Search

BACKGROUND/OBJECTIVES: Epidemiological evidence is suggestive, but inconclusive, for an association between consumption of red and processed meat and risk of stroke. We aimed to assess this association by conducting a meta-analysis of prospective cohort studies. SUBJECTS/METHODS: We performed a literature search on PubMed database through June 2012 to indentify prospective cohort studies of red and processed meat intake in relation to risk of stroke. Reference lists of the retrieved articles were also reviewed. Both fixed-effects and random-effects model were assumed to compute the summary risk estimates. RESULTS: Five large independent prospective cohort studies were identified. These studies contained a total of 2 39 251 subjects and 9593 stroke events. Comparing the highest category of consumption with lowest category, the pooled relative risks (RRs) of total stroke were 1.15 (95% confidence interval (CI), 1.05-1.25) for total meat (red and processed meat combined) (n = 4), 1.09 (95% CI, 1.01-1.18) for red meat (n = 5) and 1.14 (95% CI, 1.05-1.25) for processed meat (n = 5); the corresponding RRs of ischemic stroke (highest vs lowest quintile) were 1.15 (95% CI, 1.04-1.28), 1.13(95% CI, 1.01-1.25) and 1.19 (95% CI, 1.08-1.31). Consumption of red and/or processed meat was not associated with hemorrhagic stroke. In the dose-response analysis, the risk of stroke increased significantly by 10% and 13% for each 100g per day increment in total and red meat consumption, respectively, and by 11% for each 50g per day increment in processed meat consumption. CONCLUSION: Findings from this meta-analysis indicate that consumption of red and/or processed meat increase risk of stroke, in particular, ischemic stroke. European Journal of Clinical Nutrition (2013) 67, 91-95; doi: 10.1038/ejcn.2012.180; published online 21 November 2012 Keywords: meat; stroke; prospective studies; meta-analysis, INTRODUCTION In most developed countries, stroke remains an important cause of mortality and the most common cause of disability, and is becoming a great health burden in future decades. (1) [...]

BACKGROUND/OBJECTIVES: Epidemiological studies have suggested that dietary fiber intake may be associated with a decreased risk of stroke, but the findings have been inconsistent. We aimed to assess this association by conducting a meta- analysis of prospective cohort studies. SUBJECTS/METHODS: We performed a literature search on PubMed database through July 2012 to indentify prospective studies of dietary fiber intake in relation to risk of stroke. We also comprehensively reviewed the reference lists of the retrieved articles to identify additional studies. We used a random-effects model to compute the summary risk estimates. RESULTS: Six prospective cohort studies containing a total of 314864 subjects and 8920 stroke cases were included. The summary relative risk (RR) of stroke for the highest vs lowest category of dietary fiber intake was 0.87 (95% confidence interval (CI), 0.77-0.99). The corresponding RR in the subgroup analyses for men and women was 0.95 (95% CI, 0.83-1.08) and 0.80 (95% CI, 0.66- 0.96), respectively; and for ischemic stroke and hemorrhagic stroke was 0.83(95% CI, 0.72-0.96) and 0.86 (95% CI, 0.70-1.06), respectively. Meta-regression indicated no significant difference between gender (P-interaction = 0.18), or stroke subtypes (P- interaction = 0.85). The dose-response analysis suggested a 12% (RR = 0.88;95% CI, 0.79-0.97) reduction in risk of stroke for each 10g per day increment in dietary fiber intake. Moderate heterogeneity emerged in some of analyses, but disappeared after removing one study substantially contributing to the heterogeneity. Little evidence of publication bias was detected. CONCLUSION: Findings of this meta-analysis indicate a significant inverse dose-response relationship between dietary fiber intake and risk of stroke. European Journal of Clinical Nutrition (2013) 67, 96-100; doi: 10.1038/ejcn.2012.158; published online 17 October 2012 Keywords: prospective studies; stroke; dietary fiber; meta-analysis, INTRODUCTION In most developed countries, stroke remains an important cause of mortality and the most common cause of disability, and is becoming a great health burden in future decades. (1) [...]

Aircraft parts are often designed as thin-walled structures to reduce the weight of the aircraft. However, thin-walled structures are prone to deformation during the milling process, leading to a decrease in machining accuracy. To address this problem, a method combining milling and electrochemical machining, known as electrolytic milling, is proposed to minimize deformation and enhance the accuracy of thin-walled parts. The factors that affect the machining accuracy of electrolytic milling were analysed, and a model for predicting the thickness of the material removed was established. Electrolytic milling experiments were designed, and the model was solved. Based on the built model, the influences of feed rate, spindle speed, radial cutting depth, voltage and electrolyte concentration on material removal thickness were investigated. Compared with the milling method, the electrolytic milling method can improve the machining accuracy of thin-walled parts. Electrolytic milling experiments were conducted on box-shaped parts to verify the reliability of the proposed method., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The negative inference that consumers hold 'eavesdropping' views concerning the intelligent recommendation services of digital platforms is fostering their selective exposure to information that aligns with their preferred viewpoints. This, in turn, exacerbates their psychological defense against digital platforms, causing consumers to become more prone to verifying existing beliefs and fostering the polarization of information choices. This phenomenon directly impacts the effectiveness of smart recommendations and the accuracy of digital platforms' predictions of consumer behavior, potentially even adversely affecting brand trust and the long-term stability of platform usage. From the perspectives of self-verification and cognitive closure, this study delves into the influence of 'eavesdropping' inference cues within intelligent recommendation systems on consumers' selective exposure to information and the underlying psychological mechanisms. Experimental findings indicated: (1) Behavioral results showed that consumers who believed in eavesdropping by digital platforms, under conditions of high comprehensibility, were more inclined to selectively engage with consistent information as opposed to inconsistent information. Under conditions of low comprehensibility, however, information consistency had no significant effect on consumers' selective exposure. (2) EEG results revealed that, based on the need for cognitive closure, individuals in the high comprehensibility group, during the self-verification process, exhibited more cognitive conflict and required greater cognitive effort when presented with inconsistent information compared to those in the consistent information group. This, in turn, elicited higher N2 and N450 amplitudes. This study uncovered the psychological mechanism underlying this phenomenon. When consumers developed a skeptical perspective on perceived eavesdropping by digital platforms within intelligent recommendation systems, they promptly engaged in self-verification, driven by the need for cognitive closure. The study's findings offered practical guidance to digital platforms on how to alleviate consumer suspicions when designing intelligent recommendation services, thereby mitigating negative consumer reactions to the perception of 'eavesdropping'. This insight held significant theoretical and practical value at the intersection of digital marketing and psychology., Competing Interests: Declarations Institutional review board statement The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Huaqiao University (M2023009 2023.4.19). Written informed consent All participants in the study received written informed consent. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Green consumption is a crucial pathway towards achieving global sustainability goals. Product-oriented green advertisements can effectively stimulate consumers' latent needs and convert them into eventual purchasing intentions and behaviors, thereby promoting green consumption. Given that neuromarketing methods facilitate the understanding of consumers' decision-making processes, this study combines prospect theory and need fulfillment theory, employing event-related potentials (ERPs) as measures to explore changes in consumers' cognitive resources and emotional arousal levels when confronted with green products and advertising information. This enables inference regarding consumers' acceptance of purchasing and their psychological processes. Behavioral results indicated that message framing influences consumers' purchases, with consumers consuming more green in response to negatively framed advertisements. EEG results indicated that matching positive framing with utilitarian green products was effective in increasing consumers' cognitive attention in the early cognitive stage. In the late stage of cognition negative frames stimulated consumers' mood swings more, and the influence of product type depended on the role of message frames, and the consumption motivation induced by the product, whose influence was overridden by external evaluations such as message frames. These research findings provide an explanation for the impact of frame information on consumers' purchasing decisions at different stages, assisting marketers in devising diverse promotional strategies based on product characteristics to foster the development and practice of green consumption. This will further embed the concept of green consumption advocated by organizations such as the United Nations Environment Programme (UNEP), World Wildlife Fund (WWF), and Greenpeace into the public consciousness., (© 2024. The Author(s).)

The potential benefit of neoadjuvant toripalimab plus axitinib in cases with clear cell renal cell carcinoma (ccRCC) and inferior vena cava tumor thrombus (IVC-TT) remains unclear. NEOTAX was a phase 2 study to investigate the efficacy and safety of neoadjuvant toripalimab plus axitinib in patients with ccRCC and IVC-TT (ChiCTR2000030405). The primary endpoint was the down-staging rate of IVC-TT level. Secondary endpoints included change in TT length, response rate, percentage change in surgical approach, surgical morbidity, progression-free survival (PFS), safety, and biomarker analyses. In all, 25 patients received study treatment, 44.0% (11/25) patients had a reduction in thrombus level, and none experienced an increase in Mayo level. The median change in tumor thrombus length was -2.3 cm (range: -7.1 to 1.1 cm). Overall, 61.9% (13/21) patients experienced changes in surgical strategy compared with planned surgery, three patients experienced major complications. The median PFS was 25.3 months (95% CI: 17.0-NE). The 1-year PFS was 89.1% (95% CI: 62.7-97.2). No any of grade 4 or 5 treatment-related adverse event was identified. Biopsy samples of non-responders exhibited increased T cytotoxic cell infiltration, but these cells were predominantly PD-1 positive. Biopsy samples of responders exhibited lower T helper cells, however, their subtype, regulatory T cells remained unchanged. In surgical samples of the TT, non-responders exhibited increased CD8T_01_GZMK_CXCR4 subset T cells. NEOTAX met preset endpoints proving that toripalimab in combination with axitinib downstages IVC-TT in a significant proportion of patients leading to simplification in the procedure of surgery., (© 2024. The Author(s).)

This study aimed to investigate the expression of SF3B1 in non-small cell lung cancer, and its clinical significance, biological function, and molecular mechanisms. SF3B1 mRNA and protein levels were elevated in both lung squamous cell carcinoma and lung adenocarcinoma (LUAD) tissues based on TCGA data and immunohistochemistry. Notably, high SF3B1 expression in LUAD was significantly associated with increased lymph node metastasis. Functional experiments involving SF3B1 knockdown and overexpression demonstrated that SF3B1 facilitated the proliferation, invasion, and migration of LUAD cells. Additionally, the SF3B1 inhibitor pladienolide-B attenuated the aggressive behavior of LUAD cells both in vitro and in vivo. RNA sequencing analysis indicated that differentially expressed genes in the SF3B1 knockdown and SF3B1 inhibitor groups were enriched in ferroptosis-related pathways compared to their respective control groups. The antiferroptotic role of SF3B1 in LUAD cells was validated by detecting glutathione depletion, lipid peroxidation, and observing morphological changes using transmission electron microscopy. This process was confirmed to be independent of apoptosis and autophagy, as evidenced by the effects of the ferroptosis inducer erastin, the apoptosis inhibitor Z-VAD-FMK, and the autophagy inhibitor 3-methyladenine. Rescue experiments indicated that the antiferroptotic role of SF3B1 in LUAD is partially mediated by upregulating the expression of SLC7A11., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Identification of tumor neoantigens is indispensable for the development of cancer immunotherapies. However, we are still lacking knowledge about the potential neoantigens derived from sequences outside protein-coding regions. Here, we comprehensively characterized the immunopeptidome landscape by integrating multi-omics data in acute myeloid leukemia (AML). Both canonical and non-canonical MHC-associated peptides (MAPs) in AML were identified. We found that the quality and characteristics of ncMAPs are comparable or superior to cMAPs, suggesting ncMAPs are indispensable sources for tumor neoantigens. We further proposed a computational framework to prioritize the neoantigens by integrating additional transcriptome and immunopeptidome in normal tissues. Notably, 6 of prioritized 13 neoantigens were derived from ncMAPs. The expressions of corresponding source genes are highly related to infiltrations of immune cells. Finally, a risk model was developed, which exhibited good performance for clinical prognosis in AML. Our findings expand potential cancer immunotherapy targets and provide in-depth insights into AML treatment, laying a new foundation for precision therapies in AML., (© 2024. The Author(s).)

This cross-sectional study aimed to explore the knowledge, attitudes, and practices (KAP) regarding urinary system stones among the general public in Chengdu, China. Conducted between January and June 2023, this research targeted individuals undergoing physical examinations at the Health Management Center of Sichuan Provincial People's Hospital. Structured questionnaires were administered to collect demographic information and assess KAP related to urinary system stones. Following meticulous scrutiny, 1014 valid questionnaires were retained for analysis. The computed scores for knowledge, attitude, and practice were 9.36 ± 4.23 (possible score range 0-17), 37.75 ± 7.20 (possible score range 11-55), and 30.77 ± 4.00 (possible score range 10-50), respectively. These outcomes suggested insufficient knowledge and moderately positive attitudes and practices among the participants. Structural Equation Modeling (SEM) analysis revealed a direct impact of knowledge on attitude (β = 0.967, P < 0.001), with attitude subsequently exerting a direct influence on practice (β = 0.167, P < 0.001). This indicated an indirect impact of knowledge on practice. Additionally, there was a direct effect of knowledge on practice (β = 0.167, P < 0.001). In conclusion, the general populace in Chengdu exhibited insufficient knowledge and moderate attitudes and practices concerning urinary stones. These findings underscore the imperative for targeted educational interventions aimed at enhancing public awareness and fostering positive attitudes and practices toward urinary stone prevention and management., (© 2024. The Author(s).)

Asprosin, an adipokine, was recently discovered in 2016. Here, the correlation between asprosin and metabolic-associated fatty liver disease (MAFLD) was examined by quantitatively assessing hepatic steatosis using transient elastography and controlled attenuation parameter (CAP). According to body mass index (BMI), 1276 adult participants were enrolled and categorized into three groups: normal, overweight, and obese. The study collected and evaluated serum asprosin levels, general biochemical indices, liver stiffness measure, and CAP via statistical analysis. In both overweight and obese groups, serum asprosin and CAP were greater than in the normal group (p < 0.01). Each group showed a positive correlation of CAP with asprosin (p < 0.01). The normal group demonstrated a significant and independent positive relationship of CAP with BMI, low-density lipoprotein cholesterol (LDL-C), asprosin, waist circumference (WC), and triglycerides (TG; p < 0.05). CAP showed an independent positive association (p < 0.05) with BMI, WC, asprosin, fasting blood glucose (FBG), and TG in the overweight group, and with high-density lipoprotein cholesterol (HDL-C) showed an independent negative link (p < 0.01). CAP showed an independent positive relationship (p < 0.05) with BMI, WC, asprosin, TG, LDL-C, FBG, glycated hemoglobin A1c (HbA1c), and alanine transferase in the obese group. CAP also showed an independent positive link (p < 0.01) with BMI, WC, asprosin, TG, LDL-C, and FBG in all participants while independently and negatively correlated (p < 0.01) with HDL-C. Since asprosin and MAFLD are closely related and asprosin is an independent CAP effector, it may offer a novel treatment option for metabolic diseases and MAFLD., (© 2024. The Author(s).)

In the era of artificial intelligence, privacy empowerment illusion has become a crucial means for digital enterprises and platforms to "manipulate" users and create an illusion of control. This topic has also become an urgent and pressing concern for current research. However, the existing studies are limited in terms of their perspectives and methodologies, making it challenging to fully explain why users express concerns about privacy empowerment illusion but repeatedly disclose their personal information. This study combines the associative-propositional evaluation model (APE) and cognitive load theory, using event-related potential (ERP) technology to investigate the underlying mechanisms of how the comprehensibility and interpretability of privacy empowerment illusion cues affect users' immediate attitudes and privacy disclosure behaviours; these mechanisms are mediated by psychological processing and cognitive load differences. Behavioural research results indicate that in the context of privacy empowerment illusion cues with low comprehensibility, users are more inclined to disclose their private information when faced with high interpretability than they are when faced with low interpretability. EEG results show that in the context of privacy empowerment illusion cues with low comprehensibility, high interpretability induces greater P2 amplitudes than does low interpretability; low interpretability induces greater N2 amplitudes than does high interpretability. This study extends the scopes of the APE model and cognitive load theory in the field of privacy research, providing new insights into privacy attitudes. Doing so offers a valuable framework through which digital enterprises can gain a deeper understanding of users' genuine privacy attitudes and immediate reactions under privacy empowerment illusion situations. This understanding can help increase user privacy protection and improve their overall online experience, making it highly relevant and beneficial., (© 2024. The Author(s).)

With the rapid development of intelligent and connected vehicles, the experimental road test for the advanced driving assistance system (ADAS) is dramatically increasing around the world. Considering its high cost and hazardous situations, simulation test based on a dummy model is becoming a promising way for ADAS road test practice to reduce the experiment expanses. This study proposed a methodology for the evaluation of the performance of human and dummies with distinct designed materials based on the data extracted from the Doppler effect of millimeter-wave radar. Echo data of 8 different angles from 0 to 360 degrees, with the an interval of 45 degrees, at the same distance between the test object and the signal source is collected. Meanwhile, the echo energy is collected for correlation modeling and analysis among groups. By evaluating the performance of humans and dummies via statistical analysis, a close correlation was found which results verified the substitutability of the dummy for the ADAS experiment test. The correlation coefficient between human and dummies ranges from 0.75 to 0.93. The support vector machine (SVM) model was developed and fitted to predict the echo energy in diverse environments. The mean average error (MAE) is 5.42-11.42 in the training and testing datasets while root mean square error (RMSE) is 0.43-0.90. The methods developed in the study can simulate the real ADAS road test environment and support future experimental research., (© 2024. The Author(s).)

Glioblastoma is the most lethal primary brain tumor with glioblastoma stem cells (GSCs) atop a cellular hierarchy. GSCs often reside in a perivascular niche, where they receive maintenance cues from endothelial cells, but the role of heterogeneous endothelial cell populations remains unresolved. Here, we show that lymphatic endothelial-like cells (LECs), while previously unrecognized in brain parenchyma, are present in glioblastomas and promote growth of CCR7-positive GSCs through CCL21 secretion. Disruption of CCL21-CCR7 paracrine communication between LECs and GSCs inhibited GSC proliferation and growth. LEC-derived CCL21 induced KAT5-mediated acetylation of HMGCS1 on K273 in GSCs to enhance HMGCS1 protein stability. HMGCS1 promoted cholesterol synthesis in GSCs, favorable for tumor growth. Expression of the CCL21-CCR7 axis correlated with KAT5 expression and HMGCS1 K273 acetylation in glioblastoma specimens, informing patient outcome. Collectively, glioblastomas contain previously unrecognized LECs that promote the molecular crosstalk between endothelial and tumor cells, offering potentially alternative therapeutic strategies., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

During the re-mining of historical residual coal resources, the stress environment is complex, the surrounding rock conditions are bad, the mining roadway is significantly affected by ground pressure, the layout is difficult, and the safety is poor. Taking the recovery of isolated island coal pillar in 4# coal seam as the research background, based on the difference in the distribution morphology of the goaf on both sides of the isolated island coal pillar, the stress and failure law of the isolated island panel boundary are studied by numerical simulation method. (1) The peak stress difference of multiple goaf boundaries on both sides of the isolated island coal pillar is between 0.18 and 4.51 MPa. The peak stress is affected by the change of the length of the roof "cantilever beam" at the stopping line of the goaf, so that the peak stress of the goaf boundary is periodic. (2) The high stress is mainly concentrated in the center of the pillar. The peak stress at the end of each pillar is 35-40 MPa. The coal pillar bears high stress, and the stress zone of the original rock moves to the end of the coal pillar. (3) There is a plastic zone of 8-20 m at the corner of the end of each coal pillar. On the basis of the stress zone and failure zone distribution of the goaf boundary on both sides of the isolated island panel, the roadway layout of the isolated island panel is determined, that is, the air-return roadway of the isolated island panel is arranged at random, and the width of the isolated island coal pillar d1 is selected as 10 m. The transport roadway is arranged straight, and the transport roadway of the isolated island panel is in the width section area of the goaf X4103. The width d1 of the isolated island coal pillar is selected to be 8 m, and the length d5-d7 of the mining roadway layout in the width of the coal pillar is 24 m. The roadway of isolated island panel is divided into 4 areas for support control, and the drilling pressure relief technology is proposed for high stress roadway. Through the field monitoring data, it can be seen that the mining roadway can meet the requirements of isolated island coal pillar recovery, which provides reference for the layout and control of abandoned coal roadway in this mine and other mines., (© 2023. The Author(s).)

Birds are a kind of environmental indicator organism, which can reflect the changes in the ecological environment and biodiversity, and recognition of birdsongs can further help understand and protect birds and natural environment. Extreme learning machine (ELM) has the advantages of fast learning speed and good generalization ability, which is widely used in classification and recognition problems. Input layer weights and hidden layer thresholds are two key factors affecting ELM performance. As one of swarm intelligence optimization methods, differential evolution (DE) can be used to optimize the parameters of ELM. In order to enhance the diversity, convergence speed and global search ability of the DE population, and improve the accuracy and stability of the classification model, this paper proposes a multi-strategy differential evolution method (M-SDE) to optimize the parameters of the ELM. And the differential MFCC feature parameters, extracted from birdsongs, are applied to build classification models of M-SDE&#95;ELM and an ensemble M-SDE&#95;EnELM with optimized ELM for bird species recognition. In the experiments, the ELM models optimized by the swarm intelligence algorithms PSO and GOA are compared and analyzed by hypothesis tests with the M-SDE&#95;ELM and M-SDE&#95;EnELM. Results show that the M-SDE&#95;ELM and M-SDE&#95;EnELM can achieve a classification accuracy of 86.70% and 89.05% in the classification of nine species of birds respectively, and the recognition effect and stability of the M-SDE&#95;EnELM model outperform other models., (© 2022. The Author(s).)

Pine nuts are not only the important agent of pine reproduction and afforestation, but also the commonly consumed nut with high nutritive values. However, it is difficult to distinguish among pine nuts due to the morphological similarity among species. Therefore, it is important to improve the quality of pine nuts and solve the adulteration problem quickly and non-destructively. In this study, seven pine nuts (Pinus bungeana, Pinus yunnanensis, Pinus thunbergii, Pinus armandii, Pinus massoniana, Pinus elliottii and Pinus taiwanensis) were used as study species. 210 near-infrared (NIR) spectra were collected from the seven species of pine nuts, five machine learning methods (Decision Tree (DT), Random Forest (RF), Multilayer Perceptron (MLP), Support Vector Machine (SVM) and Naive Bayes (NB)) were used to identify species of pine nuts. 303 images were used to collect morphological data to construct a classification model based on five convolutional neural network (CNN) models (VGG16, VGG19, Xception, InceptionV3 and ResNet50). The experimental results of NIR spectroscopy show the best classification model is MLP and the accuracy is closed to 0.99. Another experimental result of images shows the best classification model is InceptionV3 and the accuracy is closed to 0.964. Four important range of wavebands, 951-957 nm, 1,147-1,154 nm, 1,907-1,927 nm, 2,227-2,254 nm, were found to be highly related to the classification of pine nuts. This study shows that machine learning is effective for the classification of pine nuts, providing solutions and scientific methods for rapid, non-destructive and accurate classification of different species of pine nuts., (© 2022. The Author(s).)

With the intensification of ecosystem damage, birds have become the symbolic species of the ecosystem. Ornithology with interdisciplinary technical research plays a great significance for protecting birds and evaluating ecosystem quality. Deep learning shows great progress for birdsongs recognition. However, as the number of network layers increases in traditional CNN, semantic information gradually becomes richer and detailed information disappears. Secondly, the global information carried by the entire input may be lost in convolution, pooling, or other operations, and these problems will weaken the performance of classification. In order to solve such problems, based on the feature spectrogram from the wavelet transform for the birdsongs, this paper explored the multi-scale convolution neural network (MSCNN) and proposed an ensemble multi-scale convolution neural network (EMSCNN) classification framework. The experiments compared the MSCNN and EMSCNN models with other CNN models including LeNet, VGG16, ResNet101, MobileNetV2, EfficientNetB7, Darknet53 and SPP-net. The results showed that the MSCNN model achieved an accuracy of 89.61%, and EMSCNN achieved an accuracy of 91.49%. In the experiments on the recognition of 30 species of birds, our models effectively improved the classification effect with high stability and efficiency, indicating that the models have better generalization ability and are suitable for birdsongs species recognition. It provides methodological and technical scheme reference for bird classification research., (© 2022. The Author(s).)

The fat mass and obesity-associated protein (FTO) is an N6-Methyladenosine (m6A) demethylase, which has been revealed to play critical roles in tumorigenesis. However, its role in the development and progression of prostate cancer (PCa) remains poorly understood. Here, we aimed to investigate the function and clinical relevance of FTO in PCa. Our results demonstrated that FTO was notably downregulated in PCa tissues compared with the paired normal tissues. In addition, the decreased expression of FTO was correlated with poor prognosis of PCa. Functional experiments showed that depletion of FTO promoted the proliferation and metastasis of PCa both in vitro and in vivo. Conversely, ectopic expression of FTO exhibited the opposite effects. Combined with RNA-sequencing, MeRIP-RT-qPCR, and mRNA stability assays indicated chloride intracellular channel 4(CLIC4) was a functional target of FTO-mediated m6A modification. FTO depletion significantly increased the m6A level of CLIC4 mRNA and then reduced the mRNA stability. In conclusion, our findings suggest that FTO suppresses PCa proliferation and metastasis through reducing the degradation of CLIC4 mRNA in an m6A dependent manner. FTO may be used as a promising novel therapeutic target and prognostic evaluation biomarker for PCa., (© 2022. The Author(s).)

The presence of pesticide residues in cowpea raises serious health concerns. In this study, a novel, sensitive, high-performance method was developed to simultaneously analyze the residues of 35 pesticides in cowpea samples from growing areas in the Hainan province of China, from November 2018 to June 2021. The method employs modified QuEChERS sample pretreatment coupled with gas chromatography-tandem mass spectrometry. The limits of quantification of the 35 pesticides in the cowpea matrix ranged from 1.0 to 8.0 μg/kg. Twenty-seven of the 35 pesticides were detected, twelve of which are banned for use on legumes in China. Residues for ten pesticides in 17.1% of the samples exceeded their MRLs, with the highest exceedance of 380% observed in difenoconazole. Moreover, 80.8% of the samples contained one or more pesticide residues, with the most frequently detected pesticide being chlorfenapyr with a detection rate of 46.3%. In addition, the pesticide triazophos was detected through different years and regions. Notably, the chronic dietary exposure risk (%ADI) of the detected pesticides, evaluated from the national estimated acceptable daily intake, was lower than 100% in Chinese people of different age groups., (© 2022. The Author(s).)

Despite advances in clinical diagnosis and treatment, the prognosis of patients with osteosarcoma (OS) remains poor, and the treatment efficacy has plateaued. Therefore, it is important to identify new therapeutic targets for OS. N 6 -methyladenosine (m 6 A) modification has been reported to participate in tumor malignancy. In this study, functional screening showed that the m 6 A demethylase FTO could be a candidate therapeutic target for OS. Upregulated FTO in OS could predict a poorer prognosis. FTO promoted the growth and metastasis of OS in vitro and in vivo. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were performed to identify DACT1 as a potential target of FTO. In vitro assays demonstrated that FTO could reduce the mRNA stability of DACT1 via m 6 A demethylation, which decreased DACT1 expression and further activated the Wnt signaling pathway. The oncogenic effect of FTO on OS was dependent on DACT1. In addition, the m 6 A reader IGF2BP1 was validated to participate in the regulation of DACT1. Entacapone, a conventional drug for Parkinson's disease, was confirmed to suppress OS via m 6 A-mediated regulation through the FTO/DACT1 axis. Our findings demonstrate that FTO may be a novel therapeutic target and that entacapone has preclinical value to be repurposed for OS., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

EGFR inhibitors have revolutionized the treatment of advanced non-small-cell lung cancer (NSCLC). Mefatinib is a novel, bioavailable, second-generation, irreversible pan-EGFR inhibitor. This phase Ib/II open-label, single-arm, multi-center study investigated the efficacy, safety, biomarker, and resistance mechanisms of mefatinib in the first-line treatment of patients with advanced EGFR-mutant NSCLC. This study included 106 patients with EGFR-mutant stage IIIB-IV NSCLC who received first-line mefatinib at a daily dose of either 60 mg (n = 51) or 80 mg (n = 55). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. The cohort achieved an ORR of 84.9% and DCR of 97.2%. The median PFS was 15.4 months and the median OS was 31.6 months. Brain metastasis was detected in 29% of patients (n = 31) at diagnosis and demonstrated an ORR of 87.1%, PFS of 12.8 months, and OS of 25.2 months. Adverse events primarily involved skin and gastrointestinal toxicities, which were well-tolerated and manageable. Analyses of mutation profiles were performed using targeted sequencing of plasma samples at baseline, first follow-up 6 weeks from starting mefatinib therapy (F1), and at progression. Patients with concurrent TP53 mutations had comparable PFS as wild-type TP53 (14.0 vs 15.4 months; p = 0.315). Furthermore, circulating tumor DNA clearance was associated with longer PFS (p = 0.040) and OS (p = 0.002). EGFR T790M was the predominant molecular mechanism of mefatinib resistance (42.1%, 16/38). First-line mefatinib provides durable PFS and an acceptable toxicity profile in patients with advanced EGFR-mutant NSCLC., (© 2021. The Author(s).)

Nicotinamide phosphoribosyltransferase (NAMPT) has been reported to be involved in infectious diseases, but it is unknown whether it plays a role in infectious pleural effusions (IPEs). We observed the levels of NAMPT in pleural effusions of different etiologies and investigated the clinical value of NAMPT in the differential diagnosis of infectious pleural effusions. A total of 111 patients with pleural effusion were enrolled in the study, including 25 parapneumonic effusions (PPEs) (17 uncomplicated PPEs, 3 complicated PPEs, and 5 empyemas), 30 tuberculous pleural effusions (TPEs), 36 malignant pleural effusions (MPEs), and 20 transudative effusions. Pleural fluid NAMPT levels were highest in the patients with empyemas [575.4 (457.7, 649.3) ng/ml], followed by those with complicated PPEs [113.5 (103.5, 155.29) ng/ml], uncomplicated PPEs [24.9 (20.2, 46.7) ng/ml] and TPEs [88 (19.4, 182.6) ng/ml], and lower in patients with MPEs [11.5 (6.5, 18.4) ng/ml] and transudative effusions [4.3 (2.6, 5.1) ng/ml]. Pleural fluid NAMPT levels were significantly higher in PPEs (P < 0.001) or TPEs (P < 0.001) than in MPEs. Moreover, Pleural fluid NAMPT levels were positively correlated with the neutrophil percentage and lactate dehydrogenase (LDH) levels and inversely correlated with glucose levels in both PPEs and TPEs, indicating that NAMPT was implicated in the neutrophil-associated inflammatory response in infectious pleural effusion. Further, multivariate logistic regression analysis showed pleural fluid NAMPT was a significant predictor distinguishing PPEs from MPEs [odds ratio (OR) 1.180, 95% confidence interval (CI) 1.052-1.324, P = 0.005]. Receiver-operating characteristic (ROC) analysis demonstrated that NAMPT was a promising diagnostic factor for the diagnosis of infectious effusions, with the areas under the curve for pleural fluid NAMPT distinguishing PPEs from MPEs, TPEs from MPEs, and IPEs (PPEs and TPEs) from NIPEs were 0.92, 0.85, and 0.88, respectively. In conclusion, pleural fluid NAMPT could be used as a biomarker for the diagnosis of infectious pleural effusions., (© 2021. The Author(s).)

Fluopyram is commonly used to control banana leaf spot, anthracnose, and scab in tropical agricultural areas. To explore its behaviour in tropical agricultural environments, dissipation, adsorption, and leaching behaviours of fluopyram in three typical banana planting soils were studied. Also, its dissipation and migration capabilities in different regions and different soil types were evaluated. The results showed that the dissipation of fluopyram was in accordance with the first-order kinetic equation in the three banana soils, but the degradation rates were quite different. The degradation half-lives in the Hainan latosol, Yunnan sandy soil, and Fujian Plain alluvial soil were 46.21 days, 36.48 days and 57.76 days, respectively. Fluopyram also exhibited high adsorption and low leachability in the three soils. The Fujian Plain alluvial soil had the highest adsorption capacity for fluopyram, while fluopyram had the low leachability in the Yunnan sandy soil., (© 2021. The Author(s).)

Soil salinization is an increasingly serious problem and decreases crop yields in the Yellow River Delta (YRD), but its effects on bacterial community and diversity at the phylum level are not well known. We used high-throughput sequencing of soil bacterial 16S rRNA to identify soil bacterial communities and diversity across a gradient of soil salinity (electrical conductivity), namely, S1: low salinity level (1.78 ds/m), S2: medium salinity level (3.16 ds/m), S3: high salinity level (17.26 ds/m), S4: extreme salinity level (34.41 ds/m), and a non-salted site as the control (CK, 0.92 ds/m). Our results indicated the significantly higher values of soil C/N ratio in S2, S3, and S4 compared with that in CK. Significantly lower values of the Shannon and Chao 1 indexes were observed in S4 compared with the CK (p < 0.05). High salinity decreased the relative abundance of Actinobacteria and Acidobacteria, but increased that of Gemmatimonadetes and Bacteroidetes. Additionally, the Shannon diversity of Bacteroidetes increased by 15.5% in S4 compared with that in the CK. Our results indicate that soil salt is a main factor regulating bacterial phyla diversity and community in the extremely saline-alkaline soils of YRD. The high abundance and diversity of Bacteroidetes can be used for saline-alkali land restoration.

We evaluated the serum levels of (1-3)-beta-D-glucan (BG) and lactate dehydrogenase (LDH) as a tool to support pneumocystis pneumonia (PCP) diagnostic procedures in non-HIV patients. We retrospectively collected non-HIV (human immunodeficiency virus) patients presenting clinical features of PCP between April 1st, 2013, and December 31st, 2018. A total of 225 included patients were tested for Pneumocystis jirovecii by polymerase chain reaction (PCR) and methenamine silver staining. Based on different exclusion criteria, 179 cases were included in the BG group, and 196 cases were included in the LDH group. In each group, cases with positive immunofluorescence (IF) microscopy and PCR were considered proven PCP, while cases with only positive PCR were considered probable PCP. Fifty patients with negative IF and PCR results and proven to be non-PCP infection were chosen randomly as the control group. The cut-off levels of BG and LDH to distinguish non-PCP from probable PCP were 110 pg/mL and 296 U/L with 88% sensitivity and 86% specificity, and 66% sensitivity and 88% specificity, respectively. The cut-off levels of BG and LDH to distinguish non-PCP from proven PCP were 285.8 pg/mL and 379 U/L with 92% sensitivity and 96% specificity, and 85% sensitivity and 77% specificity, respectively. The cut-off levels of BG and LDH to distinguish non-PCP from proven/probable PCP were 144.1 pg/mL and 363 U/L with 90% sensitivity, 86% specificity and 80% sensitivity, 76% specificity respectively. BG and LDH are reliable indicators for detecting P. jirovecii infection in HIV-uninfected immunocompromised patients.

The voltage-gated potassium channel KCNQ2 is responsible for M-current in neurons and is an important drug target to treat epilepsy, pain and several other diseases related to neuronal hyper-excitability. A list of synthetic compounds have been developed to directly activate KCNQ2, yet our knowledge of their activation mechanism is limited, due to lack of high-resolution structures. Here, we report cryo-electron microscopy (cryo-EM) structures of the human KCNQ2 determined in apo state and in complex with two activators, ztz240 or retigabine, which activate KCNQ2 through different mechanisms. The activator-bound structures, along with electrophysiology analysis, reveal that ztz240 binds at the voltage-sensing domain and directly stabilizes it at the activated state, whereas retigabine binds at the pore domain and activates the channel by an allosteric modulation. By accurately defining ligand-binding sites, these KCNQ2 structures not only reveal different ligand recognition and activation mechanisms, but also provide a structural basis for drug optimization and design.

Different fixation modalities are available for fixation of posterior malleolar fractures (PMFs), but the best method is still unclear. The purpose of this study was to carry out a comparative biomechanical analysis of three commonly used fixation constructs for PMFs using experimental and finite element analysis (FEA). 15 human cadaveric ankle specimens were randomly divided into three groups. Specimens in group-A were fixed with two anteroposterior (AP) lag screws, group-B with two posteroanterior (PA) lag screws, and for group-C, a posterior plate was used. Each model was subjected to axial load. Outcomes included loads for 0.5 mm, 1 mm, 1.5 mm, and 2 mm vertical displacements of posterior fragments were noted. 3D FE models were reconstructed from computed tomography (CT) images and subjected to vertical loads. The model's stress, fracture step-off, and resultant strains in implants were also studied in 3D FE models. Significantly higher amounts of mean compressive loads were observed to cause the same amount of vertical displacements in plate group (265 ± 60.21 N, 796 ± 57.27 N, 901.18 ± 8.88 N, 977.26 ± 13.04 N) than AP (102.7 ± 16.78 N, 169.5 ± 19.91 N, 225.32 ± 15.92 N, 269.32 ± 17.29 N) and PA (199.88 ± 31.43 N, 362.80 ± 28.46 N, 431.3 ± 28.12 N, 541.86 ± 36.05 N) lag screws respectively (P < 0.05). Simulated micro-motion analysis demonstrated that fracture step-off values in plate group (0.03 ± 0.001 mm, 0.06 ± 0.003 mm and 0.13 ± 0.010 mm) were the lowest among the three groups (P < 0.001). The cancellous bone showed the highest amount of stress in AP and PA lag groups respectively, whereas the lowest stress was noted in the plate-group. This biomechanical study concluded that posterior plating is biomechanically the most stable fixation construct for PMFs fixation. AP and PA lag screws with higher bone stress and fracture step-off values have a high tendency of bone cut-through and loss of fixation respectively.

All lung cancers patients with epidermal growth factor receptor (EGFR) mutation inevitably develop acquired resistance to EGFR tyrosine kinase inhibitors (TKI). In up to 30% of cases, the mechanism underlying acquired resistance remains unknown. MicroRNAs (miRNAs) is a group of small non-coding RNAs commonly dysregulated in human cancers and have been implicated in therapy resistance. The aim of this study was to understand the roles of novel miRNAs in acquired EGFR TKI resistance in EGFR-mutant non-small cell lung cancer (NSCLC). Here, we reported the evidence of miR-483-3p silencing and epithelial-to-mesenchymal transition (EMT) phenotype in both in vitro and in vivo EGFR-mutant NSCLC models with acquired resistance to gefitinib. In those tumor models, forced expression of miR-483-3p efficiently increased sensitivity of gefitinib-resistant lung cancer cells to gefitinib by inhibiting proliferation and promoting apoptosis. Moreover, miR-483-3p reversed EMT and inhibited migration, invasion, and metastasis of gefitinib-resistant lung cancer cells. Mechanistically, miR-483-3p directly targeted integrin β3, and thus repressed downstream FAK/Erk signaling pathway. Furthermore, the silencing of miR-483-3p in gefitinib-resistant lung cancer cells was due to hypermethylation of its own promoter. Taken together, our data identify miR-483-3p as a promising target for combination therapy to overcome acquired EGFR TKI resistance in EGFR-mutant NSCLC.

Abstact: Recent molecularly targeted approach gains advance in breast cancer treatment. However, the estimated 5-year survival rate has not met the desired expectation for improvement, especially for patients with triple-negative breast cancer (TNBC). Here we report that the lncRNA PVT1 promotes KLF5/beta-catenin signaling to drive TNBC tumorigenesis. PVT1 is upregulated in clinical TNBC tumors. Using genetic approaches targeting PVT1 in TNBC cells, we found that PVT1 depletion inhibited cell proliferation, colony formation, and orthotopic xenograft tumor growth. Mechanistically, PVT1 binds with KLF5 and increases its stability via BAP1, which upregulates beta-catenin signaling, resulting in enhanced TNBC tumorigenesis. PVT1, KLF5, and beta-catenin were also revealed to be co-expressed in clinical TNBC samples. Our findings uncover a new singaling pathway to mediate TNBC, and provide PVT1 as a new target for improving treatment of TNBC.

This corrects the article DOI: 10.1038/onc.2017.368.

BackgroundPropranolol is the first-choice treatment for severe infantile hemangioma (IH). However, 10- 30% of lesions relapse after propranolol treatment. The mechanisms underlying IH recurrence after propranolol treatment have not been completely elucidated.MethodsThis study combined an examination of hemodynamic changes with research regarding hemangioma stem cells (hscs) with differentially expressed microRNAs (miRNAs) to identify the factors affecting IH recurrence after propranolol treatment. Hemodynamic changes were monitored in 21 recurrent cases using high-frequency color Doppler ultrasound, and hscs were treated with different concentrations of propranolol. The levels of differentially expressed miRNAs and the activity of related pathways were then compared between 18 recurrent and 20 non-recurrent IH cases.ResultsDuring treatment, lesion depth and vessel density decreased, and the lesion resistance index increased. Obvious lesions and vessel signals were observed in recurrent cases compared with non-recurrent cases. Propranolol effectively inhibited hscs proliferation. Twenty-two differentially expressed miRNAs were found in the recurrent group compared with the non-recurrent group.ConclusionRecurrence may be attributed to a combination of events. Serum biomarkers and drug treatments for IH recurrence must be studied further.

We evaluated differences in the compositions of faecal microbiota between 52 end stage renal disease (ESRD) patients and 60 healthy controls in southern China using quantitative real-time polymerase chain reaction (qPCR) and high-throughput sequencing (16S ribosomal RNA V4-6 region) methods. The absolute quantification of total bacteria was significantly reduced in ESRD patients (p < 0.01). In three enterotypes, Prevotella was enriched in the healthy group whereas Bacteroides were prevalent in the ESRD group (LDA score > 4.5). 11 bacterial taxa were significantly overrepresented in samples from ESRD and 22 bacterial taxa were overrepresented in samples from healthy controls. The butyrate producing bacteria, Roseburia, Faecalibacterium, Clostridium, Coprococcus and Prevotella were reduced in the ESRD group (LDA values > 2.0). Canonical correspondence analysis (CCA) indicated that Cystatin C (CysC), creatinine and eGFR appeared to be the most important environmental parameters to influence the overall microbial communities. In qPCR analysis, The butyrate producing species Roseburia spp., Faecalibacterium prausnitzii, Prevotella and Universal bacteria, were negatively related to CRP and CysC. Total bacteria in faeces were reduced in patients with ESRD compared to that in healthy individuals. The enterotypes change from Prevotella to Bacteroides in ESRD patients. The gut microbiota was associated with the inflammatory state and renal function of chronic kidney disease.

The association between neutrophil-to-lymphocyte ratio (NLR) and differentiated thyroid cancer (DTC) is undecided. To rectify this question, we conducted a systematic meta-analysis based on 7 prospective cohort studies published between 2013 and 2015, comprising 7349 patients. Six of these cohorts included pretreatment (baseline) NLR data for patients with thyroid nodules. The meta-analysis of these 6 cohorts showed that the NLR of patients with DTC (4617 cases) was statistically similar to patients with benign nodules only (1666 cases), with a mean difference (MD) of 0.19 (95% CI: -0.09 to 0.46; I 2  = 93%; P < 0.001). No significant difference in NLR was found between patients with DTC and patients with benign nodules. Two studies addressed an association between NLR and papillary thyroid carcinoma in patients stratified by age <45 and ≥45 years (496 and 891 cases, respectively); the pooled MD was 0.09 (95% CI: -0.37 to 0.55; I 2  = 92.2%, P < 0.001). An elevated NLR seems not a reliable indicator of progressing DTC in patients with goiters, and there was no difference in NLR between patients aged <45 years and those aged ≥45 years. Well-designed and large-scale investigations are warranted to understand the value of NLR in the prognosis of DTC.

Repaglinide is an insulin secretagogue that often exhibits considerable interindividual variability in therapeutic efficacy. The current study was designed to investigate the impact of KCNQ1 genetic polymorphism on the efficacy of repaglinide and furthermore to identify the potential mechanism of action in patients with type 2 diabetes. A total of 305 patients and 200 healthy subjects were genotyped for the KCNQ1 rs2237892 polymorphism, and 82 patients with T2DM were randomized for the oral administration of repaglinide for 8 weeks. HepG2 cells were incubated with repaglinide in the absence or presence of a KCNQ1 inhibitor or the pcDNA3.1-hKCNQ1 plasmid, after which the levels of Akt, IRS-2 and PI(3)K were determined. Our data showed that repaglinide significantly decreased HOMA-IR in patients with T2DM. Furthermore, the level of HOMA-IR was significantly reduced in those patients with CT or TT genotypes than CC homozygotes. The KCNQ1 inhibitor enhanced repaglinide efficacy on insulin resistance, with IRS-2/PI(3)K/Akt signaling being up-regulated markedly. As in our clinical experiment, these data strongly suggest that KCNQ1 genetic polymorphism influences repaglinide response due to the pivotal role of KCNQ1 in regulating insulin resistance through the IRS-2/PI(3)K/Akt signaling pathway. This study was registered in the Chinese Clinical Trial Register on May 14, 2013. (No. ChiCTR-CCC13003536).

Gliomas are highly malignant brain tumors that are highly invasive and resistant to conventional therapy. Receptor tyrosine kinases (RTKs) such as PDGFRα (platelet-derived growth factor receptor-α), which show frequent aberrant activation in gliomas, are associated with a process of epithelial-mesenchymal transition (EMT), a cellular alteration that confers a more invasive and drug-resistant phenotype. Although this phenomenon is well documented in human cancers, the processes by which RTKs including PDGFRα mediate EMT are largely unknown. Here, we report that SHP-2 (encoded by PTPN11) upregulates an EMT inducer, ZEB1, to mediate PDGFRα-driven glioma EMT, invasion and growth in glioma cell lines and patient-derived glioma stem cells (GSCs) using cell culture and orthotopic xenograft models. ZEB1 and activated PDGFRα were coexpressed in invasive regions of mouse glioma xenografts and clinical glioma specimens. Glioma patients with high levels of both phospho-PDGFRα (p-PDGFRα) and ZEB1 had significantly shorter overall survival compared with those with low expression of p-PDGFRα and ZEB1. Knockdown of ZEB1 inhibited PDGFA/PDGFRα-stimulated glioma EMT, tumor growth and invasion in glioma cell lines and patient-derived GSCs. PDGFRα mutant deficient of SHP2 binding (PDGFRα-F720) or phosphoinositide 3-kinase (PI3K) binding (PDGFRα-F731/42), knockdown of SHP2 or treatments of pharmacological inhibitor for PDGFRα-signaling effectors attenuated PDGFA/PDGFRα-stimulated ZEB1 expression, cell migration and GSC proliferation. Importantly, SHP-2 acts together with PI3K/AKT to regulate a ZEB1-miR-200 feedback loop in PDGFRα-driven gliomas. Taken together, our findings uncover a new pathway in which ZEB1 functions as a key regulator for PDGFRα-driven glioma EMT, invasiveness and growth, suggesting that ZEB1 is a promising therapeutic target for treating gliomas with high PDGFRα activation., Competing Interests: The authors declare no conflict of interest.

Previous studies have observed reduced suppression of the default mode network (DMN) during cognitive tasks in schizophrenia, suggesting inefficient DMN suppression is critical for the cognitive deficits of schizophrenia. Cognitive function in schizophrenia patients, however, varies from relatively intact to severely impaired. This study, which compared the DMN suppression patterns between first-episode schizophrenia patients with (SZ-Imp) and without (SZ-Pre) impaired cognitive function, may provide further insight into the role of DMN dysfunction in cognitive deficits of schizophrenia. Independent component analysis (ICA) was applied to resting-state fMRI data to identify the DMN in each subject, and then general linear modeling based on the task-fMRI data was used to examine the different DMN activation patterns between groups. We observed that the SZ-Imp group, but not the SZ-Pre group, showed reduced suppression in the medial prefrontal cortex and posterior cingulated cortex when compared to the healthy controls (HC) group. Moreover, less DMN suppression was associated with poorer task performance in both HC and patient groups. Our findings provide the first direct evidence that disrupted DMN activity only exists in schizophrenia patients with impaired cognitive function, supporting the specific neuro-pathological role of inefficient DMN suppression in cognitive deficits of first-episode schizophrenia.

The objective of this study is to assess whether statin use is associated with beneficial effects on COPD outcomes. We conducted a systematic review and meta-analysis of all available studies describing the association between statin use and COPD mortality, exacerbations and cardiovascular events. Medline, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched, with no restrictions. The hazard ratio (HR) with 95% confidence interval (CI) was estimated. Fifteen studies with a total of 238,459 patients were included. Nine articles provided data on all-cause mortality (124,543 participants), and they gave a HR of 0.62 (95% CI 0.52 to 0.73). Three studies provided data on cancer mortality (90,077 participants), HR 0.83 (0.65 to 1.08); four studies on COPD mortality (88,767 participants), HR 0.48 (0.23 to 0.99); and three studies on cardiovascular mortality (90,041 participants), HR 0.93 (0.50 to 1.72). Six articles provided data on COPD exacerbation with or without hospitalization (129,796 participants), HR 0.64 (0.55 to 0.75). Additionally, the use of statins was associated with a significant reduction risk of myocardial infarction, but not for stroke. Our systematic review showed a clear benefit of statins in patients with COPD.

Changes of cytokines in bronchoalveolar lavage fluid (BALF) reflect immunologic reactions of the lung in pulmonary malignancies. Detection of biomarkers in BALF might serve as an important method for differential diagnosis of lung cancer. A total of 78 patients admitted into hospital with suspected lung cancer were included in our study. BALF samples were obtained from all patients, and were analyzed for TGF-β1, IL-6, and TNF-α using commercially available sandwich ELISA kits. The levels of TGF-β1 in BALF were significantly higher in patients with lung cancer compared with patients with benign diseases (P = 0.003). However, no significant difference of IL-6 (P = 0.61) or TNF-α (P = 0.72) in BALF was observed between malignant and nonmalignant groups. With a cut-off value of 10.85 pg/ml, TGF-β1 showed a sensitivity of 62.2%, and a specificity of 60.6%, in predicting the malignant nature of pulmonary disease. Our data suggest that TGF-β1 in BALF might be a valuable biomarker for lung cancer. However, measurement of IL-6 or TNF-α in BALF has poor diagnostic value in lung cancer.

Magnesium battery is potentially a safe, cost-effective, and high energy density technology for large scale energy storage. However, the development of magnesium battery has been hindered by the limited performance and the lack of fundamental understandings of electrolytes. Here, we present a study in understanding coordination chemistry of Mg(BH₄)₂ in ethereal solvents. The O donor denticity, i.e. ligand strength of the ethereal solvents which act as ligands to form solvated Mg complexes, plays a significant role in enhancing coulombic efficiency of the corresponding solvated Mg complex electrolytes. A new electrolyte is developed based on Mg(BH₄)₂, diglyme and LiBH₄. The preliminary electrochemical test results show that the new electrolyte demonstrates a close to 100% coulombic efficiency, no dendrite formation, and stable cycling performance for Mg plating/stripping and Mg insertion/de-insertion in a model cathode material Mo₆S₈ Chevrel phase.

The Hippo (Hpo) pathway controls tissue growth and organ size by regulating the activity of transcriptional co-activator Yorkie (Yki), which associates with transcription factor Scalloped (Sd) in the nucleus to promote downstream target gene expression. Here we identify a novel protein Sd-Binding-Protein (SdBP)/Tgi, which directly competes with Yki for binding to Sd through its TDU domains and inhibits the Sd-Yki transcriptional activity. We also find that SdBP retains Yki in the nucleus through the association with Yki WW domains via its PPXY motifs. Collectively, we identify SdBP as a novel component of the Hpo pathway, negatively regulating the transcriptional activity of Sd-Yki to restrict tissue growth.

CCL5 is a member of the CC chemokine family expressed in a wide array of immune and non-immune cells in response to stress signals. CCL5 expression correlates with advanced human breast cancer. However, its functional significance and mode of action have not been established. Here, we show that CCL5-deficient mice are resistant to highly aggressive, triple-negative mammary tumor growth. Hematopoietic CCL5 is dominant in this phenotype. The absence of hematopoietic CCL5 causes aberrant generation of CD11b(+)/Gr-1(+), myeloid-derived suppressor cells (MDSCs) in the bone marrow in response to tumor growth by accumulating Ly6C(hi) and Ly6G(+) MDSCs with impaired capacity to suppress cytotoxicity of CD8(+) T cells. These properties of CCL5 are observed in both orthotopic and spontaneous mammary tumors. Antibody-mediated systemic blockade of CCL5 inhibits tumor progression and enhances the efficacy of therapeutic vaccination against non-immunogenic tumors. CCL5 also helps maintain the immunosuppressive capacity of human MDSCs. Our study uncovers a novel, chemokine-independent activity of the hematopoietically derived CCL5 that promotes mammary tumor progression via generating MDSCs in the bone marrow in cooperation with tumor-derived colony-stimulating factors. The study sheds considerable light on the interplay between the hematopoietic compartment and tumor niche. Because of the apparent dispensable nature of this molecule in normal physiology, CCL5 may represent an excellent therapeutic target in immunotherapy for breast cancer as well as a broad range of solid tumors that have significant amounts of MDSC infiltration.