Aquatic life criteria of hydrothermal liquefaction wastewater via ecotoxicity test and modeling.

Wastewater resulting from hydrothermal liquefaction (HTL-AP) of biowaste is gaining attention as an emerging hazardous material. However, there is a lack of specific and systematic ecotoxicity studies on HTL-AP. This study addresses this gap by conducting acute toxicity tests on HTL-AP using typical aquatic species and integrating these results with predicted toxicity values from interspecies correlation estimation models to establish aquatic life criteria. HTL-AP exhibited significant toxicity with LC50 of 956.12-3645.4 mg/L, but demonstrated moderate toxicity compared to common freshwater pollutants like commercial microbicides, personal care products, and insect repellents. The resulting hazardous concentration for 5 % of species (HC5), the criterion maximum concentration, and the short-term water quality criteria for aquatic were 506.0, 253.0, and 168.7 mg/L, respectively. Notably, certain organisms like Misgurnus anguillicaudatus and Cipangopaludina chinensis showed high tolerance to HTL-AP, likely due to their metabolic capabilities on HTL-AP components. The significant decrease in HC5 values for some HTL-AP substances compared to pure compounds could indicate the synergistic inhibition effects among HTL-AP compositions. Furthermore, according to the established criteria, HTL-AP required significantly less diluted water (13 t) than carbendazim (1009 t) to achieve biosafety, indicating a safer release. This research establishes a preliminary water quality criterion for HTL-AP, offering a valuable reference for risk assessment and prediction in the utilization of HTL-AP within environmental contexts.

Causality between allergic diseases and kidney diseases: a two-sample Mendelian randomization study.

Background: Evidence from observational studies and clinical trials suggests that the allergic diseases (ADs) are associated with kidney diseases (KDs). However, the causal association between them remains to be determined. We used bidirectional two-sample Mendelian randomization (MR) analysis to evaluate the potential causality between them. Methods: Mendelian randomization (MR) was performed using publicly available genome-wide association study (GWAS) summary datasets. Inverse variance weighted (IVW), weighted median, MR-Egger regression, simple mode, and weighted mode methods are used to evaluate the causality between ADs and KDs. Sensitivity and heterogeneity analyses were used to ensure the stability of the results. Results: The MR results indicated that genetic susceptibility to ADs was associated with a higher risk of CKD [odds ratio (OR) = 1.124, 95% CI = 1.020-1.239, p = 0.019] and unspecified kidney failure (OR = 1.170, 95% CI = 1.004-1.363, p = 0.045) but not with kidney stone, ureter stone or bladder stone (OR = 1.001, 95% CI = 1.000-1.002, p = 0.216), other renal or kidney problem (OR = 1.000, 95% CI = 1.000-1.001, p = 0.339), urinary tract or kidney infection (OR = 1.000, 95% CI = 0.999-1.001, p = 0.604), kidney volume (OR = 0.996, 95% CI = 0.960-1.033, p = 0.812) and cyst of kidney (OR = 0.914, 95% CI = 0.756-1.105, p = 0.354). No causal evidence of KDs on ADs was found in present study. Conclusion: Results from MR analysis indicate a causal association between ADs and CKD and unspecified kidney failure. These findings partly suggest that early monitoring of CKD risk in patients with ADs is intentional.

Microfluidic paper-based analysis device applying black phosphorus nanosheets@MWCNTs-COOH: A portable and efficient strategy for detection of ß-Lactoglobulin in dairy products.

This study prepared a novel, portable and cost-effective microfluidic paper-based electrochemical analysis device (µ-PAD) using black phosphorus nanosheets@carboxylated multi-walled carbon nanotubes (BPNSs@MWCNTs-COOH) nanocomposites for ß-lactoglobulin (ß-LG) detection. At the appreciate ratio, the synthesized BPNSs@MWCNTs-COOH was demonstrated to not only serve as a high-quality substrate for the specific aptamer immobilization, but also improve the electron transfer capability of the sensing interface. The µ-PADs, utilizing BPNSs@MWCNTs-COOH and aptamer recognition, exhibited a wider detection range (10-1000 ng mL-1) and lower detection limit (LOD: 0.12 ng mL-1) for ß-LG, and demonstrated enhanced specificity, satisfactory anti-interference ability and stability. When applied to the ß-LG determination in dairy samples, the µ-PAD yielded ß-LG concentrations highly correlated with those obtained using the HPLC method (R2: 0.9982). These results emphasized the reliable performance of the developed µ-PADs in ß-LG allergen quantification, highlighting their potential as an efficient platform for the rapid screening of ß-LG allergens.

Bimetallic Ag/Au nanoclusters encapsulated in ZIF-8 framework: A novel strategy for ratiometric fluorescence detection of doxycycline in food.

This study successfully encapsulated the Ag+-doped Au nanoclusters (Ag/AuNCs) within the ZIF-8 framework to construct a novel Ag/AuNCs@ZIF-8 ratiometric fluorescent probe for the antibiotic doxycycline (DOX) detection. The incorporation of Ag+ contributed to the fluorescence enhancement of the nanoclusters through the "silver effect", consequently improving the stability of the developed bimetallic Ag/AuNCs. Furthermore, the encapsulation of bimetallic Ag/AuNCs within the ZIF-8 framework restricted their intramolecular vibrations, resulting in further amplification of fluorescence intensity at 595 nm. The ZIF-8 also sensitized the restoration of DOX green fluorescence at 515 nm. Within the concentration range of 0.001-20 µg mL-1, the ratio of fluorescence intensity (F515/F595) exhibited a favorable linearity for DOX concentration, with a detection limit of 36.8 ng mL-1. This ratiometric fluorescence approach had the promising potential for accurate and efficient quantitative detection of DOX residue in food and served as a valuable reference for rapid monitoring of food contaminants.

Ambient PM2.5 components and prevalence of chronic kidney disease: a nationwide cross-sectional survey in China.

OBJECTIVES: Chronic kidney disease (CKD) is a global public health concern, and accumulating evidence has indicated that air pollution increases the odds of CKD. However, a limited number of studies have examined the long-term effects of ambient fine particulate matter (PM2.5) components on the risk of CKD among general population; thus, major knowledge gaps remain. METHODS: Using data from a nationwide representative cross-sectional survey in China and a validated PM2.5 composition dataset, we established generalized linear models to quantify the association between five major components of PM2.5 and CKD prevalence. RESULTS: There were significant associations between long-term exposure to three PM2.5 components [including black carbon (BC), sulfate (SO42-), organic matter (OM)] and increased odds of CKD prevalence. Along with an interquartile range (IQR) increment in BC (3.3 µg/m3), SO42- (9.7 µg/m3), and OM (16.2 µg/m3) at a 4-year moving average, the odds ratios (ORs) for CKD prevalence were 1.28 (95% CI 1.07, 1.54), 1.23 (95% CI 1.03, 1.45), and 1.23 (95% CI 1.02, 1.47), respectively. We did not detect any significant association of the other two PM2.5 components [nitrate (NO3-) or ammonium (NH4+)] with CKD prevalence. Stratified analyses revealed no differences (P ≥ 0.05) in the effect estimates of subgroups based on administrative region, sex, age, and other demographic characteristics. For instance, along with an IQR increment in BC at a 4-year moving average, the ORs of CKD prevalence among males and females were 1.30 (95% CI 0.98, 1.73) and 1.29 (95% CI 1.01, 1.65), respectively. The odds of CKD were generally higher with increasing PM2.5 composition concentration. CONCLUSIONS: Our study demonstrated that long-term exposure to specific PM2.5 components including BC, SO42-, and OM increased CKD risk in the general population. This study could provide new insights into source-directed PM2.5 control and CKD prevention.

Identification of recurrent BRAF non-V600 mutations in intraductal carcinoma of the prostate in Chinese populations.

While BRAF alterations have been established as a driver in various solid malignancies, the characterization of BRAF alterations in prostate cancer (PCa) has not been thoroughly interrogated. By bioinformatics analysis, we first found that BRAF alterations were associated with advanced PCa and exhibited mutually exclusive pattern with ERG alteration across multiple cohorts. Of the most interest, recurrent non-V600 BRAF mutations were found in 3 of 21 (14.3 %) PCa patients demonstrating IDC-P morphology. Furthermore, experimental overexpression of BRAFK601E and BRAFL597R exhibited emergence of oncogenic phenotypes with intensified MAPK signaling in vitro, which could be targeted by MEK inhibitors. Comparison of the incidence of BRAF alterations in IDC-P between western and Chinese ancestry revealed an increased prevalence in the Chinese population. The BRAF mutation may represent important genetic alteration in a subset of IDC-P, highlighting the role of MAPK signaling pathway in this subtype of PCa. To the best of knowledge, this is the first description of non-V600 BRAF mutation in setting of IDC-P, which may in part explain the aggressive phenotype seen in IDC-P and could also bring more treatment options for PCa patients with IDC-P harboring such mutations.

Stigma and lesbian, gay, bisexual, transgender, and queer (and additional identities) (LGBTQ+) parent socialization self-efficacy: Mediating roles of identity and community.

In the United States, cultural forces have led to the stigmatization of lesbian, gay, bisexual, transgender, and queer (and additional identities) (LGBTQ+) parenthood. However, pushing back against this stigmatization, developing a positive LGBTQ+ identity, and investing in one's LGBTQ+ community may inform empowering narratives of future parenthood and related constructs, such as LGBTQ+ parent socialization. Perceived self-efficacy related to preparation for bias (i.e., discussions of discrimination, prejudice, or bias-based bullying) socialization is likely associated with an individual's own perceptions or experiences of stigmatization given the conceptual overlap of bias and stigma. However, other constructs related to stigmatization and socialization self-efficacy, such as positive LGBTQ+ identity or community connectedness, have yet to be simultaneously considered (to our knowledge). Further, previous research has rarely included different assessments of stigma (i.e., perceived and enacted) and/or dimensions of positive LGBTQ+ identity (i.e., authenticity and self-awareness). Thus, this study aimed to rectify these gaps and provide a greater understanding of sexual stigma and LGBTQ+ parent socialization self-efficacy. Using data from a survey-based, online, cross-sectional study of LGBTQ+ childfree adults (N = 433; Mage = 29.85 years old) in the United States, we found that experiences of enacted or perceived sexual stigma were differentially associated with LGBTQ+ parent socialization preparation for bias self-efficacy. Further, positive LGBTQ+ identity authenticity and self-awareness, as well as LGBTQ+ community connectedness played distinct roles as mediators of the relationships between sexual stigma and LGBTQ+ parent socialization self-efficacy. These findings have implications for how we might understand the role of stigma, identity, community, and socialization among future LGBTQ+ parents. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Novel treatment from a botanical formulation Si-Miao-Yong-an decoction inhibits vasa vasorum angiogenesis and stabilizes atherosclerosis plaques via the Wnt1/ß-catenin signalling pathway.

CONTEXT: Si-Miao-Yong-An (SMYA) has been widely used for the clinical treatment of atherosclerosis (AS). Yet, its complete mechanism of action is not fully understood. OBJECTIVE: To investigate the mechanism by which SMYA stabilizes AS plaques from the perspective of inhibiting vasa vasorum (VV) angiogenesis. MATERIALS AND METHODS: We used male ApoE-/- mice to establish an AS model. The mice were divided into model, SMYA (11.7 mg/kg/d), and simvastatin (SVTT) (2.6 mg/kg/d) groups. Mice were given SMYA or SVTT by daily gavage for 8 weeks. HE staining, immunofluorescence double-labelling staining, and immunohistochemical staining were used to observe the pathological changes in the plaques. Finally, the protein and mRNA expression levels of the Wnt1/ß-catenin signalling pathway were detected by Western blot and qRT-PCR, respectively. RESULTS: SMYA significantly attenuated cholesterol crystallization, and lipid accumulation in AS plaques, resulting in smaller plaque size (0.25 mm2 vs. 0.46 mm2), and lowering ratio of plaque to lumen area (20.04% vs. 38.33%) and VV density (50.64/mm2 vs. 98.02/mm2). Meanwhile, SMYA suppressed both the positive area percentage of Wnt1 (2.53 vs. 3.56), ß-catenin (3.33 vs. 5.65) and Cyclin D1 (2.10 vs. 3.27) proteins in the aortic root plaques, and mRNA expression of Wnt1 (1.38 vs. 2.09), ß-catenin (2.05 vs. 3.25) and Cyclin D1 (1.39 vs. 2.57). DISCUSSION AND CONCLUSIONS: SMYA has a protective effect against AS, which may be related to its anti-VV angiogenesis in plaques, suggesting that SMYA has the potential as a novel botanical formulation in the treatment of AS.

Review: Synthesis of metal organic framework-based composites for application as immunosensors in food safety.

Ensuring food safety continues to be one of the major global challenges. For effective food safety monitoring, fast, sensitive, portable, and efficient food safety detection strategies must be devised. Metal organic frameworks (MOFs) are porous crystalline materials that have attracted attention for use in high-performance sensors for food safety detection owing to their advantages such as high porosity, large specific surface area, adjustable structure, and easy surface functional modification. Immunoassay strategies based on antigen-antibody specific binding are one of the important means for accurate and rapid detection of trace contaminants in food. Emerging MOFs and their composites with excellent properties are being synthesized, providing new ideas for immunoassays. This article summarizes the synthesis strategies of MOFs and MOF-based composites and their applications in the immunoassays of food contaminants. The challenges and prospects of the preparation and immunoassay applications of MOF-based composites are also presented. The findings of this study will contribute to the development and application of novel MOF-based composites with excellent properties and provide insights into advanced and efficient strategies for developing immunoassays.

c-Myc-Targeting PROTAC Based on a TNA-DNA Bivalent Binder for Combination Therapy of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is highly aggressive with a poor clinical prognosis and no targeted therapy. The c-Myc protein is a master transcription factor and a potential therapeutic target for TNBC. In this study, we develop a PROTAC (PROteolysis TArgeting Chimera) based on TNA (threose nucleic acid) and DNA that effectively targets and degrades c-Myc. The TNA aptamer is selected in vitro to bind the c-Myc/Max heterodimer and appended to the E-box DNA sequence to create a high-affinity, biologically stable bivalent binder. The TNA-E box-pomalidomide (TEP) conjugate specifically degrades endogenous c-Myc/Max, inhibits TNBC cell proliferation, and sensitizes TNBC cells to the cyclin-dependent kinase inhibitor palbociclib in vitro. In a mouse TNBC model, combination therapy with TEP and palbociclib potently suppresses tumor growth. This study offers a promising nucleic acid-based PROTAC modality for both chemical biology studies and therapeutic interventions of TNBC.

Integrative applications of network pharmacology and molecular docking: An herbal formula ameliorates H9c2 cells injury through pyroptosis.

Background: QiShen YiQi pills (QSYQ) is a Traditional Chinese Medicine (TCM) formula, which has a significant effect on the treatment of patients with myocardial infarction (MI) in clinical practice. However, the molecular mechanism of QSYQ regulation pyroptosis after MI is still not fully known. Hence, this study was designed to reveal the mechanism of the active ingredient in QSYQ. Methods: Integrated approach of network pharmacology and molecular docking, were conducted to screen active components and corresponding common target genes of QSYQ in intervening pyroptosis after MI. Subsequently, STRING and Cytoscape were applied to construct a PPI network, and obtain candidate active compounds. Molecular docking was performed to verify the binding ability of candidate components to pyroptosis proteins and oxygen-glucose deprivation (OGD) induced cardiomyocytes injuries were applied to explore the protective effect and mechanism of the candidate drug. Results: Two drug-likeness compounds were preliminarily selected, and the binding capacity between Ginsenoside Rh2 (Rh2) and key target High Mobility Group Box 1 (HMGB1)was validated in the form of hydrogen bonding. 2 µM Rh2 prevented OGD-induced H9c2 death and reduced IL-18 and IL-1ß levels, possibly by decreasing the activation of the NLRP3 inflammasome, inhibiting the expression of p12-caspase1, and attenuating the level of pyroptosis executive protein GSDMD-N. Conclusions: We propose that Rh2 of QSYQ can protect myocardial cells partially by ameliorating pyroptosis, which seems to have a new insight regarding the therapeutic potential for MI.

Regional urbanicity levels modify the association between ambient air pollution and prevalence of obesity: A nationwide cross-sectional survey.

Ambient air pollution exposure may increase the risk of obesity, but the population susceptibility associated with urbanicity has been insufficiently investigated. Based on a nationwide representative cross-sectional survey on 44,544 adults, high-resolution night light satellite remote sensing products, and multi-source ambient air pollution inversion data, the present study evaluated the associations of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) concentrations with the prevalence of obesity and abdominal obesity. We further calculated the associations in regions with different urbanicity levels characterized by both administrative classification of urban/rural regions and night light index (NLI). We found that 10 µg/m3 increments in PM2.5 at 1-year moving average and in NO2 at 5-year moving average were associated with increased prevalence of obesity [odds ratios (OR) = 1.16 (1.14, 1.19); 1.12 (1.09, 1.15), respectively] and abdominal obesity [OR = 1.08 (1.07, 1.10); 1.07 (1.05, 1.09), respectively]. People in rural regions experienced stronger adverse effects than those in urban regions. For instance, a 10 µg/m3 increment in PM2.5 was associated with stronger odds of obesity in rural regions than in urban regions [OR = 1.27 (1.23, 1.31) vs 1.10 (1.05, 1.14), P for interaction <0.001]. In addition, lower NLI values were associated with constantly amplified associations of PM2.5 and NO2 with obesity and abdominal obesity (all P for interaction <0.001). In summary, people in less urbanized regions are more susceptible to the adverse effects of ambient air pollution on obesity, suggesting the significance of collaborative planning of urbanization development and air pollution control, especially in less urbanized regions.

Selection of RNA-Cleaving TNA Enzymes for Cellular Mg2+ Imaging.

Catalytic DNA-based fluorescent sensors have enabled cellular imaging of metal ions such as Mg2+ . However, natural DNA is prone to nuclease-mediated degradation. Here, we report the in vitro selection of threose nucleic acid enzymes (TNAzymes) with RNA endonuclease activities. One such TNAzyme, T17-22, catalyzes a site-specific RNA cleavage reaction with a kcat of 0.017 min-1 and KM of 675 nM. A fluorescent sensor based on T17-22 responds to an increasing concentration of Mg2+ with a limit of detection at 0.35 mM. This TNAzyme-based sensor also allows cellular imaging of Mg2+ . This work presents the first proof-of-concept demonstration of using a TNA catalyst in cellular metal ion imaging.

A review of plant antipathogenic constituents: Source, activity and mechanism.

Green prevention and control of plant pathogens is a development direction of sustainable and low-carbon agriculture given the limitation of traditional chemicals. Plant-derived antipathogenic constituents (PAPCs) exhibit the advantages of being environmental benign and a broad spectrum of target pathogens over traditional chemicals. Here, we review the research advances on plant sources, chemical compositions, activities of antipathogenic constituents in the past 20 years. Reported PAPCs are classified into categories of phenols, flavonoids, terpenoids, alkaloids and antimicrobial peptides. Angiosperms, gymnosperms and some lower plants are the main plant source of detected PAPCs. The PAPCs act on pathogens through multiple pathways including destroying cell structures, blocking key composition synthesis and inhibiting cell metabolism. The development trends of PAPCs are finally prospected. This review serves as a comprehensive review on the study of plant antipathogenic constituents and a key reference for forecasting the source, characteristic and activity of PAPC.

Understand the antibacterial behavior and mechanism of hydrothermal wastewater.

Unlocking the antibacterial potential is an emerging strategy to valorizing the toxic wastewater from hydrothermal liquefaction (HTL). Here, we investigated the response and biological mechanism of antibacterial properties of HTL wastewater. Four different biowastes i.e. microalgae, cornstalk, cow manure and swine manure were used as the feedstock of HTL to create wastewater with diverse molecule spectrum, whereas ten strains i.e. five gram-positive strains and five gram-negative strains were employed to represent typical pathogenic microorganism. HTL wastewater exhibited antibacterial potential and obvious reduction on cell viability at high inclusion ratio, although the minimum inhibitory concentration (MIC) and cell response intensity varied depending on different HTL feedstocks and strain species. The decreased ATP generation and increased H2O2 accumulation in treated cells further confirmed the inhibition of HTL wastewater on the cell metabolism. The antibacterial mechanism of HTL wastewater was confirmed, including damage to biomolecules or membranes, depletion of crucial components, disruption of metabolic circuits and imbalance of creation of redox cofactor. The complex compounds in HTL wastewater were probably attributed to the multiple inhibition pathways and the relationship among those multiple pathways was speculated. The present study contributes to the mechanism analysis of complex compound mixture and bactericide characteristics of HTL wastewater.

V7 ENB-guided thoracoscopic sublobectomy for stage IA synchronous multiple primary lung cancer.

BACKGROUND: An increasing number of patients are being diagnosed with synchronous multiple primary lung cancer (SMPLC) with the popularization of lung cancer screening programs. However, a strategy for accurate location and suitable surgery therapy is still lacking. The present study aimed to explore the accuracy and feasibility of electromagnetic navigation bronchoscopy (ENB)-guided thoracoscopic sublobectomy for stage IA SMPLC. METHODS: Patients with SMPLC who underwent ENB-guided sublobectomy from January 2020 to June 2022 were enrolled in this study. The analysis of localization accuracy of ENB and surgical outcome was conducted. RESULTS: Overall, 138 patients with 353 malignant nodules were enrolled. The tumor size was 0.7 cm (range from 0.5 to 1.1 cm). ENB localization was performed on 162 nodules, and a customized scoring system was developed to evaluate localization accuracy. The success rate of localization was 98.3% (178/181). Notably, localization accuracy was positively correlated with bronchial signs (p < 0.01) and negatively correlated with the distance from the nodule to the pleura (p = 0.02). All nodules were completely resected. Operation time, drainage volume on the third postoperative day, and catheter time were significantly correlated with the resected lesion numbers (p = 0.009, p = 0.004, and p = 0.01, respectively). CONCLUSIONS: ENB-guided uniportal video-assisted thoracoscopic sublobectomy provides accurate preoperative localization and avoids unnecessary lung resection of patients with stage IA SMPLC. However, complete resection of multilocation nodules (more than four lesions) increases the risk of postoperative complications. A new combined treatment strategy for SMPLC should be explored.

A Nucleic Acid Sequence That is Catalytically Active in Both RNA and TNA Backbones.

Threose nucleic acid (TNA) is considered a potential RNA progenitor due to its chemical simplicity, base pairing property, and capability of folding into a functional tertiary structure. However, it is unknown whether the functional property can be maintained during transition from TNA to RNA. Here, we use a toggle in vitro selection to identify nucleic acid catalyst sequences that are active in both TNA and RNA backbones. One such nucleic acid enzyme with exchangeable backbone (CAMELEON) catalyzes an RNA cleavage reaction when prepared as TNA (T) and RNA (R). Further biochemical characterization reveals that CAMELEON R and T exhibit different catalytic behaviors such as rate enhancement and magnesium dependence. Structural probing and mutagenesis experiments suggest that they likely fold into distinct tertiary structures. This work demonstrates that the catalytic activity can be preserved during backbone transition from TNA to RNA and provides further experimental support for TNA as an RNA precursor in evolution.

Effects of four cooking methods on flavor and sensory characteristics of scallop muscle.

This work aimed to explore the influence of four different cooking methods (Boiling, roasting, frying, and microwaving) on the sensory characteristics of scallop muscles. Headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) and electronic nose (e-nose) were combined to analyze the aroma of scallops. Combined with the results of free amino acids and electronic tongue (e-tongue), the taste changes of different samples were analyzed. Furthermore, texture profile and microstructure analysis jointly showed the influence of cooking methods on texture. The results showed that frying was the most suitable cooking method for scallop muscle because it resulted the best tasted products, boiled scallops retain the highest similarity to fresh scallops. Besides, a higher level of lipid oxidation and Maillard reaction resulted in significant increase in aldehydes, ketones, furans, umami, and sweet amino acid. For the boiled sample, the loss of water-soluble compounds and less fat oxidation resulted in fewer flavor substances and free amino acids, along with looser organizational structure and poorer sensory quality. The research showed that besides the texture of scallop muscle, volatile organic compounds and free amino acids as well as their mutual roles in taste and smell were also important to sensory receptivity.

QishenYiqi dripping pill protects against myocardial ischemia/reperfusion injury via suppressing excessive autophagy and NLRP3 inflammasome based on network pharmacology and experimental pharmacology.

Background: Myocardial ischemia/reperfusion (I/R) injury is associated with multiple serious clinical manifestations. Autophagy is upregulated in a short period of ischemia and further enhanced during reperfusion phase, which was considered as a "double-edged sword" in the pathological process of myocardial I/R injury. In addition, NLRP3 inflammasome triggers myocardial inflammatory response, which leads to cardiomyocyte death via pyroptosis and promotes subsequent myocardial remodelling. Qishen Yiqi Dripping Pill (QSYQ) has been recognized as a potential protective agent of cardiovascular diseases. Objective: We predicted the bioactive compounds, targets and pathways of OSYQ intervening on myocardial I/R injury by network pharmacology. Furthermore, we investigated the effect of QSYQ on myocardial I/R injury and explored its underlying mechanism via autophagy and NLRP3 Inflammasome. Methods: Bioactive compounds, targets of QSYQ and relevant targets of myocardial I/R injury were collected from public databases. The protein-protein interaction network, Gene ontology and KEGG pathway enrichment analysis were carried out to screen the key compounds, target genes, functional annotation and pivotal pathways. Molecular docking was used to validate the binding association between target genes and key bioactive ingredients. Furthermore, sixty SD rats were randomized into four groups: 1) sham, 2) model, 3) captopril and 4) QSYQ pretreatment (14 days before and after surgery). Each arm was subjected to ischemia/reperfusion surgery except sham arm (30 min coronary ligation, then reperfusion). Left ventricular (LV) function were evaluated and the hearts were used to evaluate size of myocardial infarction, cardiomyocyte fibrosis, and myocardial autophagosomes. Results: The network pharmacology revealed the mechanism of QSYQ intervening on myocardial I/R injury might be related to NOD-like receptor signaling pathway, PI3K-Akt signaling pathway, autophagy-animal, etc., Molecular-docking suggested the core target proteins had good binding association with bioactive compounds of QSYQ. The experiment confirmed that QSYQ attenuated myocardial infarct size, decreased inflammatory infiltration and collagen fiber deposition and alleviated the autophagosome and myocardium ultrastructure injury, leading to LV systolic function improvement. The possible mechanism of cardioprotection was due to regulating autophagy-related proteins, activating PI3K/Akt-mTOR signaling pathway, and inhibiting activation and assembly of NLRP3 inflammasome. Conclusion: QSYQ ameliorated myocardial I/R injury via suppressing excessive autophagy and NLRP3 Inflammasome.

Genomics Analysis and Nomogram Risk Prediction of Occult Lymph Node Metastasis in Non-Predominant Micropapillary Component of Lung Adenocarcinoma Measuring ≤ 3 cm.

Background: The efficacy of sublobar resection and selective lymph node dissection is gradually being accepted by thoracic surgeons for patients within early-stage non-small cell lung cancer (NSCLC). Nevertheless, there are still some NSCLC patients develop lymphatic metastasis at clinical T1 stage. Lung adenocarcinoma with a micropapillary (MP) component poses a higher risk of lymph node metastasis and recurrence even when the MP component is not predominant. Our study aimed to explore the genetic features and occult lymph node metastasis (OLNM) risk factors in patients with a non-predominant micropapillary component (NP-MPC) in a large of patient's cohort with surgically resected lung adenocarcinoma. Methods: Between January 2019 and December 2021, 6418 patients who underwent complete resection for primary lung adenocarcinoma at the Qilu Hospital of Shandong University. In our study, 442 patients diagnosed with lung adenocarcinoma with NP-MPC with a tumor size ≤3 cm were included. Genetic alterations were analyzed using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Abnormal protein expression of gene mutations was validated using immunohistochemistry. A nomogram risk model based on clinicopathological parameters was developed to predict OLNM. This model was invalidated using the calibration plot and concordance index. Results: In our retrospective cohort, the incidence rate of the micropapillary component was 11.17%, and OLNM was observed in 20.13% of the patients in our study. ARMS-PCR suggested that EGFR exon 19 del was the most frequent alteration in NP-MCP patients compared with other gene mutations (frequency: 21.2%, P<0.001). Patients harboring exon 19 del showed significantly higher risk of OLNM (P< 0.001). A nomogram was developed based on five risk parameters, which showed good calibration and reliable discrimination ability (C-index = 0.84) for evaluating OLNM risk. Conclusions: Intense expression of EGFR exon 19 del characterizes lung adenocarcinoma in patients with NP-MCP and it's a potential risk factor for OLNM. We firstly established a nomogram based on age, CYFRA21-1 level, tumor size, micropapillary and solid composition, that was effective in predicting OLNM among NP-MCP of lung adenocarcinoma measuring ≤ 3 cm.