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Abstract Heart failure, the leading cause of mortality and morbidity in the developed world, is characterized by cardiac ryanodine receptor 2 channels that are hyperphosphorylated, oxidized, and depleted of the stabilizing subunit calstabin-2. This results in a diastolic sarcoplasmic reticulum Ca2+ leak that impairs cardiac contractility and triggers arrhythmias. Genetic mutations in ryanodine receptor 2 can also cause Ca2+ leak, leading to arrhythmias and sudden cardiac death. Here, we solved the cryogenic electron microscopy structures of ryanodine receptor 2 variants linked either to heart failure or inherited sudden cardiac death. All are in the primed state, part way between closed and open. Binding of Rycal drugs to ryanodine receptor 2 channels reverts the primed state back towards the closed state, decreasing Ca2+ leak, improving cardiac function, and preventing arrhythmias. We propose a structural-physiological mechanism whereby the ryanodine receptor 2 channel primed state underlies the arrhythmias in heart failure and arrhythmogenic disorders.

Abstract Background The relationship between human gut microbiota and high-altitude hypoxia acclimatization remains highly controversial. This stems primarily from uncertainties regarding both the potential temporal changes in the microbiota under such conditions and the existence of any dominant or core bacteria that may assist in host acclimatization. Results To address these issues, and to control for variables commonly present in previous studies which significantly impact the results obtained, namely genetic background, ethnicity, lifestyle, and diet, we conducted a 108-day longitudinal study on the same cohort comprising 45 healthy Han adults who traveled from lowland Chongqing, 243 masl, to high-altitude plateau Lhasa, Xizang, 3658 masl, and back. Using shotgun metagenomic profiling, we study temporal changes in gut microbiota composition at different timepoints. The results show a significant reduction in the species and functional diversity of the gut microbiota, along with a marked increase in functional redundancy. These changes are primarily driven by the overgrowth of Blautia A, a genus that is also abundant in six independent Han cohorts with long-term duration in lower hypoxia environment in Shigatse, Xizang, at 4700 masl. Further animal experiments indicate that Blautia A-fed mice exhibit enhanced intestinal health and a better acclimatization phenotype to sustained hypoxic stress. Conclusions Our study underscores the importance of Blautia A species in the gut microbiota’s rapid response to high-altitude hypoxia and its potential role in maintaining intestinal health and aiding host adaptation to extreme environments, likely via anti-inflammation and intestinal barrier protection.

Abstract Background This is a retrospective cohort study from a single center of Chest Medical District of Nanjing Brain Hospital Affiliated to Nanjing Medical University, Jiangsu Province, China. It was aim to evaluate the diagnostic value of radial endobronchial ultrasound (R-EBUS) combination with rapid on-site evaluation (ROSE) guided transbronchial lung biopsy (TBLB) for peripheral pulmonary lesions in patients with emphysema. Methods All 170 patients who underwent PPLs with emphysema received an R-EBUS examination with or without the ROSE procedure, and the diagnostic yield, safety, and possible factors influencing diagnosis were analyzed between the two groups by the SPSS 25.0 software. Results The pooled and benign diagnostic yields were not different in the two groups (P = 0.224, 0.924), but the diagnostic yield of malignant PPLs was significantly higher in the group with ROSE than the group without ROSE (P = 0.042). The sensitivity of ROSE was 79.10%, the specificity, 91.67%, the positive predictive value, 98.15%, and the negative predictive value, 84.62%. The diagnostic accuracy, was 95.52%. In the group of R-EBUS + ROSE, the procedural time and the number of times of biopsy or brushing were both significantly reduced (all P

Abstract Background Cobalt (Co) is a metal which is widely used in the industrial production. The previous studies found the toxic effects of environmental Co exposure on multiple organs. However, the correlation of blood Co concentration with lung function was inconsistent in patients with chronic obstructive pulmonary disease (COPD). Methods All 771 stable COPD patients were recruited. Peripheral blood and clinical information were collected. The levels of blood Co and serum CC16 were measured. Results Cross-sectional study suggested that the level of blood Co was inversely and dose-dependently related to lung function parameters. Each 1 ppm elevation of blood Co was related to 0.598 L decline in FVC, 0.465 L decline in FEV1, 6.540% decline in FEV1/FVC%, and 14.013% decline in FEV1%, respectively. Moreover, higher age, enrolled in winter, current-smoking, higher smoking amount, and inhaled corticosteroids prominently exacerbated the negative correlation between blood Co and lung function. Besides, serum CC16 content was gradually reduced with blood Co elevation in COPD patients. Besides, serum CC16 was positively correlated with lung function, and inversely related to blood Co. Additionally, decreased CC16 substantially mediated 11.45% and 6.37% Co-triggered downregulations in FEV1 and FEV1%, respectively. Conclusion Blood Co elevation is closely related to the reductions of pulmonary function and serum CC16. CC16 exerts a significantly mediating role of Co-related to pulmonary function decrease among COPD patients.

Abstract Colorectal cancer (CRC) is a highly aggressive and life-threatening malignancy that metastasizes in ~50% of patients, posing significant challenges to patient survival and treatment. Fatty acid (FA) metabolism regulates proliferation, immune escape, metastasis, angiogenesis, and drug resistance in CRC. FA metabolism consists of three pathways: de novo synthesis, uptake, and FA oxidation (FAO). FA metabolism-related enzymes promote CRC metastasis by regulating reactive oxygen species (ROS), matrix metalloproteinases (MMPs), angiogenesis and epithelial-mesenchymal transformation (EMT). Mechanistically, the PI3K/AKT/mTOR pathway, wnt/β-catenin pathway, and non-coding RNA signaling pathway are regulated by crosstalk of enzymes related to FA metabolism. Given the important role of FA metabolism in CRC metastasis, targeting FA metabolism-related enzymes and their signaling pathways is a potential strategy to treat CRC metastasis.

Fungi are one of the most diverse groups of organisms on Earth, amongst which wood-inhabiting fungi play a crucial role in ecosystem processes and functions. Four new wood-inhabiting fungi, Xylodon cremeoparinaceus, X. luteodontioides, X. poroides and X. wumengshanensis are proposed, based on morphological features and molecular evidence. Xylodon cremeoparinaceus is distinguished by a cream hymenial surface with a pruinose hymenophore, a monomitic hyphal system with clamped generative hyphae and ellipsoid basidiospores. Xylodon luteodontioides is characterised by flavescens hymenophore surface with odontioid hymenophore, monomitic hyphal system with clamped generative hyphae and ellipsoid basidiospores. Xylodon poroides bears coriaceous basidiomata with a poroid hymenophore surface, monomitic hyphal system with clamped generative hyphae and ellipsoid basidiospores. Xylodon wumengshanensis is a distinct taxon by its grandinoid hymenophore surface, monomitic hyphal system with clamped generative hyphae and ellipsoid basidiospores. Sequences of ITS and nLSU rRNA markers of the studied samples were generated and phylogenetic analyses were performed using the Maximum Likelihood, Maximum Parsimony, and Bayesian Inference methods. The phylogram, based on the ITS+nLSU rDNA gene regions, included three genera within the Schizoporaceae as Fasciodontia, Lyomyces and Xylodon. The four new species were grouped into the genus Xylodon. The topology, based on the ITS sequences, revealed that Xylodon cremeoparinaceus was grouped closely with X. pruinosus, X. detriticus and X. ussuriensis. The taxon X. luteodontioides was sister to X. nesporii. The species X. poroides separated from X. pseudotropicus, while X. wumengshanensis was grouped with four taxa: X. patagonicus, X. radula, X. subtropicus and X. taiwanianus.

Abstract Background High Neutrophil-to-Lymphocyte Ratio (NLR), Monocyte-to-Lymphocyte Ratio (MLR), Platelet-to-Lymphocyte Ratio (PLR) were associated with worse prognosis of patients with sepsis. In-hospital mortality has been reported to be higher in patients with coronary artery disease (CAD) and sepsis than those with sepsis alone. However, the relationship between NLR, MLR, PLR and mortality in septic patients with coronary artery disease (CAD) remains unclear. The study aimed to explore the association between NLR, MLR, PLR and 28-day all-cause mortality in septic patients with CAD. Methods We performed an observational cohort study of septic patients with CAD from the Medical Information Mart for Intensive Care (MIMIC)-IV database between 2008 and 2019. The patients were categorized by three group (Q1: low levels, Q2: medium levels, Q3: high levels) based on tertiles of NLR, MLR, and PLR. The associations between NLR, MLR, PLR and 28-day all-cause mortality were examined using the Cox proportional hazards model. Subsequently, we applied receiver operating characteristic (ROC) analysis for predicting 28-day mortality in septic patients with CAD by combining NLR, MLR and PLR with the modified sequential organ failure assessment (mSOFA) scores. Results Overall 1,175 septic patients with CAD were included in the study. Observed all-cause mortality rates in 28 days were 27.1%. Multivariate Cox proportional hazards regression analysis results showed that 28-day all-cause mortality of septic patients with CAD was significantly related to rising NLR levels (adjusted hazard ratio [aHR]: 1.02; 95% confidence interval [CI]: 1.01–1.02; P

Abstract Non-alcoholic fatty liver disease (NAFLD) has become the first major chronic liver disease in developed countries. 10–20% of NAFLD patients will progress to non-alcoholic steatohepatitis (NASH), and up to 25% of NASH patients may develop cirrhosis within 10 years. Therefore, it is critical to find key targets that may treat this disease. Here, we identified C5aR1 as a highly-expressed gene in NASH mouse model through analyzing Gene Expression Omnibus (GEO) database and confirmed its higher expression in livers of NASH patients than that of NAFL patients. Meanwhile, we verified its positive correlation with patients’ serum alanine transaminase (ALT) and aspartate transaminase (AST) levels. In vivo and in vitro experiments revealed that knocking down C5aR1 in liver significantly reduced liver weight ratio and serum ALT and AST levels and attenuated inflammatory cell infiltration and cell apoptosis in the liver of NASH mice as well as enhanced the efferocytotic ability of liver macrophages, suggesting that C5aR1 may play a crucial role in the efferocytosis of liver macrophages. Furthermore, we also found that the expression levels of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3), caspase-1, IL-1β and other inflammation-related factors in the liver were significantly reduced. Our work demonstrates a potential mechanism of how C5aR1 deficiency protects against diet-induced NASH by coordinating the regulation of inflammatory factors and affecting hepatic macrophage efferocytosis.

An innovative multi-layer composite explosion containment vessel (CECV) utilizing a sliding steel plate-aluminum honeycomb-fiber cloth sandwich is put forward to improve the anti-explosion capacity of a conventional single-layer explosion containment vessel (SECV). Firstly, a series of experiments and finite element (FE) simulations of internal explosions are implemented to understand the basic anti-explosion characteristics of a SECV and the rationality of the computational models and methods is verified by the comparison between the experimental results and simulation results. Based on this, the CECV is designed in detail and a variety of FE simulations are carried out to investigate effects of the sandwich structure, the explosive quantity and the laying mode of the fiber cloth on anti-explosion performance and dynamic response of the CECV under internal explosions. Simulation results indicate that the end cover is the critical position for both the SECV and CECV. The maximum pressure of the explosion shock wave and the maximum strain of the CECV can be extremely declined compared to those of the SECV. As a result, the explosive quantity the CECV can sustain is up to 20 times of that the SECV can sustain. Besides, as the explosive quantity increases, the internal pressure of the CECV keeps growing and the plastic deformation and failure of the sandwich structure become more and more severe, yielding plastic strain of the CECV in addition to elastic strain. The results also reveal that the laying angles of the fiber cloth's five layers have an impact on the anti-explosion performance of the CECV. For example, the CECV with fiber cloth layered in 0°/45°/90°/45°/0° mode has the optimal anti-capacity, compared to 0°/0°/0°/0°/0° and 0°/30°/60°/30°/0° modes. Overall, owing to remarkable anti-explosion capacity, this CECV can be regarded as a promising candidate for explosion resistance.

Abstract Two-dimensional topological insulators hosting the quantum spin Hall effect have application potential in dissipationless electronics. To observe the quantum spin Hall effect at elevated temperatures, a wide band gap is indispensable to efficiently suppress bulk conduction. Yet, most candidate materials exhibit narrow or even negative band gaps. Here, via elegant control of van der Waals epitaxy, we have successfully grown monolayer ZrTe5 on a bilayer graphene/SiC substrate. The epitaxial ZrTe5 monolayer crystalizes in two allotrope isomers with different intralayer alignments of ZrTe3 prisms. Our scanning tunneling microscopy/spectroscopy characterization unveils an intrinsic full band gap as large as 254 meV and one-dimensional edge states localized along the periphery of the ZrTe5 monolayer. First-principles calculations further confirm that the large band gap originates from strong spin−orbit coupling, and the edge states are topologically nontrivial. These findings thus provide a highly desirable material platform for the exploration of the high-temperature quantum spin Hall effect.

Abstract Objectives To develop an interactive, non-invasive artificial intelligence (AI) system for malignancy risk prediction in cystic renal lesions (CRLs). Methods In this retrospective, multicenter diagnostic study, we evaluated 715 patients. An interactive geodesic-based 3D segmentation model was created for CRLs segmentation. A CRLs classification model was developed using spatial encoder temporal decoder (SETD) architecture. The classification model combines a 3D-ResNet50 network for extracting spatial features and a gated recurrent unit (GRU) network for decoding temporal features from multi-phase CT images. We assessed the segmentation model using sensitivity (SEN), specificity (SPE), intersection over union (IOU), and dice similarity (Dice) metrics. The classification model’s performance was evaluated using the area under the receiver operator characteristic curve (AUC), accuracy score (ACC), and decision curve analysis (DCA). Results From 2012 to 2023, we included 477 CRLs (median age, 57 [IQR: 48–65]; 173 men) in the training cohort, 226 CRLs (median age, 60 [IQR: 52–69]; 77 men) in the validation cohort, and 239 CRLs (median age, 59 [IQR: 53–69]; 95 men) in the testing cohort (external validation cohort 1, cohort 2, and cohort 3). The segmentation model and SETD classifier exhibited excellent performance in both validation (AUC = 0.973, ACC = 0.916, Dice = 0.847, IOU = 0.743, SEN = 0.840, SPE = 1.000) and testing datasets (AUC = 0.998, ACC = 0.988, Dice = 0.861, IOU = 0.762, SEN = 0.876, SPE = 1.000). Conclusion The AI system demonstrated excellent benign-malignant discriminatory ability across both validation and testing datasets and illustrated improved clinical decision-making utility. Critical relevance statement In this era when incidental CRLs are prevalent, this interactive, non-invasive AI system will facilitate accurate diagnosis of CRLs, reducing excessive follow-up and overtreatment. Key Points The rising prevalence of CRLs necessitates better malignancy prediction strategies. The AI system demonstrated excellent diagnostic performance in identifying malignant CRL. The AI system illustrated improved clinical decision-making utility. Graphical Abstract

Abstract Fibrosis is a reparative and progressive process characterized by abnormal extracellular matrix deposition, contributing to organ dysfunction in chronic diseases. The tumor suppressor p53 (p53), known for its regulatory roles in cell proliferation, apoptosis, aging, and metabolism across diverse tissues, appears to play a pivotal role in aggravating biological processes such as epithelial-mesenchymal transition (EMT), cell apoptosis, and cell senescence. These processes are closely intertwined with the pathogenesis of fibrotic disease. In this review, we briefly introduce the background and specific mechanism of p53, investigate the pathogenesis of fibrosis, and further discuss p53’s relationship and role in fibrosis affecting the kidney, liver, lung, and heart. In summary, targeting p53 represents a promising and innovative therapeutic approach for the prevention and treatment of organ fibrosis.

Abstract Mitochondria are the centers of energy and material metabolism, and they also serve as the storage and dispatch hubs of metal ions. Damage to mitochondrial structure and function can cause abnormal levels and distribution of metal ions, leading to cell dysfunction and even death. For a long time, mitochondrial quality control pathways such as mitochondrial dynamics and mitophagy have been considered to inhibit metal-induced cell death. However, with the discovery of new metal-dependent cell death including ferroptosis and cuproptosis, increasing evidence shows that there is a complex relationship between mitochondrial quality control and metal-dependent cell death. This article reviews the latest research results and mechanisms of crosstalk between mitochondrial quality control and metal-dependent cell death in recent years, as well as their involvement in neurodegenerative diseases, tumors and other diseases, in order to provide new ideas for the research and treatment of related diseases.

Background and aimThe deterioration in cognition of persons with dementia (PWD) makes their caregivers key players in their help-seeking process. This study aimed to identify the facilitators and barriers of help-seeking for persons with dementia in Asia from the perspective of their informal caregivers.MethodsA qualitative methodology was adopted in the current study. Twenty-nine informal caregivers of PWD in Singapore were interviewed between April 2019 and December 2020. All interviews were audio-recorded and transcribed verbatim for the analysis.ResultsThe transcripts were analyzed using inductive thematic analysis. The results revealed four major themes with 12 sub-themes, including (1) Barriers to diagnosis-seeking (i.e., lack of knowledge and awareness of dementia, emotional denial, resistance from PWD, and delays in the healthcare system); (2) Facilitators of diagnosis-seeking (i.e., synergy between awareness of dementia and an active diagnosis-seeking intention and incidental diagnosis resulting from seeking treatment for comorbid conditions); (3) Barriers to treatment-seeking (i.e., challenges from PWD and disease, challenges faced by caregivers when seeking treatment for PWD, and challenges imposed by the COVID-19 pandemic); (4) Facilitators of treatment-seeking (i.e., caregivers’ capabilities of handling PWD, cooperation/compliance from PWD, and an integrated care plan for PWD).ConclusionThe findings highlight the importance of raising public awareness, enabling health professionals to tailor psychosocial interventions better, and improving community support through dementia awareness and education.

Abstract When electrons moving in two dimensions (2D) are subjected to a strong uniform magnetic field, they form flat bands called Landau levels (LLs). LLs can also arise from pseudomagnetic fields (PMFs) induced by lattice distortions. In three-dimensional (3D) systems, there has been no experimental demonstration of LLs as a type of flat band thus far. Here, we report the experimental realization of a flat 3D LL in an acoustic crystal. Starting from a lattice whose bandstructure exhibits a nodal ring, we design an inhomogeneous distortion corresponding to a specific pseudomagnetic vector potential (PVP). This distortion causes the nodal ring states to break up into LLs, including a zeroth LL that is flat along all three directions. These findings suggest the possibility of using nodal ring materials to generate 3D flat bands, allowing access to strong interactions and other attractive physical regimes in 3D.

Abstract As hypothetical topological defects in the geometry of spacetime, vortex strings could have played many roles in cosmology, and their distinct features can provide observable clues about the early universe’s evolution. A key feature of vortex strings is that they can interact with Weyl fermionic modes and support massless chiral-anomaly states along strings. To date, despite many attempts to detect vortex strings in astrophysics or to emulate them in artificially created systems, observation of these vortex-string chiral modes remains experimentally elusive. Here we report experimental observations of vortex-string chiral modes using a metamaterial system. This is implemented by inhomogeneous perturbation of Yang-monopole phononic metamaterials. The measured linear dispersion and modal profiles confirm the existence of topological modes bound to and propagating along the string with the chiral anomaly. Our work provides a platform for studying diverse cosmic topological defects in astrophysics and offers applications as topological fibres in communication techniques.

Abstract In sulphur-coal symbiotic coal seams, after the mining of sulphide iron ore, when the coal resources are mined, the mine water accumulated in the roadway mining area will have a certain impact on the stability of the surrounding rock of the coal seam roadway. Taking the floor sandstone of sulfur coal symbiotic coal seam as the research object, the roof fissure water with pH values of 7.48, 4.81 and 2.62 was used as the experimental solution. 10 experimental schemes were designed to measure the compressive strength of the samples under the action of AMD, and the hydrochemical analysis of AMD was conducted. The pore structures of the samples before and after the action of AMD were analyzed. Based on the hydrochemistry and pore structure, the deterioration mechanism of compressive strength of the coal seam floor sandstone under the action of AMD was explained. The results indicated that the compressive strength of the samples decreased with the increasing action time of AMD. The compressive strength decreased with the increment of the porosity. The concentration of H+ ion in AMD was relatively small. Na2O in albite dissolved and reacted with water, leading to an increase in the concentration of Na+ ion. Soluble substances such as MgCl2 and CaSO4 in the pore structure dissolved, leading to an increase in the concentration of Ca2+ and Mg2+ ions. The dissolution of soluble substances and the physical–chemical reactions between solutions and minerals were the essential causes of the continuous deterioration of the compressive strength of the coal seam floor sandstone. The results of this study can provide a theoretical basis for the deterioration of the mechanical properties of the peripheral rock in the roadway of the sulphur coal seam, and can also provide a certain engineering reference for the sulphur coal seam roadway.

Abstract The violent goods vibration during curve negotiation is a huge threat to the vehicle running safety. Qualified load restraint assemblies that can significantly suppress the cargo vibration are necessary. This study proposes a novel method for evaluating the essential restraint strength, focusing on the relative motion between cargo and wagon. In the beginning, as a comparison, current methods are used to calculate the necessary stiffness of lashings, which are adopted to restrain the cargo vibration on the wagon. Based on the data of the field test, the accuracy of the established wagon-cargo coupled dynamics model is validated. The loaded wagon model negotiates the curve under different running and loading conditions. The simulation results and analysis demonstrate effective strategies for suppressing the vibration of the cargo and reveal the necessary lashing stiffness. The comparison among the results of different evaluation methods shows that the stability of the cargo can be improved by optimizing the lashing stiffness with the method of dynamics simulations. We hope this study will make a positive contribution to the safety of railway freight transportation.

Abstract Background Prior studies in patients with chronic obstructive pulmonary disease (COPD) had indicated a potential correlation between cadmium (Cd) exposure and reduction in lung function. Nevertheless, the influence of Cd exposure on the progression of COPD remained unknown. Exploring the relationship between Cd exposure and the progression of COPD was the aim of this investigation. Methods Stable COPD patients were enrolled. Blood samples were collected and lung function was evaluated. Regular professional follow-ups were conducted through telephone communications, outpatient services, and patients' hospitalization records. Results Each additional unit of blood Cd was associated with upward trend in acute exacerbation, hospitalization, longer hospital stay, and death within 2 years. Even after adjusting for potential confounding factors, each 1 unit rise in blood Cd still correlated with a rise in the frequencies of acute exacerbation, longer hospital stay, and death. Moreover, COPD patients with less smoking amount, lower lung function and without comorbidities were more vulnerable to Cd-induced disease deterioration. Conclusion Patients with COPD who have higher blood Cd concentration are susceptible to worse disease progression. Graphical Abstract

Abstract Solid‐state high voltage high repetitive pulse generators have a broad prospect in various applications. The high power and high‐frequency operation of the pulse generator suffer from the massive heat dissipation problem, which limits the improvement of the output parameters and even affects the lifetime. This article focuses on heat management technology for high voltage high repetitive pulse generators. Firstly, the typical circuit topology of the high repetitive pulse generators was summarised. From the perspective of different application requirements, the demands of the heat management design were concluded. Moreover, the heat generation characteristics and difficulties of solid‐state high voltage high repetitive pulse generators were analysed. Then, the different state‐of‐art cooling techniques were reviewed, and their applicability and limitations for the high voltage high repetitive generators were discussed. Finally, a flow chart for heat management design was given.

This study investigated the effects of food culture on the economic and ecological development of rural rivers and adolescents’ intentions toward tourism in high-risk leisure environments. The study applied a mixed-methods design. A questionnaire was designed and distributed to recruited participants, and 900 responses were collected and analyzed, with SPSS 26.0 used to perform basic statistical validation and Pearson’s correlation analysis. Structured interviews were conducted to collect the opinions of experts, tourists, and residents of the investigated areas. A multivariate analysis was used to analyze the results, which revealed that superior economic, societal, and ecological development is associated with greater leisure, tourism, and consumption intentions. However, varying levels of environmental literacy among tourists can present challenges. Problems such as tourism waste; overdevelopment; loss of historic architectural features; and pollution of water, forests, and air may deter young tourists from revisiting an area and diminish their willingness to engage in and share leisure experiences.

Recent research has indicated that the Phyllagathis (raphides) clade (Sonerileae, Melastomataceae) is only distantly related to the type of Phyllagathis and should be separated as a distinct genus. Phylogeny of this clade is here reconstructed with expanded taxon sampling. Four strongly supported subclades have been identified. The possible affinities of taxa that were not sampled in the analysis are discussed, based on morphological data. Perilimnastes is resurrected as the generic name of the Phyllagathis (raphides) clade. A generic description, colour figures, map of distribution, a list of included species and a key are provided for Perilimnastes. Fifteen new combinations are made plus the description of a new species. As interpreted here, Perilimnastes consists of twenty species and two varieties.

Abstract Background New technologies have brought about a new age of technology-enabled aids that can equip informal carers with the relevant resources for better care. These include but are not limited to facilitating access to healthcare providers, knowledge of caring for persons living with dementia, and sources of support for carers’ well-being. This qualitative study explores barriers to using eHealth/mHealth platforms and perceived beneficial eHealth/mHealth platform features among informal carers of persons living with dementia. Methods An exploratory qualitative study design was employed. Semi-structured interviews were conducted among 29 informal carers of persons living with dementia in Singapore recruited via convenience and snowball sampling. The interviews were audio-recorded and transcribed verbatim. Thematic analysis was used to analyse the data. Results The participants in this study identified several barriers to using eHealth/mHealth platforms, including personal preference, apprehension, poor user experience and lack of skills. On the other hand, knowledge of dementia, caring for persons living with dementia and self-care, a list of resources, social support, location monitoring and alert systems, and the ability to manage appointments and transactions were valuable features for eHealth/mHealth platforms. Conclusions Despite the underutilisation of eHealth/mHealth platforms, carers expressed a keen interest in using them if they are functional and capable of reducing their care burden. The findings from this study can contribute to developing content and features for eHealth/mHealth interventions aimed at lightening carers’ burden in their day-to-day caring routine.

The crystallography of transformation products with different cooling rates has been investigated in a typical low-carbon alloy steel, and its effect on low-temperature impact toughness uniformity in the thickness direction of heavy steel plates has been elucidated. The results show that both the full lath martenite (LM) microstructure transformed at the cooling rate of 45 K s−1 and granular bainite (GB) + lath bainite (LB) + LM microstructure transformed at the cooling rates of 3∼6 K s−1 have higher density of high-angle grain boundaries (HAGBs). The density of HAGBs in the full GB microstructure transformed at the cooling rate of 0.5 K s−1 is the lowest, and that in the LB + LM microstructure transformed at the cooling rates of 15∼22 K s−1 is the middle. In the GB + LB + LM microstructure, the division of austenite by multi-stage transformation reduces the LB and LM transformation temperatures, contributing to a weakening of variant selection and a tendency to close-packed plane grouping. Therefore, the GB + LB + LM microstructure achieves the refinement degree similar to the full LM microstructure, but slightly higher than that of the LB + LM microstructure. For the 60 mm thick heavy steel plate with ultra-fast cooling, the cooling rate decreases from 41 K s−1 at the subsurface to 14 K s−1 at the 1/4-thickness and then to 4 K s−1 at the 1/2-thickness. The full LM microstructure, LB + LM microstructure, and GB + LB + LM microstructure are obtained in sequence, resulting in a more uniform density of HAGBs. Consequently, the relatively uniform impact toughness at 143 K in the thickness direction is achieved with a small difference of ∼30 J.

Objective In the present study, we aimed to investigate the effects of enzymolysis fermentation of Chinese herbal medicines (CHMs) on egg production performance, egg quality, lipid metabolism, serum reproductive hormone levels, and the mRNA expression of the ovarian hormone receptor of laying hens in the late-laying stage. Methods A total of 360 Hy-Line Brown laying hens (age, 390 days) were randomly categorized into four groups. Hens in the control (C) group were fed a basic diet devoid of CHMs, the crushed CHM (CT), fermented CHM (FC), and enzymatically fermented CHM (EFT) groups received diets containing 2% crushed CHM, 2% fermented CHM, and 2% enzymatically fermented CHM, respectively. Results Compared with crushed CHM, the acid detergent fiber, total flavonoids, and total saponins contents of fermented CHM showed improvement (p

Deficiency of TOM5, a mitochondrial protein, causes organizing pneumonia (OP) in mice. The clinical significance and mechanisms of TOM5 in the pathogenesis of OP remain elusive. We demonstrated that TOM5 was significantly increased in the lung tissues of OP patients, which was positively correlated with the collagen deposition. In a bleomycin-induced murine model of chronic OP, increased TOM5 was in line with lung fibrosis. In vitro, TOM5 regulated the mitochondrial membrane potential in alveolar epithelial cells. TOM5 reduced the proportion of early apoptotic cells and promoted cell proliferation. Our study shed light on the roles of TOM5 in OP.

Thioacetamide (TAA) within the liver generates hepatotoxic metabolites that can be induce hepatic fibrosis, similar to the clinical pathological features of chronic human liver disease. The potential protective effect of Albiflorin (ALB), a monoterpenoid glycoside found in Paeonia lactiflora Pall, against hepatic fibrosis was investigated. The mouse hepatic fibrosis model was induced with an intraperitoneal injection of TAA. Hepatic stellate cells (HSCs) were subjected to treatment with transforming growth factor-beta (TGF-β), while lipopolysaccharide/adenosine triphosphate (LPS/ATP) was added to stimulate mouse peritoneal macrophages (MPMs), leading to the acquisition of conditioned medium. For TAA-treated mice, ALB reduced ALT, AST, HYP levels in serum or liver. The administration of ALB reduced histopathological abnormalities, and significantly regulated the expressions of nuclear receptor-related 1 protein (NURR1) and the P2X purinoceptor 7 receptor (P2×7r) in liver. ALB could suppress HSCs epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) deposition, and pro-inflammatory factor level. ALB also remarkably up-regulated NURR1, inhibited P2×7r signaling pathway, and worked as working as C-DIM12, a NURR1 agonist. Moreover, deficiency of NURR1 in activated HSCs and Kupffer cells weakened the regulatory effect of ALB on P2×7r inhibition. NURR1-mediated inhibition of inflammatory contributed to the regulation of ALB ameliorates TAA-induced hepatic fibrosis, especially based on involving in the crosstalk of HSCs-macrophage. Therefore, ALB plays a significant part in the mitigation of TAA-induced hepatotoxicity this highlights the potential of ALB as a protective intervention for hepatic fibrosis.