Search

Hepatitis B virus (HBV) exploits the endosomal sorting complexes required for transport (ESCRT)/multivesicular body (MVB) pathway for virion budding. In addition to enveloped virions, HBV-replicating cells nonlytically release non-enveloped (naked) capsids independent of the integral ESCRT machinery, but the exact secretory mechanism remains elusive. Here, we provide more detailed information about the existence and characteristics of naked capsid, as well as the viral and host regulations of naked capsid egress. HBV capsid/core protein has two highly conserved Lysine residues (K7/K96) that potentially undergo various types of posttranslational modifications for subsequent biological events. Mutagenesis study revealed that the K96 residue is critical for naked capsid egress, and the intracellular egress-competent capsids are associated with ubiquitinated host proteins. Consistent with a previous report, the ESCRT-III-binding protein Alix and its Bro1 domain are required for naked capsid secretion through binding to intracellular capsid, and we further found that the ubiquitinated Alix binds to wild type capsid but not K96R mutant. Moreover, screening of NEDD4 E3 ubiquitin ligase family members revealed that AIP4 stimulates the release of naked capsid, which relies on AIP4 protein integrity and E3 ligase activity. We further demonstrated that AIP4 interacts with Alix and promotes its ubiquitination, and AIP4 is essential for Alix-mediated naked capsid secretion. However, the Bro1 domain of Alix is non-ubiquitinated, indicating that Alix ubiquitination is not absolutely required for AIP4-induced naked capsid secretion. Taken together, our study sheds new light on the mechanism of HBV naked capsid egress in viral life cycle. Author summary: HBV-infected cells can produce various viral particles with different sizes and morphologies. Virions are complete particles with both nucleocapsids and surface antigen (HBsAg) envelope, which exploits the endosomal sorting complexes required for transport (ESCRT)/multivesicular body (MVB) pathway for budding. In addition to virion, HBV-infected cells also secrete non-enveloped (or naked) capsid particles. It remains unclear how HBV naked capsid is released from the infected cells. In this study, we further characterized the naked capsid and identified the Lysine 96 of HBV core protein as an important contact point for cellular protein Alix to mediate naked capsid secretion. We also determined NEDD4 E3 ubiquitin ligase family member AIP4 stimulates the release of naked capsid, regardless of their genome contents. AIP4 interacts with Alix and promotes its ubiquitination. However, the AIP4 protein per se rather than its E3 ubiquitin ligase activity is sufficient for Alix-induced naked capsid secretion. In summary, these findings provide new insights into a better understanding of HBV naked capsid egress. [ABSTRACT FROM AUTHOR]

Triple‐negative breast cancer (TNBC) has greater infiltration of M2‐like macrophages (TAMs), which enhances cancer cell invasion and leads to a poor prognosis. TNBC progression is mediated by both tumor cells and the tumor microenvironment (TME). Here we elucidate the mechanism of the interaction between TNBC cells and TAMs. In this study, we confirmed that CD44v5 is highly expressed in TNBC, which drives TNBC cell metastasis and promotes TAM polarization by co‐localizing with IL4Rα and inhibiting its internalization and degradation, thereby promoting activation of the STAT3/IL6 signaling axis. At the same time, TAMs also facilitate TNBC cell metastasis by secreting IL‐4, IL‐6, and other cytokines, in which the IL‐4/IL‐4R/STAT3/IL‐6 signaling axis plays the same role for TNBC cells responding to TAMs. Moreover, we found that the above progress could be suppressed when the CD44v5 domain was blocked. We demonstrated that the CD44v5/IL‐4R/STAT3/IL‐6 signaling pathway plays a key role in TNBC cell metastasis, and in TNBC cells inducing TAM polarization and responding to TAMs, promoting metastasis. Collectively, we suggest that the CD44v5 domain may be a promising target for regulating the TME of TNBC as well as treating TNBC. [ABSTRACT FROM AUTHOR]

Tripartite motif (TRIM) proteins, comprising a family of over 100 members with conserved motifs, exhibit diverse biological functions. Several TRIM proteins influence viral infections through direct antiviral mechanisms or by regulating host antiviral innate immune responses. To identify TRIM proteins modulating hepatitis B virus (HBV) replication, we assessed 45 human TRIMs in HBV-transfected HepG2 cells. Our study revealed that ectopic expression of 12 TRIM proteins significantly reduced HBV RNA and subsequent capsid-associated DNA levels. Notably, TRIM65 uniquely downregulated viral pregenomic (pg) RNA in an HBV-promoter-specific manner, suggesting a targeted antiviral effect. Mechanistically, TRIM65 inhibited HBV replication primarily at the transcriptional level via its E3 ubiquitin ligase activity and intact B-box domain. Though HNF4α emerged as a potential TRIM65 substrate, disrupting its binding site on the HBV genome did not completely abolish TRIM65's antiviral effect. In addition, neither HBx expression nor cellular MAVS signaling was essential to TRIM65-mediated regulation of HBV transcription. Furthermore, CRISPR-mediated knock-out of TRIM65 in the HepG2-NTCP cells boosted HBV infection, validating its endogenous role. These findings underscore TRIM proteins' capacity to inhibit HBV transcription and highlight TRIM65's pivotal role in this process. [ABSTRACT FROM AUTHOR]

Although pressure ulcers are related to substantial health burdens, they may be preventable. Since nurses play a fundamental role in pressure ulcer prevention, their knowledge and attitude are of great importance. This study aims to investigate the current situation and associated factors of nurses' knowledge and attitude on the prevention of pressure ulcers from both tertiary and secondary hospitals. A total of 11 347 nurses were recruited including 7108 nurses (62.6%) from tertiary hospitals and 4239 nurses (37.4%) from secondary hospitals. The median (interquartile range) of the pressure ulcer knowledge score was 51% (38%, 90%) for all the participants with the lowest scores on prevention of pressure ulcers (51.33%). The mean (standard deviation) of attitude towards pressure ulcer prevention was 39.64 (4.65) with the lowest scores on personal competency to prevent pressure ulcers (mean 3.09). The results of multivariate linear regression showed that hospital level, nurses' age, years of work experience, initial education level at work and time of last training significantly associated with nurses' knowledge of pressure ulcer prevention. Meanwhile, hospital level, job title, previous training, time of last training and subjective needs for further training had significant association with nurses' attitude towards pressure ulcer prevention (all p < 0.05). Results showed inadequate knowledge but relative positive attitudes in nurses indicating the importance to deliver continuing education and training regarding pressure ulcer prevention in practice to improve the quality of care. [ABSTRACT FROM AUTHOR]

The copper (Cu)-catalyzed electrochemical CO2 reduction provides a route for the synthesis of multicarbon (C2+) products. However, the thermodynamically favorable Cu surface (i.e. Cu(111)) energetically favors single-carbon production, leading to low energy efficiency and low production rates for C2+ products. Here we introduce in situ copper faceting from electrochemical reduction to enable preferential exposure of Cu(100) facets. During the precatalyst evolution, a phosphate ligand slows the reduction of Cu and assists the generation and co-adsorption of CO and hydroxide ions, steering the surface reconstruction to Cu (100). The resulting Cu catalyst enables current densities of > 500 mA cm−2 and Faradaic efficiencies of >83% towards C2+ products from both CO2 reduction and CO reduction. When run at 500 mA cm−2 for 150 hours, the catalyst maintains a 37% full-cell energy efficiency and a 95% single-pass carbon efficiency throughout.Copper electrocatalysts enable carbon dioxide/carbon monoxide reduction but suffer from low production rates. Here, the authors promote in situ growth of Cu(100) during electrolysis, enabling efficient and stable electrosynthesis of multicarbon products at industrially-relevant current densities [ABSTRACT FROM AUTHOR]

The copper (Cu)-catalyzed electrochemical CO2 reduction provides a route for the synthesis of multicarbon (C2+) products. However, the thermodynamically favorable Cu surface (i.e. Cu(111)) energetically favors single-carbon production, leading to low energy efficiency and low production rates for C2+ products. Here we introduce in situ copper faceting from electrochemical reduction to enable preferential exposure of Cu(100) facets. During the precatalyst evolution, a phosphate ligand slows the reduction of Cu and assists the generation and co-adsorption of CO and hydroxide ions, steering the surface reconstruction to Cu (100). The resulting Cu catalyst enables current densities of > 500 mA cm−2 and Faradaic efficiencies of >83% towards C2+ products from both CO2 reduction and CO reduction. When run at 500 mA cm−2 for 150 hours, the catalyst maintains a 37% full-cell energy efficiency and a 95% single-pass carbon efficiency throughout. Copper electrocatalysts enable carbon dioxide/carbon monoxide reduction but suffer from low production rates. Here, the authors promote in situ growth of Cu(100) during electrolysis, enabling efficient and stable electrosynthesis of multicarbon products at industrially-relevant current densities [ABSTRACT FROM AUTHOR]

Purpose: In theory, the impact of debt liquidity risk (DLR) on the firm's future growth is ambiguous. This study aims to examine the empirical relationship between the DLR and firms' growth rate using annual data for USA companies from 1976 to 2020. Design/methodology/approach: Given the longitudinal nature of the data, the author uses OLS (ordinary least squares) regression methodology with fixed effects to control for unobserved characteristics that might affect the dependent variable. Instrument variable regression is also used to address the potential endogeneity problem. Findings: The results show that firms having higher DLR, as proxied by more short-term debt, experience lower growth rate. An increase in firms' short-term debt decreases the firms' future growth rate as evidenced by lower assets, revenue and employee growth rate. Moreover, the authors' results show that small firms or firms with more investment opportunities grow fast if the firms take higher DLR. Finally, cyclical firms with higher DLR exhibit lower growth rate during the credit tighten period. The authors' results hold for both the pre-zero lower bound (ZLB) era and ZLB period. Originality/value: To the authors' best knowledge, this is one of the earliest studies to carefully examine the effects of DLR on firms' growth rate. While prior research finds that firms with higher growth potential, measured by market-to-book (MTB) ratio, use more short-term debt, the authors' research directly addresses whether DLR affects firms' future growth rate. The authors' findings also help explain why firms with high growth potential use more short-term debt. [ABSTRACT FROM AUTHOR]

Herein, the high-entropy perovskite, i.e. La(FeCoNiCrMn)O3, was prepared for simultaneous CO2 reduction and biomass upgrading. Based on the synergistic effect between the elements in the high-entropy material, an excellent CO evolution rate of 131.8 μmol g−1 h−1 and a xylonic acid yield of 63.9% were gained. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study of children with juvenile idiopathic arthritis (JIA) was to use proton magnetic resonance spectroscopy (1H-MRS) to compare the levels of five neurometabolites in the right and left insular cortexes of subjects in three groups: JIA-active, JIA-inactive, and healthy controls (HCs). Methods: Two inflammation markers and five psychometric scores were determined. 1H-MRS was used to measure the levels of total N-acetylaspartate (NAA), total choline (Cho), myo-inositol (mI), and glutamate (Glu), and the complex of glutamine and glutamate (Glx) relative to total creatine (tCr) in the right and left insular cortexes of participants. Results: Intra-group comparisons indicated that each group had higher levels of NAA/tCr, Glu/tCr, Glx/tCr, and mI/tCr in the right insula, and higher levels of Cho/tCr in the left insula. Inter-group comparisons of the right insula indicated that the JIA-active and JIA-inactive groups had higher levels of Cho/tCr than the HC group, but none of the other inter-group differences were statistically significant. The score of the Sleep Disturbance Scale for Children (SDCD) had an inverse correlation with the level of Cho/tCr in the right insular cortex of patients in the JIA-inactive group. Conclusions: Relative to the HC group, the right insular cortex of subjects in the JIA-active and the JIA-inactive groups had greater levels of Cho/tCr, suggesting increased inflammation in this region. The Cho/tCr level in the right insular cortex had an inverse correlation with SDCD score in the JIA-inactive group. Key Points • Healthy controls and JIA patients had higher levels of tNAA/tCr, Glu/tCr, Glx/tCr, and mI/tCr in the right insula, and higher levels of Cho/tCr in the left insula. • A greater level of Cho/tCr in the right insula of JIA-active and JIA-inactive patients indicated neuroinflammation in this region. • The Cho/tCr level in the right insular cortex had an inverse correlation with SDCD score in the JIA-inactive group. [ABSTRACT FROM AUTHOR]

The effects of different oxytetracycline (OTC) acclimation strategies on the electricity generation performance of microbial fuel cells (MFCs), the microbial community composition, and functional groups of biofilms were investigated by using low-dose stepwise acclimation (L-MFC) and high-dose direct acclimation (H-MFC). The results showed that H-MFC could effectively shorten the acclimation period by 10 days while achieving 94.93% OTC removal efficiency, which was 1.31% higher than that of L-MFC. Based on a higher response current and lower internal resistance, the maximum power output of the L-MFC (690.28 mV) was better than that of the H-MFC (670.26 mV). High-throughput sequencing results showed that the species diversity and richness of the bioanode in L-MFC were higher, and the main dominant groups were Geobacter (26.48%), Aquamicrobium (10.31%), and other electroactive microorganisms involved in extracellular electron transfer, while Cupriavidus (21.46%), Rhodopseudomonas (10.38%), Acidovorax (7.62%), and other OTC degradation groups were further enriched in H-MFC. The KEGG manifested that the biological process was mainly controlled by genes of the metabolism pathway. Among them, except for the up-regulation of xenobiotics biometabolism and metabolism functional genes in H-MFC by 0.46%, the other metabolism-related genes were highly expressed in L-MFC. Different OTC acclimation strategies have an effect on the electricity generation, microbial structure, and function of MFCs. [ABSTRACT FROM AUTHOR]

Purpose: The unemployment rate (UR) is the leading macroeconomic indicator used in the credit card loss forecasting. COVID-19 pandemic has caused an unprecedented level of volatility in the labor market variables, leading to new challenges to use UR in the credit risk modeling framework. This paper examines the dynamic relationship between the credit card charge-off rate and the unemployment rate over time. Design/methodology/approach: This study uses quarterly observations of charge-off rates on credit card loans of all commercial banks from Q1 1990 to Q4 2020. Univariate, multivariable, machine learning, and regime-switching time series modeling are employed in this research. Findings: The authors decompose UR into two components – temporary and permanent UR. The authors find the spike in UR during COVID-19 is mainly attributed to the surge in temporary layoffs. More importantly, the authors find that the credit card charge-off rate is primarily driven by permanent UR while temporary UR has little predictive power. During recessions, permanent UR seems to be a stronger indicator than total UR. This research highlights the importance of using permanent UR for credit risk modeling. Originality/value: The findings in the research can be applied to the credit card loss forecasting and CECL reserve models. In addition, this research also has implications for banks, macroeconomic data vendors, regulators, and policymakers. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this paper is to investigate the relationship between investors' divergence of opinions and the asset prices of foreign stocks and also examine the effect of home market country-level factors on the influence of divergency of opinions on stock price. Design/methodology/approach: The authors employ panel data estimation with fixed effects to examine the host market response in divergent opinions to the earnings announcements. The paper uses the American Depositary Receipts (ADRs) of 42 countries from 1985 to 2011. Findings: The authors find a negative relationship between differences of opinions and excess quarterly earnings announcement returns, and investors do process information asymmetrically based on good and bad earnings shocks. In addition, the authors find the negative relationship between divergent opinions and excess earnings announcement returns in ADRs is more pronounced in countries with short-sales restrictions, while other home-market country-level factors – the enforcement of insider trading law, legal origin, investor protection and rating on accounting standard – do not influence the relationship between investors' divergency of opinion and stock returns. Originality/value: This paper is among the first to bring asymmetric effects on convergence in Miller framework and enhance the understanding of price convergence documented in Miller (1977). In addition, this study incorporates home-market country-level factors in explaining the relationship between investors' divergency of opinions and stock returns. [ABSTRACT FROM AUTHOR]

Purpose: The wetland in the Yellow River Reservoir area of Sanmenxia is a habitat of mute swans and an important water source conservation area. Excessive nitrogen input can directly or indirectly threaten the ecological health of the wetland. To date, no systematic studies have investigated the effects of vegetation or environmental factors on the microbial communities, especially nitrogen-removal bacteria in the wetland of the Sanmenxia Reservoir on the Yellow River. This study aimed to uncover the correlations between nitrogen-removal bacteria communities, vegetation type, and environmental physicochemical properties in the Yellow River wetlands, laying a foundation for future studies of nitrogen cycling. Methods: Sediment profile samples were collected and metagenomic sequencing was used to study the diversity and composition of microbial communities in wetland sediment. Nitrogen isotope tracing was performed to determine the denitrification and anammox rates. Results: The dominant microorganisms of the wetland samples were bacteria. Subsequently, the community composition and taxonomic abundances were analyzed at the phylum and genus levels, which showed significant differences between-groups (P < 0.01). Nitrogen removal occurred mainly through denitrification in YJW (a sampling site, maximum denitrification rate of 1.09 mg N kg−1 day−1) and anammox in TEH (another sampling site, maximum anammox rate of 0.14 mg N kg−1 day−1). The abundance of typical anammox and denitrifying bacteria at the genus level was generally consistent with reaction rates. The factors related to microbial community diversity on the genera included NH4+–N, total organic carbon, total nitrogen, and pH, but NH4+–N was the key factor that explained the difference between YJW and TEH in terms of community structure of nitrogen-removal microbes. Three highly significant nitrogen-removal communities and five nitrogen metabolism functional genes were screened by Spearman rank correlation coefficient analysis. Conclusion: This study revealed the relationship between sediment microbial community structure, especially denitrification microorganisms, typical denitrification reaction processes, and environmental physicochemical properties in the Sanmenxia Yellow River Reservoir, which provides theoretical support for future studies on soil environmental nitrogen cycling mechanisms in this riverside wetland. [ABSTRACT FROM AUTHOR]

Background: Whether serum hepatitis B virus (HBV) RNA associates with hepatocellular carcinoma (HCC) development in chronic hepatitis B (CHB) patients has not been fully elucidated.Methods: We enrolled 2974 patients receiving nucleos(t)ide analogues (NAs) from a prospective, observational CHB cohort to investigate the effect of serum HBV RNA, measured at study entry (baseline), on HCC development, using Cox regression analyses.Results: During median follow-up of 4.4 years, 90 patients developed HCC. Patients with detectable baseline HBV RNA (n = 2072) exhibited significantly higher HCC risk than those with undetectable level (5-year HCC incidence estimated by Kaplan-Meier method: 4.1% versus 1.8%, P = .009; adjusted hazard ratio [aHR] = 2.21, P = .005). HBV RNA levels of 609-99 999 and ≥100 000 copies/mL were associated with incrementally increasing HCC risk (aHR = 2.15 and 3.05, respectively; P for trend = .003), compared to undetectable level (<609 copies/mL). Moreover, patients with single-detectable either HBV DNA or RNA and double-detectable DNA and RNA had 1.57- and 4.02-fold higher HCC risk, respectively, than those with double-undetectable DNA and RNA (P for trend = .001).Conclusions: High-level HBV RNA is associated with increased HCC risk in NAs-treated patients. Achieving undetectable HBV RNA may contribute to better clinical outcomes, indicating it could be a valuable endpoint of anti-HBV treatment. [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate whether the neurometabolites of the anterior cingulate cortex (ACC) were distinct in patients with active and inactive juvenile idiopathic arthritis (JIA) using the proton magnetic resonance spectroscopy. Methods: We measured the levels of total N-acetylaspartate (tNAA), choline (Cho), myo-inositol (ml), glutamate (Glu) and the complex of glutamate and glutamine (Glx) relative to total creatine (tCr) in ACC of each participant. Results: Compared with the healthy controls, a significant decrease of total Cho/tCr and Glx/tCr ratio in ACC occurred in active and inactive JIA group. The tCho/Cr level was negatively associated with the serum level of ESR in active JIA patients. There was no difference in NAA/tCr ratio among the three groups, which may imply that no neuron and axonal losses occurred in either active or inactive JIA patients. Conclusions: The abnormal neurometabolites in tCho/tCr and Glx/tCr in ACC may indicate that persistent dysfunction of glial cell, while neither neuron nor axonal losses occurred in active and inactive JIA patients. [ABSTRACT FROM AUTHOR]

This article first reviews scientific meanings of single-cell analysis by highlighting two key scientific problems: landscape reconstruction of cellular identities during dynamic immune processes and mechanisms of tumor origin and evolution. Secondly, the article reviews clinical demands of single-cell analysis, which are complete blood counting enabled by optoelectronic flow cytometry and diagnosis of hematologic malignancies enabled by multicolor fluorescent flow cytometry. Then, this article focuses on the developments of optoelectronic flow cytometry for the complete blood counting by comparing conventional counterparts of hematology analyzers (e.g., DxH 900 of Beckman Coulter, XN-1000 of Sysmex, ADVIA 2120i of Siemens, and CELL-DYN Ruby of Abbott) and microfluidic counterparts (e.g., microfluidic impedance and imaging flow cytometry). Future directions of optoelectronic flow cytometry are indicated where intrinsic rather than dependent biophysical parameters of blood cells must be measured, and they can replace blood smears as the gold standard of blood analysis in the near future. [ABSTRACT FROM AUTHOR]

Objective: Leveraging an integrative multimodal MRI paradigm to elaborate on the hippocampus-derived structural and functional changes in children and adolescents with juvenile idiopathic arthritis (JIA) and to explore potential correlations within the "joint-inflammation-brain" axis during the period of central neural system (CNS) development. Methods: Twenty-one patients with JIA all completed the multimodal MRI scanning, laboratory tests, and neuropsychological assessments; meanwhile, 23 matched controls were recruited. We then harnessed the spherical harmonics with a point distribution model (SPHARM-PDM) and the ROI-to-voxel functional connectivity (FC) to measure the hippocampal shape and hippocampo-cortical FC patterns. Correlation analysis was performed to explore the potential links in neuroimaging features with disease-related indices. Results: Compared to controls, JIA patients only presented an atrophic tendency in the posterior part of the bilateral hippocampus. The hippocampo-cortical FC revealed the between-group divergences mainly located at the pain matrix, striatum, and temporal lobe. Remarkably, the enhanced FC between the right hippocampus and postcentral cortex is positively correlated with the disability index, while the weakened FC of right anterior hippocampus with right insula and that of left posterior hippocampus with left superior temporal gyrus was inversely related to the erythrocyte sedimentation rate and anxiety status, separately. Conclusion: As with macroscopic damages, the altered functional-connectome patterns of the hippocampus in JIA patients might be more sensitive to detect the early neuropathological changes. Moreover, the functional disturbances were demonstrated associated with the physical disability, inflammation, and emotional status. These findings may enlighten us on the underlying neuropathological mechanism of CNS comorbidities in JIA. [ABSTRACT FROM AUTHOR]

Transition metal phosphides (TMPs) have exhibited decent performance in an oxygen evolution reaction (OER), which is a kinetic bottleneck in many energy storages and conversion systems. Most reported catalysts are composed of three or fewer metallic components. The inherent complexity of multicomponent TMPs with more than four metallic components hinders their investigation in rationally designing the structure and, more importantly, comprehending the component-activity correlation. Through hydrothermal growth and subsequent phosphorization, we reported a facile strategy for combining TMPs with tunable elemental compositions (Ni, Fe, Mn, Co, Cu) on a two-dimensional titanium carbide (MXene) flake. The obtained TMPs/MXene hybrid nanostructures demonstrate homogeneously distributed elements. They exhibit high electrical conductivity and strong interfacial interaction, resulting in an accelerated reaction kinetics and long-term stability. The results of different component catalysts' OER performance show that NiFeMnCoP/MXene is the most active catalyst, with a low overpotential of 240 mV at 10 mA·cm−2, a small Tafel slope of 41.43 mV·dec−1, and a robust long-term electrochemical stability. According to the electrocatalytic mechanism investigation, the enhanced NiFeMnCoP/MXene OER performance is due to the strong synergistic effect of the multi-elemental composition. Our work, therefore, provides a scalable synthesis route for multi-elemental TMPs and a valuable guideline for efficient MXene-supported catalysts design. [ABSTRACT FROM AUTHOR]

The balance between T helper type 1 (Th1) and T helper type 2 (Th2) cells is critical for both innate and acquired immune reactions. However, the precise mechanisms of T helper‐cell differentiation remain unclear. As an important T‐cell activation molecule, CD44 participates in the differentiation of Th1 and Th2 cells. We demonstrated that CD44 variant exon v5 (CD44 v5) is highly expressed by induced human Th2 cells. To investigate the role of the CD44 v5 domain in Th2 cell differentiation, we treated human CD4+ T cells with anti‐CD44v5 antibody and observed that the levels of phosphorylated STAT6 and GATA3 and the secretion of interleukin‐4 (IL‐4) were significantly decreased after the treatment. We also further found that the inhibition of Th2 differentiation was caused by the degradation of the alpha chain of IL‐4 receptor (IL‐4Rα), the CD44 v5 domain colocalized with IL‐4Rα on cell surface and the degradation of IL‐4Rα increased after CD44 v5 domain blocking or ablating. Our results indicated that CD44v5 antibody treatment interrupted the interaction between CD44 v5 domain and IL‐4Rα, but the CD44 v5 domain blockage would not spoil the colocalization between IL‐4R expression and T‐cell receptor and the immunological synapse formation; similar results were also found in CD44v5‐deficient CD4+ T cells. In conclusion, we revealed the function of the CD44 v5 domain in Th2 cell differentiation; blocking or ablating the CD44 v5 domain could accelerate IL‐4Rα degradation and then induce the Th2 cell inhibition. [ABSTRACT FROM AUTHOR]

Actual tourism mining models are often used to discover potential information in documents, but tourism models without human knowledge often produce unexplainable topics. This paper combines big data technology to build a personalized recommendation system for smart tourism, model the contextual information usage ontology under the tourism information system, and give the association between various ontologies. Then, this paper uses a matrix to describe each discrete attribute and interval attribute and uses a vector to model the user's preferences. In addition, this paper constructs an intelligent recommendation system based on the actual needs of travel recommendation and verifies the system in combination with experimental research. Through experimental analysis, it can be known that the intelligent tourism personalized recommendation system based on big data technology proposed in this paper has a high practical effect. [ABSTRACT FROM AUTHOR]

Geographic features play an important role in shaping the phylogeographic structures of species. Salvia miltiorrhiza Bunge is a widely studied medicinal crop. In this study, we used three cpDNA sequences (trnL–trnF, atpB–rbcL, and rpl16) to investigate the phylogeographic structure and evolutionary history of 190 S. miltiorrhiza endemic plants taken from 11 locations in the Qinling, Dabie, and Mengshan Mountains of Central China. Fifty-three total haplotypes were identified, and 50 of these were population-specific. In addition, moderate-to-high genetic differentiation was observed among the populations (mean Fst = 0.325), while phylogeographic structure was also observed based on STRUCTURE and spatial analysis of molecular variance (SAMOVA) analyses. In addition, BEAST and DIYABC analyses suggested that divergence times of the haplotypes in the AHS and ALQ2 populations of the Dabie Mountains were earlier than those in the Qinling and Mengshan Mountains. Consequently, an evolutionary scenario of S. miltiorrhiza populations in the Qinling and Mengshan Mountains diverging from populations in the Dabie Mountains was highly supported. The results reported here provide a useful framework for understanding the role of geographic features in shaping the spatial genetic variation and evolutionary history of S. miltiorrhiza plants. [ABSTRACT FROM AUTHOR]

Sn-Based perovskite materials are environmentally benign and have low toxicity with excellent light emitting ability, and are ideal choices for light-emitting diode (LED) active layers. However, the tendency of Sn2+ to be oxidized to Sn4+ leads to increased crystalline defects and chemical instability, which hamper the external quantum efficiency of LEDs. Herein, we introduce Eu2+ ions as the electron donor to provide a reducing environment to suppress the oxidation of Sn2+, and as a stabilizer to adjust the growth of the perovskite film simultaneously. Techniques such as X-ray photoelectron spectroscopy, transient absorption, and scanning electron microscopy have confirmed that Eu2+ ion doping can increase the film quality and decrease the Sn4+ defect density. Benefiting from these merits, the LED based on (PEA)2SnI4 film emits pure-red radiation with a maximum brightness of 221 cd m−2 and a high EQE up to 1.48%. [ABSTRACT FROM AUTHOR]

Introduction: Salvia miltiorrhiza is a frequently used herb in traditional Chinese medicine, and tanshinone IIA (Tan IIA) and salvianolic acid B (Sal Acid B) are two major extracts obtained from its dried root. The quality of herbal ingredients can be affected by environmental factors. Objective: To evaluate the quality of wild S. miltiorrhiza and investigate the influence of soil constituents and parameters as well as climatic conditions and factors on the content of Tan IIA and Sal Acid B. Methodology: We collected samples in 12 natural locations in the Dao Di area in China, the area in which S. miltiorrhiza grows, that results in a distinctive higher quality of medicinal materials from the harvested plant. The concentrations of Tan IIA and Sal Acid B were measured by high‐performance liquid chromatography (HPLC). Soil total carbon, total nitrogen, available nitrogen, available phosphorus, available potassium, and particle size distribution were determined. We also collected climate data using ArcGIS from the WorldClim database, and correlation tests, redundancy, and regression analyses were conducted to analyse the relationship and cluster the samples according to their chemical profile. Results: The content of Tan IIA and Sal Acid B in most of the samples was significantly different (P < 0.05). Soil available phosphorus was considered as a key factor that influenced the quality of wild S. miltiorrhiza, and we found a significant negative association between the concentration of Tan IIA in roots and soil available phosphorus. Moreover, the accumulation of Tan IIA in S. miltiorrhiza was also significantly associated with precipitation in April, May, and October, maximum temperature in January, and standard deviation of temperature seasonality. There was no significant correlation between the content of Sal Acid B and ecological factors. In addition, samples collected from Mengshan, Hexian, and Lushi locations were rich in Tan IIA and tended to cluster together, whereas samples collected from Longquan and Huoshan locations tended to cluster and were poor in Tan IIA. Conclusion: The Tan IIA content in samples collected from southern Anhui was significantly lower than that in other Dao Di locations. The content of Tan IIA was related more to the soil than the temperature. Compared with Tan IIA, Sal Acid B was less influenced by soil and climate factors. The findings of this study may provide helpful references for quality control of medicinal plants that exert pharmacological effects in humans. This work evaluated the quality of wild Salvia miltiorrhiza from Dao Di area in China based on high‐performance liquid chromatography (HPLC), and investigated the influence of soil constituents and parameters as well as climatic conditions and factors on the content of tanshinone IIA (Tan IIA) and salvianolic acid B (Sal Acid B). The Tan IIA content in samples collected from Southern Anhui was significantly lower than that in other Dao Di locations. The content of Tan IIA was related more to the soil than the temperature. Compared with Tan IIA, Sal Acid B was less influenced by soil and climate factors. [ABSTRACT FROM AUTHOR]

Coupling electrochemical CO2 reduction (CO2R) with a renewable energy source to create high‐value fuels and chemicals is a promising strategy in moving toward a sustainable global energy economy. CO2R liquid products, such as formate, acetate, ethanol, and propanol, offer high volumetric energy density and are more easily stored and transported than their gaseous counterparts. However, a significant amount (~30%) of liquid products from electrochemical CO2R in a flow cell reactor cross the ion exchange membrane, leading to the substantial loss of system‐level Faradaic efficiency. This severe crossover of the liquid product has—until now—received limited attention. Here, we review promising methods to suppress liquid product crossover, including the use of bipolar membranes, solid‐state electrolytes, and cation‐exchange membranes‐based acidic CO2R systems. We then outline the remaining challenges and future prospects for the production of concentrated liquid products from CO2. [ABSTRACT FROM AUTHOR]

The electrochemical reduction of CO2 to ethylene provides a carbon-neutral avenue for the conversion of CO2 to value-added fuels and feedstocks, so contributing to the storage of intermittent renewable electricity. The exploration of efficient electrocatalysts with high ethylene selectivity and productivity is highly desirable but remains challenging. Here, we present a Cu-based catalyst derived from a metal–organic framework (Cu-MOF) which shows enhanced performance due to its porous morphology, complex oxidation states and strong lattice strain. X-ray diffraction, X-ray photoelectron spectroscopy, and X-ray absorption spectroscopy are utilized to track the evolution of the crystal structure and oxidation states during the reaction, and the results reveal that Cu2+ ions are rapidly reduced to Cu+ and then slowly to Cu0, resulting in a Cu@CuxO core@shell structure. The tensile strain caused by the distorted grain is beneficial for the activation of CO2. Cu+/Cu0 interfaces formed through stabilized Cu+ facilitate *CO–CO dimerization, promoting conversion to C2+ products and suppressing conversion to C1 products. The optimized catalyst exhibits a 51% Faraday efficiency (FE) for ethylene and a 70% FE for C2+ products, with 20 h operational stability in an H-cell configuration, and a partial ethylene current density of 150 mA cm−2 in a flow-cell configuration. [ABSTRACT FROM AUTHOR]

Perovskite‐based light‐emitting diodes (PeLEDs) are now approaching the upper limits of external quantum efficiency (EQE); however, their application is currently limited by reliance on lead and by inadequate color purity. The Rec. 2020 requires Commission Internationale de l'Eclairage coordinates of (0.708, 0.292) for red emitters, but present‐day perovskite devices only achieve (0.71, 0.28). Here, lead‐free PeLEDs are reported with color coordinates of (0.706, 0.294)—the highest purity reported among red PeLEDs. The variation of the emission spectrum is also evaluated as a function of temperature and applied potential, finding that emission redshifts by <3 nm under low temperature and by <0.3 nm V−1 with operating voltage. The prominent oxidation pathway of Sn is identified and this is suppressed with the aid of H3PO2. This strategy prevents the oxidation of the constituent precursors, through both its moderate reducing properties and through its forming complexes with the perovskite that increase the energetic barrier toward Sn oxidation. The H3PO2 additionally seeds crystal growth during film formation, improving film quality. PeLEDs are reported with an EQE of 0.3% and a brightness of 70 cd m−2; this is the record among reported red‐emitting, lead‐free PeLEDs. [ABSTRACT FROM AUTHOR]

Geological events have been shown to be the main factors affecting the distributions and population genetic structure of species. However, the impact of the Yellow River, the second longest river in China, on the distribution and genetic structure of the endemic flora remains largely unknown. Here, we used microsatellites to evaluate the genetic structure of Tamarix austromongolica and Tamarix chinensis (343 individuals in total), two endemic tree species widely distributed along the Yellow River, as well as the role of river drainages in shaping the structure. We found that frequent gene flow resulted in low genetic differentiation among populations within species (T. austromongolica: Fst = 0.144, Nm = 1.486; T. chinensis: Fst = 0.103, Nm = 2.177); and low levels of genetic differentiation were detected between populations within species on the north and south banks. Also, high gene flow was found between populations in the upper reaches and those in the middle reaches, and middle reaches and lower reaches of the Yellow River (T. austromongolica: Fst = 0.023, Nm = 10.619; T. chinensis: Fst = 0.045, Nm = 5.306). Additionally, discriminant analysis of principal components (DAPC) and Bayesian analysis revealed a weak population structure in T. austromongolica and T. chinensis. Therefore, the Yellow River does not act as a barrier to dispersal and gene flow for Tamarix. Our findings provide support for the role of the river in shaping the spatial distribution and the genetic structure of species. [ABSTRACT FROM AUTHOR]

The present study aimed to determine whether urinary mitochondrial (mt)DNA could be combined as a non-invasive biomarker with other clinical findings of kidney injury to help diagnose early diabetic nephropathy (DN). A total of 165 patients with type 2 diabetes mellitus (T2DM) were enrolled in the present study and the mtDNA levels in urine were measured using quantitative PCR. The diagnostic value of urinary mtDNA levels in patients with T2DM was compared using estimated glomerular filtration rate (eGFR) or albumin-to-creatinine ratio staging. Spearman correlation analysis was used to analyze the correlation between urinary mtDNA and other clinical findings. Correlation factors for early DN were assessed using univariate logistic regression analysis. Urinary leukocyte and glucose levels do not interfere with urinary mtDNA levels. In patients with T2DM, the level of urinary mtDNA increases in the early stages of kidney injury and further increases with the severity of kidney injury. Urinary mtDNA levels in patients with eGFR 60-90 ml/min/1.73 m2 were higher than that in patients with eGFR >90 ml/min/1.73 m2. The levels of urinary mt89DNA and mt349DNA were negatively correlated with the eGFR level (ρ=-0.437; P<0.001; ρ=-0.390; P<0.001) and positively correlated with the level of cystatin C (ρ=0.177; P=0.025; ρ=0.144; P=0.070). Urinary mtDNA is positively correlated with early DN occurrence [odds ratio (OR), 1.330; 95% confidence interval (CI), 1.175-1.507; P<0.001; OR, 1.328; 95% CI, 1.156-1.525; P<0.001]. In conclusion, urinary mtDNA combined with other clinical indicators of kidney injury may help the diagnosis of early DN. [ABSTRACT FROM AUTHOR]

Weaning is one of the most stressful challenges in the pig’s life, which contributes to dysfunctions of intestinal and immune system, disrupts the gut microbial ecosystem, and therefore compromises the growth performance and health of piglets. To mitigate the negative impact of the stress on early-weaned piglets, effective measures are needed to promote gut health. Toward this end, we tamed a Saccharomyces cerevisiae strain and developed a probiotic Duan-Nai-An, which is a yeast culture of the tamed S. cerevisiae on egg white. In this study, we tested the performance of Duan-Nai-An on growth and health of early-weaned piglets and analyzed its impact on fecal microbiota. The results showed that Duan-Nai-An significantly improved weight gain and feed intake, and reduced diarrhea and death of early-weaned piglets. Analysis of the gut microbiota showed that the bacterial community was shaped by Duan-Nai-An and maintained as a relatively stable structure, represented by a higher core OTU number and lower unweighted UniFrac distances across the early weaned period. However, fungal community was not significantly shaped by the yeast probiotics. Notably, 13 bacterial genera were found to be associated with Duan-Nai-An feeding, including Enterococcus, Succinivibrio, Ruminococcus, Sharpea, Desulfovibrio, RFN20, Sphaerochaeta, Peptococcus, Anaeroplasma , and four other undefined genera. These findings suggest that Duan-Nai-An has the potential to be used as a feed supplement in swine production. [ABSTRACT FROM AUTHOR]

An increase in serum homocysteine level has been associated with an increased risk of vascular disease; however, the biochemical mechanisms that underlie these effects remain largely unknown. The present study aimed to use high‑performance liquid chromatography‑mass spectrometry (HPLC‑MS) to demonstrate the effects of serum homocysteine on human blood metabolites. A total of 75 fasting serum samples were investigated in the present study. Using a threshold of 15 μmol/l serum homocysteine level, samples were divided into high‑ and low‑homocysteine groups, and the serum extracts were analyzed with an HPLC‑MS‑based method. A total of 269 features exhibited significant differences and correlation with serum homocysteine levels in the electrospray ionization‑positive [ESI(+)] mode, and 69 features were identified in the ESI(‑) mode between the two groups. The principal component analysis plot revealed a separation between the high‑ and the low‑homocysteine groups. Metabolite set enrichment analysis identified arachidonic acid metabolism and linoleic acid metabolism as the two pathways with significantly enriched differences. These results revealed that arachidonic acid and linoleic acid metabolism may be associated with serum homocysteine levels and may be involved in homocysteine‑induced vascular disease. [ABSTRACT FROM AUTHOR]

Carboxypeptidase E (CPE) is one of the most important carboxypeptidases involved in biosynthesis of numerous peptide hormones and neurotransmitters and has an important role in endocrine regulation. A splice variant of CPE (CPE-ΔN) has been detected and the mechanism of CPE-ΔN action in tumorigenesis has been studied in many different cancers. The aim of this study was to examine CPE-ΔN expression in human colorectal cancer (CRC) and to evaluate its possible use as a potential prognostic marker. Two hundred nineteen primary colorectal tumors and corresponding normal tissues were included in the study. We have analyzed CPE-ΔN isoform expression by qRT-PCR and Western blot in 219 CRC patients. Correlations between CPE-ΔN mRNA expression and clinicopathological variables were determined with chi-square tests. Survival probabilities were determined using Kaplan–Meier analysis, and univariate and multivariate analyses of the prognostic factors were performed with a Cox regression model. Our results show that CPE-ΔN is overexpressed in colorectal tumor tissue and that high CPE-ΔN mRNA expression is closely correlated with tumor differentiation, pT classification, pN classification, tumor recurrence, and lymph node metastasis ( P = 0.042, 0.036, 0.031, 0.006, and 0.008, respectively). However, no correlation was observed between CPE-ΔN expression and age, gender, tumor localization, gross features, and the tumor size. In addition, patients with high CPE-ΔN expression had a significantly shorter survival ( P < 0.001, logrank test). Tumor differentiation, gross feature, pT classification, pN classification, tumor recurrence, lymph node metastasis, and CPE-ΔN status were significantly associated with poor prognosis after performing a univariate Cox survival analysis. High CPE-ΔN expression was also identified as an independent prognostic factor using a multivariate analysis ( P = 0.011). Based on these results, we can conclude that CPE-ΔN expression might be a potential prognostic marker for colorectal cancer patients. [ABSTRACT FROM AUTHOR]

The Golgi phosphoprotein GP73 is elevated in the circulation of individuals with a diagnosis of hepatocellular carcinoma. Its usefulness as a biomarker of HCC is questioned, since it has also been reported to be elevated in the circulation of people with liver cirrhosis. Regulation of GP73 by inflammatory cytokines is therefore of interest. The interleukin-6 (IL-6) family cytokines were tested for effects on GP73 mRNA and/or protein levels in human hepatoblastoma HepG2 cells. Levels of GP73 mRNA and protein were up-regulated in HepG2 cells following treatment with either proinflammatory cytokine IL-6 or the related cytokine oncostatin M (OSM). Induction required the shared receptor subunit gp130, and correlated with increased tyrosine phosphorylation of STAT3. Maximal cytokine-mediated induction was not observed in the presence of protein synthesis inhibitor cycloheximide, suggesting additional regulatory factors play an important role. ELISA measurement of GP73 and IL-6 levels in the sera of patients with pre-malignant liver disease revealed a significant correlation between circulating levels of the two proteins. Similarly, a sensitive ELISA assay was developed to measure circulating OSM. OSM levels were elevated 6-7 fold in sera from patients with either cirrhosis or HCC relative to controls without liver disease. Although there was an association between levels of GP73 and OSM in serum from people with liver cirrhosis, there was not a statistically significant correlation in HCC, suggesting that the role of the cytokines in determining circulating levels may be complex. To our knowledge, this is the first report of OSM elevation being associated with liver disease. [ABSTRACT FROM AUTHOR]

Background. The aim of the study was to assess the utility of Hemoglobin A1c (HbA1c) to identify individuals with undiagnosed DM and prediabetes (preDM) in the high risk population of Chinese people. Methods. A total of 424 high risk individuals without known diabetes, who met at least three of the high risk factors for DM (hypertension, abnormal blood lipid, family history of DM and high BMI) were selected for this study, HbA1c, fasting plasma concentrations of glucose (FPG) and a 75 g oral glucose tolerance test (OGTT) were measured. The performance of HbA1c in relation to undiagnosed DM and preDM investigated through receiver operating characteristic (ROC) curves, the reference for DM and preDM, are according to the 2011 WHO-FPG/OGTT criteria and the appropriate cut-off points of HbA1c for DM and preDM were assessed. The properties of HbA1c diagnosing DM and preDM were also compared with that of the fasting plasma glucose (FPG). Results. It was shown that the AUC (area under the curve) of the ROC curve for HbA1c predicting undiagnosed DM was similar to that of FPG, and the cut-off point of HbA1c 6.2% was optimal for predicting DM, with a sensitivity of 66%, and a specificity of 91%. Furthermore, the cut-off point of HbA1c was 5.9% for preDM with a sensitivity of 70%, a specificity of 87%. Conclusion. Collectively, this study found that the measurement of HbA1c may be efficient to diagnosis undiagnosed both DM and preDM with the cut-off point of 6.2% and 5.9%, respectively. [ABSTRACT FROM AUTHOR]