Enzymatic acylation of cyanidin-3-O-glucoside with aromatic and aliphatic acid methyl ester: Structure-stability relationships of acylated derivatives.

Anthocyanins are water-soluble pigments, but they tend to be unstable in aqueous solutions. Modification of their molecular structure offers a viable approach to alter their intrinsic properties and enhance stability. Aromatic and aliphatic acid methyl esters were used as acyl donors in the enzymatic acylation of cyanidin-3-O-glucoside (C3G), and their analysis was conducted using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). The highest conversion rate achieved was 96.41 % for cyanidin-3-O-(6″-feruloyl) glucoside. Comparative evaluations of stability revealed that aromatic acyl group-conjugated C3G exhibited superior stability enhancement compared with aliphatic acyl group derivatives. The stability of aliphatic C3G decreased with increasing carbon chain length. The molecular geometries of different anthocyanins were optimized, and energy level calculations using density functional theory (DFT) identified their sites with antioxidant activities. Computational calculations aligned with the in vitro antioxidant assay results. This study provided theoretical support for stabilizing anthocyanins and broadened the application of acylated anthocyanins as food colorants and nutrient supplements.

Modulating Solvation Shell with Acrylamide Electrolyte Additives for Reversible Zn Anodes.

The reconsideration of aqueous zinc-ion batteries (ZIBs) has been motivated by the attractive zinc metal, which stands out for its high theoretical capacity and cost efficiency. Nonetheless, detrimental side reactions triggered by the remarkable reactivity of H2O molecules and rampant dendrite growth significantly compromise the stability of the zinc metal anode. Herein, a novel approach was proposed by leveraging the unique properties of acrylamide (AM) molecules to increase the driving force for nucleation and parasitic reactions. Combined with experimental data and theoretical simulations, it is demonstrated that the incorporation of AM additive can reconstruct the solvation shell around Zn2+ and reduce the number of active H2O molecules, thereby effectively reducing the H2O molecule decomposition. Consequently, the Zn//Zn symmetric batteries with AM-containing ZnSO4 electrolytes can attain excellent long-term performances over 2000 h at 1 mA cm-2 and nearly 500 h at 10 mA cm-2. The Zn//VO2 full batteries still display improved cycling performances and a high initial discharging capacity of 227 mA h g-1 at 3 A g-1 compared to the ZnSO4 electrolyte. This electrolyte optimization strategy offers new insights for achieving long-term ZIBs and advances the progress of ZIBs in energy storage.

Research Progress on Starfish Outbreaks and Their Prevention and Utilization: Lessons from Northern China.

Starfish are keystone species as predators in benthic ecosystems, but when population outbreaks occur, this can have devastating consequences ecologically. Furthermore, starfish outbreaks and invasions can have adverse impact economically by impacting shellfish aquaculture. For example, an infestation of starfish in Qingdao led to a 50% reduction in sea cucumber production and an 80% reduction in scallop production, resulting in an economic loss of approximately RMB 100 million to oyster and other shellfish industries. Addressing the imperative need to proactively mitigate starfish invasions requires comprehensive research on their behavior and the underlying mechanisms of outbreaks. This review scrutinizes the historical patterns of outbreaks among diverse starfish species across various regions, delineates the factors contributing to the proliferation of Asterias amurensis in Chinese waters, articulates preventive and remedial strategies, and outlines the potential for the sustainable utilization of starfish.

Anthocyanins as natural bioactives with anti-hypertensive and atherosclerotic potential: Health benefits and recent advances.

BACKGROUND: Hypertension is a highly prevalent chronic metabolic illness affecting individuals of all age groups. Furthermore, it is a significant risk factor for the development of atherosclerosis (AS), as a correlation between hypertension and AS has been observed. However, the effective treatments for either of these disorders appear to be uncommon. METHODS: A systematic search of articles published in PubMed, Web of Science, ScienceDirect, Scopus, and Google Scholar databases over the last decade was performed using the following keywords: hypertension, AS, anthocyanins, antioxidants, gut microbes, health benefits, and bioactivity. RESULTS: The available research indicates that anthocyanin consumption can achieve antioxidant effects by inducing the activation of intracellular nuclear factor erythroid 2-related factor (Nrf2) and the expression of antioxidant genes. Moreover, previous reports showed that anthocyanins can enhance the human body's ability to fight against inflammation and cancer through the inhibition of inflammatory factors and the regulation of related signaling pathways. They can also protect the blood vessels and nervous system by regulating the production and function of endothelial nitric oxide synthase (eNOS). Gut microorganisms play an important role in various chronic diseases. Our research has also investigated the role of anthocyanins in the metabolism of the gut microbiota, leading to significant breakthroughs. This study not only presents a unique strategy for reducing the risk of cardiovascular diseases (CVDs) without the need for medicine but also provides insights into the development and utilization of intestinal probiotic dietary supplements. CONCLUSION: In this review, different in vitro and in vivo studies have shown that anthocyanins slow down the onset and progression of hypertension and AS through different mechanisms. In addition, gut microbial metabolites also play a crucial role in diseases through the gut-liver axis.

The efficacy of repetitive transcranial magnetic stimulation in postherpetic neuralgia: a meta-analysis of randomized controlled trials.

Purpose: This systematic review and meta-analysis aimed to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in postherpetic neuralgia (PHN). Methods: Through an extensive search in four databases until October 2023, we selected five randomized controlled trials adhering to our specific criteria, involving 257 patients in total. For continuous outcomes, the standardized mean difference (SMD) was calculated. Heterogeneity among the studies was assessed using Cochran's I 2 and Q statistics, adopting a random-effects model for I 2 values over 50%. For assessing potential publication bias, we utilized both funnel plot and Egger's test. Results: Our analysis found that rTMS reduced the overall visual analogue scale (VAS) (SMD: -1.52, 95% CI: -2.81 to -0.23, p = 0.02), VAS at 1 month post-treatment (SMD: -2.21, 95% CI: -4.31 to -0.10, p = 0.04), VAS at 3 months post-treatment (SMD: -1.51, 95% CI: -2.81 to -0.22, p = 0.02), as well as patients' global impression of change scale (PGIC) (SMD: -1.48, 95% CI: -2.87 to -0.09, p = 0.04) and short-form McGill pain questionnaire (SF-MPQ) (SMD: -1.25, 95% CI: -2.41 to -0.09, p = 0.03) compared to the sham-rTMS group. Conclusion: Our study suggests that rTMS might have a potential alleviating effect on PHN symptoms. However, due to the limited number of studies and variations in rTMS parameters, larger sample studies involving more diverse populations, as well as further clarification of the most appropriate stimulation protocol, are still needed. Systematic review registration: https://www.crd.york.ac.uk/prospero/, Identifier ID: CRD42023488420.

Prolonged Cadmium Exposure and Osteoclastogenesis: A Mechanistic Mouse and in Vitro Study.

BACKGROUND: Cadmium (Cd) is a highly toxic and widespread environmental oxidative stressor that causes a myriad of health problems, including osteoporosis and bone damage. Although nuclear factor erythroid 2-related factor 2 (NRF2) and its Cap 'n' Collar and basic region Leucine Zipper (CNC-bZIP) family member nuclear factor erythroid 2-related factor 1 (NRF1) coordinate various stress responses by regulating the transcription of a variety of antioxidant and cytoprotective genes, they play distinct roles in bone metabolism and remodeling. However, the precise roles of both transcription factors in bone loss induced by prolonged Cd exposure remain unclear. OBJECTIVES: We aimed to understand the molecular mechanisms underlying Cd-induced bone loss, focusing mainly on the roles of NRF2 and NRF1 in osteoclastogenesis provoked by Cd. METHODS: Male wild-type (WT), global Nrf2-knockout (Nrf2-/-) and myeloid-specific Nrf2 knockout [Nrf2(M)-KO] mice were administered Cd (50 or 100 ppm) via drinking water for 8 or 16 wk, followed by micro-computed tomography, histological analyses, and plasma biochemical testing. Osteoclastogenesis was evaluated using bone marrow-derived osteoclast progenitor cells (BM-OPCs) and RAW 264.7 cells in the presence of Cd (10 or 20 nM) with a combination of genetic and chemical modulations targeting NRF2 and NRF1. RESULTS: Compared with relevant control mice, global Nrf2-/- or Nrf2(M)-KO mice showed exacerbated bone loss and augmented osteoclast activity following exposure to 100 ppm Cd in drinking water for up to 16 wk. In vitro osteoclastogenic analyses suggested that Nrf2-deficient BM-OPCs and RAW 264.7 cells responded more robustly to low levels of Cd (up to 20 nM) with regard to osteoclast differentiation compared with WT cells. Further mechanistic studies supported a compensatory up-regulation of long isoform of NRF1 (L-NRF1) and subsequent induction of nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1 (NFATc1) as the key molecular events in the Nrf2 deficiency-worsened and Cd-provoked osteoclastogenesis. L-Nrf1 silenced (via lentiviral means) Nrf2-knockdown (KD) RAW cells exposed to Cd showed dramatically different NFATc1 and subsequent osteoclastogenesis outcomes compared with the cells of Nrf2-KD alone exposed to Cd, suggesting a mitigating effect of the Nrf1 silencing. In addition, suppression of reactive oxygen species by exogenous antioxidants N-acetyl-l-cysteine (2 mM) and mitoquinone mesylate (MitoQ; 0.2µM) mitigated the L-NRF1-associated effects on NFATc1-driven osteoclastogenesis outcomes in Cd-exposed Nrf2-KD cells. CONCLUSIONS: This in vivo and in vitro study supported the authors' hypothesis that Cd exposure caused bone loss, in which NRF2 and L-NRF1 responded to Cd and osteoclastogenic stimuli in a cooperative, but contradictive, manner to coordinate Nfatc1 expression, osteoclastogenesis and thus bone homeostasis. Our study suggests a novel strategy targeting NRF2 and L-NRF1 to prevent and treat the bone toxicity of Cd. https://doi.org/10.1289/EHP13849.

Anthocyanin-loaded milk-derived extracellular vesicles nano-delivery system: Stability, mucus layer penetration, and pro-oxidant effect on HepG2 cells.

Anthocyanin (ACN) has attracted considerable attention due to its wide range of physiological effects. However, challenges such as poor stability and limited bioavailability have hindered its utilization in functional foods. To address these issues, this research utilized milk-derived extracellular vesicles (MEV) as carriers for encapsulating and binding ACN through various techniques, including ultrasonic, electroporation, saponin treatment, incubation, and freeze-thaw cycles. The objective of these approaches was to enhance the stability of ACN and improve its oral delivery. Notably, the ACN-loaded MEV (MEV-ACN) prepared through ultrasonic exhibited small particle sizes and good stability under processing, storage, and simulated digestion conditions. Cellular studies revealed that MEV-ACN exhibited pro-oxidant properties and induced oxidative stress, leading to cell apoptosis with greater efficacy compared to free ACN. These findings suggest that encapsulating ACN within MEV can significantly enhance its processing and oral stability, as well as strengthening its dietary defense capabilities in anti-tumor applications.

Controlled reconstruction and application research of lateral overlying strata structure in high-gas mines with thick-hard roofs for a fully-mechanized top-caving face.

Due to the large mining area, the fully-mechanized top-caving mining with thick-hard roof is easy to form cantilever structure on the lateral roof of the working face, which on the one hand causes high stress level of adjacent roadway and serious deformation of roadway, on the other hand causes gas accumulation in corners, which brings severe challenges to safe and efficient mining of the mine. In this study, a mine facing such problems in Jincheng, China was taken as the research object. Based on the mechanical characteristics of coal and rock, the characteristics of overlying strata activity in the mining process of working face are mastered, and the dual effects of controlled transformation of lateral overlying strata structure on stress field and gas field were revealed. On this basis, roadway reinforcement and gas drainage schemes were put forward and applied. The results showed that the strength of the hard rock stratum was high in the triaxial stress environment, and it was not easily destroyed. However, once the strata exceed their strength threshold, they break down. In addition, the strength of coal is relatively low, and it is continuously deformed when the force exceeds its strength. The overlying strata structure after thick-hard roof fully-mechanized top-caving mining evolves in the following manner: "long cantilever length formed by the main roof being broken in the initial stage, voussoir beam formed by the upper hard roof being broken in the middle stage, and double cantilever beam formed by overlying strata compaction." The stress carried by upper hard rock stratum is transferred to coal pillars, which is the main reason for the high stress environment of multi-purpose roadway with large coal pillars. The controlled transformation of lateral overlying strata structure by pre-splitting and roof cutting can realize the "transfer-unloading" of coal pillar stress and the "plugging and driving" of corner gas. Based on the hydraulic fracturing reconstruction of lateral overburden structure, the grouting reinforcement scheme of roadway and dynamic gas drainage scheme were put forward. The results demonstrated that after roof cutting, the maximum deformation of the surrounding rock in the multi-purpose roadway was reduced by approximately 90 %, and the maximum concentration of corner gas was decreased by 15.28 %. This approach successfully achieved a collaborative control effect on roadway surrounding rock stability and gas emission well within the safety limits.

High-Rate and Ultra-Stable aqueous Zinc-Ion batteries enabled by Potassium-Infused ammonium vanadate nanosheets.

Aqueous zinc-ion batteries (AZIBs), defined by low expenses, superior safety, and plentiful reserves, demonstrate tremendous development potential in energy storage systems at the grid scale. Whereas the cathode instability and the limited diffusion of Zn2+ have impeded the development of AZIBs. Herein, a high-performance K-NH4V4O10 (K-NVO) cathode with K+ doping synthesized successfully through one-step hydrothermal approach. Experiments and density functional theory (DFT) calculations indicate that K-NVO has Zn2+ diffusion pathways with lower barriers for smoother transport, and lower formation energy. The combination of the rapid Zn2+ diffusion and the stable structure results in outstanding electrochemical performance of K-NVO as demonstrated in tests. K-NVO cathode achieves a specific capacity of 406 mAh g-1 at 0.2 A g-1, maintains satisfactory cyclic stability with 81.6 % capacity retention after 1000 cycles at 5 A g-1, and possesses a high energy density of 350.9 Wh kg-1. Furthermore, confirmation of the zinc storage mechanism in K-NVO was carried out through Ex situ tests, such as XRD and XPS. This research contributes a unique perspective to the formulation of high-performance cathode materials for AZIBs.

HIF-1α Contributes to Hypoxia-induced VSMC Proliferation and Migration by Regulating Autophagy in Type A Aortic Dissection.

Type A aortic dissection (AD) is a catastrophic cardiovascular disease. Hypoxia-inducible factor-1α (HIF-1α) and autophagy are reported to be upregulated in the AD specimens. However, the interaction between HIF-1α and autophagy in the pathogenesis of AD remains to be explored. HIF-1α and LC3 levels are evaluated in 10 AD and 10 normal aortic specimens. MDC staining, autophagic vacuoles, and autophagic flux are detected in human aortic smooth muscle cells (HASMCs) under hypoxia treatment. CCK-8, transwell, and wound healing assay are used to identify proliferation and migration under hypoxia treatment. Furthermore, 3-MA is used to inhibit autophagy in hypoxia-treated HASMCs. This study reveals that AD tissues highly express HIF-1α and the LC3. Autophagy is induced under hypoxia in a time-dependent manner, and autophagy is positively related to HIF-1α in HASMCs. Moreover, the proliferation and migration of HASMCs are enhanced by hypoxia, whereas the knockdown of HIF-1α attenuates this effect. Additionally, inhibiting autophagy with 3-MA ameliorates hypoxia-induced proliferation and migration of HASMCs. In summary, the above results indicate that HIF-1α facilitates HASMC proliferation and migration by upregulating autophagy in a hypoxic microenvironment. Thus, inhibition of autophagy may be a novel therapeutic target for the prevention and treatment of AD.

Nrf2 Mitigates RANKL and M-CSF Induced Osteoclast Differentiation via ROS-Dependent Mechanisms.

Nuclear factor-erythroid 2-related factor 2 (Nrf2) has been shown to be a negative regulator of osteoclast differentiation, but the precise mechanisms have not yet been established. We examined the precise roles of Nrf2 in regulating antioxidants and reactive oxygen species (ROS) levels, especially the cytoplasmic and mitochondrial ROS during osteoclastogenesis in vitro. In the current study, we found that the absence of Nrf2 promotes osteoclast differentiation in bone-marrow-derived macrophages (BMMs) and RAW 264.7 cells. The receptor activator of NF-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) significantly lowered the levels of Nrf2 and its downstream antioxidant enzymes at mRNA and/or protein levels during osteoclast differentiation in the BMMs of mice and RAW 264.7 mouse leukemic monocytes. Compared to the wild-type cells, Nrf2-deficient cells exhibited heightened sensitivity to both transient RANKL-induced cytoplasmic ROS and prolonged RANKL and M-CSF-induced cytoplasmic and mitochondrial ROS accumulation. Furthermore, exogenous antioxidant agents, including N-acetyl-cysteine (NAC), diphenyleneiodonium chloride (DPI), and mitoquinone mesylate (MitoQ), exhibited substantial capability to suppress the elevation of ROS levels during osteoclast differentiation induced by Nrf2 deficiency, and they consequently inhibited osteoclast differentiation augmented by the lack of Nrf2. The activation of phosphorylated c-FOS resulting from elevated ROS promoted osteoclast differentiation. The inhibition of c-FOS blocked osteoclast differentiation, which was elevated by Nrf2-deficiency. Taken together, these data reveal that Nrf2 effectively decreased the accumulation of intracellular ROS and the phosphorylation of c-FOS during osteoclastic differentiation by regulating antioxidant enzymes and subsequently inhibited RANKL-induced osteoclast differentiation.

Chromosome-level genome assembly of sea scallop Placopecten magellanicus provides insights into the genetic characteristics and adaptive evolution of large scallops.

Placopecten magellanicus (Gmelin, 1791), a deep-sea Atlantic scallop, holds significant commercial value as a benthic marine bivalve along the northwest Atlantic coast. Recognizing its economic importance, the need to reconstruct its genome assembly becomes apparent, fostering insights into natural resources and generic breeding potential. This study reports a high-quality chromosome-level genome of P. magellanicus, achieved through the integration of Illumina short read sequencing, PacBio HiFi sequencing, and Hi-C sequencing techniques. The resulting assembly spans 1778 Mb with a scaffold N50 of 86.71 Mb. An intriguing observation arises - the genome size of P. magellanicus surpasses that of its Pectinidae family peers by 1.80 to 2.46 times. Within this genome, 28,111 protein-coding genes were identified. Comparative genomic analysis involving five scallop species unveils the critical determinant of this expanded genome: the proliferation of repetitive sequences recently inserted, contributing to its enlarged size. The landscape of whole genome collinearity sheds light on the relationships among scallop species, enhancing our broader understanding of their genomic framework. This genome provides genomic resources for future molecular biology research on scallops and serves as a guide for the exploration of longevity-related genes in scallops.

Epileptic EEG Signal Detection Using Variational Modal Decomposition and Improved Grey Wolf Algorithm.

Epilepsy does great harm to the human body, and even threatens human life when it is serious. Therefore, research focused on the diagnosis and treatment of epilepsy holds paramount clinical significance. In this paper, we utilized variational modal decomposition (VMD) and an enhanced grey wolf algorithm to detect epileptic electroencephalogram (EEG) signals. Data were extracted from each patient's preseizure period and seizure period of 200 s each, with every 2 s as a segment, meaning 100 data points could be obtained for each patient's health period as well as 100 data points for each patient's epilepsy period. Variational modal decomposition (VMD) was used to obtain the corresponding intrinsic modal function (VMF) of the data. Then, the differential entropy (DE) and high frequency detection (HFD) of each VMF were extracted as features. The improved grey wolf algorithm is adopted for a selected channel to improve the maximum value of the channel. Finally, the EEG signal samples were classified using a support vector machine (SVM) classifier to achieve the accurate detection of epilepsy EEG signals. Experimental results show that the accuracy, sensitivity and specificity of the proposed method can reach 98.3%, 98.9% and 98.5%, respectively. The proposed algorithm in this paper can be used as an index to detect epileptic seizures and has certain guiding significance for the early diagnosis and effective treatment of epileptic patients.

Acid sphingomyelinase mediates ferroptosis induced by high glucose via autophagic degradation of GPX4 in type 2 diabetic osteoporosis.

BACKGROUND: Ferroptosis has been implicated in the pathological process of type 2 diabetic osteoporosis (T2DOP), although the specific underlying mechanisms remain largely unknown. This study aimed to clarify the role and possible mechanism of acid sphingomyelinase (ASM)-mediated osteoblast ferroptosis in T2DOP. METHODS: We treated hFob1.19 cells with normal glucose (NG) and different concentrations of high glucose (HG, 26.25 mM, 35 mM, or 43.75 mM) for 48 h. We then measured cell viability and osteogenic function, quantified ferroptosis and autophagy levels, and measured the levels of ASM and ceramide in the cells. To further investigate the specific mechanism, we examined these indicators by knocking down ASM expression, hydroxychloroquine (HCQ) treatment, or N-acetylcysteine (NAC) treatment. Moreover, a T2DOP rat model was induced and microcomputed tomography was used to observe the bone microstructure. We also evaluated the serum levels of iron metabolism-associated factors, ceramide and lipid peroxidation (LPO) and measured the expression of ASM, LC3 and GPX4 in bone tissues. RESULTS: HG inhibited the viability and osteogenic function of osteoblasts by inducing ferroptosis in a concentration-dependent manner. Furthermore, the expression of ASM and ceramide and autophagy levels were increased by HG treatment, and these factors were required for the HG-induced reactive oxygen species (ROS) generation and LPO. Similarly, inhibiting intracellular ROS also reduced HG-induced ASM activation and autophagy. ASM-mediated activation of autophagy was crucial for HG-induced degradation of GPX4, and inhibiting ASM improved osteogenic function by decreasing HG-induced autophagy, GPX4 degradation, LPO and subsequent ferroptosis. We also found that inhibiting ASM could alleviated ferroptosis and autophagy and improved osteogenic function in a T2DOP rat model. CONCLUSION: ASM-mediated autophagy activation induces osteoblast ferroptosis under HG conditions through the degradation of GPX4, providing a novel mechanistic insight into the treatment and prevention of T2DOP.

Effect of glucocorticoid for patients with type A aortic dissection undergoing surgical repair with deep hypothermic circulatory arrest: A single-center, retrospective study.

BACKGROUND: Postoperative patients with Type A aortic dissection (TAAD) often experience severe inflammatory responses caused by multiple factors perioperatively. However, the effect of postoperative glucocorticoid (GC) use, which is a potent anti-inflammatory agent, on complications or all-cause mortality is unclear. METHODS: Patients with TAAD who underwent surgical repair requiring deep hypothermic circulatory arrest between January 2020 and December 2021 were included in the study. Characteristics of patients treated with and without GCs were compared. The primary outcome was in-hospital mortality, and a composite secondary outcome was defined as in-hospital death or any major complications. Propensity score matching was used to balance baseline differences between groups. Kaplan-Meier curves were used to compare survival probability. RESULTS: A total of 393 postoperative patients with TAAD were included in the study. Forty of them (10.2%) received GC treatment at a median daily methylprednisolone-equivalent dose of 0.6 mg/kg (0.4-0.7) for a median period of 2 (1-3) days. Patients on GCs had more intraoperative blood transfusions, higher postoperative APACHE II (12 vs 9, p = .004) and SOFA (9 vs 6, p < .001) scores, worse perioperative hepatic, renal and cardiac function. The in-hospital mortality in the matched cohort did not differ between groups [GC n = 11/40 (27.5%) versus Non-GC n = 19/80 (23.8%); p = .661]. CONCLUSIONS: The propensity to use GCs correlated with the critical status of the patient. However, low dose and short-term postoperative GC treatment did not reduce in-hospital mortality rates among patients with TAAD. A more appropriate regimen should be further investigated.

FHL2 regulates microglia M1/M2 polarization after spinal cord injury via PARP14-depended STAT1/6 pathway.

Neuronal apoptosis and inflammation exacerbate the secondary injury after spinal cord injury (SCI). Four and a half domains 2 (FHL2) is a multifunctional scaffold protein with tissue- and cell-type specific effects on the regulation of inflammation, but its role in SCI remains unclear. The T10 mouse spinal cord contusion model was established, and the mice were immediately injected with lentiviruses carrying FHL2 shRNA after SCI. The results showed that FHL2 expression was increased following SCI, and then gradually decreased. Moreover, FHL2 depletion aggravated functional impairment, neuronal necrosis, and enlarged lesion cavity areas in the injured spinal cord. FHL2 deficiency facilitated neuronal apoptosis by elevating cleaved caspase 3/9 expression, neuroinflammation by regulating microglia polarization, and bone loss. Indeed, FHL2 deficiency increased the secretion of TNF-α and IL-6, M1 microglia polarization, and the activation of STAT1 pathway but decreased the secretion of IL-10 and IL-4, M2 microglia polarization, and the activation of the STAT6 pathway in the spinal cord. In vitro, FHL2 silencing promoted LPS + IFN-γ-induced microglia M1 polarization through activating the STAT1 pathway and alleviated IL-4-induced microglia M2 polarization via inhibiting the STAT6 pathway. FHL2 positively regulated the expression of poly (ADP-ribose) polymerase family member 14 (PARP14) by promoting its transcription. PARP14 overexpression inhibited FHL2 silencing-induced microglia M1 polarization and relieved the inhibitory effect of FHL2 silencing on microglia M2 polarization. Collectively, the study suggests that FHL2 reduces the microglia M1/M2 polarization-mediated inflammation via PARP14-dependent STAT1/6 pathway and thereby improves functional recovery after SCI.

No Sex-Based Differences Exist in Clinical Outcomes of Extended Aortic Arch Repair for Acute Type A Aortic Dissection.

BACKGROUND: Reports regarding the association between sex and clinical outcomes after surgical repair of acute type A aortic dissection (ATAAD) are not exhaustive and in part even conflicting. METHODS: A total of 786 eligible adult patients with ATAAD undergoing extended arch repair from January 2015 to December 2021 were included. They were divided into a female group (n = 161) and a male group (n = 625). In-hospital outcomes (surgical mortality and major postoperative morbidity) and midterm outcomes (survival and aortic reintervention) between the 2 groups were compared before and after propensity score matching (1:1). RESULTS: Compared with male patients, female patients were more likely to be older (median [interquartile range]: 57 [46-67] vs 50 [42-59] years; P < 0.001) and to have a lower body mass index, but were less likely to be current smokers. Operative death occurred in 66 patients (6.8% female vs 8.8% male), without significant differences between groups before and after matching (P = 0.422 and P > 0.999, respectively). Major postoperative morbidity was observed in 313 patients (39.8%), including 57 (35.4%) female and 256 (41.0%) male patients (P = 0.199). Sex-based grouping was not significantly associated with operative mortality or major postoperative morbidity. The 5-year cumulative survival and incidence of aortic reintervention among female patients were 90.6% and 6.0%, respectively, which were not statistically different from those observed in male patients before and after matching. CONCLUSIONS: No sex-based differences were found in terms of in-hospital and midterm outcomes of extended arch repair for ATAAD.

Septuagenarians with acute type A aortic dissection undergoing extended aortic arch repair: a retrospective cohort study.

BACKGROUND: Extended arch repair in elderly patients with acute type A aortic dissection (ATAAD) remains challenging for cardiac surgeons. Data on extended arch repair for ATAAD in septuagenarians are scarce. MATERIALS AND METHODS: Consecutive adult patients with ATAAD undergoing extended arch repair from January 2015 to December 2021 were identified. According to age at presentation, 714 eligible patients were entered into either an elderly group (septuagenarians, n =65) or a control group (patients aged less than 70, n =649). Using propensity score matching, 60 pairs of patients were successfully established at a 1:1 ratio. In-hospital outcomes (operative death and major postoperative morbidity) and midterm outcomes (survival and aortic reintervention) were compared before and after matching. RESULTS: Operative death occurred in 64 patients (9.0%), including seven septuagenarians (10.8%) and 57 (8.8%) from the control group, without significant differences between groups before and after matching ( P =0.593 and 0.774, respectively). Major postoperative morbidity was observed in 298 patients (41.7%), including 29 (44.6%) in the elderly group and 269 (41.4%) in the control group ( P =0.622). Age-based grouping was not significantly associated with operative mortality or major postoperative morbidity in the crude, multivariable, and propensity score analyses. The 5-year cumulative survival and cumulative aortic reintervention rates in the elderly group were 83.5 and 4.6%, respectively, which were not statistically different from those in the control group before and after matching. CONCLUSIONS: Extended arch repair may be safely and effectively performed in septuagenarians with ATAAD, with in-hospital and midterm outcomes comparable to those obtained in patients aged less than 70 years.

A hiPSC-derived lineage-specific vascular smooth muscle cell-on-a-chip identifies aortic heterogeneity across segments.

Aortic aneurysm (AA), a potentially lethal condition with the characteristic of aortic dilatation, can only be treated by surgical or endovascular procedures. The underlying mechanisms of AA are unclear and early preventive treatment is still insufficient due to segmental aortic heterogeneity and the limitations of current disease models. Here, we firstly established a comprehensive lineage-specific vascular smooth muscle cell (SMC)-on-a-chip model using human induced pluripotent stem cells to yield cell lineages representing different segments of the aorta and tested the constructed organ-on-a-chip model under various tensile stress conditions. Bulk RNA sequencing, RT-qPCR, immunofluorescence, western blot and FACS analyses were performed to discover the segmental aortic heterogeneity of response for tensile stress and drug testing. The appropriate stretching frequency for all lineages of SMCs was 1.0 Hz, paraxial mesoderm (PM) SMCs were more sensitive to tensile stress than lateral mesoderm (LM) SMCs and neural crest (NC) SMCs. These differences may be related to the different transcriptional profiles of the tension-stressed distinct lineage-specific vascular SMCs, specifically in relation to the PI3K-Akt signaling pathway. Also, the organ-on-a-chip displayed contractile physiology, perfect fluid coordination, and was conducive to drug testing, displaying heterogeneous segmental aortic responses. Compared with LM-SMCs and NC-SMCs, PM-SMCs were more sensitive to ciprofloxacin. The model is evaluated as a novel and suitable supplement to AA animal models for determining differential physiology and drug response in different parts of the aorta. Furthermore, this system could pave the way for disease modeling, drug testing, and the personalized treatment of patients with AA in the future.

Poly(ADP-ribose) polymerase family member 14 promotes functional recovery after spinal cord injury through regulating microglia M1/M2 polarization via STAT1/6 pathway.

Poly(ADP-ribose)polymerase family member 14 (PARP14), which is an intracellular mono(ADP-ribosyl) transferase, has been reported to promote post-stroke functional recovery, but its role in spinal cord injury (SCI) remains unclear. To investigate this, a T10 spinal cord contusion model was established in C57BL/6 mice, and immediately after the injury PARP14 shRNA-carrying lentivirus was injected 1 mm from the injury site to silence PARP14 expression. We found that PARP14 was up-regulated in the injured spinal cord and that lentivirus-mediated downregulation of PARP14 aggravated functional impairment after injury, accompanied by obvious neuronal apoptosis, severe neuroinflammation, and slight bone loss. Furthermore, PARP14 levels were elevated in microglia after SCI, PARP14 knockdown activated microglia in the spinal cord and promoted a shift from M2-polarized microglia (anti-inflammatory phenotype) to M1-polarized microglia (pro-inflammatory phenotype) that may have been mediated by the signal transducers and activators of transcription (STAT) 1/6 pathway. Next, microglia M1 and M2 polarization were induced in vitro using lipopolysaccharide/interferon-γ and interleukin-4, respectively. The results showed that PARP14 knockdown promoted microglia M1 polarization, accompanied by activation of the STAT1 pathway. In addition, PARP14 overexpression made microglia more prone to M2 polarization and further activated the STAT6 pathway. In conclusion, these findings suggest that PARP14 may improve functional recovery after SCI by regulating the phenotypic transformation of microglia via the STAT1/6 pathway.