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Abstract Roles of liver-specific genes (LSGs) in tumor initiation and progression are rarely explored in hepatocellular carcinoma (HCC). Here we show that LSGs are generally downregulated in HCC tumor tissues compared to non-HCC liver tissues, and low-LSG HCCs show poor prognosis and the activated c-Myc pathway. Among the c-Myc- and patient prognosis-associated LSGs, PGRMC1 significantly blocks c-Myc-induced orthotopic HCC formation. The role of PGRMC1 depends on its localization to the endoplasmic reticulum (ER) membrane, where PGRMC1 interacts with PERK through their ER luminal domains. This interaction in turn activates PERK in an ER stress-independent manner, which phosphorylates eIF2α and consequently inhibits c-Myc protein translation. In HCC patients, PGRMC1 level is significantly reduced in tumor tissues and negatively associated with the c-Myc signature. Patients with low-PGRMC1 in their tumors have poor prognosis. Collectively, deregulated LSGs in HCC are associated with the c-Myc pathway activation and PGRMC1 blocks c-Myc-induced hepatic carcinogenesis through promoting ER stress-independent PERK activation.

Abstract Background Intrahepatic cholangiocarcinoma (iCCA) is one of the most lethal malignancies and highly heterogeneous. We thus aimed to identify and characterize iCCA cell subpopulations with severe malignant features. Methods Transcriptomic datasets from three independent iCCA cohorts (iCCA cohorts 1–3, n = 382) and formalin-fixed and paraffin-embedded tissues from iCCA cohort 4 (n = 31) were used. An unbiased global screening strategy was established, including the transcriptome analysis with the activated malignancy/stemness (MS) signature in iCCA cohorts 1–3 and the mass spectrometry analysis of the sorted stemness reporter-positive iCCA cells. A group of cellular assays and subcutaneous tumor xenograft assay were performed to investigate functional roles of the candidate. Immunohistochemistry was performed in iCCA cohort 4 to examine the expression and localization of the candidate. Molecular and biochemical assays were used to evaluate the membrane localization and functional protein domains of the candidate. Cell sorting was performed and the corresponding cellular molecular assays were utilized to examine cancer stem cell features of the sorted cells. Results The unbiased global screening identified RRM2 as the top candidate, with a significantly higher level in iCCA patients with the MS signature activation and in iCCA cells positive for the stemness reporter. Consistently, silencing RRM2 significantly suppressed iCCA malignancy phenotypes both in vitro and in vivo. Moreover, immunohistochemistry in tumor tissues of iCCA patients revealed an unreported cell membrane localization of RRM2, in contrast to its usual cytoplasmic localization. RRM2 cell membrane localization was then confirmed in iCCA cells via immunofluorescence with or without cell membrane permeabilization, cell fractionation assay and cell surface biotinylation assay. Meanwhile, an unclassical signal peptide and a transmembrane domain of RRM2 were revealed experimentally. They were essential for RRM2 trafficking to cell membrane via the conventional endoplasmic reticulum (ER)–Golgi secretory pathway. Furthermore, the membrane RRM2-positive iCCA cells were successfully sorted. These cells possessed significant cancer stem cell malignant features including cell differentiation ability, self-renewal ability, tumor initiation ability, and stemness/malignancy gene signatures. Patients with membrane RRM2-positive iCCA cells had poor prognosis. Conclusions RRM2 had an alternative cell membrane localization. The membrane RRM2-positive iCCA cells represented a malignant subpopulation with cancer stem cell features.

Cichorium intybus L. oligo-polysaccharides (CIOs), obtained from Cichorium intybus L., is a mixture of oligosaccharides and polysaccharides. This study explores the antianxiety and antidepressant effects and mechanisms of CIOs by using acute behavioral despair and chronic unpredictable mild stress mice models and measuring the levels of 5-HT and the expression of proteins related to the BDNF/ERK and PI3K/Akt/mTOR pathways. Moreover, 56 male C57BL/6N mice were used to test behavioral despair. They were randomized into seven groups (Control, Citalopram, CIO 12.5 mg/kg, CIO 25 mg/kg, CIO 100 mg/kg, and CIO 200 mg/kg) based on body weight; they were administered with the corresponding medication daily for 7 days; and behavioral tests were conducted on them (forced swimming test (FST) and tail suspension test (TST)) after 7 days. Seventy male C57BL/6N mice were adopted in the next part of the experiment and randomly divided into seven groups (Control, CUMS, Fluoxetine, MOO, CIO 25 mg/kg, and CIO 100 mg/kg) based on the sucrose preference index. Except for the control group, the other groups were subjected to 6 weeks of CUMS. From the fifth week of stress, the corresponding drugs were administered by gavage until the end of the behavioral tests. In the behavioral despair tests, the immobility time was significantly reduced in the FST and TST after the CIO (25 and 100 mg/kg) treatment of 7 days. After 6 weeks of chronic unpredicted mild stress (CUMS) treatment, CIO (25, 50, and 100 mg/kg) administration significantly reduced the number of buried beads in the marble burying test (MBT), decreased the latency in the novelty-suppressed feeding test (NSFT), and shortened the immobility time in the FST and TST. CIO administration significantly increased the sucrose preference index in the sucrose preference test (SPT). Additionally, CIO treatment increased hippocampal 5-HT levels while upregulating the expression of BDNF, P-PI3K/PI3K, P-ERK/ERK, P-Akt/Akt, and P-mTOR/mTOR. In summary, CIO exerted promising antidepressant effects in behavioral despair and antianxiety and antidepressant effects in CUMS-induced depressive mice. Moreover, CIO therapy was facilitated by increasing the 5-HT content, alleviating the damage of hippocampal neurons, and upregulating the BDNF/ERK and PI3K/AKT/mTOR cascade. Thus, CIO is a substance with the potential to treat anxiety and depression.

Abstract Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal biliary epithelial cancer in the liver. Here, Laminin subunit gamma‐2 (LAMC2) with important oncogenic roles in iCCA is discovered. In a total of 231 cholangiocarcinoma patients (82% of iCCA patients) across four independent cohorts, LAMC2 is significantly more abundant in iCCA tumor tissue compared to normal bile duct and non‐tumor liver. Among 26.3% of iCCA patients, LAMC2 gene is amplified, contributing to its over‐expression. Functionally, silencing LAMC2 significantly blocks tumor formation in orthotopic iCCA mouse models. Mechanistically, it promotes EGFR protein translation via interacting with nascent unglycosylated EGFR in the endoplasmic reticulum (ER), resulting in activated EGFR signaling. LAMC2‐mediated EGFR translation also depends on its interaction with the ER chaperone BiP via their C‐terminus. Together LAMC2 and BiP generate a binding “pocket” of nascent EGFR and facilitate EGFR translation. Consistently, LAMC2‐high iCCA patients have poor prognosis in two iCCA cohorts. LAMC2‐high iCCA cells are highly sensitive to EGFR tyrosine kinase inhibitors (TKIs) treatment both in vitro and in vivo. Together, these data demonstrate LAMC2 as an oncogenic player in iCCA by promoting EGFR translation and an indicator to identify iCCA patients who may benefit from available EGFR‐targeted TKIs therapies.

Abstract Basin‐type insulator often has small cracks due to stress concentration. The current method cannot accurately reflect the stress condition of the insulator to find the stress concentration areas. To solve these problems, a method for detecting two‐dimensional plane stress (δ1 and δ2) within different depth ranges in a basin‐type insulator is proposed based on critically refracted longitudinal (LCR) wave. First, the acoustoelastic equation characterising the relationship between the variation of LCR wave propagation time and the plane stress was derived. Next, the propagation characteristics of LCR wave in epoxy resin samples were investigated. Then, the stress distribution within different depth ranges of the insulator subjected to hydraulic load was measured using the proposed method, including direction (θ), δ1 and δ2. The results show that the magnitude of the stress alone cannot accurately characterise the stress state. Points with equal distances to the centre have similar stress magnitudes, but their directions are not the same. With increasing depth, θ remains essentially unchanged at the same location, while δ1 and δ2 decrease, and the rate of decrease varies at different locations. Comparing the measured and simulated data, the results showed that they were in good agreement, and the maximum errors of stress value and θ were 0.69 MPa and 2.97°, respectively, which confirmed the feasibility and accuracy of the stress detection in the proposed method.

In recent years, rechargeable zinc–air batteries (ZABs) have attracted much attention owing to their high theoretical specific energy density, safety, and environmental friendliness. They are also considered a viable option for powering the grid and electric vehicles in the future. The activity and the stability of the bifunctional catalysts for the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) in ZABs remarkably influence the battery’s energy, power densities, and lifetime. Therefore, developing efficient and stable bifunctional catalysts is an important research direction. Previously, precious metal catalysts such as Pt/C, Ir/C, and Ru/C have been used to design efficient ORR and OER electrocatalysts. However, these electrocatalysts possess several issues, including limited natural abundance, high metal sintering and catalyst detachment rates from supports, and poor bifunctional activity, which limit their practical applications. As potential catalysts, nonprecious transition metal oxides exhibit the prominent advantages of manifold compositions, multiple valence states, environmental friendliness, high durability and abundance, and varying structures. Their disadvantages include poor electrical conductivity and a limited surface area. To address the abovementioned issues, current general research focuses on compounding transition metal oxides with carbon materials or other conductive substrates to simultaneously increase their specific surface area and electrical conductivity and control their morphology to expose more active sites. Furthermore, the intrinsic activity of the transition metal oxides must also be regulated through the most commonly used activity regulation methods (e.g., heteroatom doping and defect engineering). For example, perovskite and spinel-type transition metal oxides must meet a specific eg orbital occupancy to achieve the best bifunctional activity. Therefore, improving the catalytic performance requires the A- and B-site atom substitution with other alkaline and rare earth or transition metals or the introduction of oxygen vacancies to adjust the electronic structure. Spinel- and perovskite-type transition metals and manganese oxides are the research objects used in this work. The activity sources of different types of transition metal oxide catalysts and their performances in energy density, charge/discharge voltage, and cycle life of zinc–air batteries are introduced herein. The strategies and methods used to improve the catalytic performance of transition metal oxides in current research are summarized. Finally, the future development of transition metal bifunctional catalysts for oxygen reduction and evolution reactions is prospected.

According to the theory of atmospheric transmission, the atmospheric optical characteristics of a 700 mm laser ranging telescope system are obtained by the inversion of the experimental data through the telescopic multi-elevation method, and a modified model of the ranging equation of laser diffuse radar is proposed. The variation in the Aerosol Optical Depth and atmospheric transmittance under the multi-elevation method, visibility and the oblique transmission atmospheric stratification model are analyzed and discussed. The model is numerically simulated and compared with the measured data of some space debris. The results show that the relative errors of the average echo photon number obtained by the multi-elevation method are less than 15%, and the average relative errors are 4.643% and 7.934%, respectively. The model improves the calculation accuracy of the laser ranging radar equation to a certain extent.

IntroductionIn the context of declining mortality rates and increasing infectivity, it has become unavoidable for the majority of individuals to experience a COVID-19 infection at some point. This study aimed to investigate the psychological well-being of the general population during China’s transition period from strict control measures to relaxed policies in COVID-19 prevention and control, as well as the impact of COVID-19 related thoughts on emotion and life satisfaction during widespread infections.MethodsA cross-sectional study was conducted involving a sample size of 1578 participants. Participants completed self-report questionnaires assessing positive and negative emotions, thoughts about COVID-19, and satisfaction with life. Demographic characteristics such as sex, age, and education level were controlled for in the analysis.ResultsThe findings revealed that individuals who had been infected with COVID-19 (specifically the Omicron variant BA.5.2 or BF.7) reported lower levels of positive emotions compared to those who were uninfected or had recovered from the infection. There was a significant relationship between COVID-19-related thoughts, emotions, and life satisfaction. Positive COVID-19 related thoughts were found to mediate the relationship between negative emotions and satisfaction with life.DiscussionThis study represents a comprehensive examination conducted in China, focusing on assessing the impact of the COVID-19 pandemic on the general population during the critical transition period from control to relaxation. Throughout this period, the number of infections experienced fluctuations, initially rising but eventually declining over a one-month span. In such a momentous historical period, maintaining a positive perspective on COVID-19 and its management becomes paramount in enhancing the emotional well-being, life satisfaction and overall well-being of individuals.

ABSTRACT: Beam synthesizing antenna arrays are essentially demanded for on-chip millimeter wave and terahertz systems. In order to achieve a particular radiation beam, specific amplitude and phase distributions are required for all the array elements, which is conventionally realized through a properly designed feeding network. In the current work, a low-loss feeding network design approach based on epsilon-near-zero (ENZ) medium was proposed for large-scale antenna arrays with different beam requirements. Due to the infinite wavelength within the ENZ medium, a newly-discovered stair-like resonant mode was adopted for assigning a uniform phase distribution to each element, while the amplitudes and positions of these elements were optimized for generating particular beams. To implement the design philosophy in a low-loss manner, a hollow air-filled waveguide near cutoff frequency was employed to emulate the ENZ medium, and the bulk silicon microelectromechanical systems (MEMS) micromachining technology was utilized for chip-scale integration. As a specific example, a low-sidelobe antenna array at 60.0 GHz was designed, which realized an impedance bandwidth of 2.57%, a gain of 13.6 dBi and a sidelobe level as low as -20.0 dB within the size of 0.5 × 3.4λ02. This method is also compatible with a variety of applications, such as the high-directivity antenna array, non-diffractive Bessel beam antenna array, and so on. Based on this innovative concept of applying ENZ medium to the on-chip antenna array, it shows the advantages of simple structure and low loss for on-chip beam synthesis without complex lossy feeding networks.

Passive heat dissipation was a prospective solution to gratify the thermal management requirements of the continuously compact and miniaturized package. In here, we proposed an embedded heat pipe SiC interposer for the distributed power devices. The thermal effects of wick shape and filling ratio were investigated through the established VOF (volume of fluid) models. The hotspots' arrangement was identified by comparing thermal performance with hotspots' placing at 22.5°, 45°, and 90° in the vertical coordinate system. The 45° arrangement was settled by analyzing the effects on refilling path between the evaporation and condensation areas. Profited from the SiC substrate transparency, the embedded thermography visualization platform was deployed to verify the two-phase flow behaviors inside the SiC interposer with various heat fluxes. Through the Infrared imager and non–contact Raman–based thermometry, the heat transfer coefficient (90 kW/m2·°C @ 160 W/cm2), maximum temperature difference (within 2.6 °C @ 160 W/cm2), and the distributed radial and axial thermal resistances (0.167–0.178 °C/W and 0.157–0.163 °C/W) of the SiC interposer were ascertained, respectively. Towards the distributed power devices embedded heat pipe interposer, the substrate material, the wick geometry, the filling ratio, and hotspots’ arrangement need to be comprehensively optimized.

Abstract Background Emerging studies revealed that cancer stem cells (CSCs) possessed peculiar metabolic properties, which however remained largely unknown in hepatocellular carcinoma (HCC). Genetic silencing of liver-abundant miR-192-5p was a key feature for multiple groups of CSC-positive HCCs. We thus aimed to investigate essential metabolic features of hepatic CSCs via using HCCs with miR-192-5p silencing as a model. Methods Datasets from two independent HCC cohorts were used. Data integration analyses of miR-192-5p with metabolome and mRNA transcriptome data in HCC Cohort 1 were performed to investigate miR-192-5p related metabolic features, which was further validated in Cohort 2. Cellular and molecular assays were performed to examine whether and how miR-192-5p regulated the identified metabolic features. Co-culture systems consisting of HCC cells and LX2 (human hepatic stellate cell line) or THP1 (human monocyte cell line) were established to explore effects of the identified metabolic properties on stemness features of HCC cells via interacting with co-cultured non-tumor cells. Results High levels of glycolysis-related metabolites and genes were present in HCCs with low miR-192-5p and CSC-positive HCCs in two independent HCC cohorts. miR-192-5p knockout cells displayed CSC features and miR-192-5p loss led to an enhanced glycolytic phenotype via upregulating three bona fide targets, GLUT1 and PFKFB3 (two glycolytic enzymes) and c-Myc (regulating glycolytic genes’ expression). Meanwhile, c-Myc suppressed miR-192-5p transcription, ensuring a low-miR-192-5p/high-c-Myc loop to maintain hyperglycolysis. Moreover, over-produced lactic acid from hyperglycolytic HCC cells stimulated the ERK phosphorylation of co-cultured LX2 and THP1 non-tumor cells partially via NDRG3 and MCT1, which in turn promoted cell malignancy and stemness of HCC cells. Consistently, HCC patients with low level of miR-192-5p in their tumor tissues and high level of NDRG3 or MCT1 in their non-tumor tissues had the shortest overall survival. Conclusions In CSC-positive HCCs, miR-192-5p loss enhanced glycolysis and over produced lactate might further increase HCC malignant features via interacting with environmental non-tumor cells.

There has been growing interest in applying the DEM (discrete element method) to study the charging and burden distribution in a BF (blast furnace). In practice, the real particles in a BF are non-spherical. However, spherical particles have mostly been used in previous DEM investigations. Furthermore, various particle models have been developed to describe non-spherical particles. However, the effects of using different particle models on particle behavior in a BF are still unclear. Therefore, a comparative study of how the particle shape model impacts the burden charging in a BF was conducted. Specifically, the DEM using a multi-sphere model, polyhedral model, and super-ellipsoid model was first established. Then, experiments and DEM simulations of the charging and burden distribution of non-spherical quartz sand particles in a lab-scale bell-less top BF were performed. The results indicated that the number of sub-spheres, the principle of creating the particle for multi-spheres, the number of planes for polyhedrons, and the shape indices for super-ellipsoids could all affect the accuracy and efficiency. Moreover, applying the super-ellipsoid model and multi-sphere model could achieve reasonable accuracy and efficiency, with the highest simulation accuracy for the polyhedral model but at the cost of a rather heavy computational burden.

The number of hungry people is on the rise and more efforts are needed to improve the global food security status. The Food and Agriculture Organization (FAO) proposes more investment in the agricultural sector to boost production and alleviate hunger. However, there are fewer papers that distinguish enterprises investment from public investment. In this case, we take advantage of detailed investment data in the fDi Markets database to explore the global patterns of agricultural investment. In particular, we identify the top destination countries based on aggregate and sub-sectoral agricultural investment data. Then we investigate the relationship between agricultural investment and food security, which is measured by per capita protein intake. Finally, we propose some suggestions from the investment motivation perspective to help food-insecure countries to attract overseas investment. We find that developed countries are the primary sources of global agricultural investment and these sources have been becoming more diverse in the past decade. It implies the trend towards a more inclusive investment environment worldwide. However, the global distribution of agricultural investment is uneven as food-insecure countries only receive 20% of the global agricultural investment. The top three destination countries, USA, China, and Russia, have a relatively high food security level. In contrast, countries suffering from food insecurity receive fewer investment projects, and most of which are on a small scale. Given the limited socio–economic development status in food-insecure countries, it is essential for all levels of society to help them and contribute to ending hunger.

Abstract Background This study aimed to investigate the differences in the serum levels of glucose, lipid, and thyroid function markers between unipolar and bipolar depressed patients, as well as the effect of anhedonia and suicidal thoughts on the levels of these biochemical parameters. Methods A total of 287 unmedicated depressed patients from January 2016 to December 2017 were included in this study, including 92 bipolar depressions and 195 unipolar depressions. Anhedonia was determined using the item 32 of Symptom Checklist (SCL-90). Suicide ideation was assessed by item 15 of SCL-90. Results The bipolar group had significantly lower lipid levels (including triglycerides, cholesterol, low-density lipoprotein cholesterol [LDL], very low-density lipoprotein cholesterol [VLDL]) and insulin resistance index but higher levels of prolactin, low triiodothyronine (T3) and free T3 (FT3) as well as higher incidence of anhedonia as compared with the unipolar group. Depressed patients with anhedonia had significantly higher LDL level than those without anhedonia. Depressed patients with suicidal thoughts had cholesterol and high-density lipoprotein cholesterol (HDL) level. The above-mentioned differences were confirmed by logistic regression analysis. Receiver operating characteristic curve (ROC) analysis showed that the area under the ROC curve (AUC) ranged from 0.546 to 0.685. Conclusion Triglycerides, cholesterol, LDL, VLDL T3, FT3 levels were significantly different between unipolar and bipolar depressed patients, which might have the potential to be the markers for differential diagnosis. Patients with anhedonia had lower LDL level, while patients with suicidal thoughts had higher levels of cholesterol and HDL as compared with the corresponding control groups.

The prevalence and related factors of mental health impact among medical staffs who experienced the second wave of the COVID-19 pandemic in China is unknown. Therefore, this survey was conducted to investigate the prevalence and related factors of depressive, anxiety, acute stress, and insomnia symptoms in medical staffs in Kashi, Xinjiang, China during the second wave of the COVID-19 pandemic. A cross-sectional online survey was conducted among medical staffs working in First People's Hospital of Kashi, Xinjiang. The questionnaire collected demographic data and self-design questions related to the COVID-19 pandemic. The Impact of Events Scale-6, the Insomnia Severity Index, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder Scale-7, the Perceived Social Support Scale, the Chinese Big Five Personality Inventory-15, and the Trait Coping Style Questionnaire were used to measure psychological symptoms or characteristics. Binary logistic regression was carried out to examine the associations between socio-demographic factors and symptoms of depression, anxiety, stress, and insomnia. In total, data from 123 participants were finally included, among which the prevalence rate of depressive, anxiety, acute stress, and insomnia symptoms is 60.2, 49.6, 43.1, and 41.1%, respectively. The regression model revealed that minority ethnicity, being worried about infection, spending more time on following pandemic information, and neurotic personality were positively associated with the mental health symptoms, while extraversion personality, higher education level, and better social support were negatively associated. In our study, the prevalence of mental health impact was high among medical staffs in Kashi, China who experienced the second wave of the COVID-19 pandemic. Several factors were found to be associated with mental health conditions. These findings could help identify medical staffs at risk for mental health problems and be helpful for making precise mental health intervention policies during the resurgence. Our study may pave way for more research into Xinjiang during the COVID-19 pandemic.

With the integrated high-power device packaging structure rapidly developing, the embedded heat dissipation architectures are challenged by the local micro-/nanoscale massive heat flux. The slip flow molecular dynamics models were established to explore the liquid–solid interfacial thermal conductance. With stepwise declining shear forces (0.032 pN/200, 0.024 pN/200, and 0.016 pN/200 ps, respectively), the slip flow [the slip shear velocity is Si: (125.43 ± 0.92 m/s), graphite: (142.43 ± 1.92 m/s), and Cu: (180.93 ± 3.42 m/s), respectively] water–solid interfacial thermal conductance of different materials [Si: (8.11 ± 0.1) × 107 W/m2 K, graphite: (10.18 ± 0.1) × 107 W/m2 K, and Cu: (17.97 ± 0.1) × 107 W/m2 K] can be calculated. The rationality of the calculated values can be verified in the literature. The slip flow water–solid interfacial thermal conductance values are about 0.5 times higher than the static ones. It can be significantly affected by the slip shear velocity. The slip shear velocity increasing about five times can enhance the interfacial thermal conductance two times. From the water layer density distribution, it is found that the dependence of interfacial thermal conductance on velocity slip relies more on the dynamical properties than on the fluid structure. This molecular dynamics model provides an operative methodology to investigate the slip flow liquid–solid interfacial heat transfer for the various embedded cooling surfaces.

Fluidization of non-spherical particles is a common process in energy industries and chemical engineering. Understanding the fluidization of non-spherical particles is important to guide relevant processes. There already have been numerous studies which investigate the behaviors of different non-spherical particles during fluidization, but the investigations of the fluidization of polyhedral particles do not receive much attention. In this study, the investigation of the fluidization of polyhedral particles described by the polyhedron approach is conducted with a numerical CFD-DEM method. Experiments of the fluidization of three kinds of polyhedral particles are conducted under the same condition with corresponding simulations to validate the accuracy of our CFD-DEM model. The results indicate that our CFD-DEM model with the polyhedron approach can predict the behaviors of polyhedral particles with reasonable accuracy. Fluidization behaviors of different polyhedral particles are also investigated in this study. Compared to spherical particles, the motion of polyhedral particles is stronger, and mixing degree is higher under the same fluidization gas velocity.