Localization and discrimination of GG mismatch in duplex DNA by synthetic ligand-enhanced protein nanopore analysis.

Mismatched base pairs in DNA are the basis of single-nucleotide polymorphism, one of the major issues in genetic diseases. However, the changes of physical and chemical properties of DNA caused by single-site mismatches are often influenced by the sequence and the structural flexibility of the whole duplex, resulting in a challenge of direct detection of the types and location of mismatches sensitively. In this work, we proposed a synthetic ligand-enhanced protein nanopore analysis of GG mismatch on DNA fragment, inspired by in silico investigation of the specific binding of naphthyridine dimer (ND) on GG mismatch. We demonstrated that both the importing and unzipping processes of the ligand-bound DNA duplex can be efficiently slowed down in α-hemolysin nanopore. This ligand-binding induced slow-down effect of DNA in nanopore is also sensitive to the relative location of the mismatch on DNA duplex. Especially, the GG mismatch close to the end of a DNA fragment, which is hard to be detected by either routine nanopore analysis or tedious nanopore sequencing, can be well differentiated by our ND-enhanced nanopore experiment. These findings provide a promising strategy to localize and discriminate base mismatches in duplex form directly at the single-molecule level.

Deep learning-based quantification and transcriptomic profiling reveal a methyl jasmonate-mediated glandular trichome formation pathway in Cannabis sativa.

Cannabis glandular trichomes (GTs) are economically and biotechnologically important structures that have a remarkable morphology and capacity to produce, store, and secrete diverse classes of secondary metabolites. However, our understanding of the developmental changes and the underlying molecular processes involved in cannabis GT development is limited. In this study, we developed Cannabis Glandular Trichome Detection Model (CGTDM), a deep learning-based model capable of differentiating and quantifying three types of cannabis GTs with a high degree of efficiency and accuracy. By profiling at eight different time points, we captured dynamic changes in gene expression, phenotypes, and metabolic processes associated with GT development. By integrating weighted gene co-expression network analysis with CGTDM measurements, we established correlations between phenotypic variations in GT traits and the global transcriptome profiles across the developmental gradient. Notably, we identified a module containing methyl jasmonate (MeJA)-responsive genes that significantly correlated with stalked GT density and cannabinoid content during development, suggesting the existence of a MeJA-mediated GT formation pathway. Our findings were further supported by the successful promotion of GT development in cannabis through exogenous MeJA treatment. Importantly, we have identified CsMYC4 as a key transcription factor that positively regulates GT formation via MeJA signaling in cannabis. These findings provide novel tools for GT detection and counting, as well as valuable information for understanding the molecular regulatory mechanism of GT formation, which has the potential to facilitate the molecular breeding, targeted engineering, informed harvest timing, and manipulation of cannabinoid production.

Associations of Intracranial Artery Length and Branch Number on Time-of-Flight MRA With Cognitive Impairment in Hypertensive Older Males.

BACKGROUND: Hypertension-induced impairment of the cerebral artery network contributes to cognitive impairment. Characterizing the structure and function of cerebral arteries may facilitate the understanding of hypertension-related pathological mechanisms and lead to the development of new indicators for cognitive impairment. PURPOSE: To investigate the associations between morphological features of the intracranial arteries distal to the circle of Willis on time-of-flight MRA (TOF-MRA) and cognitive performance in a hypertensive cohort. STUDY TYPE: Prospective observational study. POPULATION: 189 hypertensive older males (mean age 64.9 ± 7.2 years). FIELD STRENGTH/SEQUENCE: TOF-MRA sequence with a 3D spoiled gradient echo readout and arterial spin labeling perfusion imaging sequence with a 3D stack-of-spirals fast spin echo readout at 3T. ASSESSMENT: The intracranial arteries were segmented from TOF-MRA and the total length of distal arteries (TLoDA) and number of arterial branches (NoB) were calculated. The mean gray matter cerebral blood flow (GM-CBF) was extracted from arterial spin labeling perfusion imaging. The cognitive level was assessed with short-term and long-term delay-recall auditory verbal learning test (AVLT) scores, and with montreal cognitive assessment. STATISTICAL TESTS: Univariable and multivariable linear regression were used to analyze the associations between TLoDA, NoB, GM-CBF and the cognitive assessment scores, with P < 0.05 indicating significance. RESULTS: TLoDA (r = 0.314) and NoB (r = 0.346) were significantly correlated with GM-CBF. Multivariable linear regression analyses showed that TLoDA and NoB, but not GM-CBF (P = 0.272 and 0.141), were significantly associated with short-term and long-term delay-recall AVLT scores. These associations remained significant after adjusting for GM-CBF. DATA CONCLUSION: The TLoDA and NoB of distal intracranial arteries on TOF-MRA are significantly associated with cognitive impairment in hypertensive subjects. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

The Relationship between physical activity, nutritional status, and sarcopenia in community- dwelling older adults with type 2 diabetes: a cross-sectional study.

AIM: This study was conducted in Urumqi, Xinjiang, to assess the prevalence of sarcopenia and to determine the relationship between physical activity, nutritional status, and sarcopenia among community-dwelling patients with type 2 diabetes mellitus. METHODS: Four hundred eight cases of older people patients with type 2 diabetes mellitus in the community in Urumqi, Xinjiang, from May to August 2022 were selected for a cross-sectional on-site survey, and general information questionnaires, clinical information surveys, physical function measurements, and criteria developed by the Asian sarcopenia working group in 2019 were selected for diagnosis of sarcopenia, and unifactorial and multifactorial binary Logistic regression were applied to analyze the influencing factors of T2DM combined with sarcopenia in patients with sarcopenia. RESULTS: Among the 408 patients, 84 (20.6%) had sarcopenia, with a prevalence of 12.6%, 32.1%, and 51.9% in those aged 60-70, 71- 80, and 81 or older respectively. The prevalence increased significantly with age. Adjusting for variables, the study found that FFM of the Left Leg (OR: 0.710, 95% CI: 0.612-0.804, P = 0.024), FFM of the Right Arm (OR: 0.710, 95% CI: 0.612-0.804, P < 0.001), Age (OR: 1.246, 95% CI: 1.031-1.505, P = 0.023), Fasting Blood Glucose (OR: 1.649, 95% CI: 1.066-2.550, P = 0.025), and Post-Prandial Blood Glucose (OR: 1.455, 95% CI: 0.999-2.118, P = 0.025) were independent associated factors. An increase in MNA score (OR: 0.398, 95% CI: 0.244-0.6500, P < 0.001), ASMI (OR: 0.000, 95% CI: 0.00-0.01, P < 0.001) walking energy expenditure (MET-min) (OR: 0.998, 95% CI: 0.996-0.999, P = 0.001) reduced the prevalence of sarcopenia. CONCLUSION: This study shows that increased age, increased skeletal muscle mass index, decreased right arm FFM, increased postprandial glucose, increased MNA scores, and increased walking energy expenditure (MET-min) were associated with type 2 diabetes with sarcopenia.

The Impacts of Fast-track Surgery on Postoperative Deep Venous Thrombosis Among Patients with Lower Limb Fracture.

Purpose: This research was conducted to construct an ankle pump motion counter and system with orthopedic characteristics and analyze the impacts of fast-track surgery on postoperative deep venous thrombosis (DVT) among patients with lower limb fractures. Methods: First, an ankle pump motion counter system was set up to detect postoperative rehabilitation training (Hardware design: This involves components such as an accelerometer sensor, microcontroller, circuit design, power supply, and wireless module. The accelerometer sensor is used to monitor key points and capture motion signals, while the microcontroller handles frequency calculations and generates alerts for abnormal ankle pump motion parameters. Circuit design ensures the proper functioning of the device, and the power supply meets the requirements of the ankle pump motion counter. The wireless module is used for data transmission and communication with other devices. Software design: This includes software design for both the patient and doctor sides. The software design involves defining software requirements and module divisions, designing data acquisition and filtering programs, developing programs for data parameter reading and writing, implementing communication protocols, designing data communication programs, and creating rehabilitation training plans and training record programs). Then, a retrospective analysis was carried out for the subjects (100 patients with lower limb fractures treated in Zhejiang Hospital between June 2021 and June 2022. They were randomly enrolled into control and experimental groups (50 cases each). The ankle pump motion counter was utilized for the patients in the experimental group. Before surgery, gender, age, the incidence of venous thromboembolism (VTE), and the muscle strength of both lower limbs of the two groups were recorded. After surgery, numerical rating scale (NRS) pain scores, D-dimer (D-D), and average length of hospitalization 3 d after surgery and venous thrombosis of both lower limbs 5 d after surgery of two groups were compared. Results: D-D of the control group was significantly higher than that of the experimental group 3 days after surgery (P < .05), while the NRS pain score was relatively lower (P < .05). The average hospitalization length for the experimental group was 10.2 days versus 16.2 days for the control group. The incidence of VTE 5 days after the surgery was 2% for the experimental group compared to 6% for the control group (P < .05). Conclusion: The ankle pump motion counter system has the potential to improve VTE prevention, enhance patient compliance, streamline healthcare delivery, standardize care, and enable data-driven decision-making at a wider clinical level. By accurately monitoring ankle pump exercises and providing real-time feedback, this system can contribute to better patient outcomes, save time for healthcare providers, and facilitate evidence-based practices in the prevention of postoperative DVT among patients with lower limb fractures.

WITHDRAWN: An Investigation of Risk Factors and Inflammatory Factors in Nosocomial Infections Following Total Hip Arthroplasty: Implications for Prevention and Control Strategies.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause.

Genetically predicted high serum sex hormone-binding globulin levels are associated with lower ischemic stroke risk: A sex-stratified Mendelian randomization study.

OBJECTIVE: Cross-sectional and cohort studies have found insufficient evidence of a causal relationship between sex hormone-binding globulin and ischemic stroke, only associations. Here, we performed a sex-stratified, bidirectional, two-sample Mendelian randomization analysis to evaluate whether a causal relationship exists between sex hormone-binding globulin and ischemic stroke. METHODS: Single-nucleotide polymorphisms associated with sex hormone-binding globulin and ischemic stroke were screened from genome-wide association studies summary data as instrumental variables to enable a bidirectional, two-sample Mendelian randomization study design. Inverse-variance weighted analysis was used as the main method to evaluate potential causality, and additional methods, including the weighted median and MR-Egger tests, were used to validate the Mendelian randomization results. Cochran's Q statistic, MR-Egger intercept test, and Mendelian Randomization-Pleiotropy Residual Sum and Outlier global test were used as sensitivity analysis techniques to assure the reliability of the results. Multivariable analysis was used to show the robustness of the results with key theorized confounders. RESULTS: Inverse-variance weighted analysis showed that genetically predicted higher serum sex hormone-binding globulin levels were associated with significantly decreased risk of ischemic stroke in males (odds radio = 0.934, 95 % confidence interval = 0.885-0.985, P = 0.012) and females (odds radio = 0.924, 95 % confidence interval = 0.868-0.983, P = 0.013). In an analysis of ischemic stroke subtypes, genetically predicted higher serum sex hormone-binding globulin levels were also associated with significantly decreased risk of small-vessel occlusion in both males (odds radio = 0.849, 95 % confidence interval = 0.759-0.949, P = 0.004) and females (odds radio = 0.829, 95 % confidence interval = 0.724-0.949, P = 0.006). The association remained in sensitivity analyses and multivariable analyses. The reverse analysis suggested an association between genetically predicted risk of cardioembolism and increased serum sex hormone-binding globulin in females (Beta = 0.029 nmol/L, Standard Error = 0.010, P = 0.003). CONCLUSION: Our findings provide new insight into the etiology of ischemic stroke and suggest that modulating serum sex hormone-binding globulin may be a therapeutic strategy to protect against ischemic stroke.

Clinical characteristics and outcome of dural arteriovenous fistulas secondary to cerebral venous sinus thrombosis: a primary or secondary event?

BACKGROUND: The Dural Arteriovenous Fistulas (DAVFs) secondary to cerebral venous sinus thrombosis (CVST) are rather rare. The aim of present study is to investigate the clinical and radiological features, and treatment outcome of DAVFS in patients following CVST. METHODS: Data about demographic information, clinical presentations, radiological findings, as well as treatment and outcome of DAVFs sequence to CVST were collected to analysis from January 2013 to September 2020 in this retrospective study. RESULTS: Fifteen patients with DAVFs after CVST were included in the study. The median age was 41 years (range17-76 years). Ten patients (66.67%) were male and 6 patients (33.33%) were female. The median duration of presenting CVST was 182 days (Range 20-365). Mean time from diagnosis of CVST to confirmation of DAVFs was 97 days (range 36-370 days). The most common manifestations of DAVFs following CVST were headache and visual disturbance seen in 7 patients respectively. Five patients had pulsatile tinnitus (%) and 2 had nausea/vomiting. The DAVFs are most frequently located at the transverse/sigmoid sinus (7/15, 46.67%), followed by the superior sagittal the sinus and confluence sinus (6/15, 40.00%) respectively. Angiography of DAVFs revealed Board type I in seven (46.7%) patients, Board type II and III in 4(26.7%) patients, respectively. The Cognard I was noted in seven (46.7%), Cognard IIa and IV in 3 patients, IIb and III in one patient, respectively. The main feeding arteries of DAVFs most commonly originate from the branches of the external carotid artery in 6 (40.0%) patients. The other DAVFs are conjointly supplied by multiple feeders from internal and external carotid artery and vertebral arteries. Fourteen (93.33%) patients were treated with endovascular embolization and none of the patients had permanent deficits during follow-up. CONCLUSION: Intracranial DAVFs following CVST are rare presentations. Most patients have a good outcome after timely interventional therapy. Continued observation and follow-up of (DSA) are important to find DAVFs secondary to CVST.

Artificial intelligence in glaucoma: opportunities, challenges, and future directions.

Artificial intelligence (AI) has shown excellent diagnostic performance in detecting various complex problems related to many areas of healthcare including ophthalmology. AI diagnostic systems developed from fundus images have become state-of-the-art tools in diagnosing retinal conditions and glaucoma as well as other ocular diseases. However, designing and implementing AI models using large imaging data is challenging. In this study, we review different machine learning (ML) and deep learning (DL) techniques applied to multiple modalities of retinal data, such as fundus images and visual fields for glaucoma detection, progression assessment, staging and so on. We summarize findings and provide several taxonomies to help the reader understand the evolution of conventional and emerging AI models in glaucoma. We discuss opportunities and challenges facing AI application in glaucoma and highlight some key themes from the existing literature that may help to explore future studies. Our goal in this systematic review is to help readers and researchers to understand critical aspects of AI related to glaucoma as well as determine the necessary steps and requirements for the successful development of AI models in glaucoma.

The effect of the Ankle Pump Exercise (APE) counter system assisted ankle pump motion in patients after femoral neck fracture.

OBJECTIVE: To explore the effect of the Ankle Pump Exercise (APE) counter system on moderate to high-risk Venous thromboembolism (VTE) after femoral neck fracture surgery. METHODS: From June 2021 to June 2022, a total of 140 patients with moderate and high-risk VTE after femoral neck fracture surgery treated at the Department of Orthopedics of a tertiary hospital in Zhejiang were included and divided into observation (70 cases) and control (70 cases) groups according to whether APE counter system was used or not. The control group was given routine oral propaganda, and the observation group was given a comprehensive nursing intervention with APE counter system on the basis of the control group's treatment. The compliance rates of the two groups on the postoperative 3st, 5rd, and 7th days were compared. Moreover, the General self-efficacy scale (GSES) was used to evaluate self-efficacy before and after exercise. RESULTS: The compliance rates of the control group and the observation group on the postoperative 3st, 5rd, and 7th days were 74.3% vs. 85.7%, 67.1% vs. 85.7%, and 61.4% vs. 82.9%. On the 5rd and 7th days, the compliance of the observation group was obviously higher than that of the control group. Moreover, the mean postoperative GSES score was also significantly higher than that in the control group (23.20 ± 3.516 vs. 25.31 ± 4.583, P < 0.05, values are expressed in mean ± standard). CONCLUSION: APE counter system can significantly improve the compliance and self-efficacy of patients with moderate and high-risk VTE after lower limb fracture surgery.

Identification of Potential Biomarkers for Group I Pulmonary Hypertension Based on Machine Learning and Bioinformatics Analysis.

A number of processes and pathways have been reported in the development of Group I pulmonary hypertension (Group I PAH); however, novel biomarkers need to be identified for a better diagnosis and management. We employed a robust rank aggregation (RRA) algorithm to shortlist the key differentially expressed genes (DEGs) between Group I PAH patients and controls. An optimal diagnostic model was obtained by comparing seven machine learning algorithms and was verified in an independent dataset. The functional roles of key DEGs and biomarkers were analyzed using various in silico methods. Finally, the biomarkers and a set of key candidates were experimentally validated using patient samples and a cell line model. A total of 48 key DEGs with preferable diagnostic value were identified. A gradient boosting decision tree algorithm was utilized to build a diagnostic model with three biomarkers, PBRM1, CA1, and TXLNG. An immune-cell infiltration analysis revealed significant differences in the relative abundances of seven immune cells between controls and PAH patients and a correlation with the biomarkers. Experimental validation confirmed the upregulation of the three biomarkers in Group I PAH patients. In conclusion, machine learning and a bioinformatics analysis along with experimental techniques identified PBRM1, CA1, and TXLNG as potential biomarkers for Group I PAH.

Clinical Features, Immunotherapy, and Outcomes of Anti-Leucine-Rich Glioma-Inactivated-1 Encephalitis.

OBJECTIVE: The investigators aimed to explore the clinical characteristics, immunotherapy, and outcomes of patients with antileucine-rich glioma-inactivated-1 (anti-LGI1) encephalitis. METHODS: Data on participants' clinical characteristics, laboratory findings, radiological and electroencephalogram (EEG) features, treatment, and outcomes from January 2012 to December 2016 were collected. Statistical analysis was conducted to assess the factors associated with patient functional outcome. Forty-three patients were enrolled in the study, with a predominance of males (65.1%). The median age at onset was 57 years (interquartile range [IQR]: 44.0-65.0). The median time from onset to diagnosis was 60 days (IQR: 37.0-127.0). RESULTS: The main clinical manifestations included epilepsy (100%), faciobrachial dystonic seizures (FBDS; 44.2%), cognitive dysfunction (95.3%), neuropsychiatric disturbances (76.7%), sleep disorders (58.1%), and disturbance of consciousness (48.8%). Twenty-two patients (51.2%) had hyponatremia, 31 (72.1%) had abnormal EEG results, and 30 (69.8%) had abnormal brain MRI scans, mainly involving the hippocampus (76.7%) or temporal lobe (40%). Twenty of 34 patients (58.8%) in a follow-up MRI examination exhibited hippocampal atrophy. Twenty-five patients (58.2%) were administered corticosteroids and intravenous immunoglobulin, whereas 17 patients were treated only with corticosteroids. Forty-one patients (95.3%) had favorable outcomes after a median of 21.5 months (IQR: 7-43) of follow-up. Serum sodium level was a factor associated with a disabled status (odds ratio=0.81, 95% CI=0.66, 0.98, p=0.03). Anti-LGI1 encephalitis patients were characterized by seizures, FBDS, cognitive deficits, neuropsychiatric disturbances, and hyponatremia. CONCLUSIONS: Most patients with anti-LGI1 encephalitis are nonparaneoplastic, have low recurrence rates, and have favorable prognostic outcomes. Rapid evaluation, prompt immunotherapy, and long-term follow-up are essential in the care of anti-LGI1 encephalitis patients.

The NDT80-like transcription factor CmNdt80a affects the conidial formation and germination, mycoparasitism, and cell wall integrity of Coniothyrium minitans.

AIMS: NDT80, a known transcriptional factor, regulates various targets, including regulation of meiosis, stress responses, filamentous growth, sexual development, biofilm formation, drug resistance, and virulence. But the numbers and roles of Ndt80-like genes in different fungi are highly variable. This study aims to address the numbers and functions of Ndt80-like genes in Coniothyrium minitans, a well-known biocontrol agent against Sclerotinia diseases. METHODS AND RESULTS: Here, two genes (CmNdt80a and CmNdt80b) encoding NDT80-like proteins were obtained by searching the genomic sequence of C. minitans. RT-PCR analysis showed that both CmNdt80 genes were constitutively expressed in C. minitans from the hyphal growth stage (48 hpi) to the pycnidial maturation stage (120 hpi). The roles of CmNdt80a and CmNdt80b in C. minitans were verified through gene knockout and complementation experiments. The results showed that the ΔCmNdt80a mutants exhibited a lighter colour and normal growth rate on potato dextrose agar plates. The ability of the ΔCmNdt80a mutants to produce conidia and parasitize the colony and sclerotia of Sclerotinia sclerotiorum was markedly diminished compared with the wild-type strain and complemented strain. Interestingly, the ΔCmNdt80a mutant showed less sensitivity to cell wall stressors and cell wall-degrading enzymes, and had thicker cell walls than the wild-type strain and complemented strain. However, no phenotypic consequences were discovered for the deletion of CmNdt80b. CONCLUSIONS: Two Ndt80-like genes, CmNdt80a and CmNdt80b, were present in C. minitans. CmNdt80a, but not CmNdt80b, plays a crucial role in conidiogenesis, mycoparasitism, and cell wall integrity. SIGNIFICANCE AND IMPACT OF THE STUDY: Understanding the mechanisms that regulate the conidiation and parasitism of C. minitans could help us to more efficiently utilize this biological control agent and advance our knowledge of fungal biology.

First Report of Plasmodiophora brassicae causing clubroot on Thlaspi arvense L. in Sichuan Province of China.

Pennycress (Thlaspi arvense L.), an annual herb of the mustard family Brassicacae, is native to Eurasia and now widely distributed throughout temperate North America. This species is currently being developed as a medicinal herb used to treat nephritis in China and an oilseed crop for biofuel production (Roque et al.2012). In November 2020, stunt and wilt symptoms were observed on above ground parts and swollen club-shaped galls were observed on the roots of T. arvense in most of the Chinese cabbage growing area in Kangding (30°03'"N,102°02'"E), Sichuan Province of China. The average disease incidence of swollen roots on T. arvense was 91.2% ( n=80). To identify the causal agent of this disease, the swollen roots of T. arvense were collected, crushed and observed under microscope (Fei et al.2017). Abundant resting spores were found in the root galls, which were spherical and 2.0 to 3.1 µm in diameter with an average length of 2.7 nm (n=100). The healthy roots and the root galls of T. arvense plants were further evaluated by PCR with P. brassicae-specific primers TC2F/TC2R (Cao et al. 2007). The results showed that a DNA fragment with an estimated size of 520 bp, as expected for that of P. brassicae, was consistently amplified in diseased roots, No PCR amplification occurred in the healthy roots with the TC2F/TC2R primers. Blast analysis of the 520 bp segment (GenBankMZ040496) showed the highest identity with the sequence of small subunit ribosomal RNA gene of P. brassicae (GenBankMH762161, 97.7%, E value=0). These results confirmed that the pathogen in the galled roots of T. arvense was P. brassicae. The pathogenicity of isolated P. brassicae was tested on both T. arvense and Chinese cabbage (B. campestris ssp. pekinensis). Resting spores were isolated from the diseased roots (Castlkbury et al. 1994) of T. arvense and suspended in Hoagland's solution to the final concentration of 1 × 107 spores per milliliter. Fifteen plastic pots (10 cm bottom diameter, 16 cm upper diameter, 13 cm high) were filled with soil (1 kg per pot) that was sterilized twice with high-temperature (121℃), high pressure (19 PSI) for 1.5 hours with a time interval of 2 days between. Inoculated pots received 100 mL spore suspension each. Fifteen control pots with sterilized field soil were treated with 100 mL Hoagland's solution each. Seeds of T. arvense and B. campestris were pre-germinated at 20°C on moist filter paper for 7 days and transplanted into the pots, five seedlings each and five pots per treatment. The pots were maintained in a greenhouse with 16 hours photoperiod at 24°C/16°C day/night temperature. After 7 weeks, plants in each pot were uprooted and the roots cleaned in running water and inspected for clubroot symptoms. Plants of T. arvense and Chinese cabbage in pots inoculated with resting spores showed clubroot symptoms while no disease symptoms were observed on any control plants. The disease incidence rate was 95.4% on T. arvense and 81.2% on B. campestris. Therefore, it was confirmed that P. brassicae could cause clubroot disease on T. arvense. To our knowledge, this is the first published report of clubroot disease on T. arvense in China. This finding is helpful for the management of clubroot on herbs and plants of biological origin in the cruciferous family.

Uncontrolled hypertension associates with subclinical cerebrovascular health globally: a multimodal imaging study.

OBJECTIVES: The study aimed to analyze the association between hypertension control and subclinical cerebrovascular health using a comprehensive multimodal imaging approach. METHODS: The study included 200 hypertensive older males without previous cardiovascular diseases. Clinic blood pressure (BP) was measured using a standard approach. Cerebrovascular health was evaluated using magnetic resonance imaging in the following four aspects: Intracranial atherosclerosis as determined by vessel wall imaging; Vascular rarefaction (defined as less discernible vessels on angiography) was evaluated using a custom-developed technique. Cerebral blood flow (CBF) and white matter hyperintensity (WMH) were assessed using arterial spin-labeling imaging and fluid-attenuated inversion recovery imaging, respectively. RESULTS: A total of 189 subjects had MRI scans. The mean age was 64.9 (± 7.2) years. For intracranial atherosclerosis, there was a significant association between uncontrolled hypertension and presence of intracranial plaque. When systolic and diastolic BP were analyzed separately, the association remained significant for both. For vascular rarefaction, uncontrolled hypertension was associated with less discernible vessel branches or shorter vessel length on angiography. Further analysis revealed that this is due to uncontrolled diastolic BP, but not uncontrolled systolic BP. There was an association between uncontrolled hypertension and reduced CBF, which was also mainly driven by uncontrolled diastolic BP. We also found that uncontrolled diastolic BP, but not uncontrolled systolic BP, was associated with increased WMH volume. CONCLUSIONS: Uncontrolled hypertension was associated with subclinical cerebrovascular injury globally, with both small and medium-to-large arteries being affected. KEY POINTS: • In this study, we leveraged the advantage of a series of cutting-edge MR imaging and analysis techniques and found uncontrolled hypertension is associated with subclinical globally compromised cerebrovascular health. • The detrimental consequences of uncontrolled BP affect not only the small vessels but also the medium-to-large arteries, and uncontrolled systolic and diastolic BP are both independently associated with certain types of cerebrovascular injury. • Our data suggest that cerebrovascular health is impaired globally in uncontrolled hypertension before the onset of stroke.

The electrochemiluminescence coreactant accelerator of metal-organic frameworks grafted with N-(aminobutyl)-N-(ethylisoluminol) for the ultrasensitive detection of chloramphenicol.

In this work, metal-organic frameworks (MOFs) are utilized as effective ECL coreactant accelerator to enhance the ECL responses of N-(aminobutyl)-N-(ethylisoluminol) (ABEI). Zn-based MOFs (MOF-Zn-1) were prepared by chelating Zn ions with melamine and thiophenedicarboxylic acid (TPDA), which observably accelerated the electrocatalytic oxidation of tripropylamine (TPA). Then, ABEI-MOF-Zn-1 as a high-performance ECL emitter was synthesized via an amide reaction between ABEI and mercaptopropionic acid (MPA) modified MOF-Zn-1. Strikingly, the ABEI-MOF-Zn-1 showed the 18-fold increase in the ECL signals relative to pure ABEI by using TPA as a coreactant. Moreover, ferrocene (Fc) as a quencher was first linked with capture DNA (cDNA), and then used to modify the ABEI-MOF-Zn-1, thereby constructing a label-free ECL biosensor. After the linkage between chloramphenicol (CAP) and aptamer DNA (aptDNA), the ECL response was definitely recovered by releasing L-DNA from double-stranded DNA (dsDNA, hybridization of aptDNA and L-DNA). The resultant sensor showed a wide linear range of 1.00 nM-0.10 mM (R2 = 0.99) and a low limit of detection (LOD) down to 0.11 nM for detecting CAP. This work developed a novel pattern to design an efficient ECL enhanced emitter, coupled by expanding its potential applications in clinical diagnosis.

Cellulose accumulation in the secondary cell walls is negatively correlated with the tenderness of new shoots in Camellia sinensis.

Tea, which is usually made from the new shoots of tea plants (Camellia sinensis), is one of the most popular and healthy beverages. The tenderness of new shoots plays a critical role in the production of high-quality tea; however, the factors affecting the tenderness of the new shoots of tea have not been extensively studied. Here, we show that cellulose accumulation is negatively correlated with the tenderness of new shoots, including leaves and stems, by characterizing the cellulose content and visualizing cellulose in the new shoots of two cultivars ("Huangjinya" and "Yujinxiang") via toluidine blue staining. We further found that the number of cells with secondary cell walls (SCWs) and the thickness of SCWs increased with the maturity degree of stems in both cultivars. Because cellulose is the most abundant polymer in SCW, we next identified three cellulose synthase CsCesAs, CsCesA4, 7, and 8A, through homologous alignment with Arabidopsis AtCesAs. Protein sequence analysis revealed that these proteins were closely related based on the phylogenetic analysis. We finally showed that the gene expression of the three CsCesAs was positively correlated with the maturity degree and cellulose content of the new shoots. Thus, our data suggest that cellulose accumulation, especially in the SCWs, is negatively correlated with the tenderness of new shoots in tea plants.

Urinary sodium and potassium excretion and cerebrovascular health: a multimodal imaging study.

PURPOSE: Dietary sodium and potassium intake are associated with stroke, but the potential mechanisms are unclear. We aimed to study the association between sodium and potassium intake and subclinical cerebrovascular health in hypertensive older males using multimodal magnetic resonance imaging. METHODS: A total of 189 hypertensive male subjects without previous cardiovascular or cerebrovascular disease were included. Daily urinary sodium and potassium excretion were estimated from a fasting spot urine sample using a formula approach. A dedicated cerebrovascular health imaging protocol including vessel wall imaging, angiography, arterial spin labeling imaging and T2-weighted fluid-attenuated inversion recovery imaging was performed to study intracranial atherosclerosis, vascular rarefaction (defined as fewer discernible vessels on angiography), brain perfusion and small vessel disease, respectively. RESULTS: The mean age was 64.9 (± 7.2) years. The average daily urinary and potassium excretion was 4.7 (± 1.4) g/L and 2.1 (± 0.5) g/L, respectively. Increased urinary sodium excretion was associated with decreased cerebral blood flow and elevated urinary potassium excretion was associated with reduced prevalence of intracranial plaque. The associations remained significant after adjusting for covariates, even including blood pressure control. Quadratic regression analysis indicated a marginally significant U-shaped association between urinary sodium intake and white matter hyperintensity, which lost significance in fully adjusted models. No significant association of urinary sodium and potassium excretion with other cerebrovascular health measures was noted. CONCLUSION: We concluded that in hypertensive older males without overt cardiovascular disease, increased sodium intake and reduced potassium intake are associated with impaired subclinical cerebrovascular health.

Elevated circulating growth differentiation factor 15 is related to decreased heart rate variability in chronic kidney disease patients.

BACKGROUND: Growth differentiation factor 15(GDF15) is a distant member of the superfamily of the transforming growth factor beta (TGF-ß). It has been established that increased GDF15 levels are associated with an increased risk of cardiovascular disease. However, the detail effect of GDF15 on cardiovascular system in patients with chronic kidney disease (CKD) needs detail analysis. METHODS: Patients with CKD who did not need dialysis were enrolled in the study. Blood pressure (BP), endothelial function, pulse wave velocity (PWV) and heart rate variability (HRV) were taken in all subjects. Plasma GDF15 concentration was measured by an enzyme-linked immunosorbent assay. RESULTS: Among the 355 participants, the mean age was 57.4 (±14.2) years old and the mean estimated glomerular filtration rate (eGFR) was 50.1 (±33.2) mL/min/1.73m2. The average plasma GDF15 level was 1394.7 (±610.1) pg/mL. Higher GDF15 concentrations were significantly associated with decreased eGFR and increased urine protein-to-creatinine ratio (uPCR). In multivariable models, after adjusting for potential confounders, plasma GDF15 has negative concerning with HRV parameters including the standard deviation of the normal-to-normal (NN) interval (SDNN), the square root of the mean of the sum of the squares of differences between adjacent NN intervals (RMSSD) and Triangular Index. CONCLUSION: We observed there was a link between increased plasma of GDF15 and decreased HRV. The mechanisms and prediction of GDF15 in the cardiovascular disease with CKD needs further discussion and study.

Genistein-3'-sodium sulphonate protects against lipopolysaccharide-induced lung vascular endothelial cell apoptosis and acute lung injury via BCL-2 signalling.

Under septic conditions, Lipopolysaccharide (LPS)-induced apoptosis of lung vascular endothelial cells (ECs) triggers and aggravates acute lung injury (ALI), which so far has no effective therapeutic options. Genistein-3'-sodium sulphonate (GSS) is a derivative of native soy isoflavone, which has neuro-protective effects through its anti-apoptotic property. However, whether GSS protects against sepsis-induced lung vascular endothelial cell apoptosis and ALI has not been determined. In this study, we found that LPS-induced Myd88/NF-κB/BCL-2 signalling pathway activation and subsequent EC apoptosis were effectively down-regulated by GSS in vitro. Furthermore, GSS not only reversed the sepsis-induced BCL-2 changes in expression in mouse lungs but also blocked sepsis-associated lung vascular barrier disruption and ALI in vivo. Taken together, our results demonstrated that GSS might be a promising candidate for sepsis-induced ALI via its regulating effects on Myd88/NF-κB/BCL-2 signalling in lung ECs.