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Decreased brain glutamate level has emerged as a new therapeutic approach for epilepsy. This study investigated the effect and mechanism of amiodarone, an anti-arrhythmic drug with antiepileptic activity, on glutamate release in the rat hippocampus. In a synaptosomal preparation, amiodarone reduced 4-aminopyridine-evoked Ca2+-dependent glutamate release and cytosolic Ca2+ concentration elevation. Amiodarone did not affect the 4-aminopyridine-evoked depolarization of the synaptosomal membrane potential or the Na+ channel activator veratridine-evoked glutamate release, indicating that the amiodarone-mediated inhibition of glutamate release is not caused by a decrease in synaptosomal excitability. The inhibitory effect of amiodarone on 4-aminopyridine-evoked glutamate release was markedly decreased in synaptosomes pretreated with the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel blocker ω-conotoxin MVIIC, the calmodulin antagonists W7 and calmidazolium, or the protein kinase A inhibitors H89 and KT5720. However, the intracellular Ca2+-release inhibitors dantrolene and CGP37157 had no effect on the amiodarone-mediated inhibition of glutamate release. Furthermore, amiodarone reduced the frequency of miniature excitatory postsynaptic currents without affecting their amplitude in hippocampal slices. Our data suggest that amiodarone reduces Ca2+ influx through N- and P/Q-type Ca2+ channels, subsequently reducing the Ca2+-calmodulin/protein kinase A cascade to inhibit the evoked glutamate release from rat hippocampal nerve terminals.

NogoA inhibits neurite outgrowth of motoneurons (NOM) through interaction with its receptors, Nogo66/NgR. Inhibition of Nogo receptors rescues NOM, but not to the extent exhibited by NogoA-knockout mice, suggesting the presence of other pathways. We found that NogoA-overexpressing muscle cells reduced phosphoglycerate kinase 1 (Pgk1) secretion, resulting in inhibiting NOM. Apart from its glycolytic role and independent of the Nogo66 pathway, extracellular Pgk1 stimulated NOM by triggering a reduction of p-Cofilin-S3, a growth cone collapse marker, through decreasing a novel Rac1-GTP/p-Pak1-T423/p-P38-T180/p-MK2-T334/p-Limk1-S323/p-Cofilin-S3 molecular pathway. Not only did supplementary Pgk1 enhance NOM in defective cells, but injection of Pgk1 rescued denervation in muscle-specific NogoA-overexpression of zebrafish and an Amyotrophic Lateral Sclerosis mouse model, SOD1 G93A. Thus, Pgk1 secreted from muscle is detrimental to motoneuron neurite outgrowth and maintenance.

Abstract Background Porcine pathogenic Escherichia coli (E. coli), the globally recognized important pathogen, causes significant economic loss in the field. Enterotoxigenic E. coli (ETEC) causes porcine neonatal and post-weaning diarrhea (PWD), frequently carrying F4 adhesin, F18 adhesin, Heat-Stable toxin (ST), and Heat-Labile toxin (LT). Shiga Toxin-Producing E. coli (STEC) produces F18 adhesin and Shiga toxin type 2e (stx2e), majorly leading to systemic endothelial cell damage and edema disease. In this study, hemolytic pathogenic hybrid STEC/ETEC strains carrying ST and LT genes of ETEC and the Stx2e gene of STEC isolated from pigs with PWD in Taiwan were identified. The pathogenicity of a Taiwan hybrid STEC/ETEC strain was evaluated by oral inoculation in post-weaning pigs. Results Next generation sequencing and multilocus sequence typing of two hybrid Taiwan porcine STEC/ETEC isolates indicated that these two isolates were closely related to the ST88 porcine hybrid STEC/ETEC isolated from pigs with watery diarrhea. Furthermore, the two hybrid Taiwan porcine STEC/ETEC isolates also displayed combinations of multiple resistance genes encoding mechanisms for target modification and antibiotic inactivation. Animal experiments confirmed that the Taiwan hybrid STEC/ETEC could cause watery diarrhea in post-weaning pigs with no signs of edema disease and minimal histopathological lesions. Conclusion To the best of the authors’ knowledge, the present study is the first study demonstrating intestinal pathogenicity of the hybrid STEC/ETEC in pigs. The result suggests that the hybrid STEC/ETEC should be considered as a new emerging pathogen and a new target for vaccine development.

Bacteria-based cancer therapy employs various strategies to combat tumors, one of which is delivering tumor-associated antigen (TAA) to generate specific immunity. Here, we utilized a poly-arginine extended HPV E7 antigen (9RE7) for attachment on Salmonella SL7207 outer membrane to synthesize the bacterial vaccine Salmonella-9RE7 (Sal-9RE7), which yielded a significant improvement in the amount of antigen presentation compared to the previous lysine-extended antigen coating strategy. In TC-1 tumor mouse models, Sal-9RE7 monotherapy decreased tumor growth by inducing E7 antigen-specific immunity. In addition, pairing Sal-9RE7 with adjuvant Albumin-IFNβ (Alb-IFNβ), a protein cytokine fusion, the combination significantly increased the antitumor efficacy and enhanced immunogenicity in the tumor microenvironment (TME). Our study made a significant contribution to personalized bacterial immunotherapy via TAA delivery and demonstrated the advantage of combination therapy.

Abstract Diabetic cardiomyopathy (DbCM) is characterized by diastolic dysfunction, which progresses into heart failure and aberrant electrophysiology in diabetic patients. Dyslipidemia in type 2 diabetic patients leads to the accumulation of lipid droplets (LDs) in cardiomyocytes and results in lipid toxicity which has been suggested to drive DbCM. It is aimed to explore potential pathways that may boost LDs degradation in DbCM and restore cardiac function. LDs accumulation resulted in an increase in lipid toxicity in DbCM hearts is confirmed. Microlipophagy pathway, rather than traditional macrolipophagy, is activated in DbCM hearts. RNA‐Seq data and Rab7‐CKO mice implicate that Rab7 is a major modulator of the microlipophagy pathway. Mechanistically, Rab7 is phosphorylated at Tyrosine 183, which allows the recruitment of Rab‐interacting lysosome protein (Rilp) to proceed LDs degradation by lysosome. Treating DbCM mice with Rab7 activator ML‐098 enhanced Rilp level and rescued the observed cardiac dysfunction. Overall, Rab7‐Rilp‐mediated microlipophagy may be a promising target in the treatment of lipid toxicity in DbCM is suggested.

Cystathionine γ-lyase (CSE) is a major enzyme that produces hydrogen sulfide (H2S). Herein, we report how CSE plays a previously unknown role in regulating the antioxidant effects of the mitochondria in human umbilical vein endothelial cells by releasing H2S nearby under stress conditions. We found that H2S partially promoted angiogenesis in the endothelial cells through the AKT/nuclear factor erythroid 2-related factor 2 (AKT/NRF2) signaling pathway. H2S improved mitochondrial function by altering the expressions of the mitofusin2 and dynamin-1-like mitochondrial fission proteins to inhibit oxidative stress and enhance NRF2 nuclear translocation. CSE is located only in the cytoplasm and not in the mitochondria, but it is transported to the vicinity of the mitochondria to produce H2S, which plays an antioxidant role in human umbilical vein endothelial cells under stress. The CSE mutant (with mutated CSE activity center: CSED187A) partially decreased the effects on promoting angiogenesis, resisting oxidative stress, and entering the mitochondria. These results show that CSE translocation is a unique mechanism that promotes H2S production inside the mitochondria under stress stimulation. Therefore, the CSE mutant site (CSED187A) may be a potential target for drug therapy.

As the lightest structural metal and one of the most abundant metallic elements on earth, magnesium (Mg) has been used as an “industrial metal” for lightweighting in the transportation and electronics industries, in addition to other traditional applications in aluminum alloying, steel desulfurization and protective anodes. In recent years, research has shown significant potential for Mg to become a “technology metal” in a variety of new applications from energy storage/battery to biomedical products. However, global Mg production has shown steady but moderate growth in the last three decades. Mg applications as an industry metal are still limited due to some sustainability concerns of primary Mg production, as well as a number of technical issues related to the structural and corrosion performance of commercial Mg alloys. New Mg applications as an industrial or technology metal face tremendous technical challenges, which have been reflected in the intensified global research efforts in the last twenty years. This paper will review some past and present applications, and discuss future opportunities and challenges for Mg research and applications for the global Mg community.

Recent studies have demonstrated that ferroptosis, a novel form of nonapoptotic regulated cell death plays an important role in doxorubicin (DOX)-induced cardiotoxicity (DoIC). Hydrogen sulfide (H2S) is emerging as the third important gaseous mediator in cardiovascular system. However, whether H2S has an effect on DOX-induced ferroptosis remains unknown. Here, we found that DOX not only triggered cardiomyocyte ferroptosis but also significantly inhibited the synthesis of endogenous H2S in the murine model of chronic DoIC. Application of NaHS, an H2S donor obviously activated the SLC7A11/GSH/GPx4 antioxidant pathway and thus alleviated DOX-induced ferroptosis and cardiac injury in mice. In contrast, cardiac-specific knockout of cystathionine γ-lyase gene (Cse) in mice (Csef/f/Cre+) to abolish the cardiac synthesis of endogenous H2S evidently exacerbated DOX-induced ferroptosis and cardiac dysfunction. A further suppression of SLC7A11/GSH/GPx4 pathway was obtained in Csef/f/Cre+ mice with DoIC, as compared to Csef/f/Cre− mice with DoIC. The aggravation caused by cardiac-specific Cse deficiency was remarkably rescued by exogenous supplementation of NaHS. Moreover, in DOX-stimulated H9c2 cardiomyocytes, pretreatment with NaHS dose-dependently enhanced the activity of SLC7A11/GSH/GPx4 pathway and subsequently mitigated ferroptosis and mitochondrial impairment. On the contrary, transfection with Cse siRNA in DOX-stimulated H9c2 cardiomyocytes markedly inhibited SLC7A11/GSH/GPx4 pathway, thus leading to aggravated ferroptosis and more damage to mitochondrial structure and function. In addition, the protective effect of NaHS on DOX-induced ferroptosis was closely related to the S-sulfhydrated Keap1, which in turn promoted nuclear translocation of Nrf2 and the transcription of SLC7A11 and GPx4. In conclusion, our findings suggest that H2S may exert protective effect on DoIC by inhibiting DOX-induced ferroptosis via Keap1/Nrf2-dependent SLC7A11/GSH/GPx4 antioxidant pathway.

Wound monitoring is crucial for effective healing, as nonhealing wounds can lead to tissue ulceration and necrosis. Evaluating wound recovery involves observing changes in angiogenesis. Laser speckle contrast imaging (LSCI) is vital for wound assessment due to its rapid imaging, high resolution, wide coverage, and noncontact properties. When using LSCI equipment, regions of interest (ROIs) must be delineated in lesion areas in images for quantitative analysis. However, patients with serious wounds cannot maintain constant postures because the affected areas are often associated with discomfort and pain. This leads to deviations between the drawn ROI and actual wound position when using LSCI for wound assessment, affecting the reliability of relevant assessments. To address these issues, we used the channel and spatial reliability tracker object tracking algorithm to develop an automatic ROI tracking function for LSCI systems. This algorithm is used to track and correct artificial movements in blood flow images, address the ROI position offset caused by the movement of the affected body part, increase the blood flow analysis accuracy, and improve the clinical applicability of LSCI systems. ROI tracking experiments were performed by simulating wounds, and the results showed that the intraclass correlation coefficient (ICC) ranged from 0.134 to 0.976. Furthermore, the object within the ROI affected tracking performance. Clinical assessments across wound types showed ICCs ranging from 0.798 to 0.917 for acute wounds and 0.628–0.849 for chronic wounds. We also discuss factors affecting tracking performance and propose strategies to enhance implementation effectiveness.

African swine fever (ASF) is a deadly disease of swine currently causing a worldwide pandemic, leading to severe economic consequences for the porcine industry. The control of disease spread is hampered by the limitation of available effective vaccines. Live attenuated vaccines (LAVs) are currently the most advanced vaccine prototypes, providing strong protection against ASF. However, the significant advances achieved using LAVs must be complemented with further studies to analyze vaccine-induced immunity. Here, we characterized the onset of cross-protective immunity triggered by the LAV candidate BA71ΔCD2. Intranasally vaccinated pigs were challenged with the virulent Georgia 2007/1 strain at days 3, 7 and 12 postvaccination. Only the animals vaccinated 12 days before the challenge had effectively controlled infection progression, showing low virus loads, minor clinical signs and a lack of the unbalanced inflammatory response characteristic of severe disease. Contrarily, the animals vaccinated 3 or 7 days before the challenge just showed a minor delay in disease progression. An analysis of the humoral response and whole blood transcriptome signatures demonstrated that the control of infection was associated with the presence of virus-specific IgG and a cytotoxic response before the challenge. These results contribute to our understanding of protective immunity induced by LAV-based vaccines, encouraging their use in emergency responses in ASF-affected areas.

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that causes muscle atrophy and primarily targets motor neurons (MNs). Approximately 20% of familial ALS cases are caused by gain-of-function mutations in superoxide dismutase 1 (SOD1), leading to MN degeneration and ion channel dysfunction. Previous studies have shown that n-Butylidenephthalide (BP) delays disease progression and prolongs survival in animal models of ALS. However, no studies have been conducted on models from human sources. Herein, we examined the protective efficacy of BP on MNs derived from induced pluripotent stem cells (iPSCs) of an ALS patient harboring the SOD1G85R mutation as well as on those derived from genetically corrected iPSCs (SOD1G85G). Our results demonstrated that the motor neurons differentiated from iPSC with SOD1G85R mutation exhibited characteristics of neuron degeneration (as indicated by the reduction of neurofilament expression) and ion channel dysfunction (in response to potassium chloride (KCl) and L-glutamate stimulation), in contrast to those derived from the gene corrected iPSC (SOD1G85G). Meanwhile, BP treatment effectively restored calcium ion channel function by reducing the expression of glutamate receptors including glutamate ionotropic receptor AMPA type subunit 3 (GluR3) and glutamate ionotropic receptor NMDA type subunit 1 (NMDAR1). Additionally, BP treatment activated autophagic pathway to attenuate neuron degeneration. Overall, this study supports the therapeutic effects of BP on ALS patient-derived neuron cells, and suggests that BP may be a promising candidate for future drug development.

Network Function Virtualization (NFV) decouples network functions from the underlying specialized devices, enabling network processing with higher flexibility and resource efficiency. This promotes the use of virtual network functions (VNFs), which can be grouped to form a service function chain (SFC). A critical challenge in NFV is SFC partitioning (SFCP), which is mathematically expressed as a graph-to-graph mapping problem. Given its NP-hardness, SFCP is commonly solved by approximation methods. Yet, the relevant literature exhibits a gradual shift towards data-driven SFCP frameworks, such as (deep) reinforcement learning (RL). In this article, we initially identify crucial limitations of existing RL-based SFCP approaches. In particular, we argue that most of them stem from the centralized implementation of RL schemes. Therefore, we devise a cooperative deep multi-agent reinforcement learning (DMARL) scheme for decentralized SFCP, which fosters the efficient communication of neighboring agents. Our simulation results (i) demonstrate that DMARL outperforms a state-of-the-art centralized double deep $Q$ -learning algorithm, (ii) unfold the fundamental behaviors learned by the team of agents, (iii) highlight the importance of information exchange between agents, and (iv) showcase the implications stemming from various network topologies on the DMARL efficiency.

Hsu and co-workers integrate cryo-electron tomography, cryo-electron microscopy and mass spectrometry to reveal the structural polymorphism of a pig coronavirus spike protein within intact viral particles, and how glycosylation modulates the conformational changes pertinent to host recognition.

Sonodynamic therapy (SDT) emerges as a promising non-invasive alternative for eradicating malignant tumours. However, its therapeutic efficacy remains limited due to the lack of sonosensitisers with high potency and biosafety. Previously, gold nanorods (AuNRs) have been extensively studied for their applications in photodynamic or photothermal cancer therapy, but their sonosensitising properties are largely unexplored. Here, we reported the applicability of alginate-coated AuNRs (AuNRsALG) with improved biocompatibility profiles as promising nanosonosensitisers for SDT for the first time. AuNRsALG were found stable under ultrasound irradiation (1.0 W/cm2, 5 min) and maintained structural integrity for 3 cycles of irradiation. The exposure of the AuNRsALG to ultrasound irradiation (1.0 W/cm2, 5 min) was shown to enhance the cavitation effect significantly and generate a 3 to 8-fold higher amount of singlet oxygen (1O2) than other reported commercial titanium dioxide nanosonosensitisers. AuNRsALG exerted dose-dependent sonotoxicity on human MDA-MB-231 breast cancer cells in vitro, with ∼ 81% cancer cell killing efficacy at a sub-nanomolar level (IC50 was 0.68 nM) predominantly through apoptosis. The protein expression analysis showed significant DNA damage and downregulation of anti-apoptotic Bcl-2, suggesting AuNRsALG induced cell death through the mitochondrial pathway. The addition of mannitol, a reactive oxygen species (ROS) scavenger, inhibited cancer-killing effect of AuNRsALG-mediated SDT, further verifying that the sonotoxicity of AuNRsALG is driven by the production of ROS. Overall, these results highlight the potential application of AuNRsALG as an effective nanosonosensitising agent in clinical settings.

Abstract Doxorubicin (DOX)‐induced cardiotoxicity (DoIC) is a major side effect for cancer patients. Recently, ferroptosis, triggered by iron overload, is demonstrated to play a role in DoIC. How iron homeostasis is dysregulated in DoIC remains to be elucidated. Here, the authors demonstrate that DOX challenge exhibits reduced contractile function and induction of ferroptosis‐related phenotype in cardiomyocytes, evidenced by iron overload, lipid peroxide accumulation, and mitochondrial dysfunction. Compared to Ferric ammonium citrate (FAC) induced secondary iron overload, DOX‐challenged cardiomyocytes show a dysfunction of iron homeostasis, with decreased cytoplasmic and mitochondrial iron–sulfur (FeS) cluster‐mediated aconitase activity and abnormal expression of iron homeostasis–related proteins. Mechanistically, mass spectrometry analysis identified DOX‐treatment induces p53‐dependent degradation of Parkinsonism associated deglycase (Park7) which results in iron homeostasis dysregulation. Park7 counteracts iron overload by regulating iron regulatory protein family transcription while blocking mitochondrial iron uptake. Knockout of p53 or overexpression of Park7 in cardiomyocytes remarkably restores the activity of FeS cluster and iron homeostasis, inhibits ferroptosis, and rescues cardiac function in DOX treated animals. These results demonstrate that the iron homeostasis plays a key role in DoIC ferroptosis. Targeting of the newly identified p53–Park7 signaling axis may provide a new approach to prevent DoIC.

Alzheimer's disease (AD) is one of the neurodegenerative disorders, the hallmarks of which include deposits of extracellular beta-amyloid (Aβ) as well as intracellular tau neurofibrillary tangles (NFTs) tangles. With disease progression, neuronal apoptosis combined with cerebral atrophy occurs, leading to cognitive impairment and long-term memory loss. Recently, Chlorella species have been identified as a functional food and are being explored for the prevention of various diseases widely studied to prevent or treat many neurodegenerative diseases. Hence, we for the first time investigated the neuroprotective effects of Chlorella pyrenoidosa short-chain peptides (CPPs) i.e. 10 kDa on the in vitro and in vivo neuronal injury models. Our in vitro results showed that CPP with a molecular weight of 1–3 kDa and 3–10 kDa could elevate the survival rate of Aβ1-42 or l-Glutamic acid-injured N2A cells. These treatments also inhibited Aβ and tau NFTs in N2A cells and prevented progressive neuronal cellular damage by suppressing inflammatory cytokines such as PGE2, iNOS, IL-6, TNF-α, COX-2, IL-1β, TGF-β1, and NF-κB. Further, our in vivo Aβ1-42-induced AD mice model demonstrated that 1–3 kDa or 3–10 kDa CPP could improve spatial cognition and learning memory. We also observed a decreased cell loss ratio in CA1-CA3 hippocampal regions. Taken together, our findings imply that CPPs may exert their anti-AD impact through anti-inflammatory, and anti-amyloid activities via reducing APP and tau NFT.

Abstract Background Adipose tissue homeostasis is at the heart of many metabolic syndromes such as diabetes. Previously it has been demonstrated that adipose tissues from diabetic patients are senescent but whether this contributes to diabetic cardiomyopathy (DCM) remains to be elucidated. Methods The streptozotocin (STZ) type 1 diabetic mice were established as animal model, and adult mouse ventricular myocytes (AMVMs) isolated by langendorff perfusion as well as neonatal mouse ventricular myocytes (NMVMs) were used as cell models. Senescent associated β galactosidase (SA-β-gal) staining and RT-qPCR were used to identify the presence of adipose senescence in diabetic adipose tissue. Senescent adipose were removed either by surgery or by senolytic treatment. Large extracellular vesicles (LEVs) derived from adipose tissue and circulation were separated by ultracentrifugation. Cardiac systolic and diastolic function was evaluated through cardiac ultrasound. Cardiomyocytes contraction function was evaluated by the Ionoptix HTS system and live cell imaging, mitochondrial morphology and functions were evaluated by transmission electron microscope, live cell fluorescent probe and seahorse analysis. RNA-seq for AMVMs and miRNA-seq for LEVs were performed, and bioinformatic analysis combined with RT-qPCR and Western blot were used to elucidate underlying mechanism that senescent adipose derives LEVs exacerbates myocardial metabolism. Results SA-β-gal staining and RT-qPCR identified the presence of adipose tissue senescence in STZ mice. Through surgical as well as pharmacological means we show that senescent adipose tissue participates in the pathogenesis of DCM in STZ mice by exacerbates myocardial metabolism through secretion of LEVs. Specifically, expression of miRNA-326-3p was up-regulated in LEVs isolated from senescent adipose tissue, circulation, and cardiomyocytes of STZ mice. Up-regulation of miRNA-326-3p coincided with myocardial transcriptomic changes in metabolism. Functionally, we demonstrate that miRNA-326-3p inhibited the expression of Rictor and resulted in impaired mitochondrial and contractile function in cardiomyocytes. Conclusion We demonstrate for the first time that senescent adipose derived LEVs exacerbates myocardial metabolism through up-regulated miRNA-326-3p which inhibits Rictor in cardiomyocytes. Furthermore, reducing senescence burden in adipose tissue is capable of relieving myocardial metabolism disorder in diabetes mellitus.

Background: Transumbilical laparoscopy-assisted Malone procedure (TULAM) is a single-incision laparoscopic procedure in which the appendicostomy is made at umbilicus. The aim of this study is to evaluate the outcomes of TULAM. Methods: With IRB approval, the medical records of the patients who underwent TULAM were retrospectively reviewed between July 2013 and December 2018. The data collected included ages, gender, underlying diseases, operative techniques, complications, stoma continence, parental satisfaction and follow-up duration. Results: Fifteen patients underwent TULAM at the median age of 5.0 years (2.9–10.7 years). There were 4 girls and 11 boys. Thirteen patients had anorectal malformations or cloaca; the other two patients had spina bifida. All patients presented with fecal incontinence; 9 of them had concomitant constipation. TULAM was successfully accomplished in 14 patients; one patient required conversion to the three-port procedure. The median follow-up period was 1.7 years (0.5–3.2 years). One patient required tube replacement under endoscopy guidance in the operation room. One patient required surgical revision because the appendix was disrupted after an episode of enterocolitis. All patients were socially continent with antegrade enemas. 12 patients were stoma continent, and 3 patients had minor leaking less than once a month. The stoma cosmesis was satisfactory. All parents expressed satisfaction with TULAM. Conclusion: TULAM is effective in the management of fecal incontinence and constipation, and provides a continent stoma with excellent cosmesis.

The popularization of long-term invasive tools for continuously monitoring blood pressure remains challenging. However, with the rising popularity of wearable personal health management devices, non-cuff blood pressure measurement technology that applies electrocardiography (ECG) and photoplethysmography (PPG) has gradually received increasing attention. In particular, whether blood pressure can be measured continuously by the PPG signal alone is of great interest. In this study, we aim to develop a device that includes systolic and diastolic blood pressure calculation formulas derived from characteristic waveform points in the PPG time domain and that can measure blood oxygenation and heart rate. This device applies empirical formulas developed by PPG waveforms in the PhysioNet MIMIC-II database to calculate blood pressure. The systolic and diastolic pressures are then compared with the actual blood pressures obtained from invasive blood pressure waveforms to verify the effectiveness and feasibility of the complete developed system. Overall, 263 waveforms with double peaks and 261 waveforms with only a single peak totaling 524 sets of data are used to derive the empirical formulas. The systolic blood pressure estimation result using single peak analysis has an excessively large error exceeding ±40 mmHg, providing no reference value. However, systolic blood pressure estimation is notably better in double peak analysis, with error values reducing to approximately 23 mmHg. Diastolic pressure estimation errors are low with both single (±7 mmHg) and double peak (±4 mmHg) analyses. The error is lower in double-peak analysis than in single-peak analysis for obtaining systolic pressure from PPG waves. We plan to use PPG to detect additional physiological parameters in the future, e.g., respiratory rate, heart rate variability, or irregular heartbeat, to further enhance the functionality of PPG-based wearable devices.

Cystathionine γ-lyase (CSE) is a major enzyme that produces hydrogen sulfide (H2S). Herein, we report how CSE plays a previously unknown role in regulating the antioxidant effects of the mitochondria in human umbilical vein endothelial cells by releasing H2S nearby under stress conditions. We found that H2S partially promoted angiogenesis in the endothelial cells through the AKT/nuclear factor erythroid 2-related factor 2 (AKT/NRF2) signaling pathway. H2S improved mitochondrial function by altering the expressions of the mitofusin2 and dynamin-1-like mitochondrial fission proteins to inhibit oxidative stress and enhance NRF2 nuclear translocation. CSE is located only in the cytoplasm and not in the mitochondria, but it is transported to the vicinity of the mitochondria to produce H2S, which plays an antioxidant role in human umbilical vein endothelial cells under stress. The CSE mutant (with mutated CSE activity center: CSED187A) partially decreased the effects on promoting angiogenesis, resisting oxidative stress, and entering the mitochondria. These results show that CSE translocation is a unique mechanism that promotes H2S production inside the mitochondria under stress stimulation. Therefore, the CSE mutant site (CSED187A) may be a potential target for drug therapy. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effects of feeding spray-dried porcine plasma (SDPP) on the protection afforded by the BA71∆CD2 African swine fever virus (ASFV) vaccine prototype. Two groups of pigs acclimated to diets without or with 8% SDPP were intranasally inoculated with 105 plaque-forming units (PFU) of live attenuated ASFV strain BA71∆CD2 and, three weeks later, left in direct contact with pigs infected with the pandemic Georgia 2007/01 ASFV strain. During the post-exposure (pe) period, 2/6 from the conventional diet group showed a transient peak rectal temperature >40.5 °C before day 20 pe, and some tissue samples collected at 20 d pe from 5/6 were PCR+ for ASFV, albeit showing Ct values much higher than Trojan pigs. Interestingly, the SDPP group did not show fever, neither PCR+ in blood nor rectal swab at any time pe, and none of the postmortem collected tissue samples were PCR+ for ASFV. Differential serum cytokine profiles among groups at vaccination, and a higher number of ASFV-specific IFNϒ-secreting T cells in pigs fed with SDPP soon after the Georgia 2007/01 encounter, confirmed the relevance of Th1-like responses in ASF protection. We believe that our result shows that nutritional interventions might contribute to improving future ASF vaccination strategies.

It is shown in this paper that a polymer, MA-PEG 1000-DGEBA (MP1D), exhibits antireflection, substrate-dependent photoluminescence (SDP), wide band-gap, and photoconduction characterization. MP1D was synthesized from maleic anhydride, polyethylene glycol 1000, and bisphenol-A diglycidyl ether. Self-assembled nanoparticles embedded in MP1D film and ranging from 2.5 to 31.6 nm are observed, which could be expected as scatterers to enhance light trapping and extraction. The size of the nanoparticle increases with the concentration of the MP1D solution. Besides solution concentration, the nanoparticle dimension could be modified by the chain length of polyethylene glycol in the polymer synthesis. The effects of solution concentration, annealing temperature, annealing period, and substrate on the photoluminescence (PL) of MP1D films are examined. Increasing solution concentration increases PL intensity. However, aggregation-caused quenching is explicit as the solution concentration exceeds 100 mM. PL intensity increases with annealing temperature, which could be attributed to crystallinity improvement. PL intensity increases with increasing the annealing period from 0.5 to 2 h. Nonetheless, as the annealing period exceeds 2 h, PL quenching is emerging, which could be due to aggregation. It is expected that MP1D could be a promising candidate for host materials and MP1D film could play a multifunctional role (antireflective and light-trapping functions) in optoelectronics.