Targeting the superior temporal gyrus with real-time fMRI neurofeedback: A pilot study of the indirect effects on self-referential processes in schizophrenia.

BACKGROUND: Individuals with schizophrenia (SZ) and auditory hallucinations (AHs) display a distorted sense of self and self-other boundaries. Alterations of activity in midline cortical structures such as the prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) during self-reference as well as in the superior temporal gyrus (STG) have been proposed as neuromarkers of SZ and AHs. METHODS: In this randomized, participant-blinded, sham-controlled trial, 22 adults (18 males) with SZ spectrum disorders (SZ or schizoaffective disorder) and frequent medication-resistant AHs received one session of real-time fMRI neurofeedback (NFB) either from the STG (n = 11; experimental group) or motor cortex (n = 11; control group). During NFB, participants were instructed to upregulate their STG activity by attending to pre-recorded sentences spoken in their own voice and downregulate it by ignoring unfamiliar voices. Before and after NFB, participants completed a self-reference task where they evaluated if trait adjectives referred to themselves (self condition), Abraham Lincoln (other condition), or whether adjectives had a positive valence (semantic condition). FMRI activation analyses of self-reference task data tested between-group changes after NFB (self>semantic, post>pre-NFB, experimental>control). Analyses were pre-masked within a self-reference network. RESULTS: Activation analyses revealed significantly (p < 0.001) greater activation increase in the experimental, compared to the control group, after NFB within anterior regions of the self-reference network (mPFC, ACC, superior frontal cortex). CONCLUSIONS: STG-NFB was associated with activity increase in the mPFC, ACC, and superior frontal cortex during self-reference. Modulating the STG is associated with activation changes in other, not-directly targeted, regions subserving higher-level cognitive processes associated with self-referential processes and AHs psychopathology in SZ. CLINICALTRIALS: GOV: Rt-fMRI Neurofeedback and AH in Schizophrenia; https://clinicaltrials.gov/study/NCT03504579.

Surface electromyography analysis of ankle flexor and extensor activity under different standing stability levels.

Background: To observe the activation strategies of the ankle muscles using surface electromyography (sEMG) during single-leg standing (SLS) and both-leg standing (BLS) on flat ground (FG), soft mat (SM), and BOSU ball (BB) surfaces. Methods: Thirty healthy young adults participated in the study. The muscle activities of the tibialis anterior (TA) and gastrocnemius medial (GM) were measured on the three surfaces during SLS and BLS. Electromyographic evaluations of the TA and GM were recorded during maximum voluntary isometric contractions (MVIC). Muscle activation was evaluated using MVIC%, and muscle co-contraction was evaluated using the co-contraction index (CI). Results: A statistically significant increase was observed in the MVIC% of the TA, GM, and CI on the three surfaces during SLS compared to BLS, except for the comparison of CI on BB between SLS and BLS (t = -1.35, p = 0.19). The MVIC% of the TA and GM during SLS and BLS on BB was significantly increased in comparison with FG and SM. The CI during BLS on BB increased compared to FG (t = 3.19, p < 0.01) and SM (t = 4.64, p < 0.01). The CI during BLS on SM (t = -1.46, p = 0.15) decreased when compared to FG but without statistical significance. Conclusions: SLS and unstable surfaces can induce greater muscle activation, and SLS can have a greater influence on ankle muscles.

Photothermal-promoted O2/OH generation of gold nanotetrapod @ platinum nano-islands for enhanced catalytic/photodynamic therapy.

Ultrasmall platinum (Pt) nanozymes are used for catalytic therapy and oxygen (O2)-dependent photodynamic therapy (PDT) by harnessing the dual-enzyme activities of catalase (CAT) and peroxidase (POD). However, their applications as nanocatalysts are limited due to their low catalytic activity. Herein, we constructed a photothermal-promoted bimetallic nanoplatform (AuNTP@Pt-IR808) by depositing ultrasmall Pt nano-islands and modifying 1-(5-Carboxypentyl)-2-(2-(3-(2-(1-(5-carboxypentyl)-3,3-dimethylindolin-2-ylidene)ethylidene)-2-chlorocyclohex-1-en-1-yl)vinyl)-3,3-dimethyl-3H-indol-1-ium bromide (IR808) on gold nanotetrapod (AuNTP) with CAT/POD activities to enhance PDT/catalytic therapy. In the tumor microenvironment, the ultrasmall Pt can catalyze endogenous hydrogen peroxide (H2O2) to produce O2, relieving tumor hypoxia and enhancing the PDT performance. Moreover, AuNTP integration into the bimetallic nanoplatform showed good electron transfer properties and promoted the POD activity of ultrasmall Pt. Importantly, AuNTP@Pt-IR808 possessed higher photothermal conversion performance than single AuNTPs, which enhanced photothermal therapy (PTT). It also accelerated the CAT/POD dual-enzyme activities, and promoted the generation of singlet oxygen (1O2) and hydroxyl radical (OH). By enhancing the performances of PTT/PDT/catalytic therapy, the developed AuNTP@Pt-IR808 nanoplatform demonstrated good antitumor efficacy against breast cancer.

Insights into the missing apiosylation step in flavonoid apiosides biosynthesis of Leguminosae plants.

Apiose is a natural pentose containing an unusual branched-chain structure. Apiosides are bioactive natural products widely present in the plant kingdom. However, little is known on the key apiosylation reaction in the biosynthetic pathways of apiosides. In this work, we discover an apiosyltransferase GuApiGT from Glycyrrhiza uralensis. GuApiGT could efficiently catalyze 2″-O-apiosylation of flavonoid glycosides, and exhibits strict selectivity towards UDP-apiose. We further solve the crystal structure of GuApiGT, determine a key sugar-binding motif (RLGSDH) through structural analysis and theoretical calculations, and obtain mutants with altered sugar selectivity through protein engineering. Moreover, we discover 121 candidate apiosyltransferase genes from Leguminosae plants, and identify the functions of 4 enzymes. Finally, we introduce GuApiGT and its upstream genes into Nicotiana benthamiana, and complete de novo biosynthesis of a series of flavonoid apiosides. This work reports an efficient phenolic apiosyltransferase, and reveals mechanisms for its sugar donor selectivity.

Identification of FCER1G as a key gene in multiple myeloma based on weighted gene co-expression network analysis.

PURPOSE: Although the prognosis of multiple myeloma (MM) has remarkably improved with the emerge of novel agents, it remains incurable and relapses inevitably. The molecular mechanisms of MM have not been well-studied. Herein, this study aimed to identify key genes in MM. MATERIALS AND METHODS: The GSE39754 dataset was used to screen differentially expressed genes (DEGs) and construct a co-expression network. Hub nodes were identified in the protein and protein interaction (PPI) network. Datasets GSE13591 and GSE2658 were used to validate hub genes. Moreover, function and gene set enrichment analyses were performed to elucidate the molecular pathogenesis of MM. RESULTS: In this study, 11 genes were found to be hub genes in the co-expression network, among which four genes (CD68, FCER1G, PLAUR and LCP2) were also identified as hub nodes. In the test dataset GSE13591, CD68 and FCER1G were significantly downregulated in MM. Besides, the areas under the curve (AUCs) of CD68 and FCER1G were greater than 0.8 in both the training dataset and the test dataset. Our results also confirmed that FCER1G highly expressed patients had remarkably longer survival times in MM. Function and pathway enrichment analyses suggested that hub genes were associated with epithelial mesenchymal transition, TNF-α signaling via NF-κB and inflammatory response. GSEA in our study indicated that FCER1G participated in NK cell mediated cytotoxicity and the NOD-like receptor signaling pathway. CONCLUSION: Our study identified FCER1G as a key gene in MM, providing a novel biomarker and potential molecular mechanisms of MM for further studies.

Ultrasmall gold decorated bimetallic metal-organic framework based nanoprobes for enhanced chemodynamic therapy with triple amplification.

Chemodynamic therapy (CDT) has shown potential for important applications in tumor precision therapy, but insufficient endogenous hydrogen peroxide (H2O2), overexpressed glutathione (GSH) and a weak Fenton-reaction rate greatly reduced the efficacy of CDT. Herein, a metal-organic framework (MOF) based bimetallic nanoprobe with self-supplying H2O2 was developed for enhancing CDT with triple amplification, in which ultrasmall gold nanoparticles (AuNPs) were deposited on Co-based MOFs (ZIF-67), and manganese dioxide (MnO2) nanoshells were coated to form a ZIF-67@AuNPs@MnO2 nanoprobe. In the tumor microenvironment, MnO2 depleted overexpressed GSH to produce Mn2+, and the bimetallic Co2+/Mn2+ nanoprobe accelerated the Fenton-like reaction rate. Moreover, by catalyzing glucose via ultrasmall AuNPs, the self-supplying H2O2 further promoted hydroxyl radical (˙OH) generation. Compared with those of ZIF-67 and ZIF-67@AuNPs, the ˙OH yield of ZIF-67@AuNPs@MnO2 obviously increased, due to which the cell viability decreased to 9.3%, and the tumor completely disappeared, indicating the enhanced CDT performance of the ZIF-67@AuNPs@MnO2 nanoprobe.

Improving speed and strength in long-distance running training / Aperfeiçoamento de velocidade e força no treinamento de corrida de longa distância / Perfeccionamiento de la velocidad y de la fuerza en el entrenamiento de carreras de larga distancia

ABSTRACT Introduction: Long-distance running is a typical physical endurance sport. The athletes' fitness level plays a dominant and central role in the components of their competitive ability. Whether long-distance runners can win in fierce competition depends mainly on the endurance of their physical fitness. Objective: To analyze the physical training methods of long-distance runners and discuss the improvement of speed and strength of long-distance runners through physical training. Methods: This paper uses literature materials, expert interviews, and experimental methods to research the training practice of middle and long-distance runners in colleges and universities. The data collected comprised an experimental protocol performed on volunteer long-distance runners. The above research determined the effect of physical training on speed and strength in long-distance runners. Results: After the 12-week experimental intervention, the overall strength, flexibility, and flexibility of the long-distance runners were improved, and the data were statistically significant (P<0.05). The aerobic workability and anaerobic capacity of the athletes were improved through the experiment. Conclusion: Physical training can improve the speed and strength of long-distance runners. Athletes can increase physical training with this protocol in their daily training. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A corrida de longa distância é um esporte típico de resistência física. O nível de aptidão física dos atletas desempenha um papel dominante e central nos componentes de sua capacidade competitiva. Se os corredores de longa distância podem vencer em competições acirradas depende principalmente da resistência de sua aptidão física. Objetivo: Analisar os métodos de treinamento físico dos corredores de longa distância e discutir o aperfeiçoamento da velocidade e da força dos corredores de longa distância através do treinamento físico. Métodos: Este artigo utiliza materiais de literatura, entrevistas com especialistas e métodos experimentais para conduzir pesquisas aplicadas na prática de treinamento de corredores de média e longa distância em faculdades e universidades. Os dados coletados compuseram um protocolo experimental executado em atletas de longa distância voluntários. A pesquisa acima determinou o efeito do treinamento físico sobre a velocidade e a força dos corredores de longa distância. Resultados: Após as 12 semanas de intervenção experimental, a força geral, flexibilidade e flexibilidade dos corredores de longa distância foram aprimoradas e os dados foram estatisticamente significativos (P<0,05). A trabalhabilidade aeróbica e a capacidade anaeróbica dos atletas foram melhoradas através do experimento. Conclusão: O treinamento físico pode melhorar a velocidade e a força dos corredores de longa distância. Os atletas podem incrementar o treinamento físico com este protocolo em seu treinamento diário. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La carrera de larga distancia es un deporte típico de resistencia física. El nivel de forma física de los deportistas desempeña un papel dominante y central en los componentes de su capacidad competitiva. La posibilidad de que los corredores de larga distancia puedan ganar en competiciones feroces depende principalmente de la resistencia de su estado físico. Objetivo: Analizar los métodos de entrenamiento físico de los corredores de larga distancia y discutir la mejora de la velocidad y la fuerza de los corredores de fondo mediante el entrenamiento físico. Métodos: Este trabajo utiliza materiales bibliográficos, entrevistas a expertos y métodos experimentales para llevar a cabo una investigación aplicada a la práctica del entrenamiento de corredores de media y larga distancia en colegios y universidades. Los datos recogidos comprendían un protocolo experimental realizado en atletas voluntarios de larga distancia. La investigación anterior determinó el efecto del entrenamiento físico sobre la velocidad y la fuerza en corredores de larga distancia. Resultados: Tras la intervención experimental de 12 semanas, la fuerza, la flexibilidad y la flexibilidad generales de los corredores de fondo mejoraron y los datos fueron estadísticamente significativos (P<0,05). La capacidad de trabajo aeróbico y la capacidad anaeróbica de los atletas mejoraron con el experimento. Conclusión: El entrenamiento físico puede mejorar la velocidad y la fuerza de los corredores de larga distancia. Los atletas pueden aumentar el entrenamiento físico con este protocolo en su entrenamiento diario. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Influence of upper body stretching exercises on shot put / Influência dos exercícios de alongamento da parte superior do corpo no arremesso de peso / Influencia de los ejercicios de estiramiento de la parte superior del cuerpo en el lanzamiento de peso

ABSTRACT Introduction The technique in the shot put and the ability in the throwing stage are two important factors that determine the ability of athletes. Qualified experts and coaches attach great importance to training and research on the ability of the throwing stage and the ability to throw. Objective Compare gravity load training and single incremental load training through practical means, analyzing the impacts on throwing ability in athletes. Methods The self-assessment method was used to conduct the comparative experiment on different forms of strength training in 20 college students. The experimental scheme adopts the single incremental load strength training, and the control scheme adopts the traditional barbell training. Results : After the experiment, the hand angle of group I was significantly higher than that of group II (P < 0.05); after the experiment, the shoulder angle of group I was significantly higher than that of group II (P < 0.05); after the experiment, the performance of the seated shot placed in group I was significantly higher than that of group II (P < 0.05), and there was no significant difference in the standing performance (P > 0.05). Conclusion Single incremental load training can significantly improve the throwing ability of shot put athletes. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução A técnica no arremesso de peso e a habilidade na etapa de arremessar são dois fatores importantes que determinam a habilidade dos atletas Especialistas e treinadores qualificados atribuem grande importância ao treinamento e pesquisa sobre a habilidade da fase de arremesso e a capacidade de arremessar. Objetivo Comparar o treinamento com carga gravitacional e o treinamento com carga incremental única através de meios experimentais, analisando os impactos na habilidade de arremesso nos atletas. Métodos O método de auto-avaliação foi usado para realizar o experimento comparativo de diferentes formas de treinamento de força em 20 estudantes universitários. O esquema experimental adota o treinamento único de força de carga incremental, e o esquema de controle adota o treinamento tradicional de barra. Resultados : Após o experimento, o ângulo da mão do grupo I foi significativamente maior do que o do grupo II (P < 0,05); após o experimento, o ângulo do ombro do grupo I foi significativamente maior do que o do grupo II (P < 0,05); após o experimento, o desempenho do tiro sentado colocado no grupo I foi significativamente maior do que o do grupo II (P < 0,05), e não houve diferença significativa no desempenho em pé (P > 0,05). Conclusão O treinamento com carga incremental única pode melhorar significativamente a capacidade de arremesso dos atletas de arremesso de peso. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción La técnica en el lanzamiento de peso y la habilidad en la fase de lanzamiento son dos factores importantes que determinan la habilidad de los atletas. Los especialistas y entrenadores cualificados atribuyen gran importancia a la formación y a la investigación sobre la habilidad de la fase de lanzamiento y la habilidad de lanzamiento. Objetivo Comparar el entrenamiento con carga gravitacional y el entrenamiento con carga incremental única a través de medios experimentales, analizando los impactos en la capacidad de lanzamiento en los atletas. Métodos Se utilizó el método de autoevaluación para realizar el experimento comparativo de diferentes formas de entrenamiento de fuerza en 20 estudiantes universitarios. El esquema experimental adopta el entrenamiento de fuerza con una sola carga incremental, y el esquema de control adopta el entrenamiento tradicional con barra. Resultados : Después del experimento, el ángulo de la mano del grupo I fue significativamente mayor que el del grupo II (P < 0,05); después del experimento, el ángulo del hombro del grupo I fue significativamente mayor que el del grupo II (P < 0,05); después del experimento, el rendimiento del lanzamiento de peso sentado del grupo I fue significativamente mayor que el del grupo II (P < 0,05), y no hubo diferencias significativas en el rendimiento de pie (P > 0,05). Conclusión El entrenamiento con una sola carga incremental puede mejorar significativamente la capacidad de lanzamiento de los atletas de lanzamiento de peso. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Chewing Behavior Attenuates Lung-Metastasis-Promoting Effects of Chronic Stress in Breast-Cancer Lung-Metastasis Model Mice.

We assessed the effects of chewing behavior on the lung-metastasis-promoting impact of chronic psychological-stress in mice. Human breast-cancer cells (MDA-MB-231) were injected into the tail vein of female nude mice. Mice were randomly divided into stress, stress-with-chewing, and control groups. We created chronic stress by placing mice in small transparent tubes for 45 min, 3 times a day for 7 weeks. Mice in the stress-with-chewing group were allowed to chew wooden sticks during the experimental period. The histopathological examination showed that chronic psychological-stress increased lung metastasis, and chewing behavior attenuated the stress-related lung metastasis of breast-cancer cells. Chewing behavior decreased the elevated level of the serum corticosterone, normalized the increased expression of glucocorticoid, and attenuated the elevated expression of adrenergic receptors in lung tissues. We also found that chewing behavior normalized the elevated expression of inducible nitric oxide synthase, 4-hydroxynonenal, and superoxide dismutase 2 in lung tissues, induced by chronic stress. The present study demonstrated that chewing behavior could attenuate the promoting effects of chronic psychological-stress on the lung metastasis of breast-cancer cells, by regulating stress hormones and their receptors, and the downstream signaling-molecules, involving angiogenesis and oxidative stress.

Ultrasmall Gold-Coated Mesoporous Polydopamine Nanoprobe to Enhance Chemodynamic Therapy by Self-Supplying H2O2 and Photothermal Stimulation.

Tumor microenvironment (TME) responsive chemodynamic therapy (CDT) showed an important application in inhibiting tumor growth by producing the highly toxic hydroxyl radical (·OH), but insufficient hydrogen peroxide (H2O2) and overexpressed glutathione (GSH) limited its application. Herein, by integrating photothermal therapy (PTT) and CDT, a new kind of mesoporous polydopamine (MPDA)-based cascade-reaction nanoplatform (MPDA@AuNPs-Cu) was designed for enhanced antitumor therapy, in which ultrasmall gold nanoparticles (AuNPs) with glucose oxidase (GOx)-like activity were deposited on MPDA for providing H2O2, and Cu2+ was chelated for GSH-responsive Fenton-like reaction. It was demonstrated that the MPDA@AuNPs-Cu nanoprobe showed high photothermal conversion efficiency and excellent biocompatibility. Moreover, the MPDA@AuNPs-Cu nanoprobe exhibited strong ·OH generation because of H2O2 self-generation and photothermal stimulation. Importantly, compared with MPDA-Cu, MPDA@AuNPs-Cu exhibited enhanced in vitro and in vivo CDT/PTT performance, by which the tumor growth was completely inhibited, achieving TME-responsive antitumor efficacy.

DNA Oxidative Damage as a Sensitive Genetic Endpoint to Detect the Genotoxicity Induced by Titanium Dioxide Nanoparticles.

The genotoxicity of nanomaterials has attracted great attention in recent years. As a possible occupational carcinogen, the genotoxic effects and underlying mechanisms of titanium dioxide nanoparticles (TiO2 NPs) have been of particular concern. In this study, the effect of TiO2 NPs (0, 25, 50 and 100 µg/mL) on DNA damage and the role of oxidative stress were investigated using human bronchial epithelial cells (BEAS-2B) as an in vitro model. After detailed characterization, the cytotoxicity of TiO2 NPs was detected. Through transmission electron microscopy (TEM), we found that TiO2 NPs entered the cytoplasm but did not penetrate deep into the nucleus of cells. The intracellular levels of reactive oxygen species (ROS) significantly increased in a dose-dependent manner and the ratios of GSH/GSSG also significantly decreased. The results of the normal comet assay were negative, while the Fpg-modified comet assay that specifically detected DNA oxidative damage was positive. Meanwhile, N-acetyl-L-cysteine (NAC) intervention inhibited the oxidative stress and genotoxicity induced by TiO2 NPs. Therefore, it was suggested that TiO2 NPs could induce cytotoxicity, oxidative stress and DNA oxidative damage in BEAS-2B cells. DNA oxidative damage may be a more sensitive genetic endpoint to detect the genotoxicity of TiO2 NPs.

Screening of Serum Biomarkers of Coal Workers' Pneumoconiosis by Metabolomics Combined with Machine Learning Strategy.

Pneumoconiosis remains one of the most serious global occupational diseases. However, effective treatments are lacking, and early detection is crucial for disease prevention. This study aimed to explore serum biomarkers of occupational coal workers' pneumoconiosis (CWP) by high-throughput metabolomics, combining with machine learning strategy for precision screening. A case-control study was conducted in Beijing, China, involving 150 pneumoconiosis patients with different stages and 120 healthy controls. Metabolomics found a total of 68 differential metabolites between the CWP group and the control group. Then, potential biomarkers of CWP were screened from these differential metabolites by three machine learning methods. The four most important differential metabolites were identified as benzamide, terazosin, propylparaben and N-methyl-2-pyrrolidone. However, after adjusting for the influence of confounding factors, including age, smoking, drinking and chronic diseases, only one metabolite, propylparaben, was significantly correlated with CWP. The more severe CWP was, the higher the content of propylparaben in serum. Moreover, the receiver operating characteristic curve (ROC) of propylparaben showed good sensitivity and specificity as a biomarker of CWP. Therefore, it was demonstrated that the serum metabolite profiles in CWP patients changed significantly and that the serum metabolites represented by propylparaben were good biomarkers of CWP.

Cause of death of patients with non-muscular invasive, non-metastatic muscular invasive and metastatic bladder cancer after diagnosis.

BACKGROUND: The purpose of this study was to evaluate the various causes of death among patients with non-muscular invasive bladder cancer (NMIBC), non-metastatic muscle invasive bladder cancer (non-MMIBC) and metastatic bladder cancer (MBC) after diagnosis. METHODS: With the Surveillance, Epidemiology, and Final Results database, patients diagnosed with bladder cancer from 2004 to 2015 were identified. All causes of death and the standardization mortality ratio (SMR) were analyzed. RESULTS: A total of 111,784 NMIBC, 26,546 non-MIBC and 4,678 MBC patients were identified. For NMIBC patients, 44,638 patients died during the follow-up, including 20.57% of bladder cancer, 18% of other tumors and 61.36% of non-tumor diseases. Main causes of other tumors death were cancers from lung and bronchus [n=2,860, SMR: 1.56 (1.51-1.62)], pancreas [n=506, SMR: 1.15 (1.05-1.26)], and prostate [n=442, SMR: 0.62 (0.56-0.68)]. Main causes of non-tumor deaths were diseases of heart [n=10,007, SMR: 1.15 (1.13-1.17)], chronic obstructive pulmonary disease (COPD) [n=3,153, SMR: 1.54 (1.49-1.59)], cerebrovascular diseases [n=1,704, SMR: 0.96 (0.91-1)], alzheimers [n=1,211, SMR: 0.87 (0.82-0.92)] and diabetes mellitus [n=1,047, SMR: 1.19 (1.12-1.27)]. Among the 18829 deaths in non-MMIBC patients, 62.65% patients died of bladder cancer, 11.08% of other tumors and 26.39% of non-tumor causes. Main deaths of other cancers were tumors from lung and bronchus [n=435, SMR: 1.83 (1.66-2.01)], prostate [n=192, SMR: 2.21 (1.91-2.54)]. Main causes of non-tumor death were diseases of heart [n=1717, SMR: 1.56 (1.49-1.64)], COPD [n=561, SMR: 2.18 (2.01-2.37)], and cerebrovascular diseases [n=290, SMR: 1.28 (1.14-1.44)]. Among the 4,392 deaths of MBC patients, 3,486 (79.37%) died of bladder cancer. Main cause of other deaths included diseases of heart (n=128) and prostate cancer (n=57). CONCLUSION: For NMIBC patients, leading causes of death were diseases of heart, COPD, lung and bronchus cancer, cerebrovascular diseases, Alzheimer's, and diabetes mellitus. Leading causes of deaths for non-MMIBE patients were bladder cancer, diseases of heart, COPD, lung and bronchus cancer, cerebrovascular diseases and prostate cancer. Main causes of death for MBC patients were bladder cancer itself. Our results of all causes of death and mortality risks provided useful information for bladder cancer patients.

Advances in genotoxicity of titanium dioxide nanoparticles in vivo and in vitro.

Titanium dioxide nanoparticles (TiO2 NPs) are currently one of the most widely used nanomaterials. Due to an increasing scope of applications, the exposure of humans to TiO2 NP is inevitable, such as entering the body through the mouth with food additives or drugs, invading the damaged skin with cosmetics, and entering the body through the respiratory tract during the process of production and handling. Compared with TiO2 coarse particles, TiO2 NPs have stronger conductivity, reaction activity, photocatalysis, and permeability, which may lead to greater toxicity to organisms. Given that TiO2 was classified as a category 2B carcinogen (possibly carcinogenic to humans), the genotoxicity of TiO2 NPs has become the focus of attention. There have been a series of previous studies investigating the potential genotoxicity of TiO2 NPs, but the existing research results are still controversial and difficult to conclude. More than half of studies have shown that TiO2 NPs can cause genotoxicity, suggesting that TiO2 NPs are likely to be genotoxic to humans. And the genotoxicity of TiO2 NPs is closely related to the exposure concentration, mode and time, and experimental cells/animals as well as its physicochemical properties (crystal type, size, and shape). This review summarized the latest research progress of related genotoxic effects through in vivo studies and in vitro cell tests, hoping to provide ideas for the evaluation of TiO2 NPs genotoxicity.

Novel Immunotherapies for Osteosarcoma.

Osteosarcoma (OS) is the most common primary malignant bone sarcoma mainly affecting adolescents and young adults, which often progresses to pulmonary metastasis and leads to the death of OS patients. OS is characterized as a highly heterogeneous cancer type and the underlying pathologic mechanisms triggering tumor progress and metastasis are incompletely recognized. Surgery combined with neoadjuvant and postoperative chemotherapy has elevated 5-year survival to over 70% for patients with localized OS tumors, as opposed to only 20% of patients with recurrence and/or metastasis. Therefore, novel therapeutic strategies are needed to overcome the drawbacks of conventional treatments. Immunotherapy is gaining momentum for the treatment of OS with an increasing number of FDA-approved therapies for malignancies resistant to conventional therapies. Here, we review the OS tumor microenvironment and appraise the promising immunotherapies available in the management of OS.

The Impact of Palliative Transurethral Resection of the Prostate on the Prognosis of Patients With Bladder Outlet Obstruction and Metastatic Prostate Cancer: A Population-Matched Study.

Objective: This study aimed to evaluate the survival outcomes of patients with bladder outlet obstruction (BOO) and metastatic prostate cancer (mPCa) after having a palliative transurethral resection of the prostate (pTURP) surgery. Methods: We identified patients with mPCa between 2004 and 2016 in the Surveillance, Epidemiology, and End Results (SEER) database. Patients who received pTURP and non-surgical therapy were identified. A propensity-score matching was introduced to balance the covariate. Kaplan-Meier analysis and COX regression were conducted to evaluate the overall survival (OS) and cancer-specific survival (CSS) outcomes. Results: A total of 36,003 patients were identified; 2,823 of them were in the pTURP group and 33,180 were in the non-surgical group. The survival curves of the overall cohort showed that the pTURP group was associated with worse outcomes in both OS (HR: 1.12, 95% CI: 1.07-1.18, p < 0.001) and CSS (HR: 1.08, 95% CI: 1.02-1.15, p = 0.004) compared with the non-surgical group. The mean survival time in the overall cohort of the pTURP group was shorter than the non-surgical group in both OS [35.13 ± 1.53 vs. 40.44 ± 0.59 months] and CSS [48.8 ± 1.27 vs. 55.92 ± 0.43 months]. In the matched cohort, the pTURP group had significantly lower survival curves for both OS (HR: 1.25, 95% CI: 1.16-1.35, p < 0.001) and CSS (HR: 1.23, 95% CI: 1.12-1.35, p < 0.001) than the non-surgical group. pTURP significantly reduced the survival months of the patients (36.49 ± 0.94 vs. 45.52 ± 1.23 months in OS and 50.1 ± 1.49 vs. 61.28 ± 1.74 months in CSS). In the multivariate COX analysis, pTURP increased the risk of overall mortality (HR: 1.19, 95% CI: 1.09-1.31, p < 0.001) and cancer-specific mortality CSS (HR: 1.23, 95% CI: 1.14-1.33, p < 0.001) compared with the non-surgical group. Conclusions: For mPCa patients with BOO, pTURP could reduce OS and CSS while relieving the obstruction.

Maternal chewing improves prenatal stress-induced cognitive deficit and anxiety-like behavior associated with alterations of the apoptotic response and serotonin pathway in mouse offspring.

OBJECTIVE: To examine whether maternal chewing affects prenatal stress-induced behavioral alternations associated with the changes in apoptosis-related proteins and serotonin pathway of the mouse offspring. DESIGN: Pregnant mice were assigned to control, stress, and stress/chewing groups. Stress mice were placed in restraint tubes, from gestational day 12 until parturition. Stress/chewing mice were given a wooden stick for chewing during stress period. Morris water maze and hole-board tests were applied for behavioral alterations in one-month-old male pups. Hippocampal mRNA expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X protein (Bax) was analyzed by quantitative real-time PCR. Serotonin and tryptophan hydroxylase expression level in the dorsal raphe nucleus was investigated immunohistochemically. RESULTS: Prenatal stress impaired the spatial learning, induced anxiety-like behavior, increased the ratio of hippocampal Bax/Bcl-2 expression, and decreased the expression of serotonin and tryptophan hydroxylase in dorsal raphe nucleus of the offspring. Maternal chewing ameliorated prenatal stress-induced cognitive impairment, anxiety-like behavior, and attenuated the increased ratio of hippocampal Bax/Bcl-2 expression, and the downregulated serotonin signaling in dorsal raphe nucleus of the offspring. CONCLUSIONS: Our results indicate that maternal chewing could improve prenatal stress-related anxiety-like behavior and cognitive impairment in mouse offspring, at least in part by affecting hippocampal apoptotic response and central serotonin pathway.

Metabolomics screening of serum biomarkers for occupational exposure of titanium dioxide nanoparticles.

Although nanotoxicology studies have shown that respiratory exposure of titanium dioxide nanoparticles (TiO2 NPs) could induce adverse health effects, limited biomarkers associated with occupational exposure of TiO2 NPs were reported. The purpose of this study is to screen serum biomarkers among workers occupationally exposed to TiO2 NPs using metabolomics. Compared with the control group, a total of 296 serum metabolites were differentially expressed in the TiO2 NPs-exposed group, of which the relative expression of 265 metabolites increased, and the remaining 31 decreased. Three machine learning methods including random forest (RF), support vector machines (SVM), and boruta screened eight potential biomarkers and simultaneously selected a metabolite, Liquoric acid. Through multiple linear regression analysis to adjust the influence of confounding factors such as gender, age, BMI, smoking and drinking, occupational exposure to TiO2 NPs was significantly related to the relative expression of the eight potential biomarkers. Meanwhile, the receiver operating characteristic curves (ROCs) of these potential biomarkers had good sensitivity and specificity. These potential biomarkers were related to lipid peroxidation, and had biological basis for occupational exposure to TiO2 NPs. Therefore, it was demonstrated that the serum metabolites represented by Liquoric acid were good biomarkers of occupational exposure to TiO2 NPs.

Chewing Behavior Attenuates the Tumor Progression-Enhancing Effects of Psychological Stress in a Breast Cancer Model Mouse.

We examined whether chewing behavior affects the tumor progression-enhancing impact of psychological stress. Human breast cancer cell line (MDA-MB-231) cells were inoculated into the mammary fat pads of athymic nude mice. The mice were assigned randomly to control, stress, and stress+chewing groups. Psychological stress was created by keeping mice in a transparent restraint cylinder for 45 min, three times a day, for 35 days after cell inoculation. Animals in the stress+chewing group were provided with a wooden stick for chewing on during the psychological stress period. Chewing behavior remarkably inhibited the tumor growth accelerated by the psychological stress. Immunohistochemical and Western blot findings revealed that chewing behavior during psychological stress markedly suppressed tumor angiogenesis and cell proliferation. In addition, chewing behavior decreased serum glucocorticoid levels and expressions of glucocorticoid and ß2-adrenergic receptors in tumors. Chewing behavior decreased expressions of inducible nitric oxide synthase and 4-hydroxynonenal, and increased expression of superoxide dismutase 2 in tumors. Our findings suggest that chewing behavior could ameliorate the enhancing effects of psychological stress on the progression of breast cancer, at least partially, through modulating stress hormones and their receptors, and the subsequent signaling pathways involving reactive oxygen and nitrogen species.

Exploring urine biomarkers of early health effects for occupational exposure to titanium dioxide nanoparticles using metabolomics.

Many experimental studies have demonstrated that titanium dioxide nanoparticles (TiO2 NPs) could induce adverse health effects in vivo and in vitro. But epidemiological evidence and biomarkers related to early health effects are still lacking. This study aimed to explore biomarkers in the urine samples of workers occupationally exposed to a relatively low concentration of TiO2 NPs. A cross-sectional study was conducted in Jinan, China, involving 132 employees of a TiO2 NP manufacturing plant, among which the exposed group and control group were 1 : 1 matched by confounding factors such as gender, age, BMI, smoking and drinking. Untargeted metabolomics was performed in urine samples using high performance liquid chromatography-mass spectrometry (HPLC-MS) technology. The differential metabolites between the TiO2 NP exposed group and the control group were analyzed and then screened for potential biomarkers using bioinformatics methods. Metabolomics found a total of 1760 differentially expressed metabolites in the TiO2 NP exposed group, of which 60 differential metabolites were simultaneously confirmed by one-dimensional and multi-dimensional statistical analysis. Among these 60 differential metabolites, the relative expression of 27 metabolites increased, and the remaining 33 decreased. Pathway enrichment analysis further found that the metabolic pathway of long chain acyl-coa dehydrogenase deficiency (Lcad) was significantly enriched. Ten differential metabolites were selected as potential biomarkers of occupational exposure to TiO2 NPs using machine learning methods, including dibenzyl ether, quassimarin, tryptophan, etc. The receiver operating characteristic curves (ROCs) of these potential biomarkers showed good sensitivity and specificity. These potential biomarkers also had biological basis for occupational exposure to TiO2 NPs. Therefore, urine metabolites represented by dibenzyl ether are considered as good biomarkers of early health effects for occupational exposure to TiO2 NPs.