Prelude to the Anthropocene: Two new North American Land Mammal Ages (NALMAs)

Human impacts have left and are leaving distinctive imprints in the geological record. Here we show that in North America, the human-caused changes evident in the mammalian fossil record since c. 14,000 years ago are as pronounced as earlier faunal changes that subdivide Cenozoic epochs into the North American Land Mammal Ages (NALMAs). Accordingly, we define two new North American Land Mammal Ages, the Santarosean and the Saintagustinean, which subdivide Holocene time and complete a biochronologic system that has proven extremely useful in dating terrestrial deposits and in revealing major features of faunal change through the past 66 million years. The new NALMAs highlight human-induced changes to the Earth system, and inform the debate on whether or not defining an Anthropocene epoch is justified, and if so, when it began

不同年龄和性别精神分裂症患者脑白质扩散张量成像的临床研究*

Objective: Diffusion tensor imaging (DTI) was used to analyze the changes of white matter fiber FA in patients with schizophrenia of different ages and genders, and to explore the reference of clinical imaging. Methods: Retrospective analysis of the clinical diagnosis of schizophrenia patients and healthy subjects in all 50 cases, were given routine examination of brain MRI parallel diffusion tensor imaging, comparison of different age and gender in different parts of the brain white matter changes of FA value. Results: (1) the FA values of white matter in different age groups were different between the patients and the normal group (P < 0.05). The normal group right superior frontal gyrus, left parietal lobe and left anterior cingulate gyrus of the cerebral white matter fiber FA value increased gradually before the age of 30, at the age of 30 and reached the peak gradually decreased after 30 years old. The left frontal gyrus and corpus callosum in patients with group pressure (after) of cerebral white matter fiber FA value increased gradually before the age of 30, at the age of 30 and reached the peak gradually decreased after 30 years old. (2) the FA values of white matter in different parts of male and female patients were different (P < 0.05). The white matter fiber FA in the left anterior capsule of the normal group was higher in males than in females. The FA value of bilateral occipital white matter in male patients was lower than that in female; the FA values of the central white matter in the left and right sides of the brain stem were higher in males than in females. Conclusion: the changes of FA value in the white matter of some parts of the brain in the normal group and the patient group are influenced by age and sex.  目的  运用扩散张量成像分析不同年龄和性别精神分裂症患者脑白质纤维FA值的变化，探讨临床影像学参考依据。方法  回顾性分析经临床确诊的精神分裂症患者和健康者各50例，均作颅脑MRI常规检查并行扩散张量成像，比较不同年龄和性别各部位脑白质FA值变化特点。结果  （1）患者组和正常组不同年龄各部位脑白质FA值有差异（P＜0.05）。正常组中右额上回、左顶叶及左扣带回前部脑白质纤维FA值在30岁前逐渐增高，30岁达高峰，在30岁后逐渐减少。患者组中左额上回及胼胝体压部（后）脑白质纤维FA值在30岁前逐渐增高，30岁达高峰，在30岁后逐渐减少。（2）患者组和正常组男女各部位脑白质FA值有差异（P＜0.05）。发现正常组中左侧内囊前肢脑白质纤维FA值男性较女性高。患者组中双侧枕叶脑白质纤维FA值男性较女性低；脑干左右侧中心脑白质FA值男性较女性高。结论  正常组和患者组大脑某些部位脑白质纤维FA值量的变化受年龄、性别的影响

Living grass mulching improves soil enzyme activities through enhanced available nutrients in citrus orchards in subtropical China

Living grass mulching (LGM) is an important orchard floor management that has been applied worldwide. Although LGM can effectively enhance soil nutrient availability and fertility, its effects on microbial-mediated soil nutrient cycling and main drivers are unclear. Meanwhile, the variation of enzyme activities and soil nutrient availability with LGM duration have been rarely studied. This study aims to explore the effects of mulching age and soil layer on enzyme activities and soil nutrients in citrus orchards. In this study, three LGM (Vicia villosa) treatments were applied, i.e., mulching for eight years, mulching for four years, and no mulching (clean tillage). Their effects on the enzyme activities and soil nutrients were analyzed in different soil layers of citrus orchards in subtropical China, i.e., 0-10, 10-20, and 20-40 cm. Compared to clean tillage, mulching for four years had fewer effects on enzyme activities and soil nutrients. In contrast, mulching for eight years significantly increased available nitrogen (N), phosphorus (P) nutrients, β-glucosidase, and cellobiohydrolase activities in the soil layer of 0-20 cm. In the soil layer of 0-40 cm, microbial biomass carbon (C), N, P, N-acetylglucosaminidase, leucine aminopeptidase, and acid phosphatase activities also increased (P < 0.05). Mulching for eight years significantly promoted C, N, and P-cycling enzyme activities and total enzyme activities by 2.45-6.07, 9.29-54.42, 4.42-7.11, and 5.32-14.91 times, respectively. Redundancy analysis shows that mulching treatments for eight and four years had soil layer-dependent positive effects on soil enzyme activities. Microbial C and P showed the most significant positive correlation with enzyme activities, followed by moisture content, organic C, and available N (P < 0.05). Available nutrients contributed almost 70% to affect enzyme activities significantly and were the main drivers of the enzyme activity variation. In summary, LGM could improve soil enzyme activities by increasing available nutrients. The promotion effect was more significant under mulching for eight years. Therefore, extending mulching age and improving nutrient availability are effective development strategies for sustainable soil management in orchard systems. Our study can provide valuable guidelines for the design and implementation of more sustainable management practices in citrus orchards

Membrane Fusion Involved in Neurotransmission: Glimpse from Electron Microscope and Molecular Simulation

Membrane fusion is one of the most fundamental physiological processes in eukaryotes for triggering the fusion of lipid and content, as well as the neurotransmission. However, the architecture features of neurotransmitter release machinery and interdependent mechanism of synaptic membrane fusion have not been extensively studied. This review article expounds the neuronal membrane fusion processes, discusses the fundamental steps in all fusion reactions (membrane aggregation, membrane association, lipid rearrangement and lipid and content mixing) and the probable mechanism coupling to the delivery of neurotransmitters. Subsequently, this work summarizes the research on the fusion process in synaptic transmission, using electron microscopy (EM) and molecular simulation approaches. Finally, we propose the future outlook for more exciting applications of membrane fusion involved in synaptic transmission, with the aid of stochastic optical reconstruction microscopy (STORM), cryo-EM (cryo-EM), and molecular simulations

Polymeric micelles based on poly(ethylene glycol) block poly(racemic amino acids) hybrid polypeptides: conformation-facilitated drug-loading behavior and potential application as effective anticancer drug carriers

In this work, racemic hybrid polypeptides poly(ethylene glycol) (PEG)-b-poly(racemic-leucine) (PRL) copolymers with different leucine residues have been synthesized and characterized. Using docetaxel as a model molecule, the high drug-loaded spherical micelles based on PEG-PRL were prepared successfully using dialysis, with a tunable particle size from 170 nm to 250 nm obtained by changing the length of the hydrophobic blocks. Facilitated drug-loading behavior (higher drug-loading ability and easier drug-loading process) of PEG-PRL compared with their corresponding levo forms (PEG-b-poly[levo leucine]) was observed and clarified for the first time. With this facilitation, the highest drug-loading content and efficiency of PEG-PRL micelles can achieve 11.2% ± 0.4% and 67.2% ± 2.4%, respectively. All drug-loaded PEG-PRL micelles exhibit a similar release behavior with a sustained release up to 72 hours. The PEG-PRL was shown to be nontoxic against MCF-7 and human umbilical vein endothelial cells up to a concentration of 100 μg/mL, displaying a good biocompatibility. Also, the docetaxel-loaded PEG-PRL micelles were more toxic than the free drug against MCF-7 human breast cancer cells – both dose and time dependent. Therefore, these high docetaxel-loaded micelles based on racemic hybrid polypeptides appear to be a novel promising nanomedicine for anticancer therapy

Glioma in Schizophrenia: Is the Risk Higher or Lower?

Whether persons with schizophrenia have a higher or lower incidence of cancer has been discussed for a long time. Due to the complex mechanisms and characteristics of different types of cancer, it is difficult to evaluate the exact relationship between cancers and schizophrenia without considering the type of tumor. Schizophrenia, a disabling mental illness that is now recognized as a neurodevelopmental disorder, is more correlated with brain tumors, such as glioma, than other types of tumors. Thus, we mainly focused on the relationship between schizophrenia and glioma morbidity. Glioma tumorigenesis and schizophrenia may share similar mechanisms; gene/pathway disruption would affect neurodevelopment and reduce the risk of glioma. The molecular defects of disrupted-in-schizophrenia-1 (DISC1), P53, brain-derived neurotrophic factor (BDNF) and C-X-C chemokine receptors type 4 (CXCR4) involved in schizophrenia pathogenesis might play opposite roles in glioma development. Many microRNAs (miRNAs) such as miR-183, miR-9, miR-137 and miR-126 expression change may be involved in the cross talk between glioma prevalence and schizophrenia. Finally, antipsychotic drugs may have antitumor effects. All these factors show that persons with schizophrenia have a decreased incidence of glioma; therefore, epidemiological investigation and studies comparing genetic and epigenetic aberrations involved in both of these complex diseases should be performed. These studies can provide more insightful knowledge about glioma and schizophrenia pathophysiology and help to determine the target/strategies for the prevention and treatment of the two diseases

Cytokine-Induced Killer Cells As Pharmacological Tools for Cancer Immunotherapy

Cytokine-induced killer (CIK) cells are a heterogeneous population of effector CD3+CD56+ natural killer T cells, which can be easily expanded in vitro from peripheral blood mononuclear cells. CIK cells work as pharmacological tools for cancer immunotherapy as they exhibit MHC-unrestricted, safe, and effective antitumor activity. Much effort has been made to improve CIK cells cytotoxicity and treatments of CIK cells combined with other antitumor therapies are applied. This review summarizes some strategies, including the combination of CIK with additional cytokines, dendritic cells, check point inhibitors, antibodies, chemotherapeutic agents, nanomedicines, and engineering CIK cells with a chimeric antigen receptor. Furthermore, we briefly sum up the clinical trials on CIK cells and compare the effect of clinical CIK therapy with other immunotherapies. Finally, further research is needed to clarify the pharmacological mechanism of CIK and provide evidence to formulate uniform culturing criteria for CIK expansion

Three-Dimensional Human Alveolar Stem Cell Culture Models Reveal Infection Response to SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the cause of a present pandemic, infects human lung alveolar type 2 (hAT2) cells. Characterizing pathogenesis is crucial for developing vaccines and therapeutics. However, the lack of models mirroring the cellular physiology and pathology of hAT2 cells limits the study. Here, we develop a feeder-free, long-term, three-dimensional (3D) culture technique for hAT2 cells derived from primary human lung tissue and investigate infection response to SARS-CoV-2. By imaging-based analysis and single-cell transcriptome profiling, we reveal rapid viral replication and the increased expression of interferon-associated genes and proinflammatory genes in infected hAT2 cells, indicating a robust endogenous innate immune response. Further tracing of viral mutations acquired during transmission identifies full infection of individual cells effectively from a single viral entry. Our study provides deep insights into the pathogenesis of SARS-CoV-2 and the application of defined 3D hAT2 cultures as models for respiratory diseases

Expression of HIF-1alpha and VEGF in colorectal cancer: association with clinical outcomes and prognostic implications

<p>Abstract</p> <p>Background</p> <p>Hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) are frequently overexpressed in numerous types of cancers and are known to be important regulators of angiogenesis. Until now, few studies have been carried out to investigate the prognostic role of these factors in solid tumors, especially in colorectal cancer (CRC). The purpose of this study was to evaluate the expression of HIF-1α and VEGF in CRC tissues, and to analyze the association of these two factors with several clinical and pathological characteristics, and patients' survival.</p> <p>Methods</p> <p>Paraffin-embedded tissue samples were retrospectively collected from 71 CRC patients, who received surgical resection between 2001 and 2002, with a median follow-up of 5 years. We examined the patterns of expression of HIF-1α and VEGF by immunohistochemistry method. Statistical analysis was performed with univariate tests and multivariate Cox proportional hazards model to evaluate the differences.</p> <p>Results</p> <p>Expression of HIF-1α and VEGF was positively observed in 54.93% and 56.34% among the patients, respectively. HIF-1α and VEGF status were significantly associated with tumor stage, lymph nodes and liver metastases (<it>P </it>< 0.05). Expression of both HIF-1α and VEGF remained significantly associated with overall survival (OS) (<it>P </it>< 0.01), and HIF-1α was positively correlative to VEGF in CRC (r = 0.72, <it>P </it>< 0.001).</p> <p>Conclusions</p> <p>HIF-1α and VEGF could be used as biomarkers indicating tumors in advanced stage and independently implied poor prognosis in patients with CRC. Treatment that inhibits HIF-1α might be a promising targeted approach in CRC to exhibit its potential to improve outcomes in future perspective, just as VEGF targeting has proved to be.</p