A computational approach to estimate postmortem interval using postmortem computed tomography of multiple tissues based on animal experiments.

The estimation of postmortem interval (PMI) is a complex and challenging problem in forensic medicine. In recent years, many studies have begun to use machine learning methods to estimate PMI. However, research combining postmortem computed tomography (PMCT) with machine learning models for PMI estimation is still in early stages. This study aims to establish a multi-tissue machine learning model for PMI estimation using PMCT data from various tissues. We collected PMCT data of seven tissues, including brain, eyeballs, myocardium, liver, kidneys, erector spinae, and quadriceps femoris from 10 rabbits after death. CT images were taken every 12 h until 192 h after death, and HU values were extracted from the CT images of each tissue as a dataset. Support vector machine, random forest, and K-nearest neighbors were performed to establish PMI estimation models, and after adjusting the parameters of each model, they were used as first-level classification to build a stacking model to further improve the PMI estimation accuracy. The accuracy and generalized area under the receiver operating characteristic curve of the multi-tissue stacking model were able to reach 93% and 0.96, respectively. Results indicated that PMCT detection could be used to obtain postmortem change of different tissue densities, and the stacking model demonstrated strong predictive and generalization abilities. This approach provides new research methods and ideas for the study of PMI estimation.

TIPE2 deficiency prolongs mouse heart allograft survival by facilitating immature DCs-induced Treg generation.

It has been reported that deletion of tumor necrosis factor-α-induced protein-8 like 2 (TNFAIP8L2, TIPE2) facilitates the activation of T-cell receptors. However, the role of TIPE2 in T-cell-mediated acute transplant rejection remains unclear. To illustrate the underlying cellular mechanisms, we transplanted BALB/c hearts into C57BL/6 wild-type (WT) or C57BL/6 mice deficient for TIPE2 (TIPE2-/-) and found that TIPE2-/- recipient mice showed significantly prolonged survival of heart allografts and suppressed maturation of CD11c+ dendritic cells (DCs), which largely abolished the activation and proliferation of alloreactive T cells and their cytotoxic activity. TIPE2-/- DCs increased CD4+CD25+Foxp3+CD127- regulatory T cells (Tregs)generation, likely by inhibiting DCs maturation and CD80 and CD86 expression. Administration of anti-CD25 abolished the allograft survival induced by TIPE2 deficiency. Moreover, TIPE2 deficiency increased IL-10 production in T cells and in recipient serum and allografts. Mechanistic studies revealed that TIPE2-/- restrained the maturation of DCs via inhibition of PI3K/AKT phosphorylation during alloantigen stimulation. Taken together, TIPE2 deficiency in recipient mice inhibited acute rejection by increasing Tregs generated by immature DCs. Thus, TIPE2 could be a therapeutic target for suppressing rejection in organ transplantation.

Polysaccharides from Paecilomyces hepiali Prevent Acute Colitis in Association with Modulating Gut Microbiota and Treg/Th17 Immune Balance in Mice.

Cordyceps exopolysaccharide (CEP) has shown emerging potential in adjustment of gut microbiota and immune cell function. In this study, a water-soluble CEP with a molecular weight of 58.14 kDa was extracted from the fermentation broth of Paecilomyces hepiali, an endophytic fungus of Cordyceps sinensis. Our results indicated that Paecilomyces hepiali polysaccharide (PHP) showed significantly preventive potential on dextran sulfate sodium (DSS)-induced colitis in mice, which can prevent colon shortening, reduce intestinal epithelial cell (IEC) destruction, suppress inflammatory cell infiltration, and regulate the balance between regulatory T (Treg) cells and T helper type 17 (Th17) cells. Meanwhile, the disturbed gut microbiota was partially restored after PHP treatment. Further Pearson correlation coefficient analyses exhibited that the alteration of the gut microbiota was significantly related to adjustment of the IEC barrier and Treg/Th17 balance. In conclusion, all findings proposed that purified PHP has the potential to develop into a promising agent for colitis prevention and adjuvant therapy via maintaining intestinal homeostasis of gut microbiota and immune system.

Evaluating renal iron overload in diabetes mellitus by blood oxygen level-dependent magnetic resonance imaging: a longitudinal experimental study.

BACKGROUND: Iron overload plays a critical role in the pathogenesis of diabetic nephropathy. Non-invasive evaluation of renal iron overload in diabetes in the management and intervention of diabetic nephropathy is of great significance. This study aimed to explore the feasibility of blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in evaluating renal iron overload in diabetes using a rabbit model. METHODS: The rabbits were randomly divided into control, iron-overload (I), diabetes (D), and diabetes with iron-overload (DI) groups (each n = 19). The diabetes models were generated by injecting intravenous alloxan solution, and the iron-overload models were generated by injecting intramuscular iron-dextran. BOLD MRI was performed immediately (week 0) and at week 4, 8, and 12 following modeling. The differences in renal cortex (CR2*) and outer medulla R2* (MR2*) and the ratio of MR2*-CR2* (MCR) across the different time points were compared. RESULTS: Iron was first deposited in glomeruli in the I group and in proximal tubular cells in renal cortex in the D group. In the DI group, there was iron deposition in both glomeruli and proximal tubular cells at week 4, and the accumulation increased subsequently. The degree of kidney injury and iron overload was more severe in the DI group than those in the I and D groups at week 12. At week 8 and 12, the CR2* and MR2* in the DI group were higher than those in the I and D groups (all P < 0.05). The MCR in the I, D, and DI groups decreased from week 0 to 4 (all P < 0.001), and that in the I group increased from week 8 to 12 (P = 0.034). CR2* and MR2* values displayed different trends from week 0-12. Dynamic MCR curves in the D and DI groups were different from that in the I group. CONCLUSION: It presents interactions between diabetes and iron overload in kidney injury, and BOLD MRI can be used to evaluate renal iron overload in diabetes.

Mechanism of subchronic vinyl chloride exposure combined with a high-fat diet on hepatic steatosis.

Vinyl chloride (VC) is a common industrial organic chlorine and environmental pollutant. In recent years, the dietary structure of residents especially Chinese has gradually shifted to western dietary patterns. VC aggravates dietary fatty acid-induced hepatic steatosis, but its mechanism is still unclear. And if the risk factors for steatosis persist, more severe diseases such as fibrosis and cirrhosis will occur. Therefore, we studied the effects and mechanisms of VC (160 and 800 mg/m3 ) and its metabolite (chloroacetaldehyde, 2.25, 4.5, and 9 µM) on hepatic steatosis of high-fat diet (HFD)-fed mice and palmitic acid (PA, 100 µM) treated HepG2 cells. Liver and serum biochemical indicators and pathological staining of the liver showed that the hepatic steatosis of VC combined with HFD groups was more severe than that of single-exposure groups (HFD group, low-dose VC group, and high-dose VC group). Moreover, VC enhanced HFD-induced oxidative stress (OS) and endoplasmic reticulum stress (ERS) and further upregulated the expression of sterol regulatory element-binding protein 1 (SREBP-1) and FAS. Besides, antioxidants and ERS inhibitors reduced the steatosis of HepG2 cells induced by VC metabolites and PA. These results suggest that VC exposure can enhance the degree of hepatic steatosis in HFD-fed mice. VC combined with HFD led to OS and ERS and upregulated the expression of de novo lipogenesis-related proteins, which may be related to the occurrence of hepatic steatosis. And the increased expression of CYP2E1 induced by VC combined with HFD may be the cause of OS.

Chronic maternal hepatitis B virus infection and pregnancy outcome- a single center study in Kunming, China.

BACKGROUND: Chinese population has a high prevalence of chronic hepatitis B virus (HBV) infection, the impact of which on pregnancy outcome remains controversial. A single-center retrospective cohort study was performed in Kunming, a multi-ethnic city in south-western China to examine this issue. METHODS: The singleton pregnancies delivering at ≥28 weeks gestation under our care in 2005-2017 constituted the study cohort. Maternal characteristics and pregnancy outcome were compared between mothers with and without seropositivity for hepatitis B surface antigen (HBsAg) determined at routine antenatal screening. RESULTS: Among the 49,479 gravidae in the cohort, the 1624 (3.3%) HBsAg seropositive gravidae had a lower incidence of nulliparity (RR 0.963, 95% CI 0.935-0.992) and having received tertiary education (RR 0.829, 95% CI 0.784-0.827). There was no significant difference in the medical history, pregnancy complications, or labor or perinatal outcome, except that HBV carriers had significantly lower incidence of labor induction (RR 0.827, 95% CI 0.714-0.958) and of small-for-gestational age (SGA) infants (RR 0.854, 95% CI 0.734-0.994). On regression analysis, maternal HBV carriage was independently associated with spontaneous labor (aRR 1.231, 95% CI 1.044-1.451) and reduced SGA infants (aRR 0.842, 95% CI 0.712-0.997). CONCLUSIONS: Our 3.3% prevalence of maternal HBV infection was around the lower range determined in the Chinese population. The association with spontaneous labor and reduced SGA infants could have helped to promote the perpetuation of the infection through enhanced survival of the offspring infected at birth, thus explaining the high prevalence in the Chinese population.

Impact of childbirth policy changes on obstetric workload over a 13-year period in a regional referral center in China - implications on service provision planning.

BACKGROUND: We aimed to appraise the impact of the changing national childbirth policy since 2002, currently allowing two children per family, on obstetric workload in a regional referral center in China. METHODS: In a retrospective cohort study, temporal changes were examined in relation with maternal demographics, incidence of women with high risk pregnancies and resource statistics in our hospital in managing singleton viable pregnancies (birth from 28 weeks gestational age onwards) for the period 2005-2017. RESULTS: During this 13-year period, the number of singleton livebirths from 28 weeks gestational age onwards was 49,479. Annual numbers of births increased from 1,941 to 2005 to 5,777 in 2017. There were concomitant and significant increases in the incidence of multiparous women (10.6-50.8 %), of age ≥35 years (6.5-24.3 %), with prior caesarean Sec. (2.6-23.6 %), with ≥3 previous pregnancy terminations (1.0-4.9 %), with pre-gestational diabetes (0.2-0.9 %), and with chronic hypertension (0.2-1.2 %). There were associated increases in beds and staff complement and reduced average hospital stay. Nevertheless, while the workload of medical staff remained stable with increasing staff complement, that of midwives increased significantly as reflected by the total births: midwife ratio which increased from 194.1:1 to 320.9:1 (p < 0.001). CONCLUSIONS: In our hospital, progressively increasing numbers of annual births in combination with an increased incidence of women with high risk pregnancies took place following the revised national childbirth policy. Only the increase in medical and nursing, but not midwifery, staff was commensurate with workload. Remedial measures are urgently required before the anticipated progressive increase in care demand would overwhelm maternity care with potentially disastrous consequences.

Deregulation of the cell cycle and related microRNA expression induced by vinyl chloride monomer in the hepatocytes of rats.

Vinyl chloride (VC) is a confirmed human carcinogen associated with hepatocellular carcinoma and angiosarcoma. However, the role of microRNAs (miRNAs) in liver cell cycle changes under VC exposure remains unclear, which prevents research on the mechanism of VC-induced carcinogenesis. In this study, male rats were injected intraperitoneally with VC (0, 5, 25, and 125 mg/kg body weight) for 6, 8, and 12 weeks. Cell cycle analysis of liver cells, miRNA-222, miRNA-199a, miRNA-195, and miRNA-125b expression in the liver and serum, and target protein expression were performed at different time points. The results showed a higher percentage of hepatocytes in the G1/G0 and S phases at the end of 6 and 12 weeks of VC exposure, respectively. MiRNA-222 expression decreased initially and then increased, whereas miRNA-199a, miRNA-195, and miRNA-125b expression increased initially and then decreased, which corresponded with changes in cell cycle distribution and related target proteins expression (p27, cyclinA, cyclinD1, and CDK6). The corresponding expression levels of miRNAs in serum did not change. Dynamic changes in miR-222, miR-199a, miR-195, and miR-125b induced by VC can lead to cell cycle deregulation by affecting cell cycle-related proteins, and these miRNAs can serve as early biomarkers for malignant transformation caused by VC.

Live birth after cervical ectopic uterus transplantation in mice.

An ideal animal model is a prerequisite for the basic research of uterus transplantation. This study aimed to develop a new cervical ectopic uterus transplantation mice model, which was established by vascular anastomosis of the right common iliac artery and vein of the donor with the right common carotid artery and external jugular vein of the recipient, respectively, using the cuff method. The survival status of the transplanted uterus was assessed by macroscopic observation and histological examination after surgery, and the function of the graft uterus was tested by verifying whether the pregnancy is possible. A total of 40 transplants were performed, of which only 1 failed due to donor hemorrhage. After 26 transplants, the total operation time reduced to 52.4 ± 3.8 minutes, of which the total ischemia time took 6.6 ± 1.1 minutes. Sixty days after transplantation, all the graft uteri had a good blood supply and spontaneous contraction. The histology showed no significant difference between the transplanted uterus and the native. Embryo transfer experiments have proven that the transplanted uterus has uterine function. In conclusion, this new model is an effective and simple mice model for the studies of the scientific issues related to uterus transplantation.

Combination of N, N'-dicyclohexyl-N-arachidonic acylurea and tacrolimus prolongs cardiac allograft survival in mice.

Current immunosuppressive agents for organ transplantation are not ideal because of their strong toxicity and adverse effects. Hence, there is an urgent need to develop novel immunosuppressive agents. The compound N, N'-dicyclohexyl-N-arachidonic acylurea (DCAAA) is a novel highly unsaturated fatty acid from the traditional Chinese medicinal plant Radix Isatidis. In this study, we systematically investigated the toxicity, immunosuppressive effect and mechanisms underlying the activity of DCAAA. The toxicity tests showed that DCAAA treatment did not lead to red blood cell hemolysis and did not affect the liver and kidney functions in mice. The lymphocyte transformation test showed that DCAAA treatment inhibited lymphocyte proliferation in a dose-dependent manner. An in vivo cardiac allotransplantation experiment showed that DCAAA treatment could suppress the immune rejection and significantly prolong the survival of cardiac allografts in recipient mice by reducing the proportion of CD4+ T cells in the spleen and grafts, concentration of interferon-γ in the supernatant and serum and infiltration of inflammatory cells into the grafts. Moreover, a combination treatment with DCAAA and tacrolimus had a synergistic effect in preventing acute rejection of heart transplants. In vitro molecular biology experiments showed that DCAAA treatment inhibited activation of the T-cell receptor-mediated phosphoinostide 3-kinase-protein kinase B pathway, thereby arresting cell cycle transition from the G1 to the S phase, and inhibiting lymphocyte proliferation. Overall, our study reveals a novel, low-toxicity immunosuppressive agent that has the potential to reduce the toxic side effects of existing immunosuppressive agents when used in combination with them.

Arsenic trioxide ameliorates experimental autoimmune encephalomyelitis in C57BL/6 mice by inducing CD4+ T cell apoptosis.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by severe white matter demyelination. Because of its complex pathogenesis, there is no definite cure for MS. Experimental autoimmune encephalomyelitis (EAE) is an ideal animal model for the study of MS. Arsenic trioxide (ATO) is an ancient Chinese medicine used for its therapeutic properties with several autoimmune diseases. It is also used to inhibit acute immune rejection due to its anti-inflammatory and immunosuppressive properties. However, it is unclear whether ATO has a therapeutic effect on EAE, and the underlying mechanisms have not yet been clearly elucidated. In this study, we attempted to assess whether ATO could be used to ameliorate EAE in mice. METHODS: ATO (0.5 mg/kg/day) was administered intraperitoneally to EAE mice 10 days post-immunization for 8 days. On day 22 post-immunization, the spinal cord, spleen, and blood were collected to analyze demyelination, inflammation, microglia activation, and the proportion of CD4+ T cells. In vitro, for mechanistic studies, CD4+ T cells were sorted from the spleen of naïve C57BL/6 mice and treated with ATO and then used for an apoptosis assay, JC-1 staining, imaging under a transmission electron microscope, and western blotting. RESULTS: ATO delayed the onset of EAE and alleviated the severity of EAE in mice. Treatment with ATO also attenuated demyelination, alleviated inflammation, reduced microglia activation, and decreased the expression levels of IL-2, IFN-γ, IL-1ß, IL-6, and TNF-α in EAE mice. Moreover, the number and proportion of CD4+ T cells in the spinal cord, spleen, and peripheral blood were reduced in ATO-treated EAE mice. Finally, ATO induced CD4+ T cell apoptosis via the mitochondrial pathway both in vitro and in vivo. Additionally, the administration of ATO had no adverse effect on the heart, liver, or kidney function, nor did it induce apoptosis in the spinal cord. CONCLUSIONS: Overall, our findings indicated that ATO plays a protective role in the initiation and progression of EAE and has the potential to be a novel drug in the treatment of MS.

Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4.

The emergence of immune checkpoint inhibitors (ICIs), mainly including anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) monoclonal antibodies (mAbs), has shaped therapeutic landscape of some type of cancers. Despite some ICIs have manifested compelling clinical effectiveness in certain tumor types, the majority of patients still showed de novo or adaptive resistance. At present, the overall efficiency of immune checkpoint therapy remains unsatisfactory. Exploring additional immune checkpoint molecules is a hot research topic. Recent studies have identified several new immune checkpoint targets, like lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), T cell immunoglobulin and ITIM domain (TIGIT), V-domain Ig suppressor of T cell activation (VISTA), and so on. The investigations about these molecules have generated promising results in preclinical studies and/or clinical trials. In this review, we discussed the structure and expression of these newly-characterized immune checkpoints molecules, presented the current progress and understanding of them. Moreover, we summarized the clinical data pertinent to these recent immune checkpoint molecules as well as their application prospects.

Next generation chimeric antigen receptor T cells: safety strategies to overcome toxicity.

Chimeric antigen receptor T (CAR-T) cell therapy is an emerging and effective cancer immunotherapy. Especially in hematological malignancies, CAR-T cells have achieved exciting results. Two Anti-CD19 CAR-T therapies have been approved for the treatment of CD19-positive leukemia or lymphoma. However, the application of CAR-T cells is obviously hampered by the adverse effects, such as cytokines release syndrome and on-target off-tumor toxicity. In some clinical trials, patients quitted the treatment of CAR-T cells due to life-threatening toxicity. Seeking to alleviate these toxicities or prevent the occurrence, researchers have developed a number of safety strategies of CAR-T cells, including suicide genes, synthetic Notch receptor, on-switch CAR, combinatorial target-antigen recognition, bispecific T cell engager and inhibitory CAR. This review summarized the preclinical studies and clinical trials of the safety strategies of CAR-T cells and their respective strengths and weaknesses.

Evaluation of renal dysfunction using texture analysis based on DWI, BOLD, and susceptibility-weighted imaging.

OBJECTIVE: To explore the value of texture analysis based on diffusion-weighted imaging (DWI), blood oxygen level-dependent MRI (BOLD), and susceptibility-weighted imaging (SWI) in evaluating renal dysfunction. METHODS: Seventy-two patients (mean age 53.72 ± 13.46 years) underwent MRI consisting of DWI, BOLD, and SWI. According to their estimated glomerular filtration rate (eGFR), the patients were classified into either severe renal function impairment (sRI, eGFR < 30 mL/min/1.73 m2), non-severe renal function impairment (non-sRI, eGFR ≥ 30 mL/min/1.73 m2, and < 80 mL/min/1.73 m2), or control (CG, eGFR ≥ 80 mL/min/1.73 m2) groups. Thirteen texture features were extracted and then were analyzed to select the most valuable for discerning the three groups with each imaging method. A ROC curve was performed to compare the capacities of the features to differentiate non-sRI from sRI or CG. RESULTS: Six features proved to be the most valuable for assessing renal dysfunction: 0.25QuantileDWI, 0.5QuantileDWI, HomogeneityDWI, EntropyBOLD, SkewnessSWI, and CorrelationSWI. Three features derived from DWI (0.25QuantileDWI, 0.5QuantileDWI, and HomogeneityDWI) were smaller in sRI than in non-sRI; EntropyBOLD and CorrelationSWI were smaller in non-sRI than in CG (p < 0.05). 0.25QuantileDWI, 0.5QuantileDWI, and HomogeneityDWI showed similar capacities for differentiating sRI from non-sRI. Similarly, EntropyBOLD and CorrelationSWI showed equal capacities for differentiating non-sRI from CG. CONCLUSION: Texture analysis based on DWI, BOLD, and SWI can assist in assessing renal dysfunction, and texture features based on BOLD and SWI may be suitable for assessing renal dysfunction during early stages. KEY POINTS: • Texture analysis based on MRI techniques allowed for assessing renal dysfunction. • Texture features based on BOLD and SWI, but not DWI, may be suitable for assessing renal function impairment during early stages. • SWI exhibited a similar capacity to BOLD for assessing renal dysfunction.

EGFR-TKIs resistance via EGFR-independent signaling pathways.

Tyrosine kinase inhibitors (TKIs)-treatments bring significant benefit for patients harboring epidermal growth factor receptor (EGFR) mutations, especially for those with lung cancer. Unfortunately, the majority of these patients ultimately develop to the acquired resistance after a period of treatment. Two central mechanisms are involved in the resistant process: EGFR secondary mutations and bypass signaling activations. In an EGFR-dependent manner, acquired mutations, such as T790 M, interferes the interaction between TKIs and the kinase domain of EGFR. While in an EGFR-independent manner, dysregulation of other receptor tyrosine kinases (RTKs) or abnormal activation of downstream compounds both have compensatory functions against the inhibition of EGFR through triggering phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) signaling axes. Nowadays, many clinical trials aiming to overcome and prevent TKIs resistance in various cancers are ongoing or completed. EGFR-TKIs in accompany with the targeted agents for resistance-related factors afford a promising first-line strategy to further clinical application.

MAT1 correlates with molecular subtypes and predicts poor survival in breast cancer.

OBJECTIVE: Menage a trois 1 (MAT1) is a targeting subunit of cyclin-dependent kinase-activating kinase and general transcription factor IIH kinase, which modulates cell cycle, transcription and DNA repair. Its dysregulation is responsible for diseases including cancers. To further explore the role of MAT1 in breast cancer, we investigated the pathways in which MAT1 might be involved, the association between MAT1 and molecular subtypes, and the role of MAT1 in clinical outcomes of breast cancer patients. METHODS: We conducted immunohistochemistry staining on tissue microarray and immunofluorescence staining on sections of MAT1 stable breast cancer cells. Also, we performed Kyoto Encyclopedia of Genes and Genomes pathway analysis, correlation analysis and prognosis analysis on public databases. RESULTS: MAT1 was involved in multiple pathways including normal physiology signaling and disease-related signaling. Furthermore, MAT1 positively correlated with the protein status of estrogen receptor and progesterone receptor, and was enriched in luminal-type and human epidermal growth factor receptor 2-enriched breast cancer in comparison with basal-like subtype at both mRNA and protein levels. Correlation analysis revealed significant association between MAT1 mRNA amount and epithelial markers, mesenchymal markers, cancer stem cell markers, apoptosis markers, transcription markers and oncogenes. Consistently, the results of immunofluorescence stain indicated that MAT1 overexpression enhanced the protein abundance of epidermal growth factor receptor, vimentin, sex determining region Y-box 2 and sine oculis homeobox homolog 1. Importantly, Kaplan-Meier Plotter analysis reflected that MAT1 could serve as a prognostic biomarker predicting worse relapse-free survival and metastasis-free survival. CONCLUSIONS: MAT1 is correlated with molecular subtypes and is associated with unfavorable prognosis for breast cancer patients.

Targeting interlukin-6 to relieve immunosuppression in tumor microenvironment.

Immunotolerance is one of the hallmarks of malignant tumors. Tumor cells escape from host immune surveillance through various mechanisms resulting in tumor progression and therapeutic resistance. Interlukin-6 is a proinflammatory cytokine involved in many physiological and pathological processes by integrating with multiple intracellular signaling pathways. Aberrant expression of interlukin-6 is associated with the growth, metastasis, and chemotherapeutic resistance in a wide range of cancers. Interlukin-6 exerts immunosuppressive capacity mostly by stimulating the infiltrations of myeloid-derived suppressor cells, tumor-associated neutrophils, and cancer stem-like cells via Janus-activated kinase/signal transducer and activator of transcription 3 pathway in tumor microenvironment. On this foundation, blockage of interlukin-6 signal may provide potential approaches to novel therapies. In this review, we introduced interlukin-6 pathways and summarized molecular mechanisms related to interlukin-6-induced immunosuppression of tumor cell. We also concluded recent clinical studies targeting interlukin-6 as an immune-based therapeutic intervention in patients with cancer.

Synthesis of Platinum Nanotubes and Nanorings via Simultaneous Metal Alloying and Etching.

Metallic nanotubes represent a class of hollow nanostructures with unique catalytic properties. However, the wet-chemical synthesis of metallic nanotubes remains a substantial challenge, especially for those with dimensions below 50 nm. This communication describes a simultaneous alloying-etching strategy for the synthesis of Pt nanotubes with open ends by selective etching Au core from coaxial Au/Pt nanorods. This approach can be extended for the preparation of Pt nanorings when Saturn-like Au core/Pt shell nanoparticles are used. The diameter and wall thickness of both nanotubes and nanorings can be readily controlled in the range of 14-37 nm and 2-32 nm, respectively. We further demonstrated that the nanotubes with ultrathin side walls showed superior catalytic performance in oxygen reduction reaction.