Association between Peripheral Arterial Lactate Levels and Malignant Brain Edema Following Endovascular Treatment for Ischemic Stroke.

AIMS: To investigate the factors of postoperative malignant brain edema (MBE) in patients with acute ischemic stroke (AIS) treated with endovascular treatment (EVT). BACKGROUND: MBE is a severe complication following EVT for AIS, and it is essential to identify risk factors early. Peripheral arterial lactate (PAL) levels may serve as a potential predictive marker for MBE. OBJECTIVE: To determine whether immediate postoperative PAL levels and the highest PAL level within 24 hours of EVT are independently associated with MBE development in AIS patients. METHODS: We retrospectively analyzed patients with AIS who underwent EVT from October 2019 to October 2022. Arterial blood was collected every 8 h after EVT to measure PAL, and record the immediate postoperative PAL and the highest PAL level within 24 h. Brain edema was evaluated using brain computed tomography scans within 7 days of EVT. RESULTS: The study included 227 patients with a median age of 71 years, of whom 59.5% were male and MBE developed in 25.6% of patients (58/227). Multivariate logistic regression analysis showed that the immediate postoperative PAL (odds ratio, 1.809 [95% confidence interval (CI), 1.215-2.693]; p = 0.004) and the highest PAL level within 24 h of EVT (odds ratio, 2.259 [95% CI, 1.407-3.629]; p = 0.001) were independently associated with MBE. The area under the curve for predicting MBE based on the highest PAL level within 24 hours of EVT was 0.780 (95% CI, 0.711-0.849). CONCLUSION: Early increase in PAL levels is an independent predictor of MBE after EVT in AIS patients.

Amyloid-ß but not tau accumulation is strongly associated with longitudinal cognitive decline.

OBJECTIVE: Alzheimer's disease (AD) pathology is featured by the extracellular accumulation of amyloid-ß (Aß) plaques and intracellular tau neurofibrillary tangles in the brain. We studied whether Aß and tau accumulation are independently associated with future cognitive decline in the AD continuum. METHODS: Data were acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI) public database. A total of 1272 participants were selected based on the availability of Aß-PET and CSF tau at baseline and of those 777 participants with follow-up visits. RESULTS: We found that Aß-PET and CSF tau pathology were related to cognitive decline across the AD clinical spectrum, both as potential predictors for dementia progression. Among them, Aß-PET (A + T- subjects) is an independent reliable predictor of longitudinal cognitive decline in terms of ADAS-13, ADNI-MEM, and MMSE scores rather than tau pathology (A - T+ subjects), indicating tau accumulation is not closely correlated with future cognitive impairment without being driven by Aß deposition. Of note, a high percentage of APOE ε4 carriers with Aß pathology (A+) develop poor memory and learning capacity. Interestingly, this condition is not recurrence in terms of the ADNI-MEM domain when adding APOE ε4 status. Finally, the levels of Aß-PET SUVR related to glucose hypometabolism more strongly in subjects with A + T- than A - T+ both happen at baseline and longitudinal changes. CONCLUSIONS: In conclusion, Aß-PET alone without tau pathology (A + T-) measure is an independent reliable predictor of longitudinal cognitive decline but may nonetheless forecast different status of dementia progression. However, tau accumulation alone without Aß pathology background (A - T+) was not enough to be an independent predictor of cognitive worsening.

Dry eye and decreased tear film stability in primary acquired nasolacrimal duct obstruction patients.

PURPOSE: Exploring the prevalence of dry eye (DE) and the changes of tear film stability in patients with primary acquired obstruction of the nasolacrimal duct (PANDO). METHODS: In this cross-sectional, observational study, 370 eyes in 223 patients with PANDO were assessed. The ocular surface disease index (OSDI) was used to evaluate ocular surface symptoms, and the Keratograph 5M non-invasive ocular surface analyser was used to assess ocular surface parameters. According to the TFOS DEWS II criteria, patients with OSDI ≥ 13 and NIKBUT < 10 s were diagnosed with DE. RESULTS: Of the 223 PANDO patients, 65 (29.1%) met the diagnostic criteria for DE. Compared with patients without DE, PANDO patients with DE were significantly older (p < 0.001), had a longer duration of epiphora (p = 0.023), and more likely to have a positive regurgitation on pressure over the lacrimal sac (ROPLAS) sign (p = 0.003). Multifactorial analysis showed that older age, positive ROPLAS and hypertension were significant independent predictors of DE (p < 0.05). Among the 147 unilateral PANDO patients without DE, the TMH, NIKBUT-first, NIKBUT-average and bulbar erythema scores were significantly higher in the PANDO sides. CONCLUSIONS: This study illustrated the prevalence of DE in PANDO patients was 29.1% and DE is more likely to occur in those who are older, have hypertension and are positive for ROPLAS. In addition, in patients with unilateral nasolacrimal duct obstruction, a decrease in tear film stability was observed in the healthy eye.

Cation vacancy modulated Cu3P-CoP heterostructure electrocatalyst for boosting hydrogen evolution at high current densities and coupling Zn-H2O battery.

Exploiting highly efficient, cost-effective and stable electrocatalysts is key to decreasing hydrogen evolution reaction (HER) kinetics energy barrier. Herein, the alkaline HER kinetics energy barrier can greatly reduce by the joint strategies of the cation vacancy and heterostructure engineering, which is seldom explored and remains ambiguous. In this study, an efficient and stable copper foam-supported Cu3P-CoP heterostructure electrocatalyst with cation vacancy defects (defined as Cu3P-CoP-VAl/CF) was designed for HER via the successive coprecipitation, electrodeposition, alkali etching and phosphorization treatments. As anticipated, the as-obtained Cu3P-CoP-VAl/CF electrocatalyst reveals a remarkable catalytic activity for HER with a low overpotential of 205 mV at a current density of 100 mA·cm-2, a high turnover frequency value of 1.05 s-1 at an overpotential of 200 mV and a small apparent activation energy (Ea) of 9 kJ·mol-1, while shows superior long-term stability at large current densities of 100 and 240 mA·cm-2. Systematic experiment and characterization data demonstrate that the formed cation vacancy could optimize the Ea, leading to the decrease of the kinetic barriers of Cu3P-CoP/CF heterostructure, as well as the established heterogeneous interface induced a synergistic effect between biphasic components on boosting the kinetics toward HER. The results of density functional theory disclose that the synergistic effect of Cu3P-CoP heterostructure could decrease the energy barrier and optimize Gibbs free energy of hydrogen adsorption, resulting in the enhancement of intrinsic catalytic activity of Cu3P-CoP-VAl/CF. More significantly, the alkali-cell assembled by Cu3P-CoP-VAl/CF (cathode) and RuO2/CF (anode) behaves outstanding water splitting performance, delivering a current density of 10 mA·cm-2 at a relatively small applied voltage of 1.58 V, along with encouraging long-term durability. In addition, the alkaline Zn-H2O battery with Cu3P-CoP-VAl/CF as the cathode has been fabricated for the simultaneous generation of electricity and hydrogen, which displays a large power density of up to 4.1 mW·cm-2. The work demonstrates that rational strategy for the design of competent electrocatalysts can effectively accelerate the kinetics of HER, which supplies valuable insights for practical applications in overall water splitting.

Fucoidan from Apostichopus japonicus ameliorates alcoholic liver disease by regulating gut-liver axis homeostasis.

Long-term and excessive alcohol consumption can lead to the development of alcoholic liver disease (ALD), characterized by oxidative damage, intestinal barrier injury, and disruption of intestinal microbiota. In this study, we extracted fucoidan (Aj-FUC) from Apostichopus japonicus using enzymatic methods and characterized its structure. The ALD model was established in male Balb/c mice using 56° Baijiu, with silymarin as a positive control. Mice were orally administered 100 mg/kg·bw and 300 mg/kg·bw of Aj-FUC for 28 days to evaluate its effects on liver injury in ALD mice and explore its potential role in modulating the gut-liver axis. The results showed significant improvements in histopathological changes and liver disease in the Aj-FUC group. Aj-FUC treatment significantly increased the levels of glutathione (GSH) and glutathione peroxidase (GSH-Px) while weakly reduced the elevation of malondialdehyde (MDA) induced by ALD. It also regulated the Nrf2/HO-1 signaling pathway, collectively alleviating hepatic oxidative stress. Aj-FUC intervention upregulated the expression of ZO-1 and Occludin, thus contributing to repair the intestinal barrier. Additionally, Aj-FUC increased the content of short-chain fatty acids (SCFAs) and regulated the imbalance in gut microbiota. These results suggested that Aj-FUC alleviates ALD by modulating the gut-liver axis homeostasis. It may prove to be a useful dietary supplement in the treatment of alcoholic liver damage.

CD4+ T-Cell Senescence in Neurodegenerative Disease: Pathogenesis and Potential Therapeutic Targets.

With the increasing proportion of the aging population, neurodegenerative diseases have become one of the major health issues in society. Neurodegenerative diseases (NDs), including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by progressive neurodegeneration associated with aging, leading to a gradual decline in cognitive, emotional, and motor functions in patients. The process of aging is a normal physiological process in human life and is accompanied by the aging of the immune system, which is known as immunosenescence. T-cells are an important part of the immune system, and their senescence is the main feature of immunosenescence. The appearance of senescent T-cells has been shown to potentially lead to chronic inflammation and tissue damage, with some studies indicating a direct link between T-cell senescence, inflammation, and neuronal damage. The role of these subsets with different functions in NDs is still under debate. A growing body of evidence suggests that in people with a ND, there is a prevalence of CD4+ T-cell subsets exhibiting characteristics that are linked to senescence. This underscores the significance of CD4+ T-cells in NDs. In this review, we summarize the classification and function of CD4+ T-cell subpopulations, the characteristics of CD4+ T-cell senescence, the potential roles of these cells in animal models and human studies of NDs, and therapeutic strategies targeting CD4+ T-cell senescence.

Ba2+-doping introduced piezoelectricity and efficient Ultrasound-Triggered bactericidal activity of brookite TiO2 nanorods.

Exploring highly efficient ultrasound-triggered catalysts is pivotal for various areas. Herein, we presented that Ba2+ doped brookite TiO2 nanorod (TiO2: Ba) with polarization-induced charge separation is a candidate. The replacement of Ba2+ for Ti4+ not only induced significant lattice distortion to induce polarization but also created oxygen vacancy defects for facilitating the charge separation, leading to high-efficiency reactive oxygen species (ROS) evolution in the piezo-catalytic processes. Furthermore, the piezocatalytic ability to degrade dye wastewater demonstrates a rate constant of 0.172 min-1 and achieves a 100 % antibacterial rate at a low dose for eliminating E. coli. This study advances that doping can induce piezoelectricity and reveals that lattice distortion-induced polarization and vacancy defects engineering can improve ROS production, which might impact applications such as water disinfection and sonodynamic therapy.

Astaxanthin Ameliorates Skeletal Muscle Atrophy in Mice With Cancer Cachexia.

Astaxanthin (AST) is a natural marine carotenoid with a variety of biological activities. This study aimed to demonstrate the possible mechanisms by which AST improves skeletal muscle atrophy in cancer cachexia. In this study, the effects of different doses of AST (30 mg/kg b.w., 60 mg/kg b.w. and 120 mg/kg b.w.) on skeletal muscle functions were explored in mice with cancer cachexia. The results showed that AST (30, 60 and 120 mg/kg b.w.) could effectively protect cachexia mice from body weight and skeletal muscle loss. AST dose-dependently ameliorated the decrease in myofibres cross-sectional area and increased the expression of myosin heavy chain (MHC). AST treatment decreased both the serum and muscle level of IL-6 but not TNF-α in C26 tumor-bearing cachexia mice. Moreover, AST alleviated skeletal muscle atrophy by decreasing the expression of two muscle-specific E3 ligases MAFBx and MuRF-1. AST improved mitochondrial function by downregulating the levels of muscle Fis1, LC3B and Bax, upregulating the levels of muscle Mfn2 and Bcl-2. In conclusion, our study show that AST might be expected to be a nutritional supplement for cancer cachexia patients.

Nuclear lamina component KAKU4 regulates chromatin states and transcriptional regulation in the Arabidopsis genome.

BACKGROUND: The nuclear lamina links the nuclear membrane to chromosomes and plays a crucial role in regulating chromatin states and gene expression. However, current knowledge of nuclear lamina in plants is limited compared to animals and humans. RESULTS: This study mainly focused on elucidating the mechanism through which the putative nuclear lamina component protein KAKU4 regulates chromatin states and gene expression in Arabidopsis leaves. Thus, we constructed a network using the association proteins of lamin-like proteins, revealing that KAKU4 is strongly associated with chromatin or epigenetic modifiers. Then, we conducted ChIP-seq technology to generate global epigenomic profiles of H3K4me3, H3K27me3, and H3K9me2 in Arabidopsis leaves for mutant (kaku4-2) and wild-type (WT) plants alongside RNA-seq method to generate gene expression profiles. The comprehensive chromatin state-based analyses indicate that the knockdown of KAKU4 has the strongest effect on H3K27me3, followed by H3K9me2, and the least impact on H3K4me3, leading to significant changes in chromatin states in the Arabidopsis genome. We discovered that the knockdown of the KAKU4 gene caused a transition between two types of repressive epigenetics marks, H3K9me2 and H3K27me3, in some specific PLAD regions. The combination analyses of epigenomic and transcriptomic data between the kaku4-2 mutant and WT suggested that KAKU4 may regulate key biological processes, such as programmed cell death and hormone signaling pathways, by affecting H3K27me3 modification in Arabidopsis leaves. CONCLUSIONS: In summary, our results indicated that KAKU4 is directly and/or indirectly associated with chromatin/epigenetic modifiers and demonstrated the essential roles of KAKU4 in regulating chromatin states, transcriptional regulation, and diverse biological processes in Arabidopsis.

A chromosome-level genome assembly of the spider mite Tetranychus piercei McGregor.

Despite the rapid advances in sequencing technology, limited genomic resources are currently available for phytophagous spider mites, which include many important agricultural pests. One of these pests is Tetranychus piercei (McGregor), a serious banana pest in East Asia exhibiting remarkable tolerance to high temperature. In this study, we assembled a high-quality genome of T. piercei using a combination of PacBio long reads and Illumina short reads sequencing. With the assistance of chromatin conformation capture technology, 99.9% of the contigs were anchored into three pseudochromosomes with a total size of 86.02 Mb. Repetitive elements, accounting for 14.16% of this genome (12.20 Mb), are predominantly composed of long-terminal repeats (30.7%). By combining evidence of ab initio prediction, transcripts, and homologous proteins, we annotated 11,881 protein-coding genes. Both the genome and proteins have high BUSCO completeness scores (>94%). This high-quality genome, along with reliable annotation, provides a valuable resource for investigating the high-temperature tolerance of this species and exploring the genomic basis that underlies the host range evolution of spider mites.

Optical coherence tomography angiography for the differentiation of diabetic nephropathy from non-diabetic renal disease.

BACKGROUND: To provide a new non-invasive method for the differentiation of diabetic nephropathy (DN) from non-diabetic renal disease (NDRD) by assessing retinal microstructure using optical coherence tomography angiography (OCTA). METHODS: OCTA parameters were recorded and their relationship with DN was analysed. A differential diagnosis regression model for DN was established, and the diagnostic efficiency was evaluated. RESULTS: Based on the pathological results of renal biopsy, 31 DN patients and 35 NDRD patients were included. Multivariate logistic regression analysis showed that DN was independently associated with the following parameters: 15.3 mm-1 ≤ vessel density (VD) full < 17.369 mm-1 (odds ratio [OR]=8.523; 95% confidence interval [CI]=1.387-52.352; P = 0.021), VD full < 15.3 mm-1 (OR=8.202; 95% CI=1.110-60.623; P = 0.039), DM duration > 60 months (OR=7.588; 95% CI=1.569-36.692; P = 0.012), and estimated glomerular filtration rate < 60 mL/min/1.73 m2 (OR=24.484; 95% CI=4.308-139.142; P < 0.001). The area under the receiver operating characteristic curve was 0.911, indicating a high diagnostic efficiency. CONCLUSIONS: VD full < 17.369 mm-1, DM duration > 60 months, and eGFR < 60 mL/min/1.73 m2 may indicate the presence of DN. OCTA may be an effective non-invasive method for identifying DN and NDRD.

UPLC-Q-Exactive Orbitrap-MS and network pharmacology for deciphering the active compounds and mechanisms of stir-fried Raphani Semen in treating functional dyspepsia.

BACKGROUND: As a traditional digestive medicine, stir-fried Raphani Semen (SRS) has been used to treat food retention for thousands of years in China. Modern research has shown that SRS has a good therapeutic effect on functional dyspepsia (FD). However, the active components and mechanism of SRS in the treatment of FD are still unclear. OBJECTIVE: The purpose of this study is to elucidate the material basis and mechanism of SRS for treating FD based on UPLC-Q-Exactive Orbitrap MS/MS combined with network pharmacology and molecular docking. METHODS: The compounds of SRS water decoction were identified by UPLC-Q-Exactive Orbitrap MS/MS and the potential targets of these compounds were predicted by Swiss Target Prediction. FD-associated targets were collected from disease databases. The overlapped targets of SRS and FD were imported into STRING to construct Protein-Protein Interaction (PPI) network. Then, the Metascape was used to analyze Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway after introducing overlapped targets. Finally, the active components and core targets were obtained by analyzing the "component-target-pathway" network, and the affinity between them was verified by molecular docking. RESULTS: 53 components were identified, and 405 targets and 1487 FD-related targets were collected. GO and KEGG analysis of 174 overlapped targets showed that SRS had important effects on hormone levels, serotonin synapses, calcium signaling pathway and cAMP signaling pathway. 7 active components and 15 core targets were screened after analyzing the composite network. Molecular docking results showed that multiple active components had high affinity with most core targets. CONCLUSION: SRS can treat FD through a variety of pathways, which provides a direction for the modern application of SRS in FD treatment.

Controllable La Deficiency Engineering within Perovskite Oxides for Enhanced Overall Water Splitting.

Recently, perovskite (ABO3) nanomaterials have been widely explored as a class of versatile electrocatalysts for oxygen evolution reactions (OER) due to their remarkable compositional flexibility and structural tunability, but their poor electrical conductivity hinders hydrogen evolution reaction (HER) activity and further limits the large-scale application of perovskite oxide in overall water splitting (OWS). In this study, hollow-nanotube-structure LaxCo0.4Fe0.6O3-δ (x = 1.0, 0.9, and 0.8) perovskites with superior HER/OER activity were synthesized on nickel-iron alloy foam (denoted LaxCoFe/NFF) using hydrothermal with a subsequent calcination strategy. Among them, La0.9CoFe/NFF not only exhibited extraordinary HER electrocatalytic performance (160.5 mV@10 mA cm-2 and 241.0 mV@100 mA cm-2) and stability (20 h@10 mA cm-2), but also displayed significant OER electrocatalytic activity (234.7 mV@10 mA cm-2 and 296.1 mV@100 mA cm-2) and durability (20 h@10 mA cm-2), outperforming many recently reported HER/OER perovskite catalysts. The increase in oxygen vacancies caused by the introduction of La deficiency leads to the expansion of the lattice, which greatly accelerates the HER/OER process of La0.9CoFe/NFF. Additionally, the naturally porous skeleton can prevent catalysts from aggregating as well as delay the corrosion and dissolution of catalysts in the electrolyte under high applied potentials. Furthermore, the assembled two-electrode configuration, utilizing La0.9CoFe/NFF (cathode and anode) electrodes, only requires a low cell voltage of 1.573 V at 10 mA cm-2 for robust alkaline OWS, accompanied by remarkable durability over 20 h. This work provides inspiration for the design and preparation of high-performance and stable bifunctional perovskite electrocatalysts for OWS.

[Association between auditory processing and problem behaviors in preschool children: the mediating role of executive function]. / å¬å¤„ç†ä¸Žå­¦é¾„å‰å„¿ç«¥é—®é¢˜è¡Œä¸ºçš„å ³ç³»ï¼šæ‰§è¡ŒåŠŸèƒ½çš„ä¸­ä»‹ä½œç”¨.

OBJECTIVES: To investigate the association between auditory processing and problem behaviors in preschool children, as well as the mediating role of executive function. METHODS: A total of 2 342 preschool children were selected from 7 kindergartens in Nanjing, China from June to August 2021. They were evaluated using Preschool Auditory Processing Assessment Scale, Conners Parent Symptom Questionnaire, and Behavior Rating Inventory of Executive Functioning-Preschool version. Children with different demographic features were compared in the scores and the abnormality rates of auditory processing, problem behaviors, and executive function. The influencing factors of the total scores of auditory processing, problem behaviors, and executive function were evaluated using multiple linear regression analysis. Whether executive function was a mediating factor between auditory processing and executive function was examined. RESULTS: Sex and grade were the main influencing factors for the total score of auditory processing (P<0.05), and sex, grade, parental education level, and family economic status were the main influencing factors for the total scores of problem behaviors and executive function (P<0.05). The auditory processing score (rs=0.458, P<0.05) and problem behavior score (rs=0.185, P<0.05) were significantly positively correlated with the executive function score, and the auditory processing score was significantly positively correlated with the problem behavior score (rs=0.423, P<0.05). Executive function played a partial mediating role between auditory processing and problem behaviors, and the mediating effect accounted for 33.44% of the total effect. CONCLUSIONS: Auditory processing can directly affect the problem behaviors of preschool children and indirectly affect problem behaviors through executive function.

KAKU4 regulates leaf senescence through modulation of H3K27me3 deposition in the Arabidopsis genome.

Lamins are the major components of the nuclear lamina, which regulate chromatin structure and gene expression. KAKU4 is a unique nuclear lamina component in the nuclear periphery, modulates nuclear shape and size in Arabidopsis. The knowledge about the regulatory role of KAKU4 in leaf development remains limited. Here we found that knockdown of KAKU4 resulted in an accelerated leaf senescence phenotype, with elevated levels of H2O2 and hormones, particularly SA, JA, and ABA. Our results demonstrated the importance of KAKU4 as a potential negative regulator in age-triggered leaf senescence in Arabidopsis. Furthermore, we conducted combination analyses of transcriptomic and epigenomic data for the kaku4 mutant and WT leaves. The knockdown of KAKU4 lowered H3K27me3 deposition in the up-regulated genes associated with hormone pathways, programmed cell death, and leaf senescence, including SARD1, SAG113/HAI1, PR2, and so forth. In addition, we found the functional crosstalks between KAKU4 and its associated proteins (CRWN1/4, PNET2, GBPL3, etc.) through comparing multiple transcriptome datasets. Overall, our results indicated that KAKU4 may inhibit the expression of a series of genes related to hormone signals and H2O2 metabolism by affecting the deposition of H3K27me3, thereby suppressing leaf senescence.

Caloric Restriction Rejuvenates Skeletal Muscle Growth in Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a major clinical problem, with limited treatments. HFpEF is characterized by a distinct, but poorly understood, skeletal muscle pathology, which could offer an alternative therapeutic target. In a rat model, we identified impaired myonuclear accretion as a mechanism for low myofiber growth in HFpEF following resistance exercise. Acute caloric restriction rescued skeletal muscle pathology in HFpEF, whereas cardiac therapies had no effect. Mechanisms regulating myonuclear accretion were dysregulated in patients with HFpEF. Overall, these findings may have widespread implications in HFpEF, indicating combined dietary with exercise interventions as a beneficial approach to overcome skeletal muscle pathology.

Establishing chronic models of age-related macular degeneration via long-term iron ion overload.

Age-related macular degeneration (AMD) is characterized by the degenerative senescence in the retinal pigment epithelium (RPE) and photoreceptors, which is accompanied by the accumulation of iron ions in the aging retina. However, current models of acute oxidative stress are still insufficient to simulate the gradual progression of AMD. To address this, we established chronic injury models by exposing the aRPE-19 cells, 661W cells, and mouse retina to iron ion overload over time. Investigations at the levels of cell biology and molecular biology were performed. It was demonstrated that long-term treatment of excessive iron ions induced senescence-like morphological changes, decreased cell proliferation, and impaired mitochondrial function, contributing to apoptosis. Activation of the mitogen-activated protein kinase (MAPK) pathway and the downstream molecules were confirmed both in the aRPE-19 and 661W cells. Furthermore, iron ion overload resulted in dry AMD-like lesions and decreased visual function in the mouse retina. These findings suggest that chronic exposure to overloading iron ions plays a significant role in the pathogenesis of retinopathy and provide a potential model for future studies on AMD.NEW & NOTEWORTHY To explore the possibility of constructing reliable research carriers on age-related macular degeneration (AMD), iron ion overload was applied to establish models in vitro and in vivo. Subsequent investigations into cellular physiology and molecular biology confirmed the presence of senescence in these models. Through this study, we hope to provide a better option of feasible methods for future researches into AMD.

Modified Conjoint Fascial Sheath and Levator Muscle Complex Suspension for the Correction of Simple Severe Congenital Ptosis in Pediatrics and the Effect on Refractive Status.

PURPOSE: To evaluate the outcomes of modified combined fascia sheath and levator muscle complex suspension to correct severe congenital ptosis in pediatrics and the effect on refractive status. METHODS: This prospective, case series study enrolled patients (aged ≤18 years) with simple severe congenital ptosis at Zhongshan Ophthalmic Center. All patients were treated with combined fascia sheath + levator muscle suspension and followed up for 3 months. Preoperative and postoperative cycloplegic refraction and the best-corrected visual acuity were performed. The types of astigmatism include with-the-rule, against-the-rule, and oblique. RESULTS: Thirty-six patients (50 eyes) were enrolled. The mean age was 7.11 ± 3.72 years. The surgery success rate was 90.0%. Following surgery, the eyelid contour of all eyes exhibited natural symmetry and satisfactory curvature. The eyelid height difference in OUs was ≤1 mm for 42 eyes. For 47 eyes, the eyelid crease was symmetry. Two eyes had conjunctival prolapse, and 1 eye developed trichiasis. After surgery, cylinder power changed from mean -1.14 ± 1.27 D to -1.54 ± 1.25 D ( p < 0.001) and best-corrected visual acuity improved from mean 0.205 ± 0.217 logarithm of the minimum angle of resolution to 0.168 ± 0.176 logarithm of the minimum angle of resolution ( p = 0.048). The quantities of with-the-rule increased from 35 eyes to 41 eyes, oblique from 4 eyes to 6 eyes, while against-the-rule decreased from 11 eyes to 3 eyes ( p = 0.01). CONCLUSIONS: Combined fascia sheath + levator muscle suspension under general anesthesia is effective and safe for severe congenital ptosis in pediatrics. However, astigmatism increased and the types of astigmatism changed after surgery.

Identification and characterization of an L-type lectin from obscure puffer Takifugu obscurus in response to bacterial infection.

L-type lectins (LTLs) contain a carbohydrate recognition domain homologous to leguminous lectins, and have functions in selective protein trafficking, sorting and targeting in the secretory pathway of animals. In this study, a novel LTL, designated as ToERGIC-53, was cloned and identified from obscure puffer Takifugu obscurus. The open reading frame of ToERGIC-53 contained 1554 nucleotides encoding 517 amino acid residues. The deduced ToERGIC-53 protein consisted of a signal peptide, a leguminous lectin domain (LTLD), a coiled-coil region, and a transmembrane region. Quantitative real-time PCR showed that ToERGIC-53 was expressed in all examined tissues, with the highest expression level in the liver. The expression of ToERGIC-53 was significantly upregulated after infection with Vibrio harveyi and Staphylococcus aureus. Recombinant ToERGIC-53-LTLD (rToERGIC-53-LTLD) protein could not only agglutinate and bind to one Gram-positive bacterium (S. aureus) and three Gram-negative bacteria (V. harveyi, V. parahaemolyticus and Aeromonas hydrophila), but also bind to glycoconjugates on the surface of bacteria such as lipopolysaccharide, peptidoglycan, mannose and galactose. In addition, rToERGIC-53-LTLD inhibited the growth of bacteria in vitro. All these results suggested that ToERGIC-53 might be a pattern recognition receptor involved in antibacterial immune response of T. obscurus.

Identify production area, growth mode, species, and grade of Astragali Radix using metabolomics "big data" and machine learning.

BACKGROUND: Astragali Radix (AR) is a widely used herbal medicine. The quality of AR is influenced by several key factors, including the production area, growth mode, species, and grade. However, the markers currently used to distinguish these factors primarily focus on secondary metabolites, and their validation on large-scale samples is lacking. PURPOSE: This study aims to discover reliable markers and develop classification models for identifying the production area, growth mode, species, and grade of AR. METHODS: A total of 366 batches of AR crude slices were collected from six provinces in China and divided into learning (n = 191) and validation (n = 175) sets. Three ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods were developed and validated for determining 22 primary and 10 secondary metabolites in AR methanol extract. Based on the quantification data, seven machine learning algorithms, such as Nearest Neighbors and Gradient Boosted Trees, were applied to screen the potential markers and build the classification models for identifying the four factors associated with AR quality. RESULTS: Our analysis revealed that secondary metabolites (e.g., astragaloside IV, calycosin-7-O-ß-D-glucoside, and ononin) played a crucial role in evaluating AR quality, particularly in identifying the production area and species. Additionally, fatty acids (e.g., behenic acid and lignoceric acid) were vital in determining the growth mode of AR, while amino acids (e.g., alanine and phenylalanine) were helpful in distinguishing different grades. With both primary and secondary metabolites, the Nearest Neighbors algorithm-based model was constructed for identifying each factor of AR, achieving good classification accuracy (>70%) on the validation set. Furthermore, a panel of four metabolites including ononin, astragaloside II, pentadecanoic acid, and alanine, allowed for simultaneous identification of all four factors of AR, offering an accuracy of 86.9%. CONCLUSION: Our findings highlight the potential of integrating large-scale targeted metabolomics and machine learning approaches to accurately identify the quality-associated factors of AR. This study opens up possibilities for enhancing the evaluation of other herbal medicines through similar methodologies, and further exploration in this area is warranted.