Circular RNA circFBXO7 attenuates non-small cell lung cancer tumorigenesis by sponging miR-296-3p to facilitate KLF15-mediated transcriptional activation of CDKN1A.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Altered phenotypic and metabolic characteristics of FOXP3+CD3+CD56+ natural killer T (NKT)-like cells in human malignant pleural effusion.

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 (Treg) 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 Treg 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.

High-risk early-stage lung adenocarcinoma patients are identified by an immune-related circadian clock gene signature.

Background: Twenty-four-hour oscillations of circadian rhythms control comprehensive biological processes in the human body. In lung adenocarcinoma (LUAD), chronic circadian rhythm disruption is positively associated with tumorigenesis. However, few studies focus on circadian clock gene signatures (CGSs) for prognosis evaluation of patients with early-stage LUAD. Methods: In this study, we aimed to construct a robust prognostic circadian rhythm-related biomarker from multiple public databases, including the Gene Expression Omnibus database and The Cancer Genome Atlas database. The least absolute shrinkage and selection operator (LASSO)-penalized Cox regression model was performed to select optimal circadian clock gene pairs. Bioinformatic analyses were performed to estimate the abundance of different immune cells and immunohistochemical analyses were conducted to validate the differential proportion of tumor-infiltrating lymphocytes in different groups. Results: Results demonstrated that the CGS could accurately identify patients with early-stage LUAD at a high risk in the training dataset [hazard ratio (HR) =3.06; 95% confidence interval (CI): 2.47-3.78; P<0.001], testing dataset (HR =2.44; 95% CI: 1.74-3.43; P<0.001), and validation dataset (HR =2.09, 95% CI: 1.09-4.00; P=0.023). Bioinformatic and immunohistochemical analyses demonstrated that the abundance of tumor-infiltrating CD4+ T cells was higher in the low-CGS groups. Integration of the CGS and clinical characteristics improved the accuracy of the CGS in predicting overall survival (OS) of patients with early-stage LUAD. Conclusions: In conclusion, the CGS was an independent immune-related circadian biomarker that could identify early-stage LUAD patients with different OS.

Cancer-associated fibroblasts: Vital suppressors of the immune response in the tumor microenvironment.

Since the "seed and soil" hypothesis was proposed, the biological functions of the tumor microenvironment (TME), especially its stromal components, have received increasing attention. Cancer-associated fibroblasts (CAFs) are the major components of the stromal region, providing material support for tumor cell proliferation, migration, and invasion. Furthermore, CAFs are important mediators of suppressing immune responses by attracting the accumulation of immunosuppressive cells through cytokine/chemokine secretion. In this review, we summarized the major cytokines, chemokines and metabolites, including transforming growth factor-ß (TGF-ß), interleukin-6 (IL-6), C-X-C chemokine ligand (CXCL)12, C-C chemokine ligand (CCL) 2, prostaglandin E2 (PGE2), and other factors, by which CAFs suppress the immune systems in a variety of cancers. More importantly, we highlight potential therapeutic strategies to alleviate the immunosuppression produced by CAFs, thereby inhibiting tumor progression.

Retrospective analysis of laboratory-acquired infection in China / 中国热带医学

@#Abstract: Objective To collect the cases of laboratory-acquired infections (LAI) reported in literatures in China, summarize the infection routes and causes of LAI in China, in order to improve laboratory staff's understanding of its occupational health and safety risks. Methods　The cases of laboratory-acquired infection reported in domestic literatures were collected from PubMed, CNKI, Wanfang Database, CBM China Biomedical Literature Database up to April 11, 2022, retrospectively analyze the number and causes of LAI reports, the main risk factors of LAI and its harm to society, the consequences of LAI or the leakage of pathogenic microorganisms, and put forward the relevant countermeasures of biological safety. Results　A total of 22 LAI reports were collected, reviewed and integrated into 21 reports. There were 7 kinds of pathogenic microorganisms. The main pathogenic microorganisms were hantavirus (42.86%, n=9) and Brucella (33.33%, n=7). There were 122 cases and 3 deaths in the laboratory. Most of the reports came from research laboratories (66.67%, n=14). The main route of infection was inhalation of aerosol (42.86%, n=9), followed by transdermal route (38.09%, n=8). Conclusions Failure to report LAI events will increase the risk of pathogenic microorganisms spreading to people outside the laboratory and the environment through infected laboratory staff. Local health institutions and laboratories should be encouraged to report LAI cases as a powerful tool for monitoring accidental leakage of pathogenic microorganisms and further improving laboratory biosafety. The laboratory needs strong biosafety measures to protect staff's health and prevent environmental pollution caused by accidental leakage of pathogenic microorganisms.

Amorphous TiO2 Bridges Stabilized WS2 Membranes with Excellent Filtration Stability and Photocatalysis-Driving Self-Cleaning Ability.

Two-dimensional (2D) membranes as a new type of water filtration membrane have shown great potential in water separation and purification. However, their long-term stability under cross-flow conditions and their antifouling property are two main concerns for practical separation and purification processes. In this work, a strategy of nanoparticle bridges based on amorphous TiO2 is developed to link adjacent WS2 nanosheets on a WS2 membrane surface, leading to a strong membrane surface with excellent stability during 204 h of continuous cross-flow filtration. Moreover, the amorphous TiO2 bridges also form a TiO2/WS2 heterojunction on the WS2 membrane surface, exhibiting an impressive photocatalysis-driving self-cleaning property by pollutant photodegradation. And the flux recovery ratio (FRR) exceeds 95% after three cycles of separation experiments. The excellent long-term stability and photocatalysis-driving self-cleaning property of the WS2/TiO2 membrane provide a new approach to construct robust 2D membranes.

Development and Validation of a Prognostic Autophagy-Related Gene Pair Index Related to Tumor-Infiltrating Lymphocytes in Early-Stage Lung Adenocarcinoma.

The role of autophagy in lung cancer is context-dependent and complex. Recent studies have reported the important role of autophagy in tumor immune escape. However, the association between autophagy and tumor-infiltrating lymphocytes (TILs) in early-stage lung adenocarcinoma (LUAD) remains unclear. In this study, we aimed to develop and validate the autophagy-related gene pair index (ATGPI) and autophagy clinical prognostic index (ACPI) in multiple LUAD cohorts, including The Cancer Genome Atlas (TCGA) cohort, Gene Expression Omnibus cohorts, and one cohort from Union Hospital, Wuhan (UH cohort), using a Cox proportional hazards regression model with the least absolute shrinkage and selection operator. Multivariate Cox regression analysis demonstrated that there was a significant difference in overall survival (OS) between patients with high and low ATGPI in the testing [hazard ratio (HR) = 1.97; P < 0.001] and TCGA validation (HR = 2.25; P < 0.001) cohorts. Time-dependent receiver operating characteristic curve analysis was also performed. We found that high ATGPI could accurately identify patients with early-stage LUAD with shorter OS, with the areas under the curve of 0.703 and 0.676 in the testing and TCGA validation cohorts, respectively. Concordance index (C-index) was used to evaluate the efficiency of ATGPI and ACPI. The C-index of ACPI was higher than that of ATGPI in the testing (0.71 vs. 0.66; P < 0.001), TCGA validation (0.69 vs. 0.65; P = 0.028), and UH (0.80 vs. 0.70; P = 0.015) cohorts. TIL analysis demonstrated that the proportions of tumor-infiltrating CD4+ T cells were lower in the high-ATGPI group than in the low-ATGPI group in both the TCGA validation and UH cohorts. These results indicate the potential clinical use of ATG signatures which are associated with TILs, in identifying patients with early-stage LUAD with different OS.

Pleural effusion as an indicator for the poor prognosis of COVID-19 patients.

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.

Co-infection of SARS-COV-2 and Influenza A Virus: A Case Series and Fast Review.

Coronavirus disease 2019 (COVID-19) occurs in the influenza season and has become a global pandemic. The present study aimed to examine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infection with influenza A virus (IAV) in an attempt to provide clues for the antiviral interventions of co-infected patients. We described two patients who were co-infected with SARS-CoV-2 and IAV treated at Wuhan Union Hospital, China. In addition, we performed a review in PubMed, Web of Science and CNKI (from January 1 up to November 1, 2020) with combinations of the following key words: "COVID-19, SARS-COV-2, influenza A and co-infection". A total of 28 co-infected patients were enrolled in the analysis. Of the 28 patients, the median age was 54.5 years (IQR, 34.25-67.5) and 14 cases (50.0%) were classified as severe types. The most common symptoms were fever (85.71%), cough (82.14%) and dyspnea (60.71%). Sixteen patients had lymphocytopenia on admission and 23 patients exhibited abnormal radiological changes. The median time from symptom onset to hospital admission was 4 days (IQR, 3-6), and the median time of hospital stay was 14 days (IQR, 8.5-16.75). In conclusion, patients with SARS-COV-2 and IAV co-infection were similar to those infected with SARS-COV-2 alone in symptoms and radiological images. SARS-COV-2 co-infection with IAV could lead to more severe clinical condition but did not experience longer hospital stay compared with patients infected with SARS-COV-2 alone.

Therapeutic Effects of Transcranial Magnetic Stimulation on Visuospatial Neglect Revealed With Event-Related Potentials.

This study aimed to investigate changes in attention processing after low-frequency repetitive transcranial magnetic stimulation (rTMS) over the left posterior parietal cortex to better understand its role in visuospatial neglect (VSN) rehabilitation. The current study included 10 subacute stroke patients with VSN consecutively recruited from the inpatient stroke rehabilitation center at Xuanwu Hospital (the teaching hospital affiliated with Capital Medical University) between March and November 2019. All patients performed a battery of tasks (including line bisection, line cancellation, and star cancellation tests) two weeks before treatment and at the beginning and end of treatment; the attentive components of the test results were analyzed. In addition, low-frequency rTMS was used to stimulate the left posterior parietal cortex for 14 days and event-related potential data were collected before and after the stimulation. Participants were evaluated using a target-cue paradigm and pencil-paper tests. No significant differences were detected on the battery of tasks before rTMS. However, we found that rTMS treatment significantly improved the response times and accuracy rates of patients with VSN. After rTMS, the treatment side (left) amplitude of P300 following an event-related potential was higher than that before treatment (left target, p = 0.002; right target, p = 0.047). Thus, our findings suggest that rTMS may be an effective treatment for VSN. The observed increase in event-related potential amplitude supports the hypothesized compensational role of the contralesional hemisphere in terms of residual performance. Our results provide electrophysiological evidence that may help determine the mechanisms mediating the therapeutic effects of rTMS.

Tumor-associated macrophages: A promising target for a cancer immunotherapeutic strategy.

Macrophages, a type of myeloid immune cell, play essential roles in fighting against pathogenic invasion and activating T cell-mediated adaptive immune responses. As a major constituent of the tumor microenvironment (TME), macrophages play a complex role in tumorigenesis and tumor progression. They can inhibit tumor growth by releasing proinflammatory cytokines and exerting cytotoxic activities but principally contribute to tumor progression by promoting tumor proliferation, angiogenesis, and metastasis. The tumor-promoting hallmarks of macrophages have aroused widespread interest in targeting tumor-associated macrophages (TAMs) for cancer immunotherapy. Increasing preclinical and clinical studies suggest that TAMs are a promising target for cancer immunotherapy. To date, TAM-targeted therapeutic strategies have mainly been divided into two kinds: inhibiting pro-tumor TAMs and activating anti-tumor TAMs. We reviewed the heterogeneous and plastic characteristics of macrophages in the TME and the feasible strategies to target TAMs in cancer immunotherapy and summarized the complementary effect of TAM-targeted therapy with traditional treatments or other immunotherapies.

Diarrhea Is Associated With Prolonged Symptoms and Viral Carriage in Corona Virus Disease 2019.

BACKGROUND & AIMS: We compared clinical, laboratory, radiological, and outcome features of patients with SARS-CoV-2 infection (COVID-19) with pneumonia, with vs without diarrhea. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Accumulation of TNFR2-expressing regulatory T cells in malignant pleural effusion of lung cancer patients is associated with poor prognosis.

BACKGROUND: Regulatory T cells (Tregs) may represent a major cellular mechanism in immune suppression by dampening the anti-tumor response in malignant pleural effusion (MPE). Tumor necrosis factor receptor type II (TNFR2) has emerged as a novel identification for the maximally suppressive subset of Tregs in the tumor environment. At present, the significance of TNFR2 expression on Tregs in MPE remains unclear. METHODS: The distribution of TNFR2+cells in Tregs and effector T cells (Teffs) in MPE, peripheral blood (PB), and tuberculosis pleural effusion (TPE) were determined. The associations between TNFR2+Tregs frequencies present in MPE and the clinical and laboratorial characteristics of patients with lung cancer were investigated. The immunosuppressive phenotype of TNFR2+Tregs in MPE was analyzed. The effects of the TNF-TNFR2 interaction on the immunosuppressive function of Tregs was explored. The efficacy of targeting TNFR2 for MPE therapy was examined. The source of TNF in MPE was identified. RESULTS: We observed that markedly higher levels of TNFR2 were expressed in MPE Tregs compared with the levels expressed in MPE Teffs, PB Tregs, or in TPE Tregs. The frequencies of TNFR2+Tregs were positively correlated with the number of tumor cells in MPE, as well as the volume of MPE. High frequencies of TNFR2+Tregs in MPE indicated short survival time and poor performance status for MPE patients. Compared to TNFR2-Tregs, TNFR2+Tregs expressed higher levels of immunosuppressive molecules cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed cell death-ligand 1 (PD-L1), and replicating marker Ki-67. Consequently, the proportions of interferon gamma (IFN-γ)-producing cytotoxic T lymphocytes (CTLs) were significantly increased after TNFR2 blockade. Furthermore, tumor necrosis factor (TNF), through interaction with TNFR2, enhanced the suppressive capacity of Tregs by up-regulating CTLA-4 and PD-L1 expression. Interestingly, T helper 1 (Th1) and T helper 17 (Th17) cells are the major source of TNF in MPE, suggesting that MPE Teffs may paradoxically promote tumor growth by boosting MPE Treg activity via the TNF-TNFR2 pathway. CONCLUSIONS: Our data expanded the immunosuppressive mechanism present in MPE induced by Tregs, and provides novel insight for the diagnosis, disease evaluation, and treatment of MPE patients.

Interleukin-26 upregulates interleukin-22 production by human CD4+ T cells in tuberculous pleurisy.

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.

Visual-spatial neglect after right-hemisphere stroke: behavioral and electrophysiological evidence.

BACKGROUND: Visual-spatial neglect (VSN) is a neuropsychological syndrome, and right-hemisphere stroke is the most common cause. The pathogenetic mechanism of VSN remains unclear. This study aimed to investigate the behavioral and event-related potential (ERP) changes in patients with or without VSN after right-hemisphere stroke. METHODS: Eleven patients with VSN with right-hemisphere stroke (VSN group) and 11 patients with non-VSN with right-hemisphere stroke (non-VSN group) were recruited along with one control group of 11 age- and gender-matched healthy participants. The visual-spatial function was evaluated using behavioral tests, and ERP examinations were performed. RESULTS: The response times in the VSN and non-VSN groups were both prolonged compared with those of normal controls (P < 0.001). In response to either valid or invalid cues in the left side, the accuracy in the VSN group was lower than that in the non-VSN group (P < 0.001), and the accuracy in the non-VSN group was lower than that in controls (P < 0.05). The P1 latency in the VSN group was significantly longer than that in the control group (F[2, 30] = 5.494, P = 0.009), and the N1 amplitude in the VSN group was significantly lower than that in the control group (F[2, 30] = 4.343, P = 0.022). When responding to right targets, the left-hemisphere P300 amplitude in the VSN group was significantly lower than that in the control group (F[2, 30] = 4.255, P = 0.025). With either left or right stimuli, the bilateral-hemisphere P300 latencies in the VSN and non-VSN groups were both significantly prolonged (all P < 0.05), while the P300 latency did not differ significantly between the VSN and non-VSN groups (all P > 0.05). CONCLUSIONS: Visual-spatial attention function is impaired after right-hemisphere stroke, and clinicians should be aware of the subclinical VSN. Our findings provide neuroelectrophysiological evidence for the lateralization of VSN.

[Bioavailability of Dissolved Organic Carbon in Rivers for Typical Vegetation Types in the Permafrost Regions on the Qinghai-Tibet Plateau].

Samples collected from 12 rivers with typical vegetation types in the permafrost regions on the Qinghai-Tibetan Plateau were incubated in the laboratory, and the relationships among the vegetation types, river discharges, the compositions of dissolved organic carbon (DOC), permafrost areas, riverine DOC concentration, biodegradability of dissolved organic carbon (BDOC), and the biodegradation kinetics were examined. The results showed that the DOC concentrations of typical vegetation types in the basin, such as alpine meadow (AM), alpine swamp meadow-alpine meadow (ASM-AM), alpine meadow-alpine steppe (AM-AS), and alpine meadow-alpine steppe-bare soil (AM-AS-BL), were (5.17±0.21), (5.02±0.50), (3.55±0.25), and (2.79±0.41) mg ·L-1, respectively. The values for the bioavailability of river DOC of different vegetation types were (23.54±2.62)%, (23.66±3.31)%, (18.17±5.26)%, and (11.72±15.56)%, respectively. Correspondingly, the riverine DOC aromaticity increased along with the vegetation cover, while the biodegradation and degradation rates decreased gradually. During the incubation, the reaction of BDOC was in accordance with the first-order kinetics equation. Furthermore, the BDOC in continuous permafrost regions of the rivers was greater than that in the non-continuous permafrost regions. The BDOC in higher discharges were lower than those with lower discharges. Taken together, the results suggested that the vegetation types were the main controlling factors for the BDOC, and BDOC was also related to the discharge and permafrost.

The Significance of Tumor Necrosis Factor Receptor Type II in CD8+ Regulatory T Cells and CD8+ Effector T Cells.

Tumor necrosis factor (TNF) is a pleiotropic cytokine that has both pro-inflammatory and anti-inflammatory functions. The biological functions of TNF are mediated by two receptors, TNF receptor type I (TNFR1) and TNF receptor type II (TNFR2). TNFR1 is expressed universally on almost all cell types and has been extensively studied, whereas TNFR2 is mainly restricted to immune cells and some tumor cells and its role is far from clarified. Studies have shown that TNFR2 mediates the stimulatory activity of TNF on CD4+Foxp3+ regulatory T cells (Tregs) and CD8+Foxp3+ Tregs, and is involved in the phenotypic stability, proliferation, activation, and suppressive activity of Tregs. TNFR2 can also be expressed on CD8+ effector T cells (Teffs), which delivers an activation signal and cytotoxic ability to CD8+ Teffs during the early immune response, as well as an apoptosis signal to terminate the immune response. TNFR2-induced abolition of TNF receptor-associated factor 2 (TRAF2) degradation may play an important role in these processes. Consequently, due to the distribution of TNFR2 and its pleiotropic effects, TNFR2 appears to be critical to keeping the balance between Tregs and Teffs, and may be an efficient therapeutic target for tumor and autoimmune diseases. In this review, we summarize the biological functions of TNFR2 expressed on CD8+Foxp3+ Tregs and CD8+ Teffs, and highlight how TNF uses TNFR2 to coordinate the complex events that ultimately lead to efficient CD8+ T cell-mediated immune responses.

Medical thoracoscopy in China-the present status and the future.

Medical thoracoscopy (MT) refers to a minimally invasive procedure to inspect and perform a biopsy of the pleural space, as well as to perform therapeutic interventions, in a nonintubated patient under local anesthesia. This procedure provides the physician a window into the pleural space. Over the past two decades, MT has been developed very rapidly in China. We performed a review of the published data on MT in China, and estimated the present status, the challenges, and future perspectives of MT. From the data we conduct that MT is widely used well in China, not only in the diagnosis of exudative pleural effusions, but also in the management of pleural diseases, such as tuberculous pleural effusion, malignant pleural effusion and spontaneous pneumothorax. Meanwhile, it is noteworthy that few prospective clinical trials, lack of routine follow-up of MT are current domestic problems for diagnosis and management in pleural effusion. Consequently, more prospective, randomized clinical trials are needed to assess the diagnostic value and treatment superiorities of MT compared with traditional methods or other subjects in China in the future.

CNTF protects neurons from hypoxic injury through the activation of STAT3pTyr705.

The aim of the present study was to investigate whether ciliary neurotrophic factor (CNTF) plays its neuroprotective role following hypoxic injury through the activation of signal transducer and activator of transcription 3 (STAT3) signaling. Firstly, to determine whether CNTF exerts its effects via STAT3 following hypoxic injury, cultured neurons from the cerebral cortex of mice were prepared and a neuronal model of hypoxia was then established. The neurons exposed to hypoxia were then pre-treated with CNTF and transfected with small interference RNA (siRNA) targeting STAT3 (STAT3 siRNA) using polybrene, or with STAT3Tyr705 mutant or STAT3Ser727 mutant using an electroporation system. The survival, proliferation and neurite outgrowth of the neurons subjected to different treatments were also determined. RT-qPCR and western blot analysis were employed to examine the expression levels of STAT3, p-STAT3Tyr705 and p-STAT3Ser727 following treatment with CNTF and other treatments. Our results revealed that treatment with CNTF: i) protected neurons from hypoxic injury by promoting survival and neurite growth; ii) induced a significant increase in the levels of STAT3, STAT3pTyr705 and the STAT3pTyr705/STAT3 ratio; it did not however, significantly affect the levels of STAT3pSer727 in the hypoxic cerebral cortex neurons. Transfection of the hypoxic neurons pre-treated with CNTF with STAT3 siRNA or STAT3Tyr705 neutralized the protective effects exerted by CNTF. The findings of our study thus demonstrate that CNTF protects neurons from hypoxic injury through the activation of STAT3pTyr705.

[Sources of dissolved organic carbon and the bioavailability of dissolved carbohydrates in the tributaries of Lake Taihu].

Surface water samples of Yincungang and Chendonggang Rivers were collected from September 2012 to August 2013 in Lake Taihu. Water temperature, Chlorophyll a and bacterial abundance were analyzed, as well as dissolved organic carbon (DOC) concentrations, stable carbon isotope of DOC (Δ13C(DOC)), specific UV absorbance (SUVA254 ) and dissolved carbohydrates concentrations. Δ13C(DOC) ranged from -27.03% per thousand ± 0.30% per thousand to -23.38%per thousand ± 0.20% per thousand, indicating a terrestrial source. Both the autochthonous and allochthonous sources contributed to the carbohydrates pool in the tributaries. Significant differences in PCHO (polysaccharides) and MCHO (monosaccharides) concentrations were observed between spring-summer and autumn-winter (P < 0.01, n = 12; P < 0.01, n = 12), which might be caused by the variation in the sources and bioavailability of carbohydrates. PCHO contributed a major fraction to TCHO (total dissolved carbohydrates) in autumn and winter, which could be explained by the accumulation of undegradable PCHO limited by the low water temperature; MCHO contributed a major fraction to TCHO in spring and summer, which might be caused by the transformation from PCHO by microbes at high water temperature.