Predicting lymphovascular invasion in N0 stage non-small cell lung cancer: A nomogram based on Dual-energy CT imaging and clinical findings.

PURPOSE: To construct a nomogram for predicting lymphovascular invasion (LVI) in N0 stage non-small cell lung cancer (NSCLC) using dual-energy computed tomography (DECT) findings combined with clinical findings. METHODS: We retrospectively recruited 135 patients with N0 stage NSCLC from two hospitals underwent DECT before surgery and were divided into development cohort (n = 107) and validation cohort (n = 28). The clinical findings (baseline characteristics, biochemical markers, serum tumor markers and Immunohistochemical markers), DECT-derived parameters (iodine concentration [IC], effective atomic number [Eff-Z] and normalized iodine concentration [NIC], iodine enhancement [IE] and NIC ratio [NICr]) and Fractal dimension (FD) were collected and measured. A nomogram was constructed using significant findings to predict LVI in N0 stage NSCLC and was externally validated. RESULTS: Multivariable analysis revealed that lymphocyte count (LYMPH, odds ratio [OR]: 3.71, P=0.014), IC in arterial phase (ICa, OR: 1.25, P=0.021), NIC in venous phase (NICv, OR: 587.12, P=0.009) and FD (OR: 0.01, P=0.033) were independent significant factors for predicting LVI in N0 stage NSCLC, and were used to construct a nomogram. The nomogram exhibited robust predictive capabilities in both the development and validation cohort, with AUCs of 0.819 (95 % CI: 72.6-90.4) and 0.844 (95 % CI: 68.2-95.8), respectively. The calibration plots showed excellent agreement between the predicted probabilities and the actual rates of positive LVI, on external validation. CONCLUSIONS: Combination of clinical and DECT imaging findings could aid in predicting LVI in N0 stage NSCLC using significant findings of LYMPH, ICa, NICv and FD.

Leveraging cfDNA fragmentomic features in a stacked ensemble model for early detection of esophageal squamous cell carcinoma.

In this study, we develop a stacked ensemble model that utilizes cell-free DNA (cfDNA) fragmentomics for the early detection of esophageal squamous cell carcinoma (ESCC). This model incorporates four distinct fragmentomics features derived from whole-genome sequencing (WGS) and advanced machine learning algorithms for robust analysis. It is validated across both an independent validation cohort and an external cohort to ensure its generalizability and effectiveness. Notably, the model maintains its robustness in low-coverage sequencing environments, demonstrating its potentials in clinical settings with limited sequencing resources. With its remarkable sensitivity and specificity, this approach promises to significantly improve the early diagnosis and management of ESCC. This study represents a substantial step forward in the application of cfDNA fragmentomics in cancer diagnostics, emphasizing the need for further research to fully establish its clinical efficacy.

Status and development of research on clear cell carcinoma of the ovary-a visualization-based bibliometric analysis.

Background: Clear cell carcinoma of the ovary (CCCO) is a relatively rare type of epithelial ovarian cancer (EOC) that has unique biological characteristics and clinical features. Researchers have paid less attention to this disease than to other types of EOCs. However, in recent years, research in this area has still progressed. In this paper, a bibliometric analysis is used to integrate and analyse the literature in the field of CCCO in the past 20 years to determine research development, better understand the current status of research, and provide a reference for future study directions in this field. Methods: With CCCO as the research subject, relevant publications indexed in the Web of Science (WOS) core dataset from September 2003 to September 2023 were retrieved. After screening the publications, we used EXCEL, VOSviewer, CiteSpace, Charticulator, Gephi, OriginPro and other tools to perform in-depth analyses of and to visualize the data. Results: Through a comprehensive analysis of the literature in this field, we found that research on CCCO experienced a relatively rapid increase in 2006 and is now in a period of relatively high fluctuation. The quality of the literature in this field is generally high. In this field, countries in East Asia and North America play core roles, with Japan accounting for the most studies. A stable research group has been formed in this field, and extensive collaboration has occurred among the various research groups. In the past 20 years, basic research and clinical research in the field of CCCO have developed together, and a healthy development model in which basic and clinical research promote each other has formed. Research in this field has been continuously developed from a preliminary understanding of clinical features to in-depth explorations of the pathogenesis and the continuous optimization of treatment methods. The key molecular events in the pathogenesis and development of this disease and the application of novel antitumour drugs for this disease are the current research focuses and the future development direction in this field. Conclusions: Research on CCCO has progressed significantly in the past 20 years, but there are still many important issues regarding its pathogenesis and treatment that need to be addressed, and therefore, more research in this area should be conducted in the future. The study of key molecular events and the use of novel antitumour drugs are future development directions in this field.

Omics-imaging signature-based nomogram to predict the progression-free survival of patients with hepatocellular carcinoma after transcatheter arterial chemoembolization.

BACKGROUND: Enhanced magnetic resonance imaging (MRI) is widely used in the diagnosis, treatment and prognosis of hepatocellular carcinoma (HCC), but it can not effectively reflect the heterogeneity within the tumor and evaluate the effect after treatment. Preoperative imaging analysis of voxel changes can effectively reflect the internal heterogeneity of the tumor and evaluate the progression-free survival (PFS). AIM: To predict the PFS of patients with HCC before operation by building a model with enhanced MRI images. METHODS: Delineate the regions of interest (ROI) in arterial phase, portal venous phase and delayed phase of enhanced MRI. After extracting the combinatorial features of ROI, the features are fused to obtain deep learning radiomics (DLR)_Sig. DeLong's test was used to evaluate the diagnostic performance of different typological features. K-M analysis was applied to assess PFS in different risk groups, and the discriminative ability of the model was evaluated using the C-index. RESULTS: Tumor diameter and diolame were independent factors influencing the prognosis of PFS. Delong's test revealed multi-phase combined radiomic features had significantly greater area under the curve values than did those of the individual phases (P < 0.05).In deep transfer learning (DTL) and DLR, significant differences were observed between the multi-phase and individual phases feature sets (P < 0.05). K-M survival analysis revealed a median survival time of high risk group and low risk group was 12.8 and 14.2 months, respectively, and the predicted probabilities of 6 months, 1 year and 2 years were 92%, 60%, 40% and 98%, 90%,73%, respectively. The C-index was 0.764, indicating relatively good consistency between the predicted and observed results. DTL and DLR have higher predictive value for 2-year PFS in nomogram. CONCLUSION: Based on the multi-temporal characteristics of enhanced MRI and the constructed Nomograph, it provides a new strategy for predicting the PFS of transarterial chemoembolization treatment of HCC.

Analysis of optical properties and response mechanism of H2S fluorescent probe based on rhodamine derivatives.

H2S plays a crucial role in numerous physiological and pathological processes. In this project, a new fluorescent probe, SG-H2S, for the detection of H2S, was developed by introducing the recognition group 2,4-dinitrophenyl ether. The combination of rhodamine derivatives can produce both colorimetric reactions and fluorescence reactions. Compared with the current H2S probes, the main advantages of SG-H2S are its wide pH range (5-9), fast response (30 min), and high selectivity in competitive species (including biological mercaptan). The probe SG-H2S has low cytotoxicity and has been successfully applied to imaging in MCF-7 cells, HeLa cells, and BALB/c nude mice. We hope that SG-H2S will provide a vital method for the field of biology.

Long noncoding RNA VPS9D1-AS1 promotes the progression of endometrial cancer via regulation of the miR-187-3p/S100A4 axis.

VPS9D1-AS1 functions as an oncogene in many cancers. However, its role and potential mechanism in the progression of endometrial cancer (EC) are not fully understood. VPS9D1-AS1 levels in EC and adjacent normal tissues were investigated using the TCGA-UCEC cohort and 24 paired clinical samples. The roles of VPS9D1-AS1 and miR-187-3p in cell cycle, proliferation, and apoptosis were evaluated by loss- and gain-of-function experiments. In addition, the effect of VPS9D1-AS1 on tumor growth was further investigated in vivo. Rescue experiments were performed to investigate the involvement of the miR-187-3p/S100A4 axis in VPS9D1-AS1 knockdown-mediated antitumor effects. VPS9D1-AS1 was highly expressed in EC tissues. VPS9D1-AS1 knockdown, similar to miR-187-3p overexpression, significantly inhibited cell proliferation, inhibited colony formation, induced cell cycle arrest, and facilitated apoptosis of KLE cells. MiR-187-3p bound directly to VPS9D1-AS1 and the 3'UTR of S100A4. Furthermore, VPS9D1-AS1 negatively regulated miR-187-3p while positively regulating S100A4 expression in EC cells. MiR-187-3p knockdown or S100A4 overexpression partially reversed the tumor suppressive function of VPS9D1-AS1 knockdown. The results suggest that VPS9D1-AS1 affects EC progression by regulating the miR-187-3p/S100A4 axis. This may provide a promising therapeutic target to help treat EC.

Initial experience using ultrasound, automated breast volume scanner, and elastography for primary leiomyosarcoma of the breast: A rare case report.

Background: Primary leiomyosarcoma of the breast was a rare malignant tumor. Due to the extremely low morbidity and insufficient understanding of its imageological characteristics, there was a risk of misdiagnosis. In this case report, we presented the features of conventional US, elastography, automated breast volume scanner (ABVS), computed tomography (CT), and pathological findings of a case of primary leiomyosarcoma of the breast. Case presentation: A 74-year-old woman detected a mass of the left breast by palpation. Both ultrasound and CT revealed a solid mass in the outer quadrant of the left breast. After admission, she underwent a modified radical unilateral mastectomy under general anesthesia (resection of the lesion with left breast reserved). Furthermore, the intraoperative frozen section revealed malignant spindle cells, and the postoperative histopathology revealed primary leiomyosarcoma of the breast. After discharge, the patient was generally in good condition after the procedure and was asked to seek medical treatment in the oncology department. Findings on various imaging examinations and clinical data were carefully evaluated. Additionally, we also reviewed the associated kinds of literature. Conclusion: We reported the features of conventional US, elastography, ABVS, CT, and pathological findings of a rare case of primary leiomyosarcoma of the breast. Overall, our findings indicated that the above-mentioned features generally predict malignancy. However, compared to other malignant breast lesions, the features of this case were not specific enough.

Relationship between different clinical characteristics and pericoronary adipose tissue attenuation values quantified from coronary computed tomographic angiography (CCTA) in patients without coronary heart disease (CHD).

Background: Pericoronary adipose tissue (PCAT) is a sensor of vascular inflammation. Elevated PCAT attenuation values indicate the presence of coronary inflammation in patients. However, it is unclear which clinical characteristics are associated with increased PCAT attenuation values in patients without coronary heart disease (CHD). The study aims to investigate the relationship between increased PCAT attenuation values and clinical characteristics of patients without CHD. Methods: We recruited 785 eligible patients without CHD who underwent coronary computed tomographic angiography (CCTA). Clinical data were recorded for each patient, and PCAT attenuation values for the left anterior descending branch (LADPCAT), left circumflex branch (LCXPCAT), and right coronary artery (RCAPCAT) were quantified by CCTA using fully automated software. Univariate and multivariate analyses were performed to identify the associations between different clinical characteristics and elevated LADPCAT, LCXPCAT, and RCAPCAT. Results: Univariate analysis showed body mass index (BMI) to be positively associated with LADPCAT (rs=0.109), LCXPCAT (rs=0.076), and RCAPCAT (rs=0.083). Moreover, the duration of smoking, and drinking was positively associated with LADPCAT (rs=0.099, 0.165). Hyperlipidemia was positively associated with LADPCAT (rs=0.089) and RCAPCAT (rs=0.334), while statin use was negatively associated with RCAPCAT (rs=-0.145). Multivariate analysis showed that the significant determinants of LADPCAT were BMI (ß=0.359, P=0.001), duration of smoking (ß=2.612, P=0.002), drinking (ß=4.106, P<0.001), and hyperlipidemia (ß=1.664, P=0.027). LCXPCAT was associated with BMI (ß=0.218, P=0.024), while RCAPCAT was associated with hyperlipidemia (ß=6.110, P<0.001) and statin use (ß=-3.338, P<0.001). Conclusions: In patients without CHD, the PCAT attenuation values measured using CCTA were associated with various clinical characteristics. LADPCAT was associated with BMI, smoking duration, drinking, and hyperlipidemia. On the other hand, LCXPCAT was associated with BMI, while RCAPCAT was associated with hyperlipidemia and statin use.

Feedback of chain elongation microorganisms on iron-based conductive materials: Enhanced microbial functions and biotoxicity adaptation mechanisms.

Despite the increased research efforts aimed at understanding iron-based conductive materials (CMs) for facilitating chain elongation (CE) to produce medium chain fatty acids (MCFAs), the impact of these materials on microbial community functions and the adaptation mechanisms to their biotoxicity remain unclear. This study found that the supply of zero-valent iron (ZVI) and magnetite enhanced the MCFAs carbon-flow distribution by 26 % and 52 %, respectively. Metagenomic analysis revealed the upregulation of fatty acid metabolism, pyruvate metabolism and ABC transporters with ZVI and magnetite. The predominant functional microorganisms were Massilibacterium and Tidjanibacter with ZVI, and were Petrimonas and Candidatus_Microthrix with magnetite. Furthermore, it was demonstrated that CE microorganisms respond and adapt to the biotoxicity of iron-based CMs by adjusting Two-component system and Quorum sensing for the first time. In summary, this study provided a new deep-insight on the feedback mechanisms of CE microorganisms on iron-based CMs.

Efficacy and Safety of Programmed Death 1/Programmed Death-Ligand 1 Plus Cytotoxic T-Lymphocyte-Associated Antigen 4 Inhibitors for Advanced or Metastatic Non-Small Cell Lung Cancer: A Meta-analysis Based on Randomized Controlled Trials.

BACKGROUND: This meta-analysis aims to investigate the efficacy and safety of programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) combined with cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors for patients with advanced or metastatic non-small cell lung cancer (NSCLC). METHODS: Authors conducted a comprehensive search of PubMed, Embase, Cochrane Library, Web of Science, Scopus, and Medline for randomized controlled trials comparing the prognosis and safety of PD-1/PD-L1 plus CTLA-4 inhibitors with other therapies for advanced or metastatic NSCLC. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used as effect sizes. The primary outcomes of this study were overall survival (OS) and progression-free survival. RESULTS: A total of 4943 patients diagnosed with stage III/IV advanced or metastatic NSCLC were included in the analysis of the 6 randomized controlled trials. The results showed that patients receiving dual immunotherapy with PD-1/PD-L1 plus CTLA-4 inhibitors had a longer survival time compared with the control group (HR = 0.88, P = 0.044). However, no statistically significant difference was observed in progression-free survival (HR = 0.95, P = 0.579). Subgroup analysis revealed better OS in the interventional group for patients aged >65 years (HR = 0.88, P = 0.076), smokers (HR = 0.81, P = 0.036), and those with a tumor mutational burden (TMB) ≥20 mut/Mb (HR = 0.66, P < 0.001). Conversely, the control group demonstrated superior OS in patients with TMB <20 mut/Mb (HR = 1.14, P = 0.048). In addition, the statistical results indicated a lower incidence rate of any-grade anemia in the dual immunotherapy group compared with the control group (RR = 0.32, P = 0.04). CONCLUSIONS: This meta-analysis demonstrates the effectiveness and safety of dual immunotherapy with PD-1/PD-L1 plus CTLA-4 inhibitors for treating advanced or metastatic NSCLC. Its efficacy is influenced by certain clinical and pathological factors, such as age, smoking status, and TMB.

Aggregation-Augmented Magnetism of Lanthanide-Doped Nanoparticles and Enabling Magnetic Levitation-Based Exosome Sensing.

Due to the presence of unpaired electron orbitals in most lanthanide ions, lanthanide-doped nanoparticles (LnNPs) exhibit paramagnetism. However, as to biosensing applications, the magnetism of LnNPs is so weak that can hardly be employed in target separation. Herein, it is discovered that the magnetism of the LnNPs is highly associated with their concentration in a confined space, enabling aggregation-augmented magnetism to make them susceptive to a conventional magnet. Accordingly, a magnetic levitation (Maglev) sensing system is designed, in which the target exosomes can specifically introduce paramagnetic LnNPs to the microbeads' surface, allowing aggregation-augmented magnetism and further leverage the microbeads' levitation height in the Maglev device to indicate the target exosomes' content. It is demonstrated that this Maglev system can precisely distinguish healthy people's blood samples from those of breast cancer patients. This is the first work to report that LnNPs hold great promise in magnetic separation-based biological sample sorting, and the LnNP-permitted Maglev sensing system is proven to be promising for establishing a new generation of biosensing devices.

GLP-2 ameliorates D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a signaling pathway in C2C12 cells and mice.

BACKGROUND: The study aimed to investigate the effect of Glucagon-like peptide-2 (GLP-2) on muscle aging in vivo and in vitro. METHODS: Six-week-old C57BL/6J mice were administered with D-galactose (200 mg/kg/day, intraperitoneally) for 8weeks, followed by daily subcutaneous injections of GLP-2 (300 or 600 µg/kg/day) for 4weeks. Skeletal muscle function and mass were evaluated using relative grip strength and muscle weight. The sizes and types of muscle fibers and apoptosis were assessed through histological analysis, immunofluorescence staining, and TUNEL staining, respectively. C2C12 myotubes were treated with D-galactose (40 mg/mL) and GLP-2. Protein expression of differentiation-related myogenic differentiation factor D (MyoD), myogenin (MyoG), and myosin heavy chain (Myhc), degradation-related Muscle RING finger 1 (MuRF-1), and muscle atrophy F-box (MAFbx)/Atrogin-1, and apoptosis-related B-cell leukemia/lymphoma 2 (Bcl-2) and Bax, were assessed using western blots. The Pi3k inhibitor LY294002 was applied to investigate whether GLP-2 regulated myogenesis and myotube aging via IGF-1/Pi3k/Akt/FoxO3a signaling pathway. RESULTS: The results demonstrated that GLP-2 significantly reversed the decline in muscles weight, relative grip strength, diameter, and cross-sectional area of muscle fibers induced by D-galactose in mice. Apart from suppressing the expressions of MuRF-1 and Atrogin-1 in the muscles and C2C12 myotubes, GLP-2 significantly increased the expressions of MyoD, MyoG, and Myhc compared to the D-galactose. GLP-2 significantly suppressed cell apoptosis. Western blot analysis indicated that the regulation of GLP-2 may be attributed to the activation of theIGF-1/Pi3k/Akt/FoxO3a phosphorylation pathway. CONCLUSIONS: This study suggested that GLP-2 ameliorated D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a pathway.

Migration Patterns and Potential Risk Assessment of Trace Elements in the Soil-Plant System in the Production Area of the Chinese Medicinal Herb Scrophularia ningpoensis Hemsl.

Scrophularia ningpoensis Hemsl. holds a prominent place among Chinese medicinal herbs. Assessing the soil-plant system of its origin is crucial for ensuring medication safety. Although some trace elements are essential for the normal functioning of living organisms, exposure to higher concentrations is harmful to humans, so in order to assess the possible health risk of trace elements in the soil-plant system of Scrophularia ningpoensis Hemsl. origin for human assessment, we used non-carcinogenic risk (HI) and carcinogenic risk (CR) for their evaluation. In this paper, the following trace elements were studied in the soil-Scrophularia ningpoensis Hemsl. system: manganese (Mn), iron (Fe), cobalt (Co), zinc (Zn), selenium (Se), molybdenum (Mo), arsenic (As) and lead (Pb). Correlation and structural equation analyses showed that the effect of soil in the root zone on the plant was much greater than the effect of soil in the non-root zone on the plant. The single-factor pollution index (Pi) showed that the soil in the production area of Scrophularia ningpoensis Hemsl. was polluted to a certain extent, notably with Pb showing the highest average Pi values of 0.94 and 0.89 in the non-root and root zones, respectively. Additionally, the Nemerow composite pollution indices (PN) for both zones indicated an alert range. Regarding health risks, exposure to soil in the non-root zone posed higher non-carcinogenic risk (HI) and carcinogenic risk (CR) compared to the root zone, although neither zone presented a significant carcinogenic risk. The potential non-carcinogenic risk (HI) and carcinogenic risk (CR) from consuming Scrophularia ningpoensis Hemsl. leaves and stems were more than ten times higher than that of roots. However, the carcinogenic risk (CR) values for both the soil and plant of interest in the soil- Scrophularia ningpoensis Hemsl. system did not exceed 10-4, and therefore no significant carcinogenic risk existed.

Multifunctional fluorescence/photoacoustic bimodal imaging of γ-glutamyltranspeptidase in liver disorders under different triggering conditions.

Hepatocellular carcinoma (HCC) seriously threatens the human health. Previous investigations revealed that γ-glutamyltranspeptidase (GGT) was tightly associated with the chronic injury, hepatic fibrosis, and the development of HCC, therefore might act as a potential indicator for monitoring the HCC-related processes. Herein, with the contribution of a structurally optimized probe ETYZE-GGT, the bimodal imaging in both far red fluorescence (FL) and photoacoustic (PA) modes has been achieved in multiple HCC-related models. To our knowledge, this work covered the most comprehensive models including the fibrosis and developed HCC processes as well as the premonitory induction stages (autoimmune hepatitis, drug-induced liver injury, non-alcoholic fatty liver disease). ETYZE-GGT exhibited steady and practical monitoring performances on reporting the HCC stages via visualizing the GGT dynamics. The two modes exhibited working consistency and complementarity with high spatial resolution, precise apparatus and desirable biocompatibility. In cooperation with the existing techniques including testing serum indexes and conducting pathological staining, ETYZE-GGT basically realized the universal application for the accurate pre-clinical diagnosis of as many HCC stages as possible. By deeply exploring the mechanically correlation between GGT and the HCC process, especially during the premonitory induction stages, we may further raise the efficacy for the early diagnosis and treatment of HCC.

The efficacy and safety of adding PD-1 blockade to induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) for locoregionally advanced nasopharyngeal carcinoma: an observational, propensity score-matched analysis.

BACKGROUND: Despite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC  plus cisplatin CCRT ) for LANPC patients. METHODS: From January 2020 to November 2022, 347 patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0) were included. Of the 347 patients, 268 patients were treated with standard treatment (IC-CCRT), and 79 received PD-1 blockade plus IC-CCRT (PD-1 group). For the PD-1 group, PD-1 blockade was given intravenously once every 3 weeks for up to 9 cycles (3 induction and 6 adjuvant). The primary endpoint was disease-free survival (DFS) (i.e. freedom from local/regional/distant failure or death). The propensity score matching (PSM) with the ratio of 1:2 was performed to control confounding factors. RESULTS: After PSM analysis, 150 patients receiving standard treatment and 75 patients receiving additional PD-1 blockade remained in the current analysis. After three cycles of IC, the PD-1 group had significantly higher rates of complete response (defined as disappearance of all target lesions; 24% vs. 9%; P = 0.006) and complete biological response (defined as undetectable cell-free Epstein-Barr virus DNA, cfEBV DNA; 79% vs. 65%; P = 0.046) than that in the standard group. And the incidence of grade 3-4 toxicity during IC was 47% in the PD-1 group and 41% in the standard group, with no significant difference (P = 0.396). During follow-up period, additional PD-1 blockade to standard treatment improved 3-year DFS from 84 to 95%, with marginal statistical significance (HR, 0.28; 95%CI, 0.06-1.19; P = 0.064). CONCLUSION: Additiaonl PD-1 blockade to gemcitabine and cisplatin IC and adjuvant treatment results in significant improvement in tumor regression, cfEBV DNA clearance, superior DFS, and comparable toxicity profiles in high-risk LANPC patients.

Therapeutic administration of Luteolin protects against Escherichia coli-derived Lipopolysaccharide-triggered inflammatory response and oxidative injury.

Endometritis reduces reproductive effectiveness and leads to significant financial losses in the dairy sector. Luteolin is a natural phyto-flavonoid compound with many biological activities. However, the therapeutic effect of Luteolin against lipopolysaccharides (LPS)-induced endometritis has not yet been explored. A total of eighty female Kunming mice were randomly assigned into four treatment groups (n = 20). Following a successful initiation of the endometritis model by LPS, Luteolin was intraperitoneally administered three times, at six-hour intervals between each injection in the Luteolin groups. The histopathological findings revealed that Luteolin significantly alleviated uterine injury induced by LPS. Moreover, Luteolin suppressed the synthesis of pro-inflammatory mediators [interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α] while promoting the synthesis of an anti-inflammatory mediator (IL-10) altered by LPS. Furthermore, Luteolin significantly mitigated the LPS-induced oxidative stress by scavenging malondialdehyde (MDA) and reactive oxygen species (ROS), accumulation and boosting the capacity of antioxidant enzyme activities such as superoxide dismutase 1 (SOD1), catalase (CAT), and glutathione peroxidase 1 (Gpx1) in the uterine tissue of mice. Additionally, injection of Luteolin markedly increased the expression of Toll-like receptors (TLR) 4 both at mRNA and protein levels under LPS stimulation. Western blotting and ELISA findings demonstrated that Luteolin suppressed the activation of the NF-κB pathway in response to LPS exposure in the uterine tissue of mice. Notably, Luteolin enhanced the anti-oxidant defense system by activating the Nrf2 signaling pathway under LPS exposure in the uterine tissue of mice. Conclusively, our findings demonstrated that Luteolin effectively alleviated LPS-induced endometritis via modulation of TLR4-associated Nrf2 and NF-κB signaling pathways.

Arbuscular Mycorrhizal Fungi Improve Lycium barbarum Potassium Uptake by Activating the Expression of LbHAK.

Arbuscular mycorrhizal (AM) fungi can establish a mutualistic relationship with the roots of most terrestrial plants to increase plant nutrient uptake. The effects of potassium uptake and transport by AM symbiosis are much less reported compared to other nutrients. In this research, a heterologous yeast system was used to verify that the LbHAK has capacity for potassium uptake. The split-roots system implemented using seedlings of Lycium barbarum confirmed that R. irregularis locally induced LbHAK expression, which means that LbHAK is only expressed in mycorrhizal roots. Furthermore, the impacts of overexpression of LbHAK on the growth, nutrients and water uptake, and transport of mycorrhizal tobacco (inoculation with Rhizophagus irregularis) at 0.2 mM and 2 mM K conditions were assessed. The mycorrhizal tobacco growth and potassium accumulation were significantly enhanced through LbHAK overexpression in tobacco. In addition, overexpression of LbHAK substantially enhanced phosphorus content, while stimulating the expression of NtPT4, Rir-AQP1, and Rir-AQP2 in mycorrhizal tobacco. Moreover, LbHAK overexpression greatly promoted AM colonization. LbHAK has a potential role in facilitating potassium absorption through the mycorrhizal pathway, and overexpression of LbHAK in tobacco may promote the transport of potassium, phosphorus, and water from AM fungi to tobacco. These data imply the important roles played by the LbHAK in AM-fungi-induced potassium uptake in L. barbarum and in improving plant nutrients and AM colonization.

Artificial intelligence enables precision diagnosis of cervical cytology grades and cervical cancer.

Cervical cancer is a significant global health issue, its prevalence and prognosis highlighting the importance of early screening for effective prevention. This research aimed to create and validate an artificial intelligence cervical cancer screening (AICCS) system for grading cervical cytology. The AICCS system was trained and validated using various datasets, including retrospective, prospective, and randomized observational trial data, involving a total of 16,056 participants. It utilized two artificial intelligence (AI) models: one for detecting cells at the patch-level and another for classifying whole-slide image (WSIs). The AICCS consistently showed high accuracy in predicting cytology grades across different datasets. In the prospective assessment, it achieved an area under curve (AUC) of 0.947, a sensitivity of 0.946, a specificity of 0.890, and an accuracy of 0.892. Remarkably, the randomized observational trial revealed that the AICCS-assisted cytopathologists had a significantly higher AUC, specificity, and accuracy than cytopathologists alone, with a notable 13.3% enhancement in sensitivity. Thus, AICCS holds promise as an additional tool for accurate and efficient cervical cancer screening.

Activation of the Nrf2/ARE signaling pathway ameliorates hyperlipidemia-induced renal tubular epithelial cell injury by inhibiting mtROS-mediated NLRP3 inflammasome activation.

Dyslipidemia is the most prevalent independent risk factor for patients with chronic kidney disease (CKD). Lipid-induced NLRP3 inflammasome activation in kidney-resident cells exacerbates renal injury by causing sterile inflammation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that modulates the cellular redox balance; however, the exact role of Nrf2 signaling and its regulation of the NLRP3 inflammasome in hyperlipidemia-induced kidney injury are poorly understood. In this study, we demonstrated that activation of the mtROS-NLRP3 inflammasome pathway is a critical contributor to renal tubular epithelial cell (RTEC) apoptosis under hyperlipidemia. In addition, the Nrf2/ARE signaling pathway is activated in renal tubular epithelial cells under hyperlipidemia conditions both in vivo and in vitro, and Nrf2 silencing accelerated palmitic acid (PA)-induced mtROS production, mitochondrial injury, and NLRP3 inflammasome activation. However, the activation of Nrf2 with tBHQ ameliorated mtROS production, mitochondrial injury, NLRP3 inflammasome activation, and cell apoptosis in PA-induced HK-2 cells and in the kidneys of HFD-induced obese rats. Furthermore, mechanistic studies showed that the potential mechanism of Nrf2-induced NLRP3 inflammasome inhibition involved reducing mtROS generation. Taken together, our results demonstrate that the Nrf2/ARE signaling pathway attenuates hyperlipidemia-induced renal injury through its antioxidative and anti-inflammatory effects through the downregulation of mtROS-mediated NLRP3 inflammasome activation.

Engineered lactococcus lactis intrapleural therapy promotes regression of malignant pleural effusion by enhancing antitumor immunity.

Intrapleural immunotherapies have emerged as a prominent field in treating malignant pleural effusion (MPE). Among these, bacteria-based intrapleural therapy has exerted an anti-MPE effect by immuno-stimulating or cytotoxic properties. We previously engineered a probiotic Lactococcus lactis (FOLactis) expressing a fusion protein of Fms-like tyrosine kinase 3 and co-stimulator OX40 ligands. FOLactis activates tumor antigen-specific immune responses and displays systemic antitumor efficacy via intratumoral delivery. However, no available lesions exist in the pleural cavity of patients with MPE for intratumoral administration. Therefore, we further optimize FOLactis to treat MPE through intrapleural injection. Intrapleural administration of FOLactis (I-Pl FOLactis) not only distinctly suppresses MPE and pleural tumor nodules, but also significantly extends noticeable survival in MPE-bearing murine models. The proportion of CD103+ dendritic cells (DCs) in tumor-draining lymph nodes increases three-fold in FOLactis group, compared to the wild-type bacteria group. The enhanced DCs recruitment promotes the infiltration of effector memory T and CD8+ T cells, as well as the activation of NK cells and the polarization of macrophages to M1. Programmed death 1 blockade antibody combination further enhances the antitumor efficacy of I-Pl FOLactis. In summary, we first develop an innovative intrapleural strategy based on FOLactis, exhibiting remarkable efficacy and favorable biosafety profiles. These findings suggest prospective clinical translation of engineered probiotics for managing MPE through direct administration into the pleural cavity.