Angiography-based hemodynamic features predict recurrent ischemic events after angioplasty and stenting of intracranial vertebrobasilar atherosclerotic stenosis.

OBJECTIVES: To assess the predictive value of hemodynamic features for stroke relapse in patients with intracranial vertebrobasilar atherosclerotic stenosis treated with percutaneous transluminal angioplasty and stenting (PTAS) using quantitative digital subtraction angiography (q-DSA). METHODS: In this retrospective longitudinal study, patients with intracranial vertebrobasilar atherosclerotic stenosis and who underwent PTAS treatment between January 2012 and May 2020 were enrolled. The q-DSA assessment was performed before and after PTAS. ROIs 1-4 were placed along the vertebral artery, proximal and distal basilar artery, and posterior cerebral artery; ROIs 5-8 were in 5 mm and 10 mm proximal and distal to the lesion, respectively. Relative time to peak (rTTP) was defined as the difference in TTP between ROIs. Cox regression analyses were performed to determine risk factors for recurrent stroke. RESULTS: A total of 137 patients (mean age, 62 years ± 10 [standard deviation], 83.2% males) were included, and 26 (19.0%) patients had stroke relapse during follow-up (median time of 42.6 months [interquartile range, 19.7-60.7]). Preprocedural rTTP4-1 (adjusted hazard ratio (HR) = 2.270; 95% CI 1.371-3.758; p = 0.001) and preprocedural rTTP8-5 (adjusted HR = 0.240; 95% CI 0.088-0.658; p = 0.006) were independently associated with the recurrent stroke. These hemodynamic parameters provided an incremental prognostic value for stroke relapse (AUC, 0.817 [0.704-0.931]; the net reclassification index, 0.431 [0.057-0.625]; and the integrated discrimination index, 0.140 [0.035-0.292]). CONCLUSIONS: In patients with intracranial vertebrobasilar atherosclerosis treated with PTAS, preprocedural prolonged TTP of the target vessel and shortened trans-stenotic TTP difference were associated with stroke relapse. Q-DSA-defined hemodynamic parameters provided incremental predictive value over conventional parameters for stroke recurrence. CLINICAL RELEVANCE STATEMENT: Quantitative DSA analysis enables intuitive observation and semi-quantitative evaluation of peri-therapeutic cerebral blood flow. More importantly, quantitative DSA-defined hemodynamic parameters have the potential for risk stratification of patients with intracranial atherosclerotic stenosis. KEY POINTS: Semi-quantitative angiography-based parameters can reflect pre- and postprocedural subtle changes in blood flow in patients with intracranial atherosclerotic stenosis. Although angioplasty procedures can significantly improve blood flow status, patients with more restricted baseline blood flow still show a higher risk of stroke recurrence. Angiography-based hemodynamic features possess prognostic value and can serve as clinical markers to assess stroke risk of patients with intracranial atherosclerotic stenosis.

Greenhouse gases monitoring instrument on a GF-5 satellite-II: correction of spatial and frequency-dependent phase distortion.

Interference data obtained by a spatial heterodyne spectrometer (SHS) is subject to various error factors and suffers from complex phase distortion. Traditional phase correction methods, such as the Amplitude, Merzt, and Forman methods, extract phase distortion in the spectral domain and correct it, which cannot effectively correct spatial phase distortion. Through theoretical derivation and numerical simulation, the spatial phase distortion is firstly determined and corrected in the interference domain. The frequency-dependent phase distortion is then extracted in the spectral domain and corrected. This novel phase distortion correction method named the phase decomposition method was applied to the in-orbit interference data of Greenhouse gases Monitoring Instrument-II (GMI-II). Compared with traditional phase correction methods, the root-mean-square error of the spectrum corrected using the phase decomposition method is reduced by 81.37%.

Greenhouse gas monitoring instrument on the GF-5 satellite-II: on-orbit spectral calibration.

The greenhouse gas monitoring instruments were carried on the Gaofen-5-II satellite, which was launched into orbit from the Taiyuan Satellite Launch Center on September 7, 2021. In order to improve the on-orbit data quantification level, a calibration device based on diffuse reflector system was designed, which can realize on-orbit spectral and radiation calibration. In this paper, the principle of standard spectral line selection is given, and the characteristic spectral lines that can be used for on-orbit spectral calibration are extracted. The wavelength deviation evaluation function is established by using the method of matching the high-resolution reference spectrum after the linear function of the convolution instrument with the on-orbit calibration measurement spectrum, and finally using the Levenberg-Marquardt algorithm to evaluate the function. The optimization solution is the on-orbit wavelength calibration result. According to the above method, the on-orbit calibration data are processed. After calibration, the maximum deviation of the on-orbit spectral offset is changed from 0.133 to 0.009c m -1, and variations in magnitude less than 10% of the spectral resolution for C O 2 (1.57 µm) band have been detected.

Correction of invalid data based on spatial dimension information of a temporally and spatially modulated spatial heterodyne interference imaging spectrometer.

Considering the distribution characteristics of interference data of a temporally and spatially modulated spatial heterodyne interference imaging spectrometer, an algorithm based on spatial dimension baseline of interference data for the detection and correction of invalid data is proposed. The intensity ratio of the target interference data far away from the zero optical path difference has been extracted and calculated, and the intensity of the interference data is compensated; the baseline of the compensated interference data is carried out along the spatial dimension direction, and the deviation matrix is calculated, and combined with the 3σ method for the detection and correction of invalid data. A simulation experiment is carried out in the laboratory to obtain the target push-sweep imaging interference data, and the spectrum is the output spectrum of the integrating sphere halogen tungsten lamp. The experimental results show that the invalid data in the interference data (including invalid data near zero optical path difference) can be effectively identified and corrected using the invalid data detection and correction algorithm described in this paper, which has a good effect on the correction of fixed invalid data and flash pixel.

Cholesterol Crystals are Associated with Carotid Plaque Vulnerability: An Optical Coherence Tomography Study.

OBJECTIVE: Vulnerable carotid plaque is associated with cerebrovascular events. Cholesterol crystals are often seen in the atherosclerotic plaques. However, the potential role of cholesterol crystals in carotid plaques destabilization is unknown. We aimed to identify the association between cholesterol crystals and carotid plaque vulnerability. METHODS: Optical coherence tomography assessment of carotid plaque was performed in 95 patients. Clinical characteristics and plaque morphology were examined. The differences in plaque characteristics (thrombus, calcification, neovascularization, and macrophage accumulations) and clinical parameters (age, symptom, coronary heart disease, total cholesterol, triglycerides, and C-reactive protein) between patients with or without cholesterol crystals were analyzed with multivariate logistic regression. RESULTS: Among 66 patients with acceptable carotid atherosclerotic optical coherence tomography images, 16 were with and 50 were without cholesterol crystals. 56.3% patients (9 of 16) with cholesterol crystals had cerebrovascular ischemic symptom related to ipsilateral internal carotid artery, whereas only 26.0% patients (13 of 50) without cholesterol crystals had symptom (OR, 3.66; 95% CI, 1.13-11.82; P = .025). 75.0% of the plaques with cholesterol crystals had concomitant macrophage accumulation (OR, 4.14; 95% CI, 1.17-14.65; P = .04). In segments with cholesterol crystals, a higher presence of calcification could be demonstrated compared to those without cholesterol crystals (62.5% versus 32.0%, P = .03). 70.0% plaques with cholesterol crystals and calcification were classified as symptomatic plaques (OR, 6.38; 95% CI, 1.46-27.91; P = .01). No association between plaque rupture and cholesterol crystals was identified. Multivariate logistic regression showed that age and macrophage accumulation were independently associated with cholesterol crystals. CONCLUSIONS: Carotid atherosclerotic plaques with cholesterol crystals were more likely to have concomitant macrophage and calcification accumulations. Patients with cholesterol crystals plaque experienced more cerebrovascular symptoms. Thus, cholesterol crystals, especially together with macrophage and calcification, may serve as an important component of venerable carotid plaques.

Corneal Collagen Crosslinking Combined with Phototherapeutic Keratectomy and Photorefractive Keratectomy for Corneal Ectasia after Laser in situ Keratomileusis.

PURPOSE: The aim of this study was to analyze the effects of corneal crosslinking (CXL) combined with phototherapeutic keratectomy (PTK) and photorefractive keratectomy (PRK) in halting the progression and improving the visual function of corneal ectasia after laser in situ keratomileusis (LASIK). METHODS: PTK-PRK-CXL was performed on 14 eyes of 14 patients who developed corneal ectasia after LASIK. The visual acuity, spherical refraction and cylinder, corneal topography indices, thinnest corneal thickness (TCT), and endothelial cell count were evaluated at baseline and at 1, 3, 6, and 12 months postoperatively. RESULTS: The mean uncorrected visual acuity improved significantly from 0.64 ± 0.36 logMAR preoperatively to 0.19 ± 0.12 logMAR at 12 months of follow-up (p < 0.001), while the mean best corrected visual acuity improved from 0.21 ± 0.14 logMAR at baseline to 0.04 ± 0.10 logMAR at 12 months postoperatively (p < 0.001). A significant decrease was observed in Kmax and Kmean values from 52.51 ± 6.74 and 43.55 ± 3.37 D at baseline to 45.72 ± 5.18 (p < 0.001) and 40.60 ± 3.05 D (p < 0.001) at the 1-year follow-up. The mean TCT decreased significantly from 419.07 ± 36.56 µm before treatment to 320.93 ± 39.78 µm at 12 months of follow-up (p < 0.001), and there was no significant endothelial cell loss (p > 0.05) beyond 6 months after treatment. CONCLUSION: PTK-PRK-CXL is a promising procedure to halt the progression of post-LASIK keratectasia with significant visual quality improvement.

Emergent loading dose of antiplatelets for stenting after IV rt-PA in acute ischemic stroke: a feasibility study.

BACKGROUND: A loading dose of antiplatelets reduces in-stent thrombosis after stent implantation. However, whether it is safe in patients undergoing acute stenting after intravenous recombinant tissue plasminogen activator (rt-PA) is unclear. METHODS: A case series of acute ischemic stroke patients treated with intravenous rt-PA followed by emergent stenting were prospectively included in Jinling Hospital Stroke Unit. An emergent loading dose of antiplatelets (aspirin 300 mg and clopidogrel 300 mg) were administered to all patients through a nasogastric tube immediately before stenting. Clinical and angiographic outcomes were evaluated in these patients. RESULTS: A total of 12 patients were included. The median of NIHSS score on admission was 15 points (interquartile range 11-19). The median of time from stroke symptom onset to start IV rt-PA and stent placement was 172 min (interquartile range 123.75-189) and 311.5 min (interquartile range 285.5-349.5), respectively. All patients reached complete or partial recanalization (TICI ≥2a). One patient occurred hemorrhagic transformation at 24 h following the emergent loading dose of antiplatelets. A favorable outcome as defined by mRS ≤2 at 90 days was obtained in 58.3% (7/12) of all patients. CONCLUSION: Our finding preliminary suggested that an emergent loading dose of antiplatelets may be safe and feasible for acute stenting after IV rt-PA.

Lack of improvement following endovascular therapy in patients with acute ischemic stroke.

BACKGROUND: Recent randomized trials have consistently demonstrated a clinical benefit of endovascular therapy (ET) over best medical therapy (including intravenous (IV) thrombolysis in eligible patients) or IV thrombolysis only in selected patients with acute ischemic stroke (AIS) due to proximal occlusion in the carotid territory. Previous study demonstrates that lack of improvement (LOI) at 24 hours is an independent predictor of poor outcome and death at 3 months in patients with AIS treated with IV alteplase. However, LOI at 24 hours following ET has not been studied systematically. The purpose of this study is to identify predictors of LOI at 24 hours in patients with AIS after ET as well as the relationship between LOI and unfavorable outcome at 3 months. METHODS: A total of 98 consecutive patients with AIS treated with ET in two separate stroke centers from 2010 to 2014 were retrospectively reviewed. Data on demographics, preexisting vascular risk factors, occlusion site, pre- and post-treatment modified Treatment in Cerebral Ischemia (mTICI) classification, collaterals and National Institutes of Health Stroke Scale (NIHSS) score on admission as well as 24 hours after the endovascular procedurals were collected. LOI was defined as a reduction of 3 points or less on the NIHSS at 24 hours compared with baseline. A 3-month functional outcome was assessed using the modified Rankin scale (mRS). Unfavorable outcome was prespecified as a score of more than 2 on the mRS. The onset-to-reperfusion time (ORT) was defined as time to mTICI 2b or 3 or end of procedure. Long ORT was defined as time to reperfusion beyond 6 hours. Poor reperfusion was defined as mTICI ≦2a. The pretreatment collateral circulation extent was graded as poor (grades 0-1) or good (grades 2-4). RESULTS: Among the 98 patients with AIS who were treated with ET, LOI was present in 48 (49%) subjects. Multivariate analysis indicated that poor collaterals (odds ratio [OR] 3.25; 95% confidence interval [CI]: 1.29-8.19; p = 0.012) and long ORT (OR 3.97, 95% CI: 1.66-9.54; p = 0.002) were independent predictors of LOI. LOI (OR 7.18, 95% CI: 2.39-21.61; p < 0.001) was independently associated with unfavorable outcome at 3 months. CONCLUSION: Among patients with AIS treated with ET, as an independent predictor of unfavorable outcome, LOI at 24 hours is associated with poor collaterals and long ORT.

Correlation study between small vessel disease and early neurological deterioration in patients with mild/moderate acute ischemic stroke.

AIMS: Cerebral small vessel disease (SVD) refers to a group of pathological processes that affect small arteries, arterioles, venules, and capillaries of the brain. We hypothesized that imaging markers of SVD could be associated with neurological deterioration during acute phase of mild/moderate ischemic stroke. METHODS: We performed a prospective cohort with 687 consecutive patients with acute ischemic stroke and also with admission NIHSS score below 12 points. Imaging markers of SVD include silent lacunar infarction, deep cerebral microbleeds (CMBs), brain atrophy, periventricular and semiovale white matter hyperintensities, basal ganglia and semiovale enlarged perivascular spaces as well as SVD burden rating scale, which were evaluated and calculated, respectively. Early neurology deterioration (END) was defined as an increment of NIHSS score ≥2 points in the first 72 h after admission. RESULTS: None of these imaging markers and rating scale of SVD significantly correlated with END after adjusted for major confounders. Post hoc analysis indicated similar negative results in different age, TOAST classification and infarction location subgroups. Only silent infarction (OR 2.42, 95%CI 1.33-5.10) and deep CMBs (OR 2.10, 95%CI 1.08-3.72) seemed to be predictors for END in female patients. However, due to the increased type I error in multiple comparisons, these relationships should not be regarded as statistically significant. CONCLUSION: In patients with mild/moderate acute ischemic stroke, imaging markers of SVD did not correlate with END.

Severity assessment of intracranial large artery stenosis by pressure gradient measurements: A feasibility study.

BACKGROUND: Fractional flow reserve (FFR)-guided revascularization strategy is popular in coronary intervention. However, the feasibility of assessing stenotic severity in intracranial large arteries using pressure gradient measurements still remains unclear. METHODS: Between March 2013 and May 2014, 12 consecutive patients with intracranial large artery stenosis (including intracranial internal carotid artery, middle cerebral M1 segment, intracranial vertebral artery, and basilar artery) were enrolled in this study. The trans-stenotic pressure gradient was measured before and/or after percutaneous transluminal angioplasty and stenting (PTAS), and was then compared with percent diameter stenosis. A Pd /Pa cut-off of ≤0.70 was used to guide stenting of hemodynamically significant stenoses. The device-related and procedure-related serious adverse events and recurrent cerebral ischemic events were recorded. RESULTS: The target vessel could be reached in all cases. No technical complications occurred due to the specific study protocol. Excellent pressure signals were obtained in all patients. For seven patients who performed PTAS, the mean pre-procedural pressure gradient decreased from 59.0 ± 17.2 to 13.3 ± 13.6 mm Hg after the procedure (P < 0.01). Only one patient who refused stenting experienced a TIA event in the ipsilateral MCA territory. No recurrent ischemic event was observed in other patients. CONCLUSION: Mean trans-stenotic pressure gradients can be safely and easily measured with a 0.014-inch fluid-filled guide wire in intracranial large arteries. © 2016 Wiley Periodicals, Inc.

Predictors for vascular cognitive impairment in stroke patients.

BACKGROUND: Around two thirds stroke patients may suffer from vascular cognitive impairment (VCI). Our previous study has validated the NINDS-CSN harmonization standard for VCI diagnosis in Chinese. In this study, we aimed to investigate the predictors for VCI in Chinese post-stroke patients. METHODS: We compared epidemiological, clinical, and neuroimaging data (number, size and location of acute infarcts and lacunes, severities of white matter hyperintensities and brain atrophy) between stroke patients with and without VCI. Univariate and logistic regression analyses were utilized to determine VCI predictors. RESULTS: Fifty-six consecutive patients (age, 63.8 ± 8.3 years; female, 37.5%) were recruited at a mean interval of 7.1 months after stroke onset, and 31 (55.4%) patients were diagnosed with VCI based on a validated 60-min neuropsychological battery. VCI patients were older (p = 0.023), less educated (p = 0.001), more likely to be female (p < 0.001), had a recurrent stroke (p = 0.028), and described higher apathy (p = 0.022) and worse pre-stroke cognition (p = 0.048) than cognitively normal patients. Lower educational level (adjusted odds ratio [OR] 0.750, 95% confidence interval [CI], 0.573-0.981; p = 0.035), female sex (adjusted OR 8.288, 95% CI, 1.522-45.113; p = 0.014), recurrent stroke (adjusted OR 11.327, 95% CI, 1.335-96.130, p = 0.026), and global cortical atrophy (adjusted OR 5.730, 95% CI, 1.128-29.101, p = 0.035) were independently associated with VCI in post-stroke patients. CONCLUSIONS: Lower education, female sex, recurrent stroke and global cortical atrophy were associated with VCI in Chinese stroke patients.

Association of C7673T polymorphism in apolipoprotein B gene with ischemic stroke in the Chinese population: a meta-analysis.

BACKGROUND: Epidemiological studies have evaluated the association between the C7673T polymorphism in apolipoprotein B (apoB) gene and ischemic stroke (IS), but the results are still debatable even in the Chinese population. This meta-analysis was therefore designed to clarify these controversies. METHODS: All of the relevant studies were identified from PubMed, Embase, Chinese National Knowledge Infrastructure database and Chinese Wanfang database up to 31 October 2014. Statistical analyses were conducted with Revman 5.2 and STATA 12.0 software. Odds ratio (OR) with 95% confidence interval (CI) values were applied to evaluate the strength of the association. A fixed or random effect model was selected for pooling data based on the heterogeneity test. Publication bias was assessed by Begg's test and Egger's test. RESULTS: A significant association was found between the C7673T polymorphism in apoB gene and IS under the heterozygous genetic model (OR = 1.868, 95% CI = 1.160-3.007) and the allelic genetic model (OR = 1.742, 95% CI = 1.294-2.346), respectively. In the subgroup analysis by the geographic region, T allele could increase the risk of IS in northern Chinese (OR = 2.359, 95% CI: 1.425-3.907), but not in southern Chinese individuals (OR = 1.485, 95% CI: 0.778-2.832). Further stratification for source of controls showed that statistical significance was found among the population-based studies. CONCLUSION: Our meta-analysis revealed that C7673T polymorphism in apoB gene was significantly associated with increased IS risk in the Chinese population.

Validation of NINDS-CSN neuropsychological battery for vascular cognitive impairment in Chinese stroke patients.

BACKGROUND: The NINDS-Canadian Stroke Network (NINDS-CSN) recommended a neuropsychological battery of three protocols to diagnose vascular cognitive impairment (VCI), however, due to culture and language differences, the battery cannot be directly used in China. Validation of the battery in mandarin Chinese is lacking. Our study investigated the reliability and validity of the adapted Chinese versions of the battery in stroke patients with high probability of VCI. METHODS: Fifty mild stroke patients (median of National Institute of Health Stroke Scale [NIHSS] score, 2) and 50 stroke-free normal controls were recruited. All subjects' demographics, clinical history, and stroke severity were recorded. The NINDS-CSN neuropsychological protocols were adapted into the Chinese versions. External validity, defined as the ability of the protocol summary scores to differentiate stroke patients from controls, was determined using the area under the curve (AUC) of the receiver operating characteristics curve. We also evaluated internal consistency and intra-rater reliability. RESULTS: Stroke patients performed significantly poorer than controls on all three protocols (F statistics between 24.9 and 31.4, P < 0.001). External validity evaluated by AUCs was 0.88 (95% confidence interval [CI], 0.81-0.95), 0.88 (95% CI, 0.81-0.94), and 0.86 (95% CI, 0.79-0.94) for the 60-min, 30-min and 5-min protocols, respectively. Cronbach's alpha of the cognitive tests was 0.87 for all subjects. Intra-rater reliability was acceptable with intraclass correlation coefficients 0.90, 0.83 and 0.75 for the 60-min, 30-min and 5-min protocols, respectively. CONCLUSIONS: The adapted Chinese versions of three NINDS-CSN neuropsychological protocols were valid and reliable for assessing VCI in Chinese patients with mild stroke.

Telephone-based cognitive screening for stroke patients in China.

BACKGROUND: Valid telephone assessment for cognitive impairment is lacking in stroke settings. We investigated the feasibility and validity of the 5-minute National Institute of Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) protocol and six-item screener (SIS) in stroke patients by telephone administration. METHODS: Patients were assessed with a comprehensive face-to-face neuropsychological assessment after three months of stroke onset, followed by the 5-minute NINDS-CSN protocol (30 points) and SIS (6 points) at least one month later. Administration time was recorded for the telephone tests. Validity of both tests was determined using the area under the receiver operating characteristics curve (AUC). RESULTS: Eighty-nine patients (age, 62.9 ± 8.6 years; male, 65.2%) received a face-to-face assessment and 80 completed telephone tests. The time required to administer the 5-minute NINDS-CSN protocol was 4.3 ± 1.0 minutes, and SIS 57.3 ± 17.7 seconds. Validity of detecting cognitive impairment as assessed by AUC was 0.86 (95% CI, 0.78-0.94) for 5-minute NINDS-CSN protocol, and 0.74 (95% CI, 0.63-0.85) for SIS. Sensitivity and specificity were optimal with the cut-off values of 23.5/24 for the 5-minute NINDS-CSN protocol, and 4/5 for SIS. CONCLUSIONS: Both the telephone-based 5-minute NINDS-CSN protocol and SIS were feasible and valid in screening cognitive impairment after stroke in China.

Enhancing the yield of Xenocoumacin 1 in Xenorhabdus nematophila YL001 by optimizing the fermentation process.

Xenocoumacin 1 (Xcn 1), antibiotic discovered from secondary metabolites of Xenorhabdus nematophila, had the potential to develop into a new pesticide due to its excellent activity against bacteria, oomycetes and fungi. However, the current low yield of Xcn1 limits its development and utilization. To improve the yield of Xcn1, response surface methodology was used to determine the optimal composition of fermentation medium and one factor at a time approach was utilized to optimize the fermentation process. The optimal medium composed of in g/L: proteose peptone 20.8; maltose 12.74; K2HPO4 3.77. The optimal fermentation conditions were that 25 °C, initial pH 7.0, inoculum size 10%, culture medium 75 mL in a 250 mL shake flask with an agitation rate of 150 rpm for 48 h. Xenorhabdus nematophila YL001 was produced the highest Xcn1 yield (173.99 mg/L) when arginine was added to the broth with 3 mmol/L at the 12th h. Compared with Tryptic Soy Broth medium, the optimized fermentation process resulted in a 243.38% increase in Xcn1 production. The obtained results confirmed that optimizing fermentation technology led to an increase in Xcn1 yield. This work would be helpful for efficient Xcn1 production and lay a foundation for its industrial production.

Antifungal Activity and Mechanism of Xenocoumacin 1, a Natural Product from Xenorhabdus nematophila against Sclerotinia sclerotiorum.

Sclerotinia sclerotiorum (Lib.) de Bary, a polyphagous necrotrophic fungal pathogen, has brought about significant losses in agriculture and floriculture. Until now, the most common method for controlling S. sclerotiorum has been the application of fungicides. Xenocoumacin 1 (Xcn1) is a potential biopesticide having versatile antimicrobial activities, generated by Xenorhabdus nematophila. This study was intended to isolate Xcn1 from X. nematophila YL001 and clarify its efficacies for S. sclerotiorum control. Xcn1 demonstrated a wider antifungal spectrum against 10 plant-pathogenic fungi. It also exhibited a strong inhibitory effect on the mycelial growth of S. sclerotiorum with an EC50 value of 3.00 µg/mL. Pot experiments indicated that Xcn1 effectively inhibited disease extension on oilseed rape and broad bean plants caused by S. sclerotiorum. Morphological and ultrastructural observations revealed that the hyphae of S. sclerotiorum became twisted, shriveled, and deformed at the growing points after treatment with Xcn1 at 3.00 µg/mL and that the subcellular fractions also became abnormal concurrently, especially the mitochondrial structure. Moreover, Xcn1 also increased cell membrane permeability and decreased the content of exopolysaccharide as well as suppressing the activities of polygalacturonase and cellulase of S. sclerotiorum, but exerted no effects on oxalic acid production. This study demonstrated that Xcn1 has great potential to be developed as a new biopesticide for the control of S. sclerotiorum.

Transcriptome analysis of adipose tissue in grazing cattle: Identifying key regulators of fat metabolism.

The taste and tenderness of meat are the main determinants of carcass quality in many countries. This study aimed to discuss the mechanisms of intramuscular fat deposition in grazing and house-breeding cattle. We performed transcriptome analysis to characterize messenger RNA and microRNA (miRNA) expression profiles. A total of 456 and 66 differentially expressed genes (DEGs) and differentially expressed (DE) miRNAs were identified in the adipose tissue of grazing and house-breeding cattle. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified the association of DEGs with fatty acid metabolism, fatty acid degradation, peroxisome proliferator-activated receptors signaling pathway, adenosine monophosphate-activated protein kinase signaling pathway, adipocytokine signaling pathway, and the association of DE miRNAs with mitogen-activated protein kinase signaling pathway. Apolipoprotein L domain containing 1, pyruvate dehydrogenase kinase 4, and sphingosine-1-phosphate lyase 1 genes may be the key regulators of fat metabolism in grazing cattle. Finally, we found that miR-211 and miR-331-5p were negatively correlated with the elongation of very long-chain fatty acids protein 6 (ELOVL6), and miR-331-5p might be the new regulator involved in fat metabolism. The results indicated that ELOVL6 participated in various functions and pathways related to fat metabolism. Meanwhile, miR-331-5p, as a new regulator, might play an essential role in this process. Our findings laid a more in-depth and systematic research foundation for the formation mechanism and characteristics of adipose tissue in grazing cattle.

Efficient chemo-immunotherapy leveraging minimalist electrostatic complex nanoparticle as "in situ" vaccine integrated tumor ICD and immunoagonist.

INTRODUCTION: Immunotherapy has unprecedentedly opened up a series of neoteric tactics for cancer treatment. As a burgeoning approach, chemo-immunotherapy has innovatively expanded the accomplishments of conventional chemotherapeutic agents for cancer governing. OBJECTIVES: An efficacious chemo-immunotherapy leveraging minimalist electrostatic complex nanoparticle (NP) integrated tumor immunogenic cell death (ICD) and immunoagonist was developed as a watertight "in situ" vaccine for cancer therapy through convenient intratumoral administration with minimized systemic toxicity. METHODS: Chemical-modified pH-sensitive cis-aconityl-doxorubicin (CAD) and immunoadjuvant unmethylated cytosine-phosphate-guanine (CpG) were co-packaged by polycationic polyethylenimine (PEI) though electrostatic-interaction to construct PEI/CpG/CAD NP. By intratumoral injection, this positively charged NP could be detained at tumor site and endocytosed by tumor cells effortlessly. Then, doxorubicin was released through cis-aconityl cleavage induced by endosomal-acidity and further triggered tumor ICD, the moribund tumor cells could release damage-associated molecular patterns (DAMPs) to recruit dendritic cells (DCs). Meanwhile, the entire tumor debris derived into diversified antigens and cooperated with immunostimulatory CpG to excite DC maturation and activated comprehensive antitumor immunity. RESULTS: Prominent tumor suppression was achieved in aggressive mouse melanoma tumor model, which verified the feasibility and effectiveness of this minimalist CAD/CpG-codelivered NP. CONCLUSION: This study has provided a convenient and promising paradigm for potent cancer chemo-immunotherapy.

A transposon insertion in the promoter of OsUBC12 enhances cold tolerance during japonica rice germination.

Low-temperature germination (LTG) is an important agronomic trait for rice (Oryza sativa). Japonica rice generally has greater capacity for germination at low temperatures than the indica subpopulation. However, the genetic basis and molecular mechanisms underlying this complex trait are poorly understood. Here, we report that OsUBC12, encoding an E2 ubiquitin-conjugating enzyme, increases low-temperature germinability in japonica, owing to a transposon insertion in its promoter enhancing its expression. Natural variation analysis reveals that transposon insertion in the OsUBC12 promoter mainly occurs in the japonica lineage. The variation detected in eight representative two-line male sterile lines suggests the existence of this allele introgression by indica-japonica hybridization breeding, and varieties carrying the japonica OsUBC12 locus (transposon insertion) have higher low-temperature germinability than varieties without the locus. Further molecular analysis shows that OsUBC12 negatively regulate ABA signaling. OsUBC12-regulated seed germination and ABA signaling mainly depend on a conserved active site required for ubiquitin-conjugating enzyme activity. Furthermore, OsUBC12 directly associates with rice SUCROSE NON-FERMENTING 1-RELATED PROTEIN KINASE 1.1 (OsSnRK1.1), promoting its degradation. OsSnRK1.1 inhibits LTG by enhancing ABA signaling and acts downstream of OsUBC12. These findings shed light on the underlying mechanisms of UBC12 regulating LTG and provide genetic reference points for improving LTG in indica rice.

The Characterization of Subcutaneous Adipose Tissue in Sunit Sheep at Different Growth Stages: A Comprehensive Analysis of the Morphology, Fatty Acid Profile, and Metabolite Profile.

Adipose tissue is a crucial economically significant trait that significantly influences the meat quality and growth performance of domestic animals. To reveal the changes in adipose tissue metabolism during the growth of naturally grazing sheep, we evaluated the thickness, adipocyte morphology, fatty acid profile, and metabolite profile of subcutaneous adipose tissue (SAT) from naturally grazing Sunit sheep at 6, 18, and 30 months of age (referred to as Mth-6, Mth-18, and Mth-30, respectively). The fat thickness and adipocyte number were significantly increased with the growth of the sheep (p < 0.05), and the increase of which from Mth-18 to Mth-30 was less than that from Mth-6 to Mth-18. Additionally, the alpha-linolenic acid metabolism was enhanced and fatty acid (FA) elongation increased with growth. The metabolomic analysis revealed 76 differentially expressed metabolites (DEMs) in the SAT in different growth stages. Interestingly, we observed elongation of FAs in lipids correlated with sheep growth. Furthermore, the expression of acylcarnitines was downregulated, and fatty acid amides, aspartic acid, acetic acid and phosphocholine were upregulated in Mth-18 and Mth-30 compared to Mth-6. Altogether, the study found that the difference in SAT in Mth-6 was great compared to Mth-18 and Mth-30. An increase in fat deposition via adipocyte proliferation with the growth of the sheep in naturally grazing. The DEMs of acylcarnitines, fatty acid amides, aspartic acid, acetic acid, and phosphocholine emerged as potential key regulators of adipose tissue metabolism. These findings illustrate the variation in and metabolic mechanism of sheep adipose tissue development under natural grazing, thus providing valuable insights into improving the edible quality of sheep meat and developing the mutton sheep industry.