Genotype and phenotype correlation of PHACTR1-related neurological disorders.

BACKGROUND: PHACTR1 (phosphatase and actin regulators) plays a key role in cortical migration and synaptic activity by binding and regulating G-actin and PPP1CA. This study aimed to expand the genotype and phenotype of patients with de novo variants in PHACTR1 and analyse the impact of variants on protein-protein interaction. METHODS: We identified seven patients with PHACTR1 variants by trio-based whole-exome sequencing. Additional two subjects were ascertained from two centres through GeneMatcher. The genotype-phenotype correlation was determined, and AlphaFold-Multimer was used to predict protein-protein interactions and interfaces. RESULTS: Eight individuals carried missense variants and one had CNV in the PHACTR1. Infantile epileptic spasms syndrome (IESS) was the unifying phenotype in eight patients with missense variants of PHACTR1. They could present with other types of seizures and often exhibit drug-resistant epilepsy with a poor prognosis. One patient with CNV displayed a developmental encephalopathy phenotype. Using AlphaFold-Multimer, our findings indicate that PHACTR1 and G-actin-binding sequences overlap with PPP1CA at the RPEL3 domain, which suggests possible competition between PPP1CA and G-actin for binding to PHACTR1 through a similar polymerisation interface. In addition, patients carrying missense variants located at the PHACTR1-PPP1CA or PHACTR1-G-actin interfaces consistently exhibit the IESS phenotype. These missense variants are mostly concentrated in the overlapping sequence (RPEL3 domain). CONCLUSIONS: Patients with variants in PHACTR1 can have a phenotype of developmental encephalopathy in addition to IESS. Moreover, our study confirmed that the variants affect the binding of PHACTR1 to G-actin or PPP1CA, resulting in neurological disorders in patients.

Diagnostic performance of Node Reporting and Data System (Node-RADS) for assessing mesorectal lymph node in rectal cancer by CT.

BACKGROUND: To compare the diagnostic performance of the Node-RADS scoring system and lymph node (LN) size in preoperative LN assessment for rectal cancer (RC), and to investigate whether the selection of size as the primary criterion whereas morphology as the secondary criterion for LNs can be considered the preferred method for clinical assessment. METHODS: Preoperative CT data of 146 RC patients treated with radical resection surgery were retrospectively analyzed. The Node-RADS score and short-axis diameter of size-prioritized LNs and the morphology-prioritized LNs were obtained. The correlations of Node-RADS score to the pN stage, LNM number and lymph node ratio (LNR) were investigated. The performances on assessing pathological lymph node metastasis were compared between Node-RADS score and short-axis diameter. A nomogram combined the Node-RADS score and clinical features was also evaluated. RESULTS: Node-RADS score showed significant correlation with pN stage, LNM number and LNR (Node-RADS of size-prioritized LN: r = 0.600, 0.592, and 0.606; Node-RADS of morphology-prioritized LN: r = 0.547, 0.538, and 0.527; Node-RADSmax: r = 0.612, 0.604, and 0.610; all p < 0.001). For size-prioritized LN, Node-RADS achieved an AUC of 0.826, significantly superior to short-axis diameter (0.826 vs. 0.743, p = 0.009). For morphology-prioritized LN, Node-RADS exhibited an AUC of 0.758, slightly better than short-axis diameter (0.758 vs. 0.718, p = 0.098). The Node-RADS score of size-prioritized LN was significantly better than that of morphology-prioritized LN (0.826 vs. 0.758, p = 0.038). The nomogram achieved the best diagnostic performance (AUC = 0.861) than all the other assessment methods (p < 0.05). CONCLUSIONS: The Node-RADS scoring system outperforms the short-axis diameter in predicting lymph node metastasis in RC. Size-prioritized LN demonstrates superior predictive efficacy compared to morphology-prioritized LN. The nomogram combined the Node-RADS score of size-prioritized LN with clinical features exhibits the best diagnostic performance. Moreover, a clear relationship was demonstrated between the Node-RADS score and the quantity-dependent pathological characteristics of LNM.

Acute kidney injury in hospitalized patients with nonmalignant pleural effusions: a retrospective cohort study.

BACKGROUND: Nonmalignant pleural effusion (NMPE) is common and remains a definite health care problem. Pleural effusion was supposed to be a risk factor for acute kidney injury (AKI). Incidence of AKI in NMPE patients and whether there is correlation between the size of effusions and AKI is unknown. OBJECTIVE: To assess the incidence of AKI in NMPE inpatients and its association with effusion size. STUDY DESIGN AND METHOD: We conducted a retrospective cohort study of inpatients admitted to the Chinese PLA General Hospital with pleural effusion from 2018-2021. All patients with pleural effusions confirmed by chest radiography (CT or X-ray) were included, excluding patients with diagnosis of malignancy, chronic dialysis, end-stage renal disease (ESRD), community-acquired AKI, hospital-acquired AKI before chest radiography, and fewer than two serum creatinine tests during hospitalization. Multivariate logistic regression and LASSO logistic regression models were used to identify risk factors associated with AKI. Subgroup analyses and interaction tests for effusion volume were performed adjusted for the variables selected by LASSO. Causal mediation analysis was used to estimate the mediating effect of heart failure, pneumonia, and eGFR < 60 ml/min/1.73m2 on AKI through effusion volume. RESULTS: NMPE was present in 7.8% of internal medicine inpatients. Of the 3047 patients included, 360 (11.8%) developed AKI during hospitalization. After adjustment by covariates selected by LASSO, moderate and large effusions increased the risk of AKI compared with small effusions (moderate: OR 1.47, 95%CI 1.11-1.94 p = 0.006; large: OR 1.86, 95%CI 1.05-3.20 p = 0.028). No significant modification effect was observed among age, gender, diabetes, bilateral effusions, and eGFR. Volume of effusions mediated 6.8% (p = 0.005), 4.0% (p = 0.046) and 4.6% (p < 0.001) of the effect of heart failure, pneumonia and low eGFR on the development of AKI respectively. CONCLUSION: The incidence of AKI is high among NMPE patients. Moderate and large effusion volume is independently associated with AKI compared to small size. The effusion size acts as a mediator in heart failure, pneumonia, and eGFR.

Red blood cell distribution width-to-monocyte ratio for predicting 90-day mortality of COVID-19 in patients with chronic kidney disease during the Omicron period: a prospective single-center study.

We aimed to test whether red blood cell distribution width (RDW) to monocyte percentage ratio (RMR) was associated with the acute-phase prognosis of coronavirus disease 2019 (COVID-19) in chronic kidney disease (CKD) patients. Prospective enrollment and 90-day follow-up of CKD patients with COVID-19 were conducted from December 1, 2022 to January 31, 2023. Demographics, clinical data, and laboratory and radiographic findings were collected, and multiple logistic regression, subgroup analysis, and receiver operating characteristic (ROC) curve analysis were performed. A total of 218 patients were enrolled, with a mean age of 59 years and 69.7% being male. The 90-day mortality rate was 24.8%. The lnRMR level was 5.18 (4.91-5.43) and emerged as an independent risk factor (OR: 3.01, 95% CI: 1.72-5.85). The lnRMR-mortality association was consistent across sex, age, CKD stage, COVID-19 vaccination, and comorbidity subgroups. The area under the ROC curve of lnRMR was 0.737 (95% CI: 0.655-0.819). Our findings indicate that lnRMR is a simple and practical predictor for identifying high-risk CKD patients during the acute phase of COVID-19.

Transcriptomic landscapes reveal development-related physiological processes in the two-spotted spider mite, Tetranychus urticae.

The two-spotted spider mite (Tetranychus urticae Koch, TSSM) is recognized as one of the most problematic spider mite pests. However, the precise gene expression patterns across its key developmental stages remain elusive. Here, we performed a comprehensive transcriptome analysis of TSSM eggs, nymphs and adult females using publicly available RNA sequencing (RNA-seq) data to elucidate the overarching transcriptomic differences between these developmental stages. Principal component analysis and hierarchical clustering analysis unveiled distinct separations among samples across different developmental stages, regardless of their Wolbachia infection status. Differential expression analysis revealed 4,089,2,762, and 1,282 core genes specifically enriched in eggs, nymphs, and adults, respectively. KEGG and GO enrichment analyses showed upregulation of genes in eggs are associated with proteolysis, Wnt signaling pathway, DNA transcription, RNA biosynthetic and metabolic processes, as well as protein folding, sorting, and degradation pathways. Meanwhile, nymphs exhibited increased abundance of genes related to chitin/amino sugar metabolic processes, G protein-coupled receptor signaling pathways, monoatomic ion transport, and neurotransmitter transport pathways. Pathways involving sphingolipid and carbohydrate metabolic processes, proteolysis, lipid transport, and localization were particularly enriched in older females. Altogether, our findings suggest that the egg stage exhibits higher activity in cell differentiation processes, the nymph stage is more involved in chitin development, and the adult stage shows increased metabolic and reproductive activity. This study enhances our understanding of the molecular mechanisms underlying TSSM development and paves the way for further research into the intricate physiological processes of TSSM.

Causal effects of inflammatory bowel disease on risk of type 2 diabetes: a two-sample multivariable Mendelian randomization study.

AIM: This study aimed to explore the causal association between inflammatory bowel disease (IBD) and the risk of type 2 diabetes (T2D) based on a two-sample Mendelian randomization (MR) study. METHODS: Summary single nucleotide polymorphism (SNP)-phenotype association data were obtained from published two genome-wide association studies (GWAS) including SNPs related to IBD, UC, or CD in European participants (n = 71,997) and East Asian participants (n = 16,805). Two GWAS including SNPs associated with T2D included 655,666 Europeans and 433,540 East Asians. A series of screening processes were performed to select qualified instrumental SNPs strongly related to exposure. We applied the inverse variance weighted (IVW), the MR-Egger regression, and the weighted median to estimate the causal effects of IBD, ulcerative colitis (UC) or Crohn' disease (CD) on T2D. Cochran's Q test was conducted to evaluate the statistical heterogeneity between SNPs in the IVW method. The leave-one-out analysis was employed to assess whether the results were caused by any single SNP associated with IBD, UC, or CD. Odds ratio (OR) and 95% confidence interval (CI) were calculated. RESULTS: The IVW results demonstrated that IBD could increase the risk of T2D in the European population (OR = 1.0230, 95%CI: 1.0073-1.0390). UC was positively associated with the risk of T2D according to the weighted median (OR = 1.0274, 95%CI: 1.0009-1.0546) and IVW (OR = 1.0244, 95%CI: 1.0071-1.0421) results in the European population. The IVW results indicated that the CD was positively associated with the risk of T2D in the European population (OR = 1.0187, 95%CI: 1.0045-1.0330). In the East Asian population, there are no associations between the IBD, UC, or CD and the risk of T2D (all P > 0.05). MVMR results revealed that the causal effect UC on T2D was still statistically significant after including body mass index (BMI) or low-density lipoprotein (LDL). CONCLUSION: IBD, UC, or CD had causal effects on the risk of T2D in the European population, which might provide evidence for the prevention of T2D in patients with IBD, UC, or CD.

POLR3-related leukodystrophy caused by biallelic POLR3A and 1C pathogenic variants: a single-center experience.

Objectives: This study aimed to investigate the clinical, radiological, and genetic features of POLR3-related leukodystrophy caused by mutations in POLR3A or POLR1C. Methods: Fourteen Chinese patients with POLR3-related leukodystrophy were enrolled in this cross-sectional observational study. The clinical manifestations, brain MRI and genetic tests of the patients were evaluated. Results: Thirteen patients had biallelic variants in POLR3A (92.9%), and one had biallelic variants in POLR1C (7.1%). The median age at disease onset was 9 months. A total of 85.7% of the patients presented with motor delay, abnormal gait, and intelligence disability in the first 2 years of life. Intellectual disability can be categorized based on its severity. It varied from mild (which involves difficulty concentrating) to very severe (with no smiling or laughing or never being able to speak since birth). Short stature was observed in all patients, and delayed dentition was observed in 64.3% of them. Furthermore, three out of 14 patients had myopia. Hypomyelination was invariably present in all patients, whereas myelination of the basal ganglia was preserved in only six out of 14 patients. All the mutations were compound heterozygous and included missense (n = 25), deletion (n = 1), and splice site variants (n = 2). A total of 78.6% of the patients with POLR3A were identified as carrying the c.1771-6C>G variant or the c.1771-7C>G variant. Conclusion: The phenotypic diversity of POLR3-HLD associated with pathogenic variants ranges from mild to very severe for neurological and non-neurological symptoms. Most patients presented symptoms in the first 2 years of life. The c.1771-6C>G or c.1771-7C>G variant is the most frequent mutation site in POLR3A in Chinese individuals.

A bibliometric analysis of research on the health impacts of ozone air pollution.

Ground-level ozone (O3) is one of the major air pollutants. A large body of literature has linked O3 air pollution to various adverse human health effects. The objective of this study is to attain a comprehensive and in-depth understanding of the progress and frontiers of research on O3 and human health. We used bibliometric methods to summarize publications on O3 air pollution and public health between 1990 and 2022 obtained from the Web of Science Core Collection database. VOSviewer and R software were used for bibliometric analysis and visualization. A total of 4501 relevant papers were included in the analysis. There has been a significant increase in the number of publications since 2013, with the USA being the major contributor, followed by China and England. Harvard University was the most prolific research institution, followed by the US Environmental Protection Agency and the University of North Carolina System. Professor Joel Schwartz was the most published author and has established a complex network of national and international collaborations. Co-occurrence analysis of keywords suggested evolving research hotspots, from toxicological studies to population-based epidemiological studies and from the respiratory system to the extra-pulmonary system. Research on O3 and its human health effects has progressed rapidly over the past few decades, but academic disparities still persist between developed and developing countries. There is an urgent need to strengthen international cooperation to address the public health challenges posed by rising O3 air pollution in the future.

Lead specifically declines tyrosine hydroxylase activity to induce the onset of Parkinson's disease through disrupting dopamine biosynthesis in fly models.

Parkinson's disease (PD) is one of the fastest-growing neurodegenerative diseases and has been linked to the exposure to numerous environmental neurotoxins. Although lead (Pb) exposure has been related to the development of PD, the molecular target of Pb to cause the onset of PD is insufficiently investigated. Herein, we explored the effects of Pb exposure on behavior, pathophysiology, and gene expression of wild-type (WT) fly (Drosophila melanogaster) by comparison with its PD model. After exposure to Pb, the WT flies showed PD-like locomotor impairments and selective loss of dopaminergic (DAergic) neurons, displaying similar phenotypes to fly PD model (PINK1). Transcriptomic analysis showed the similarity in gene expression profiles between Pb treatment WT flies and PINK1 mutant flies. Moreover, Pb exposure resulted in endogenous dopamine deficits in WT flies. Analyses of gene expression and enzyme activity confirmed that Pb exposure reduced tyrosine hydroxylase (TH) activity and led to failure of dopamine synthesis. Furthermore, molecular dynamics simulation confirmed that Pb was adsorbed by TH and subsequently inhibited the enzymatic activity. Exogenous injection of L-dopa and melatonin could partially rescue the pathological phenotypes of Pb-exposed flies and PD fly model. Antagonist injection of microRNA-133, which negatively regulated the expression of TH gene, ultimately rescued in the manifestation of PD phenotypes in flies. Involvement of TH overexpression mutants of fly strongly promoted the resistance to Pb exposure and rescued both behavior and the number of DAergic neurons. Therefore, our study elucidates the Pb molecular target in dopamine pathway and mechanism underlying the risks of Pb exposure on the occurrence of PD at environmentally-relevant concentrations.

Unlocking digital potential: Exploring the drivers of employee dynamic capability on employee digital performance in Chinese SMEs-moderation effect of competitive climate.

While dynamic capabilities have been described as crucial for achieving organizational performance in dynamic environments, there has been limited scholarly distinction between dynamic capabilities and employee dynamic capabilities (EDC), especially in the digital era. Consequently, a knowledge gap has emerged. To address this void, this paper aims to investigate the driving factors of EDC and their impact on employee digital performance (EDP). Simultaneously, incorporating the competitive climate (CC) as a moderating variable between employee dynamic capabilities and employee digital performance addresses theoretical gaps in specific regions in China, particularly in small and medium-sized enterprises (SMEs). This study utilizes survey data from SMEs in four Chinese provinces: Shanghai, Guizhou, Guangdong, and Anhui. It employs CB-SEM (AMOS) to analyze the new conceptual framework. Firstly, the research uncovers that the positive relationship between digital capabilities and employee digital performance necessitates employee dynamic capabilities as a mediator. Secondly, there exists a direct and indirect relationship between organizational learning and employee digital performance. Finally, this study discerns that the competitive climate moderates the relationship between employee dynamic capabilities and employee digital performance. This finding demonstrates remarkable alignment with the competitive culture in specific regions of China. The research results encourage SMEs to seize the opportunities presented by emerging digital technologies and industry digitization trends. They should commit to embracing new digital technologies, enhancing digital capability, strengthening organizational learning, fostering a positive competitive climate, and focusing on the development of employee dynamic capability to enhance their competitive edge. The findings of this research contribute not only to academic inquiry but also furnish pertinent decision-making references for relevant departments.

A Luminescent Cd-MOF Used as a Chemosensor for High-Efficiency Sensing of Fe3+, Cr(IV), Trinitrophenol, and Colchicine.

A Cd-MOF was constructed based on 3,5-bis(4-carboxyphenyl) pyridine under solvothermal conditions. Its structure and phase purity were verified by single-crystal X-ray diffraction. Thereafter, some studies on the morphology, structure, and luminescent properties of the compound were carried out. The compound exhibited a highly sensitive response to Fe3+, Cr(IV), trinitrophenol (TNP), and colchicine based on the fluorescence-quenching mechanism. The possible mechanism of luminescence quenching was discussed in detail.

CT-based radiomics for differentiating peripherally located pulmonary sclerosing pneumocytoma from carcinoid.

BACKGROUND: Pulmonary sclerosing pneumocytoma (PSP) and pulmonary carcinoid (PC) are difficult to distinguish based on conventional imaging examinations. In recent years, radiomics has been used to discriminate benign from malignant pulmonary lesions. However, the value of radiomics based on computed tomography (CT) images to differentiate PSP from PC has not been well explored. PURPOSE: We aimed to investigate the feasibility of radiomics in the differentiation between PSP and PC. METHODS: Fifty-three PSP and fifty-five PC were retrospectively enrolled and then were randomly divided into the training and test sets. Univariate and multivariable logistic analyses were carried to select clinical predictor related to differential diagnosis of PSP and PC. A total of 1316 radiomics features were extracted from the unenhanced CT (UECT) and contrast-enhanced CT (CECT) images, respectively. The minimum redundancy maximum relevance and the least absolute shrinkage and selection operator were used to select the most significant radiomics features to construct radiomics models. The clinical predictor and radiomics features were integrated to develop combined models. Two senior radiologists independently categorized each patient into PSP or PC group based on traditional CT method. The performances of clinical, radiomics, and combined models in differentiating PSP from PC were investigated by the receiver operating characteristic (ROC) curve. The diagnostic performance was also compared between the combined models and radiologists. RESULTS: In regard to differentiating PSP from PC, the area under the curves (AUCs) of the clinical, radiomics, and combined models were 0.87, 0.96, and 0.99 in the training set UECT, and were 0.87, 0.97, and 0.98 in the training set CECT, respectively. The AUCs of the clinical, radiomics, and combined models were 0.84, 0.92, and 0.97 in the test set UECT, and were 0.84, 0.93, and 0.98 in the test set CECT, respectively. In regard to the differentiation between PSP and PC, the combined model was comparable to the radiomics model, but outperformed the clinical model and the two radiologists, whether in the test set UECT or CECT. CONCLUSIONS: Radiomics approaches show promise in distinguishing between PSP and PC. Moreover, the integration of clinical predictor (gender) has the potential to enhance the diagnostic performance even further.

A generalized seizure type: Myoclonic-to-tonic seizure.

BACKGROUND AND PURPOSE: To test the hypothesis that myoclonic seizures can evolve to tonic seizures, we documented the electroclinical features of this under-recognized seizure type. METHODS: We observed a distinct seizure pattern starting with myoclonus without returning to an interictal state, which subsequently evolved into generalized tonic seizures. The detailed symptomatic and electroencephalographic characteristics of this seizure were extracted, and the clinical manifestations, drug curative responses in patients with this seizure were reviewed and analyzed. RESULTS: The onset of all seizures was characterized by a preceding period of myoclonus and bursts of generalized spike or poly-spike slow wave discharges with high amplitude. This was closely followed by the occurrence of tonic seizures, which were distinguished by bursts of generalized fast activity at 10 Hz or higher frequency. This under-recognized seizure type has been designated as myoclonic-to-tonic (MT) seizure. The number of patients identified with MT seizures in this study was 34. The prevalence rate of MT seizures was found to be higher in males. While MT seizures typically included a tonic component, it should be noted that some patients experiencing this seizure type never presented with isolated tonic seizures. Generalized Epilepsy not further defined (GE) accounted for approximately one-third of the diagnosed cases, followed by Lennox-Gastaut syndrome and Epilepsy with Myoclonic-Atonic seizures. In comparison to other types of epilepsy, GE with MT seizures demonstrated a more favorable prognosis. CONCLUSIONS: The classification of myoclonic-to-tonic seizure represents a novel approach in comprehending the ictogenesis of generalized seizures and can provide valuable assistance to clinicians in epilepsy diagnosis.

Uric acid mediates the relationship between mixed heavy metal exposure and renal function in older adult people.

Background: Population aging is a pivotal trend observed globally, and the exposure to heavy metals can exacerbate the aging process and lead to kidney damage. However, the impact of combined heavy metal exposure on renal function among older individuals remains elusive. Our study employs machine learning techniques to delve into the effects and underlying mechanisms of mixed exposure to heavy metals on the renal function of the aging population. Methods: This study extracted comprehensive data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2015 and 2020. A total of 3,175 participants aged 60 years and above, with complete information on six metals - lead, cadmium, manganese, cobalt, mercury, and selenium, along with relevant covariates, were included in the study. To assess the impact of single or mixed metal exposure on the renal function of older adult individuals, various statistical techniques were employed: multiple logistic regression, weighted quantitative sum (WQS) regression, Bayesian kernel machine regression (BKMR), and mediation effects analysis. Results: Multiple logistic regression revealed that selenium and manganese were protective factors for chronic kidney disease (CKD). Cobalt was a risk factor for CKD. High concentrations of lead, cadmium, and cobalt were risk factors for urinary albumin creatinine ratio (ACR). WQS analyses revealed that mixed metal exposure was positively correlated with estimated glomerular filtration rate (eGFR) but negatively correlated with CKD. Selenium and manganese can neutralize the effects of other metals on eGFR. Mixed metal exposure was positively correlated with ACR, with lead and cadmium having a substantial effect. Mediation analysis showed that uric acid (UA) had a mediating effect of 9.7% and -19.7% in the association between mixed metals exposure and proteinuria and CKD, respectively. Conclusion: The impact of heavy metals on renal function in the older adult differs from that of adolescents and adults. This study suggests that elevated levels of mixed metals exposure are linked to proteinuria and CKD, with UA serving as a mediating factor.

Characterization of tomato autophagy-related SlCOST family genes.

Autophagy is a eukaryote-specific cellular process that can engulf unwanted targets with double-membrane autophagosomes and subject them to the vacuole or lysosome for breaking down and recycling, playing dual roles in plant growth and environmental adaptions. However, perception of specific environmental signals for autophagy induction is largely unknown, limiting its application in agricultural usage. Identification of plant-unique DUF641 family COST1 (Constitutively Stressed 1) protein directly links drought perception and autophagy induction, shedding light on manipulating autophagy for breeding stress tolerant crops. In this study, we performed a genome-wide analysis of DUF641/COST family in tomato, and identified five SlCOST genes SlCOST1, -2, -3, -4, and -5. SlCOST genes show both overlapping and distinct expression patterns in plant growth and stress responding. In addition, SlCOST1, -3, -4, -5 proteins demonstrate co-localization with autophagy adaptor protein ATG8e, and all five SlCOST proteins show interactions ATG8e in planta. However, only SlCOST1, the closest ortholog of Arabidopsis AtCOST1, can restore cost1 mutant to WT level, suggesting conserved role of COST1 and functional diversification of SlCOST family in tomato. Our study provides clues for future investigation of autophagy-related COST family and its promising implementations in breeding crops with robust environmental plasticity.

Actin-depolymerizing factors 8 and 11 promote root hair elongation at high pH.

A root hair is a polarly elongated single-celled structure that derives from a root epidermal cell and functions in uptake of water and nutrients from the surrounding environment. Previous reports have demonstrated that short periods of high pH inhibit root hair extension; but the effects of long-term high-pH treatment on root hair growth are still unclear. Here, we report that the duration of root hair elongation is significantly prolonged with increasing external pH, which counteracts the effect of decreasing root hair elongation rate and ultimately produces longer root hairs, whereas loss of actin-depolymerizing factor 8 and 11 (ADF8/11) function causes shortening of root hair length at high pH (pH 7.4). Accumulation of ADF8/11 at the tips of root hairs is inhibited by high pH, and increasing environmental pH affects the actin filament (F-actin) meshwork at the root hair tip. At high pH, the tip-focused F-actin meshwork is absent in root hairs of the adf8/11 mutant, actin filaments are disordered at the adf8/11 root hair tips, and actin turnover is attenuated. Secretory and recycling vesicles do not aggregate in the apical region of adf8/11 root hairs at high pH. Together, our results suggest that, under long-term exposure to high extracellular pH, ADF8/11 may establish and maintain the tip-focused F-actin meshwork to regulate polar trafficking of secretory/recycling vesicles at the root hair tips, thereby promoting root hair elongation.

Epigenome-wide association study on short-, intermediate- and long-term ozone exposure in Han Chinese, the NSPT study.

Epidemiological and epigenetic studies have acknowledged ambient ozone exposure associated with inflammatory and cardiovascular disease. However, the molecular mechanisms still remained unclear, and epigenome-wide analysis in cohort were lacking, especially in Chinese. We included blood-derived DNA methylation for 3365 Chinese participants from the NSPT cohort and estimated individual ozone exposure level of short-, intermediate- and long-term, based on a validated prediction model. We performed epigenome-wide association studies which identified 59 CpGs and 30 DMRs at a strict genome-wide significance (P < 5 ×10-8). We also conducted comparison on the DNA methylation alteration corresponding to different time windows, and observed an enhanced differentiated methylation trend for intermediate- and long-term exposure, while the short-term exposure associated methylation changes did not retain. The targeted genes of methylation alteration were involved in mechanism related to aging, inflammation disease, metabolic syndrome, neurodevelopmental disorders, and oncogenesis. Underlying pathways were enriched in biological activities including telomere maintenance process, DNA damage response and megakaryocyte differentiation. In conclusion, our study is the first EWAS on ozone exposure conducted in large-scale Han Chinese cohort and identified associated DNA methylation change on CpGs and regions, as well as related gene functions and pathways.

Correlation between vertebral bone mineral density and multi-level virtual non-calcium imaging parameters from dual-layer spectral detector computed tomography.

Background: Virtual non-calcium (VNCa) imaging based on dual-energy computed tomography (CT) plays an increasingly important role in diagnosing spinal diseases. However, the utility of VNCa technology in the measurement of vertebral bone mineral density (BMD) is limited, especially the VNCa CT value at multiple calcium suppression levels and the slope of VNCa curve. This retrospective cross-sectional study aimed to explore the correlation between vertebral BMD and new VNCa parameters from dual-layer spectral detector CT. Methods: The dual-layer spectral detector CT and quantitative CT (QCT) data of 4 hydroxyapatite (HAP) inserts and 667 vertebrae of 234 patients (132 male and 102 female) who visited a university teaching hospital between April and May 2023 were retrospectively analyzed. The BMD values of 3 vertebrae (T12, L1, and L2) and inserts were measured using QCT, defined as QCT-BMD. The VNCa CT values and the slope λ of the VNCa attenuation curve of vertebrae and inserts were recorded. The correlations between VNCa parameters (VNCa CT value, slope λ) and QCT-BMD were analyzed. Results: For the vertebrae, the correlation coefficient ranged from -0.904 to 0.712 (all P<0.05). As the calcium suppression index (CaSI) increased, the correlation degree exhibited a decrease first and then increased, with the best correlation (r=-0.904, P<0.001) observed at the index of 25%. In contrast, the correlation coefficient for the inserts remained relatively stable (r=-0.899 to -1, all P<0.05). For the vertebrae, the values of 3 slopes λ (λ1, λ2, and λ3) derived from the VNCa attenuation curve were 6.50±1.99, 3.75±1.15, and 2.04±0.62, respectively. Regarding the inserts, the λ1, λ2, and λ3 values were 11.56 [interquartile range (IQR): 2.40-22.62], 6.68 (IQR: 1.39-13.49), and 3.63 (IQR: 0.75-7.8), respectively. For the vertebrae, all 3 correlation coefficients between 3 slopes λ and QCT-BMD were 0.956 (all P<0.05). For the inserts, the 3 correlation coefficients were 0.996, 0.998, and 1 (all P<0.05), respectively. Conclusions: A promising correlation was detected between VNCa CT parameters and QCT-BMD in vertebrae, warranting further investigation to explore the possibility of VNCa imaging to assess BMD.