Peroxiredoxin 3 has a crucial role in the macrophage polarization by regulating mitochondrial homeostasis.

Acute lung injury (ALI) is one of the life-threatening complications of sepsis, and macrophage polarization plays a crucial role in the sepsis-associated ALI. However, the regulatory mechanisms of macrophage polarization in ALI and in the development of inflammation are largely unknown. In this study, we demonstrated that macrophage polarization occurs in sepsis-associated ALI and is accompanied by mitochondrial dysfunction and inflammation, and a decrease of PRDX3 promotes the initiation of macrophage polarization and mitochondrial dysfunction. Mechanistically, PRDX3 overexpression promotes M1 macrophages to differentiate into M2 macrophages, and enhances mitochondrial functional recovery after injury by reducing the level of glycolysis and increasing TCA cycle activity. In conclusion, we identified PRDX3 as a critical hub integrating oxidative stress, inflammation, and metabolic reprogramming in macrophage polarization. The findings illustrate an adaptive mechanism underlying the link between macrophage polarization and sepsis-associated ALI.

The mechanism of Semen Persicae-Flos Carthami in treating hypertrophic scar: A study based on network pharmacological analysis and in vitro experiments.

Traditional medicine believes that hypertrophic scar (HS) falls into the category of "blood stasis". Chinese herbs for promoting blood circulation and removing blood stasis, activating meridians, and relieving pain are usually selected to treat HS by traditional Chinese medicine (TCM). Both Semen Persicae (SP) and Flos Carthami (FC) are confirmed to be effective for HS. Clinically, SP and FC are often used in combination with each other. However, the pharmacodynamic mechanism and molecular target of SP-FC in the treatment of HS are still unclear. Therefore, this study is intended to explore the mechanism and target of SP-FC in the treatment of HS through network pharmacology combined with in vitro cell and molecular biology experiments. Target genes of SP-FC were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and targets of HS-related diseases were searched from databases such as Disgenet and GeneCards. Based on the targets searched and obtained, a Venn diagram was plotted to acquire common targets of SP-FC-HS. Next, STRING 11.0 was employed for protein-protein interaction (PPI) network analysis of common targets; and cytoscape 3.9.0 for connection relationship analysis of PPI and plotting of a "drug-component-target" network diagram. Besides, a modified explant culture method was applied to separate primary hypertrophic scar fibroblasts (HSFs); MTT assay to detect cell viability of HSFs after treatment by SP-FC for 24 h; Annexin V-FITC/PI double staining combined with flow cytometry to test apoptosis; western blot to check the protein expression level of p53; and real-time fluorescence quantitative PCR to determine mRNA level of p53. In the analysis of network pharmacology, 269 pharmacological targets of SP, 449 pharmacological targets of FC, and 2569 targets of HS-related diseases were screened from the databases. After plotting the Venn diagram, 116 common targets of SP-FC-HS were acquired. In vitro experiments showed that the expression of p53 in HSFs was decreased. SP-FC significantly reduces the viability of HSFs, increases p53 levels in HSFs, and promotes apoptosis. SP-FC can reduce scar formation by promoting p53 expression.

Akkermansia muciniphila might improve anti-PD-1 therapy against HCC by changing host bile acid metabolism.

PD-1 monoclonal antibodies (mAb) have demonstrated remarkable efficacy in a variety of cancers, including Hepatocellular carcinoma (HCC). However, the patient response rates remain suboptimal, and a significant proportion of initial responders may develop resistance to this therapeutic approach. Akkermansia muciniphila (AKK), a microorganism implicated in multiple human diseases, has been reported to be more abundant in patients who exhibit favorable responses to PD-1mAb. However, the underlying mechanism has yet to be elucidated. In our study, we found that AKK could enhance the efficacy of PD-1mAb against HCC in a tumor-bearing mouse model. It promotes HCC tumor cells apoptosis and raise the CD8+ T proportion in the tumor microenvironment. Additionally, AKK downregulates PD-L1 expression in tumor cells. Furthermore, the analysis of metabonomics demonstrates that AKK induces alterations in the host's bile acid metabolism, leading to a significant increase in serum TUDCA levels. Considering the immunosuppresive roles of TUDCA in HCC development, it is plausible to speculate that AKK may reinforce the immunotherapy of PD-1mAb against HCC through its impact on bile acid metabolism.

Association of lipoprotein lipase (LPL) gene variants with hyperlipidemic acute pancreatitis in southeastern Chinese population

ABSTRACT Objective: The study aims to explore the relationship between lipoprotein lipase (LPL) variants and hyperlipidemic acute pancreatitis (HLAP) in the southeastern Chinese population. Subjects and methods: In total, 80 participants were involved in this study (54 patients with HLAP and 26 controls). All coding regions and intron-exon boundaries of the LPL gene were sequenced. The correlations between variants and phenotypes were also analysed. Results: The rate of rare LPL variants in the HLAP group is 14.81% (8 of 54), higher than in controls. Among the detected four variants (rs3735959, rs371282890, rs761886494 and rs761265900), the most common variant was rs371282890. Further analysis demonstrated that subjects with rs371282890 "GC" genotype had a 2.843-fold higher risk for HLAP (odds ratio [OR]: 2.843, 95% confidence interval [CI]: 1.119-7.225, p = 0.028) than subjects with the "CC" genotype. After adjusting for sex, the association remained significant (adjusted OR: 3.083, 95% CI: 1.208-7.869, p = 0.018). Subjects with rs371282890 "GC" genotype also exhibited significantly elevated total cholesterol, triglyceride and non-high-density lipoprotein cholesterol levels in all the participants and the HLAP group (p < 0.05). Conclusion: Detecting rare variants in LPL might be valuable for identifying higher-risk patients with HLAP and guiding future individualised therapeutic strategies.

Glycine Decarboxylase (GLDC) Plays a Crucial Role in Regulating Energy Metabolism, Invasion, Metastasis and Immune Escape for Prostate Cancer.

Glycine decarboxylase (GLDC) is one of the core enzymes for glycine metabolism, and its biological roles in prostate cancer (PCa) are unclear. First, we found that GLDC plays a central role in glycolysis in 540 TCGA PCa patients. Subsequently, a metabolomic microarray showed that GLDC enhanced aerobic glycolysis in PCa cells, and GLDC and its enzyme activity enhanced glucose uptake, lactate production and lactate dehydrogenase (LDH) activity in PCa cells. Next, we found that GLDC was highly expressed in PCa, was directly regulated by hypoxia-inducible factor (HIF1-α) and regulated downstream LDHA expression. In addition, GLDC and its enzyme activity showed a strong ability to promote the migration and invasion of PCa both in vivo and in vitro. Furthermore, we found that the GLDC-high group had a higher TP53 mutation frequency, lower CD8+ T-cell infiltration, higher immune checkpoint expression, and higher immune exclusion scores than the GLDC-low group. Finally, the GLDC-based prognostic risk model by applying LASSO Cox regression also showed good predictive power for the clinical characteristics and survival in PCa patients. This evidence indicates that GLDC plays crucial roles in glycolytic metabolism, invasion and metastasis, and immune escape in PCa, and it is a potential therapeutic target for prostate cancer.

The pan-cancer multi-omics landscape of key genes of sialylation combined with RNA-sequencing validation.

BACKGROUND: Sialylation, the process of salivary acid glycan synthesis, plays a pivotal function in tumor growth, immune escape, tumor metastasis, and resistance to drugs. However, the association between sialylation and prognosis, tumor microenvironment (TME), and treatment response in a variety of cancers remains unclear. METHODS: A comprehensive survey of the expression profile, prognostic value, and genetic and epigenetic alterations of sialylation-related genes was performed in pan-cancer. Subsequently, the single-sample gene set enrichment analysis (ssGSEA) algorithm was used to compute sialylation pathway scores in pan-cancer. Correlations of sialylation pathway scores with clinical features, prognosis, and TME were evaluated using multiple algorithms. Finally, the efficacy of the sialylation pathway score in determining the effect of immunotherapy was evaluated. The expression of sialylation-related genes were verified by RNA-sequencing. RESULTS: Significant differences were observed in sialylation-related genes expression between tumors and adjacent normal tissues for most cancer types. Sialylation pathway scores differed according to the type of tumor, where the poor prognosis was correlated with high sialylation pathway scores in uveal melanoma (UVM) and pancreatic adenocarcinoma (PAAD). In addition, sialylation pathway scores were positively associated with the ImmuneScore, StromalScore and immune-related pathways. Moreover, the level of immune cells infiltration was higher in tumors with higher sialylation pathway scores. Finally, patients with high sialylation pathway scores were more sensitive to immunotherapy. CONCLUSION: Sialylation-related genes are essential in pan-cancer. The sialylation pathway score may be used as a biomarker in oncology patients.

The efficacy and mechanism of Angelica sinensis (Oliv.) Diels root aqueous extract based on RNA sequencing and 16S rDNA sequencing in alleviating polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) leads to persistent anovulation, hyperandrogenism, insulin resistance, and polycystic ovary, and is mainly characterized by menstrual disorders, and reproductive dysfunction. Angelica sinensis (Oliv.) Diels root has been used in many classical formulas of traditional Chinese medicine, and is commonly used to treat various gynecological diseases. PURPOSE: To investigate the protective effect of water extract of A. sinensis root (WEA) on PCOS rats, and the mechanism by RNA sequencing, and 16S rDNA sequencing. METHODS: The PCOS rat model was established by letrozole combined with high-fat diet (gavage; 2 months), and treated with WEA (gavage; 2 g/kg, 4 g/kg or 8 g/kg; 1 month). To evaluate the therapeutic effect of WEA on PCOS rats, vaginal smear, hematoxylin-eosin staining, and biochemical indicators detection were performed. The rat ovarian tissue was analyzed by RNA sequencing, and the results were verified by qRT-PCR, and Western blot. 16S rDNA sequencing was used to analyze the gut microbiota of rats. RESULTS: The results of the vaginal smear, and hematoxylin-eosin staining showed that WEA improved estrous cycle disorder, and ovarian tissue lesions. WEA (4 g/kg or 8 g/kg; 1 months) alleviated hormone disorders, insulin resistance, and dyslipidemia. RNA sequencing showed that WEA intervention significantly changed the expressions of 2756 genes, which were enriched in phosphatidylinositol3-kinase/phosphorylated protein kinase B (PI3K/AKT), peroxisome proliferator-activated receptor (PPAR), mitogen-activated protein kinase (MAPK), AMP-activated protein kinase (AMPK), and insulin signaling pathways. 16S rDNA sequencing found that WEA increased the species diversity of gut microbiota, and regulated the abundance of some microbiota (genus level: Dubosiella, Bifidobacterium, Coriobacteriaceae (UCG-002), and Treponema; species level: Bifidobacterium animalis, Lactobacillus murinus, and Lactobacillus johnsonii). CONCLUSION: WEA regulated hormone, and glycolipid metabolism disorders, thereby relieving the PCOS induced by letrozole combined with high-fat diet. The mechanism was related to the regulation of PI3K/AKT, PPAR, MAPK, AMPK, and insulin signaling pathways in ovarian tissues, and the maintenance of gut microbiota homeostasis. Clarifying the efficacy and mechanism of WEA in alleviating PCOS based on RNA sequencing and 16S rDNA sequencing will guide the more reasonable clinical use of WEA.

The Effect of Bergenin on Isonicotinic Acid Hydrazide and Rifampicin-Induced Liver Injury Revealed by RNA Sequencing.

Bergenin (BER), a natural component of polyphenols, has a variety of pharmacological activities, especially in improving drug metabolism, reducing cholestasis, anti-oxidative stress and inhibiting inflammatory responses. The aim of this study was to investigate the effects of BER on liver injury induced by isonicotinic acid hydrazide (INH) and rifampicin (RIF) in mice. The mice model of liver injury was established with INH (100 mg/kg)+RIF (100 mg/kg), and then different doses of BER were used to intervene. The pathological morphology and biochemical indicators of mice were detected. Meanwhile, RNA sequencing was performed to screen the differentially expressed genes and signaling pathways. Finally, critical differentially expressed genes were verified by qRT-PCR and Western blot. RNA sequencing results showed that 707 genes were significantly changed in the INH+RIF group compared with the Control group, and 496 genes were significantly changed after the BER intervention. These differentially expressed genes were mainly enriched in the drug metabolism, bile acid metabolism, Nrf2 pathway and TLR4 pathway. The validation results of qRT-PCR and Western blot were consistent with the RNA sequencing. Therefore, BER alleviated INH+RIF-induced liver injury in mice. The mechanism of BER improving INH+RIF-induced liver injury was related to regulating drug metabolism enzymes, bile acid metabolism, Nrf2 pathway and TLR4 pathway.

Hybridized Chain Reaction-Amplified Alkaline Phosphatase-Induced Ag-Shell Nanostructure for the Sensitive and Rapid Surface-Enhanced Raman Scattering Immunoassay of Exosomes.

Exosomes are small extracellular vesicles that can be utilized as noninvasive biomarkers for diagnosis and treatment of cancer and other diseases. This study reports on a strategy involving a hybridized chain reaction-amplified chain coupled with an alkaline phosphatase-induced Ag-shell nanostructure for the ultrasensitive and rapid surface-enhanced Raman scattering immunoassay of exosomes. Exosomes from prostate cancer were captured using prostate-specific membrane antigen aptamer-modified magnetic beads; then, the hybridized chain reaction-amplified chain was released, incorporating a large number of functional moieties with signal amplification effects. Moreover, the steps of traditional immunoassay were simplified using magnetic materials, and the rapid, sensitive, and accurate detection of exosomes was achieved. Results could be obtained within 40 min with a detection limit of 19 particles/µL. Furthermore, the sera of human prostate cancer patients could be easily distinguished from those of healthy controls, highlighting the potential use of exosome analysis in clinical diagnostics.

Epidemiological updates of post-traumatic related limb osteomyelitis in china: a 10 years multicentre cohort study.

BACKGROUND: Post-traumatic related limb osteomyelitis (PTRLO) is a complex bone infection. Currently, there are no available microbial data on a national scale that can guide appropriate antibiotic selection, and explore the dynamic changes in dominant pathogens over time. This study aimed to conduct a comprehensive epidemiological analysis of PTRLO in China. METHODS: The study was approved by the Institutional Research Board (IRB), and 3526 PTRLO patients were identified from 212 394 traumatic limb fracture patients at 21 hospitals between 1 January 2008 and 31 December 2017. A retrospective analysis was conducted to investigate the epidemiology of PTRLO, including changes in infection rate (IR), pathogens, infection risk factors and antibiotic resistance and sensitivity. RESULTS: The IR of PTRLO increased gradually from 0.93 to 2.16% (Z=14.392, P <0.001). Monomicrobial infection (82.6%) was significantly higher than polymicrobial infection (17.4%) ( P <0.001). The IR of Gram-positive (GP) and Gram-negative (GN) pathogens showed a significant increase from the lowest 0.41% to the highest 1.15% (GP) or 1.62% (GN), respectively. However, the longitudinal trend of GP vs. GN's composition did not show any significance (Z=±1.1918, P >0.05). The most prevalent GP strains were Methicillin-sensitive Staphylococcus aureus (MSSA) (17.03%), Methicillin-resistant Staphylococcus aureus (MRSA) (10.46%), E. faecalis (5.19%) and S. epidermidis (4.87%). In contrast, the dominant strains GN strains were Pseudomonas Aeruginosa (10.92%), E. cloacae (10.34%), E. coli (9.47%), Acinetobacter Baumannii (7.92%) and Klebsiella Pneumoniae (3.33%). In general, the high-risk factors for polymicrobial infection include opened-fracture (odds ratio, 2.223), hypoproteinemia (odds ratio, 2.328), and multiple fractures (odds ratio, 1.465). It is important to note that the antibiotics resistance and sensitivity analysis of the pathogens may be influenced by complications or comorbidities. CONCLUSIONS: This study provides the latest data of PTRLO in China and offers trustworthy guidelines for clinical practice. (China Clinical Trials.gov number, ChiCTR1800017597).

Determining the spatial non-stationarity underlying social and natural environment in thyroid cancer in China.

BACKGROUND: Light at night (LAN) is a physiological environmental factor related to thyroid cancer (TC). The spatial relationship between the number of TC incident cases, LAN, air pollution and other macro social factors and stationarity needs to be further examined to provide evidence for regional control of TC. METHODS: Spatial econometrics methods for spatial nonstationarity were used to explore the impacts of LAN, air pollutants, economic factors, and population size on the number of TC incident cases in 182 Chinese prefecture-level cities and the local coefficients were further tested for nonstationarity. Temporally weighted regression (TWR), geographically weighted regression (GWR), and geographically and temporally weighted regression (GTWR) were compared in this study for model selection. RESULTS: Based on the ordinary least squares (OLS), LAN, air pollutants, and urbanization all significantly affected the number of TC incident cases. GWR had the best goodness of fit, and the coefficients of all the variables passed the nonstationarity test. The strong positive impact of LAN was mainly concentrated in North China, air pollutants in Central China and neighboring regions, and urbanization in the eastern coast of China. CONCLUSIONS: The locational factors of the prefecture-level city influence the spatial pattern of the number of TC incident cases. Governments should pay attention to this influence, adhere to the Health in All Policies principle, and formulate region-specific policies based on regional characteristics, which this study provides updated evidence for.

Dibenzothiophene Removal from Fuel Oil by Metal-Organic Frameworks: Performance and Kinetics.

Desulfurization of organic sulfur in the fuel oil is essential to cut down the emission of sulfur dioxide, which is a major precursor of the acid rain and PM2.5. Currently, hydrodesulfurization is regarded as a state-of-art technology for the desulfurization of fuel oil. However, due to the stringent legislation of the fuel oil, the deep desulfurization technology is urgent to be developed. Adsorptive desulfurization method is promising due to the high selectivity and easy operation. The development of efficient adsorbent is important to advance this technology into industrial application. In this work, the five types of metal-organic frameworks (MOFs), including Cu-BTC, UMCM-150, MIL-101(Cr), UIO-66, and Cu-ABTC were synthesized for the adsorption of dibenzothiophene (DBT), a typical organic sulfur compound in the fuel oil. The experimental results revealed that the adsorption capacity of the five MOFs followed the order of Cu-ABTC, UMCM-150, Cu-BTC, MIL-101(Cr), and UIO-66, which adsorption capacities were 46.2, 34.2, 28.3, 26.3, and 22.0 mgS/g, respectively. The three types of Cu-based MOFs such as Cu-ABTC, UMCM-150, and Cu-BTC outperformed the Cr-based MOFs, MIL-101, and Zr-based MOFs, UIO-66. Since the surface area and pore volumes of the Cu-based MOFs were not the greatest among the tested five MOFs, the physical properties of the MOFs were not the only limited factor for the DBT adsorption. The π-complexation between DBT and linkers/metal in the MOFs was also important. Kinetic analysis showed that the DBT adsorption onto the five tested MOFs follows the pseudo-second-order kinetics, confirming that the chemical π-complexation was also contributed to the DBT adsorption. Furthermore, the operation parameters such as oil-adsorbent ratio, initial sulfur concentration and adsorption temperature for the DBT adsorption onto Cu-ABTC were optimized to be 100:1 g/g, 1000 mgS/L and 30 °C, respectively. This work can provide some insights into the development of efficient adsorbent for the organic sulfur adsorption.

Artificial Nucleotide Aptamer-Based Field-Effect Transistor for Ultrasensitive Detection of Hepatoma Exosomes.

An aptamer-based field-effect transistor (Apta-FET) is a well-developed assay method with high selectivity and sensitivity. Due to the limited information density that natural nucleotide library holds, the Apta-FET faces fundamental restriction in universality to detect various types of analytes. Herein, we demonstrate a type of Apta-FET sensors based on an artificial nucleotide aptamer (AN-Apta-FET). The introduction of an artificial nucleotide increases the diversity of the potential aptamer structure and expands the analyte category of the Apta-FET. The AN-Apta-FET specifically detects hepatoma exosomes, which traditional Apta-FET fails to discriminate from other tumor-derived exosomes, with a limit of detection down to 242 particles mL-1. The AN-Apta-FET distinguishes serum samples of hepatocellular carcinoma patients within 9 min from those of healthy people, showing the potential as a comprehensive assay tool in future disease diagnosis.

Decreased frequency of a novel T-lymphocyte subset, CD3+ CD4- CD7+ CD57- T cells, in hepatitis B virus-related end-stage liver disease might contribute to disease progression.

CD7 and CD57 are related to the differentiation and functional stages of CD8+ T cells. However, the role of their combined presence in CD8+ T cells in patients with chronic hepatitis B virus (HBV) infection, especially those with end-stage liver disease, remains unclear. Blood samples from healthy volunteers and patients with chronic hepatitis B were analyzed via Luminex assay and ELISA to measure plasma cytokine levels. Further, recombinant IL-22 was used to stimulate peripheral blood mononuclear cells from healthy volunteers, and the frequency of CD3+ CD4- CD7+ CD57- T cells and apoptosis rates were investigated via flow cytometry. Patients with end-stage liver disease, particularly those with acute to chronic liver failure, showed decreased CD3+ CD4- CD7+ CD57- T cell frequency. Furthermore, the prevalence of CD3+ CD4- CD7+ CD57- T cells was negatively correlated with disease severity, prognosis, and complications (ascites). We also observed that IL-22 promoted apoptosis and brought about a decrease in the number of CD3+ CD4- CD7+ CD57- T cells in a dose-dependent manner. CD3+ CD4- CD7+ CD57- T cells displayed a B and T lymphocyte attenuator (BTLA)high CD25high CD127high immunosuppressive phenotype and showed low interferon-γ, tumor necrosis factor-α, granzyme A, and perforin expression levels. The present findings will elucidate the pathogenesis of HBV-related end-stage liver disease and aid the identification of novel drug targets.

Plasma cell subtypes analyzed using artificial intelligence algorithm for predicting biochemical recurrence, immune escape potential, and immunotherapy response of prostate cancer.

Background: Plasma cells as an important component of immune microenvironment plays a crucial role in immune escape and are closely related to immune therapy response. However, its role for prostate cancer is rarely understood. In this study, we intend to investigate the value of a new plasma cell molecular subtype for predicting the biochemical recurrence, immune escape and immunotherapy response in prostate cancer. Methods: Gene expression and clinicopathological data were collected from 481 prostate cancer patients in the Cancer Genome Atlas. Then, the immune characteristics of the patients were analyzed based on plasma cell infiltration fractions. The unsupervised clustering based machine learning algorithm was used to identify the molecular subtypes of the plasma cell. And the characteristic genes of plasma cell subtypes were screened out by three types of machine learning models to establish an artificial neural network for predicting plasma cell subtypes. Finally, the prediction artificial neural network of plasma cell infiltration subtypes was validated in an independent cohort of 449 prostate cancer patients from the Gene Expression Omnibus. Results: The plasma cell fraction in prostate cancer was significantly decreased in tumors with high T stage, high Gleason score and lymph node metastasis. In addition, low plasma cell fraction patients had a higher risk of biochemical recurrence. Based on the differential genes of plasma cells, plasma cell infiltration status of PCa patients were divided into two independent molecular subtypes(subtype 1 and subtype 2). Subtype 1 tends to be immunosuppressive plasma cells infiltrating to the PCa region, with a higher likelihood of biochemical recurrence, more active immune microenvironment, and stronger immune escape potential, leading to a poor response to immunotherapy. Subsequently, 10 characteristic genes of plasma cell subtype were screened out by three machine learning algorithms. Finally, an artificial neural network was constructed by those 10 genes to predict the plasma cell subtype of new patients. This artificial neural network was validated in an independent validation set, and the similar results were gained. Conclusions: Plasma cell infiltration subtypes could provide a potent prognostic predictor for prostate cancer and be an option for potential responders to prostate cancer immunotherapy.

Beneficial shift of rhizosphere soil nutrients and metabolites under a sugarcane/peanut intercropping system.

Intercropping systems have been studied as a sustainable agricultural planting pattern to increase soil quality and crop yields. However, the relationships between metabolites and soil physicochemical properties remain poorly understood under sugarcane/peanut intercropping system. Thus, we determined the rhizosphere soil physicochemical properties, and analyzed rhizosphere soil metabolites and root metabolites by metabolomics method under monoculture and intercropping patterns of sugarcane and peanut. The results showed that pH, the contents of total phosphorus (P), total potassium (K), available nitrogen (N), available phosphorus (P), and available potassium (K) were higher in rhizosphere soil of intercropping peanut than monoculture peanut, and the content of total P was higher in rhizosphere soil of intercropping sugarcane than monoculture sugarcane. Sugarcane/peanut intercropping also significantly increased the activities of acid phosphatase and urease in rhizosphere soil. The metabolomics results showed that 32 metabolites, mainly organic acids and their derivatives (25.00%), nucleotides and their metabolites (18.75%), were detected in root and rhizosphere soil samples. In the MP-S (rhizosphere soil of monoculture peanut) vs. IP-S (rhizosphere soil of intercropping peanut) comparison, 47 differential metabolites (42 upregulated) were screened, including glycerolipids (19.15%), organic acids and their derivatives (17.89%), and amino acids and their metabolites (12.77%). In the MS-S (rhizosphere soil of monoculture sugarcane) vs. IS-S (rhizosphere soil of intercropping sugarcane) comparison, 51 differential metabolites (26 upregulated) were screened, including heterocyclic compounds (15.69%), glycerolipids (11.76%), and organic acids and their derivatives (9.80%). The metabolite species from MP-S, MS-S, IP-S, and IS-S were similar, but some metabolite contents were significantly different, such as adenine, adenosine, maltotriose, thermozeaxanthin-13 and PE-NMe (20:0/24:0). Adenine and adenosine were detected in root and rhizosphere soils, and their levels were increased in the intercropping treatment, which were mainly related to enhanced purine metabolism in root and rhizosphere soils under the sugarcane/peanut intercropping system. Importantly, adenine and adenosine were significantly positively correlated with total P and total K contents, acid phosphatase and urease activities, and pH. This study clarified that the sugarcane/peanut intercropping system could improve soil nutrients and enzymes and was related to purine metabolism.

ACO1 and IREB2 downregulation confer poor prognosis and correlate with autophagy-related ferroptosis and immune infiltration in KIRC.

Background: ACO1 and IREB2 are two homologous cytosolic regulatory proteins, which sense iron levels and change iron metabolism-linked molecules. These two genes were noticeably decreased in kidney renal clear cell carcinoma (KIRC), which confer poor survival. Meanwhile, there is a paucity of information about the mechanisms and clinical significance of ACO1 and IREB2 downregulation in renal cancers. Methods: The expression profiles of ACO1 and IREB2 were assessed using multiple public data sets via several bioinformatics platforms. Clinical and pathological information was utilized to stratify cohorts for comparison. Patient survival outcomes were evaluated using the Kaplan-Meier plotter, a meta-analysis tool. The correlations of ACO1 and IREB2 with ferroptosis were further evaluated in The Cancer Genome Atlas (TCGA)-KIRC database. Tumor immune infiltration was analyzed using the CIBERSORT, TIMER, and GEPIA data resources. ACO1 antagonist sodium oxalomalate (OMA) and IREB2 inhibitor sodium nitroprusside (SNP) was used to treat renal cancer ACHN cells together with sorafenib. Results: KIRC patients with low ACO1 or IREB2 contents exhibited a remarkably worse survival rate in contrast with those with high expression in Kaplan-Meier survival analyses. Meanwhile, ACO1 and IREB2 regulate autophagy-linked ferroptosis along with immune cell invasion in the tumor microenvironment in KIRC patients. Blocking the activation of these two genes by their inhibitors OMA and SNP ameliorated sorafenib-triggered cell death, supporting that ACO1 and IREB2 could be participated in its cytotoxic influence on renal cancer cells. Conclusion: ACO1 and IREB2 downregulation in renal cancers were correlated with cancer aggressiveness, cellular iron homeostasis, cytotoxic immune cell infiltration, and patient survival outcomes. Our research is integral to verify the possible significance of ACO1 and IREB2 contents as a powerful signature for targeted treatment or novel immunotherapy in clinical settings.

Picosecond infrared laser driven sample delivery for simultaneous liquid-phase and gas-phase electron diffraction studies.

Here, we report on a new approach based on laser driven molecular beams that provides simultaneously nanoscale liquid droplets and gas-phase sample delivery for femtosecond electron diffraction studies. The method relies on Picosecond InfraRed Laser (PIRL) excitation of vibrational modes to strongly drive phase transitions under energy confinement by a mechanism referred to as Desorption by Impulsive Vibrational Excitation (DIVE). This approach is demonstrated using glycerol as the medium with selective excitation of the OH stretch region for energy deposition. The resulting plume was imaged with both an ultrafast electron gun and a pulsed bright-field optical microscope to characterize the sample source simultaneously under the same conditions with time synchronization equivalent to sub-micrometer spatial resolution in imaging the plume dynamics. The ablation front gives the expected isolated gas phase, whereas the trailing edge of the plume is found to consist of nanoscale liquid droplets to thin films depending on the excitation conditions. Thus, it is possible by adjusting the timing to go continuously from probing gas phase to solution phase dynamics in a single experiment with 100% hit rates and very low sample consumption (<100 nl per diffraction image). This approach will be particularly interesting for biomolecules that are susceptible to denaturation in turbulent flow, whereas PIRL-DIVE has been shown to inject molecules as large as proteins into the gas phase fully intact. This method opens the door as a general approach to atomically resolving solution phase chemistry as well as conformational dynamics of large molecular systems and allow separation of the solvent coordinate on the dynamics of interest.

Identification of the gossypol derivatives as androgen receptor inhibitor.

Prostate cancer (PCa) is the most frequently diagnosed male malignant tumor and remains the second leading cause of male cancer mortality in western countries. The development of novel antiandrogens to circumvent the drug resistance in anti-PCa treatment is highly demanded. Herein, we identified that gossypol (GOS) specificly inhibited the AR signaling. Further optimization of GOS derivatives led to the discovery of compound XY-32. XY-32 efficiently inhibits AR signaling with the IC50 of 1.23 µM. XY-32 downregulates both the full-length AR and the AR variable splice AR-V7 via suppressing the mRNA expression. It inhibits the proliferation of CRPC cells such as the LNCaP cells, the PC-3 cells, and enzalutamide resistance 22Rv1 cells. The work demonstrates the GOS derivatives represent a novel series of anti-androgen to conquer the acquired AR mutations or AR splice variants induced drug resistance of mCRPC.

3D Printed Bioinspired Stents with Photothermal Effects for Malignant Colorectal Obstruction.

Stent placement is an effective palliation therapy for malignant colorectal obstruction. However, recurrent obstruction is a common severe complication caused by tumor ingrowth into the stent lumen. Conventional covered stents play a part in preventing the tumor from growing inward but at the expense of significantly increasing the risk of stent migration. Therefore, there is an urgent demand to develop stents with sustained antitumor and antimigration abilities. Herein, we propose a facile method for fabricating multifunctional bioinspired colorectal stents using 3D printing technology. Inspired by high-adhesion biological structures (gecko feet, tree frog toe pads, and octopus suckers) in nature, different types of bioinspired colorectal stents are designed to reduce migration. After functionalization with graphene oxide (GO), bioinspired colorectal stents show excellent and controllable photothermal performance, which is validated by effective ablation of colon cancer cells in vitro and tumors in vivo. Besides, the bioinspired colorectal stents demonstrate the feasibility of transanal placement and opening of the obstructed colon. More importantly, the facile manufacturing process of multifunctional bioinspired colorectal stents is appealing for mass production. Hence, the developed multifunctional bioinspired colorectal stents exhibit a highly promising potential in clinical applications.