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Perilla leaf oil (PLO) is a global premium vegetable oil with abundant nutrients and substantial economic value, rendering it susceptible to potential adulteration by unscrupulous entrepreneurs. The addition of cinnamon oil (CO) is one of the main adulteration avenues for illegal PLOs. In this study, new and real-time ambient mass spectrometric methods were developed to detect CO adulteration in PLO. First, atmospheric solids analysis probe tandem mass spectrometry combined with principal component analysis and principal component analysis-linear discriminant analysis was employed to differentiate between authentic and adulterated PLO. Then, a spectral library was established for the instantaneous matching of cinnamaldehyde in the samples. Finally, the results were verified using the SRM mode of ASAP-MS/MS. Within 3 min, the three methods successfully identified CO adulteration in PLO at concentrations as low as 5% v/v with 100% accuracy. The proposed strategy was successfully applied to the fraud detection of CO in PLO.

Asunto(s)

Cinnamomum zeylanicum , Contaminación de Alimentos , Hojas de la Planta , Aceites de Plantas , Contaminación de Alimentos/análisis , Aceites de Plantas/química , Aceites de Plantas/análisis , Hojas de la Planta/química , Cinnamomum zeylanicum/química , Perilla/química , Espectrometría de Masas en Tándem/métodos , Espectrometría de Masas/métodos

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Lyotropic chiral nematic cellulose nanocrystals (CNCs) have attracted significant attention and great progress has been made. Investigating their physical parameters, especially the twist elastic constant (K22), is pivotal for advancing our comprehension of fundamental viscoelastic property of chiral nematic phase. In this study, we demonstrate a straightforward method to simultaneously estimate K22 and helical twisting power (Kt) of chiral nematic CNCs. This method involves analyzing rheology properties and electro-response of CNCs, focusing on the rotational dynamics and structural reconfiguration of CNC tactoids under an electric field. By examining the rotation dynamics of CNC tactoids under an electric field, together with the viscosity characterization, the anisotropic dielectric susceptibility (∆χ) of chiral nematic CNC along the helix axis was determined. Subsequently, K22/∆χn was extracted by analyzing CNC tactoid pitch evolution under an electric field, employing the de Gennes model. The K22 for different concentrated CNCs is finally estimated by integrating experimental results and theory. It is shown that the chiral nematic CNCs present concentration-dependent K22, ranging from 0.05 to 0.14 pN, while Kt spans from 0.06 to 0.14 pN/µm. This study offers a comprehensive understanding of the CNC fundamental viscoelastic property and opens up new avenues for K22 measurement in other lyotropic liquid crystals.

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Ocular metastasis is a rare type of distant metastasis of lung cancer. Limited information is available regarding ocular symptoms, diagnosis, treatment, and prognosis. We reported 16 patients diagnosed with ocular metastasis from lung cancer treated at our hospital from January 1988 to March 2024 and conducted a systematic review of 100 patients retrieved from the PubMed database from January 2014 to December 2023. A pooled analysis was performed using individual-level patient data to generate the hazard ratio (HR) of the association between patient characteristics and overall survival. A total of 116 patients, 100 patients from the literature and 16 patients from our center, diagnosed with ocular metastasis from lung cancer were included in this study. Choroid metastasis was presented in 77 (66.4%) patients and was significantly associated with the onset of lung cancer with ocular symptoms and decreased vision; iris metastasis was significantly associated with small cell lung cancer (SCLC), high intraocular pressure, and ocular pain. Multivariate analyses revealed that males (HR, 2.488; 95% confidence interval [CI], 1.127-5.495), age ≥ 60 years (HR, 3.196; 95% CI, 1.391-7.341), and onset with ocular symptoms (HR, 4.312; 95% CI, 1.675-11.099) were significantly associated with overall survival. For non-SCLC (NSCLC) patients, compared with chemotherapy, targeted therapy (HR, 0.238; 95% CI, 0.087-0.651) and combined therapy (HR, 0.133; 95% CI, 0.017-0.822) have greater therapeutic efficacy. Chemotherapy combined with immunotherapy and targeted therapy are more effective than chemotherapy alone for ocular metastatic NSCLC patients. For patients with targetable mutations, new-generation tyrosine kinase inhibitors (TKIs) are preferred.

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Bacterial biofilms are the major etiology agent of peri-implant disease. Chemical decontamination is a promising treatment strategy against bacterial biofilms; however, its applications are limited by its low efficiency and poor biocompatibility. In contrast to three conventional cleaners (sterile saline, hydrogen peroxide, and chlorhexidine), this study used resveratrol and naringin solutions to remove mature Staphylococcus aureus and Porphyromonas gingivalis biofilm on sandblasted (with large grit and acid-etched (SLA) titanium surface. To determine changes in surface characteristics, the surface wettability and roughness were measured, and micromorphology was observed by scanning electron microscopy. With crystal violet (CV) and live/dead bacterial staining, residual plaque quantity and composition were measured. The biocompatibility was tested using pH and cytotoxicity, as well as by osteoblasts (MC3T3-E1) adhesion, proliferation, and differentiation, and fibroblasts (L-929) proliferation were also analyzed. It was found that resveratrol and naringin solutions were more effective in restoring surface characteristics and also showed that less plaque and viable bacteria were left. Naringin removed S. aureus biofilms better than chlorhexidine. Alkaline resveratrol and naringin solutions increased cell adhesion, proliferation, and osteogenic differentiation without any cytotoxicity. Resveratrol increased the expression of mRNA and protein associated with osteogenesis. In conclusion, resveratrol and naringin effectively restored SLA titanium surface characteristics and decontaminated the biofilm with good biocompatibility, suggesting their therapeutic potential as chemical decontaminants. IMPORTANCE: Bacterial biofilms are considered the primary etiology of peri-implant disease. Physical cleaning is the most common way to remove bacterial biofilm, but it can cause grooving, melting, and deposition of chemicals that alter the surface of implants, which may hamper biocompatibility and re-osseointegration. Chemical decontamination is one of the most promising treatments but is limited by low efficiency and poor biocompatibility. Our study aims to develop safer, more effective chemical decontaminants for peri-implant disease prevention and treatment. We focus on resveratrol and naringin, two natural compounds, which have shown to be more effective in decontaminating biofilms on dental implant surfaces and exerting better biocompatibility. This research is groundbreaking as it is the first exploration of natural plant extracts' impact on mature bacterial biofilms on rough titanium surfaces. By advancing this knowledge, we seek to contribute to more effective and biocompatible strategies for combating peri-implant diseases, enhancing oral health, and prolonging implant lifespan.

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Background: A high body mass index (BMI) increases the risk of hypertension. However, little is known about the dose-dependent association between BMI and hypertension. Therefore, this study investigated the prevalence of hypertension in 7568 subjects from the Jiangsu Province, Eastern China, and analyzed the dose-response relationship between BMI and hypertension risk. Methods: The eligible subjects completed a structured questionnaire and clinical biochemical indicators were measured according to standardized protocols. Multivariate logistic regression models were used to evaluate the association between BMI and hypertension. Restricted cubic spline (RCS) analysis was used to analyze the dose-response relationship between BMI and hypertension risk. Moreover, sensitivity analysis was performed to verify the robustness of our findings. Results: The prevalence of hypertension was 35.3 % in the total population. BMI was significantly associated with systolic and diastolic blood pressure. The fully-adjusted odds ratio (OR) with 95 % confidence interval (CI) for hypertension was 1.17 (1.15, 1.19) for every 1 kg/m2 increase in BMI. Furthermore, the OR (95 % CI) for hypertension in the highest BMI group (Obesity) was 4.14 (3.45, 4.96) after adjusting for covariates compared with the normal group. Multivariable adjusted RCS analysis showed a positive and linear dose-response relationship between BMI and hypertension risk both in male and female populations (all P for non-linearity > 0.05). Conclusion: Our study demonstrated a positive and linear dose-response relationship between BMI and the risk of hypertension. The results of this study provide evidence for BMI-related clinical interventions to reduce the risk of hypertension.

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Rationale: Immunosuppressive tumor microenvironment (iTME) plays an important role in carcinogenesis, and some macrophage subsets are associated with iTME generation. However, the sub-population characterization of macrophages in oral carcinogenesis remains largely unclear. Here, we investigated the immunosuppressive status with focus on function of a macrophage subset that expressed indoleamine 2,3 dioxygenase 1 (Macro-IDO1) in oral carcinogenesis. Methods: We built a single cell transcriptome atlas from 3 patients simultaneously containing oral squamous cell carcinoma (OSCC), precancerous oral leukoplakia (preca-OLK) and paracancerous tissue (PCA). Through single-cell RNA sequencing and further validation using multicolor immunofluorescence staining and the in vitro/in vivo experiments, the immunosuppressive cell profiles were built and the role of a macrophage subset that expressed indoleamine 2,3 dioxygenase 1 (Macro-IDO1) in the malignant transformation of oral leukoplakia was evaluated. Results: The iTME formed at preca-OLK stage, as evidenced by increased exhausted T cells, Tregs and some special subsets of macrophages and fibroblasts. Macro-IDO1 was predominantly enriched in preca-OLK and OSCC, distributed near exhausted T cells and possessed tumor associated macrophage transformation potentials. Functional analysis revealed the established immunosuppressive role of Macro-IDO1 in preca-OLK and OSCC: enriching the immunosuppression related genes; having an established level of immune checkpoint score; exerting strong immunosuppressive interaction with T cells; positively correlating with the CD8-exhausted. The immunosuppression related gene expression of macrophages also increased in preca-OLK/OSCC compared to PCA. The use of the IDO1 inhibitor reduced 4NQO induced oral carcinogenesis in mice. Mechanistically, IFN-γ-JAK-STAT pathway was associated with IDO1 upregulation in OLK and OSCC. Conclusions: These results highlight that Macro-IDO1-enriched in preca-OLK possesses a strong immunosuppressive role and contributes to oral carcinogenesis, providing a potential target for preventing precancerous legions from transformation into OSCC.

Asunto(s)

Transformación Celular Neoplásica , Indolamina-Pirrol 2,3,-Dioxigenasa , Leucoplasia Bucal , Macrófagos , Neoplasias de la Boca , Análisis de la Célula Individual , Microambiente Tumoral , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenasa/genética , Leucoplasia Bucal/inmunología , Leucoplasia Bucal/genética , Leucoplasia Bucal/patología , Humanos , Macrófagos/inmunología , Macrófagos/metabolismo , Animales , Ratones , Microambiente Tumoral/inmunología , Transformación Celular Neoplásica/genética , Neoplasias de la Boca/inmunología , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Análisis de la Célula Individual/métodos , Análisis de Secuencia de ARN , Masculino , Tolerancia Inmunológica , Femenino , Carcinogénesis/inmunología , Carcinogénesis/genética

RESUMEN

It is known that magnesium phosphate cements (MPCs) show appreciable mechanical strength and biocompatibility, but the hydration reaction processes often lead to intense heat release while the hydration products present weak resistance to mechanical decay and low bioactivity. Herein we developed an MPC-based system, which was low-heat-releasing and fast-curing in this study, by compounding with self-curing calcium silicate cements (CSCs). The MPC composed of magnesium oxide (MgO), potassium dihydrogen phosphate (KH2PO4), disodium hydrogen phosphate (Na2HPO4), magnesium hydrogen phosphate trihydrate (MgHPO4·3H2O) and chitosan were weakly basic, which would be more stable in vivo. The physicochemical properties indicated that the addition of CSCs could increase the final setting time while decrease the heat release. Meanwhile, the CSCs could endow MPC substrate with apatite re-mineralization reactivity, especially, which add 25 wt.% CSCs showed the most significant apatite deposition. What's more, the mechanical evolution in buffer demonstrated CSCs could enhance and sustain the mechanical strength during degradation, and the internal constructs of cement implants could still be reconstructed by µCT analysis in rabbit femoral bone defect model in vivo. Particularly, appropriate CSCs adjusted the biodegradation and promoted new bone tissue regeneration in vivo. Totally, the MPC/CSCs composite system endows bioactivity and sustains mechanical strength of the MPC, which may be promising for expending the clinical applications of MPC-based bone cements.

RESUMEN

Background: Calvatia gigantea (CG) is widely used as a traditional Chinese medicine for wound treatment. In this study, we aimed to determine the effects of CG extract (CGE) on diabetic wound healing and the commensal wound microbiome. Method: A wound model was established using leptin receptor-deficient db/db mice, with untreated mice as the control group and CGE-treated mice as the treatment group. The wound healing rate, inflammation and histology were analyzed. Additionally, wound microbiome was evaluated via 16S ribosomal RNA (rRNA) gene sequencing. Results: CGE significantly accelerated the healing of diabetic ulcer wounds, facilitated re-epithelialization, and downregulated the transcription levels of the inflammatory cytokines, interleukin-1ß and tumor necrosis factor-α. Furthermore, CGE treatment positively affected the wound microbiome, promoting diversity of the microbial community and enrichment of Escherichia-Shigella bacteria in the CGE-treated group. Conclusions: Overall, CGE enhanced diabetic wound healing by modulating the wound microbiome and facilitating macrophage polarization during inflammation. These findings suggest modulation of the commensal wound microbiome using medicinal plants as a potential therapeutic strategy for diabetic wounds.

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Introduction: Grape is of high economic value. Colletotrichum viniferum, a pathogen causing grape ripe rot and leaf spot, threatens grape production and quality. Methods: This study investigates the interplay between C. viniferum by Cytological study and transcriptome sequencing. Results: Different grapevine germplasms, V. vinifera cv. Thompson Seedless (TS), V. labrusca accession Beaumont (B) and V. piasezkii Liuba-8 (LB-8) were classified as highly sensitive, moderate resistant and resistant to C. viniferum, respectively. Cytological study analysis reveals distinct differences between susceptible and resistant grapes post-inoculation, including faster pathogen development, longer germination tubes, normal appressoria of C. viniferum and absence of white secretions in the susceptible host grapevine. To understand the pathogenic mechanisms of C. viniferum, transcriptome sequencing was performed on the susceptible grapevine "TS" identifying 236 differentially expressed C. viniferum genes. These included 56 effectors, 36 carbohydrate genes, 5 P450 genes, and 10 genes involved in secondary metabolism. Fungal effectors are known as pivotal pathogenic factors that modulate plant immunity and affect disease development. Agrobacterium-mediated transient transformation in Nicotiana benthamiana screened 10 effectors (CvA13877, CvA01508, CvA05621, CvA00229, CvA07043, CvA05569, CvA12648, CvA02698, CvA14071 and CvA10999) that inhibited INF1 (infestans 1, P. infestans PAMP elicitor) induced cell death and 2 effectors (CvA02641 and CvA11478) that induced cell death. Additionally, transcriptome analysis of "TS" in response to C. viniferum identified differentially expressed grape genes related to plant hormone signaling (TGA, PR1, ETR, and ERF1/2), resveratrol biosynthesis genes (STS), phenylpropanoid biosynthesis genes (PAL and COMT), photosynthetic antenna proteins (Lhca and Lhcb), transcription factors (WRKY, NAC, MYB, ERF, GATA, bHLH and SBP), ROS (reactive oxygen species) clearance genes (CAT, GSH, POD and SOD), and disease-related genes (LRR, RPS2 and GST). Discussion: This study highlights the potential functional diversity of C. viniferum effectors. Our findings lay a foundation for further research of infection mechanisms in Colletotrichum and identification of disease response targets in grape.

RESUMEN

Lanthanide clusters with high magnetic entropy and an exquisite structure have always been a hot research direction. Herein, two delicately structured lanthanide clusters were synthesized using isonicotinic acid (HIN) as a ligand by the solvothermal method, namely {[Gd4(IN)4(µ3-OH)4(OAc)2(H2O)6]·Cl2·7H2O}n (1) and {[Dy4(IN)4(µ3-OH)4(OAc)2(H2O)6]·Cl2·8H2O}n (2). Structural analysis indicates that the two compounds exhibit comparable structures, and both have the same cubane-like Ln4 metal skeleton and form an interesting dragonfly molecular configuration by connecting to HIN. Moreover, {Ln4} serves as the fundamental structural unit for the construction of a 1D channel of 1, with a diameter of approximately 10.08 Å, which is connected to each other by extra {Ln4} units to form an exquisite porous 3D structure of 1. Cl- exists as an anion-template in its 3D structure, balancing the charge and maintaining its structural stability. Magnetic measurements indicate that 1 exhibits a rather satisfactory magnetic entropy change, reaching a maximum value of -ΔSmaxm = 31.59 J kg-1 K-1 at 2 K for ΔH = 7 T.

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The trachea is essential for proper airflow to the lungs for gas exchange. Frequent congenital tracheal malformations affect the cartilage, causing the collapse of the central airway during the respiratory cycle. We have shown that Notum, a Wnt ligand de-acylase that attenuates the canonical branch of the Wnt signaling pathway, is necessary for cartilaginous mesenchymal condensations. In Notum deficient tracheas, chondrogenesis is delayed, and the tracheal lumen is narrowed. It is unknown if Notum attenuates non-canonical Wnt signaling. Notably, we observed premature tracheal chondrogenesis after mesenchymal deletion of the non-canonical Wnt5a ligand. We hypothesize that Notum and Wnt5a are required to mediate the timely formation of mesenchymal condensations, giving rise to the tracheal cartilage. Ex vivo culture of tracheal tissue shows that chemical inhibition of the Wnt non-canonical pathway promotes earlier condensations, while Notum inhibition presents delayed condensations. Furthermore, non-canonical Wnt induction prevents the formation of cartilaginous mesenchymal condensations. On the other hand, cell-cell interactions among chondroblasts increase in the absence of mesenchymal Wnt5a. By performing an unbiased analysis of the gene expression in Wnt5a and Notum deficient tracheas, we detect that mRNA of genes essential for chondrogenesis and extracellular matrix formation are upregulated by E11.5 in Wnt5a mutants. The expression profile supports the premature and delayed chondrogenesis observed in Wnt5a and Notum deficient tracheas, respectively. We conclude that Notum and Wnt5a are necessary for proper tracheal cartilage patterning by coordinating timely chondrogenesis. Thus, these studies shed light on molecular mechanisms underlying congenital anomalies of the trachea.

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During the summer of 2024, COVID-19 cases surged globally, driven by variants derived from JN.1 subvariants of SARS-CoV-2 that feature new mutations, particularly in the N-terminal domain (NTD) of the spike protein. In this study, we report on the neutralizing antibody (nAb) escape, infectivity, fusion, and stability of these subvariants-LB.1, KP.2.3, KP.3, and KP.3.1.1. Our findings demonstrate that all of these subvariants are highly evasive of nAbs elicited by the bivalent mRNA vaccine, the XBB.1.5 monovalent mumps virus-based vaccine, or from infections during the BA.2.86/JN.1 wave. This reduction in nAb titers is primarily driven by a single serine deletion (DelS31) in the NTD of the spike, leading to a distinct antigenic profile compared to the parental JN.1 and other variants. We also found that the DelS31 mutation decreases pseudovirus infectivity in CaLu-3 cells, which correlates with impaired cell-cell fusion. Additionally, the spike protein of DelS31 variants appears more conformationally stable, as indicated by reduced S1 shedding both with and without stimulation by soluble ACE2, and increased resistance to elevated temperatures. Molecular modeling suggests that the DelS31 mutation induces a conformational change that stabilizes the NTD and strengthens the NTD-Receptor-Binding Domain (RBD) interaction, thus favoring the down conformation of RBD and reducing accessibility to both the ACE2 receptor and certain nAbs. Additionally, the DelS31 mutation introduces an N-linked glycan modification at N30, which shields the underlying NTD region from antibody recognition. Our data highlight the critical role of NTD mutations in the spike protein for nAb evasion, stability, and viral infectivity, and suggest consideration of updating COVID-19 vaccines with antigens containing DelS31.

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The article by Shin et al. provides valuable insights into the correlation between the gastric mucosa-associated gastric microbiome (MAM) and metachronous recurrence. However, the use of the Cox proportional hazards model in their analysis presents several limitations. The study may result in mixed censoring outcomes, and the assumption of constant hazard ratios over time may not hold. Considering these limitations, future research should adopt alternative approaches, such as the accelerated failure time (AFT) model, to provide a more comprehensive understanding of the relationship between gastric MAM and metachronous recurrence.

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While the critical role of NKX2-1 and its transcriptional targets in lung morphogenesis and pulmonary epithelial cell differentiation is increasingly known, mechanisms by which chromatin accessibility alters the epigenetic landscape and how NKX2-1 interacts with other co-activators required for alveolar epithelial cell differentiation and function are not well understood. Combined deletion of the histone methyl transferases Prdm3 and Prdm16 in early lung endoderm causes perinatal lethality due to respiratory failure from loss of AT2 cells and the accumulation of partially differentiated AT1 cells. Combination of single-cell RNA-seq, bulk ATAC-seq, and CUT&RUN data demonstrate that PRDM3 and PRDM16 regulate chromatin accessibility at NKX2-1 transcriptional targets critical for perinatal AT2 cell differentiation and surfactant homeostasis. Lineage specific deletion of PRDM3/16 in AT2 cells leads to lineage infidelity, with PRDM3/16 null cells acquiring partial AT1 fate. Together, these data demonstrate that NKX2-1-dependent regulation of alveolar epithelial cell differentiation is mediated by epigenomic modulation via PRDM3/16.

Asunto(s)

Células Epiteliales Alveolares , Diferenciación Celular , Cromatina , Proteínas de Unión al ADN , Factor Nuclear Tiroideo 1 , Factores de Transcripción , Animales , Factor Nuclear Tiroideo 1/metabolismo , Factor Nuclear Tiroideo 1/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Cromatina/metabolismo , Ratones , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/citología , Ratones Noqueados , Pulmón/citología , Pulmón/metabolismo , Linaje de la Célula , Femenino

RESUMEN

OBJECTIVE: To investigate the correlation between glucose and lipid metabolism, renal function, and retinopathy in patients with diabetic retinopathy (DR) based on optical coherence tomography angiography (OCTA). METHODS: A total of 584 diabetic patients who underwent treatment at The Second Affiliated Hospital of Dalian Medical University from March 2022 to June 2023 were retrospectively selected as research participants. They were categorized into a NDR group (n=366) and a DR group (n=218) based on the presence or absence of DR. Relevant indexes of glucose and lipid metabolism, renal function, and OCTA findings were collected. Logistic regression analysis was applied to identify the influencing factors of diabetes mellitus complicated with DR. ROC curves were drawn to examine the diagnostic value of the screened influencing factors for diabetes mellitus complicated with DR. Finally, Spearman correlation coefficients were calculated to examine the relevance between influencing factors and the severity of DR Lesions. RESULTS: Logistic regression showed that high levels of angiography 3 × 3 inner vascular density (IVD_33) and angiography 3 × 3 inner perfusion density (IPD_33) were protective factors for diabetes mellitus complicated with DR, and diabetic peridiabetic vascular disease (DPVD), elevated blood urea nitrogen (BUN), and urea levels were risk factors for diabetes mellitus complicated with DR (all P<0.05). ROC curve displayed that the areas under the curve (AUC) of IVD_33, DPVD, BUN, IPD_33, and Urea in predicting diabetes mellitus with DR were 0.779, 0.705, 0.621, 0.723, and 0.632, respectively. The AUC of combined prediction with OCTA index was higher than that of combined prediction without OCTA index (0.781 VS 0.84, P<0.05). Spearman correlation coefficient displayed that IVD_33 and IPD_33 were negatively correlated with the severity of DR, whereas DPVD and Urea showed a positive correlation (P<0.05). CONCLUSION: Our findings provide valuable insights for the initial clinical assessment of diabetic patients with DR and aid in the early determination of DR severity. Corresponding intervention measures should be formulated as early as possible to remedy patients' outcomes.

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This study investigated the effects of incorporating different levels of Euglena gracilis microalgae powder (MP) on the dough properties, rheology, and quality attributes of Chinese steamed bread (CSB) for the first time. Moderate levels of MP (2%) reinforced the gluten network and improved protein structure, while higher levels (4-8%) adversely affected the gluten network and rheological properties. The addition of MP decreased the specific volume, pore number, and pore density of CSB, but increased pore size, hardness, and chewiness. It also imparted a yellow color to the CSB and slowed down moisture loss during storage. Notably, MP effectively increased the protein and lipid content of CSB, enhancing its nutritional value. The results suggest that optimizing the MP level is crucial to achieve nutritional enhancement while maintaining desirable texture and sensory attributes. An addition of 2% MP can strike a balance between nutrition and the overall quality of the final product.

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The systemic immune-inflammatory index (SII) has been identified as an independent prognostic factor for multiple diseases. However, the impact of SII on outcome of acute-on-chronic liver failure (ACLF) is scant. A retrospective study enrolled patients with ACLF treated with artificial liver support system. Restricted cubic spline (RCS) (knots at the 10th, 50th, and 90th percentiles) and Cox proportional hazards models were applied to investigate the relationship between SII and 90-day transplant-free survival and overall survival in patients with ACLF. A total of 258 patients with ACLF were included. The 90-day transplant-free survival rate and overall survival rate were 58.5% and 66.3%. The SII was 465.5 (277.3-804.4). Adjusted RCS models showed linear exposure-response relationship between SII and 90-day transplant-free survival (P for overall < 0.001, P for nonlinear = 0.154) and 90-day overall survival (P for overall < 0.001, P for nonlinear = 0.103), and adjusted Cox models confirmed the positive relationship. Compared with patients with SII < 480, patients with ≥ 480 had more serious  condition, lower 90-day transplant-free survival rate (46.8% vs. 69.7%, adjusted HR (95% CI) for transplant or death: 2.13 (1.40-3.23), P < 0.001), and lower 90-day overall survival rate (56.3% vs. 75.8%; adjusted HR (95% CI) for death: 2.26 (1.42-3.61), P = 0.001). Stratified Cox models suggested no potential modifiers in the relationship between SII and 90-day transplant-free survival. Our findings suggested SII was positively associated with poor short-term prognosis of ACLF.

Asunto(s)

Insuficiencia Hepática Crónica Agudizada , Inflamación , Humanos , Insuficiencia Hepática Crónica Agudizada/mortalidad , Insuficiencia Hepática Crónica Agudizada/inmunología , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Tasa de Supervivencia , Modelos de Riesgos Proporcionales

RESUMEN

Several observational studies have reported a correlation between the gut microbiota (GM) and the risk of acute pancreatitis (AP). However, the causal relationship between them remains uncertain. We conducted a 2-sample Mendelian randomization (MR) study using pooled data from genome-wide association studies of 211 taxa (131 genera, 35 families, 20 orders, 16 classes, and 9 phyla) and AP patients. We evaluated the causal relationship between the GM and AP using methods such as inverse-variance weighting, MR-Egger, weighted medians, simple mode, and weighted mode. Cochran Q test, MR-Egger regression intercept analysis, and MR-PRESSO were used to examine the heterogeneity, multipotency, and outlier values of the variables, respectively. The reverse causal relationship between AP and the GM was assessed with reverse MR. In total, 5 gut microbial taxa were significantly associated with AP. The inverse-variance weighting results indicated that Acidaminococcaceae (odds ratio [OR]: 0.81, 95% confidence interval [CI]: 0.66-1.00, P = .045) and Ruminococcaceae UCG004 (OR: 0.85, 95% CI: 0.72-0.99, P = .040) were protective factors against the occurrence of AP. Coprococcus 3 (OR: 1.32, 95% CI: 1.03-1.70, P = .030), Eisenbergiella (OR: 1.13, 95% CI: 1.00-1.28, P = .043), and the Eubacterium fissicatena group (OR: 1.18, 95% CI: 1.05-1.33, P = .006) were risk factors for the development of AP. A comprehensive sensitivity analysis proved our results to be reliable. Reverse MR analysis did not indicate any causal relationship between AP and the GM. This study revealed a complex causal relationship between 5 GM taxa and AP, providing new insights into the diagnostic and therapeutic potential of the GM in AP patients.

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Microbioma Gastrointestinal , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Pancreatitis , Humanos , Microbioma Gastrointestinal/genética , Pancreatitis/microbiología , Pancreatitis/epidemiología

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Soil nitrogen addition induces the generation and proliferation of some bacterial virulence, yet the interactive mechanisms between the two remain unclear. Here we investigated the variation of virulence genes (VGs) abundance during soil nitrogen transformation, and explored the biological mechanism and key pathways involved in the regulation of VGs by nitrogen transformation. The results showed that the diversity and abundance of virulence genes in soil under high nitrogen input (100 mg/kg) were markedly higher than those under low nitrogen input (50 mg/kg), suggesting a trade-off between the prevalence of virulence genes and nitrogen metabolism. Nutritional/metabolic factor, regulation, immune modulation and motility were the dominant virulence types. Linear regression analysis showed that soil nitrogen mineralization and nitrification rate were closely correlated with the abundance of virulence genes, mainly involving adherence, nutritional/metabolic factors and immune modulation (p < 0.05). Structural equations indicated that microbial community succession associated with nitrogen transformation largely contributed to the changes in VGs abundance. Metagenomic analysis revealed that major virulence genes pilE, pchB, and galE were regulated by nitrogen-functional genes gdh, ureC, and amoC, implying that microbial nitrogen transformation influences immune modulation, nutritional/metabolic factors, and adherence-like virulence. The meta-transcriptome reiterated their co-regulation, and the key pathway may be glutamate/urea> α-ketoglutarate/ammonia > pyruvate/amino acid. The outcome provides strong evidence on the linkage between microbial nitrogen transformation and pathogenic virulence factors development in the soil environment, which will aid in the effective suppression of the prevalence of soil pathogenic virulence.

Asunto(s)

Nitrógeno , Microbiología del Suelo , Suelo , Nitrógeno/metabolismo , Virulencia , Suelo/química