Fatigue Behavior of the FGH96 Superalloy under High-Temperature Cyclic Loading.

Strain-controlled low-cycle fatigue (LCF) tests and stress-controlled creep-fatigue interaction (CFI) tests on the FGH96 superalloy were carried out at 550 °C to obtain the cyclic softening/hardening characteristics at different strain amplitudes and ratcheting strain characteristics under different hold time. The failure mechanism of the FGH96 superalloy under different loading conditions was analyzed through fracture observations. The results show that the FGH96 superalloy exhibits different cyclic softening/hardening characteristics at different strain amplitudes, and the introduction of the hold time at peak stress exacerbates the ratcheting strain of the FGH96 superalloy under asymmetric stress cycles. Fracture observations show that the magnitude of the strain amplitude, high-temperature oxidation, and the introduction of the hold time will affect the mechanical properties of the FGH96 superalloy and change its fracture mode.

China's wetland soil organic carbon pool: New estimation on pool size, change, and trajectory.

Robust estimates of wetland soil organic carbon (SOC) pools are critical to understanding wetland carbon dynamics in the global carbon cycle. However, previous estimates were highly variable and uncertain, due likely to the data sources and method used. Here we used machine learning method to estimate SOC storage and their changes over time in China's wetlands based on wetland SOC density database, associated geospatial environmental data, and recently published wetland maps. We built a database of wetland SOC density in China that contains 809 samples from 181 published studies collected over the last 20 years as presented in the published literature. All samples were extended and standardized to a 1-m depth, on the basis of the relationship between SOC density data from soil profiles of different depths. We used three different machine learning methods to evaluate their robustness in estimating wetland SOC storage and changes in China. The results indicated that random forest model achieved accurate wetland SOC estimation with R2 being .65. The results showed that average SOC density of top 1 m in China's wetlands was 25.03 ± 3.11 kg C m-2 in 2000 and 26.57 ± 3.73 kg C m-2 in 2020, an increase of 6.15%. SOC storage change from 4.73 ± 0.58 Pg in 2000 to 4.35 ± 0.61 Pg in 2020, a decrease of 8.03%, due to 13.6% decreased in wetland area from 189.12 × 103 to 162.8 × 103 km2 in 2020, despite the increase in SOC density during the same time period. The carbon accumulation rate was 107.5 ± 12.4 g C m-2 year-1 since 2000 in wetlands with no area changes. Climate change caused variations in wetland SOC density, and a future warming and drying climate would lead to decreases in wetland SOC storage. Estimates under Shared Socioeconomic Pathway 1-2.6 (low-carbon emissions) suggested that wetland SOC storage in China would not change significantly by 2100, but under Shared Socioeconomic Pathway 5-8.5 (high-carbon emissions), it would decrease significantly by approximately 5.77%. In this study, estimates of wetland SOC storage were optimized from three aspects, including sample database, wetland extent, and estimation method. Our study indicates the importance of using consistent SOC density and extent data in estimating and projecting wetland SOC storage.

Mapping global distribution of mangrove forests at 10-m resolution.

Mangrove forests deliver incredible ecosystem goods and services and are enormously relevant to sustainable living. An accurate assessment of the global status of mangrove forests warrants the necessity of datasets with sufficient information on spatial distributions and patch patterns. However, existing datasets were mostly derived from âˆ¼30 m resolution satellite imagery and used pixel-based image classification methods, which lacked spatial details and reasonable geo-information. Here, based on Sentinel-2 imagery, we created a global mangrove forest dataset at 10-m resolution, namely, High-resolution Global Mangrove Forests (HGMF_2020), using object-based image analysis and random forest classification. We then analyzed the status of global mangrove forests from the perspectives of conservation, threats, and resistance to ocean disasters. We concluded the following: (1) globally, there were 145,068 km2 mangrove forests in 2020, among which Asia contained the largest coverage (39.2%); at the country level, Indonesia had the largest amount of mangrove forests, followed by Brazil and Australia. (2) Mangrove forests in South Asia were estimated to be in the better status due to the higher proportion of conservation and larger individual patch size; in contrast, mangrove forests in East and Southeast Asia were facing intensive threats. (3) Nearly, 99% of mangrove forest areas had a patch width greater than 100 m, suggesting that nearly all mangrove forests were efficient in reducing coastal wave energy and impacts. This study reports an innovative and up-to-date dataset and comprehensive information on mangrove forests status to contribute to related research and policy implementation, especially for supporting sustainable development.

Uniaxial Compressive Stress-Strain Model of Jujube Nucleus Concrete following Exposure to Elevated Temperatures.

Aiming to provide a solution for natural resource consumption and agricultural waste pollution, jujube nucleus is utilized as a substitute for coarse aggregate in the preparation of lightweight aggregate concrete. The effect of the jujube nucleus (JN) replacement ratio and the elevated temperature on the uniaxial compressive stress-strain curves of jujube nucleus concrete (JNC) are experimentally studied. The results show that the failure of the JNC prisms became more serious with the increase in the JN replacement ratio. The linear proportion in ascending branch and the descending slope of the stress-strain curves for JNC increased gradually with the increase in the JN replacement ratio and elevated temperature, which is probably owing to the higher porosity and lower stiffness of the jujube nucleus, compared to natural aggregate. Moreover, as the JN replacement ratio and the elevated temperature increase, the peak stress and elastic modulus in the stress-strain curves of JNC decrease gradually, whilst an increase in the peak strain shows up, which is possibly due to the growth of hydrate calcium silicate and calcium hydroxide hampered by sucrose molecules. Based on the test results, a series of theoretical formulas are proposed to predict the compressive performance of JNC. A material constitutive model is developed for describing the stress-strain relationship of JNC by considering the JN replacement ratio and elevated temperature.

Invasion of Spartina alterniflora in the coastal zone of mainland China: Control achievements from 2015 to 2020 towards the Sustainable Development Goals.

The Sustainable Development Goals (SDGs) and the Convention on Biological Diversity's 15th Conference of the Parties (CBD COP15) both emphasized the urgency of protecting biological diversity. Spartina alterniflora (S. alterniflora), as an invasive species in China, has posed severe biodiversity challenges, demanding nationwide control and management. This study aims to assess the effectiveness of S. alterniflora management during China's SDGs implementation from 2015 to 2020. Landsat images acquired in 2015 (the beginning year of SDGs), 2018, and 2020 (the end year of SDGs' targets 6.6, 14.2, 14.5, and 15.8 related to alien invasion) were applied to quantify the spatiotemporal dynamics of S. alterniflora extent. The results revealed a consistent shrinkage of S. alterniflora, with a net areal reduction of 2610 ha from 2015 to 2020, implying the effectiveness of control measures on S. alterniflora invasion. Provinces including Zhejiang, Jiangsu, and Shanghai have succeeded in controlling S. alterniflora, evidenced by the sharp reduction in S. alterniflora area by 4908 ha, 2176 ha, and 1034 ha, respectively, from 2015 to 2020. However, better management of S. alterniflora is needed in regions with more severe S. alterniflora invasion, e.g., Shandong, Fujian, and Guangdong provinces. Our results suggest that relevant policies, regulations, and ecological restoration projects implemented by national or local governments in China received satisfactory results in S. alterniflora control. Nevertheless, S. alterniflora potential utilities and its governance effectiveness should be objectively evaluated and weighed to obtain the greatest ecological benefits and promote sustainable coastal ecosystems. The results of this study are expected to provide important baseline information benefitting the formulation of coastal protection and restoration strategies in China.

An emerging coastal wetland management dilemma between mangrove expansion and shorebird conservation.

Coastal wetlands around the world have been degraded by human activities. Global declines in the extent of important habitats including mangroves, salt marsh and tidal flats necessitate mitigation and restoration efforts, however some well-meaning management actions, particularly mangrove afforestation and breakwater construction, can inadvertently cause further loss and degradation if these actions are not planned carefully. In particular, there is a potential conflict between mangrove and shorebird conservation, because mangrove afforestation and restoration may occur at the expense of bare tidal flats, which form the main foraging habitats for threatened coastal migratory shorebirds as well as supporting other coastal organisms. Here, we present several case studies that illustrate the trade-off between mangroves and bare tidal flats. To investigate whether these examples reflect an emerging broad-scale issue, we use satellite imagery to develop a detailed quantification of the change in mangrove habitat extent in 22 important shorebird areas in mainland China between 2000 and 2015. Our results indicate that 1) the extent of mangroves across all sites expanded significantly between 2000 and 2015 (p < 0.01, n = 14) while tidal flat extent in the same areas declined significantly within the same period (p < 0.01, n = 21); 2) among the 14 sites where mangroves were present, the dual threat of mangrove expansion and tidal flat loss have considerably reduced shorebird habitat in eight of these sites. To ensure effective conservation of both mangroves and shorebirds, we propose a decision tree framework for resolving this emerging dilemma between mangrove afforestation and shorebird protection, which requires careful consideration of alternative management strategies. This article is protected by copyright. All rights reserved.

Assessing the Ecosystem Health of Coastal Wetland Vegetation (Suaeda salsa) Using the Pressure State Response Model, a Case of the Liao River Estuary in China.

Suaeda salsa (S. salsa) is an important ecological barrier and tourism resource in coastal wetland resources, and assessing changes in its health is beneficial for protecting the ecological health of wetlands and increasing finances. The aim was to explore improvements in the degradation of S. salsa communities in the Liao River Estuary National Nature Reserve since a wetland restoration project was carried out in Panjin, Liaoning Province, China, in 2015. In this study, landscape changes in the reserve were assessed based on Sentinel-2 images classification results from 2016 to 2019. A pressure-state-response framework was constructed to assess the annual degradation of S. salsa communities within the wetlands. The assessment results show that the area of S. salsa communities and water bodies decreased annually from 2016 to 2019, and the increased degradation indicators indicate a state of continued degradation. The area of types such as aquaculture ponds and Phragmites australis communities did not change much, while the estuarine mudflats increased year by year. The causes of S. salsa community degradation include anthropogenic impacts from abandoned aquaculture ponds and sluice control systems but also natural impacts from changes in the tidal amplitude and soil properties of the mudflats. The results also indicate that the living conditions of S. salsa in the Liao River estuary wetlands are poor and that anthropogenic disturbance is necessary to restore the original vegetation abundance.

Targeting IL-21 to tumor-reactive T cells enhances memory T cell responses and anti-PD-1 antibody therapy.

T cell rejuvenation by PD-1/PD-L1 blockade, despite emerging as a highly promising therapy for advanced cancers, is only beneficial for a minority of treated patients. There is evidence that a lack of efficient T cell activation may be responsible for the failure. Here, we demonstrate that IL-21 can be targeted to tumor-reactive T cells by fusion of IL-21 to anti-PD-1 antibody. To our surprise, the fusion protein PD-1Ab21 promotes the generation of memory stem T cells (TSCM) with enhanced cell proliferation. PD-1Ab21 treatment show potent antitumor effects in established tumor-bearing mice accompanied with an increased frequency of TSCM and robust expansion of tumor-specific CD8+ T cells with a memory phenotype, and is superior to a combination of PD-1 blockade and IL-21 infusion. Therefore, we have developed a potential strategy to improve the therapeutic effects of immune checkpoint blockade by simultaneously targeting cytokines to tumor-reactive T cells.

Wetland changes in the Amur River Basin: Differing trends and proximate causes on the Chinese and Russian sides.

According to the United Nations Sustainable Development Goals (SDGs), understanding the extent of wetlands, their change trends and the proximate causes is important for the conservation of wetlands and endangered waterfowls. Here we studied the world's ninth largest river basin, the Amur River Basin (ARB), with a land area of 2.08 million km2. Our objectives were to address the information deficiencies of spatially explicit wetland distributions and their changes and to quantify the proximate causes of these changes in various periods in the ARB. A hybrid approach combining object-based and hierarchical decision-trees classification (HOHC) was applied to Landsat series images to obtain multitemporal land cover datasets from 1980 to 2016. Further quantitative analysis revealed that the ARB held 184,561 km2 of wetlands in 2016, accounting for 9% of the whole basin area. Among these, 59% of the wetlands were identified on the Russian side, while 40% were on the Chinese side, and 1% were on the Mongolian side. The ARB lost 22% of its wetland (52,246 km2) from 1980 to 2016, with a consistent net loss from 1980 to 2010 but an area gain from 2010 to 2016. Human activities dominated the consistent wetland losses on the Chinese side of the ARB, of which cropland expansion was the primary proximate cause of wetland loss (69%). Conversely, the wetlands on the Russian side had consistent losses from 1980 to 2010 followed by a gain from 2010 to 2016, which could be attributed to climate change. These quantified data will inform decision-making on wetland conservation and benefit scientific studies depending on spatially explicit wetland information.

Association of MSH2 Expression With Tumor Mutational Burden and the Immune Microenvironment in Lung Adenocarcinoma.

Immune checkpoint blockade (ICB) therapies that target programmed cell death 1 (PD1) and PD1 ligand 1 (PDL1) have demonstrated promising benefits in lung adenocarcinoma (LUAD), and tumor mutational burden (TMB) is the most robust biomarker associated with the efficacy of PD-1-PD-L1 axis blockade in LUAD, but the assessment of TMB by whole-exome sequencing (WES) is rather expensive and time-consuming. Although targeted panel sequencing has been developed and approved by the US Food and Drug Administration (FDA) to estimate TMB, we found that its predictive accuracy for ICB response was significantly lower than WES in LUAD. Given that previous studies were mainly focusing on genomic variations to explore surrogate biomarkers of TMB, we turned to examine the transcriptome-based correlation with TMB in this study. Combining three immunotherapeutic cohorts with two independent The Cancer Genome Atlas (TCGA) datasets, we revealed that the expression of mutS homolog 2 (MSH2), one of the most crucial genes involved in DNA mismatch repair (MMR) pathway, was the strongest feature associated with increased TMB in multivariate analysis. Furthermore, MSH2 expression also displayed a significantly positive correlation with smoking signature while an inverse association with MMR deficiency (MMRd) signature in LUAD. More importantly, high expression of MSH2 markedly correlated with increased PD-L1 expression and CD8+ T cell infiltration, both suggesting a prominent immunotherapy-responsive microenvironment in LUAD. Notably, detecting MSH2 expression is much easier, faster, and cheaper than TMB in clinical practice. Taken together, this study demonstrates the association of MSH2 expression with TMB and the immune microenvironment in LUAD. MSH2 expression may be developed as a potential surrogate biomarker of TMB to identify ICB responders in LUAD.

Rapid Invasion of Spartina Alterniflora in the Coastal Zone of Mainland China: Spatiotemporal Patterns and Human Prevention.

Given the extensive spread and ecological consequences of exotic Spartina alterniflora (S. alterniflora) over the coast of mainland China, monitoring its spatiotemporal invasion patterns is important for the sake of coastal ecosystem management and ecological security. In this study, Landsat series images from 1990 to 2015 were used to establish multi-temporal datasets for documenting the temporal dynamics of S. alterniflora invasion. Our observations revealed that S. alterniflora had a continuous expansion with the area increasing by 50,204 ha during the considered 25 years. The largest expansion was identified in Jiangsu Province during the period of 1990-2000, and in Zhejiang Province during the periods 2000-2010 and 2010-2015. Three noticeable hotspots for S. alterniflora invasion were Yancheng of Jiangsu, Chongming of Shanghai, and Ningbo of Zhejiang, and each had a net area increase larger than 5000 ha. Moreover, an obvious shrinkage of S. alterniflora was identified in three coastal cities including the city of Cangzhou of Hebei, Dongguan, and Jiangmen of Guangdong. S. alterniflora invaded mostly into mudflats (>93%) and shrank primarily due to aquaculture (55.5%). This study sheds light on the historical spatial patterns in S. alterniflora distribution and thus is helpful for understanding its invasion mechanism and invasive species management.

Sensitive, selective and simultaneous electrochemical detection of multiple heavy metals in environment and food using a lowcost Fe3O4 nanoparticles/fluorinated multi-walled carbon nanotubes sensor.

Multiple heavy metals pollution in environment and food has become an ever-increasing concern and poses a serious threat towards humans and animals. To broad the multiple heavy metals detection, Fe3O4 nanoparticles, Fe3O4/multi-walled carbon nanotubes (Fe3O4/MWCNTs) and Fe3O4/fluorinated multi-walled carbon nanotubes (Fe3O4/F-MWCNTs) nanocomposites were synthesized by hydrothermal method and constructed as a simultaneous electrochemical sensor, respectively. Compared the catalytic performances of the three electrochemical sensors for the simultaneous detection of Cd2+, Pb2+, Cu2+, and Hg2+, the results showed that the Fe3O4/F-MWCNTs sensor demonstrated preponderant performance. It showed the sensitivity of 108.79, 125.91, 160.85, and 312.65 µA mM-1 cm-2 toward Cd2+, Pb2+, Cu2+, and Hg2+, respectively, which was obviously higher than that of Fe3O4/MWCNTs and Fe3O4. Additionally, the Fe3O4/F-MWCNTs sensor exhibited the wider linear detection ranges of 0.5-30.0, 0.5-30.0, 0.5-30.0, and 0.5-20.0 µM for Cd2+, Pb2+, Cu2+, and Hg2+, respectively. The limit of detections of the Fe3O4/F-MWCNTs sensor were 0.05, 0.08, 0.02, and 0.05 nM (signal to noise ratio of 3) for Cd2+, Pb2+, Cu2+, and Hg2+, respectively, fulfilling the governmental requests of the World Health Organization, China and Indian. The excellent agreement was recorded between the lowcost Fe3O4/F-MWCNTs sensor and typical methods (inductively coupled plasma mass spectrometry or atomic fluorescence spectrometry) in river water and soybean samples. Additionally, the sensor also exhibited excellent performances in selectivity, recovery, stability, and reproducibility. This proposal sensor provides a promising strategy to monitor multiple targets in the environment and food.

Simultaneous voltammetric determination of cadmium(II), lead(II), mercury(II), zinc(II), and copper(II) using a glassy carbon electrode modified with magnetite (Fe3O4) nanoparticles and fluorinated multiwalled carbon nanotubes.

A method is described for the simultaneous voltammetric determination of the heavy metal ions cadmium(II), lead(II), mercury(II), zinc(II), and copper(II) using a glassy carbon electrode (GCE) modified with magnetite (Fe3O4) nanoparticles and fluorinated multiwalled carbon nanotubes (Fe3O4/F-MWCNTs). The Fe3O4/F-MWCNT composite was synthesized by a hydrothermal method and characterized by X-ray photoelectron spectroscopy, X-ray diffraction, transmission electron microscopy, scanning electron microscopy, elemental mapping, electrochemical impedance spectroscopy, and square wave stripping voltammetry. Under the optimum conditions, the electrode displays excellent response to the ions. Figures of merit for Cd(II), Pb(II), Hg(II), Zn(II), and Cu(II), respectively, include (a) high electrochemical sensitivity (29.88, 43.50, 120.86, 47.34 and 90.31 (µA µM-1 cm-2), (b) well separated peaks (at -0.70, -0.53, +0.37, -1.11 and + 0.01 V vs. Ag/AgCl); (c) low limits of detection (0.014, 0.0084, 0.0039, 0.012, and 0.0053 µM); and (d) wide linear ranges (0.048-30.0, 0.028-30.0, 0.013-32.5, 0.039-32.5, and 0.017-31.5 µM). The modified GCE displays satisfying selectivity in the presence of potentially interfering other metal ions, stability for 30 days, and reproducibility of electrodes (with a relative standard deviation between 1.2 and 4.8% for n = 6). The modified GCE was applied to the determination of several heavy metal ions in (spiked) water and rice samples, and the results agreed well with data obtained by atomic fluorescence spectrometry or inductively coupled plasma-mass spectrometry. The dramatic performance probably result from the semi-ionic C-F bond on F-MWCNTs surface with a strong negative charge, the good electrical conductivity of the F-MWCNTs and Fe3O4, the synergistic interaction between Fe3O4 and F-MWCNTs, and the nafion conductive membrane improving the stability of the modified layer and enhanced cation adsorption. Graphical abstract An environmentally-friendly, low-cost, high-throughput Fe3O4/fluorinated multi-walled carbon nanotube composite (Fe3O4/F-MWCNTs) modified glassy carbon electrode is described. It was applied to simultaneous electrochemical determination of Cd(II), Pb(II), Hg(II), Zn(II), and Cu(II) by square wave stripping voltammetry.

Mapping Forest Cover in Northeast China from Chinese HJ-1 Satellite Data Using an Object-Based Algorithm.

Forest plays a significant role in the global carbon budget and ecological processes. The precise mapping of forest cover can help significantly reduce uncertainties in the estimation of terrestrial carbon balance. A reliable and operational method is necessary for a rapid regional forest mapping. In this study, the goal relies on mapping forest and subcategories in Northeast China through the use of high spatio-temporal resolution HJ-1 imagery and time series vegetation indices within the context of an object-based image analysis and decision tree classification. Multi-temporal HJ-1 images obtained in a single year provide an opportunity to acquire phenology information. By analyzing the difference of spectral and phenology information between forest and non-forest, forest subcategories, decision trees using threshold values were finally proposed. The resultant forest map has a high overall accuracy of 0.91 ± 0.01 with a 95% confidence interval, based on the validation using ground truth data from field surveys. The forest map extracted from HJ-1 imagery was compared with two existing global land cover datasets: GlobCover 2009 and MCD12Q1 2009. The HJ-1-based forest area is larger than that of MCD12Q1 and GlobCover and more closely resembles the national statistics data on forest area, which accounts for more than 40% of the total area of the Northeast China. The spatial disagreement primarily occurs in the northern part of the Daxing'an Mountains, Sanjiang Plain and the southwestern part of the Songliao Plain. The compared result also indicated that the forest subcategories information from global land cover products may introduce large uncertainties for ecological modeling and these should be cautiously used in various ecological models. Given the higher spatial and temporal resolution, HJ-1-based forest products could be very useful as input to biogeochemical models (particularly carbon cycle models) that require accurate and updated estimates of forest area and type.

APOBEC3B and APOBEC mutational signature as potential predictive markers for immunotherapy response in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is known to carry heavy mutation load. Besides smoking, cytidine deaminase APOBEC3B plays a key role in the mutation process of NSCLC. APOBEC3B is also reported to be upregulated and predicts bad prognosis in NSCLC. However, targeting APOBEC3B high NSCLC is still a big challenge. Here we show that APOBEC3B upregulation is significantly associated with immune gene expression, and APOBEC3B expression positively correlates with known immunotherapy response biomarkers, including: PD-L1 expression and T-cell infiltration in NSCLC. Importantly, APOBEC mutational signature is specifically enriched in NSCLC patients with durable clinical benefit after immunotherapy and APOBEC mutation count can be better than total mutation in predicting immunotherapy response. In together, this work provides evidence that APOBEC3B upregulation and APOBEC mutation count can be used as novel predictive markers in guiding NSCLC checkpoint blockade immunotherapy.

Arthritis of large joints shown as a rare clinical feature of cytokine release syndrome after chimeric antigen receptor T cell therapy: A case report.

RATIONALE: Chimeric antigen receptor (CAR)-T cell therapy is a novel type of therapy that is being used in an increasing number of patients with acute lymphoblastic leukemia (ALL). Cytokine release syndrome (CRS) is the most common complication following CAR-T treatment, but the current understanding of the clinical manifestations and pathogenesis of CRS is still limited. PATIENT CONCERNS: A 34-year-old male patient was diagnosed with ALL in June 2015. Complete remission (CR) was achieved after induction chemotherapy. The patient received 8 cycles of consolidation chemotherapy to maintain CR. In May 2017, the patient had recurrent ALL. Induction chemotherapy was given again, but without remission. In October 2017, CAR-T cell therapy was given. On October 14, the patient was pretreated with an FC regimen (fludarabine phosphate 50 mg qd on days 1-3; cyclophosphamide 0.4 g qd on days 1-3). CAR-T cells were infused on October 19 and October 20, with the number of infused cells at 2 × 10/kg and 1 × 10/kg, respectively. On October 25, the patient had a high fever, swelling, and pain in the large joints of the limbs, and joint effusion. DIAGNOSIS: This patient was diagnosed with relapsed ALL, and he developed CRS after CAR-T therapy. INTERVENTIONS: Tacilizumab (400 mg) was infused after CRS was diagnosed, and another dose of tacilizumab (240 mg) was given 6 days later. The pain was also treated with an analgesic drug. Methylprednisolone (1 mg/kg) was given to treat arthritis of the large joints. OUTCOMES: The patient's temperature was back to normal within 1 hour following the treatment of tacilizumab, but the pain in the large joints was progressively aggravated. The joint swelling and pain were obviously alleviated after the treatment of methylprednisolone, and the joint mobility was gradually recovered. LESSONS: CRS after CAR-T therapy can manifest as a high fever with swelling and pain in the large joints of the limbs, similar to rheumatoid arthritis. Tocilizumab can lower the body temperature, but it has no significant effect on arthritis. Glucocorticoids can rapidly alleviate joint swelling and pain.

Genomic sequencing identifies a few mutations driving the independent origin of primary liver tumors in a chronic hepatitis murine model.

With the development of high-throughput genomic analysis, sequencing a mouse primary cancer model provides a new opportunity to understand fundamental mechanisms of tumorigenesis and progression. Here, we characterized the genomic variations in a hepatitis-related primary hepatocellular carcinoma (HCC) mouse model. A total of 12 tumor sections and four adjacent non-tumor tissues from four mice were used for whole exome and/or whole genome sequencing and validation of genotyping. The functions of the mutated genes in tumorigenesis were studied by analyzing their mutation frequency and expression in clinical HCC samples. A total of 46 single nucleotide variations (SNVs) were detected within coding regions. All SNVs were only validated in the sequencing samples, except the Hras mutation, which was shared by three tumors in the M1 mouse. However, the mutated allele frequency varied from high (0.4) to low (0.1), and low frequency (0.1-0.2) mutations existed in almost every tumor. Together with a diploid karyotype and an equal distribution pattern of these SNVs within the tumor, these results suggest the existence of subclones within tumors. A total of 26 mutated genes were mapped to 17 terms describing different molecular and cellular functions. All 41 human homologs of the mutated genes were mutated in the clinical samples, and some mutations were associated with clinical outcomes, suggesting a high probability of cancer driver genes in the spontaneous tumors of the mouse model. Genomic sequencing shows that a few mutations can drive the independent origin of primary liver tumors and reveals high heterogeneity among tumors in the early stage of hepatitis-related primary hepatocellular carcinoma.

COSMIC: somatic cancer genetics at high-resolution.

COSMIC, the Catalogue of Somatic Mutations in Cancer (http://cancer.sanger.ac.uk) is a high-resolution resource for exploring targets and trends in the genetics of human cancer. Currently the broadest database of mutations in cancer, the information in COSMIC is curated by expert scientists, primarily by scrutinizing large numbers of scientific publications. Over 4 million coding mutations are described in v78 (September 2016), combining genome-wide sequencing results from 28 366 tumours with complete manual curation of 23 489 individual publications focused on 186 key genes and 286 key fusion pairs across all cancers. Molecular profiling of large tumour numbers has also allowed the annotation of more than 13 million non-coding mutations, 18 029 gene fusions, 187 429 genome rearrangements, 1 271 436 abnormal copy number segments, 9 175 462 abnormal expression variants and 7 879 142 differentially methylated CpG dinucleotides. COSMIC now details the genetics of drug resistance, novel somatic gene mutations which allow a tumour to evade therapeutic cancer drugs. Focusing initially on highly characterized drugs and genes, COSMIC v78 contains wide resistance mutation profiles across 20 drugs, detailing the recurrence of 301 unique resistance alleles across 1934 drug-resistant tumours. All information from the COSMIC database is available freely on the COSMIC website.

Antibody Therapies in Cancer.

Antibody-based immunotherapy has become a standard treatment for a variety of cancers. Many well-developed antibodies disrupt signaling of various growth factor receptors for the treatment of a number of cancers by targeting surface antigens expressed on tumor cells. In recent years, a new family of antibodies is currently emerging in the clinic, which target immune cells rather than cancer cells. These immune-targeted therapies strive to augment antitumor immune responses by antagonizing immunosuppressive pathways or providing exogenous immune-activating stimuli, which have achieved dramatic results in several cancers. The future of cancer therapies is likely to combine these approaches with other treatments, including conventional therapies, to generate more effective treatments.