Steering Geometric Reconstruction of Bismuth with Accelerated Dynamics for CO2 Electroreduction.

Bismuth-based materials have emerged as promising catalysts in the electrocatalytic reduction of CO2 to formate. However, the reasons for the reconstruction of Bi-based precursors to form bismuth nanosheets are still puzzling, especially the formation of defective bismuth sites. Herein, we prepare bismuth nanosheets with vacancy-rich defects (V-Bi NS) by rapidly reconstructing Bi19Cl3S27 under negative potential. Theoretical analysis reveals that the introduction of chlorine induces the generation of intrinsic electric field in the precursor, thereby increasing the electron transfer rate and further promoting the metallization of trivalent bismuth. Meanwhile, in situ Raman and ex situ XRD tests verify that Bi19Cl3S27 has a faster reconstruction rate than Bi2S3. The formed V-Bi NS exhibits up to 96% HCOO- Faraday efficiency and 400 mA cm-2 HCOO- partial current densities, and its ECSA normalized formate current density and yield are 2.2 times higher than those of intact bismuth nanosheets (I-Bi NS). Density functional theory (DFT) calculations indicate that bismuth vacancies with electron-rich aggregation reduce the activation energy of CO2 to *CO2- radicals and stabilize the adsorption of the key intermediate *OCHO, thus facilitating the reaction kinetics of formate production.

Association between protein intake, serum albumin and blood eosinophil in US asthmatic adults.

Background: Presently, numerous studies have indicated that protein consumption and levels of blood albumin serve as important biomarkers for a range of respiratory illnesses. However, there have been few investigations into the correlation between protein consumption, serum albumin, and asthma. Methods: Our analysis incorporated 2509 asthmatics from the 2011-2018 NHANES dataset. The investigation employed three linear regression models and XGBoost model to investigate the potential link between protein intake, serum albumin levels, and blood eosinophil counts (BEOC) in patients with asthma. The trend test, generalized additive model (GAM), and threshold effect model were utilized to validate this correlation. As well, we undertook stratified analyses to look at the correlation of serum albumin with BEOC among distinct populations. Results: In the univariable regression model, which did not account for any covariates, we observed a positive correlation between protein intake and BEOC. However, univariable and multivariable regression analyses all suggested a negative connection of serum albumin with BEOC in asthma populations. In Model C, which took into account all possible factors, BEOC dropped by 2.82 cells/uL for every unit increase in serum albumin (g/L). Additionally, the GAM and threshold effect model validated that serum albumin and BEOC showed an inverted U-shaped correlation. Conclusion: Our investigation discovered there was no independent link between asthmatics' protein intake and BEOC. However, we observed an inverted U-shaped relationship between serum albumin levels and BEOC, suggesting a possible relationship between the overall nutritional status of asthmatics and immune system changes. Our findings provide new directions for future research in the field of asthma management and therapy.

Interleukin-27 Promotes the Generation of Myeloid-derived Suppressor Cells to Alleviate Graft-versus-host Disease.

BACKGROUND: Stimulation of myeloid-derived suppressor cell (MDSC) formation represents a potential curative therapeutic approach for graft-versus-host disease (GVHD), which significantly impacts the prognosis of allogeneic hematopoietic stem cell transplantation. However, the lack of an effective strategy for inducing MDSC production in vivo has hindered their clinical application. In our previous study, MDSC expansion was observed in interleukin (IL)-27-treated mice. METHODS: In this study, we overexpressed exogenous IL-27 in mice using a recombinant adeno-associated virus vector to investigate its therapeutic and exacerbating effects in murine GVHD models. RESULTS: In our study, we demonstrated that exogenous administration of IL-27 significantly suppressed GVHD development in a mouse model. We found that IL-27 treatment indirectly inhibited the proliferation and activation of donor T cells by rapidly expanding recipient and donor myeloid cells, which act as MDSCs after irradiation or under inflammatory conditions, rather than through regulatory T-cell expansion. Additionally, IL-27 stimulated MDSC expansion by enhancing granulocyte-monocyte progenitor generation. Notably, we verified that IL-27 signaling in donor T cells exerted an antagonistic effect on GVHD prevention and treatment. Further investigation revealed that combination therapy involving IL-27 and T-cell depletion exhibited remarkable preventive effects on GVHD in both mouse and xenogeneic GVHD models. CONCLUSIONS: Collectively, these findings suggest that IL-27 promotes MDSC generation to reduce the incidence of GVHD, whereas targeted activation of IL-27 signaling in myeloid progenitors or its combination with T-cell depletion represents a potential strategy for GVHD therapy.

Heterophase Intermetallic Compounds for Electrocatalytic Hydrogen Production at Industrial-Scale Current Densities.

Heterophase nanomaterials have sparked significant research interest in catalysis due to their distinctive properties arising from synergistic effects of different components and the formed phase boundary. However, challenges persist in the controlled synthesis of heterophase intermetallic compounds (IMCs), primarily due to the lattice mismatch of distinct crystal phases and the difficulty in achieving precise control of the phase transitions. Herein, orthorhombic/cubic Ru2Ge3/RuGe IMCs with engineered boundary architecture are synthesized and anchored on the reduced graphene oxide. The Ru2Ge3/RuGe IMCs exhibit excellent hydrogen evolution reaction (HER) performance with a high current density of 1000 mA cm-2 at a low overpotential of 135 mV. The presence of phase boundaries enhances charge transfer and improves the kinetics of water dissociation while optimizing the processes of hydrogen adsorption/desorption, thus boosting the HER performance. Moreover, an anion exchange membrane electrolyzer is constructed using Ru2Ge3/RuGe as the cathode electrocatalyst, which achieves a current density of 1000 mA cm-2 at a low voltage of 1.73 V, and the activity remains virtually undiminished over 500 h.

Constructing Ru-O-TM Bridge in NiFe-LDH Enables High Current Hydrazine-assisted H2 Production.

Hydrazine oxidation-assisted water splitting is a critical technology to tackle the high energy consumption in large-scale H2 production. Ru-based electrocatalysts hold promise for synergetic hydrogen reduction (HER) and hydrazine oxidation (HzOR) catalysis but are hindered by excessive superficial adsorption of reactant intermediate. Herein, this work designs Ru cluster anchoring on NiFe-LDH (denoted as Ruc/NiFe-LDH), which effectively enhances the intermediate adsorption capacity of Ru by constructing Ru─O─Ni/Fe bridges. Notably, it achieves an industrial current density of 1 A cm-2 at an unprecedentedly low voltage of 0.43 V, saving 3.94 kWh m-3 H2 in energy, and exhibits remarkable stability over 120 h at a high current density of 5 A cm-2. Advanced characterizations and theoretical calculation reveal that the presence of Ru─O─Ni/Fe bridges widens the d-band width (Wd) of the Ru cluster, leading to a lower d-band center and higher electron occupation on antibonding orbitals, thereby facilitating moderate adsorption energy and enhanced catalytic activity of Ru.

Pulmonary alveolar microlithiasis combined with gastric mucosal calcification: a case report.

Background: Pulmonary alveolar microlithiasis (PAM) is a rare disease whose clinical and imaging manifestations are non-specific, characterized by the deposition of microliths, which primarily consist of calcium and phosphorus, within the alveoli. In the cases of PAM, patients combined with calcification of other organs such as gastric mucosal calcification are less common. Case presentation: A 59-year-old woman was admitted to our hospital due to cough producing white, foamy sputum, accompanied by dyspnea and fever for 20 days. The CT scan showed diffuse ground-glass opacities and calcification of the gastric mucosa. Lung tissue biopsy revealed the presence of calcification and granulomatous foreign bodies in the interstitium and alveolar cavity. In the later stages, she developed painful skin petechiae. For this patient, the diagnosis of PAM, gastric mucosal calcification, and purpura fulminans was made. However, the genetic test results hinted that the patient and her son had a heterozygous mutation in the FBN1 gene, but her daughter's genetic test results were normal. Although the patient received anti-infection treatment, steroids, and oxygen therapy, her condition did not improve. Conclusion: We reported a rare case of PAM combined with calcification of other organs and purpura fulminans. Treatment of steroids did not show any benefit. The causative mechanism and effective treatment of this disease remain unclear. More treatments need to be explored.

Relationship between triglyceride-glucose index and blood eosinophils among asthmatic individuals in the USA.

BACKGROUND: Presently, the majority of investigations primarily evaluate the correlation between triglyceride-glucose index (TyGI) with lung diseases, such as asthma. However, they did not delve into the correlation between TyGI and inflammatory responses related to the disease. Few studies have explored the association between TyGI and blood eosinophil count (BEOC). Thus, National Health and Nutrition Examination Survey (NHANES) data were used in this study to evaluate the correlation between TyGI and BEOC in individuals with asthma. METHODS: This study investigated 3902 individuals with asthma. Linear regression analysis was performed to investigate the association between TyGI and BEOC in patients with asthma. Subsequently, the GAM and threshold effect models were used to validate the presence of either a nonlinear or linear association between TyGI and BEOC. Finally, stratified analyses were conducted to ascertain the correlations between different subgroups. RESULTS: Four linear regression models confirmed a positive linear correlation between TyGI and BEOC in patients with asthma. In Model D, which controlled for all covariates, BEOC increased by 12.44 cells/uL for every extra unit of TyGI. The GAM and threshold effect models further verified the positive linear correlation between TyGI and BEOC. The XGBoost model indicated that the six most significant variables influencing BEOC, in order of relative importance, were age, cholesterol level, body mass index (BMI), poverty-to-income ratio (PIR), BNEUC, and TyGI. CONCLUSIONS: In patients with asthma, the study discovered a linear positive correlation between TyGI and BEOC. This indicates a potential connection between TyGI and alterations in the immune status of individuals with asthma, which may help detect abnormalities in a timely manner and provide a reference for clinical decision-making. This study offers fresh insights for the future exploration of the management and treatment of asthma.

The mitochondrial carboxylase PCCA interacts with Listeria monocytogenes phospholipase PlcB to modulate bacterial survival.

Listeria monocytogenes, a prominent foodborne pathogen responsible for zoonotic infections, owes a significant portion of its virulence to the presence of the phospholipase PlcB. In this study, we performed an in-depth examination of the intricate relationship between L. monocytogenes PlcB and host cell mitochondria, unveiling a novel participant in bacterial survival: the mitochondrial carboxylase propionyl-coenzyme A carboxylase (PCCA). Our investigation uncovered previously unexplored levels of interaction and colocalization between PCCA and PlcB within host cells, with particular emphasis on the amino acids 504-508 of PCCA, which play a pivotal role in this partnership. To assess the effect of PCCA expression on L. monocytogenes proliferation, PCCA expression levels were manipulated by siRNA-si-PCCA or pCMV-N-HA-PCCA plasmid transfection. Our findings demonstrated a clear inverse correlation between PCCA expression levels and the proliferation of L. monocytogenes. Furthermore, the effect of L. monocytogenes infection on PCCA expression was investigated by assessing PCCA mRNA and protein expression in HeLa cells infected with L. monocytogenes. These results indicate that L. monocytogenes infection did not significantly alter PCCA expression. These findings led us to propose that PCCA represents a novel participant in L. monocytogenes survival, and its abundance has a detrimental impact on bacterial proliferation. This suggests that L. monocytogenes may employ PlcB-PCCA interactions to maintain stable PCCA expression, representing a unique pro-survival strategy distinct from that of other intracellular bacterial pathogens. IMPORTANCE: Mitochondria represent attractive targets for pathogenic bacteria seeking to modulate host cellular processes to promote their survival and replication. Our current study has uncovered mitochondrial carboxylase propionyl-coenzyme A carboxylase (PCCA) as a novel host cell protein that interacts with L. monocytogenes PlcB. The results demonstrate that PCCA plays a negative regulatory role in L. monocytogenes infection, as heightened PCCA levels are associated with reduced bacterial survival and persistence. However, L. monocytogenes may exploit the PlcB-PCCA interaction to maintain stable PCCA expression and establish a favorable intracellular milieu for bacterial infection. Our findings shed new light on the intricate interplay between bacterial pathogens and host cell mitochondria, while also highlighting the potential of mitochondrial metabolic enzymes as antimicrobial agents.

Breaking Highly Ordered PtPbBi Intermetallic with Disordered Amorphous Phase for Boosting Electrocatalytic Hydrogen Evolution and Alcohol Oxidation.

Constructing amorphous/intermetallic (A/IMC) heterophase structures by breaking the highly ordered IMC phase with disordered amorphous phase is an effective way to improve the electrocatalytic performance of noble metal-based IMC electrocatalysts because of the optimized electronic structure and abundant heterophase boundaries as active sites. In this study, we report the synthesis of ultrathin A/IMC PtPbBi nanosheets (NSs) for boosting hydrogen evolution reaction (HER) and alcohol oxidation reactions. The resulting A/IMC PtPbBi NSs exhibit a remarkably low overpotential of only 25 mV at 10 mA cm-2 for the HER in an acidic electrolyte, together with outstanding stability for 100 h. In addition, the PtPbBi NSs show high mass activities for methanol oxidation reaction (MOR) and ethanol oxidation reaction (EOR), which are 13.2 and 14.5 times higher than those of commercial Pt/C, respectively. Density functional theory calculations demonstrate that the synergistic effect of amorphous/intermetallic components and multimetallic composition facilitate the electron transfer from the catalyst to key intermediates, thus improving the catalytic activity of MOR. This work establishes a novel pathway for the synthesis of heterophase two-dimensional nanomaterials with high electrocatalytic performance across a wide range of electrochemical applications.

Application of interpretable machine learning algorithms to predict distant metastasis in ovarian clear cell carcinoma.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) represents a subtype of ovarian epithelial carcinoma (OEC) known for its limited responsiveness to chemotherapy, and the onset of distant metastasis significantly impacts patient prognoses. This study aimed to identify potential risk factors contributing to the occurrence of distant metastasis in OCCC. METHODS: Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we identified patients diagnosed with OCCC between 2004 and 2015. The most influential factors were selected through the application of Gaussian Naive Bayes (GNB) and Adaboost machine learning algorithms, employing a Venn test for further refinement. Subsequently, six machine learning (ML) techniques, namely XGBoost, LightGBM, Random Forest (RF), Adaptive Boosting (Adaboost), Support Vector Machine (SVM), and Multilayer Perceptron (MLP), were employed to construct predictive models for distant metastasis. Shapley Additive Interpretation (SHAP) analysis facilitated a visual interpretation for individual patient. Model validity was assessed using accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and the area under the receiver operating characteristic curve (AUC). RESULTS: In the realm of predicting distant metastasis, the Random Forest (RF) model outperformed the other five machine learning algorithms. The RF model demonstrated accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and AUC (95% CI) values of 0.792 (0.762-0.823), 0.904 (0.835-0.973), 0.759 (0.731-0.787), 0.221 (0.186-0.256), 0.974 (0.967-0.982), 0.353 (0.306-0.399), and 0.834 (0.696-0.967), respectively, surpassing the performance of other models. Additionally, the calibration curve's Brier Score (95%) for the RF model reached the minimum value of 0.06256 (0.05753-0.06759). SHAP analysis provided independent explanations, reaffirming the critical clinical factors associated with the risk of metastasis in OCCC patients. CONCLUSIONS: This study successfully established a precise predictive model for OCCC patient metastasis using machine learning techniques, offering valuable support to clinicians in making informed clinical decisions.

Efficacy of Electroacupuncture Combined with Chinese Herbal Medicine on Pain Intensity for Chronic Sciatica Secondary to Lumbar Disc Herniation: Study Protocol for a Randomised Controlled Trial.

Purpose: Chinese herbal medicine and electroacupuncture (EA) have been used to control pain for many decades in China. We aim to explore the efficacy of intervening patients whose discogenic sciatica symptoms lasting longer than 3 months with these conservative treatments. Patients and Methods: This is a single-center, parallel-group, patient-unblinded Randomized Controlled Trial (RCT) with blinded outcome assessment and statistician. One hundred and twenty-four patients will be assigned randomly into 2 groups including conservative treatment group (Shenxie Zhitong capsule combined with EA treatment) and Nonsteroidal Anti-inflammatory Drugs (Nonsteroidal Anti-inflammatory Drugs, NSAIDs) control group (Celecoxib) in a 1:1 ratio. The trial involves a 4-week treatment along with follow-up for 6 months. The primary outcome is the leg pain intensity measured by the visual analogue scale (VAS) at 6 months after randomization. Secondary outcomes include leg pain intensity at other time points, back pain intensity, leg pain and back pain frequency, functional status, quality of life, return to work status and satisfaction of patients. Adverse events will also be recorded. Strengths and Limitations of This Study: Through this study, we want to observe the efficacy of electroacupuncture combined with Chinese herbal medicine on pain intensity for chronic sciatica secondary to Lumbar Disc Herniation. If the final results are favorable, it is expected to be a safe, economical, and effective treatment for patients. The study design has the following limitations: the setup of control group was less than perfect; patients and doctors could not be blinded in this trial; we skipped the feasibility study. We have tried our best to minimize adverse impacts. Trial Registration: ChiCTR2300070884 (Chinese Clinical Trial Registry, http://www.chictr.org.cn, registered on 25th April 2023).

Metal-Sulfur Interfaces as the Primary Active Sites for Catalytic Hydrogenations.

The determination of catalytically active sites is crucial for understanding the catalytic mechanism and providing guidelines for the design of more efficient catalysts. However, the complex structure of supported metal nanocatalysts (e.g., support, metal surface, and metal-support interface) still presents a big challenge. In particular, many studies have demonstrated that metal-support interfaces could also act as the primary active sites in catalytic reactions, which is well elucidated in oxide-supported metal nanocatalysts but is rarely reported in carbon-supported metal nanocatalysts. Here, we fill the above gap and demonstrate that metal-sulfur interfaces in sulfur-doped carbon-supported metal nanocatalysts are the primary active sites for several catalytic hydrogenation reactions. A series of metal nanocatalysts with similar sizes but different amounts of metal-sulfur interfaces were first constructed and characterized. Taking Ir for quinoline hydrogenation as an example, it was found that their catalytic activities were proportional to the amount of the Ir-S interface. Further experiments and density functional theory (DFT) calculations suggested that the adsorption and activation of quinoline occurred on the Ir atoms at the Ir-S interface. Similar phenomena were found in p-chloronitrobenzene hydrogenation over the Pt-S interface and benzoic acid hydrogenation over the Ru-S interface. All of these findings verify the predominant activity of metal-sulfur interfaces for catalytic hydrogenation reactions and contribute to the comprehensive understanding of metal-support interfaces in supported nanocatalysts.

Assessment of sedation by automated pupillometry in critically ill patients: a prospective observational study.

BACKGROUND: Quantitative measurement of pupil change has not been assessed against the Richmond Agitation and Sedation Scale (RASS) and spectral edge frequency (SEF) during sedation. The aim of this study was to evaluate pupillometry against these measures in sedated critically ill adult patients. METHODS: In ventilated and sedated patients, pupillary variables were measured by automated pupillometry at each RASS level from -5 to 0 after discontinuation of hypnotics, while processed electroencephalogram variables were displayed continuously and SEF was recorded at each RASS level. Correlations were made between percentage pupillary light reflex (%PLR) and RASS, and between %PLR and SEF. The ability of %PLR to differentiate light sedation (RASS ≥-2), moderate (RASS =-3), and deep sedation (RASS ≤-4) was assessed by areas under receiver operating characteristic (ROC) curves. RESULTS: A total of 163 paired measurements were recorded in 38 patients. With decreasing sedation depth, median %PLR increased progressively from 20% (interquartile range 17-25%) to 36% (interquartile range 33-40%) (P<0.001). Strong correlations were found between %PLR and RASS (Rho=0.635) and between %PLR and SEF (R=0.641). Area under the curve (AUC) of 0.87 with a %PLR threshold of 28% differentiated moderate/light sedation from deep sedation with sensitivity of 83% and specificity of 83%. An AUC of 0.82 with a threshold of 31% distinguished light sedation from moderate/deep sedation with a sensitivity of 81% and a specificity of 75%. CONCLUSIONS: Quantitative assessment of %PLR correlates with other indicators of sedation depth in critically ill patients.

Integrative leaf anatomy structure, physiology, and metabolome analyses revealed the response to drought stress in sainfoin at the seedling stage.

INTRODUCTION: Sainfoin (Onobrychis viciaefolia) is a vital legume forage, and drought is the primary element impeding sainfoin growth. OBJECTIVE: The anatomical structure, physiological indexes, and metabolites of the leaves of sainfoin seedlings with a drought-resistant line of P1 (DRL) and a drought-sensitive material of 2049 (DSM) were analyzed under drought (-1.0 MPa) with polyethylene glycol-6000 (PEG-6000). METHODS: The leaf anatomy was studied by the paraffin section method. The related physiological indexes were measured by the hydroxylamine oxidation method, titanium sulfate colorimetric method, thiobarbituric acid method, acidic ninhydrin colorimetric method, and Coomassie brilliant blue method. The metabolomics analysis was composed of liquid chromatography tandem high-resolution mass spectrometry (LC-MS/MS). RESULTS: The results revealed that the thickness of the epidermis, palisade tissue, and sponge tissue of DRL were significantly greater than those of DSM. The leaves of DRL exhibited lower levels of superoxide anion (O2 •-) production rate, hydrogen peroxide (H2O2) content, and malondialdehyde (MDA) content compared with DSM, while proline (Pro) content and soluble protein (SP) content were significantly higher than those of DSM. A total of 391 differential metabolites were identified in two samples. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment showed that the primary differential metabolites were concentrated into the tyrosine metabolism; isoquinoline alkaloid biosynthesis; ubiquinone and other terpenoid quinone biosynthesis; neomycin, kanamycin, and gentamicin biosynthesis; and anthocyanin biosynthesis metabolic pathways. CONCLUSION: Compared with DSM, DRL had more complete anatomical structure, lower active oxygen content, and higher antioxidant level. The results improved our insights into the drought-resistant mechanisms in sainfoin.

Dissolution-Induced Surface Reconstruction of Ni0.95 Pt0.05 Si/p-Si Photocathode for Efficient Photoelectrochemical H2 Production.

Metal silicide/Si photoelectrodes have demonstrated significant potential for application in photoelectrochemical (PEC) water splitting to produce H2 . To achieve an efficient and economical hydrogen evolution reaction (HER), a paramount consideration lies in attaining exceptional catalytic activity on the metal silicide surface with minimal use of noble metals. Here, this study presents the design and construction of a novel Ni0.95 Pt0.05 Si/p-Si photocathode. Dopant segregation is used to achieve a Schottky barrier height as high as 1.0 eV and a high photovoltage of 420 mV. To achieve superior electrocatalytic activity for HER, a dissolution-induced surface reconstruction (SR) strategy is proposed to in situ convert surface Ni0.95 Pt0.05 Si to highly active Pt2 Si. The resulting SR Ni0.95 Pt0.05 Si/p-Si photocathode exhibits excellent HER performance with an onset potential of 0.45 V (vs RHE) and a high maximum photocurrent density of 40.5 mA cm-2 and a remarkable applied bias photon-to-current efficiency (ABPE) of 5.3% under simulated AM 1.5 (100 mW cm-2 ) illumination. The anti-corrosion silicide layer effectively protects Si, ensuring excellent stability of the SR Ni0.95 Pt0.05 Si/p-Si photoelectrode. This study highlights the potential for achieving efficient PEC HER using bimetallic silicide/Si photocathodes with reduced Pt consumption, offering an auspicious perspective for the cost-effective conversion of solar energy to chemical energy.

Molecular mechanisms of Codonopsis pilosula in inhibiting hepatocellular carcinoma growth and metastasis.

BACKGROUND: Liver cancer, one of the most common types of cancer worldwide, accounts for millions of cases annually. With its multi-target and wide-ranging therapeutic effects, traditional Chinese medicine has emerged as a potential approach for treating various tumors. Codonopsis pilosula, a traditional herb, is known for its anti-inflammatory and antioxidant properties. In this study, we investigated the potential molecular mechanisms of Codonopsis pilosula in regulating the inhibition of CDK1 and the modulation of PDK1/ß-catenin, which are involved in hepatocellular carcinoma growth and metastasis. STUDY DESIGN/METHODS: Firstly, we screened the active chemical constituents of Codonopsis pilosula and identified their respective target proteins using the Herb database. Then, we applied the GeneCards database and transcriptome sequencing analysis to screen for critical genes associated with the occurrence and development of liver cancer. The intersection of the target proteins and disease-related genes was used to determine the potential targets of Codonopsis pilosula in hepatocellular carcinoma. Protein-protein interaction analysis and GO/KEGG analysis were subsequently performed to uncover the pathways through which Codonopsis pilosula acts on liver cancer. The Huh-7 cell line, exhibiting the highest sensitivity to Codonopsis pilosula polysaccharide solution (CPP) intervention, was chosen for subsequent studies. Cell viability was evaluated using the CCK-8 assay, colony formation assay was conducted to determine cell proliferation capacity, flow cytometry was used to analyze cell cycle, TUNEL staining was performed to assess cell apoptosis, scratch assay was carried out to evaluate cell migration ability, the expression of EMT-related proteins was detected and analyzed, and cell sphere formation assay was conducted to investigate cell stemness. Finally, a liver cancer animal model was established, and different doses of CPP were administered via gavage the next day. The expression levels of CDK1, PDK1, and ß-catenin in mouse liver tissues were detected and analyzed, immunohistochemistry staining was performed to assess the expression of tumor cell proliferation-related proteins Ki67 and PCNA in mouse xenografts, and TUNEL staining was carried out to evaluate cell apoptosis in mouse liver tissues. After intervention with CDK1 expression, the expression levels of CDK1, PDK1, and ß-catenin proteins and mRNA in each group of cells were detected using Western blot and RT-qPCR. RESULTS: Through network pharmacology analysis, transcriptome sequencing, and bioinformatics analysis, 35 target genes through which Codonopsis pilosula acts on liver cancer were identified. Among them, CDK1, with the highest degree in the PPI network, was considered an essential target protein for Codonopsis pilosula in treating liver cancer. In vitro cell experiments revealed that CPP could inhibit the expression of CDK1/PDK1/ß-catenin signaling axis factors, suppress cell proliferation, decrease cell migration ability, influence the EMT process, and reduce cell stemness by inhibiting CDK1 and affecting the PDK1/ß-catenin signaling axis. Similarly, in vivo experiments demonstrated that CPP could regulate the CDK1/PDK1/ß-catenin signaling axis, inhibit tumor growth, and induce cell apoptosis. CONCLUSION: Codonopsis pilosula may inhibit hepatocellular carcinoma growth by suppressing CDK1 and affecting the PDK1/ß-catenin signaling axis, limiting cell EMT and reducing cell stemness. These findings provide insights into the potential therapeutic role of Codonopsis pilosula in liver cancer.

Antimicrobial peptides: An alternative to antibiotic for mitigating the risks of Antibiotic resistance in aquaculture.

The utilization of antibiotics increases the prevalence of antibiotic resistance genes (ARGs) in various matrices and poses the potential risk of ARG transmission, garnering global attention. Antimicrobial peptides (AMPs) represent a promising novel category of antimicrobials that may address the urgent issue of antibiotic resistance. Here, a zebrafish cultivation assay in which zebrafish were fed a diet supplemented with AMP (Cecropin A) or antibiotics was conducted to determine the effects of the intervention on the microorganisms and antibiotic resistance spectrum in zebrafish gut samples. Cecropin A treatment decreased the α-diversity of the microbiota. Moreover, NMDS (nonmetric multidimensional scaling) results revealed that the ß-diversity in the microbiota was more similar between the control (CK) and Cecropin A samples than between the antibiotic treatment groups. The absolute quantity of ARGs in the AMP treatment was less than that observed in the antibiotic treatment. The findings indicated that FFCH7168, Chitinibacter and Cetobacterium were the most significant biomarkers detected in the CK, Cecropin A and antibiotic treatments, respectively. Although the use of antibiotics notably enhanced the occurrence of multidrug-resistant bacteria, the application of Cecropin A did not lead to this phenomenon. The results indicated that the application of AMPs can effectively manage and control ARGs in aquaculture.

Targeting the intracellular neurexin interactome by in vivo proximity ligation.

In a recent study, Profes, Tiroumalechetty, and colleagues used the in vivo proximity ligation technique TurboID to scrupulously characterize the interactome of the intracellular domain (ICD) of neurexin, revealing that this domain may be involved in presynaptic actin assembly by interacting with actin-associated proteins.

Dose-response relationship between sleep duration and cardiovascular metabolic multimorbidity among older adults in China: A nationwide survey.

AIMS AND OBJECTIVES: The purpose of this study was to explore the relationship between the duration of sleep per day and cardiovascular metabolic multimorbidity (CMM) in older adults and to identify how many hours of sleep per day can lead to a lower risk of CMM in older adults. BACKGROUND: CMM are a common syndrome in the older adults. There may be an association between sleep duration and CMM in older adults, with both insomnia and sleep deprivation having an impact on the health of older adults. Therefore, it is important to explore the possibility that older adults who sleep for a few hours per day may have a lower prevalence of CMM. METHODS: The study included 9710 older adults. The sleep duration in this study was assessed by the question "How many hours of sleep do you currently get in a day? ". Older adults were defined as having CMM when they had two or more of the five categories of hypertension, diabetes, heart disease, stroke or cardiovascular disease, dyslipidemia. We used multivariate logistic regression analysis to explore the association among sleep duration and CMM. Restrictive cubic splines were used to examine the shape of the association among sleep duration and the CMM. The STROBE checklist was used for this cross-sectional study. RESULTS: The mean age was 84.78 ± 11.73 years, with 55.5 % being female. Of the total sample, 21.3 % were CMM. When all covariates were adjusted, there was dose-response relationship between sleep duration and CMM. The dose-response relationship between CMM and sleep duration showed that older adults had a lower risk of cardiovascular and metabolic multimorbidity when they slept 9 h and 10 h per day. CONCLUSION: With the increasing population of older adults, the number of older adults suffering from CMM continues to rise, and adequate sleep time can effectively prevent the occurrence of CMM. We should pay attention to the sleep problem of the older adults. RELEVANCE TO CLINICAL PRACTICE: This study provided information for healthcare providers to identify circumstances that increase cardiovascular metabolic multimorbidity and suggest the appropriate sleep duration per day to reduce the risk of disease in older adults. PATIENT OR PUBLIC CONTRIBUTION: Because of the public database data used in this study, all data were collected by survey agency personnel, so this section is not applicable to this study.

Remazolam affects the phenotype and function of astrocytes to improve traumatic brain injury by regulating the Cx43.

PURPOSE: To explore the mechanism by which Remazolam affects the phenotype and function of astrocytes to improve traumatic brain injury (TBI). METHODS: The oxygen -glucose deprivation/recovery (OGD/R) cell model was constructed to simulate the pathological state of astrocytes in a TBI environment. The viability of astrocytes was measured by CCK-8, and the cytoskeleton changes were observed by Phalloidin- TRITC staining. The expressions of differentiation markers, Cx43 and phosphorylated Cx43 (P-Cx43) of A1/A2 astrocytes were detected by Western blot, and the complement C3 and S100A10 of A1/A2 astrocytes were detected by ELISA. The TBI rat model was established. The water content of brain tissue was measured by dry-wet specific gravity method, the pathological morphology of brain tissue in cortical injury area was observed by HE staining method, ROS was detected by fluorescence quantitative method, Cx43 expression was detected by immunohistochemistry method, and the differentiation markers of A1/A2 astrocytes were detected by immunofluorescence. RESULTS: In the TBI environment, astrocytes showed decreased cell viability, blurred skeleton, and increased expression of Cx43. In TBI rats, the water content of brain tissue increased, the brain tissue in the cortex injury area was seriously damaged, ROS and Cx43 expression were significantly increased, and mainly distributed in A2 astrocytes. Remazolam can reverse the above results after the intervention. CONCLUSION: Remazolam affects the phenotype and function of astrocytes to improve TBI via regulating Cx43, and plays a role in protecting the neurological function of TBI rats.