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This study evaluated the diagnostic value of the automated UF-5000 parameters and compared it with that of aberrant erythrocytes and acanthocytes classified by microscopy for identifying IgA glomerular hematuria to propose a predictive model for clinical use. It also compared correlations between erythrocyte parameters and malformed erythrocytes. Urine samples from 53 biopsy-proven IgA hematuria cases and 143 non-IGA nephropathic hematuria cases as controls were analyzed. The ratio of small red blood cells to nonlysed red blood cells (UF-sRBC%) and lysed red blood cells (lysed RBCs) showed good diagnostic performance for IgA glomerular hematuria (area under the curve [AUC] = 0.857 [P = 0.000] and AUC = 0.860 [P = 0.000], respectively). Combining UF-sRBC%, lysed RBCs, and urine protein dry chemistry improved the diagnostic accuracy (AUC = 0.967; positive predictive value [PPV] = 91.89%; negative predictive value [NPV] = 93.10%; P = 0.000). This approach surpassed traditional microscopy for aberrant erythrocytes (AUC = 0.895; PPV = 62.27%; NPV = 88.66%; P = 0.008) and acanthocytes (AUC = 0.868; PPV = 72.97%; NPV = 83.65%; P = 0.006). The erythrocyte size index was negatively correlated with the proportion of urinary aberrant erythrocytes (r = - 0.787; P = 0.000). The UF-5000 erythrocyte parameters facilitate rapid identification of IgA nephropathy and could replace manual microscopy., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Pancreatic cancer (PC) is one of the most aggressive malignancies worldwide, and few effective therapeutics are available. Osthole (OST), a natural coumarin, has been proven to be a potential anticancer compound. In this study, we found that OST significantly inhibited PC growth both in vitro and in vivo. Notably, the anti-PC effect of OST is mediated by excessive autophagosome accumulation and consequent apoptosis in PC cells. Mechanistically, OST increased the number of autophagosomes via two pathways. First, OST induced autophagy initiation by suppressing the Akt/mTOR signaling pathway. Second, OST induced autophagic arrest by blocking autophagosome-lysosome fusion. Consistently, inhibition of autophagy initiation restored PC cell growth, whereas autophagic flux inhibitors exacerbated the antitumor effect of OST in PC cells, suggesting a cytotoxic role of OST-induced autophagosome accumulation. In addition, we found that OST upregulates the expression of activating transcription factor 3 (ATF3), resulting in inactivation of the Akt/mTOR signaling pathway and autophagy initiation in PC cells. ATF3 overexpression increased the activation of autophagy, and inhibition of ATF3 expression decreased autophagy. Taken together, our study provides new insights into the OST-induced growth inhibitory effect on PC cells, suggesting a promising potential therapeutic role of OST for PC treatment., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

To evaluate the differences in the agreement between wedged hepatic venous pressure (WHVP) and portal venous pressure (PVP) at different hepatic venous pressure gradient (HVPG) levels to identify specific HVPG thresholds where WHVP can reliably estimate PVP, thus enhancing the accuracy of risk stratification and treatment decision-making for portal hypertension (PHT) patients. A multicenter study of 616 patients with PHT from three centers was stratified into five groups by their HVPG: HVPG < 12 (group A), 12 ≤ HVPG < 16 mmHg (group B), 16 ≤ HVPG < 20 mmHg (group C), 20 ≤ HVPG < 24 mmHg (group D), HVPG ≥ 24 mmHg (group E). Concordance was analyzed using Pearson's correlation coefficient (R), the intraclass correlation coefficient (ICC), and Bland‒Altman analysis in each HVPG stratum. Correlation and agreement between WHVP and PVP varied by HVPG group. Highest agreement was observed in the range of 20 ≤ HVPG < 24 mmHg. (R = 0.55, ICC = 0.68). The proportion of patients with a discrepancy between WHVP and PVP that was greater than 10% of the PVP value was highest in group A (95.7%) and lowest in group D (48.4%). Overestimation of PVP was more common in group E (44.5%), and underestimation of PVP was more common in group A (94.6%). This study does not confirm the usefulness of hepatic vein pressure measurements to predict the PVP and PPG. The means of WHVP and PVP were significantly different in ranges A, B, C, and E., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical statements: The study was approved by the Ethics Committee and Institutional Review Board of Beijing Shijitan Hospital, Beijing You’an Hospital and the Fifth Medical Center of Chinese PLA General Hospital., (© 2024. The Author(s).)

Navigating toward destinations with rewards is a common behavior among animals. The ventral tegmental area (VTA) has been shown to be responsible for reward coding and reward cue learning, and its response to other variables, such as kinematics, has also been increasingly studied. These findings suggest a potential relationship between animal navigation behavior and VTA activity. However, the deep location and small volume of the VTA pose significant challenges to the precision of electrode implantation, increasing the uncertainty of measurement results during animal navigation and thus limiting research on the role of the VTA in goal-directed navigation. To address this gap, we innovatively designed and fabricated low-curvature microelectrode arrays (MEAs) via a novel backside dry etching technique to release residual stress. Histological verification confirmed that low-curvature MEAs indeed improved electrode implantation precision. These low-curvature MEAs were subsequently implanted into the VTA of the rats to observe their electrophysiological activity in a freely chosen modified T-maze. The results of the behavioral experiments revealed that the rats could quickly learn the reward probability corresponding to the left and right paths and that VTA neurons were deeply involved in goal-directed navigation. Compared with those in no-reward trials, VTA neurons in reward trials presented a significantly greater firing rate and larger local field potential (LFP) amplitude during the reward-consuming period. Notably, we discovered place fields mapped by VTA neurons, which disappeared or were reconstructed with changes in the path-outcome relationship. These results provide new insights into the VTA and its role in goal-directed navigation. Our designed and fabricated low-curvature microelectrode arrays can serve as a new device for precise deep brain implantation in the future., (© 2024. The Author(s).)

Infection after anterior cruciate ligament reconstruction (ACLR) is a rare and catastrophic postoperative complication. The aims of this study were to investigate the diagnostic, treatment and rehabilitation measures for postoperative infection following after ACLR. A retrospective study was conducted on 1500 patients who underwent ACLR between January 2011 and January 2022. Twenty patients who met the criteria for summarizing the incidence patterns and treatment experiences were selected for a complete investigation of their diagnostic, therapeutic, and rehabilitation processes, as well as outpatient follow-up results. Among the 20 patients who developed postoperative infections, Staphylococcus aureus was the main pathogen (80%). The clinical manifestations mainly included fever (80%) and knee joint pain (100%). Laboratory tests demonstrated that C-reactive protein (CRP) levels were greater than 50 mmol/L in fifteen patients (75%). All of the patients received intravenous antibiotic therapy. Five patients (25%) of tendon socket infection were treated with continuous negative pressure suction irrigation, whereas the other fifteen patients with intra-articular infection were treated with arthroscopic debridement and continuous flushing. The Lysholm score of the affected knee was compared before treatment and 6 months after treatment, and the difference was statistically significant (t = 20.78, P < 0.001). The success rate of treatment was 100%, and there were no significant differences between patients who received secondary treatment and functional exercise and those who underwent ACLR in terms of knee joint function or range of motion during the same time period. Infection was rare after ACLR, however it was fatal, and the main pathogen was Staphylococcus aureus. Early diagnosis and a comprehensive treatment approach are pivotal for the successful management of postoperative infections following ACLR. The results of this study contribute valuable clinical insights for further refining surgical procedures, enhancing infection prevention measures, and optimizing rehabilitation protocols., (© 2024. The Author(s).)

Solar energy plays an important role in renewable energy generation, with the advantages of low pollution, easy installation, and relatively easy access. However, photovoltaic (PV) modules are susceptible to cause localized shading from external factors such as leaves in the canopy, surrounding buildings, etc., which would affect power generation efficiency and even pose safety risks. Existing methods cannot perform well in real-time conditions. This paper proposes a real-time shading monitoring method for the PV module based on computer vision. The gamma transform and histogram matching were adopted to enhance key features and adjust the global gamut strength distribution in the image of the PV module; then the gray-level slicing method finished the segmentation to detect the shadow from the video. All processing can be realized in the real-time monitor camera and the detection results can be displayed on the HMI in PC with high efficiency and low cost. According to tests in the practical complex environment, the method can have enough detection performance and high real-time performance with an accuracy of 0.98, and the F0.5 and F2 values are 0.87 and 0.85, respectively. The metrics of the proposed method are higher than those of the existing Canny detection method, the Random Forest detection method, and the CNN detection method. In addition, the average time required by the proposed method to process a frame is 0.721 s. In addition, the average time required by the method to process an image frame is 0.721 s, which has good real-time performance., (© 2024. The Author(s).)

In the realm of e-commerce, personalized recommendations are a crucial component in enhancing user experience and optimizing sales efficiency. To address the inherent sparsity challenge prevalent in collaborative filtering algorithms within personalized recommendation systems, we propose a novel hybrid e-commerce recommendation algorithm based on the User-Nearest-Neighbor model. By integrating the user nearest neighbor model with other recommendation algorithms, this approach effectively mitigates data sparsity and facilitates a more nuanced understanding of the user-product relationship, consequently elevating recommendation quality and enhancing user experience. Taking into account considerations such as data scale and recommendation performance, we conducted experiments utilizing the Spark distributed platform. Empirical findings demonstrate the superiority of our hybrid algorithm over standalone collaborative filtering algorithms across various recommendation indicators., (© 2024. The Author(s).)

Printed circuit board (PCB) may display diverse surface defects in manufacturing. These defects not only influence aesthetics but can also affect the performance of the PCB and potentially damage the entire board. Thus, achieving efficient and highly accurate detection of PCB surface defects is fundamental for quality control in fabrication. The rapidly advancing deep learning (DL) technology holds promising prospects for providing accurate and efficient detection methods for surface defects on PCB. To facilitate DL model training, it is imperative to compile a comprehensive dataset encompassing diverse surface defect types found on PCB at a significant scale. This work categorized PCB surface defects into 9 distinct categories based on factors such as their causes, locations, and morphologies and developed a dataset of PCB surface defect (DsPCBSD+). In DsPCBSD+, a total of 20,276 defects were annotated manually by bounding boxes on the 10,259 images. This openly accessible dataset is aimed accelerating and promoting further researches and advancements in the field of DL-based detection of PCB surface defect., (© 2024. The Author(s).)

Microplastics (MPs) are defined as plastic particles smaller than 5 mm in size, and nanoplastics (NPs) are those MPs with a particle size of less than 1000 nm or 100 nm. The prevalence of MPs in the environment and human tissues has raised concerns about their potential negative effects on human health. Macrophages are the major defence against foreign substances in the intestine, and can be polarized into two types: the M1 phenotype and the M2 phenotype. However, the effect of NPs on the polarization of macrophages remains unclear. Herein, we selected polystyrene, one of the most plastics in the environment and controlled the particle sizes at 50 nm and 500 nm respectively to study the effects on the polarization of macrophages. We used mouse RAW264.7 cell line models in this macrophage-associated study. Experiments on cell absorption showed that macrophages could quickly ingest polystyrene nanoplastics of both diameters with time-dependent uptake. Compared to the untreated group and 10 μg/mL treatment group, macrophages exposed to 50 μg/mL groups (50 nm and 500 nm) had considerably higher levels of CD86, iNOS, and TNF-α, but decreased levels of aCD206, IL-10, and Arg-1. According to these findings, macrophage M1 and M2 polarization can both be induced and inhibited by 50 μg/mL 50 nm and 500 nm polystyrene nanoplastics. This work provided the first evidence of a possible MPs mode of action with appropriate concentration and size through the production of polarized M1, providing dietary and environmental recommendations for people, particularly those with autoimmune and autoinflammatory illnesses., (© 2024. The Author(s).)

In the feedrate scheduling of complex curve direct interpolation, dynamic constraints such as axis acceleration and jerk are related to the actual state of the tool. Most existing methods convert dynamic constraints to velocity constraints at sampling points. However, it cannot guarantee the dynamic constraints are satisfied between sampling points. Addressing the issue, this paper proposes a dynamic look-ahead feedrate scheduling method based on sliding mode velocity control, which generates the motion command considering dynamic constraints in every interpolation cycle. To dynamically generate commands based on the current tool state, the acceleration and deceleration method based on sliding mode velocity control has been proposed, which can control tool state to transition to the command state with any initial state. To ensure sufficient distance for acceleration and deceleration, this paper uses braking distance to dynamically estimate the look-ahead distance. Then the minimum value within the look-ahead interval is selected as the command velocity for this scheduling cycle and the actual motion command is determined based on the dynamic constraints of each axis. Simulation and experiment results prove that compared with the existing method, this method effectively reduces the overshoot of dynamic constraints without significantly increasing the machining time. The analysis of real-time computation time has demonstrated the potential of the method proposed in this paper for real-time applications., (© 2024. The Author(s).)

Despite limited research on refractory and/or endocrine therapy failure in elderly metastatic breast cancer (MBC) patients, a prior study showed that low-dose oral cyclophosphamide (CY) can improve the overall survival rate of MBC patients, possibly through the immunoregulation of regulatory T cells (Tregs). We preliminarily investigated the combination of endocrine therapy (ET) with oral low-dose CY as salvage therapy in elderly patients via peripheral blood regulatory T-cell analyses. In addition, we evaluated the associations of tumor tertiary lymphoid structures (TLSs) with therapeutic outcomes. HR+/HER2- advanced breast cancer patients who received low-dose CY combined with ET or ET only from April 2015 to August 2021 were enrolled in this retrospective study. The primary outcome was the clinical control rate (CCR), and the secondary outcome was progression-free survival (PFS). Circulating T lymphocyte subpopulations represented by Tregs were monitored during treatment by flow cytometry methods. TLSs wereconfirmed by hematoxylin-eosin staining of pretreatment specimens, and CD3, CD4, and Foxp3 were detected using Opal multicolor immunofluorescence. A total of 85 patients who received CY + ET and 50 patients who received ET only were enrolled, the percentage of patients who received CCR was 73% (62/85) vs. 70% (45/50), and the objective response rate (ORR) was 28% (24/85) vs. 24% (12/50). No deaths occurred during the study period. The mean PFS time was 13 vs. 11 months (P = 0.03). In the CY + ET group, decreases in CD4+/CD25+/Foxp3+ T cells (P < 0.001) were favorable for both clinical control and prolonged PFS (P < 0.001). Compared with patients without TLSs, those with TLSs were more likely to have better clinical control and PFS (mean time = 6 months), and a greater number of Treg cells during TLS pretreatment correlated with longer PFS (P = 0.043). Oral low-dose CY combined with standard ET exerts immunological effects by decreasing Treg levels to achieve improved clinical responses. Moreover, patients with TLSs might benefit more from such therapy than those without TLSs, and a high Treg cell count in TLSs before treatment predicts better therapeutic efficacy., (© 2024. The Author(s).)

Previous studies have shown that a higher intensity of physical activity (PA) is associated with a lower risk of cognitive impairment (CI), whereas hypertension is associated with higher CI. However, there are few studies on the association between PA intensity and cognitive function in hypertensive patients. This study investigated the association between PA intensity and cognitive function in hypertensive patients. A total of 2035 hypertensive patients were included in this study, including 407 hypertensive patients with CI and 1628 hypertensive patients with normal cognitive function matched 1:4 by age and sex. The International Physical Activity Questionnaire-Long Form and the Mini-mental State Examination were used to evaluate PA intensity, total metabolic equivalents, and cognitive function in patients with hypertension. Multivariate logistic regression was used to analyze the correlation between PA intensity and CI in hypertensive patients. The Spearman correlation coefficient was used to analyze the correlation between PA intensity and the total score of each component of the MMSE and the correlation between PA total metabolic equivalents and cardiac structure in hypertensive patients. After adjusting for all confounding factors, PA intensity was negatively associated with CI in hypertensive patients (OR = 0.608, 95% CI: 0.447-0.776, P < 0.001), and this association was also observed in hypertensive patients with education level of primary school and below and junior high school and above (OR = 0.732, 95% CI: 0.539-0.995, P = 0.047; OR = 0.412, 95% CI: 0.272-0.626, P < 0.001). The intensity of PA in hypertensive patients was positively correlated with orientation (r = 0.125, P < 0.001), memory (r = 0.052, P = 0.020), attention and numeracy (r = 0.151, P < 0.001), recall ability (r = 0.110, P < 0.001), and language ability (r = 0.144, P < 0.001). PA total metabolic equivalents in hypertensive patients were negatively correlated with RVEDD and LAD (r = - 0.048, P = 0.030; r = - 0.051, P = 0.020) and uncorrelated with LVEDD (r = 0.026, P = 0.233). Higher PA intensity reduced the incidence of CI in hypertensive patients. Therefore, hypertensive patients were advised to moderate their PA according to their circumstances., (© 2024. The Author(s).)

Epidermal growth factor receptor (EGFR) exon 19 deletion is a major driver for the drug resistance of non-small cell lung cancer (NSCLC). Identification small inhibitor capable of selectively inhibiting EGFR-19del NSCLC is a desirable strategy to overcome drug resistance in NSCLC. This study aims to screen an inhibitor for EGFR exon 19 deletion cells and explore its underlying mechanism. High through-put screen was conducted to identify an inhibitor for EGFR-19del NSCLC cells. And tenovin-3 was identified as a selective inhibitor of PC9 cells, an EGFR-19del NSCLC cells. Tenovin-3 showed particular inhibition effect on PC9 cells proliferation through inducing apoptosis and ferroptosis. Mechanistically, tenovin-3 might induce the apoptosis and ferroptosis of PC9 cells through mitochondrial pathway, as indicated by the change of VDAC1 and cytochrome c (cyt c). And bioinformatics analyses showed that the expression levels of SLC7A11 and CPX4 were correlated with NSCLC patient's survival. Our findings provide evidences for tenovin-3 to be developed into a novel candidate agent for NSCLC with EGFR exon 19 deletion. Our study also suggests that inducing ferroptosis may be a therapeutic strategy for NSCLC with EGFR exon 19 deletion., (© 2024. The Author(s).)

Potassium testing is an essential test in emergency medicine. Turnaround time (TAT) is the time between specimen receipt by the laboratory and the release of the test report. A brief in-laboratory TAT increases emergency department effectiveness. Optimizing processes to shorten TAT using other tools requires extensive time, resources, training, and support. Therefore, we aimed to find a convenient way to shorten TAT, identify risk factors affecting the timeliness of emergency potassium test reporting, and verify the intervention's effects. The dependent variable was emergency potassium reporting time > 30 or < 30 min. Logistic analysis was performed on monitorable factors, such as sex, age, potassium results, number of items, specimen processing time (including centrifugation and time before specimen loading), critical value ratio, instrument status, shift where the report was issued, specimen status, and work experience, as independent variables. In the multivariate analysis, work experience, instrument failure rate, and specimen processing time were risk factors for emergency blood potassium reporting exceeding 30 min. Improvement measures were implemented, significantly decreasing the timeout rate for acute potassium reporting. Our study confirms the usefulness of logistics in reducing the time required to report potassium levels in the emergency department, providing a new perspective on quality management., (© 2024. The Author(s).)

Chemotherapeutic drugs will affect the process of spermatogenesis. However, most current studies on the effects of chemotherapeutic drugs on spermatogenesis are based on mouse models, with a shortage of human body evidence. In addition, the mechanism of chemotherapeutic drugs causing spermatogenesis disorder is not clear. Therefore, we have collected the testicular tissues of an inguinal-lipoma patient whose testes were resected after chemotherapy and a patient who had normal spermatogenesis disorder and underwent single-nucleus RNA sequencing (snRNA-Seq). After quality control, we obtained a total of 27,957 high-quality cells, including 18,612 normal cells and 9,345 drug-treated cells, which were all used in analyzing the mechanism of chemotherapeutic drugs causing spermatogenesis disorder. This study has provided data resources and references for exploring the mechanism of chemotherapeutic drugs causing spermatogenesis disorder with the insight of protecting the spermatogenic abilities of male tumor patients receiving chemotherapy., (© 2024. The Author(s).)

This study aimed to investigate the molecular mechanism of sporotrichosis and identify possible novel therapeutic targets. Total RNA was extracted from skin lesion samples from sporotrichosis patients and used to construct a long-chain RNA transcriptome library and miRNA transcriptome library for whole transcriptome sequencing. The differentially expressed genes (DEGs) between the groups were identified, and then Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis enrichment analyses were performed based on the DEGs. An lncRNA-miRNA-mRNA ceRNA network was constructed. The expressions of JAK/STAT pathway-related proteins were detected in the patient and control tissues using RT-qPCR and Western blot analysis. Enrichment analysis showed that the DEGs were mainly enriched in various infectious diseases and immune response-related signaling pathways. Competing endogenous RNA network analysis was performed and identified the hub lncRNAs, miRNAs, and mRNAs. Compared with the control group, the mRNA expressions of SOCS3, IL-6, and JAK3 were significantly upregulated, while the expression of STAT3 did not change significantly. Also, the protein expressions of SOCS3, IL-6, JAK3, and STAT3, as well as phosphorylated JAK3 and STAT3, were significantly upregulated. We identified 671 lncRNA DEGs, 3281 mRNA DEGs, and 214 miRNA DEGs to be involved in Sporothrix globosa infection. The study findings suggest that the JAK/STAT pathway may be a therapeutic target for sporotrichosis., (© 2024. The Author(s).)

The development of economical and efficient roadbed silt reinforcement technology not only guides the proficient utilization of silt resources but also fosters the green development of geotechnical engineering construction. Ensuring the robust dynamic stability of the roadbed is pivotal for the safe operation of vehicular traffic. In this context, employing recycled polyester fibers and inorganic curing agents, this paper leverages dynamic triaxial testing and scanning electron microscopy (SEM) methods to scrutinize the dynamic characteristics and microscopic mechanisms of recycled fiber polymer modified roadbed silt. The findings indicate that: (1) with a fiber content of 0.2%, the fiber-modified soil sample exhibits minimal damage, maximal dynamic strength and dynamic elastic modulus, and optimum resilience to dynamic loads; (2) akin to fiber-reinforced sand, an elevation in confining pressure can induce the creation of a quasi-cohesive force in fiber-reinforced soil, equivalently enhancing the confining pressure and thereby amplifying its strength; and (3) the surfaces of microparticles in the enhanced soil structure are enveloped with cementitious substances, while smaller soil particles coalesce to form aggregates that fill inter-particle pores, cultivating a denser and more stable improved soil structure and augmenting the dynamic characteristics of the improvement investment., (© 2023. Springer Nature Limited.)

Increasing evidences demonstrate that chlorogenic acid (CGA), a polyphenol with multiple effects such as anti-inflammatory and anti-oxidation, protects against myocardial ischemia-reperfusion injury (MIRI) in vitro and in vivo. But its detailed cardiac protection mechanism is still unclear. The MIRI mice model was established by ligating the left anterior descending branch (LAD) of the left coronary artery in C57BL/6 mice. Sixty C57BL/6 mice were randomly divided into four groups. CGA group and CGA + I/R group (each group n = 15) were gavaged with 30 mg/kg/day CGA for 4 weeks. Sham group and I/R group mice (each group n = 15) were administered equal volumes of saline. In vitro MIRI model was constructed by hypoxia and reoxygenation of HL-1 cardiomyocytes. The results showed that CGA pretreatment reduced myocardial infarction size and cTnT contents in serum, simultaneously reduced the levels of Lnc Neat1 expression and attenuated NLRP3 inflammasome-mediated pyroptosis in myocardial tissue. Consistent with in vivo results, the pretreatment of 0.2 μM and 2 μM CGA for 12 h in HL-1 cardiomyocytes depressed hypoxia/reoxygenation-induced Lnc Neat1 expression, NLRP3 inflammasome activation and pyroptosis. Lnc Neat1 shRNA transfection mediated by lentivirus in HL-1 cardiomyocytes significantly reduced activation of NLRP3 inflammasome and pyroptosis. Our findings suggest that CGA protects against MIRI by depressing Lnc Neat1 expression and NLRP3 inflammasome-mediated pyrotosis. Inhibiting the levels of Lnc Neat1 expression may be a therapeutic strategy for MIRI., (© 2023. Springer Nature Limited.)

Cancer cell receives extracellular signal inputs to obtain a stem-like status, yet how tumor microenvironmental (TME) neural signals steer cancer stemness to establish the hierarchical tumor architectures remains elusive. Here, a pan-cancer transcriptomic screening for 10852 samples of 33 TCGA cancer types reveals that cAMP-responsive element (CRE) transcription factors are convergent activators for cancer stemness. Deconvolution of transcriptomic profiles, specification of neural markers and illustration of norepinephrine dynamics uncover a bond between TME neural signals and cancer-cell CRE activity. Specifically, neural signal norepinephrine potentiates the stemness of proximal cancer cells by activating cAMP-CRE axis, where ATF1 serves as a conserved hub. Upon activation by norepinephrine, ATF1 potentiates cancer stemness by coordinated trans-activation of both nuclear pluripotency factors MYC/NANOG and mitochondrial biogenesis regulators NRF1/TFAM, thereby orchestrating nuclear reprograming and mitochondrial rejuvenating. Accordingly, single-cell transcriptomes confirm the coordinated activation of nuclear pluripotency with mitochondrial biogenesis in cancer stem-like cells. These findings elucidate that cancer cell acquires stemness via a norepinephrine-ATF1 driven nucleus-mitochondria collaborated program, suggesting a spatialized stemness acquisition by hijacking microenvironmental neural signals., (© 2023. The Author(s).)

The Moon is the closest natural satellite to mankind, with valuable resources on it, and is an important base station for mankind to enter deep space. How to establish a reasonable lunar Global Navigation Satellite System (GNSS) to provide real-time positioning, navigation, and timing (PNT) services for Moon exploration and development has become a hot topic for many international scholars. Based on the special spatial configuration characteristics of Libration point orbits (LPOs), the coverage capability of Halo orbits and Distant Retrograde Orbit (DRO) in LPOs is discussed and analyzed in detail. It is concluded that the Halo orbit with a period of 8 days has a better coverage effect on the lunar polar regions and the DRO has a more stable coverage effect on the lunar equatorial regions, and the multi-orbital lunar GNSS constellation with the optimized combination of DRO and Halo orbits is proposed by combining the advantages of both. This multi-orbital constellation can make up for the fact that a single type of orbit requires a larger number of satellites to fully cover the Moon, using a smaller number of satellites for the purpose of providing PNT services to the entire lunar surface. We designed simulation experiments to test whether the multi-orbital constellations meet the full lunar surface positioning requirements, and compare the coverage, positioning, and occultation effects of the four constellation designs that pass the test, and finally obtain a set of well-performing lunar GNSS constellations. The results indicate that the multi-orbital lunar GNSS constellation combining DRO and Halo orbits can cover 100% of the Moon surface, provides there are more than 4 visible satellites at any time on the Moon surface, which meets the navigation and positioning requirements, and the Position Dilution of Precision (PDOP) value is stable within 2.0, which can meet the demand for higher precision Moon surface navigation and positioning., (© 2023. The Author(s).)

The androgen receptor (AR) plays an essential role in prostate cancer progression and is a key target for prostate cancer treatment. However, patients with prostate cancer undergoing androgen deprivation therapy eventually experience biochemical relapse, with hormone-sensitive prostate cancer progressing into castration-resistant prostate cancer (CRPC). The widespread application of secondary antiandrogens, such as enzalutamide, indicates that targeting AR remains the most efficient method for CRPC treatment. Unfortunately, neither can block AR signaling thoroughly, leading to AR reactivation within several months. Here, we report an approach for suppressing reactivated AR signaling in the CRPC stage. A combination of the protein phosphatase 1 subunit α (PP1α)-specific inhibitor tautomycin and enzalutamide synergistically inhibited cell proliferation and AR signaling in LNCaP and C4-2 cells, as well as in AR variant-positive 22RV1 cells. Our results revealed that enzalutamide competed with residual androgens in CRPC, enhancing tautomycin-mediated AR degradation. In addition, the remaining competitive inhibitory role of enzalutamide on AR facilitated tautomycin-induced AR degradation in 22RV1 cells, further decreasing ARv7 levels via a full-length AR/ARv7 interaction. Taken together, our findings suggest that the combination of tautomycin and enzalutamide could achieve a more comprehensive inhibition of AR signaling in CRPC. AR degraders combined with AR antagonists may represent a new therapeutic strategy for CRPC., (© 2022. The Author(s).)

A water-bursting evaluation of the coal seam floor is critical to ensure safety of coal mine production. The vulnerability index method based on AHP is selected for this study's evaluation method. Water pressure, measured specific yield, equivalent thickness of effective aquiclude, brittle rock thickness under mining pressure damage zone, distribution of faults, distribution of collapse column, distribution of endpoints, and the intersection of fault are taken as the evaluation index based on the analysis of geological data in the study area. The authors assessed the threat posed by the two aquifers in the lower portion of the coal seam. Separate evaluations were conducted on the Benxi and Ordovician limestone aquifers. The results' veracity was confirmed by comparing the obtained results to the water bursting point and a few boreholes. The evaluation results provide recommendations for the safe operation of coal mines., (© 2022. The Author(s).)

Implantable drug-delivery microsystems have the capacity to locally meet therapeutic requirements by maximizing local drug efficacy and minimizing potential side effects. The internal organs of the human body including the esophagus, gastrointestinal tract, and respiratory tract, with anfractuos contours, all manifest with endoluminal lesions often located in a curved or zigzag area. The ability of localized drug delivery for these organs using existing therapeutic modalities is limited. Spraying a drug onto these areas and using the adhesion and water absorption properties of the drug powder to attach to lesion areas can provide effective treatment. This study aimed to report the development and application of microsystems based on microshockwave delivery of drugs. The devices comprised a warhead-like shell with a powder placed at the head of the device and a flexible rod that could be inserted at the tail. These devices had the capacity to deposit drugs on mucous membranes in curved or zigzag areas of organs in the body. The explosive impact characteristics of the device during drug delivery were analyzed by numerical simulation. In the experiment of drug delivery in pig intestines, we described the biosafety and drug delivery capacity of the system. We anticipate that such microsystems could be applied to a range of endoluminal diseases in curved or zigzag regions of the human body while maximizing the on-target effects of drugs., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2022.)

Chronic inflammatory bowel disease (IBD) is strongly associated with the development of colitis-associated tumorigenesis (CAT). Despite recent advances in the understanding of polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) responses in cancer, the mechanisms of these cells during this process remain largely uncharacterized. Here, we discovered a glycoprotein, olfactomedin-4 (OLFM4), was highly expressed in PMN-MDSCs from colitis to colorectal cancer (CRC), and its expression level and PMN-MDSC population positively correlated with the progression of IBD to CRC. Moreover, mice lacking OLFM4 in myeloid cells showed poor recruitment of PMN-MDSCs, impaired intestinal homeostasis, and delayed development from IBD to CRC, and increased response to anti-PD1 therapy. The main mechanism of OLFM4-mediated PMN-MDSC activity involved the NF-κB/PTGS2 pathway, through the binding of LGALS3, a galactoside-binding protein expressed on PMN-MDSCs. Our results showed that the OLFM4/NF-κB/PTGS2 pathway promoted PMN-MDSC recruitment, which played an essential role in the maintenance of intestinal homeostasis, but showed resistance to anti-PD1 therapy in CRC., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer affecting many people worldwide. Although the 5-year survival rate is 65% in localized disease, after metastasis, the survival rate is <10%. Emerging evidence has shown that microRNAs (miRNAs) play a crucial regulatory role in the progression of ccRCC. Here, we show that miR-335, an anti-onco-miRNA, is downregulation in tumor tissue and inhibited ccRCC cell proliferation, invasion, and migration. Our studies further identify the H3K9me1/2 histone demethylase KDM3A as a new miR-335-regulated gene. We show that KDM3A is overexpressed in ccRCC, and its upregulation contributes to the carcinogenesis and metastasis of ccRCC. Moreover, with the overexpression of KDM3A, YAP1 was increased and identified as a direct downstream target of KDM3A. Enrichment of KDM3A demethylase on YAP1 promoter was confirmed by CHIP-qPCR and YAP1 was also found involved in the cell growth and metastasis inhibitory of miR-335. Together, our study establishes a new miR-335/KDM3A/YAP1 regulation axis, which provided new insight and potential targeting of the metastasized ccRCC., (© 2021. The Author(s).)

We aim to assess the effects of different air pollutants on meibomian gland dysfunction (MGD). As a prospective multicenter study, 864 patients were recruited from four different regions (i.e., coal, oil, steel, and living). The oil region had a significantly lower temperature and higher O 3 and SO 2 concentrations than other regions. Notably, participants in oil region presented with more frequent and serious MGD signs and higher cytokine levels (median interleukin 6 [IL-6] in oil: 2.66, steel: 0.96, coal: 0.38, living: 0.56; IL-8 in oil: 117.52, steel: 46.94, coal: 26.89, living: 33; vascular endothelial growth factor [VEGF] in oil: 25.09, steel: 14.02, coal: 14.02, living: 28.47). The short-term fluctuations of cytokine levels were associated with the changes in gas levels (PM 2.5 and IL-8: β = 0.016 [0.004-0.029]; O 3 and IL-6: β = 0.576 [0.386-0.702]; O 3 and IL-8: β = 0.479 [0.369-0.890]; SO 2 and VEGF: β = 0.021 [0.001-0.047]). After long-term exposure, lid margin neovascularization (r = 0.402), meibomian gland (MG) expression (r = 0.377), MG secretion (r = 0.303), MG loss (r = 0.404), and tear meniscus height (r = - 0.345) were moderately correlated with air quality index (AQI). Individuals in oil region had more serious MGD signs and higher cytokine levels. MGD is susceptible to long-term exposure to high AQI., (© 2022. The Author(s).)

Cancer cell-derived extracellular vesicles (EVs) have extensive application in the formation of their environment, including metastasis. This study explored the ability of gastric cancer (GC) cell-derived EVs-mediated microRNA-129-5p/E2F transcription factor 7/mitogen-activated protein kinase/extracellular regulated protein kinase (miR-129-5p/E2F7/MAPK/ERK) axis to affect the peritoneal metastasis of GC by delivering lncRNA small nucleolar RNA host gene 12 (SNHG12). EV-derived lncRNA and SNHG12/miR-129-5p/E2F7 network were determined by bioinformatics analysis. The regulatory relationship among SNHG12, miR-129-5p, and E2F7 was verified using a combination of dual-luciferase reporter gene, RNA immunoprecipitation, and RNA pull-down assays. The SNHG12, miR-129-5p, and E2F7 expression was measured by RT-qPCR. After GC cell-derived EVs were isolated and co-cultured with human peritoneal mesothelial cells (HPMCs), the uptake of EVs by HPMCs was observed under laser scanning confocal microscopy. Cell viability and apoptosis were examined using cell counting kit-8 and flow cytometry, respectively. Western blot analysis was performed to measure the mesothelial-mesenchymal transition (MMT)-related protein expression. The pathological and morphological characteristics of metastatic tumors in nude mice were observed by hematoxylin-eosin staining. A high SNHG12 expression was correlated with the poor prognosis of patients with GC. GC-derived EVs led to increased HPMC apoptosis and MMT by transferring SNHG12, whereas the knockdown of SNHG12 annulled the aforementioned results. SNHG12 sponged miR-129-5p to boost E2F7 expression and activate the MAPK/ERK signaling, thus inducing HPMC apoptosis and MMT. In vivo experiments further verified that EVs derived from GC cells promoted peritoneal metastasis in nude mice. GC cell-derived EVs elevated the E2F7 expression and activated the MAPK/ERK signaling to promote peritoneal metastasis through the delivery of SNHG12., (© 2022. The Author(s).)

Medulloblastoma (MB) is one of the most common childhood malignant brain tumors (WHO grade IV), traditionally divided into WNT, SHH, Group 3, and Group 4 subgroups based on the transcription profiles, somatic DNA alterations, and clinical outcomes. Unlike WNT and SHH subgroup MBs, Group 3 and Group 4 MBs have similar transcriptomes and lack clearly specific drivers and targeted therapeutic options. The recently revised WHO Classification of CNS Tumors has assigned Group 3 and 4 to a provisional non-WNT/SHH entity. In the present study, we demonstrate that Kir2.1, an inwardly-rectifying potassium channel, is highly expressed in non-WNT/SHH MBs, which promotes tumor cell invasion and metastasis by recruiting Adam10 to enhance S2 cleavage of Notch2 thereby activating the Notch2 signaling pathway. Disruption of the Notch2 pathway markedly inhibited the growth and metastasis of Kir2.1-overexpressing MB cell-derived xenograft tumors in mice. Moreover, Kir2.1 high /nuclear N2ICD high MBs are associated with the significantly shorter lifespan of the patients. Thus, Kir2.1 high /nuclear N2ICD high can be used as a biomarker to define a novel subtype of non-WNT/SHH MBs. Our findings are important for the modification of treatment regimens and the development of novel-targeted therapies for non-WNT/SHH MBs., (© 2022. The Author(s).)

Ketamine is a non-competitive channel blocker of N-methyl-D-aspartate (NMDA) receptors 1 . A single sub-anaesthetic dose of ketamine produces rapid (within hours) and long-lasting antidepressant effects in patients who are resistant to other antidepressants 2,3 . Ketamine is a racemic mixture of S- and R-ketamine enantiomers, with S-ketamine isomer being the more active antidepressant 4 . Here we describe the cryo-electron microscope structures of human GluN1-GluN2A and GluN1-GluN2B NMDA receptors in complex with S-ketamine, glycine and glutamate. Both electron density maps uncovered the binding pocket for S-ketamine in the central vestibule between the channel gate and selectivity filter. Molecular dynamics simulation showed that S-ketamine moves between two distinct locations within the binding pocket. Two amino acids-leucine 642 on GluN2A (homologous to leucine 643 on GluN2B) and asparagine 616 on GluN1-were identified as key residues that form hydrophobic and hydrogen-bond interactions with ketamine, and mutations at these residues reduced the potency of ketamine in blocking NMDA receptor channel activity. These findings show structurally how ketamine binds to and acts on human NMDA receptors, and pave the way for the future development of ketamine-based antidepressants., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

RNase III DROSHA is upregulated in multiple cancers and contributes to tumor progression by hitherto unclear mechanisms. Here, we demonstrate that DROSHA interacts with β-Catenin to transactivate STC1 in an RNA cleavage-independent manner, contributing to breast cancer stem-like cell (BCSC) properties. DROSHA mRNA stability is enhanced by N 6 -methyladenosine (m 6 A) modification which is activated by AURKA in BCSCs. AURKA stabilizes METTL14 by inhibiting its ubiquitylation and degradation to promote DROSHA mRNA methylation. Moreover, binding of AURKA to DROSHA transcript further strengthens the binding of the m 6 A reader IGF2BP2 to stabilize m 6 A-modified DROSHA. In addition, wild-type DROSHA, but not an m 6 A methylation-deficient mutant, enhances BCSC stemness maintenance, while inhibition of DROSHA m 6 A modification attenuates BCSC traits. Our study unveils the AURKA-induced oncogenic m 6 A modification as a key regulator of DROSHA in breast cancer and identifies a novel DROSHA transcriptional function in promoting the BCSC phenotype.

Circular RNAs (circRNAs) play essential roles in tumorigenesis and tumor progression. CircRNA GFRA1 (circGFRA1) was dysregulated in many cancer samples and acted as an independent marker for prediction of survivals in various cancer patients. However, the functions and molecular mechanisms of circGFRA1 in hepatocellular carcinoma (HCC) remain unclear. We collected 62 HCC tissues and normal adjacent tissues to evaluate the expression of circGFRA1 and the relationship between circGFRA1 expression and HCC patients' survival. We carried out a list of characterization experiments to investigate the roles and underling mechanisms of circGFRA1 and miR-498 in HCC progressions. CircGFRA1 was greatly increased in HCC tissues and cells, and the over-expression of circGFRA1 was intimately related with the advanced clinical stage and poor survival of HCC patients. The expression of circGFRA1 was negatively correlated with the expression of miR-498, but a positive correlation was found between circGFRA1 and NAP1L3 expression in HCC tissues. Silencing circGFRA1 inhibited the growth and invasion of hepatocellular carcinoma. Moreover, miR-498 over-expression or NAP1L3 inhibition could abrogate the oncogene role of circGFRA1 in HCC in vivo. Our findings indicated that circGFRA1 contributed to HCC progression by modulating the miR-498/NAP1L3 axis in HCC.

The purpose of this study was to explore the investigative mechanism of salidroside (SAL) on LPS-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The exosomes from RLE-6TN are extracted and identified by transmission electron microscopy, particle size analysis and protein marker detection, and co-cultured with NR8383 cells. The ALI/ARDS model of SD rats was established by LPS (10 mg/kg) intratracheal instillation. Following a four-hour intratracheal instillation of LPS, 50 μl of RLE-6TN exosomes were injected through the tail vein. After that, SAL and miR-146a antagomir were injected into the tail vein for 72 h, respectively. As the changes of HE stain, body weight and ALI score are observed. The expression of miR-146a, TLR4, NF-kB, IRAK1, TRAF6 and their related proteins were detected by RT-PCR and Western blot, respectively. TNF-α, IL-6, IL-8 and IL-1 β inflammatory factors were detected by ELISA. The expression of miR-146a, NF-kB, IRAK, TRAF6 and related inflammatory factors in LPS-induced NR8383 was significantly higher than that in the control group, while SAL has greatly reduced the expression of TLR4 mediated NF-kB inflammatory pathway and related inflammatory factors. SAL can significantly improve the LPS-induced lung morphological abnormalities, slowed down the rate of weight loss in rats, and reducing the ALI score. The expression trend of NF-kB, IRAK, TRAF6 and related inflammatory factors in rats' lung tissues was consistent with that in NR8383 cells. SAL has a protective effect on ALI/ARDS caused by sepsis, which is likely to be developed to a potential treatment for the disease. To sum up, this study provides a new theoretical basis for the treatment of ALI/ARDS with SAL.

Stable electroluminescence from micro-pixelated light-emitting diode (μLED) occurs when electrons and holes are continuously injected from external electrodes. Different from the general recognition, in this work, μLED works in an operation mode, namely, non-electrical contact and non-carrier injection mode, and can be 'wirelessly' lit up without external charge injection, which is different from the general recognition. Inherent holes and electrons in μLEDs can provide sufficient carriers for radiative recombination under alternating-current electric field. A possible model related to the diffusion of majority carrier and the drift of minority carrier in μLED was proposed, which is further confirmed by the employment of a 'carrier pump'. Finally, the intrinsic characteristics of the device-in-capacitor, namely, self-protection against electrical breakdown, were discussed. This work demonstrates a new device configuration and an alternative operating mode for μLED and provides a research manner to obtain advanced μLED-based technology.

NUSAP1, which is a microtubule-associated protein involved in mitosis, plays essential roles in diverse biological processes, especially in cancer biology. In this study, NUSAP1 was found to be overexpressed in GBM tissues in a grade-dependent manner compared with normal brain tissues. NUSAP1 was also highly expressed in GBM patients, dead patients, and GBM cells. In addition, NUSAP1 was found to participate in cell proliferation, apoptosis, and DNA damage in GBM cells. Ataxia telangiectasia and Rad3-related protein (ATR) are a primary sensor of DNA damage, and ATR is also a promising target in cancer therapy. Here, we found that NUSAP1 positively regulated the expression of ATR. Mechanistically, NUSAP1 suppressed the ubiquitin-dependent proteolysis of ATR. The SAP (SAF-A/B, Acinus, and PIAS) domain is a common motif of many SUMO (small ubiquitin-like modifier) E3 ligases, and this domain is involved in substrate recognition and ligase activity. This study further demonstrated that the SAP domain of NUSAP1 promoted the sumoylation of ATR, and thereby antagonized the ubiquitination of ATR. These results suggest that NUSAP1 stabilizes ATR by sumoylation. Moreover, NUSAP1 potentiated chemotherapeutic resistance to temozolomide (TMZ) and doxorubicin (DOX) through its SAP domain. Overall, this study indicates that NUSAP1 is a promising therapeutic target in GBM.

We conducted pot experiments to assess the bioavailability of cadmium (Cd) in contaminated rhizosphere soil and accumulation in rice organs in response to nitrogen (N) supply ((NH 4 ) 2 SO 4 , NH 4 NO 3 , NH 4 Cl). The results showed that the concentration of bioavailable Cd in rice rhizosphere soil was (NH 4 ) 2 SO 4 treatment > NH 4 Cl treatment > NH 4 NO 3 treatment at the same level of N application and growth period; the Cd concentration in rice roots was (NH 4 ) 2 SO 4 treatment > NH 4 NO 3 treatment > NH 4 Cl treatment; and the Cd concentration in rice straw was NH 4 NO 3 treatment > NH 4 Cl. The Cd concentration in rice roots, straws, and seeds at the maturity stage was (NH 4 ) 2 SO 4 treatment > NH 4 Cl treatment. With the same N fertilizer, excessive N promoted Cd accumulation in rice at later growth stages. This suggested that sulfate (SO 4 2- ) influenced Cd concentration in rice. NH 4 Cl application maintained a low Cd level in different rice organs with the same N level. This confirmed that NH 4 Cl levels for Cd-contaminated paddy soil with high-S-content could obtain rice grains with Cd concentrations below the food safety standards (0.2 or 0.4 mg·kg 4 Cl levels for Cd-contaminated paddy soil with high-S-content could obtain rice grains with Cd concentrations below the food safety standards (0.2 or 0.4 mg·kg -1 ).

Schistosomiasis japonicum is a major zoonosis that seriously harms human health and affects social and economic development in China. The control of Oncomelania Hupensis, the only intermediate host of schistosome japonicum, is one of the integrated measures for schistosomiasis control in China. Acquiring updated elevation data of snail habitat environment, as well as it's spatial analysis, play an important role for the risk evaluation and precise control of schistosomiasis transmission and prevalence. Currently, the elevation database of snail habitat environment in schistosomiasis epidemic areas has not been available in the world, which affects the development of research and application work regarding to snail control. Google Earth(GE) can provide massive information related to topography, geomorphology and ground objects of a region due to its indisputable advantages such as wide use, free charge and rapidly updating. In this paper, taking the Poyang lake region as a example, we extracted elevation data of snail-inhabited environment of the lake from GE and established a elevation correction regression model(CRM) for acquiring accurate geospatial elevations, so as to provide a decision-making reference for snail control and risk evaluation of schistosomiasis in China. We developed a GE Application Programming Interface(API) program to extract elevation data from GE, which was compared with the actual elevation data obtained from topographic map of the Poyang Lake bottom. Then, a correction regression model was established and evaluated by 3 index, Mean Absolute Error(MAE), Root Mean Squared Error(RMSE) and Index of Agreement(IOA) for the accuracy of the model. The elevation values extracted from GE in 15086 sample grid points of the lake ranged from 8.5 m to 24.8 m. After the sample points were divided randomly to three groups, the mean elevations of three groups were 13.49 m, 13.52 m and 13.65 m, respectively, with standard deviation ranged from 2.04-2.06. The mean elevation among three groups has no statistic difference (F = 1.536, P = 0.215). A elevation correction regression model was established as y = 6.228 + 0.485×. the evaluation results for the accuracy of the model showed that the MAE and RMSE before correction was 1.28 m and 3.95 m respectively, higher than that after correction, which were 0.74 and 1.30 m correspondingly. The IOA before correction (-0.40)was lower than that after correction(0.34). Google Earth can directly or indirectly get access to massive information related to topography, geomorphology and ground objects due to its indisputable advantages. However, it still needs to be converted into more reliable and accurate data by combining with pre-processing tools. This study used self-developed API program to extract elevation data from GE through precisely locating and improved the accuracy of elevation by using a correction regression model, which can provide reliable data sources for all kinds of spatial data researches and applications.

Hexokinase-II (HK2) is a key enzyme involved in glycolysis, which is required for breast cancer progression. However, the underlying post-translational mechanisms of HK2 activity are poorly understood. Here, we showed that Proviral Insertion in Murine Lymphomas 2 (PIM2) directly bound to HK2 and phosphorylated HK2 on Thr473. Biochemical analyses demonstrated that phosphorylated HK2 Thr473 promoted its protein stability through the chaperone-mediated autophagy (CMA) pathway, and the levels of PIM2 and pThr473-HK2 proteins were positively correlated with each other in human breast cancer. Furthermore, phosphorylation of HK2 on Thr473 increased HK2 enzyme activity and glycolysis, and enhanced glucose starvation-induced autophagy. As a result, phosphorylated HK2 Thr473 promoted breast cancer cell growth in vitro and in vivo. Interestingly, PIM2 kinase inhibitor SMI-4a could abrogate the effects of phosphorylated HK2 Thr473 on paclitaxel resistance in vitro and in vivo. Taken together, our findings indicated that PIM2 was a novel regulator of HK2, and suggested a new strategy to treat breast cancer.

To date, the unpleasant trade-off between crystallization speed and thermal stability for most phase change materials is detrimental to achieve phase change memory (PCM) with both features of high-speed and good-retention. However, it is proved that Al doping in Sb 2 Te, served as storage media in PCM, favors both a high writing speed (6 ns) and a good retention (103 °C), as well as a low power consumption. Judging by experimental and theoretical investigations, doped Al atoms prefer to replace Sb in Sb 2 Te lattice, strongly bonded with 6 Te atoms, to form a homogeneous phase. While in amorphous Al doped Sb 2 Te (AST), Al atoms are in tetrahedral environment, firmly bonded with four Sb/Te atoms. The strong bonding in Al centered tetrahedron in amorphous AST can obstruct the collective motion of Sb atoms near the matrix boundary, leading to the improvement in thermal stability and the confinement in grain size.

Sustainably feeding a growing population is a grand challenge, and one that is particularly difficult in regions that are dominated by smallholder farming. Despite local successes, mobilizing vast smallholder communities with science- and evidence-based management practices to simultaneously address production and pollution problems has been infeasible. Here we report the outcome of concerted efforts in engaging millions of Chinese smallholder farmers to adopt enhanced management practices for greater yield and environmental performance. First, we conducted field trials across China's major agroecological zones to develop locally applicable recommendations using a comprehensive decision-support program. Engaging farmers to adopt those recommendations involved the collaboration of a core network of 1,152 researchers with numerous extension agents and agribusiness personnel. From 2005 to 2015, about 20.9 million farmers in 452 counties adopted enhanced management practices in fields with a total of 37.7 million cumulative hectares over the years. Average yields (maize, rice and wheat) increased by 10.8-11.5%, generating a net grain output of 33 million tonnes (Mt). At the same time, application of nitrogen decreased by 14.7-18.1%, saving 1.2 Mt of nitrogen fertilizers. The increased grain output and decreased nitrogen fertilizer use were equivalent to US$12.2 billion. Estimated reactive nitrogen losses averaged 4.5-4.7 kg nitrogen per Megagram (Mg) with the intervention compared to 6.0-6.4 kg nitrogen per Mg without. Greenhouse gas emissions were 328 kg, 812 kg and 434 kg CO 2 equivalent per Mg of maize, rice and wheat produced, respectively, compared to 422 kg, 941 kg and 549 kg CO 2 equivalent per Mg without the intervention. On the basis of a large-scale survey (8.6 million farmer participants) and scenario analyses, we further demonstrate the potential impacts of implementing the enhanced management practices on China's food security and sustainability outlook.

Abnormalities in epigenetic modifiers are emerging as driving events in prostate cancer (PCa). The histone methyltransferase KMT2D, a frequently aberrant epigenetic modifier in various tumors, has an undefined role in PCa. Moreover, little is known regarding KMT2D's mutation in Chinese patients or its downstream signaling pathways and targets. Here, we profiled the mutational spectrum of 32 significantly PCa-associated genes by using disease-targeted sequencing, and found that KMT2D was highly mutated (63.04%, 29/46) in Chinese patients. Moreover, high KMT2D transcription was also associated with poor prognosis in an independent cohort (n = 51). In KMT2D-knockdown PC-3 and DU145 cells, cell proliferation (P < 0.01), invasion (P < 0.001), and migration (P < 0.01) were consequently suppressed. KMT2D depletion effectively suppressed tumor growth by 92.21% in vivo. Notably, integrative analyses of RNAseq and ChIPseq characterized two crucial genes downregulated by KMT2D, leukemia inhibitory factor receptor (LIFR) and Kruppel-like factor-4 (KLF4), which are regulators in PI3K/Akt and EMT, respectively. Our present study revealed that KMT2D epigenetically activates PI3K/Akt pathway and EMT by targeting LIFR and KLF4 and thus serves as a putative epigenetic-based target for treating PCa.

Despite recent progress in the preparation of feeder cells for human induced pluripotent stem cells (hiPSCs), there remain issues which limit the acquisition of feeder cells in large scale. Approaches for obtaining feeder cells quickly on a large scale are in immediate need. To reach this goal, we established suspension-adhesion method (SAM) and three-dimensional (3D) suspension method (3DSM). In SAM, mouse embryonic fibroblast (MEF) growth were fully inhibited by 10 μg/ml mitomycin-C (MMC) in 0.5 hours, and the feeder cells generated display higher adherent and recovery rates as well as longer survival time compared to conventional method (CM). 3DSM, an optimized method of SAM in which MEFs were cultured and MMC treated in suspension, was developed to lower the costs and workload using CELLSPIN System. The yield of feeder cells is several times the yield of SAM while the adherent and recovery rates and the capacity of supporting hiPSCs growth were not sacrificed. Hence, 3DSM is an economical and easy way to generate large-scale feeder cells for hiPSCs cultures.

Morphology, composition, and mixing state of individual particles emitted from crop residue, wood, and solid waste combustion in a residential stove were analyzed using transmission electron microscopy (TEM). Our study showed that particles from crop residue and apple wood combustion were mainly organic matter (OM) in smoldering phase, whereas soot-OM internally mixed with K in flaming phase. Wild grass combustion in flaming phase released some Cl-rich-OM/soot particles and cardboard combustion released OM and S-rich particles. Interestingly, particles from hardwood (pear wood and bamboo) and softwood (cypress and pine wood) combustion were mainly soot and OM in the flaming phase, respectively. The combustion of foam boxes, rubber tires, and plastic bottles/bags in the flaming phase released large amounts of soot internally mixed with a small amount of OM, whereas the combustion of printed circuit boards and copper-core cables emitted large amounts of OM with Br-rich inclusions. In addition, the printed circuit board combustion released toxic metals containing Pb, Zn, Sn, and Sb. The results are important to document properties of primary particles from combustion sources, which can be used to trace the sources of ambient particles and to know their potential impacts in human health and radiative forcing in the air.

Based on our initial genome-wide association study (GWAS) on esophageal squamous cell carcinoma (ESCC) in Han Chinese, we conducted a follow-up study to examine the single nucleotide polymorphisms (SNPs) associated with family history (FH) of upper gastrointestinal cancer (UGI) cancer in cases with ESCC. We evaluated the association between SNPs and FH of UGI cancer among ESCC cases in a stage-1 case-only analysis of the National Cancer Institute (NCI, 541 cases with FH and 1399 without FH) and Henan GWAS (493 cases with FH and 869 without FH) data (discovery phase). The top SNPs (or their surrogates) from discovery were advanced to a stage-2 evaluation in additional Henan subjects (2801 cases with FH and 3136 without FH, replication phase). A total of 19 SNPs were associated with FH of UGI cancer in ESCC cases with P < 10 -5 in the stage-1 meta-analysis of NCI and Henan GWAS data. In stage-2, the association for rs79747906 (located at 18p11.31, P = 5.79 × 10 -6 in discovery) was replicated (P = 0.006), with a pooled-OR of 1.59 (95%CI: 1.11-2.28). We identified potential genetic variants associated with FH of UGI cancer. Our findings may provide important insights into new low-penetrance susceptibility regions involved in the susceptibility of families with multiple UGI cancer cases.

Optical modulation is a crucial operation in photonics for network data processing with the aim to overcome information bottleneck in terms of speed, energy consumption, dispersion and cross-talking from conventional electronic interconnection approach. However, due to the weak interactions between photons, a facile physical approach is required to efficiently manipulate photon-photon interactions. Herein, we demonstrate that transparent glass ceramics containing LaF 3 : Tm 3+ (Er 3+ ) nanocrystals can enable fast-slow optical modulation of blue/green up-conversion fluorescence upon two-step excitation of two-wavelengths at telecom windows (0.8-1.8 μm). We show an optical modulation of more than 1500% (800%) of the green (blue) up-conversion fluorescence intensity, and fast response of 280 μs (367 μs) as well as slow response of 5.82 ms (618 μs) in the green (blue) up-conversion fluorescence signal, respectively. The success of manipulating laser at telecom windows for fast-slow optical modulation from rear-earth single-doped glass ceramics may find application in all-optical fiber telecommunication areas.