Hypo-attenuating Berry Sign as a Novel Imaging Marker of Ruptured Aneurysm in Patients with Subarachnoid Hemorrhage; a Diagnostic Accuracy Study.

Introduction: Aneurysmal subarachnoid hemorrhage (SAH) constitutes a life-threatening condition, and identifying the ruptured aneurysm is essential for further therapy. This study aimed to evaluate the diagnostic accuracy of hypo-attenuating berry sign (HBS) observed on computed tomography (CT) scan in distinguishing ruptured aneurysms. Methods: In this diagnostic accuracy study, patients who had SAH and underwent non-enhanced brain CT scan were recruited. The HBS was defined as a hypo-attenuating area with an identifiable border in the blood-filled hyper-dense subarachnoid space. The screening performance characteristics of HBS in identifying ruptured aneurysms were calculated considering the digital subtraction angiography (DSA) as the gold standard. Results: A total of 129 aneurysms in 131 patients were analyzed. The overall sensitivity and specificity of HBS in the diagnosis of aneurysms were determined to be 78.7% (95%CI: 73.1% - 83.4%) and 70.7% (95%CI: 54.3% - 83.4%), respectively. Notably, the sensitivity increased to 90.9% (95%CI: 84.3% - 95.0%) for aneurysms larger than 5mm. The level of inter-observer agreement for assessing the presence of HBS was found to be substantial (kappa=0.734). The diagnostic accuracy of HBS in individuals exhibited enhanced specificity, sensitivity, and reliability when evaluating patients with a solitary aneurysm or assessing ruptured aneurysms. The multivariate logistic regression analysis revealed a statistically significant relationship between aneurysm size and the presence of HBS (odds ratios of 1.667 (95%CI: 1.238 - 2.244; p < 0.001) and 1.696 (95%CI: 1.231 - 2.335; p = 0.001) for reader 1 and reader 2, respectively). Conclusions: The HBS can serve as a simple and easy-to-use indicator for identifying a ruptured aneurysm and estimating its size in SAH patients.  .

Loss of CHCHD2 Stability Coordinates with C1QBP/CHCHD2/CHCHD10 Complex Impairment to Mediate PD-Linked Mitochondrial Dysfunction.

Novel CHCHD2 mutations causing C-terminal truncation and interrupted CHCHD2 protein stability in Parkinson's disease (PD) patients were previously found. However, there is limited understanding of the underlying mechanism and impact of subsequent CHCHD2 loss-of-function on PD pathogenesis. The current study further identified the crucial motif (aa125-133) responsible for diminished CHCHD2 expression and the molecular interplay within the C1QBP/CHCHD2/CHCHD10 complex to regulate mitochondrial functions. Specifically, CHCHD2 deficiency led to decreased neural cell viability and mitochondrial structural and functional impairments, paralleling the upregulation of autophagy under cellular stresses. Meanwhile, as a binding partner of CHCHD2, C1QBP was found to regulate the stability of CHCHD2 and CHCHD10 proteins to maintain the integrity of the C1QBP/CHCHD2/CHCHD10 complex. Moreover, C1QBP-silenced neural cells displayed severe cell death phenotype along with mitochondrial damage that initiated a significant mitophagy process. Taken together, the evidence obtained from our in vitro and in vivo studies emphasized the critical role of CHCHD2 in regulating mitochondria functions via coordination among CHCHD2, CHCHD10, and C1QBP, suggesting the potential mechanism by which CHCHD2 function loss takes part in the progression of neurodegenerative diseases.

Enhancing HIF-1α-P2X2 signaling in dorsal raphe serotonergic neurons promotes psychological resilience.

Major depressive disorder (MDD) is a devastating condition. Although progress has been made in the past seven decades, patients with MDD continue to receive an inadequate treatment, primarily due to the late onset of first-line antidepressant drugs and to their acute withdrawal symptoms. Resilience is the ability to rebound from adversity in a healthy manner and many people have psychological resilience. Revealing the mechanisms and identifying methods promoting resilience will hopefully lead to more effective prevention strategies and treatments for depression. In this study, we found that intermittent hypobaric hypoxia training (IHHT), a method for training pilots and mountaineers, enhanced psychological resilience in adult mice. IHHT produced a sustained antidepressant-like effect in mouse models of depression by inducing long-term (up to 3 months after this treatment) overexpression of hypoxia-inducible factor (HIF)-1α in the dorsal raphe nucleus (DRN) of adult mice. Moreover, DRN-infusion of cobalt chloride, which mimics hypoxia increasing HIF-1α expression, triggered a rapid and long-lasting antidepressant-like effect. Down-regulation of HIF-1α in the DRN serotonergic (DRN5-HT) neurons attenuated the effects of IHHT. HIF-1α translationally regulated the expression of P2X2, and conditionally knocking out P2rx2 (encodes P2X2 receptors) in DRN5-HT neurons, in turn, attenuated the sustained antidepressant-like effect of IHHT, but not its acute effect. In line with these results, a single sub-anesthetic dose of ketamine enhanced HIF-1α-P2X2 signaling, which is essential for its rapid and long-lasting antidepressant-like effect. Notably, we found that P2X2 protein levels were significantly lower in the DRN of patients with MDD than that of control subjects. Together, these findings elucidate the molecular mechanism underlying IHHT promoting psychological resilience and highlight enhancing HIF-1α-P2X2 signaling in DRN5-HT neurons as a potential avenue for screening novel therapeutic treatments for MDD.

Resveratrol suppresses neuroinflammation to alleviate mechanical allodynia by inhibiting Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway in a rat model of spinal cord injury.

Background: Neuropathic pain (NP) is one of intractable complications of spinal cord injury (SCI) and lacks effective treatment. Resveratrol (Res) has been shown to possess potent anti-inflammatory and anti-nociceptive effects. In this study, we investigated the analgesic effect of Res and its underlying mechanism in a rat model of SCI. Methods: The rat thoracic (T10) spinal cord contusion injury model was established, and mechanical thresholds were evaluated during an observation period of 21 days. Intrathecal administration with Res (300 µg/10 µl) was performed once a day for 7 days after the operation. On postoperative day 7, the expressions of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA) and Real-time quantitative PCR (RT-qPCR), the expression of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway was determined by western blot and RT-qPCR, and the co-labeled phospho-STAT3 (p-STAT3) with neuronal nuclear antigen (NeuN), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule 1 (Iba-1) were explored by double immunofluorescence staining in the lumbar spinal dorsal horns. The temporal changes of p-STAT3 were investigated by western blot on the 1st, 3rd, 7th, 14th, and 21st days after the operation. Results: Intrathecal administration with Res for 7 successive days alleviated mechanical allodynia of rats during the observation period. Meanwhile, treatment with Res suppressed the production of pro-inflammatory factors TNF-α, IL-1ß and IL-6, and inhibited the expressions of phospho-JAK2 and p-STAT3 in the lumbar spinal dorsal horns on postoperative day 7. Additionally, the protein expression of p-STAT3 was significantly increased on the 1st day following the operation and remained elevated during the next 21 days, immunofluorescence suggested that the up-regulated p-STAT3 was co-located with glial cells and neurons. Conclusion: Our current results indicated that intrathecal administration with Res effectively alleviated mechanical allodynia after SCI in rats, and its analgesic mechanism might be to suppress neuroinflammation by partly inhibiting JAK2/STAT3 signaling pathway.

Jinfeng pills ameliorate premature ovarian insufficiency induced by cyclophosphamide in rats and correlate to modulating IL-17A/IL-6 axis and MEK/ERK signals.

ETHNOPHARMACOLOGICAL RELEVANCE: Jinfeng Pill (JFP) is a classical Chinese medicine formula and composed of 9 herbs, including Epimedium brevicornu Maxim (Yinyanghuo), Cervus elaphus Linnaeus (Lurong), Panax ginseng C.A.Mey. (Renshen), Equus asinus (EJiao), Ligustrum lucidum W.T.Aiton (Nvzhenzi), Reynoutria multiflora (Thunb.) Moldenke (Heshouwu), Curculigo orchioides Gaertn (Xianmao), Neolitsea cassia (L.) Kosterm. (Rougui) and Leonurus japonicus Houtt. (Yimucao). The formula is clinically used to regulate menstrual cycle and alleviate polycystic ovarian syndrome due to its capabilities of ovulation induction. It is therefore presumed that JFP could be used for the therapy of premature ovarian insufficiency (POI) but the assumed efficacy has not been fully substantiated in experiment. AIM OF STUDY: To evaluate the effectiveness of JFP on cyclophosphamide (CTX)-induced POI and preliminarily explore its potential mechanisms of action. MATERIAL AND METHODS: An experimental rat model of POI was established by using CTX induction to assess the efficacy of JFP. The potential targets of action for JFP alleviating POI were predicted by the combination of network pharmacology and transcriptomics and finally validating by RT-qPCR and Western blot. RESULTS: JFP alleviated the damages of ovarian tissue induced by CTX in the rat model of POI via significantly decreasing serum levels of FSH and LH and the ratio of FSH/LH and increasing the levels of E2 and AMH, accompanied with promoting ovarian folliculogenesis and follicle maturity and reversing the depletion of follicle pool. With the analysis of network pharmacology, pathways in cancer, proteoglycans in cancer, PI3K-AKT, TNF and FoxO signaling pathways were predicted to be influenced by JFP. The results of RNA-seq further revealed that IL-17 signaling pathway was the most important pathway regulated by both CTX and JFP, following by transcriptional misregulation in cancer and proteoglycans in cancer. Combining the two analytical methods, JFP likely targeted genes associated with immune regulation, including COX-2, HSP90AA1, FOS, MMP3 and MAPK11 and pathways, including IL-17,Th17 cell differentiation and TNF signaling pathway. Finally, JFP was validated to regulate the mRNA expression of FOS, FOSB, FOSL1, MMP3, MMP13 and COX-2 and decrease the release of IL-17A and the protein expression of IL-6 and suppress the phosphorylation of MEK1/2 and ERK1/2 in CTX induced POI rats. CONCLUSION: Jinfeng Pill is effective to ameliorate the symptoms of POI induced by CTX in the model of rats and its action is likely associated with suppressing IL-17A/IL-6 axis and the activity of MEK1/2-ERK1/2 signaling.

CHD1 deletion stabilizes HIF1α to promote angiogenesis and glycolysis in prostate cancer.

Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.

[Metabolomics study on the difference of tongue coating metabolites between patients with intra-oral halitosis and healthy individual].

PURPOSE: To analyze the difference of metabolites of tongue coating between patients with intra-oral halitosis and healthy individuals by untargeted metabolomics, and to explore significant differences in metabolites of intra-oral halitosis as biomarkers. METHODS: The untargeted metabolomics of tongue coating samples from 12 patients with intra-oral halitosis and 12 healthy individuals were studied by liquid chromatography and mass spectrometry combined with principal component analysis and orthogonal partial least squares discriminant analysis. The value of variable importance in projection ＞1 and P＜0.05 of Student's t test in the orthogonal partial least squares-discriminant analysis model were used as the criteria to screen and determine the differential metabolites. RESULTS: There were differences in the metabolites of tongue coating between patients with intra-oral halitosis and healthy individuals, and 11 different metabolites were identified. They were valyl-arginine, glycine-phenylalanine, tryptophyl-proline, deoxyadenosine, 4,5-dihydroniveusin A, N-acetyl-DL-tryptophan, paramethasone acetate, cyclopentanol, [(2-hexylcyclopentylidene) amino]thiourea, L-pipecolic acid and taurine. In the intra-oral halitosis group, the expressions of Glycine-phenylalanine and N-acetyl-DL-tryptophan were significantly up-regulated, while the expressions of taurine were significantly down-regulated. CONCLUSIONS: There are differences in the metabolites of tongue coating between patients with intra-oral halitosis and healthy individuals. The differential metabolites with diagnostic value may be used as diagnostic markers of intra-oral halitosis.

Pulsed electromagnetic fields for the management of knee osteoarthritis: multicentre, randomised, controlled, non-inferiority trial protocol.

INTRODUCTION: Pulsed electromagnetic field (PEMF) is an available treatment for knee osteoarthritis (KOA), which is the most common cause of pain and disability. Nonetheless, whether the clinical effects are like that of most used drugs is unclear. Thus, this study aims to determine the effect of PEMF on pain relief by comparing them with the positive drug (celecoxib). Furthermore, this clinical trial aims to evaluate the effect of PEMF on function and quality of life with a long-term follow-up. METHODS AND ANALYSIS: This two-armed, non-inferiority, randomised, controlled trial will be conducted in the outpatient physiatry/physiotherapy clinic or inpatient ward of 17 hospitals in China. A total of 428 individuals will be included who are more than 40 years of age with diagnosed KOA. The participants will be randomly allocated to the PEMF group: receiving a 6-week PEMF (15 Hz, 30 mT) at a frequency of 40 min per day, 5 days per week plus sham drug (n=214), or drug group: receiving a 6-week celecoxib 200 mg combined with sham PEMF (n=214). Clinical outcomes will be measured at baseline (T0), mid-term of intervention (T1), post-intervention (T2), 10, 18 and 30 weeks (T3-5) of follow-up after randomisation. The primary outcome will be the Western Ontario and McMaster Universities (WOMAC) pain index. The secondary outcomes will be WOMAC function and stiffness, pain measured by numerical rating score, quality of life, 6-minute walk test, pain catastrophising scale and responder index. ETHICS AND DISSEMINATION: The trial is performed following the Declaration of Helsinki. The study protocol and consent form have been approved by the Ethics Committee on Biomedical Research of West China Hospital of Sichuan University (#2021-220). All patients will give informed consent before participation and the trial is initiated after approval. Results of this trial will be disseminated through publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2100052131.

Effects of tele-exercise rehabilitation intervention on women at high risk of osteoporotic fractures: study protocol for a randomised controlled trial.

INTRODUCTION: Premenopausal and postmenopausal osteoporosis and associated fragility fractures are major public health problems. Exercise, especially moderate-to-high-intensity impact exercise, has been recommended as an effective, low-cost non-pharmacological strategy for bone strength improvement; however, evidence on fracture risk is limited. In addition, maintaining regular training is currently a problem. Therefore, this study aims to conduct a randomised controlled trial of moderate-to-high-intensity tele-exercise intervention using a tele-rehabilitation app and quantify its effects on vertical fracture and fall prevention in women at high risk of osteoporotic fractures. METHODS AND ANALYSIS: In this multicentre, randomised controlled trial, 794 women at high risk of osteoporotic fractures will be recruited and randomised into either the tele-exercise rehabilitation or control group. Participants in the control group will receive routine remote rehabilitation, while those in the intervention group will be provided with a 6-month tele-exercise rehabilitation. The primary outcomes are the percentage of participants with one or more new vertebral fractures and incidence of falls. Intention-to-treat, full analysis set and per-protocol approaches will be used for outcome analyses. ETHICS AND DISSEMINATION: The study was approved by the biomedical research ethics committee of the West China Hospital of Sichuan University (2021-579). Written informed consent will be obtained from each participant after agreeing to participate in the study. The study findings will be presented at national and international scientific conferences and published in peer-reviewed journals. Results are propagated regardless of the magnitude or direction of the impact. Authorship is assigned according to authorship guidelines as defined by the International Board of Medical Journal Editors, and each author's role is based on journal requirements for publication. TRIAL REGISTRATION NUMBER: The study was registered with the Chinese Clinical Trial Registry (ChiCTR2200058780) prior to recruitment (May 2022).

Clinical performance of the IMMY cryptococcal antigen lateral flow assay in dogs and cats.

BACKGROUND: Cryptococcal lateral flow antigen assays (CLFAs) have been assessed in comparison to the latex cryptococcal antigen agglutination test but their clinical performance is unknown. OBJECTIVE: Determine clinical performance of IMMY CLFA (Immuno-Mycologics Inc, Oklahoma) using patients with and without cryptococcosis as the reference standard. ANIMALS: One-hundred ninety-seven serum samples from client-owned dogs and cats. METHODS: Review of medical records of a referral population of dogs and cats that had CLFA performed between 2012 and 2020. Animals were classified as cryptococcosis positive (Cr+) or negative (Cr-) based on clinical information. Clinical diagnosis was used to calculate positive and negative percent agreement of the CLFA. RESULTS: Twelve specimens (4 canine, 8 feline) were obtained from Cr+ animals and had positive CLFA results. One-hundred eighty-five specimens (139 canine, 46 feline) were collected from Cr- animals. Negative CLFA results were recorded in 129 canine and 44 feline Cr- samples. Positive CLFA results were noted for 10 canine and 2 feline Cr- samples. Positive percent agreement of CLFA was 100% (confidence interval [CI], 39.8%-100% dogs; 63.1%-100% cats). Negative percent agreements were 92.8% (CI, 87.2%-96.5%) for dogs and 95.7% (CI, 85.2%-99.5%) for cats. CONCLUSIONS AND CLINICAL IMPORTANCE: A negative IMMY CLFA result enables reliable exclusion of cryptococcal infection in dogs and cats. By contrast, a positive result must be interpreted cautiously and further testing should be performed to verify a diagnosis of cryptococcosis.

Recent Advances in Zinc Hydroxystannate-Based Flame Retardant Polymer Blends.

During the combustion of polymeric materials, plenty of heat, smoke, and toxic gases are produced that may cause serious harm to human health. Although the flame retardants such as halogen- and phosphorus-containing compounds can inhibit combustion, they cannot effectively reduce the release of toxic fumes. Zinc hydroxystannate (ZHS, ZnSn(OH)6) is an environmentally friendly flame retardant that has attracted extensive interest because of its high efficiency, safety, and smoke suppression properties. However, using ZHS itself may not contribute to the optimal flame retardant effect, which is commonly combined with other flame retardants to achieve more significant efficiency. Few articles systematically review the recent development of ZHS in the fire safety field. This review aims to deliver an insight towards further direction and advancement of ZHS in flame retardant and smoke suppression for multiple polymer blends. In addition, the fire retarded and smoke suppression mechanism of ZHS will be demonstrated and discussed in depth.

Receptor-Interacting Protein Kinase 3 Inhibition Relieves Mechanical Allodynia and Suppresses NLRP3 Inflammasome and NF-κB in a Rat Model of Spinal Cord Injury.

Background: Neuroinflammation is critical in developing and maintaining neuropathic pain after spinal cord injury (SCI). The receptor-interacting protein kinase 3 (RIPK3) has been shown to promote inflammatory response by exerting its non-necroptotic functions. In this study, we explored the involvement of RIPK3 in neuropathic pain after SCI. Methods: Thoracic (T10) SCI rat model was conducted, and the mechanical threshold in rats was measured. The expressions of RIPK3, nod-like receptor family pyrin domain-containing protein 3 (NLRP3), caspase-1, and nuclear factor-κB (NF-κB) were measured with western blotting analysis or quantitative real-time polymerase chain reaction (qRT-PCR). Double immunofluorescence staining was used to explore the colabeled NLRP3 with NeuN, glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule 1 (IBA1). In addition, enzyme-linked immunosorbent assay (ELISA) was applied to analyze the levels of proinflammatory factors interleukin 1 beta (IL-1ß), interleukin 18 (IL-18), and tumor necrosis factor alpha (TNF-α). Results: The expression of RIPK3 was elevated from postoperative days 7-21, which was consistent with the development of mechanical allodynia. Intrathecal administration of RIPK3 inhibitor GSK872 could alleviate the mechanical allodynia in SCI rats and reduce the expression levels of RIPK3. The activation of NLRP3 inflammasome and NF-κB was attenuated by GSK872 treatment. Furthermore, immunofluorescence suggested that NLRP3 had colocalization with glial cells and neurons in the L4-L6 spinal dorsal horns. In addition, GSK872 treatment reduced the production of inflammatory cytokines. Conclusion: Our findings indicated that RIPK3 was an important facilitated factor for SCI-induced mechanical allodynia. RIPK3 inhibition might relieve mechanical allodynia by inhibiting NLRP3 inflammasome, NF-κB, and the associated inflammation.

Comparing the efficacy and safety of short-term spinal cord stimulation and pulsed radiofrequency for zoster-related pain: A systematic review and meta-analysis.

BACKGROUND: Pulsed radiofrequency (PRF) is a commonly used method for the treatment of zoster-related pain in the clinic. However, PRF therapy has a high recurrence rate and many adverse reactions. Recent studies have shown that short-term spinal cord stimulation (stSCS) can effectively alleviate zoster-related pain. Due to the lack of evidence, it is unclear whether stSCS is superior to PRF in the efficacy of treating zoster-related pain. OBJECTIVE: This study aimed to compare the efficacy and safety of stSCS and PRF for zoster-related pain. METHODS: We searched seven electronic databases from the establishment of the database to January 2021. Related randomized controlled trials were included in this meta-analysis. After extracting the data and evaluating the methodological quality of the included trials, the outcome indicators were statistically analyzed by using RevManV.5.3. RESULTS: This meta-analysis included 6 trials with a total of 509 patients. Compared with PRF group, stSCS group showed lower pain intensity (standardized mean difference=-0.83, 95%CI [-1.37, -0.30], P=.002), better sleep quality (mean difference=-1.43, 95%CI [-2.29, -0.57], P=.001), lower pain rating index scores, and less incidence of adverse events (RR=0.32, 95%CI [0.12, 0.83], P<.05). However, the efficacies of PRF and stSCS for treating postherpetic neuralgia were consistent in the response rate (RR= 1.10, 95% CI [0.82, 1.48], P=.51) and the complete remission rate (RR=1.05, 95% CI [0.66, 1.68], P=.84). CONCLUSIONS: In this study, stSCS showed a better analgesic effect and higher safety than PRF. Our meta-analysis results suggested that stSCS may be a feasible and safe invasive treatment for zoster-related pain. However, high-quality, randomized controlled trials with large sample sizes are needed to further verify our conclusions.

Alterations in the expression level of visfatin in the lungs of piglets infected with PRRSV and its effect on PRRSV replication.

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease caused by PRRS virus (PRRSV), characterized by sow reproductive failure and respiratory symptoms in pigs of all ages. PRRSV mainly causes severe lung damage by invading alveolar macrophages. Visfatin is closely related to acute lung injury, immune response and inflammation along with virus invasion to the host. Therefore, the current study was performed to clarify the relationship between visfatin and PRRSV infection. We used ternary piglets to construct a piglet model to explore the expression of visfatin and tight junction protein in lung injury induced by PRRSV infection, and then further studied the inhibition effect of visfatin on PRRSV replication by PRRSV infection of Marc-145 cells. Our results indicated that both PRRSV attenuated and virulent infections could damage the lung tissues, which could not only lead to severe inflammatory reaction (such as increased expression of TNF-α, TGF-ß, IL-8 and IL-10) in lung tissues of piglets, but also brought about the sharp decrease of ZO-1 and Tricellulin expressions resulting in impaired alveolar epithelial barrier. Meanwhile, we found significantly up-regulated expression of visfatin in lungs and serum of pigs after PRRSV infection that were related to both the degree of lung injury and the virulence of PRRSV strain. Moreover, visfatin might inhibit the PRRSV infection to Marc-145 cells in time dependent fashion. Hence, the current investigation provides the novel information about the effect of visfatin and PRRSV co-culture on Marc-145 cells and the effect of visfatin on PRRSV proliferation at different time points.

Understanding the Clinical Implications of Intracranial Arterial Calcification Using Brain CT and Vessel Wall Imaging.

Background and Purpose: Intracranial arterial calcification (IAC) has been the focus of much attention by clinicians and researchers as an indicator of intracranial atherosclerosis, but correlations of IAC patterns (intimal or medial) with the presence of atherosclerotic plaques and plaque stability are still a matter of debate. Our study aimed to assess the associations of IAC patterns identified on computed tomography (CT) with the presence of plaque detected on vessel wall magnetic resonance imaging and plaque stability. Materials and Methods: Patients with stroke or transient ischemic attack and intracranial artery stenosis were recruited. IAC was detected and localized (intima or media) on non-contrast CT images. Intracranial atherosclerotic plaques were identified using vessel wall magnetic resonance imaging and matched to corresponding CT images. Associations between IAC patterns and culprit atherosclerotic plaques were assessed by using multivariate regression. Results: Seventy-five patients (mean age, 63.4 ± 11.6 years; males, 46) were included. Two hundred and twenty-one segments with IAC were identified on CT in 66 patients, including 86 (38.9%) predominantly intimal calcifications and 135 (61.1%) predominantly medial calcifications. A total of 72.0% of intimal calcifications coexisted with atherosclerotic plaques, whereas only 10.2% of medial calcifications coexisted with plaques. Intimal calcification was more commonly shown in non-culprit plaques than culprit plaques (25.9 vs. 9.4%, P = 0.008). The multivariate mixed logistic regression adjusted for the degree of stenosis showed that intimal calcification was significantly associated with non-culprit plaques (OR, 2.971; 95% CI, 1.036-8.517; P = 0.043). Conclusion: Our findings suggest that intimal calcification may indicate the existence of a stable form of atherosclerotic plaque, but plaques can exist in the absence of intimal calcification especially in the middle cerebral artery.

Visfatin Regulates Inflammatory Mediators in Mouse Intestinal Mucosa Through Toll-Like Receptors Signaling Under Lipopolysaccharide Stress.

Visfatin is a multifunctional protein involved in inflammatory immune stress. The aim of current study was to explore the role of visfatin in lipopolysaccharide (LPS)-induced intestinal mucosal inflammation and to confirm its cellular effect in inflammatory immune response through silencing of Toll-like receptors (TLRs). We divided Kunming mice into three groups: Saline group, LPS group, and LPS + visfatin group and performed hematoxylin and eosin staining, immunohistochemistry, quantitative polymerase chain reaction, Western blot, enzyme linked immunosorbent assay and RNA-seq analysis. Pretreatment of visfatin improves LPS-stimulated reduction of tight junction protein 1 (ZO-1) and secretory immunoglobulin A, inhibits overexpression of Claudin-1 and vascular endothelial growth factor, and reduces intestinal mucosal damage and inflammation. RNA-seq analysis of cellular transcriptomes indicated that visfatin is involved in down-regulation of mRNA level of TLR4 as well as attenuation of protein levels of TLR8 and nucleotide-binding oligomerization domain-containing protein 2, revealing that visfatin could reduce intestinal mucosal inflammation through TLR signaling pathway in mice ileum. In RAW264.7 cells, the genes silencing of Toll/IL-1R family, such as TLR4, TLR2, and IL-1R1, was accompanied by decreased expressions of inflammatory factors (TNF-α, IL-1ß, IL-6 and MCP-1) along with lower cellular visfatin levels. Hence, visfatin maintains the intestinal mucosal barrier structure and attenuates the intestinal mucosal inflammation through the TLR signaling pathway. Likewise, the Toll/IL-1R family regulates the release of visfatin, which can participate in the inflammatory reaction through the regulation of inflammatory factors.

Vertebrobasilar Junction Angle Over 90°: A Potential Imaging Marker Associated With Vertebrobasilar Atherosclerosis.

Objective: Whether the cerebral vascular variations play an important role in the progression of intracranial atherosclerosis is yet largely unclear. We aimed to investigate the relationship between the magnitude of the vertebrobasilar junction (VBJ) angle and the imaging features of vertebrobasilar artery atherosclerosis. Methods: Adult patients with acute ischemic stroke or transient ischemic attack undergoing a 3.0-tesla vessel wall magnetic resonance imaging (VW-MRI) scanning were consecutively included. Imaging features of vertebrobasilar artery atherosclerosis were assessed on the reconstructed short axis of VW-MRI at the most stenotic site. The VBJ angle degree was measured on magnetic resonance angiography and classified into the angle ≥90° or <90°. Results: Among 68 patients (mean age = 63.5 ± 9.4 years old; 63.2% were male) with vertebrobasilar atherosclerosis, 33 had a VBJ angle ≥90° and 35 had a VBJ angle <90°. Compared to the vertebrobasilar plaques with VBJ angle <90°, those with VBJ angle ≥90° had a heavier plaque burden (84.35 vs. 70.58%, p < 0.001) and higher prevalence of intraplaque hemorrhage (17.1 vs. 3.3%, p = 0.01). In the regression analyses, the VBJ angle ≥90° was also robustly associated with plaque burden (odds ratio, 1.11; 95% confidential interval, 1.043-1.18; p = 0.001) and intraplaque hemorrhage (odds ratio, 5.776; 95% confidential interval, 1.095-30.46; p = 0.039) of vertebrobasilar atherosclerosis. Conclusion: The VBJ angle over 90° might aggravate the vessel wall condition of the atherosclerotic vertebrobasilar arteries, which might serve as a potential risk factor for vertebrobasilar atherosclerosis.

Optimization and bioactivity verification of porcine recombinant visfatin with high expression and low endotoxin content using pig liver as template.

In order to obtain the porcine recombinant visfatin protein with high expression and low endotoxin content, the current study aims to express and verify the biological activity of the purified porcine recombinant visfatin protein. Firstly, four different expression strains were successfully constructed. Then they were simultaneously induced at 37 °C for 4 h and 16 °C for 16 h. The results showed that Visfatin-pET28a-Transetta was the best strain with high protein expression and purity at 16 °C induction for 16 h. After that, endotoxin was reduced from the recombinant visfatin until the residual endotoxin was less than one endotoxin units per milliliter (EU/mL). Finally, the purified porcine recombinant visfatin protein was incubated with RAW264.7 cells. The results of cell counting kit-8 (CCK-8) showed the survival rate of the cells first increased and then decreased with the increase in visfatin concentration. When the concentration of visfatin was 700 ng/mL, the survival rate of the cells was the highest. Thereafter, control (PBS), Visfatin and Visfatin + PolymyxinB (Ploy.B) groups were incubated with the RAW264.7 cells for 6 h. Real-time quantitative polymerase chain reaction (RT-qPCR) and Enzyme Linked Immuno-Sorbent Assay (ELISA) results showed that, as compared to the control group, the expressions of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 in Visfatin group were significantly increased (P < 0.05). However, there was no significant difference between the Visfatin and Visfatin + Poly.B groups, indicating that porcine recombinant visfatin protein promoted the inflammatory activity of RAW264.7 cells while the residual endotoxin did not play a role, suggesting biological activity of porcine recombinant visfatin protein.

Encapsulated Polyethyleneimine Enables Synchronous Nanostructure Construction and In Situ Functionalization of Nanofiltration Membranes.

Highly permselective nanostructured membranes are desirable for the energy-efficient molecular sieving on the subnanometer scale. The nanostructure construction and charge functionalization of the membranes are generally carried out step by step through the conventional layer-by-layer coating strategy, which inevitably brings about a demanding contradiction between the permselective performance and process efficiency. For the first time, we report the concurrent construction of the well-defined molecular sieving architectures and tunable surface charges of nanofiltration membranes through precisely controlled release of the nanocapsule decorated polyethyleneimine and carbon dioxide. This novel strategy not only substantially shortens the fabrication process but also leads to impressive performance (permeance up to 37.4 L m-2 h-1 bar-1 together with a rejection 98.7% for Janus Green B-511 Da) that outperforms most state-of-art nanofiltration membranes. This study unlocks new avenues to engineer next-generation molecular sieving materials simply, precisely, and cost efficiently.