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Studies investigating the relationship between dietary vitamin B1 intake and risk of Hyperuricemia (HU) are scarce, the present study aimed to examine the association of dietary vitamin B1 intake and HU among adults. This cross-sectional study included 5750 adults whose data derived from National Health and Nutrition Examination Survey (NHANES) from March 2017 to March 2020. The dietary intake of vitamin B1 was assessed using 24-h dietary recall interviews. The characteristics of study participants were grouped into five levels according to the levels of vitamin B1 quintile. Multivariate logistic regression analysis was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of HU, according to the vitamin B1 intake quintile for male and female separately. The dose–response relationship was determined by the restricted cubic spline (RCS). Smoothed curve fitting was used to assess serum uric acid concentration versus dietary vitamin B1 intake in the study population. The prevalence of hyperuricemia was 18.90% (20.15% and 17.79% for males and females, respectively) in the United States from March 2017 to March 2020. Multiple logistic regression analyses showed that in the male population, the HU ratio (OR) of vitamin B1 intake in Q2 to Q5 compared with the lowest quintile (Q1) was 0.75 (95% CI 0.52, 1.09), 0.70 (95% CI 0.48, 1.02), 0.66 (95% CI 0.44, 0.99) and 0.55 (95% CI 0.34, 0.90). The P for trend was 0.028. In women, the ORs for vitamin B1 intake Q2 to Q5 were 0.87 (95% CI 0.64, 1.19), 0.97 (0.68–1.38), 1.05 (0.69–1.60) and 0.75 (0.42–1.34), respectively. The P for trend was 0.876. The RCS curve revealed a linear relationship between vitamin B1 intake and the risk of hyperuricemia in men (P nonlinear = 0.401). Smoothed curve fitting demonstrated a negative association between vitamin B1 intake and serum uric acid concentration in men, whereas there was no significant association between dietary vitamin B1 intake and the risk of hyperuricemia in women. In the US adult population, dietary vitamin B1 intake was negatively associated with hyperuricemia in males. [ABSTRACT FROM AUTHOR]

Despite the success of immunotherapy in treating hepatocellular carcinoma (HCC), HCC remains a severe threat to health. Here, a crucial transcription factor, SOX12, is revealed that induces the immunosuppression of liver tumor microenvironment. Overexpressing SOX12 in HCC syngeneic models increases intratumoral regulatory T‐cell (Treg) infiltration, decreases CD8+T‐cell infiltration, and hastens HCC metastasis. Hepatocyte‐specific SOX12 knockout attenuates DEN/CCl4‐induced HCC progression and metastasis, whereas hepatocyte‐specific SOX12 knock‐in accelerates these effects. Mechanistically, SOX12 transcriptionally activates C‐C motif chemokine ligand 22 (CCL22) expression to promote the recruitment and suppressive activity of Tregs. Moreover, SOX12 transcriptionally upregulates CD274 expression to suppress CD8+T‐cell infiltration. Either knockdown of CCL22 or PD‐L1 dampens SOX12‐mediated HCC metastasis. Blocking of CC chemokine receptor 4 (CCR4), a receptor for CCL22, by inhibitor C‐021 or Treg‐specific knockout of CCR4 inhibits SOX12‐mediated HCC metastasis. Transforming growth factor‐β1 (TGF‐β1)/TGFβR1‐Smad2/3/4 is identified as a key upstream signaling for SOX12 overexpression in HCC cells. Combining C‐021 or TGFβR1 inhibitor galunisertib with anti‐PD‐L1 exhibits an enhanced antitumor effect in two HCC models. Collectively, the findings demonstrate that SOX12 contributes to HCC immunosuppression through the CCL22/CCR4‐Treg and PD‐L1‐CD8+T axes. Blocking of CCR4 or TGFβR1 improves the efficacy of anti‐PD‐L1 in SOX12‐mediated HCC. [ABSTRACT FROM AUTHOR]

Background: Aesthetic injections have become increasingly popular for maintaining a youthful appearance. However, with the rise of SARS-CoV-2, there have been concerns about potential complications. This study aims to summarize and understand the complications that occur in individuals who have received cosmetic injections after SARS-CoV-2 infection or vaccination. By doing so, we hope to provide recommendations to minimize these complications and ensure the safety of aesthetic treatments in the current COVID-19 era. Methods: The PRISMA guidelines, the Preferred Reporting Program for Systematic Reviews and Meta-Analyses, were used for this review. Databases including PubMed, EMBASE, Medline, Web of Science and ScienceDirect were searched. The last search time of each database was May 10, 2023. In addition, relevant references were manually searched. Results: A total of 26 studies containing 139 patients were searched. The complication with the highest percentage of reported patients was delayed inflammatory response (DIR) (n = 68; 48.92%), followed by diminished efficacy (n = 45; 32.37%) and filler reaction (n = 12; 8.63%). The remaining complications include hypersensitivity reactions, symptomatic hypercalcemia, sub-acute hypersensitive reactions, hyperalgesia, infection, fat necrosis and granulomatous reaction. Conclusions: Cosmetic injectable procedures are generally safe but may have adverse effects, particularly during the pandemic. It is important for individuals to fully understand these risks beforehand. Clinicians should be knowledgeable about adverse event mechanisms and management to prevent issues. Industry leaders should strengthen risk management efforts to ensure safe and steady development of cosmetic injections. Overall, a comprehensive understanding, effective communication and risk management are crucial for the safe use of cosmetic injectable procedures. Level of Evidence III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Cement is known to be brittle and usually reinforced with fibers. However, there is a lack of effective chemical bonding between organic fibers and inorganic cement, resulting in a weaker interfacial bonding strength. In this paper, amino hyperbranched polymer (HBP) was used to modify the surface of polyacrylonitrile (PAN) fibers, and then silica nanoparticles (SiO2 NPs) were grafted on the surface of modified PAN fibers to realize the inorganic treatment of organic fibers. The modified PAN fibers applied to cement concrete can significantly enhance the interfacial strength between the fibers and cement. The morphology and chemical composition of the modified PAN fibers were characterized by scanning electron microscope, atomic force microscope, electron energy dispersive spectroscopy, and Fourier transform infrared spectroscopy, and the influence of grafting conditions on grafting effect was analyzed. The results show that SiO2 NPs were evenly distributed on the surface of PAN fiber. When SiO2 NPs concentration was 4%, grafting temperature was 50°C, and grafting time was 4 h, the grafting degree of SiO2 NPs grafted PAN fiber can reach to 1.4%. After coating with SiO2 NPs, the pullout bonding strength of the PAN fiber was increased from 5.5 to 6.5 cN. [ABSTRACT FROM AUTHOR]

Background: NUP98 rearrangements (NUP98-r) are rare but overrepresented mutations in pediatric acute myeloid leukemia (AML) patients. NUP98-r is often associated with chemotherapy resistance and a particularly poor prognosis. Therefore, characterizing pediatric AML with NUP98-r to identify aberrations is critically important. Methods: Here, we retrospectively analyzed the clinicopathological features, genomic and transcriptomic landscapes, treatments, and outcomes of pediatric patients with AML. Results: Nine patients with NUP98-r mutations were identified in our cohort of 142 patients. Ten mutated genes were detected in patients with NUP98-r. The frequency of FLT3-ITD mutations differed significantly between the groups harboring NUP98-r and those without NUP98-r (P = 0.035). Unsupervised hierarchical clustering via RNA sequencing data from 21 AML patients revealed that NUP98-r samples clustered together, strongly suggesting a distinct subtype. Compared with that in the non-NUP98-r fusion and no fusion groups, CMAHP expression was significantly upregulated in the NUP98-r samples (P < 0.001 and P = 0.001, respectively). Multivariate Cox regression analyses demonstrated that patients harboring NUP98-r (P < 0.001) and WT1 mutations (P = 0.030) had worse relapse-free survival, and patients harboring NUP98-r (P < 0.008) presented lower overall survival. Conclusions: These investigations contribute to the understanding of the molecular characteristics, risk stratification, and prognostic evaluation of pediatric AML patients. [ABSTRACT FROM AUTHOR]

Background: Alanine aminotransferase (ALT) is widely used to screen patients with hepatic diseases. However, the current reference ranges (< 50 U/L) were developed by laboratories and have not been validated in populations with a large number of healthy individuals. Methods: This study collected venous blood and anthropometric data from a total of 13,287 healthy children aged 3 months to 18 years who underwent routine physical examinations in the Department of Pediatric Healthcare. We applied the least mean square algorithm to establish age- and sex-related reference percentiles of serum levels of transaminases. For validation, we recruited 4276 children and adolescents with obesity/overweight who underwent evaluation and metabolic tests in the hospital. Using receiver operating characteristic curves, we determined age- and sex-specific upper limit percentiles of liver enzymes for fatty liver diseases. Results: This study revealed a significant correlation between serum transaminase levels and age and sex (P < 0.01). These transaminase levels exhibited age- and sex-specific patterns. Among individuals in the non-alcoholic fatty liver disease (NAFLD) cohort, elevated ALT levels displayed a positive association with clinical markers of disease severity, including homeostatic model assessment of insulin resistance, waist–hip ratio, and serum uric acid levels (P < 0.01). According to the receiver operating characteristic curves, ALT levels at the 92.58th percentile for boys and the 92.07th percentile for girls yielded the highest accuracy and specificity. Conclusions: This study provides age- and sex-specific reference ranges for ALT, aspartate aminotransferase, and γ-glutamyltransferase in Chinese children and adolescents, making it the largest population study to date. Furthermore, the study establishes a precise upper limit for ALT levels, facilitating their use in NAFLD screening. CoEzBqA-ybMqMjKK3XNXmu Video Abstract [ABSTRACT FROM AUTHOR]

Chinese Olea europaea leaves, rich in verbascosides, were extracted using ultrasound-assisted extraction (UAE) and wall-breaking extraction (WBE) with deep eutectic solvents (Optimal UAE: 55 min, 200 mL/g liquid–solid ratio, 20% moisture, yielding 206.23 ± 0.58 mg GAE/g total phenolic content (TPC) and 1.59 ± 0.04% verbascoside yield (VAY); Optimal WBE: 140 s, 210 mL/g, 30% moisture, giving 210.69 ± 0.97 mg GAE/g TPC and 1.33 ± 0.2% VAY). HPLC analysis showed that young leaves accumulated higher TPC and phenolic compounds. Among the five olive varieties, Koroneiki and Chemlal showed the highest TPC in UAE, while Arbosana and Chemlal excelled in WBE. WBE yielded a higher TPC and rutin, whereas UAE marginally increased other phenolics. Additionally, the DPPH• assay showed that WBE-extracted verbascoside-rich extracts (VREs) of Chemlal exhibited high antioxidant activity (EC50 of 57 mg/mL), but Koroneiki-VREs exhibited lower activity against the ABTS•+ radical (EC50 of 134 mg/mL). Remarkably, the UAE/WBE-extracted Chemlal-VREs promoted the normal esophageal Het-1A cell line at 25 μg/mL for 24 h; yet, the esophageal cancer Eca-109 cells were sensibly inhibited, especially at 50 μg/mL; and the cell viability decreased dramatically. The results confirmed WBE as a relatively efficient method, and the Chemlal variety may be an excellent source of verbascoside. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to optimize the formulation of a C60-modified self-microemulsifying drug delivery system loaded with triptolide (C60-SMEDDS/TP) and evaluate the cytoprotective effect of the C60-SMEDDS/TP on normal human cells. Results: The C60-SMEDDS/TP exhibited rapid emulsification, an optimal particle size distribution of 50 ± 0.19 nm (PDI 0.211 ± 0.049), and a near-neutral zeta potential of −1.60 mV. The release kinetics of TP from the C60-SMEDDS/TP exhibited a sustained release profile and followed pseudo-first-order release kinetics. Cellular proliferation and apoptosis analysis indicated that the C60-SMEDDS/TP (with a mass ratio of TP: DSPE-PEG-C60 = 1:10) exhibited lower toxicity towards L02 and GES-1 cells. This was demonstrated by a higher IC50 (40.88 nM on L02 cells and 17.22 nM on GES-1 cells) compared to free TP (21.3 nM and 11.1 nM), and a lower apoptosis rate (20.8% on L02 cells and 26.3% on GES-1 cells, respectively) compared to free TP (50.5% and 47.0%) at a concentration of 50 nM. In comparison to the free TP group, L02 cells and GES-1 cells exposed to the C60-SMEDDS/TP exhibited a significant decrease in intracellular ROS and an increase in mitochondrial membrane potential (ΔψM). On the other hand, the C60-SMEDDS/TP demonstrated a similar inhibitory effect on BEL-7402 cells (IC50 = 28.9 nM) and HepG2 cells (IC50 = 107.6 nM), comparable to that of the free TP (27.2 nM and 90.4 nM). The C60-SMEDDS/TP group also exhibited a similar intracellular level of ROS and mitochondrial membrane potential compared to the SMEDDS/TP and free TP groups. Method: Fullerenol-Grafted Distearoyl Phosphatidylethanolamine-Polyethylene Glycol (DSPE-PEG-C60) was synthesized and applied in the self-microemulsifying drug delivery system. The C60-SMEDDS/TP was formulated using Cremophor EL, medium-chain triglycerides (MCT), PEG-400, and DSPE-PEG-C60, and loaded with triptolide (TP). The toxicity and bioactivity of the C60-SMEDDS/TP were assessed using normal human liver cell lines (L02 cells), normal human gastric mucosal epithelial cell lines (GES-1 cells), and liver cancer cell lines (BEL-7402 cells and HepG2 cells). The production of reactive oxygen species (ROS) after the C60-SMEDDS/TP treatment was assessed using 2′,7′-dichlorofluorescein diacetate (DCFDA) staining. The alterations in mitochondrial membrane potential (ΔψM) were assessed by measuring JC-1 fluorescence. Conclusions: The cytoprotection provided by the C60-SMEDDS/TP favored normal cells (L02 and GES-1) over tumor cells (BEL-7402 and HepG2 cells) in vitro. This suggests a promising approach for the safe and effective treatment of TP. [ABSTRACT FROM AUTHOR]

Polyelectrolyte brushes (PEBs) are commonly used to modify surface that have attracted great research interest. The dielectric permittivity of the grafted surface is typically significantly different from that of solution, which results in surface polarization (SP) effect with a jump of electric field. It is thus important to study how SP alters the PEB's structure and properties. In this work, the SP effects on PEB structure was studied using a statistical thermodynamic theory. The free energy functional to describe SP effect was constructed by using the image-charge method. Meanwhile, the electrostatic potential was solved from a modified Poisson-Boltzmann equation taking the ion solvation effect into consideration. In the absence of SP, the thickness of PEB exhibited a continuous collapse transition when decreasing the solvent quality. In the presence of SP, the collapse became a jump-like transition. Free energy analysis showed that the long-range Coulombic interaction dominated the transition because of the enhanced counterion condensation in the presence of SP. The theory provides an effective tool to study SP effect on PEBs, and the results explain the underlying physics in PEB collapse transition. [ABSTRACT FROM AUTHOR]

In order to ascertain the impact of working water flow rate and inlet pressure on the performance of the liquid–gas jet pump with square nozzle, the pumping volume ratio and efficiency of the liquid–gas jet pump with square nozzle were experimentally investigated at different inlet pressures and working water flow rates. Furthermore, the internal flow characteristics of the liquid–gas jet pump with square nozzle were explored through the utilization of visualization technology in the self-designed square-nozzle liquid–gas jet pump experimental setup. The findings indicate that the pumping ratio of the liquid–gas jet pump increases in conjunction with an elevation in the inlet pressure. Liquid–gas jet pump efficiency is higher at lower inlet pressures, up to 42.48%, and drops rapidly as inlet pressure increases. The pumping volume ratio of the liquid–gas jet pump increases significantly as the working water flow rate increases, and the working water flow rate exerts a minimal effect on the working efficiency of the liquid–gas jet pump. In the context of extreme vacuum conditions, a considerable number of droplets undergo substantial reflux in the posterior section of the throat, with a notable absence of bubbles in the diffusion tube. The size and number of bubbles diminish gradually along the axial direction. The objective of this paper is to provide a reference point for determining the optimal operational parameters for a square-nozzle liquid–gas jet pump in a practical context. [ABSTRACT FROM AUTHOR]

Summary: Higher‐order chromatin structure is critical for regulation of gene expression. In plants, light profoundly affects the morphogenesis of emerging seedlings as well as global gene expression to ensure optimal adaptation to environmental conditions. However, the changes and functional significance of chromatin organization in response to light during seedling development are not well documented. We constructed Hi‐C contact maps for the cotyledon, apical hook and hypocotyl of soybean subjected to dark and light conditions. The resulting high‐resolution Hi‐C contact maps identified chromosome territories, A/B compartments, A/B sub‐compartments, TADs (Topologically Associated Domains) and chromatin loops in each organ. We observed increased chromatin compaction under light and we found that domains that switched from B sub‐compartments in darkness to A sub‐compartments under light contained genes that were activated during photomorphogenesis. At the local scale, we identified a group of TADs constructed by gene clusters consisting of different numbers of Small Auxin‐Upregulated RNAs (SAURs), which exhibited strict co‐expression in the hook and hypocotyl in response to light stimulation. In the hypocotyl, RNA polymerase II (RNAPII) regulated the transcription of a SAURs cluster under light via TAD condensation. Our results suggest that the 3D genome is involved in the regulation of light‐related gene expression in a tissue‐specific manner. [ABSTRACT FROM AUTHOR]

Chemical warfare agents represent a severe threat to mankind and their efficient decontamination is a global necessity. However, traditional disposal strategies have limitations, including high energy consumption, use of aggressive reagents and generation of toxic byproducts. Here, inspired by the compartmentalized architecture and detoxification mechanism of bacterial micro-compartments, we constructed oil-in-water Pickering emulsion droplets stabilized by hydrogen-bonded organic framework immobilized cascade enzymes for decontaminating mustard gas simulant (2-chloroethyl ethyl sulfide, CEES) under sweet conditions. Two exemplified droplet systems were developed with two-enzyme (glucose oxidase/chloroperoxidase) and three-enzyme (invertase/glucose oxidase/chloroperoxidase) cascades, both achieving over 6-fold enhancement in decontamination efficiency compared with free enzymes and >99% selectivity towards non-toxic sulfoxide. We found that the favored mass transfer of sugars and CEES from their respective phases to approach the cascade enzymes located at the droplet surface and the facilitated substrate channeling between proximally immobilized enzymes were key factors in augmenting the decontamination efficacy. More importantly, the robustness of immobilized enzymes enabled easy reproduction of both the droplet formation and detoxification performance over 10 cycles, following long-term storage and in far-field locations. [ABSTRACT FROM AUTHOR]

Chemerin is an adipokine that contributes to metabolism regulation. Nucleus tractus solitarius (NTS) is the first relay station in the brain for accepting various visceral afferent activities for regulating cardiovascular activity. However, the roles of chemerin in the NTS in regulating sympathetic activity and blood pressure are almost unknown. This study aimed to determine the role and potential mechanism of chemerin in the NTS in modulating sympathetic outflow and blood pressure. Bilateral NTS microinjections were performed in anaesthetized adult male Sprague–Dawley rats. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were continuously recorded. Chemerin and its receptor chemokine‐like receptor 1 (CMKLR1) were highly expressed in caudal NTS (cNTS). Microinjection of chemerin‐9 to the cNTS increased RSNA, MAP and HR, which were prevented by CMKLR1 antagonist α‐NETA, superoxide scavenger tempol or N‐acetyl cysteine, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors diphenyleneiodonium or apocynin. Chemerin‐9 increased superoxide production and NADPH oxidase activity in the cNTS. The increased superoxide production induced by chemerin‐9 was inhibited by α‐NETA. The effects of cNTS microinjection of chemerin‐9 on the RSNA, MAP and HR were attenuated by the pretreatment with paraventricular nucleus (PVN) microinjection of NMDA receptor antagonist MK‐801 rather than AMPA/kainate receptor antagonist CNQX. These results indicate that chemerin‐9 in the NTS increases sympathetic outflow, blood pressure and HR via CMKLR1‐mediated NADPH oxidase activation and subsequent superoxide production in anaesthetized normotensive rats. Glutamatergic inputs in the PVN are needed for the chemerin‐9‐induced responses. [ABSTRACT FROM AUTHOR]

Deep graph clustering (DGC) has been a promising method for clustering graph data in recent years. However, existing research primarily focuses on optimizing clustering outcomes by improving the quality of embedded representations, resulting in slow-speed complex models. Additionally, these methods do not consider changes in node similarity and corresponding adjustments in the original structure during the iterative optimization process after updating node embeddings, which easily falls into the representation collapse issue. We introduce an Efficient Graph Auto-Encoder (EGAE) and a dynamic graph weight updating strategy to address these issues, forming the basis for our proposed Fast DGC (FastDGC) network. Specifically, we significantly reduce feature dimensions using a linear transformation that preserves the original node similarity. We then employ a single-layer graph convolutional filtering approximation to replace multiple layers of graph convolutional neural network, reducing computational complexity and parameter count. During iteration, we calculate the similarity between nodes using the linearly transformed features and periodically update the original graph structure to reduce edges with low similarity, thereby enhancing the learning of discriminative and cohesive representations. Theoretical analysis confirms that EGAE has lower computational complexity. Extensive experiments on standard datasets demonstrate that our proposed method improves clustering performance and achieves a speedup of 2–3 orders of magnitude compared to state-of-the-art methods, showcasing outstanding performance. The code for our model is available at https://github.com/Marigoldwu/FastDGC. Furthermore, we have organized a portion of the DGC code into a unified framework, available at https://github.com/Marigoldwu/A-Unified-Framework-for-Deep-Attribute-Graph-Clustering. [ABSTRACT FROM AUTHOR]

Background: The combination of Sorafenib and transcatheter arterial chemoembolization (TACE) exhibits limited efficacy in the treatment of certain advanced hepatocellular carcinomas (HCC), and the molecular mechanisms underlying resistance to this combination remain unclear. Objective: This study aims to underscore the distinctive contribution of GeoMx DSP technology in elucidating the molecular intricacies of HCC resistance to the Sorafenib and TACE combination. Methods: Patients with advanced HCC during the waiting period before liver transplantation were classified into sensitive and resistant groups based on their response to Sorafenib and TACE combination therapy. Employing GeoMx DSP technology for comprehensive gene expression profiling, we identified pivotal molecular targets linked to resistance against combination therapy. Results: The investigation scrutinized intra-tumoral and inter-individual variances, unveiling a spectrum of crucial molecular targets, such as PLG, PLVAP, immunoglobulin genes, ORM1, and NR4A1, among others. Additionally, we explored signaling pathways associated with treatment responsiveness, including the PPAR signaling pathway. Notably, we emphasized the significance of the immune microenvironment characterized by heightened SPP1 expression in HCC resistance to combination therapy. In the resistant group, SPP1+ tumor-associated macrophage (TAM) infiltration was notably pronounced (p = 0.037), while T-cell depletion showed a mitigated presence (p = 0.013). Conclusion: The study reveals intra- and inter-individual heterogeneity in HCC that is differentially responsive to the combination of Sorafenib and TACE, highlighting multiple key molecular targets associated with treatment resistance. The immune microenvironment is important, and in particular, SPP1+ TAM infiltration may play a key role. Meanwhile, the introduction of immunotherapy in patients resistant to combination therapy may lead to positive results. [ABSTRACT FROM AUTHOR]

Background: There are serious complications associated with hyaluronic acid (HA) facial injections, including vision impairment due to retinal artery ischemia. In this study, we put forth a clinically relevant model of retinal ischemia and reperfusion in rabbit. We used this to verify the efficacy of hyaluronidase intra-artery thrombolysis in the treatment of hyaluronic acid-induced retinal artery occlusion. Methods: Retinal artery ischemia was induced by injecting HA into the ophthalmic artery (OA) of adult chinchilla rabbit, and reperfusion was achieved by intra-artery thrombolysis therapy with hyaluronidase following 60 min and 4 h of occlusion. Digital subtraction angiography (DSA) and fundus fluorescein angiography (FFA) were used to evaluate blood flow in the retina. Electroretinogram (ERG), hematoxylin and eosin staining and transmission electron microscope were used to evaluate the structure and function of the retina after ischemia and reperfusion following 60 min and 4 h of occlusion. Results: DSA and FFA images confirmed occlusion of the ophthalmic and central retinal arteries, as well as reperfusion after hyaluronidase thrombolysis. ERG indicated retinal dysfunction following ischemia, and thrombolysis partially rescued its impairment following 4 h of occlusion. Hematoxylin and eosin staining and TUNEL staining revealed ischemia-induced histological damages in the retina at different time windows, and hyaluronidase thrombolysis partially mitigated these damages. Conclusions: We report a method to establish a HA-induced retinal artery occlusion animal model. Hyaluronidase intra-artery thrombolysis was used to recanalize the embolized OA at different time points. Using our method, we achieved retinal reperfusion, and an improvement was observed in the visual function of rabbits after hyaluronidase thrombolysis following 4 h of occlusion. We believe that hyaluronidase intra-artery thrombolysis is an effective method to treat HA-induced retinal artery occlusion in clinic. Level of Evidence II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to preliminarily investigate the association and possible mechanisms between Helicobacter. pylori (H. pylori) infection and type 2 diabetes mellitus (T2DM) through data collection, statistical analysis, and bioinformatics analysis. Methods: A retrospective cohort study, including a total of 4406 participants who attended annual health checkups at Xian GEM Flower Changqing Hospital, was conducted to explore the correlation between the incidence of T2DM and H. pylori infection. To uncover the potential mechanisms underlying the interaction between the two diseases, differentially expressed genes (DEGs) common to T2DM and H. pylori infection were identified using the GEO database and Venn diagrams. These DEGs were then analyzed through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) analysis. Results: In total, 2053 participants were classified into the H. pylori-positive group and 2353 into the H. pylori-negative group. H. pylori infection was associated with a higher risk of T2DM occurrence (adjusted HR 1.59; 95% CI 1.17–2.15, P = 0.003). The average disease-free survival time was 34.81 months (95% CI 34.60-35.03 months) in the H. pylori positive group and 35.42 months (95% CI 35.28–35.56 months) in the H. pylori negative group. Multivariate analysis and subgroup analyses also showed that H. pylori infection increased the risk of developing T2DM. A total of 21 DEGs between T2DM and H. pylori infection were identified and enriched in 7 signaling pathways, indicating specific protein interactions. Conclusions: The prevalence of T2DM was associated with H. pylori infection. T2DM and H. pylori infection may interact with each other through metabolic and immune pathways. [ABSTRACT FROM AUTHOR]

Superconductivity in a highly correlated kagome system has been theoretically proposed for years (refs. 1–5), yet the experimental realization is hard to achieve6,7. The recently discovered vanadium-based kagome materials8, which exhibit both superconductivity9–11 and charge-density-wave orders12–14, are nonmagnetic8,9 and weakly correlated15,16. Thus these materials are unlikely to host the exotic superconductivity theoretically proposed. Here we report the discovery of a chromium-based kagome metal, CsCr3Sb5, which is contrastingly featured with strong electron correlations, frustrated magnetism and characteristic flat bands close to the Fermi level. Under ambient pressure, this kagome metal undergoes a concurrent structural and magnetic phase transition at 55 K, with a stripe-like 4a0 structural modulation. At high pressure, the phase transition evolves into two transitions, possibly associated with charge-density-wave and antiferromagnetic spin-density-wave orderings. These density-wave-like orders are gradually suppressed with pressure and, remarkably, a superconducting dome emerges at 3.65–8.0 GPa. The maximum of the superconducting transition temperature, Tcmax = 6.4 K, appears when the density-wave-like orders are completely suppressed at 4.2 GPa, and the normal state exhibits a non-Fermi-liquid behaviour, reminiscent of unconventional superconductivity and quantum criticality in iron-based superconductors17,18. Our work offers an unprecedented platform for investigating superconductivity in correlated kagome systems.The emergence of superconductivity under pressure is reported in a chromium-based kagome metal, CsCr3Sb5, which has strong electron correlations, frustrated magnetism and characteristic flat bands close to the Fermi level. [ABSTRACT FROM AUTHOR]

Background: Spontaneous Coronary Artery Dissection (SCAD) is an acute coronary event of uncertain origin. SCAD occurs when the coronary artery wall dissects non-traumatically and non-atherosclerotically, leading to the formation of an intramural hematoma or intimal tear, ultimately compressing and restricting the true lumen, or even occluding it. The management of SCAD remains controversial despite modern imaging techniques. In addition to supportive drug therapy, percutaneous coronary intervention (PCI) is another option that can be used as an effective treatment modality. Case presentation: We describe A 50-year-old male with SCAD presented to the hospital emergency department complaining of chest pain. Coronary angiography incidentally showed spiral dissection from the proximal to distal right coronary artery (RCA). Three overlapping coroflex stents were deployed from the distal to the proximal RCA. Conclusions: To stabilize the coronary artery in Acute Coronary Syndrome (ACS) patients due to SCAD, prompt interventions such as stenting and angioplasty are needed. However, it is necessary to pay attention to the clinical condition of patients and quick diagnosis for the recovery of patients and reduction of complications. [ABSTRACT FROM AUTHOR]

The electrosynthesis of valuable chemical feedstocks and fuels through the CO2 reduction reaction (CO2RR) provides a promising approach to solve the global warming problem and the energy crisis. Numerous studies have been devoted to developing electrocatalysts; however, few studies focus on Pb actives sites as well as the defect engineering of active sites. Herein, an O vacancy-rich PbCO3 electrocatalyst (O-PbCO3) derived Pb2(OH)2(CH3COO)2 precatalyst is reported. X-ray photoelectron spectroscopy (XPS) and electron paramagnetic resonance (EPR) results prove the existence of O vacancies while the X-ray absorption fine structure (XAFS) results reveal the distorted structure of the O-PbCO3. Electrochemical measurements of the O-PbCO3 sample exhibit a remarkable selectivity and activity towards formate of over 90% in a wide range of current densities of 50 to 400 mA cm−2. Further in situ surface-enhanced infrared absorption spectroscopy (SEIRAS) characterization indicates that the O vacancies can optimize the adsorption of the *HCOO intermediate for enhanced CO2RR performance. [ABSTRACT FROM AUTHOR]

Background: TSPAN7 is an important factor in tumor progression. However, the precise function of TSPAN7 and its role in pan-cancer are not clear. Methods: Based on Xinhua cohort incorporating 370 patients with kidney neoplasm, we conducted differential expression analysis by immunohistochemistry between tumor and normal tissues, and explored correlations of TSPAN7 with patients' survival. Subsequently, we conducted a pan-cancer study, and successively employed differential expression analysis, competing endogenous RNA (ceRNA) analysis, protein-protein interaction (PPI) analysis, correlation analysis of TSPAN7 with clinical characteristics, tumor purity, tumor genomics, tumor immunity, and drug sensitivity. Last but not least, gene set enrichment analysis was applied to identify enriched pathways of TSPAN7. Results: In Xinhua cohort, TSPAN7 expression was significantly up-regulated (P-value = 0.0019) in tumor tissues of kidney neoplasm patients. High TSPAN7 expression was associated with decreases in overall survival (OS) (P-value = 0.009) and progression-free survival (P-value = 0.009), and it was further revealed as an independent risk factor for OS (P-value = 0.0326, HR = 5.66, 95%CI = 1.155–27.8). In pan-cancer analysis, TSPAN7 expression was down-regulated in most tumors, and it was associated with patients' survival, tumor purity, tumor genomics, tumor immunity, and drug sensitivity. The ceRNA network and PPI network of TSPAN7 were also constructed. Last but not least, the top five enriched pathways of TSPAN7 in various tumors were identified. Conclusion: TSPAN7 served as a promising biomarker of various tumors, especially kidney neoplasms, and it was closely associated with tumor purity, tumor genomics, tumor immunology, and drug sensitivity in pan-cancer level. [ABSTRACT FROM AUTHOR]

Background: Chitinase-3 like-protein-1 (CHI3L1) is a member of the mammalian chitinase-like proteins and elevated serum CHI3L1 level has been proved to be associated with poor prognosis in hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between serum CHI3L1 levels and body composition parameters in patients with HCC after liver transplantation (LT). Methods: This retrospective study enrolled 200 patients after LT for HCC. Blood samples were collected and serum concentrations of CHI3L1 were measured by enzyme-linked immunosorbent assay. Computer tomography (CT) were used to estimate skeletal muscle and adipose tissue mass. Spearman's rank correlation test was performed to assess associations between serum CHI3L1 levels and these body composition parameters. A Cox proportional-hazards regression model was performed to identify independent prognostic factors. Overall survival (OS) and recurrence-free survival (RFS) curves were constructed using the Kaplan-Meier method and compared by the log-rank test. Results: Total 71 patients (35.5%) were diagnosed with myosteatosis according to skeletal muscle radiation attenuation (SMRA). The 5-year OS rates were 66.9% in non-myosteatosis group, significantly higher than 49.5% in myosteatosis group (p = 0.025), while the RFS of myosteatosis group (5-year RFS: 52.6%) or non-myosteatosis group (5-year RFS: 42.0%) shown no significant difference (p = 0.068). The serum CHI3L1 level were significantly negative correlated with SMRA (r = -0.3, p < 0.001). Interestingly, in patients with myosteatosis, Kaplan-Meier analysis revealed that elevated serum CHI3L1 levels were associated with worse OS (p < 0.001) and RFS (p = 0.047). However, in patients without myosteatosis, Kaplan-Meier analysis found elevated serum CHI3L1 levels were not associated with OS (p = 0.070) or RFS (p = 0.104). Conclusions: Elevated CHI3L1 was negatively correlated with SMRA, and predicted poorer prognosis in Chinese population after LT for HCC, especially in those patients with concomitant myosteatosis. Monitoring serum CHI3L1 can predict prognosis and effectively guide individual nutrition intervention. [ABSTRACT FROM AUTHOR]

Background: TSPAN7 is an important factor in tumor progression. However, the precise function of TSPAN7 and its role in pan-cancer are not clear. Methods: Based on Xinhua cohort incorporating 370 patients with kidney neoplasm, we conducted differential expression analysis by immunohistochemistry between tumor and normal tissues, and explored correlations of TSPAN7 with patients' survival. Subsequently, we conducted a pan-cancer study, and successively employed differential expression analysis, competing endogenous RNA (ceRNA) analysis, protein-protein interaction (PPI) analysis, correlation analysis of TSPAN7 with clinical characteristics, tumor purity, tumor genomics, tumor immunity, and drug sensitivity. Last but not least, gene set enrichment analysis was applied to identify enriched pathways of TSPAN7. Results: In Xinhua cohort, TSPAN7 expression was significantly up-regulated (P-value = 0.0019) in tumor tissues of kidney neoplasm patients. High TSPAN7 expression was associated with decreases in overall survival (OS) (P-value = 0.009) and progression-free survival (P-value = 0.009), and it was further revealed as an independent risk factor for OS (P-value = 0.0326, HR = 5.66, 95%CI = 1.155–27.8). In pan-cancer analysis, TSPAN7 expression was down-regulated in most tumors, and it was associated with patients' survival, tumor purity, tumor genomics, tumor immunity, and drug sensitivity. The ceRNA network and PPI network of TSPAN7 were also constructed. Last but not least, the top five enriched pathways of TSPAN7 in various tumors were identified. Conclusion: TSPAN7 served as a promising biomarker of various tumors, especially kidney neoplasms, and it was closely associated with tumor purity, tumor genomics, tumor immunology, and drug sensitivity in pan-cancer level. [ABSTRACT FROM AUTHOR]

In mass production, injection molding plays a vital role in manufacturing various parts with complex settings. As perfluoroalkoxy alkane (PFA) injection‐molded products are widely used in immersion system, dimensional quality needs more attention. However, there is limited research on the dimension defects of PFA injection‐molded products. This study focused on the influence of mold design and process parameters on PFA part shrinkage, using mold flow simulation and orthogonal testing separately. Several gate locations and sizes were simulated to minimize shrinkage in mold design. Displacements varied with gate locations, and shrinkage decreased with larger gate sizes. The Taguchi method analyzed process parameters' impact on shrinkage. The results indicated that the injection rate had the most significant effect on the shrinkage of tube length, while melt temperature, holding pressure, and screw speed affected the shrinkage of tubes' outside diameter. Different flow directions exhibited variance in shrinkage. Using max–min normalization, the two shrinkage values reached 0.00972, whereas the smallest value obtained in the orthogonal experiment was 0.1545 in run 3. Thus, optimizing mold design and process parameters were two effective methods to reduce shrinkage. This study reduced shrinkage and improved the quality of PFA injection molding parts for semiconductor systems. [ABSTRACT FROM AUTHOR]

Kombucha is a well-known fermented beverage traditionally made from black tea infusion. Recent studies have focused on finding alternative materials to create novel kombucha beverages with various health benefits. In this study, we prepared and evaluated two novel kombucha beverages using Rhodiola rosea and Salvia miltiorrhiza as materials. The effects of fermentation with the residue of these plants on the kombucha were also investigated. The antioxidant activities, total phenolic contents, and concentrations of the bioactive compounds of the kombucha beverages were determined by the Trolox equivalent antioxidant capacity test, ferric-reducing antioxidant power test, Folin–Ciocalteu method, and high-performance liquid chromatography, respectively. The results revealed that the kombucha beverages made with Rhodiola rosea and Salvia miltiorrhiza had strong antioxidant capacities and abundant phenolic contents. Additionally, the kombucha fermented with Rhodiola rosea residue had higher FRAP, TEAC and TPC values than that fermented without residue. On the other hand, the Salvia miltiorrhiza kombucha fermented with residue had similar FRAP and TEAC values but lower TPC values compared to that fermented without residue. The correlation analysis showed that gallic acid, salidroside, and tyrosol were responsible for the antioxidant abilities and total phenolic contents of the Rhodiola rosea kombucha, and salvianolic acid A and salvianolic acid B contributed to the antioxidant abilities of the Salvia miltiorrhiza kombucha. Furthermore, the kombucha fermented with Rhodiola rosea residue had the highest sensory scores among the kombucha beverages studied. These findings suggest that Rhodiola rosea and Salvia miltiorrhiza are suitable for making novel kombucha beverages with strong antioxidant abilities and abundant phenolic contents, which can be used in preventing and managing oxidative stress-related diseases. [ABSTRACT FROM AUTHOR]

Background: This study aims to evaluate the association of metabolic syndrome (MetS) with the risk of all-cause mortality in elderly patients with acute respiratory distress syndrome (ARDS). Methods: Elderly ARDS patients (≥ 65 years) enrolled from our hospital between January 2018 and July 2023 were divided into the MetS group or the non-MetS group. The outcomes were 28-day and 90-day all-cause mortality rates in the total population and two subgroups stratified by age (65–75 years and ≥ 75 years). Multivariate Cox regression was employed to assess the association of MetS with all-cause mortality, after controlling for potential cofounding factors. Results: A total of 946 patients were divided into the MetS group (n = 410) or the non-MetS group (n = 536). The 28-day and 90-day all-cause mortality rates were significantly higher for MetS group compared to non-MetS group in the total population and two subgroups (all P < 0.01). Multivariate Cox regression indicated that MetS was significantly associated with a higher risk of 90-day all-cause mortality in the total population (HR = 1.62, 95% CI: 1.22–2.15; P < 0.01), and subgroups of patients aged 65–75 years (HR = 1.52, 95% CI: 1.04–2.21; P = 0.03) and ≥ 75 years (HR = 1.90, 95% CI: 1.23–2.94; P < 0.01). Moreover, with each MetS criterion added from 0 to 1 to 2, 3, and 4 of 4 criteria, both 28-day and 90-day all-cause mortality rates significantly increased (both P < 0.01). Conclusion: MetS was associated with higher risks of 28-day and 90-day all-cause mortality in elderly patients with ARDS. [ABSTRACT FROM AUTHOR]

Although immune checkpoint inhibitors (anti-PD-1 antibody, anti-PD-L1 antibody, and anti-CTLA-4 antibody) have displayed considerable success in the treatment of malignant tumors, the therapeutic effect is still unsatisfactory for a portion of patients. Therefore, it is imperative to develop strategies to enhance the effect of these ICIs. Increasing evidence strongly suggests that the key to this issue is to transform the tumor immune microenvironment from a state of no or low immune infiltration to a state of high immune infiltration and enhance the tumor cell-killing effect of T cells. Therefore, some combination strategies have been proposed and this review appraise a summary of 39 strategies aiming at enhancing the effectiveness of ICIs, which comprise combining 10 clinical approaches and 29 foundational research strategies. Moreover, this review improves the comprehensive understanding of combination therapy with ICIs and inspires novel ideas for tumor immunotherapy. [ABSTRACT FROM AUTHOR]

A facile strategy to construct superhydrophobic coatings was carried out by one‐pot process using novel nano zero‐valent iron and hydrogen peroxide as trigger in ethanol and Tris buffer mixed system containing dopamine and 1H,1H,2H,2H‐perfluorodecanethiol (PFDT) for the first time. The polydopamine (PDA) modified by PFDT composite coating can be deposited onto various substrates including glass slides, polyurethane sheets, polytetrafluoroethylene wafers, 304 stainless steel sheets, and polyurethane sponges, revealing excellent hydrophobicity with the water contact angles from 157.1° to 162.2° and the sliding angle lower than 1°. The flourier transformed infrared spectroscopy and x‐ray photoelectron spectroscopy information of the composite coating demonstrated the successful covalent interaction between catechol group in PDA and thiol group of PFDT via Michael addition reaction. As‐prepared PFDT/PDA composite coatings exhibited enhanced chemical stability in highly acidic solutions for 6 days, alkaline aqueous solutions for 5 days, salty solutions (3.5 wt%) for 28 days, and polar organic solvents for 24 h, respectively, as well as resistance to algae adhesion. The excellent corrosion resistance and chemical stability of the composite coating and their simple, time saving and inexpensive construction process are expected to be widely applied in various areas, including marine anti‐corrosion, anti‐fouling, and oil–water separation. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic esophagitis is a chronic inflammatory disorder of the esophagus. This real-world study used patient and physician surveys to describe the clinical characteristics and disease burden of eosinophilic esophagitis—overall and in a subgroup of patients with dysphagia despite treatment. Methods: Data analyzed in this study were collected in 2020 from US and EU patients with eosinophilic esophagitis. Eligible patients were aged ≥ 12 years with a diagnosis of eosinophilic esophagitis, had an esophageal count of ≥ 15 eosinophils/high-power field at diagnosis, and were currently prescribed treatment for eosinophilic esophagitis. Results: Overall, 1001 patients were included, of whom 356 (36%) had dysphagia despite treatment. Demographics and clinical characteristics were similar in both populations. The severity of eosinophilic esophagitis was mild in more patients overall (69%) versus those with dysphagia despite treatment (48%). Patient disease history was similar in both populations, with some exceptions: common patient-reported symptoms were dysphagia (70% and 86%) and heartburn/acid reflux (55% and 49%), and common physician-reported symptoms were dysphagia (75% and 91%) and food impaction (46% and 52%). Treatment history was similar in both populations; overall, the most common treatments were proton pump inhibitors (83%) and topical corticosteroids (51%). Patients reported slightly more days with symptoms, higher impacts on activities of daily living, and slightly higher anxiety or depression in the dysphagia-despite-treatment population versus the overall population. Conclusions: Eosinophilic esophagitis presents severe symptoms and comorbidities that substantially impact patients' well-being and quality of life. Greater awareness of and novel treatments for eosinophilic esophagitis are needed. [ABSTRACT FROM AUTHOR]

The operating state of axle box bearings is crucial to the safety of high-speed trains, and the vibration acceleration signal is a commonly used bearing-health-state monitoring signal. In order to extract hidden characteristic frequency information from the vibration acceleration signal of axle box bearings for fault diagnosis, a method for extracting the fault characteristic frequency based on principal component analysis (PCA) fusion and the optimal bandpass filtered denoising signal analytic energy operator (AEO) demodulation spectrum is proposed in this paper. PCA is used to measure the dimension reduction and fusion of three-direction vibration acceleration, reducing the interference of irrelevant noise components. A new type of multi-channel bandpass filter bank is constructed to obtain filtering signals in different frequency intervals. A new, improved average kurtosis index is used to select the optimal filtering signals for different channel filters in a bandpass filter bank. A dimensionless characteristic index characteristic frequency energy concentration coefficient (CFECC) is proposed for the first time to describe the energy prominence ability of characteristic frequency in the spectrum and can be used to determine the bearing fault type. The effectiveness and applicability of the proposed method are verified using the simulation signals and experimental signals of four fault bearing test cases. The results demonstrate the effectiveness of the proposed method for fault diagnosis and its advantages over other methods. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is one of the most heterogeneous tumors. However, research on normal tissue adjacent to the tumor (NAT) is very limited. We performed multi‐regional omics sequencing on 150 samples to assess the genetic basis and immune microenvironment in NAT and matched primary tumor or lymph node metastases. NATs demonstrated different mutated genes compared with GC, and NAT genomes underwent independent evolution with low variant allele frequency. Mutation profiles were predominated by aging and smoking‐associated signatures in NAT instead of signatures associated with genetic instability. Although the immune microenvironment within NATs shows substantial intra‐patient heterogeneity, the proportion of shared TCR clones among NATs is five times higher than that of tumor regions. These findings support the notion that subclonal expansion is not pronounced in NATs. We also demonstrated remarkable intra‐patient heterogeneity of GCs and revealed heterogeneity of focal amplification of CD274 (encoding PD‐L1) that leads to differential expression. Finally, we identified that monoclonal seeding is predominant in GC, which is followed by metastasis‐to‐metastasis dissemination in individual lymph nodes. These results provide novel insights into GC carcinogenesis. © 2024 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with high incidence, recurrence, and metastasis rates. The emergence of immunotherapy has improved the treatment of advanced HCC, but problems such as drug resistance and immune-related adverse events still exist in clinical practice. The immunosuppressive tumor microenvironment (TME) of HCC restricts the efficacy of immunotherapy and is essential for HCC progression and metastasis. Therefore, it is necessary to elucidate the mechanisms behind immunosuppressive TME to develop and apply immunotherapy. This review systematically summarizes the pathogenesis of HCC, the formation of the highly heterogeneous TME, and the mechanisms by which the immunosuppressive TME accelerates HCC progression and metastasis. We also review the status of HCC immunotherapy and further discuss the existing challenges and potential therapeutic strategies targeting immunosuppressive TME. We hope to inspire optimizing and innovating immunotherapeutic strategies by comprehensively understanding the structure and function of immunosuppressive TME in HCC. [ABSTRACT FROM AUTHOR]

Aggregate-induced emission luminogens (AIEgens) have been widely used in biological imaging, chemical sensing, and disease treatments. The rational design and construction of AIEgens have received considerable research interests during the last few years. Herein, molecular docking-aided AIEgen design has been reasonably proposed and AIEgen TBQZY with excellent 1O2 generation ability has been synthesized. The newly developed TBQZY could efficiently kill S. epidermidis and methicillin-resistant S. epidermidis (MRSE) by tightly binding to bacteria and triggering the accumulation of 1O2 in bacteria. TBQZY specifically regulated the immune system and polarized macrophages from M1 to M2 to accelerate the elimination of biofilm in vivo. In addition, healing acceleration was observed in chronic wounds treated with TBQZY, and side effects were negligible. Meanwhile, TBQZY had extraordinary potential for combating drug-resistant bacteria in the clinical setting. This research not only provided new concepts for the design of AIEgens, but also shed some lights on the discovery of drugs against drug-resistant bacteria. [ABSTRACT FROM AUTHOR]

Context Dysthyroid optic neuropathy (DON) is a serious vision-threatening complication of thyroid-associated ophthalmopathy (TAO). Exploration of the underlying mechanisms of DON is critical for its timely clinical diagnosis. Objective We hypothesized that TAO patients with DON may have altered brain functional networks. We aimed to explore the alterations of static and dynamic functional connectomes in patients with and without DON using resting-state functional magnetic resonance imaging with the graph theory method. Methods A cross-sectional study was conducted at a grade A tertiary hospital with 66 TAO patients (28 DON and 38 non-DON) and 30 healthy controls (HCs). Main outcome measures included topological properties of functional networks. Results For static properties, DON patients exhibited lower global efficiency (Eg), local efficiency, normalized clustering coefficient, small-worldness (σ), and higher characteristic path length (Lp) than HCs. DON and non-DON patients both exhibited varying degrees of abnormalities in nodal properties. Meanwhile, compared with non-DON, DON patients exhibited abnormalities in nodal properties in the orbitofrontal cortex and visual network (VN). For dynamic properties, the DON group exhibited higher variance in Eg and Lp than non-DON and HC groups. A strengthened subnetwork with VN as the core was identified in the DON cohort. Significant correlations were found between network properties and clinical variables. For distinguishing DON, the combination of static and dynamic network properties exhibited optimal diagnostic performance. Conclusion Functional network alterations were observed both in DON and non-DON patients, providing novel insights into the underlying neural mechanisms of disease. Functional network properties may be potential biomarkers for reflecting the progression of TAO from non-DON to DON. [ABSTRACT FROM AUTHOR]

To explore the usefulness of neutrophil-to-lymphocyte count ratio (NLR), procalcitonin (PCT), and interleukin-6 (IL-6) for the severity assessment of bacterial sepsis. This study enrolled 100 patients with bacterial sepsis (disease group) who presented to Jinhua Central Hospital between March 2022 and March 2023 and 90 healthy individuals (control group). The patients were categorized into sepsis (64 cases), severe sepsis (18 cases), and septic shock (18 cases) groups according to the disease severity. The groups were compared in terms of the NLR, PCT, and IL-6, as well as the usefulness of these parameters, both alone and in combination, for the severity assessment of bacterial sepsis. The NLR, PCT, and IL-6 levels were significantly different among the three groups, with increasing values corresponding with disease aggravation. The area under the curve (AUC) values of the combinations of NLR, PCT, and IL-6 levels were higher than those of single markers. The sensitivity and AUC value of the combination of PCT and IL-6 levels were the highest (0.87), with a similar AUC value of the combination of NLR, PCT, and IL-6 (0.865); however, the specificity was significantly improved with the latter (0.938 vs. 0.859). NLR, PCT, and IL-6 levels are significantly increased in bacterial sepsis, and the combination of PCT, and IL-6 levels can improve the sensitivity of the evaluation ability for severe sepsis, and is more economical. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the combined performance of orbital MRI and intracranial visual pathway diffusion kurtosis imaging (DKI) in diagnosing dysthyroid optic neuropathy (DON). Methods: We retrospectively enrolled 61 thyroid-associated ophthalmopathy (TAO) patients, including 25 with DON (40 eyes) and 36 without DON (72 eyes). Orbital MRI–based apical muscle index (MI), diameter index (DI) of the optic nerve (ON), area index (AI) of the ON, apparent diffusion coefficient (ADC) and signal intensity ratio (SIR) of the ON, DKI-based kurtosis fractional anisotropy (KFA) and mean kurtosis (MK) of the optic tract (OT), optic radiation (OR), and Brodmann areas (BAs) 17, 18, and 19 were measured and compared between groups. The diagnostic performances of models were evaluated using receiver operating characteristic curve analyses and compared using the DeLong test. Results: TAO patients with DON had significantly higher apical MI, apical AI, and SIR of the ON, but significantly lower ADC of the ON than those without DON (p < 0.05). Meanwhile, the DON group exhibited significantly lower KFA across the OT, OR, BA17, BA18, and BA19 and lower MK at the OT and OR than the non-DON group (p < 0.05). The model integrating orbital MRI and intracranial visual pathway DKI parameters performed the best in diagnosing DON (AUC = 0.926), with optimal diagnostic sensitivity (80%) and specificity (94.4%), followed by orbital MRI combination (AUC = 0.890), and then intracranial visual pathway DKI combination (AUC = 0.832). Conclusion: Orbital MRI and intracranial visual pathway DKI can both assist in diagnosing DON. Combining orbital and intracranial imaging parameters could further optimize diagnostic efficiency. Clinical relevance statement: The novel finding could bring novel insights into the precise diagnosis and treatment of dysthyroid optic neuropathy, accordingly, contributing to the improvement of the patients' prognosis and quality of life in the future. Key Points: • Orbital MRI and intracranial visual pathway diffusion kurtosis imaging can both assist in diagnosing dysthyroid optic neuropathy. • Combining orbital MRI and intracranial visual pathway diffusion kurtosis imaging optimized the diagnostic efficiency of dysthyroid optic neuropathy. [ABSTRACT FROM AUTHOR]

The Dahongshan Group, situated at the southwestern margin of the Yangtze Block, represents a geological unit characterized by relatively high-grade metamorphism in the region. This paper investigates the garnet-biotite schist from the Laochanghe Formation of the Dahongshan Group, employing an integrated approach that includes petrological analysis, phase equilibrium modeling, and zircon U–Pb dating. The schist is mainly composed of garnet, biotite, plagioclase, quartz, rutile, and ilmenite. Phase equilibrium modeling revealed the peak metamorphic conditions of 8–9 kbar and 635–675 °C. By further integrating the prograde metamorphic profile of garnet and geothermobarometric results, a clockwise P–T metamorphic evolution path is constructed, which includes an increase in temperature and pressure during the prograde stage. LA–ICP–MS zircon U–Pb dating and zircon Ti thermometry constrains the post-peak metamorphic age of 831.2 ± 7.2 Ma. Integrated with previously reported results, it is revealed that the southwestern margin of the Yangtze Block experienced a large-scale regional metamorphism during the Neoproterozoic (890–750 Ma), which is related to the collisional orogenic process. This may be associated with the late-stage assembly of the Rodinia supercontinent or with local compression and subduction processes during the breakup of the Rodinia supercontinent. [ABSTRACT FROM AUTHOR]

Background: Cholangiocarcinoma (CCA), a primary hepatobiliary malignancy, is characterized by a poor prognosis and a lack of effective treatments. Therefore, the need to explore novel therapeutic approaches is urgent. While the role of Peptidylprolyl Cis/Trans Isomerase, NIMA-Interacting 1 (PIN1) has been extensively studied in various tumor types, its involvement in CCA remains poorly understood. Methods: In this study, we employed tissue microarray (TMA), reverse transcription-polymerase chain reaction (RT-PCR), and The Cancer Genome Atlas (TCGA) database to assess the expression of PIN1. Through in vitro and in vivo functional experiments, we investigated the impact of PIN1 on the adhesion and metastasis of CCA. Additionally, we explored downstream molecular pathways using RNA-seq, western blotting, co-immunoprecipitation, immunofluorescence, and mass spectrometry techniques. Results: Our findings revealed a negative correlation between PIN1 overexpression and prognosis in CCA tissues. Furthermore, high PIN1 expression promoted CCA cell proliferation and migration. Mechanistically, PIN1 functioned as an oncogene by regulating ANXA2 phosphorylation, thereby promoting CCA adhesion. Notably, the interaction between PIN1 and ANXA2 was facilitated by RACK1. Importantly, pharmacological inhibition of PIN1 using the FDA-approved drug all-trans retinoic acid (ATRA) effectively suppressed the metastatic potential of CCA cells in a nude mouse lung metastasis model. Conclusion: Overall, our study emphasizes the critical role of the PIN1/RACK1/ANXA2 complex in CCA growth and functionality, highlighting the potential of targeting PIN1 as a promising therapeutic strategy for CCA. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is a common cause of brain metastases, approximately 40% of patients with lung cancer will develop brain metastases at some point during their disease. Hypofractionated stereotactic radiotherapy (HSRT) has been demonstrated to be effective in controlling limited brain metastases. However, there is still no conclusive on the optimal segmentation of HSRT. The aim of our study was to explore the correlation between the HSRT dosage and its treatment effect and toxicity. Methods: A retrospective analysis was conducted on patients with non-small cell lung cancer (NSCLC) brain metastasis at Hangzhou Cancer Hospital from 1 January 2019 to 1 January 2021. The number of brain metastases did not exceed 10 in all patients and the number of fractions of HSRT was 5. The prescription dose ranges from 25 to 40 Gy. The Kaplan–Meier method was used for estimation of the localised intracranial control rate (iLC). Adverse radiation effects (AREs) were evaluated according to CTCAE 5.0. This study was approved by the Institutional Ethics Review Board of the Hangzhou Cancer Hospital (#73/HZCH-2022). Results: Forty eligible patients with a total of 70 brain metastases were included in this study. The 1-year iLC was 76% and 89% in the prescribed dose ≤ 30 Gy and > 30 Gy group, respectively (P < 0.05). For patients treated with HSRT combined with targeted therapy, immunotherapy and chemotherapy, the 1-year iLC was 89%, 100%, and 45%, respectively. No significant associations were observed between the number, maximum diameter, location, and type of pathology of brain metastases. The rate of all-grade AREs was 33%. Two patients who received a total dose of 40 Gy developed grade 3 headache, the rest of the AREs were grade 1–2. Conclusions: Increasing the prescription dose of HSRT improves treatment effect but may also exacerbate the side effects. Systemic therapy might impact the iLC rate, and individualized treatment regimens need to be developed. [ABSTRACT FROM AUTHOR]

Actin filament assembly and the regulation of its mechanical properties are fundamental processes essential for eukaryotic cell function. Residue E167 in vertebrate actins forms an inter-subunit salt bridge with residue K61 of the adjacent subunit. Saccharomyces cerevisiae actin filaments are more flexible than vertebrate filaments and have an alanine at this position (A167). Substitution of this alanine for a glutamic acid (A167E) confers Saccharomyces cerevisiae actin filaments with salt-dependent stiffness similar to vertebrate actins. We developed an optimized cryogenic electron microscopy workflow refining sample preparation and vitrification to obtain near-atomic resolution structures of wild-type and A167E mutant Saccharomyces cerevisiae actin filaments. The difference between these structures allowed us to pinpoint the potential binding site of a filament-associated cation that controls the stiffness of the filaments in vertebrate and A167E Saccharomyces cerevisiae actins. Through an analysis of previously published high-resolution reconstructions of vertebrate actin filaments, along with a newly determined high-resolution vertebrate actin structure in the absence of potassium, we identified a unique peak near residue 167 consistent with the binding of a magnesium ion. Our findings show how magnesium can contribute to filament stiffening by directly bridging actin subunits and allosterically affecting the orientation of the DNase-I binding loop of actin, which plays a regulatory role in modulating actin filament stiffness and interactions with regulatory proteins. Actin filament assembly and the regulation of its mechanical properties are fundamental processes essential for eukaryotic cell function, however, the molecular mechanisms that govern the mechanical properties of the actin filaments formed from different species are not fully understood. Here, the authors report high-resolution cryo-EM reconstructions of yeast actin from Saccharomyces cerevisiae and propose how the mechanism of the stiffening of the actin filament is affected by magnesium cations. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between caesarean scar defects and abnormal uterine bleeding through systematic literature review. Methods: PubMed, Web of Science, Cochrane Library and Embase databases were searched based on PRISMA 2020 to include studies exploring abnormal uterine bleeding in women with caesarean scar defects. The combined relative risk (RR) of uterine bleeding, combined prevalence of abnormal uterine bleeding and combined RR of intermenstrual uterine bleeding were calculated using a fixed- or random-effects model. Results: Ten studies involving 1,183 women with caesarean scar defects met the inclusion criteria for this study. Compared with women without caesarean scar defects, those with caesarean scar defects had a higher risk of abnormal uterine bleeding (RR: 3.22, 95% CI: 1.83–5.66) and intermenstrual bleeding (RR: 2.93, 95% CI: 1.91–4.50). The prevalence of abnormal uterine bleeding was approximately 0.46 (95% CI: 0.27–0.64), and across populations, women with a previous caesarean section who had undergone imaging specifically for gynaecological disease had a significantly higher prevalence of abnormal uterine bleeding (0.77, 95% CI: 0.65–0.89) than those with at least one caesarean Sect. (0.25, 95% CI: 0.10–0.39). Conclusion: A significant association was observed between caesarean scar defects and abnormal uterine bleeding, with the former being a risk factor for the latter. However, previous studies have differed in the definition of caesarean scar defects and abnormal uterine bleeding, and more high-quality studies are needed to further investigate the relevant definitions and study results in the future. [ABSTRACT FROM AUTHOR]

Common challenges in cryogenic electron microscopy, such as orientation bias, conformational diversity, and 3D misclassification, complicate single particle analysis and lead to significant resource expenditure. We previously introduced an in silico method using the maximum Feret diameter distribution, the Feret signature, to characterize sample heterogeneity of disc-shaped samples. Here, we expanded the Feret signature methodology to identify preferred orientations of samples containing arbitrary shapes with only about 1000 particles required. This method enables real-time adjustments of data acquisition parameters for optimizing data collection strategies or aiding in decisions to discontinue ineffective imaging sessions. Beyond detecting preferred orientations, the Feret signature approach can serve as an early-warning system for inconsistencies in classification during initial image processing steps, a capability that allows for strategic adjustments in data processing. These features establish the Feret signature as a valuable auxiliary tool in the context of single particle analysis, significantly accelerating the structure determination process. [ABSTRACT FROM AUTHOR]

Objective Approximately 10% of pregnant individuals report a penicillin allergy, yet most are not truly allergic. Allergy verification during pregnancy is safe and recommended; however, many hospitals lack the infrastructure to execute testing. Our aim was to evaluate the cost of developing and implementing a penicillin allergy referral program for pregnant individuals at an academic institution and to compare costs of care between patients who were referred and not referred through the program. Study Design We conducted an economic analysis of our institution's antepartum penicillin allergy referral program. We prospectively collected detailed resource utilization data and conducted the analysis from the program's perspective, accounting for costs related to program development, allergy verification, antibiotic cost, and delivery hospitalization. Costs were compared between patients who were referred for evaluation versus patients who were not referred using bivariate tests as well as quantile regression adjusting for baseline differences. A sensitivity analysis was performed for allergy testing cost. All cost estimates were inflation adjusted to 2021 U.S. dollars. Results The startup cost of program development and educational initiatives was $19,920, or 86 per patient. The median allergy evaluation cost was $397 (interquartile range: $303–663). There was no significant difference in maternal (median: $13,579 vs. 13,999, p = 0.94) or neonatal (median: $3,565 vs. 3,577, p = 0.55) delivery hospitalization cost or antibiotic cost (median: $1.57 vs. 3.87, p = 0.10) between referred and nonreferred patients. Overall, the total cost per person did not differ significantly between study groups (median: $18,931 vs. 18,314, p = 0.69). Conclusion The cost of developing a penicillin allergy referral program in pregnancy was modest and did not significantly alter short-term cost of care with potential for long-term cost benefit. Verification of a reported penicillin allergy is an integral part of antibiotic stewardship, and the pregnancy period should be utilized as an important opportunity to perform this evaluation. Key Points The cost of developing and implementing an antepartum penicillin allergy referral program is modest. Program cost did not significantly alter short-term cost with a potential for long-term cost benefit. Penicillin allergy verification is an important part of antibiotic stewardship and should be expanded. [ABSTRACT FROM AUTHOR]

As an excellent material for flexible sensors, conductive hydrogels have broad prospects in the field of wearable devices. In this study, a series of PVA/EG conductive hydrogels with different mass ratios of PVA were prepared by mixing the hydrogel base polyvinyl alcohol (PVA) with ethylene glycol (EG). The structures and morphologies of 10%, 20%, and 30% PVA/EG hydrogels were characterized, among which, the 20% PVA/EG hydrogel exhibited higher relative background intensity, crystalline content, and more surface pores. The sensing properties of the 20% PVA/EG conductive hydrogel, including sensitivity, linearity, response time, stability, and temperature reliability, were tested using a universal materials testing machine. The results showed that the sensitivity coefficient of the conductive hydrogel reached up to 0.74, the linear correlation coefficient reached 0.987, the response time was as low as 80 ms, and the relative resistance change remained relatively constant during 50 cycles of 15% stretching. Moreover, the hydrogel sample continued to function normally at -20 °C. Finally, the conductive hydrogel samples were attached to different parts of the body, such as fingers, spine, and feet, for motion experiments, validating the feasibility of the conductive hydrogel in various human motion monitoring scenarios. [ABSTRACT FROM AUTHOR]

Blood doping remains a significant problem that threatens the integrity of sport. The current indirect method for detecting blood doping involves the longitudinal measurement of an athlete's haematological variables and identification of suspicious results that are indicative of doping (i.e., the athlete biological passport). While this has played a significant role in the protection of clean sport, improvements are needed. The development of a transcriptomic test, that can be used to detect the use of blood doping has been discussed and researched for decades and yet, an anti-doping test that can be adopted by the World Anti-Doping Agency (WADA) is yet to be established. With recent advancements in our understanding, as well as in methods of sample collection, the possibility of a transcriptomic test that can be used by WADA, is imminent. There are, however, several practical considerations that must first be made, that will be highlighted in this perspective article. [ABSTRACT FROM AUTHOR]