Despite tre mendous research efforts have been devoted to the analysis of nanoparticles (NPs)biohazard,the potential mechanism for nanotoxicity has not yet been syste mati-cal y elucidated.This review intends to point out the confusions about nanotoxicity in the field and tries to look into the mecha-nism from a new perspective.Currently,there are three puzzles:① no relationship between dose and toxicity could be observed in nanotoxicity;②there is a theory for the″size effects″,however, it cannot explain some cases contrary to the doctrine;③ NPs made of different materials with various sizes could have the same toxic effects through sti mulating oxidative stress.In fact, human body is co mposed of various biological molecules,and the biological function of a living syste m is reflected by the inter-actions and conversions of those molecules.NPs,on the other hand,are the invader of human body which has no ability to transport or convert or digest the foreigner.Thus,NPs could cause celldamage due to the physical blockage of micro-circula-tion,celldestruction due to membrane rando m insertion,and celldysfunction due to physical contacting with big biological mole-cules.The physical damages caused by various NPs could be divided into three categories:adhesion lesion,card inlay and puncture.Above al ,by analyzing wide spectrum of NPs varying in co mposition,shape and size,the author draws a conclusion that physical damage is the origin of nanotoxicity.

Objective To research the activated brain areas of decision making under uncertainty reward processing on healthy volunteers.Method The E-Prime programs were presented 3 kinds of tasks of the decision under uncertain reward processing.15 right-handed healthy volunteers made a response after receiving the task.At the same time,the GE 3.0T magnetic resonance scanner scanned the brains areas of subjects.Individual analysis and group analysis was done with SPM8 software,then the brain activating regions and the peak intensity were gotten.Results Orbitofrontal cortex was activated in certainty,peak intensity 2.4328 ± 0.1949 (P ＜ 0.05).Prefrontal cortex,occipital lobe,parietal lobe,posterior lobe of cerebellum,limbic lobe and midbrain were activated under the risk reward processing,peak intensity 2.4228 ± 1.3762 (P ＜ 0.05).When under ambiguity reward processing,prefrontal cortex,temporal lobe,occipital lobe,left inferior frontal gyrus and posterior lobe of cerebellum were activated,peak intensity 2.4056 ± 0.4222 (P ＜ 0.05).Compared with the task under certainty,posterior lobe of cerebellum,gyri subtemporalis and gyri fusiformis,inferior parietal lobule,anterior central convolution,orbitofrontal cortex,ventrolateral prefrontal cortex,both frontopolar and supramarginal gyrus were activated in task under risk (P ＜0.05) ;and both frontopolar were activated in task under ambiguity (P ＜ 0.05).Compared with the task under risk,dorsolateral prefrontal cortex and posterior lobe of cerebellum were activated in task under ambiguity (P ＜ 0.05).Conclusion There are differences in different types of reward processing of decision making.

Nowadays, nanotechnologies have shown wide application foreground in the biomedical field of medicine laboratory tests, drug delivery, gene therapy and bioremediation. However, in recent years, nanomaterials have been labeled poisonous, because of the disputes and misunderstandings of mainstream views on their safety. Besides, for the barriers of technical issues in preparation like: (1) low efficacy (poor PK & PD and low drug loading), (2) high cost (irreproducibility and difficulty in scale up), little of that research has been successfully translated into commercial products. Currently, along with the new theory of "physical damage is the origin of nanotoxicity", biodegradability and biocompatibility of nanomaterials are listed as the basic principle of safe application of nanomaterials. Combining scientific design based on molecular level with precision control of process engineering will provide a new strategy to overcome the core technical challenges. New turning point of translational medicine in nanotechnology may emerge.

Objective To investigate the genetic aberrations in extranodal marginal zone lymphoma of mueosa-associated lymphoid tissue (MALT) lymphomas from different sites of the body in Chinese patients. Methods Two hundred and seventeen paraffin-embedded MALT lymphoma specimens from 11 major sites were studied with interphase fluorescence in situ hybridization (FISH) to detect t(11; 18) (q21;q21)/API2-MALT1, t(1; 14) (p22; q32)/IGH-BCL10, (14; 18) (q32; q21)/IGH-MALT1 and BCL6 gene involved chromosome translocations. Results These translocations were mutually exclusive and detected in 21% (46/217) of the cases, including t(11;18) (q21;q21) API2-MALT1 13% (29/217), t (1;14)(p22 ;q32) IGH-BCLIO in 1% (3/217), t(14;18) (q32;q21) IGH-MALT1 1% (2/217), BCL6 involved translocation in 2% (4/217) and IGH-unknown translocation partner in 4% (8/217). t(11; 18) (q21;q21)API2-MALT1 was found with the highest frequency in MALT lymphoma from lungs (47% , 8/17) and small intestine (29%, 4/14), followed by salivary gland (17%, 1/6), stomach (14%, 12/84) and ocular adnexae (6% , 4/68). t(1 ;14) (p22;q32) was only detected in lungs (12%, 2/17) and stomach (1%, 1/84). t(14;18) (q32;q21) was mainly detected in lungs (6%, 1/17) and ocular adnexae (2%, 1/68). BCL6 gene involved translocation was detected in salivary gland (17% , 1/6) and stomach (4%, 3/84). Conclusions It is demonstrated that the four translocatidns occur with markedly variable frequencies in MALT lymphoma of different sites in Chinese patients. The distributions of these chromosome translocations in Chinese patients are slightly different from those reported in western patients.

Objective: To elucidate clinical characteristics and build a prognostic nomogram for patients with vulvar cancer. Methods: The study population was drawn from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly assigned to training and validation sets. Cox proportional hazards model and competing risk model were used to identify the prognostic parameters of overall survival (OS) and cancer-specific survival (CSS) to construct a nomogram. The nomogram was assessed by concordance index (C-index), area under the curve (AUC), calibration plot, and decision curve analysis (DCA). Results: A total of 20,716 patients were included in epidemiological analysis, of whom 7,025 patients were selected in survival analysis, including 4,215 and 2,810 in training and validation sets, respectively. The multivariate Cox model showed that the predictors for OS were age, marital status, histopathology, differentiation and tumor node metastasis (TNM) stages, whether to undergo surgery and chemotherapy. However, the predictors for CSS were age, race, differentiation and TNM stages, whether to undergo surgery and radiation. The C-index for OS and CSS in the training set were 0.76 and 0.80. The AUC in the training set for 1-, 3- and 5-year OS and CSS were 0.84, 0.81, 0.80 and 0.88, 0.85, 0.83, respectively, which was similar in the validation set. The calibration curves showed good agreement between prediction and actual observations. DCA revealed that the nomogram had a better discrimination than TNM stages. Conclusions The nomogram showed accurate prognostic prediction in OS and CSS for vulvar cancer, which could provide guidance to clinical practice.

DNA methylation is a prevalent epigenetic modification in vertebrates, and it has been shown to be involved the regulation of gene expression and embryo development. However, it remains unclear how DNA methylation regulates sexual development, especially in species without sex chromosomes. To determine this, we utilized zebrafish to investigate DNA methylation reprogramming during juvenile germ cell development and adult female-to-male sex transition. We reveal that primordial germ cells (PGCs) undergo significant DNA methylation reprogramming during germ cell development, and the methylome of PGCs is reset to an oocyte/ovary-like pattern at 9 days post fertilization (9 dpf). When DNA methyltransferase (DNMT) activity in juveniles was blocked after 9 dpf, the zebrafish developed into females. We also show that Tet3 is involved in PGC development. Notably, we find that DNA methylome reprogramming during adult zebrafish sex transition is similar to the reprogramming during the sex differentiation from 9 dpf PGCs to sperm. Furthermore, inhibiting DNMT activity can prevent the female-to-male sex transition, sug-gesting that methylation reprogramming is required for zebrafish sex transition. In summary, DNA methylation plays important roles in zebrafish germ cell development and sexual plasticity.

Lung cancer is the most threatening tumor disease to human health. Early detection is crucial to improve the survival rate and recovery rate of lung cancer patients. Existing methods use the two-dimensional multi-view framework to learn lung nodules features and simply integrate multi-view features to achieve the classification of benign and malignant lung nodules. However, these methods suffer from the problems of not capturing the spatial features effectively and ignoring the variability of multi-views. Therefore, this paper proposes a three-dimensional (3D) multi-view convolutional neural network (MVCNN) framework. To further solve the problem of different views in the multi-view model, a 3D multi-view squeeze-and-excitation convolution neural network (MVSECNN) model is constructed by introducing the squeeze-and-excitation (SE) module in the feature fusion stage. Finally, statistical methods are used to analyze model predictions and doctor annotations. In the independent test set, the classification accuracy and sensitivity of the model were 96.04% and 98.59% respectively, which were higher than other state-of-the-art methods. The consistency score between the predictions of the model and the pathological diagnosis results was 0.948, which is significantly higher than that between the doctor annotations and the pathological diagnosis results. The methods presented in this paper can effectively learn the spatial heterogeneity of lung nodules and solve the problem of multi-view differences. At the same time, the classification of benign and malignant lung nodules can be achieved, which is of great significance for assisting doctors in clinical diagnosis.
Humans ; Lung/pathology* ; Lung Neoplasms/pathology* ; Neural Networks, Computer ; Tomography, X-Ray Computed/methods*