Associations of cereal fiber intake with rheumatoid arthritis mediated by dietary inflammatory index: insights from NHANES 2011-2020.

Rheumatoid Arthritis (RA) is an increasingly prevalent inflammatory disorder worldwide. Its complex etiology has recently brought dietary factors, particularly fiber intake, into focus as potential influencers. Our study investigates the intricate relationship between various sources of dietary fiber and RA, emphasizing the mediating role of the Dietary Inflammatory Index (DII). Leveraging data from the National Health and Nutrition Examination Survey spanning 2011 to 2020. We meticulously assessed dietary fiber intake through dual 24 h dietary recall interviews, while RA diagnoses were established based on comprehensive medical surveys. The relationships between fiber intake, RA prevalence, and DII mediation were analyzed using sophisticated multivariate logistic regression and mediation analysis. Among our study cohort, 7% were diagnosed with RA. We observed a notable inverse correlation between increased total fiber intake, particularly 5 g/day increments, and the incidence of RA, with cereal fiber intake emerging as the primary mitigating factor. Intriguingly, the DII played a significant role in mediating this association, especially regarding cereal fiber. Our findings reveal a significant association between higher cereal fiber consumption and a reduced prevalence of RA. Additionally, the DII stands out as a pivotal mediator in this relationship, highlighting dietary management's critical role in preventing and managing RA.

An Integrative Nomogram for Identifying Cognitive Impairment Using Seizure Type and Cerebral Small Vessel Disease Neuroimaging Markers in Patients with Late-Onset Epilepsy of Unknown Origin.

INTRODUCTION: Cognitive impairment (CI) is a common comorbidity in patients with late-onset epilepsy of unknown origin (LOEU). However, limited data are available on effective screening methods for CI at an early stage. We aimed to develop and internally validate a nomogram for identifying patients with LOEU at risk of CI and investigate the potential moderating effect of education on the relationship between periventricular white matter hyperintensities (PVHs) and cognitive function. METHODS: We retrospectively reviewed the clinical data of 61 patients aged ≥ 55 years diagnosed with LOEU. The main outcome was CI, reflected as an adjusted Montreal Cognition Assessment score of < 26 points. A nomogram based on a multivariable logistic regression model was constructed. Its discriminative ability, calibration, and clinical applicability were tested using calibration plots, the area under the curve (AUC), and decision curves. Internal model validation was conducted using the bootstrap method. The moderating effect of education on the relationship between PVH and cognitive function was examined using hierarchical linear regression. RESULTS: Forty-four of 61 (72.1%) patients had CI. A nomogram incorporating seizure type, total cerebral small vessel disease burden score, and PVH score was built to identify the risk factors for CI. The AUC of the model was 0.881 (95% confidence interval: 0.771-0.994) and 0.78 (95% confidence interval: 0.75-0.8) after internal validation. Higher educational levels blunted the negative impact of PVH on cognitive function. CONCLUSION: Our nomogram provides a convenient tool for identifying patients with LOEU who are at risk of CI. Moreover, our findings demonstrate the importance of education for these patients.

Threshold effects and inflection points of flavonoid intake in dietary anti-inflammatory effects: Evidence from the NHANES.

Flavonoids have been shown to be beneficial in a variety of inflammatory and metabolic diseases because of their anti-inflammatory and antioxidant properties. However, previous epidemiological studies have only demonstrated a negative correlation between flavonoid intake on inflammatory markers, and the optimal intake of dietary flavonoids and subclasses in terms of dietary anti-inflammatory efficacy remains undetermined. This study was based on 3 cycles (2007-2010, 2017-2018) of the National Health and Nutrition Examination Survey and the corresponding expanded flavonoid database. Weighted multiple linear regression was used to assess linear relationships between flavonoid intake and Dietary inflammation index (DII). Smoothed curve fit and a generalized additive model were used to investigate the nonlinear relationships and threshold effects, the 2-tailed linear regression model was used to find potential inflection points. A total of 12,724 adults were included in the study. After adjusting for potential confounders, flavonoid intake was significantly associated with DII, with the strongest negative association effect for flavonols (-0.40 [-0.45, -0.35]). In subgroup analyses stratified by sex, race, age, body mass index, education levels, and diabetes, flavonol intake maintained a significant negative linear correlation with DII. In addition, we found significant nonlinear relationships (L-shaped relationships) and threshold effects between total flavonoids, flavan-3-ols, and flavanols and DII, with inflection points of 437.65 mg/days, 157.79 mg/days, and 46.36 mg/days, respectively. Our results suggest a threshold for the dietary anti-inflammatory capacity of flavonoid intake in U.S. adults.

Associated factors with stimulation induced seizures and the relevance with surgical outcomes.

OBJECTIVE: To analyze the associated factors with stimulation-induced seizures (SIS) and the relevant factors in predicting surgical outcomes. METHODS: We analyzed 80 consecutive epilepsy patients explored by stereo-electroencephalography with routine electrical stimulation mapping (ESM). If seizures induced by ESM, patients were classified as SIS-positive (SIS-P); otherwise, SIS-negative (SIS-N). Patients received radical surgery were further classified as favorable (Engel I) and unfavorable (Engel II-IV) groups. RESULTS: Of the 80 patients included, we identified 44 (55.0%) and 36(45.0%) patients in the SIS-P and SIS-N groups, respectively. Multivariate analysis revealed that the seizure onset pattern (SOP) of preceding repetitive epileptiform discharges following LVFA (PRED→LVFA) (OR 3.319, 95% CI 1.200-9.183, P = 0.021) and pathology of focal cortical dysplasia (FCD) type II (OR 3.943, 95% CI 1.093-14.226, P = 0.036) were independent factors influencing whether the electrical stimulation can induce a seizure. Among the patients received radical surgery, there were 55 and 15 patients in the favorable and unfavorable groups separately. Multivariate analysis revealed that the SOP of PRED→LVFA induced seizures by stimulation (OR 11.409, 95% CI 1.182-110.161, P = 0.035) and bilateral implantation (OR 0.048, 95% CI 0.005-0.497, P = 0.011) were independent factors affecting surgical outcomes. The previous epilepsy surgery had a trend to be a negative factor with SIS (OR 0.156, 95% CI 0.028-0.880, P = 0.035) and surgical outcomes (OR 0.253, 95% CI 0.053-1.219, P = 0.087). CONCLUSION: ESM is a highly valuable method for localizing the seizure onset zone. The SOP of PRED→LVFA and FCD type II were associated with elicitation of SIS by ESM, whereas a previous epilepsy surgery showed a negative association. Furthermore, the SOP of PRED→LVFA together with SIS in the same patient predicted favorable surgical outcomes, whereas bilateral electrode implantation predicted unfavorable outcomes.

Disturbance of functional brain networks and cognitive decline in Parkinson's disease: Severe cerebral small vessel disease aggravates this relationship.

INTRODUCTION: Several studies have identified a relationship between functional brain network disturbance and cognitive decline in people with Parkinson's disease (PwP); however, few studies have explored whether cerebral small vessel disease (CSVD) burden modifies this relationship. This study aimed to investigate the potential moderating effect of CSVD on the relationship between functional brain network disturbance and cognitive decline in PwP. METHODS: We prospectively recruited 61 PwP from Beijing Tiantan Hospital between October 2021 to September 2022. The Montreal Cognitive Assessment (MoCA) score was used to assess cognition. CSVD imaging markers were evaluated following the STandards for ReportIng Vascular changes on nEuroimaging instructions, and the CSVD burden score was calculated. The functional connectivity indicator was obtained and calculated using quantitative electroencephalography examination. The moderating effect of CSVD burden on the relationship between functional brain network disturbance and cognitive decline was examined using hierarchical linear regression. RESULTS: Forty-six of 61 (75.4%) PwP had cognitive impairment. Higher global weighted phase lag index (wPLI) values in beta1 bands were significantly associated with lower adjusted MoCA scores. CSVD burden aggravated the effect of the global wPLI in beta1 bands on adjusted MoCA scores. This effect was reinforced by the high level of CSVD burden. CONCLUSIONS: Higher wPLI indicates a possible pathological activation of functional brain networks that are associated with cognitive decline in PwP, and the high level of CSVD burden aggravates this relationship.

Cerebral microbleeds is associated with dementia in Parkinson's disease.

INTRODUCTION: Emerging evidence suggests that cerebral small vessel disease (CSVD) may worsen cognitive functions in Parkinson's disease (PD). However, the effect of microbleeds on cognitive function in patients with PD remains unknown. This study explored the association between the presence, number and location of microbleeds with dementia in PD patients. METHODS: This cross-sectional study included 431 patients with PD from Beijing Tiantan Hospital from May 2016 to August 2019. Cognition assessments (MMSE, MoCA) were performed for these patients. MRI imaging sequences were obtained and reviewed independently by two well-trained readers who were blind to all clinical data. Spearman's correlation analysis and logistic regression model analysis were further used for the assessments. RESULTS: An association between cerebral microbleeds with cognitive ability and dementia in PD patients was revealed. A significance was observed between the total number of microbleeds and two widely used scores of cognitive assessments (Spearman R = - 0.120 to MMSE with a p = 0.016, and - 0.117 to MoCA with a p = 0.020). In detail, infratentorial microbleeds were associated with the level of cognition in PD patients (Spearman R = - 0.099 to MMSE with a p = 0.049, and - 0.116 to MoCA with a p = 0.021). Furthermore, logistic regression analysis results also confirmed such correlations between the number of microbleeds and cognitive ability after adjusting for age, cholesterol level, Hamilton Anxiety Scale, Hamilton Depression Scale, and white matter hyperintensity Fazekas score (OR 3.28, p = 0.035, 95% CI 1.090-9.892). CONCLUSIONS: The occurrence of microbleeds, especially in the infratentorial locations, may worsen the cognitive function of PD patients and result in dementia. Management of cerebral vascular disease could be beneficial to patients with PD.

A genetic analysis of Chinese patients with early-onset Parkinson' s disease.

Genetic factors play an important role in early-onset Parkinson's disease (EOPD). The genetic spectrum of patients with EOPD varies widely among different ethnicities, with extensive investigations having been performed in Caucasian populations; however, research in Chinese populations remains limited. In this study, we performed multiplex ligation-dependent probe amplification assay and whole-exome sequencing in 15 unrelated Chinese EOPD patients with age of onset before 40 years. Among them, a patient carried compound heterozygous exon duplications in Parkin (exon 3 duplication and exon 4 duplication) (6.67 %) and two patients carried the homozygous pathogenic variant (p.D331Y) in PLA2G6 (13.33 %). Three novel variants in EIF4G1 (p.P1043S, p.R1505Q, and p.P266A) were identified and classified as uncertain significance. Additionally, a risk variant in GBA (p.L483P) was detected in one patient (6.67 %). PLA2G6 (13.33 %) was the most common causative gene among our EOPD patients. Furthermore, detailed clinical features were presented. Our results broaden the genetic spectrum and clinical phenotypic spectrum of EOPD patients.

Application Value of Nursing Intervention under the Guidance of Risk Prevention Management Concept in Preventing Vascular Access Infection in Patients Undergoing Maintenance Hemodialysis.

Objective: To explore the application value of nursing intervention under the guidance of risk prevention management concept in preventing vascular access infection in patients undergoing maintenance hemodialysis (MHD). Methods: A total of 100 MHD patients who were admitted to the intensive care unit (ICU) of our hospital from May 2019 to May 2020 were enrolled. Based on the principle of double-blind grouping, patients were randomly divided into the risk management group and control group, with 50 cases in each group. The control group was given routine nursing, while the risk management group was given nursing intervention under the guidance of risk prevention management concept on the basis of the control group. The nursing intervention effect and incidence of vascular access infection were compared between the two groups. The psychological status and quality of life in both the groups were evaluated by the self-rating anxiety scale (SAS), self-rating depression scale (SDS), and Short Form 36 Health Survey (SF-36). Results: After intervention, biochemical indexes (serum albumin, creatinine, and hemoglobin) and body mass in the risk management group were significantly higher than those in the control group, while malnutrition-inflammation score (MIS) was significantly lower than the control group (P < 0.05). After intervention, SAS and SDS scores in both the groups were significantly decreased, which were significantly lower in the risk management group than in the control group (P < 0.05). At 8 w and 12 w after intervention, incidence rates of vascular access infection in risk management group were significantly lower than those in the control group (10.00% vs. 26.00% and 12.00% vs. 34.00%, P < 0.05). After intervention, SF-36 scores in each dimension of both the groups were significantly increased, which were significantly higher in the risk management group than in the control group (P < 0.05). Conclusion: The implementation of nursing intervention under the guidance of risk prevention management concept for MHD patients can effectively improve biochemical indexes, nutritional status, and body mass and reduce the incidence of vascular access infection, which is of great significance for improving psychological status and quality of life.

Effect of cerebral small vessel disease on cognitive impairment in Parkinson's disease: a systematic review and meta-analysis.

Background: The occurrence of various cerebrovascular diseases can easily induce cognitive impairment in the elderly. Therefore, it is of great clinical significance to correctly understand the relationship between these key pathogenic factors and cognitive impairment of Parkinson's disease. To explore the effect of cerebrovascular disease on cognitive impairment in Parkinson's disease by meta-analysis. Methods: PubMed, Medline, Embase, and Web of Science databases were selected as the sources for the literature search. English language articles were included. Literature related to this study were published from January 2001 to January 2021. Literature was screened and the quality was evaluated. RevMan 5.3 software was used to perform the meta-analysis on the effects of cerebrovascular disease on cognitive impairment in Parkinson's disease. Results: Six articles were finally included, involving a total of 5,552 cases. Of these, 2,684 were positive cases, accounting for 48.3%. Compared with patients with non-Parkinson's cognitive impairment, patients with cognitive impairment in Parkinson's disease caused by cerebral small vessel disease had significant differences in executive ability (OR =1.62, 95% CI: 1.21-2.16, P=0.001), memory (OR =1.48, 95% CI: 1.30-1.68, P<0.00001), information processing (OR =0.60, 95% CI: 0.35-1.03, P=0.07), language communication (OR= 4.72, 95% CI: 3.26-6.85, P<0.00001), and overall cognitive function (OR =0.72, 95% CI: 0.52-0.99, P=0.05). Conclusions: A total of 6 studies were included in this meta-analysis on the influence of cerebral small vessel disease on cognitive impairment in Parkinson's disease. This study shows that cerebrovascular disease has different effects on all aspects of cognitive function of Parkinson's disease.

Status of higher TGF-ß1 and TGF-ß2 levels in the aqueous humour of patients with diabetes and cataracts.

BACKGROUND: Transforming growth factor (TGF) is a cytokine that acts on the proliferation, migration, differentiation, and apoptosis of cells and the accumulation of extracellular matrix components. Very few studies have precisely evaluated the concentration of TGF-ß in the aqueous humour (AH) of diabetic and cataract (DMC) eyes due to the low expression of proteins in the AH or other reasons. The concentrations of TGF-ß1, -ß2, and -ß3 in the AH of the DMC group were compared with those of the age-related cataract (ARC) group. METHODS: We collected AH and lens epithelium samples from 33 DMC patients and 36 ARC patients. Luminex liquid suspension chip detection was applied to detect the concentration of TGF-ß1, -ß2, and -ß3 in the AH samples. The expression of TGFB1/2/3 in lens epithelium samples was determined by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The concentrations of TGF-ß1 and TGF-ß2 in AH samples of DMC eyes were higher than those of ARC eyes. The differences in TGF-ß1 and TGF-ß2 between the two groups were statistically significant (P value = 0.001 for TGF-ß1, P value = 0.023 for TGF-ß2). The difference of the correlation between TGF-ß1 and glycosylated haemoglobin was significant (P value = 0.011, and Pearson correlation coefficient = 0.306). The difference of the correlation between TGF-ß2 and glycosylated haemoglobin was significant (P value = 0.026, and Pearson correlation coefficient = 0.269). The mRNA expression levels of TGFB1 and TGFB2 were upregulated in DMC epithelium samples compared with ARC epithelium samples. The differences in TGFB1 and TGFB2 between the two groups were statistically significant (P value for TGFB1 = 0.041, P value for TGFB2 = 0.021). CONCLUSIONS: The concentrations of TGF-ß1 and TGF-ß2 in AH samples were significantly higher in DMC eyes than in ARC eyes. The higher the glycosylated haemoglobin was, the higher the concentrations of TGF-ß1 and -ß2 were. The mRNA expression of TGFB1 and TGFB2 was significantly upregulated in DMC epithelial samples compared with ARC epithelial samples, suggesting the proinflammatory status of the anterior chamber of DMC eyes.

Long Noncoding RNA SLC20A1-1 Induces Nucleus Pulposus Apoptosis by Sponging miR-146a-5p.

Background: Intervertebral disc degeneration (IDD) is a common cause of lower back pain and is characterized by cellular apoptosis, senescence, and extracellular matrix degradation. In the current study, we aimed to identify the effect of the long noncoding RNA SLC20A1-1 on tumor necrosis factor α (TNF-α)-induced apoptosis of nuclear pulposus cells (NPCs). Materials and Methods: NPCs were induced by TNF-α and used as an in vitro model. The mRNA expression of SLC20A1-1 was detected by quantitative real-time PCR (qPCR) both in clinical samples and in vitro. The scratch assay, Transwell invasion assay, CCK-8 assay, and flow cytometry were used to measure cell migration, growth, and apoptosis. The binding site between SLC20A1-1 and miR-146a-5p was assessed by a dual-luciferase reporter assay. Results: The expression of SLC20A1-1 was significantly upregulated in herniated lumbar discs, and TNF-α induced SLC20A1-1 expression in NPCs. Overexpression of SLC20A1-1 inhibited NPC growth, promoted NPC apoptosis, and enhanced macrophage recruitment and migration. The effect of SLC20A1-1 on NPCs and macrophages could be reversed by etanercept treatment. Moreover, we found that SLC20A1-1 could suppress miR-146a-5p to induce TRAF6 and caspase 3 expression. Conclusion: Overall, SLC20A1-1, an IDD regulator, is involved in TNF-α-induced NPC apoptosis by sponging miR-146a-5p. Clinical Trial Registration number: NMU20210325.

Interictal pattern on scalp electroencephalogram predicts excellent surgical outcome of epilepsy caused by focal cortical dysplasia.

OBJECTIVE: Focal cortical dysplasia (FCD) represents an essential cause of drug-resistant epilepsy with surgery as an effective treatment option. This study aimed to identify the important predictors of favorable surgical outcomes and the impact of the interictal scalp electroencephalogram (EEG) patterns in predicting postsurgical seizure outcomes. METHODS: We retrospectively evaluated 210 consecutive patients between 2015 and 2019. They were diagnosed with FCD by pathology, underwent resection, and had at least one year of postsurgical follow-up. Predictors of seizure freedom were analyzed. RESULTS: Based on the information at the latest follow-up, seizure outcome was classified as Engel Class I (seizure-free) in 81.4% and Engel Class II-IV (non-seizure-free) in 18.6% of patients. There were 43, 105, and 62 cases of FCD type I, type II, and type III, respectively. The interictal EEG showed a repetitive discharge pattern (REDP) in 87 (41.4%) patients, polyspike discharge pattern (PDP) in 41 (19.5%), and the coexistence of REDP and PDP in the same location in 32 (15.2%) patients. The analyzed patterns in order of frequency were repetitive discharges lasting 5 seconds or more (32.4%); polyspikes (16.7%); RED type 1 (11.4%); continuous epileptiform discharges occupying >80% of the recording (11.4%); RED type 2 (6.2%); brushes (3.3%); focal, fast, continuous spikes (2.4%); focal fast rhythmic epileptiform discharges (1.43%); and frequent rhythmic bursting epileptiform activity (1.4%). The coexistence of REDP and PDP in the same location on scalp EEG and complete resection of the assumed epileptogenic zone (EZ) was independently associated with favorable postsurgical prognosis. SIGNIFICANCE: Resective epilepsy surgery for intractable epilepsy caused by FCD has favorable outcomes. Interictal scalp EEG patterns were revealed to be predictive of excellent surgical outcomes and may help clinical decision-making and enable better presurgical evaluation.

Perivascular space in Parkinson's disease: Association with CSF amyloid/tau and cognitive decline.

OBJECTIVE: Whether perivascular space (PVS) visible on magnetic resonance imaging (MRI) represents glymphatic dysfunction and whether this imaging marker is pathologic in Parkinson's disease (PD) have been controversial. The objective was to determine whether PVS visible on MRI is independently associated with cognitive decline in patients with PD, and to test whether pathologic proteins in the CSF (such as Aß42) mediate the pathologic role of PVS. METHODS: A total of 341 patients with Parkinson's disease from Parkinson's Progression Marker Initiative (PPMI) cohort was included in the present study. PVS in the basal ganglia (BG-PVS) and centrum semiovale were evaluated with a semiquantitative scale. Changes in the Montreal Cognitive Assessment (MoCA) score and the absolute MoCA score at the 3-year assessment were considered the main cognitive outcome. A multivariable linear regression model was used to test the association between PVS and cognitive decline. A mixed linear model and path analysis were used to test the interaction among PVS, CSF biomarkers and cognitive decline. RESULTS: BG-PVS was associated with cognitive decline in patients with PD at the 3-year follow-up independent of age, baseline cognition, motor and nonmotor function, presynaptic dopaminergic deficiency, and CSF biomarkers. The interaction between BG-PVS and Aß42/tTau, Aß42/pTau, and Aß42 levels was significantly predictive of 3-year cognitive decline. Path analysis confirmed that CSF Aß42/tTau levels partially mediated the pathologic effect of BG-PVS on cognitive outcome in PD. CONCLUSIONS: BG-PVS is independently associated with cognitive decline in PD, and this association may be partially mediated by toxic CSF proteins.

Case report:Multiple abscesses caused by Porphyromonas gingivalis diagnosed by metagenomic next-generation sequencing.

Background: Extraoral infection by Porphyromonas gingivalis (P. gingivalis) is extremely rare and challenging to diagnose because the fastidious pathogen is difficult to culture by traditional methods. We report the first case of a patient with multiple abscesses in muscles and the brain with dura empyema due to P. gingivalis, which was diagnosed by metagenomic next-generation sequencing (mNGS). Case presentation: A 65-year-old male patient was admitted to our hospital for multiple lumps in his body. Brain magnetic resonance imaging (MRI) and lower-limb computed tomography (CT) revealed multiple abscesses in the brain and muscles. A diagnosis of P. gingivalis infection was made based on mNGS tests of blood, cerebrospinal fluid (CSF), and pus samples, as the traditional bacterial culture of these samples showed negative results. Target antibiotic therapy with meropenem and metronidazole was administered, and CT-guided percutaneous catheter drainage of abscesses in both thighs was performed. The size of muscle abscesses reduced significantly and neurological function improved. The patient was followed up for 4 months. No abscesses re-appeared, and the remaining abscesses in his backside and both legs were completely absorbed. He can speak fluently and walk around freely without any neurological deficits. Conclusion: Metagenomic next-generation sequencing is helpful for early diagnosis and subsequent treatment of P. gingivalis-associated multiple abscesses.

Sleep-Related Hypermotor Epilepsy: Etiology, Electro-Clinical Features, and Therapeutic Strategies.

Sleep-related hypermotor epilepsy (SHE) is a group of clinical syndromes with heterogeneous etiologies. SHE is difficult to diagnose and treat in the early stages due to its diverse clinical manifestations and difficulties in differentiating from non-epileptic events, which seriously affect patients' quality of life and social behavior. The overall prognosis for SHE is unsatisfactory, but different etiologies affect patients' prognoses. Surgical treatment is an effective method for carefully selected patients with refractory SHE; nevertheless, preoperative assessment remains challenging because of the low sensitivity of noninvasive scalp electroencephalogram and imaging to detect abnormalities. However, through a careful analysis of semiology, the clinician can deduce the potential epileptogenic zone. This paper summarizes the research status of the background, etiology, electro-clinical features, diagnostic criteria, prognosis, and treatment of SHE to provide a more in-depth understanding of its pathophysiological mechanism, improve the accuracy in the diagnosis of this group of syndromes, and further explore more targeted therapy plans.

AXDND1, a novel testis-enriched gene, is required for spermiogenesis and male fertility.

Spermiogenesis is a complex process depending on the sophisticated coordination of a myriad of testis-enriched gene regulations. The regulatory pathways that coordinate this process are not well understood, and we demonstrate here that AXDND1, as a novel testis-enriched gene is essential for spermiogenesis and male fertility. AXDND1 is exclusively expressed in the round and elongating spermatids in humans and mice. We identified two potentially deleterious mutations of AXDND1 unique to non-obstructive azoospermia (NOA) patients through selected exonic sequencing. Importantly, Axdnd1 knockout males are sterile with reduced testis size caused by increased germ cell apoptosis and sloughing, exhibiting phenotypes consistent with oligoasthenoteratozoospermia. Axdnd1 mutated late spermatids showed head deformation, outer doublet microtubules deficiency in the axoneme, and loss of corresponding accessory structures, including outer dense fiber (ODF) and mitochondria sheath. These phenotypes were probably due to the perturbed behavior of the manchette, a dynamic structure where AXDND1 was localized. Our findings establish AXDND1 as a novel testis-enrich gene essential for spermiogenesis and male fertility probably by regulating the manchette dynamics, spermatid head shaping, sperm flagellum assembly.

Association of Trimethylamine N-Oxide and Its Precursor With Cerebral Small Vessel Imaging Markers.

Background: High plasma levels of trimethylamine N-oxide (TMAO) and its precursor choline have been linked to stroke; however, their association with cerebral small vessel disease remains unclear. Here we evaluated the association of plasma levels of TMAO and choline with imaging markers of cerebral small vessel disease, including white matter hyperintensities, lacunes, and cerebral microbleeds. Methods: We performed a baseline cross-sectional analysis of a multicenter hospital-based cohort study from 2015 to 2018. The data were collected from 30 hospitals in China and included 1,098 patients with ischemic stroke/transient ischemic attack aged ≥18 years. White matter hyperintensities, lacunes, and cerebral microbleeds were evaluated with the patients' demographic, clinical, and laboratory information removed. White matter hyperintensities were rated using the Fazekas visual grading scale, while the degree of severity of the lacunes and cerebral microbleeds was defined by the number of lesions. Results: Increased TMAO levels were associated with severe white matter hyperintensities [adjusted odds ratio (aOR) for the highest vs. lowest quartile, 1.5; 95% confidence interval (CI), 1.0-2.1, p = 0.04]. High TMAO levels were more strongly associated with severe periventricular white matter hyperintensities (aOR for the highest vs. lowest quartile, 1.6; 95% CI, 1.1-2.3, p = 0.009) than deep white matter hyperintensities (aOR for the highest vs. lowest quartile, 1.3; 95% CI, 0.9-1.9, p = 0.16). No significant association was observed between TMAO and lacunes or cerebral microbleeds. Choline showed trends similar to that of TMAO in the association with cerebral small vessel disease. Conclusions: In patients with ischemic stroke or transient ischemic attack, TMAO and choline appear to be associated with white matter hyperintensities, but not with lacunes or cerebral microbleeds; TMAO and choline were associated with increased risk of a greater periventricular, rather than deep, white matter hyperintensities burden.

Monocarboxylate transporter 1 promotes proliferation and invasion of renal cancer cells by mediating acetate transport.

One hallmark of renal cell carcinoma (RCC) is metabolic reprogramming, which involves elevation of glycolysis and upregulation of lipid metabolism. However, the mechanism of metabolic reprogramming is incompletely understood. Monocarboxylate transporter 1 (MCT1) promotes transport for lactate and pyruvate, which are crucial for cell metabolism. The aim of present study was to investigate the function of MCT1 on RCC development and its mechanism on metabolic reprogramming. The results showed that MCT1 messenger RNA and protein levels significantly increased in cancer tissues of ccRCC compared to normal tissue. MCT1 was further found to mainly located in the cell membrane of RCC. The knockdown of MCT1 by RNAi significantly inhibited proliferation and migration of 786-O and ACHN cells. MCT1 also induced the expressions of proliferation marker Ki-67 and invasion marker SNAI1. Moreover, we also showed that acetate treatment could upregulate the expression of MCT1, but not other MCT isoforms. On the other hand, MCT1 was involved in acetate transport and intracellular histone acetylation. In summary, this study revealed that MCT1 is abnormally high in ccRCC and promotes cancer development. The regulatory effect of MCT1 on cell proliferation and invasion maybe mediated by acetate transport.

Cerebral small vessel disease may worsen motor function, cognition, and mood in Parkinson's disease.

INTRODUCTION: Emerging evidence has suggested that cerebral small vessel disease (CSVD) may worsen motor function and cognition in Parkinson's disease (PD). However, the effect of CSVD on anxiety and depression in patients with PD remains unknown. This study explored the multi-dimensional effects of CSVD on PD outcomes (motor, cognition, and depression/anxiety). METHODS: This cross-sectional study included 431 patients with PD from Beijing Tiantan Hospital from May 2016 to August 2019. CSVD imaging markers were assessed and the four-point CSVD burden score was calculated. Motor function (MDS-UPDRS III score and subscores), cognition (MMSE, MoCA), anxiety (HAMA), and depression (HAMD) were assessed in these patients. The associations of CSVD with these outcomes were analyzed using the Spearman's correlation and multivariable linear regression models. RESULTS: Motor dysfunction, cognitive impairment, depression, and anxiety were significantly worse in patients with severe CSVD than in those with mild CSVD. Multivariable linear regression showed that CSVD burden was significantly associated with motor dysfunction (MDS-UPDRS III score and rigidity and bradykinesia subscores), impaired cognition, and high levels of depression and anxiety. A marginally significant association was observed between CSVD burden and gait/postural instability in multivariable regression analysis. Among the CSVD imaging markers, white matter hyperintensity, number of lacunes, and microbleeds were positively correlated with the severity of motor, cognitive, and emotional impairments, while the perivascular space in the basal ganglia was only correlated with cognitive impairments. CONCLUSIONS: Comorbid CSVD may affect multiple functional domains in patients with PD. Management of cerebrovascular disease may improve PD outcomes.