The Role of Microvascular Obstruction and Intra-Myocardial Hemorrhage in Reperfusion Cardiac Injury. Analysis of Clinical Data.

Microvascular obstruction (MVO) of coronary arteries promotes an increase in mortality and major adverse cardiac events in patients with acute myocardial infarction (AMI) and percutaneous coronary intervention (PCI). Intramyocardial hemorrhage (IMH) is observed in 41-50% of patients with ST-segment elevation myocardial infarction and PCI. The occurrence of IMH is accompanied by inflammation. There is evidence that microthrombi are not involved in the development of MVO. The appearance of MVO is associated with infarct size, the duration of ischemia of the heart, and myocardial edema. However, there is no conclusive evidence that myocardial edema plays an important role in the development of MVO. There is evidence that platelets, inflammation, Ca 2 + overload, neuropeptide Y, and endothelin-1 could be involved in the pathogenesis of MVO. The role of endothelial cell damage in MVO formation remains unclear in patients with AMI and PCI. It is unclear whether nitric oxide production is reduced in patients with MVO. Only indirect evidence on the involvement of inflammation in the development of MVO has been obtained. The role of reactive oxygen species (ROS) in the pathogenesis of MVO is not studied. The role of necroptosis and pyroptosis in the pathogenesis of MVO in patients with AMI and PCI is also not studied. The significance of the balance of thromboxane A2, vasopressin, angiotensin II, and prostacyclin in the formation of MVO is currently unknown. Conclusive evidence regarding the role of coronary artery spasm in the development of MVhasn't been established. Correlation analysis of the neuropeptide Y, endothelin-1 levels and the MVO size in patients with AMI and PCI has not previously been performed. It is unclear whether epinephrine aggravates reperfusion necrosis of cardiomyocytes. Dual antiplatelet therapy improves the efficacy of PCI in prevention of MVO. It is unknown whether epinephrine or L-type Ca 2 + channel blockers result in the long-term improvement of coronary blood flow in patients with MVO.

A Homozygous Variant in NAA60 Is Associated with Primary Familial Brain Calcification.

BACKGROUND: Primary familial brain calcification (PFBC) is a monogenic disorder characterized by bilateral calcifications in the brain. The genetic basis remains unknown in over half of the PFBC patients, indicating the existence of additional novel causative genes. NAA60 was a recently reported novel causative gene for PFBC. OBJECTIVE: The aim was to identify the probable novel causative gene in an autosomal recessive inherited PFBC family. METHODS: We performed a comprehensive genetic study on a consanguineous Chinese family with 3 siblings diagnosed with PFBC. We evaluated the effect of the variant in a probable novel causative gene on the protein level using Western blot, immunofluorescence, and coimmunoprecipitation. Possible downstream pathogenic mechanisms were further explored in gene knockout (KO) cell lines and animal models. RESULTS: We identified a PFBC co-segregated homozygous variant of c.460_461del (p.D154Lfs*113) in NAA60. Functional assays showed that this variant disrupts NAA60 protein localization to Golgi and accelerated protein degradation. The mutant NAA60 protein alters its interaction with the PFBC-related proteins PiT2 and XPR1, affecting intracellular phosphate homeostasis. Further mass spectrometry analysis in NAA60 KO cell lines revealed decreased expression of multiple brain calcification-associated proteins, including reduced folate carrier (RFC), a folate metabolism-related protein. CONCLUSIONS: Our study replicated the identification of NAA60 as a novel causative gene for autosomal recessive PFBC, demonstrating our causative variant leads to NAA60 loss of function. The NAA60 loss of function disrupts not only PFBC-related proteins (eg, PiT2 and XPR1) but also a wide range of other brain calcification-associated membrane protein substrates (eg, RFC), and provided a novel probable pathogenic mechanism for PFBC. © 2024 International Parkinson and Movement Disorder Society.

Evolutionary Game Dynamics with Environmental Feedback in a Network with Two Communities.

Recent developments of eco-evolutionary models have shown that evolving feedbacks between behavioral strategies and the environment of game interactions, leading to changes in the underlying payoff matrix, can impact the underlying population dynamics in various manners. We propose and analyze an eco-evolutionary game dynamics model on a network with two communities such that players interact with other players in the same community and those in the opposite community at different rates. In our model, we consider two-person matrix games with pairwise interactions occurring on individual edges and assume that the environmental state depends on edges rather than on nodes or being globally shared in the population. We analytically determine the equilibria and their stability under a symmetric population structure assumption, and we also numerically study the replicator dynamics of the general model. The model shows rich dynamical behavior, such as multiple transcritical bifurcations, multistability, and anti-synchronous oscillations. Our work offers insights into understanding how the presence of community structure impacts the eco-evolutionary dynamics within and between niches.

Macrophage-derived extracellular vesicles represent a promising endogenous iron-chelating therapy for iron overload and cardiac injury in myocardial infarction.

BACKGROUND: Cardiac iron overload and ferroptosis greatly contribute to the poor prognosis of myocardial infarction (MI). Iron chelator is one of the most promising strategies for scavenging excessive iron and alleviating cardiac dysfunction post MI. However, various side effects of existing chemical iron chelators restrict their clinical application, which calls for a more viable and safer approach to protect against iron injury in ischemic hearts. RESULTS: In this study, we isolated macrophage-derived extracellular vesicles (EVs) and identified macrophage-derived EVs as a novel endogenous biological chelator for iron. The administration of macrophage-derived EVs effectively reduced iron overload in hypoxia-treated cardiomyocytes and hearts post MI. Moreover, the oxidative stress and ferroptosis induced by excessive iron were considerably suppressed by application of macrophage-derived EVs. Mechanistically, transferrin receptor (TfR), which was inherited from macrophage to the surface of EVs, endowed EVs with the ability to bind to transferrin and remove excess protein-bound iron. EVs with TfR deficiency exhibited a loss of function in preventing MI-induced iron overload and protecting the heart from MI injury. Furthermore, the iron-chelating EVs were ultimately captured and processed by macrophages in the liver. CONCLUSIONS: These results highlight the potential of macrophage-derived EVs as a powerful endogenous candidate for iron chelation therapy, offering a novel and promising therapeutic approach to protect against iron overload-induced injury in MI and other cardiovascular diseases.

IP3R1-mediated MAMs formation contributes to mechanical trauma-induced hepatic injury and the protective effect of melatonin.

INTRODUCTION: There is a high morbidity and mortality rate in mechanical trauma (MT)-induced hepatic injury. Currently, the molecular mechanisms underlying liver MT are largely unclear. Exploring the underlying mechanisms and developing safe and effective medicines to alleviate MT-induced hepatic injury is an urgent requirement. The aim of this study was to reveal the role of mitochondria-associated ER membranes (MAMs) in post-traumatic liver injury, and ascertain whether melatonin protects against MT-induced hepatic injury by regulating MAMs. METHODS: Hepatic mechanical injury was established in Sprague-Dawley rats and primary hepatocytes. A variety of experimental methods were employed to assess the effects of melatonin on hepatic injury, apoptosis, MAMs formation, mitochondrial function and signaling pathways. RESULTS: Significant increase of IP3R1 expression and MAMs formation were observed in MT-induced hepatic injury. Melatonin treatment at the dose of 30 mg/kg inhibited IP3R1-mediated MAMs and attenuated MT-induced liver injury in vivo. In vitro, primary hepatocytes cultured in 20% trauma serum (TS) for 12 h showed upregulated IP3R1 expression, increased MAMs formation and cell injury, which were suppressed by melatonin (100 µmol/L) treatment. Consequently, melatonin suppressed mitochondrial calcium overload, increased mitochondrial membrane potential and improved mitochondrial function under traumatic condition. Melatonin's inhibitory effects on MAMs formation and mitochondrial calcium overload were blunted when IP3R1 was overexpressed. Mechanistically, melatonin bound to its receptor (MR) and increased the expression of phosphorylated ERK1/2, which interacted with FoxO1 and inhibited the activation of FoxO1 that bound to the IP3R1 promoter to inhibit MAMs formation. CONCLUSION: Melatonin prevents the formation of MAMs via the MR-ERK1/2-FoxO1-IP3R1 pathway, thereby alleviating the development of MT-induced liver injury. Melatonin-modulated MAMs may be a promising therapeutic therapy for traumatic hepatic injury.

[Role of mitochondrial dynamics in diabetic cardiomyopathy and regulatory mechanisms].

Cardiovascular complications are the leading cause of death in diabetic patients. Among them, diabetic cardiomyopathy (DCM) is a type of specific cardiomyopathy excluding myocardial damage caused by hypertension and coronary heart disease. It is characterized by abnormal metabolism of cardiomyocytes and gradual decline of cardiac function. The clinical manifestations of DCM are impaired diastolic function in early stage and impaired systolic function in late stage. Eventually it developed into heart failure. Mitochondria are the main organelles that provide energy in cardiomyocytes. Mitochondrial dynamics refers to the dynamic process of mitochondrial fusion and fission, which is an important approach for mitochondrial quality control. Mitochondrial dynamics plays a crucial role in maintaining mitochondrial homeostasis and cardiac function. The proteins that regulate mitochondrial fission are mainly Drp1 and its receptors, Fis1, MFF, MiD49 and MiD51. The protein that performs mitochondrial outer membrane fusion is Mfn1/2, and the inner membrane fusion protein is Opa1. This paper reviews recent progress on mitochondrial dynamics in DCM. The main contents are as follows: mitochondrial dynamics imbalance in both type 1 and 2 DCM is manifested as increased fission and inhibited fusion. The molecular mechanism of the former is mainly associated with up-regulated Drp1 and down-regulated Opa1, while the molecular mechanism of the latter is mainly associated with up-regulated Drp1 and down-regulated Mfn1/2. Increased mitochondrial fission and inhibited fusion can lead to mitochondrial dysfunction and promote the development of DCM. The active ingredients of the traditional Chinese medicine such as punicalagin, paeonol and endogenous substance melatonin can improve mitochondrial function and alleviate the symptoms of DCM by inhibiting mitochondrial fission or promoting mitochondrial fusion. This article is helpful to further understand the role and mechanism of mitochondrial dynamics in DCM, and provide new treatment methods and intervention strategies for clinical DCM patients based on mitochondrial dynamics.

[Dielectric properties of tidal volume changes in rabbit lung tissue in the 100 MHz~1 GHz band].

This paper investigates the variation of lung tissue dielectric properties with tidal volume under in vivo conditions to provide reliable and valid a priori information for techniques such as microwave imaging. In this study, the dielectric properties of the lung tissue of 30 rabbits were measured in vivo using the open-end coaxial probe method in the frequency band of 100 MHz to 1 GHz, and 6 different sets of tidal volumes (30, 40, 50, 60, 70, 80 mL) were set up to study the trends of the dielectric properties, and the data at 2 specific frequency points (433 and 915 MHz) were analyzed statistically. It was found that the dielectric coefficient and conductivity of lung tissue tended to decrease with increasing tidal volume in the frequency range of 100 MHz to 1 GHz, and the differences in the dielectric properties of lung tissue for the 6 groups of tidal volumes at 2 specific frequency points were statistically significant. This paper showed that the dielectric properties of lung tissue tend to vary non-linearly with increasing tidal volume. Based on this, more accurate biological tissue parameters can be provided for bioelectromagnetic imaging techniques such as microwave imaging, which could provide a scientific basis and experimental data support for the improvement of diagnostic methods and equipment for lung diseases.

Regulation of autophagy of the heart in ischemia and reperfusion.

Ischemia/reperfusion (I/R) of the heart leads to increased autophagic flux. Preconditioning stimulates autophagic flux by AMPK and PI3-kinase activation and mTOR inhibition. The cardioprotective effect of postconditioning is associated with activation of autophagy and increased activity of NO-synthase and AMPK. Oxidative stress stimulates autophagy in the heart during I/R. Superoxide radicals generated by NADPH-oxidase acts as a trigger for autophagy, possibly due to AMPK activation. There is reason to believe that AMPK, GSK-3ß, PINK1, JNK, hexokinase II, MEK, PKCα, and ERK kinases stimulate autophagy, while mTOR, PKCδ, Akt, and PI3-kinase can inhibit autophagy in the heart during I/R. However, there is evidence that PI3-kinase could stimulate autophagy in ischemic preconditioning of the heart. It was found that transcription factors FoxO1, FoxO3, NF-κB, HIF-1α, TFEB, and Nrf-2 enhance autophagy in the heart in I/R. Transcriptional factors STAT1, STAT3, and p53 inhibit autophagy in I/R. MicroRNAs could stimulate and inhibit autophagy in the heart in I/R. Long noncoding RNAs regulate the viability and autophagy of cardiomyocytes in hypoxia/reoxygenation (H/R). Nitric oxide (NO) donors and endogenous NO could activate autophagy of cardiomyocytes. Activation of heme oxygenase-1 promotes cardiomyocyte tolerance to H/R and enhances autophagy. Hydrogen sulfide increases cardiac tolerance to I/R and inhibits apoptosis and autophagy via mTOR and PI3-kinase activation.

Continuously Flow Photothermal Catalysis Efficiently CO2 Reduction Over S-Scheme 2D/0D Bi5 O7 I-OVs/Cd0.5 Zn0.5 S Heterojunction with Strong Interfacial Electric Field.

Using CO2 , water, and sunlight to produce solar fuel is a very attractive process, which can synchronously reduce carbon and convert solar energy into hydrocarbons. However, photocatalytic CO2 reduction is often limited by the low selectivity of reduction products and poor photocatalytic activity. In this study, S-scheme Bi5 O7 I-OVs/Cd0.5 Zn0.5 S (Bi5 O7 I-OVs/CZS-0.5) heterojunction with strong interfacial electric field (IEF) is prepared by in situ growth method. The performance of reduction CO2 to CO is studied by continuous flow photothermal catalytic (PTC) CO2 reduction platform. 12.5% Bi5 O7 I-OVs/CZS-0.5 shows excellent CO yield of 58.6 µmol g-1  h-1 and selectivity of 98.4%, which are 35.1 times than that of CZS-0.5 under visible light. The charge transfer path of the S-scheme through theoretical calculation (DFT), in situ irradiation Kelvin probe force microscope (ISI-KPFM) and in situ irradiation X-ray photoelectron spectroscopy (ISI-XPS) analysis, is verified. The study can provide useful guidance and reference for improving activity by oxygen vacancy induced strong IEF and the development of a continuous flow PTC CO2 reduction system.

NiS/Cd0.6 Zn0.4 S Schottky Junction Bifunctional Photocatalyst for Sunlight-Driven Highly Selective Catalytic Oxidation of Vanillyl Alcohol Towards Vanillin Coupled with Hydrogen Evolution Reaction.

Selective oxidation of biomass-based molecules to high-value chemicals in conjunction with hydrogen evolution reaction (HER) is an innovative photocatalysis strategy. The key challenge is to design bifunctional photocatalysts with suitable band structures, which can achieve highly efficient generation of high-value chemicals and hydrogen. Herein, NiS/Cd0.6 Zn0.4 S Schottky junction bifunctional catalysts are constructed for sunlight-driven catalytic vanillyl alcohol (VAL) selective oxidation towards vanillin (VN) coupling HER. At optimal conditions, the 8% NiS/Cd0.6 Zn0.4 S photocatalyst achieves high activity of VN production (3.75 mmol g-1 h-1 ) and HER (3.84 mmol g-1 h-1 ). It also exhibits remarkable VAL conversion (66.9%), VN yield (52.1%), and selectivity (77.8%). The photocatalytic oxidation of VAL proceeds a carbon-centered radical mechanism via the cleavage of αC-H bond. Experimental results and theoretical calculations show that NiS with metallic properties enhances the electron transfer capability. Importantly, a Ni-S-Cd "electron bridge" formed at the interface of NiS/Cd0.6 Zn0.4 S further improves the separation/transfer of electrone/h+ pairs and also furnishes HER active sites due to its smaller the |ΔGH* | value, thereby resulting in a remarkably HER activity. This work sheds new light on the selective catalytic oxidation VAL to VN coupling HER, with a new pathway towards achieving its efficient HER efficiency.

Structural Transformation by Crystal Engineering Endows Aqueous Zinc-Ion Batteries with Ultra-long Cyclability.

Manganese oxide is a promising cathode material for aqueous zinc batteries. However, its weak structural stability, low electrical conductivity, and sluggish reaction kinetics lead to rapid capacity fading. Herein, a crystal engineering strategy is proposed to construct a novel MnO2 cathode material. Both experimental results and theoretical calculations demonstrate that Al-doping plays a crucial role in phase transition and doping-superlattice structure construction, which stabilizes the structure of MnO2 cathode materials, improves conductivity, and accelerates ion diffusion dynamics. As a result, 1.98% Al-doping MnO2 (AlMO) cathode shows an incredible 15 000 cycle stability with a low capacity decay rate of 0.0014% per cycle at 4 A g-1 . Additionally, it provides superior specific capacity of 311.2 mAh g-1 at 0.1 A g-1 and excellent rate performance (145.2 mAh g-1 at 5.0 A g-1 ). To illustrate the potential of 1.98%AlMO to be applied in actual practice, flexible energy storage devices are fabricated and measured. These discoveries provide a new insight for structural transformation via crystal engineering, as well as a new avenue for the rational design of electrode material in other battery systems.

Construction of Ternary Bismuth-Based Heterojunction by Using (BiO)2 CO3 as Electron Bridge for Highly Efficient Degradation of Phenol.

Inspired by nature, it has been considered an effective approach to design artificial photosynthetic system by fabricating Z-scheme photocatalysts to eliminate environmental issues and alleviate the global energy crisis. However, the development of low cost, environment-friendly, and high-efficient photocatalysts by utilizing solar energy still confronts huge challenge. Herein, we constructed a Bi2 O3 /(BiO)2 CO3 /Bi2 MoO6 ternary heterojunction via a facile solvothermal method and calcination approach and used it as a photocatalyst for the degradation of phenol. The optimized Bi2 O3 /(BiO)2 CO3 /Bi2 MoO6 heterojunction delivers a considerable activity for phenol photodegradation with an impressive removal efficiency of 98.8 % and about total organic carbon (TOC) of 68 % within 180 min under visible-light irradiation. The excellent photocatalytic activity was ascribed to the formation of a Z-scheme heterojunction, more importantly, the presence of (BiO)2 CO3 as an electron bridge greatly shortens the migration distance of photogenerated electron from ECB of Bi2 O3 to EVB of Bi2 MoO6 , thus prolonging the lifetime of photogenerated electrons, which is verified by trapping experiments, electron spin-resonance spectroscopy (ESR) results, and density functional theory (DFT) calculations. This work provides a potential strategy to fabricate highly efficient Bi-based Z-scheme photocatalysts with wide application prospects in solar-to-fuel conversion and environmental protection.

The Influence of Breathing Exercises on Regional Ventilation in Healthy and Patients with Chronic Obstructive Pulmonary Disease.

We hypothesized that the respiratory exercises have uniform effects on ventilation in healthy subjects but the effects varied in patients with chronic obstructive pulmonary disease (COPD). In this study, a total of 30 healthy volunteers and 9 patients with COPD were included. Data were recorded continuously during (1) diaphragmatic breathing; (2) pursed lip breathing with full inhalation; (3) pursed lip combining diaphragmatic breathing. The sequence of the three breathing exercises was randomized using machine generated random permutation. Spatial and temporal ventilation distributions were evaluated with electrical impedance tomography. Results showed that, tidal volume was significantly larger during various breathing exercises compared to quiet tidal breathing, in both healthy and COPD (p < 0.01). However, for other EIT-based parameters, statistical significances were only observed in healthy volunteers, not in patients. Diaphragmatic breathing alone might not be able to decrease functional residual capacity in COPD and the effect varied largely from patient to patient (6:3, decrease vs. increase). Ventilation distribution moved toward ventral regions in healthy during breathing exercises (p < 0.0001). Although this trend was observed in the COPD, the differences were not significant. Ventilation became more homogeneous when diaphragmatic breathing technique was implemented (p < 0.0001). Again, the improvements were not significant in COPD. Regional ventilation delay was relatively high in COPD and comparable in various breathing periods. In conclusions, the impact of pursed lip and diaphragmatic breathing varied in different patients with COPD. Breathing exercise may need to be individualized to maximize the training efficacy with help of EIT.

[Study on the difference of high frequency dielectric properties of biological tissues measured by air and packed coaxial probe].

In this paper, the differences between air probe and filled probe for measuring high-frequency dielectric properties of biological tissues are investigated based on the equivalent circuit model to provide a reference for the methodology of high-frequency measurement of biological tissue dielectric properties. Two types of probes were used to measure different concentrations of NaCl solution in the frequency band of 100 MHz-2 GHz. The results showed that the accuracy and reliability of the calculated results of the air probe were lower than that of the filled probe, especially the dielectric coefficient of the measured material, and the higher the concentration of NaCl solution, the higher the error. By laminating the probe terminal, liquid intrusion could be prevented, to a certain extent, to improve the accuracy of measurement. However, as the frequency decreased, the influence of the film on the measurement increased and the measurement accuracy decreased. The results of the study show that the air probe, despite its simple dimensional design and easy calibration, differs from the conventional equivalent circuit model in actual measurements, and the model needs to be re-corrected for actual use. The filled probe matches the equivalent circuit model better, and therefore has better measurement accuracy and reliability.

Evolutionary Kuramoto dynamics.

Biological systems have a variety of time-keeping mechanisms ranging from molecular clocks within cells to a complex interconnected unit across an entire organism. The suprachiasmatic nucleus, comprising interconnected oscillatory neurons, serves as a master-clock in mammals. The ubiquity of such systems indicates an evolutionary benefit that outweighs the cost of establishing and maintaining them, but little is known about the process of evolutionary development. To begin to address this shortfall, we introduce and analyse a new evolutionary game theoretic framework modelling the behaviour and evolution of systems of coupled oscillators. Each oscillator is characterized by a pair of dynamic behavioural dimensions, a phase and a communication strategy, along which evolution occurs. We measure success of mutations by comparing the benefit of synchronization balanced against the cost of connections between the oscillators. Despite the simple set-up, this model exhibits non-trivial behaviours mimicking several different classical games-the Prisoner's Dilemma, snowdrift games, coordination games-as the landscape of the oscillators changes over time. Across many situations, we find a surprisingly simple characterization of synchronization through connectivity and communication: if the benefit of synchronization is greater than twice the cost, the system will evolve towards complete communication and phase synchronization.

Tislelizumab Combined with Carboplatin-Paclitaxel for Treatment of Metastatic or Recurrent Endometrial Cancer: a Retrospective Clinical Study.

BACKGROUND: Metastatic or recurrent endometrial cancers with low survival rate had no standard or limited therapy choice. The aim of our study was to determine the efficiency and safety of tislelizumab combined with carboplatin-paclitaxel as a front-line therapy for patients with metastatic or recurrent endometrial cancer. METHODS: This clinical retrospective cohort study examined 24 Chinese patients with metastasis or recurrence but had not yet received treatment. The therapeutic regimen consisted of 6 cycles of intravenous paclitaxel (175 mg/m2) and carboplatin (target AUC: 5 mg/mL/min) with tislelizumab (200 mg) once every 3 weeks, and then intravenous tislelizumab (200 mg) once every 3 weeks until disease progression or unacceptable toxicity. RESULTS: At the 18-month follow-up, 8 patients were still receiving treatment, 13 were dead, and 3 withdrew. The objective response rate (ORR) was 62.5%, the disease control rate was 75.00%. The ORR was 77.78% for patients positive for PD-L1 and 69.23% for patients positive for MSI-H. The median overall survival time was 11.50 months, and the median progression-free survival time was 6.00 months. Half of the patients experienced 3 - 4 grade adverse events. There were no allergic reactions or treatment-related deaths. CONCLUSIONS: Tislelizumab combined with carboplatin-paclitaxel was used as a front-line therapy, had a beneficial effect and was safe for patients with metastatic or recurrent endometrial cancer.

Fast Iterative Shrinkage-Thresholding Algorithm with Continuation for Brain Injury Monitoring Imaging Based on Electrical Impedance Tomography.

Electrical impedance tomography (EIT) is low-cost and noninvasive and has the potential for real-time imaging and bedside monitoring of brain injury. However, brain injury monitoring by EIT imaging suffers from image noise (IN) and resolution problems, causing blurred reconstructions. To address these problems, a least absolute shrinkage and selection operator model is built, and a fast iterative shrinkage-thresholding algorithm with continuation (FISTA-C) is proposed. Results of numerical simulations and head phantom experiments indicate that FISTA-C reduces IN by 63.2%, 47.2%, and 29.9% and 54.4%, 44.7%, and 22.7%, respectively, when compared with the damped least-squares algorithm, the split Bergman, and the FISTA algorithms. When the signal-to-noise ratio of the measurements is 80-50 dB, FISTA-C can reduce IN by 83.3%, 72.3%, and 68.7% on average when compared with the three algorithms, respectively. Both simulation and phantom experiments suggest that FISTA-C produces the best image resolution and can identify the two closest targets. Moreover, FISTA-C is more practical for clinical application because it does not require excessive parameter adjustments. This technology can provide better reconstruction performance and significantly outperforms the traditional algorithms in terms of IN and resolution and is expected to offer a general algorithm for brain injury monitoring imaging via EIT.

Activation of κ-opioid receptor inhibits inflammatory response induced by sodium palmitate in human umbilical vein endothelial cells.

OBJECTIVES: The current study aims to investigate the effect of κ-opioid receptor (κ-OR) activation on sodium palmitate (SP)-induced human umbilical vein endothelial cells (HUVECs) inflammatory response and elucidate the underlying mechanisms. METHODS: A hyperlipidemic cell model was established and treated with κ-OR agonist (U50,488H), and antagonist (norbinaltorphimine, nor-BNI), or inhibitors targeting PI3K, Akt or eNOS (LY294002, MK2206-2HCl or L-NAME, respectively). Furthermore, the expression levels of NLRP3, caspase-1, p-Akt, Akt, p-eNOS, and total eNOS were evaluated. Additionally, the production of reactive oxygen species, and levels of inflammatory factors, such as TNF-α, IL-1ß, IL-6, IL-1 and adhesion molecules, such as ICAM-1, VCAM-1, P-selectin, and E-selectin were determined. The adherence rates of the neutrophils and monocytes were assessed as well. RESULTS: The SP-induced hyperlipidemic cell model demonstrated increased expression of NLRP3 and caspase-1 proteins (P < 0.05) and elevated ROS levels (P < 0.01), and decreased phosphorylated-Akt and phosphorylated-eNOS expression (P < 0.05). In addition, SP significantly increased TNF-α, IL-1ß, IL-6, ICAM-1, VCAM-1, P-selectin, and E-selectin levels (P < 0.01), decreased IL-10 levels (P < 0.01), and increased the adhesion rates of monocytes and neutrophils (P < 0.01). The SP-induced inflammatory response in HUVECs was ameliorated by κ-OR agonist, U50,488H. However, the protective effect of U50,488H was abolished by κ-OR antagonist, nor-BNI, and inhibitors of PI3K, Akt and eNOS. CONCLUSION: Our findings suggest that κ-OR activation inhibits SP-induced inflammation by activating the PI3K/Akt/eNOS signaling pathway.

Role of calcitonin gene-related peptide in pain regulation in the parabrachial nucleus of naive rats and rats with neuropathic pain.

Researches have shown that calcitonin gene-related peptide (CGRP) plays a pivotal role in pain modulation. Nociceptive information from the periphery is relayed from parabrachial nucleus (PBN) to brain regions implicated involved in pain. This study investigated the effects and mechanisms of CGRP and CGRP receptors in pain regulation in the PBN of naive and neuropathic pain rats. Chronic sciatic nerve ligation was used to model neuropathic pain, CGRP and CGRP 8-37 were injected into the PBN of the rats, and calcitonin receptor-like receptor (CLR), a main structure of CGRP receptor, was knocked down by lentivirus-coated CLR siRNA. The hot plate test (HPT) and the Randall Selitto Test (RST) was used to determine the latency of the rat hindpaw response. The expression of CLR was detected with RT-PCR and western blotting. We found that intra-PBN injecting of CGRP induced an obvious anti-nociceptive effect in naive and neuropathic pain rats in a dose-dependent manner, the CGRP-induced antinociception was significantly reduced after injection of CGRP 8-37, Moreover, the mRNA and protein levels of CLR, in PBN decreased significantly and the antinociception CGRP-induced was also significantly lower in neuropathic pain rats than that in naive rats. Knockdown CLR in PBN decreased the expression of CLR and the antinociception induced by CGRP was observably decreased. Our results demonstrate that CGRP induced antinociception in PBN of naive or neuropathic pain rats, CGRP receptor mediates this effect. Neuropathic pain induced decreases in the expression of CGRP receptor, as well as in CGRP-induced antinociception in PBN.

Biallelic loss-of-function mutations in JAM2 cause primary familial brain calcification.

Primary familial brain calcification is a monogenic disease characterized by bilateral calcifications in the basal ganglia and other brain regions, and commonly presents motor, psychiatric, and cognitive symptoms. Currently, four autosomal dominant (SLC20A2, PDGFRB, PDGFB, XPR1) and one autosomal recessive (MYORG) causative genes have been identified. Compared with patients with autosomal dominant primary familial brain calcification, patients with the recessive form of the disease present with more severe clinical and imaging phenotypes, and deserve more clinical and research attention. Biallelic mutations in MYORG cannot explain all autosomal recessive primary familial brain calcification cases, indicating the existence of novel autosomal recessive genes. Using homozygosity mapping and whole genome sequencing, we detected a homozygous frameshift mutation (c.140delT, p.L48*) in the JAM2 gene in a consanguineous family with two affected siblings diagnosed with primary familial brain calcification. Further genetic screening in a cohort of 398 probands detected a homozygous start codon mutation (c.1A>G, p.M1?) and compound heterozygous mutations [c.504G>C, p.W168C and c.(67+1_68-1)_(394+1_395-1), p.Y23_V131delinsL], respectively, in two unrelated families. The clinical phenotypes of the four patients included parkinsonism (3/4), dysarthria (3/4), seizures (1/4), and probable asymptomatic (1/4), with diverse onset ages. All patients presented with severe calcifications in the cortex in addition to extensive calcifications in multiple brain areas (lenticular nuclei, caudate nuclei, thalamus, cerebellar hemispheres, ± brainstem; total calcification scores: 43-77). JAM2 encodes junctional adhesion molecule 2, which is highly expressed in neurovascular unit-related cell types (endothelial cells and astrocytes) and is predominantly localized on the plasma membrane. It may be important in cell-cell adhesion and maintaining homeostasis in the CNS. In Chinese hamster ovary cells, truncated His-tagged JAM2 proteins were detected by western blot following transfection of p.Y23_V131delinsL mutant plasmid, while no protein was detected following transfection of p.L48* or p.1M? mutant plasmids. In immunofluorescence experiments, the p.W168C mutant JAM2 protein failed to translocate to the plasma membrane. We speculated that mutant JAM2 protein resulted in impaired cell-cell adhesion functions and reduced integrity of the neurovascular unit. This is similar to the mechanisms of other causative genes for primary familial brain calcification or brain calcification syndromes (e.g. PDGFRB, PDGFB, MYORG, JAM3, and OCLN), all of which are highly expressed and functionally important in the neurovascular unit. Our study identifies a novel causative gene for primary familial brain calcification, whose vital function and high expression in the neurovascular unit further supports impairment of the neurovascular unit as the root of primary familial brain calcification pathogenesis.