Chondroitin Sulfate from Halaelurus burgeri Skin Inhibits Hepatic Endoplasmic Reticulum Stress and Inflammation, and Regulates Gut Microbiota.

SCOPE: Previous study has demonstrated the chemical structure of chondroitin sulfate (CHS) from Halaelurus burgeri skin and its effects on insulin resistance. However, the precise impact of this phenomenon on endoplasmic reticulum (ER) stress and inflammation, which contribute to insulin resistance, remains unclear. This study is to investigate the impact of CHS on ER stress, inflammatory response and signaling, and gut microbiota in high-fat diet (HFD)-fed mice. METHODS AND RESULTS: HFD-fed C57BL/6J mice receive dietary gavage intervention of CHS for 18 weeks. Blood, liver tissue, and feces are harvested for further investigation. Results show that CHS inhibits ER stress, accompanied by lowered blood glucose, nitric oxide (NO), reactive oxygen (ROS), and free fatty acids (FFA) levels, and increases hepatic glycogen accumulation. Moreover, hepatic inflammation is improved by CHS treatment via inactivation of Toll-like receptor 4 (TLR4) signaling and its downstream c-jun N-terminal kinase (JNK) and nuclear factor kappa B (NFκB) pathways. Additionally, CHS regulates gut microbiota, particularly the decline in the Firmicutes to Bacteroidetes ratio. CHS also lowers fecal lipopolysaccharide and elevates several fecal short chain fatty acids. CONCLUSION: These findings suggest that CHS from H. burgeri skin may be an alternative functional food supplement for anti-ER stress, anti-inflammtion, and regulation of gut microbiota.

Palladium-Catalyzed Asymmetric Tandem Carbonylation-Heck Reaction of Cyclopentenes to Access Chiral Bicyclo[3.2.1]octenes.

A palladium-catalyzed asymmetric tandem carbonylation-Heck reaction of cyclopentenes with carbon monoxide (CO) has been disclosed. This desymmetrization procedure afforded a series of bicyclo[3.2.1]octenes with one chiral quaternary and one tertiary carbon center in good yields with good enantioselectivities. This reaction proceeds via an acyl-palladium intermediate, followed by migratory insertion of the alkenes.

Experimental progress in Eu(Al,Ga)4topological antiferromagnets.

The non-trivial magnetic and electronic phases occurring in topological magnets are often entangled, thus leading to a variety of exotic physical properties. Recently, the BaAl4-type compounds have been extensively investigated to elucidate the topological features appearing in their real- and momentum spaces. In particular, the topological Hall effect and the spin textures, typical of the centrosymmetric Eu(Al,Ga)4family, have stimulated extensive experimental and theoretical research. In this topical review, we discuss the latest findings regarding the Eu(Al,Ga)4topological antiferromagnets and related materials, arising from a vast array of experimental techniques. We show that Eu(Al,Ga)4represents a suitable platform to explore the interplay between lattice-, charge-, and spin degrees of freedom, and associated emergent phenomena. Finally, we address some key questions open to future investigation.

Seeking the optimal gestational weight gain according to the pre-pregnancy body mass index: a cross-sectional study from Shanghai, China.

OBJECTIVES: Maternal nutritional status is closely related to fetal intrauterine development and an abnormal birth weight increases various disease risks across life stages. To better guide pregnancy weight gain, we aimed to explore the optimal weight gain for pregnant women with different body mass indexes (BMIs). METHODS: This retrospective cohort study included 68,981 women with singleton live birth between January 2017 and October 2021 in maternity centres in Shanghai, China. The fluctuations of the incidence of small and large for gestational age (small for gestational age (SGA) and LGA, respectively) were recorded at different maternal pre-pregnancy BMI (p-BMI) and different gestational weight gain (GWG) groups to find the lowest point of abnormal fetal weight incidence. The optimal GWG was then determined using a linear regression equation. RESULT: The lowest risk of LGA/SGA was associated with a maternal p-BMI of 19.46 kg/m2. For pregnant women with maternal p-BMI below 24 kg/m2, we confirmed an optimal GWG linear equation: opt GWG (kg) = -1.94 × p-BMI (kg/m²) + 51, which showed an excellent degree of fit. Women who were overweight and obese could not achieve the lowest risk of LGA/SGA despite controlling their GWG; hence, their BMI should be normalized before pregnancy. CONCLUSION: By merely using the pre-pregnancy BMI, this study has established the optimal GWG equation, with the goal of achieving the appropriate fetal gestational age. It is a practical measure to ensure desirable pregnancy outcomes and meet the health economics requirements.

Novel therapeutic targets for primary open-angle glaucoma identified through multicenter proteome-wide mendelian randomization.

Background: This study aimed to identify novel therapeutic targets for primary open-angle glaucoma (POAG). Methods: The summary-data-based Mendelian randomization (SMR) method was used to evaluate the genetic association between plasma proteins and POAG. Two sets of plasma protein quantitative trait loci (pQTLs) data considered exposures were obtained from the Icelandic Decoding Genetics Study and UK Biobank Pharma Proteomics Project. The summary-level genome-wide association studies data for POAG were extracted from the latest Round 10 release of the FinnGen consortium (8,530 cases and 391,275 controls) and the UK Biobank (4,737 cases and 458,196 controls). Colocalization analysis was used to screen out pQTLs that share the same variant with POAG as drug targets identified. The two-sample Mendelian randomization, reverse causality testing and phenotype scanning were performed to further validate the main findings. Protein-protein interaction, pathway enrichment analysis and druggability assessment were conducted to determine whether the identified plasma proteins have potential as drug targets. Results: After systematic analysis, this study identified eight circulating proteins as potential therapeutic targets for POAG. Three causal proteins with strong evidence of colocalization, ROBO1 (OR = 1.38, p = 1.48 × 10-4, PPH4 = 0.865), FOXO3 (OR = 0.35, p = 4.34 × 10-3, PPH4 = 0.796), ITIH3 (OR = 0.89, p = 2.76 × 10-4, PPH4 = 0.767), were considered tier one targets. Five proteins with medium support evidence of colocalization, NCR1 (OR = 1.25, p = 4.18 × 10-4, PPH4 = 0.682), NID1 (OR = 1.38, p = 1.54 × 10-3, PPH4 = 0.664), TIMP3 (OR = 0.91, p = 4.01 × 10-5, PPH4 = 0.659), SERPINF1 (OR = 0.81, p = 2.77 × 10-4, PPH4 = 0.59), OXT (OR = 1.17, p = 9.51 × 10-4, PPH4 = 0.526), were classified as tier two targets. Additional sensitivity analyses further validated the robustness and directionality of these findings. According to druggability assessment, Pimagedine, Resveratrol, Syringaresinol and Clozapine may potentially be important in the development of new anti-glaucoma agents. Conclusion: Our integrated study identified eight potential associated proteins for POAG. These proteins play important roles in neuroprotection, extracellular matrix regulation and oxidative stress. Therefore, they have promising potential as therapeutic targets to combat POAG.

Mendelian insights: Irritable bowel syndrome as a predictor of upper urinary tract calculi.

Patients with irritable bowel syndrome (IBS) have a notably higher rate of consultations in urology clinics compared to other clinics. They often present with symptoms such as lumbar pain, dysuria, and urinary difficulty that are also associated with upper urinary tract calculi (UUTC). UUTC are the leading cause of nephrectomy in non-oncological cases, early screening for high-risk populations is deemed necessary. We investigated the relationship between IBS and UUTC using a two-sample Mendelian randomization (MR) approach, with the primary analysis conducted using the inverse variance weighting method. To enhance the robustness of our findings, we conducted sensitivity analyses employing Cochran Q test, MR-Egger intercept, and MR-PRESSO. Additionally, we included type 2 diabetes in a multivariate Mendelian randomization analysis for further exploration. Our two-sample MR analysis, employing the inverse variance weighting method, suggested a positive association between IBS and UUTC, with an odds ratio of 1.47, a 95% confidence interval from 1.01 to 2.15, and a P-value of .442. Both weighted median and MR Egger analyses also indicated that IBS may be a risk factor for UUTC, although the results were not statistically significant. The Cochran Q test revealed no evidence of heterogeneity (P > .05). The MR-Egger intercept and MR-PRESSO analyses did not support the presence of pleiotropy (P > .05), and no outliers were detected by MR-PRESSO. Sensitivity analyses reinforce the reliability of our findings. Multivariate MR analysis further confirmed that IBS is a risk confirmed factor for UUTC, with significant results (P < .05). IBS is identified as one of the etiological factors for UUTC, enhancing our understanding of the gut-kidney axis. The specific mechanisms underlying this association warrant further investigation. Clinicians should consider the importance of monitoring for UUTC in patients with IBS.

Vaccine literacy, vaccination intention, and their correlation among adults in Mainland China: a cross-sectional study.

BACKGROUND: Vaccination is one of the most economic and effective strategies for preventing infectious diseases. However, public intention to be vaccinated is, to a certain degree, influenced by issues related to vaccine hesitancy, anti-vaccine movement, and public concerns about safety and adverse effects. Vaccine literacy is considered as a positive factor in improving vaccination intention, however, the correlation between vaccine literacy and vaccination intention has not been thoroughly investigated in mainland China. This study aims to (1) explore the correlation between vaccine literacy and vaccination intention among adults in mainland China; (2) investigate whether participants could seek out vaccine information on their own initiative and whether they knew basic information of common vaccines. METHODS: An online cross-sectional survey was conducted on 614 adult participants from 27 May to 8 June 2023 by a convenience sampling. Data were collected by using the questionnaire of demographic characteristics, vaccine literacy, vaccination intention, initiative of seeking out vaccine information, and basic vaccine quiz about common vaccines. Data were analyzed by using IBM SPSS version 24.0 at a significance level of 0.05. RESULTS: The mean scores of functional, and interactive-critical vaccine literacy were 2.97 ± 0.70 and 2.73 ± 0.66; the vaccination intentions of influenza, hepatitis B, COVID-19 and HPV were 58.5%, 80.0%, 71.3% and 62.9% respectively; interactive-critical vaccine literacy was significantly and positively associated with vaccination intention. The results also showed: 71.4% of the participants could seek out vaccine information on their own initiative, however, a certain proportion of the participants merely knew vaccine names and did not know basic information of common vaccines, especially influenza vaccine and hepatitis B vaccine. CONCLUSIONS: There is still room for improvement in vaccine literacy, vaccination intention of influenza and HPV vaccines, and basic vaccine information. Based on the significantly positive correlation between interactive-critical vaccine literacy and vaccination intention, it is advisable to harness vaccine literacy to boost vaccination intention by communicating and learning basic information of common vaccines.

Axiomatic design for safe construction considering lean and ergonomic principles: an application in Turkey.

This study proposes a systematic approach based on axiomatic design incorporating lean and ergonomic principles within the proposed design. The contribution to the body of knowledge is to keep construction workers safe by fostering a secure construction environment. Axiomatic design and lean approaches are combined to address human factors and eliminate wastes that hinder a safe construction environment. The application of the proposed system is set in the context of the construction industry. The methodology provides the construction sector with a road map toward reducing the occurrence of accidents and serves as a complementary approach between lean and ergonomic principles. The design solution has been validated and partially applied in a metro construction firm. Results show that the design solution can improve the efficiency of the construction phases by adopting a value-maximization strategy and has the potential to improve the safety and ergonomics of construction projects.

The influence of adverse events on inpatient outcomes in a tertiary hospital using a diagnosis-related group database.

Adverse events (AEs) are a significant concern for healthcare systems. However, it is difficult to evaluate their influence because of the complexity of various medical services. This study aimed to assess the influence of AEs on the outcomes of hospitalized patients using a diagnosis-related group (DRG) database. We conducted a case-control study of hospitalized patients at a multi-district tertiary hospital with 2200 beds in China, using data from a DRG database. An AE refers to an unintended physical injury caused or contributed to by medical care that requires additional hospitalization, monitoring, treatment, or even death. Relative weight (RW), a specific indicator of DRG, was used to measure the difficulty of diagnosis and treatment, disease severity, and medical resources utilized. The primary outcomes were hospital length of stay (LOS) and hospitalization costs. The secondary outcome was discharge to home. This study applied DRG-based matching, Hodges-Lehmann estimate, regression analysis, and subgroup analysis to evaluate the influence of AEs on outcomes. Two sensitivity analyses by excluding short LOS and changing adjustment factors were performed to assess the robustness of the results. We identified 2690 hospitalized patients who had been divided into 329 DRGs, including 1345 patients who experienced AEs (case group) and 1345 DRG-matched normal controls. The Hodges-Lehmann estimate and generalized linear regression analysis showed AEs led to prolonged LOS (unadjusted difference, 7 days, 95% confidence interval [CI] 6-8 days; adjusted difference, 8.31 days, 95% CI 7.16-9.52 days) and excess hospitalization costs (unadjusted difference, $2186.40, 95% CI: $1836.87-$2559.16; adjusted difference, $2822.67, 95% CI: $2351.25-$3334.88). Logistic regression analysis showed AEs were associated with lower odds of discharge to home (unadjusted odds ratio [OR] 0.66, 95% CI 0.54-0.82; adjusted OR 0.75, 95% CI 0.61-0.93). The subgroup analyses showed that the results for each subgroup were largely consistent. LOS and hospitalization costs increased significantly after AEs in complex diseases (RW ≥ 2) and in relation to high degrees of harm subgroups (moderate harm and above groups). Similar results were obtained in sensitivity analyses. The burden of AEs, especially those related to complex diseases and severe harm, is significant in China. The DRG database serves as a valuable source of information that can be utilized for the evaluation and management of AEs.

Artificial intelligence in plant breeding.

Harnessing cutting-edge technologies to enhance crop productivity is a pivotal goal in modern plant breeding. Artificial intelligence (AI) is renowned for its prowess in big data analysis and pattern recognition, and is revolutionizing numerous scientific domains including plant breeding. We explore the wider potential of AI tools in various facets of breeding, including data collection, unlocking genetic diversity within genebanks, and bridging the genotype-phenotype gap to facilitate crop breeding. This will enable the development of crop cultivars tailored to the projected future environments. Moreover, AI tools also hold promise for refining crop traits by improving the precision of gene-editing systems and predicting the potential effects of gene variants on plant phenotypes. Leveraging AI-enabled precision breeding can augment the efficiency of breeding programs and holds promise for optimizing cropping systems at the grassroots level. This entails identifying optimal inter-cropping and crop-rotation models to enhance agricultural sustainability and productivity in the field.

Biological aging mediates the association between periodontitis and cardiovascular disease: results from a national population study and Mendelian randomization analysis.

BACKGROUND: The relationship between periodontitis and cardiovascular disease (CVD) has been extensively studied, but the role of biological aging in this relationship remains poorly understood. This study is dedicated to investigating the effect of periodontitis on the incidence of CVD and to elucidating the potential mediating role of biological aging. Furthermore, this study will seek to elucidate the causal association between periodontitis, CVD, and biological aging. METHODS: We included 3269 participants from the National Health and Nutrition Examination Survey (2009-2014) with diagnostic information on periodontitis and composite CVD events. Biological aging was evaluated by utilizing both the Klemera-Doubal method's calculated biological age (KDMAge) and phenotypic age (PhenoAge). Logistic regression, restricted cubic spline (RCS) analysis, and subgroup analysis were used for data analysis. Mediation analysis was employed to explore the mediating role of biological aging. Subsequently, Mendelian randomization (MR) analyses were performed using genome-wide association study databases to explore potential causal relationships between periodontitis, CVD, and biological aging. RESULTS: Periodontitis was associated with a higher risk of CVD. Participants with periodontitis were found to have increased levels of biological aging, and elevated levels of biological aging were associated with increased CVD risk. Mediation analyses showed a partial mediating effect of biological aging (PhenoAge: 44.6%; KDMAge: 22.9%) between periodontitis and CVD risk. MR analysis showed that periodontitis played a causal role in increasing the risk of small vessel stroke, while myocardial infarction was found to increase the risk of periodontitis. In addition, reverse MR analysis showed that phenotypic aging can increase the risk of periodontitis, and there is a two-way causal relationship between CVD and biological aging. CONCLUSIONS: Periodontitis is associated with an increased CVD risk, partially mediated by biological aging, with a complex causal interrelationship. Targeted interventions for periodontal health may slow the biological aging processes and reduce CVD risk.

Enhancing boundary detection of radiofrequency ablation lesions through photoacoustic mapping.

Atrial fibrillation (A-fib) is the most common type of heart arrhythmia, typically treated with radiofrequency catheter ablation to isolate the heart from abnormal electrical signals. Monitoring the formation of ablation-induced lesions is crucial for preventing recurrences and complications arising from excessive or insufficient ablation. Existing imaging modalities lack real-time feedback, and their intraoperative usage is in its early stages. A critical need exists for an imaging-based lesion indexing (LSI) method that directly reflects tissue necrosis formation. Previous studies have indicated that spectroscopic photoacoustic (sPA) imaging can differentiate ablated tissues from their non-ablated counterparts based on PA spectrum variation. In this paper, we introduce a method for detecting ablation lesion boundaries using sPA imaging. This approach utilizes ablation LSI, which quantifies the ratio between the signal from ablated tissue and the total tissue signal. We enhance boundary detection accuracy by adapting a regression model-based compensation. Additionally, the method was cross-validated with clinically used intraoperative monitoring parameters. The proposed method was validated with ex vivo porcine cardiac tissues with necrotic lesions created by different ablation durations. The PA-measured lesion size was compared with gross pathology. Statistical analysis demonstrates a strong correlation (R > 0.90) between the PA-detected lesion size and gross pathology. The PA-detected lesion size also exhibits a moderate to strong correlation (R > 0.75) with local impedance changes recorded during procedures. These results suggest that the introduced PA imaging-based LSI has great potential to be incorporated into the clinical workflow, guiding ablation procedures intraoperatively.

Infrared and Harsh Light Visible Image Fusion Using an Environmental Light Perception Network.

The complementary combination of emphasizing target objects in infrared images and rich texture details in visible images can effectively enhance the information entropy of fused images, thereby providing substantial assistance for downstream composite high-level vision tasks, such as nighttime vehicle intelligent driving. However, mainstream fusion algorithms lack specific research on the contradiction between the low information entropy and high pixel intensity of visible images under harsh light nighttime road environments. As a result, fusion algorithms that perform well in normal conditions can only produce low information entropy fusion images similar to the information distribution of visible images under harsh light interference. In response to these problems, we designed an image fusion network resilient to harsh light environment interference, incorporating entropy and information theory principles to enhance robustness and information retention. Specifically, an edge feature extraction module was designed to extract key edge features of salient targets to optimize fusion information entropy. Additionally, a harsh light environment aware (HLEA) module was proposed to avoid the decrease in fusion image quality caused by the contradiction between low information entropy and high pixel intensity based on the information distribution characteristics of harsh light visible images. Finally, an edge-guided hierarchical fusion (EGHF) module was designed to achieve robust feature fusion, minimizing irrelevant noise entropy and maximizing useful information entropy. Extensive experiments demonstrate that, compared to other advanced algorithms, the method proposed fusion results contain more useful information and have significant advantages in high-level vision tasks under harsh nighttime lighting conditions.

Loss of Smek1 Induces Tauopathy and Triggers Neurodegeneration by Regulating Microtubule Stability.

Suppressor of Mek1 (Smek1) is a regulatory subunit of protein phosphatase 4. Genome-wide association studies have shown the protective effect of SMEK1 in Alzheimer's disease (AD). However, the physiological and pathological roles of Smek1 in AD and other tauopathies are largely unclear. Here, the role of Smek1 in preventing neurodegeneration is investigated in tauopathy. Smek1 is downregulated in the aged human brain. Through single-cell sequencing, a novel neuronal cluster is identified that possesses neurodegenerative characteristics in Smek1-/- mice. Smek1 deficiency caused markedly more severe motor and cognitive impairments in mice, as well as neuronal loss, gliosis, and tau hyperphosphorylation at major glycogen synthase kinase 3ß (Gsk3ß) sites. Protein-protein interaction analysis revealed that the Ran-binding domain (RanBD) in the N-terminus of Smek1 facilitated binding with kinesin family member 2A (Kif2a). Depletion of Smek1 resulted in cytoplasmic aggregation of Kif2a, axon outgrowth defects, and impaired mitochondrial axonal trafficking. Downregulation of Kif2a markedly attenuated tau hyperphosphorylation and axon outgrowth defects in shSmek1 cells. For the first time, this study demonstrates that Smek1 deficiency progressively induces neurodegeneration by exacerbating tau pathology and mitochondrial dysfunction in an age-dependent manner.

Antioxidant synergistic anti-inflammatory effect in the MAPK/NF-κB pathway of peptide KGEYNK (KK-6) from giant salamander (Andrias davidianus).

BACKGROUND: Giant salamander protein peptide is a peptide with rich functional properties. Giant salamander protein peptide KGEYNK (KK-6) is a peptide with both antioxidant and anti-inflammatory properties. The antioxidant and anti-inflammatory mechanisms of KK-6 are still unclear. When we studied the functional mechanism of KK-6, we found that the antioxidant property of KK-6 has a synergistic and promoting effect on anti-inflammatory properties. RESULTS: KK-6 enhances cellular resistance to LPS via the MAPK/NF-κB signaling pathway, leading to increased levels of inflammatory factors: interleukin-1ß (764.81 ng mL-1), interleukin-6 (1.06 ng mL-1) and tumor necrosis factor-α (4440.45 ng mL-1). KK-6 demonstrates potent antioxidant properties by activating the Nrf2 signaling pathway, resulting in elevated levels of antioxidant enzymes (glutathione peroxidase: 0.03 µg mL-1; superoxide dismutase: 0.589 µg mL-1) and a reduction in the concentration of the oxidative product malondialdehyde (967.05 µg mL-1). CONCLUSION: Our findings highlight the great potential of KK-6, a peptide extracted from giant salamander protein, as a remedy for intestinal inflammation. Through its dual role as an antioxidant and anti-inflammatory agent, KK-6 offers a promising avenue for alleviating inflammation-related damage and oxidative stress. This study lays the foundation for further exploration of giant salamander products and highlights their importance in health and novel food development. © 2024 Society of Chemical Industry.

Phonon excitations in Eu2Ir2O7probed by inelastic x-ray scattering.

The study of phonon dynamics and its interplay with magnetic ordering is crucial for understanding the unique quantum phases in the pyrochlore iridates. Here, through inelastic x-ray scattering on a single crystal sample of the pyrochlore iridate Eu2Ir2O7, we map out the phonon excitation spectra in Eu2Ir2O7and compare them with the theoretical phonon spectra calculated using the density functional theory. Possible phonon renormalization across the magnetic long-range order transition is observed in our experiments, which is consistent with the results of the previous Raman scattering experiments.

Cardiac-gated spectroscopic photoacoustic imaging for ablation-induced necrotic lesion visualization.

Radiofrequency (RF) ablation is a minimally invasive therapy for atrial fibrillation. Conventional RF procedures lack intraoperative monitoring of ablation-induced necrosis, complicating assessment of completeness. While spectroscopic photoacoustic (sPA) imaging shows promise in distinguishing ablated tissue, multi-spectral imaging is challenging in vivo due to low imaging quality caused by motion. Here, we introduce a cardiac-gated sPA imaging (CG-sPA) framework to enhance image quality using a motion-gated averaging filter, relying on image similarity. Necrotic extent was calculated based on the ratio between spectral unmixed ablated tissue contrast and total tissue contrast, visualizing as a continuous color map to highlight necrotic area. The validation of the concept was conducted in both ex vivo and in vivo swine models. The ablation-induced necrotic lesion was successfully detected throughout the cardiac cycle through CG-sPA imaging. The results suggest the CG-sPA imaging framework has great potential to be incorporated into clinical workflow to guide ablation procedures intraoperatively.

Long-term HBV infection of engineered cultures of induced pluripotent stem cell-derived hepatocytes.

BACKGROUND: HBV infects ~257 million people and can cause hepatocellular carcinoma. Since current drugs are not curative, novel therapies are needed. HBV infects chimpanzee and human livers. However, chimpanzee studies are severely restricted and cost-prohibitive, while transgenic/chimeric mouse models that circumvent the species barrier lack natural HBV infection and disease progression. Thus, in vitro human models of HBV infection are useful in addressing the above limitations. Induced pluripotent stem cell-derived hepatocyte-like cells mitigate the supply limitations of primary human hepatocytes and the abnormal proliferation/functions of hepatoma cell lines. However, variable infection across donors, deficient drug metabolism capacity, and/or low throughput limit iHep utility for drug development. METHODS: We developed an optimal pipeline using combinations of small molecules, Janus kinase inhibitor, and 3',5'-cAMP to infect iHep-containing micropatterned co-cultures (iMPCC) with stromal fibroblasts within 96-well plates with serum-derived HBV and cell culture-derived HBV (cHBV). Polyethylene glycol was necessary for cell-derived HBV but not for serum-derived HBV infection. RESULTS: Unlike iHep monocultures, iMPCCs created from 3 iHep donors could sustain HBV infection for 2+ weeks. Infected iMPCCs maintained high levels of differentiated functions, including drug metabolism capacity. HBV antigen secretion and gene expression patterns in infected iMPCCs in pathways such as fatty acid metabolism and cholesterol biosynthesis were comparable to primary human hepatocyte-MPCCs. Furthermore, iMPCCs could help elucidate the effects of interferons and direct-acting antiviral drugs on the HBV lifecycle and any hepatotoxicity; iMPCC response to compounds was similar to primary human hepatocyte-MPCCs. CONCLUSIONS: The iMPCC platform can enable the development of safe and efficacious drugs against HBV and ultimately help elucidate genotype-phenotype relationships in HBV pathogenesis.

Subnanoscale Ion Beam Modification-Assisted Smoothing of Heterostructure Surfaces.

Glass ceramic (GC) is the most promising material for objective lenses for extreme ultraviolet lithography that must meet the subnanometer precision, which is characterized by low values of high spatial frequency surface roughness (HSFR). However, the HSFR of GC is typically degraded during ion beam figuring (IBF). Herein, a developed method for constructing molecular dynamics (MD) models of GC was presented, and the formation mechanisms of surface morphologies were investigated. The results indicated that the generation of the dot-like microstructure was the result of the difference in the erosion rate caused by the difference in the intrinsic properties between ceramic phases (CPs) and glass phases (GPs). Further, the difference in the microstructure of the IBF surface under different beam angles was mainly caused by the difference in the two types of sputtering. Quantum mechanical calculations showed that the presence of interstitial atoms would result in electron rearrangement and that the electron localization can lead to a reduction in CP stability. To obtain a homogeneous surface, the effects of beam parameters on the heterogeneous surface were systematically investigated based on the proposed MD model. Then, a novel ion beam modification (IBM) method was proposed and demonstrated by TEM and GIXRD. The range of ion beam smoothing parameters that could effectively converge the HSFR of the modified surface was determined through numerous experiments. Using the optimized beam parameters, an ultrathin homogeneous modified surface within 3 nm was obtained. The HSFR of GC smoothed by ion beam modification-assisted smoothing (IBMS) dropped from 0.348 to 0.090 nm, a 74% reduction. These research results offer a deeper understanding of the morphology formation mechanisms of the GC surfaces involved in ion beam processing and may point to a new approach for achieving ultrasmooth heterostructure surfaces down to the subnanometer scale.

Impacts of stream drying depend on stream network size and location of drying.

Stream drying is increasing globally, with widespread impacts on stream ecosystems. Here, we investigated how the impacts of drying on stream ecosystem connectivity might depend on stream network size and the location of drying within the stream network. Using 11 stream networks from across the United States, we simulated drying scenarios in which we varied the location and spatial extent of drying. We found that the rate of connectivity loss varied with stream network size, such that larger stream networks lost connectivity more rapidly than smaller stream networks. We also found that the rate of connectivity loss varied with the location of drying. When drying occurred in the mainstem, even small amounts of drying resulted in rapid losses in ecosystem connectivity. When drying occurred in headwater reaches, small amounts of drying had little impact on connectivity. Beyond a certain threshold, however, connectivity declined rapidly with further increases in drying. Given the increasing stream drying worldwide, our findings underscore the need for managers to be particularly vigilant about fragmentation when managing at large spatial scales and when stream drying occurs in mainstem reaches.