Myeloid-derived suppressor cells (MDSCs) are expanded in tumor microenvironments, including that of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC). The link between MDSC expansion ...and EBV infection in NPC is unclear. Here, we show that EBV latent membrane protein 1 (LMP1) promotes MDSC expansion in the tumor microenvironment by promoting extra-mitochondrial glycolysis in malignant cells, which is a scenario for immune escape initially suggested by the frequent, concomitant detection of abundant LMP1, glucose transporter 1 (GLUT1) and CD33+ MDSCs in tumor sections. The full process has been reconstituted in vitro. LMP1 promotes the expression of multiple glycolytic genes, including GLUT1. This metabolic reprogramming results in increased expression of the Nod-like receptor family protein 3 (NLRP3) inflammasome, COX-2 and P-p65 and, consequently, increased production of IL-1β, IL-6 and GM-CSF. Finally, these changes in the environment of malignant cells result in enhanced NPC-derived MDSC induction. One key step is the physical interaction of LMP1 with GLUT1 to stabilize the GLUT1 protein by blocking its K48-ubiquitination and p62-dependent autolysosomal degradation. This work indicates that LMP1-mediated glycolysis regulates IL-1β, IL-6 and GM-CSF production through the NLRP3 inflammasome, COX-2 and P-p65 signaling pathways to enhance tumor-associated MDSC expansion, which leads to tumor immunosuppression in NPC.
Disposal of wastewater often results in high nutrient loading into aquatic environments, which may lead to favorable conditions for undesirable phytoplankton blooms. Microalgae are efficient in ...removing nitrogen, phosphorus, and toxic metals from wastewater under controlled environments. If key nutrients in the wastewater stream can be used to grow microalgae for biofuel production, the nutrients can be removed, thus significantly reducing the risk of harmful phytoplankton overgrowth. This review paper summarizes the major nutrient components of different wastewater streams, the mechanisms of algal nutrient uptake, nutrient removal performance of various species of microalgae when cultured in wastewater, and current microalgae production systems. Finally, new algae cultivation technologies applicable for biofuel production and nutrient recovery in polluted water bodies are discussed.
• Clinical characteristics and immune-inflammatory parameters were compared between non-severe and severe patients with coronavirus disease 2019 (COVID-19).• High level of interleukin-6 (IL-6), ...C-reactive protein (CRP) and hypertension were independent predictors for the severity of COVID-19.• IL-6 has the highest predictive value among other single immune-inflammatory parameters. The risk model based on IL-6, CRP and hypertension enlarged the predictability.• The dynamic change of IL-6 in the severe cases were parallel to the amelioration of this disease, implied a potential value for monitoring the process of severe cases.
To explore the clinical value of immune-inflammatory markers to assess the severity of coronavirus disease 2019 (COVID-19).
127 consecutive hospitalized patients with confirmed COVID-19 were enrolled in this study, and classified into non-severe and severe groups. Demographics, symptoms, underlying diseases and laboratory data were collected and assessed for predictive value.
Of 127 COVID-19 patients, 16 cases (12.60%) were classified into the severe group. High level of interleukin-6 (IL-6), C-reaction protein (CRP) and hypertension were independent risk factors for the severity of COVID-19. The risk model based on IL-6, CRP and hypertension had the highest area under the receiver operator characteristic curve (AUROC). Additionally, the baseline IL-6 was positively correlated with other immune-inflammatory parameters and the dynamic change of IL-6 in the severe cases were parallel to the amelioration of the disease.
Our study showed that high level of IL-6, CRP and hypertension were independent risk factors for assessing the severity of COVID-19. The risk model established upon IL-6, CRP and hypertension had the highest predictability in this study. Besides, IL-6 played a pivotal role in the severity of COVID-19 and had a potential value for monitoring the process of severe cases.
Summary
The expansion of myeloid‐derived suppressor cells (MDSCs) correlates with tumorigenesis in colorectal cancer (CRC). Here, we found a significant association between CD33+ MDSC number and ...Yes‐associated protein 1 (YAP1) and phosphatase and tensin homologue (PTEN) levels in CRC patients (P < 0·05). Moreover, the CD33+ MDSCs, YAP1 and PTEN were identified as predictors for the prognosis of CRC patients (P < 0·05). Notably, CD33+ MDSCs were an independent survival predictor for CRC patients through a Cox model analysis. In vitro data determined that the expression levels of YAP1 and PTEN in CRC‐derived cell lines were associated with CRC‐derived MDSC induction, and the blockade of YAP1 and PTEN decreased CRC‐derived MDSC induction. A mechanistic analysis revealed that YAP1 promoted CRC‐derived MDSC induction by suppressing PTEN expression to up‐regulate COX‐2, P‐AKT and P‐p65 in CRC‐derived cells, leading to secretion of the cytokine granulocyte–macrophage colony‐stimulating factor. Our findings establish a novel mechanism of pro‐tumorigenic MDSC induction mediated by ectopic YAP1 and PTEN expression in CRC.
The correlations between YAP1, PTEN and MDSCs were identified in patients with colorectal cancer. The clinical significance of YAP1, PTEN and CD33+ MDSCs were determined and a mechanism of MDSC expansion mediated by the YAP1/PTEN/GM‐CSF pathway was established.
Stimulator of interferon genes (STING), a major adaptor protein in antiviral innate immune signaling, is considered as one of the most important regulators of antiviral and antitumor immunity. ...Although STING agonists are now intensively studied in clinical trials as a new class of adjuvants to boost cancer immunotherapy, the tumor-intrinsic role of the STING pathway in shaping the tumor microenvironment remains controversial. Here, we discovered that STING plays a vital role in regulation of myeloid-derived suppressor cell (MDSC) differentiation and antitumor immunity in Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC). Mechanistic analyses reveal that STING represses NPC-derived MDSC induction by enhancing SOCS1 expression in both tumor cells and MDSCs. SOCS1 physically interacts with STAT3 through its SH2 domain to prevent STAT3 phosphorylation and dimerization, resulting in reduced MDSC induction via inhibition of GM-CSF and IL-6 production. Notably, reduced tumoral STING expression was found to be significantly associated with a poor prognosis for NPC patients. Our findings reveal a novel mechanism linking STING to tumor microenvironmental cytokine production and MDSC induction.
Oral administration of resveratrol is able to ameliorate the progression of diabetic nephropathy (DN); however, its mechanisms of action remain unclear. Recent evidence suggested that the gut ...microbiota is involved in the metabolism therapeutics. In the current study, we sought to determine whether the anti-DN effects of resveratrol are mediated through modulation of the gut microbiota using the genetic db/db mouse model of DN. We demonstrate that resveratrol treatment of db/db mice relieves a series of clinical indicators of DN. We then show that resveratrol improves intestinal barrier function and ameliorates intestinal permeability and inflammation. The composition of the gut microbiome was significantly altered in db/db mice compared to control db/m mice. Dysbiosis in db/db mice characterized by low abundance levels of Bacteroides, Alistipes, Rikenella, Odoribacter, Parabacteroides, and Alloprevotella genera were reversed by resveratrol treatment, suggesting a potential role for the microbiome in DN progression. Furthermore, fecal microbiota transplantation, derived from healthy resveratrol-treated db/m mice, was sufficient to antagonize the renal dysfunction, rebalance the gut microbiome and improve intestinal permeability and inflammation in recipient db/db mice. These results indicate that resveratrol-mediated changes in the gut microbiome may play an important role in the mechanism of action of resveratrol, which provides supporting evidence for the gut–kidney axis in DN.
Four polysaccharide fractions (P‐1: 71.40%, P‐2: 1.95%, P‐3: 1.14%, P‐4: 1.64%) were isolated from crude Polygonatum sibiricum polysaccharide (PSP), processed by water extraction, ethanol ...precipitation, and further separated with diethylaminoethyl cellulose‐52 anion‐exchange chromatography. Their molecular weights and monosaccharide compositions were characterized by high performance gel chromatography with evaporative light scattering detector and ultraviolet–visible detector. The antioxidant activity of four polysaccharides fractions were assessed by the electron transfer menchanism (DPPH, ferric reducing power, and ABST assays) and chelation of transition metals (Fe2+ and Cu2+ chelation ability). The highest content fraction P‐1 exhibited the lowest antioxidant activity, and the ranking of antioxidant capacity was P‐4 > P‐3 > P‐2 > PSP > P‐1. After processed by microwave‐assisted degradation, the molecular weight of P‐1 was decreased from 2.99 × 105 to 2.33 × 103 Da, while the antioxidant activity of degraded P‐1 was about eightfold higher than natural P‐1. These results indicated that the proposed microwave‐assisted degradation approach was an efficacious methodology to improve their bioactivity by lower the molecular weight of polysaccharides.
Practical Application
This study provided an environmentally friendly, convenient and efficient microwave‐assisted degradation technology to process the neutral polysaccharides from Polygonatum sibiricum. The results could be used for the development and utilization of various plant polysaccharides as a kind of food supplement in our daily life.
Abstract
We have collected 10,025 foreground–background quasar pairs with projected distances
d
p
< 500 kpc from the large quasar catalog of the Sloan Digital Sky Survey DR16Q. We investigate the ...properties of the Mg
ii
absorption lines with
W
r
> 0.15 Å around foreground quasars, including both the line of sight (LOS; of foreground quasars) and transverse (TRA; perpendicular to the LOS) absorptions. Both the equivalent width (the correlation coefficient
ρ
= −0.915 and the probability
P
< 10
−4
of no correlation) and incident rate (
ρ
= −0.964 and
P
< 10
−6
) of TRA Mg
ii
absorption lines are obviously anticorrelated with projected distance. The incident rate of TRA Mg
ii
absorption lines is obviously (>4
σ
) greater than that of LOS Mg
ii
absorption lines at projected distances
d
p
< 200 kpc, while the TRA and LOS Mg
ii
both have similar (<3
σ
) incident rates at scales
d
p
> 200 kpc. The anisotropic radiation from quasars would be the most possible interpretation for the anisotropic absorption around quasars. This could also indicate that the quasar radiation is not obviously impacting the gas halos of quasars at scales
d
p
> 200 kpc.
•A novel Contrastive Multi-Task Convolutional Neural Network (CMT-CNN) is proposed for automatic COVID-19 diagnosis.•The main task is to diagnose COVID-19 from other pneumonia and normal controls. ...The auxiliary task is self-supervised contrastive learning to acquire transformation-invariant representations.•A series of interpretable transformations are defined for medical image augmentation.•Extensive experiments demonstrate that the auxiliary task can significantly improve the generalization of CNN on both CT and X-ray datasets.
Computed tomography (CT) and X-ray are effective methods for diagnosing COVID-19. Although several studies have demonstrated the potential of deep learning in the automatic diagnosis of COVID-19 using CT and X-ray, the generalization on unseen samples needs to be improved. To tackle this problem, we present the contrastive multi-task convolutional neural network (CMT-CNN), which is composed of two tasks. The main task is to diagnose COVID-19 from other pneumonia and normal control. The auxiliary task is to encourage local aggregation though a contrastive loss: first, each image is transformed by a series of augmentations (Poisson noise, rotation, etc.). Then, the model is optimized to embed representations of a same image similar while different images dissimilar in a latent space. In this way, CMT-CNN is capable of making transformation-invariant predictions and the spread-out properties of data are preserved. We demonstrate that the apparently simple auxiliary task provides powerful supervisions to enhance generalization. We conduct experiments on a CT dataset (4,758 samples) and an X-ray dataset (5,821 samples) assembled by open datasets and data collected in our hospital. Experimental results demonstrate that contrastive learning (as plugin module) brings solid accuracy improvement for deep learning models on both CT (5.49%-6.45%) and X-ray (0.96%-2.42%) without requiring additional annotations. Our codes are accessible online.
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