Anomalously enhanced ion transport and uptake in functionalized angstrom-scale two-dimensional channels.

Emulating angstrom-scale dynamics of the highly selective biological ion channels is a challenging task. Recent work on angstrom-scale artificial channels has expanded our understanding of ion transport and uptake mechanisms under confinement. However, the role of chemical environment in such channels is still not well understood. Here, we report the anomalously enhanced transport and uptake of ions under confined MoS2-based channels that are ~five angstroms in size. The ion uptake preference in the MoS2-based channels can be changed by the selection of surface functional groups and ion uptake sequence due to the interplay between kinetic and thermodynamic factors that depend on whether the ions are mixed or not prior to uptake. Our work offers a holistic picture of ion transport in 2D confinement and highlights ion interplay in this regime.

TRIM29 facilitates gemcitabine resistance via MEK/ERK pathway and is modulated by circRPS29/miR-770-5p axis in PDAC.

AIMS: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease. Chemotherapy based on gemcitabine (GEM) remains the first-line drug for patients with advanced PDAC. However, GEM resistance impairs its therapeutic effectiveness. Therefore, identifying effective therapeutic targets are urgently needed to overcome GEM resistance. METHODS: The clinical significance of Tripartite Motif Containing 29 (TRIM29) was identified by exploring GEO datasets and TCGA database and its potential biological functions were predicted by GSEA analysis. The regulatory axis was established by bioinformatics analysis and validated by mechanical experiments. Then, in vitro and in vivo assays were performed to validate the roles of TRIM29 in PDAC GEM resistance. RESULTS: High TRIM29 expression was associated with poor prognosis of PDAC and functional experiments demonstrated that TRIM29 promoted GEM resistance in PDAC GEM-resistant (GR) cells. Furthermore, we revealed that circRPS29 promoted TRIM29 expression via competitive interaction with miR-770-5p and then activated MEK/ERK signaling pathway. Additionally, both in vitro and in vivo functional experiments demonstrated that circRPS29/miR-770-5p/TRIM29 axis promoted PDAC GEM resistance via activating MEK/ERK signaling pathway. CONCLUSION: Our results identify the significance of the signaling axis, circRPS29/miR-770-5p/TRIM29-MEK/ERK, in PDAC GEM resistance, which will provide novel therapeutic targets for PDAC treatment.

Desymmetrization-Addition Reaction of Cyclopropenes to Imines via Synergistic Photoredox and Cobalt Catalysis.

Herein, we designed a reaction for the desymmetrization-addition of cyclopropenes to imines by leveraging the synergy between photoredox and asymmetric cobalt catalysis. This protocol facilitated the synthesis of a series of chiral functionalized cyclopropanes with high yield, enantioselectivity, and diastereoselectivity (44 examples, up to 93% yield and >99% ee). A possible reaction mechanism involving cyclopropene desymmetrization by Co-H species and imine addition by Co-alkyl species was proposed. This study provides a novel route to important chiral cyclopropanes and extends the frontier of asymmetric metallaphotoredox catalysis.

Fine particulate matter 2.5 induces susceptibility to Pseudomonas aeruginosa infection via expansion of PD-L1high neutrophils in mice.

BACKGROUND: Exposure to PM2.5 has been implicated in a range of detrimental health effects, particularly affecting the respiratory system. However, the precise underlying mechanisms remain elusive. METHODS: To address this objective, we collected ambient PM2.5 and administered intranasal challenges to mice, followed by single-cell RNA sequencing (scRNA-seq) to unravel the heterogeneity of neutrophils and unveil their gene expression profiles. Flow cytometry and immunofluorescence staining were subsequently conducted to validate the obtained results. Furthermore, we assessed the phagocytic potential of neutrophils upon PM2.5 exposure using gene analysis of phagocytosis signatures and bacterial uptake assays. Additionally, we utilized a mouse pneumonia model to evaluate the susceptibility of PM2.5-exposed mice to Pseudomonas aeruginosa infection. RESULTS: Our study revealed a significant increase in neutrophil recruitment within the lungs of PM2.5-exposed mice, with subclustering of neutrophils uncovering subsets with distinct gene expression profiles. Notably, exposure to PM2.5 was associated with an expansion of PD-L1high neutrophils, which exhibited impaired phagocytic function dependent upon PD-L1 expression. Furthermore, PM2.5 exposure was found to increase the susceptibility of mice to Pseudomonas aeruginosa, due in part to increased PD-L1 expression on neutrophils. Importantly, monoclonal antibody targeting of PD-L1 significantly reduced bacterial burden, dissemination, and lung inflammation in PM2.5-exposed mice upon Pseudomonas aeruginosa infection. CONCLUSIONS: Our study suggests that PM2.5 exposure promotes expansion of PD-L1high neutrophils with impaired phagocytic function in mouse lungs, contributing to increased vulnerability to bacterial infection, and therefore targeting PD-L1 may be a therapeutic strategy for reducing the harmful effects of PM2.5 exposure on the immune system.

Parallel CNN-Deep Learning Clinical-Imaging Signature for Assessing Pathologic Grade and Prognosis of Soft Tissue Sarcoma Patients.

BACKGROUND: Traditional biopsies pose risks and may not accurately reflect soft tissue sarcoma (STS) heterogeneity. MRI provides a noninvasive, comprehensive alternative. PURPOSE: To assess the diagnostic accuracy of histological grading and prognosis in STS patients when integrating clinical-imaging parameters with deep learning (DL) features from preoperative MR images. STUDY TYPE: Retrospective/prospective. POPULATION: 354 pathologically confirmed STS patients (226 low-grade, 128 high-grade) from three hospitals and the Cancer Imaging Archive (TCIA), divided into training (n = 185), external test (n = 125), and TCIA cohorts (n = 44). 12 patients (6 low-grade, 6 high-grade) were enrolled into prospective validation cohort. FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T/Unenhanced T1-weighted and fat-suppressed-T2-weighted. ASSESSMENT: DL features were extracted from MR images using a parallel ResNet-18 model to construct DL signature. Clinical-imaging characteristics included age, gender, tumor-node-metastasis stage and MRI semantic features (depth, number, heterogeneity at T1WI/FS-T2WI, necrosis, and peritumoral edema). Logistic regression analysis identified significant risk factors for the clinical model. A DL clinical-imaging signature (DLCS) was constructed by incorporating DL signature with risk factors, evaluated for risk stratification, and assessed for progression-free survival (PFS) in retrospective cohorts, with an average follow-up of 23 ± 22 months. STATISTICAL TESTS: Logistic regression, Cox regression, Kaplan-Meier curves, log-rank test, area under the receiver operating characteristic curve (AUC)，and decision curve analysis. A P-value <0.05 was considered significant. RESULTS: The AUC values for DLCS in the external test, TCIA, and prospective test cohorts (0.834, 0.838, 0.819) were superior to clinical model (0.662, 0.685, 0.694). Decision curve analysis showed that the DLCS model provided greater clinical net benefit over the DL and clinical models. Also, the DLCS model was able to risk-stratify patients and assess PFS. DATA CONCLUSION: The DLCS exhibited strong capabilities in histological grading and prognosis assessment for STS patients, and may have potential to aid in the formulation of personalized treatment plans. TECHNICAL EFFICACY: Stage 2.

Correlating Nitrate Adsorption with the Local Environments of FeCoNiCuZn High-Entropy Alloy Catalysts Using Machine Learning.

The electrocatalytic nitrate reduction to ammonia holds significant values for water remediations and energy applications, which quests for the development of highly effective catalysts with considerable stability and selectivity. Recently, high-entropy alloys (HEAs) are attracting growing attention for electrocatalytic processes. Nonetheless, studies of HEA-based nitrate reduction to ammonia are still at the early stage, and it remains unclear how the HEA compositions affect the adsorption and activation of the reaction intermediates. Herein, high-throughput density functional theory (DFT) calculations were integrated with machine learning to investigate the dependence of nitrate adsorption on the FeCoNiCuZn HEA structures. In particular, a total of 1268 different structures were sampled and constructed from the multidimensional configuration space, followed by the DFT calculations to investigate the Gibbs free energy of nitrate adsorption (i.e., ΔGNO3) on different surface microstructures. Four regression models were successfully developed, which can accurately predict ΔGNO3 using the HEA structures as the input features. Through the analysis of the feature importance, it was found that the active sites are crucial for nitrate adsorption; meanwhile, the local environments also play a considerable role. The dependence of the ΔGNO3 and adsorption geometries on the HEA compositions demonstrates that the compositional modulation of the HEA catalysts could be a promising avenue for facile adsorption and activation of reaction intermediates. Overall, this work will contribute to the probabilistic optimization of the HEA microstructures for enhanced electrochemical nitrate reduction.

MMP14high macrophages orchestrate progressive pulmonary fibrosis in SR-Ag-induced hypersensitivity pneumonitis.

Fibrotic hypersensitivity pneumonitis (FHP) is a fatal interstitial pulmonary disease with limited treatment options. Lung macrophages are a heterogeneous cell population that exhibit distinct subsets with divergent functions, playing pivotal roles in the progression of pulmonary fibrosis. However, the specific macrophage subpopulations and underlying mechanisms involved in the disease remain largely unexplored. In this study, a decision tree model showed that matrix metalloproteinase-14 (MMP14) had higher scores for important features in the up-regulated genes in macrophages from mice exposed to the Saccharopolyspora rectivirgula antigen (SR-Ag). Using single-cell RNA sequencing (scRNA-seq) analysis of hypersensitivity pneumonitis (HP) mice profiles, we identified MMP14high macrophage subcluster with a predominant M2 phenotype that exhibited higher activity in promoting fibroblast-to myofibroblast transition (FMT). We demonstrated that suppressing toll-like receptor 2 (TLR2) and nuclear factor kappa-B (NF-κB) could attenuate MMP14 expression and exosome secretion in macrophages stimulation with SR-Ag. The exosomes derived from MMP14-overexpressing macrophages were found to be more effective in regulating the transition of fibroblasts through exosomal MMP14. Importantly, it was observed that the transfer of MMP14-overexpressing macrophages into mice promoted lung inflammation and fibrosis induced by SR-Ag. NSC-405020 binding to the hemopexin domain (PEX) of MMP-14 ameliorated lung inflammation and fibrosis induced by SR-Ag in mice. Thus, MMP14-overexpressing macrophages may be an important mechanism contributing to the exacerbation of allergic reactions. Our results indicated that MMP14 in macrophages has the potential to be a therapeutic target for HP.

GFPBW1, a ß-glucan from Grifola frondosa as vaccine adjuvant: APCs activation and maturation.

Adjuvants for vaccines with characteristics of improving adaptive immunity particularly via leverage of antigen presenting cells (APCs) are currently lacking. In a previous work we obtained a new soluble 300 kDa homogeneous ß-glucan named GFPBW1 from the fruit bodies of Granola frondosa. GFPBW1 could activate macrophages by targeting dendritic cell associated C-type lectin 1 (Dectin-1)/Syk/NF-κB signaling to achieve antitumour effects. In this study the adjuvant effects of GFPBW1 were explored with OVA-antigen and B16-OVA tumor model. We showed that GFPBW1 (5, 50, 500 µg/mL) dose-dependently promoted activation and maturation of APCs in vitro by increasing CD80, CD86 and MHC II expression. We immunized female mice with OVA in combination with GFPBW1 (50 or 300 µg) twice with an interval of two weeks. GFPBW1 markedly and dose-dependently increased OVA-specific antibody titers of different subtypes including IgG1, IgG2a, IgG2b and IgG3, suggesting that it could serve as an adjuvant for both Th1 and Th2 type immune responses. Furthermore, GFPBW1 in combination with aluminum significantly increased the titers of OVA-specific IgG2a and IgG2b, but not those of IgG1, suggesting that GFPBW1 could be used as a co-adjuvant of aluminum to compensate for Th1 deficiency. For mice immunized with OVA plus GFPBW1, no obvious pathological injury was observed in either major organs or injection sites, and no abnormalities were noted for any of the hematological parameters. When GFPBW1 served as an adjuvant in the B16-OVA cancer vaccine models, it could accomplish entire tumor suppression with preventive vaccines, and enhance antitumour efficacy with therapeutic vaccines. Differentially expressed genes were found to be enriched in antigen processing process, specifically increased tumor infiltration of DCs, B1 cells and plasma cells in the OVA plus GFPBW1 group, in accordance with its activation and maturation function of APCs. Collectively, this study systematically describes the properties of GFPBW1 as a novel potent and safe adjuvant and highlights its great potential in vaccine development.

Association of remnant cholesterol with coronary artery ectasia: a cross-sectional study.

OBJECTIVE: Coronary artery ectasia (CAE) is a condition characterized by the localized or widespread dilation of one or more coronary arteries. The majority of CAE patients do not present with clinical symptoms, and the exact cause of CAE remains unclear. Therefore, a retrospective analysis was conducted to explore the potential causes of CAE. METHODS: This study was a retrospective analysis of patients who underwent coronary angiography at Guangdong Provincial People's Hospital between January 2017 and July 2022, of whom 679 patients were ultimately enrolled in the study. Among them, 260 patients were diagnosed with CAE, whereas 419 patients with normal coronary results composed the control group. Remnant cholesterol (RC) was calculated as total cholesterol (TC) minus high-density lipoprotein cholesterol (HDL-C) minus low-density lipoprotein cholesterol (LDL-C). The association between RC levels and the risk of CAE was assessed via multivariable logistic models. RESULTS: Out of the 679 patients who participated in this study, with an average age of 59.9 years, 38.3% were diagnosed with CAE. Patients with CAE had higher RC levels than did those without CAE (P = 0.001). A significant positive association was observed between RC levels and the risk of CAE, with a multivariable adjusted odds ratio (OR) of 1.950 (95% confidence interval [CI]: 1.163-3.270). There was a significant positive association between RC levels and the risk of CAE in both single-vessel and multivessel dilation cases, as well as in isolated CAE and dilation secondary to coronary atherosclerosis. According to the subgroup analyses, RC levels were positively associated with the risk of CAE in participants with hypertension (OR, 1.065; 95% CI, 1.034-1.098). CONCLUSION: RC levels are positively correlated with CAE, implying that a focus on RC could be beneficial in CAE research.

Oxidative stress-mediated activation of FTO exacerbates impairment of the epithelial barrier by up-regulating IKBKB via N6-methyladenosine-dependent mRNA stability in asthmatic mice exposed to PM2.5.

In order to comprehend the underlying mechanisms contributing to the development and exacerbation of asthma resulting from exposure to fine particulate matter (PM2.5), we established an asthmatic model in fat mass and obesity-associated gene knockdown mice subjected to PM2.5 exposure. Histological analyses using hematoxylin-eosin (HE) and Periodic Acid-Schiff (PAS) staining revealed that the down-regulation of the fat mass and obesity-associated gene (Fto) expression significantly ameliorated the pathophysiological alterations observed in asthmatic mice exposed to PM2.5. Furthermore, the down-regulation of Fto gene expression effectively attenuated damage to the airway epithelial barrier. Additionally, employing in vivo and in vitro models, we elucidated that PM2.5 modulated FTO expression by inducing oxidative stress. Asthmatic mice exposed to PM2.5 exhibited elevated Fto expression, which correlated with increased levels of reactive oxygen species. Similarly, when cells were exposed to PM2.5, FTO expression was up-regulated in a ROS-dependent manner. Notably, the administration of N-acetyl cysteine successfully reversed the PM2.5-induced elevation in FTO expression. Concurrently, we performed transcriptome-wide Methylated RNA immunoprecipitation Sequencing (MeRIP-seq) analysis subsequent to PM2.5 exposure. Through the implementation of Gene Set Enrichment Analysis and m6A-IP-qPCR, we successfully identified inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB) as a target gene regulated by FTO. Interestingly, exposure to PM2.5 led to increased expression of IKBKB, while m6A modification on IKBKB mRNA was reduced. Furthermore, our investigation revealed that PM2.5 also regulated IKBKB through oxidative stress. Significantly, the down-regulation of IKBKB effectively mitigated epithelial barrier damage in cells exposed to PM2.5 by modulating nuclear factor-kappa B (NF-κB) signaling. Importantly, we discovered that decreased m6A modification on IKBKB mRNA facilitated by FTO enhanced its stability, consequently resulting in up-regulation of IKBKB expression. Collectively, our findings propose a novel role for FTO in the regulation of IKBKB through m6A-dependent mRNA stability in the context of PM2.5-induced oxidative stress. Therefore, it is conceivable that the utilization of antioxidants or inhibition of FTO could represent potential therapeutic strategies for the management of asthma exacerbated by PM2.5 exposure.

Aflatoxin B1 inhibited the development of primary myoblasts of grass carp (Ctenopharyngodon idella) by degrading extracellular matrix.

According to the International Agency for Research on Cancer (IARC), aflatoxin B1 (AFB1) has been recognized as a major contaminant in food and animal feed and which is a common mycotoxin with high toxicity. Previous research has found that AFB1 inhibited zebrafish muscle development. However, the potential mechanism of AFB1 on fish muscle development is unknown, so it is necessary to conduct further investigation. In the present research, the primary myoblast of grass carp was used as a model, we treated myoblasts with AFB1 for 24 h. Our results found that 5 µM AFB1 significantly inhibited cell proliferation and migration (P < 0.05), and 10 µM AFB1 promoted lactate dehydrogenase (LDH) release (P < 0.05). Reactive oxygen species (ROS), protein carbonyl (PC) and malondialdehyde (MDA) levels were increased in 15, 5 and 10 µM AFB1 (P < 0.05), respectively. Catalase (CAT), glutathione peroxidase (GPx) and total superoxide dismutase (T-SOD) activities were decreased in 10, 10 and 15 µM AFB1 (P < 0.05), respectively. Furthermore, 15 µM AFB1 induced oxidative damage by Nrf2 pathway, also induced apoptosis in primary myoblast of grass carp. Meanwhile, 15 µM AFB1 decreased MyoD gene and protein expression (P < 0.05). Importantly, 15 µM AFB1 decreased the protein expression of collagen Ⅰ and fibronectin (P < 0.05), and increased the protein levels of urokinase plasminogen activator (uPA), matrix metalloproteinase 9 (MMP-9), matrix metalloproteinase 2 (MMP-2), and p38 mitogen-activated protein kinase (p38MAPK) (P < 0.05). As a result, our findings suggested that AFB1 damaged the cell morphology, induced oxidative damage and apoptosis, degraded ECM components, in turn inhibiting myoblast development by activating the p38MAPK/urokinase-type plasminogen activator (uPA)/matrix metalloproteinase (MMPs)/extracellular matrix (ECM) signaling pathway.

HO-1 upregulation promotes mitophagy-dependent ferroptosis in PM2.5-exposed hippocampal neurons.

Fine particulate matter (PM2.5) has been extensively implicated in the pathogenesis of neurodevelopmental disorders, but the underlying mechanism remains unclear. Recent studies have revealed that PM2.5 plays a role in regulating iron metabolism and redox homeostasis in the brain, which is closely associated with ferroptosis. In this study, the role and underlying mechanism of ferroptosis in PM2.5-induced neurotoxicity were investigated in mice, primary hippocampal neurons, and HT22 cells. Our findings demonstrated that exposure to PM2.5 could induce abnormal behaviors, neuroinflammation, and neuronal loss in the hippocampus of mice. These effects may be attributed to ferroptosis induced by PM2.5 exposure in hippocampal neurons. RNA-seq analysis revealed that the upregulation of iron metabolism-related protein Heme Oxygenase 1 (HO-1) and the activation of mitophagy might play key roles in PM2.5-induced ferroptosis in HT22 cells. Subsequent in vitro experiments showed that PM2.5 exposure significantly upregulated HO-1 in primary hippocampal neurons and HT22 cells. Moreover, PM2.5 exposure activated mitophagy in HT22 cells, leading to the loss of mitochondrial membrane potential, alterations in the expression of autophagy-related proteins LC3, P62, and mTOR, as well as an increase in mitophagy-related protein PINK1 and PARKIN. As a heme-degradation enzyme, the upregulation of HO-1 promotes the release of excess iron, genetically inhibiting the upregulation of HO-1 in HT22 cells could prevent both PM2.5-induced mitophagy and ferroptosis. Furthermore, pharmacological inhibition of mitophagy in HT22 cells reduced levels of ferrous ions and lipid peroxides, thereby preventing ferroptosis. Collectively, this study demonstrates that HO-1 mediates PM2.5-induced mitophagy-dependent ferroptosis in hippocampal neurons, and inhibiting mitophagy or ferroptosis may be a key therapeutic target to ameliorate neurotoxicity following PM2.5 exposure.

Lightweight and Real-Time Infrared Image Processor Based on FPGA.

This paper presents an FPGA-based lightweight and real-time infrared image processor based on a series of hardware-oriented lightweight algorithms. The two-point correction algorithm based on blackbody radiation is introduced to calibrate the non-uniformity of the sensor. With precomputed gain and offset matrices, the design can achieve real-time non-uniformity correction with a resolution of 640×480. The blind pixel detection algorithm employs the first-level approximation to simplify multiple iterative computations. The blind pixel compensation algorithm in our design is constructed on the side-window-filtering method. The results of eight convolution kernels for side windows are computed simultaneously to improve the processing speed. Due to the proposed side-window-filtering-based blind pixel compensation algorithm, blind pixels can be effectively compensated while details in the image are preserved. Before image output, we also incorporated lightweight histogram equalization to make the processed image more easily observable to the human eyes. The proposed lightweight infrared image processor is implemented on Xilinx XC7A100T-2. Our proposed lightweight infrared image processor costs 10,894 LUTs, 9367 FFs, 4 BRAMs, and 5 DSP48. Under a 50 MHz clock, the processor achieves a speed of 30 frames per second at the cost of 1800 mW. The maximum operating frequency of our proposed processor can reach 186 MHz. Compared with existing similar works, our proposed infrared image processor incurs minimal resource overhead and has lower power consumption.

Evaluation of the risk prediction model of pressure injuries in hospitalized patient: A systematic review and meta-analysis.

AIMS AND OBJECTIVES: The main aim of this study is to synthesize the prevalent predictive models for pressure injuries in hospitalized patients, with the goal of identifying common predictive factors linked to pressure injuries in hospitalized patients. This endeavour holds the potential to provide clinical nurses with a valuable reference for providing targeted care to high-risk patients. BACKGROUND: Pressure injuries (PIs) are a frequently occurring health problem throughout the world. There are mounting studies about risk prediction model of PIs reported and published. However, the prediction performance of the models is still unclear. DESIGN: Systematic review and meta-analysis: The Cochrane Library, PubMed, Embase, CINAHL, Web of Science and Chinese databases including CNKI (China National Knowledge Infrastructure), Wanfang Database, Weipu Database and CBM (China Biology Medicine). METHODS: This systematic review was conducted following PRISMA recommendations. The databases of Cochrane Library, PubMed, Embase, CINAHL, Web of Science, and CNKI, Weipu Database, Wanfang Database and CBM were searched for all studies published before September 2023. We included studies with cohort, case-control designs, reporting the development of risk model and have been validated externally and internally among the hospitalized patients. Two researchers selected the retrieved studies according to the inclusion and exclusion criteria, and critically evaluated the quality of studies based on the CHARMS checklist. The PRISMA guideline was used to report the systematic review and meta-analysis. RESULTS: Sixty-two studies were included, which contained 99 pressure injuries risk prediction models. The AUC (area under ROC curve) of modelling in 32 prediction models were reported ranged from .70 to .99, while the AUC of verification in 38 models were reported ranged from .70 to .98. Gender (OR = 1.41, CI: .99 ~ 1.31), age (WMD = 8.81, CI: 8.11 ~ 9.57), diabetes mellitus (OR = 1.64, CI: 1.36 ~ 1.99), mechanical ventilation (OR = 2.71, CI: 2.05 ~ 3.57), length of hospital stay (WMD = 7.65, CI: 7.24 ~ 8.05) were the most common predictors of pressure injuries. CONCLUSION: Studies of PIs risk prediction model in hospitalized patients had high research quality, and the risk prediction models also had good predictive performance. However, some of the included studies lacked of internal or external validation in modelling, which affected the stability and extendibility. The aged, male patient in ICU, albumin, haematocrit, low haemoglobin level, diabetes, mechanical ventilation and length of stay in hospital were high-risk factors for pressure injuries in hospitalized patients. In the future, it is recommended that clinical nurses, in practice, select predictive models with better performance to identify high-risk patients based on the actual situation and provide care targeting the high-risk factors to prevent the occurrence of diseases. RELEVANCE TO CLINICAL PRACTICE: The risk prediction model is an effective tool for identifying patients at the risk of developing PIs. With the help of risk prediction tool, nurses can identify the high-risk patients and common predictive factors, predict the probability of developing PIs, then provide specific preventive measures to improve the outcomes of these patients. REGISTRATION NUMBER (PROSPERO): CRD42023445258.

Blood biomarkers for post-stroke cognitive impairment: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Post-stroke cognitive impairment (PSCI) is a frequent consequence of stroke, which affects the quality of life and prognosis of stroke survivors. Numerous studies have indicated that blood biomarkers may be the key determinants for predicting and diagnosing cognitive impairment, but the results remain varied. Therefore, this meta-analysis aims to summarize potential biomarkers associated with PSCI. METHODS: PubMed, Web of Science, Embase, and Cochrane Library were comprehensively searched for studies exploring blood biomarkers associated with PSCI from inception to 15 April 2022. RESULTS: 63 studies were selected from 4,047 references, which involves 95 blood biomarkers associated with the PSCI. We meta-analyzed 20 potential blood biomarker candidates, the results shown that the homocysteine (Hcy) (SMD = 0.35; 95 %CI: 0.20-0.49; P < 0.00001), c-reactive protein (CRP) (SMD = 0.49; 95 %CI: 0.20-0.78; P = 0.0008), uric acid (UA) (SMD = 0.41; 95 %CI: 0.06-0.76; P = 0.02), interleukin 6 (IL-6) (SMD = 0.92; 95 % CI: 0.27-1.57; P = 0.005), cystatin C (Cys-C) (SMD = 0.58; 95 %CI: 0.28-0.87; P = 0.0001), creatinine (SMD = 0.39; 95 %CI: 0.23-0.55; P < 0.00001) and tumor necrosis factor alpha (TNF-α) (SMD = 0.45; 95 %CI: 0.08-0.82; P = 0.02) levels were significantly higher in patients with PSCI than in the non-PSCI group. CONCLUSION: Based on our findings, we recommend that paramedics focus on the blood biomarkers levels of Hcy, CRP, UA, IL-6, Cys-C, creatinine and TNF-α in conjunction with neuroimaging and neuropsychological assessment to assess the risk of PSCI, which may help with early detection and timely preventive measures. At the same time, other potential blood biomarkers should be further validated in future studies.

Traditional Chinese medicine Qingre Huoxue decoction enhances wound healing in through modulation of angiogenic and inflammatory pathways.

This study investigates the therapeutic potential of Qingre Huoxue Decoction (QHD), a traditional Chinese herbal formulation, in promoting wound healing in an imiquimod-induced murine model of psoriasis. The research was driven by the need for effective wound healing strategies in psoriatic conditions, where conventional treatments often fall short. Employing a combination of in vivo and in vitro methodologies, we assessed the effects of QHD on key factors associated with wound healing. Our results showed that QHD treatment significantly reduced the expression of angiogenic proteins HIF-1α, FLT-1, and VEGF, and mitigated inflammatory responses, as evidenced by the decreased levels of pro-inflammatory cytokines and increased expression of IL-10. Furthermore, QHD enhanced the expression of genes essential for wound repair. In vitro assays with HUVECs corroborated the anti-angiogenic effects of QHD. Conclusively, the study highlights QHD's efficacy in enhancing wound healing in psoriatic conditions by modulating angiogenic and inflammatory pathways, presenting a novel therapeutic avenue in psoriasis wound management.

[Pseudomonas Aeruginosa Affects the Function of Pulmonary Vascular Endothelial Cells].

Objective To investigate the impact of Pseudomonas aeruginosa(PA) infection on the function of pulmonary vascular endothelial cells,and explore the mechanism of this bacterium in exacerbating lung inflammation in mice. Methods Two hours after human lung microvascular endothelial cell(HULEC-5a) were infected with the PA strain PAO1,the mRNA levels of autophagy-related gene 5(ATG5),6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3),and calcium adhesion protein 5(CDH5) were determined by reverse transcription real-time fluorescent quantitative PCR(RT-qPCR).The protein levels of ATG5,PFKFB3,and vascular endothelial calcium adhesion protein(VE-cadherin) were detected by immunofluorescence.After the expression of ATG5 and PFKFB3 was respectively knocked down by small interfering RNA(siRNA),RT-qPCR was employed to measure the mRNA levels of ATG5,PFKFB3,and CDH5,and immunofluorescence to detect the protein levels of PFKFB3 and VE-cadherin.In addition,the lactate assay kit was used to determine the level of lactate in the cells.After mice were infected with PAO1,lung inflammation was assessed through histopathological section staining.Confocal microscopy was employed to capture and analyze fluorescence-labeled PFKFB3 and VE-cadherin in endothelial cells. Results Compared with the control group,the HULEC-5a cells infected with PAO1 showed up-regulated mRNA and protein levels of PFKFB3(all P<0.05),down-regulated mRNA level of CDH5(P=0.023),disrupted continuity and down-regulated protein level of VE-cadherin(P<0.001),and elevated lactate level(P=0.017).Compared with PAO1-infected HULEC-5a cells,knocking down PFKFB3 led to the up-regulated mRNA level of CDH5(P=0.043),lowered lactate level(P=0.047),and restored continuity of VE-cadherin;knocking down ATG5 led to up-regulated mRNA and protein levels of PFKFB3(P=0.013 and P=0.003),elevated lactate level(P=0.015),and down-regulated mRNA level of CDH5(P=0.020) and protein level of VE-cadherin(P=0.001).The HE staining results showed obvious red blood cell leakage,inflammatory cell infiltration,alveolar septal widening,and partial detachment of vascular endothelial cells in the alveoli of PA-infected mice.Immunofluorescence staining showed up-regulated expression of PFKFB3 and decreased fluorescence signal of VE-cadherin in endothelial cells of infected mice compared with normal mice. Conclusion PA may regulate the PFKFB3 pathway via AGT5 to disrupt the function of pulmonary vascular endothelial cells,thereby exacerbating the inflammation in the lungs of mice.

[Current landscape and emerging trends in academic development of traditional Chinese medicine in new era].

The discipline development is the pillar for the development of traditional Chinese medicine( TCM). The academic progress in TCM is the commanding height of the discipline development of TCM. To lead and promote the development and academic progress of TCM, the China Association of Chinese Medicine has summarized the Top Ten Academic Achievements in Traditional Chinese Medicine during 2020-2022, the Major Scientific Problems, Engineering Technical Problems, and Industrial Technical Problems in Traditional Chinese Medicine during 2019-2023, and the Remarkable Research Achievements of Traditional Chinese Medicine during 2012-2022. Based on the above research reports and the research achievements awarded the national science and technology prizes in TCM in the last 20 years and according to the current situation and layout of TCM discipline development, this paper reviews the major research achievements of TCM in the last two decades and the latest research progress in TCM during 2020-2023. The major scientific, engineering technical, and industrial technical problems in TCM are analyzed and the emerging trends of TCM are prospected in accordance with the development laws and characteristics of TCM. This review provides new ideas and reference for the high-quality development of TCM in the new era.

An Artificial Enzyme for Asymmetric Nitrocyclopropanation of α,ß-Unsaturated Aldehydes-Design and Evolution.

The introduction of an abiological catalytic group into the binding pocket of a protein host allows for the expansion of enzyme chemistries. Here, we report the generation of an artificial enzyme by genetic encoding of a non-canonical amino acid that contains a secondary amine side chain. The non-canonical amino acid and the binding pocket function synergistically to catalyze the asymmetric nitrocyclopropanation of α,ß-unsaturated aldehydes by the iminium activation mechanism. The designer enzyme was evolved to an optimal variant that catalyzes the reaction at high conversions with high diastereo- and enantioselectivity. This work demonstrates the application of genetic code expansion in enzyme design and expands the scope of enzyme-catalyzed abiological reactions.

Comparative physiological and transcriptomic analysis of two salt-tolerant soybean germplasms response to low phosphorus stress: role of phosphorus uptake and antioxidant capacity.

BACKGROUND: Phosphorus (P) and salt stress are common abiotic stressors that limit crop growth and development, but the response mechanism of soybean to low phosphorus (LP) and salt (S) combined stress remains unclear. RESULTS: In this study, two soybean germplasms with similar salt tolerance but contrasting P-efficiency, A74 (salt-tolerant and P-efficient) and A6 (salt-tolerant and P-inefficient), were selected as materials. By combining physiochemical and transcriptional analysis, we aimed to elucidate the mechanism by which soybean maintains high P-efficiency under salt stress. In total, 14,075 differentially expressed genes were identified through pairwise comparison. PageMan analysis subsequently revealed several significantly enriched categories in the LP vs. control (CK) or low phosphorus + salt (LPS) vs. S comparative combination when compared to A6, in the case of A74. These categories included genes involved in mitochondrial electron transport, secondary metabolism, stress, misc, transcription factors and transport. Additionally, weighted correlation network analysis identified two modules that were highly correlated with acid phosphatase and antioxidant enzyme activity. Citrate synthase gene (CS), acyl-coenzyme A oxidase4 gene (ACX), cytokinin dehydrogenase 7 gene (CKXs), and two-component response regulator ARR2 gene (ARR2) were identified as the most central hub genes in these two modules. CONCLUSION: In summary, we have pinpointed the gene categories responsible for the LP response variations between the two salt-tolerant germplasms, which are mainly related to antioxidant, and P uptake process. Further, the discovery of the hub genes layed the foundation for further exploration of the molecular mechanism of salt-tolerant and P-efficient in soybean.