Serum tumor markers (carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 72-4, carbohydrate antigen 24-2, ferritin) and gastric cancer prognosis correlation.

BACKGROUND: Gastric cancer is a kind of malignant tumor which is prevalent all over the world. Although some progress has been made in the treatment of gastric cancer, its prognosis is still not optimistic, so it is of great significance to find reliable prognostic indicators to guide the treatment and management of patients with gastric cancer. AIM: To explore the relationship between serum levels of five biomarkers [carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, CA72-4, CA24-2, and ferritin] and prognosis in patients with gastric cancer. METHODS: This study included 200 patients with gastric adenocarcinoma, and conducted an in-depth analysis of their baseline characteristics, relationship between tumor markers and staging, and prognosis. The study found that CA19-9 has a significant correlation with tumor stage, the average levels of CA24-2, CEA, CA72-4 and ferritin were slightly increased disregarding the stage of tumor. Survival analysis showed that increases in CEA, CA19-9, CA24-2, and ferritin were all associated with shortened overall survival of patients. Further multivariate analysis revealed that elevated serum CA72-4 levels were an independent adverse prognostic factor. RESULTS: This study reveals that there is a significant correlation between the expression levels of serum tumor markers CEA, CA19-9, CA72-4, CA24-2 and ferritin in patients with gastric cancer and prognosis, and can be used as important indicators for prognostic evaluation of gastric cancer. In particular, markers that appear abnormally elevated initially may help identify gastric cancer patients with poor prognosis. CONCLUSION: Serum CEA and CA19-9 play an important role in the prognosis assessment of gastric cancer, and are effective tools to guide clinical practice and optimize individualized treatment strategies for gastric cancer patients.

T cell exhaustion methylation signature drives differential immune responses in glioblastoma.

BACKGROUND: Methylation-related signatures play crucial roles in tumorigenesis and progression. However, their roles in the immune response in primary glioblastoma (GBM) remains unclear. METHODS: We analyzed the differential expression of specific members of T cell exhaustion-related pathways in GBM from the perspective of T cell exhaustion. We further screened for significantly negatively correlated methylation sites as candidate methylation markers for T cell exhaustion. Using consensus clustering, we divided the samples into two categories with significant differences in overall survival (OS). We then performed univariate and multivariate Cox regression analyses to construct the T Cell Exhaustion Methylation (TEXM) signature. Finally, we confirmed that this signature served as an independent prognostic factor, and further characterized it in terms of drug resistance and immunotherapy. RESULTS: We identified 95 significantly differentially expressed T cell exhaustion-related genes and 51 methylation markers associated with T cell exhaustion. The cancer samples were classified according to methylation site markers, thus indicating two subtypes with significant differences in OS: subtype A and subtype B. Tumor scores, stromal scores, tumor purity, and ESTIMATE scores all showed significant differences between subtypes (P < 0.05). Univariate Cox regression analysis identified five methylation sites significantly associated with OS, and multivariate Cox regression analysis was used to construct the TEXM signature model by using these five methylation sites. Significant differences in OS were found between the groups with high and low TEXM signature scores, on the basis of calculation of the TEXM signature scores of tumor samples and using the median score to divide them into high and low score groups. Survival analysis revealed that the high score group had poorer OS and DFS than the low score group in the validation set. Notably, we observed a significant difference in drug sensitivity between the high and low TEXM signature score groups, with the high score group showing higher drug resistance and poorer prognosis. The tumor immune state, as predicted with Tracking Tumor Immunophenotype (TIP), revealed significant differences in antitumor immune scores between the high and low TEXM signature score groups. Finally, we identified 43 significantly differentially regulated metabolism-associated biological processes. CONCLUSION: The epigenetic methylation-related TEXM signature plays a key role in driving differential immune responses in GBM.

CRISPR-Cas13-mediated RNA editing in the silkworm Bombyx mori.

The CRISPR-Cas13 system, an RNA-guided editing tool, has emerged as a highly efficient and stable RNA editing technique. Although the CRISPR-Cas13 system has been developed in several insect species, its application in lepidopterans has not yet been reported. In the present study, we evaluated the RNA cleavage activity of the CRISPR-Cas13 system in the silkworm ( Bombyx mori), a model lepidopteran insect, both ex vivo and in vivo. We established two stable silkworm BmE cell lines expressing PspCas13b and CasRx, respectively. Further analysis demonstrated that both PspCas13b and CasRx effectively down-regulated the transcription of exogenously-introduced target and endogenous genes in these cell lines. In addition, we generated two transgenic silkworm strains, one expressing CasRx and the other expressing RNA-guided CRISPR RNA targeting Sex combs reduced ( Scr). Further crossing experiments showed that CasRx induced a down-regulation of Scr transcription in silkworms, which impaired systemic growth of larvae. Overall, this study demonstrated that the CRISPR-Cas13 RNA editing system works efficiently in the silkworm, providing a potential alternative approach for RNA manipulation in lepidopteran insects.

Integrated analysis to identify biological features and molecular markers of poorly cohesive gastric carcinoma (PCC).

As one of the two main histologic subtypes of gastric cancer (GC), diffuse-type gastric cancer (DGC) containing poorly cohesive gastric carcinoma (PCC) components has a worse prognosis and does not respond well to typical therapies. Despite the large number of studies revealing the complex pathogenic network of DGC, the molecular heterogeneity of DGC is still not fully understood. We obtained single-cell RNA-seq data and bulk data from the tumor immune single cell hub, the public gene expression omnibus, and the cancer genome atlas databases. A series of bioinformatics analyses were performed using R software. Immunofluorescence staining, hematoxylin and eosin staining, western blot, and functional experiments were used for experimental validation. Caudin-3, -4 and -7 were lowly expressed in DGC and their expression levels were further reduced in PCC. The PCC components were mainly located in the deeper layers of the DGC and had a high level of hypoxic Wnt/ß-catenin signaling and stemness. We further identified Insulin Like Growth Factor Binding Protein 7 (IGFBP7) as a marker for PCC components in the deep layer. IGFBP7 is stimulated by hypoxia and promotes cancer cell invasiveness and reduced claudin expression. In addition, programmed death-1 ligand (PD-L1) was specifically expressed in the deep layer, reflecting deep layer-specific immunosuppression. The PCC components are predominantly situated in the deeper layers of DGC. Initial molecular characterization of these PCC components revealed distinct features, including low expression of claudin-3, -4, and -7, high expression of IGFBP7, and the presence of PD-L1. These molecular traits may partially account for the pronounced tumor heterogeneity observed in GC.

SIRT6 alleviates senescence induced by Porphyromonas gingivalis in human gingival fibroblasts.

OBJECTIVE: Bidirectional influences between senescence and inflammation are newly discovered. This study aimed to clarify the roles and mechanism of Porphyromonas gingivalis (P. gingivalis) in exacerbating senescence in human gingival fibroblasts (HGFs). DESIGN: Subgingival plaque and gingivae were collected from twenty-four periodontitis patients and eighteen periodontally healthy subjects. Quantities of P. gingivalis in subgingival plaque were explored using real-time PCR and the expressions of p53, p21 and SIRT6 in gingivae were detected by IHC. Moreover, senescence in HGFs was induced by P. gingivalis lipopolysaccharide (LPS) and the expressions of senescence-related ß-galactosidase (SA-ß-gal), p53, p21 and senescence-associated secretory phenotype (IL-6 and IL-8) with or without treatment by SIRT6 activator UBCS039 were explored by IHC, western blot and ELISA, respectively. In addition, the levels of SIRT6, Nrf2, HO-1 and reactive oxygen species (ROS) were examined by western blot and flow cytometry. RESULTS: Quantities of P. gingivalis in subgingival plaque and semi-quantitative scores of p53 and p21 in gingivae of periodontitis patients were increased compared with healthy controls (p < 0.05), while SIRT6 score in periodontitis patients was decreased (p < 0.001). Quantities of P. gingivalis were positively correlated with p53 and p21 scores (0.6 < r < 0.9, p < 0.01), and negatively correlated with SIRT6 score (-0.9 < r<-0.6, p < 0.01). Moreover, P. gingivalis LPS increased the levels of SA-ß-gal, p53, p21, IL-6, IL-8 and ROS and decreased the levels of SIRT6, Nrf2 and HO-1 in HGFs, which was rescued by UBCS039 (p < 0.05). CONCLUSIONS: P. gingivalis LPS could induce senescence of HGFs, which could be reversed by SIRT6 via Nrf2-HO-1 signaling pathway.

Corneal nerve changes by anti-glaucoma medications examined by in vivo confocal microscopy.

AIM: To evaluate the effects of antiglaucoma eye drops on corneal nerves by in vivo confocal microscopy (IVCM). METHODS: This study comprised 79 patients diagnosed with glaucoma and 16 healthy control individuals. Among the glaucoma patients, 54 were treated with medication, while 25 remained untreated. Central corneal images were evaluated by IVCM, and then ACCMetrics was used to calculate the following parameters: corneal nerve fiber density (CNFD), branch density (CNBD), fiber length (CNFL), total branch density (CTBD), fiber area (CNFA), fiber width (CNFW), and fractal dimension (CNFrD). The correlation between IVCM parameters and drugs was evaluated using non-parametric measurements of Spearman's rank correlation coefficient. RESULTS: The CNFD was reduced in glaucoma groups compared to healthy subjects (P<0.01). Patients using anti-glaucoma medications exhibited poorer confocal parameters compared to untreated patients. As the number of medications and usage count increased, CNFD, CNBD, CNFL, CTBD, CNFA, and CNFrD experienced a decline, while CNFW increased (all P<0.01). For the brinzolamide-therapy group, there was a significant decrease in CNFD and CNFL compared to the other monotherapy groups (P<0.001). In the absence of medication, CNFD in males was lower than that in females (P<0.05). Among patients under medication therapy, CNFD remained consistent between males and females. CONCLUSION: Antiglaucoma eye drops affect the microstructure of corneal nerves. IVCM and ACCMetrics are useful tools that could be used to evaluate the corneal nerve changes.

Enhancing intracranial efficacy prediction of osimertinib in non-small cell lung cancer: a novel approach through brain MRI radiomics.

Introduction: Osimertinib, a third-generation EGFR-TKI, is known for its high efficacy against brain metastases (BM) in non-small cell lung cancer (NSCLC) due to its ability to penetrate the blood-brain barrier. This study aims to evaluate the use of brain MRI radiomics in predicting the intracranial efficacy to osimertinib in NSCLC patients with BM. Materials and methods: This study analyzed 115 brain metastases from NSCLC patients with the EGFR-T790M mutation treated with second-line osimertinib. The primary endpoint was intracranial response, and the secondary endpoint was intracranial progression-free survival (iPFS). We performed tumor delineation, image preprocessing, and radiomics feature extraction. Using a 5-fold cross-validation strategy, we built radiomic models with eight feature selectors and eight machine learning classifiers. The models' performance was evaluated by the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis. Results: The dataset of 115 brain metastases was divided into training and validation sets in a 7:3 ratio. The radiomic model utilizing the mRMR feature selector and stepwise logistic regression classifier showed the highest predictive accuracy, with AUCs of 0.879 for the training cohort and 0.786 for the validation cohort. This model outperformed a clinical-MRI morphological model, which included age, ring enhancement, and peritumoral edema (AUC: 0.794 for the training cohort and 0.697 for the validation cohort). The radiomic model also showed strong performance in calibration and decision curve analyses. Using a radiomic-score threshold of 199, patients were classified into two groups with significantly different median iPFS (3.0 months vs. 15.4 months, p < 0.001). Conclusion: This study demonstrates that MRI radiomics can effectively predict the intracranial efficacy of osimertinib in NSCLC patients with brain metastases. This approach holds promise for assisting clinicians in personalizing treatment strategies.

Tryptophan regulates the expression of IGFBP1 in bovine endometrial epithelial cells in vitro via the TDO2-AHR pathway.

BACKGROUND: This study aimed to identify the roles of L-tryptophan (Trp) and its rate-limiting enzymes on the receptivity of bovine endometrial epithelial cells. Real-time PCR was conducted to analyze the differential expression of genes between different groups of bovine endometrial epithelial cells. Western blot was performed to detect Cyclooxygenase-2 (COX2) expression after treatment with Trp or kynurenine (the main metabolites of Trp). The kynurenine assay was used to examine if Trp or prostaglandin E2 (PGE2) can increase the production of kynurenine in the bovine endometrial epithelial cells. RESULTS: Trp significantly stimulates insulin growth factor binding protein 1 (IGFBP1) expression, a common endometrial marker of conceptus elongation and uterus receptivity for ruminants. When bovine endometrial epithelial cells are treated with Trp, tryptophan hydroxylase-1 remains unchanged, but tryptophan 2,3-dioxygenase 2 (TDO2) is significantly increased, suggesting tryptophan is mainly metabolized through the kynurenine pathway. Kynurenine significantly stimulates IGFBP1 expression. Furthermore, Trp and kynurenine significantly increase the expression of aryl hydrocarbon receptor (AHR). CH223191, an AHR inhibitor, abrogates the induction of Trp and kynurenine on IGFBP1. PGE2 significantly induces the expression of TDO2, AHR, and IGFBP1. CONCLUSIONS: The regulation between Trp / kynurenine and PGE2 may be crucial for the receptivity of the bovine uterus.

Intercellular adhesion molecule-1 (ICAM-1): From molecular functions to clinical applications in cancer investigation.

Intercellular adhesion molecule-1 (ICAM-1) is a versatile molecule that plays a critical role in various physiological and pathological processes, particularly in tumor development where its impact is bidirectional. On the one hand, it augments the immune response by promoting immune cell migration, infiltration, and the formation of immunological synapses, thus facilitating potent antitumor effects. Simultaneously, it contributes to tumor immune evasion and influences metastasis by mediating transendothelial migration (TEM), epithelial-to-mesenchymal transition (EMT), and epigenetic modification of tumor cells. Despite its significant potential, the full clinical utility of ICAM-1 has yet to be fully realized. In this review, we thoroughly examine recent advancements in understanding the role of ICAM-1 in tumor development, its relevance in predicting therapeutic efficacy and prognosis, as well as the progress in clinical translational research on anti-ICAM-1-based therapies, encompassing including monoclonal antibodies, immunotherapy, antibody-drug conjugate (ADC), and conventional treatments. By shedding light on these innovative strategies, we aim to underscore ICAM-1's significance as a valuable and multifaceted target for cancer treatment, igniting enthusiasm for further research and facilitating translation into clinical applications.

Lysosomal TFEB-TRPML1 Axis in Astrocytes Modulates Depressive-like Behaviors.

Lysosomes are important cellular structures for human health as centers for recycling, signaling, metabolism and stress adaptation. However, the potential role of lysosomes in stress-related emotions has long been overlooked. Here, it is found that lysosomal morphology in astrocytes is altered in the medial prefrontal cortex (mPFC) of susceptible mice after chronic social defeat stress. A screen of lysosome-related genes revealed that the expression of the mucolipin 1 gene (Mcoln1; protein: mucolipin TRP channel 1) is decreased in susceptible mice and depressed patients. Astrocyte-specific knockout of mucolipin TRP channel 1 (TRPML1) induced depressive-like behaviors by inhibiting lysosomal exocytosis-mediated adenosine 5'-triphosphate (ATP) release. Furthermore, this stress response of astrocytic lysosomes is mediated by the transcription factor EB (TFEB), and overexpression of TRPML1 rescued depressive-like behaviors induced by astrocyte-specific knockout of TFEB. Collectively, these findings reveal a lysosomal stress-sensing signaling pathway contributing to the development of depression and identify the lysosome as a potential target organelle for antidepressants.

Bone marrow mesenchymal stem cells in treatment of peripheral nerve injury.

Peripheral nerve injury (PNI) is a common neurological disorder and complete functional recovery is difficult to achieve. In recent years, bone marrow mesenchymal stem cells (BMSCs) have emerged as ideal seed cells for PNI treatment due to their strong differentiation potential and autologous transplantation ability. This review aims to summarize the molecular mechanisms by which BMSCs mediate nerve repair in PNI. The key mechanisms discussed include the differentiation of BMSCs into multiple types of nerve cells to promote repair of nerve injury. BMSCs also create a microenvironment suitable for neuronal survival and regeneration through the secretion of neurotrophic factors, extracellular matrix molecules, and adhesion molecules. Additionally, BMSCs release pro-angiogenic factors to promote the formation of new blood vessels. They modulate cytokine expression and regulate macrophage polarization, leading to immunomodulation. Furthermore, BMSCs synthesize and release proteins related to myelin sheath formation and axonal regeneration, thereby promoting neuronal repair and regeneration. Moreover, this review explores methods of applying BMSCs in PNI treatment, including direct cell transplantation into the injured neural tissue, implantation of BMSCs into nerve conduits providing support, and the application of genetically modified BMSCs, among others. These findings confirm the potential of BMSCs in treating PNI. However, with the development of this field, it is crucial to address issues related to BMSC therapy, including establishing standards for extracting, identifying, and cultivating BMSCs, as well as selecting application methods for BMSCs in PNI such as direct transplantation, tissue engineering, and genetic engineering. Addressing these issues will help translate current preclinical research results into clinical practice, providing new and effective treatment strategies for patients with PNI.

Clinical significance of peripheral blood immune cells in patients with gastric cancer after surgery.

BACKGROUND: Gastric cancer is one of the most common malignant tumors worldwide, and surgical resection is one of the main ways to treat gastric cancer. However, the immune status of postoperative patients is crucial for prognosis and survival, and immune cells play an important role in this process. Therefore, it is helpful to understand the immune status of postoperative patients by evaluating the levels of peripheral blood immune cells, especially total T cells (CD3+), helper T cells (CD3+CD4+), and suppressor T cells (CD3+CD8+), and its relationship to survival. AIM: To analyzed the immune cells in peripheral blood of patients with gastric cancer after surgery, detect the levels of total T cells, helper T cells and suppressor T cells. METHODS: A total of 58 patients with gastric cancer who received surgical treatment were included in the retrospective study. Flow cytometry was used to detect the level of peripheral blood immune cells and analyze the correlation between total T cells, helper T cells and inhibitory T cells. To explore the relationship between these immune markers and patient survival. RESULTS: The results showed that the levels of total T cells, helper T cells, and suppressor T cells changed in patients after gastric cancer surgery. There was a significant positive correlation between total T cells, helper T cells and suppressor T cells (r = 0.35, P < 0.01; r = 0.56, P < 0.01). However, there was a negative correlation between helper T cells and suppressor T cells (r = -0.63, P < 0.01). Follow-up showed that the survival rate of patients in the high-level total T cell group was significantly higher than that in the low-level group (28.87 ± 24.98 months vs 18.42 ± 16.21 months). The survival curve shows that the curve of patients in the high-level group is shifted to the upper right, and that of the low-level group is shifted downward. There was no significant difference between the levels of helper T cells and suppressor T cells and patient survival time. CONCLUSION: By detecting peripheral blood immune cells with flow cytometry, we can initially evaluate the immune status of patients after gastric cancer surgery and initially explore its relationship with patient survival.

N-formylmethionine-leucyl-phenylalanine protects against irradiation-induced damage to hematopoiesis and intestines.

BACKGROUND: Ionizing radiation (IR), including radiotherapy, can exert lasting harm on living organisms. While liposaccharide (LPS) offers resistance to radiation damage, it also induces toxic responses. Thankfully, an LPS analogue called N-formylmethionine-leucyl-phenylalanine (fMLP) holds the potential to mitigate this toxicity, offering hope for radiation protection. METHODS: Survival of C57BL/6 mice exposed to IR after administration with fMLP/LPS/WR-2721 or saline was recorded. Cell viability and apoptosis assay of bone marrow (BMC), spleen and small intestinal epithelial (HIECs) cells were tested by Cell Counting Kit-8 (CCK-8) and flow cytometry assay. Tissue damage was evaluated by Hematoxilin and Eosin (H&E), Ki-67, and TUNEL staining. RNA sequencing was performed to reveal potential mechanisms of fMLP-mediated radiation protection. Flow cytometry and western blot were performed to verify the radiation protection mechanism of fMLP on the cell cycle. RESULTS: The survival rates of C57BL/6 mice exposed to ionizing radiation after administering fMLP increased. fMLP demonstrated low toxicity in vitro and in vivo, maintaining cell viability and mitigating radiation-induced apoptosis. Moreover, it protected against tissue damage in the hematopoietic and intestinal system. RNA sequencing shed light on fMLP's potential mechanism, suggesting its role in modulating innate immunity and cell cycling. This was evidenced by its ability to reverse radiation-induced G2/M phase arrests in HIECs. CONCLUSION: fMLP serves as a promising radioprotective agent, preserving cells and radiosensitive tissues from IR. Through its influence on the cell cycle, particularly reversing radiation-induced arrest in G2/M phases, fMLP offers protection against IR's detrimental effects.

Vitamin B-6 Prevents Heart Failure with Preserved Ejection Fraction Through Downstream of Kinase 3 in a Mouse Model.

BACKGROUND: There is an urgent need to develop an efficient therapeutic strategy for heart failure with preserved ejection fraction (HFpEF), which is mediated by phenotypic changes in cardiac macrophages. We previously reported that vitamin B-6 inhibits macrophage-mediated inflammasome activation. OBJECTIVES: We sought to examine whether the prophylactic use of vitamin B-6 prevents HFpEF. METHODS: HFpEF model was elicited by a combination of high-fat diet and Nω-nitro-l-arginine methyl ester supplement in mice. Cardiac function was assessed using conventional echocardiography and Doppler imaging. Immunohistochemistry and immunoblotting were used to detect changes in the macrophage phenotype and myocardial remodeling-related molecules. RESULTS: Co-administration of vitamin B-6 with HFpEF mice mitigated HFpEF phenotypes, including diastolic dysfunction, cardiac macrophage phenotypic shifts, fibrosis, and hypertrophy. Echocardiographic improvements were observed, with the E/E' ratio decreasing from 42.0 to 21.6 and the E/A ratio improving from 2.13 to 1.17. The exercise capacity also increased from 295.3 to 657.7 min. However, these beneficial effects were negated in downstream of kinase (DOK) 3-deficient mice. Mechanistically, vitamin B-6 increased DOK3 protein concentrations and inhibited macrophage phenotypic changes, which were abrogated by an AMP-activated protein kinase inhibitor. CONCLUSIONS: Vitamin B-6 increases DOK3 signaling to lower risk of HFpEF by inhibiting phenotypic changes in cardiac macrophages.

A bibliometric analysis of transcranial alternating current stimulation.

Background: Transcranial alternating current stimulation (tACS) can apply currents of varying intensity to the scalp, modulating cortical excitability and brain activity. tACS is a relatively new neuromodulation intervention that is now widely used in clinical practice. Many papers related to tACS have been published in various journals. However, there are no articles that objectively and directly introduce the development trend and research hotspots of tACS. Therefore, the aim of this study is to use CiteSpace to visually analyze the recent tACS-related publications, systematically and in detail summarize the current research hotspots and trends in this field, and provide valuable information for future tACS-related research. Material and methods: The database Web of Science Core Collection Science Citation Index Expanded was used and searched from build to 4 August 2023. Using the CiteSpace to analyze the authors, institutions, countries, keywords, co-cited authors, journals, and references. Results: A total of 677 papers were obtained. From 2008 to 2023, the number of publications shows an increasing trend, albeit with some fluctuations. The most productive country in this field was Germany. The institution with the highest number of publications is Carl von Ossietzky University of Oldenburg (n = 50). According to Bradford's law, 7 journals are considered core journals in the field. Herrmann, CS was the author with the most publications (n = 40), while Antal, A was the author with the highest number of co-citations (n = 391) and betweenness centrality (n = 0.16). Disease, neural mechanisms of the brain and electric stimulation are the major research areas in the field. The effect of tACS in different diseases, multi-site stimulation, combined treatment and evaluation are the future research hotspots and trends. Conclusion: tACS has research value and research potential, and more and more researchers are paying attention to it. The findings of this bibliometric study provide the current status and trends in the clinical research of tACS and may help researchers to identify hotspots s and explore new research directions in this field.

Additive effect of metabolic dysfunction-associated fatty liver disease on left ventricular function and global strain in type 2 diabetes mellitus patients: a 3.0 T cardiac magnetic resonance feature tracking study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and metabolic-associated fatty liver disease (MAFLD) are both metabolic disorders that negatively impact the cardiovascular system. This study comprehensively analyzed the additive effect of MAFLD on left ventricular function and global strain in T2DM patients by cardiac magnetic resonance (CMR). METHODS: Data of 261 T2DM patients, including 109 with and 152 without MAFLD, as well as 73 matched normal controls from our medical center between June 2015 and March 2022 were retrospectively analyzed. CMR-derived parameters, including LV function and global strain parameters, were compared among different groups. Univariate and multivariate linear regression analyses were conducted to investigate the impact of various factors on LV function and global strain. RESULTS: Our investigation revealed a progressive deterioration in LV functional parameters across three groups: control subjects, T2DM patients without MAFLD, and T2DM patients with MAFLD. Statistically significant increases in left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), left ventricular mass index (LVMI) were observed, along with decreases in left ventricular ejection fraction (LVEF) and left ventricular global function index (LVGFI). Among these three groups, significant reductions were also noted in the absolute values of LV global radial, circumferential, and longitudinal peak strains (GRPS, GCPS, and GLPS), as well as in peak systolic (PSSR) and peak diastolic strain rates (PDSR). MAFLD was identified as an independent predictor of LVEF, LVMI, LVGFI, GRPS, GCPS, and GLPS in multivariate linear analysis. Besides, the incidence of late gadolinium enhancement was higher in MAFLD patients than in non-MAFLD patients (50/109 [45.9%] vs. 42/152 [27.6%], p = 0.003). Furthermore, escalating MAFLD severity was associated with a numerical deterioration in both LV function parameters and global strain values. CONCLUSIONS: This study thoroughly compared CMR parameters in T2DM patients with and without MAFLD, uncovering MAFLD's adverse impact on LV function and deformation in T2DM patients. These findings highlight the critical need for early detection and comprehensive management of cardiac function in T2DM patients with MAFLD.

[Effects of Acid Mine Drainage Leakage on Bacterial Communities in Desert Grassland Soil Profiles].

Acid mine drainage （AMD） is of great concern owing to its safety hazards and environmental risks. However, little is known about the effects of AMD leakage on soil physicochemical properties and bacterial communities in ecologically fragile desert steppe soils, especially in the soil profile. Therefore, an AMD-contaminated profile and clean profile were used as research objects respectively to investigate the effects of AMD on soil physicochemical properties and bacterial community composition, structure, and interactions in soil layers at different depths of desert grassland and, based on this, to analyze the driving factors of bacterial community changes. The results showed that AMD significantly decreased the pH and increased electrical conductivity （EC） and heavy metal content in the upper （0-40 cm） soil layer of the profile. The AMD-contaminated profile bacteria were dominated by Proteobacteria, Firmicutes, and Actinobacterota, whereas clean profile bacteria were dominated by Firmicutes and Bacteroidota, with Thermithiobacillus and Alloprevotella being the biomarkers for the contaminated and clean profiles, respectively. AMD contamination significantly reduced bacterial diversity and significantly altered bacterial community structure in the upper soil layers of the profile. The results of redundancy analysis showed that soil physicochemical properties explained 57.21% of the variation in bacterial community changes, with EC, TP, TN, As, Zn, and Pb being the main drivers of bacterial community changes. Network analyses showed that AMD contamination increased profile complexity, modularity, and intra-community competition, thereby improving bacterial community stability and resilience. In conclusion, the study provided useful information on the effects of AMD pollution on soil physicochemical properties and bacterial communities in desert steppe soils, which may help to improve the understanding of the ecological hazards of AMD pollution on soils in extreme habitats.

Post-transfer adaptation of HGT-acquired genes and contribution to guanine metabolic diversification in land plants.

Horizontal gene transfer (HGT) is a major driving force in the evolution of prokaryotic and eukaryotic genomes. Despite recent advances in distribution and ecological importance, the extensive pattern, especially in seed plants, and post-transfer adaptation of HGT-acquired genes in land plants remain elusive. We systematically identified 1150 foreign genes in 522 land plant genomes that were likely acquired via at least 322 distinct transfers from nonplant donors and confirmed that recent HGT events were unevenly distributed between seedless and seed plants. HGT-acquired genes evolved to be more similar to native genes in terms of average intron length due to intron gains, and HGT-acquired genes containing introns exhibited higher expression levels than those lacking introns, suggesting that intron gains may be involved in the post-transfer adaptation of HGT in land plants. Functional validation of bacteria-derived gene GuaD in mosses and gymnosperms revealed that the invasion of foreign genes introduced a novel bypass of guanine degradation and resulted in the loss of native pathway genes in some gymnosperms, eventually shaping three major types of guanine metabolism in land plants. We conclude that HGT has played a critical role in land plant evolution.

The combined detection of carcinoembryonic antigen, carcinogenic antigen 125, and carcinogenic antigen 19-9 in colorectal cancer patients.

BACKGROUND: Hepatic metastases are common and difficult to treat after colorectal cancer (CRC) surgery. The predictive value of carcinoembryonic antigen (CEA), cancer antigen (CA) 125 and CA19-9 combined tests for liver metastasis is unclear. AIM: To evaluate predictive value of combined tests for CEA, CA125, and CA19-9 levels in patients with liver metastases of CRC. METHODS: The retrospective study included patients with CRC alone (50 cases) and patients with CRC combined with liver metastases (50 cases) who were hospitalized between January 2021 and January 2023. Serum CEA, CA125 and CA19-9 levels were compared between the two groups, and binary logistic regression was used to analyze the predictive value of the combination of these tumor markers in liver metastasis. In addition, we performed receiver operating characteristic (ROC) curve analysis to assess its diagnostic accuracy. RESULTS: The results showed that the serum CEA, CA125 and CA19-9 levels in the CRC with liver metastasis group were significantly higher than those in the CRC alone group. Specifically, the average serum CEA level in the CRC with liver metastasis group was 162.03 ± 810.01 ng/mL, while that in the CRC alone group was 5.71 ± 9.76 ng/mL; the average serum CA125 levels were 43.47 ± 83.52 U/mL respectively. and 13.5 ± 19.68 U/mL; the average serum CA19-9 levels were 184.46 ± 473.13 U/mL and 26.55 ± 43.96 U/mL respectively. In addition, binary logistic regression analysis showed that CA125 was significant in predicting CRC liver metastasis (P < 0.05). ROC curve analysis results showed that the areas under the ROC curves of CEA, CA125 and CA19-9 were 0.607, 0.692 and 0.586. CONCLUSION: These results suggest that combined detection of these tumor markers may help early detection and intervention of CRC liver metastasis, thereby improving patient prognosis.

The predictors to self-reported and performance-based physical function in knee osteoarthritis patients: a cross-sectional study.

Background: Osteoarthritis (OA) knee patients have limited ability in physical function, or difficulties with physical tasks and activities may develop disability. This study aimed to observe the predictors of self-reported and performance-based physical function in patients with knee OA by analyzing the impacts of demographic, pathological, and muscle impairment factors. Methods: 135 knee OA patients participated in this study to complete self-reported questionnaires using Knee Injury and Osteoarthritis Outcome Score (KOOS). When measuring performance-based physical function, a 6-meter gait speed (6MGS) test was measured to evaluate their mobility, and a 5-time Sit-to-Stand test (5STS) was assessed to evaluate their balance. Pain intensity, knee extensor and flexor muscle strength, age, body mass index (BMI), durations of symptoms, and radiographic severity were also collected. Spearman correlation and stepwise multiple linear regression were used to explore the association and predictors in self-reported and performance-based physical function. Results: BMI and durations of symptoms did not indicate any significant correlation with either self-reported or performance-based physical function. Age is significantly negatively associated with 6MGS (r 2 = -0.383, p < 0.01), while knee extensor muscle strength has a moderate correlation with 5STS (r 2 = -0.528, p < 0.01). In the stepwise multiple linear regression models, pain intensity (ß = 0.712, p < 0.001), knee flexor muscle strength (ß = 0.112, p = 0.042) were significantly associated with self-reported physical function in daily activities and contributed to 55.0% of the variance in KOOS-PF score. Knee muscle strength, including knee extensor (5STS: ß = -0.428, p < 0.001) and flexor muscle strength (6MGS: ß = 0.367, p < 0.001), were the main predictors with performance-based physical function. Conclusion: Pain intensity was the leading risk factor of self-reported physical function, and knee flexor muscle strength contributed as well. The severity of knee OA, durations of symptoms and BMI did not contribute to physical function. However, knee extensor and flexor muscle strength were the main predictors of performance-based performance. Our results show that strengthening of weak knee muscles in both quadriceps and hamstring muscle strength should be considered a priory consideration in knee OA no matter if people are in the early or end-stage of knee OA.