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Rationale: Lung cancer is the leading cause of cancer death worldwide, and treatment options are limited to mainly cytotoxic agents. Here we reveal a novel role of miR-150 in non-small cell lung cancer (NSCLC) development and seek potential new therapeutic targets. Methods: The miR-150-mediated autophagy dysfunction in NSCLC cells were examined using molecular methods in vitro and in vivo. The upstream regulatory element and downstream target of miR-150 were identified in vitro and validated in vivo. Potential therapeutic methods (anti-c-myc or anti-miR-150) were tested in vitro and in vivo. Clinical relevance of the c-myc/miR-150/EPG5 axis in NSCLC was validated in human clinical samples and large genomics database. Results: miR-150 blocked the fusion of autophagosomes and lysosomes through directly repressing EPG5. The miR-150-mediated autophagy defect induced ER stress and increased cellular ROS levels and DNA damage response, and promoted NSCLC cell proliferation and tumor growth. Knockdown of EPG5 promoted NSCLC cell proliferation, and attenuated the effects of miR-150. c-myc gene was identified as a miR-150 transcriptional factor which increased miR-150 accumulation, therefore pharmacologically or genetically inhibiting c-myc/miR-150 expression significantly inhibited NSCLC cell growth in vitro and in vivo. Both c-myc and miR-150 were significantly over-expressed in NSCLC, while EPG5 was down-regulated in NSCLC. Expression levels of these molecules were well correlated, and also well correlated with patient survival. Conclusions: Our findings suggest that c-myc/miR-150/EPG5 mediated dysfunction of autophagy contributes to NSCLC development, which may provide a potential new diagnostic and therapeutic target in NSCLC.

Abstract Background Global distributions and trends of the risk-attributable burdens of chronic obstructive pulmonary disease (COPD) have rarely been systematically explored. To guide the formulation of targeted and accurate strategies for the management of COPD, we analyzed COPD burdens attributable to known risk factors. Methods Using detailed COPD data from the Global Burden of Disease study 2019, we analyzed disability-adjusted life years (DALYs), years lived with disability (YLDs), years of life lost (YLLs), and deaths attributable to each risk factor from 1990 to 2019. Additionally, we calculated estimated annual percentage changes (EAPCs) during the study period. The population attributable fraction (PAF) and summary exposure value (SEV) of each risk factor are also presented. Results From 1990 to 2019, the age-standardized DALY and death rates of COPD attributable to smoking and household air pollution, occupational particles, secondhand smoke, and low temperature presented consistently declining trends in almost all socio-demographic index (SDI) regions. However, the decline in YLD was not as dramatic as that of the death rate. In contrast, the COPD burden attributable to ambient particulate matter, ozone, and high temperature exposure showed undesirable increasing trends in the low- and low-middle-SDI regions. In addition, the age-standardized DALY and death rates attributable to each risk factor except household air pollution and low temperature were the highest in the low-middle-SDI region. In 2019, the COPD burden attributable to smoking ambient particulate matter, ozone, occupational particles, low and high temperature was obviously greater in males than in females. Meanwhile, the most important risk factors for female varied across regions (low- and low-middle-SDI regions: household air pollution; middle-SDI region: ambient particles; high-middle- and high-SDI region: smoking). Conclusions Increasing trends of COPD burden attributable to ambient particulate matter, ozone, and high temperature exposure in the low-middle- and low-SDI regions call for an urgent need to implement specific and effective measures. Moreover, considering the gender differences in COPD burdens attributable to some risk factors such as ambient particulate matter and ozone with similar SEV, further research on biological differences between sexes in COPD and relevant policy-making of disease prevention are required.

Two-dimensional electron gas is precisely confined at the interface of insulating oxide thin films and substrates, e.g., LaAlO3/SrTiO3(STO) and, thus, shows 2D electronic transport features. Here, we report a high mobility electron state at the interface of a Cr2O3 film and a STO substrate, which is realized by depositing a Cr film onto a STO (111) substrate in high vacuum (1 × 10−10 mbar) using molecular beam epitaxy. At a substrate temperature of 700 °C, the deposited Cr films capture oxygen atoms from STO substrates, resulting in the formation of an insulating Cr2O3 layer and an oxygen-deficient STO layer. Due to the presence of high mobility electrons [1.5 × 104 cm2V−1 s−1 at 1.8 K] at the Cr2O3/STO interface, both out-of-plane and in-plane Shubnikov–de Haas oscillations are observed at low temperatures (<3 K), which suggests that the highly conducting electron gas has extended into the STO bulk along the thickness direction with a certain depth to allow electrons to complete the cyclotron motion. [ABSTRACT FROM AUTHOR]

The emergence of biomagnetism imaging has led to the development of ultrasensitive and compact spin-exchange relaxation-free (SERF) atomic magnetometers that promise high-resolution magnetocardiography (MCG) and magnetoencephalography (MEG). However, conventional optical components are not compatible with nanofabrication processes that enable the integration of atomic magnetometers on chips, especially for elliptically polarized laser-pumped SERF magnetometers with bulky optical systems. In this study, an elliptical-polarization pumping beam (at 795 nm) is achieved through a single-piece metasurface, which results in an SERF magnetometer with a high sensitivity reaching 10.61 fT/Hz1/2 by utilizing a 87Rb vapor cell with a 3 mm inner diameter. To achieve the optimum theoretical polarization, our design combines a computer-assisted optimization algorithm with an emerging metasurface design process. The metasurface is fabricated with 550 nm thick silicon-rich silicon nitride on a 2 × 2 cm2 SiO2 substrate and features a 22.17° ellipticity angle (a deviation from the target polarization of less than 2%) and more than 80% transmittance. This study provides a feasible approach for on-chip polarization control of future all-integrated atomic magnetometers, which will further pave the way for high-resolution biomagnetism imaging and portable atomic sensing applications. [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated the role of N6-methyladenosine (m6A) RNA methylation in various biological processes, our research is the first to elucidate its specific impact on LCAT mRNA stability and adipogenesis in poultry. Results: The 6 100-day-old female chickens were categorized into high (n = 3) and low-fat chickens (n = 3) based on their abdominal fat ratios, and their abdominal fat tissues were processed for MeRIP-seq and RNA-seq. An integrated analysis of MeRIP-seq and RNA-seq omics data revealed 16 differentially expressed genes associated with to differential m6A modifications. Among them, ELOVL fatty acid elongase 2 (ELOVL2), pyruvate dehydrogenase kinase 4 (PDK4), fatty acid binding protein 9 (PMP2), fatty acid binding protein 1 (FABP1), lysosomal associated membrane protein 3 (LAMP3), lecithin-cholesterol acyltransferase (LCAT) and solute carrier family 2 member 1 (SLC2A1) have ever been reported to be associated with adipogenesis. Interestingly, LCAT was down-regulated and expressed along with decreased levels of mRNA methylation methylation in the low-fat group. Mechanistically, the highly expressed ALKBH5 gene regulates LCAT RNA demethylation and affects LCAT mRNA stability. In addition, LCAT inhibits preadipocyte proliferation and promotes preadipocyte differentiation, and plays a key role in adipogenesis. Conclusions: In conclusion, ALKBH5 mediates RNA stability of LCAT through demethylation and affects chicken adipogenesis. This study provides a theoretical basis for further understanding of RNA methylation regulation in chicken adipogenesis. [ABSTRACT FROM AUTHOR]

Grazing affects plant community characteristics and the relationship between above-ground biomass and diversity, which has become a hot topic in grassland ecosystem research in recent years. The present study investigated grassland vegetation in the Two Rivers pastoral area based on 60 sampling points using sampling methods. The effects of grazing on the structural characteristics of plant communities were analysed using the α-diversity index, and the relationship between species diversity and the above-ground biomass of plant communities, as well as their changes, was explored. The results showed that grazing disturbance decreased the number of family species in the grassland plant communities and the similarity between communities; grazing activities significantly decreased the above-ground biomass of the grassland plant communities; the height and cover also showed a decreasing trend (p < 0.01), but the density of the grassland plant communities improved (p < 0.01). The Margalef index, the Shannon–Wiener index, and the Simpson index of the grassland plant communities all showed different degrees of decrease after grazing, while the Alatalo index showed an increase; biomass was positively correlated with the Margalef, Shannon–Wiener, and Alatalo indices and negatively correlated with the Simpson index (p < 0.01). Therefore, in the management and maintenance of grasslands, the impact of grazing on the structural characteristics of plant communities should be taken into account, and reasonable response policies should be implemented according to the actual local situation. This study provides a theoretical basis for grassland maintenance and management and the sustainable development of ecosystems in the pastoral areas of the two river sources of the Altay Mountains. [ABSTRACT FROM AUTHOR]

Inorganic zeolites have excellent molecular sieving properties, but they are difficult to process into macroscopic structures. In this work, we use metal–organic framework (MOF) glass as substrates to engineer the interface with inorganic zeolites, and then assemble the discrete crystalline zeolite powders into monolithic structures. The zeolites are well dispersed and stabilized within the MOF glass matrix, and the monolith has satisfactory mechanical stabilities for membrane applications. We demonstrate the effective separation performance of the membrane for 1,3‐butadiene (C4H6) from other C4 hydrocarbons, which is a crucial and challenging separation in the chemical industry. The membrane achieves a high permeance of C4H6 (693.00±21.83 GPU) and a high selectivity over n‐butene, n‐butane, isobutene, and isobutane (9.72, 9.94, 10.31, and 11.94, respectively). This strategy opens up new possibilities for developing advanced membrane materials for difficult hydrocarbon separations. [ABSTRACT FROM AUTHOR]

Perovskite CaIrO 3 is theoretically predicted to be a Dirac node semimetal near the Mott transition, which possesses a considerable interplay between electron correlations and spin–orbit coupling. Electron correlations can significantly tune the behavior of relativistic Dirac fermions. Here, we have grown high-quality perovskite CaIrO 3 thin films on different substrates using oxide molecular beam epitaxy to modulate both electron correlations and Dirac electron states. Through in situ angle-resolved photoemission spectroscopy, we demonstrate a systematic evolution of the bandwidth and effective mass of J eff = 1 / 2 band in perovskite CaIrO 3 induced by strain. The bandwidth of the J eff = 1 / 2 band undergoes an evident increase under in-plane compressive strain, which could be attributed to the weakening of electron correlations. The compressive strain can potentially shift the position of the Dirac node relative to the Fermi level and play a vital role in the transition from hole-type to electron-type transport characteristics. Our work provides a feasible approach for manipulating the topological Dirac electron states by engineering the strength of electron correlations. [ABSTRACT FROM AUTHOR]

Design for Safety (DFS) is a crucial tool that assists humans in paying closer attention to safety and health in project life cycles of buildings and other facilities. Analyzing DFS through a bibliometric perspective can facilitate the development of new theories, promote disciplinary content, and reveal the direction of development in the subject area. This paper presents a systematic, holistic, and comprehensive overview of the global literature focused on DFS, summarizing the number of publications, research hotspots, research methods, and distribution. Scientific publications are a measure of academic level and scientific strength of institutions and individuals, and this article provides an overview of interdisciplinary research on DFS from 1 January 1997 to 31 December 2020, based on literature related to DFS in the Web of Science database (WoS-database). The paper highlights current research hotspots, ideas, and trends around the world, offering a global overview of contemporary and interdisciplinary research in DFS. By utilizing both keyword clustering and co-citation clustering techniques, the paper proposes the 4P framework (i.e., purpose, people, procedures, and phenomena) to better understand current global achievements and to achieve a complex structure for future development. This concise description of DFS trends may provide a logical mechanism for assessing and understanding the development of DFS research.

(1-x)Pb(Zn1/3Nb2/3)O3-xPbTiO3 ((1-x)PZN-xPT in short) is one of the most important piezoelectric materials. In this work, we extensively investigated (1-x)PZN-xPT (x = 0.07–0.11) ferroelectric single crystals using in-situ synchrotron μXRD, complemented by TEM and PFM, to correlate microstructures with phase transitions. The results reveal that (i) at 25 °C, the equilibrium state of (1-x)PZN-xPT is a metastable orthorhombic phase for x = 0.07 and 0.08, while it shows coexistence of orthorhombic and tetragonal phases for x = 0.09 and x = 0.11, with all ferroelectric phases accompanied by ferroelastic domains; (ii) upon heating, the phase transformation in x = 0.07 is Orthorhombic → Monoclinic → Tetragonal → Cubic. The coexistence of ferroelectric tetragonal and paraelectric cubic phases was in-situ observed in x = 0.08 above Curie temperature (TC), and (iii) phase transition can be explained by the evolution of the ferroelectric and ferroelastic domains. These results disclose that (1-x)PZN-xPT are in an unstable regime, which is possible factor for its anomalous dielectric response and high piezoelectric coefficient.

Background and aimsThe epidemiological characteristics of MAFLD and its relationship with atrial fibrillation (AF) are limited in China. Therefore, we explored the epidemiological characteristics of MAFLD from adults along with the association of MAFLD and 12-ECG diagnosed AF in a nationwide population from health check-up centers.MethodsThis observational study used cross-sectional and longitudinal studies with 2,083,984 subjects from 2009 to 2017. Age-, sex-, and regional-standardized prevalence of MAFLD was estimated. Latent class analysis (LCA) was used to identify subclusters of MAFLD. Multivariable logistic regression and mixed-effects Cox regression models were used to analyze the relationship between MAFLD and AF.ResultsThe prevalence of MAFLD increased from 22.75% to 35.58% during the study period, with higher rates in males and populations with high BMI or resided in northern regions. The MAFLD population was clustered into three classes with different metabolic features by LCA. Notably, a high proportion of MAFLD patients in all clusters had overweight and prediabetes or diabetes. The MAFLD was significantly associated with a higher risk of AF in the cross-sectional study and in the longitudinal study. In addition, the coexistence of prediabetes or diabetes had the largest impact on subsequent AF.ConclusionOur findings suggested a high prevalence of MAFLD and a high prevalence of other metabolic diseases in the MAFLD population, particularly overweight and glucose dysregulation. Moreover, MAFLD was associated with a significantly higher risk for existing and subsequent subclinical AF in the Chinese population.

BackgroundLenvatinib, regorafenib and anti-programmed cell death protein-1 (PD-1) immunotherapy have shown promising clinical outcomes in patients with advanced hepatocellular carcinoma (HCC) after sorafenib failure, respectively. However, the combination of the two treatments has not been reported. We compared the efficacy of PD-1 inhibitors with lenvatinib (PL) and PD-1 inhibitors plus regorafenib (PR) in patients with advanced HCC in this study.MethodsWe conducted a retrospective study of advanced HCC patients who undergone PD-1 inhibitors combined with lenvatinib or regorafenib after failure of sorafenib at Second Affiliated Hospital of Nanchang University from July 2018 and December 2020. The overall survival (OS), progression-free survival (PFS), effective rates and treatment-related adverse events (TRAEs) were investigated.ResultsIn total, 61 patients met the criteria and were included in the present study, and they were divided into the PL group (n = 32) and PR group (n = 29). The overall response rate (ORR) (12.5%vs. 10.3%, respectively; p = 0.557) and disease control rate (DCR) (71.9%vs. 58.6%, respectively; p < 0.207) were higher in the PL group than in the PR group, but there was no statistical difference.Furthermore, median PFS and OS were not significantly different between the two groups in Kaplan-Meier survival analysis (PFS: 5.3 months vs 4.0 months, p = 0.512; OS: 14.1 months vs 13.7 months, p = 0.764 for the PL group vs PR group). The most common treatment-related adverse events (TRAEs) were hand -foot skin reaction (24/61,39.3%), hypertension (20/61,32.8%) and hypothyroidism (13/61,21.3%). The frequent TRAEs (≥Grade 3) during PD-1 inhibitors plus lenvatinib or regorafenib treatment were hand-foot skin reaction (5/29,12.4%), thrombocytopenia (2/29 6.90%) and proteinuria (n =2/32,6.25%).ConclusionsCombination of lenvatinib/regorafenib and PD-1 inhibitors is a promising therapy for HCC patients after sorafenib failure.

BackgroundThe purpose of the study was to assess the efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) who are undergoing hepatic arterial infusion chemotherapy (HAIC) combined with programmed cell death protein-1 (PD-1) antibody and lenvatinib.MethodsWe retrospectively evaluated 61 patients treated with HAIC combined with PD-1 antibody and lenvatinib at the Second Affiliated Hospital of Nanchang University between September 2020 and January 2022 for advanced HCC. We analyzed tumor response, progression free survival (PFS), and treatment-related adverse events (TRAEs).ResultsThe objective response rate (ORR) was 36.1% (RECIST 1.1)/57.4% (mRECIST) and the disease control rate (DCR) was 82.0%. The overall median PFS was 6.0 months, 6.7 months for first-line treatment, and 4.3 months for second-line treatment. The most common TRAEs were neutropenia (50.8%), abdominal pain (45.9%), and aspartate aminotransferase increase (39.3%).ConclusionHepatic arterial infusion chemotherapy combined with PD-1 antibody and lenvatinib is effective in the treatment of advanced HCC, and the TRAEs are generally controllable.

ObjectiveTo investigate the analgesic mechanism of electroacupuncture (EA) in rats with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).MethodsThirty male SD rats were randomly divided into sham group, model group and EA group, with ten rats in each group. The CP/CPPS model was prepared by injecting 50 μL of complete Freund’s adjuvant (CFA) into the ventral lobes of the prostate tissue, and the sham group was injected with the same dose of saline. After 14 days of modeling, EA was applied to Guanyuan (CV4), Zhongji (CV3), Sanyinjiao (SP6) and Huiyang (BL35) in the EA group. After four courses, H&E staining was performed to observe the prostate tissue morphology, transcriptome sequencing (RNA-Seq) was performed for each group, and the selected signaling pathways were verified by qRT-PCR.ResultsThe RNA-Seq analysis results suggested that the analgesic effect of EA on CP/CPPS may be achieved by regulating prostate gene expression, which may be related to multiple biological processes and signaling pathways. qRT-PCR results showed that the vanillic acid receptor subtype 1 of the transient receptor potential (TRPV1), phospholipase C (PLC), protein kinase C (PKC), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA) were all upregulated in the model group compared to the sham group (p < 0.01). Compared with the model group, TRPV1, PLC, PKC, cAMP, and PKA were all downregulated in the EA group (p < 0.05, p < 0.01).ConclusionThe analgesic mechanism of EA on CP/CPPS may be achieved through modulation of cAMP-PKA-TRPV1/PLC-PKC-TRPV1 signaling pathway.