Risk factors for ischemic stroke in patients with Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms.

BACKGROUND: Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-negative MPNs) are linked with various complications, notably ischemic stroke. The study aims to identify risk factors for ischemic stroke in Ph-negative MPNs patients. METHODS: Patients were categorized into two groups based on whether they had experienced ischemic stroke. Subsequently, an analysis of demographics, biochemical makers, and genetic mutations (JAK2V617F and CALR mutations), was conducted to identify potential associations with an elevated risk of ischemic stroke in individuals with Ph-negative MPNs. RESULTS: A total of 185 patients diagnosed with Ph-negative MPNs participated in the study, including 82 with essential thrombocythemia (ET), 78 with polycythemia vera (PV), and 25 with primary myelofibrosis (PMF). Among these, 57 patients (30.8 %) had a history of ischemic stroke. Independent risk factors associated with ischemic stroke in Ph-negative MPNs patients included hypertension (OR = 5.076) and smoking (OR = 5.426). Among ET patients, smoking (OR = 4.114) and an elevated percentage of neutrophils (OR = 1.080) were both positively correlated with ischemic stroke incidence. For PV patients, hypertension (OR = 4.647), smoking (OR = 6.065), and an increased percentage of lymphocytes (OR = 1.039) were independently associated with ischemic stroke. Regardless of the presence of the JAK2V617F mutation, hypertension was the sole positively and independently associated risk factor for ischemic stroke. The odds ratios for patients with the JAK2V617F mutation was 3.103, while for those without the mutation, it was 11.25. CONCLUSIONS: Hypertension was a more substantial factor associated with an increased incidence of ischemic stroke in Ph-negative MPNs patients.

H2O2-dependent oxidation of the transcription factor GmNTL1 promotes salt tolerance in soybean.

Reactive oxygen species (ROS) play an essential role in plant growth and responses to environmental stresses. Plant cells sense and transduce ROS signaling directly via hydrogen peroxide (H2O2)-mediated posttranslational modifications (PTMs) on protein cysteine residues. Here, we show that the H2O2-mediated cysteine oxidation of NAC WITH TRANS-MEMBRANE MOTIF1-LIKE 1 (GmNTL1) in soybean (Glycine max) during salt stress promotes its release from the endoplasmic reticulum (ER) membrane and translocation to the nucleus. We further show that an oxidative posttranslational modification on GmNTL1 residue Cys-247 steers downstream amplification of ROS production by binding to and activating the promoters of RESPIRATORY BURST OXIDASE HOMOLOG B (GmRbohB) genes, thereby creating a feed-forward loop to fine-tune GmNTL1 activity. In addition, oxidation of GmNTL1 Cys-247 directly promotes the expression of CATION H+ EXCHANGER 1 (GmCHX1)/SALT TOLERANCE-ASSOCIATED GENE ON CHROMOSOME 3 (GmSALT3) and Na+/H+ Antiporter 1 (GmNHX1). Accordingly, transgenic overexpression of GmNTL1 in soybean increases the H2O2 levels and K+/Na+ ratio in the cell, promotes salt tolerance, and increases yield under salt stress, while an RNA interference-mediated knockdown of GmNTL1 elicits the opposite effects. Our results reveal that the salt-induced oxidation of GmNTL1 promotes its relocation and transcriptional activity through an H2O2-mediated posttranslational modification on cysteine that improves resilience of soybean against salt stress.

Mechanism of action and side effects of colchicine based on biomechanical properties of cells.

Many diseases are related to changes in the biomechanical properties of cells; their study can provide a theoretical basis for drug screening and can explain the internal working of living cells. In this study, the biomechanical properties of nephrocytes (VERO cells), hepatocytes (HL-7702 cells), and hepatoma cells (SMCC-7721 cells) in culture were detected by atomic force microscopy (AFM) to analyse the side effects of colchicine at different concentrations (0.1 µg/mL (A) and 0.2 µg/mL (B)) at the nanoscale for 2, 4 and 6 h. Compared with the corresponding control cells, the damage to the treated cells increased in a dose-dependent manner. Among normal cells, the injury of nephrocytes (VERO cells) was markedly worse than that of hepatocytes (HL-7702 cells) in both colchicine solutions A and B. Based on the analyses of biomechanical properties, the colchicine solution reduced the rate of division and inhibited metastasis of SMCC-7721 cells. By comparing these two concentrations, we found that the anticancer effect of colchicine solution A was greater than that of solution B. Studying the mechanical properties of biological cells can help understand the mechanism of drug action at the molecular level and provide a theoretical basis for preventing the emergence and diagnosis of diseases at the nanoscale.

Ultrasound-Guided Percutaneous Drainage of Iliopsoas Abscess With Septicemia in an Adolescent: A Case Report and Literature Review.

Introduction: Iliopsoas abscess with septicemia in the pediatric population is rare. Early diagnosis and effective management of this emergent disorder remain challenging for clinicians. Case Presentation: A 14-year-old girl presented with right lateral and posterior hip pain and fever for 7 days before admission. Blood culture was positive for Staphylococcus aureus. Enhanced magnetic resonance imaging revealed abscesses located in the right iliopsoas muscle and on the surface deep to the fascia of the right sacroiliac joint that were 6.8 cm × 6.2 cm × 5.7 cm and 3.7 cm × 3.5 cm × 2.1 cm, respectively. A diagnosis of right iliopsoas abscesses with septicemia was made. The patient received intravenous antibiotics, underwent ultrasound-guided percutaneous catheter drainage, and recovered uneventfully. Medical literature regarding this issue published in the English language during the last two decades was reviewed. Discussion: Primary synchronous psoas and iliacus muscle abscesses are rare and emergent disorders in the pediatric age group. The diagnosis is generally delayed owing to the deep anatomic location and nonspecific signs and symptoms. A comprehensive medical history, meticulous physical examination, and judicious use of imaging studies could establish a timely and accurate diagnosis. Surgeons should be aware of the occurrence of multiple abscesses. Prompt and adequate antibiotic therapy accompanied by a mini-invasive approach, such as ultrasound-guided, laparoscopic, or video-retroperitoneoscopic drainage of the infectious focus, if indicated and feasible, is important to achieve a good outcome in the management of iliopsoas abscess.

Direct and Inverse Reduced-Form Models for Reciprocal Calculation of BC Emissions and Atmospheric Concentrations.

Atmospheric black carbon (BC) concentrations are governed by both emissions and meteorological conditions. Distinguishing these effects enables quantification of the effectiveness of emission mitigation actions by excluding meteorological effects. Here, we develop reduced-form models in both direct (RFDMs) and inverse (RFIMs) modes to estimate ambient BC concentrations. The models were developed based on outputs from multiyear simulations under three conditional scenarios with realistic or fixed emissions and meteorological conditions. We established a set of probabilistic functions (PFs) to quantify the meteorological influences. A significant two-way linear relationship between multiyear annual emissions and mean ambient BC concentrations was revealed at the grid cell scale. The correlation between them was more significant at grid cells with high emission densities. The concentrations and emissions at a given grid cell are also significantly correlated with emissions and concentrations of the surrounding areas, respectively, although to a lesser extent. These dependences are anisotropic depending on the prevailing winds and source regions. The meteorologically induced variation at the monthly scale was significantly higher than that at the annual scale. Of the major meteorological parameters, wind vectors, temperature, and relative humidity were found to most significantly affect variation in ambient BC concentrations.

Investigation of the mechanical effects of targeted drugs on cancerous cells based on atomic force microscopy.

Cancer is currently drawing more and more attention as the leading factor in death worldwide. However, little research has been directed towards investigating the micro/nanoscale mechanical properties of cancer cells treated by targeted drugs to evaluate the model systems of targeted drugs using atomic force microscopy (AFM) nano-indentation, especially in light of the multiple drugs targeting various cancerous cells. This paper aims to compare the mechanical effects of sorafenib tosylate and osimertinib mesylate on hepatoma carcinoma cells and lung cancerous cells using atomic force microscopy from the perspective of a model system based on nano-indentation at the micro/nanoscale, which has rarely been investigated. The Sneddon model is applied to fit the force-distance curves, and the mechanical properties, i.e., Young's moduli, can then be calculated. For the SMMC-7721 cells, osimertinib mesylate is a more effective inhibitor than sorafenib tosylate. For the A549 cells, osimertinib mesylate and sorafenib tosylate both have an obvious inhibitory effect. The experimental results may make possible contributions to the diagnosis and treatment of early-stage cancers.

TIGIT modulates sepsis-induced immune dysregulation in mice with preexisting malignancy.

TIGIT is a recently identified coinhibitory receptor that is upregulated in the setting of cancer and functionally contributes to the impairment of antitumor immunity. However, its role during sepsis is unknown. Because patients with cancer are 10 times more likely to die of sepsis than previously healthy (PH) patients with sepsis, we interrogated the role of TIGIT during sepsis in the context of preexistent malignancy. PH mice or cancer (CA) mice inoculated with lung carcinoma cells were made septic by cecal ligation and puncture (CLP). We found that sepsis induced TIGIT upregulation predominantly on Tregs and NK cells in both PH and CA mice. Anti-TIGIT Ab improved the 7-d survival of CA septic mice but not PH mice after CLP. Treatment of CA septic animals but not PH septic animals with anti-TIGIT mAb significantly reversed sepsis-induced loss of CD4+ T cells, CD8+ T cells, Foxp3+ Treg, and CD19+ B cells in the spleen, which was the result of decreased caspase-3+ apoptotic cells. In sum, we found that anti-TIGIT Ab reversed sepsis-induced T cell apoptosis in CA septic mice and led to a significant survival benefit, suggesting its use as a potential immunotherapy to improve outcomes in septic patients with cancer.

Updated Global Black Carbon Emissions from 1960 to 2017: Improvements, Trends, and Drivers.

Accurate estimation of black carbon (BC) emissions is essential for assessing the health and climate impact of this pollutant. Past emission inventories were associated with high uncertainty due to data limitations, and recent information has provided a unique updating opportunity. Moreover, understanding the drivers that cause temporal emission changes is of research value. Here, we update the global BC emission estimates using new data on the activities and emission factors (EFs). The new inventory covers 73 detailed sources at 0.1° × 0.1° spatial resolution and monthly temporal resolution from 1960 to 2017. The estimated annual emissions were 32% higher than the average of several previous inventories, which was primarily due to field-measured EFs for residential stoves and differentiated EFs for motor vehicles. In addition, the updated emissions show an inverse U-shaped temporal trend, which was mainly driven by the interaction between the positive effects of population growth, per capita energy consumption, and vehicle fleet and the negative effects of residential energy switching, stove upgrading, phasing out of beehive coke ovens, and reduced EFs for vehicles and industrial processes. Urbanization caused a significant increase in urban emissions accompanied by a more significant decline in rural emissions.

Tumor-Specific T Cells Exacerbate Mortality and Immune Dysregulation during Sepsis.

Sepsis induces significant immune dysregulation characterized by lymphocyte apoptosis and alterations in the cytokine milieu. Because cancer patients exhibit a 10-fold greater risk of developing sepsis compared with the general population, we aimed to understand how pre-existing malignancy alters sepsis-induced immune dysregulation. To address this question, we assessed the impact of tumor-specific CD8+ T cells on the immune response in a mouse model of cecal ligation and puncture (CLP)-induced sepsis. Tumor-bearing animals containing Thy1.1+ tumor-specific CD8+ T cells were subjected to CLP, and groups of animals received anti-Thy1.1 mAb to deplete tumor-specific CD8+ T cells or isotype control. Results indicated that depleting tumor-specific T cells significantly improved mortality from sepsis. The presence of tumor-specific CD8+ T cells resulted in increased expression of the 2B4 coinhibitory receptor and increased apoptosis of endogenous CD8+ T cells. Moreover, tumor-specific T cells were not reduced in number in the tumors during sepsis but did exhibit impaired IFN-γ production in the tumor, tumor draining lymph node, and spleen 24 h after CLP. Our research provides novel insight into the mechanisms by which pre-existing malignancy contributes to increased mortality during sepsis.

A novel model for regional indoor PM2.5 quantification with both external and internal contributions included.

PM2.5 (particulate matter with an aerodynamic size ≤ 2.5 µm) of indoor origins is a dominant contributor to the overall air pollution exposure. Although some sophisticated models have been developed to simulate indoor air quality for individual households, it is still challenging to quantify indoor PM2.5 on a regional scale, which is critical for health impact assessments. In this study, a new model was developed to predict indoor PM2.5 concentrations by quantifying the external penetration, as well as the internal contributions. The model was parameterized based on a set of simultaneously measured indoor and outdoor PM2.5 concentrations at five-second temporal resolution for 53 households in Beijing. This study found that indoor PM2.5 concentrations were significantly correlated with those in the outdoor environment with an approximately 1-h lag-time on average. Outdoor-to-indoor penetration dominated the contribution to indoor PM2.5 during polluted hours with relatively high ambient PM2.5 concentrations, while the indoor PM2.5, during clean hours, was contributed by internal sources, including smoking, cooking, incense burning, and human disturbance. The influence of windows, house area, and air purifier use was addressed in the new model. The model was applied to evaluate indoor PM2.5 concentrations in six urban districts of Beijing via an uncertainty analysis. The model was developed based on and applied to households using clean residential energy, and it would be interesting also important to evaluate it in households using solid fuels.

Fibrin-associate diffuse large B-Cell lymphoma arising in a left atrial myxoma: A case report and literature review✰,✰✰.

We report a 60-year-old male with fibrin-associated diffuse large B-cell lymphoma (fa-DLBCL) in left atrial myxoma. Echocardiography showed a mass (63 mm × 33 mm) in the left atrium. Histological inspection indicated fa-DLBCL on the surface of atrial myxoma incidentally, together with extensive fibrinous like exudation on myxoma surface. Malignant cells were localized in solid sheets and nests at the peripheral area of the fibrinous exudation which were positive for B-lineage markers (CD20+, CD79a+, PAX-5+) and in situ hybridization of EBV-encoded RNA (EBER). PCR amplification showed clonal rearrangement of immunoglobulin heavy chain (IgH) genes. The patient was still alive with no recurrence in the 35-month follow-up after surgery. We also did a detailed clinicopathological analysis and literature review, which indicated that fa-DLBCL was a heterogeneous entity.

Preexisting malignancy abrogates the beneficial effects of CXCR4 blockade during sepsis.

Patients with cancer are at an increased risk of developing and dying from sepsis. We previously reported that blockade of the chemokine receptor CXCR4 resulted in decreased CD4+ T cell exhaustion and improved survival in a model of polymicrobial sepsis in previously healthy mice. Here, we sought to determine whether CXCR4 blockade could improve mortality and immune dysregulation during sepsis complicated with malignancy. Results in animals inoculated with a lung cancer cell line and subjected to CLP 3 weeks later indicated that CXCR4 was up-regulated on naïve and central memory T cells following sepsis. Of note, and in contrast to results in previously healthy mice, CXCR4 blockade failed to improve survival in cancer septic animals; instead, it actually significantly worsened survival. In the setting of cancer, CXCR4 blockade failed to result in T cell egress from the bone marrow, reverse lymphopenia in the spleen, or reverse T cell exhaustion. Mechanistically, elevated expression of CD69 on naïve T cells in the bone marrow of cancer septic animals was associated with their inability to egress from the bone marrow in the setting of CXCR4 blockade. In conclusion, these results illuminate the differential impact of CXCR4 blockade on sepsis pathophysiology in the setting of cancer and highlight the need for personalized therapy during sepsis.

A disulfiram-loaded electrospun poly(vinylidene fluoride) nanofibrous scaffold for cancer treatment.

Disulfiram (DSF), an FDA approved drug for the treatment of alcoholism, has shown its effectiveness against diverse cancer types. Thus, we developed a disulfiram-loaded scaffold using the electrospinning method to enhance the stability of DSF and to facilitate its appropriate distribution to tumor tissues. The drug release profile of the disulfiram-loaded scaffold was examined by high-performance liquid chromatography. We obtained mechanical and morphological characterizations of A549 cells treated with different scaffolds by various techniques to evaluate its antitumor properties. This work revealed that the cells after the treatment with the disulfiram-loaded scaffold exhibited a lower height and a larger elastic modulus compared with the untreated cells and those treated with the neat electrospun fibers. The changes were the indicators of cell apoptosis. Taken collectively, the results indicate that DSF was successfully incorporated into the electrospun fibers, and the disulfiram-loaded scaffold has great potential for inhibiting the regional recurrence of cancer.

2B4 but not PD-1 blockade improves mortality in septic animals with preexisting malignancy.

In addition to its well-known beneficial effects for the treatment of several types of cancer, PD-1 blockade has shown encouraging results in preclinical models of sepsis and in a recent clinical trial in sepsis. Because cancer is the most common comorbidity in septic patients, here we aimed to determine the efficacy of PD-1 checkpoint blockade in the setting of sepsis complicated with preexisting malignancy. In a model of established lung cancer followed by cecal ligation and puncture-induced (CLP-induced) sepsis, PD-1 blockade exhibited no therapeutic effect on sepsis survival. This diminished efficacy of PD-1 blockade in cancer septic animals (septic animals with cancer) was characterized by a reduction in both the quality and quantity of PD-1+ responder cells. Specifically, CD8+ T cells isolated from cancer septic animals exhibited decreased CD28 expression and a reduction in the CXCR5+PD-1+ subset. In addition, flow cytometric analysis of T cells isolated from cancer septic animals revealed 2B4 as another possible checkpoint under these conditions. Administration of anti-2B4 to cancer septic animals significantly improved sepsis survival and was associated with increased T cell costimulatory receptor expression and decreased coinhibitory receptor expression. These results illustrate functions of coinhibitory receptors in the setting of sepsis complicated with cancer.

Correlation analysis between ultrasonography and mammography with other risk factors related to breast cancer.

Value and correlation analysis between ultrasound and mammography in the diagnosis and other risk factors related to breast cancer were explored. A total of 1,473 patients who underwent breast color ultrasonography and molybdenum target X-ray examination in Binzhou Medical University Hospital from March 2017 to August 2018 were collected, and the patient's ultrasound and mammography results were compared, also the pathological biopsy was used as the reference golden criteria to calculate the value of both test methods and the value of combined diagnosis in breast cancer. The risk factors associated with breast cancer were analyzed. Among the 1,473 patients, 387 breast cancer patients were detected by ultrasonography, 351 by mammography and 339 cases by combined diagnosis. A total of 314 cases were diagnosed as breast cancer after pathological biopsy. However, there were significant differences in tumor size, stages, and BI-RADS grades (P<0.05). There was no significant difference in the diagnostic efficacy between ultrasonography and mammography (P>0.05), however, the diagnostic efficacy of ultrasonography combined with mammography was significantly better than the two single tests (P<0.05). After logistic regression analysis, there was no significant correlation between residence address, height, blood type, ethnicity, or education with breast cancer (P>0.05). However, age, fertility status, and BMI were all risk factors related to breast cancer (OR>1; P<0.05). In conclusion, ultrasonography combined with mammography can effectively improve the early diagnosis rate of breast cancer, however, the patient's age, birth status, and BMI may affect the results of ultrasonography and mammography. In clinical practice, it is necessary to determine the imaging results in combination with the actual situation of the patients to improve the diagnosis rate of breast cancer.

Sepsis erodes CD8+ memory T cell-protective immunity against an EBV homolog in a 2B4-dependent manner.

Epstein-Barr virus (EBV) reactivation commonly occurs following sepsis, but the mechanisms underlying this are unknown. We utilized a murine EBV homolog (gHV) and the cecal ligation and puncture model of polymicrobial sepsis to study the impact of sepsis on gHV reactivation and CD8+ T cell immune surveillance following a septic insult. We observed a significant increase in the frequency of gHV-infected germinal center B cells on day 7 following sepsis. This increase in viral load was associated with a concomitant significant decrease in the frequencies of gHV-specific CD8+ T cells, as measured by class I MHC tetramers corresponding to the immunodominant viral epitopes. Phenotypic analysis revealed an increased frequency of gHV-specific CD8+ T cells expressing the 2B4 coinhibitory receptor in septic animals compared with sham controls. We sought to interrogate the role of 2B4 in modulating the gHV-specific CD8+ T cell response during sepsis. Results indicated that in the absence of 2B4, gHV-specific CD8+ T cell populations were maintained during sepsis, and gHV viral load was unchanged in 2B4-/- septic animals relative to 2B4-/- sham controls. WT CD8+ T cells upregulated PD-1 during sepsis, whereas 2B4-/- CD8+ T cells did not. Finally, adoptive transfer studies revealed a T cell-intrinsic effect of 2B4 coinhibition on virus-specific CD8+ T cells and gHV viral load during sepsis. These data demonstrate that sepsis-induced immune dysregulation erodes antigen-specific CD8+ responses against a latent viral infection and suggest that blockade of 2B4 may better maintain protective immunity against EBV in the context of sepsis.

Murine Pancreatic Cancer Alters T Cell Activation and Apoptosis and Worsens Survival After Cecal Ligation and Puncture.

Patients with cancer who develop sepsis have a markedly higher mortality than patients who were healthy prior to the onset of sepsis. Potential mechanisms underlying this difference have previously been examined in two preclinical models of cancer followed by sepsis. Both pancreatic cancer/pneumonia and lung cancer/cecal ligation and puncture (CLP) increase murine mortality, associated with alterations in lymphocyte apoptosis and intestinal integrity. However, pancreatic cancer/pneumonia decreases lymphocyte apoptosis and increases gut apoptosis while lung cancer/CLP increases lymphocyte apoptosis and decreases intestinal proliferation. These results cannot distinguish the individual roles of cancer versus sepsis since different models of each were used. We therefore created a new cancer/sepsis model to standardize each variable. Mice were injected with a pancreatic cancer cell line and 3 weeks later cancer mice and healthy mice were subjected to CLP. Cancer septic mice had a significantly higher 10-day mortality than previously healthy septic mice. Cancer septic mice had increased CD4 T cells and CD8 T cells, associated with decreased CD4 T cell apoptosis 24 h after CLP. Further, splenic CD8+ T cell activation was decreased in cancer septic mice. In contrast, no differences were noted in intestinal apoptosis, proliferation, or permeability, nor were changes noted in local bacterial burden, renal, liver, or pulmonary injury. Cancer septic mice thus have consistently reduced survival compared with previously healthy septic mice, independent of the cancer or sepsis model utilized. Changes in lymphocyte apoptosis are common to cancer model and independent of sepsis model, whereas gut apoptosis is common to sepsis model and independent of cancer model. The host response to the combination of cancer and sepsis is dependent, at least in part, on both chronic comorbidity and acute illness.

Analysis of Colchicine-Induced Effects on Hepatoma and Hepatocyte Cells by Atomic Force Microscopy.

Biomechanical properties of cells are altered by many diseases. Cancer cell metastasis is related to the properties such as the cell stiffness that influences cell proliferation, differentiation and migration. In this paper, we used an atomic force microscope to analyze the colchicine-induced effects on the mechanical properties of hepatocyte (HL-7702 cells) and hepatoma cells (SMCC-7721 cells) in culture at the nanoscale. The cells were exposed to a solution with a normal dose of colchicine for two, four and six hours. Surface topographic images showed that colchicine decreased the stability of the cytoskeleton. After the same six-hour treatment in a solution with a normal dose of colchicine, the biomechanical properties of HL-7702 cells were almost unchanged. However, the stiffness and the adhesion force of the SMCC-7721 cells were clearly increased (more than twofold of the normal values), especially after four hours. The deformability of SMCC-7721 cancer cells was significantly decreased within the six-hour treatment in the solution with a normal dose of colchicine. Analysis of the biomechanical properties of post-treatment hepatoma cells provided a complementary explanation for the mechanism of action of colchicine on cells at the nanoscale. This method is expected to allow the monitoring of potential metastatic cancer cell changes, thus preventing the emergence and the transmission of disease, and improving the diagnosis of cancer.

Pre-existing malignancy results in increased prevalence of distinct populations of CD4+ T cells during sepsis.

The presence of pre-existing malignancy in murine hosts results in increased immune dysregulation and risk of mortality following a septic insult. Based on the known systemic immunologic changes that occur in cancer hosts, we hypothesized that the presence of pre-existing malignancy would result in phenotypic and functional changes in CD4+ T cell responses following sepsis. In order to conduct a non-biased, unsupervised analysis of phenotypic differences between CD4+ T cell compartments, cohorts of mice were injected with LLC1 tumor cells and tumors were allowed to grow for 3 weeks. These cancer hosts and age-matched non-cancer controls were then subjected to CLP. Splenocytes were harvested at 24h post CLP and flow cytometry and SPADE (Spanning-tree Progression Analysis of Density-normalized Events) were used to analyze populations of CD4+ cells most different between the two groups. Results indicated that relative to non-cancer controls, cancer mice contained more resting memory CD4+ T cells, more activated CD4+ effectors, and fewer naïve CD4+ T cells during sepsis, suggesting that the CD4+ T cell compartment in cancer septic hosts is one of increased activation and differentiation. Moreover, cancer septic animals exhibited expansion of two distinct subsets of CD4+ T cells relative to previously healthy septic controls. Specifically, we identified increases in both a PD-1hi population and a distinct 2B4hi BTLAhi LAG-3hi population in cancer septic animals. By combining phenotypic analysis of exhaustion markers with functional analysis of cytokine production, we found that PD-1+ CD4+ cells in cancer hosts failed to make any cytokines following CLP, while the 2B4+ PD-1lo cells in cancer mice secreted increased TNF during sepsis. In sum, the immunophenotypic landscape of cancer septic animals is characterized by both increased CD4+ T cell activation and exhaustion, findings that may underlie the observed increased mortality in mice with pre-existing malignancy following sepsis.

Study of morphological and mechanical features of multinuclear and mononuclear SW480 cells by atomic force microscopy.

This article studies the morphological and mechanical features of multinuclear and mononuclear SW480 colon cancer cells by atomic force microscopy to understand their drug-resistance. The SW480 cells were incubated with the fullerenol concentrations of 1 mg/ml and 2 mg/ml. Morphological and mechanical features including the height, length, width, roughness, adhesion force and Young's modulus of three multinuclear cell groups and three mononuclear cell groups were imaged and analyzed. It was observed that the features of multinuclear cancer cells and mononuclear cancer cells were significantly different after the treatment with fullerenol. The experiment results indicated that the mononuclear SW480 cells were more sensitive to fullerenol than the multinuclear SW480 cells, and the multinuclear SW480 cells exhibited a stronger drug-resistance than the mononuclear SW480 cells. This work provides a guideline for the treatments of multinuclear and mononuclear cancer cells with drugs.