Identification of patients with internet gaming disorder via a radiomics-based machine learning model of subcortical structures in high-resolution T1-weighted MRI.

It is of vital importance to establish an objective and reliable model to facilitate the early diagnosis and intervention of internet gaming disorder (IGD). A total of 133 patients with IGD and 110 healthy controls (HCs) were included. We extracted radiomic features of subcortical structures in high-resolution T1-weighted MRI. Different combinations of four feature selection methods (analysis of variance, Kruskal-Wallis, recursive feature elimination and relief) and ten classification algorithms were used to identify the most robust combined models for distinguishing IGD patients from HCs. Furthermore, a nomogram incorporating radiomic signatures and independent clinical factors was developed. Calibration curve and decision curve analyses were used to evaluate the nomogram. The combination of analysis of variance selector and logistic regression classifier identified that the radiomic model constructed with 20 features from the right caudate nucleus and amygdala showed better IGD screening performance. The radiomic model produced good areas under the curves (AUCs) in the training, validation and test cohorts (AUCs of 0.961, 0.903 and 0.895, respectively). In addition, sex, internet addiction test scores and radiomic scores were included in the nomogram as independent risk factors for IGD. Analysis of the correction curve and decision curve showed that the clinical-radiomic model has good reliability (C-index: 0.987). The nomogram incorporating radiomic features of subcortical structures and clinical characteristics achieved satisfactory classification performance and could serve as an effective tool for distinguishing IGD patients from HCs.

Spatiotemporal patterns of net regional productivity and its causes throughout Ordos, China.

A comprehensive understanding of the terrestrial carbon sink is essential for proficient regional carbon management. However, previous studies predominantly relied on net ecosystem productivity (NEP) as an indicator of regional carbon sink, overlooking the impacts of carbon emissions from physical processes and carbon leakage associated with anthropogenic activities. In this study, net region productivity (NRP), a vital metric representing carbon sink dynamics in regional multi-landscape ecosystems, was employed to systematically analyze the patterns, trends, and causes of carbon sink in Ordos. The results revealed that spatially averaged NRP in Ordos was 70.334 g·m-2·a-1, indicating a carbon sink effect. The coefficient of variation of NRP was 68.035%, with a higher NRP in the southern region. Normalized difference vegetation index (NDVI) predominantly controlled the spatial heterogeneity of NRP in Ordos, while precipitation emerged as the primary climatic factor influencing spatial differences in NRP. Regional variations in the impact of environmental factors on NRP were evident. In most areas, NRP showed a notable increasing trend influenced by various factors. Specifically, the simultaneous rise in NDVI and improvements in hydrothermal conditions contributed to the gradual elevation of NRP, each with varying degrees of influence across Ordos and its sub-regions.

Mass spectrometry imaging-based metabolomics highlights spatial metabolic alterations in three types of liver injuries.

Liver's distinctive function renders it highly susceptible to diverse damage sources. Characterizing the metabolic profiles and spatial signatures in different liver injuries is imperative for early diagnosis and etiology-oriented treatment. In this comparative study, we conducted whole-body spatial metabolomics on zebrafish with liver injury induced by ethanol (EtOH), acetaminophen (APAP), and thioacetamide (TAA). The two specific levels, the whole-body and liver-specific metabolic profiles, as well as their regional distributions, were systematically mapped in situ by mass spectrometry imaging, which is distinct from conventional LC-MS and GC-MS methods. We found that liver injury regions exhibited more pronounced metabolic reprogramming than the entire organism, leading to significant alterations in eight fatty acids, three phospholipids, and four low-molecular-weight metabolites. More importantly, fatty acids as well as small molecule metabolites including glutamine, glutamate, taurine and malic acid displayed contrasting changes between alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). In addition, phospholipids, including Lyso PC (16:0) and Lyso PE (18:0), demonstrated notable down-regulation in all damaged liver, whereas PC (34:1) underwent upregulation. This study not only deepens insights into distinct potential biomarkers for liver injuries, but also underscores spatial metabolomics as a powerful tool to elucidate possible pathogenic mechanisms in other metabolic diseases.

Inhibition of PPP1R15A alleviates osteoporosis via suppressing RANKL-induced osteoclastogenesis.

Osteoporosis results from overactivation of osteoclasts. There are currently few drug options for treatment of this disease. Since the successful development of allosteric inhibitors, phosphatases have become attractive therapeutic targets. Protein phosphatase 1, regulatory subunit 15 A (PPP1R15A), is a stress-responsive protein, which promotes the UPR (unfolded protein response) and restores protein homeostasis. In this study we investigated the role of PPP1R15A in osteoporosis and osteoclastogenesis. Ovariectomy (OVX)-induced osteoporosis mouse model was established, osteoporosis was evaluated in the left femurs using micro-CT. RANKL-stimulated osteoclastogenesis was used as in vitro models. We showed that PPP1R15A expression was markedly increased in BMMs derived from OVX mice and during RANKL-induced osteoclastogenesis in vitro. Knockdown of PPP1R15A or application of Sephin1 (a PPP1R15A allosteric inhibitor in a phase II clinical trial) significantly inhibited osteoclastogenesis in vitro. Sephin1 (0.78, 3.125 and 12.5 µM) dose-dependently mitigated the changes in NF-κB, MAPK, and c-FOS and the subsequent nuclear factor of activated T cells 1 (NFATc1) translocation in RANKL-stimulated BMMs. Both Sephin1 and PPP1R15A knockdown increased the phosphorylated form of eukaryotic initiation factor 2α (eIF2α); knockdown of eIF2α reduced the inhibitory effects of Sephin1 on NFATc1-luc transcription and osteoclast formation. Furthermore, Sephin1 or PPP1R15A knockdown suppressed osteoclastogenesis in CD14+ monocytes from osteoporosis patients. In OVX mice, injection of Sephin1 (4, 8 mg/kg, i.p.) every two days for 6 weeks significantly inhibited bone loss, and restored bone destruction and decreased TRAP-positive cells. This study has identified PPP1R15A as a novel target for osteoclast differentiation, and genetic inhibition or allosteric inhibitors of PPP1R15A, such as Sephin1, can be used to treat osteoporosis. This study revealed that PPP1R15A expression was increased in osteoporosis in both human and mice. Inhibition of PPP1R15A by specific knockdown or an allosteric inhibitor Sephin1 mitigated murine osteoclast formation in vitro and attenuated ovariectomy-induced osteoporosis in vivo. PPP1R15A inhibition also suppressed pathogenic osteoclastogenesis in CD14+ monocytes from osteoporosis patients. These results identify PPP1R15A as a novel regulator of osteoclastogenesis and a valuable therapeutic target for osteoporosis.

Spatially Resolved Metabolomics Combined with the 3D Tumor-Immune Cell Coculture Spheroid Highlights Metabolic Alterations during Antitumor Immune Response.

The metabolic cross-talk between tumor and immune cells plays key roles in immune cell function and immune checkpoint blockade therapy. However, the characterization of tumor immunometabolism and its spatiotemporal alterations during immune response in a complex tumor microenvironment is challenging. Here, a 3D tumor-immune cell coculture spheroid model was developed to mimic tumor-immune interactions, combined with mass spectrometry imaging-based spatially resolved metabolomics to visualize tumor immunometabolic alterations during immune response. The inhibition of T cells was simulated by coculturing breast tumor spheroids with Jurkat T cells, and the reactivation of T cells can be monitored through diminishing cancer PD-L1 expressions by berberine. This system enables simultaneously screening and imaging discriminatory metabolites that are altered during T cell-mediated antitumor immune response and characterizing the distributions of berberine and its metabolites in tumor spheroids. We discovered that the transport and catabolism of glutamine were significantly reprogrammed during the antitumor immune response at both metabolite and enzyme levels, corresponding to its indispensable roles in energy metabolism and building new biomass. The combination of spatially resolved metabolomics with the 3D tumor-immune cell coculture spheroid visually reveals metabolic interactions between tumor and immune cells and possibly helps decipher the role of immunometabolic alterations in tumor immunotherapy.

Abnormal neonatal brain microstructure in gestational diabetes mellitus revealed by MRI texture analysis.

To investigate the value of MRI texture analysis in evaluating the effect of gestational diabetes mellitus (GDM) on neonatal brain microstructure development, we retrospectively collected images of neonates undergoing head MRI scans, including a GDM group (N1 = 37) and a healthy control group (N2 = 34). MaZda texture analysis software was used to extract the texture features from different sequence images and perform dimensionality reduction, and then the texture features selected by the lowest misjudgement rate method were imported into SPSS software for statistical analysis. In our study, we found that GDM affects the development of the microstructure of the neonatal brain, and different combinations of texture features have different recognition performances, such as different sequences and different brain regions. As a consequence, texture analysis combining multiple conventional MRI sequences has a high recognition performance in revealing the abnormal development of the brain microstructure of neonates born of mothers with GDM.

Involvement of Rictor/mTORC2/Akt/GLUT4 pathway in the regulation of energy metabolism in the gastric smooth muscle of diabetic rats.

Diabetes mellitus can be accompanied by a variety of complications. The purpose of the present study was to characterize the Rictor/mTOR complex 2 (mTORC2)/Akt/glucose transporter 4 (GLUT4) pathway and its effects on energy metabolism in the gastric smooth muscle of diabetic rats. Diabetes was induced in rats using streptozotocin and their phenotype was compared with untreated rats. The relationship between gastric motility and energy metabolism was analyzed by comparing the contraction and ATP metabolism of muscle strips. Western blotting was used to detect the expression of key proteins in the pathway. The diabetic rats demonstrated less frequent and less powerful gastric smooth muscle contractions. The concentrations of ADP, AMP, and ATP, and the energy charge in gastric smooth muscle changed in different periods of diabetes, and these changes were consistent with changes in mechanistic target of rapamycin (mTOR) protein content. The expression of the key intermediates in signal transduction in the Rictor/mTORC2/Akt/GLUT4 pathway also underwent significant changes. Rictor protein expression increased during the development of diabetes, but the activation of mTORC2 did not increase with the increase in Rictor expression. GLUT4 translocation is regulated by Akt and its expression change during the development of diabetes. These findings suggest that altered energy metabolism is present in gastric smooth muscle that is associated with changes in the Rictor/mTORC2/Akt/GLUT4 pathway. Rictor/mTORC2/Akt/GLUT4 pathway may be involved in the regulation of energy metabolism in the gastric smooth muscle of diabetic rats and the development of diabetic gastroparesis.

CT for the evaluation of myocardial extracellular volume with MRI as reference: a systematic review and meta-analysis.

OBJECTIVE: Myocardial extracellular volume (ECV) fraction is an important imaging biomarker in clinical decision-making. CT-ECV is a potential alternative to MRI for ECV quantification. We conducted a meta-analysis to comprehensively assess the reliability of CT for ECV quantification with MRI as a reference. METHODS: We systematically searched PubMed, EMBASE, and the Cochrane Library for relevant articles published since the establishment of the database in July 2022. The articles comparing CT-ECV with MRI as a reference were included. Meta-analytic methods were applied to determine the pooled weighted bias, limits of agreement (LOA), and correlation coefficient (r) between CT-ECV and MRI-ECV. RESULTS: Seventeen studies with a total of 459 patients and 2231 myocardial segments were included. The pooled mean difference (MD), LOA, and r for ECV quantification at the per-patient level was (0.07%; 95% LOA: - 0.42 to 0.55%) and 0.89 (95% CI: 0.86-0.91), respectively, while on the per-segment level was (0.44%; 95% LOA: 0.16-0.72%) and 0.84 (95% CI: 0.82-0.85), respectively. The pooled r from studies with the ECViodine method for ECV quantification was significantly higher compared to those with the ECVsub method (0.94 (95% CI: 0.91-0.96) vs. 0.84 (95% CI: 0.80-0.88), respectively, p = 0.03). The pooled r from septal segments was significantly higher than those from non-septal segments (0.88 (95% CI: 0.86-0.90) vs. 0.76 (95% CI: 0.71-0.90), respectively, p = 0.009). CONCLUSION: CT showed a good agreement and excellent correlation with MRI for ECV quantification and is a potentially attractive alternative to MRI. CLINICAL RELEVANCE STATEMENT: The myocardial extracellular volume fraction can be acquired using a CT scan, which is not only a viable alternative to myocardial extracellular volume fraction derived from MRI but is also less time-consuming and costly for patients. KEY POINTS: • Noninvasive CT-ECV is a viable alternative to MRI-ECV for ECV quantification. • CT-ECV using the ECViodine method showed more accurate myocardial ECV quantification than ECVsub. • Septal myocardial segments showed lower measurement variability than non-septal segments for the ECV quantification.

Effectiveness of nurse-led multidisciplinary interventions in primary health care: A systematic review and meta-analysis.

AIM: This review aimed to synthesize the available evidence on the effectiveness of nurse-led multidisciplinary interventions in primary health care. METHODS: The following Chinese and English databases were searched for relevant articles: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang and Chinese Biomedical Literature Database (CBM), from the establishment of the databases until the last updating search 1 April 2022. Two researchers screened the studies independently and extracted the data. Meta-analysis was performed using the RevMan 5.3 software. RESULTS: A total of 12 studies were included in this review. It was found that nurse-led multidisciplinary interventions significantly shortened patients' length of stay in hospital (standardized mean differences [SMD] = -1.28, 95%CI: -2.03 to -0.54; P<0.001) and decreased incidences of complications (RR = 0.24, 95%CI:0.10 to 0.54; P = 0.0006) compared to the control group, and lowered patients' anxiety levels (SMD = -1.21, 95%CI: -1.99 to -0.44; P<0.01) and depression levels (SMD = -1.85, 95%CI: -3.42 to -0.28; P<0.0001). Furthermore, the results of subgroup analysis indicated that nurse-led multidisciplinary interventions had significant effects on patients' self-management ability (SMD = 4.45, 95%CI:2.45 to 6.44; P<0.0001) and quality of life (SMD = 1.01, 95%CI: 0.63 to 1.40; P<0.0001) compared to the control group. CONCLUSIONS: Nurse-led multidisciplinary interventions had strong effects in primary health care, contributing to shorten patients' length of stay in hospital, decrease incidences of complications and reduce the levels of anxiety and depression. Moreover, nurse-led multidisciplinary interventions also improved patients' self-management ability and quality of life.

Associations between the kynurenine pathway and the brain in patients with major depressive disorder-A systematic review of neuroimaging studies.

Previous studies have indicated that an imbalance in the kynurenine (KYN) pathway is an important pathophysiological mechanism of depression. Several studies have reported that an imbalance in the KYN pathway and its metabolites is associated with abnormalities in cerebral structure and function in depression, but the available evidence has been inconsistent. In this review, we systematically reviewed and integrated the findings concerning the associations between the KYN pathway and the brain in patients with major depressive disorder (MDD). A total of 22 neuroimaging studies were ultimately included in the present study. The neuroimaging modalities used in the studies included structural magnetic resonance imaging (MRI), diffusion tensor imaging, functional MRI, magnetic resonance spectroscopy, arterial spin labelling and positron emission tomography. The results revealed that an imbalance in the KYN pathway was associated with structural and functional abnormalities in several brain regions in patients with MDD. The brain regions most frequently associated with an imbalance in the KYN pathway were cortical regions (i.e., anterior cingulate cortex and orbitofrontal cortex), subcortical regions (i.e., striatum, thalamus and amygdala) and white matter fibres (i.e., inner capsule and left superior longitudinal tract). Our study provides robust evidence that cerebral abnormalities associated with the KYN pathway may be the underlying pathophysiological mechanisms of MDD. Future prospective studies are needed to further elucidate the causal relationships between the imbalanced KYN pathway and cerebral abnormalities in patients with MDD.

The Underappreciated Placebo Effects and Responses in Randomized Controlled Trials on Neck Pain: A Systematic Review With Meta-analysis.

OBJECTIVE: To quantify placebo effects and responses in randomized controlled trials (RCTs) on neck pain and explore how they would influence the treatment of neck pain. DATA SOURCES: We searched MEDLINE (PubMed), EMBASE (Ovid), CINAHL (EBSCO), Physiotherapy Evidence Database (PEDro), and World Health Organization International Clinical Trials Registry Platform from the inception of August 15, 2021, to identify relevant RCTs. STUDY SELECTION AND DATA EXTRACTION: The abstracts and full texts of potential studies were independently screened, and data extraction was also independently performed by 2 researchers. Scales of the score measuring neck pain and the scores both at baseline and the endpoint were extracted. DATA SYNTHESIS: A total of 60 RCTs were included. The mean improvement in the pain score after placebo treatment was 15.65 (mean difference [MD]=-15.65, 95% confidence interval; CI [-19.19, -12.12]; P<.05), which we defined as the placebo response. In the active groups, it was 25.91 (MD=-25.91, 95% CI [-29.15, -22.68]; P<.05), and in the no-treatment groups, it was 5.80 (MD=-5.80, 95% CI [13.28, 1.69]; P=.13). Using the 3 MDs from the 3 groups, the placebo effect was calculated to account for 38.0% of the pain score improvement in the active group. CONCLUSIONS: The pain scores of patients with neck pain were reduced after treatment with placebos, but the magnitude of pain score reduction was not clinically significant enough. The 38.0% amount of pain score reduction in patients treated with active interventions was caused by placebo. Interventions with considerable clinically significance for neck pain were still required.

A review of burnout in college English teachers in China.

College English teachers' job burnout has become prominent in the field of education. Using China National Knowledge Infrastructure (CNKI) database, this review research on burnout of college English language teachers in China from 2006 to 2021. The review demonstrates key research areas including teacher burnout severity and influencing variables related to teacher burnout. Individual factors, such as age, gender, marital status, educational background, professional title, and years of teaching experience are associated with burnout rates. University type and level, teaching-related role overload, scientific research stress induced by promotion, limited job autonomy, a stern hierarchical organizational system, and opaque operating rules are influencing factors discussed. Possible ways to reduce burnout across micro, meso, and macro-levels, along with practical implications and limitations are discussed.

[Aerosol Optical Characteristics with Ground-based Measurements via Sun Photometer and Its Relationship with PM Particle Concentration in Chang'an].

The simultaneous quantitative investigation of aerosol ground observation data and particle concentration data is important for a better understanding of the vertical distribution characteristics of air pollution and formulating reasonable air pollution control measures in Chang'an, Xi'an. CE-318 measurements from October 2018 to April 2021 were systematically analyzed to reveal the seasonal and yearly variations in atmospheric aerosols in Chang'an. Then, the relationship between AOD and particle concentration in different seasons and different pollution degrees was explored. The obtained results were as follows:① the seasonal variation in AOD in Chang'an was determined, whereby autumn (1.02)>winter (1.00)>summer (0.63)>spring (0.47). Distinct monthly and inter-annual differences in AOD were observed, showing that the annual average of AOD in 2019 was higher than that in 2020. ② Obvious seasonal and monthly differences in aerosol main control modes were observed; the dominant mode of aerosols gradually changed from coarse mode to fine mode from spring to winter. The seasonal variation in the main control mode of aerosols in 2019 was similar to that in the whole observation period. The seasonal aerosol Angstrom wavelength index (Angstrom) was evenly distributed in 2020, and aerosol particles existed in coarse mode form. Generally speaking, the aerosol type in Chang'an was mostly mixed aerosol throughout the whole observation period. ③ Significant seasonal variations in the relationship between AOD and Angstrom was shown, in which the air pollution in spring was dominated by coarse mode aerosol particles. The local pollution in summer was caused by coarse and fine mode aerosol particles, and the fine mode particles were dominant when the pollution was obvious. The characteristic distribution of Angstrom in autumn and winter was similar; in case of local pollution, the coarse mode aerosol particles were dominant, and in case of obvious pollution, the fine mode aerosol particles were dominant. ④ The monthly concentration variation trend of PM2.5 and PM10 in Chang'an consistent with the maximum and minimum values appeared in January and summer, respectively. Seasonal variation in the concentration of PM2.5 and PM10 was apparent, with the highest values in winter. ⑤ A positive correlation between AOD and particulate matter concentration in different seasons and pollution levels was obtained during the observation periods, but the correlation coefficient differed. The specific characteristics were as follows:the correlation between AOD and PM2.5 concentration was greater than that with PM10 concentration; the correlation between AOD and particle concentration in autumn and winter was greater than that in spring and summer; and the correlation between AOD and particulate matter concentration was greater in polluted weather. Particle concentration was the most important determinant of AOD change, followed by relative humidity, which was the meteorological factor with the highest interpretation rate of AOD change in Chang'an. This indicates that a higher correlation between AOD and particle concentration would benefit from a reasonable humidity correction of AOD.

Incidence of multiple myeloma in Kailuan cohort: A prospective community-based study in China.

BACKGROUND: Previous retrospective studies showed that the incidence and mortality rates for MM in China were lower than those in western countries. A large-scale prospective study on incidence and mortality rates of MM is still lacking. METHODS: Based on the prospective Kailuan Cohort study in China, we included all patients with MM in Kailuan Cohort from June 1, 2008 to December 31, 2016. Using the numbers of diagnosed cases and deaths during the study period as the numerators and the corresponding observed person-years as the denominators respectively, we calculated crude incidence and mortality rates. The 95% confidence intervals for crude incidence rate and mortality rate were estimated base on Poisson distribution. Rates were standardized by direct standardization according to the China population in 2000 and Segi' world standard population. RESULTS: A total of 22 members from Kailuan Cohort were first diagnosed with MM between 2008 and 2016. The calculated crude incidence rates were 2.8 (95% CI, 1.7-4.2) per 100,000 person-years for all participants. The standardized incidence rate was 0.9 per 100,000 person-years (95% CI, 0.5-2.1) when standardized by 2000 China population census data, and 1.0 per 100,000 person-years (95% CI, 0.6-1.8) when standardized by Segi's world standard population (WSP). The calculated crude mortality rates were 2.3 (95% CI, 1.4-3.6) per 100,000 person-years. The mortality standardized by 2000 China population census data was 0.7 per 100,000 person-years (95% CI, 0.3-1.9), and 0.9 per 100,000 population (95% CI, 0.5-1.7) when standardized by Segi's WSP. Both incidence and mortality for males were higher than that for females almost in all age groups. Both rates increased steadily with age. CONCLUSION: In this community-based prospective cohort study, we found that the incidence of MM in China was far lower than that in American and Europe.

Endocrine regulation of cancer stem cell compartments in breast tumors.

Cancer cells within breast tumors exist within a hierarchy in which only a small and rare subset of cells is able to regenerate growths with the heterogeneity of the original tumor. These highly malignant cancer cells, which behave like stem cells for new cancers and are called "cancer stem cells" or CSCs, have also been shown to possess increased resistance to therapeutics, and represent the root cause underlying therapy failures, persistence of residual disease, and relapse. As >90% of cancer deaths are due to refractory tumors, identification of critical molecular drivers of the CSC-state would reveal vulnerabilities that can be leveraged in designing therapeutics that eradicate advanced disease and improve patient survival outcomes. An expanding and complex body of work has now described the exquisite susceptibility of CSC pools to the regulatory influences of local and systemic hormones. Indeed, breast CSCs express a plethora of hormonal receptors, which funnel hormonal influences over every aspect of breast neoplasia - be it tumor onset, growth, survival, invasion, metastasis, or therapy resistance - via directly impacting CSC behavior. This article is intended to shed light on this active area of investigation by attempting to provide a systematic and comprehensive overview of the available evidence directly linking hormones to breast CSC biology.

The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer.

The development of triple-negative breast cancer (TNBC) is critically regulated by certain tumor-microenvironment-associated cells called mesenchymal stem/stromal cells (MSCs), which we and others have shown promote TNBC progression by activating pro-malignant signaling in neighboring cancer cells. Characterization of these cascades would better our understanding of TNBC biology and bring about therapeutics that eliminate the morbidity and mortality associated with advanced disease. Here, we focused on the emerging class of RNAs called long non-coding RNAs or lncRNAs and utilized a MSC-supported TNBC progression model to identify specific family members of functional relevance to TNBC pathogenesis. Indeed, although some have been described to play functional roles in TNBC, activities of lncRNAs as mediators of tumor-microenvironment-driven TNBC development remain to be fully explored. We report that MSCs stimulate robust expression of LINC01119 in TNBC cells, which in turn induces suppressor of cytokine signaling 5 (SOCS5), leading to accelerated cancer cell growth and tumorigenesis. We show that LINC01119 and SOCS5 exhibit tight correlation across multiple breast cancer gene sets and that they are highly enriched in TNBC patient cohorts. Importantly, we present evidence that the LINC01119-SOCS5 axis represents a powerful prognostic indicator of adverse outcomes in TNBC patients, and demonstrate that its repression severely impairs cancer cell growth. Altogether, our findings identify LINC01119 as a major driver of TNBC development and delineate critical non-coding RNA theranostics of potential translational utility in the management of advanced TNBC, a class of tumors in most need of effective and targeted therapy.

In vivo library screening identifies the metabolic enzyme aldolase A as a promoter of metastatic lung colonization.

Elucidations of the factors that promote the growth of disseminated tumor cells (DTCs) into life-threatening lesions stand to provide much needed prognostic and therapeutic targets of translational utility for patients with metastatic cancer. To identify such regulators, we conducted gain-of-function cDNA library screening to discover genes that foster prostate cancer cell colonization of mouse lungs as an experimental model. Our efforts identified the metabolic enzyme aldolase A (ALDOA) as a driver of cancer cell motility, anchorage-independent growth, and metastatic colonization, and as a prognosticator of adverse patient outcome across many malignancies, including prostate, breast, pancreatic, and liver cancers. Metabolomics coupled with biochemical and functional analyses revealed that ALDOA triggered the activation of adenosine-5'-monophosphate (AMP)-activated protein kinase (AMPK), which we demonstrate played essential promalignant activities in ALDOA-expressing cells. Collectively, these findings unveiled vivo approaches to identify metastatic colonization regulators and uncovered previously undescribed roles for ALDOA-AMPK pathway in tumor progression.

[Spatiotemporal Distribution of Aerosol Optical Depth Based on Landsat Data in the Hinterland of the Guanzhong Basin and Its Relationship with Urbanization].

Aerosol optical depth (AOD) is one of the most fundamental optical properties of aerosols that characterizes the attenuation of light by aerosols and is an indicator of regional air pollution. Based on the blue band surface reflectance database from the MOD09A1 products for the period 2000-2019 and the ASTER spectral database, AOD was estimated from Landsat TM/OLI data using the deep blue algorithm (DB). Multi-year average/annual average and seasonal AOD values for the period 2000-2019 were then calculated to analyze the spatial characteristics and temporal variations of AOD using the empirical orthogonal function method (EOF). Furthermore, the impacts of urbanization on the spatio-temporal distribution of AOD were analyzed. The obtained results are summarized as follows:① The multi-year average AOD spatial distribution in the hinterland of the Guanzhong Basin was significantly affected by topography and human activities, with higher AOD values and variationsin areas of low altitude and high-intensity human activities compared to the surrounding mountains. Thus, changes in AOD in the study area are mainly affected by anthropogenic factors. AOD also showed significant seasonal variations, whereby spring (0.34) > summer (0.33) > autumn (0.23) > winter (0.12), and the largest regional differences occurred in summer; ② The annual average AOD (from 2000-2019) showed the trend of "increase-decrease-increase", and reached a maximum in 2005, with the high AOD area gradually moving to the south. The distribution of AOD values in spring and summer was relatively discrete, while it is in a low-value agglomeration state in winter; ③ Three main AOD spatial distribution modes were identified based on the EOF, which had cumulative contribution rate of 83.0%. The spatial distribution trend of AOD showed regional consistency, with feature vectors consistent with the altitude, thus reflecting the difference of AOD at different altitudes. Taking the Qinling Mountains as the dividing line, the AOD presented the "north-south" pattern, AOD showed a "north-south" pattern, reflecting the uniqueness of the regional development in the Guanzhong Basin compared to the southern Qinling Mountains. The "southeast-northwest" distribution pattern indicated that the AOD presented a reverse change trend between urban and non-urban; and ④ The results of correlation analysis between the AOD and urbanization revealed a positive correlation with permanent population density (R2=0.707, P<0.05), impervious surface density (R2=0.377, P<0.05), and industrial POI density (R2=0.727, P<0.5). These results are significant for improving the monitoring of air quality in the Guanzhong Basin and for the construction of an urban ecological environment.

A Non-Lipolysis Nanoemulsion Improved Oral Bioavailability by Reducing the First-Pass Metabolism of Raloxifene, and Related Absorption Mechanisms Being Studied.

OBJECTIVE: A non-lipolysis nanoemulsion (NNE) was designed to reduce the first-pass metabolism of raloxifene (RAL) by intestinal UDP-glucuronosyltransferases (UGTs) for increasing the oral absorption of RAL, coupled with in vitro and in vivo studies. METHODS: In vitro stability of NNE was evaluated by lipolysis and the UGT metabolism system. The oral bioavailability of NNE was studied in rats and pigs. Finally, the absorption mechanisms of NNE were investigated by in situ single-pass intestinal perfusion (SPIP) in rats, Madin-Darby canine kidney (MDCK) cells model, and lymphatic blocking model. RESULTS: The pre-NNE consisted of isopropyl palmitate, linoleic acid, Cremophor RH40, and ethanol in a weight ratio of 3.33:1.67:3:2. Compared to lipolysis nanoemulsion of RAL (RAL-LNE), the RAL-NNE was more stable in in vitro gastrointestinal buffers, lipolysis, and UGT metabolism system (p < 0.05). The oral bioavailability was significantly improved by the NNE (203.30%) and the LNE (205.89%) relative to the suspension group in rats. However, 541.28% relative bioavailability was achieved in pigs after oral NNE intake compared to the suspension and had two-fold greater bioavailability than the LNE (p < 0.05). The RAL-NNE was mainly absorbed in the jejunum and had high permeability at the intestine of rats. The results of both SPIP and MDCK cell models demonstrated that the RAL-NNE was absorbed via endocytosis mediated by caveolin and clathrin. The other absorption route, the lymphatic transport (cycloheximide as blocking agent), was significantly improved by the NNE compared with the LNE (p < 0.05). CONCLUSION: A NNE was successfully developed to reduce the first-pass metabolism of RAL in the intestine and enhance its lymphatic transport, thereby improving the oral bioavailability. Altogether, NNE is a promising carrier for the oral delivery of drugs with significant first-pass metabolism.

The treatment option of progressive disease in breast cancer during neoadjuvant chemotherapy: a single-center experience.

Patients' responses to breast cancer neoadjuvant chemotherapy (NACT) differ because of heterogeneous tumor characteristics. Reports about NACT progression are sporadic. Here we enrolled 1187 patients who received NACT in our cancer center between January 1, 2007, and December 31, 2016. We analyzed the characteristics and treatments of patients with progressive disease (PD) or non-PD or pathological complete response (pCR). In total, 45 (3.8%) patients had PD. PD patients were associated with a significantly worse disease-free survival (DFS) (hazard ratio (HR) = 3.77; 95% CI, 1.77 to 8.00; P =.001) and overall survival (OS) (HR = 3.85; 95% CI, 1.77 to 8.35; P =.001). For the PD patients, 28 (62.2%) patients received mastectomy immediately after PD, and 17 (37.8%) changed to chemotherapy. DFS and OS exhibited no significant differences between these two salvage therapies. After a change to second chemotherapy, 58.8% (10/17) patients had PD or SD. With the exception of tumor size, pretreatment T stage, and histology type, no other significant differences were noted between PD and pCR patients. Our results demonstrated that PD patients were associated with a significantly worse prognosis. Based on these results, we suggest to give the addition of trastuzumab to HER-2 positive patients instead of changing the chemotherapy regimen and proceeding to surgery instead of further chemotherapy once patients have PD during NACT. Given that some similar characteristics exist between PD and pCR patients, more studies to identify novel molecular markers to predict disease response to NACT should be performed.