ATF2/BAP1 Axis Mediates Neuronal Apoptosis After Subarachnoid Hemorrhage via P53 Pathway.

BACKGROUND: Neuronal apoptosis plays an essential role in the pathogenesis of brain injury after subarachnoid hemorrhage (SAH). BAP1 (BRCA1-associated protein 1) is considered to exert pro-apoptotic effects in multiple diseases. However, evidence supporting the effect of BAP1 on the apoptotic response to SAH is lacking. Therefore, we aimed to confirm the role of BAP1 in SAH-induced apoptosis. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to detect BAP1 expression in the cerebrospinal fluid. Endovascular perforation was performed in mice to induce SAH. Lentiviral short hairpin RNA targeting BAP1 mRNA was transduced into the ipsilateral cortex of mice with SAH to investigate the role of BAP1 in neuronal damage. Luciferase and coimmunoprecipitation assays were performed to investigate the mechanism through which BAP1 participates in hemin-induced SAH. RESULTS: First, BAP1 expression was upregulated in the cerebrospinal fluid of patients with SAH and positively associated with unfavorable outcomes. ATF2 (activating transcription factor-2) then regulated BAP1 expression by binding to the BAP1 promoter. In addition, BAP1 overexpression enhanced P53 activity and stability by reducing P53 proteasome-mediated degradation. Subsequently, elevated P53 promoted neuronal apoptosis via the P53 pathway. Inhibition of the neuronal BAP1/P53 axis significantly reduced neurological deficits and neuronal apoptosis and improved neurological dysfunction in mice after SAH. CONCLUSIONS: Our results suggest that the neuronal ATF2/BAP1 axis exerts a brain-damaging effect by modulating P53 activity and stability and may be a novel therapeutic target for SAH.

MIKC type MADS-box transcription factor LcSVP2 is involved in dormancy regulation of the terminal buds in evergreen perennial litchi (Litchi chinensis Sonn.).

SHORT VEGETATIVE PHASE (SVP), a member of the MADS-box transcription factor family, has been reported to regulate bud dormancy in deciduous perennial plants. Previously, three LcSVPs (LcSVP1, LcSVP2 and LcSVP3) were identified from litchi genome, and LcSVP2 was highly expressed in the terminal buds of litchi during growth cessation or dormancy stages and down-regulated during growth stages. In this study, the role of LcSVP2 in governing litchi bud dormancy was examined. LcSVP2 was highly expressed in the shoots, especially in the terminal buds at growth cessation stage, whereas low expression was showed in roots, female flowers and seeds. LcSVP2 was found to be located in the nucleus and have transcription inhibitory activity. Overexpression of LcSVP2 in Arabidopsis thaliana resulted in a later flowering phenotype compared to the wild-type control. Silencing LcSVP2 in growing litchi terminal buds delayed re-entry of dormancy, resulting in significantly lower dormancy rate. The treatment also significantly up-regulated litchi FLOWERING LOCUS T2 (LcFT2). Further study indicates that LcSVP2 interacts with an AP2-type transcription factor, SMALL ORGAN SIZE1 (LcSMOS1). Silencing LcSMOS1 promoted budbreak and delayed bud dormancy. Abscisic acid (200 mg/L), which enforced bud dormancy, induced a short-term increase in the expression of LcSVP2 and LcSMOS1. Our study reveals that LcSVP2 may play a crucial role, likely together with LcSMOS1, in dormancy onset of the terminal bud and may also serve as a flowering repressor in evergreen perennial litchi.

Rheological characterization of chia seed gum as a thickening agent used for dysphagia management.

Dysphagia has emerged as a serious health issue facing contemporary society. Consuming thickened liquids is an effective approach for improving the swallowing safety for dysphagia patients. The thickening effect of chia seed gum (CSG), a novel thickener, in different dispersing media (water, orange juice, and skim milk) was investigated. Moreover, the potential application of CSG for dysphagia management was evaluated by comparison with xanthan gum (XG) and guar gum (GG). The thickened liquids prepared with 0.4 %-1.2 % (w/v) CSG, XG, and GG could be classified into levels 1-4, 2-4, and 1-3, respectively, according to the International Dysphagia Diet Standardization Initiative (IDDSI) framework. All the thickened liquids displayed shear-thinning characteristics that facilitated safe swallowing. The viscosities (η50) of CSG dissolved in water (0.202-1.027 Pa·s) were significantly greater than those of CSG dissolved in orange juice (0.070-0.690 Pa·s) and skim milk (0.081-0.739 Pa·s), indicating that CSG had a greater thickening effect in water than in orange juice and skim milk. Compared with those prepared with GG, the thickened liquids prepared with CSG and XG exhibited greater viscoelasticity, better water-holding capacity, and more compact networks. The findings suggested that CSG can be used as a potential thickener for thickening liquid foods to manage dysphagia.

Subcellular localization of viral proteins after porcine epidemic diarrhea virus infection and their roles in the viral life cycle.

Porcine epidemic diarrhea virus (PEDV) is one of the most devastating diseases affecting the pig industry globally. Due to the emergence of novel strains, no effective vaccines are available for prevention and control. Investigating the pathogenic mechanisms of PEDV may provide insights for creating clinical interventions. This study constructed and expressed eukaryotic expression vectors containing PEDV proteins (except NSP11) with a 3' HA tag in Vero cells. The subcellular localization of PEDV proteins was examined using endogenous protein antibodies to investigate their involvement in the viral life cycle, including endocytosis, intracellular trafficking, genome replication, energy metabolism, budding, and release. We systematically analyzed the potential roles of all PEDV viral proteins in the virus life cycle. We found that the endosome sorting complex required for transport (ESCRT) machinery may be involved in the replication and budding processes of PEDV. Our study provides insight into the molecular mechanisms underlying PEDV infection. IMPORTANCE: The global swine industry has suffered immense losses due to the spread of PEDV. Currently, there are no effective vaccines available for clinical protection. Exploring the pathogenic mechanisms of PEDV may provide valuable insights for clinical interventions. This study investigated the involvement of viral proteins in various stages of the PEDV lifecycle in the state of viral infection and identified several previously unreported interactions between viral and host proteins. These findings contribute to a better understanding of the pathogenic mechanisms underlying PEDV infection and may serve as a basis for further research and development of therapeutic strategies.

Use of the Neuroform Atlas Stent or LVIS Jr Stent for Treatment of Unruptured Intracranial Aneurysms in Parent Arteries of <2 mm in Diameter: A Multicenter Experience.

BACKGROUND AND PURPOSE: The Neuroform Atlas stent and the LVIS Jr stent are intracranial microstent systems for the treatment of wide-neck intracranial aneurysms. Hence, this study aimed to compare the efficacy and safety of the Neuroform Atlas stent and the LVIS Jr stent for the treatment of unruptured intracranial aneurysms in parent arteries of <2 mm in diameter. MATERIALS AND METHODS: From March 2022 to April 2023, the clinical and imaging data of 135 patients with unruptured intracranial aneurysms treated with stent-assisted coiling using the Neuroform Atlas or LVIS Jr stent in parent arteries of <2 mm in diameter were retrospectively analyzed. Stent apposition was evaluated by high-resolution conebeam CT (HR-CBCT). Immediate aneurysm-embolization attenuation and occlusion at 6-month follow-up were evaluated using 2D DSA and the modified Raymond-Roy classification. Adverse events were recorded. Multivariate logistic regression analysis was undertaken to determine the independent factors affecting incomplete stent apposition. RESULTS: One hundred thirty-five patients (135 aneurysms) underwent stent-assisted coiling (66 Neuroform Atlas stents and 69 LVIS Jr stents). Intraoperative HR-CBCT showed that 1 Neuroform Atlas stent and 11 LVIS Jr stents had incomplete stent apposition at the aneurysm neck (P < .05). Perioperative complications occurred in 3 cases (2.22%). These comprised 2 cases of neurologic complications (1 case of distal intracranial vascular embolism and 1 case of cerebral parenchymal hemorrhage) and 1 case of severe postprocedural gastrointestinal hemorrhage. DSA follow-up showed 3 cases of aneurysm recurrence in the LVIS Jr group. Multivariate regression analysis showed that a stent angle of ≥75° (OR, 23.963; P = .005) or a parent artery diameter mismatch ratio of ≥1.25 (OR, 8.043; P = .037) were risk factors for incomplete stent apposition, especially for the LVIS Jr stent (OR, 20.297; P = .015). CONCLUSIONS: The Neuroform Atlas stent and LVIS Jr stent are efficacious in the treatment of unruptured intracranial aneurysms in parent arteries of <2 mm in diameter. Apposition of the LVIS Jr stent was worse than in the Neuroform Atlas stent at the neck of some aneurysms.

The cellular-centered view of hypoxia tumor microenvironment: Molecular mechanisms and therapeutic interventions.

Cancer is a profoundly dynamic, heterogeneous and aggressive systemic ailment, with a coordinated evolution of various types of tumor niches. Hypoxia plays an indispensable role in the tumor micro-ecosystem, drastically enhancing the plasticity of cancer cells, fibroblasts and immune cells and orchestrating intercellular communication. Hypoxia-induced signals, particularly hypoxia-inducible factor-1α (HIF-1α), drive the reprogramming of genetic, transcriptional, and proteomic profiles. This leads to a spectrum of interconnected processes, including augmented survival of cancer cells, evasion of immune surveillance, metabolic reprogramming, remodeling of the extracellular matrix, and the development of resistance to conventional therapeutic modalities like radiotherapy and chemotherapy. Here, we summarize the latest research on the multifaceted effects of hypoxia, where a multitude of cellular and non-cellular elements crosstalk with each other and co-evolve in a synergistic manner. Additionally, we investigate therapeutic approaches targeting hypoxic niche, encompassing hypoxia-activated prodrugs, HIF inhibitors, nanomedicines, and combination therapies. Finally, we discuss some of the issues to be addressed and highlight the potential of emerging technologies in the treatment of cancer.

The IL-33-ST2 axis plays a vital role in endometriosis via promoting epithelial-mesenchymal transition by phosphorylating ß-catenin.

OBJECTIVES: Interleukin 33 (IL-33) is a crucial inflammatory factor that functions as an alarm signal in endometriosis (EMs). Epithelial-mesenchymal transition (EMT), a process related to inflammatory signals, intracellular reactive oxygen species (ROS) production, and lipid peroxidation, have been proposed as potential mechanisms that contribute to the development and progression of EMs. IL-33 is highly upregulated in the ectopic milieu. Moreover, ectopic endometrial cells constitutively express interleukin-33 receptor ST2 (IL-33R). However, the role of IL-33/ST2 in the EMT of EMs remains largely unknown. In this study, we aimed to mechanistically determine the role of IL-33/ST2 in EMs-associated fibrosis. MATERIALS AND METHODS: We established a non-lethal oxidative stress model to explore the conditions that trigger IL-33 induction. We performed α-smooth muscle actin (α-SMA) protein detection, cell counting kit-8 (CCK-8) assays, and scratch assays to analyze the impact of IL-33 on primary endometrial stromal cells (ESCs) proliferation and invasion. Clinical samples from patients with or without EMs were subjected to immunohistochemical (IHC) and and immunofluorescence(IF) staining to assess the clinical relevance of IL-33 receptor ST2 and EMT-related proteins. Furthermore, we used the ectopic human endometrial epithelial cell line 12Z and normal human epithelial cell line EEC to evaluate the effects of IL-33 on Wnt/ß-catenin signaling. The effect of IL-33 on EMT-associated fibrosis was validated in vivo by intraperitoneal injections of IL-33 and antiST2. RESULTS: We observed that ectopic milieu, characterized by ROS, TGF-ß1, and high level of estrogen, triggers the secretion of IL-33 from ectopic ESCs. Ectopic endometrial lesions exhibited higher level of fibrotic characteristics and ST2 expression than that in the normal endometrium. Exogenous recombinant human (rhIL-33) enhanced ESC migration and survival. Similarly, 12Z cells displayed a higher degree of EMT characteristics with elevated expression of CCN4 and Fra-1, downstream target genes of the WNT/ß-catenin pathway, than that observed in EECs. Conversely, blocking IL-33 with neutralizing antibodies, knocking down ST2 or ß-catenin with siRNA, and ß-catenin dephosphorylation abolished its effects on EMT promotion. In vivo validation demonstrated that IL-33 significantly promotes EMs-related fibrosis through the activation of Wnt/ß-catenin signaling. CONCLUSION: Our data strongly support the vital role of the IL-33/ST2 pathway in EMs-associated fibrosis and emphasize the importance of the EMT in the pathophysiology of fibrosis. Targeting the IL-33/ST2/Wnt/ß-catenin axis may hold promise as a feasible therapeutic approach for controlling fibrosis in EMs.

Regulating the activity of GABAergic neurons in the ventral pallidum alters the general anesthesia effect of propofol.

The full mechanism of action of propofol, a commonly administered intravenous anesthetic drug in clinical practice, remains elusive. The focus of this study was the role of GABAergic neurons which are the main neuron group in the ventral pallidum (VP) closely associated with anesthetic effects in propofol anesthesia. The activity of VP GABAergic neurons following propofol anesthesia in Vgat-Cre mice was observed via detecting c-Fos immunoreactivity by immunofluorescence and western blotting. Subsequently, chemogenetic techniques were employed in Vgat-Cre mice to regulate the activity of VP GABAergic neurons. The role of VP GABAergic neurons in generating the effects of general anesthesia induced by intravenous propofol was further explored through behavioral tests of the righting reflex. The results revealed that c-Fos expression in VP GABAergic neurons in Vgat-Cre mice dramatically decreased after propofol injection. Further studies demonstrated that chemogenetic activation of VP GABAergic neurons during propofol anesthesia shortened the duration of anesthesia and promoted wakefulness. Conversely, the inhibition of VP GABAergic neurons extended the duration of anesthesia and facilitated the effects of anesthesia. The results obtained in this study suggested that regulating the activity of GABAergic neurons in the ventral pallidum altered the effect of propofol on general anesthesia.

[Synthesis of fluorinated nitrogen-rich porous organic polymers and removal of perfluorooctanoic acid from water].

Perfluorooctanoic acid (PFOA) is a persistent contaminant with detrimental effects on the natural environment. This persistence leads to potential enrichment and osmotic transfer, which can affect normal circulation in the environment. PFOA poses significant threats to both the natural environment and human health. Therefore, the development of cost-effective, highly efficient, and environment-friendly PFOA adsorbents is a crucial endeavor. This paper presents the catalyst-free one-pot synthesis of fluorinated nitrogen-rich porous organic polymers (POP-3F) via a Schiff-base condensation reaction. The reaction between the nitrogen-rich compound 1,4-bis(2,4-diamino-1,3,5-triazine)benzene and p-trifluoromethylbenzaldehyde yielded POP-3F. The introduction of fluorine atoms into the nitrogen-rich porous organic polymer enhanced its hydrophobicity, thereby facilitating favorable fluoro-fluorine interactions with PFOA and, thus, improving the efficacy of the adsorbent. Scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), solid-state nuclear magnetic resonance (ssNMR) spectroscopy, X-ray photoelectron spectroscopy (XPS), nitrogen adsorption-desorption analysis, and thermogravimetric analysis (TGA) were used to confirm the successful synthesis and characterization of POP-3F. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was conducted in negative electrospray ionization (ESI) mode coupled with multi-reaction monitoring mode (MRM). The instrument was equipped with an Atlantis T3 column (100 mm×2.1 mm, 3 µm), and analysis was conducted using an external standard method. The influences of various factors on PFOA adsorption by POP-3F, including pH, salt concentration, and humic acid presence, were investigated. The highest PFOA removal rate (98.6%) was achieved at a pH of 2, indicating the applicability of POP-3F for the effective removal of PFOA from acidic industrial wastewater. The removal rate of PFOA was unaffected by increases in NaCl concentration. This phenomenon can be attributed to electrostatic interactions between the protonated secondary amines in POP-3F and deprotonated PFOA. Upon the addition of NaCl, a double electric layer is formed on the POP-3F surface, with Cl- ions in the outer layer and Na+ ions in the inner layer, which weakened these interactions. Humic acid is competitively adsorbed with PFOA. However, POP-3F demonstrated good removal rates even in the presence of high humic acid concentrations in water. Adsorption isotherm and kinetics experiments were conducted at the optimal pH to explore the relevant adsorption mechanism. The results showed a rapid initial adsorption rate, with 95.4% PFOA removal within 5 min. Optimal adsorption equilibrium was achieved within 6 h, and the removal rate decreased by only 0.3% after 24 h. This finding indicates that POP-3F exhibits sustained efficacy for PFOA removal. Langmuir fitting analysis revealed a theoretical maximum adsorption capacity of 191 mg/g for POP-3F; this value surpasses those of activated carbon materials and most other adsorbents, highlighting the superior PFOA-adsorption performance of POP-3F. Additionally, matrix effects minimally affected the removal of PFOA by POP-3F, with only a slight reduction (0.1%) observed in simulated natural water. The recyclability of POP-3F was assessed over five adsorption-desorption cycles. The removal efficenecy exhibited a minor decrease of only 0.67% after five cycles. These results demonstrate the recyclability of the proposed adsorbent, which translates into cost reduction through reusability. This characteristic renders POP-3F a promising candidate for the economical and efficient removal of PFOA from wastewater in practical applications.

Prevalence, treatment efficacy, and risk factors of vascular complications in acute pancreatitis: A case-control study.

OBJECTIVE: We aimed to investigate the prevalence of vascular complications in acute pancreatitis (AP), to compare patient outcomes using various treatments, and to explore the related risk factors. METHODS: Consecutive AP patients admitted from January 2010 to July 2017 were retrospectively included. Demographics, vascular complications, laboratory indices, and imaging findings were collected. Univariate and multivariate analyses were used to explore potential risk factors of vascular complications. RESULTS: Of 3048 AP patients, 808 (26.5%) had vascular complications, including visceral vein thrombosis, sinistral portal hypertension, and arterial complications. And 38 (4.7%) patients received anticoagulant therapy and had a higher rate of recanalization (P < 0.001). Bleeding occurred in 95 (11.8%) patients, who received further treatment. Multivariate analysis identified male gender (odds ratio [OR] 1.650, 95% confidence interval [CI] 1.101-2.472), hyperlipidemia (OR 1.714, 95% CI 1.356-2.165), disease recurrence (OR 3.727, 95% CI 2.713-5.118), smoking (OR 1.519, 95% CI 1.011-2.283), hemoglobin level (OR 0.987, 95% CI 0.981-0.993), white blood cell (WBC) count (OR 1.094, 95% CI 1.068-1.122), non-vascular local complications (OR 3.018, 95% CI 1.992-4.573), computed tomography severity index (CTSI) (OR 1.425, 95% CI 1.273-1.596), and acute physiology and chronic health evaluation (APACHE) II score (OR 1.057, 95% CI 1.025-1.090) were related to vascular complications. CONCLUSIONS: Vascular complications in AP is prevalent and their treatment is challenging. Further investigations are warranted to determine the optimal treatment strategy. Independent risk factors included male gender, hyperlipidemia, disease recurrence, smoking, WBC count, non-vascular local complications, CTSI, and APACHE II score.

A clinical comparative study of dual LVIS devices and single flow diversion stenting for the treatment of unruptured V3-V4 vertebral artery dissection.

PURPOSE: This study aims to compare the efficacy and safety of using overlapping low-profile visualized intraluminal support (LVIS) devices and flow diversion (FD) for the treatment of unruptured vertebral artery dissection (VAD) in the V3-V4 segments. METHODS: The clinical and imaging data of 71 patients with unruptured VAD in the V3-V4 segments who underwent either dual LVIS stenting (d-LVIS group) or single FD stenting (FD group) at our center from September 2014 to December 2021 were retrospectively analyzed. RESULTS: Immediate postoperative angiography revealed no significant difference in the degree of occlusion between the two groups in treating vertebral artery dissecting aneurysms (with or without noncompact coiling). However, the d-LVIS group had significantly higher fluoroscopy exposure time and total radiation exposure dose compared to the FD group. During the perioperative period, two cases of pontine infarction and one case of acute thrombosis were encountered. One patient died from subarachnoid hemorrhage during the follow-up period. For dissecting the aneurysm, angiographic follow-up (8.56 ± 1.96 months) showed similar healing outcomes between the two groups (with or without noncompact coiling). However, seven patients (7/40, 17.5%) showed poor healing and one patient showed mild in-stent stenosis. For simple dissection, angiographic follow-up (8.78 ± 1.83 months) showed patent lumens in both groups, with all dissections healing well, and two patients having mild in-stent stenosis. CONCLUSION: Both methods could effectively treat unruptured VAD in V3-V4 segments. Nevertheless, simple FD implantation is relatively easier to perform and involves lower radiation exposure.

Dihydroartemisinin-driven TOM70 inhibition leads to mitochondrial destabilization to induce pyroptosis against lung cancer.

Enhancement of malignant cell immunogenicity to relieve immunosuppression of lung cancer microenvironment is essential in lung cancer treatment. In previous study, we have demonstrated that dihydroartemisinin (DHA), a kind of phytopharmaceutical, is effective in inhibiting lung cancer cells and boosting their immunogenicity, while the initial target of DHA's intracellular action is poorly understood. The present in-depth analysis aims to reveal the influence of DHA on the highly expressed TOM70 in the mitochondrial membrane of lung cancer. The affinity of DHA and TOM70 was analyzed by microscale thermophoresis (MST), pronase stability, and thermal stability. The functions and underlying mechanism were investigated using western blots, qRT-PCR, flow cytometry, and rescue experiments. TOM70 inhibition resulted in mtDNA damage and translocation to the cytoplasm from mitochondria due to the disruption of mitochondrial homeostasis. Further ex and in vivo findings also showed that the cGAS/STING/NLRP3 signaling pathway was activated by mtDNA and thereby malignant cells underwent pyroptosis, leading to enhanced immunogenicity of lung cancer cells in the presence of DHA. Nevertheless, DHA-induced mtDNA translocation and cGAS/STING/NLRP3 mobilization were synchronously attenuated when TOM70 was replenished. Finally, DHA was demonstrated to possess potent anti-lung cancer efficacy in vitro and in vivo. Taken together, these data confirm that TOM70 is an important target for DHA to disturb mitochondria homeostasis, which further activates STING and arouses pyroptosis to strengthen immunogenicity against lung cancer thereupon. The present study provides vital clues for phytomedicine-mediated anti-tumor therapy.

O-GlcNAcylation in ischemic diseases.

Protein glycosylation is an extensively studied field, with the most studied forms being oxygen or nitrogen-linked N-acetylglucosamine (O-GlcNAc or N-GlcNAc) glycosylation. Particular residues on proteins are targeted by O-GlcNAcylation, which is among the most intricate post-translational modifications. Significantly contributing to an organism's proteome, it influences numerous factors affecting protein stability, function, and subcellular localization. It also modifies the cellular function of target proteins that have crucial responsibilities in controlling pathways related to the central nervous system, cardiovascular homeostasis, and other organ functions. Under conditions of acute stress, changes in the levels of O-GlcNAcylation of these proteins may have a defensive function. Nevertheless, deviant O-GlcNAcylation nullifies this safeguard and stimulates the advancement of several ailments, the prognosis of which relies on the cellular milieu. Hence, this review provides a concise overview of the function and comprehension of O-GlcNAcylation in ischemia diseases, aiming to facilitate the discovery of new therapeutic targets for efficient treatment, particularly in patients with diabetes.

Pyridostigmine attenuates hypertension by inhibiting activation of the renin-angiotensin system in the hypothalamic paraventricular nucleus.

Activation of the renin-angiotensin system (RAS) triggers oxidative stress and an inflammatory response in the hypothalamic paraventricular nucleus (PVN), in turn increasing the sympathetic hyperactivity that is a major cause of hypertension. Pyridostigmine has cardioprotective effects by suppressing the RAS of myocardial tissue. However, whether pyridostigmine attenuates hypertension by inhibiting the RAS of the PVN remains unclear. We thus investigated the effect and mechanism of pyridostigmine on two-kidney one-clip (2K1C)-induced hypertension. 2K1C rats received pyridostigmine, or not, for 8 weeks. Cardiovascular function, hemodynamic parameters, and autonomic activity were measured. The PVN levels of pro-/anti-inflammatory cytokines, oxidative stress, and RAS signaling molecules were evaluated. Our results showed that hypertension was accompanied by cardiovascular dysfunction and an autonomic imbalance characterized by enhanced sympathetic but diminished vagal activity. The PVN levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS), NOX-2, and malondialdehyde (MDA) increased; those of IL-10 and superoxide dismutase (SOD) decreased. Moreover, the RAS signaling pathway was activated, as evidenced by increased levels of the angiotensin-converting enzyme (ACE), angiotensin II (Ang II), and the Ang II type 1 receptor (AT1R) and a decreased AT2R level. Pyridostigmine lowered blood pressure and improved cardiovascular function, associated with restoration of the autonomic balance. Meanwhile, pyridostigmine decreased PVN IL-6, TNF-α, ROS, NOX-2, and MDA levels and increased IL-10 and SOD levels. Additionally, pyridostigmine suppressed PVN ACE, Ang II, and AT1R levels and increased AT2R expression. Pyridostigmine attenuated hypertension by inhibiting PVN oxidative stress and inflammation induced by the RAS.

Systematic evaluation and meta-analysis of the effects of major dietary patterns on cognitive function in healthy adults.

PURPOSE: Evidence shows diet promotes brain health. Combining foods and nutrients may have beneficial synergistic effects, but the effects on cognitive function interventions are inconsistent. So, a meta-analysis of RCTs was conducted to examine the specific effects on cognitive function. METHODS: We searched four databases from creation to April 2023. Eligible randomized controlled trials were identified. A random-effects meta-analysis was used to combine standardized mean differences (SMD) (95% confidence intervals [CI]), and homogeneity tests for a variance were calculated. RESULTS: A total of 19 studies involving 12,119 participants were included in this systematic review. The dietary intervention group had a positive effect on overall cognitive functioning compared to the control group (SMD = 0.14, 95% CI [0.08, 0.20], P < 0.00001). The dietary intervention improved executive function, processing speed and language skills (SMD = -0.10, 95% CI [-0.17,-0.04], P = 0.002, I2 = 0%), (SMD = -0.16, 95% CI [-0.23,-0.09], P < 0.00001, I2 = 0%), (SMD = 0.10, 95% CI [0.01, 0.20], P = 0.03, I2 = 0%). The dietary intervention had no effect on delayed memory and spatial ability (SMD = 0.04, 95% CI [-0.02, 0.09], P = 0.20, I2 = 0%), (SMD = 0.08, 95% CI [-0.01, 0.16], P = 0.08, I2 = 0%). CONCLUSION: The Mediterranean diet, a diet with restricted caloric intake, a diet incorporating aerobic exercise, a low-carbohydrate diet, and a healthy lifestyle diet (increased intake of fruits and vegetables, and weight and blood pressure management) appear to have positive effects on cognitively healthy adults, as reflected in their overall cognitive, processing speed, executive, and language functions. PROSPERO REGISTRATION NUMBER: CRD42023414704.

Morphine timing-dependent modulation of TRPV1 phosphorylation correlates with differential morphine effects on myocardial ischemia/reperfusion injury.

Opioids are used for pain relief in patients suffering from acute myocardial ischemia or infarction. Clinical and laboratory studies demonstrate that morphine treated patients or the experimental animal model suffering acute myocardial ischemia and reperfusion, may worsen myocardial viability. As transient receptor potential vanilloid 1 (TRPV1) plays important roles in pain sensation and cardio-protection, we query whether opioids may exacerbate myocardial viability via interaction with TRPV1 activity in the pain relief. We found the co-expressions of TRPV1 and opioid µ, δ and κ receptors in adult rat cardiomyocytes. Intravenous injection of morphine (0.3 mg/kg) at 20 min after induction of myocardial ischemia, in the rat model of acute myocardial ischemia and reperfusion, induced significant reduction of phosphorylated TRPV1 (p-TRPV1) in the ventricular myocardium and increase in serum cardiac troponin I (cTnI), compared with the ischemia/reperfusion controls (all P < 0.05). The effects of morphine were completely reversed by selective opioid µ, δ and κ receptor antagonists. While significant upregulation of p-TRPV1 (P < 0.05) and improvement of ±dP/dt max (all P < 0.05) were detected in the animals giving the same dose of morphine before induction of myocardial ischemia. The changes in p-TRPV1 correlate with the alterations of cTnI (r = -0.5840, P = 0.0283) and ±dP/dt max (r = 0.8084, P = 0.0005 and r = -0.8133, P = 0.0004, respectively). The findings of this study may indicate that potentiation and attenuation of TRPV1 sensitivity correlate with the improvement of the cardiac performance and the aggravation of myocardial viability, respectively, by giving morphine before and during myocardial ischemia and reperfusion.

The self-boosting ultrafast removal of Cr(VI) and organic dye in textile wastewater through sulfite-induced redox processes.

The treatment of textile wastewater containing harmful metal ions poses a significant challenge in industrial applications due to its environmental impact. In this study, the use of sulfite for treating simulated dye wastewater containing New Coccine (NC) and Cr(VI) was investigated. The removal of NC was influenced by the redox reaction between Cr(VI) and sulfite, demonstrating a strong self-boosting effect of Cr(VI) on NC removal. Remarkable NC decoloration (95%) and Cr(VI) reduction (90%) were achieved within 1 min, highlighting the effectiveness of the treatment. Quenching experiments and electron paramagnetic resonance (EPR) technology confirmed that singlet oxygen (1O2) was the main oxidative agent for organic dye removal and SO4•-, •OH and Cr(V) were also identified as key contributors to NC degradation. The Cr(VI)/sulfite system exhibited higher efficiency in degrading azo dyes, such as NC and Congo Red (CR), compared to non-azo dyes like Methylene Blue (MB). This superiority may be attributed to the action of Cr(V) on azo groups. Additionally, the COD removal experiments were conducted on the actual dye wastewater, showing the excellent performance of the Cr(VI)/Sulfite system in treating industrial textile wastewater. This approach presents a promising strategy for effective "waste control by waste", offering great potential for addressing challenges related to dye wastewater treatment and environmental pollution control in practical industrial scenarios.

Brownification increases the abundance of microorganisms related to carbon and nitrogen cycling in shallow lakes.

Brownification in aquatic ecosystems under global change has attracted attention. The composition and quantity of dissolved organic matter transported from various land use types to lakes differ significantly, causing varying ecological effects of lake brownification by region. Bacterial communities make a significant contribution to the material cycle of ecosystems and are sensitive to environmental changes. In this study, a series of mesocosm systems were used to simulate forest lakes and urban lakes with different degrees of brownification, and a high-throughput amplicon sequencing technique was used to explore the changes in the composition, structure, and function of bacterial communities in shallow lakes undergoing brownification. Principal coordinate analysis (PCoA) and Jensen‒Shannon distance typing analysis both indicated significant differences in bacterial communities between forest lakes and urban lakes. The α diversity of bacterial communities in urban lakes increased with the degree of brownification. However, whether forest lakes or urban lakes, brownification increased the abundance of carbon cycling-related bacterial phyla (Proteobacteria, Poribacteria, and Chloroflexi) and nitrogen cycling-related bacterial genera (Microbacteriaceae, Limnohabitans, Comamonadaceae, Bacillus, and Rhizobiales_Incertae_Sedis). Additionally, the carbon and nitrogen cycling functions of bacterial communities in forest lakes are dominant, while those in urban lakes are dominated by functions related to light. Our study has preliminarily revealed that lake brownification promotes the growth of carbon and nitrogen cycling microorganisms, providing a new paradigm for understanding the response of lake ecosystems in different catchment areas to environmental changes and the carbon and nitrogen cycling processes in shallow lake ecosystems.

The role of the CXCR6/CXCL16 axis in the pathogenesis of fibrotic disease.

CXC chemokine receptor 6 (CXCR6), a seven-transmembrane domain G-protein-coupled receptor, plays a pivotal regulatory role in inflammation and tissue damage through its interaction with CXC chemokine ligand 16 (CXCL16). This axis is implicated in the pathogenesis of various fibrotic diseases and correlates with clinical parameters that indicate disease severity, activity, and prognosis in organ fibrosis, including afflictions of the liver, kidney, lung, cardiovascular system, skin, and intestines. Soluble CXCL16 (sCXCL16) serves as a chemokine, facilitating the migration and recruitment of CXCR6-expressing cells, while membrane-bound CXCL16 (mCXCL16) functions as a transmembrane protein with adhesion properties, facilitating intercellular interactions by binding to CXCR6. The CXCR6/CXCL16 axis is established to regulate the cycle of damage and repair during chronic inflammation, either through modulating immune cell-mediated intercellular communication or by independently influencing fibroblast homing, proliferation, and activation, with each pathway potentially culminating in the onset and progression of fibrotic diseases. However, clinically exploiting the targeting of the CXCR6/CXCL16 axis requires further elucidation of the intricate chemokine interactions within fibrosis pathogenesis. This review explores the biology of CXCR6/CXCL16, its multifaceted effects contributing to fibrosis in various organs, and the prospective clinical implications of these insights.