A novel electrochemical sensor with NiSx@MoS2 composite for efficient NO2- sensing.

Excess nitrites are potentially threatening to human health, so it is urgent to develop accurate and sensitive methods. The development of sensors can provide early warning of possible hazards and alert people to protect public health. This work presents an NiSx@MoS2-composite with excellent electrochemical activity, representing a key finding for highly sensitive NO2- detection and sensor development. With the assistance of NiSx@MoS2, this electrochemical sensor has excellent quantitative detection performance. It has a wide detection range (0.0001-0.0020 mg/mL) and a low detection limit (1.863*10-5 mg/mL) for NO2-. This electrochemical sensor maintains excellent specificity among numerous interferences, and it completes the accurate detection of different real food samples. Pleasingly, the electrochemical sensor has satisfactory repeatability stability, and potential for practical applications. It would demonstrate tremendous potential in scientific dietary guidance, food safety detection and other fields.

Stiff extracellular matrix drives the differentiation of mesenchymal stem cells toward osteogenesis by the multiscale 3D genome reorganization.

Extracellular matrix (ECM) stiffness is a major driver of stem cell fate. However, the involvement of the three-dimensional (3D) genomic reorganization in response to ECM stiffness remains unclear. Here, we generated comprehensive 3D chromatin landscapes of mesenchymal stem cells (MSCs) exposed to various ECM stiffness. We found that there were more long-range chromatin interactions, but less compartment A in MSCs cultured on stiff ECM than those cultured on soft ECM. However, the switch from compartment B in MSCs cultured on soft ECM to compartment A in MSCs cultured on stiff ECM included genes encoding proteins primarily enriched in cytoskeleton organization. At the topologically associating domains (TADs) level, stiff ECM tends to have merged TADs on soft ECM. These merged TADs on stiff ECM include upregulated genes encoding proteins enriched in osteogenesis, such as SP1, ETS1, and DCHS1, which were validated by quantitative real-time polymerase chain reaction and found to be consistent with the increase of alkaline phosphatase staining. Knockdown of SP1 or ETS1 led to the downregulation of osteogenic marker genes, including COL1A1, RUNX2, ALP, and OCN in MSCs cultured on stiff ECM. Our study provides an important insight into the stiff ECM-mediated promotion of MSC differentiation towards osteogenesis, emphasizing the influence of mechanical cues on the reorganization of 3D genome architecture and stem cell fate.

How sediment dredging alters phosphorus dynamics in a lowland rural river?

China's lowland rural rivers are facing severe eutrophication problems due to excessive phosphorus (P) from anthropogenic activities. However, quantifying P dynamics in a lowland rural river is challenging due to its complex interaction with surrounding areas. A P dynamic model (River-P) was specifically designed for lowland rural rivers to address this challenge. This model was coupled with the Environmental Fluid Dynamics Code (EFDC) and the Phosphorus Dynamic Model for lowland Polder systems (PDP) to characterize P dynamics under the impact of dredging in a lowland rural river. Based on a two-year (2020-2021) dataset from a representative lowland rural river in the Lake Taihu Basin, China, the coupled model was calibrated and achieved a model performance (R2>0.59, RMSE<0.04 mg/L) for total P (TP) concentrations. Our research in the study river revealed that (1) the time scale for the effectiveness of sediment dredging for P control was ∼300 days, with an increase in P retention capacity by 74.8 kg/year and a decrease in TP concentrations of 23% after dredging. (2) Dredging significantly reduced P release from sediment by 98%, while increased P resuspension and settling capacities by 16% and 46%, respectively. (3) The sediment-water interface (SWI) plays a critical role in P transfer within the river, as resuspension accounts for 16% of TP imports, and settling accounts for 47% of TP exports. Given the large P retention capacity of lowland rural rivers, drainage ditches and ponds with macrophytes are promising approaches to enhance P retention capacity. Our study provides valuable insights for local environmental departments, allowing a comprehensive understanding of P dynamics in lowland rural rivers. This enable the evaluation of the efficacy of sediment dredging in P control and the implementation of corresponding P control measures.

The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons.

JOURNAL/nrgr/04.03/01300535-202501000-00029/figure1/v/2024-05-14T021156Z/r/image-tiff Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory. Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1; however, whether KIF21A modulates dendritic structure and function in neurons remains unknown. In this study, we found that KIF21A was distributed in a subset of dendritic spines, and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines. Furthermore, the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity. Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching, and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1, but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1. Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals' cognitive abilities. Taken together, our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.

Crystal structure regulation of trititanium pentoxide for advanced zero-strain lithium storage anode.

Significant advancements have been made in electric vehicles and consumer devices. However, lithium-ion batteries with commercial graphite anodes still face challenges owing to their sluggish lithium-ion kinetics, low lithiation potential, and limited cycle stability. Consequently, there is a considerable research interest in developing new anode materials with rich resources, "zero-strain" characteristics for long-term cycling, and outstanding electrochemical properties. In this study, we thoroughly examine the relationship between the structure and electrochemical characteristics of λ and ß phases of titanium pentoxides (Ti3O5). The findings indicate that the ß phase of Ti3O5 exhibits a overall electrochemical performance compared to the λ phase. Moreover, ß-Ti3O5 electrodes deliver a low, yet safe average operating potential of 0.82 V versus Li/Li+ and a reversible specific capacity of 181.9 mA h/g at 0.1 A/g, thereby significantly outperforming λ-Ti3O5 electrodes, with a value of only 55.7 mA h/g. The performance difference can be primarily attributed to the changes in the crystal structure, with the ß phase exhibiting a lower energy barrier for lithium-ion diffusion than the λ-phase. Moreover, the ß-Ti3O5 electrodes exhibit an good rate performance (capacity retention of 49.5 % at 10 A/g) and good cycling stability (absence of capacity degradation after 2000 cycles at 1.0 A g-1). These advantages suggest that ß-Ti3O5 is a promising anode material for reliable, rapid-charging, and secure lithium-ion storage.

Integrated multi-omics revealed that dysregulated lipid metabolism played an important role in RA patients with metabolic diseases.

OBJECTIVES: Patients with rheumatoid arthritis (RA) commonly experience a high prevalence of multiple metabolic diseases (MD), leading to higher morbidity and premature mortality. Here, we aimed to investigate the pathogenesis of MD in RA patients (RA_MD) through an integrated multi-omics approach. METHODS: Fecal and blood samples were collected from a total of 181 subjects in this study for multi-omics analyses, including 16S rRNA and internally transcribed spacer (ITS) gene sequencing, metabolomics, transcriptomics, proteomics and phosphoproteomics. Spearman's correlation and protein-protein interaction networks were used to assess the multi-omics data correlations. The Least Absolute Shrinkage and Selection Operator (LASSO) machine learning algorithm were used to identify disease-specific biomarkers for RA_MD diagnosis. RESULTS: Our results found that RA_MD was associated with differential abundance of gut microbiota such as Turicibacter and Neocosmospora, metabolites including decreased unsaturated fatty acid, genes related to linoleic acid metabolism and arachidonic acid metabolism, as well as downregulation of proteins and phosphoproteins involved in cholesterol metabolism. Furthermore, a multi-omics classifier differentiated RA_MD from RA with high accuracy (AUC: 0.958). Compared to gouty arthritis and systemic lupus erythematosus, dysregulation of lipid metabolism showed disease-specificity in RA_MD. CONCLUSIONS: The integration of multi-omics data demonstrates that lipid metabolic pathways play a crucial role in RA_MD, providing the basis and direction for the prevention and early diagnosis of MD, as well as new insights to complement clinical treatment options.

Transcriptome and targeted metabolome analysis of lipid profiles, nutrients compositions and volatile compounds in longissimus dorsi of different pig breeds.

Objective: Improving meat quality is important for commercial production and breeding. The molecular mechanism of intramuscular fat (IMF) deposition and meat characteristics remain further study. Methods: This study aimed to study the mechanism of IMF deposition and meat characteristics including redox potential, nutrients compositions and volatile compounds in longissimus dorsi (LD) by comparing with different pig breeds including Shanghai white (SW), Duroc x (Landrace Yorkshire) (DLY) and Laiwu (LW) pigs. Results: Results showed that the contents of IMF, triglyceride (TG), total cholesterol (TC), and redox potential parameters were lower, while the content of MDA and activity of lactate dehydrogenase (LDH) were higher in LD of SW pigs compared with LW pigs (p<0.05). No differences were observed about these parameters between SW and DLY pigs. Also, the contents of medium-long chain fatty acids and γ-aminobutyric acid (GABA) were higher, while Asp was lower in LD of SW pigs compared with LW pigs (p<0.05). Volatile compounds results showed that 6 ketones, 4 alkenes, 11 alkanes, 2 aldehydes, 1 alcohol were increased and cholesterol was decreased in SW pigs compared with LW pigs. Transcriptome results showed that differential expressed genes involved in lipid synthesis, metabolism and transport in LD between SW and LW pigs, which were further verified by qPCR. Spearman correlation showed that HSL and Nedd4 were positively related to contents of TG and IMF, while negatively related to volatile compounds and fatty acids (p<0.05). Plin3 and Mgll were negatively related to contents of TG, IMF and cholesterol, while positively related to MDA, LDH, and volatile compounds (p<0.05). PPARA was negatively related to contents of TC and IMF, and activity of SOD, while positively related to volatile compounds (p<0.05). Conclusion: Our study provided new insights into potential mechanisms of IMF deposition, nutrients composition and volatile compounds of muscular tissues of different pig breeds.

Hydrolysis products of agricultural waste can serve as microbial fertilizer enhancers to promote the growth of maize crops.

Efficient utilization of agricultural wastes and reduction of chemical fertilizer inputs are crucial for sustainable development of agriculture. Plant growth promoting rhizobacteria (PGPR) are widely used as biofertilizers to partially replace chemical fertilizers in agricultural production. The functional performance of PGPR strains is closely related to their root colonization capacity. Some organic acids from root exudates can recruit PGPR to colonize the root. In this study, agricultural organic wastes such as mushroom bran and tobacco waste materials were used to produce organic acids through the hypoxic hydrolysis process. The hydrolysis conditions were optimized to maximize the production of a mixture of complex organic acids from the hypoxic hydrolysis of these materials, employing both single-factor and orthogonal experimental methods. The diluted hydrolysates were tested for their effects on the rhizosphere colonization of the PGPR strain Bacillus amyloliquefaciens SQR9 using fluorogenic quantitative PCR in greenhouse pot experiments. The results demonstrated that hypoxic hydrolysates from tobacco waste and mushroom bran significantly enhanced the colonization of SQR9 in the maize rhizosphere. Specifically, a 2000-fold dilution of tobacco waste hydrolysate yielded the most effective result, while a 5000-fold dilution of mushroom bran hydrolysate provided the best outcome. All treatments combining these hydrolysates with SQR9 significantly increased maize stem dry weight, indicating that with appropriate treatment, such as anaerobic fermentation, these agricultural organic wastes can serve as synergistic agents of microbial fertilizers, contributing to agricultural sustainability.

Association between Systemic Immune-Inflammation Index (SII) and New-Onset In-Hospital Heart Failure in Patients with STEMI after Primary PCI.

Background: The systemic immune-inflammation index (SII) is a proven, reliable inflammatory marker of the atherosclerotic process. Additionally, inflammation is one of the most important mechanisms of heart failure (HF) after myocardial infarction (MI). However, it is not clear whether SII is related to the risk of in-hospital HF in patients with MI. Thus, we aimed to explore the relationship between SII and the risk of new-onset in-hospital HF in ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (pPCI). Methods: A total of 5586 patients with STEMI underwent pPCI at seven clinical sites in China from January 2015 to August 2021. The patients were divided into two groups based on the SII values. The association between SII and new-onset in-hospital HF in STEMI patients was assessed using logistic regression analysis. Results: Ultimately, 3808 STEMI patients with Killip class I who were treated with pPCI were included. All included patients were divided into two groups based on the calculated SII (Q1 SII: <1707.31 (×109/L), Q2 SII: ≥1707.31 (×109/L)). After unadjusted and multivariate adjustment for age, gender, vital signs, smoking, hypertension, diabetes mellitus, etc., the odds ratio (OR) of the in-hospital HF risk in Q2 was 1.378-1.427 times the Q1 in the calibration Models 1 to 5. Subgroup analysis showed that the OR of Q2 was 1.505-fold higher of Q1 in males and 1.525-fold in older people (≥60 years). Sensitivity analysis showed that after excluding patients who had previously experienced HF, MI, or underwent PCI, elevated SII was still associated with a significant increase in the risk of in-hospital HF. Conclusions: Elevated SII is associated with an increased risk of in-hospital HF in STEMI patients treated with pPCI, particularly in male and older patients. Clinical Trial Registration: The Chinese STEMI pPCI Registry was registered with ClinicalTrials.gov (NCT04996901, https://www.clinicaltrials.gov/study/NCT04996901?cond=NCT04996901&rank=1).

Real-Time Fluorescence Visualization of the Dynamic Distribution of Zn2+ Ions during Osteoblast Differentiation.

The differentiation and maturation of osteoblasts are essential for bone formation. Zn2+ plays a crucial role in cell differentiation and is involved in osteogenic differentiation. The concentration and distribution of Zn2+ in the nucleus and cytoplasm indicate the differentiation states of osteoblasts. However, there is an absence of a real-time method for monitoring the dynamic fluctuations of endogenous Zn2+ within the nucleus. Here, a novel Zn2+ fluorescent probe (NTAD-N1) with nuclear membrane permeability was designed and developed, allowing for distribution throughout the entire cell, including the nucleus. The NTAD-N1 probe successfully showed the dynamic distribution and concentration changes of Zn2+ in the nucleus and cytoplasm of preosteoblast MC3T3-E1 during the 21-day differentiation period. The results showed that free Zn2+ increased significantly during differentiation of osteoblasts (2-21 days). Importantly, after 4 days of differentiation, osteoblasts are mainly distributed in the nucleus, which is confirmed by metallothionein expression. Subsequently, the level of free Zn2+ in the cytoplasm remained at a high level, which promoted the increase in alkaline phosphatase activity and inhibited the activity of cis-aconitase in the tricarboxylic acid cycle, resulting in the accumulation of citric acid. This series of events promotes the formation of mineralized nodules. In the process of osteoblast differentiation, the detection time of Zn2+ (≤7 days) is ahead of the late marker of alkaline phosphatase (14 days) and mineralized nodules (14-21 days). This indicates that Zn2+ can be used as a biomarker and an intervention point for early differentiation of osteoblasts.

Derivation of induced pluripotent stem cell from a Baraitser-Winter Cerebrofrontofacial syndrome with ACTB mutation.

Baraitser-Winter Cerebrofrontofacial syndrome (BWCFF, OMIM: 243310) is a rare congenital developmental disorder marked by distinct facial dysmorphisms, coloboma, diminutive stature, and cognitive impairment, as initially described by Baraitser and Winter in 1988. Here, we derived human induced pluripotent stem cells (hiPSCs) from a 4-year-old male patient diagnosed with Baraitser-Winter Cerebrofrontofacial syndrome and harbouring a mutation in the ACTB gene. The newly established hiPSC line exhibited normal karyotypes and demonstrated the capacity to differentiate into all three germ layers. Additionally, these hiPSCs maintained their original genotype and expressed markers of pluripotency. Patient-derived hiPSCs would serve as a valuable tool for in vitro modelling of Baraitser-Winter Cerebrofrontofacial syndrome and reveal the potential pathogenesis induced by ACTB gene mutations.

Restructuring the interfacial active sites to generalize the volcano curves for platinum-cobalt synergistic catalysis.

Computationally derived volcano curve has become the gold standard in catalysis, whose practical application usually relies on empirical interpretations of composition or size effects by the identical active site assumption. Here, we present a proof-of-concept study on disclosing both the support- and adsorbate-induced restructuring of Pt-Co bimetallic catalysts, and the related interplays among different interfacial sites to propose the synergy-dependent volcano curves. Multiple characterizations, isotopic kinetic investigations, and multiscale simulations unravel that the progressive incorporation of Co into Pt catalysts, driven by strong Pt-C bonding (metal-support interfaces) and Co-O bonding (metal-adsorbate interfaces), initiates the formation of Pt-rich alloys accompanied by isolated Co species, then Co segregation to epitaxial CoOx overlayers and adjacent Co3O4 clusters, and ultimately structural collapse into amorphous alloys. Accordingly, three distinct synergies, involving lattice oxygen redox from Pt-Co alloy/Co3O4 clusters, dual-active sites engineering via Pt-rich alloy/CoOx overlayer, and electron coupling within exposed alloy, are identified and quantified for CO oxidation (gas-phase), ammonia borane hydrolysis (liquid-phase), and hydrogen evolution reaction (electrocatalysis), respectively. The resultant synergy-dependent volcano curves represent an advancement over traditional composition-/size-dependent ones, serving as a bridge between theoretical models and experimental observations in bimetallic catalysis.

Dual RNA-seq reveals distinct families of co-regulated and structurally conserved effectors in Botrytis cinerea infection of Arabidopsis thaliana.

BACKGROUND: Botrytis cinerea is a broad-host-range pathogen causing gray mold disease and significant yield losses of numerous crops. However, the mechanisms underlying its rapid invasion and efficient killing of plant cells remain unclear. RESULTS: In this study, we elucidated the dynamics of B. cinerea infection in Arabidopsis thaliana by live cell imaging and dual RNA sequencing. We found extensive transcriptional reprogramming events in both the pathogen and the host, which involved metabolic pathways, signaling cascades, and transcriptional regulation. For the pathogen, we identified 591 candidate effector proteins (CEPs) and comprehensively analyzed their co-expression, sequence similarity, and structural conservation. The results revealed temporal co-regulation patterns of these CEPs, indicating coordinated deployment of effectors during B. cinerea infection. Through functional screening of 48 selected CEPs in Nicotiana benthamiana, we identified 11 cell death-inducing proteins (CDIPs) in B. cinerea. CONCLUSIONS: The findings provide important insights into the transcriptional dynamics and effector biology driving B. cinerea pathogenesis. The rapid infection of this pathogen involves the temporal co-regulation of CEPs and the prominent role of CDIPs in host cell death. This work highlights significant changes in gene expression associated with gray mold disease, underscoring the importance of a diverse repertoire of effectors crucial for successful infection.

Dynamic changes of media prefrontal cortex astrocytic activity in response to negative stimuli in male mice.

Astrocytes play significant roles in regulating the central stress response. Chronic stress impairs the structure and function of astrocytes in many brain regions such as media prefrontal cortex (mPFC) in multiple neuropsychiatric conditions, but the astrocytic dynamics on the timescale of behavior remains unclear. Here, we recorded mPFC astrocytic activity in freely behaving mice and found that astrocytes are activated immediately by different aversive stimuli. Astrocyte specific GCaMP6s calcium indicator were virally expressed in mPFC astrocytes and fiber photometry experiments revealed that astrocytes are activated by tail-restraint (TRT), foot shock (FS), open arm exploration, stressor of height, predator odor and social defeat (SD) stress. ΔF/F analyses demonstrated that an unpredictable stimulus such as elevated platform stress (EPS) at the initial encounter induced the most intense and rapid changes in astrocytic calcium activity, while a predictable 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) stimulus resulted in the weakest response with a longer peak latency. In TRT, FS or SD test, a somatic stimulus led to higher average calcium activity level and faster average peak latency in repeated trails. Similar to TMT stimulus, astrocytic calcium activity in elevated plus maze (EPM) test exhibited a smaller average change in amplitude and the longest peak latency during open arm exploration. Moreover, astrocytic calcium activity exhibited different changes across behavioral states in SD tests. Our findings show that mPFC astrocytes exhibit distinct patterns of calcium activity in response to various negative stimuli, indicating that the dynamic activity of astrocytes may reflect the stress-related behavioral state under different stimulus conditions.

Comparing the prevalence and influencing factors of postpartum depression in primiparous and multiparous women in China.

Background: Few studies have compared the influencing factors of postpartum depression between primiparous and multiparous women. Therefore, this study is aimed to investigate the prevalence and influencing factors of postpartum depression in primiparous and multiparous women, and provide reference suggestions for clinical nursing. Methods: A total of 429 postpartum women who gave birth at a Maternal and Child Health Hospital in Shandong Province, China, from April to June 2024, were recruited by convenience sampling. A Sociodemographic Questionnaire, Edinburgh Postpartum Depression Scale, Pittsburgh Sleep Quality Index, and Perceived Social Support Scale were used for investigation. SPSS 26.0 was used to analyze the data, and multivariate regression was employed to analyze the influencing factors of postpartum depression between primiparous and multiparous women. Results: The total prevalence of postpartum depression among 429 postpartum women (191 primiparas and 238 multiparas) was 22.14%. The prevalence of postpartum depression among primiparous and multiparous women were 21.99% and 22.27%, respectively, with no statistically significant difference [OR=1.016, 95% CI (0.642, 1.608)]. Sleep quality is a common protective factor for postpartum depression in both primiparous and multiparous women, while perceived social support is another protective factor for multiparous women. The risk factors are different in both two group, there is no risk factor found in primiparous women, the newborns health and women's expectation on newborns gender are risk factors for postpartum depression in multiparous women. Conclusions: Both primiparous and multiparous women have a high risk of postpartum depression. In order to promote the mental health of postpartum women, precise nursing measures should be adopted for different parity of postpartum women in clinical practice.

Integrated single-cell and spatial transcriptomics reveal microenvironment disruptions by androgen in mouse ovary.

Elevated levels of androgen are risk factors for disrupted follicular maturation in the polycystic ovary syndrome (PCOS), a reproductive disease in women. As essential cell types for follicular maturation, granulosa and thecal cells respond to androgen, but their responses are unclear at the subpopulation level. Using single-cell RNA sequencing and spatial transcriptomics, we examined the subpopulation and function alterations in an androgen-induced PCOS-like mouse model. The results demonstrated that the granulosa cell subset 5 (GC5) was active in inflammation and the thecal cell subtype 2 (TC2) had an enhanced activity in lipid metabolism. The two subsets were expanded in population size and intercellular signaling pathways, such as Ptn-Ncl and Mdk-Ncl. The results reveal that androgen induced landscape and function shifts in the two cell types under the condition of impaired follicular maturation. The study characterizes the ovarian microenvironment in responses to androgen in PCOS mice.

The development of a machine learning model to train junior ophthalmologists in diagnosing the pre-clinical keratoconus.

Purpose: This study aims to evaluate the diagnostic performance of a machine learning model (ML model) to train junior ophthalmologists in detecting preclinical keratoconus (PKC). Methods: A total of 1,334 corneal topography images (The Pentacam HR system) from 413 keratoconus eyes, 32 PKC eyes and 222 normal eyes were collected. Five junior ophthalmologists were trained and annotated the images with or without the suggestions proposed by the ML model. The diagnostic performance of PKC was evaluated among three groups: junior ophthalmologist group (control group), ML model group and ML model-training junior ophthalmologist group (test group). Results: The accuracy of the ML model between the eyes of patients with KC and NEs in all three clinics (99% accuracy, area under the receiver operating characteristic (ROC) curve AUC of 1.00, 99% sensitivity, 99% specificity) was higher than that for Belin-Ambrósio enhanced ectasia display total deviation (BAD-D) (86% accuracy, AUC of 0.97, 97% sensitivity, 69% specificity). The accuracy of the ML model between eyes with PKC and NEs in all three clinics (98% accuracy, AUC of 0.96, 98% sensitivity, 98% specificity) was higher than that of BAD-D (69% accuracy, AUC of 0.73, 67% sensitivity, 69% specificity). The diagnostic accuracy of PKC was 47.5% (95%CI, 0.5-71.6%), 100% (95%CI, 100-100%) and 94.4% (95%CI, 14.7-94.7%) in the control group, ML model group and test group. With the assistance of the proposed ML model, the diagnostic accuracy of junior ophthalmologists improved with statistical significance (p < 0.05). According to the questionnaire of all the junior ophthalmologists, the average score was 4 (total 5) regarding to the comprehensiveness that the AI model has been in their keratoconus diagnosis learning; the average score was 4.4 (total 5) regarding to the convenience that the AI model has been in their keratoconus diagnosis learning. Conclusion: The proposed ML model provided a novel approach for the detection of PKC with high diagnostic accuracy and assisted to improve the performance of junior ophthalmologists, resulting especially in reducing the risk of missed diagnoses.

Intravitreal Dexamethasone Implants for Macular Edema Secondary to Acute Retinal Necrosis.

PURPOSE: To assess the effectiveness and risk of intravitreal injection of dexamethasone implants in treating macular edema (ME) secondary to acute retinal necrosis (ARN). METHODS: In this retrospective, noncomparative case series study, five patients who developed secondary ME after ARN and received an intravitreal dexamethasone implant injection were enrolled. The features of secondary ME on OCT and the outcomes of dexamethasone intravitreal implanting were presented. RESULTS: The mean age of the patients was 59 years (range, 51-61 years). All patients had unilateral involvement, and all 5 eyes showed mild to moderate anterior uveitis, retinal necrosis, and vasculitis. Herpes zoster virus was detected in all eyes using PCR, and timely antiviral and anti-inflammatory treatment was performed. Aqueous humor samples were negative for herpes zoster virus DNA, and resolution of viral retinitis was noted upon the occurrence of ME. Additionally, three eyes received pars plana vitrectomy with silicone oil prior to ME development. All eyes presented with intraretinal fluid, hyper-reflective foci, and impairments of the external limiting membrane/ellipsoid zone at varying degrees on OCT images. Epiretinal membrane was exhibited in 80% of eyes, but no vitreoretinal traction was detected. Subretinal fluid was visible in 60% of eyes. ME was relieved effectively in all eyes after intravitreal dexamethasone implanting. One of these patients experienced three episodes of ME. No recurrence of retinal necrosis or corticosteroid-associated ocular hypertension was observed during the follow-up period. CONCLUSION: Intravitreal injection of dexamethasone implants can effectively alleviate ME secondary to ARN and improve visual acuity with no adverse reactions.

Macular edema secondary to acute retinal necrosis was characterized by the presence of intraretinal fluid, hyper-reflective foci, and external limiting membrane/ellipsoid zone fracture. The intravitreal injection of dexamethasone implants effectively alleviated this type of edema with no adverse reactions.

ASGR1 Deficiency Inhibits Atherosclerosis in Western Diet-Fed ApoE-/- Mice by Regulating Lipoprotein Metabolism and Promoting Cholesterol Efflux.

BACKGROUND: Atherosclerosis is the most common cause of cardiovascular diseases. Clinical studies indicate that loss-of-function ASGR1 (asialoglycoprotein receptor 1) is significantly associated with lower plasma cholesterol levels and reduces cardiovascular disease risk. However, the effect of ASGR1 on atherosclerosis remains incompletely understood; whether inhibition of ASGR1 causes liver injury remains controversial. Here, we comprehensively investigated the effects and the underlying molecular mechanisms of ASGR1 deficiency and overexpression on atherosclerosis and liver injury in mice. METHODS: We engineered Asgr1 knockout mice (Asgr1-/-), Asgr1 and ApoE double-knockout mice (Asgr1-/-ApoE-/-), and ASGR1-overexpressing mice on an ApoE-/- background and then fed them different diets to assess the role of ASGR1 in atherosclerosis and liver injury. RESULTS: After being fed a Western diet for 12 weeks, Asgr1-/-ApoE-/- mice exhibited significantly decreased atherosclerotic lesion areas in the aorta and aortic root sections, reduced plasma VLDL (very-low-density lipoprotein) cholesterol and LDL (low-density lipoprotein) cholesterol levels, decreased VLDL production, and increased fecal cholesterol contents. Conversely, ASGR1 overexpression in ApoE-/- mice increased atherosclerotic lesions in the aorta and aortic root sections, augmented plasma VLDL cholesterol and LDL cholesterol levels and VLDL production, and decreased fecal cholesterol contents. Mechanistically, ASGR1 deficiency reduced VLDL production by inhibiting the expression of MTTP (microsomal triglyceride transfer protein) and ANGPTL3 (angiopoietin-like protein 3)/ANGPTL8 (angiopoietin-like protein 8) but increasing LPL (lipoprotein lipase) activity, increased LDL uptake by increasing LDLR (LDL receptor) expression, and promoted cholesterol efflux through increasing expression of LXRα (liver X receptor-α), ABCA1 (ATP-binding cassette subfamily A member 1), ABCG5 (ATP-binding cassette subfamily G member 5), and CYP7A1 (cytochrome P450 family 7 subfamily A member 1). These underlying alterations were confirmed in ASGR1-overexpressing ApoE-/- mice. In addition, ASGR1 deficiency exacerbated liver injury in Western diet-induced Asgr1-/-ApoE-/- mice and high-fat diet-induced but not normal laboratory diet-induced and high-fat and high-cholesterol diet-induced Asgr1-/- mice, while its overexpression mitigated liver injury in Western diet-induced ASGR1-overexpressing ApoE-/- mice. CONCLUSIONS: Inhibition of ASGR1 inhibits atherosclerosis in Western diet-fed ApoE-/- mice, suggesting that inhibiting ASGR1 may serve as a novel therapeutic strategy to treat atherosclerosis and cardiovascular diseases.

The Mediating Effect of Psychological Resilience and Coping Style on Fear of Recurrence and Reproductive Concerns in Breast Cancer Patients of Childbearing Age.

Objective: Fear of recurrence and reproductive concerns are great public health concerns among breast cancer patients in childbearing age. The purpose of this study was to explore whether psychological resilience and coping styles play mediating roles in fear of recurrence and reproductive concerns among Chinese breast cancer patients in childbearing age. Methods: A total of 1267 breast cancer patients of childbearing age completed the questionnaires, including a brief demographic questionnaire survey. The Chinese version of the Fear of Cancer Recurrence Scale and the Chinese version of the Reproductive Concerns Scale were used to assess the fear of recurrence and reproductive concerns, respectively. And the psychological resilience scale and the simple coping style questionnaire were used to evaluate breast cancer patients' psychological resilience and coping style during childbearing age. Mediation analyses were conducted by using PROCESS macro in the SPSS software. Results: Fear of recurrence had both direct and indirect effects on Reproductive Concerns. psychological resilience and coping style were not only independent mediators in the relationship between fear of recurrence and Reproductive Concerns but also chain mediators. Conclusion: The results of the current study highlight the crucial role of early intervention for Reproductive Concerns with a focus on fear of recurrence of breast cancer patients of childbearing age, more especially, on those with poorer psychological resilience and coping style.