Disordered metabolic states, which are characterised by hypoxia and elevated levels of metabolites, particularly lactate, contribute to the immunosuppression in the tumour microenvironment (TME). ...Excessive lactate secreted by metabolism-reprogrammed cancer cells regulates immune responses via causing extracellular acidification, acting as an energy source by shuttling between different cell populations, and inhibiting the mechanistic (previously ‘mammalian’) target of rapamycin (mTOR) pathway in immune cells. This review focuses on recent advances in the regulation of immune responses by lactate, as well as therapeutic strategies targeting lactate anabolism and transport in the TME, such as those involving glycolytic enzymes and monocarboxylate transporter inhibitors. Considering the multifaceted roles of lactate in cancer metabolism, a comprehensive understanding of how lactate and lactate-targeting therapies regulate immune responses in the TME will provide insights into the complex relationships between metabolism and antitumour immunity.
Display omitted
•The PtO@Ti3C2/TiO2 composite is obtained via Ti3C2 MXene in-situ conversion and following PtO nanodots photo-deposition.•The Ti3C2 MXene and PtO nanodots effectively separate the ...photogenerated electrons and holes.•The PtO nanodots also largely suppress the hydrogen back reaction.•The PtO@Ti3C2/TiO2 composite demonstrates remarkable photocatalytic H2 production efficiency.
Increasing the separation efficiency of photogenerated carriers and preventing the hydrogen back oxidation are two key challenges in photocatalytic hydrogen production. Herein, we report a promising PtO@Ti3C2/TiO2 photocatalyst to overcome these two challenges by in-situ growing TiO2 nanosheets on Ti3C2 MXene (to improve charge separation) and depositing PtO nanodots (to diminish hydrogen back reaction) for enhanced photocatalytic hydrogen production. Within this design principle, the photogenerated electrons and holes in the PtO@Ti3C2/TiO2 composites flow in opposite direction into PtO and Ti3C2 respectively, resulting in effective separation of the photogenerated electrons and holes. Beyond, the higher oxidation state of PtO nanodots also largely suppresses the undesirable hydrogen back oxidation reaction. Thereby the PtO@Ti3C2/TiO2 composite demonstrates remarkable hydrogen production efficiency. Our work here indicates that rational design of dual co-catalysts could not only promote the separation of photogenerated carriers for enhanced hydrogen production, but also inhibit the reverse reaction of hydrogen production.
Background
Coronavirus Disease 19 (COVID‐19) is a global health concern that has become a pandemic over the past few months. This study aims at understanding the clinical manifestations of COVID‐19 ...patients with pleural effusion.
Methods
COVID‐19 patients were retrospectively enrolled from the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. Pharyngeal swabs from patients were tested using real‐time polymerase chain reaction. Patients with COVID‐19 were divided into two groups based on their computed tomography (CT) scans for the presence of pleural effusion at admission. We compared the clinical features, laboratory findings, scans and clinical outcomes between the two groups.
Results
Pleural effusion was observed in 9.19% of the patients. Patients with pleural effusion were more likely to be severe or critical cases. Moreover, patients with pleural effusion were associated with increased mortality. Of the 799 discharged patients, patients with pleural effusion had longer hospital stays and duration of viral shedding since the onset of symptoms as compared with that for patients without pleural effusion. After discharge, 217 patients visited for a follow‐up CT re‐examination at the Union Hospital. The CT scans showed that patients with pleural effusion required a longer time to resolve the lung inflammation after the onset of COVID‐19 as compared with the time required by patients without pleural effusion.
Conclusion
This population of patients requires special attention and pleural effusion may be an indicator of poor prognosis in COVID‐19 patients.
We compared clinical, laboratory, radiological, and outcome features of patients with SARS-CoV-2 infection (COVID-19) with pneumonia, with vs without diarrhea.
We performed a retrospective, ...single-center analysis of 84 patients with SARS-CoV-2 pneumonia in Wuhan Union Hospital, China, from January 19 through February 7, 2020. Cases were confirmed by real-time reverse-transcriptase PCR of nasal and pharyngeal swab specimens for SARS-CoV-2 RNA. Blood samples were analyzed for white blood cell count, lymphocyte count, alanine aminotransferase, creatine kinase, lactate dehydrogenase, D-dimer, C-reactive protein, and in some cases, immunoglobulins, complement, lymphocyte subsets, and cytokines. Virus RNA was detected in stool samples by real-time PCR.
Of the 84 patients with SARS-CoV-2 pneumonia, 26 (31%) had diarrhea. The duration of fever and dyspnea in patients with diarrhea was significantly longer than those without diarrhea (all P < .05). Stool samples from a higher proportion of patients with diarrhea tested positive for virus RNA (69%) than from patients without diarrhea (17%) (P < .001). As of February 19, a lower proportion of patients with diarrhea had a negative result from the latest throat swab for SARS-CoV-2 (77%) than patients without diarrhea (97%) (P = .010), during these patients' hospitalization. Of 76 patients with a negative result from their latest throat swab test during hospitalization, a significantly higher proportion of patients with diarrhea had a positive result from the retest for SARS-CoV-2 in stool (45%) than patients without diarrhea (20%) (P = .039).
At a single center in Wuhan, China, 31% of patients with SARS-CoV-2 pneumonia had diarrhea. A significantly higher proportion of patients with diarrhea have virus RNA in stool than patients without diarrhea. Elimination of SARS-CoV-2 from stool takes longer than elimination from the nose and throat.
With improvements in treatments for primary tumor and brain metastases (BM), the life expectancy of patients with advanced cancers is increasing; thus, helping patients with BM maintain quality of ...life is becoming increasingly important. Sense of coherence (SOC) has been found to be closely related to health-related quality of life (HRQoL) in patients with chronic diseases, however, this relationship has not been validated in patients with BM. This study first examined the relationship between SOC and HRQoL in patients with BM, and further identified factors associated with SOC in these patients. Patients with BM reported lower scores for most of the functioning subscales and for the general rating of quality of life, and higher scores for most of the symptom subscales, compared with a normative sample. SOC was significantly correlated with most aspects of HRQoL in patients with BM. Further, SOC in the patients was associated with awareness of the disease, possession of religious belief, and type of primary cancer. These results validate the close relationship between SOC and HRQoL in patients with BM, and indicate that SOC is associated with awareness of illness and religious belief.
IL-26 is a potentially important player in host defense and may be a pathogenic factor in the chronic inflammatory disorders of humans. However, the involvement of IL-26 in tuberculous pleural ...effusion (TPE) has not been investigated. The concentration of IL-26 was determined in pleural fluids and sera from patients with pleural effusions. Flow cytometry was performed to identify the cell origin of IL-26. The effects of tuberculosis-specific antigen (ESAT-6/CFP-10) on IL-26 expression of CD4
+
T cell were explored. The impacts of IL-26 on modulating CD4
+
T cell polarization were also investigated. The concentrations of IL-26 were much higher in tuberculous, malignant, and infectious PE than those in the corresponding serum. The expression of IL-26 on CD4
+
T cells was much higher in tuberculous PE than those in the corresponding serum, and pleural Th1 and Th17 cells might be the major cell sources of IL-26. The addition of ESAT-6/CFP-10 to CD4
+
T cells led to increasing the number of IL-26–producing CD4
+
T cells and IL-26 expression on Th1 and Th17 cells. IL-26 could induce the differentiation and generation of IL-22 by memory and naive CD4
+
T cells. IL-26 also upregulated the mRNA encoding CC-chemokine ligand 20 (CCL20) and CCL22 by mononuclear cells isolated from TPE. This study implies that pleural Th1 and Th17 cells are the major cell sources of IL-26, which could induce the differentiation and generation of Th22 cells by CD4
+
T cells, suggesting the involvement of IL-26 in the pathogenesis of human TPE.
Key messages
IL-26 is overexpressed in TPE patients and presents a higher concentration in pleural effusion than the corresponding peripheral blood.
Pleural Th1 and Th17 cells might be the major cell sources of IL-26 in TPE patients.
IL-26 promotes IL-22 secretion and Th22 generation by CD4
+
T cells isolated from TPE patients.
IL-26 may play an active role in the pathogenesis of tuberculous pleurisy.
•Circular RNA circFBXO7 overexpression suppressed NSCLC cells proliferation.•Circular RNA circFBXO7 directly inhibited miR-296-3p as a ceRNA.•KLF15 bound to the promoter of CDKN1A gene directly and ...promoted its expression.•Mouse homologous circular RNA circFbxo7 overexpression also suppressed tumor growth.•The novel circFBXO7/miR-296-3p/KLF15/CDKN1A axis regulated NSCLC cell proliferation.
Accumulating evidence indicates that circular RNAs (circRNAs) play important roles in various cancers. Hsa_circ_0008832 (circFBXO7) is a circRNA generated from the second exon of the human F-box only protein 7 (FBXO7). Mouse circFbxo7 is a circRNA generated from the second exon of mouse F-box only protein 7 (Fbxo7). The role of human circFBXO7 and mouse circFbxo7 in non-small cell lung cancer (NSCLC) has not been reported.
The expression of circFBXO7 was measured by quantitative real-time PCR. Survival analysis was performed to explore the association between the expression of circFBXO7 and the prognosis of patients with NSCLC. Lung cancer cell lines were transfected with plasmids. Cell proliferation, cell cycle, and tumorigenesis were evaluated to assess the effects of circFBXO7. Fluorescence in situ hybridization assay was used to identify the location of circFBXO7 and circFbxo7 in human and mouse lung cancer cells. Luciferase reporter assay was conducted to confirm the relationship between circFBXO7 and microRNA.
In this study, we found that circFBXO7 was downregulated in NSCLC tissues and cell lines. NSCLC patients with high circFBXO7 expression had prolonged overall survival. Overexpression of circFBXO7 inhibited cell proliferation both in vitro and in vivo. Mechanistically, we demonstrated that circFBXO7 upregulated the expression of miR-296-3p target gene Krüppel-like factor 15 (KLF15) and KLF15 transactivated the expression of CDKN1A.
CircFBXO7 acts as a tumor suppressor by a novel circFBXO7/miR-296-3p/KLF15/CDKN1A axis, which may serve as a potential biomarker and therapeutic target for NSCLC.
Display omitted
Malignant pleural effusion (MPE) is a functional 'cold' tumor microenvironment in which the antitumor activity of CD8
T cells and natural killer T (NKT)-like cells is suppressed and the function of ...regulatory T (T
) cells is enhanced. Using flow cytometry and immunofluorescence staining, we detected a distinct subset of NKT-like cells expressing FOXP3 in MPE. Through single-cell RNA sequencing (scRNA-seq) analysis, we found that the glycolysis pathway and pyruvate metabolism were highly activated in FOXP3
NKT-like cells. Similar to T
cells, FOXP3
NKT-like cells highly expressed monocarboxylate transporter 1 (MCT1) and lactate dehydrogenase B to uptake and utilize lactate, thereby maintaining their immunosuppressive function and hyperlactylation in MPE. Furthermore, we found that MCT1 small molecule inhibitor 7ACC2 significantly reduced FOXP3 expression and histone lactylation levels in NKT-like cells in vitro. In conclusion, we reveal for the first time the altered phenotypic and metabolic features of FOXP3
NKT-like cells in human MPE.
Abstract
Active crystal facets can generate special properties for various applications. Herein, we report a (001) faceted nanosheet-constructed hierarchically porous TiO2/rGO hybrid architecture ...with unprecedented and highly stable lithium storage performance. Density functional theory calculations show that the (001) faceted TiO2 nanosheets enable enhanced reaction kinetics by reinforcing their contact with the electrolyte and shortening the path length of Li+ diffusion and insertion-extraction. The reduced graphene oxide (rGO) nanosheets in this TiO2/rGO hybrid largely improve charge transport, while the porous hierarchy at different length scales favors continuous electrolyte permeation and accommodates volume change. This hierarchically porous TiO2/rGO hybrid anode material demonstrates an excellent reversible capacity of 250 mAh g–1 at 1 C (1 C = 335 mA g–1) at a voltage window of 1.0–3.0 V. Even after 1000 cycles at 5 C and 500 cycles at 10 C, the anode retains exceptional and stable capacities of 176 and 160 mAh g–1, respectively. Moreover, the formed Li2Ti2O4 nanodots facilitate reversed Li+ insertion-extraction during the cycling process. The above results indicate the best performance of TiO2-based materials as anodes for lithium-ion batteries reported in the literature.
A hierarchically porous TiO2/rGO hybrid architecture with active (001) facets exhibits unprecedented and highly stable lithium storage performance for TiO2-based anodes.
PDF
