Hierarchically porous MOF@COF structures with ultrafast gas diffusion rate for C2H6/C2H4 separation.

For ethylene purification, C2H6-selective metal-organic frameworks (MOFs) show great potential to directly produce polymer-grade C2H4 from C2H6/C2H4 mixtures. Most C2H6-traping MOFs are ultra-microporous structures so as to strengthen multiple supramolecular interactions with C2H6. However, the narrowed pore channels of C2H6-traping MOFs cause large guest diffusion barriers, greatly hampering their practical applications. Herein, we present a feasible strategy by precisely constructing hierarchically porous MOF@COF core-shell structures to address this issue. Additional mesoporous diffusion channels were incorporated between MOF crystals through the construction of the COF shell, thereby enhancing the gas adsorption kinetics. Notably, designing a core-shell MOF@COF structure with an optimal coating amount of mesoporous COF shell will further improve the gas diffusion rate. Breakthrough experiments reveal that the tailored MOF@COF composites can effectively achieve C2H6/C2H4 separation and maintain its separation performance over five continuous measurement cycles. This investigation opens up a new avenue to solve the diffusion/transfer issues and provides more opportunities and potentials for MOF@COF composites in practical separation applications.

Lactobacillus acidophilus and Bacillus subtilis significantly change the growth performance, serum immunity and cecal microbiota of Cherry Valley ducks during the fattening period.

This study explored the effects of a Bacillus subtilis and Lactobacillus acidophilus mixture containing the co-fermented products of the two probiotics on growth performance, serum immunity and cecal microbiota of Cherry Valley ducks. This study included 480 one-day-old Cherry Valley ducks divided into four feeding groups: basal diet (control group) and basal diet supplemented with 300, 500, or 700 mg/kg of the probiotic powder; the ducks were raised for 42 days. Compared with the control group, body weight on day 42 and the average daily gain on days 15-42 significantly increased (p < 0.05), and the feed conversion rate significantly decreased (p < 0.05) in the experimental groups. Furthermore, the serum immunoglobulin (Ig) A, IgG, IgM, and interleukin (IL)-4 levels increased significantly (p < 0.05), and IL-1ß, IL-2, and tumor necrosis factor-α decreased significantly (p < 0.05) in the experimental groups. Finally, Sellimonas, Prevotellaceae NK3B31 group, Lachnospiraceae NK4A136 group and Butyricoccus played an important role in the cecal microbiota of the experimental group. Thus, the probiotic powder has impacts on the growth performance, serum immunity and cecal microbiota of Cherry Valley Ducks.

Establishment of an in vitro model of monocyte-like THP-1 cells for trained immunity induced by bacillus Calmette-Guérin.

BACKGROUND: Mycobacteria bloodstream infections are common in immunocompromised people and usually have disastrous consequences. As the primary phagocytes in the bloodstream, monocytes and neutrophils play critical roles in the fight against bloodstream mycobacteria infections. In contrast to macrophages, the responses of monocytes infected with the mycobacteria have been less investigated. RESULTS: In this study, we first established a protocol for infection of non-adherent monocyte-like THP-1 cells (i.e. without the differentiation induced by phorbol 12-myristate 13-acetate (PMA) by bacillus Calmette-Guérin (BCG). Via the protocol, we were then capable of exploring the global transcriptomic profiles of non-adherent THP-1 cells infected with BCG, and found that NF-κB, MAPK and PI3K-Akt signaling pathways were enhanced, as well as some inflammatory chemokine/cytokine genes (e.g. CCL4, CXCL10, TNF and IL-1ß) were up-regulated. Surprisingly, the Akt-HIF-mTOR signaling pathway was also activated, which induces trained immunity. In this in vitro infection model, increased cytokine responses to lipopolysaccharides (LPS) restimulation, higher cell viability, and decreased Candida albicans loads were observed. CONCLUSIONS: We have first characterized the transcriptomic profiles of BCG-infected non-adherent THP-1 cells, and first developed a trained immunity in vitro model of the cells.

Multi-omics analysis reveals that linoleic acid metabolism is associated with variations of trained immunity induced by distinct BCG strains.

Trained immunity is one of the mechanisms by which BCG vaccination confers persistent nonspecific protection against diverse diseases. Genomic differences between the different BCG vaccine strains that are in global use could result in variable protection against tuberculosis and therapeutic effects on bladder cancer. In this study, we found that four representative BCG strains (BCG-Russia, BCG-Sweden, BCG-China, and BCG-Pasteur) covering all four genetic clusters differed in their ability to induce trained immunity and nonspecific protection. The trained immunity induced by BCG was associated with the Akt-mTOR-HIF1α axis, glycolysis, and NOD-like receptor signaling pathway. Multi-omics analysis (epigenomics, transcriptomics, and metabolomics) showed that linoleic acid metabolism was correlated with the trained immunity-inducing capacity of different BCG strains. Linoleic acid participated in the induction of trained immunity and could act as adjuvants to enhance BCG-induced trained immunity, revealing a trained immunity-inducing signaling pathway that could be used in the adjuvant development.

Development and Validation of a Nomogram for Prognosis Prediction in Patients with Synchronous Primary Thyroid and Breast Cancer Based on SEER Database.

This study aimed to develop prognostic prediction models for patients diagnosed with synchronous thyroid and breast cancer (TBC). Utilizing the SEER database, key predictive factors were identified, including T stage of thyroid cancer, T stage of breast cancer, M stage of breast cancer, patient age, thyroid cancer surgery type, and isotope therapy. A nomogram predicting 5-year and 10-year survival rates was constructed and validated, exhibiting strong performance (C-statistic: 0.79 in the development cohort (95% CI: 0.74-0.84), and 0.82 in the validation cohort (95% CI: 0.77-0.89)). The area under the Receiver Operator Characteristic (ROC) curve ranged from 0.798 to 0.883 for both cohorts. Calibration and decision curve analyses further affirmed the model's clinical utility. Stratifying patients into high-risk and low-risk groups using the nomogram revealed significant differences in survival rates (P < 0.0001). The successful development and validation of this nomogram for predicting 5-year and 10-year survival rates in patients with synchronous TBC hold promise for similar patient populations, contributing significantly to cancer research.

TGF-α/EGFR signaling promotes lipopolysaccharide-induced abnormal elastin deposition and alveolar simplification.

Bronchopulmonary dysplasia (BPD) is characterized by shortened secondary septa and fewer, larger alveoli. Elastin deposition to the distal tips of the secondary septa is critical for elongation of the secondary septa. Alveolar myofibroblasts, which are thought to migrate to the septal tips during alveolarization, are mainly responsible for elastin production and deposition. Antenatal exposure to inflammation induces abnormal elastin deposition, thereby increasing the risk of developing BPD. Here, we found that lipopolysaccharide (LPS) significantly increased the expression of transforming growth factor-α (TGF-α) in an LPS-induced rat model of BPD and in LPS-treated human pulmonary epithelial cells (BEAS-2B). In addition, in vitro experiments suggested that LPS upregulated TGF-α expression via toll-like receptor 4 (TLR4)/tumor necrosis factor α-converting enzyme (TACE) signaling. Increased TGF-α levels via its receptor epidermal growth factor receptor (EGFR)-induced lysyl oxidase (LOX) overactivation and cell division cycle 42 (Cdc42) activity inhibition of myofibroblasts. Similarly, in vivo LOX overactivation and inhibition of Cdc42 activity were observed in the lungs of LPS-exposed pups. LOX overactivation led to abnormal elastin deposition, and inhibition of Cdc42 activity disturbed the directional migration of myofibroblasts and disrupted elastin localization. Most importantly, the EGFR inhibitor erlotinib partially rescued LOX overactivation and Cdc42 activity inhibition, and improved elastin deposition and alveolar development in antenatal LPS-treated rats. Taken together, our data suggest that TGF-α/EGFR signaling is critically involved in the regulation of elastin deposition and represents a novel therapeutic target.

m6A/HOXA10-AS/ITGA6 axis aggravates oxidative resistance and malignant progression of laryngeal squamous cell carcinoma through regulating Notch and Keap1/Nrf2 pathways.

As the second most prevalent malignant tumor of head and neck, laryngeal squamous cell carcinoma (LSCC) imposes a substantial health burden on patients worldwide. Within recent years, resistance to oxidative stress and N6-methyladenosine (m6A) of RNA have been proved to be significantly involved in tumorigenesis. In current study, we investigated the oncogenic role of m6A modified long non coding RNAs (lncRNAs), specifically HOXA10-AS, and its downstream signaling pathway in the regulation of oxidative resistance in LSCC. Bioinformatics analysis revealed that heightened expression of HOXA10-AS was associated with the poor prognosis in LSCC patients, and N (6)-Methyladenosine (m6A) methyltransferase-like 3 (METTL3) was identified as a factor in promoting m6A modification of HOXA10-AS and further intensify its RNA stability. Mechanistically, HOXA10-AS was found to play as a competitive endogenous RNA (ceRNA) by sequestering miR-29 b-3p and preventing its downregulation of Integrin subunit alpha 6 (ITGA6), ultimately enhancing the oxidative resistance of tumor cells and promoting the malignant progression of LSCC. Furthermore, our research elucidated the mechanism by which ITGA6 accelerates Keap1 proteasomal degradation via enhancing TRIM25 expression, leading to increased Nrf2 stability and exacerbating its aberrant activation. Additionally, we demonstrated that ITGA6 enhances γ-secretase-mediated Notch signaling activation, ultimately promoting RBPJ-induced TRIM25 transcription. The current study provides the evidence supporting the effect of m6A modified HOXA10-AS and its downstream miR-29 b-3p/ITGA6 axis on regulating oxidative resistance and malignant progression in LSCC through the Notch and Keap1/Nrf2 pathways, and proposed that targeting this axis holds promise as a potential therapeutic approach for treating LSCC.

Enhanced corrosion of 2205 duplex stainless steel by Acetobacter aceti through synergistic electron transfer and organic acids acceleration.

Acetobacter aceti is a microbe that produces corrosive organic acids, causing severe corrosion of industrial equipment. Previous studies have focused on the organic acid corrosion of A. aceti, but neglected the possibility that it has electron transfer corrosion. This study found that electron transfer and organic acids can synergistically promote the corrosion of 2205 duplex stainless steel (DSS). Electrochemical measurement results showed that corrosion of 2205 DSS was more severe in the presence of A. aceti. Surface analysis indicated a thick biofilm formed on the steel surface, with low pH and dissolved oxygen concentrations under the biofilm. Corrosion intensified when A. aceti lacked a carbon source, suggesting that A. aceti can corrode metals by using metallic substrates as electron donors, in addition to its acidic by-products.

REGγ Mitigates Radiation-Induced Enteritis by Preserving Mucin Secretion and Sustaining Microbiome Homeostasis.

Radiation-induced enteritis, a significant concern in abdominal radiation therapy, is associated closely with gut microbiota dysbiosis. The critical mucus layer plays a pivotal role in preventing the translocation of commensal and pathogenic microbes. Although the significant expression of REGγ in intestinal epithelial cells is well established, its role in modulating the mucus layer and gut microbiota remains enigmatic. The current study revealed notable changes in gut microorganisms and metabolites in irradiated mice lacking REGγ, as opposed to wild-type mice. Concomitant with gut microbiota dysbiosis, REGγ deficiency facilitated the infiltration of neutrophils and macrophages, thereby exacerbating intestinal inflammation after irradiation. Furthermore, fluorescence in situ hybridization assays unveiled an augmented proximity of bacteria to intestinal epithelial cells in REGγ knockout mice after irradiation. Mechanistically, deficiency of REGγ led to diminished goblet cell populations and reduced expression of key goblet cell markers, Muc2 and Tff3, observed in both murine models, minigut organoid systems and human intestinal goblet cells, indicating the intrinsic role of REGγ within goblet cells. Interestingly, although administration of broad-spectrum antibiotics did not impact the alteration of goblet cell numbers and MUC2 secretion, it effectively attenuated inflammation levels in the ileum of irradiated REGγ absent mice, aligning them with their wild-type counterparts. Collectively, these findings highlight the crucial contribution of REGγ in counteracting radiation-triggered microbial imbalances and cell-autonomous regulation of mucin secretion.

Exploring a novel long-acting glucagon-like peptide-1 receptor agonist built on the albumin-binding domain and XTEN scaffolds.

In recent years, glucagon-like peptide-1 (GLP-1) has demonstrated considerable potential in the treatment of type 2 diabetes (T2D) and obesity. However, the half-life of naturally occurring GLP-1 is quite short in vivo. Two common strategies employed for half-life extension are the use of the Albumin-binding domain (ABD) and XTEN polypeptide, which operate through different mechanisms. In this study, we designed an innovative GLP-1 receptor agonist with an extended duration of action. This new construct incorporated an albumin binding domain (ABD) and an XTEN sequence (either XTEN144 or XTEN288) as carriers. We referred to these fusion proteins as GLP-ABD-XTEN144 and GLP-ABD-XTEN288. In an E. coli system, the said constructs were efficaciously produced in substantial quantity. It was observed from in vitro studies that the fusion protein GLP-ABD-XTEN144 demonstrated a five times stronger affinity towards human serum albumin (HSA), boasting a binding affinity (Kd) of 5.50 nM. This was in contrast to GLP-ABD-XTEN288, whose Kd value was registered at 27.78 nM. Moreover, GLP-ABD-XTEN144 presented a half-life of 12.9 h in mice, thus exceeding the corresponding value for GLP-ABD-XTEN288, 7.32 h in mice. Both these fusion proteins significantly mitigated non-fasting blood sugar levels and overall food consumption for 48 h subsequent to a one-time injection in mice. Notably, GLP-ABD-XTEN144 exhibited more pronounced hypoglycemic activity and food inhibitory effects than GLP-ABD-XTEN288. The designed GLP-ABD-XTEN144 fusion protein shows promising prospects for clinical application in T2D treatment. Our findings also suggest that ABD and XTEN polypeptides synergistically contribute to half-life extension, further enhancing the pharmacokinetic characteristics of a payload.

Celecoxib alleviates the DSS-induced ulcerative colitis in mice by enhancing intestinal barrier function, inhibiting ferroptosis and suppressing apoptosis.

INTRODUCTION: Ulcerative colitis (UC) is an inflammatory intestine disease characterized by dysfunction of the intestinal mucosal barrier, ferroptosis, and apoptosis. Previous researches suggest that celecoxib, a nonsteroidal anti-inflammatory drug, holds promise in alleviating inflammation in UC. Therefore, this study aims to investigate the effects and mechanisms of celecoxib in UC. METHODS: To identify ferroptosis-related drugs and genes associated with UC, we utilized the Gene Expression Omnibus (GEO), FerrDb databases, and DGIdb database. Subsequently, we established a 2.5% DSS (Dextran sulfate sodium)-induced colitis model in mice and treated them with 10 mg/kg of celecoxib to validate the bioinformatics results. We evaluated histological pathologies, inflammatory response, intestinal barrier function, ferroptosis markers, and apoptosis regulators. RESULTS: Celecoxib treatment significantly ameliorated DSS-induced UC in mice, as evidenced by the body weight change curve, colon length change curve, disease activity index (DAI) score, and histological index score. Celecoxib treatment reduced the level of pro-inflammatory factors and promoted the expressions of intestinal tight junction proteins such as Claudin-1 and Occludin, thereby restoring the integrity of the intestinal mucosal barrier. Furthermore, celecoxib treatment reversed the ferroptosis characteristics in DSS-induced mice by increasing glutathione (GSH), decreasing malondialdehyde (MDA), and increasing the expression of GPX-4 and xCT. Additionally, apoptosis was induced in mice with UC, as evidenced by increased Caspase3, BAD, P53, BAX, Caspase9 and Aifm1 production, and decreased expression of BCL-XL and BCL2. Celecoxib treatment significantly reversed the apoptotic changes in DSS-induced mice. CONCLUSION: Our findings suggest that celecoxib effectively treats DSS-induced UC in mice by inhibiting ferroptosis and apoptosis.

Celecoxib enhancing intestinal barrier functionCelecoxib alleviates ferroptosis in DSS-induces ulcerative colitisCelecoxib effectively alleviates apoptosis signaling pathway.

Discovery of novel 2,3,4,5-tetrahydrospiro[benzo[c]azepine-1,1'-cyclohexan]-5-ol derivatives as PARP-1 inhibitors.

As an essential marker of cancer treatment, PARP-1 inhibitors could effectively kill tumor cells through a mechanism known as synthetic lethality and are used to treat a variety of cancers. In order to explore novel PARP-1 inhibitors, a series of 22 novel erythrina derivatives were reported and preliminarily explored their mechanism of action. The antitumor activities against four human cancer cell lines including A549, OVCAR-3, HCT-116, and MCF-7 were evaluated, and the preliminary SARs were summarized. Among them, compound 11b exhibited better anti-proliferative effects against A549 cells (IC50 = 1.95 µM). The SI results showed that compound 11b had low toxicity. Moreover, compound 11b displayed excellent PARP-1 inhibitory activities with IC50 values of 19.24 nM. In addition, molecular docking studies provided the rational binding modes of compound 11b in complexes with PARP-1. The flow cytometry assays revealed that compound 11b could induce apoptosis of A549 cells (P < 0.001). Simultaneously, compound 11b could effectively reduce the formation of PAR (P < 0.001). The ADMET prediction results indicated compound 11b had similar properties to rucaparib. Collectively, compound 11b has potential research value for further investigation.

Renin-angiotensin system inhibitors improve the survival of cholangiocarcinoma: a propensity score-matched cohort study.

BACKGROUND: Hypertension is a risk factor for cholangiocarcinoma (CCA). The effect of anti-hypertensive drugs on the prognosis of CCA is not clear. METHODS: This is a retrospective study of 102 patients (56.9% males, median age 66 years) diagnosed with CCA and hypertension concurrently and received radical surgery (R0), with a median follow-up of 36.7 months. Kaplan-Meier analysis, Cox regressions, and propensity score (PS) matching were applied for statistical analysis. RESULTS: Results of multivariable cox analysis showed that renin-angiotensin system inhibitors (RASis) usage was a protective factor for progression-free survival (PFS) (hazard ratio [HR] = 0.55, 95% confidence interval [95% CI]: 0.32-0.96) and overall survival (OS) (HR = 0.40, 95% CI: 0.20-0.79), respectively. Calcium channel blockers, diuretics, and ß-blockers didn't show significant associations. The association of RASis usage and PFS and OS was derived by PS matching, with a cohort of 28 RASis users and 56 RASis non-users. The median PFS and OS of RASis users (PFS, 17.6 months (9.2-34.4); OS, 24.8 months (16.5-42.3)) were longer than RASis non-users (PFS, 10.5 months (4.1-24.1); OS, 14.6 months (10.6-28.4)). The 1 year, 2 years, and 3 years' survival rates of RASis users (89.1%, 77.0%, and 65.5%) were higher than RASis non-users (70.9%, 54.0%, and 40.0%). CONCLUSIONS: RASis usage improves the survival of patients with CCA and hypertension concurrently.

[Esophageal Angiolipoma:Report of One Case and Literature Review].

Esophageal angiolipoma is a rare disease with unspecific clinical manifestations.This paper reported a case of esophageal angiolipoma confirmed by upper gastrointestinal endoscopy and summarized the clinical manifestations,endoscopic and pathological features,treatment and prognosis of the patients by reviewing the relevant literature,aiming to provide references for clinical diagnosis and treatment of this disease in the future.

Preoperative CT-guided localization of pulmonary nodules with low-dose radiation.

Background: Video-assisted thoracoscopic surgery (VATS) has been widely accepted for the treatment of pulmonary nodules. Prior to VATS, pulmonary nodules can be labeled by computed tomography (CT)-guided hook wire localization, but multiple scans are required, which increases the total radiation dose. We aimed to assess the effectiveness and risks of using low-dose radiation CT to locate lung nodules prior to VATS. Methods: This study included 158 patients who underwent VATS resection after CT-guided hook wire localization. Based on the CT tube voltage, patients were split into two groups: the low-voltage group (Group A) received 80 kV, while the high-voltage group (Group B) received 120 kV. The two groups' image quality, radiation exposure, localization success and complication rates were compared. The frequencies of intraoperative complications and the types of lung nodules were also compared between the groups. Results: Successful nodule mapping was obtained in 158 patients. There was no significant difference in age, sex ratio or BMI between the two groups. Subjective imaging quality in both groups met the requirements for location (≥2 points). The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in Group A were lower than those in Group B (P<0.05). Furthermore, the dose length product (DLP) and effective dose (ED) in Group A were lower than those in Group B (P<0.05). Conclusions: Low-dose radiation CT-guided localization is safe and feasible for identifying uncertain pulmonary nodules before VATS, enabling a significant radiation dose reduction while maintaining mapping accuracy and not increasing complication risk.

Balancing the Crystallinity and Film Formation of Metal-Organic Framework Membranes through In Situ Modulation for Efficient Gas Separation.

Polycrystalline metal-organic framework (MOF) layers hold great promise as molecular sieve membranes for efficient gas separation. Nevertheless, the high crystallinity tends to cause inter-crystalline defects/cracks in the nearby crystals, which makes crystalline porous materials face a great challenge in the fabrication of defect-free membranes. Herein, for the first time, we demonstrate the balance between crystallinity and film formation of MOF membrane through a facile in situ modulation strategy. Monocarboxylic acid was introduced as a modulator to regulate the crystallinity via competitive complexation and thus concomitantly control the film-forming state during membrane growth. Through adjusting the ratio of modulator acid/linker acid, an appropriate balance between this structural "trade-off" was achieved. The resulting MOF membrane with moderate crystallinity and coherent morphology exhibits molecular sieving for H2 /CO2 separation with selectivity up to 82.5.

Drug-induced lactate confers ferroptosis resistance via p38-SGK1-NEDD4L-dependent upregulation of GPX4 in NSCLC cells.

Ferroptosis is a newly defined non-apoptotic programmed cell death resulting from the accumulation of lipid peroxides. Whether ferroptosis plays any role in chemotherapy remains to be established. Here, we reported that ferroptosis represents a part of the chemotherapeutic drug etoposide-induced cell death response in Small Cell Lung Cancer (SCLC) cells and adaptive signaling molecule lactate protects Non-Small Cell Lung Cancer (NSCLC) from etoposide-induced ferroptosis. Lactate derived from metabolic reprogramming increases the expression of glutathione peroxidase 4 (GPX4) to promote ferroptosis resistance in NSCLC. Furthermore, we identified E3-ubiquitin ligase NEDD4L as a major regulator of GPX4 stability. Mechanistically, Lactate increases mitochondrial ROS generation and drives activation of the p38-SGK1 pathway, which attenuates the interaction of NEDD4L with GPX4 and subsequent ubiquitination and degradation of GPX4. Our data implicated the role of ferroptosis in chemotherapeutic resistance and identified a novel post-translational regulatory mechanism for the key Ferroptosis mediator GPX4.

SUMO specific peptidase 3 halts pancreatic ductal adenocarcinoma metastasis via deSUMOylating DKC1.

In the past few decades, advances in the outcomes of patients suffering from pancreatic ductal adenocarcinoma (PDAC) have lagged behind these gained in the treatment of many other malignancies. Although the pivotal role of the SUMO pathway in PDAC has been illustrated, the underlying molecule drivers have yet to be fully elucidated. In the present study, we identified SENP3 as a potential suppressor of PDAC progression through an in vivo metastatic model. Further studies revealed that SENP3 inhibited PDAC invasion in a SUMO system dependent fashion. Mechanistically, SENP3 interacted with DKC1 and, as such, catalyzed the deSUMOylation of DKC1, which accepted SUMO3 modifiers at three lysine residues. SENP3-mediated deSUMOylation caused DKC1 instability and disruption of the interaction between snoRNP proteins, which contributed to the impaired migration ability of PDAC. Indeed, overexpression of DKC1 abated the anti-metastasis effect of SENP3, and DKC1 was elevated in PDAC specimens and associated with a poor prognosis in PDAC patients. Collectively, our findings shed light on the essential role of SENP3/DKC1 axis in the progression of PDAC.

The synergized diagnostic value of VTQ with chemokine CXCL13 in lung tumors.

Virtual Touch Tissue Quantification (VTQ) offers several advantages in the diagnosis of various lung diseases. Chemokine expression levels, such as CXCL13, play a vital role in the occurrence and development of tumors and aid in the diagnosis process. The purpose of this study was to evaluate the combined value of VTQ and changes in CXCL13 expression levels for the diagnosis of lung tumors. A total of 60 patients with thoracic nodules and pleural effusion were included, with 30 of them having malignant pleural effusion (based on pathology) and the remaining 30 having benign thoracic nodules and pleural effusion. The relative expression level of CXCL13 was measured in the collected pleural effusions using Enzyme-Linked Immunosorbent Assay (ELISA). The relationship between CXCL13 expression levels and various clinical features was analyzed. A Receiver Operating Characteristic (ROC) curve analysis was conducted on the VTQ results and relative expression levels of CXCL13, and the areas under the curve, critical values, sensitivity, and specificity were calculated. Multivariate analysis incorporating multiple indicators was performed to determine the accuracy of lung tumor diagnosis. The results showed that the expression levels of CXCL13 and VTQ were significantly higher in the lung cancer group compared to the control group (P < 0.05). In the Non-Small Cell Lung Cancer (NSCLC) group, CXCL13 expression levels increased with later TNM staging and poorer tumor differentiation. The expression level of CXCL13 in adenocarcinoma was higher than that in squamous cell carcinoma. The ROC curve analysis revealed that CXCL13 had an area under the curve (AUC) of 0.74 (0.61, 0.86) with an optimal cut-off value of 777.82 pg/ml for diagnosing lung tumors. The ROC curve analysis of VTQ showed an AUC of 0.67 (0.53, 0.82) with a sensitivity of 60.0% and a specificity of 83.3%, and an optimal diagnostic cut-off of 3.33 m/s. The combination of CXCL13 and VTQ for diagnosing thoracic tumors had an AUC of 0.842 (0.74, 0.94), which was significantly higher than either factor alone. The results of the study demonstrate the strong potential of combining VTQ results with chemokine CXCL13 expression levels for lung tumor diagnosis. Additionally, the findings suggest that elevated relative expression of CXCL13 in cases of malignant pleural effusion caused by non-small cell lung cancer may indicate a poor prognosis. This provides promising potential for using CXCL13 as a screening tool and prognostic indicator for patients with advanced lung cancer complicated by malignant pleural effusion.

Dietary methionine restriction alleviates oxidative stress and inflammatory responses in lipopolysaccharide-challenged broilers at early age.

In this study, we investigated the effect of dietary methionine restriction (MR) on the antioxidant function and inflammatory responses in lipopolysaccharide (LPS)-challenged broilers reared at high stocking density. A total of 504 one-day-old male Arbor Acre broiler chickens were randomly divided into four treatments: 1) CON group, broilers fed a basal diet; 2) LPS group, LPS-challenged broilers fed a basal diet; 3) MR1 group, LPS-challenged broilers fed a methionine-restricted diet (0.3% methionine); and 4) MR2 group, LPS-challenged broilers fed a methionine-restricted diet (0.4% methionine). LPS-challenged broilers were intraperitoneally injected with 1 mg/kg body weight (BW) of LPS at 17, 19, and 21 days of age, whereas the CON group was injected with sterile saline. The results showed that: LPS significantly increased the liver histopathological score (p < 0.05); LPS significantly decreased the serum total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity at 3 h after injection (p < 0.05); the LPS group had a higher content of Interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF)-α, but a lower content of IL-10 than the CON group in serum (p < 0.05). Compared with the LPS group, the MR1 diet increased catalase (CAT), SOD, and T-AOC, and the MR2 diet increased SOD and T-AOC at 3 h after injection in serum (p < 0.05). Only MR2 group displayed a significantly decreased liver histopathological score (p < 0.05) at 3 h, while MR1 and MR2 groups did so at 8 h. Both MR diets significantly decreased serum LPS, CORT, IL-1ß, IL-6, and TNF-α contents, but increased IL-10 content (p < 0.05). Moreover, the MR1 group displayed significantly increased expression of nuclear factor erythroid 2-related factor 2 (Nrf2), CAT, and GSH-Px at 3 h; the MR2 group had a higher expression of Kelch-like ECH-associated protein 1 (Keap1), SOD, and GSH-Px at 8 h (p < 0.05). In summary, MR can improve antioxidant capacity, immunological stress, and liver health in LPS-challenged broilers. The MR1 and MR2 groups experienced similar effects on relieving stress; however, MR1 alleviated oxidative stress more rapidly. It is suggested that precise regulation of methionine levels in poultry with stress may improve the immunity of broilers, reduce feed production costs, and increase production efficiency in the poultry industry.