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Dissolution of gas into flowing water inside a porous medium is important in various hydrogeology processes, such as geological carbon sequestration (GCS). The dissolution rate of CO2 controls the amount of CO2 injection and the safety of the GCS process. In this report, we investigated the dissolution behavior of four gas species, i.e., CO2, O2, N2, and Ar, into flowing water inside a porous medium by using micro-tomography. The trapped gas characteristics can be observed, and thus interfacial area and mass transfer coefficient can be calculated. Compared with the other gases, we found that the dissolution behavior of CO2 gas is unique, and the mass transfer coefficient is one order of magnitude lower than other gases. We believe that the high dissolution ratio of CO2 gas could have generated a layer of the high solute region around the trapped CO2 gas, disrupting the mass transfer process.

Based on a dual-loop optoelectronic oscillator (OEO) with Vernier effect, a scheme of fiber Bragg grating (FBG) interrogation system with an improved scale factor has been proposed and experimentally demonstrated. Functioning as the optical carrier of the OEO, the reflection signal of two cascaded FBGs is divided into two optical beams by using a wavelength division multiplexer (WDM). The two optical beams at different wavelengths travel along single mode fibers with different lengths. After combined together by another WDM, the two optical beams go through a section of dispersion compensation fiber (DCF). The oscillating frequency shift of the OEO is determined by the overall time delay, which is affected by the wavelength change of the sensing FBG. Thus, the wavelength change of the sensing FBG can be converted into the oscillating frequency shift of the OEO. Furthermore, due to the length difference between the two optical beams, an obvious Vernier effect has been generated in the frequency response of the OEO. By detecting the frequency shift of the envelope peak of the frequency response curve, the sensitivity of the sensing interrogation can be enhanced greatly. A proof-of-concept OEO-based FBG sensor for axial strain sensing experiment is performed. The experimental results show that the sensitivity is about 0.31 KHz/μϵ for a single-loop OEO. By employing Vernier effect, the sensitivity can be improved to -11 KHz/μϵ, which is 35 times higher than that of the single-loop OEO.

Hydrodynamic fingering induced by gel formation shares common features with growing biofilms, bacterial colonies, and the instability of a confined chemical garden. Fluid displacement with gel formation is also essential in various engineering applications, including CO2 leakage remediation from storage reservoirs and enhanced oil recovery. We conducted Hele-Shaw cell displacement experiments for a miscible fluid system using skim milk and aqueous citric acid solution. This study aimed to investigate the effects of gel film formation on the fingering instability of a miscible fluid system and develop a mathematical model of the sequential growth of gel film formation at the fingertip. We found that the gel film formation thickens with time, resulting in instability at the interface. A distinctive fingering pattern, resembling tentacles, appears where miscibility is suppressed, and the growth of the finger is localized at the fingertip. The finger width remains constant with increasing flow rate, whereas the number of fingers increases linearly before the fingers merge. The gap width significantly limits the finger width. Finally, a mathematical model of sequential film thickness growth for a bubble-like fingertip structure was developed. This model is based upon the interplay between the diffusion of citric acid through the existing gel film formation and elongation of the fingertip. The model provides an understanding of the fundamental mechanism of the growth of the bubble-like fingertip.

Micromodels are important for studying various pore-scale phenomena in hydrogeology. However, the fabrication of a custom micromodel involves complicated steps with cost-prohibitive equipment. The direct fabrication of micromodels with a 3D printer can accelerate the fabrication steps and reduce the cost. A stereolithography (SLA) 3D printer is one of the best options because it has sufficient printing performance for micromodel fabrication and is relatively inexpensive. However, it is not without drawbacks. In this report, we explored the capability of an SLA 3D printer for micromodel fabrication. Various parameters affecting the printing results, such as the effects of geometries, dimensions, printing axis configurations, printing thickness resolutions, and pattern thicknesses were investigated using microtomography for the first time. Eventually, the most optimal printing configuration was then also discussed. In the end, a complete micromodel was printed, assembled, and used for fluid displacement experiments. As a demonstration, viscous and capillary fingerings were successfully performed using this micromodel design.

BaZr1-xYxO3-δ (x = 0, 0.04, 0.08, 0.12) crucibles with doping different contents of Y2O3 were prepared by the pressureless sintering method, and the interfacial reaction behaviors in TiAl alloy melt was investigated using vacuum induction melting. The results revealed that the BaZrO3 ceramics contained a small amount of monoclinic ZrO2 and Ba-rich areas. With increasing Y2O3 doping content, yttrium-rich cubic ZrO2 instead of monoclinic ZrO2 generated and the average grain size decreased significantly. The results after melting showed that the thickness of the reaction layer of the BaZr1-xYxO3-δ decreased from hundreds of microns to tens of microns with the increase of the Y2O3 content. Moreover, the zirconium content in the alloy decreased. Overall, the BaZr0.96Y0.04O3-δ ceramic crucible had a small thickness of the reaction layer and slight oxygen contamination in the alloys. This study offers new insights for the further development of Y2O3-doped BaZrO3 ceramics used in melting TiAl alloys.

Abstract Association of prodromal Parkinson’s disease (PD) with risk of PD and risk of mortality in individuals with PD warrant investigation through large-scale prospective study. We included 501,475 participants without PD at baseline. Eight prodromal features were measured. Incident PD cases were identified via hospital admission, death register, and self-report. Cox regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs). Multivariable-adjusted HRs3+vs.0 prodromal PD features and 95%CIs were 3.12 (2.58–3.78) for men and 2.71 (2.11–3.47) for women. Prodromal PD predicted only PD onset occurred during the first 6 years of follow-up (HR3+vs.0 prodromal features = 10.5; 95% CI: 8.60–12.9), but not after 6 years (HR = 1.00; 95%CI: 0.76-1.32). The presence of prodromal PD conferred a higher risk of mortality among participants with PD. Having prodromal PD were associated with higher probability of developing PD in short-term and higher risk of mortality among individuals with PD.

Type 2 diabetes mellitus (T2DM) patients always develop osteoporosis (OP). We examined correlations of N-terminal mid-fragment of osteocalcin (N-MID) and cystatin C (Cys C) levels with glycolipid metabolism, bone metabolism markers, and bone mineral density (BMD) in elderly T2DM-OP patients. Grouping was performed as per whether T2DM patients developed OP (OP group) or not (N-OP group). N-MID and Cys C were measured using enzyme-linked immunosorbent assay, with correlations with glycolipid metabolism, bone metabolism indicators, and BMD analyzed using Pearson’s correlation coefficient. Elderly T2DM-OP patients showed elevated disease duration, age, body mass index, glycated hemoglobin (HbA1c), Homer’s insulin resistance (HOMA-IR), total cholesterol (TC), beta-carboxy-terminal crosslinked telopeptide of type 1 collagen (β-CTX), tartrate-resistant acid phosphatase 5b (TRACP-5b), N-MID and Cys C levels, and reduced high-density lipoprotein cholesterol (HDL-C), bone alkaline phosphatase (B-ALP), aminoterminal propeptide of type I procollagen (PINP), carboxyterminal propeptide of type I procollagen (PICP), BMD, and calcium supplementation. N-MID and Cys C were positively correlated with HbA1c, HOMA-IR, TC, β-CTX, and TRACP-5b and negatively with HDL-C, B-ALP, PINP, PICP, and BMD in elderly T2DM-OP patients. Conclusively, the abnormal elevations of serum N-MID and Cys C were associated with glycolipid metabolism disorder, abnormal bone metabolism, and decreased BMD in elderly T2DM-OP patients.

Dielectric chiral metasurface is a new type of planar and efficient chiral optical device that shows strong circular dichroism or optical activity, which has important application potential in optical sensing and display. However, the two types of chiral optical responses in conventional chiral metasurfaces are often interdependent, as their modulation of the amplitudes and phases of orthogonal circularly polarized components is correlated, which limits the further progress of chiral meta-devices. Here we propose a new scheme for independently designing the circular dichroism and optical activity of chiral metasurfaces to further control the polarization and wavefront of transmitted waves. Inspired by mixtures of chiral molecular isomers, we use the dielectric isomer resonators to form “super-units” instead of single meta-atoms for chiral responses in terahertz band, which is called racemic metasurface. By introducing two levels of Pancharatnam-Berry phases between meta-atoms and “super-units”, the polarization rotation angle and wavefront of the beam can be designed without the far-field circular dichroism. We demonstrate the strong control ability on terahertz waves of this scheme through simulation and experiments. In addition, this new type of device with near-field chirality but no far-field circular dichroism may also have important value in optical sensing and other technologies.

Abstract Bipolar disorder (BD) is linked to an increased risk of neurodegenerative diseases such as dementia and Parkinson disease (PD), yet several uncertainties still remain and the extent to which the associations could be explained by BD-related medications (antipsychotics, lithium, and antiepileptics) was unknown. This study included 501,233 UK Biobank participants (mean [standard deviation] age, 56.5 [8.10] years; 54.4% women), free of dementia and PD at baseline. After a median 13.8 year follow-up, 9422 cases of dementia and 3457 PD cases were identified. Participants with BD had a significantly higher risk of dementia (adjusted hazard ratio [HR] 2.52, 95% CI 2.00–3.19) and PD (adjusted HR 2.88, 95% CI 2.03-4.08). Findings suggest that up to two-thirds of the association of neurodegenerative diseases with BD may be mediated by BD-related medications. Further research is needed to confirm these findings and explore the underlying mechanisms.

BackgroundElectronic health records (EHRs) facilitate the accessibility and sharing of patient data among various health care providers, contributing to more coordinated and efficient care. ObjectiveThis study aimed to summarize the evolution of secondary use of EHRs and their interoperability in medical research over the past 25 years. MethodsWe conducted an extensive literature search in the PubMed, Scopus, and Web of Science databases using the keywords Electronic health record and Electronic medical record in the title or abstract and Medical research in all fields from 2000 to 2024. Specific terms were applied to different time periods. ResultsThe review yielded 2212 studies, all of which were then screened and processed in a structured manner. Of these 2212 studies, 2102 (93.03%) were included in the review analysis, of which 1079 (51.33%) studies were from 2000 to 2009, 582 (27.69%) were from 2010 to 2019, 251 (11.94%) were from 2020 to 2023, and 190 (9.04%) were from 2024. ConclusionsThe evolution of EHRs marks an important milestone in health care’s journey toward integrating technology and medicine. From early documentation practices to the sophisticated use of artificial intelligence and big data analytics today, EHRs have become central to improving patient care, enhancing public health surveillance, and advancing medical research.

IntroductionProvision of agricultural productive services to farmers is crucial for integrating them into the modern agricultural system. However, small-scale farmers often face difficulties in accessing these services. One internationally recognized approach to addressing this issue is the government-led provision of productive services to small-scale farmers. In China, production services are provided through village collectives, which are economic organizations established in townships and villages to manage collective assets, develop resources and economy, and provide services to members. Farmer participation in these services can enhance inclusive service dynamics, improving access to services and promoting rural equity.MethodsFarmers’ subjective evaluations directly reflect their access to collective agricultural productive services. This study utilized a binary logit model to analyze the impact and mechanism of farmer participation in cooperatives on the collective supply of agricultural productive services. The study involved 3,900 farmers from 29 provinces (autonomous regions and municipalities) in China.Results and discussionThis study proposes for the first time a “cooperative+collective” model for the provision of productive services. In China, safeguarding social equity is one of the important objectives of the Government, and safeguarding and supporting the interests of small-scale farmers is crucial to safeguarding social equity. Participation in cooperatives increased farmers’ access to agricultural productive services. The analysis revealed that farmers have significantly increased their level of access to agricultural production services through participation in the “cooperative+collective” model of productive services. Farmers have participation in cooperatives helped integrate and expand farmers’ demand, leading to the continuous operation and expansion of business scale, thereby enhancing the collective supply of agricultural productive services. Furthermore, those income low-income, older farmers derived more benefits from participating in cooperatives in terms of accessing these services. This study offers empirical evidence supporting the effectiveness of collective agricultural services.

Abstract Sleep disturbances, including rapid eye movement sleep behavior disorder (RBD), excessive daytime sleepiness, and insomnia, are common non-motor manifestations of Parkinson’s disease (PD). Little is known about the underlying mechanisms, partly due to the inability of current rodent models to adequately mimic the human PD sleep phenotype. Clinically, increasing studies have reported that variants of the glucocerebrosidase gene (GBA) increase the risk of PD. Here, we developed a mouse model characterized by sleep–wakefulness by injecting α-synuclein preformed fibronectin (PFF) into the sublaterodorsal tegmental nucleus (SLD) of GBA L444P mutant mice and investigated the role of the GBA L444P variant in the transition from rapid eye movement sleep behavior disorder to PD. Initially, we analyzed spectral correlates of REM and NREM sleep in GBA L444P mutant mice. Importantly, EEG power spectral analysis revealed that GBA L444P mutation mice exhibited reduced delta power during non-rapid eye movement (NREM) sleep and increased theta power (8.2–10 Hz) in active rapid eye movement (REM) sleep phases. Our study revealed that GBA L444P-mutant mice, after receiving PFF injections, exhibited increased sleep fragmentation, significant motor and cognitive dysfunctions, and loss of dopaminergic neurons in the substantia nigra. Furthermore, the over-expression of GBA-AAV partially improved these sleep disturbances and motor and cognitive impairments. In conclusion, we present the initial evidence that the GBA L444P mutant mouse serves as an essential tool in understanding the complex sleep disturbances associated with PD. This model further provides insights into potential therapeutic approaches, particularly concerning α-synuclein accumulation and its subsequent pathological consequences.

Objective: This study aims to evaluate the effectiveness of the Quality Risk Management (QRM) system in hospital pharmacy intravenous admixture services (PIVAS). Methods: Failure Modes and Effects Analysis (FMEA) and risk matrix methods were used to systematically assess the critical risk points in PIVAS. By collecting and comparing relevant data from 2019 to 2023, key performance indicators (KPIs) before and after the implementation of the QRM system were quantitatively evaluated. Results: The results showed that the safety and efficiency of pharmacy services significantly improved after the implementation of the QRM system. The medication error rate significantly decreased from 3.2% to 1.1%, the average medication preparation time reduced from 15.5 min to 8.2 min, and staff satisfaction increased from 6.0 to 8.5 points. Other indicators, such as cross-contamination rates and handling errors, also showed significant improvement (all outcomes p

Abstract Metabolic dysfunction‐associated steatotic liver disease (MASLD) represents an impending global health challenge. Current management strategies often face setbacks, emphasizing the need for preclinical models that faithfully mimic the human disease and its comorbidities. The liver disease progression aggravation diet (LIDPAD), a diet‐induced murine model, extensively characterized under thermoneutral conditions and refined diets is introduced to ensure reproducibility and minimize species differences. LIDPAD recapitulates key phenotypic, genetic, and metabolic hallmarks of human MASLD, including multiorgan communications, and disease progression within 4 to 16 weeks. These findings reveal gut‐liver dysregulation as an early event and compensatory pancreatic islet hyperplasia, underscoring the gut‐pancreas axis in MASLD pathogenesis. A robust computational pipeline is also detailed for transcriptomic‐guided disease staging, validated against multiple harmonized human hepatic transcriptomic datasets, thereby enabling comparative studies between human and mouse models. This approach underscores the remarkable similarity of the LIDPAD model to human MASLD. The LIDPAD model fidelity to human MASLD is further confirmed by its responsiveness to dietary interventions, with improvements in metabolic profiles, liver histopathology, hepatic transcriptomes, and gut microbial diversity. These results, alongside the closely aligned changing disease‐associated molecular signatures between the human MASLD and LIDPAD model, affirm the model's relevance and potential for driving therapeutic development.

Abstract Solid tumors are complex ecosystems with heterogeneous 3D structures, but the spatial intra-tumor heterogeneity (sITH) at the macroscopic (i.e., whole tumor) level is under-explored. Using a phylogeographic approach, we sequence genomes and transcriptomes from 235 spatially informed sectors across 13 hepatocellular carcinomas (HCC), generating one of the largest datasets for studying sITH. We find that tumor heterogeneity in HCC segregates into spatially variegated blocks with large genotypic and phenotypic differences. By dissecting the transcriptomic heterogeneity, we discover that 30% of patients had a “spatially competing distribution” (SCD), where different spatial blocks have distinct transcriptomic subtypes co-existing within a tumor, capturing the critical transition period in disease progression. Interestingly, the tumor regions with more advanced transcriptomic subtypes (e.g., higher cell cycle) often take clonal dominance with a wider geographic range, rejecting neutral evolution for SCD patients. Extending the statistical tests for detecting natural selection to many non-SCD patients reveal varying levels of selective signal across different tumors, implying that many evolutionary forces including natural selection and geographic isolation can influence the overall pattern of sITH. Taken together, tumor phylogeography unravels a dynamic landscape of sITH, pinpointing important evolutionary and clinical consequences of spatial heterogeneity in cancer.

Energetic Semiconductor bridge (ESCB) based on reactive multilayered films (RMFs) has a promising application in the miniature and intelligence of initiator and pyrotechnics device. Understanding the ignition enhancement mechanism of RMFs on semiconductor bridge (SCB) during the ignition process is crucial for the engineering and practical application of advanced initiator and pyrotechnics devices. In this study, a one-dimensional (1D) gas-solid two-phase flow ignition model was established to study the ignition process of ESCB to charge particles based on the reactivity of Al/MoO3 RMFs. In order to fully consider the coupled exothermic between the RMFs and the SCB plasma during the ignition process, the heat release of chemical reaction in RMFs was used as an internal heat source in this model. It is found that the exothermal reaction in RMFs improved the ignition performance of SCB. In the process of plasma rapid condensation with heat release, the product of RMFs enhanced the heat transfer process between the gas phase and the solid charge particle, which accelerated the expansion of hot plasma, and heated the solid charge particle as well as gas phase region with low temperature. In addition, it made up for pressure loss in the gas phase. During the plasma dissipation process, the exothermal chemical reaction in RMFs acted as the main heating source to heat the charge particle, making the surface temperature of the charge particle, gas pressure, and gas temperature rise continuously. This result may yield significant advantages in providing a universal ignition model for miniaturized ignition devices.

Thymoma with Immunodeficiency (Good's Syndrome, GS) is a rare association between thymoma and immunodeficiency, first described over 60 years ago. Patients with GS typically present with thymomas, reduced or absent B cells in the peripheral blood, hypogammaglobulinemia, and defects in cell-mediated immunity. We report the case of a 67-year-old woman diagnosed with GS following the development of a progressive, severe, refractory pulmonary infection and diffuse panbronchiolitis (DPB). She also had diabetes, characterized by anti-glutamic acid decarboxylase antibody positivity, leading to a diagnosis of latent autoimmune diabetes in adults (LADA). A thorough review of existing literature revealed that GS is often confirmed after multiple episodes of opportunistic infections or autoimmune diseases post-thymoma surgery. Due to their immunodeficiency, GS patients frequently suffer from recurrent infections over extended periods, and some succumb to severe infections. Regular immunoglobulin infusions may be effective in treating GS.

Free-living amoebae (FLA) are prevalent in nature and man-made environments, and they can survive in harsh conditions by forming cysts. Studies have discovered that some FLA species are able to show pathogenicity to human health, leading to severe infections of central nervous systems, eyes, etc. with an extremely low rate of recovery. Therefore, it is imperative to establish a surveillance framework for FLA in environmental habitats. While many studies investigated the risks of independent FLA, interactions between FLA and surrounding microorganisms determined microbial communities in ecosystems and further largely influenced public health. Here we systematically discussed the interactions between FLA and different types of microorganisms and corresponding influences on behaviors and health risks of FLA in the environment. Specifically, bacteria, viruses, and eukaryotes can interact with FLA and cause either enhanced or inhibited effects on FLA infectivity, along with microorganism community changes. Therefore, considering the co-existence of FLA and other microorganisms in the environment is of great importance for reducing environmental health risks.

Abstract Chronic wounds are often infected with biofilm bacteria and characterized by high oxidative stress. Current dressings that promote chronic wound healing either require additional processes such as photothermal irradiation or leave behind gross amounts of undesirable residues. We report a dual-functionality hydrogel dressing with intrinsic antibiofilm and antioxidative properties that are synergistic and low-leaching. The hydrogel is a crosslinked network with tethered antibacterial cationic polyimidazolium and antioxidative N-acetylcysteine. In a murine diabetic wound model, the hydrogel accelerates the closure of wounds infected with methicillin-resistant Staphylococcus aureus or carbapenem-resistant Pseudomonas aeruginosa biofilm. Furthermore, a three-dimensional ex vivo human skin equivalent model shows that N-acetylcysteine promotes the keratinocyte differentiation and accelerates the re-epithelialization process. Our hydrogel dressing can be made into different formats for the healing of both flat and deep infected chronic wounds without contamination of the wound or needing other modalities such as photothermal irradiation.

ABSTRACT: Objectives: Several linezolid population pharmacokinetic (popPK) models have been established to facilitate optimal therapy; however, their extrapolated predictive performance to other clinical sites is unknown. This study aimed to externally evaluate the predictive performance of published pharmacokinetic models of linezolid in adult patients. Methods: For the evaluation dataset, 150 samples were collected from 70 adult patients (72.9% of which were critically ill) treated with linezolid at our center. Twenty-five published popPK models were identified from PubMed and Embase. Model predictability was evaluated using prediction-based, simulation-based, and Bayesian forecasting-based approaches to assess model predictability. Results: Prediction-based diagnostics found that the prediction error within ±30% (F30) was less than 40% in all models, indicating unsatisfactory predictability. The simulation-based prediction- and variability-corrected visual predictive check and normalized prediction distribution error test indicated large discrepancies between the observations and simulations in most of the models. Bayesian forecasting with one or two prior observations significantly improved the models’ predictive performance. Conclusion: The published linezolid popPK models showed insufficient predictive ability. Therefore, their sole use is not recommended, and incorporating therapeutic drug monitoring of linezolid in clinical applications is necessary.

Objective: Previous drug repositioning studies have suggested that parthenolide may be a differentiation-inducing agent for glioma cells. This study aimed to experimentally verify the neuronal differentiation-inducing effects and proliferative impact of parthenolide on human glioma cells and explore its potential mechanisms. Methods: HE staining was used to observe the morphological changes in human glioma cell lines U87 and A172 induced by parthenolide. Immunocytochemistry was conducted to detect the expression of differentiation markers. The Ki-67 detection and CCK-8 assay were used to assess the effects of parthenolide on cell proliferation. The sphere formation assay was conducted to evaluate the self-renewal. Glioma stem cells (GSCs) derived from U87 cells were utilized to assess the ability of parthenolide to induce differentiation in GSCs. Western blot was used to detect the expression of histone deacetylase 1 (HDAC1). Bioinformatics analysis based on the CGGA database was conducted to evaluate the role of HDAC1 in glioma. Results: Parthenolide (4 μM) altered the morphology of U87 and A172 cells, as elongated cell projections were observed. Parthenolide induced glioma cells to express neuronal markers NeuN, MAP2, SYP, and NEFL, but not astrocyte or oligodendrocyte markers. Parthenolide significantly inhibited proliferation and self-renewal in glioma cells. Similar effects were observed in U87 GSCs. Furthermore, parthenolide downregulated HDAC1 expression in glioma cells, and the bioinformatics analysis revealed a potential relationship between neuronal characteristics and low expression of HDAC1 in glioma. Conclusion: Parthenolide induced neuronal differentiation and inhibited the cell proliferation in human glioma cells, which might be associated with the inhibition of HDAC1.

The gradual integration of digital technology into traditional Chinese villages has triggered a shift in income distribution from labor to capital, posing challenges to the wage growth of employed peasants. Based on the theory of empowerment, this paper explores the mechanisms of credit availability and talent loss in the interplay between digital capabilities and wage augmentation among employed peasants. This study empirically examines or validates the mechanism of digital capabilities on wage growth for employed peasants through the entropy weight method, the OLS linear model, the mediation effect model, and propensity score matching while using survey data from 490 farmer entrepreneurs as samples. The findings are as follows. (1) The digital capabilities of farmer entrepreneurs have a significant positive impact on the wage growth of employed peasants, and this result remains robust after a series of robustness checks. In terms of hierarchical effects, digital foundational capabilities > digital application capabilities > digital innovation capabilities. (2) Credit availability and talent loss mediate the relationship between digital capabilities and wage growth for employed peasants. (3) The digital capabilities of farmer entrepreneurs who are young, highly educated, and have a low family-dependency ratio exert a more pronounced influence on the wage growth of employed peasants. Additionally, lower policy uncertainty enhances the effect of digital capabilities on wage growth for employed peasants. The study uncovers the empowerment mechanism of digital advancements embedded during the entrepreneurial journey, enriches research on digital capabilities and common prosperity, and provides a feasible path for governments to formulate reasonable entrepreneurship and digital promotion policies.

Prolonged consumption of animal-derived foods containing high levels of lincomycin (LIN) residues can adversely impact human health. Therefore, it is essential to develop specific antibodies and immunoassay methods for LIN. This study utilized computational chemistry to predict the efficacy of LIN haptens prior to chemical synthesis, with subsequent confirmation obtained through an immunization experiment. A hybridoma cell line named LIN/1B11 was established, which is specific to LIN. The optimized indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) method exhibited high specificity for detecting LIN residues, with an IC50 value of 0.57 ± 0.03 µg/kg. The method effectively detected LIN residues in pork and milk samples, achieving a limit of detection (LOD) ranging from 0.81 to 1.20 µg/kg and a limit of quantification (LOQ) ranging from 2.09 to 2.29 µg/kg, with recovery rates between 81.9% and 108.8%. This study offers a valuable tool for identifying LIN residues in animal-derived food products. Furthermore, the efficient hapten prediction method presented herein improves antibody preparation efficiency and provides a simple method for researchers in screening haptens.

Type 2 diabetes (T2D) is often accompanied with an induction of retinaldehyde dehydrogenase 1 (RALDH1 or ALDH1A1) expression and a consequent decrease in hepatic retinaldehyde (Rald) levels. However, the role of hepatic Rald deficiency in T2D progression remains unclear. In this study, we demonstrated that reversing T2D-mediated hepatic Rald deficiency by Rald or citral treatments, or liver-specific Raldh1 silencing substantially lowered fasting glycemia levels, inhibited hepatic glucogenesis, and downregulated phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) expression in diabetic db/db mice. Fasting glycemia and Pck1/G6pc mRNA expression levels were strongly negatively correlated with hepatic Rald levels, indicating the involvement of hepatic Rald depletion in T2D deterioration. A similar result that liver-specific Raldh1 silencing improved glucose metabolism was also observed in high-fat diet-fed mice. In primary human hepatocytes and oleic acid-treated HepG2 cells, Rald or Rald + RALDH1 silencing resulted in decreased glucose production and downregulated PCK1/G6PC mRNA and protein expression. Mechanistically, Rald downregulated direct repeat 1-mediated PCK1 and G6PC expression by antagonizing retinoid X receptor α, as confirmed by luciferase reporter assays and molecular docking. These results highlight the link between hepatic Rald deficiency, glucose dyshomeostasis, and the progression of T2D, whilst also suggesting RALDH1 as a potential therapeutic target for T2D.

Objective: Subarachnoid hemorrhage (SAH) was a stroke with high occurrence and mortality. At the early stage, SAH patients have severe cerebral injury which is contributed by inflammation. In this study, we aimed to explore the anti-inflammation effect of low-dose IL-2 in SAH mice. Methods: The 12-week-old C57BL/6J male mice were conducted with SAH surgery (Internal carotid artery puncture method). Different dose of IL-2 was injected intraperitoneally for 1 h, 1 day, and 2 days after SAH. Single-cell suspension and flow cytometry were used for the test of regulatory T (Treg) cells. Immunofluorescence staining was used to investigate the phenotypic polarization of microglia and inflammation response around neurons. Enzyme-Linked Immuno-sorbent Assay (ELISA) was applied to detect the level of pro-inflammatory factors. Results: Low-dose IL-2 could enrich the Treg cells and drive the microglia polarizing to M2. The level of pro-inflammatory factors, IL-1α, IL-6, and TNF-α decreased in the low-dose IL-2 group. The inflammation response around neurons was attenuated. Low-dose IL-2 could increase the number of Treg cells, which could exert a neuroprotective effect against inflammation after SAH. Conclusion: Low-dose IL-2 had the potential to be an effective clinical method to inhibit inflammation after SAH.

Purpose Ticagrelor is an antiplatelet drug, and its use increases the risk of bleeding. Coronary artery disease is significantly influenced by the widespread occurrence of diabetes mellitus. In order to decrease the incidence of clinical adverse events, a novel bleeding and thrombosis score is developed in this research. Methods We conducted a retrospective analysis of patient data from two medical centers who were diagnosed with diabetes mellitus and treated with ticagrelor. We gathered information on every patient from the electronic database of the hospital and follow-up. The collected data were statistically analyzed to obtain risk factors for bleeding and ischemic events. Results A total of 851 patients with diabetes mellitus who have been administered ticagrelor are included in our investigation. A total of 76 patients have bleeding events and 80 patients have ischemic events. The analysis of multiple variables indicates that characteristics like the age of >65, having a previous occurrence of bleeding, experiencing anemia, using aspirin, and taking atorvastatin are linked to a higher likelihood of bleeding. Additionally, the age of >65, smoking, having a history of blood clots, and having a BMI ≥ 30 are found to increase the risk of ischemia. Conclusion The A 4 B score established in this study was better than the HAS-BLED score，and the same is true for the ABST score to the CHA 2 DS-VASc score. This new risk assessment model can potentially detect patients who are at high risk for bleeding and ischemic events. For high-risk patients, the dose of ticagrelor can be adjusted appropriately or the medication can be adjusted.(2023-09-11, ChiCTR2300075627)

Summary: Iron overload is closely associated with metabolic dysfunction. However, the role of iron in the hypothalamus remains unclear. Here, we find that hypothalamic iron levels are increased, particularly in agouti-related peptide (AgRP)-expressing neurons in high-fat-diet-fed mice. Using pharmacological or genetic approaches, we reduce iron overload in AgRP neurons by central deferoxamine administration or transferrin receptor 1 (Tfrc) deletion, ameliorating diet-induced obesity and related metabolic dysfunction. Conversely, Tfrc-mediated iron overload in AgRP neurons leads to overeating and adiposity. Mechanistically, the reduction of iron overload in AgRP neurons inhibits AgRP neuron activity; improves insulin and leptin sensitivity; and inhibits iron-induced oxidative stress, endoplasmic reticulum stress, nuclear factor κB signaling, and suppression of cytokine signaling 3 expression. These results highlight the critical role of hypothalamic iron in obesity development and suggest targets for treating obesity and related metabolic disorders.

Rapamycin, an established mTOR inhibitor in clinical practice, is widely recognized for its therapeutic efficacy. Ridaforolimus, a non-prodrug rapalog, offers improved aqueous solubility, stability, and affinity compared to rapamycin. In recent years, there has been a surge in clinical trials involving ridaforolimus. We searched PubMed for ridaforolimus over the past decade and selected clinical trials of ridaforolimus to make a summary of the research progress of ridaforolimus in clinical trials. The majority of these trials explored the application of ridaforolimus in treating various tumors, including endometrial cancer, ovarian cancer, prostate cancer, breast cancer, renal cell carcinoma, and other solid tumors. These trials employed diverse drug combinations, incorporating agents such as ponatinib, bicalutamide, dalotuzumab, MK-2206, MK-0752, and taxanes. The outcomes of these trials unveiled the diverse potential applications of ridaforolimus in disease treatment. Our review encompassed analyses of signaling pathways, ridaforolimus as a single therapeutic agent, its compatibility in combination with other drugs, and an assessment of adverse events (AEs). We conclude by recommending further research to advance our understanding of ridaforolimus’s clinical applications.

3D numerical simulation on the steam velocity field and flow resistance configuration in the fullscale low-temperature multi-effect desalination (LT-MED) evaporator were conducted and analyzed. The complicated two-phase water-vapor flow through the tube bundle was modeled using the single- phase vapor flow through the porous media (PM) model, which could simplify the effect of anfractuous geometry of the flow path and interactions between the two phases in the tube bundle. A PM model has been validated by additional experimental results. 3D numerical results were justified between the literature and real LT-MED plants. The numerical results suggest that the steam velocity in the tube bundle ranges from 1 to 12 m/s and presents different variation trends along the direction of the tube row, tube column, and tube length. In the axial channel, steam velocity first exhibits a rising tendency up to maximum of 50 m/s close to the outlet and then greatly decreases beyond the outlet. The components of steam flow resistance comprise tube bundle, demister, steam channel, and tube-side condensation resistances. The largest flow resistance is contributed by the axial steam channel, accounting for 57.6% proportion. The small steam flow resistance with a total of 381.6 Pa in the first-effect evaporator causes a significant reduction in the effective heat transfer temperature difference by a proportion of 12.2%. This study endeavors to find a new possibility of numerical simulation for the entire LT-MED evaporator, which could provide a good reference to engineering-optimized design and modeling of the LT-MED running condition. [ABSTRACT FROM AUTHOR]

Abstract This analysis was conducted to inform dose selection of a combination of nivolumab plus ipilimumab for the treatment of sorafenib‐experienced patients with hepatocellular carcinoma (HCC). CheckMate 040 is an open‐label, multicohort, phase I/II trial in adults with advanced HCC that evaluated nivolumab monotherapy (0.1–10 mg/kg once every 2 weeks [q2w]) and the following three combinations of nivolumab plus ipilimumab: (1) nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (q3w) for four doses, followed by nivolumab monotherapy 240 mg q2w (arm A); (2) nivolumab 3 mg/kg plus ipilimumab 1 mg/kg q3w for four doses, followed by nivolumab monotherapy 240 mg q2w (arm B); and (3) nivolumab 3 mg/kg q2w plus ipilimumab 1 mg/kg every 6 weeks continuously (arm C). Exposure‐response relationships (efficacy and safety) were characterized using nivolumab and ipilimumab concentrations after the first dose (Cavg1) as the exposure measure. Objective tumor response (OTR) and overall survival (OS) improvements were associated with increased ipilimumab exposure (OTR: odds ratio 1.45, 95% confidence interval [CI], 1.13–1.86; OS: hazard ratio 0.86, 95% CI 0.75–0.98), but not nivolumab exposure (OTR: odds ratio 0.99, 95% CI 0.97–1.02; OS: hazard ratio 1.08, 95% CI 0.89–1.32). Hepatic treatment‐related and immune‐mediated adverse events were more common in arm A than in arms B or C. Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg q3w for four doses, followed by nivolumab monotherapy 240 mg q2w had the most favorable benefit:risk profile in patients with advanced HCC.

Objective: Clusterin is closely correlated with insulin resistance and its associated comorbidities. This study aimed to investigate the correlation between serum clusterin levels and non-alcoholic fatty liver disease (NAFLD) and further explore the mediating role of insulin resistance in this relationship. Methods: This study enrolled 195 inpatients (41 males and 154 females) a ged 18–61 years. Twenty-four patients were followed up for 12 months afte r bariatric surgery. Serum clusterin levels were measured using a sandwich enzyme-linked immunosorbent assay. Fatty liver disease was diagnosed on the basis of liver ultrasonography. The fatty liver index (FLI) was calculated to quantify the degree of hepa tic steatosis. The mediating role of homeostasis model assessment-insulin resistance (HOMA-IR) was assessed using mediation analysis. Results: Participants with NAFLD had significantly higher serum clusterin levels than those without NAFLD (444.61 (325.76–611.52) mg/L vs 294.10 (255 .20–373.55) mg/L, P < 0.01). With increasing tertiles of serum clusterin levels, t he prevalence of NAFLD displayed an upward trend (P < 0.01). Multivariate linear regression analysis showed that serum clusterin levels were a positive determinant of FLI (standardized β = 0.271, P < 0.001) after adjusting for multiple metabolic risk factors. Serum clusterin levels significantly decreased after bariatric surgery (298.77 (262.56–358.10) mg/L vs 520.55 (354.94–750.21) mg/L, P < 0.01). In the mediation analysis, HOMA-IR played a mediating role in the correlation between serum clusterin levels and FLI; the estimated percentage of the total effect was 17.3%. Conclusion: Serum clusterin levels were associated with NAFLD. In addition, insulin resistance partially mediated the relationship between serum clusterin levels and FLI.

Based on the unique insulator-metal phase transition property of vanadium dioxide (VO2), we propose an integrated metasurface with a switchable mechanism between ultra-broadband absorption and polarization conversion, operating in the terahertz (THz) frequency range. The designed metasurface device is constructed using a stacked structure composed of VO2 quadruple rings, a dielectric layer, copper stripes, VO2 film, a dielectric layer, and a copper reflection layer. Our numerical simulations demonstrate that our proposed design, at high temperatures (above 358 K), exhibits an ultra-broadband absorption ranging from 4.95 to 18.39 THz, maintaining an absorptivity greater than 90%, and achieves a relative absorption bandwidth of up to 115%, significantly exceeding previous research records. At room temperature (298 K), leveraging VO2’s insulating state, our proposed structure transitions into an effective polarization converter, without any alteration to its geometry. It enables efficient conversion between orthogonal linear polarizations across 3.51 to 10.26 THz, with cross-polarized reflection exceeding 90% and a polarization conversion ratio over 97%. More importantly, its relative bandwidth reaches up to 98%. These features highlight its wide-angle, extensive bandwidth, and high-efficiency advantages for both switching functionalities. Such an ultra-broadband convertible design offers potential applications in optical switching, temperature dependent optical sensors, and other tunable THz devices in various fields.

In high-tech areas such as nuclear fusion, aerospace, and high-performance tools, tungsten and its alloys are indispensable due to their high melting point, low thermal expansion, and excellent mechanical properties. The rise of Additive Manufacturing (AM) technologies, particularly Laser Powder Bed Fusion (L-PBF), has enabled the precise and rapid production of complex tungsten parts. However, cracking and densification remain major challenges in printing tungsten samples, and considerable efforts have been made to study how various processing conditions (such as laser power, scanning strategy, hatch spacing, scan speed, and substrate preheating) affect print quality. In this review, we comprehensively discuss various critical processing parameters and the impact of oxygen content on the control of the additive manufacturing process and the quality of the final parts. Additionally, we introduce additive manufacturing-compatible W materials (pure W, W alloys, and W-based composites), summarize the differences in their mechanical properties, densification, and microstructure, and further provide a clear outlook for developing additive manufactured W materials.

China’s urban–rural dichotomy has resulted in a widening gap between urban and rural areas, posing significant challenges to rural development. This study aims to investigate the spatio-temporal differentiation and driving mechanisms of rural industry integration within the Chengdu–Chongqing Economic Circle in China. Using panel data from 2011 to 2020, we employed the entropy weight TOPSIS method to construct a comprehensive index that charts the evolution of rural industry integration across various districts and counties. Additionally, we utilized fixed-effect and spatio-temporally weighted regression models to analyze the underlying driving forces behind this integration. Our findings reveal a dynamic and varied landscape of rural industry integration, with different levels of depth and breadth across various subsystems. Spatially, we observed a transition from a dispersed to a more concentrated agglomeration pattern within the Chengdu–Chongqing Economic Circle. This shift suggests a diffusion effect emanating from core metropolitan areas, as well as an attracting force exerted by adjacent metropolitan circles. In terms of drivers, market demand, openness level, financial development, policy support, and agricultural insurance breadth significantly contribute to rural industry integration. However, technological progress and rural human capital exhibit a weaker correlation. Notably, our models identified pronounced spatial–temporal heterogeneity among these influencing factors, highlighting a nuanced and dynamic relationship between them. Overall, our study emphasizes the crucial role of rural industry integration in bridging the urban–rural divide and fostering sustainable agricultural development and rural revitalization. The insights gained from this research provide valuable guidance for policymakers and stakeholders seeking to optimize rural development strategies and unlock the potential of integrated rural industries.

In this work, we introduce a novel coherent perfect absorber, accentuating its novelty by emphasizing the broad bandwidth, reduced thickness, tunable property, and straightforward design achieved through the use of an asymmetric graphene metasurface. This design incorporates both square and circular graphene patches arranged on either side of a silicon substrate. With an optimized structural design, this absorber consistently captures over 90% of incoming waves across the frequency range of 1.65 to 4.49 THz, with a graphene Fermi level of 0.8 eV, and the whole device measures just 1.5 um thick. This makes our absorber significantly more effective and compact than previous designs. The absorber’s effectiveness can be significantly enhanced by combining the metasurface’s geometric design with the graphene Fermi level. It is anticipated that this ultrathin, wideband coherent perfect absorption device will play a crucial role in emerging on-chip THz communication technologies, including light modulators, photodetectors, and so on.

Hepatic encephalopathy (HE) is often associated with endogenous serotonin (5-HT) disorders. However, the reason for elevated brain 5-HT levels due to liver failure remains unclear. This study aimed to investigate the mechanism by which liver failure increases brain 5-HT levels and the role in behavioral abnormalities in HE. Using bile duct ligation (BDL) rats as a HE model, we verified the elevated 5-HT levels in the cortex but not in the hippocampus and striatum, and found that this cortical 5-HT overload may be caused by BDL-mediated inhibition of UDP-glucuronosyltransferase 1A6 (UGT1A6) expression and activity in the cortex. The intraventricular injection of the UGT1A6 inhibitor diclofenac into rats demonstrated that the inhibition of brain UGT1A6 activity significantly increased cerebral 5-HT levels and induced HE-like behaviors. Co-immunofluorescence experiments demonstrated that UGT1A6 is primarily expressed in astrocytes. In vitro studies confirmed that NH4Cl activates the ROS-ERK pathway to downregulate UGT1A6 activity and expression in U251 cells, which can be reversed by the oxidative stress antagonist N-acetyl-l-cysteine and the ERK inhibitor U0126. Silencing Hepatocyte Nuclear Factor 4α (HNF4α) suppressed UGT1A6 expression whilst overexpressing HNF4α increased Ugt1a6 promotor activity. Meanwhile, both NH4Cl and the ERK activator TBHQ downregulated HNF4α and UGT1A6 expression. In the cortex of hyperammonemic rats, we also found activation of the ROS-ERK pathway, decreases in HNF4α and UGT1A6 expression, and increases in brain 5-HT content. These results prove that the ammonia-mediated ROS-ERK pathway activation inhibits HNF4α expression to downregulate UGT1A6 expression and activity, thereby increasing cerebral 5-HT content and inducing manic-like HE symptoms. This is the first study to reveal the mechanism of elevated cortical 5-HT concentration in a state of liver failure and elucidate its association with manic-like behaviors in HE.