Inhibition of JNK Signaling Overcomes Cancer-Associated Fibroblast-Mediated Immunosuppression and Enhances the Efficacy of Immunotherapy in Bladder Cancer.

Currently, only 20-40% of cancer patients benefit from immune checkpoint inhibitors. Understanding the mechanisms underlying the immunosuppressive tumor microenvironment (TME) and characterizing dynamic changes in the immunological landscape during treatment are critical for improving responsiveness to immunotherapy. Here, we identified JNK signaling in cancer-associated fibroblasts (CAFs) as a regulator of the immunosuppressive tumor microenvironment. Single-cell RNA sequencing of bladder cancer treated with a JNK inhibitor revealed enhanced cytotoxicity and effector functions of CD8+ T cells. In untreated tumors, CAFs interacted frequently with CD8+ T cells and mediated their exhaustion. JNK inhibition abrogated the immunosuppression function of CAFs by downregulating the expression of TSLP, thereby restoring CD8+ T cell cytotoxicity. In addition, blockade of CAF-derived TSLP in combination with anti-PD1 treatment promoted tumor elimination by CD8+ T cells in vivo. Collectively, these results indicate that JNK signaling plays an important immunosuppressive role in the tumor microenvironment by promoting expression of TSLP in CAFs and suggest that inhibiting JNK signaling could be a promising immunotherapeutic strategy for cancer treatment.

Prediction of Solubility of Proteins in Escherichia coli Based on Functional and Structural Features Using Machine Learning Methods.

Protein solubility is a critical parameter that determines the stability, activity, and functionality of proteins, with broad and far-reaching implications in biotechnology and biochemistry. Accurate prediction and control of protein solubility are essential for successful protein expression and purification in research and industrial settings. This study gathered information on soluble and insoluble proteins. In characterizing the proteins, they were mapped to STRING and characterized by functional and structural features. All functional/structural features were integrated to create a 5768-dimensional binary vector to encode proteins. Seven feature-ranking algorithms were employed to analyze the functional/structural features, yielding seven feature lists. These lists were subjected to the incremental feature selection, incorporating four classification algorithms, one by one to build effective classification models and identify functional/structural features with classification-related importance. Some essential functional/structural features used to differentiate between soluble and insoluble proteins were identified, including GO:0009987 (intercellular communication) and GO:0022613 (ribonucleoprotein complex biogenesis). The best classification model using support vector machine as the classification algorithm and 295 optimized functional/structural features generated the F1 score of 0.825, which can be a powerful tool to differentiate soluble proteins from insoluble proteins.

Internal migrants as drivers of long-distance cross-regional transmission of tuberculosis in China.

OBJECTIVES: Internal migrants in China frequently travel between their hometowns and the cities where they work, creating ample opportunities for cross-regional transmission of tuberculosis (TB). The aim of this study was to explore the role of internal migrants in transmitting TB across different regions and the contribution of cross-region transmission to China's TB burden. METHODS: The study included a total of 8,664 TB patients and their Mycobacterium tuberculosis isolates, collected from two large cities and three rural regions. Genomic clusters were defined as having a genomic distance of < 12-SNPs. Cross-regional clusters were defined as clusters containing patients from at least two regions, indicative of cross-regional transmission. RESULTS: A total of 2403 clustered cases (27.7%) were grouped into 845 clusters, of which 142 (16.8%) were cross-regional. An increased risk for cross-regional transmission was found for internal migrants (aOR=1.45, 95% CI 1.13-1.87), individuals less than 55 years (aOR=2.73, 95% CI 1.81-4.13), and housekeepers/factory workers (aOR=1.16, 95% CI 0.90-1.50). Among 200 cross-regional transmission events identified by transmission inference, 96 occurred between urban patients, 98 between urban and rural patients, and only 6 between rural patients. Notably, 93.5% (187/200) of cross-regional transmission events involved internal migrants. Epidemiological data showed that just 5.5% of cross-regional transmission events involved patients from the same township or neighboring counties, where the transmission likely occurred. CONCLUSION: The mobility of the internal migrant population appears to be responsible for most cross-regional transmission of TB in China. The magnitude and dynamics of cross-regional transmission should be addressed in future strategies to reduce the incidence of TB in China.

Exogenous Substances Used to Relieve Plants from Drought Stress and Their Associated Underlying Mechanisms.

Drought stress (DS) is one of the abiotic stresses that plants encounter commonly in nature, which affects their life, reduces agricultural output, and prevents crops from growing in certain areas. To enhance plant tolerance against DS, abundant exogenous substances (ESs) have been attempted and proven to be effective in helping plants relieve DS. Understanding the effect of each ES on alleviation of plant DS and mechanisms involved in the DS relieving process has become a research focus and hotspot that has drawn much attention in the field of botany, agronomy, and ecology. With an extensive and comprehensive review and summary of hundred publications, this paper groups various ESs based on their individual effects on alleviating plant/crop DS with details of the underlying mechanisms involved in the DS-relieving process of: (1) synthesizing more osmotic adjustment substances; (2) improving antioxidant pathways; (3) promoting photosynthesis; (4) improving plant nutritional status; and (5) regulating phytohormones. Moreover, a detailed discussion and perspective are given in terms of how to meet the challenges imposed by erratic and severe droughts in the agrosystem through using promising and effective ESs in the right way and at the right time.

cNPAS2 induced ß cell dysfunction by regulating KANK1 expression in type 2 diabetes.

BACKGROUND: Diabetes mellitus type 2 (T2DM) is formed by defective insulin secretion with the addition of peripheral tissue resistance of insulin action. It has been affecting over 400 million people all over the world. AIM: To explore the pathogenesis of T2DM and to develop and implement new prevention and treatment strategies for T2DM. METHODS: Receiver operating characteristic (ROC) curve analysis was used to conduct diagnostic markers. The expression level of genes was determined by reverse transcription-PCR as well as Western blot. Cell proliferation assays were performed by cell counting kit-8 (CCK-8) tests. At last, T2DM mice underwent Roux-en-Y gastric bypass surgery. RESULTS: We found that NPAS2 was significantly up-regulated in islet ß cell apoptosis of T2DM. The ROC curve revealed that NPAS2 was capable of accurately diagnosing T2DM. NPAS2 overexpression did increase the level of KANK1. In addition, the CCK-8 test revealed knocking down NPAS2 and KANK1 increased the proliferation of MIN6 cells. At last, we found that gastric bypass may treat type 2 diabetes by down-regulating NPAS2 and KANK1. CONCLUSION: This study demonstrated that NPAS2 induced ß cell dysfunction by regulating KANK1 expression in type 2 diabetes, and it may be an underlying therapy target of T2DM.

Efficacy of different analgesic strategies combined with conventional physiotherapy program for treating chronic shoulder pain: a systematic review and network meta-analysis.

BACKGROUND: This study aims to investigate the efficacy of five analgesic strategies combined with conventional physiotherapy program (CPT) in managing chronic shoulder pain. METHODS: Two authors independently screened studies, extracted data using a pre-formatted chart, and assessed bias using the Cochrane Risk of Bias tool. A network meta-analysis was performed by the Stata 17.0 and R 4.3.2 software. RESULTS: A total of 14 studies with 862 subjects were identified. These analgesic strategies included extracorporeal shock wave therapy (ESWT), suprascapular nerve block (SSNB), corticosteroid injection (CSI), hyaluronic acid injection (HAI), and kinesio taping (KT). ESWT plus CPT was the most efficient intervention in alleviating pain intensity and improving physical function. SSNB plus CPT was the optimal intervention in improving shoulder mobility. Compared to CPT alone, CSI + CPT only significantly improved the SPADI total score, but showed no difference in pain intensity or shoulder mobility. HAI + CPT showed no significant difference in improving pain intensity, physical function, or shoulder mobility compared to CPT alone. Adding KT to CPT did not yield additional benefits in improving shoulder mobility. CONCLUSION: Overall, in managing chronic shoulder pain, ESWT + CPT was the most effective intervention for reducing pain intensity and improving physical function. SSNB + CPT was optimal for enhancing shoulder mobility. Future rigorous clinical trials with larger sample sizes and higher methodological rigor are strongly required to confirm the current results.

Effect of cooking methods on flavor profiles of Xuanwei Ham: Analytical insights into aromatic composition and sensory attributes.

To examine flavor variations in Xuanwei ham due to different cooking methods, we selected one-year cured Xuanwei ham and applied four techniques: dry frying (DF), baking (BA), steaming (ST), and boiling (BO). Organoleptic evaluation revealed ST received the highest overall sensory score. High-performance liquid chromatography (HPLC) revealed that the total nucleotide content was significantly different (P < 0.05), lactic acid predominated the measured organic acids. Solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) and chromatography-electronic nose (GC-E-Nose) data indicated that ST resulting in significantly higher total volatile compounds than the other methods (P < 0.05). SPME-GC-MS detected 55 volatile compounds, and 12 characteristic flavor substances were identified using orthogonal partial least squares discriminant analysis (OPLS-DA) (VIP > 1). This study aimed to support comprehensive research on the flavor characteristics of cooked Xuanwei ham and guide the selection of appropriate processing methods.

Sex disparities of clinical manifestations in acute pulmonary embolism and predictive value for in-hospital mortality: Insights from CURES.

BACKGROUND: Pulmonary embolism (PE) is a common and potentially fatal disease, with differences in mortality rates among PE patients of different sexes. This study aims to investigate the disparities in clinical manifestations and in-hospital mortality rates between sexes in PE patients, as well as the association of clinical symptoms with in-hospital mortality. METHODS: We analyzed data from the China pUlmonary thromboembolism REgistry Study (CURES), a nationwide, multicenter, prospective registry focusing on patients with acute PE. Using propensity score matching (PSM) to pair male and female patients with PE, we explored the correlation between clinical symptoms and in-hospital mortality through multivariable regression analysis. RESULTS: A total of 15,203 patients with acute PE were enrolled, and 380 died during hospitalization. The incidence of chest pain, hemoptysis, and palpitations was significantly higher in males compared to females. The incidence of dyspnea, fever, and syncope was higher in females. Hemoptysis and dyspnea were associated with increased in-hospital mortality in males, whereas dyspnea, fever, and palpitations were linked to higher mortality in females. Overall, males exhibited a higher in-hospital mortality than females (2.9 % vs. 2.1 %, p = 0.002). After matching 13,130 patients using the PSM method, the mortality rate of males remained higher than that of females (2.7 % vs. 2.1 %, p = 0.020). CONCLUSIONS: Our study demonstrates that male patients with PE have a higher risk of in-hospital mortality than females. Significant differences in clinical symptoms between sexes are associated with increased mortality risk, emphasizing the need for clinical awareness.

Mechanistic characterisation of a fungal fusicoccane-type diterpene synthase involved in the biosynthesis of talaro-7,13-diene.

The cyclisation mechanism of the fungal fusicoccane (FC)-type diterpene synthase (DTS) TadA was investigated by extensive isotopic labelling experiments, and the pH-dependency of the product selectivity of this enzyme was explored. These studies provide new insights into the cyclisation mechanisms of FC-type DTSs.

Combined release of LL37 peptide and zinc ion from a mussel-inspired coating on porous titanium for infected bone defect repairing.

Implant-associated infections impose great burden on patient health and public healthcare. Antimicrobial peptides and metal ions are generally incorporated onto implant surface to deter bacteria colonization. However, it is still challenging to efficiently prevent postoperative infections at non-cytotoxic dosages. Herein, a scaffold based on porous titanium coated with a mussel-inspired dual-diameter TiO2 nanotubes is developed for loading dual drugs of LL37 peptide and Zn2+ with different sizes and characteristics. Benefiting from in-situ formed polydopamine layer and dual-diameter nanotubular structure, the scaffold provides an efficient platform for controllable drugs elution: accelerated release under acidic condition and sustained release for up to 28 days under neutral/alkalescent circumstances. Such combination of dual drugs simultaneously enhanced antibacterial efficacy and osteogenesis. In antibacterial test, LL37 peptide serving as bacteria membrane puncture agent, and Zn2+ acting as ROS generator, cooperatively destroyed bacterial membrane integrity and subsequently damaged bacterial DNA, endowing dual-drug loaded scaffold with remarkable bactericidal efficiency of > 92 % in vitro and > 99 % in vivo. Noteworthily, dual-drug loaded scaffold promoted bone-implant osteointegration under infectious microenvironment, overmatching single-drug load ones. It provides a promising strategy on surface modification of implant for infected bone defect repairing.

Modulating rice digestibility: Mechanisms of ultrasound, oleic acid and moist-heat treatments influence structural, physicochemical and digestive properties.

The research compared the combined effect of ultrasound (160 W, 2 min), oleic acid (15%, 11 h), and moist-heat treatment (HMT, 25% moisture content, 110 °C, 2 h) with their individual treatment on rice grains. The results showed that ultrasound treatment created pores and cracks in the rice grains, facilitating an easier penetration for oleic acid to develop amylose-oleic acid complex during HMT. Compared to native raw rice (NR), both single and combined treatments significantly altered the morphology, reduced swelling power and solubility, enhanced hydrophilicity, thus changing the moisture distribution, thermal and pasting characteristics. Notably, the combined treatment of three techniques significantly increased the relative crystallinity, accompanied by the highest digestive resistance, and the content of resistant starch was increased from 20.53% in NR to 31.75%, much higher than the other treatments. These findings provide potential for the manufacturers to rationally and flexibly employ this low digestible rice in health food products.

Association of EEG and cognitive impairment in overweight and non-overweight patients with schizophrenia.

OBJECTIVE: Schizophrenia (SCZ) is a globally prevalent, severe chronic mental disorder, with cognitive dysfunction being one of its core symptoms. Notably, overweight is exceedingly common among individuals with SCZ, and overweight can also impact cognitive function. Therefore, the relationship between overweight and cognition in SCZ is a clinical issue that is in need of research attention. METHODS: This study enrolled 77 patients with SCZ, including 36 overweight and 41 non-overweight patients. The Positive and Negative Syndrome Scale (PANSS) was used to assess symptom severity, while cognitive functions were evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Electroencephalography (EEG) testing was performed, with power spectral analysis conducted across various frequency bands (δ, θ, α, ß, low γ, and high γ). RESULTS: Compared to non-overweight SCZ patients, those overweight exhibited significantly lower RBANS total and index scores in immediate memory, visuospatial/constructional abilities, and delayed memory. EEG spectral analysis revealed that overweight SCZ patients demonstrated significantly lower oscillation power ratios in the ß, low γ, and high γ frequency bands compared to their non-overweight counterparts. Correlation analyses indicated a significant positive relationship between ß wave activity and RBANS total scores among overweight SCZ patients, suggesting that reduced ß power correlates with more severe cognitive dysfunction. CONCLUSION: Our findings indicate that overweight SCZ patients experience more severe cognitive impairments in a resting state than those who are not overweight, with significant differences in EEG spectrum observed in the ß and γ frequency bands. Additionally, our study establishes a correlation between various EEG spectrum dimensions and cognition. This research highlights the effects of overweight on cognition in individuals with SCZ. Additionally, employing EEG technology to study cognitive function in overweight SCZ patients can offer valuable electrophysiological insights.

Risk Factors Analysis and Prediction of Rotator Cuff Tears: A Retrospective Study.

AIM: Rotator cuff tears (RCTs) are a major cause of shoulder pain and disability, affecting millions worldwide. Understanding the risk factors and developing reliable predictive measures for RCTs is essential for early diagnosis, targeted prevention, and effective treatment of this patient population. This study seeks to enhance our understanding by analyzing the acromiohumeral distance (AHD) and Constant-Murley Score (CMS) in patients with and without RCTs, thereby aiding the development of a predictive model aimed at improving clinical outcomes and prevention strategies in rotator cuff pathology. METHODS: This retrospective analysis involved 201 patients with shoulder pain, categorized into RCT (n = 72) and no RCTs (N-RCTs, n = 129) groups based on Magnetic Resonance Imaging (MRI) findings. We compared demographics, AHD, CMS, and rotator cuff status between groups and utilized logistic regression for identifying RCT predictors, leading to the development of a multifactorial predictive model. RESULTS: The mean AHD was 6.60 ± 1.12 mm. The RCT group showed a marginally higher AHD than the N-RCT group (p = 0.669). CMS scores were significantly lower in the RCT group (p < 0.001). Dominant side involvement (Odds Ratio (OR) 2.244), type III acromion (OR 6.106), and lower CMS (OR 0.938) significantly correlated with RCTs. The predictive model demonstrated an area under the curve (AUC) of 0.701 for RCT diagnosis. CONCLUSIONS: Reduced CMS, dominance of the affected side, and type III acromion emerged as key risk factors for RCTs. Our predictive model, incorporating these factors, holds promise for RCT diagnosis, with future studies needed for further validation.

Identification of three novel P450 enzymes involved in the oxidative modification of a newly discovered fusicoccane diterpene.

Fusicoccane (FC)-type diterpenoids are a class of diterpenoids characterized by a unique 5-8-5 ring system and exhibit diverse biological activities. Recently, we identified a novel FC-type diterpene synthase MgMS, which produces a myrothec-15(17)-en-7-ol (1) hydrocarbon skeleton, however, its tailoring congeners have not been elucidated. Here, we discovered two additional gene clusters Bn and Np, each encoding a highly homologous terpene synthase to MgMS but distinct tailoring enzymes. Heterologous expression of the terpene synthases BnMS and NpMS yielded the same product as MgMS. Subsequent introduction of three P450 enzymes MgP450, BnP450 and NpP450 from individual gene clusters resulted in four new FC-type diterpenoids 2-5. Notably, MgP450 serves as the first enzyme responsible for hydroxylation of the C19 methyl group, whereas NpP450 functions as a multifunctional P450 enzyme involved in the oxidations at C5, C6, and C19 positions of the 5-8-5 tricyclic skeleton. C5 oxidation of the hydrocarbon skeleton 1 led to broadening of the NMR signals and incomplete spectra, which was resolved by high-temperature NMR spectral analysis.

Identification of gene and protein signatures associated with long-term effects of COVID-19 on the immune system after patient recovery by analyzing single-cell multi-omics data using a machine learning approach.

Viral infections significantly impact the immune system, and impact will persist until recovery. However, the influence of severe acute respiratory syndrome coronavirus 2 infection on the homeostatic immune status and secondary immune response in recovered patients remains unclear. To investigate these persistent alterations, we employed five feature-ranking algorithms (LASSO, MCFS, RF, CATBoost, and XGBoost), incremental feature selection, synthetic minority oversampling technique and two classification algorithms (decision tree and k-nearest neighbors) to analyze multi-omics data (surface proteins and transcriptome) from coronavirus disease 2019 (COVID-19) recovered patients and healthy controls post-influenza vaccination. The single-cell multi-omics dataset was divided into five subsets corresponding to five immune cell subtypes: B cells, CD4+ T cells, CD8+ T cells, Monocytes, and Natural Killer cells. Each cell was represented by 28,402 scRNA-seq (RNA) features, 3 Hash Tag Oligo (HTO) features, 138 Cellular indexing of transcriptomes and epitopes by sequencing (CITE) features and 23,569 Single Cell Transform (SCT) features. Some multi-omics markers were identified and effective classifiers were constructed. Our findings indicate a distinct immune status in COVID-19 recovered patients, characterized by low expression of ribosomal protein (RPS26) and high expression of immune cell surface proteins (CD33, CD48). Notably, TMEM176B, a membrane protein, was highly expressed in monocytes of COVID-19 convalescent patients. These observations aid in discerning molecular differences among immune cell subtypes and contribute to understanding the prolonged effects of COVID-19 on the immune system, which is valuable for treating infectious diseases like COVID-19.

Transmission of tuberculosis in rural Henan, China: a prospective population-based genomic spatial epidemiological study.

The incidence of tuberculosis (TB) has declined more slowly in rural than urban areas in China, and data on the patterns of transmission and the high-risk populations in rural areas remains scarce. We conducted a population-based study of culture-positive pulmonary TB patients diagnosed in rural Linzhou City, Henan Province from July 2018 to February 2023. Genomic clusters were defined based on whole-genome sequencing and risk factors for clustering were identified by logistic regression. Transmission events were inferred with phybreak and transmission links were sought through epidemiological investigation of clustered patients. Logistic regression was used to explore the relationship between genomic differences of patient isolates and geographical distances of patient residences. Spatial hotspots were defined using kernel density estimation. Of 455 culture-positive patients, 430 were included in the final analysis. Overall, 192 (44.7%,192/430) patients were grouped into 49 clusters. Clusters containing ≥5 patients accounted for 18.4% (9/49) of the clusters and clustering was highest in student patients. No super-spreaders were detected. Confirmed epidemiologic links were identified for only 18.2% of clustered patients. The clustering risk decreased rapidly with increasing distances between patient residences, but 77.6% of clustered patient pairs lived ≥5.0 km apart. Both the Central Subdistrict and Rencun Township were identified as hotspots for TB transmission. Recent transmission appears to be an important driver of the TB burden in Linzhou. The formulation of effective strategies to reduce TB incidence in rural areas will require further studies to identify high-risk populations and venues where local inhabitants congregate and transmit the infection.

Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Disease: Success Rate and Complications among Different Patient Populations.

INTRODUCTION: Balloon pulmonary angioplasty (BPA) is an effective intervention for patients with chronic thromboembolic pulmonary disease (CTEPD). We aimed to identify the patient group with a low success rate or high complication rate of BPA, which is still unclear. METHODS: Both CTEPD patients with or without pulmonary hypertension (CTEPH and NoPH-CTEPD) were included. CTEPH patients were divided into groups with or without pulmonary endarterectomy (PEA-CTEPH and NoPEA-CTEPH). The efficacy and safety of BPA were compared among the groups. RESULTS: There were 450, 66, and 41 sessions in the NoPEA-CTEPH, PEA-CTEPH, and NoPH-CTEPD groups, respectively. The success rate (≥1 degree improvement in flow grade) in the PEA-CTEPH group was 94.5%, significantly lower than that in the NoPEA-CTEPH (97.1%) and NoPH-CTEPD (98.4%) groups (p = 0.014). The percentage of complete flow recovery in treated vessels was also lower in PEA-CTEPH group. BPA-related complication rate in NoPEA-CTEPH, PEA-CTEPH, and NoPH-CTEPD patients was 6.1%, 6.0%, and 0.0%, respectively (p = 0.309). One BPA-related death occurred (solely in NoPEA-CTEPH). Mean pulmonary artery pressure ≥41.5 mm Hg was a predictor of BPA-related complications. NoPEA-CTEPH patients had more improvement in 6-min walk distance (6MWD, 87 ± 93 m NoPEA-CTEPH vs. 40 ± 43 m PEA-CTEPH vs. 18 ± 20 m NoPH-CTEPD, p = 0.012). CONCLUSIONS: BPA was safe and effective for all CTEPD groups with less improvement for the PEA-CTEPH and NoPH-CTEPD groups. The success rate of BPA was lower in the PEA-CTEPH group and the complication rate was lower in the NoPH-CTEPD group. Pre-BPA treatment to lower pulmonary artery pressure should not be overlooked in CTEPD patients.

A Review of the Risk Factors and Approaches to Prevention of Post-Reperfusion Syndrome During Liver Transplantation.

Post-reperfusion syndrome (PRS) is a severe and highly lethal syndrome that occurs after declamping the portal vein forceps during liver transplantation. It is marked by severe hemodynamic disturbances manifested by decreased mean arterial pressure, increased heart rate and elevated pulmonary artery pressure. The complex pathogenesis of PRS remains understudied. It is generally believed to be related to the large amount of acidic, cold blood that enters the circulation after release of the portal clamp. This blood is rich in oxygen-free radicals and metabolic toxins, which not only aggravate the ischemia-reperfusion injury of the liver but also further attack the systemic organs indiscriminately. Considering the range of possible adverse prognoses including acute kidney injury, delirium and graft nonfunction, it is imperative that clinicians increase their awareness and prevention of PRS. The aim of this article is to review the current risk factors, pathophysiological mechanisms and prevention strategies for PRS.

The relationship between intracranial atherosclerosis and white matter hyperintensity in ischemic stroke patients: a retrospective cross-sectional study using high-resolution magnetic resonance vessel wall imaging.

Background: Both intracranial atherosclerosis and white matter hyperintensity (WMH) are prevalent among the stroke population. However, the relationship between intracranial atherosclerosis and WMH has not been fully elucidated. Therefore, the aim of this study was to investigate the relationship between the characteristics of intracranial atherosclerotic plaques and the severity of WMH in patients with ischemic stroke using high-resolution magnetic resonance vessel wall imaging. Methods: Patients hospitalized with ischemic stroke and concurrent intracranial atherosclerosis at Beijing Tsinghua Changgung Hospital, a tertiary comprehensive stroke center, who underwent high-resolution magnetic resonance vessel wall imaging and conventional brain magnetic resonance imaging were continuously recruited from January 2018 to December 2018. Both intracranial plaque characteristics (plaque number, maximum wall thickness, luminal stenosis, T1 hyperintensity, and plaque length) and WMH severity (Fazekas score and volume) were evaluated. Spearman correlation or point-biserial correlation analysis was used to determine the association between clinical characteristics and WMH volume. The independent association between intracranial plaque characteristics and the severity as well as WMH score was analyzed using logistic regression. The associations of intracranial plaque characteristics with total white matter hyperintensity (TWMH) volume, periventricular white matter hyperintensity (PWMH) volume and deep white matter hyperintensity (DWMH) volume were determined using multilevel mixed-effects linear regression. Results: A total of 159 subjects (mean age: 64.0±12.5 years; 103 males) were included into analysis. Spearman correlation analysis indicated that age was associated with TWMH volume (r=0.529, P<0.001), PWMH volume (r=0.523, P<0.001) and DWMH volume (r=0.515, P<0.001). Point-biserial correlation analysis indicated that smoking (r=-0.183, P=0.021) and hypertension (r=0.159, P=0.045) were associated with DWMH volume. After adjusting for confounding factors, logistic regression analysis showed plaque number was significantly associated with the presence of severe WMH [odds ratio (OR), 1.590; 95% CI, 1.241-2.035, P<0.001], PWMH score of 3 (OR, 1.726; 95% CI, 1.074-2.775, P=0.024), and DWMH score of 2 (OR, 1.561; 95% CI, 1.150-2.118, P=0.004). Intracranial artery luminal stenosis was associated with presence of severe WMH (OR, 1.032; 95% CI, 1.002-1.064, P=0.039) and PWMH score of 2 (OR, 1.057; 95% CI, 1.008-1.109, P=0.023). Multilevel mixed-effects linear regression analysis showed that plaque number was associated with DWMH volume (ß=0.128; 95% CI, 0.016-0.240; P=0.026) after adjusted for age and sex. Conclusions: In ischemic stroke patients, intracranial atherosclerotic plaque characteristics as measured by plaque number and luminal stenosis were associated with WMH burden.

Smart RNA Sequencing Reveals the Toxicological Effects of Diisobutyl Phthalate (DiBP) in Porcine Oocytes.

Diisobutyl phthalate (DiBP) is commonly used in the plastics industry, and recent studies have shown that environmental exposure and accumulation in the food chain caused inflammation in some organs. However, the underlying mechanisms by which DiBP affects oocyte quality have not yet been fully defined. We used immunostaining and fluorescence to evaluate the effects of DiBP exposure and demonstrated that it impaired the morphology of matured porcine oocytes through generation of cytoplasmic fragmentation, accompanied by the perturbed dynamics of the spindle and actin cytoskeleton, misdistributed endoplasmic reticulum, as well as partial exocytosis of cortical granules and ovastacin. Moreover, analysis of Smart RNA-seq found that DiBP-induced aberrant oocyte maturation could be induced by abnormal mitochondrial function and apoptosis. Importantly, we discovered that supplementation with pyrroloquinoline quinone (PQQ) significantly attenuated the meiotic abnormalities induced by DiBP exposure through the modulation of reactive oxygen species levels. Our findings demonstrated that DiBP exposure adversely affects oocyte meiotic maturation and that PQQ supplementation was an effective strategy to protect oocyte quality against DiBP exposure.