Paranasal sinus occupancy assessed from magnetic resonance images-associations with clinical indicators in patients with systemic lupus erythematosus.

OBJECTIVES: Nasal, paranasal sinus and mucosal disorders are common symptoms in autoimmune rheumatic diseases. Soft tissue changes and fluid accumulation in the osteomeatal complexes and paranasal sinuses manifest as opaqueness on radiological images which can be assessed using visual scoring and computational methods on CT scans, but their results do not always correlate. Using MRI, we investigate the applicability of different image analysis methods in SLE. METHODS: We assessed paranasal sinus opaqueness on MRI from 51 SLE patients, using three visual scoring systems and expert-delineated computational volumes, and examined their association with markers of disease activity, inflammation, endothelial dysfunction and common small vessel disease (SVD) indicators, adjusting for age and sex-at-birth. RESULTS: The average paranasal sinus volume occupation was 4.55 (6.47%) [median (interquartile range) = 0.67 (0.25-2.65) ml], mainly in the maxillary and ethmoid sinuses. It was highly correlated with Lund-Mackay (LM) scores modified at 50% opaqueness cut-off (Spearman's ρ: 0.71 maxillary and 0.618 ethmoids, P < 0.001 in all), and with more granular variations of the LM system. The modified LM scores were associated with SVD scores (0: B = 5.078, s.e. = 1.69, P = 0.0026; 2: B = -0.066, s.e. = 0.023, P = 0.0045) and disease activity (anti-dsDNA: B = 4.59, s.e. = 2.22, P = 0.045; SLEDAI 3-7: 2.86 < B < 4.30; 1.38 < s.e. < 1.63; 0.0083 ≤ P ≤ 0.0375). Computationally derived percent opaqueness yielded similar results. CONCLUSION: In patients with SLE, MRI computational assessment of sinuses opaqueness and LM scores modified at a 50% cut-off may be useful tools in understanding the relationships among paranasal sinus occupancy, disease activity and SVD markers.

BAG3 Overexpression Attenuates Ischemic Stroke Injury by Activating Autophagy and Inhibiting Apoptosis.

BACKGROUND: The ubiquitin-proteasome system (UPS) and autophagy are 2 major protein degradation pathways in eukaryotic cells. We previously identified a switch from UPS to autophagy with changes in BAG3 (B-cell lymphoma 2-associated-athanogene 3) expression after cerebral ischemia in mice. BAG3 is an antiapoptotic-cochaperone that is directly involved in cellular protein quality control as a mediator for selective macroautophagy. Here, we aimed to investigate the role of BAG3 in ischemic stroke. METHODS: Middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen-glucose deprivation/reoxygenation were used to mimic cerebral ischemia in vivo and in vitro. The UPS inhibitor MG132 and autophagy inhibitor 3-MA (3-methyladenine) were administered to mice to identify how BAG3 was involved after MCAO/R. Adeno-associated virus and lentiviral vector were used to regulate BAG3 expression in vivo and in vitro, respectively. Behavioral tests, 2,3,5-triphenyltetrazolium chloride staining, and Hematoxylin & Eosin staining were performed to evaluate cerebral injury following MCAO/R, and a Cell Counting kit-8 assay was conducted to assess oxygen-glucose deprivation/reoxygenation-induced injury in cells. Brain tissues and cell lysates were collected and analyzed for UPS activation, autophagy, and apoptosis. RESULTS: The UPS inhibitor alleviated MCAO injury in mice and increased autophagy and BAG3 expression, whereas the autophagy inhibitor exacerbated MCAO/R-induced injury. In addition, BAG3 overexpression significantly improved neurological outcomes, reduced infarct volume in vivo, and enhanced cell survival by activating autophagy and suppressing apoptosis in vitro. CONCLUSIONS: Our findings indicate that BAG3 overexpression activates autophagy and inhibits apoptosis to prevent cerebral ischemia/reperfusion and hypoxia/reoxygenation injury, suggesting a potential therapeutic benefit of BAG3 expression in cerebral ischemia.

TET2-mediated Cdkn2A DNA hydroxymethylation in midbrain dopaminergic neuron injury of Parkinson's disease.

It has been reported that abnormal epigenetic modification is associated with the occurrence of Parkinson's disease (PD). Here, we found that a ten-eleven translocation 2 (TET2), a staff of the DNA hydroxylases family, was increased in dopaminergic neurons in vitro and in vivo. Genome-wide mapping of DNA 5-hydroxymethylcytosine (5-hmC)-sequencing has revealed an aberrant epigenome 5-hmC landscape in 1-methyl-4-phenylpyridinium iodide (MPP+)-induced SH-SY5Y cells. The TET family of DNA hydroxylases could reverse DNA methylation by oxidization of 5-methylcytosine (5-mC) to 5-hmC. However, the relationship between modification of DNA hydroxymethylation and the pathogenesis of PD is not clear. According to the results of 5-hmC-sequencing studies, 5-hmC was associated with gene-rich regions in the genomes related to cell cycle, especially gene-cyclin-dependent kinase inhibitor 2A (Cdkn2A). Downregulation of TET2 expression could significantly rescue MPP+-stimulated SH-SY5Y cell damage and cell cycle arrest. Meanwhile, knockdown of Tet2 expression in the substantia nigra pars compacta of MPTP-induced PD mice resulted in attenuated MPTP-induced motor deficits and dopaminergic neuronal injury via p16 suppression. In this study, we demonstrated a critical function of TET2 in PD development via the CDKN2A activity-dependent epigenetic pathway, suggesting a potential new strategy for epigenetic therapy.

Rotenone, an environmental toxin, causes abnormal methylation of the mouse brain organoid's genome and ferroptosis.

More and more reports have pointed out that rotenone, as an insecticide, has high neurotoxicity and reproductive toxicity to livestock and mammals. As a highly physiological correlation system of internal organs, quasi-organs have great potential in the fields of drug toxicity and efficacy test, toxicology research, developmental biology and so on. In this study, brain organs (mBOs) derived from mouse neural stem cells were used to investigate the effects of rotenone on the physiological activity and epigenetic modification of mBOs. At the same time, Rotenone could significantly stimulate the increase of the concentration of LPO, lactic acid and hydroxyl radical in mBOs, and inhibit the expression of neuronal marker Tuj1, CHAT, PAX6 and so on. Further analysis showed that Rotenonem could induce mitochondrial damage in mBOs. The results of qPCR and Western blot showed that Rotenone could up-regulate the expressions of ferroptosis promoting protein p53, Cox2 and so on, while inhibit the expressions of negative regulatory protein of ferroptosis GPX4, FTH1, SLC7A11. In addition, the results of RRBS-Seq sequencing showed that the methylation modification at DMR level in Rotenone-treated mBOs group was significantly higher than that in Ctrl group. The results of KEGG analysis showed that compared with Ctrl, the genes with hypermethylation of promoter and Genebody in Rotenone-treated mBOs were mainly located in the Neuro active ligand-receptor interaction signal transduction pathway. In summary, rotenone can significantly lead to abnormal methylation of mouse brain organs, and lead to the loss of normal physiological function of neurons by inducing ferroptosis.

Restless abdomen: a spectrum or a phenotype variant of restless legs syndrome?

BACKGROUND: With the growing awareness of restless legs syndrome (RLS), sensory disorders similar to RLS but initially confined to the arms, abdomen, and perineum have been reported. One of them is restless abdomen, which refers to a restless sensation in abdomen. Our study is designed to evaluate the clinical phenotype of restless abdomen and investigate its relationship with RLS. METHODS: We enrolled 10 patients with restless abdomen according to RLS diagnostic criteria, excluding the requiring of leg involvement. Laboratory examinations were performed to exclude mimics and notable comorbidities. RESULTS: All 10 patients had RLS like symptoms in the abdomen and otherwise satisfied all other RLS diagnostic criteria, and responded to dopaminergic therapy. CONCLUSIONS: Neurologists and gastroenterologists should be aware that RLS-related restlessness can occur in extra-leg anatomy in the absence of episodes of worsening or augmentation of restlessness.

Neurology practice and stroke services across East China: a multi-site, county-level hospital-based survey.

BACKGROUND: Neurological disorders are an economic and public health burden which requires efficient and adequate medical resources. Currently, little is known about the status of the quality of neurological care services available in China. As neurological primary care is mostly provided at the county hospital level, investigation of this geographical level is required. The aim of this study is to evaluate currently available neurology care services in Yangtze River Delta Urban Agglomerations in east China. METHODS: A multi-site, county-level hospital-based observational survey was conducted in east China from January 2017 to December 2017. A questionnaire was made to assess hospital and the departmental patient care capabilities, human resources and technical capacity in neurology departments. RESULTS: Of 228 hospitals across the Yangtze River Delta Urban Agglomerations, 217 documents were returned. Of these, 22 were excluded due to invalid hospital information or duplicate submission. Overall, most hospitals have neurology departments (162, 83.1%) while less than half of the hospitals have a stroke center (80, 41.0%) and neurology emergency department (46, 23.6%). Among 162 hospitals with neurology department, 5 were excluded due to inadequate sharing, leaving 157 hospitals for analysis. About 84.1% of these neurology departments can administer intravenous thrombolysis while about one third of them has the ability to perform arterial thrombectomy (36.9%). In addition, 46.2% of hospitals can carry out computed tomography angiography (CTA) in emergency room. Tertiary care hospitals are much more equipped with modern medical resources compared to the secondary hospitals. In four administrative regions, the neurology services are better in more economically advanced regions. CONCLUSIONS: Neurological care services need to be enhanced at the county-level hospitals to improve health care delivery.

Restless legs syndrome in end stage renal disease patients undergoing hemodialysis.

BACKGROUND: The prevalence of Restless legs syndrome (RLS) in End Stage Renal Disease (ESRD) patients is higher than that in the general population. However, the associations of RLS within the ESRD population are inconsistent and RLS is usually neglected in dialysis centers, although it impairs the life quality among ESRD patients. We aim to investigate the prevalence of RLS in patients with ESRD undergoing maintenance hemodialysis and evaluate the risk factors of developing RLS and the effect of RLS on quality of life among ESRD patients. METHODS: ESRD patients undergoing maintenance hemodialysis in Shanghai General Hospital dialysis unit from July 2016 to October 2016 were enrolled in the study. RLS was diagnosed according to the criteria of the International Restless Legs Syndrome Study Group (IRLSSG). IRLSSG Severity Scale was used to evaluate the severity of RLS. Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality, and Hospital Anxiety and Depression Scale (HADS) was used to estimate anxiety and depression. Serologic and historic variables were analyzed to determine predictors of RLS in the ESRD population. RESULTS: A total of 137 ESRD patients were enrolled. The prevalence of RLS among the ESRD patients was 20.44%. The risk of RLS was increased significantly in females (OR = 2.729, p = 0.032) and daily alcohol drinkers (OR = 4.716, p = 0.022). RLS increased the risks of sleep disorders (25/28, 89.3% vs 73/109, 67.0%, p = 0.02) and sedative hypnotics intake (7/28, 25.0% vs 10/109, 9.2%, p = 0.047) and impaired the sleep quality (7/109 vs 11/28, p = 0.001) according to PSQI sum scores. CONCLUSION: A high RLS prevalence among the ESRD patients undergoing hemodialysis was confirmed. ESRD patients who are women and drinking alcohol have a higher risk of RLS. The sleep quality was significantly impaired and sleeping medication use was more common among the ESRD patients with RLS.

Planting age of peach affects soil metal accumulation and distribution in soil profile.

Changes in soil available metal, particularly, distribution changes in the soil profile relative to long-term peach cultivation, have not been studied thoroughly. Soil samples at depths of up to 100 cm in the soil profile were taken from peach orchards that were cultivated for 7, 15, and 50 years. We analyzed available metals (Zn, Fe, Mn, Al, and Cu), soil pH, total nitrogen (TN), nitrate nitrogen (NO3--N), and ammonium nitrogen (NH4+-N) in different soil layers (0-10 cm, 10-20 cm, 20-40 cm, 40-60 cm, 60-80 cm, and 80-100 cm). The results showed that available metals were enriched in the topsoil (0-20 cm) after 50 years of peach cultivation, with the highest contents of available Fe (1.0 mg kg-1), Al (188.2 mg kg-1), and Cu (0.7 mg kg-1) in the 10-20 cm layer and Zn (11.7 mg kg-1) in the 0-10 cm layer. The soil pH in the 0-40 cm layer decreased with increasing periods of peach cultivation, with the lowest pH (4.2) in the 10-20 cm layer after 50 years of peach cultivation. Soil pH was negatively correlated with available metals (R = - 0.579, P < 0.05 for Zn, R = - 0.727, P < 0.01 for Fe, R = - 0.792, P < 0.01 for Mn, R = - 0.690, P < 0.01 for Al, and R = - 0.783, P < 0.01 for Cu). The highest contents of NO3--N (212.9 mg kg-1) and NH4+-N (10.2 mg kg-1) were observed in the 50-year-old 0-10 cm layer, and soil pH was correlated negatively with the contents of NO3--N and NH4+-N. Overall, our results indicated that the continuous input of nitrogen fertilizers may play an important role in soil acidification, and soil acidification may result in high accumulation of available metals in soil after long-term peach cultivation.

Shanghai cognitive intervention of mild cognitive impairment for delaying progress with longitudinal evaluation-a prospective, randomized controlled study (SIMPLE): rationale, design, and methodology.

BACKGROUND: Mild cognitive impairment is an early stage of Alzheimer's disease. Increasing evidence has indicated that cognitive training could improve cognitive abilities of MCI patients in multiple cognitive domains, making it a promising therapeutic approach for MCI. However, the effect of long-time training has not been widely explored. It is also necessary to evaluate the extent how it could reduce the convertion rate from MCI to AD. METHODS/DESIGN: The SIMPLE study is a multicenter, randomized, single-blind prospective clinical trial assessing the effects of computerized cognitive training on different cognitive domains in MCI patients. It is carried out in 7 centers in China. The study population includes patients aged 50-85, and they are randomly allocated to the training or control group. The primary outcome is to compare the conversion rate of MCI within 36-month follow-up. Structural and functional MRI will be used to interpret the effect of cognitive training. The cognitive training comprises a variety of games related with cognitive domains such as attention, memory, visualspatial ability and executive function. We cautiously set 50% reduction in the rate of conversion as estimated effect. With 80-90% statistical power and 12% as the overall probability of conversion within the study period, 600-800 patients are finally required in the study. The first patent has been recruited in April 2017. DISCUSSION: Previous studies suggested the benefit of cognitive training for MCI, but neither long-time nor Chinese culture were investigated. The SIMPLE designs and utilizes an improved computerized cognitive training approach and assesses its effects on MCI progress. In addition, neural activities explaining the effects on cognition function changes will be revealed, which could in turn to imply more useful therapeutic approaches. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03119051.

SIRT3 deacetylated and increased citrate synthase activity in PD model.

SIRT3 have been found to be neuroprotective in many neurological diseases, but its detail mechanism is only partially understood. In this study, MPP+ was used to treat SH-SY5Y cells as the cellular model of PD to test the role of SIRT3 and the mechanism may be involved in. We focused on the changes and relationship between SIRT3 and the key mitochondrial enzymes citrate synthase (CS) and isocitrate dehydrogenase 2 (IDH2). We found MPP+ decreased SIRT3 expression. And our results showed that the enzymatic activities of CS and IDH2 were significantly reduced in MPP+ treatment cells, while protein acetylation of CS and IDH2 increased. However overexpressed-SIRT3 partially reversed at least, the decline of CS activity and the increase of CS protein acetylation. IDH2 did not showed the same changes. The study suggested that SIRT3 deacetylated and activated CS activity. Hence, we conclude that SIRT3 exhibits neuroprotection via deacetylating and increasing mitochondrial enzyme activities.

The epigenetic regulation of HIF-1α by SIRT1 in MPP(+) treated SH-SY5Y cells.

Both silent information regulator 1 (SIRT1) and hypoxia inducible factor 1 (HIF-1) have been found to play important roles in the pathophysiology of Parkinson's disease (PD). However, their mechanisms and their relationship still require further study. In the present study, we focused on the change and relationship of SIRT1 and HIF-1α in PD. PD cell models were established by using methyl-4-phenylpyridinium (MPP(+)), which induced inhibition of cell proliferation, cell cycle arrest and apoptosis. We found that the expression of HIF-1α and its target genes VEGFA and LDHA increased and that SIRT1 expression was inhibited in MPP(+) treated cells. With further analysis, we found that the acetylation of H3K14 combined with the HIF-1α promoter was dramatically increased in cells treated with MPP(+), which resulted in the transcriptional activation of HIF-1α. Moreover, the acetylation of H3K14 and the expression of HIF-1α increased when SIRT1 was knocked down, suggesting that SIRT1 was involved in the epigenetic regulation of HIF-1α. At last, phenformin, another mitochondrial complex1 inhibitor, was used to testify that the increased HIF-1a was not due to off target effects of MPP(+). Therefore, our results support a link between PD and SIRT1/HIF-1α signaling, which may serve as a clue for understanding PD.

Effects of volatile organic compounds produced by Bacillus amyloliquefaciens on the growth and virulence traits of tomato bacterial wilt pathogen Ralstonia solanacearum.

The production of volatile organic compounds (VOCs) by microbes is an important characteristic for their selection as biocontrol agents against plant pathogens. In this study, we identified the VOCs produced by the biocontrol strain Bacillus amyloliquefaciens T-5 and evaluated their impact on the growth and virulence traits of tomato bacterial wilt pathogen Ralstonia solanacearum. The results showed that the VOCs of strain T-5 significantly inhibited the growth of R. solanacearum in agar medium and in soil. In addition, VOCs significantly inhibited the motility traits, root colonization, biofilm formation, and production of antioxidant enzymes and exopolysaccharides by R. solanacearum. However, no effect of VOCs on the production of hydrolytic enzymes by R. solanacearum was observed. The strain T-5 produced VOCs, including benzenes, ketones, aldehydes, alkanes, acids, and one furan and naphthalene compound; among those, 13 VOCs showed 1-10 % antibacterial activity against R. solanacearum in their produced amounts by T-5; however, the consortium of all VOCs produced on agar medium, in sterilized soil, and in natural soil showed 75, 62, and 85 % growth inhibition of R. solanacearum, respectively. The real-time PCR analysis further confirmed the results when the expression of different virulence- and metabolism-related genes in R. solanacearum cells was decreased after exposure to the VOCs of strain T-5. The results of this study clearly revealed the significance of VOCs in the control of plant pathogens. This information would help to better comprehend the microbial interactions mediated by VOCs in nature and to develop safer strategies to control plant disease.

A retrospective study of 23 cases with subacute combined degeneration.

PURPOSE: To study retrospectively the diverse presentations, ancillary tests and neuroimaging in patients with subacute combined degeneration (SCD). METHODS: Twenty-three Chinese patients with SCD were included in this study. The clinical presentations and laboratory data including comprehensive metabolic panel, serum folic acid, vitamin B12 levels, gastroscopy and images of spinal cord on magnetic resonance imaging (MRI) were evaluated. Rating scales for localizations of lesions and functional disabilities were used to define the severity of neurological impairment. RESULTS: No difference was found between men and women in the age of disease onset. For most of the patients, sensory symptoms, oftentimes as initial symptoms, occurred earlier than motor symptoms. The signs of the disease were more obvious than the symptoms. Six patients had sensory deficit levels mimicking transverse myelopathy. Anemia was not always detected in our patients with SCD. Normal or even elevated serum levels of vitamin B12 were found in seven patients. Spinal cord lesions on MRI were observed in six patients and the clinical and neuroimaging findings were not necessarily consistent. CONCLUSIONS: The sensory symptoms occur earlier than the motor symptoms in SCD patients. SCD patients may have sensory deficit level. Normal or even elevated serum levels of vitamin B12 may occur in patients with SCD.

Rotenone affects p53 transcriptional activity and apoptosis via targeting SIRT1 and H3K9 acetylation in SH-SY5Y cells.

The protein deacetylase SIRT1 has been recognized to exert its protective effect by directly deacetylasing histone and many other transcriptional factors including p53. However, the effect of SIRT1 on p53 expression at the transcriptional level still remains to be elucidated. In this study, we found that rotenone treatment decreased cell viability, induced apoptosis, reduced SIRT1 level, and promoted p53 expression. Pre-treatment with resveratrol, a SIRT1 activator, could attenuate rotenone-induced cell injury and p53 expression, whereas down-regulation of SIRT1 directly increased p53 expression. Moreover, chromatin immunoprecipitation experiments showed that SIRT1 bound to H3K9 within the p53 promoter region, and this binding resulted in decreased H3K9 acetylation and increased H3K9 tri-methylation, thereby inhibiting p53 gene transcription. In conclusion, our data indicate that rotenone promotes p53 transcription and apoptosis through targeting SIRT1 and H3K9. This leads to nigrostriatal degeneration, the main pathogenic mechanism of motor features of Parkinson's disease. SIRT1, a deacetylase enzyme, has neuroprotective effects for Parkinson's disease via targeting various factors. Resveratrol activated SIRT1 can target H3K9 and regulate p53 gene expression at the transcriptional level, thus inhibiting p53 transcription to enhance neuroprotection, alleviating rotenone induced dopaminergic neurodegeneration. We think these findings should provide a new strategy for the treatment of Parkinson's disease.

Effects of volatile organic compounds from Streptomyces albulus NJZJSA2 on growth of two fungal pathogens.

A Streptomyces albulus strain NJZJSA2 was isolated from the forest soil sample of Tzu-chin Mountain (Nanjing China) and identified based on its morphological and physiological properties and 16S rDNA gene sequence analysis. The strain S. albulus NJZJSA2 was evaluated for the production of antifungal volatile organic compounds (VOCs) against two fungal pathogens. Results showed that the VOCs generated by S. albulus NJZJSA2 inhibited mycelial growth of Sclerotinia sclerotiorum (SS) and Fusarium oxysporum (FO) by 100 and 56.3%, respectively. The germination of SS sclerotia and FO conidia was completely inhibited in the presence of VOCs produced by S. albulus NJZJSA2 in vitro. In soil, the VOCs delayed the germination of SS sclerotia and inhibited the germination of FO conidia for 45 days. The strain S. albulus NJZJSA2 was able to produce 13 VOCs based on GC/MS analyses. Among those, six compounds were purchased and used for the antifungal activity assay. Three relatively abundant VOCs, 4-methoxystyrene, 2-pentylfuran, and anisole were proved to have antifungal activity. Microscopy analysis showed that the pathogen hyphae were shriveled and damaged after treatment with 4-methoxystyrene. These results suggest that the S. albulus strain NJZJSA2 produce VOCs that not only reduce the growth of SS and FO, but also significantly inhibit the SS sclerotia and FO conidia. The results are useful for the better understanding of biocontrol mechanisms by S. albulus strains and will help to improve the biological control efficiency of lethal plant diseases.

Oligodendroglia-to-pericyte conversion after lipopolysaccharide exposure is gender-dependent.

To investigate the sex-dependent differentiation of Sox10 cells and their response to pathological conditions such as lipopolysaccharide (LPS) exposure or ischemia, we utilized Sox10 Cre-ERT2, tdTomato mice. Tamoxifen administration induced the expression of red fluorescent protein (RFP) in these cells, facilitating their subsequent tracking and analysis after LPS injection and ischemia via immunofluorescence staining. Propidium iodide (PI) was injected to label necrotic cells following LPS administration. We found that the conversion of Sox10 cells to pericytes in female mice was significantly higher than in male mice, especially in those exposed to LPS. After LPS injection, the number of PI+ necrotic cells were significantly greater in females than in males. Moreover, RFP+ cells did not co-localize with glial fibrillary acidic protein (GFAP) or cluster of differentiation 11b (CD11b). Similarly, after brain ischemia, RFP+ cells did not express cluster of differentiation 13 (CD13), neuronal nuclei (NeuN), GFAP, or ionised calcium binding adaptor molecule 1 (Iba-1). These findings indicate that the conversion of Sox10 cells to pericytes following LPS exposure is sex-dependent, with neither male nor female groups showing differentiation into other cell types after LPS exposure or under ischemic conditions. The differences in LPS-induced necrosis of pericytes between sexes may explain the variations in the conversion of Sox10 cells to pericytes in both sexes.

Dynamic change of neutrophil-to-lymphocyte ratio and its predictive value of prognosis in acute ischemic stroke.

OBJECTIVE: The present research aimed to explore the dynamic change of the neutrophil-to-lymphocyte ratio (NLR) and its relationship with functional outcome following an acute ischemic stroke (AIS), whether receiving intravenous thrombolysis (IVT) or not. METHODS: We retrospectively analyzed data that were prospectively acquired from patients with AIS treated with IVT or not. For patients receiving IVT, the NLR was based on a blood test performed prior to IVT (d0) and at different time points after disease onset (d1, d3, d7). In addition, in the non-IVT group, the NLR was obtained at different time points after disease onset (d1, d3, d7). Follow-ups were performed 3 months after onset via telephone. In addition, a good outcome was defined as a modified Rankin scale (mRS) ≤1; a poor outcome means 2 ≤ mRS ≤ 6. RESULTS: A total of 204 AIS patients were included in this study. The NLR presented a dynamic change as it increased to its peak at day 1 and gradually declined to its baseline at day 7, no matter whether patients were receiving IVT or not. Patients with poor outcomes have a higher NLR at various time points. The results of multivariate logistic regression analysis demonstrated that the National Institutes of Health Stroke Scale (NIHSS), NLR d1, NLR d3, and NLR d7 were independently associated with functional outcomes. The area under the receiver operating characteristic curve of NLR in predicting outcomes was as follows: NLR d3 demonstrated robust predictive power within the IVT therapy cohort, whereas NLR d7 was predictive in the non-IVT cohort. However, the most potent predictor emerged as the combination of NIHSS and NLR. CONCLUSION: NLR has the potential to predicate diagnosis for AIS, especially when combined with the NIHSS score.

Deciphering soil resistance and virulence gene risks in conventional and organic farming systems.

Organic farming is a sustainable agricultural practice emphasizing natural inputs and ecological balance, and has garnered significant attention for its potential health and environmental benefits. However, a comprehensive evaluation of the emergent contaminants, particularly resistance and virulence genes within organic farming system, remains elusive. Here, a total of 36 soil samples from paired conventional and organic vegetable farms were collected from Jiangsu province, China. A systematic metagenomic approach was employed to investigate the prevalence, dispersal capability, pathogenic potential, and drivers of resistance and virulence genes across both organic and conventional systems. Our findings revealed a higher abundance of antibiotic resistance genes (ARGs), biocide resistance genes (BRGs), and virulence factor genes (VFGs) in organic farming system, with ARGs exhibiting a particularly notable increase of 10.76% compared to the conventional one. Pathogens such as Pseudomonas aeruginosa, Escherichia coli, and Mycobacterium tuberculosis were hosts carrying all four gene categories, highlighting their potential health implications. The neutral community model captured 77.1% and 71.9% of the variance in community dynamics within the conventional and organic farming systems, respectively, indicating that stochastic process was the predominant factor shaping gene communities. The relative smaller m value calculated in organic farming system (0.021 vs 0.023) indicated diminished gene exchange with external sources. Moreover, farming practices were observed to influence the resistance and virulence gene landscape by modifying soil properties, managing heavy metal stress, and steering mobile genetic elements (MGEs) dynamics. The study offers insights that can guide agricultural strategies to address potential health and ecological concerns.