Effects of carbon source variability on enhanced Bio-hydrogen production.

This study investigated how glucose, starch, and rapeseed oil, three common food waste components with diverse molecular and physicochemical characteristics, influenced hydrogen production and microbial communities in dark fermentation under varying carbon/nitrogen (C/N) ratios. The results indicated that glucose and starch groups, significantly increased hydrogen yields to 235 mL H2/gVS (C/N = 40) and 234 mL H2/gVS (C/N = 40), respectively, while rapeseed oil, with a lower yield of 30 mL H2/gVS (C/N = 20), demonstrated a negative impact. Additionally, an accumulation of propionate was observed with increasing carbon source complexity, suggesting that simpler carbon sources favored hydrogen production and bacterial growth. Conversely, lipid-based materials required rigorous pre-treatment to mitigate their inhibitory effects on hydrogen generation. Overall, this study underscores the importance of carbon source selection, especially glucose and starch, for enhancing hydrogen production and microbial growth in dark fermentation, while highlighting the challenges posed by lipid-rich substrates that require intensive pre-treatment to optimize yields.

Comparative Metabolomic Analysis Reveals the Differences in Nonvolatile and Volatile Metabolites and Their Quality Characteristics in Beauty Tea with Different Extents of Punctured Leaves by Tea Green Leafhopper.

The fresh leaves were processed into beauty tea from the Camellia sinensis "Jinxuan" cultivar, which were punctured by tea green leafhoppers to different extents. Low-puncturing dry tea (LPDT) exhibited a superior quality. Altogether, 101 and 129 differential metabolites, including tea polyphenols, lipids, and saccharides, were identified from the fresh leaves and dry beauty tea, respectively. Most metabolite levels increased in the fresh leaves punctured by leafhoppers, but the opposite was observed for the dry beauty tea. According to relative odor activity values (rOAVs) and partial least-squares discriminant analysis (PLS-DA), four characteristic volatiles, including linalool, geraniol, benzeneacetaldehyde, and dihydrolinalool, were selected. Mechanical injury to leaves caused by leafhoppers, watery saliva secreted by the leafhopper, and different water contents of the fresh leaves in different puncturing degrees are the possible reasons for the difference in the quality of the beauty tea with different levels of puncturing. Overall, this study identified a wide range of chemicals that are affected by the degrees of leafhopper puncturing.

Electrical stimulation facilitates NADPH production in pentose phosphate pathway and exerts an anti-inflammatory effect in macrophages.

Macrophages play an important role as effector cells in innate immune system. Meanwhile, macrophages activated in a pro-inflammatory direction alter intracellular metabolism and damage intact tissues by increasing reactive oxygen species (ROS). Electrical stimulation (ES), a predominant physical agent to control metabolism in cells and tissues, has been reported to exert anti-inflammatory effect on immune cells. However, the mechanism underlying the anti-inflammatory effects by ES is unknown. This study aimed to investigate the effect of ES on metabolism in glycolytic-tricarboxylic acid cycle (TCA) cycle and inflammatory responses in macrophages. ES was performed on bone marrow-derived macrophages and followed by a stimulation with LPS. The inflammatory cytokine expression levels were analyzed by real-time polymerase chain reaction and ELISA. ROS production was analyzed by CellRox Green Reagent and metabolites by capillary electrophoresis-mass spectrometry. As a result, ES significantly reduced proinflammatory cytokine expression levels and ROS generation compared to the LPS group and increased glucose-1-phosphate, a metabolite of glycogen. ES also increased intermediate metabolites of the pentose phosphate pathway (PPP); ribulose-5-phosphate, rebose-5 phosphate, and nicotinamide adenine dinucleotide phosphate, a key factor of cellular antioxidation systems, as well as α-Ketoglutarate, an anti-oxidative metabolite in the TCA cycle. Our findings imply that ES enhanced NADPH production with enhancement of PPP, and also decreased oxidative stress and inflammatory responses in macrophages.

Recent progress of self-immobilizing and self-precipitating molecular fluorescent probes for higher-spatial-resolution imaging.

Flourished in the past two decades, fluorescent probe technology provides researchers with accurate and efficient tools for in situ imaging of biomarkers in living cells and tissues and may play a significant role in clinical diagnosis and treatment such as biomarker detection, fluorescence imaging-guided surgery, and photothermal/photodynamic therapy. In situ imaging of biomarkers depends on the spatial resolution of molecular probes. Nevertheless, the majority of currently available molecular fluorescent probes suffer from the drawback of diffusing from the target region. This leads to a rapid attenuation of the fluorescent signal over time and a reduction in spatial resolution. Consequently, the diffused fluorescent signal cannot accurately reflect the in situ information of the target. Self-immobilizing and self-precipitating molecular fluorescent probes can be used to overcome this problem. These probes ensure that the fluorescent signal remains at the location where the signal is generated for a long time. In this review, we introduce the development history of the two types of probes and classify them in detail according to different design strategies. In addition, we compare their advantages and disadvantages, summarize some representative studies conducted in recent years, and propose prospects for this field.

Invasive and Native Plants Differentially Respond to Exogenous Phosphorus Addition in Root Growth and Nutrition Regulated by Arbuscular Mycorrhizal Fungi.

Plant invasion has severely damaged ecosystem stability and species diversity worldwide. The cooperation between arbuscular mycorrhizal fungi (AMF) and plant roots is often affected by changes in the external environment. Exogenous phosphorus (P) addition can alter the root absorption of soil resources, thus regulating the root growth and development of exotic and native plants. However, it remains unclear how exogenous P addition regulates the root growth and development of exotic and native plants mediated by AMF, affecting the exotic plant invasion. In this experiment, the invasive plant Eupatorium adenophorum and native plant Eupatorium lindleyanum were selected and cultured under intraspecific (Intra-) competition and interspecific (Inter-) competition conditions, involving inoculation with (M+) and without AMF (M-) and three different levels of P addition including no addition (P0), addition with 15 mg P kg-1 soil (P15), and addition with 25 mg P kg-1 soil (P25) for the two species. Root traits of the two species were analyzed to study the response of the two species' roots to AMF inoculation and P addition. The results showed that AMF significantly promoted the root biomass, length, surface area, volume, tips, branching points, and carbon (C), nitrogen (N), and P accumulation of the two species. Under M+ treatment, the Inter- competition decreased the root growth and nutrient accumulation of invasive E. adenophorum but increased the root growth and nutrient accumulation of native E. lindleyanum relative to the Intra- competition. Meanwhile, the exotic and native plants responded differently to P addition, exhibiting root growth and nutrient accumulation of invasive E. adenophorum increased with P addition, whereas native E. lindleyanum reduced with P addition. Further, the root growth and nutrition accumulation of native E. lindleyanum were higher than invasive E. adenophorum under Inter- competition. In conclusion, exogenous P addition promoted the invasive plant but reduced the native plant in root growth and nutrient accumulation regulated by AMF, although the native plant outcompeted the invasive plant when the two species competed. The findings provide a critical perspective that the anthropogenic P fertilizer addition might potentially contribute to the successful invasion of exotic plants.

Harmonic radiation contribution and X-ray transmission at the Small Quantum Systems instrument of European XFEL.

Transmission measurements of the soft X-ray beamline to the Small Quantum Systems (SQS) scientific instrument at the SASE3 undulator of European XFEL are presented. Measurements are reported for a wide range of photon energies (650 eV to 2400 eV), using X-ray gas monitors as well as a bolometric radiometer. The results are in good agreement with simulations for the beam transport and show a transmission of up to 80% over the whole photon energy range. The contribution of second- and third-harmonic radiation of the soft X-ray undulator is determined at selected photon energies by performing transmission measurements using a gas absorber to provide variable attenuation of the incoming photon flux. A comparison of the results with semi-analytic calculations for the generation of free-electron laser pulses in the SASE3 undulator reveals an influence of apertures along the beam transport on the exact harmonic content to be accounted for at the experiment. The second-harmonic content is measured to be in the range of 0.1% to 0.3%, while the third-harmonic contributed a few percent to the SASE3 emission. For experiments at the SQS instrument, these numbers can be reduced through specific selections of the mirror reflection angles.

Skeletal myotube-derived extracellular vesicles enhance itaconate production and attenuate inflammatory responses of macrophages.

Introduction: Macrophages play an important role in the innate immunity. While macrophage inflammation is necessary for biological defense, it must be appropriately controlled. Extracellular vesicles (EVs) are small vesicles released from all types of cells and play a central role in intercellular communication. Skeletal muscle has been suggested to release anti-inflammatory factors, but the effect of myotube-derived EVs on macrophages is unknown. As an anti-inflammatory mechanism of macrophages, the immune responsive gene 1 (IRG1)-itaconate pathway is essential. In this study, we show that skeletal muscle-derived EVs suppress macrophage inflammatory responses, upregulating the IRG1-itaconate pathway. Methods: C2C12 myoblasts were differentiated into myotubes and EVs were extracted by ultracentrifugation. Skeletal myotube-derived EVs were administered to mouse bone marrow-derived macrophages, then lipopolysaccharide (LPS) stimulation was performed and inflammatory cytokine expression was measured by RT-qPCR. Metabolite abundance in macrophages after addition of EVs was measured by CE/MS, and IRG1 expression was measured by RT-PCR. Furthermore, RNA-seq analysis was performed on macrophages after EV treatment. Results: EVs attenuated the expression of LPS-induced pro-inflammatory factors in macrophages. Itaconate abundance and IRG1 expression were significantly increased in the EV-treated group. RNA-seq analysis revealed activation of the PI3K-Akt and JAK-STAT pathways in macrophages after EV treatment. The most abundant miRNA in myotube EVs was miR-206-3p, followed by miR-378a-3p, miR-30d-5p, and miR-21a-5p. Discussion: Skeletal myotube EVs are supposed to increase the production of itaconate via upregulation of IRG1 expression and exhibited an anti-inflammatory effect in macrophages. This anti-inflammatory effect was suggested to involve the PI3K-Akt and JAK-STAT pathways. The miRNA profiles within EVs implied that miR-206-3p, miR-378a-3p, miR-30d-5p, and miR-21a-5p may be responsible for the anti-inflammatory effects of the EVs. In summary, in this study we showed that myotube-derived EVs prevent macrophage inflammatory responses by activating the IRG1-itaconate pathway.

Clinical characteristics of a patient with de novo acute promyelocytic leukemia with JAK2 v617f mutation.

BACKGROUND: The V617F mutation of Janus-associated kinase 2 (JAK2) is common in myeloproliferative neoplasms (MPN). JAK2 V617F mutation can be detected in patients with de novo acute myeloid leukemia (AML), but de novo acute promyelocytic leukemia (APL) with JAK2 V617F mutation is rare. CASE PRESENTATION: We report a case of APL with both the t(15;17) translocation as well as the JAK2 V617F mutation that transformed into MPN (PV/ET). CONCLUSIONS: A de novo APL patient presented initially with JAK2 V617F. After ATRA and ATO dual induction and chemotherapy consolidation, the patient achieved complete remission (CR) with undetectable PML/RARα. However, the JAK2 V617F remained positive, and the patient developed MPN (PV/ET) 22 months later, which responded well to interferon therapy.AML, acute myeloid leukemia; APL, acute promyelocytic leukemia; ATRA, all-trans retinoic acid; ATO, arsenic trioxide; BM, bone marrow; CR, complete remission; ET, essential thrombocythemia; Hb, hemoglobin; JAK2, Janus-associated kinase 2; MPN, myeloproliferative neoplasms; PLT, platelets; PMF, primary myelofibrosis; PML/RARα; PV, polycythemia vera; WBC, white blood cells.

Five EMT-Related Gene Signatures Predict Acute Myeloid Leukemia Patient Outcome.

Background: The epithelial mesenchymal transition (EMT) gene has been shown to be significantly associated with the prognosis of solid tumors; however, there is a lack of models for the EMT gene to predict the prognosis of AML patients. Methods: First, we downloaded clinical data and raw transcriptome sequencing data from the TCGA database of acute myeloid leukemia (AML) patients. All currently confirmed EMT-related genes were obtained from the dbEMT 2.0 database, and 30% of the TCGA data were randomly selected as the test set. Univariate Cox regression analysis, random forest, and lasso regression were used to optimize the number of genes for model construction, and multivariate Cox regression was used for model construction. Area under the ROC curve was used to assess the efficacy of the model application, and the internal validation set was used to assess the stability of the model. Results: A total of 173 AML samples were downloaded, and a total of 1184 EMT-related genes were downloaded. The results of univariate batch Cox regression analysis suggested that 212 genes were associated with patient prognosis, random forest and lasso regression yielded 18 and 8 prognosis-related EMT genes, respectively, and the results of multifactorial COX regression model suggested that 5 genes, CBR1, HS3ST3B1, LIMA1, MIR573, and PTP4A3, were considered as independent risk factors affecting patient prognosis. The model ROC results suggested that the area under the curve was 0.868 and the internal validation results showed that the area under the curve was 0.815. Conclusion: During this study, we constructed a signature model of five EMT-related genes to predict overall survival in patients with AML; it will provide a useful tool for clinical decision making.

Recent research progress in galactose-based fluorescent probes for detection of biomarkers of liver diseases.

The liver is the largest detoxification organ in the human body, with an array of functions that help support metabolism, immunity, digestion, and vitamin storage, among other functions, and maintains the health and stability of the internal environment. Liver injury causes the concentration fluctuation of related biomarkers, small molecules, and enzymes, and in turn, the structure and function of the liver are changed by those alterations. With the principles of early detection, early diagnosis, and early treatment, it is crucial to design and synthesise a tool for detecting related biomarkers during liver damage and lesion, among which fluorescent probes have attracted attention in recent years. In the course of liver diseases, the asialoglycoprotein receptors (ASGPR) are overexpressed on the hepatoma cells, which can specifically recognize the galactose variant. Several galactose-based fluorescent probes have been developed to target hepatocytes via specific receptor-mediated endocytosis and release fluorophores after reacting with specific small molecules and enzyme biomarkers. The change in fluorescence intensity reflects the level of substances, such as reactive oxygen species, reactive nitrogen species, reactive sulfur species, enzymes or metal ions, etc. The application of fluorescent probes in vivo can aid in monitoring the dynamic changes of endogenous and exogenous biomarkers. This Highlight provides an update on the progress, limitations, and prospects of galactose-based fluorescent probes applications in the early diagnosis of liver diseases.

Identification of LINC00654-NINL Regulatory Axis in Diffuse Large B-Cell Lymphoma In Silico Analysis.

Background: The long non-coding RNA (lncRNA)-mRNA regulation network plays an important role in the development of diffuse large B-cell lymphoma (DLBCL). This study uses bioinformatics to find an innovative regulation axis in DLBCL that will provide a positive reference for defining the mechanism of disease progression. Methods: Batch Cox regression was used to screen prognosis-related lncRNAs, and a random forest model was used to identify hub lncRNA. The clinical value of the lncRNA was evaluated and Spearman correlation analysis was used to predict the candidate target genes. Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were used to define the biological function of the lncRNA. A batch Cox regression model, expression validation, and Spearman correlation analysis were used to select the best downstream target genes. The expression and prognostic value validation of this gene was conducted using public data. Gene Set Enrichment Analysis (GSEA) was performed to explore potential mechanisms for this gene in DLBCL. Results: LINC00654 was identified as the hub lncRNA and 1443 mRNAs were selected as downstream target genes of the lncRNA. The target genes were enriched in the regulation of GTPase and Notch signaling pathways. After validation, the ninein-like (NINL) gene was selected as the potential target of LINC00654 and the LINC00654-NINL axis was constructed. Patients with better responses to therapy were shown to have high NINL gene expression (p-value = 0.036). NINL also had high expression in the DB cell line and low expression in the OCILY3 cell line. Survival analysis showed that high NINL expression was a risk factor for overall survival (OS) and disease-specific survival (DSS) within older patients and those with advanced-stage cancer. GSEA results showed that NINL may be involved in neutrophil-mediated immunity and NF-κB signaling. Conclusion: This study identified a novel LncRNA00654-NINL regulatory axis in DLBCL, which could provide a favorable reference for exploring the possible mechanisms of disease progression.

Comprehensive Analyses of Mutation-Derived Long-Chain Noncoding RNA Signatures of Genome Instability in Kidney Renal Papillary Cell Carcinoma.

Background: The role of long-chain noncoding RNA (lncRNA) in genomic instability has been demonstrated to be increasingly importance. Therefore, in this study, lncRNAs associated with genomic instability were identified and kidney renal papillary cell carcinoma (KIRP)-associated predictive features were analysed to classify high-risk patients and improve individualised treatment. Methods: The training (n = 142) and test (n = 144) sets were created using raw RNA-seq and patient's clinical data of KIRP obtained from The Cancer Genome Atlas (TCGA).There are 27 long-chain noncoding RNAs (lncRNAs) that are connected with genomic instability, these lncRNAs were identified using the 'limma' R package based on the numbers of somatic mutations and lncRNA expression profiles acquired from KIRP TCGA cohort. Furthermore, Cox regression analysis was carried out to develop a genome instability-derived lncRNA-based gene signature (GILncSig), whose prognostic value was confirmed in the test cohort as well as across the entire KIRP TCGA dataset. Results: A GILncSig derived from three lncRNAs (BOLA3-AS1, AC004870, and LINC00839), which were related with poor KIRP survival, was identified, which was split up into high- and low-risk groups. Additionally, the GILncSig was found to be an independent prognostic predictive index in KIRP using univariate and multivariate Cox analysis. Furthermore, the prognostic significance and characteristics of GilncSig were confirmed in the training test and TCGA sets. GilncSig also showed better predictive performance than other prognostic lncRNA features. Conclusion: The function of lncRNAs in genomic instability and the genetic diversity of KIRP were elucidated in this work. Moreover, three lncRNAs were screened for prediction of the outcome of KIRP survival and novel insights into identifying cancer biomarkers related to genomic instability were discussed.

Regulation of transforming growth factor-beta1 by circANKS1B/miR-515-5p affects the metastatic potential and cisplatin resistance in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common oral cancer, with an increasing worldwide incidence and a worsening prognosis. Emerging evidence confirms that circular RNAs (circRNAs) play a critical role in tumor progression via sponging miRNAs. A previous study substantiated the function of circANKS1B in several cancers. However, its role in OSCC remains unclear. This study revealed the high expression of circANKS1B in OSCC tissues and cells. Moreover, the expression level of circANKS1B was highly positively correlated with the expression of transforming growth factor-beta1 (TGF-ß1) in OSCC tissues. Additionally, overexpression of circANKS1B enhanced the protein expression of TGF-ß1 in OSCC cells, while its inhibition reduced TGF-ß1 protein levels. Noticeably, the loss-function of circANKS1B restrained OSCC cell invasion, migration, and epithelial to mesenchymal transition (EMT) by decreasing N-cadherin expression and enhancing E-cadherin expression. Furthermore, the knockdown of circANKS1B sensitized OSCC cells to cisplatin by suppressing cell viability and increasing cell apoptosis and caspase-3 activity. Mechanically, bioinformation software (circinteractome and starBase 3.0) and dual-luciferase reporter assays corroborated that circANKS1B could sponge miR-515-5p. Moreover, miR-515-5p could directly target TGF-ß1 to suppress its expression. Importantly, inhibition of miR-515-5p or supplementation with TGF-ß1 overturned the effects of circANKS1B knockdown on cell invasion, migration, and cisplatin resistance. Thus, these findings highlight that circANKS1B might act as an oncogenic gene to facilitate the metastatic potential and cisplatin resistance in OSCC by sponging miR-515-5p to regulate TGF-ß1. Collectively, circANKS1B may be a promising target for therapy and overcoming chemoresistance in OSCC.

Durable Cord Blood Cell Engraftment in a Patient with Severe Aplastic Anemia after a Matched Sibling Bone Marrow Transplantation and an Unrelated Cord Blood Transplantation.

OBJECTIVE: Severe aplastic anemia (SAA) is a fatal bone marrow failure disease. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a matched sibling donor is the first-line treatment for older SAA patients. However, the number of CD34+ cells collected from a matched donor is often lower than expected. To overcome the problem, this study was conducted to combine a matched sibling donor with an unrelated cord blood transplantation for the treatment of a patient with SAA. CASE REPORT: A 45-year-old male patient with SAA was treated with a sibling-matched allo-HSCT. Due to the low amount of donor CD34+ cells, an unrelated umbilical cord blood stem cell transplantation (UCBT) with 9/10 HLA matching was subsequently carried out. Successful hematopoietic reconstitution was achieved by the dual transplantation. Unexpectedly, beginning in the fourth month after transplantation, the sibling donor chimerism was transformed to a stable and complete UCB source. CONCLUSION: This study provides evidence that UCB-derived HSCs have a higher capacity for hematopoietic reconstitution, suggesting that UCB plus an HLA-matched sibling donor is a good alternative for older patients with SAA.

Effect of hydrogen bond donor molecules ethylene glycerol and lactic acid on electrochemical interfaces in choline chloride based-deep eutectic solvents.

Choline chloride (ChCl)-based-deep eutectic solvents (DESs) are widely used in electrochemical fields. In this work, the effect of two types of hydrogen bond donor (HBD) molecules, ethylene glycerol and lactic acid (LA), on electrochemical interfaces between the Au electrode and DESs has been investigated by employing voltammetry and electrochemical impedance spectroscopy. The anodic dissolution and passivation behaviors of the Au electrode are revealed in both ethaline and ChCl:LA. In ChCl:LA, the anodic dissolution of Au is slowed down, and the passivation film is relatively dense and stable due to the existence of the carboxyl group in HBD molecule LA. In the double layer region, the lifting and formation of Au(111) surface reconstruction and a disorder-order phase transition of the chloride ion adlayer were observed in the two DESs. Moreover, compared with ethaline, an extra pair of current peaks appears in ChCl-LA possibly due to the adsorption and desorption of LA on the Au(111) surface, which might imply the stronger interaction of LA with the Au electrode in ChCl:LA. HBD LA could even have marked an impact on the disorder-order phase transition of the chloride ion adlayer. The above results provide new insight into the significant effect of HBD molecules on the anodic dissolution and the passivation of the Au electrode and the electrochemical behaviors in the double layer region.

Lipid Metabolism in Regulation of Macrophage Functions.

Macrophages are cells of the innate immune system that regulate the maintenance of tissue homeostasis, host defense during pathogen infection, and tissue repair in response to tissue injury. Recent studies indicate that macrophage functions are influenced by cellular metabolism, including lipid metabolism. Here, we review how macrophage lipid metabolism can be dynamically altered in different physiological and pathophysiological contexts and the key regulators involved. We also describe how alterations in lipid metabolism are integrated with the signaling pathways that specify macrophage functions, allowing for coordinated control of macrophage biology. Finally, we discuss how dysregulated lipid metabolism contributes to perturbed macrophage functions in settings such as atherosclerosis and pathogen infections.

Overexpression of heme oxygenase-1 in bone marrow stromal cells promotes multiple myeloma resistance through the JAK2/STAT3 pathway.

AIMS: Bone marrow stromal cells (BMSCs) have been reported to interact with multiple myeloma (MM) and exert a vital function of the survival of MM cells. Heme oxygenase-1 (HO-1), a cytoprotective enzyme, has the potential to become a hematological malignancies targeted gene. This study aimed to investigate the role of HO-1 in MM resistance of BMSCs and its possible mechanisms. MAIN METHODS: In this study, the expression of related proteins was detected by RT-qPCR and Western blot. HO-1 expression was regulated by lentivirus transfection. Cell viability and apoptosis were detected by Flow cytometry and CCK-8. Cytokine secretion was assayed by ELISA. The survival and carcinogenic abilities was detected by clone formation assay. KEY FINDINGS: HO-1 expression in the BMSCs of stage III MM patients was substantially increased, compared with that of healthy donors and stage I/II patients. The results of co-culture of BMSCs and MM cells indicated that, the upregulated HO-1 inhibited the apoptosis of co-cultured MM cells, while downregulated HO-1 promoted the chemosensitivity of co-cultured MM cells, moreover, the upregulated HO-1 in BMSCs increased the colony-formation ability of MM cells. This protective capability may be regulated by CXCL12/CXCR4 signaling. High HO-1 expression in BMSCs can promote the phosphorylation of the JAK2/STAT3 pathway, thereby increasing secretion of SDF-1 in BMSCs and activating CXCL12/CXCR4 signaling. In addition, direct contact between BMSCs and MM cells may cause drug resistance. SIGNIFICANCE: These results indicated that the regulation of HO-1 in BMSCs may be a new effective method of MM therapy.

MDMX phosphorylation-dependent p53 downregulation contributes to an immunosuppressive tumor microenvironment.

A role of tumor-suppressive activity of p53 in the tumor microenvironment (TME) has been implicated but remains fairly understudied. To address this knowledge gap, we leveraged our MdmxS314A mice as recipients to investigate how implanted tumor cells incapacitate host p53 creating a conducive TME for tumor progression. We found that tumor cell-associated stress induced p53 downregulation in peritumor cells via an MDMX-Ser314 phosphorylation-dependent manner. As a result, an immunosuppressive TME was developed, as reflected by diminished immune cell infiltration into tumors and compromised macrophage M1 polarization. Remarkably, ablation of MDMX-Ser314 phosphorylation attenuated p53 decline in peritumor cells, which was associated with mitigation of immunosuppression and significant tumor growth delay. Our data collectively uncover a novel role of p53 in regulating the tumor immune microenvironment, suggesting that p53 restoration in the TME can be exploited as a potential strategy of anticancer therapy.

Parotitis due to Burkholderia cepacia infection after autologous hematopoietic stem cell transplantation.

Burkholderia cepacia predominantly causes opportunistic infections in hospitalized and immunocompromised patients such as patients with cystic fibrosis, cancer, or human immunodeficiency virus (HIV). Nonetheless, Burkholderia cepacia is infrequently reported to cause infection in hematopoietic stem cell transplantation (HSCT) recipients. Herein, we report a rare case of suppurative parotitis in a 31-year-old patient with T-cell lymphoblastic lymphoma (T-LBL) who underwent auto-HSCT. The secretion from the Stensen duct was collected, and Burkholderia cepacia was detected using the VITEK-2 identification system. Additionally, sensitive antibiotic therapy against this bacterium was also effective. This is the first case of parotitis triggered by Burkholderia cepacia after auto-HSCT, and it is also the first reported domestic case. This case emphasizes the importance of considering bacterial infections in general and Burkholderia cepacia specifically in HSCT patients with post-transplant parotitis.

[Neutrophil-Lymphocyte Ratio as a Prognostic Predictor in Patients with Newly Diagnosed Angioimmunoblastic T Cell Lymphoma].

OBJECTIVE: To investigate the prognostic evaluation value of neutrophil-lymphocyte ratio (NLR) in patients with newly diagnosed angioimmunoblastic T cell lymphoma (AITL). METHODS: Clinical data of 39 patients with newly diagnosed AITL in our hospital from March 2010 to August 2018 were colleated and retrospective analyzied, and the relationship between NLR before treatment and the prognosis of AITL patients was analyzed. RESULTS: Among 39 AITL patients, the median value of NCR was 5.43. Based on the cut-off value (5.43), all the patients were divided into 2 groups: high NLR group (5.43, n=20) and a low NLR group (＜5.43, n=19). The total effective rate of treatment was lower in the high NLR group as compered with low NLR group (P=0.041). Univariate analysis showed that, age ＞60 years old, extranodal involvement＞1 as well as high NLR were the independent risk factors that affected overall survival (OS) in newly diagnosed AITL patients. Multivariate Cox analysis showed that extranodal involvement＞1 and high NLR were the independent risk factors that affected OS in newly diagnosed AITL patients. CONCLUSION: The NLR may be an independent prognostic factor in patients with newly diagnosed AITL. High NLR associated with poor prognosis.