The role of ALDH2 rs671 polymorphism and C-reactive protein in the phenotypes of male ALS patients.

Background: The aldehyde dehydrogenase 2 (ALDH2) rs671 (A) allele has been implicated in neurodegeneration, potentially through oxidative and inflammatory pathways. The study aims to investigate the effects of the ALDH2 rs671 (A) allele and high sensitivity C-reactive protein (hs-CRP) on the clinical phenotypes of amyotrophic lateral sclerosis (ALS) in male and female patients. Methods: Clinical data and ALDH2 rs671 genotype of 143 ALS patients, including 85 males and 58 females, were collected from January 2018 to December 2022. All patients underwent assessment using the Chinese version of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Complete blood count and metabolic profiles were measured. Clinical and laboratory parameters were compared between carriers and non-carriers of the rs671 (A) allele in males and females, respectively. The significant parameters and rs671 (A) Allele were included in multivariate linear regression models to identify potential contributors to motor and cognitive impairment. Mediation analysis was employed to evaluate any mediation effects. Results: Male patients carrying rs671 (A) allele exhibited higher levels of hs-CRP than non-carriers (1.70 mg/L vs. 0.50 mg/L, p = 0.006). The rs671 (A) allele was identified as an independent risk factor for faster disease progression only in male patients (ß = 0.274, 95% CI = 0.048-0.499, p = 0.018). The effect of the rs671 (A) allele on the executive function in male patients was fully mediated by hs-CRP (Indirect effect = -1.790, 95% CI = -4.555--0.225). No effects of the rs671 (A) allele or hs-CRP were observed in female ALS patients. The effects of the ALDH2 rs671 (A) allele and the mediating role of hs-CRP in male patients remained significant in the sensitivity analyses. Conclusion: The ALDH2 rs671 (A) allele contributed to faster disease progression and hs-CRP mediated cognitive impairment in male ALS patients.

Association between apathy and caregiver burden in patients with amyotrophic lateral sclerosis: a cross-sectional study.

OBJECTIVES: To investigate the relationship among patients' apathy, cognitive impairment, depression, anxiety, and caregiver burden in amyotrophic lateral sclerosis (ALS). DESIGN: A cross-sectional study design was used. SETTING: The study was conducted at a tertiary hospital in Wuhan, Hubei, China. PARTICIPANTS: A total of 109 patients with ALS and their caregivers were included. OUTCOME MEASURES: Patients with ALS were screened using the Edinburgh Cognitive and Behavioural Screen, Beck Depression Inventory-II, Generalised Anxiety Disorder-7 and Apathy Scale to assess their cognition, depression, anxiety and apathy, respectively. The primary caregivers completed the Zarit Burden Interview. The association between apathy, cognitive impairment, depression, anxiety and caregiver burden was analysed using logistic regression. Mediation models were employed to investigate the mediating effect of patients' apathy on the relationship between depression/anxiety and caregiver burden. RESULTS: Patients in the high caregiver burden group exhibited significantly higher levels of depression, anxiety and apathy compared with those in the low caregiver burden group (p<0.05). There was a positive association observed between caregiver burden and disease course (rs=0.198, p<0.05), depression (rs=0.189, p<0.05), anxiety (rs=0.257, p<0.05) and apathy (rs=0.388, p<0.05). There was a negative association between caregiver burden and the Revised ALS Functional Rating Scale (rs=-0.275, p<0.05). Apathy was an independent risk factor for higher caregiver burden (OR 1.121, 95% CI 1.041 to 1.206, p<0.05). Apathy fully mediated the relationship between depression and caregiver burden (ß=0.35, 95% CI 0.16 to 0.54, p<0.05) while partially mediating the relationship between anxiety and caregiver burden (ß=0.34, 95% CI 0.16 to 0.52, p<0.05). CONCLUSIONS: Apathy, depression and anxiety exerted a detrimental impact on caregiver burden in individuals with ALS. Apathy played a mediating role in the relationship between depression and caregiver burden and between anxiety and caregiver burden. These findings underscore the importance of identifying apathy and developing interventions for its management within the context of ALS.

Monoexponential and advanced diffusion-weighted imaging for hepatic fibrosis staging based on high inter-examiner reliability.

OBJECTIVES: To determine the diagnostic efficiencies of multiple diffusion-weighted imaging (DWI) techniques for hepatic fibrosis (HF) staging under the premise of high inter-examiner reliability. METHODS: Participants with biopsy-confirmed HF were recruited and divided into the early HF (EHF) and advanced HF (AHF) groups; healthy volunteers (HVs) served as controls. Two examiners analyzed intravoxel incoherent motion (IVIM) using the IVIM-DWI and diffusion kurtosis imaging (DKI) models. Intravoxel incoherent motion-DWI, DKI, and diffusion tensor imaging parameters with intraclass correlation coefficients (ICCs) of ≥0.6 were used to create regression models: HVs vs. EHF and EHF vs. AHF. RESULTS: We enrolled 48 HVs, 59 EHF patients, and 38 AHF patients. Mean, radial, and axial kurtosis; fractional anisotropy; mean, radial, and axial diffusivity; and α exhibited excellent reliability (ICCs: 0.80-0.98). Fractional anisotropy of kurtosis, f, and apparent diffusion coefficient showed good reliability (ICCs: 0.69-0.92). The real (0.58-0.67), pseudo- (0.27-0.76), and distributed diffusion coefficients (0.58-0.67) showed low reliability. In the HVs versus (vs.) EHF model, α (p=0.008) and ADC (p=0.011) presented statistical differences (area under curve [AUC]: 0.710). In the EHF vs. AHF model, α (p=0.04) and distributed diffusion coefficient (p=0.02) presented significant differences (AUC: 0.758). CONCLUSION: Under the premise of high inter-examiner reliability, DWI and IVIM-derived stretched-exponential model parameters may help stage HF.

Modulating amacrine cell-derived dopamine signaling promotes optic nerve regeneration and preserves visual function.

As part of the central nervous system, the optic nerve, composed of axons from retinal ganglion cells (RGCs), generally fails to regenerate on its own when injured in adult mammals. An innovative approach to promoting optic nerve regeneration involves manipulating the interactions between amacrine cells (ACs) and RGCs. Here, we identified a unique AC subtype, dopaminergic ACs (DACs), that responded early after optic nerve crush by down-regulating neuronal activity and reducing retinal dopamine (DA) release. Activating DACs or augmenting DA release with levodopa demonstrated neuroprotective effects and modestly enhanced axon regeneration. Within this context, we pinpointed the DA receptor D1 (DRD1) as a critical mediator of DAC-derived DA and showed that RGC-specific Drd1 overexpression effectively overcame subtype-specific barriers to regeneration. This strategy markedly boosted RGC survival and axon regeneration after crush and preserved vision in a glaucoma model. This study unveils the crucial role of DAC-derived DA signaling in optic nerve regeneration, holding promise for therapeutic insights into neural repair.

Chlorantraniliprole Resistance in Spodoptera frugiperda: Resistance Monitoring, Resistance Risk, and Resistance Mechanisms.

Spodoptera frugiperda is a significant global pest, and chlorantraniliprole (CAP) is extensively used in China for its control. Understanding CAP resistance in S. frugiperda is crucial for effective management of this pest. Field populations exhibited varying degrees of resistance to CAP (RR = 1.74-5.60-fold). After 10 generations of selection, the CAP-resistant strain developed over 10-fold resistance, with a realized heritability (h2) of 0.10. Genetic analysis reveals inheritance patterns as autosomal, incomplete recessive, and monofactorial. The CAP-resistant strain showed limited cross-resistance to lufenuron and tetrachlorantraniliprole, negative cross-resistance to spinetoram, and no observed cross-resistance to other insecticides. Biochemical analysis suggested that P450-mediated detoxification is the primary resistance mechanism, with 26 genes overexpressed in the CAP-resistant strain. Additionally, the knockdown of CYP4L13, CYP6B39, CYP6B40, and CYP4G74 significantly increased the sensitivity of the resistant larvae to CAP. These findings highlight the resistance risk of CAP in S. frugiperda and emphasize the crucial role of P450 enzymes in resistance.

Investigation of lambda-cyhalothrin resistance in Spodoptera frugiperda: Heritability, cross-resistance, and mechanisms.

Lambda-cyhalothrin, a representative pyrethroid insecticide widely used for Spodoptera frugiperda control in China, poses challenges due to the development of resistance. This study investigates the realized heritability, inheritance pattern, cross-resistance, and resistance mechanisms to lambda-cyhalothrin. After 21 generations of selection, the lambda-cyhalothrin-resistant strain (G21) developed a 171.11-fold resistance compared to a relatively susceptible strain (RS-G9), with a realized heritability (h2) of 0.11. Cross-resistance assays revealed that lambda-cyhalothrin-resistant strains showed no significant cross-resistance to the majority of tested insecticides. Genetic analysis indicated that lambda-cyhalothrin resistance in S. frugiperda was autosomal, incompletely dominant, and polygenic inheritance. The P450 enzyme inhibitor PBO significantly enhanced lambda-cyhalothrin toxicity in the resistant strains. Compared with the RS-G9 strain, the P450 enzyme activity was significantly increased and multiple P450 genes were significantly up-regulated in the lambda-cyhalothrin-resistant strains. RNAi targeting the most overexpressed P450 genes (CYP337B5 and CYP321B1) significantly increased the susceptibility of resistant S. frugiperda larvae to lambda-cyhalothrin. This study provides comprehensive insights into lambda-cyhalothrin resistance in S. frugiperda, and the results are helpful for developing effective resistance management strategies of this pest.

Prevalence and risk factors for dementia and mild cognitive impairment among older people in Southeast China: a community-based study.

BACKGROUND: With the aging population, the number of individuals with dementia in China is increasing rapidly. This community-based study aimed to investigate the prevalence and risk factors for dementia and mild cognitive impairment (MCI) among older adults in China. METHODS: In this study, 20,070 individuals aged ≥ 65 were recruited between January 1, 2022, and February 1, 2023, from ten communities in Xiamen City, China. We collected data on age, sex, level of education, and medical history, as well as global cognition and functional status. The prevalence of dementia and MCI was examined, and the risk factors for different groups were assessed. RESULTS: The overall prevalence of dementia and MCI was approximately 5.4% (95% confidence interval [CI], 5.1-5.7) and 7.7% (95% CI, 7.4-8.1), respectively. The results also indicated that dementia and MCI share similar risk factors, including older age, female sex, hypertension, and diabetes mellitus. Compared with individuals with no formal education, those with > 6 years of education had an odds ratio for MCI of 1.83 (95% CI, 1.49-2.25). We also found that only 5.5% of the positive participants chose to be referred to the hospital for further diagnosis and treatment during follow-up visits. CONCLUSIONS: This study estimated the prevalence and risk factors for dementia and MCI among individuals aged ≥ 65 years in Southeast China. These findings are crucial for preventing and managing dementia and MCI in China.

A first-principles study on Ni-decorated MoS2 for efficient formaldehyde degradation over a wide temperature range.

The development of a high-efficiency, low-cost, and environmentally friendly catalyst for formaldehyde degradation is crucial for addressing the issue of indoor formaldehyde pollution. Given that modern individuals spend over 90% of their time indoors, effectively tackling indoor formaldehyde pollution holds significant importance. Therefore, this paper proposes an efficient catalyst for formaldehyde degradation: surface modification of MoS2 by single-atom Ni, which can convert formaldehyde into harmless H2O and CO2. The DFT method is employed to systematically investigate the oxidative degradation pathways of formaldehyde on the surface of Ni-doped MoS2. The research focuses on two common oxidative degradation pathways in both the L-H mechanism and E-R mechanism. Our findings demonstrate that these four reaction paths occur spontaneously within the temperature range of 300-800 K with a reaction equilibrium constant greater than 105. Moreover, even under extreme temperature conditions (100 K), the reaction rate remains favorable. Furthermore, our findings indicate that the minimum activation energy is merely 0.91 eV and H2O and CO2 only need to overcome an energy barrier of 0.71 eV for desorption from the catalyst surface. This substantiates its potential application both in indoor environments and under extreme temperature conditions. This theoretical research provides innovative ideas and strategies for effectively oxidizing formaldehyde.

Contributing factors related to abnormal uterine bleeding in perimenopausal women: a case-control study.

Abnormal uterine bleeding (AUB) during the menopausal transition results in reproductive endocrine disorders and both physiological and pathological changes, substantially impacting women's health. This study aimed to investigate the factors influencing AUB in perimenopausal women. Between April 2021 and June 2022, 120 perimenopausal women with AUB in the menopausal transition, diagnosed and treated at the Gynaecology Department of Kunming Tongren Hospital, were included in the case group. Concurrently, women undergoing routine health examinations at the same hospital were randomly selected as the control group. Univariate and multivariate logistic regression analyses identified factors related to AUB. The univariate analysis revealed significant associations (P < 0.05) between AUB and several factors, including age, body mass index (BMI), age at menarche, gravidity, and intrauterine device (IUD) placement in perimenopausal women. The multivariate regression analysis indicated that the independent risk factors for AUB include benign endometrial lesions (odds ratio [OR] 5.243, 95% confidence interval [CI] 3.082-9.458, P < 0.001), endometrial thickness ≥ 10 mm (OR 1.573, 95% CI 0.984-3.287, P < 0.001), age ≥ 50 years (OR 2.045, 95% CI 1.035-4.762, P = 0.001), BMI ≥ 25 kg/m2 (OR 2.436, 95% CI 1.43-4.86, P = 0.002), and IUD placement (OR 2.458, 95% CI 1.253-4.406, P < 0.001). Abnormal uterine bleeding during the menopausal transition is associated with several factors, including age, BMI, and IUD placement, highlighting the importance of early screening for these risk factors in the diagnosis and treatment of AUB.

miR-317-3p and miR-283-5p Play a Crucial Role in Regulating the Resistance to Indoxacarb in Spodoptera frugiperda by Targeting GSTs4.

Spodoptera frugiperda is primarily controlled through chemical insecticides. Our RNA-seq data highlight the overexpression of GSTs4 in indoxacarb-resistant S. frugiperda. However, the exact role of GSTs4 in indoxacarb resistance and its regulatory mechanisms remains elusive. Therefore, we investigated the functional role of GSTs4 in S. frugiperda and explored the underlying post-transcriptional regulatory mechanisms. GSTs4 was highly overexpressed (27.6-fold) in the indoxacarb-resistant strain, and GSTs4 silencing significantly increases the susceptibility of S. frugiperda to indoxacarb, increasing mortality by 27.3%. miR-317-3p and miR-283-5p can bind to the 3'UTR of GSTs4, and the targeting relationship was confirmed by dual-luciferase reporter assays. Injecting miR-317-3p and miR-283-5p agomirs reduces GSTs4 levels by 64.8 and 42.3%, respectively, resulting in an increased susceptibility of S. frugiperda to indoxacarb. Conversely, the administration of miR-317-3p and miR-283-5pantagomirs increases GSTs4 expression and reduces larval susceptibility to indoxacarb. These findings demonstrate that miR-317-3p and miR-283-5p contribute to indoxacarb resistance in S. frugiperda by regulating the overexpression of GSTs4.

Intracellular Zn2+ promotes extracellular matrix remodeling in dexamethasone-treated trabecular meshwork.

Given the widespread application of glucocorticoids in ophthalmology, the associated elevation of intraocular pressure (IOP) has long been a vexing concern for clinicians, yet the underlying mechanisms remain inconclusive. Much of the discussion focuses on the extracellular matrix (ECM) of trabecular meshwork (TM). It is widely agreed that glucocorticoids impact the expression of matrix metalloproteinases (MMPs), leading to ECM deposition. Since Zn2+ is vital for MMPs, we explored its role in ECM alterations induced by dexamethasone (DEX). Our study revealed that in human TM cells treated with DEX, the level of intracellular Zn2+ significantly decreased, accompanied by impaired extracellular Zn2+ uptake. This correlated with changes in several Zrt-, Irt-related proteins (ZIPs) and metallothionein. ZIP8 knockdown impaired extracellular Zn2+ uptake, but Zn2+ chelation did not affect ZIP8 expression. Resembling DEX's effects, chelation of Zn2+ decreased MMP2 expression, increased the deposition of ECM proteins, and induced structural disarray of ECM. Conversely, supplementation of exogenous Zn2+ in DEX-treated cells ameliorated these outcomes. Notably, dietary zinc supplementation in mice significantly reduced DEX-induced IOP elevation and collagen content in TM, thereby rescuing the visual function of the mice. These findings underscore zinc's pivotal role in ECM regulation, providing a novel perspective on the pathogenesis of glaucoma.NEW & NOTEWORTHY Our study explores zinc's pivotal role in mitigating extracellular matrix dysregulation in the trabecular meshwork and glucocorticoid-induced ocular hypertension. We found that in human trabecular meshwork cells treated with dexamethasone, intracellular Zn2+ significantly decreased, accompanied by impaired extracellular Zn2+ uptake. Zinc supplementation rescues visual function by modulating extracellular matrix proteins and lowering intraocular pressure, offering a direction for further exploration in glaucoma management.

Screening potential biomarkers associated with insulin resistance in high-fat diet-fed mice by integrating metagenomics and untargeted metabolomics.

Insulin resistance is the primary pathophysiological basis for metabolic syndrome and type 2 diabetes. Gut microbiota and microbiota-derived metabolites are pivotal in insulin resistance. However, identifying the specific microbes and key metabolites with causal roles is a challenging task, and the underlying mechanisms require further exploration. Here, we successfully constructed a model of insulin resistance in mice induced by a high-fat diet (HFD) and screened potential biomarkers associated with insulin resistance by integrating metagenomics and untargeted metabolomics. Our findings showed a significant increase in the abundance of 30 species of Alistipes in HFD mice compared to normal diet (ND) mice, while the abundance of Desulfovibrio and Candidatus Amulumruptor was significantly lower in HFD mice than in ND mice. Non-targeted metabolomics analysis identified 21 insulin resistance-associated metabolites, originating from the microbiota or co-metabolized by both the microbiota and the host. These metabolites were primarily enriched in aromatic amino acid metabolism (tryptophan metabolism, tyrosine metabolism, and phenylalanine metabolism) and arginine biosynthesis. Further analysis revealed a significant association between the three distinct genera and 21 differentiated metabolites in the HFD and ND mice. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of representative genomes from 12 species of the three distinct genera further revealed the functional potential in aromatic amino acid metabolism and arginine biosynthesis. This study lays the groundwork for future investigations into the mechanisms through which the gut microbiota and its metabolites impact insulin resistance. IMPORTANCE: In this study, we aim to identify the microbes and metabolites linked to insulin resistance, some of which have not been previously reported in insulin resistance-related studies. This adds a complementary dimension to existing research. Furthermore, we establish a correlation between alterations in the gut microbiota and metabolite levels. These findings serve as a foundation for identifying the causal bacterial species and metabolites. They also offer insights that guide further exploration into the mechanisms through which these factors influence host insulin resistance.

Field-of-view optimized and constrained undistorted single shot intravoxel incoherent motion diffusion-weighted imaging of the cervix during the menstrual cycle: A prospective study.

OBJECTIVE: To provide insight into the biological characteristics of the healthy cervix by defining intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) parameters across the menstrual cycle. METHODS: Forty-three females of reproductive age (18-45 years old) were included in this prospective study. Conventional magnetic resonance imaging (MRI) and IVIM-DWI scans were performed at multiple time-points across the menstrual cycle: T1 (menses), T2 (follicular phase), T3 (luteal phase). Intra- and interobserver repeatability of the IVIM-DWI values were evaluated with intraclass correlation coefficients (ICC), and D* was excluded from the analyses due to poor repeatability. Differences in each IVIM-DWI parameter among T1, T2, and T3 were explored. Subjects were stratified by age and parity for subgroup analyses (younger [18 - < 30 years] vs. older [≥30-45 years]; parity 0 vs. parity 1 and 2). Correlations between subject age and IVIM-DWI parameters were assessed. The overlap for each IVIM-DWI parameter among T1, T2, and T3 was evaluated. RESULTS: ADC and D values of the cervix were significantly lower at T3 compared with T1 (p = 0.02 and 0.03) or T2 (p < 0.01 and < 0.01). In younger subjects (n = 26), ADC and D values were significantly lower at T3 compared with T1 (p < 0.01 and p = 0.02) or T2 (p = 0.03 and p = 0.04). In older subjects (n = 17), ADC values were significantly higher at T2 compared with T1 (p = 0.01) or T3 (p = 0.01). There were significant differences in ADC values at T1 in subgroup analyses stratified by age and parity (both p < 0.01). There was a moderate correlation between age and ADC values at T1. Overlap for IVIM-DWI parameters across the menstrual cycle was >50%. CONCLUSION: ADC and D values of the heathy cervix differed across the menstrual cycle. Age and parity may influence the ADC value.

Matrix metalloproteinase-9 inhibition prevents aquaporin-4 depolarization-mediated glymphatic dysfunction in Parkinson's disease.

INTRODUCTION: The glymphatic system offers a perivascular pathway for the clearance of pathological proteins and metabolites to optimize neurological functions. Glymphatic dysfunction plays a pathogenic role in Parkinson's disease (PD); however, the molecular mechanism of glymphatic dysfunction in PD remains elusive. OBJECTIVE: To explore whether matrix metalloproteinase-9 (MMP-9)-mediated ß-dystroglycan (ß-DG) cleavage is involved in the regulation of aquaporin-4 (AQP4) polarity-mediated glymphatic system in PD. METHODS: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD and A53T mice were used in this study. The glymphatic function was evaluated using ex vivo imaging. TGN-020, an AQP4 antagonist, was administered to investigate the role of AQP4 in glymphatic dysfunction in PD. GM6001, an MMP-9 antagonist, was administered to investigate the role of the MMP-9/ß-DG pathway in regulating AQP4. The expression and distribution of AQP4, MMP-9, and ß-DG were assessed using western blotting, immunofluorescence, and co-immunoprecipitation. The ultrastructure of basement membrane (BM)-astrocyte endfeet was detected using transmission electron microscopy. Rotarod and open-field tests were performed to evaluate motor behavior. RESULTS: Perivascular influx and efflux of cerebral spinal fluid tracers were reduced in MPTP-induced PD mice with impaired AQP4 polarization. AQP4 inhibition aggravated reactive astrogliosis, glymphatic drainage restriction, and dopaminergic neuronal loss in MPTP-induced PD mice. MMP-9 and cleaved ß-DG were upregulated in both MPTP-induced PD and A53T mice, with reduced polarized localization of ß-DG and AQP4 to astrocyte endfeet. MMP-9 inhibition restored BM-astrocyte endfeet-AQP4 integrity and attenuated MPTP-induced metabolic perturbations and dopaminergic neuronal loss. CONCLUSION: AQP4 depolarization contributes to glymphatic dysfunction and aggravates PD pathologies, and MMP-9-mediated ß-DG cleavage regulates glymphatic function through AQP4 polarization in PD, which may provide novel insights into the pathogenesis of PD.

Reduced Zn2+ promotes retinal ganglion cells survival and optic nerve regeneration after injury through inhibiting autophagy mediated by ROS/Nrf2.

The molecular mechanism of how reduced mobile zinc (Zn2+) affected retinal ganglion cell (RGC) survival and optic nerve regeneration after optic nerve crush (ONC) injury remains unclear. Here, we used conditionally knocked out ZnT-3 in the amacrine cells (ACs) of mice (CKO) in order to explore the role of reactive oxygen species (ROS), nuclear factor erythroid 2-related factor 2 (NFE2L2, Nrf2) and autophagy in the protection of RGCs and axon regeneration after ONC injury. We found that reduced Zn2+ can promote RGC survival and axonal regeneration by decreasing ROS, activating Nrf2, and inhibiting autophagy. Additionally, autophagy after ONC is regulated by ROS and Nrf2. Visual function in mice after ONC injury was partially recovered through the reduction of Zn2+, achieved by using a Zn2+ specific chelator N,N,N',N'-tetrakis-(2-Pyridylmethyl) ethylenediamine (TPEN) or through CKO mice. Overall, our data reveal the crosstalk between Zn2+, ROS, Nrf2 and autophagy following ONC injury. This study verified that TPEN or knocking out ZnT-3 in ACs is a promising therapeutic option for the treatment of optic nerve damage and elucidated the postsynaptic molecular mechanism of Zn2+-triggered damage to RGCs after ONC injury.

Experimental Study on Bio-Reinforcement of Calcareous Sand through Hydrochloric Acid Solution Precipitation into Cementing Solution.

Microbially induced carbonate precipitation (MICP) technology holds great potential in enhancing soil properties. MICP can be employed to enhance the stability and strength of diverse sandy soil, but it has the shortcoming of low curing efficiency. In response to the identified problem, this study aims to investigate an optimized treatment protocol that involves formulating a cementing solution in a hydrochloric acid (HCl) solution to enhance the solidification rate in the MICP reaction and evaluate its effectiveness. The results indicate that when preparing a 1 M cementing solution in a 0.2 M HCl solution, it promotes the rapid bonding of calcareous sand particles, resulting in an unconfined compressive strength (UCS) of 1312.6 kPa in the sand column after five treatments. Compared to the conventional test group, the experimental group containing HCl exhibited an approximately 1357% increase in UCS. The analysis unveiled the pivotal role of metal ions dissolved from calcareous sand by HCl in enhancing the UCS of MICP-treated calcareous sand. The proposed experimental methodology serves as a valuable tool for designing treatment strategies for MICP-cemented calcareous sand in practical engineering applications.

Field-of-view optimized and constrained undistorted single-shot study of intravoxel incoherent motion and diffusion-weighted imaging of the uterus during the menstrual cycle: a prospective study.

PURPOSE: This study aimed to compare the variability of the uterus during the menses phase (MP), follicular phase (FP), and luteal phase (LP) of the menstrual cycle using intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). METHODS: This prospective study was conducted at the Guangdong Provincial Hospital of Traditional Chinese Medicine between January 2022 and January 2023. Women of childbearing age (18-45 years) with appropriate progesterone levels were included in this study. Conventional magnetic resonance imaging and IVIM-DWI scans were performed during the MP, FP, and LP. The differences in IVIM-DWI-derived parameters between these phases were then compared, and the overlap was quantitatively described. RESULTS: The apparent diffusion coefficient (ADC) and pure molecular diffusion coefficient (D) values from the endometrium, uterine junctional zone (UJZ), and myometrium indicated statistical differences between the MP and FP and the MP and LP (ADC: endometrium, both P < 0.001; UJZ, P = 0.008 and P < 0.001, respectively; myometrium, P = 0.033 and P = 0.006, respectively; D: endometrium, both P < 0.001; UJZ, P = 0.008 and P = 0.006, respectively; myometrium, P = 0.041 and P = 0.045, respectively). The perfusion-related diffusion coefficient (D*) values from the myometrium indicated statistical differences between the FP and MP and the FP and LP (D*: myometrium, P = 0.049 and P = 0.009, respectively). The overlapping endometrium ratios between the MP and FP or LP were lower than 50% in the ADC and D values (ADC: overlapping of MP and FP: 33.33%, overlapping of MP and LP: 23.33%; D: overlapping of MP and FP: 40.00%, overlapping of MP and LP: 43.33%). CONCLUSION: The ADC and IVIM-derived parameters indicated differences in the uterus in diverse phases of the menstrual cycle, especially in the endometrium in relation to ADC and D values.

Selective deletion of zinc transporter 3 in amacrine cells promotes retinal ganglion cell survival and optic nerve regeneration after injury.

Vision depends on accurate signal conduction from the retina to the brain through the optic nerve, an important part of the central nervous system that consists of bundles of axons originating from retinal ganglion cells. The mammalian optic nerve, an important part of the central nervous system, cannot regenerate once it is injured, leading to permanent vision loss. To date, there is no clinical treatment that can regenerate the optic nerve and restore vision. Our previous study found that the mobile zinc (Zn2+) level increased rapidly after optic nerve injury in the retina, specifically in the vesicles of the inner plexiform layer. Furthermore, chelating Zn2+ significantly promoted axonal regeneration with a long-term effect. In this study, we conditionally knocked out zinc transporter 3 (ZnT3) in amacrine cells or retinal ganglion cells to construct two transgenic mouse lines (VGATCreZnT3fl/fl and VGLUT2CreZnT3fl/fl, respectively). We obtained direct evidence that the rapidly increased mobile Zn2+ in response to injury was from amacrine cells. We also found that selective deletion of ZnT3 in amacrine cells promoted retinal ganglion cell survival and axonal regeneration after optic nerve crush injury, improved retinal ganglion cell function, and promoted vision recovery. Sequencing analysis of reginal ganglion cells revealed that inhibiting the release of presynaptic Zn2+ affected the transcription of key genes related to the survival of retinal ganglion cells in postsynaptic neurons, regulated the synaptic connection between amacrine cells and retinal ganglion cells, and affected the fate of retinal ganglion cells. These results suggest that amacrine cells release Zn2+ to trigger transcriptomic changes related to neuronal growth and survival in reginal ganglion cells, thereby influencing the synaptic plasticity of retinal networks. These results make the theory of zinc-dependent retinal ganglion cell death more accurate and complete and provide new insights into the complex interactions between retinal cell networks.

Icariin alleviates ferroptosis-related atherosclerosis by promoting autophagy in xo-LDL-induced vascular endothelial cell injury and atherosclerotic mice.

Vascular endothelial cells (VECs) are located between the blood plasma and the vascular tissue, and the ferroptosis (iron-dependent programmed cell death) of VECs can lead to a range of cardiovascular diseases. Icariin is the main active ingredient of Epimedium brevicornum Maxim., which can improve endothelial cell dysfunction. In the present study, the protective effects of icariin on oxidised low-density lipoprotein (ox-LDL)-treated VECs and high-fat diet-fed Apolipoprotein E-deficient mice were investigated. Inflammatory fibrosis in tissues and inflammatory factors in serum and cell supernatants were detected, and mitochondrial membrane potential and the expression levels of ferroptosis-associated proteins were also detected. The results revealed that icariin reduced the endothelial atherosclerotic plaque area and collagen fibres in aortic sinus tissue, and increased the viability and mitochondrial membrane potential, whereas it reduced the reactive oxygen species levels of VECs. The nucleation of transcription factor EB (TFEB) and subsequent autophagy were negatively associated with ferroptosis in endothelial cells, and the more prominent the autophagy, the lower the levels of ferroptosis. Furthermore, by co-treating the cells with icariin and the two autophagy inhibitors, Bafilomycin A1 (blocking autophagosome and lysosome fusion) and 3-methyladenine (blocking autophagosome formation), respectively, the promoting effects of icariin on autophagy were found to be mediated through the process of autophagosome-lysosome fusion. In in vivo experiments, icariin reduced ferroptosis, alleviated atherosclerotic lesions and increased the rate of TFEB nucleation. Additionally, it was found that ARG304, THR308 and GLN311 were the optimal binding sites for the interaction between icariin and TFEB. Taken together, these results suggest that the fusion of autophagosomes and lysosomes promoted by icarrin enhances autophagy and thus reduces ferroptosis. Therefore, icariin may be a potential candidate for the prevention of ferroptosis of VECs and, thus, for the treatment of cardiovascular diseases.

Alleviating early demyelination in ischaemia/reperfusion by inhibiting sphingosine-1-phosphate receptor 2 could protect visual function from impairment.

Retinal ischaemia/reperfusion (I/R) injury is a common cause of retinal ganglion cell (RGC) apoptosis and axonal degeneration, resulting in irreversible visual impairment. However, there are no available neuroprotective and neurorestorative therapies for retinal I/R injury, and more effective therapeutic approaches are needed. The role of the myelin sheath of the optic nerve after retinal I/R remains unknown. Here, we report that demyelination of the optic nerve is an early pathological feature of retinal I/R and identify sphingosine-1-phosphate receptor 2 (S1PR2) as a therapeutic target for alleviating demyelination in a model of retinal I/R caused by rapid changes in intraocular pressure. Targeting the myelin sheath via S1PR2 protected RGCs and visual function. In our experiment, we observed early damage to the myelin sheath and persistent demyelination accompanied by S1PR2 overexpression after injury. Blockade of S1PR2 by the pharmacological inhibitor JTE-013 reversed demyelination, increased the number of oligodendrocytes, and inhibited microglial activation, contributing to the survival of RGCs and alleviating axonal damage. Finally, we evaluated the postoperative recovery of visual function by recording visual evoked potentials and assessing the quantitative optomotor response. In conclusion, this study is the first to reveal that alleviating demyelination by inhibiting S1PR2 overexpression may be a therapeutic strategy for retinal I/R-related visual impairment.