Quantitative evaluation and mechanism analysis of soil chemical factors affecting rice yield in saline-sodic paddy fields.

Salinization and sodication have become an important abiotic stress affecting soil fertility and crop production in the western of the Songnen Plain in Northeast China. And rice cultivation is considered as one of the most effective biological methods to reclaim saline-sodic soils and ensure food security. However, it is difficult to select the optimal measures to regulate rice growth for increasing yield, because the independent and comprehensive influences of the soil limitation factors on rice yield are not quantitatively evaluated. In this study, the hierarchical partitioning (HP) and the structural equation model (SEM) were used to quantitatively evaluate the influences of salinization parameters, salt ion concentrations and soil nutrients to identify the dominant limitation factors and obstacle mechanism for rice yield. The results showed that soil pH was the key index in salinization parameters, [CO32- + HCO3-] was the key index in salt ion concentrations and available nitrogen (AN) was the key index in soil nutrients to impact rice yield, which independent influences reached 53.7 %, 45.4 % (negative) and 53.2 % (positive), respectively. Soil pH was determined by [CO32- + HCO3-], and the negative effect of alkali stress on rice yield mainly caused by [CO32- + HCO3-] was greater than that of salt stress mainly caused by [Na+] in saline-sodic paddy fields. Among the soil chemical factors, soil pH and AN were the most important explanatory variables of rice yield in saline-sodic paddy fields, which standardized total effects were - 0.32 and 0.40, respectively. Furthermore, the AN showed a more significant negative correlation with soil pH and a higher yield-increasing potential in severe saline-sodic soils (9 ≤ pH < 10) than that in moderate saline-sodic soils (8 ≤ pH < 9). Therefore, decreasing [CO32- + HCO3-] and increasing the content of AN are key to improve rice yield in saline-sodic paddy fields.

Thrombolysis increases the risk of persistent headache attributed to ischemic stroke: A prospective observational study.

BACKGROUND AND OBJECTIVE: Persistent headache attributed to ischemic stroke (PHPIS) is increasingly acknowledged and was added to the 2018 ICHD-3. Intravenous thrombolysis (IVT) is a common treatment for acute ischemic stroke. It remains unknown whether this treatment influences the occurrence of a persistent poststroke headache. We aimed to describe the incidence and clinical characteristics of persistent headaches occurring after acute ischemic stroke in patients with or without IVT and explore the risk factors. METHODS: A prospective observational study was performed between the 234 individuals who received IVT and 226 individuals without IVT in 5 stroke units from Wuhan, China. Subjects were followed for 6 months after stroke via a structured questionnaire. RESULTS: Age, gender, vascular risk factors, and infarct location/ circulation distribution did not differ between the groups, although IVT group had higher initial NIHSS scores. At the end of the follow-up, 12.0% (55/460) of subjects reported persistent headaches after ischemic stroke. The prevalence of persistent headache was significantly higher in the IVT group than non-IVT group (15.4% vs. 8.4%, p = .021). Patients with younger age (p = .033; OR 0.97; 95% CI 0.939-0.997), female sex (p = .007; OR 2.40; 95% CI 1.269-4.520), posterior circulation infarct (p = .024; OR 2.19; 95% CI 1.110-4.311), and IVT (p = .005; OR 2.51; 95% CI 1.313-4.782) were more likely to develop persistent headache after ischemic stroke. CONCLUSION: The potential influence of IVT should be considered when assessing persistent poststroke headache. Future studies will investigate the underlying mechanisms.

Correlations of Plasma Biomarkers and Imaging Characteristics of Cerebral Small Vessel Disease.

Cerebral small vessel disease (CSVD), which is a group of pathological processes affecting cerebral microvessels, leads to functional loss in the elderly population and mostly presents as cognitive impairment and gait decline. CSVD is diagnosed based on brain imaging biomarkers, but blood biomarkers are of great significance for the early diagnosis and progression prediction of CSVD and have become a research focus because of their noninvasiveness and easy accessibility. Notably, many blood biomarkers have been reported to be associated with CSVD in a relatively large population, particularly serum neurofilament light chain (NfL), which has been regarded as a promising biomarker to track the variation trend in WMH and to predict the further status of white matter hyperintensities (WMH) and lacunar infarcts. And neuro-glio-vascular unit structure and blood-brain barrier function have been proposed as underlying mechanisms of CSVD. The article starts from the neuroimaging markers of CSVD, including recent small subcortical infarcts (RSSI), white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMB), enlarged perivascular spaces (EPVS), cerebral atrophy, and the combined small vessel disease score, and attempts to systematically review and summarize the research progress regarding the blood biomarkers of CSVD that form the changes in the neuro-glio-vascular unit structure and blood-brain barrier function.

Development of a cellular model to study CCR8 signaling in tumor-infiltrating regulatory T cells.

The human CC chemokine receptor 8 (CCR8) is specifically expressed on tumor-infiltrating regulatory T cells (TITRs) and is a promising drug target for cancer immunotherapy. However, the role of CCR8 signaling in TITR biology and the effectiveness of CCR8 small molecule antagonists as TITR-targeting immunotherapy remain subjects of ongoing debate. In this work, we generated a novel cellular model of TITRs by culturing peripheral blood mononuclear cell-derived regulatory T cells in medium containing tumor cell-conditioned medium, CD3/CD28 activator, interleukin-2 and 1α,25-dihydroxyvitamin D3. This cellular model (named TITR mimics) highly and stably expressed a series of TITR signature molecules, including CCR8, FOXP3, CD30, CD39, CD134, CD137, TIGIT and Tim-3. Moreover, TITR mimics displayed robust in vitro immunosuppressive activity. To unravel the functional role of CCR8 in TITR mimics, a chemotaxis assay was performed showing strong and CCR8-specific migration toward CCL1, the natural chemokine agonist of CCR8. However, either stimulation (with CCL1) or blocking (with the small molecule antagonist NS-15) of CCR8 signaling did not affect the immunosuppressive activity, proliferation and survival of TITR mimics. Collectively, our work provides a method for the generation of TITR mimics in vitro, which can be used to study TITR biology and to evaluate drug candidates targeting TITRs. Furthermore, our findings suggest that CCR8 signaling primarily regulates migration of these cells.

Mismatch of MRI White Matter Hyperintensities and Gait Function in Patients With Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease (CSVD) is closely related to gait disorders. Previous studies have found a negative correlation between the severity of MRI white matter hyperintensities (WMH) and gait speed. However, not every individual with WMH experiences a gait disorder. PURPOSE: To investigate the mechanisms underlying the mismatch between the severity of MRI WMH and gait impairment, in particular in subjects with severe WMH (Fazekas 3, scale 0-3) resulting from vascular disease. STUDY TYPE: Cohort. POPULATION: 54 subjects with severe WMH and gait disorder (WMH-GD; 29 males) and 114 subjects with severe WMH with no gait disorder (WMH-nGD; 60 males). FIELD STRENGTH/SEQUENCE: 3T/diffusion tensor imaging (DTI), and T1-weighted, T2-weighted, FLAIR, DWI, SWI. ASSESSMENT: Trace-based spatial statistics analysis (TBSS) approach (fractional anisotropy, FA; mean diffusivity; radial diffusivity; axial diffusivity); Cognitive assessment; Conventional MRI markers of CSVD (WMH, enlarged perivascular spaces, lacunae, and cerebral microbleeds); Gait parameters (gait speed; cadence; stride length; gait cycle duration; step duration; time-up-and-go test, TUG). Gait disorder was defined as a TUG time exceeding 12 sec. STATISTICAL TESTS: The t-tests, Mann-Whitney U tests, Chi-square tests, and partial correlation analysis (Pearson or Spearman) were used. P < 0.05 with threshold-free cluster enhancement corrected was considered statistically significant for TBSS. RESULTS: After adjusting for age, sex, height, and other conventional MRI markers of CSVD, the WMH-nGD group showed significantly decreased FA values in the corpus callosum, bilateral superior longitudinal fasciculus, left corona radiata, and left posterior thalamic radiation. There was a significant association between FA values and TUG time, gait speed, and stride length in multiple WM tracts, independent of other conventional CSVD markers. DATA CONCLUSION: This study provides evidence for microstructural damage of specific fibers in WMH-GD subjects compared to WMH-nGD subjects. This may explain the mismatch between WMH and gait impairment in subjects with severe WMH. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3.

Type A personality, sleep quality, and cerebral small vessel disease: investigating the mediating role of sleep in a community-based study.

Purpose: Type A behavior pattern (TABP) is a personality type characterized by rapid speech, impatience, competition, and hostility. Asymptomatic cerebral small vessel disease (CSVD) is often endemic in older adults. Individuals with TABP commonly experience suboptimal sleep quality, and a correlation exists between sleep disturbances and CSVD. We investigated the relationship between TABP and CSVD markers and further explored the mediating role of sleep quality in the relationship between TABP and CSVD. Methods: A cross-sectional survey included 764 community-dwelling adults aged 55-85 years. The TABP Scale and the Pittsburgh Sleep Quality Index (PSQI) were used to assess personality and sleep quality, respectively. Linear and logistic regression analyses were used to examine relationships between variables of interest. In addition, mediation analyses with bootstrapping were used to test whether sleep quality mediated the relationship between TABP and CSVD. Results: Of the 764 participants [median age 65 (61-69) years, 59.9% female], the population with type A personality accounted for 44.8%. After adjusting for covariates, TABP scores (p = 0.03) and PSQI scores (p < 0.001) were significantly correlated with CSVD. In addition, sleep quality partially mediated the association between type A behavior and CSVD, and the mediating effect was 10.67%. Conclusion: This study showed that type A behavior was a risk factor for CSVD among older community-dwelling adults and that sleep quality mediated the relationship between type A behavior and CSVD. Changing type A behavior may help improve sleep quality, which may in turn reduce the prevalence of CSVD.

Current Knowledge about Headaches Attributed to Ischemic Stroke: Changes from Structure to Function.

Headaches are common after ischemic stroke (IS). Unlike primary headaches, headaches attributed to IS have specific clinical features. This review describes the epidemiology, clinical characteristics, risk factors, and influence of IS headaches. Previous reports were summarized to show the correlations between headaches and structural lesions in the cerebral cortex, subcortical white matter, deep gray matter nuclei, brainstem, and cerebellum. However, the substantial heterogeneity of IS, subjective evaluations of headaches, and inadequate cohort studies make it difficult to explore the pathophysiology of headaches attributed to IS. In our recommendation, favorable imaging techniques, such as magnetic resonance imaging and positron emission tomography, may provide new insights into mechanical studies of IS headaches from structure to function. It may also be helpful to extend the research field by targeting several shared signal transducers between headaches and IS. These markers might be neuropeptides, vasoactive substances, ion channels, or electrophysiologic changes.

Internal validation of an improved system for forensic application: a 41-plex Y-STR panel.

Y-chromosome short tandem repeats (Y-STRs) have a unique role in forensic investigation. However, low-medium mutating Y-STRs cannot meet the requirements for male lineage differentiation in inbred populations, whereas rapidly mutating (RM) high-resolution Y-STRs might cause unexpected exclusion of paternal lineages. Thus, combining Y-STRs with low and high mutation rates helps to distinguish male individuals and lineages in family screening and analysis of genetic relationships. In this study, a novel 6-dye, 41-plex Y-STR panel was developed and validated, which included 17 loci from the Yfiler kit, nine RM Y-STR loci, 15 low-medium mutating Y-STR loci, and three Y-InDels. Developmental validation was performed for this panel, including size precision testing, stutter analysis, species specificity analysis, male specificity testing, sensitivity testing, concordance evaluation, polymerase chain reaction inhibitors analysis, and DNA mixture examination. The results demonstrated that the novel 41-plex Y-STR panel, developed in-house, was time efficient, accurate, and reliable. It showed good adaptability to directly amplify a variety of case-type samples. Furthermore, adding multiple Y-STR loci significantly improved the system's ability to distinguish related males, making it highly informative for forensic applications. In addition, the data obtained were compatible with the widely used Y-STR kits, facilitating the search and construction of population databases. Moreover, the addition of Y-Indels with short amplicons improves the analyses of degraded samples. Key Points: A novel multiplex comprising 41 Y-STR and 3 Y-InDel was developed for forensic application.The multiplex included rapidly mutating Y-STRs and low-medium mutating Y-STRs, which is compatible with many commonly used Y-STR kits.The multiplex is a powerful tool for distinguishing related males, familial searching, and constructing DNA databases.

Effect of PCSK9 inhibition in combination with statin therapy on intracranial atherosclerotic stenosis: A high-resolution MRI study.

Introduction: Intracranial atherosclerotic stenosis (ICAS) is a common cause of stroke worldwide. Evolocumab, a proprotein convertase subtilisin/kexin type-9 inhibitor (PCSK9i), effectively lowers low-density lipoprotein (LDL) and produces favorable changes in coronary atherosclerosis. This study aimed to determine the effects of PCSK9i on intracranial plaques in moderate-intensity statin-treated individuals with ICAS. Methods: This prospective, observational study monitored the imaging and clinical outcomes of individuals with ICAS who were consecutively treated with moderate-intensity statins with or without PCSK9i. Individuals underwent monthly visits and repeat high-resolution MRI (HR-MRI) at week 12. The primary outcome was a change in HR-MRI after 12 weeks of treatment and the secondary outcome was major vascular events during follow-up. Results: Forty-nine individuals were studied (PCSK9i group: 26 individuals with 28 abnormal vascular regions; statin group: 23 with 27 regions). The PCSK9i group showed a significant reduction in the normalized wall index (0.83 vs. 0.86, p = 0.028) and stenosis degree (65.5 vs. 74.2%, p = 0.01). Similarly, a greater percentage of individuals with a good response to the efficacy of treatment were treated in the PCSK9i group than that in the statin group (75 vs. 44.4%, p = 0.021). The incidence of major vascular events was overall similar between the groups. The treatment options (OR = 8.441, p = 0.01) and prior diabetes (OR = 0.061, p = 0.001) were significantly associated with the efficacy of treatment. Discussion: Statin and PCSK9i combination treatment stabilized intracranial atherosclerotic plaques more often compared to statins alone, as documented by HR-MRI. Further study is warranted to determine if combination treatment improves clinical outcomes in ICAS.

Differences in Gray Matter Volume in Cerebral Small Vessel Disease Patients with and without Sleep Disturbance.

Recently, there has been increased interest in the relationship between cerebral small vessel disease (CSVD) and circadian rhythm disruption, particularly sleep disturbance. However, the neural mechanism of sleep disturbance in CSVD patients remains poorly understood. The purpose of this study is to explore the gray matter alterations in CSVD patients with and without sleep disturbance. 59 patients with CSVD and 40 healthy controls (HC) were recruited for the present study. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. CSVD patients were categorized into either the good sleepers group (CSVD-GS, n = 23) or the poor sleepers group (CSVD-PS, n = 36) based on PSQI score. Voxel-based morphometry (VBM) analysis was used to assess differences in gray matter volume (GMV) between groups. Multivariate regression analyses were performed to investigate the relationships between sleep quality, GMV, and white matter hyperintensities (WMH). We observed GMV differences between the three groups in the bilateral caudate, right thalamus, bilateral calcarine cortex, left precentral gyrus, right orbitofrontal cortex, left cingulate gyrus, and right sub-gyral temporal lobe. Additionally, the CSVD-PS group exhibited decreased GMV in the bilateral calcarine cortex yet increased GMV in the right caudate compared to the CSVD-GS group. In fully adjusted models, GMV of the right caudate and bilateral calcarine cortex was associated with sleep quality in CSVD patients. The present study revealed structural brain alterations in CSVD patients with sleep disturbance. These findings may provide novel insights into the neural mechanisms of sleep disturbance in CSVD.

Elevated RANTES levels are associated with increased risk of cerebral atherosclerotic stenosis.

BACKGROUND: Cerebral atherosclerotic stenosis (CAS) is a significant factor in the development of acute ischemic stroke (AIS). Previous studies have reported that cytokines are involved in atherosclerotic diseases, although the relationship between serum levels of the chemokine RANTES (regulated on activation, normal T-cell expressed and secreted) and the presence of CAS remains unclear. METHODS: In total, 127 participants (65 non-AIS controls and 62 patients with AIS) were involved in this study. CAS was defined as the presence of ≥ 50% stenosis in major intracranial or extracranial artery by a Digital Substraction Angiography (DSA) examination, and we classified all participants into four groups according to stroke and CAS status. Serum concentrations of 8 cytokines, including RANTES, were measured by the Human ProcartaPlex Multiplex Immunoassay Kit. RESULTS: Seventy-eight participants (61.41%) had CAS, of which 39 cases with AIS and 39 case with non-AIS. Patients with CAS had higher RANTES levels compared to non-CAS patients in both the non-AIS group (10.54 ± 0.80 vs. 13.20 ± 0.71, p = 0.016) and stroke group (11.96 ± 0.87 vs. 15.03 ± 0.75, p = 0.011), and multivariate logistic regression analysis showed that the RANTES level is independently associated with CAS in both the non-AIS group (adjusted odds ratio (OR), 1.07; 95% CI, 1.02-1.12, P = 0.004) and stroke group (adjusted OR, 1.32; 95% CI, 1.10-1.58, P = 0.003). CONCLUSION: Patients with CAS have higher levels of serum RANTES than non-CAS patients regardless of stroke status suggesting that RANTES may play an important role in the formation of CAS.

Proteomic Difference Analysis of Whole Blood and Bloodstains.

OBJECTIVES: To study the changes of protein levels in peripheral blood after it dried. METHODS: The proteins from whole blood and bloodstains were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and normalized by the label-free quantification (LFQ) method. The differential proteins were analyzed by using R 4.2.1 software, limma and edgeR package. The analysis of biological function, signaling pathway and subcellular localization for the differential proteins was then performed. RESULTS: A total of 623 and 596 proteins were detected in whole blood and bloodstains, respectively, of which 31 were statistically significant in the quantitative results, including 10 up-regulated and 21 down-regulated proteins in bloodstains. CONCLUSIONS: The protein abundances in whole blood and bloodstains are highly correlated, and the variation of protein abundances may be related to the changes of endogenous and structural proteins in cells. The application of proteomics technology can assist the screening and identification of protein biomarkers, thereby introducing new biomarkers for forensic research.

Efficiency Analysis of Uncle-Nephew Relationship Identification by Increasing STR Markers and Adding Reference Samples.

OBJECTIVES: To estimate the system efficiency of uncle-nephew relationship identification by increasing STR markers and adding reference samples based on the test results of simulated data and real samples, so as to provide references for selecting the appropriate number of STRs and reference samples for uncle-nephew relationship identification. METHODS: Five common models of uncle-nephew relationship identification were constructed by adding different reference samples. In each model, the likelihood ratio (LR) for 10 000 pairs of uncle-nephew relationships and 10 000 pairs of unrelated individuals were simulated by detecting 19, 39 or 55 STRs, and the system efficiency at different thresholds was simulated. The samples of the Han population in Zhejiang were collected, and 55 autosomal STRs were obtained by using SiFaSTRTM 23plex kit, Goldeneye® DNA ID 22NC kit and AGCU 21+1 PCR amplification kit. When 19, 39 and 55 STRs were detected, the LR of each model and system efficiency under different thresholds were calculated and compared with the simulation results. RESULTS: Under the same detection system, the calculated results of simulated data and corresponding true samples were basically consistent. In the same model, there was a positive correlation between the system efficiency of uncle-nephew relationship identification and the number of STRs detected. Moreover, the system efficiency of introducing relatives was higher than identifying only two individuals. The order of preference for the introduction of relatives was the full sibling (or mother) of the uncle and the full sibling (or mother) of the nephew. CONCLUSIONS: The system efficiency of uncle-nephew relationship identification could be improved by increasing the number of STRs and introducing known relatives, which would provide the basis for selecting the most appropriate detection system and reference individuals in actual cases.

Improving the system power of complex kinship analysis by combining multiple systems.

Complex kinship analysis is a critical issue in forensic genetics. To address this issue, 55 STRs and 94 SNPs collected from four commercial forensic typing kits [three kits were based on a capillary electrophoresis (CE) platform and one was based on a next-generation sequencing (NGS) platform] were employed to test the system power for 2nd-degree and 3rd-degree kinship analysis. To measure the kinship index in related individuals, likelihood ratios (LRs) were calculated based on length and sequence polymorphism information (LRlength and LRsequence, respectively) from simulation as well as true pedigree samples. LRs calculated based on sequence information are generally higher than those based on length information. The sensitivity, specificity, and effectiveness to distinguish the 2nd- and 3rd-degree kinship were estimated from four marker sets with different numbers of markers. As expected, system power for kinship analysis improved by increasing the number of markers and using LRsequence, instead of LRlength. Furthermore, the system power based on 55 STRs from the CE platform is equal to the 40 STRs and 94 SNPs from one CE kit and the kit based on NGS platform for both 2nd-degree and 3rd-degree kinship analysis. For discrimination of 2nd-degree kinship, the system effectiveness is 86.63% with an error ratio < 0.01 using the 55 STRs from the CE platform. Using sequence information from the 55 STRs and 94 SNPs, the system effectiveness is 94.43%, with an error ratio < 0.001 for 2nd-degree kinship analysis and 64.34% with an error ratio < 0.05 for 3rd-degree kinship analysis, indicating that these markers are powerful for 2nd-degree kinship analysis and can be used for 3rd-degree kinship analysis.

Designed synthesis of an sp2 carbon-conjugated fluorescent covalent organic framework for selective detection of Fe3.

A new fully conjugated covalent organic framework material (COFTFPPy-ThDAN) has been synthesized via the Knoevenagel condensation reaction using 1,3,6,8-tetra(4-formylphenyl)pyrene (TFPPy) as the chromogenic unit and 2,2'-([2,2'-bithiophene]-5,5'-diyl)diacetonitrile (ThDAN) as the linker. The COFTFPPy-ThDAN has been successfully prepared under the optimized conditions and showed excellent crystallinity and chemical stability. Especially, it was able to maintain its crystallinity even when immersed under harsh conditions such as HCl (3 M) and NaOH (3 M). Meanwhile, COFTFPPy-ThDAN exhibited good fluorescence properties, which could remain relatively stable under different pH conditions. Moreover, COFTFPPy-ThDAN was further employed for the detection of Fe3+ with high sensitivity and selectivity with a limit of detection (LOD) of 1.26 µM. COFTFPPy-ThDAN with high stability and fluorescence is a promising material for chemical sensing.

Effect of Moderate-to-Severe Iodine Deficiency in Early Pregnancy on Subclinical Hypothyroidism: A Longitudinal Study in an Iodine-Sufficient Region in China.

Objective: To investigate iodine status among pregnant women in an iodine-sufficient region in China after the implementation of revised universal salt iodization (USI) standards in 2012 and assess the association between urinary iodine concentrations (UIC) in early pregnancy and the incidence of subclinical hypothyroidism (SCH) in euthyroid women negative for antithyroid Ab during different trimesters. Methods: We measured the iodine status of 1,264 pregnant women, and performed follow-up assessment of thyroid function at 20 and 30 weeks of gestation among a cohort of 250 euthyroid women. We assessed the association of UIC in the 1st trimester with the incidence of SCH in subsequent trimesters. UIC and serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured. Results: The median UIC was 135.95 µg/L among 1,264 women. Serum FT4 level was significantly higher in the group of UIC 150 to 249 µg/L compared with other UIC groups (P < 0.001). TSH was significantly higher in the UIC more than or equal to 250 µg/L group than the UIC 150 to 249 g/L group (P = 0.043). Of the 250 euthyroid women negative for antithyroid Ab (TSH value of 2.5-3.55 mU/L) in the 1st trimester, pregnant women with UIC lower than 100 µg/L in the 1st trimester exhibited a significantly increased risk of SCH (odds ratio [OR] = 2.47; 95% confidence interval [CI] = 1.22-5.71; P = 0.012, according to the Chinese Medical Association criteria; OR = 5.22, 95% CI = 1.73-6.09, P = 0.004, according to ATA criteria) during the latter half of pregnancy compared with the UIC 150 to 249 µg/L group. Conclusion: Moderate-to-severe iodine deficiency (UIC lower than 100 µg/L) in the 1st trimester was associated with a significantly higher risk of SCH during the 2nd or 3rd trimesters among euthyroid pregnant women who had negative for antithyroid Ab. Women with SCH during pregnancy require regular UIC tests to maintain appropriate iodine status.

Aptamers against Pathogenic Bacteria: Selection Strategies and Apta-assay/Aptasensor Application for Food Safety.

Pathogenic bacteria are primarily kinds of detrimental agents that cause mankind illness via contaminated food with traits of multiple types, universality, and low content. In view of the detection demands for rapidity, aptamer recognition factors emerged as a substitution for antibodies, which are short single strands of nucleic acid selected via in vitro. They display certain superiorities over antibodies, such as preferable stability, liable modification, and cost-efficiency. Taking advantage of the situation, numerous aptamers against pathogenic bacteria have been successfully selected and applied, yet there are still restrictions on commercial availability. In this review, the strategies/approaches to key sections in pathogen aptamers SELEX and post-SELEX are summarized and sorted out. Recently, optical, electrochemical, and piezoelectric aptamer-based assays or sensors dedicated to pathogen detection have been critically reviewed. Ultimately, the existing challenges and future trends in this field are proposed to further promote development prospects.

Ultrasensitive detection of tumor-derived small extracellular vesicles based on nonlinear hybridization chain reaction fluorescence signal amplification and immunomagnetic separation.

Small extracellular vesicles (sEVs) have attracted wide attention as a promising tumor biomarker. However, sensitive and selective detection of sEVs is challenging due to the low levels of sEVs in the early stage of cancers. Herein, a novel fluorescent sensor was developed for the detection of sEVs with high sensitivity and selectivity based on nonlinear hybridization chain reaction (nHCR) signal amplification and immunomagnetic separation. Firstly, sEVs were captured and enriched by CD63 antibody conjugated magnetic beads via antibody-antigen reactions. Then, cholesterol-modified DNA probes were anchored spontaneously on lipid membranes of sEVs through efficient hydrophobic interactions between the cholesterol moiety and the phospholipid bilayer of sEVs. The simultaneous recognition of the transmembrane protein and the phospholipid bilayer structure of the sEVs could effectively eliminate interferences from free proteins. The sticky ends of the cholesterol-modified DNA probes acted as the initiator to trigger nHCR to form a hyperbranched network of DNA structure that could recruit more fluorescent signal molecules for signal amplification. Under the optimal conditions, the nHCR-based strategy showed high sensitivity for the detection of sEVs with a limit of detection of 80 particles per µL. In addition, the as-constructed method was successfully applied for the analysis of clinical samples. It provides a sensitive and selective platform for the isolation and detection of sEVs in the early diagnosis of cancers.

Association of Excessive Daytime Sleepiness with Cerebral Small Vessel Disease in Community-Dwelling Older Adults.

Purpose: Excessive daytime sleepiness (EDS) and cerebral small vessel disease (CSVD) are common problems among older adults; however, their association is not clear. The present study aimed to investigate the frequency of EDS in CSVD patients and the relationship between EDS and neuroimaging markers of CSVD. Patients and Methods: We conducted a cross-sectional study among 1076 community-dwelling older adults aged 55-85 years. EDS was measured using the Epworth Sleepiness Scale (ESS), and EDS was defined as an ESS score greater than 10. Binary logistic regression was performed to assess the association between EDS and neuroimaging markers of CSVD. Results: Of the 1076 participants (mean age: 65.58 ± 6.46 years, 60.5% female), the prevalence of EDS was 10.0%. EDS was more frequent in participants with CSVD than in the total sample (20.0% vs 10.0%, p <0.001). In fully adjusted models, EDS was significantly correlated with CSVD burden (OR = 1.39, 95% CI 1.16 to 1.68, p <0.001), the severity of white matter hyperintensities (WMH) (OR = 1.33, 95% CI 1.14 to 1.54, p <0.001), and presence of lacunes (OR = 2.47, 95% CI 1.53 to 4.00, p <0.001) but not with the presence of cerebral microbleeds (CMBs) (OR=1.54, 95% CI 0.92 to 2.56, p = 0.099) or severity of enlarged perivascular spaces (EPVS) in basal ganglia (OR = 1.16, 95% CI 0.70 to 1.92, p = 0.564). Conclusion: We found a high frequency of EDS symptoms in CSVD individuals. Further, EDS was significantly associated with WMH, lacunes, and CSVD burden. Our findings further suggest patients with CSVD may exhibit abnormal sleep-wake patterns.

Non-immobilized GO-SELEX of aptamers for label-free detection of thiamethoxam in vegetables.

Due to the massive use of thiamethoxam (TMX) pesticide and the accumulated potential hazards exposure, the detection of TMX is of great significance to food and ecological safety. In this study, aptamers with affinity for TMX were obtained through graphene oxide assisted systematic evolution of ligands by exponential enrichment (GO-SELEX). After 9 rounds of positive and counter selection, 5 candidate sequences were obtained, among which seq.20 had the highest affinity for TMX, and its dissociation constant (Kd) was 210.47 ± 79.37 nM. Then, the aptamer was further truncated based on structural analysis. The truncated aptamers (seq.20-1, seq.20-2) exhibited higher affinity (Kd = 118.34 ± 13.85 nM, Kd = 123.35 ± 29.80 nM), which seq.20-2 had only 37 bases. Furthermore, circular dichroism spectroscopy showed that TMX induced the conformation of aptamer from B-form structure to hairpin structure, and then formed a stable TMX-ssDNA complex. Finally, the truncated aptamer (seq.20-2) and the original aptamer (seq.20) were used as recognition elements to construct colorimetric aptasensors based on gold nanoparticles for the detection of TMX. It was found that the sensitivity of the former (LOD = 1.67 ± 0.12 nM, S/N = 3) was better than that of the latter (LOD = 3.33 ± 0.23 nM, S/N = 3). Feasibility of truncated aptamer as recognition element in the detection of TMX in vegetable samples was preliminarily verified.