Leptospira-specific immunoglobulin Y (IgY) is protective in infected hamsters.

Leptospirosis, a globally significant zoonotic disease caused by pathogenic Leptospira, continues to threaten the health and public safety of both humans and animals. Current clinical treatment of leptospirosis mainly relies on antibiotics but their efficacy in severe cases is controversial. Passive immunization has a protective effect in the treatment of infectious diseases. In addition, chicken egg yolk antibody (IgY) has gained increasing attention as a safe passive immunization agent. This study aimed to investigate whether hens produce specific IgY after immunization with inactivated Leptospira and the protective effect of specific IgY against leptospirosis. First, it was demonstrated that specific IgY could be extracted from the eggs of hens vaccinated with inactivated Leptospira and that specific IgY can specifically recognize and bind homotypic Leptospira with a high titre, as shown by MAT and ELISA. Next, we tested the therapeutic effects of IgY in early and late leptospirosis using a hamster model. The results showed that early specific IgY treatment increased the survival rate of hamsters to 100%, alleviated pathological damage to the liver, kidney, and lung, reduced leptospiral burden, and restored haematological indices as well as functional indicators of the liver and kidney. The therapeutic effect of early specific IgY was comparable to that of doxycycline. Late IgY treatment also enhanced the survival rate of hamsters and improved the symptoms of leptospirosis similar to early IgY treatment. However, the therapeutic effect of late IgY treatment was better when combined with doxycycline. Furthermore, no Leptospira colonization was observed in the kidneys, livers, or lungs of the surviving hamsters treated with specific IgY. Mechanistically, IgY was found to inhibit the growth and adhesion to cells of Leptospira. In conclusion, passive immunotherapy with specific IgY can be considered an effective treatment for leptospirosis, and may replace antibiotics regarding its therapeutic effects.

Distribution characteristics and microbial synergistic degradation potential of polyethylene and polypropylene in freshwater estuarine sediments.

The microbial degradation of polyethylene (PE) and polypropylene (PP) resins in rivers and lakes has emerged as a crucial issue in the management of microplastics. This study revealed that as the flow rate decreased longitudinally, ammonia nitrogen (NH4+-N), heavy fraction of organic carbon (HFOC), and small-size microplastics (< 1 mm) gradually accumulated in the deep and downstream estuarine sediments. Based on their surface morphology and carbonyl index, these sediments were identified as the potential hot zone for PE/PP degradation. Within the identified hot zone, concentrations of PE/PP-degrading genes, enzymes, and bacteria were significantly elevated compared to other zones, exhibiting strong intercorrelations. Analysis of niche differences revealed that the accumulation of NH4+-N and HFOC in the hot zone facilitated the synergistic coexistence of key bacteria responsible for PE/PP degradation within biofilms. The findings of this study offer a novel insight and comprehensive understanding of the distribution characteristics and synergistic degradation potential of PE/PP in natural freshwater environments.

Choriocarcinoma That Had Transferred to the Right Inferior Pulmonary Vein and Left Atrium: A Case Report.

Here, we present a case of choriocarcinoma with metastasis only to the right inferior pulmonary vein and heart, which is unusual, as the skipping of lung metastasis is extremely rare. The 34-year-old patient presented with cough and hemoptysis. The diagnosis was challenging due to the absence of gynecological abnormalities and elevated ß-HCG levels, only revealing a cardiac mass upon imaging. While no abnormalities were found through gynecological ultrasound or gynecological examination, the serum human chorionic gonadotropin ß subunit (ß-HCG) level was abnormally raised. Echocardiography showed a left atrial myxoma with a size of approximately 6.3×1.81 cm. A left atrial mass resection was performed during cardiac surgery, where it was found that the left atrial mass had originated from the right inferior pulmonary vein. It was approximately 6×3×3 cm in size, with a flesh-red color and firm tissue. Postoperative pathology and immunohistochemistry indicated choriocarcinoma. The cardiac surgery unearthed a mass originating from the right inferior pulmonary vein. Its size and characteristics, along with the chemotherapy regimens that followed, are crucial details for understanding treatment approaches for such atypical cases. Highlight the patient's recovery post-treatment and the effectiveness of the chemotherapy regimen. This offers insights into the potential for successful treatment outcomes in atypical choriocarcinoma cases. The patient underwent chemotherapy regimens with etoposide, cisplatin (EP) ,etoposide, and methotrexate, and dactinomycin alternating with cyclophosphamide and vincristine (EMACO). A satisfactory result was achieved. This case enhances understanding of choriocarcinoma metastasis patterns. It underscores the need for a multidisciplinary approach in diagnosing and managing such rare presentations.

The m6A methyltransferase METTL5 promotes neutrophil extracellular trap network release to regulate hepatocellular carcinoma progression.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, it has a poor prognosis due to its highly invasive and metastatic nature. Consequently, identifying effective prognostic markers and potential therapeutic targets has been extensively investigated. METTL5, an 18S rRNA methyltransferase, is abnormally high in HCC. But its biological function and prognostic significance in HCC remain largely unelucidated. This study aimed to investigate the role of METTL5 in HCC progression, and elucidate its possible molecular mechanisms in HCC via transcriptome sequencing, providing new insights for identifying new HCC prognostic markers and therapeutic targets. METHODS: The METTL5 expression in HCC and paracancerous tissues was analyzed using HCC immunohistochemical microarrays and bioinformatic retrieval methods to correlate METTL5 with clinicopathological features and survival prognosis. We constructed a METTL5 knockdown hepatocellular carcinoma cell line model and an animal model to determine the effect of METTL5 on hepatocellular carcinoma progression. Subsequently, RNA sequencing was performed to analyze the molecular mechanism of METTL5 in HCC based on the sequencing results, and relevant experiments were performed to verify it. RESULTS: We found that METTL5 expression was elevated in hepatocellular carcinoma tissues and correlated with poor patient prognosis, and in the analysis of clinicopathological features showed a correlation with TNM staging. In hepatocellular carcinoma cell lines with knockdown of METTL5, the malignant biological behavior was significantly reduced both in vitro and in vivo. Based on the sequencing results as well as the results of GO functional enrichment analysis and KEGG pathway enrichment analysis, we found that METTL5 could promote the generation and release of neutrophil extracellular capture network (NETs) and might further accelerate the progression of HCC. CONCLUSION: The m6A methyltransferase METTL5 is overexpressed in hepatocellular carcinoma (HCC) and correlates with poor prognosis. METTL5 accelerates malignant progression of HCC by promoting generation and release of the neutrophil extracellular traps (NETs) network, providing new insights for clinical biomarkers and immunotherapeutic targets in HCC prognosis.

High expression of SULF1 is associated with adverse prognosis in breast cancer brain metastasis.

BACKGROUND: Breast cancer is the most common cancer in women, and in advanced stages, it often metastasizes to the brain. However, research on the biological mechanisms of breast cancer brain metastasis and potential therapeutic targets are limited. METHODS: Differential gene expression analysis (DEGs) for the datasets GSE43837 and GSE125989 from the GEO database was performed using online analysis tools such as GEO2R and Sangerbox. Further investigation related to SULF1 was conducted using online databases such as Kaplan-Meier Plotter and cBioPortal. Thus, expression levels, variations, associations with HER2, biological processes, and pathways involving SULF1 could be analyzed using UALCAN, cBioPortal, GEPIA2, and LinkedOmics databases. Moreover, the sensitivity of SULF1 to existing drugs was explored using drug databases such as RNAactDrug and CADSP. RESULTS: High expression of SULF1 was associated with poor prognosis in advanced breast cancer brain metastasis and was positively correlated with the expression of HER2. In the metastatic breast cancer population, SULF1 ranked top among the 16 DEGs with the highest mutation rate, reaching 11%, primarily due to amplification. KEGG and GSEA analyses revealed that the genes co-expressed with SULF1 were positively enriched in the 'ECM-receptor interaction' gene set and negatively enriched in the 'Ribosome' gene set. Currently, docetaxel and vinorelbine can act as treatment options if the expression of SULF1 is high. CONCLUSIONS: This study, through bioinformatics analysis, unveiled SULF1 as a potential target for treating breast cancer brain metastasis (BM).

UNVEILING THE PROTECTIVE MECHANISMS OF PUERARIN AGAINST ACUTE LUNG INJURY: A COMPREHENSIVE EXPLORATION OF THE ROLES AND MECHANISMS OF MST1/ERS SIGNALING.

OBJECTIVES: Puerarin, the principal active constituent extracted from Pueraria, is believed to confer protection against sepsis-induced lung injury. The study aimed to elucidate the role and mechanism of Mst1/ERS in puerarin-mediated protection against acute lung injury (ALI). METHODS: Monolayer vascular endothelial cell permeability was assessed by gauging the paracellular flow of FITC-dextran 40,000 (FD40). ELISA was employed for the quantification of inflammatory cytokines. Identification of target proteins was conducted through Western blotting. Histological alterations and apoptosis were scrutinized using H&E staining and TUNEL staining, respectively. The ultrastructure of the endoplasmic reticulum was observed via transmission electron microscopy. RESULTS: Puerarin significantly protected mice from LPS-induced ALI, reducing lung interstitial width, neutrophil and lymphocyte infiltration, pulmonary interstitial and alveolar edema, and lung apoptosis. Puerarin treatment also markedly attenuated levels of TNF-α and IL-1ß in both alveolar lavage fluid and serum. Furthermore, puerarin significantly attenuated LPS-induced increases in Mst1, GRP78, CHOP, and Caspase12 protein expression and blunted LPS-induced decrease in ZO-1 protein expression in lung tissues. Puerarin obviously reduced endoplasmic reticulum expansion and vesiculation. Similarly, puerarin significantly mitigated the LPS-induced reduction in HUVEC cell viability and ZO-1 expression. Puerarin also attenuated LPS-induced increase in apoptosis, TNF-α and IL-1ß, FD40 flux, and Mst1, GRP78, CHOP, and Caspase12 expression in HUVEC cells. Nevertheless, the inhibitory impact of puerarin on vascular endothelial cell injury, lung injury, and endoplasmic reticulum stress (ERS) was diminished by Mst1 overexpression. CONCLUSION: These findings demonstrated that the Mst1/ERS signaling pathway played a pivotal role in the development of LPS-induced vascular endothelial cell dysfunction and ALI. Puerarin exhibited the ability to attenuate LPS-induced vascular endothelial cell dysfunction and ALI by inhibiting the Mst1/ERS signaling pathway.

[The experience on the construction of the cluster prevention and control system for COVID-19 infection in designated hospitals during the period of "Category B infectious disease treated as Category A"].

The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.

Preparation of O-g-C3N4 nanowires/Bi2O2CO3 porous plate composite photocatalysts for the efficient degradation of tetracycline hydrochloride in wastewater.

Both g-C3N4 and Bi2O2CO3 are good photocatalysts for the removal of antibiotic pollutants, but their morphological modulation and catalytic performance need to be further improved. In this study, the calcination-hydrothermal method is used to prepare a O-g-C3N4@Bi2O2CO3 (CN@BCO) composite photocatalyst from dicyandiamide and bismuth nitrate. The prepared catalyst is characterized through various methods, including X-ray diffraction (XRD) and transmission electron microscopy (TEM). Further, the effects of different parameters, such as catalyst concentration and initial pH of the reaction solution, on its photocatalytic activity are investigated. The results show that the CN@BCO sample achieves an optimal degradation rate of 98.1% for tetracycline hydrochloride (TCH) with a concentration of 20 mg/L and a removal rate of 69.4% for total organic carbon (TOC) at 40 min. The quenching experiments show that ·O2-, h+, and ·OH participate in the photocatalytic process, with ·O2- being the most dominant active species. The toxicity of the predicted TCH degradation intermediates is analyzed using Toxicity Estimation Software Tool (TEST). Overall, the CN@BCO composite exhibits excellent photocatalytic performance, making it a promising candidate for environmental purification and wastewater treatment.

In vivo research on 3D-printed composite PLGA and PDLLA-HA absorbable scaffolds for repairing radius defects in rabbits.

OBJECTIVES: Despite being an important research topic in oral biomaterials, few studies have demonstrated the differences between poly(d,l-lactide-co-glycolide)/hydroxyapatite (PLGA/HA) and poly(d,l-lactic acid)/hydroxyapatite (PDLLA/HA). In this study, PLGA/HA and PDLLA/HA scaffolds were prepared using three-dimensional (3D) printing technology and implanted into radius defects in rabbits to assess their effects on bone regeneration. METHODS: In this study, 6 mm × 4 mm bone defects were generated in the bilateral radii of rabbits. 3D-printed PLGA/HA and PDLLA/HA scaffolds were implanted into the defects. X-ray imaging, micro-computed tomography, and hematoxylin-eosin staining were performed to observe the degradation of the materials, the presence of new bone, and bone remodeling in the bone defect area. RESULTS: The PLGA/HA scaffolds displayed complete degradation at 20 weeks, whereas PDLLA/HA scaffolds exhibited incomplete degradation. Active osteoblasts were detected in both groups. The formation of new bone, bone marrow cavity reconstruction, and cortical bone remodeling were better in the PLGA/HA group than in the PDLLA/HA group. CONCLUSIONS: PLGA/HA scaffolds performed better than PDLLA/HA scaffolds in repairing bone defects, making the former scaffolds more suitable as bone substitutes at the same high molecular weight.

Evaluation of Left Ventricular Function in Patients With Severe Aortic Stenosis Utilizing Automated Cardiac Motion Quantitation Techniques.

OBJECTIVE: The objective of this study is to explore the patterns of alteration in left ventricular systolic function among patients with severe aortic stenosis (SAS) through the application of automatic myocardial motion quantification (aCMQ) techniques. Furthermore, we seek to ascertain dependable quantitative markers for the assessment of impaired left ventricular function in patients with SAS and an ejection fraction (EF) ≥ 60%. METHODS: Seventy patients who underwent echocardiography and received a diagnosis of severe aortic stenosis (SAS) in the hospital from November 2021 to August 2022 were selected for the SAS group and categorized into three subgroups based on ejection fraction (EF)-SAS group with EF ≥ 60%, SAS group with EF ranging from 50% to 59%, and SAS group with EF < 50%. Concurrently, 30 healthy individuals were recruited at the hospital during the same timeframe to serve as the control group. Participants from both groups underwent standard transthoracic echocardiography to assess conventional echocardiographic parameters. Dynamic images were examined using automatic myocardial motion quantification (aCMQ) software to derive longitudinal peak strain (LPS) parameters, which were then subjected to statistical analysis. RESULTS: In comparison to the control group participants, the measurements of ascending aorta diameter (AoD), left atrium diameter (LAD), interventricular septal end diastolic thickness (IVSd), left ventricular posterior wall end diastolic thickness (LVPWd), peak systolic velocity (Vmax), and mean pressure gradient (MPG) were significantly higher in the SAS groups (p < 0.05). When compared to participants in the SAS group with an EF ≥ 60%, the values of IVSd, LVPWd, Vmax, and MPG in the SAS group with EF ranging from 50% to 59% were significantly elevated (p < 0.05). Similarly, left ventricular end-diastolic diameter (LVEDD), the ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity (E/e'), and the ratio of early to late diastolic mitral inflow velocities (E/A) in the SAS group with EF < 50% were significantly elevated (p < 0.05). The absolute values of longitudinal peak strain (LPS) in the SAS groups were significantly lower in comparison to those in the control group (p < 0.05). Furthermore, all measurements of left ventricular global longitudinal systolic peak strain (GLPS) showed a positive correlation with MPG, a moderate negative correlation with aortic valve area index (AVAI), and a moderate positive correlation with E/A. CONCLUSIONS: Patients with SAS and an EF < 50% exhibited the most profound impairment in left ventricular myocardial function. Utilizing the aCMQ technique enables the precise and quantitative evaluation of the severity of impaired left ventricular systolic function in patients within the SAS group with an EF ≥ 60%.

Rapid in situ mutation detection in extracellular vesicle-DNA.

A PCR- and sequencing-free mutation detection assay facilitates cancer diagnosis and reduces over-reliance on specialized equipment. This benefit was highlighted during the pandemic when high demand for viral nucleic acid testing often sidelined mutation analysis. This shift led to substantial challenges for patients on targeted therapy in tracking mutations. Here, we report a 30-minute DNA mutation detection technique using Cas12a-loaded liposomes in a microplate reader, a fundamental laboratory tool. CRISPR-Cas12a complex and fluorescence-quenching (FQ) probes are introduced into tumor-derived extracellular vesicles (EV) through membrane fusion. When CRISPR-RNA hybridizes with the DNA target, activated Cas12a can trans-cleave FQ probes, resulting in fluorescence signals for the quantification of DNA mutation. Future advancements in multiplex and high-throughput mutation detection using this assay will streamline self-diagnosis and treatment monitoring at home.

Identification of potential cell death-related biomarkers for diagnosis and treatment of osteoporosis.

BACKGROUND: This study aimed to identify potential biomarkers for the diagnosis and treatment of osteoporosis (OP). METHODS: Data sets were downloaded from the Gene Expression Omnibus database, and differentially programmed cell death-related genes were screened. Functional analyses were performed to predict the biological processes associated with these genes. Least absolute shrinkage and selection operator (LASSO), support vector machine (SVM), and random forest (RF) machine learning algorithms were used to screen for characteristic genes, and receiver operating characteristics were used to evaluate the diagnosis of disease characteristic gene values. Gene set enrichment analysis (GSEA) and single-sample GSEA were conducted to analyze the correlation between characteristic genes and immune infiltrates. Cytoscape and the Drug Gene Interaction Database (DGIdb) were used to construct the mitochondrial RNA-mRNA-transcription factor network and explore small-molecule drugs. Reverse transcription real-time quantitative PCR (RT-qPCR) analysis was performed to evaluate the expression of biomarker genes in clinical samples. RESULTS: In total, 25 differential cell death genes were identified. Among these, two genes were screened using the LASSO, SVM, and RF algorithms as characteristic genes, including BRSK2 and VPS35. In GSE56815, the area under the receiver operating characteristic curve of BRSK2 was 0.761 and that of VPS35 was 0.789. In addition, immune cell infiltration analysis showed that BRSK2 positively correlated with CD56dim natural killer cells and negatively correlated with central memory CD4 + T cells. Based on the data from DGIdb, hesperadin was associated with BRSK2, and melagatran was associated with VPS35. BRSK2 and VPS35 were expectably upregulated in OP group compared with controls (all p < 0.05). CONCLUSIONS: BRSK2 and VPS35 may be important diagnostic biomarkers of OP.

Targeting SIRT3 sensitizes glioblastoma to ferroptosis by promoting mitophagy and inhibiting SLC7A11.

Glioblastoma (GBM) cells require large amounts of iron for tumor growth and progression, which makes these cells vulnerable to destruction via ferroptosis induction. Mitochondria are critical for iron metabolism and ferroptosis. Sirtuin-3 (SIRT3) is a deacetylase found in mitochondria that regulates mitochondrial quality and function. This study aimed to characterize SIRT3 expression and activity in GBM and investigate the potential therapeutic effects of targeting SIRT3 while also inducing ferroptosis in these cells. We first found that SIRT3 expression was higher in GBM tissues than in normal brain tissues and that SIRT3 protein expression was upregulated during RAS-selective lethal 3 (RSL3)-induced GBM cell ferroptosis. We then observed that inhibition of SIRT3 expression and activity in GBM cells sensitized GBM cells to RSL3-induced ferroptosis both in vitro and in vivo. Mechanistically, SIRT3 inhibition led to ferrous iron and ROS accumulation in the mitochondria, which triggered mitophagy. RNA-Sequencing analysis revealed that upon SIRT3 knockdown in GBM cells, the mitophagy pathway was upregulated and SLC7A11, a critical antagonist of ferroptosis via cellular import of cystine for glutathione (GSH) synthesis, was downregulated. Forced expression of SLC7A11 in GBM cells with SIRT3 knockdown restored cellular cystine uptake and consequently the cellular GSH level, thereby partially rescuing cell viability upon RSL3 treatment. Furthermore, in GBM cells, SIRT3 regulated SLC7A11 transcription through ATF4. Overall, our study results elucidated novel mechanisms underlying the ability of SIRT3 to protect GBM from ferroptosis and provided insight into a potential combinatorial approach of targeting SIRT3 and inducing ferroptosis for GBM treatment.

Metformin Protects Against Acute Kidney Injury Induced by Lipopolysaccharide via Up-Regulating the MCPIP1/SIRT1 Pathway.

In the present study, we aimed to explore the effect and underlying mechanism of metformin on lipopolysaccharide (LPS)-induced acute kidney injury (AKI). A total of 24 BALB/C mice were randomly divided into four groups: control group, LPS group and metformin group (50 or 100 mg/kg). The histological changes and cell apoptosis in kidney tissues were detected by hematoxylin-eosin staining and terminal-deoxynucleotidyl transferase-mediated nick end labeling assay, respectively. Enzyme-linked immunosorbent assay was applied to determine serum levels of blood urea nitrogen (BUN), kidney injury molecule-1 (Kim-1), creatinine (Cre), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß). Western blotting analysis were carried out to confirm the expressions of monocyte chemotactic protein-inducible protein 1 (MCPIP1), silent information regulator sirtuin 1 (SIRT1), and NF-κB p65 (acetyl K310). Compared with the control group, the mice in LPS group had glomerular capillary dilatation, renal interstitial edema, tubular cell damage and apoptosis. The serum levels of BUN, KIM-1, Cre, TNF-α, and IL-1ß in LPS group were significantly higher than those in control group. Moreover, LPS also elevated the expressions of MCPIP1 and NF-κB p65 (acetyl K310) but decreased the expression of SIRT1 in kidney tissues. However, metformin distinctly decreased LPS-induced renal dysfunction, the serum levels of BUN, KIM-1, Cre, TNF-α, and IL-1ß. In addition, metformin markedly increased the expressions of MCPIP1 and SIRT1 but decreased the expression of NF-κB p65 (acetyl K310) in kidney tissues. Metformin prevented LPS-induced AKI by up-regulating the MCPIP1/SIRT1 signaling pathway and subsequently inhibiting NF-κB-mediated inflammation response.

Transcription Factor MAZ Potentiates the Upregulated NEIL3-mediated Aerobic Glycolysis, Thereby Promoting Angiogenesis in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is characterized by high vascularity and notable abnormality of blood vessels, where angiogenesis is a key process in tumorigenesis and metastasis. The main functions of Nei Like DNA Glycosylase 3 (NEIL3) include DNA alcoholization repair, immune response regulation, nervous system development and function, and DNA damage signal transduction. However, the underlying mechanism of high expression NEIL3 in the development and progression of HCC and whether the absence or silencing of NEIL3 inhibits the development of cancer remain unclear. Therefore, a deeper understanding of the mechanisms by which increased NEIL3 expression promotes cancer development is needed. METHODS: Expression of NEIL3 and its upstream transcription factor MAZ in HCC tumor tissues was analyzed in bioinformatics efforts, while validation was done by qRT-PCR and western blot in HCC cell lines. The migration and tube formation capacity of HUVEC cells were analyzed by Transwell and tube formation assays. Glycolytic capacity was analyzed by extracellular acidification rate, glucose uptake, and lactate production levels. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter gene assays were utilized to investigate specific interactions between MAZ and NEIL3. RESULTS: NEIL3 and MAZ were substantially upregulated in HCC tissues and cells. NEIL3 was involved in modulating the glycolysis pathway, suppression of which reversed the stimulative impact of NEIL3 overexpression on migration and angiogenesis in HUVEC cells. MAZ bound to the promoter of NEIL3 to facilitate NEIL3 transcription. Silencing MAZ reduced NEIL3 expression and suppressed the glycolysis pathway, HUVEC cell migration, and angiogenesis. CONCLUSION: MAZ potentiated the upregulated NEIL3-mediated glycolysis pathway and HCC angiogenesis. This study provided a rationale for the MAZ/NEIL3/glycolysis pathway as a possible option for anti-angiogenesis therapy in HCC.

Adsorption mechanism of Ca2+, Mg2+, Fe3+, and Al3+ ions in phosphoric acid-nitric acid solution on 001 × 7 and S957 resins.

Selective removal of Ca2+ and Mg2+ ions using the 001 × 7 resin and Fe3+ and Al3+ ions using the S957 resin is able to achieve the deep purification of the phosphoric acid-nitric acid solution, but the adsorption behaviors of Fe3+ and Al3+ ions are seriously suppressed by phosphoric acid. In order to understand the interaction mechanism of separation processes and the influence of phosphoric acid, we first studied the bonding form of Ca2+, Mg2+, Fe3+, and Al3+ ions on 001 × 7 and S957 resins using FT-IR and XPS techniques; subsequently, quantum chemistry computation was carried out to further explore the bonding mechanism between the functional groups on resins and metal ions. FT-IR and XPS results reveal that for the adsorption process on the 001 × 7 resin, hydroxyls from sulfonic acid groups combine with Ca2+ and Mg2+ ions. Whereas Fe3+ and Al3+ ions are adsorbed on the S957 resin through an exchange reaction with hydroxyls on the phosphonic acid group but not on the sulfonic acid group. Quantum chemistry computation results reveal that the phosphonic acid group has a larger binding energy with Fe3+ and Al3+ ions. Thus, the S957 resin still presents great adsorption performance for Fe3+ and Al3+ ions despite the influence of dihydrogen phosphate ions in the phosphoric acid-nitric acid solution.

The Natural Products as Novel Anti-obesity Agents: Mechanisms Based on Adipose Tissue.

Obesity presently stands as a formidable global public health concern, exerting a profound impact on human life and well-being. Despite the plethora of pharmacological interventions targeting obesity, their extensive use in clinical settings is hindered by the emergence of numerous adverse reactions during drug interventions. Naturally occurring compounds or extracts found in traditional Chinese medicine, fruits, and vegetables, possessing various attributes, such as metabolic modulation, thermogenic induction, appetite alteration, and inhibition of lipase activity and fat synthesis, have positioned themselves as potential anti-obesity pharmaceutical candidates. Promoting thermogenesis through the browning of adipose tissue, reducing fat tissue generation and ectopic deposition, along with the regulation of adipose factors, has emerged as a primary focus in the treatment of obesity. This shift underscores the pivotal role of adipose tissue as a critical target in obesity management. This study delves into various approaches based on adipose tissue, providing an overview of the efficacy of bioactive components derived from medicinal plants and fruits for treating obesity through adipose tissue modulation. Insights are drawn from both animal experiments and clinical applications, with a discussion of potential mechanisms underlying these effects. In conclusion, we have determined that natural compounds are significant candidates for the treatment of obesity, and adipose tissue represents a crucial target in the therapeutic process. We hope that our research will contribute novel perspectives for the development of future pharmaceuticals and dietary supplements, as well as provide innovative directions for clinical trials in the field.

Temporal profiling of sediment microbial communities in the Three Gorges Reservoir Area discovered time-dissimilarity patterns and multiple stable states.

Microbial communities play vital roles in cycling nutrients and maintaining water quality in aquatic ecosystems. To better understand the dynamics of microbial communities and to pave way to effective ecological remediation, it's essential to reveal the temporal patterns of the communities and to identify their states. However, research exploring the dynamic changes of microbial communities needs a large amount of time-series data, which could be an extravagant requirement for a single study. In this research, we overcame this challenge by conducting a meta-analysis of years of accumulations of 16S rRNA high-throughput sequencing data from the Three Gorges Reservoir Area (TGRA), an ecological and environmental hotspot. For better understanding the microbial communities time-dissimilarity dynamics, three microbial communities time-dissimilarity patterns were hypothesized, and the linear pattern in the TGRA was validated. In addition, to explore the stability of microbial communities in the TGRA, two alternative stable states were revealed, and their differences in community richness, alpha diversity indices, community composition, ecological network topological properties, and metabolic functions were demonstrated. In short, two states of microbial communities showed distinct richness and alpha diversity indices, and the communities in one state were more dominated by Halomonas and Nitrosopumilaceae genera, facilitating nitrogen cycling metabolic processes; whilst the main genera of the other state were Bathyarchaeia and Methanosaeta, which favored methane-related metabolism. Moreover, different studies and environmental differences between mainstream and tributaries were attributed as the potential inducing factors of the state division. Our study provides a comprehensive insight into the dynamics and stability of microbial communities in the TGRA, and a reference for future studies on microbial community dynamics.

Conditional knockout of the NSD2 gene in mouse intestinal epithelial cells inhibits colorectal cancer progression.

BACKGROUND: Nuclear receptor-binding SET domain 2 (NSD2) is a histone methyltransferase, that catalyzes dimethylation of lysine 36 of histone 3 (H3K36me2) and is associated with active transcription of a series of genes. NSD2 is overexpressed in multiple types of solid human tumors and has been proven to be related to unfavorable prognosis in several types of tumors. METHODS: We established a mouse model in which the NSD2 gene was conditionally knocked out in intestinal epithelial cells. We used azoxymethane and dextran sodium sulfate to chemically induce murine colorectal cancer. The development of colorectal tumors were investigated using post-necropsy quantification, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with wild-type (WT) control mice, NSD2fl/fl -Vil1-Cre mice exhibited significantly decreased tumor numbers, histopathological changes, and cytokine expression in colorectal tumors. CONCLUSIONS: Conditional knockout of NSD2 in intestinal epithelial cells significantly inhibits colorectal cancer progression.

Diallyl disulfide induces DNA damage and growth inhibition in colorectal cancer cells by promoting POU2F1 ubiquitination.

Previous studies have demonstrated that diallyl disulfide (DADS) exhibits potent anti-tumor activity. However, the pharmacological actions of DADS in inhibiting the growth of colorectal cancer (CRC) cells have not been clarified. Herein, we show that DADS treatment impairs the activation of the pentose phosphate pathway (PPP) to decrease PRPP (5-phosphate ribose-1-pyrophosphate) production, enhancing DNA damage and cell apoptosis, and inhibiting the growth of CRC cells. Mechanistically, DADS treatment promoted POU2F1 K48-linked ubiquitination and degradation by attenuating the PI3K/AKT signaling to up-regulate TRIM21 expression in CRC cells. Evidently, TRIM21 interacted with POU2F1, and induced the K272 ubiquitination of POU2F1. The effects of DADS on the enhanced K272 ubiquitination of POU2F1, the PPP flux, PRPP production, DNA damage and cell apoptosis as well as the growth of CRC tumors in vivo were significantly mitigated by TRIM21 silencing or activating the PI3K signaling in CRC cells. Conversely, the effects of DADS were enhanced by TRIM21 over-expression or inhibiting the PI3K/AKT signaling in CRC cells. Collectively, our findings reveal a novel mechanism by which DADS suppresses the growth of CRC by promoting POU2F1 ubiquitination, and may aid in design of novel therapeutic intervention of CRC.