be inhibited after C-176 treated. The inhibition expression of Sema7a prevent BF-EV to induce macrophage polarization. Further analysis reveals that there is no direct interaction between Sting and Sema7a, but Sgpl1 can interact with Sting or Sema7a. BF-EV promote the expression of Sgpl1, which the phenomenon can be inhibited after C-176 treated. Importantly, overexpression of Sgpl1 reversed the effect of C-176 for Sema7a expression, while inhibit Sema7a expression has limitation influence for Sting and Sgpl1 expression. In conclusion, this study confirms that Sting-Sgpl1-Sema7a is a key mechanism by which BF-EV regulates macrophage polarization.

B cells in head and neck squamous cell carcinoma: current opinion and novel therapy.

Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumour. Despite advancements in surgery, radiotherapy and chemotherapy, which have improved the prognosis of most patients, a subset of patients with poor prognoses still exist due to loss of surgical opportunities, postoperative recurrence, and metastasis, among other reasons. The tumour microenvironment (TME) is a complex organization composed of tumour, stromal, and endothelial cells. Communication and interaction between tumours and immune cells within the TME are increasingly being recognized as pivotal in inhibiting or promoting tumour development. Previous studies on T cells in the TME of HNSCC have yielded novel therapeutic possibilities. However, the function of B cells, another adaptive immune cell type, in the TME of HNSCC patients has yet to be determined. Recent studies have revealed various distinct subtypes of B cells and tertiary lymphoid structures (TLSs) in the TME of HNSCC patients, which are believed to impact the efficacy of immune checkpoint inhibitors (ICIs). Therefore, this paper focuses on B cells in the TME to explore potential directions for future immunotherapy for HNSCC.

Metal Clusters Based Multifunctional Materials for Solar Cells.

As a multifunctional material, metal clusters have recently received some attention for their application in solar cells.This review delves into the multifaceted role of metal clusters in advancing solar cell technologies, covering diverse aspects from electron transport and interface modification to serving as molecular precursors for inorganic materials and acting as photosensitizers in metal-cluster sensitized solar cells (MCSSCs). The studies conducted by various researchers illustrate the crucial impact of metal clusters, such as gold nanoclusters (Au NCs), on enhancing solar cell efficiency through size-dependent effects, distinct interface behaviors, and tailored interface engineering. From optimizing charge transfer rates to improving light absorption and reducing carrier recombination, metal clusters prove instrumental in shaping the landscape of solar energy conversion.The promising performance of metal-cluster sensitized solar cells, coupled with their scalability and flexibility, positions them as a exciting avenue for future clean energy applications. The article concludes by emphasizing the need for continued interdisciplinary research and technological innovation to unlock the full potential of metal clusters in contributing to sustainable and high-performance solar cells.

Transformation to small cell lung cancer is irrespective of EGFR and accelerated by SMAD4-mediated ASCL1 transcription independently of RB1 in non-small cell lung cancer.

OBJECTIVES: Histological transformation to small cell lung cancer (SCLC) has been identified as a mechanism of TKIs resistance in EGFR-mutant non-small cell lung cancer (NSCLC). We aim to explore the prevalence of transformation in EGFR-wildtype NSCLC and the mechanism of SCLC transformation, which are rarely understood. METHODS: We reviewed 1474 NSCLC patients to investigate the NSCLC-to-SCLC transformed cases and the basic clinical characteristics, driver gene status and disease course of them. To explore the potential functional genes in SCLC transformation, we obtained pre- and post-transformation specimens and subjected them to a multigene NGS panel involving 416 cancer-related genes. To validate the putative gene function, we established knocked-out models by CRISPR-Cas 9 in HCC827 and A549-TP53-/- cells and investigated the effects on tumor growth, drug sensitivity and neuroendocrine phenotype in vitro and in vivo. We also detected the expression level of protein and mRNA to explore the molecular mechanism involved. RESULTS: We firstly reported an incidence rate of 9.73% (11/113) of SCLC transformation in EGFR-wildtype NSCLC and demonstrated that SCLC transformation is irrespective of EGFR mutation status (P = 0.16). We sequenced 8 paired tumors and identified a series of mutant genes specially in transformed SCLC such as SMAD4, RICTOR and RET. We firstly demonstrated that SMAD4 deficiency can accelerate SCLC transition by inducing neuroendocrine phenotype regardless of RB1 status in TP53-deficient NSCLC cells. Further mechanical experiments identified the SMAD4 can regulate ASCL1 transcription competitively with Myc in NSCLC cells and Myc inhibitor acts as a potential subsequent treatment agent. CONCLUSIONS: Transformation to SCLC is irrespective of EFGR status and can be accelerated by SMAD4 in non-small cell lung cancer. Myc inhibitor acts as a potential therapeutic drug for SMAD4-mediated resistant lung cancer. Video Abstract.

Fat accumulation in striped hamsters (Cricetulus barabensis) reflects the temperature of prior cold acclimation.

BACKGROUND: Proper adjustments of metabolic thermogenesis play an important role in thermoregulation in endotherm to cope with cold and/or warm ambient temperatures, however its roles in energy balance and fat accumulation remain uncertain. Our study aimed to investigate the effect of previous cold exposure (10 and 0 °C) on the energy budgets and fat accumulation in the striped hamsters (Cricetulus barabensis) in response to warm acclimation. The body mass, energy intake, resting metabolic rate (RMR) and nonshivering thermogenesis (NST), serum thyroid hormone levels (THs: T3 and T4), and the activity of brown adipose tissue (BAT), indicated by cytochrome c oxidase (COX) activity and uncoupling protein 1 (ucp1) expression, were measured following exposure to the cold (10 °C and 0 °C) and transition to the warm temperature (30 °C). RESULTS: The hamsters at 10 °C and 0 °C showed significant increases in energy intake, RMR and NST, and a considerable reduction in body fat than their counterparts kept at 21 °C. After being transferred from cold to warm temperature, the hamsters consumed less food, and decreased RMR and NST, but they significantly increased body fat content. Interestingly, the hamsters that were previously exposed to the colder temperature showed significantly more fat accumulation after transition to the warm. Serum T3 levels, BAT COX activity and ucp1 mRNA expression were significantly increased following cold exposure, and were considerably decreased after transition to the warm. Furthermore, body fat content was negatively correlated with serum T3 levels, BAT COX activity and UCP1 expression. CONCLUSION: The data suggest that the positive energy balance resulting from the decreased RMR and NST in BAT under the transition from the cold to the warm plays important roles in inducing fat accumulation. The extent of fat accumulation in the warm appears to reflect the temperature of the previous cold acclimation.

Melatonin restores hepatic lipid metabolic homeostasis disrupted by blue light at night in high-fat diet-fed mice.

Artificial light at night (ALAN) is an emerging environmental pollutant that threatens public health. Recently, ALAN has been identified as a risk factor for obesity; however, the role of ALAN and its light wavelength in hepatic lipid metabolic homeostasis remains undetermined. We showed that chronic dim (~5 lx) ALAN (dLAN) exposure significantly promoted hepatic lipid accumulation in obese or diabetic mice, with the most severe effect of blue light and little effect of green or red light. These metabolic phenotypes were attributed to blue rather than green or red dLAN interfering with hepatic lipid metabolism, especially lipogenesis and lipolysis. Further studies found that blue dLAN disrupted hepatic lipogenesis and lipolysis processes by inhibiting hepatic REV-ERBs. Mechanistically, feeding behavior mediated the regulation of dLAN on hepatic REV-ERBs. In addition, different effects of light wavelengths at night on liver REV-ERBs depended on the activation of the corticosterone (CORT)/glucocorticoid receptor (GR) axis. Blue dLAN could activate the CORT/GR axis significantly while other wavelengths could not. Notably, we demonstrated that exogenous melatonin could effectively inhibit hepatic lipid accumulation and restore the hepatic GR/REV-ERBs axis disrupted by blue dLAN. These findings demonstrate that dLAN promotes hepatic lipid accumulation in mice via a short-wavelength-dependent manner, and exogenous melatonin is a potential therapeutic approach. This study strengthens the relationship between ALAN and hepatic lipid metabolism and provides insights into directing ambient light.

Superhydrophilic Dendritic FeP/Cu3P Electrocatalyst for Urea Splitting via the Intramolecular Mechanism.

The electrocatalytic overall urea splitting can achieve the dual goals of urea treatment and hydrogen energy acquisition. Herein, we exploited the principle of precipitation dissolution equilibrium to obtain bimetallic phosphide FeP/Cu3P/CF for the simultaneous oxidation of urea and reduction of water and comprehensively reveal the inherent molecular thermodynamic mechanisms on the surface of catalysts. The excellent electrochemical performance can be derived from the super water affinity and synergistic effect. Especially, the theoretical calculation unveils that the synergistic effect between FeP and Cu3P can lower the activation energy required for urea electrooxidation, thereby promoting urea splitting. In situ differential electrochemical mass spectrometry (in situ DEMS) measurements further demonstrated that urea oxidation on FeP/Cu3P/CF proceeded according to the intramolecular mechanism. This work has laid the foundation for constructing highly efficient superhydrophilic bifunctional electrocatalysts.

Rewc-GNN Algorithm for the Property Prediction of Large-Scale Crystals.

The space group of a crystal describes the symmetry and periodic arrangement of its structure. As the fundamental element in the structure, it plays a vital role in determining the physical and chemical properties of crystals. The investigation of crystal space group information allows for the prediction of material properties, thereby providing guidance for material design and synthesis to enhance their performance or functionality. Currently prevalent first-principles-based computational methods exhibit good accuracy, but they rely heavily on computing resources, greatly limiting the efficiency of material screening. In this paper, our study is oriented toward the prediction the spatial group of crystals, and an algorithm named Rewc, based on graph neural networks (GNNs) is proposed. This algorithm encodes all atoms and the interactions between atoms in the crystal as features by combining Floyd algorithm and k-hop message passing and employs multilayer convolutional networks to extract connections between k layers. This allows for the automatic learning of more representative atomic vector representations through iterations of feature information for each atom and its neighbors. Experimental results demonstrate that the Rewc framework exhibits reliable accuracy and good generalization capabilities in predicting the crystal structure compared to previous GNN methods.

Monitoring of copper adsorption on biochar using spectral induced polarization method.

Copper contaminant generated from mining and industrial smelting poses potential risks to human health. Biochar, as a low-energy and cost-effective biomaterial, holds value in Cu remediation. Spectral Induced Polarization (SIP) technique is employed in this study to monitor the Cu remediation processes of by biochar in column experiments. Cation exchange at low Cu2+ concentrations and surface complexation at high Cu2+ concentrations are identified as the major mechanisms for copper retention on biochar. The normalized chargeability (mn) from SIP signals linearly decreased (R2 = 0.776) with copper retention under 60 mg/L Cu influent; while mn linearly increases (R2 = 0.907, 0.852) under high 300 and 700 mg/L Cu influents. The characteristic polarizing unit sizes (primarily the pores adsorbing Cu2+) calculated from Schwartz equation match well with experimental results by mercury intrusion porosimetry (MIP). It is revealed that Cu2+ was driven to small pores (∼3 µm) given high concentration gradient (influent Cu2+ concentration of 700 mg/L). Comparing to activated carbon, biochar is identified as an ideal adsorbent for Cu remediation, given its high adsorption capacity, cost-effectiveness, carbon-sink ability, and high sensitivity to SIP responses - the latter facilitates its performance assessment.

A Bayesian adaptive design approach for stepped-wedge cluster randomized trials.

BACKGROUND: The Bayesian group sequential design has been applied widely in clinical studies, especially in Phase II and III studies. It allows early termination based on accumulating interim data. However, to date, there lacks development in its application to stepped-wedge cluster randomized trials, which are gaining popularity in pragmatic trials conducted by clinical and health care delivery researchers. METHODS: We propose a Bayesian adaptive design approach for stepped-wedge cluster randomized trials, which makes adaptive decisions based on the predictive probability of declaring the intervention effective at the end of study given interim data. The Bayesian models and the algorithms for posterior inference and trial conduct are presented. RESULTS: We present how to determine design parameters through extensive simulations to achieve desired operational characteristics. We further evaluate how various design factors, such as the number of steps, cluster size, random variability in cluster size, and correlation structures, impact trial properties, including power, type I error, and the probability of early stopping. An application example is presented. CONCLUSION: This study presents the incorporation of Bayesian adaptive strategies into stepped-wedge cluster randomized trials design. The proposed approach provides the flexibility to stop the trial early if substantial evidence of efficacy or futility is observed, improving the flexibility and efficiency of stepped-wedge cluster randomized trials.

Polystyrene nano-plastics impede skeletal muscle development and induce lipid accumulation via the PPARγ/LXRß pathway in vivo and in vitro in mice.

Nano-plastics (NPs) have emerged as a significant environmental pollutant, widely existing in water environment, and pose a serious threat to health and safety with the intake of animals. Skeletal muscle, a vital organ for complex life activities and functional demands, has received limited attention regarding the effects of NPs. In this study, the effects of polystyrene NPs (PS-NPs) on skeletal muscle development were studied by oral administration of different sizes (1 mg/kg) of PS-NPs in mice. The findings revealed that PS-NPs resulted in skeletal muscle damage and significantly hindered muscle differentiation, exhibiting an inverse correlation with PS-NPs particle size. Morphological analysis demonstrated PS-NPs caused partial disruption of muscle fibers, increased spacing between fibers, and lipid accumulation. RT-qPCR and western blots analyses indicated that PS-NPs exposure downregulated the expression of myogenic differentiation-related factors (Myod, Myog and Myh2), activated PPARγ/LXRß pathway, and upregulated the expressions of lipid differentiation-related factors (SREBP1C, SCD-1, FAS, ACC1, CD36/FAT, ADIPOQ, C/EBPα and UCP-1). In vitro experiments, C2C12 cells were used to confirm cellular penetration of PS-NPs (0, 100, 200, 400 µg/mL) through cell membranes along with activation of PPARγ expression. Furthermore, to verify LXRß as a key signaling molecule, silencing RNA transfection experiments were conducted, resulting in no increase in the expressions of PPARγ, LXRß, SREBP1C, FAS, CD36/FAT, ADIPOQ, C/EBPα and UCP-1 even after exposure to PS-NPs. However, the expressions of SCD-1and ACC1 remained unaffected. The present study evidenced that exposure to PS-NPs induced lipid accumulation via the PPARγ/LXRß pathway thereby influencing skeletal muscle development.