Search

The Ti 2 AlNb and Mo-modified Ti 2 AlNb alloys were fabricated by hot isostatic pressing, and then underwent annealing treatment at 800 °C for 1, 2 and 3 h respectively. To evaluate the tensile properties of the two kinds of alloys, tensile tests were conducted at ambient temperature and 650 °C in this study. For the Ti 2 AlNb alloy, the room-temperature ultimate tensile strength (UTS) was 700–900 MPa, and the highest elongation to failure (ε f) reached 6.2% after aging for 2 h at 800 °C. Since the Mo addition promoted the precipitation of the coarse B2+O colony structure near the grain boundary, the Mo-modified Ti 2 AlNb alloy exhibited decreased UTS and ε f at room temperature. As for the high-temperature performance of both the Ti 2 AlNb and Mo-modified Ti 2 AlNb alloys, the UTS reached approximately 700 MPa and the ε f exceeded 3.0%. Meanwhile, the two kinds of alloys presented the same tendency that both the high-temperature UTS and ε f increased firstly and then decreased as the aging time increased. Among them the specimens after aging at 800 °C for 2 h for both alloys acquired the highest UTS and ε f. Moreover, the Mo-modified alloy exhibited a better high-temperature ductility than that at room temperature, which is associated with the B2↔O phase transformation during the loading at 650 °C. The Mo addition effectively refined the lath of the precipitates in the grain and the grain size of the matrix, and it induced abundant dislocations. Thus, the Mo-modified Ti 2 AlNb alloy aged for 1 and 3 h exhibited superior high-temperature mechanical properties than those of the Ti 2 AlNb alloy. [ABSTRACT FROM AUTHOR]

Background: Worldwide, hepatocellular carcinoma (HCC) is the second most lethal cancer, although early-stage HCC is amenable to curative treatment and can facilitate long-term survival. Early detection has proved difficult, as proteomics, transcriptomics, and genomics have been unable to discover suitable biomarkers., Methods: To find new biomarkers of HCC, we utilized a spatial omics N-glycan imaging method to identify altered glycosylation in cancer tissue (n = 53) and in paired serum of individuals with HCC (n = 23). Glycoproteomics identified the glycoproteins carrying these N-glycan structures, and we utilized an antibody array-based glycan imaging method to examine all the N-glycans associated with the identified glycoproteins. N-glycans from the examined glycoproteins were used to create machine learning algorithms, which were tested in a case-control sample set of 100 patients with cirrhosis and HCC and 101 matched patients with cirrhosis alone., Results: Spatial glycan imaging identifies thirteen branched, fucosylated, and high mannose glycans as altered in HCC tissue and in matched patient serum. Glycoproteomics identifies over 50 proteins containing these changes, of which sixteen glycoproteins were selected for further testing in an independent patient set. Algorithms using a combination of glycan and glycoproteins accurately differentiate early-stage and all HCC from cirrhosis with AUROC values of 0.88-0.97., Conclusions: In conclusion, we present the development and application of a new biomarker platform, which can identify effective biomarkers for the early detection of HCC. This platform may also apply to other diseases, in which changes in N-linked glycosylation are known to occur., Competing Interests: Competing interests: The authors declare the following competing interests: A.S.M., P.M.A., and R.R.D. are listed as inventors on a patent filed by MUSC on the technology described in this manuscript. Authors M.W., S.G., M.F.B., J.D., A.D., C.B., H.L., D.S., G.H., A.B., S.-O.R., D.L., L.B., J.B., S.C., Y.K., N.K., Y.H., L.Q., A.Y., P.G., and A.S. declare no competing interest., (© 2024. The Author(s).)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Molecular modification strategy exhibits great potential for electrocatalytic CO 2 reduction. Here, DFT calculations were applied to study the mechanism of CO 2 electroreduction on glycine modified copper. The results indicate that the interaction between the modified molecule and the intermediate could change the reaction energy of CO 2 electroreduction.

Objective: This study sought to identify circulating proteins causally linked to Inflammatory Bowel Disease (IBD) traits through a Mendelian Randomization (MR) analytical framework., Methods: Using a large-scale, two-sample MR approach, we estimated the genetic links of numerous plasma proteins with IBD and its subtypes, leveraging information from the Inflammatory Bowel Disease Genetics Consortium. To assess the robustness of MR findings, methods like Bayesian colocalization, and Steiger filtering analysis, evaluation of protein-altering variants. Further insights into IBD's underlying mechanisms and therapeutic targets were gleaned from single-cell sequencing analyses, protein-protein interaction assessments, pathway enrichment analyses, and evaluation of drug targets., Results: By cis-only MR analysis, we identified 83 protein-phenotype associations involving 27 different proteins associated with at least one IBD subtype. Among these proteins, DAG1, IL10, IL12B, IL23R, MST1, STAT3 and TNFRSF6B showed overlapping positive or negative associations in all IBD phenotypes. Extending to cis + trans MR analysis, we further identified 117 protein-feature associations, including 44 unique proteins, most of which were not detected in the cis-only analysis. In addition, by performing co-localization analysis and Steiger filtering analysis on the prioritized associations, we further confirmed the causal relationship between these proteins and the IBD phenotype and verified the exact causal direction from the protein to the IBD-related feature., Conclusion: MR analysis facilitated the identification of numerous circulating proteins associated with IBD traits, unveiling protein-mediated mechanisms and promising therapeutic targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Hu, Liang, Zhao, Zhang, Xu, Zhang and Zhang.)

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., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

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., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

The copper (Cu)-catalyzed electrochemical CO 2 reduction provides a route for the synthesis of multicarbon (C 2+ ) 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 C 2+ 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 C 2+ products from both CO 2 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., (© 2024. The Author(s).)

Objective: The aim of this study of children with juvenile idiopathic arthritis (JIA) was to use proton magnetic resonance spectroscopy ( 1 H-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. 1 H-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., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Importance: The biogenesis and clinical application of serum HBV pgRNA have been a research hotspot in recent years. This study further characterized the heterogeneity of the 3' terminus of capsid RNA by utilizing a variety of experimental systems conditionally supporting HBV genome replication and secretion, and reveal that the 3' truncation of capsid pgRNA is catalyzed by cellular ribonuclease(s) and viral RNaseH at positions after and before 3' DR1, respectively, indicating the 3' DR1 as a boundary between the encapsidated portion of pgRNA for reverse transcription and the 3' unprotected terminus, which is independent of pgRNA length and the 3' terminal sequence. Thus, our study provides new insights into the mechanism of pgRNA encapsidation and reverse transcription, as well as the optimization of serum HBV RNA diagnostics., Competing Interests: The authors declare no conflict of interest.

Acidic water electrolysis enables the production of hydrogen for use as a chemical and as a fuel. The acidic environment hinders water electrolysis on non-noble catalysts, a result of the sluggish kinetics associated with the adsorbate evolution mechanism, reliant as it is on four concerted proton-electron transfer steps. Enabling a faster mechanism with non-noble catalysts will help to further advance acidic water electrolysis. Here, we report evidence that doping Ba cations into a Co 3 O 4 framework to form Co 3- x Ba x O 4 promotes the oxide path mechanism and simultaneously improves activity in acidic electrolytes. Co 3- x Ba x O 4 catalysts reported herein exhibit an overpotential of 278 mV at 10 mA/cm 2 in 0.5 M H 2 SO 4 electrolyte and are stable over 110 h of continuous water oxidation operation. We find that the incorporation of Ba cations shortens the Co-Co distance and promotes OH adsorption, findings we link to improved water oxidation in acidic electrolyte.

Objective: To understand the status of therapeutic drug monitoring (TDM) in China Mainland, and thus lay down the foundation for further improvement in TDM., Methods: In the present study, a nationwide questionnaire survey was conducted, which was distributed and collected using a mobile-based application. Clinicians, pharmacists, and clinical laboratory physicians belonging to different levels of public hospitals were involved as subjects/objects. The contents of the survey included TDM implementation in their hospital and information regarding their opinions and suggestions on TDM work. Mann-Whitney test was used to compare the difference between top tertiary hospitals and non-top tertiary hospitals., Results: A total of 475 questionnaires were collected, 383 from top tertiary hospitals (3A hospitals) and 92 from non-top tertiary hospitals (other than 3A hospitals). A total of 240 clinicians, TDM pharmacists, and clinical laboratory physicians were involved, with an effective rate of 50.5%. Top tertiary hospitals were associated with certain advantages, such as the number of TDM testing facilities, annual sample size, number of monitoring varieties, and interpretation rate of monitoring reports, compared with non-top tertiary hospitals. In particular, β-lactamase inhibitor, olanzapine, carbamazepine, and glucocorticoids seemed to be the main projects that clinicians wanted to assess. The drugs for which TDM was commonly performed included vancomycin, valproic acid, carbamazepine, phenytoin sodium, and methotrexate. The most commonly used detection methods include high-performance liquid chromatography, immunization, 2D-LC, and LC-MS. The monitoring concentration range was found to be inconsistent for most of the drugs. Currently, no unified regulation exists for TDM charges in China, which is no more than ¥200 in general. Clinicians rely on pharmacists for professional guidance. Importantly, improvement in the interpretation of monitoring reports, proficiency testing, and cooperation with clinical departments may aid in improving the level of TDM service., Conclusions: This survey objectively reflected the current status of TDM work in hospitals in China, and provided a strong reference base for devising strategies for improvement and effective execution of TDM work., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.)

Direct electrolysis of pH-neutral seawater to generate hydrogen is an attractive approach for storing renewable energy. However, due to the anodic competition between the chlorine evolution and the oxygen evolution reaction (OER), direct seawater splitting suffers from a low current density and limited operating stability. Exploration of catalysts enabling an OER overpotential below the hypochlorite formation overpotential (≈490 mV) is critical to suppress the chloride evolution and facilitate seawater splitting. Here, a proton-adsorption-promoting strategy to increase the OER rate is reported, resulting in a promoted and more stable neutral seawater splitting. The best catalysts herein are strong-proton-adsorption (SPA) materials such as palladium-doped cobalt oxide (Co 3- x Pd x O 4 ) catalysts. These achieve an OER overpotential of 370 mV at 10 mA cm -2 in pH-neutral simulated seawater, outperforming Co 3 O 4 by a margin of 70 mV. Co 3- x Pd x O 4 catalysts provide stable catalytic performance for 450 h at 200 mA cm -2 and 20 h at 1 A cm -2 in neutral seawater. Experimental studies and theoretical calculations suggest that the incorporation of SPA cations accelerates the rate-determining water dissociation step in neutral OER pathway, and control studies rule out the provision of additional OER sites as a main factor herein., (© 2023 Wiley-VCH GmbH.)

Background: Skin tear knowledge is an important predictor of the decreased incidence and management of skin tears, and the knowledge level among Chinese nurses is unknown so far. A validated instrument for measuring skin tear knowledge is urgent., Objective: To culturally adapt the skin tear knowledge assessment instrument (OASES) into Chinese and verify its validity and reliability in the Chinese context., Methods: The cultural adaptation process for OASES into Chinese was established on Beaton's translation model. Content validity was determined by the 8-expert group in wound care. A nationwide psychometric validation study was performed on a convenience sample of 3333 nurses from 113 tertiary hospitals, of whom 98 nurses finished the test-retest procedure for reliability analysis. Item validity (item difficulty and discriminating index) and construct validity (known-groups technique) were tested., Results: The content validity index was 0.88-1.00. The item validity was as follows: Item difficulty ranged from 0.16 to 0.86, with an average value of 0.52; the discriminating index varied between 0.05 and 0.61. The known-group technique demonstrated excellent construct validity with a significant difference between predefined groups with theoretically expected higher knowledge scores and theoretically expected lower knowledge scores (P < 0.001). For the test-retest reliability, the Intraclass correction coefficient (ICC) during a 14-day interval for the overall tool was 0.79 (95% CI = 0.71-0.86), and Cohen's kappa value for each item varied from 0.17 to 0.62., Conclusions: The Chinese version of OASES was validated to be suitable for skin tear knowledge assessment with acceptable psychometric properties, through which the knowledge and training priorities of skin tear among Chinese nurses can be quantified., Competing Interests: Declarations of competing interest None., (Copyright © 2022 Tissue Viability Society / Society of Tissue Viability. Published by Elsevier Ltd. All rights reserved.)

Elastic strains in metallic catalysts induce enhanced selectivity for carbon dioxide reduction (CO 2 R) toward valuable multicarbon (C 2+ ) products. However, under working conditions, the structure of catalysts inevitably undergoes reconstruction, hardly retaining the initial strain. Herein, we present a metal/metal oxide synthetic strategy to introduce and maintain the tensile strain in a copper/ceria heterostructure, enabled by the presence of a thin interface layer of Cu 2 O/CeO 2 . The tensile strain in the copper domain and deficient electron environment around interfacial Cu sites resulted in strengthened adsorption of carbonaceous intermediates and promoted *CO dimerization. The strain effect in the copper/ceria heterostructure leads to an improved C 2+ selectivity with a maximum Faradaic efficiency of 76.4% and a half-cell power conversion efficiency of 49.1%. The fundamental insights gained from this system can facilitate the rational design of heterostructure catalysts for CO 2 R.

Calreticulin (CALR) mutations are frequent, disease-initiating events in myeloproliferative neoplasms (MPNs). Although the biological mechanism by which CALR mutations cause MPNs has been elucidated, there currently are no clonally selective therapies for CALR-mutant MPNs. To identify unique genetic dependencies in CALR-mutant MPNs, we performed a whole-genome clustered regularly interspaced short palindromic repeats (CRISPR) knockout depletion screen in mutant CALR-transformed hematopoietic cells. We found that genes in the N-glycosylation pathway (among others) were differentially depleted in mutant CALR-transformed cells as compared with control cells. Using a focused pharmacological in vitro screen targeting unique vulnerabilities uncovered in the CRISPR screen, we found that chemical inhibition of N-glycosylation impaired the growth of mutant CALR-transformed cells, through a reduction in MPL cell surface expression. We treated Calr-mutant knockin mice with the N-glycosylation inhibitor 2-deoxy-glucose (2-DG) and found a preferential sensitivity of Calr-mutant cells to 2-DG as compared with wild-type cells and normalization of key MPNs disease features. To validate our findings in primary human cells, we performed megakaryocyte colony-forming unit (CFU-MK) assays. We found that N-glycosylation inhibition significantly reduced CFU-MK formation in patient-derived CALR-mutant bone marrow as compared with bone marrow derived from healthy donors. In aggregate, our findings advance the development of clonally selective treatments for CALR-mutant MPNs., (© 2022 by The American Society of Hematology.)

The carbon-carbon (C-C) bond formation is essential for the electroconversion of CO 2 into high-energy-density C 2+ products, and the precise coupling pathways remain controversial. Although recent computational investigations have proposed that the OC-COH coupling pathway is more favorable in specific reaction conditions than the well-known CO dimerization pathway, the experimental evidence is still lacking, partly due to the separated catalyst design and mechanistic/spectroscopic exploration. Here, we employ density functional theory calculations to show that on low-coordinated copper sites, the *CO bindings are strengthened, and the adsorbed *CO coupling with their hydrogenation species, *COH, receives precedence over CO dimerization. Experimentally, we construct a fragmented Cu catalyst with abundant low-coordinated sites, exhibiting a 77.8% Faradaic efficiency for C 2+ products at 300 mA cm -2 . With a suite of in situ spectroscopic studies, we capture an *OCCOH intermediate on the fragmented Cu surfaces, providing direct evidence to support the OC-COH coupling pathway. The mechanistic insights of this research elucidate how to design materials in favor of OC-COH coupling toward efficient C 2+ production from CO 2 reduction.

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.

In the digital era, the health information presented on virtual platforms plays a pivotal role in supporting people's active and healthy life. The ageing, especially ageing women, are more likely to seek and accept health information through online media platforms. The study shows that short health videos on social media platforms are extremely popular among ageing women in China for the accessing of virtual coaching. Adopting the qualitative methodology of in-depth interview and discourse analysis, the study investigates virtual coaching with short health video practice among 39 Chinese ageing women in different fields, who are all over sixty years old. Specifically, with the analytical tools of transitivity and generic structure analysis, the study explores the impacts of short health videos on Chinese ageing women's cognition, behavior and interpersonal relationships. The result shows that virtual practice and coaching via short health videos can build health awareness and a dynamic new lifestyle, and motivate women to positively practice physical activity and maintain positive interpersonal relationships. Factors affecting the effectiveness of short health videos are discussed for future research in the field of modeling and intervention.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Weng, Yi, Liang, Lin, Zheng, Xiao and Han.)

Abstract: Chronic hepatitis B virus (HBV) infection remains a global health burden. Timely and effective antiviral therapy is beneficial for patients with HBV infection. With existing antiviral drugs, including nucleos(t)ide analogs and interferon-alfa, patients can achieve viral suppression with improved prognosis. However, the rate of hepatitis B surface antigen loss is low. To achieve a functional cure and even complete cure in chronic hepatitis B patients, new antivirals need to be developed. In this review, we summarized the advantages and disadvantages of existing antiviral drugs and focused on new antivirals including direct-acting antiviral drugs and immunotherapeutic approaches., (Copyright © 2022 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Metal borides/borates have been considered promising as oxygen evolution reaction catalysts; however, to date, there is a dearth of evidence of long-term stability at practical current densities. Here we report a phase composition modulation approach to fabricate effective borides/borates-based catalysts. We find that metal borides in-situ formed metal borates are responsible for their high activity. This knowledge prompts us to synthesize NiFe-Boride, and to use it as a templating precursor to form an active NiFe-Borate catalyst. This boride-derived oxide catalyzes oxygen evolution with an overpotential of 167 mV at 10 mA/cm 2 in 1 M KOH electrolyte and requires a record-low overpotential of 460 mV to maintain water splitting performance for over 400 h at current density of 1 A/cm 2 . We couple the catalyst with CO reduction in an alkaline membrane electrode assembly electrolyser, reporting stable C 2 H 4 electrosynthesis at current density 200 mA/cm 2 for over 80 h., (© 2021. The Author(s).)

Compassionate use may play an important role in responding to major public health emergencies. The Jinyintan Hospital in Wuhan launched the III phase of clinical trials of antiviral drug-remdesivir on February 6, 2020. As an unapproved drug, remdesivir raised great concerns about compassionate use in China. Compassionate use is therapeutic use of unauthorized drugs outside of clinical trials. It is used for critically ill patients with life-threatening diseases and no effective treatment means in China. Patients voluntarily apply to their medical institutions. The Center for Drug Evaluation, National Medical Products Administration shall conduct scientific and reasonable review, approval, and supervision on patients' application for compassionate medication. By analyzing and comparing the current situation of compassionate use at home and abroad, it is expected to provide thinking for the development of compassionate use system in China.

Background and Purpose: The optimal recanalization strategy for acute ischemic stroke with large vessel occlusion continues to be an area of active interest. Network meta-analysis can provide insight when direct comparative evidence is lacking., Methods: A systematic review of the literature using PubMed, Embase, the Cochrane Central Register of Controlled Trials, and SinoMed was performed, and a search was conducted for clinical trials on ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and StrokeCenter.org. Four independent reviewers conducted the study selection, data abstraction, and quality assessments., Results: The literature review identified 17 trials including 3236 patients and 8 ongoing clinical trials. Sample sizes ranged from 7 to 656 participants. Intravenous thrombolysis (IVT) was the most common intervention, followed by IVT plus mechanical thrombectomy (MT), IVT plus intraarterial thrombolysis, intraarterial thrombolysis alone, and MT alone. In the pooled network meta-analysis, IVT+MT was associated with a higher rate of independent functioning. In contrast, IVT was ranked as the most ineffective treatment strategy with respect to neurological functions, while direct MT was ranked as the least safe intervention with respect to all-cause mortality. Also, irrespective of assessment tools, endovascular treatment plus IVT led to higher successful recanalization rate than thrombolysis alone., Conclusions: Compared with other recanalization treatments, IVT+MT seems to be the most effective strategy, without increasing detrimental effects, for thrombolysis-eligible patients with large vessel occlusion-acute ischemic stroke. To improve the current evidentiary basis for recanalization treatment, future trials and real-world studies are warranted and should use unified definitions of symptomatic intracranial hemorrhage and recanalization.

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.

Purpose: Cholangiocarcinoma (CCA) is a malignancy of the bile ducts. The purpose of this discovery study was to identify effective serum markers for surveillance of cholangiocarcinoma., Experimental Design: Using a glycomic method, patients with CCA were determined to have increased levels of alpha-1,3 and alpha-1,6 linked fucosylated glycan. Proteomic analysis of the serum fucosylated proteome identified proteins such as alpha-2-macroglobulin, kininogen, hemopexin, fetuin-A, alpha-1 anti-trypsin, and ceruloplasmin as being hyperfucosylated in HCC. The levels of these glycoproteins in 109 patients with CCA, primary sclerosing cholangitis (PSC), and control patients were compared to the performance of CA-19-9, the current "gold standard" assay for cholangiocarcinoma., Results: Fucosylated Fetuin-A (fc-Fetuin-A) had the best ability to differentiate CCA from PSC, with an AUROC of 0.812 or 0.8665 at differentiating CCA from those with PSC or other liver disease. CA-19-9 had poor ability to differentiate PSC from cholangiocarcinoma (AUROC of 0.625)., Conclusion and Clinical Relevance: Using glycomic and proteomic methods we identified a set of proteins that contain altered glycan in the sera of those with CCA. One of these proteins, fucosylated Fetuin-A may have value in the surveillance of people at risk for the development of cholangiocarcinoma., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Sulfate-modifying factor 2 (SUMF2), a member of the formylglycine-generating enzyme family, was earlier found to play a role in the regulation of interleukin (IL)-13 expression and secretion in airway smooth muscle cells. IL-13 is a T helper 2 cytokine that plays important roles in the pathogenesis of asthma. However, there is little evidence of the potential role of SUMF2 in the cellular inflammatory responses in asthma. Here, using an ovalbumin-induced asthma rat model, we show that SUMF2 gene expression is significantly decreased in allergic asthma rats. Moreover, several pathological changes were observed in the lung tissue and IL-13 was found to be overexpressed in the ovalbumin-induced asthma model. Additional studies on the lung bronchial epithelial tissues, peripheral blood lymphocytes and bronchoalveolar lavage fluid of the OVA-induced asthma rats showed that SUMF2 mRNA and protein expression were attenuated. However, there was only a little significant correlation was found between SUMF2 and IL-13 expression. These results indicate that SUMF2 may mediate airway inflammation in allergic asthma by modulating the expression of IL-13. More data from in vivo experiments are needed to clearly understand the role of SUMF2 in asthma.

Breast cancer is the most common cancer in women around the world. However, the molecular mechanisms underlying breast cancer pathogenesis are only partially understood. Here, in this study, we found that miR-1228 was up-regulated in breast cancer cell lines and tissues. Ectopic expression of miR-1228 mimics leads to promoted cell growth, invasion and migration. Using bioinfomatic analysis and 3'UTR luciferase reporter assay, we determined SCAI can be directly targeted by miR-1228, which can down-regulate endogenous SCAI protein level. Furthermore, our findings demonstrate that SCAI was down-regulated in breast cancer cell lines and tissues. Rescue experiment demonstrated that miR-1228 promoted cell growth is attenuated by over-expression of MOAP1 and miR-1228 promoted cell invasion and migration can be attenuated by over-expression of SCAI. Taken together, this study provides evidences that miR-1228 serves as an oncogene to promote breast cancer proliferation, invasion and migration, which may become a critical therapeutic target for breast cancer treatment.

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.

Background: To evaluate the relationship between temperature and hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) levels in Harbin of China and analyze whether these would affect diagnosis and control of diabetes., Methods: Two groups were investigated: 1. Routine patients come from outpatients, 2. Research subjects including 224 healthy volunteers and 391 diabetic patients, who had 5 blood specimens collected between February and June 2010. Fasting plasma glucose and hemoglobin A1c were detected., Results: In non-diabetic patients, mean HbA1c concentrations for all temperature categories were not significantly different, but mean FPG level was higher at cooler temperatures (p < 0.05). In the diabetic group, mean HbA1c concentrations were higher at cool temperatures than at very cold temperatures (p < 0.05), but mean FPG level was higher at cold temperature than at other temperature categories (p < 0.05). Both the within- and the between-subject coefficients of variation (CVs) for HbA1c were smaller than for FPG., Conclusions: During the year of this study, there were substantial temperature fluctuations but HbA1c concentration was more stable than FPG in non-diabetic individuals. It is therefore unlikely that temperature-related variation in HbA1c could affect the use of HbA1c as a diagnostic test for type 2 diabetes, but could affect the use of HbA1c as a glycemia control test for diabetes.

Allergic asthma is a chronic inflammatory disease characterized by the infiltration of inflammatory cells, the elevated production of cytokines and enhanced airway hyperreactivity (AHR). CD44 is a widely expressed cell adhesion molecule that is involved in lymphocyte adhesion to inflamed endothelium. Previous studies showed that pulmonary eosinophils and CD4⁺ T cells express high levels of CD44 in bronchoalveolar lavage fluid following antigen administration. The aim of this study was to investigate whether interleukin (IL)-13 is capable of modulating CD44 expression in lung tissue and lymphocytes, further promoting inflammatory cell recruitment into the lungs and exacerbating asthmatic responses. Six- to eight-week-old male Balb/c mice were used. Quantitative PCR and immunohistochemistry were employed to determine the effect on CD44 expression. Our findings showed that IL-13 may play a significant role during the challenge phase in that CD44 expression was up-regulated in lung tissue and lymphocytes following IL-13 treatment, resulting in inflammatory cells infiltrating into lungs and enhancing AHR.

To investigate the potential of gene therapy for the treatment of chronic diseases such as hypertension, chronic heart failure, and chronic renal failure, we established the neonatal rat fibroblast line engineered to secrete the mutant human atrial natriuretic peptide (mhANP), and then transplanted the cell line into young spontaneously hypertensive rats (SHR) subcutaneously. We found that a single transplantation of the cell line caused an obvious rise in the concentration of mhANP in serum 7 d after transplantation ((135 +/- 8) vs (106 +/- 7) pg/mL, P < 0.01). The animals' blood pressure in test group was always remarkably lower than that of empty vector group within 42 d after transplantation, even though the blood pressure in all groups was constantly increasing in the process of ontogeny ((175 +/- 10) mm Hg vs (189 +/- 12) mm Hg, P < 0.05). A maximal blood pressure reduction of 33 mm Hg ((157 +/- 9) mm Hg vs (124 +/- 112) mm Hg, P < 0.01) was observed 14 d post cell transplantation. There was a marked increase in urine volume in test group from second week after treatment beginning ((5.9 +/- 0.7) mL/6 h vs (4.3 +/- 0.8) mL/6 h, P < 0.01) and the effect lasted 14 d ((6.1 +/- 1.1) mL/6 h vs (4.0 +/- 0.8) mL/6 h, P < 0.01), however the statistical difference in concentration of K+ and Na+ in serum and urine was not observed. The results suggested that subcutaneous implantation of fibroblasts-expressing mhANP significantly reduced blood pressure in young SHR during the period of ontogeny and efficiently improved their renal function and the somatic gene transfer of mhANP may have potential value in the treatment of human chronic diseases such as hypertension, chronic heart failure, and chronic renal failure.

Objective: To prolong the half-life and enhance the biological activity of the human atrial natriuretic peptide (hANP), a peptide hormone, which is synthesized and released mainly by cardiac atrial myocytes and possesses potent natriuretic, diretic, and vasorelaxant properties., Methods: The site-directed mutation technique based on polymerase chain reaction was performed to get the mutant of the human ANP gene (mhANP), and the retroviral expression vector, pLHY24, in which mhANP gene is under the transcriptional control of the human cytomegalovirus promoter, was constructed. The naked plasmid DNA of pLHY24 and positive control vector, pLHY19, in which the wild-type hNAP gene is in the same conditions as mhANP gene in pLHY24, and negative control vector, pLNCX without purpose gene, at a dose of 5 mg/kg body weight was injected intramuscularly into the rats with experimental renal disorder induced with adriamycin (ADR), respectively., Results: DNA sequencing result proved that the respected mhANP gene with the point mutations of TTC(131)/Phe-->TCC/Ser and ATG(135)/Met-->ATA/Ile has been obtained. In comparison with negative control group (87 +/- 7.1 pg/ml), a single intramuscular injection of expression vector harboring mhANP or hANP gene resulted in an obvious increase in plasma level of mhANP (107 +/- 7.8 pg/ml, t = 4.65, P < 0.01) or hANP (113 +/- 8.6 pg/ml, t = 5.71, P < 0.01) 5 days after injection. A significant elevation in the ratio of urine volume to body weight was occurred after both of mhANP gene and hANP gene delivery as compared with negative control and the effect lasted for more than 15 days. The diuretic activity of mhANP gene delivery was 1.6-, 2.0-, and 1.9-fold higher than that of hANP gene 5, 10, and 15 days after gene transfer, respectively. However, there were no statistical differences in the concentrations of K(+) and Na(+) in urine., Conclusions: Both of mhANP and hANP gene delivery into the rats with experimental nephropathy could improve their directic function obviously and the diuretic activity of the former is stronger than that of the latter significantly.

Objective: To study the inhibitive effect of subcutaneous implantation of capsule filled with fibroblasts engineered to secrete the mutant human atrial natriuretic peptide (mhANP) on blood pressure in young spontaneously hypertensive rats (SHR) and to explore the feasibility of gene therapy for the treatment of hypertension., Methods: A recombinant retroviral vector pLHY24 bearing mhANP cDNA was constructed. Primary fibroblasts derived from the skin of new born SHR were cultured and transfected with the vector pLHY24 to establish a genetically modified fibroblast line or transfected with the blank vector pLNCX. Then the two kinds of cell culture were put into specially made capsules with microholes. The capsules filled with the genetically modified allogenic fibroblasts and those with blank vector were implanted into the dorsal subcutaneous tissues of two groups of 10 young SHR respectively. The plasma ANP, blood pressure, urine volume, potassium and sodium concentrations in urine, and body weight were determined every week for 7 weeks., Results: After delivery of retroviral vector bearing mhANP gene into the packaging cell PA317 and the primary fibroblasts, immunoreactive mhANP were detected in the cell culture medium at the concentration of (5.84 +/- 0.07) and (13.37 +/- 2.36) ng.10(-6) cells.24 h(-1) respectively. One week after implantation of the genetically modified allogenic fibroblasts the plasma level of mhANP was 131 pg/ml +/- 8 pg/ml, significantly higher than that in control group (104 pg/ml +/- 7 pg/ml, t = 8.62, P < 0.001). Although the blood pressure increased along with aging after the gene transfer, an obvious delay of blood pressure increase was seen significantly lower in test group [from (129 +/- 9) to (169 +/- 9) mm Hg] than that in the control group [from (145 +/- 10) to (181 +/- 9) mm Hg, P < 0.05 or 0.01]. A maximal blood pressure reduction of 28 mm Hg in young SHR was observed 7 days after transplantation as compared with controls. In addition, there was an obvious increase in urine volume of test group 2 weeks after transplantation and the effect lasted for more than 2 weeks. However, there were no statistical differences in body weight and the concentrations of K(+) and Na(+) in urine., Conclusion: Subcutaneous implantation of the encapsulated genetically modified fibroblasts engineered to secrete mutant ANP causes a lowering effect of blood pressure in young SHR.