Enzyme-accelerated catalytic DNA circuits enable rapid and one-pot detection of bacterial pathogens.

Catalytic DNA circuits, serving as signal amplification strategies, can enable simple and accurate detection of pathogenic bacteria in complex matrices but suffer from low reaction rates and depths. Herein, we design an enzyme-accelerated catalytic hairpin assembly (EACHA) in which duplex DNA products are converted into hairpin reactants to continue participating in the next circuit reaction with the assistance of RNase H. Profiting from the high recyclability of the reactants, EACHA exhibits an approximately 37.6-fold enhancement in the rate constant and a two-order-of-magnitude improvement in sensitivity compared to conventional catalytic hairpin assembly (CHA). By integrating an allosteric probe with EACHA, a one-pot method is developed for rapid and direct detection of S. enterica Enteritidis (S. Enteritidis). This method is capable of detecting 15 CFU mL-1 of S. Enteritidis within 20 min, which is superior to that of real-time PCR. By testing 60 milk samples, we demonstrate this method's high accuracy in discriminating contaminated samples, with an area under the curve (AUC) of 0.997. Moreover, this method can be employed to accurately diagnose early-stage infected mice, with an AUC of 1.00 for feces samples and 0.986 for serum samples. Therefore, this study offers a simple and feasible method for identifying pathogens in complex matrices.

GlycoSS: A DNA Glycosignal Sieve for Deciphering Spatially Resolved EpCAM-Specific Glycoforms.

Malignant transformation of cancer is often accompanied by aberrant glycopatterns. Epithelial-mesenchymal transition (EMT) is a crucial biological process in cancer migration and invasion, accelerating cancer deterioration. High-precision analysis of protein-glycan spatial profiling in the EMT process is essential for elucidating glycosylation functions and cancer progression. However, the diversity of glycans in composition and conformation complicates their spatial analysis. Here, we develop a DNA glycosignal sieve (GlycoSS) visualization platform for screening glycoform expression with a protein spatial dimension. GlycoSS utilizes protein-anchored DNA nanoscanners of distinct lengths to control glycosignal readout, enabling protein-glycan distance modulations, and simultaneously orthogonally amplify glycoform output through signal amplification by an exchange reaction. Using GlycoSS, we screened EpCAM-specific hypoglycosylated glycoform signals in different breast cancer cell subtypes, especially characterizing the spatial distribution of glycans on the MCF-7 cell surface. Considering that the EpCAM-specific N-glycan dysregulation in EMT is pivotal, GlycoSS revealed dynamic glycan fluctuations during IGF-1-induced EMT, revealing that the N-glycans were positively associated with tumor malignancy and metastasis. GlycoSS is anticipated to accelerate the identification of aberrant N-glycosylation in tumor progression, advancing systemic glycobiology insights. Notably, GlycoSS is capable of analyzing diverse glycoprotein profiles, offering additional dimensions into the role of glycoprotein nanoenvironments in regulating membrane protein function.

ETS1 deficiency in macrophages suppresses colorectal cancer progression by reducing the F4/80+TIM4+ macrophage population.

Tumor-associated macrophages (TAMs) take on pivotal and complex roles in the tumor microenvironment (TME); however, their heterogeneity in the TME remains incompletely understood. ETS proto-oncogene 1 (ETS1) is a transcription factor that is mainly expressed in lymphocytes. However, its expression and immunoregulatory role in colorectal cancer (CRC)-associated macrophages remain unclear. In the study, the expression levels of ETS1 in CD68+ macrophages in the CRC microenvironment were significantly higher than those in matched paracarcinoma tissues. Importantly, ETS1 increased the levels of chemokines C-C motif chemokine ligand 2 (CCL2) and C-X-C motif chemokine ligand 10 (CXCL10) in lipopolysaccharide-stimulated THP-1 cells. It also boosted the migration and invasion of CRC cells during the in vitro co-culture. In the ETS1 conditional knockout mouse model, ETS1 deficiency in macrophages ameliorated the histological changes in DSS-induced ulcerative colitis mouse models and prolonged the survival in an azomethane/dextran sodium sulfate (AOM/DSS)-induced CRC model. ETS1 deficiency in macrophages substantially inhibited tumor formation, reduced F4/80+TIM4+ macrophages in the mesenteric lymph nodes, and decreased CCL2 and CXCL10 protein levels in tumor tissues. Moreover, ETS1 deficiency in macrophages effectively prevented liver metastasis of CRC and reduced the infiltration of TAMs into the metastasis sites. Subsequent studies have indicated that ETS1 upregulated the expression of T-cell immunoglobulin mucin receptor 4 in macrophages through the signal transducer and activator of the transcription 1 signaling pathway activated by the autocrine action of CCL2/CXCL10. Collectively, ETS1 deficiency in macrophages potentiates antitumor immune responses by repressing CCL2 and CXCL10 expression, shedding light on potential therapeutic strategies for CRC.

The effect mechanism of perceived entrepreneurial environment on Chinese college students' entrepreneurial intention: chain mediation model test.

Introduction: This study aimed to explore the effect of perceived entrepreneurial environment among Chinese college students' entrepreneurial intention and its underlying mechanism. Methods: Based on a survey of 445 college students from 5 universities with the perceived entrepreneurial environment assessment scale, the achievement motivation scale, the entrepreneurial self-efficacy scale, and the entrepreneurial intention questionnaire. Results: There were significant correlations among perceived entrepreneurial environment, achievement motivation, entrepreneurial self-efficacy, and entrepreneurial intention, and perceived entrepreneurial environment could significantly positively predict entrepreneurial intention. Achievement motivation and entrepreneurial self-efficacy played significant mediating roles between the perceived entrepreneurial environment and entrepreneurial intention. There were three paths that perceived entrepreneurial environment to influence entrepreneurial intention: One was the mediating role of achievement motivation; The second was the mediating role of entrepreneurial self-efficacy; The third was the chain-mediated role of both achievement motivation and entrepreneurial self-efficacy. Discussion: The internal mechanism of the relationship between perceived entrepreneurial environment and entrepreneurial intention enriches the research results of entrepreneurial psychology among college students and provides a theoretical basis for training and guiding the entrepreneurship of college students.

Circ-IP6K2 suppresses tumor progression by modulating the miR-1292-5p/CAMK2N1 signal in clear cell renal cell carcinoma.

Renal cell carcinoma (RCC) is a malignant tumor originating from the epithelial cells of the renal tubules. The clear cell RCC subtype is closely linked to a poor prognosis due to its rapid progression. Circular RNA (circRNA) is a novel class of regulatory RNA molecules that play a role in the development of ccRCC, although their functions have not been fully elucidated. In this study, we identified a significant downregulation of circ-IP6K2 in ccRCC tissues based on data from the GSE100186 dataset. The decreased expression of circ-IP6K2 correlated with the progression of TNM stage and histological grade, and was also associated with decreased overall survival rates in ccRCC patients. Moreover, our findings revealed that circ-IP6K2 expression suppressed proliferation, migration, and invasion capabilities in vitro, and inhibited xenograft growth in vivo. Mechanistically, circ-IP6K2 acted as a sponge for miR-1292-5p in ccRCC cells, which in turn targeted the 3'UTR of CAMK2N1, leading to a decrease in its expression. CAMK2N1 was identified as a tumor suppressor that negatively regulated the ß-catenin/c-Myc oncogenic signaling pathway. Additionally, we confirmed a positive correlation between the expression of circ-IP6K2 and CAMK2N1 in ccRCC. Circ-IP6K2 functions to impede the progression of ccRCC by modulating the miR-1292-5p/CAMK2N1 axis. These findings shed new light on the molecular mechanisms driving ccRCC progression and suggest potential therapeutic targets for the treatment of ccRCC.

Mitochondrial activity related genes of mast cells identify poor prognosis and metastasis of ovarian cancer.

The pro-tumorigenic or anti-tumorigenic role of tumor infiltrating mast cells (TIMs) in tumors depends not only on the type of cancer and the degree of tumor progression, but also on their location in the tumor bulk. In our investigation, we employed immunohistochemistry to reveal that the mast cells (MCs) in the tumor stroma are positively correlated with metastasis of ovarian cancer (OC), but not in the tumor parenchyma. To delve deeper into the influence of different culture matrix stiffness on MCs' biological functions within the tumor parenchymal and stromal regions, we conducted a transcriptome analysis of the mouse MC line (P815) cultured in two-dimensional (2D) or three-dimensional (3D) culture system. Further research has found that the softer 3D extracellular matrix stiffness could improve the mitochondrial activity of MCs to promote proliferation by increasing the expression levels of mitochondrial activity-related genes, namely Pet100, atp5md, and Cox7a2. Furthermore, employing LASSO regression analysis, we identified that Pet100 and Cox7a2 were closely associated with the prognosis of OC patients. These two genes were subsequently employed to construct a risk score model, which revealed that the high-risk group model as one of the prognostic factors for OC patients. Additionally, the XCell algorithm analysis showed that the high-risk group displayed a broader spectrum of immune cell infiltrations. Our research revealed that TIMs in the tumor stroma could promote the metastasis of OC, and mitochondrial activity-related proteins Pet100/Cox7a2 can serve as biomarkers for prognostic evaluation of OC.

DUSP22 inhibits lung tumorigenesis by suppression of EGFR/c-Met signaling.

DUSP22, an atypical dual-specificity phosphatase enzyme, plays a significant role in regulating multiple kinase signaling pathways by dephosphorylation. Our study demonstrated that decreased DUSP22 expression is associated with shorter disease-free survival, advanced TNM (tumor, lymph nodes, and metastasis), cancer stage, and higher tumor grade in lung adenocarcinoma (LUAD) patients. Exogenous DUSP22 expression reduces the colony-forming capacity of lung cancer cells and inhibits xenograft tumor growth primarily by targeting EGFR and suppressing its activity through dephosphorylation. Knockdown of DUSP22 using shRNA enhances EGFR dependency in HCC827 lung cancer cells and increases sensitivity to gefitinib, an EGFR inhibitor. Consistently, genetic deletion of DUSP22 enhances EGFRdel (exon 19 deletion)-driven lung tumorigenesis and elevates EGFR activity. Pharmacological inhibition of DUSP22 activates EGFR, ERK1/2, and upregulates downstream PD-L1 expression. Additionally, lentiviral deletion of DUSP22 by shRNA enhances lung cancer cell migration through EGFR/c-Met and PD-L1-dependent pathways. Gefitinib, an EGFR inhibitor, mechanistically suppresses migration induced by DUSP22 deletion and inhibits c-Met activity. Furthermore, cabozantinib, a c-Met inhibitor, reduces migration and attenuates EGFR activation caused by DUSP22 deletion. Collectively, our findings support the hypothesis that loss of DUSP22 function in lung cancer cells confers a survival advantage by augmenting EGFR signaling, leading to increased activation of downstream c-Met, ERK1/2, and PD-L1 axis, ultimately contributing to the progression of advanced lung cancer.

Ubiquitin-specific protease-7 promotes expression of airway mucin MUC5AC via the NF-κB signaling pathway.

Chronic obstructive pulmonary disease (COPD) and other respiratory diseases frequently present with airway mucus hypersecretion, which not only affects the patient's quality of life but also poses a constant threat to their life expectancy. Ubiquitin-specific protease 7 (USP7), a deubiquitinating enzyme, affects cell differentiation, tissue growth, and disease development. However, its role in airway mucus hypersecretion induced by COPD remains elusive. In this study, USP7 expression was significantly upregulated in airway epithelial samples from patients with COPD, and USP7 was also overexpressed in mouse lung and human airway epithelial cells in models of airway mucus hypersecretion. Inhibition of USP7 reduced the expression of nuclear factor kappa B (NF-κB), phosphorylated-NF-κB (p-NF-κB), and phosphonated inhibitor of nuclear factor kappa B (p-IκBα), and alleviated the airway mucus hypersecretion in vivo and in vitro. Further research revealed that USP7 stimulated airway mucus hypersecretion through the activation of NF-κB nuclear translocation. In addition, the expression of mucin 5AC (MUC5AC) was suppressed by the NF-κB inhibitor erdosteine. These findings suggest that USP7 stimulates the NF-κB signaling pathway, which promotes airway mucus hypersecretion. This study identifies one of the mechanisms regulating airway mucus secretion and provides a new potential target for its prevention and treatment.

Response surface optimization of sludge dewatering process: synergistic enhancement by ultrasonic, chitosan and sludge-based biochar.

Due to the colloidal stability, the high compressibility and the high hydration of extracellular polymeric substances (EPS), it is difficult to efficiently dehydrate sludge. In order to enhance sludge dewatering, the process of ultrasonic (US) cracking, chitosan (CTS) re-flocculation and sludge-based biochar (SBB) skeleton adsorption of water-holding substances to regulate sludge dewaterability was proposed. Based on the response surface method, the prediction model of the specific resistance to filtration (SRF) and sludge cake moisture content (MC) was established. The US cracking time and the dosage of CTS and SBB were optimized. The results showed that the optimal parameters of the three were 5.08 s, 10.1 mg/g dry solids (DS) and 0.477 g/g DS, respectively. Meantime, the SRF and MC were 5.4125 × 1011 m/kg and 76.8123%, which significantly improved the sludge dewaterability. According to the variance analysis, it is found that the fitting degree of SRF and MC model is good, which also confirms that there is significant interaction and synergy between US, CTS and SBB, and the contribution of CTS and SBB is greater. Moreover, the process significantly improves the sludge's calorific value and makes its combustion more durable.

Machine Learning-Based Multiparametric Magnetic Resonance Imaging Radiomics Model for Preoperative Predicting the Deep Stromal Invasion in Patients with Early Cervical Cancer.

Deep stromal invasion is an important pathological factor associated with the treatments and prognosis of cervical cancer patients. Accurate determination of deep stromal invasion before radical hysterectomy (RH) is of great value for early clinical treatment decision-making and improving the prognosis of these patients. Machine learning is gradually applied in the construction of clinical models to improve the accuracy of clinical diagnosis or prediction, but whether machine learning can improve the preoperative diagnosis accuracy of deep stromal invasion in patients with cervical cancer was still unclear. This cross-sectional study was to construct three preoperative diagnostic models for deep stromal invasion in patients with early cervical cancer based on clinical, radiomics, and clinical combined radiomics data using the machine learning method. We enrolled 229 patients with early cervical cancer receiving RH combined with pelvic lymph node dissection (PLND). The least absolute shrinkage and selection operator (LASSO) and the fivefold cross-validation were applied to screen out radiomics features. Univariate and multivariate logistic regression analyses were applied to identify clinical predictors. All subjects were divided into the training set (n = 160) and testing set (n = 69) at a ratio of 7:3. Three light gradient boosting machine (LightGBM) models were constructed in the training set and verified in the testing set. The radiomics features were statistically different between deep stromal invasion < 1/3 group and deep stromal invasion ≥ 1/3 group. In the training set, the area under the curve (AUC) of the prediction model based on radiomics features was 0.951 (95% confidence interval (CI) 0.922-0.980), the AUC of the prediction model based on clinical predictors was 0.769 (95% CI 0.703-0.835), and the AUC of the prediction model based on radiomics features and clinical predictors was 0.969 (95% CI 0.947-0.990). The AUC of the prediction model based on radiomics features and clinical predictors was 0.914 (95% CI 0.848-0.980) in the testing set. The prediction model for deep stromal invasion in patients with early cervical cancer based on clinical and radiomics data exhibited good predictive performance with an AUC of 0.969, which might help the clinicians early identify patients with high risk of deep stromal invasion and provide timely interventions.

Functionalized tetrahedral DNA frameworks for the capture of circulating tumor cells.

Identification and characterization of circulating tumor cells (CTCs) from blood samples of patients with cancer can help monitor parameters such as disease stage, disease progression and therapeutic efficiency. However, the sensitivity and specificity of current multivalent approaches used for CTC capture is limited by the lack of control over the ligands' position. In this Protocol Update, we describe DNA-tetrahedral frameworks anchored with aptamers that can be configured with user-defined spatial arrangements and stoichiometries. The modified tetrahedral DNA frameworks, termed 'n-simplexes', can be used as probes to specifically target receptor-ligand interactions on the cell membrane. Here, we describe the synthesis and use of n-simplexes that target the epithelial cell adhesion molecule expressed on the surface of CTCs. The characterization of the n-simplexes includes measuring the binding affinity to the membrane receptors as a result of the spatial arrangement and stoichiometry of the aptamers. We further detail the capture of CTCs from patient blood samples. The procedure for the preparation and characterization of n-simplexes requires 11.5 h, CTC capture from clinical samples and data processing requires ~5 h per six samples and the downstream analysis of captured cells typically requires 5.5 h. The protocol is suitable for users with basic expertise in molecular biology and handling of clinical samples.

GRP78 inhibitor HA15 increases the effect of Bortezomib on eradicating multiple myeloma cells through triggering endoplasmic reticulum stress.

Bortezomib (BTZ), a selective proteasome inhibitor, exhibits a significant efficacy in the therapy of multiple myeloma (MM) partly through triggering endoplasmic reticulum (ER) stress-dependent apoptosis. However, sensitivity to BTZ varies greatly among patients. ER stress functions as a double-edged sword in regulating cell survival depending on cell context and ER stress extent. The major aim of this study was to investigate whether GRP78 inhibitor, HA15, increased the therapeutic effect of BTZ on MM to through further increasing ER stress and shifting the balance towards cell apoptosis. The biological role of BTZ and HA15 was assessed using Cell counting kit- (CCK-) 8, colony formation, and Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labelling (TUNEL) assay. We found that BTZ combined with HA15 remarkably decreased MM cell viability more effective than BTZ monotherapy, though low dose of HA15 did not exhibit a significant cytotoxicity to MM cells. BTZ combined with HA15 also repressed colony formation ability of MM cell and accelerated MM cell apoptosis compared with BTZ monotherapy. Mechanistically, HA15 synergized with BTZ to trigger ER stress, as evidence by significantly increased expression of ER stress markers (GRP78, ATF4, CHOP, and XBP1). Importantly, unfolded protein response (UPR) inhibitor significantly damaged the effect of BTZ combined with HA15 on accelerating MM cell death. In vivo, combination treatment with BTZ and HA15 inhibited tumor growth more effective than BTZ alone, whereas these effects were blocked by UPR inhibitor. Taken together, these results demonstrate that ER stress is a critical pathway in regulating MM cell survival, and that combination treatment with BTZ and HA15 may be an effective strategy to treat MM patients that fail to respond to BTZ monotherapy.

The Burden of Attention-Deficit/Hyperactivity Disorder Traits in Adult Patients with Major Depressive Disorder in Japan.

Purpose: Symptoms of attention-deficit/hyperactivity disorder (ADHD) often overlap with and are hidden by those of mood disorders, including major depressive disorder (MDD), resulting in adult ADHD patients being misdiagnosed as MDD. This study aims to examine if diagnosed MDD patients are more likely to exhibit ADHD traits and if the presence of ADHD traits increases the humanistic burden, including the impairment of health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), and health-care resource utilization (HRU), on MDD patients in Japan. Methods: This study utilized existing National Health and Wellness Survey (NHWS) data. The 2016 Japan NHWS is an internet-based survey comprising a total of 39,000 respondents, including those with MDD and/or ADHD. A randomly selected subset of the respondents responded to the Japanese-version Adult ADHD self-report scale (ASRS-v1.1; ASRS-J) symptom checklist. Respondents were considered ASRS-J-positive if the total score was ≥36. The HRQoL, WPAI, and HRU were assessed. Results: Among MDD patients (n = 267), 19.9% were screened ASRS-J-positive, while 4.0% of non-MDD respondents (n = 8885) were ASRS-J-positive. There was a significant association between MDD status and ASRS-J status (crude odds-ratio [OR]: 5.9) as well as between MDD status and ADHD-diagnosis status (crude OR: 22.6). MDD patients who were ASRS-J positive experienced significantly lower HRQoL and higher WPAI than those who were ASRS-J negative. Limitations of this study include potential recall bias owing to the self-report nature of the survey and lack of objective confirmation of MDD diagnosis through review of medical records. Conclusion: This study demonstrated a significant association between MDD status and exhibiting ADHD traits. Adult MDD patients screened ASRS-J-positive experienced significantly higher humanistic burden than patients screened ASRS-J-negative. Our results emphasize the importance of ensuring appropriate screening of ADHD and looking out for potentially hidden ADHD symptoms when diagnosing and treating MDD in adulthood.

DNA-Guided Extracellular-Vesicle Metallization with High Catalytic Activity for Accurate Diagnosis of Pulmonary Nodules.

Sensitive and specific analysis of extracellular vesicles (EVs) offers a promising minimally invasive way to identify malignant pulmonary nodules from benign lesions. However, accurate analysis of EVs is subject to free target proteins in blood samples, which compromises the clinical diagnosis value of EVs. Here a DNA-guided extracellular-vesicle metallization (DEVM) strategy is described for ultrasensitive and specific analysis of EV protein biomarkers and classification of pulmonary nodules. The facile DEVM process mainly includes the incorporation of DNA labeled with cholesterol and thiol groups into EV membranes and subsequent deposition of Au3+ and Pt4+ to allow the DNA-functionalized EVs to be encapsulated with AuPt nanoshells. It is found that the synthesized AuPt-metallized EVs possess extrinsic peroxidase-like activity. Utilizing the feature of the catalytic metal nanoshells just growth on the EV membranes, the DEVM method enables multiparametric recognition of target proteins and EV membranes and can produce an amplified colorimetric signal, avoiding the interference of free proteins. By profiling four surface proteins of EVs from 48 patients with pulmonary nodules, the highest area under the receiver operating characteristic curve (0.9983) is obtained. Therefore, this work provides a feasible EVs analysis tool for accurate pulmonary nodules management.

Target response controlled enzyme activity switch for multimodal biosensing detection.

How to achieve delicate regulation of enzyme activity and empower it with more roles is the peak in the field of enzyme catalysis research. Traditional proteases or novel nano-enzymes are unable to achieve stimulus-responsive activity modulation due to their own structural limitations. Here, we propose a novel Controllable Enzyme Activity Switch, CEAS, based on hemin aggregation regulation, to deeply explore its regulatory mechanism and develop multimodal biosensing applications. The core of CEAS relies on the dimerizable inactivation of catalytically active center hemin and utilizes a DNA template to orderly guide the G4-Hemin DNAzyme to tightly bind to DNA-Hemin, thereby shutting down the catalytic ability. By customizing the design of the guide template, different target stimulus responses lead to hemin dimerization dissociation and restore the synergistic catalysis of G4-Hemin and DNA-Hemin, thus achieving a target-regulated enzymatic activity switch. Moreover, the programmability of CEAS allowed it easy to couple with a variety of DNA recognition and amplification techniques, thus developing a series of visual protein detection systems and highly sensitive fluorescent detection systems with excellent bioanalytical performance. Therefore, the construction of CEAS is expected to break the limitation of conventional enzymes that cannot be targetable regulated, thus enabling customizable enzymatic reaction systems and providing a new paradigm for controllable enzyme activities.

Non-invasive brain stimulation for limb motor function and daily living activity improvement in acute stroke: A meta-analysis.

OBJECTIVE: To evaluate the effect of non-invasive brain stimulation (NIBS) in improving limb motor dysfunction and daily living activity during at the phase of acute stroke. MATERIALS AND METHODS: Randomized controlled trials about the effect of NIBS on hemiparesis in acute stroke were retrieved from databases of China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Data, CBM, PubMed, Embase, Cochrane Library, and Web of Science from inception until January 3rd 2022. The quality of the trials was assessed, and the data were extracted according to the Cochrane Handbook for Systematic Reviews of Interventions. A statistical analysis was carried out using Review Manager 5.3 and STATA 14. The effect size was evaluated by using the weighed mean difference (WMD) and a 95% confidence interval (CI). The stability and sensitivity of the results and sources of heterogeneity were also analyzed. RESULTS: 12 studies involving 639 patients were included. Our meta-analysis showed that NIBS could improve the Fugl-Meyer Assessment (weighed mean difference = 3.96, 95% confidence interval = 3.45 to 4.48) and Barthel Index (weighed mean difference = 12.29, 95% confidence interval = 4.93 to 19.66), while reducing the National Institutes of Health Stroke Scale (weighed mean difference = -2.37, 95% confidence interval = -3.43 to -1.31). CONCLUSION: NIBS is effective in improving paretic limb motor function and activities of daily living in patients during at the phase of acute stroke.

Digital economy and pollution reduction-Mechanism and regional heterogeneity.

The digital economy and ecological environment are two major issues related to high-quality economic development. Scholars have not yet reached a unified conclusion about the link between the digital economy and pollution emissions, and the impact mechanism of the former on the latter needs further study. Using data from 278 Chinese cities from 2010 to 2019, this research employs coupling coordination analysis, fixed effect analysis and mediation analysis to examine the heterogeneous impact mechanisms of the expansion of the digital economy on urban pollution reduction from many angles. It discovers that, first, the growth of the digital economy has decreased the discharge of urban pollutants overall. Second, the impact mechanisms of the digital economy are heterogeneous. From a regional perspective, industrial structure supererogation plays an intermediary role in the relationship between digital economy development and pollution reduction in the eastern and central regions, but the mediating effect is not significant in the western and northeastern regions. In terms of the city development level, industrial structure supererogation has significantly mediated the relationship between the growth of the digital economy and the reduction of pollution in first- and second-tier cities, but this mediating effect is not significant in third-tier and other cities. Third, the above conclusions are still valid after the robustness test is carried out using instrumental variable estimation, replacement of the estimation method, and replacement of explanatory variables. This study is a useful contribution to research on the effects of the digital economy and the factors influencing pollution reduction. The results advance the study of the digital economy and also have practical implications for improving China's ecological environment and fostering high-quality economic growth. Finally, we provide policy suggestions for the coordinated promotion of the digital economy's development, industrial structure supererogation and environmental pollution reduction.

A CT-Based Radiomics Nomogram Combined with Clinic-Radiological Characteristics for Preoperative Prediction of the Novel IASLC Grading of Invasive Pulmonary Adenocarcinoma.

RATIONALE AND OBJECTIVES: The novel International Association for the Study of Lung Cancer (IASLC) grading system of invasive lung adenocarcinoma (ADC) demonstrated a remarkable prognostic effect and enabled numerous patients to benefit from adjuvant chemotherapy. We sought to build a CT-based nomogram for preoperative prediction of the IASLC grading. MATERIALS AND METHODS: This work retrospectively analyzed the CT images and clinical data of 303 patients with pathologically confirmed invasive ADC. The histological subtypes and radiological characteristics of the patients were re-evaluated. Radiomics features were extracted, and the optimal subset of features was established by ANOVA, spearman correlation analysis, and the least absolute shrinkage and selection operator (LASSO). Univariate and multivariate analyses identified the independent clinical and radiological variables. Finally, multivariate logistic regression analysis incorporated clinical, radiological, and optimal radiomics features into the nomogram. Receiver operating characteristic (ROC) curve, and accuracy were applied to assess the model's performance. Decision curve analysis (DCA), and calibration curve were applied to assess the clinical usefulness. RESULTS: Nine selected CT image features were used to develop the radiomics model. The accuracy, precision, sensitivity, and specificity of the radiomics model outperformed the clinic-radiological model in the training and testing sets. Integrating Radscore with independent radiological characteristics showed higher prediction performance than clinic-radiological characteristics alone in the training (AUC, 0.915 vs. 0.882; DeLong, p < 0.05) and testing (AUC, 0.838 vs. 0.782; DeLong, p < 0.05) sets. Good calibration and decision curve analysis demonstrated the clinical usefulness of the nomogram. CONCLUSION: Radiomics features effectively predict high-grade ADC. The combined nomogram may facilitate selecting patients who benefit from adjuvant treatment.

MMP11 and MMP14 contribute to the interaction between castration-resistant prostate cancer and adipocytes.

Previous studies have demonstrated that adipocytes promote prostate cancer (PCa) cell progression, which facilitates the development of PCa into castration-resistant prostate cancer (CRPC); however, the underlying mechanisms are still not fully understood. Matrix metalloproteinases (MMPs) are a group of proteases responsible for the degradation of extracellular matrix (ECM) and the activation of latent factors. In our study, we detected that MMP11 expression was increased in PCa patients and that a high level of MMP11 was correlated with poor prognosis. Furthermore, siRNA knockdown of MMP11 in CRPC cells not only blocked the delipidation and dedifferentiation of mature adipocytes but also reduced the lipid uptake and utilization of CRPC cells in a cell co-culture model. The number of mitophagosomes and the expression level of Parkin were increased in MMP11-silenced CRPC cells. Moreover, we found that simultaneous downregulation of MMP14 and MMP11 expression may benefit patient survival. Indeed, MMP11/14 knockdown in CRPC cells significantly decreased lipid metabolism and cell invasion, at least partly through the mTOR/HIF1α/MMP2 signaling pathway. Importantly, MMP11/14 knockdown dramatically delayed tumor growth in a xenograft mouse model. Consistently, the decreased lipid metabolism, Ki67 and MMP2 expression, as well as the increased Parkin level were also confirmed in in vivo experiments, further demonstrating the mechanisms responsible for the tumor-promoting effects of MMP11/14. Collectively, our study elucidated the role of MMP11 and MMP14 in the bidirectional crosstalk between adipocytes and CRPC cells and provided the rationale of targeting MMP11/14 for the treatment of CRPC patients.