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Magnesium alloys, noted for their substantial mechanical strength and exceptional biocompatibility, are increasingly being considered for use in biodegradable implants. However, their rapid degradation and significant hydrogen release have limited their applications in orthopaedics. In this study, a novel Mg-RE-Sr alloy was created by friction stir processing to modify its microstructure and enhance its degradation performance. Through microstructural characterization, the friction stir processing effectively refined the grains, accelerated the re-dissolution of precipitates, and ensured a uniform distribution of these phases. The processed alloy demonstrated improved comprehensive properties, with an in vitro corrosion rate of approximately 0.4 mm/y and increases in ultimate tensile strength and elongation by 37 % and 166 %, respectively. Notably, in vivo experiments involving a rat subcutaneous implantation model revealed a slower degradation rate of 0.09 mm/y and a uniform degradation process, basically achieving the requirements for ideal performance in orthopaedic applications. The superior degradation characteristics were attributed to the synergistic effect of attenuated galvanic corrosion and the formation of a dense Y(OH)3/Y2O3 film induced by an exceptional microstructure with a highly solid-soluted matrix and uniformly refined precipitates. Meanwhile, the alloys exhibited excellent biocompatibility and did not cause undesirable inflammation or produce toxic degradation products. These improvements in biocompatibility and degradation characteristics indicate great promise for the use of this friction stir processed alloy in osteosynthesis systems in the clinical setting.

Abstract Background Cerebral venous thrombosis (CVT) is a rare but serious condition that can lead to significant morbidity and mortality. Virchow’s triad elucidates the role of blood hypercoagulability, blood flow dynamics, and endothelial damage in the pathogenesis of CVT. Cerebral venous congestion (CVC) increases the risk of cerebral venous sinus thrombosis and can lead to recurrent episodes and residual symptoms. However, the precise mechanism by which blood congestion leads to thrombosis remains unclear. Our objective was to investigate the cellular and molecular alterations linked to CVC through analysis of the pathological morphology of venous sinus endothelial cells and transcriptomic profiling. Results This study demonstrated a remarkable correlation between CVC and the phenotypic transformation of endothelial cells from an anticoagulant to a procoagulant state. The findings revealed that cerebral venous stasis results in tortuous dilatation of the venous sinuses, with slow blood flow and elevated pressure in the sinuses and damaged endothelial cells of the retroglenoid and internal jugular vein ligation (JVL) rat model. Mechanistically, analysis of transcriptomic results of cerebral venous sinus endothelial cells showed significant activation of platelet activation, complement and coagulation cascades pathway in the JVL rats. Furthermore, the expression of von Willebrand factor (vWF) and coagulation factor VIII (F8) in the complement and coagulation cascades and Fgg and F2 in the platelet activation was increased in the cerebral venous sinuses of JVL rats than in sham rats, suggesting that endothelial cell injury in the venous sinus induced by CVC has a prothrombotic effect. In addition, endothelial cell damage accelerates coagulation and promotes platelet activation. Significantly, the concentrations of vWF, F2 and F8 in venous sinus blood of patients with internal jugular vein stenosis were higher than in their peripheral blood. Conclusion Collectively, our data suggest that CVC can induce endothelial cell damage, which then exhibits a procoagulant phenotype and ultimately increases the risk of CVT. This research contributes to our understanding of the pathophysiology of CVC associated with procoagulant factors and reexamines the components of Virchow’s triad in the context of CVC.

Quantum power system state estimation (QPSSE) offers an inspiring direction for tackling the challenge of state estimation through quantum computing. Nevertheless, the current bottlenecks originate from the scarcity of practical and scalable QPSSE methodologies in the noisy intermediate-scale quantum (NISQ) era. This paper devises a NISQ−QPSSE algorithm that facilitates state estimation on real NISQ devices. Our new contributions include: (1) A variational quantum circuit (VQC)-based QPSSE formulation that empowers QPSSE analysis utilizing shallow-depth quantum circuits; (2) A variational quantum linear solver (VQLS)-based QPSSE solver integrating QPSSE iterations with VQC optimization; (3) An advanced NISQ-compatible QPSSE methodology for tackling the measurement and coefficient matrix issues on real quantum computers; (4) A noise-resilient method to alleviate the detrimental effects of noise disturbances. The encouraging test results on the simulator and real-scale systems affirm the precision, universality, and scalability of our QPSSE algorithm and demonstrate the vast potential of QPSSE in the thriving NISQ era.

Abstract Background Overactivated microglia are a key contributor to Parkinson’s disease (PD) by inducing neuroinflammation. CD200R1, a membrane glycoprotein mainly found on microglia, is crucial for maintaining quiescence with its dysregulation linked to microglia’s abnormal activation. We and other groups have reported a decline in CD200R1 levels in several neurological disorders including PD. However, the mechanism regulating CD200R1 expression and the specific reasons for its reduction in PD remain largely unexplored. Given the pivotal role of transcription factors in gene expression, this study aimed to elucidate the transcriptional regulation of CD200R1 and its implications in PD. Methods The CD200R1 promoter core region was identified via luciferase assays. Potential transcription factors were predicted using the UCSC ChIP-seq database and JASPAR. NFKB1 binding to the CD200R1 core promoter was substantiated through electrophoretic mobility shift and chromatin immunoprecipitation assays. Knocking-down or overexpressing NFKB1 validated its regulatory effect on CD200R1. Correlation between decreased CD200R1 and deficient NFKB1 was studied using Genotype-Tissue Expression database. The clinical samples of the peripheral blood mononuclear cells were acquired from 44 PD patients (mean age 64.13 ± 9.78, 43.2% male, median Hoehn-Yahr stage 1.77) and 45 controls (mean age 64.70 ± 9.41, 52.1% male). NFKB1 knockout mice were utilized to study the impact of NFKB1 on CD200R1 expression and to assess their roles in PD pathophysiology. Results The study identified the CD200R1 core promoter region, located 482 to 146 bp upstream of its translation initiation site, was directly regulated by NFKB1. Significant correlation between NFKB1 and CD200R1 expression was observed in human PMBCs. Both NFKB1 and CD200R1 were significantly decreased in PD patient samples. Furthermore, NFKB1-/- mice exhibited exacerbated microglia activation and dopaminergic neuron loss after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. Conclusion Our study identified that NFKB1 served as a direct regulator of CD200R1. Reduced NFKB1 played a critical role in CD200R1 dysregulation and subsequent microglia overactivation in PD. These findings provide evidence that targeting the NFKB1-CD200R1 axis would be a novel therapeutic strategy for PD.

Abstract Controllable droplet propulsion on solid surfaces plays a crucial role in various technologies. Many actuating methods have been developed; however, there are still some limitations in terms of the introduction of additives, the versatilities of solid surfaces, and the speed of transportation. Herein, we have demonstrated a universal droplet propulsion method based on dynamic surface-charge wetting by depositing oscillating and opposite surface charges on dielectric films with unmodified surfaces. Dynamic surface-charge wetting propels droplets by continuously inducing smaller front contact angles than rear contact angles. This innovative imbalance is built by alternately storing and spreading opposite charges on dielectric films, which results in remarkable electrostatic forces under large gradients and electric fields. The method exhibits excellent droplet manipulation performance characteristics, including high speed (~130 mm/s), high adaptability of droplet volume (1 μL–1 mL), strong handling ability on non-slippery surfaces with large contact angle hysteresis (CAH) (maximum angle of 35°), significant programmability and reconfigurability, and low mass loss. The great application potential of this method has been effectively demonstrated in programmable microreactions, defogging without gravity assistance, and surface cleaning of photovoltaic panels using condensed droplets.

Retinal neovascularization (RNV), a typical pathological manifestation involved in most neovascular diseases, causes retinal detachment, vision loss, and ultimately irreversible blindness. Repeated intravitreal injections of anti-VEGF drugs were developed against RNV, with limitations of incomplete responses and adverse effects. Therefore, a new treatment with a better curative effect and more prolonged dosage is demanding. Here, we induced macrophage polarization to anti-inflammatory M2 phenotype by inhibiting cGAS-STING signaling with an antagonist C176, appreciating the role of cGAS-STING signaling in the retina in pro-inflammatory M1 polarization. C176-loaded and phosphatidylserine-modified dendritic mesoporous silica nanoparticles were constructed and examined by a single intravitreal injection. The biosafe nanoparticles were phagocytosed by retinal macrophages through a phosphatidylserine-mediated “eat me” signal, which persistently release C176 to suppress STING signaling and thereby promote macrophage M2 polarization specifically. A single dosage can effectively alleviate pathological angiogenesis phenotypes in murine oxygen-induced retinopathy models. In conclusion, these C176-loaded nanoparticles with enhanced cell uptake and long-lasting STING inhibition effects might serve as a promising way for treating RNV.

Phytopathogens can continuously cause serious losses worldwide to crop, fruit, and vegetable yields. The excessive use of conventional fungicides in pathogen management has raised severe environmental and health side effects and induced fungicide-resistant pathogen strains. RNA-based spray-induced gene silencing (SIGS) has emerged as an ecologically sustainable pathogen control approach. Here, we introduce the SIGS mechanism in plant pathogens, summarize the application of SIGS in controlling plant pathogens, and highlight the major considerations of SIGS. In addition, we propose the future perspectives of SIGS in crop protection and disease management.

Abstract Anthropogenic and climatic changes affect the water and energy cycles in High Mountain Asia (HMA), home to over two billion people and the largest reservoirs of freshwater outside the polar zone. Despite their significant importance for water management, consistent and reliable estimates of water storage and fluxes over the region are lacking because of the high uncertainties associated with the estimates of atmospheric conditions and human management. Here, we relied on multivariate data assimilation (MVDA) to provide estimates of energy and water storage and fluxes that reflect the processes occurring in the region such as greening and irrigation-driven groundwater depletion. We developed and employed an ensemble precipitation estimate by blending different precipitation products thereby reducing the uncertainties and inconsistencies associated with precipitation in HMA. Then, we assimilated five variables that capture the changes in hydrology in response to climate change and anthropogenic activities. Overall, our results have shown that MVDA has allowed a better representation of the land surface processes including greening and irrigation-driven groundwater depletion in HMA.

Abstract Purpose To investigate the associations between the most popular social media platform WeChat usage and cognitive performance among the middle-aged and older Chinese population using data from a nationally representative survey. Methods In total, 17,472 participants (≥ 45 years old) from the China Health and Retirement Longitudinal Study (CHARLS, Wave 4, 2018) were analyzed. Cognitive performance including episodic memory and executive function was assessed using Mini-Mental Status Examination (MMSE). Other confounding variables included socio-economic characteristics, medical status, and lifestyle-related information. Multiple linear regression models were used to test the association between cognitive performance and WeChat usage by introducing covariates hierarchically. Subgroup analyses of age and gender were conducted to estimate the robustness of the primary findings. Results After adjusting for multiple confounders across all linear models, WeChat usage is significantly associated with executive function, episodic memory, and global cognitive performance (all p values

Abstract Background Global climate change is one of the major challenges facing the world today, and forests play a crucial role as significant carbon sinks and providers of ecosystem services in mitigating climate change and protecting the environment. China, as one of the largest developing countries globally, owns 60% of its forest resources collectively. Evaluating the carbon sequestration cost of collective forests not only helps assess the contribution of China’s forest resources to global climate change mitigation but also provides important evidence for formulating relevant policies and measures. Results Over the past 30 years, the carbon sequestration cost of collective forests in China has shown an overall upward trend. Except for coastal provinces, southern collective forest areas, as well as some southwestern and northeastern regions, have the advantage of lower carbon sequestration costs. Furthermore, LSTM network predictions indicate that the carbon sequestration cost of collective forests in China will continue to rise. By 2030, the average carbon sequestration cost of collective forests is projected to reach 125 CNY per ton(= 16.06 Euros/t). Additionally, there is spatial correlation in the carbon sequestration cost of collective forests. Timber production, labor costs, and labor prices have negative spatial spillover effects on carbon sequestration costs, while land opportunity costs, forest accumulation, and rural resident consumption have positive spatial spillover effects. Conclusion The results of this study indicate regional disparities in the spatial distribution of carbon sequestration costs of collective forests, with an undeniable upward trend in future cost growth. It is essential to focus on areas with lower carbon sequestration costs and formulate targeted carbon sink economic policies and management measures to maximize the carbon sequestration potential of collective forests and promote the sustainable development of forestry.

Aiming at the problem of early inter-turn short circuit fault of axial flux stator coreless motor, a method for early inter-turn short circuit fault diagnosis and positioning of axial flux stator coreless motor based on the phase difference of zero sequence component and stator current component was proposed. Firstly, according to the characteristics of extremely small stator winding inductance, a mathematical model of inter-turn short circuit fault was established. Secondly, Fourier analysis of the short-circuit current, phase current and zero-sequence component before and after the fault was carried out, and the inter-turn short-circuit fault was identified by the change of the amplitude of the zero-sequence voltage fundamental wave.Finally, the fault phase was located by comparing the initial phase difference between the zero-sequence voltage fundamental wave and the stator three-phase current. The results show that the absolute value of the difference between initial phase of the phase current fundamental wave and the initial phase of the zero sequence voltage fundamental wave of the inter-turn short-circuit fault phase is approximately 180°, while the phase difference of the healthy phase is quite different from 180°. Based on the phase difference, the diagnosis and positioning of the early inter-turn short circuit fault of axial flux ironless motor can be realized, which provides some reference for the diagnosis of inter-turn short circuit fault of permanent magnet motor.

Abstract Background Brain function and neuronal activity depend on a constant supply of blood from the cerebral circulation. The cerebral venous system (CVS) contains approximately 70% of the total cerebral blood volume; similar to the cerebral arterial system, the CVS plays a prominent role in the maintenance of central nervous system (CNS) homeostasis. Impaired venous autoregulation, which can appear in forms such as cerebral venous congestion, may lead to metabolic abnormalities in the brain, causing severe cerebral functional defects and even chronic tinnitus. However, the role of cerebral venous congestion in the progression of tinnitus is underrecognized, and its pathophysiology is still incompletely understood. This study elucidated the specific pathogenetic role of cerebral venous congestion in the onset and persistence of tinnitus and the possible neurophysiological mechanisms. Results We found that a rat model of cerebral venous congestion exhibited tinnitus-like behavioral manifestations at 14 days postoperatively; from that point onward, they showed signs of persistent tinnitus without significant hearing impairment. Subsequent neuroimaging and neurochemical findings showed CNS homeostatic plasticity disturbance in rats with cerebral venous congestion, reflected in increased neural metabolic activity, ultrastructural synaptic changes, upregulated synaptic efficacy, reduced inhibitory synaptic transmission (due to GABA deficiency), and elevated expression of neuroplasticity-related proteins in central auditory and extra-auditory pathways. Conclusion Collectively, our data suggest that alternations in CNS homeostatic plasticity may play a vital role in tinnitus pathology caused by cerebral venous congestion. These findings provide a new perspective on tinnitus related to cerebral venous congestion and may facilitate the development of precise interventions to interrupt its pathogenesis.

Abstract Background Oral microbial dysbiosis contributes to the development of oral squamous cell carcinoma (OSCC). Our previous study showed that Prevotella intermedia (P. intermedia) were enriched in the oral mucosal surface, plaque, and saliva of patients with OSCC. Intratumoral microbiome could reshape the immune system and influence the development of various tumors. However, the invasion status of human OSCC tissues by P. intermedia and the pathway through which intratumoral P. intermedia potentiates tumor progression remain unexplored. Methods P. intermedia in human OSCC or normal tissues was detected by FISH. A mouse OSCC cell line SCC7 was adopted to investigate the effects of heat-killed P. intermedia treatment on cell proliferation, invasion, and cytokine release by using CCK-8 assay, transwell invasion assay and ELISA. Moreover, we established a mouse transplanted tumor model by using SCC7 cells, injected heat-killed P. intermedia into tumor tissues, and investigated the effects of heat-killed P. intermedia on tumor growth, invasion, cytokine levels, immune cell infiltrations, and expression levels by using gross observation, H&E staining, ELISA, immunohistochemistry, mRNA sequencing, and transcriptomic analysis. Results Our results indicated that P. intermedia were abundant in OSCC and surrounding muscle tissues. Heat-killed P. intermedia promoted SCC7 cell proliferation, invasion and proinflammatory cytokine secretions, accelerated transplanted tumor growth in mice, exacerbate muscle and perineural invasion of OSCC, elevated the serum levels of IL-17A, IL-6, TNF-α, IFN-γ, and PD-L1, induced Treg cells M2 type macrophages in mouse transplanted tumors. The data of transcriptomic analysis revealed that heat-killed P. intermedia increased the expression levels of inflammatory cytokines and chemokines while reduced the expression levels of some tumor suppressor genes in mouse transplanted tumors. Additionally, IL-17 signaling pathway was upregulated whereas GABAergic system was downregulated by heat-killed P. intermedia treatment. Conclusions Taken together, our results suggest that P. intermedia could inhibit the expression of tumor suppressors, alter the tumor microenvironment, and promote the progression of OSCC.

AbstractBackground The burden of carbapenem-resistant gram-negative bacteria (CRGNB) among solid organ transplant (SOT) recipients has not been systematically explored. Here, we discern the risk factors associated with CRGNB infection and colonization in SOT recipients.Methods This study included observational studies conducted among CRGNB-infected SOT patients, which reported risk factors associated with mortality, infection or colonization. Relevant records will be searched in PubMed, Embase and Web of Science for the period from the time of database construction to 1 March 2023.Results A total of 23 studies with 13,511 participants were included, enabling the assessment of 27 potential risk factors. The pooled prevalence of 1-year mortality among SOT recipients with CRGNB was 44.5%. Prolonged mechanical ventilation, combined transplantation, reoperation and pre-transplantation CRGNB colonization are salient contributors to the occurrence of CRGNB infections in SOT recipients. Renal replacement therapy, post-LT CRGNB colonization, pre-LT liver disease and model for end-stage liver disease score increased the risk of infection. Re-transplantation, carbapenem use before transplantation and ureteral stent utilization increaesd risk of CRGNB colonization.Conclusion Our study demonstrated that SOT recipients with CRGNB infections had a higher mortality risk. Invasive procedure may be the main factor contribute to CRGNB infection.

ObjectiveIn this study, we collected perioperative and postoperative follow-up data from patients with endometrial cancer (EC) at different stages to evaluate the role of sentinel lymph node biopsy (SLNB) in endometrial cancer surgery.MethodsA total of 186 endometrial cancer patients undergoing radical hysterectomy from January 2018 to April 2022 were retrospectively analyzed. Patients were classified into four groups. Group A comprised patients diagnosed with stage IA grade 1 and 2 endometrioid EC who underwent SLNB. Group B comprised patients with stage IA grade 1 and 2 endometrioid EC who did not undergo SLNB. Group C comprised patients with higher-grade endometrioid EC, wherein systematic lymph node dissection was performed based on SLNB results. Group D comprised patients with higher-grade endometrioid EC who did not undergo SLNB and instead underwent direct systematic lymph node dissection. Clinical, pathological data, and follow-up information for all patients were collected.ResultsIn Group A and B, SLNB was performed on 36 out of 67 patients with IA stage 1 and 2 endometrial cancer, yielding a SLN positivity rate of 5.6%. There were no significant differences observed between the two groups regarding perioperative outcomes and postoperative follow-up. Conversely, among 119 patients with higher-grade endometrial cancer, 52 underwent SLNB, with 20 patients exhibiting SLN positivity, resulting in a SLN positivity rate of 38.4%. However, the decision to undergo SLNB did not yield significant differences in perioperative outcomes and postoperative follow-up among these patients.ConclusionFor stage IA grade 1 and 2 endometrioid EC, the incidence of lymph node positivity is low, omitting SLNB in this subpopulation is a feasible option. In other stages of endometrioid EC, there is no significant difference in perioperative and postoperative follow-up data between patients undergoing routine systematic lymphadenectomy and those undergoing systematic lymphadenectomy based on SLNB results. Therefore, if SLNB is not available, the standard procedure of PLND remains an option to obtain information about lymph node status, despite the surgical complications associated with this procedure.

Abstract Background Astragaloside IV (AS‐IV) is the most active monomer in the traditional Chinese herbal medicine Radix Astragali, which has a wide range of antiviral, anti‐inflammatory, and antifibrosis pharmacological effects, and shows protective effects in acute lung injury. Methods This study utilized the immunofluorescence, flow cytometry, enzyme‐linked immunosorbent assay, quantitative reverse transcription‐polymerase chain reaction, western blot, and hematoxylin and eosin staining methods to investigate the mechanism of AS‐IV in reducing viral pneumonia caused by influenza A virus in A549 cells and BALB/c mice. Results The results showed that AS‐IV suppressed reactive oxygen species production in influenza virus‐infected A549 cells in a dose‐dependent manner, and subsequently inhibited the activation of nucleotide‐binding oligomerization domain‐like receptor thermal protein domain associated protein 3 inflammasome and Caspase‐1, decreased interleukin (IL) ‐1β and IL‐18 secretion. In BALB/c mice infected with Poly (I:C), oral administration of AS‐IV can significantly reduce Poly (I:C)‐induced acute pneumonia and lung pathological injury. Conclusions AS‐IV alleviates the inflammatory response induced by influenza virus in vitro and lung flammation and structural damage caused by poly (I:C) in vivo.

Background: Epidemiological studies have reported associations between heavy metals and renal function. However, longitudinal studies are required to further validate these associations and explore the interactive effects of heavy metals on renal function and their directional influence. Method: This study, conducted in Northeast China from 2016 to 2021, included a four-time repeated measures design involving 384 participants (1536 observations). Urinary concentrations of chromium (Cr), cadmium (Cd), manganese (Mn), and lead (Pb) were measured, along with renal biomarkers including urinary microalbumin (umAlb), urinary albumin-to-creatinine ratio (UACR), N-acetyl-β-D-glucosaminidase (NAG), and β2-microglobulin (β2-MG) levels. Estimated glomerular filtration rate (eGFR) was calculated. A Linear Mixed Effects Model (LME) examined the association between individual metal exposure and renal biomarkers. Subsequently, Quantile g-computation and Bayesian Kernel Machine Regression (BKMR) models assessed the overall effects of heavy metal mixtures. Marginal Effect models examined the directional impact of metal interactions in the BKMR on renal function. Result: Results indicate significant impacts of individual and combined exposures of Cr, Cd, Pb, and Mn on renal biomarkers. Metal interactions in the BKMR model were observed, with synergistic effects of Cd-Cr on NAG, umAlb, UACR; Cd-Pb on NAG, UACR; Pb-Cr on umAlb, UACR, eGFR-MDRD, eGFR-EPI; and an antagonistic effect of Mn-Pb-Cr on UACR. Conclusion: Both individual and combined exposures to heavy metals are associated with renal biomarkers, with significant synergistic interactions leading to renal damage. Our findings elucidate potential interactions among these metals, offering valuable insights into the mechanisms linking multiple metal exposures to renal injury.

Abstract Tumor-secreted factors contribute to the development of a microenvironment that facilitates the escape of cancer cells from immunotherapy. In this study, we conduct a retrospective comparison of the proteins secreted by hepatocellular carcinoma (HCC) cells in responders and non-responders among a cohort of ten patients who received Nivolumab (anti-PD-1 antibody). Our findings indicate that non-responders have a high abundance of secreted RNase1, which is associated with a poor prognosis in various cancer types. Furthermore, mice implanted with HCC cells that overexpress RNase1 exhibit immunosuppressive tumor microenvironments and diminished response to anti-PD-1 therapy. RNase1 induces the polarization of macrophages towards a tumor growth-promoting phenotype through activation of the anaplastic lymphoma kinase (ALK) signaling pathway. Targeting the RNase1/ALK axis reprograms the macrophage polarization, with increased CD8+ T- and Th1- cell recruitment. Moreover, simultaneous targeting of the checkpoint protein PD-1 unleashes cytotoxic CD8+ T-cell responses. Treatment utilizing both an ALK inhibitor and an anti-PD-1 antibody exhibits enhanced tumor regression and facilitates long-term immunity. Our study elucidates the role of RNase1 in mediating tumor resistance to immunotherapy and reveals an RNase1-mediated immunosuppressive tumor microenvironment, highlighting the potential of targeting RNase1 as a promising strategy for cancer immunotherapy in HCC.

Objective(s): The present study investigated the effect and its underlying mechanisms of fucoidan on Type 1 diabetes mellitus (T1DM) in non-obese diabetic (NOD) mice. Materials and Methods: Twenty 7-week-old NOD mice were used in this study, and randomly divided into two groups (10 mice in each group): the control group and the fucoidan treatment group (600 mg/kg. body weight). The weight gain, glucose tolerance, and fasting blood glucose level in NOD mice were detected to assess the development of diabetes. The intervention lasted for 5 weeks. The proportions of Th1/Th2 cells from spleen tissues were tested to determine the anti-inflammatory effect of fucoidan. Western blot was performed to investigate the expression levels of apoptotic markers and autophagic markers. Apoptotic cell staining was visualized through TdT-mediated dUTP nick-end labeling (TUNEL). Results: The results suggested that fucoidan ameliorated T1DM, as evidenced by increased body weight and improved glycemic control of NOD mice. Fucoidan down-regulated the Th1/Th2 cells ratio and decreased Th1 type pro-inflammatory cytokines’ level. Fucoidan enhanced the mitochondrial autophagy level of pancreatic cells and increased the expressions of Beclin-1 and LC3B II/LC3B I. The expression of p-AMPK was up-regulated and p-mTOR1 was inhibited, which promoted the nucleation of transcription factor EB (TFEB), leading to autophagy. Moreover, fucoidan induced apoptosis of pancreatic tissue cells. The levels of cleaved caspase-9, cleaved caspase-3, and Bax were up-regulated after fucoidan treatment. Conclusion: Fucoidan could maintain pancreatic homeostasis and restore immune disorder through enhancing autophagy via the AMPK/mTOR1/TFEB pathway in pancreatic cells.

Traditional grid analytics heavily rely on accurate power system models, especially dynamic ones for generators, controllers, and loads. However, obtaining comprehensive models is impractical in real operations due to inaccessible parameters and consumer privacy. This necessitates dynamic equivalencing for unknown subsystems, which employs physics-informed machine learning and neural ordinary differential equations (ODE-NET) to preserve dynamic behaviors post-disturbances. The contributions include: 1) A neural dynamic equivalence (NeuDyE) formulation enabling continuous-time, data-driven dynamic equivalence, eliminating the need for acquiring inaccessible system details; 2) Introduction of Physics-Informed NeuDyE learning (PI-NeuDyE) to actively control NeuDyE’s closed-loop accuracy; 3) Driving Port NeuDyE (DP-NeuDyE), a practical application of NeuDyE, reducing the number of inputs required for training. Extensive case studies on the 140-bus NPCC system validate the generalizability and accuracy of both PI-NeuDyE and DP-NeuDyE. These analyses cover various scenarios, including limitations in data accessibility. Test results demonstrate the scalability and practicality of NeuDyE, showcasing its potential application in ISO and utility control centers for online transient stability analysis and planning purposes.

Remote sensing (RS) imagery captures the earth's ever-changing landscapes, reflecting evolving land cover patterns propelled by natural processes and human activities. However, existing RS scene classification methods mainly operate under a closed-set hypothesis, which stumbles when encountering novel emerging scenes. This article addresses the intricate task of RS scene classification without labels for novel scenes under incremental learning, termed class-incremental novel category discovery. We propose a contrastive learning-based novel category discovery pipeline tailored for RS image scene classification, enhancing the ability to learn unlabeled novel class data. Furthermore, within this pipeline, we introduce a positive pair filter to identify more positive sample pairs from novel classes, improving the feature representation capability on unlabeled data. Besides, our contrastive learning pipeline incorporates an old-feature replaying method to alleviate catastrophic forgetting in old classes. Extensive evaluations across three public RS datasets showcase the superiority of our method over state-of-the-art approaches.

Abstract Background The management of post-refractive surgery dry eye disease (DED) can be challenging in clinical practice, and patients usually show an incomplete response to traditional artificial tears, especially when it is complicated with ocular pain. Therefore, we aim to investigate the efficacy of combined topical 0.05% cyclosporine A and 0.1% sodium hyaluronate treatment in post-refractive surgery DED patients with ocular pain unresponsive to traditional artificial tears. Methods We enrolled 30 patients with post-refractive surgery DED with ocular pain who were unresponsive to traditional artificial tears. Topical 0.05% cyclosporine A and 0.1% sodium hyaluronate were used for 3 months. They were evaluated at baseline and 1 and 3 months for dry eye and ocular pain symptoms and objective parameters, including Numerical Rating Scale (NRS), Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-Eye), tear break-up time (TBUT), Schirmer I test (SIt), corneal fluorescein staining (CFS), corneal sensitivity, and corneal nerve morphology. In addition, tear levels of inflammatory cytokines and neuropeptides were measured using the Luminex assay. Results After 3 months of treatment, patients showed a statistically significant improvement in the ocular surface disease index (OSDI), TBUT, SIt, CFS, and corneal sensitivity (all P

Abstract Introduction Chronic ocular pain, particularly prevalent in patients with dry eye disease and post-femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) surgery, presents with unclear clinical characteristics and an undefined pathogenesis. In this study, we aimed to compare clinical characteristics and tear neuropeptide concentrations in patients with dry eye disease (DED) with and without chronic ocular pain following FS-LASIK, and investigate correlations between ocular pain, clinical characteristics, and tear neuropeptide levels. Methods Thirty-eight post–FS-LASIK patients with DED were assigned to two groups: those with chronic ocular pain and those without chronic ocular pain. Dry eye, ocular pain, and mental health-related parameters were evaluated using specific questionnaires and tests. The morphology of corneal nerves and dendritic cells (DCs) was evaluated by in vivo confocal microscopy. Function of corneal innervation was evaluated by corneal sensitivity. Concentrations of tear cytokines (interleukin [IL]-6, IL-23, IL-17A, and interferon-γ) and neuropeptides (α-melanocyte-stimulating hormone, neurotensin, β-endorphin, oxytocin, and substance P [SP]) were measured using the Luminex assay. Results Most patients with chronic ocular pain experienced mild to moderate pain; the most common types included stimulated pain (provoked by wind and light), burning pain, and pressure sensation. More severe dry eye (P

Large-scale distributed generation (DG) access to the distribution network brings many uncertainties to the distribution network, considering the impact of different types of distributed power supply on the optimization results as well as the uncertainty and correlation of wind energy, photovoltaic power generation, and load. A metaheuristic algorithm the Improved Beluga Whale Optimization Algorithm (IBWO) is used to optimize the capacity and location of DG. This algorithm incorporates the elite reverse learning strategy and cyclone foraging strategy while adjusting the balance factor to enhance the diversity of the algorithm population and further balance local search capability with global search capability. This study optimizes the configuration of distributed energy resources considering the uncertainty and correlation of wind power, photovoltaic power, and load. The optimization objective is to reduce active power loss, improve voltage stability, and minimize investment and operating costs. By conducting simulations on IEEE 33-bus and IEEE 118-bus test cases, the active power network losses are enhanced by 55.49% and 45.39% respectively, and the algorithm outperforms other methods regarding other data, demonstrating its superiority and effectiveness.

Incorporating β-glucan-rich oat bran (OB) can attenuate postprandial glycemic response (PPGR) in solid foods, but its effect in liquid matrices is unclear. This study investigated the ability of differently processed low-dose-β-glucan-containing beverages to lower PPGR, and the mechanisms of action. Twenty participants consumed five malt beverages made from cocoa powder: intact OB (Intact), OB treated with enzymatic hydrolysis (EnzymA, EnzymB) or extrusion (Extr), or no OB (Ctrl). Four-hour postprandial incremental areas under the curve (iAUC) and peak incremental concentrations (iCmax) of glucose, insulin, glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), and paracetamol were evaluated. The molecular weight (MW) and extractability of the β-glucan in all the test products were also assessed. The three-hour glucose iAUC significantly decreased by −26%, −28%, −32%, and −38% in Intact, EnzymA, EnzymB, and Extr, respectively, and the insulin levels of the oat-containing products were also significantly lower compared to Ctrl. Intact and Extr elicited a lower insulin iCmax and GLP-1 3 h iAUC compared to Ctrl. However, the GIP and paracetamol levels were not changed. All the processed OBs improved β-glucan extractability and lowered the MW of β-glucan compared to Intact. In conclusion, low-dose oat β-glucan in a beverage significantly reduced PPGR, with effects maintained across different oat processing methods.

Haze refers to an atmospheric phenomenon with extremely low visibility, which has significant impacts on human health and safety. Water vapor alters the scattering properties of atmospheric particulate matter, thus affecting visibility. A comprehensive analysis of the role of water vapor in haze formation is of great scientific significance for forecasting severe pollution weather events. This study investigates the distribution characteristics and variations of water vapor during haze weather in Changchun City (44°N, 125.5°E) in autumn and winter seasons, aiming to reveal the relationship between haze and atmospheric water vapor content. Analysis of observational results for a period of two months (October to November 2023) from a three-wavelength Raman lidar deployed at the site reveals that atmospheric water vapor content is mainly concentrated below 5 km, accounting for 64% to 99% of the total water vapor below 10 km. Furthermore, water vapor content in air pollution exhibits distinct stratification characteristics with altitude, especially within the height range of 1–3 km, where significant water vapor variation layers exist, showing spatial consistency with inversion layers. Statistical analysis of haze events at the site indicates a high correlation between the concentration variations of PM2.5 and PM10 and the variations in average water vapor mixing ratio (WVMR). During haze episodes, the average WVMR within 3 km altitude is 3–4 times higher than that during clear weather. Analysis of spatiotemporal height maps of aerosols and water vapor during a typical haze event suggests that the relative stability of the atmospheric boundary layer may hinder the vertical transport and diffusion of aerosols. This, in turn, could lead to a sharp increase in aerosol extinction coefficients through hygroscopic growth, thereby possibly exacerbating haze processes. These observational findings indicate that water vapor might play a significant role in haze formation, emphasizing the potential importance of observing the vertical distribution of water vapor for better simulation and prediction of haze events.

Objective To investigate differential associations of traditional and novel adiposity indices with visual impairment (VI) in the middle-aged and older Chinese population.Methods and analysis Based on the China Health and Retirement Longitudinal Study, 7750 Chinese older adults aged over 45 were included at baseline 2011, and 4133 participants who accomplished all three interviews from 2011 to 2015 were adapted for longitudinal analyses. We enrolled six adiposity indices, including the body mass index (BMI), waist-to-height ratio (WHtR), weight-adjusted-waist index (WWI), a body shape index (ABSI), body roundness index (BRI) and conicity index (ConI). Visual status and other covariates included sociodemographic characteristics, medical supports and lifestyle-related factors. Cross-sectional correlations were assessed using univariate and multivariate logistic regression analyses. For longitudinal analysis, generalised linear models with generalised estimating equations were used to determine the association between time-varying adiposity and visual status.Results Higher levels of WHtR/WWI/ABSI/BRI/ConI were significantly associated with an increased prevalence of VI, whereas a higher BMI was associated with a decreased prevalence of VI. Only WWI was significantly related to the prevalence of VI after adjustment for multiple confounders in both cross-sectional and longitudinal analyses (all p values

Abstract The critical gelation conditions observed in dilute aqueous solutions of multiple nanoscale uranyl peroxide molecular clusters are reported, in the presence of multivalent cations. This gelation is dominantly driven by counterion‐mediated attraction. The gelation areas in the corresponding phase diagrams all appear in similar locations, with a characteristic triangle shape outlining three critical boundary conditions, corresponding to the critical cluster concentration, cation/cluster ratio, and the degree of counterion association with increasing cluster concentration. These interesting phrasal observations reveal general conditions for gelation driven by electrostatic interactions in hydrophilic macroionic solutions.

AimsTo investigate the association between socioeconomic position (SEP) and sensory impairments (SIs).MethodsWe used data from the China Health and Retirement Longitudinal Study (CHARLS) (2015). Logistic regressions estimated the odds ratio for associations of SEP with SIs. In addition, Mendelian randomization (MR) analysis was conducted to assess the causal relationship between them with the inverse variance weighting (IVW) estimator. MR-Egger, simple median, weighted median, maximum likelihood, and robust adjusted profile score were employed for sensitivity analyses.ResultsIn the observational survey, we enrolled 19,690 individuals aged 45 and above. SEP was negatively associated with SIs. Adjusted odds of vision impairment were higher for illiterate (1.50; 95%CI: 1.19, 1.91), less than elementary school diploma (1.76; 95%CI: 1.39, 2.25), middle school diploma (1.53; 95%CI: 1.21, 1.93) and lower income (all p

Background: The impact of heavy metals on liver function has been examined in numerous epidemiological studies. However, these findings lack consistency and longitudinal validation. Methods: In this study, we conducted three follow-up surveys with 426 participants from Northeast China. Blood and urine samples were collected, along with questionnaire information. Urine samples were analyzed for concentrations of four metals (chromium [Cr], cadmium [Cd], lead [Pb], and manganese [Mn]), while blood samples were used to measure five liver function indicators (alanine aminotransferase [ALT], aspartate aminotransferase [AST], albumin [ALB], globulin [GLB], and total protein [TP]). We utilized a linear mixed-effects model (LME) to explore the association between individual heavy metal exposure and liver function. Joint effects of metal mixtures were investigated using quantile g-computation and Bayesian kernel machine regression (BKMR). Furthermore, we employed BKMR and Marginal Effect models to examine the interaction effects between metals on liver function. Results: The LME results demonstrated a significant association between urinary heavy metals (Cr, Cd, Pb, and Mn) and liver function markers. BKMR results indicated positive associations between heavy metal mixtures and ALT, AST, and GLB, and negative associations with ALB and TP, which were consistent with the g-comp results. Synergistic effects were observed between Cd-Cr on ALT, Mn-Cr and Cr-Pb on ALB, while an antagonistic effect was found between Mn-Pb and Mn-Cd on ALB. Additionally, synergistic effects were observed between Mn-Cr on GLB and Cd-Cr on TP. Furthermore, a three-way antagonistic effect of Mn-Pb-Cr on ALB was identified. Conclusion: Exposure to heavy metals (Cr, Cd, Mn, Pb) is associated with liver function markers, potentially leading to liver damage. Moreover, there are joint and interaction effects among these metals, which warrant further investigation at both the population and mechanistic levels.

Summary: Here, we present a protocol for the examination of immune cells in the murine conjunctiva and lacrimal gland using flow cytometry. We describe steps for dissection, preparation of high-quality single-cell suspensions, utilization of comprehensive staining panels, and optimization of flow cytometry voltage. We then detail procedures for compensation adjustments and the implementation of effective gating strategies.For complete details on the use and execution of this protocol, please refer to Ma et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Circularly polarized light (CPL) adds a unique dimension to optical information processing and communication. Integrating CPL sensitivity with light learning and memory in a photonic artificial synapse (PAS) device holds significant value for advanced neuromorphic vision systems. However, the development of such systems has been impeded by the scarcity of suitable CPL active optoelectronic materials. In this work, we employ a helical chiral perovskite hybrid combined with single-wall carbon nanotubes to achieve circularly polarized ultraviolet neuromorphic vision sensing and imaging. The heterostructure demonstrates long-term charge storage as evidenced by multiple-pulsed transient absorption measurements and highly sensitive circular polarization-dependent photodetection, thereby enabling efficient CPL-resolved synaptic and neuromorphic behaviors. Significantly, our PAS sensor arrays adeptly visualize, discriminate, and memorize distinct circularly polarized images with up to 93% recognition accuracy in spiking neural network simulations. These findings underscore the pivotal role of chiral perovskites in advancing PAS technology and circular polarization-enhanced ultraviolet neuromorphic vision systems.

With the continual deployment of power-electronics-interfaced renewable energy resources, increasing privacy concerns due to deregulation of electricity markets, and the diversification of demand-side activities, traditional knowledge-based power system dynamic modeling methods are faced with unprecedented challenges. Data-driven modeling has been increasingly studied in recent years because of its lesser need for prior knowledge, higher capability of handling large-scale systems, and better adaptability to variations of system operating conditions. This paper discusses about the motivations and the generalized process of data-driven modeling, and provides a comprehensive overview of various state-of-the-art techniques and applications. It also comparatively presents the advantages and disadvantages of these methods and provides insight into outstanding challenges and possible research directions for the future.

This study aims to compare the restraint performance of two child restraint systems (CRSs) used on airplanes—a rear-facing child seat (RFCS) and the child aviation restraint system (CARES)—for 1.5-year-old children, along with their compatibility with different types of aircraft seats. 16 g longitudinal dynamic tests were conducted on two types of aircraft seats with CRSs. Results indicate poor compatibility of CARES with Type A seats, significantly increasing the risk of head, neck, and abdominal injuries, with Nij exceeding the acceptable limit. In contrast, CARES exhibited good compatibility with Type B seats and effectively protected children. RFCS tests demonstrated effective injury risk reduction on both types of seats. It can be found that the performance of CARES depends on restraint status and seat dimensions; RFCSs provide adequate protection for 1.5-year-olds. Optimal protection can be achieved with smaller restrain angles of CRS and using thinner seat cushions. Compared to CARES, RFCSs better adapt to various aircraft seat structures, offering superior child protection.

Abstract Background and purpose Cortical vein thrombosis (CVT) is a rare form of cerebral venous sinus thrombosis (CVST) in adolescent patients that has received little attention. We aimed to analyze the clinical and radiological features of adolescents with CVST and investigate the effects of CVT involvement. Methods Patients aged ≥ 10 to ≤ 18 years and diagnosed with CVST were identified at Xuanwu Hospital, Capital Medical University between January 2015 and August 2022 and divided into two groups according to the presence or absence of cortical vein involvement. Additionally, the patients were also categorized based on their sex. Clinical features, radiological characteristics, and 12-month follow-up outcomes were compared between the two groups. Results Fifty-three adolescents, including 21 with CVT, were included (mean age: 15.2 ± 1.8 years; females, 54.7%). The CVT group was more likely to experience seizures (P = 0.028) and deterioration (28.6% vs. 6.2%, P = 0.047) during hospitalization than the non-CVT group. Poor short-term outcomes, based on the modified Rankin Scale (mRS) score at discharge, were more common in adolescents with CVT (P = 0.007). The proportions of patients showing edema (42.9% vs. 6.2%, P = 0.004) and mass effect (P = 0.015) were significantly higher in the CVT group. Recanalization was observed in 61.9% and 82.1% of the patients in the CVT and non-CVT groups, respectively, during the first imaging review (median, 22 days). After a 12-month follow-up, female adolescents had more frequent resident secondary headaches than male adolescents (52.9% vs. 12.5%; P = 0.014). Conclusions Cortical vein involvement in adolescents with CVST was associated with a higher risk of epilepsy at presentation, deterioration during hospitalization, edema, and mass effect on acute imaging. Moreover, cortical vein involvement may lead to worse short-term outcomes. Sex differences require consideration in etiological analyses and prolonged follow-ups.

Abstract Background The US Food and Drug Administration (FDA) regulates goods accounting for 20% of US consumers’ total expenditure. The agency’s potential susceptibility to corporate lobbying and political influence may adversely affect the its abilities to fulfill its duties as a vital federal agency. This study assesses whether the FDA’s product recall classifications in recall scenarios are influenced by firms’ lobbying activities. Methods The universe of all FDA recalls between 2012 and 2019 is obtained from the FDA’s website. Firm names are matched to federal-level lobbying data obtained from the Center for Responsive Politics – a non-profit and nonpartisan organization that tracks lobbying expenditures and campaign contributions. Analyses are conducted using ordinary-least-squares regressions, in which the dependent variable is recall classification and independent variables are three different measures of firms’ lobbying activities in the one year prior to the recall. Results Firms that engage in lobbying appear more likely to receive favourable classifications from the FDA. When examining the above results by product type, we find that classification of food recalls seems to be subject to lobbying influence, but the same does not appear to be true for drug and device recalls. Evidence is consistent with the conjecture that the distinction between medical and food firms may be a result of medical firms targeting lobbying efforts at FDA approvals, rather than recalls. Conclusions Between 2012 and 2019, the FDA’s product recall classifications seem to be significantly influenced by firms’ lobbying activities. Lobbying firms appear to have received more favorable (i.e., less severe) recall classifications compared to non-lobbying firms.

Background: The etiology and motor presentation differs between pediatric- and adult-onset dystonia. Emerging evidence has demonstrated that non-motor symptoms are frequent in adult dystonia, which affect the quality of life. By contrast, little is known about the frequency and severity of such presentations in pediatric-onset individuals. Here, we investigated the motor and non-motor symptoms in a large cohort of Chinese patients with isolated dystonia and compared between pediatric-onset and adult-onset groups.Methods: In this retrospective study, 34 pediatric-onset patients and 197 adult-onset patients with isolated dystonia were recruited. Motor impairment was assessed by the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Non-motor symptoms were evaluated through several validated scales, including fatigue (by Fatigue Severity Scale, FSS), excessive daytime sleepiness (by Epworth Sleepiness Scale, ESS), sleep disturbance (by Pittsburgh Sleep Quality Index, PSQI), anxiety (by Beck Anxiety Inventory, BAI) and depression (by Beck Depression Inventory 21, BDI-21).Results: Generalized dystonia was more common in pediatric-onset patients and focal dystonia was more common in adult-onset patients (p < 0.001). Generally, the BFMDRS score in total pediatric-onset group was higher than adult-onset group (p = 0.002). No differences was found in BFMDRS score between pediatric-onset and adult-onset patients with cervical and multifocal subtype dystonia. Compared with adult-onset group, pediatric-onset group had a lower rate of sleep disturbance (p < 0.0001) and similar rates of fatigue, excessive daytime sleepiness, depression and anxiety. Logistic regression analysis on patients with cervical dystonia indicated that the adult-onset and motor severity were independently associated with increased odds of sleep disturbance (p = 0.03) and depression (p = 0.01), respectively.Conclusion: Pediatric-onset dystonia patients were less likely to display focal dystonia. Most non-motor symptoms in pediatric-onset patients were comparable to their adult-onset counterparts. Non-motor presentations may to some extent correlate with motor symptoms, but their underlying pathophysiology need to be investigated further.

With a dynamical mass of 3 M _Jup , the recently discovered giant planet AF Lep b is the lowest-mass imaged planet with a direct mass measurement. Its youth and spectral type near the L/T transition make it a promising target to study the impact of clouds and atmospheric chemistry at low surface gravities. In this work, we present JWST/NIRCam imaging of AF Lep b. Across two epochs, we detect AF Lep b in F444W (4.4 μ m) with signal-to-noise ratios of 9.6 and 8.7, respectively. At the planet’s separation of 320 mas during the observations, the coronagraphic throughput is ≈7%, demonstrating that NIRCam’s excellent sensitivity persists down to small separations. The F444W photometry of AF Lep b affirms the presence of disequilibrium carbon chemistry and enhanced atmospheric metallicity. These observations also place deep limits on wider-separation planets in the system, ruling out 1.1 M _Jup planets beyond 15.6 au (0.″58), 1.1 M _Sat planets beyond 27 au (1″), and 2.8 M _Nep planets beyond 67 au (2.″5). We also present new Keck/NIRC2 $L^{\prime} $ imaging of AF Lep b; combining this with the two epochs of F444W photometry and previous Keck $L^{\prime} $ photometry provides limits on the long-term 3–5 μ m variability of AF Lep b on timescales of months to years. AF Lep b is the closest-separation planet imaged with JWST to date, demonstrating that planets can be recovered well inside the nominal (50% throughput) NIRCam coronagraph inner working angle.

A noisy environment can considerably impact drivers' attention and fatigue, endangering driving safety. Consequently, this study designed a simulated driving experimental scenario to analyse the effects of noise generated during urban rail transit train operation on drivers' functional brain networks. The experiment recruited 16 participants, and the simulated driving scenario was conducted at noise levels of 50, 60, 70, and 80 dB. Functional connectivity between all electrode pairs across various frequency bands was evaluated using the weighted phase lag index (WPLI), and a brain network based on this was constructed. Graph theoretic analysis employed network global efficiency, degree, and clustering coefficient as metrics. Significant increases in the WPLI values of theta and alpha frequency bands were observed in high noise environments (70 dB, 80 dB), as well as enhanced brain synchronisation. Furthermore, concerning the topological metrics of brain networks, it was observed that the global efficiency of brain networks in theta and alpha frequency ranges, as well as the node degree and clustering coefficients, experienced substantial growth in high noise environments (70 dB, 80 dB) as opposed to 50 dB and 60 dB. This finding indicates that high-noise environments impact the reorganisation of functional brain networks, leading to a preference for network structures with improved global efficiency. Such findings may improve our understanding of the neural mechanisms of driving under noise exposure, and thus potentially reduce road accidents to some extent.

The unprecedented medium-resolution ( R _λ ∼ 1500–3500) near- and mid-infrared (1–18 μ m) spectrum provided by JWST for the young (140 ± 20 Myr) low-mass (12–20 M _Jup ) L–T transition (L7) companion VHS 1256 b gives access to a catalog of molecular absorptions. In this study, we present a comprehensive analysis of this data set utilizing a forward-modeling approach applying our Bayesian framework, ForMoSA . We explore five distinct atmospheric models to assess their performance in estimating key atmospheric parameters: T _eff , log( g ), [M/H], C/O, γ , f _sed , and R . Our findings reveal that each parameter’s estimate is significantly influenced by factors such as the wavelength range considered and the model chosen for the fit. This is attributed to systematic errors in the models and their challenges in accurately replicating the complex atmospheric structure of VHS 1256 b, notably the complexity of its clouds and dust distribution. To propagate the impact of these systematic uncertainties on our atmospheric property estimates, we introduce innovative fitting methodologies based on independent fits performed on different spectral windows. We finally derived a T _eff consistent with the spectral type of the target, considering its young age, which is confirmed by our estimate of log( g ). Despite the exceptional data quality, attaining robust estimates for chemical abundances [M/H] and C/O, often employed as indicators of formation history, remains challenging. Nevertheless, the pioneering case of JWST’s data for VHS 1256 b has paved the way for future acquisitions of substellar spectra that will be systematically analyzed to directly compare the properties of these objects and correct the systematics in the models.

We present a performance analysis for the aperture masking interferometry (AMI) mode on board the James Webb Space Telescope Near Infrared Imager and Slitless Spectrograph (JWST/NIRISS). Thanks to self-calibrating observables, AMI accesses inner working angles down to and even within the classical diffraction limit. The scientific potential of this mode has recently been demonstrated by the Early Release Science (ERS) 1386 program with a deep search for close-in companions in the HIP 65426 exoplanetary system. As part of ERS 1386, we use the same data set to explore the random, static, and calibration errors of NIRISS AMI observables. We compare the observed noise properties and achievable contrast to theoretical predictions. We explore possible sources of calibration errors and show that differences in charge migration between the observations of HIP 65426 and point-spread function calibration stars can account for the achieved contrast curves. Lastly, we use self-calibration tests to demonstrate that with adequate calibration NIRISS F380M AMI can reach contrast levels of ∼9–10 mag at ≳ λ / D . These tests lead us to observation planning recommendations and strongly motivate future studies aimed at producing sophisticated calibration strategies taking these systematic effects into account. This will unlock the unprecedented capabilities of JWST/NIRISS AMI, with sensitivity to significantly colder, lower-mass exoplanets than lower-contrast ground-based AMI setups, at orbital separations inaccessible to JWST coronagraphy.

Abstract Purpose The purpose of this study was to test the hypothesis that brain white matter hyperintensities (WMH) are more common in patients receiving epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) and identify clinical risk factors associated with WMH. Experimental design This multiple‐center, prospective cohort study was conducted from March 2017 to July 2020. Two groups of patients with non‐small cell lung cancer (NSCLC) who received or did not receive EGFR‐TKI were included and followed up for more than 24 months. The progression of WMH was defined as an increase of ≥1 point on the Fazekas visual rating scale between the baseline and at the 2‐year follow‐up. A modified Poisson regression model was performed to evaluate risk factors on increased WMH load. Results Among 286 patients with NSCLC, 194 (68%) patients with NSCLC who received EGFR‐TKI and 92 (32%) patients with NSCLC without EGFR‐TKI treatment were analyzed. Modified Poisson regression analysis showed that EGFR‐TKI treatment was independently associated with the WMH progression (EGFR‐TKI: aRR 2.72, 95% confidence interval [CI] 1.46–5.06, p = .002). Interleukin (IL)‐2, IL‐4, and IL‐10 were associated with increased WMH in the adjusted model (IL‐2: aRR 1.55 [95% CI 1.06–2.25], p = .023; IL‐4: aRR 1.66 [95% CI 1.13–2.43], p = .010; IL‐10: aRR 1.48 [95% CI 1.06–2.06], p = .020). Conclusion Patients with NSCLC who received EGFR‐TKI may be at higher risk of developing WMH or worsening of WMH burden. The impact of increased WMH lesions in these patients is to be further assessed. IL‐2, IL‐4, and IL‐10 may be used as potential biomarkers to monitor the risk of increased WMH burden

BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) has emerged as a potentially effective neuromodulation technique for addressing neurological disorders, including disorders of consciousness. Expanding upon our prior clinical study, which demonstrated the superior effectiveness of a 4-week taVNS treatment in patients with minimally conscious state (MCS) compared to those in a vegetative state/unresponsive wakefulness state, the aim of this investigation was to evaluate the safety and therapeutic efficacy of taVNS in individuals with MCS through a sham-controlled randomized double-blind clinical trial.MethodsA cohort of 50 adult patients (male = 33, female = 17) diagnosed with a MCS were randomly assigned to either the active taVNS (N = 25) or sham taVNS (N = 25) groups. The treatment period lasted for 4 weeks, followed by an 8-week follow-up period. The Coma Recovery Scale-Revised (CRS-R) and Glasgow Coma Scale (GCS) were administered at baseline and weekly during the initial 4 weeks. Additionally, the Disability Rating Scale (DRS) was used to assess the patients’ functional abilities via telephone at week 12. Furthermore, various neurophysiological measures, including electroencephalogram (EEG), upper-limb somatosensory evoked potentials (USEP), brainstem auditory evoked potentials (BAEP), and P300 event-related potentials (P300), were employed to monitor changes in brain activity and neural conduction pathways.ResultsThe scores for the active taVNS group in the CRS-R and GCS showed greater improvement over time compared to the sham taVNS group (CRS-R: 1-week, Z = −1.248, p = 0.212; 2-week, Z = −1.090, p = 0.276; 3-week, Z = −2.017, p = 0.044; 4-week, Z = −2.267, p = 0.023. GCS: 1-week, Z = −1.325, p = 0.185; 2-week, Z = −1.245, p = 0.213; 3-week, Z = −1.848, p = 0.065; 4-week, Z = −1.990, p = 0.047). Additionally, the EEG, USEP, BAEP, and P300 also demonstrated significant improvement in the active taVNS group compared to the sham taVNS group at week 4 (EEG, Z = −2.086, p = 0.037; USEP, Z = −2.014, p = 0.044; BAEP, Z = −2.298, p = 0.022; P300 amplitude, Z = −1.974, p = 0.049; P300 latency, t = 2.275, p = 0.027). Subgroup analysis revealed that patients with MCS derived greater benefits from receiving taVNS treatment earlier (CRS-R, Disease duration ≤ 1-month, mean difference = 8.50, 95% CI = [2.22, 14.78], p = 0.027; GCS, Disease duration ≤ 1-month, mean difference = 3.58, 95% CI = [0.14, 7.03], p = 0.044). By week 12, the active taVNS group exhibited lower Disability Rating Scale (DRS) scores compared to the sham taVNS group (Z = −2.105, p = 0.035), indicating a more favorable prognosis for MCS patients who underwent taVNS. Furthermore, no significant adverse events related to taVNS were observed during treatment.ConclusionThe findings of this study suggest that taVNS may serve as a potentially effective and safe intervention for facilitating the restoration of consciousness in individuals diagnosed with MCS. This therapeutic approach appears to enhance cerebral functioning and optimize neural conduction pathways.Clinical trial registrationhttp://www.chictr.org.cn, Identifier ChiCTR2200066629.

Adhesives are commonly assessed by two properties: strength and toughness. Here we study how strength and toughness are affected by adhesive thickness. We sandwich gelatin adhesives of various thicknesses between glass substrates. The transparency of the adhesives and substrates enables us to observe crack nucleation and growth. We measure strength by lap shear of samples without precrack, and measure toughness by lap shear of samples with precrack. Our data show a characteristic adhesive thickness, about 0.5 mm. For adhesives below the characteristic thickness, strength is independent of thickness, but toughness increases with thickness. For adhesives above the characteristic thickness, strength decreases as thickness increases, but toughness is a constant. Strength scatters narrowly for samples of a thin adhesive, but broadly for samples of a thick adhesive. By contrast, toughness scatters narrowly for samples of all thicknesses. This work shows the importance of assessing adhesives of various thicknesses.

Abstract Background The long-term use of visual display terminals (VDT) is linked to an increased risk of dry eye disease (DED). Numerous studies have indicated that ocular mucins play a vital role in the pathogenesis of DED. Therefore, we aimed to evaluate (1) whether mRNA levels of membrane-associated mucins (MAMs), including MUC1, MUC4, MUC16, and MUC20, as well as MUC5AC are altered in conjunctival cells of VDT users with and without DED and (2) the relationship between mucin levels and subjective and objective tests of DED in VDT users. Methods Seventy-nine VDT users were enrolled and divided into DED (n = 53) and control (n = 26) groups. All participants were evaluated for parameters of DED using the Ocular Surface Disease Index (OSDI) questionnaire, tear breakup time (TBUT), corneal fluorescein staining (CFS), lissamine green (LG) staining, and tear meniscus height (TMH). Based on the conjunctival impression cytology (CIC) method, differences in MUC1, MUC4, MUC16, MUC20, and MUC5AC mRNA expression levels were observed between the DED and control groups, and between symptomatic and asymptomatic participants. Results The DED group showed significantly decreased MUC1, MUC16, and MUC20 expressions (all P

Abstract Background The epidermis of cotton ovule produces fibers, the most important natural cellulose source for the global textile industry. However, the molecular mechanism of fiber cell growth is still poorly understood. Results Here, we develop an optimized protoplasting method, and integrate single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) to systematically characterize the cells of the outer integument of ovules from wild type and fuzzless/lintless (fl) cotton (Gossypium hirsutum). By jointly analyzing the scRNA-seq data from wildtype and fl, we identify five cell populations including the fiber cell type and construct the development trajectory for fiber lineage cells. Interestingly, by time-course diurnal transcriptomic analysis, we demonstrate that the primary growth of fiber cells is a highly regulated circadian rhythmic process. Moreover, we identify a small peptide GhRALF1 that circadian rhythmically controls fiber growth possibly through oscillating auxin signaling and proton pump activity in the plasma membrane. Combining with scATAC-seq, we further identify two cardinal cis-regulatory elements (CREs, TCP motif, and TCP-like motif) which are bound by the trans factors GhTCP14s to modulate the circadian rhythmic metabolism of mitochondria and protein translation through regulating approximately one third of genes that are highly expressed in fiber cells. Conclusions We uncover a fiber-specific circadian clock-controlled gene expression program in regulating fiber growth. This study unprecedentedly reveals a new route to improve fiber traits by engineering the circadian clock of fiber cells.

Efficient acquisition of crop leaf moisture information holds significant importance for agricultural production. This information provides farmers with accurate data foundations, enabling them to implement timely and effective irrigation management strategies, thereby maximizing crop growth efficiency and yield. In this study, unmanned aerial vehicle (UAV) multispectral technology was employed. Through two consecutive years of field experiments (2021–2022), soybean (Glycine max L.) leaf moisture data and corresponding UAV multispectral images were collected. Vegetation indices, canopy texture features, and randomly extracted texture indices in combination, which exhibited strong correlations with previous studies and crop parameters, were established. By analyzing the correlation between these parameters and soybean leaf moisture, parameters with significantly correlated coefficients (p < 0.05) were selected as input variables for the model (combination 1: vegetation indices; combination 2: texture features; combination 3: randomly extracted texture indices in combination; combination 4: combination of vegetation indices, texture features, and randomly extracted texture indices). Subsequently, extreme learning machine (ELM), extreme gradient boosting (XGBoost), and back propagation neural network (BPNN) were utilized to model the leaf moisture content. The results indicated that most vegetation indices exhibited higher correlation coefficients with soybean leaf moisture compared with texture features, while randomly extracted texture indices could enhance the correlation with soybean leaf moisture to some extent. RDTI, the random combination texture index, showed the highest correlation coefficient with leaf moisture at 0.683, with the texture combination being Variance1 and Correlation5. When combination 4 (combination of vegetation indices, texture features, and randomly extracted texture indices) was utilized as the input and the XGBoost model was employed for soybean leaf moisture monitoring, the highest level was achieved in this study. The coefficient of determination (R2) of the estimation model validation set reached 0.816, with a root-mean-square error (RMSE) of 1.404 and a mean relative error (MRE) of 1.934%. This study provides a foundation for UAV multispectral monitoring of soybean leaf moisture, offering valuable insights for rapid assessment of crop growth.

The ocular surface microenvironment, containing the cornea, conjunctiva, and lacrimal gland, constitutes the mucosal frontline of the eye and houses a myriad of immune cells. As a part of unconventional T cells, gamma delta (γδ) T cells differ in the development and functions from canonical alpha beta (αβ) T cells. They are predominantly situated in mucosal sites throughout the body, including ocular surface tissues. Recent research has elucidated that γδ T cells serve as the primary interleukin-17A (IL-17A) source in the conjunctiva. They play a pivotal role in preserving ocular surface homeostasis and exhibit both protective and pathogenic roles in ocular surface diseases. This review delves into the general profiles of γδ T cells, their distribution in ocular surface tissues, and consolidates current insights into their functions in different conditions including dry eye disease, infectious keratitis, corneal wound healing, anterior chamber-associated immune deviation, allergic conjunctival disease, and diabetic ocular surface disease. The aim is to provide a systemic perspective on γδ T cells in the ocular surface microenvironment and outline potential directions for future studies.