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BACKGROUND: Yeast is often used to build cell factories to produce various chemicals or nutrient substances, which means the yeast has to encounter stressful environments. Previous research reported that unsaturated fatty acids were closely related to yeast stress resistance. Engineering unsaturated fatty acids may be a viable strategy for enhancing the stress resistance of cells. RESULTS: In this study, two desaturase genes, OLE1 and FAD2 from Z. rouxii, were overexpressed in S. cerevisiae to determine how unsaturated fatty acids affect cellular stress tolerance of cells. After cloning and plasmid recombination, the recombinant S. cerevisiae cells were constructed. Analysis of membrane fatty acid contents revealed that the recombinant S. cerevisiae with overexpression of OLE1 and FAD2 genes contained higher levels of fatty acids C16:1 (2.77 times), C18:1 (1.51 times) and C18:2 (4.15 times) than the wild‐type S. cerevisiae pY15TEF1. In addition, recombinant S. cerevisiae cells were more resistant to multiple stresses, and exhibited improved membrane functionality, including membrane fluidity and integrity. CONCLUSION: These findings demonstrated that strengthening the expression of desaturases was beneficial to stress tolerance. Overall, this study may provide a suitable means to build a cell factory of industrial yeast cells with high tolerance during biological manufacturing. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Membrane bioreactor (MBR), as a biological unit for wastewater treatment, has been proven to have the advantages of simple structure and high pollutant removal rate. However, membrane fouling limits its wide application, and it is crucial to adopt effective membrane fouling control methods. As a new type of membrane fouling control technology, electrically-enhanced MBR (EMBR) has attracted more interest recently. It uses the driving force of electric field to make pollutants flocculate or move away from the membrane surface to achieve the purpose of inhibiting membrane fouling. This paper expounds the configuration of EMBR in recent years, including the location of membrane components, the way of electric field application and the selection of electrode and membrane materials, and provides the latest development information in various aspects. The enhanced effect of electric field on the removal of comprehensive and refractory pollutants is outlined in detail. And from the perspective of sludge properties (EPS, SMP, sludge particle size, zeta potential and microbial activity), the influence of electric field on sludge characteristics and the relationship between the changes of sludge properties in EMBR and membrane fouling are discussed. Moreover, the electrochemical mechanisms of electric field alleviating membrane fouling are elucidated from electrophoresis, electrostatic repulsion, electroflocculation, electroosmosis, and electrochemical oxidation, and the regeneration and stability of EMBR are assessed. The existing challenges and future research directions are also proposed. This review could provide theoretical guidance and further studies for subsequent topic, and promoting the wide engineering applications of EMBR. [Display omitted] • EMBR is a new electrochemical wastewater treatment technology. • EMBR strengthens the degradation of pollutants. • EMBR can alleviate membrane fouling. • Electric field affects sludge properties and microbial activity. • Multiple electrochemical actions synergistically promote the operation of EMBR. [ABSTRACT FROM AUTHOR]

Objectives: Carbon dots (CDs) are one of the most promising carbon‐based materials in bioimaging and drug/gene delivery applications. In this study, we have attempted to study the drug carrying capacity of highly fluorescent CDs for delivery of doxorubicin (DOX) and investigate the therapeutic activity of the CDs‐DOX drug delivery system. Materials and methods: Carbon dots were synthesized by means of a hydrothermal approach with mixing citric acid and ethylenediamine. The properties of CDs were characterized in respects of spectral property, zeta potential, particle morphology and chemical composition. The drug loading efficiency (DLE) and release profile of CDs‐DOX were determined by a fluorescence spectrophotometer. We investigated the cellular toxicity and pharmaceutical activity of CDs and CDs‐DOX in L929 cells and MCF‐7 cells by the CCK‐8 assay. We also studied the cellular uptake of CDs‐DOX with the methods of confocal microscopy and flow cytometry. In addition, the effect of CDs‐DOX on cell apoptosis was assessed by flow cytometry. Results: The obtained CDs possessed good biocompatibility and showed a potential capacity of promoting proliferation. DOX was successfully conjugated to CDs through electrostatic interaction, and the results of the DLE and loading content (DLC) suggested a relatively high drug loading capacity of CDs. Compared with free DOX, the CDs‐DOX complex had a higher cellular uptake and better anti‐tumour efficacy on MCF‐7 cells. Conclusions: The results of this study indicated that the CDs‐DOX drug delivery system had a potential value in cancer chemotherapeutic application. [ABSTRACT FROM AUTHOR]

Increasingly more attention has been paid to morphological studies of biomaterials and the physicochemical and biological properties thereof in various applications. Herein, the morphology of hydroxyapatite (HAP) has been evolved into three morphologies (short rod-, flake flower-, and dandelion-like) by using different surfactants under hydrothermal treatments. Moreover, the influences of morphology on selective adsorption of heavy metal ions and antibacterial activity were evaluated in detail. The results showed that selective adsorption of heavy metal ions by HAP was dependent on the morphology, but was independent of the antibacterial activity. Also, morphological evolution mechanism, influencing factors for adsorption, kinetics, isotherms and possible adsorption mechanisms were discussed in this study. The maximum adsorption capacities under the Langmuir model were also shown to depend on the morphology of HAP, with the highest adsorption capacity reaching up to 819.7 mg g − 1 for dandelion-like structures, which may resulted from such structures having multi-adsorbing sites. In sum, the study provides a material having specific morphologies for high-efficient and selective removal of Pb 2 + , and offers guidance for modification of antibacterial activity of biomaterials. [ABSTRACT FROM AUTHOR]

Five canine distemper virus monoclonal antibodies were developed by immunizing BALB/c mice with a traditional vaccine strain Snyder Hill. Among these monoclonal antibodies, four antibodies recognized both field and vaccine strains of canine distemper virus without neutralizing ability. One monoclonal antibody, 1A4, against hemagglutinin protein of canine distemper virus was found to react only with vaccine strain virus but not field isolates, and showed neutralizing activity to vaccine strain virus. These monoclonal antibodies could be very useful tools in the study of the pathogenesis of canine distemper virus and the development of diagnostic reagents. [ABSTRACT FROM AUTHOR]

Targeted drug delivery is urgently needed for cancer therapy, and green synthesis is important for the biomedical use of drug delivery systems in the human body. In this work, we report two targeted delivery systems for anticancer drugs based on tea polyphenol functionalized and reduced graphene oxide (TPGs). The obtained TPGs demonstrated an efficient doxorubicin loading capacity as high as 3.430 × 106mg g-1 and 3.932 × 104mg g-1, and exhibited pH-triggered release. Furthermore, the kinetic models, adsorption isotherms, and possible loading mechanisms were investigated in details. Compared to TPG1 and free doxorubicin, TPG2 is biocompatible to normal cells even at high concentrations and promotes tumor cells death by delivering the doxorubicin mainly to the nuclei. These results were confirmed using cell viability tests and confocal laser microscopy. Moreover, apoptosis tests showed that the mechanism of cancer cell death induced by TPG1 and TPG2 might follow the similar mechanisms. Taken together, these results demonstrate that TPGs provide a multifunctional drug delivery system with a greater loading capacity and pH-sensitive drug release for enhanced cancer therapy. The high drug payload capability and enhanced antitumor efficacy demonstrate that we developed systems are promising for various biomedical applications and cancer therapy. [ABSTRACT FROM AUTHOR]

In this work, a graphene oxide functionalized Zn-based metal–organic framework (ZnMOF) was synthesised under a one-pot condition. This ZnMGO composite had high luminescence and good water dispersibility. The luminescence of the aqueous ZnMGO composite was efficiently and selectively quenched by Cu2+ ions through interactions between Cu2+ and the ligand. The detection limit was measured at concentrations as low as 1.00 μM. This robust ZnMGO composite demonstrated a fast response and high sensitivity (Ksv = 3.07 × 104 M−1) for Cu2+ ions in aqueous solution. Moreover, the possible luminescence mechanism in terms of energy migration or electron transfer was further explored, and the quenching mechanism was discovered to be based on the collapse of the crystal structure with the help of various characterizations. Remarkably, it is the first time that this excellent ability possessed by the ZnMGO composite has been used to rapidly detect Cu2+ ions in aqueous solution. The work does not only contribute to extend the potential application of ZnMGO composites, but it also aims to make a contribution within the biological sciences. [ABSTRACT FROM AUTHOR]

The present study outlines a one-step route to the preparation and functionalization of graphene nanosheets from graphene oxide using tea polyphenols as a simultaneous reductant and functionalization reagent. This method uses a 'green' reductant and is free of additional functionalization reagents, thus it is environmentally friendly, simple, and low-cost. The resulting functionalized graphene nanosheets have a mostly single-layer structure, are stable, and have very good water dispersibility. The structure, composition, and morphology of the resulting material were characterized by using various methods including, X-ray diffraction (XRD), UV/Vis spectroscopy, Raman spectroscopy, detailed X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Among other possible applications of the functionalized graphene, we discuss its use as an adsorbent for heavy-metal ions in aqueous solutions. [ABSTRACT FROM AUTHOR]

Abstract: SiO2/graphene composite was prepared through a simple two-step reaction, including the preparation of SiO2/graphene oxide and the reduction of graphene oxide (GO). The composite was characterized by UV–Vis spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscope, and X-ray photoelectron spectroscopy, and what is more, the adsorption behavior of as-synthesized SiO2/graphene composite was investigated. It was interestingly found that the composite shows high efficiency and high selectivity toward Pb(II) ion. The maximum adsorption capacity of SiO2/graphene composite for Pb(II) ion was found to be 113.6mgg−1, which was much higher than that of bare SiO2 nanoparticles. The results indicated that SiO2/graphene composite with high adsorption efficiency and fast adsorption equilibrium can be used as a practical adsorbent for Pb(II) ion. [Copyright &y& Elsevier]

The accumulation of ethanol has a negative effect on the viability and fermentation performance of microorganisms during the production of fermented foods because of its toxicity. In this study, we investigated the effect of co-culture with Tetragenococcus halophilus on ethanol stress resistance of Zygosaccharomyces rouxii. The result showed that co-culture with T. halophilus promoted cell survival of Z. rouxii under ethanol stress, and the tolerance improved with increasing co-culture time when ethanol content was 8%. Physiological analysis showed that the co-cultured Z. rouxii cells maintained higher intracellular content of trehalose and amino acids including tyrosine, tryptophan, arginine and proline after 8% ethanol stress for 90 min. The membrane integrity analysis and biophysical analysis of the cell surface indicated that the presence of ethanol resulted in cell membrane damage and changes of Young's modulus value and roughness of cell surface. While the co-cultured Z. rouxii cells exhibited better membrane integrity, stiffer and smoother cell surface than single-cultured cells under ethanol stress. As for transcriptomic analyses, the genes involved in unsaturated fatty acid biosynthesis, trehalose biosynthesis, various types of N-glycan biosynthesis, inositol phosphate metabolism, MAPK signaling pathway and tight junction had higher expression in co-cultured Z. rouxii cells with down-regulation of majority of gene expression after stress. And these genes may function in the improvement of ethanol tolerance of Z. rouxii in co-culture. Image 1 • Co-culture with T. halophilus promoted ethanol tolerance of Z. rouxii. • The biophysical analysis of cell surface indicated co-cultured Z. rouxii maintaining better cell surface property. • Transcriptomics elucidated the effect of co-culture and ethanol stress on gene expression of Z. rouxii. [ABSTRACT FROM AUTHOR]

In this study, the novel polysaccharides named HSP-0 M and HSP-0.1 M were successfully purified from Huangshui (HS), and their structural properties and bioactivities were investigated. Structural analysis revealed that HSP-0 M had a molecular weight of 493.87 kDa and was composed of arabinose, galactose, glucose, xylose, and mannose in a molar ratio of 1.48:1.09:26.52:1.33:1.00. On the other hand, HSP-0.1 M was made up of fructose, arabinose, galactose, glucose, xylose, mannose, ribose, galacturonic acid and glucuronic acid in a ratio of 2.67:26.00:29.10:36.83:16.22:30.53:1.00:1.43:3.64 with a molecular weight of 157.6 kDa. Methylated and 2D NMR analyses indicated that T-Glc p -(1 → 4)-Glc p -(1 → 2)-Glc p -(1 → 3)-Glc p was the primary chain of HSP-0 M, and the backbone of HSP-0.1 M was made up of →3)-Gal p -(1 → 6)-Man p -(1 → 3)-Glc p -(1 → 6)-Glc p -(1 → 2)-Man p -(1 → 6)-Glc p -(1 → 3)-Gal p. Morphological research showed that both polysaccharides were homogeneous as well as exhibit a web-like structure and an irregular lamellar structure. Furthermore, HSP-0 M demonstrated the capacity to safeguard Lactococcus lactis from damage caused by low temperatures and freeze-drying, while HSP-0.1 M exhibited noteworthy antioxidant activity. These results established a theoretical foundation for the applications of HSPs in food products, cosmetics, and medicines. • Two novel polysaccharides (HSP-0 M and HSP-0.1 M) from Huangshui were purified. • The structures and morphologies of two HSPs were comprehensively elaborated. • Bioactivities with antioxidant, cryoprotective and lyophilized protective activities of two HSPs were investigated. • HSP-0.1 M exhibited significant antioxidant activity. • HSP-0 M presented cryoprotective and freeze-drying protective effects on L. lactis MG1363. [ABSTRACT FROM AUTHOR]

In this article, by creating a novel distributed full‐form dynamic linearization based model‐free adaptive containment control (FFDL‐MFACC) approach, the containment control problem of networked heterogeneous autonomous surface vehicles (ASVs), suffering from complex external disturbances and unavailable kinetic model‐information, is resolved. In light of the data‐driven strategy, a full‐form dynamic linearization‐based data model is efficiently established. Then, by further deploying the commonly used rotation matrix, a distributed FFDL‐MFACC scheme is thereafter developed such that accurate tracking of a predefined convex hull spanned for all follower vehicles can be achieved. Afterwards, a disturbance observer is further designed to accurately estimate the lumped disturbances and the estimation is served as a compensation within the distributed full‐form dynamic linearization. Rigorously theoretical analysis indicates the devised distributed FFDL‐MFACC method can ensure the asymptotic containment tracking of networked heterogeneous ASVs. Finally, simulation results are illustrated to verify the advantages of the devised approach. [ABSTRACT FROM AUTHOR]

• Characterization of ZnO NPs via different tools analysis. • ZnO NPs possess the property of selective removal of heavy metal ions from dental wastewater. • High removal performance was achieved in the wide pH range of 3–7. • Study of the Cr3+ ions adsorption on kinetic and isotherm models. Zinc oxide nanoparticles (ZnO-NPs) was synthesized using the traditional hydrothermal method and its characterization as well as adsorption performance of heavy metal ions were studied. X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) confirmed hexagonal structures and functional groups. N 2 adsorption-desorption techniques suggested the Brunauer-Emmett-Teller (BET) specific surface area was 26.777 m2/g, indicating the potential in removal process. Scanning electron microscopy-energy dispersive X-ray (SEM-EDX) further ensured the possible interactions of ZnO-NPs and heavy metal ions. Batch adsorption experiments showed higher affinity towards Cr3+, and the maximal adsorption capacity was 88.547 mg/g at the optimum conditions (pH 3–7, 1 g/L adsorbent, 20 min contacting time, and 20 mg/L initial Cr3+ ions). The adsorption process showed best fit with the pseudo-second-order and Langmuir isotherm model, suggesting a chemisorption procedure and monolayer type removal. The ZnO-NPs could remove Cr3+ ions selectively, and hold the potential application for dental wastewater purification treatment. [ABSTRACT FROM AUTHOR]

Microfibril-associated glycoprotein-1 (MAGP1), a crucial extracellular matrix protein, contributes to the initiation and progression of different cancers. However, the role of MAGP1 in laryngeal cancer is not clear. The purpose of this study was to investigate the clinical significance and biological function of MAGP1 in laryngeal cancer. MAGP1 was upregulated in public databases and laryngeal cancer tissues, and high MAGP1 expression led to a poor prognosis and was identified as an independent prognostic marker. Knocking-down MAGP1 inhibited laryngeal cancer cell growth and metastasis. According to gene set enrichment analysis, high MAGP1 expression revealed enrichment in Wnt/β-catenin signaling and knocking-down MAGP1 in laryngeal cancer cells also caused degradation, de-activation, re-location and loss of stability of β-catenin. Additionally, we observed MAGP1 in laryngeal cancer cells inhibits angiogenesis in an MMP7-dependent way. In conclusion, our study suggests a clinical role of MAGP1 in laryngeal cancer, signifying its potential as a therapeutic target in the future. [ABSTRACT FROM AUTHOR]

Reperfusion after ischemia would cause massive myocardial injury, which leads to oxidative stress (OS). Calcium homeostasis imbalance plays an essential role in myocardial OS injury. CaV1.2 calcium channel mediates calcium influx into cardiomyocytes, and its activity is modulated by a region of calpastatin (CAST) domain L, CSL54-64. In this study, the effect of Ahf-caltide, derived from CSL54-64, on myocardial OS injury was investigated. Ahf-caltide decreased the levels of LDH, MDA and ROS and increased heart rate, coronary flow, cell survival and SOD activity during OS. In addition, Ahf-caltide permeated into H9c2 cells and increased CaV1.2, CaVβ2 and CAST levels by inhibiting protein degradation. At different Ca2+ concentrations (25 nM, 10 μM, 1 mM), the binding of CSL to the IQ motif in the C terminus of the CaV1.2 channel was increased in a H2O2 concentration-dependent manner. CSL54-64 was predicted to be responsible for the binding of CSL to CaV1.2. In conclusion, Ahf-caltide exerted a cardioprotective effect on myocardial OS injury by stabilizing CaV1.2 protein expression. Our study, for the first time, proposed that restoring calcium homeostasis by targeting the CaV1.2 calcium channel and its regulating factor CAST could be a novel treatment for myocardial OS injury. [ABSTRACT FROM AUTHOR]

Straw returning has been demonstrated as a beneficial approach for the utilization of renewable biomass source, which contributes to reducing environmental pollution and strengthening the sustainability of agriculture. However, information on how microorganisms respond to different straw return modes (SRMs) at varying nitrogen fertilizer levels (NFLs) in the black soil is still limited. The community composition, network pattern, and modular function of bacteria and fungi are investigated under three SRMs, including straw removal (CK), crushed straw incorporation (SD), and biochar incorporation (BC) at three NFLs (0, 144, and 240 kg N ha−1, respectively) mainly using Illumina MiSeq technique based on a long‐term maize field experiment. Results showed that bacterial richness, diversity, and fungal richness decreased with NFL reduction. However, these decreases can be compensated by SD and BC, demonstrating superiority for BC at reduced NFLs. SD and BC differed in their effects on the bacterial and fungal abundances (showing increments only in SD) and fungal Shannon diversity (remaining stable only in BC irrespective of NFLs). Microbial communities were substantially affected by SRMs and interacted with NFLs, which were driven by soil NH4+‐N, available potassium, total nitrogen, and pH. In addition, SD induced a network characterized by its highly complex (average degree 10.259 vs. 3.364) and stable structure (average clustering coefficient 0.503 vs. 0.239), Ascomycota as predominating keystone taxa, and abundant N‐cycling related bacteria, while BC formed a network comprising a superior modular structure (modularity 2.599 vs. 0.912), dominant symbiotic fungi, and soil bulk density as specific shaping factor, indicating that network pattern, keystone taxa, modular function, and determining factors shifted between SD and BC co‐occurrence networks. These results deepen insights into the response divergence of bacteria and fungi to SRMs and NFLs, providing a scientific basis for selecting the suitable strategy for sustainable straw utilization in the black soil area. [ABSTRACT FROM AUTHOR]

Physical injury carried by dried process was an inevitable and hostile problem which could seriously affect the quality and viability of microbial agents. In this study, heat preadaptation was successfully applied as a pretreatment to fight against the physical stresses encountered during freeze-dried and spray-dried process and develop a high activity Tetragenococcus halophilus powder. The results indicated T. halophilus cells maintained a higher viability in dried powder when cells were treated with heat preadaptation before dried process. Flow cytometry analysis illustrated that heat preadaptation contributed to maintain a high membrane integrity during dried process. Besides, glass transition temperatures of dried powder increased when cells were preheated, which further verified that higher stability was obtained in group preadaptation during shelf life. Additionally, dried powder prepared by heat shock presented a better fermentation performance, suggesting heat preadaptation may be a promising strategy to prepare bacterial powder by freeze drying or spray drying. • Heat preadaptation contributes to improve dried powder properties of T. halophilus. • Higher intact of cell membrane were maintained through heat preadaptation. • Shelf life and fermentation performance of dried powder were improved by heat shock. [ABSTRACT FROM AUTHOR]

Chemotherapy is widely applied against various kinds of carcinoma. Generally, chemotherapeutic agents, such as Doxorubicin (DOX), Paclitaxel (PTX), 5-Fluorouracil (5-FU), Methotrexate (MTX), and Vinblastine (VLB) are combined with a view to maximizing their efficacy. Unfortunately, chemotherapeutics are indiscriminate and also kill normal healthy cells, resulting in serious side effects. This non-productive and destructive distribution of chemotherapeutics is regarded as one of the largest problems associated with chemotherapy. Recently, the application of carbon dots (CDs) in cancer therapy has attracted considerable attention due to their attractive properties, such as biocompatibility and low toxicity. We report herein on the fabrication of CD-DOX antitumor drug complexes, from the combination of CDs and DOX, with a view to providing a novel and efficient strategy for cancer treatment. CDs were synthesized by hydrothermal treatment of milk, a simple and environmentally friendly synthetic process. DOX was conjugated to the CDs through electrostatic interactions via the multiple surface CD functional groups. The CD-DOX complexes exhibited pH-dependent DOX release behavior. A cytotoxicity study demonstrated that the CDs were non-cytotoxic in the range of concentrations used. Compared to free DOX, the CD-DOX complexes were significantly more destructive to the adenoid cystic carcinoma cell line (ACC-2), but exhibited lower toxicity to a mouse fibroblast cell line (L929). Confocal microscopy and flow cytometry confirmed that CD-DOX complexes increased cancer therapy efficiency through the localization of a much higher quantity of drugs in the nuclei of tumor cells and induced a higher rate of apoptosis in ACC-2 cells, compared to DOX alone. [ABSTRACT FROM AUTHOR]

Cav1.2 Ca2+ channels, a type of voltage-gated L-type Ca2+ channel, are ubiquitously expressed, and the predominant Ca2+ channel type, in working cardiac myocytes. Cav1.2 channels are regulated by the direct interactions with calmodulin (CaM), a Ca2+-binding protein that causes Ca2+-dependent facilitation (CDF) and inactivation (CDI). Ca2+-free CaM (apoCaM) also contributes to the regulation of Cav1.2 channels. Furthermore, CaM indirectly affects channel activity by activating CaM-dependent enzymes, such as CaM-dependent protein kinase II and calcineurin (a CaM-dependent protein phosphatase). In this article, we review the recent progress in identifying the role of apoCaM in the channel 'rundown' phenomena and related repriming of channels, and CDF, as well as the role of Ca2+/CaM in CDI. In addition, the role of CaM in channel clustering is reviewed. [ABSTRACT FROM AUTHOR]

Cataplexy is one of the symptoms of type 1 narcolepsy, characterized by a sudden loss of muscle tone. It can be seen as a behavioral index of salience, predominantly positive emotion, since it is triggered by laughter in humans and palatable foods in mice. In our previous study using chemogenetic techniques in narcoleptic mice (orexin neuron-ablated mice), we found that the rostral nucleus accumbens (NAc) shell is needed for chocolate-induced cataplexy. In this study, we investigated whether a short-lasting stimulation/inhibition of the NAc by optogenetics led to a similar result. Photo-illumination to the NAc in the channel rhodopsin-expressing mice showed a higher incidence (34.9 ± 5.1%) of cataplexy-like behavior than the control mice (17.8 ± 3.1%, P = 0.0056). Meanwhile, inactivation with archaerhodopsin did not affect incidence. The episode duration of cataplexy-like behavior was not affected by activation or inactivation. Immunohistochemical analysis revealed that photo-illumination activated channel rhodopsin-expressing NAc shell neurons. Thus, activation of the NAc, whether transient (light stimulation) or longer-lasting (chemical stimulation in our previous study), facilitates cataplexy-like behaviors and contributes to the induction but not maintenance in them. On the other hand, our study's result from optogenetic inhibition of the NAc (no effect) was different from chemogenetic inhibition (reduction of cataplexy-like behavior) in our previous study. We propose that the initiation of cataplexy-like behavior is facilitated by activation of the NAc, while NAc-independent mechanisms determine the termination of the behavior. [ABSTRACT FROM AUTHOR]

Na V 1.5 channel is an integral membrane protein involved in the initiation and conduction of action potentials. IQ motif is located in the C-terminal domain of Na V 1.5 sodium channel, which is highly conserved in human sodium channel subtypes. IQ motif is involved in the Ca2+-dependent regulation through interaction with the regulatory proteins such as calpastatin domain L (CS L). Mutations in SCN5A, the gene encoding Na V 1.5 channel, have been linked to many cardiac arrhythmias, such as Long QT syndrome type 3 (LQT3) and Brugada syndrome (BRS). LQT3-associated mutations in Na V 1.5 IQ motif, IQ Q1909R and IQ R1913H , have been reported to affect the late I Na. A BRS-associated mutation in Na V 1.5 IQ motif, IQ A1924T, has been reported to affect the peak I Na. But the detailed pathogenic mechanisms of LQT3 and BRS remains unclear. To explore the binding properties of CS L to IQ motif and its muants associated with LQT3/BRS, molecular docking and GST pull down assay were performed in this study. As a result, S58 and E59 in CS L activating channel effect region L54-64 were involved in the conformation of the CS L /IQ WT complex by protein-protein docking. IQ motif could bind to CS L in a [CS L ]-dependent and [Ca2+]-dependent manner by pull down assay. However, the binding affinities of IQ Q1909R and IQ R1913H to CS L were decreased and its reaction rates with CS L were slower. The binding characteristics of IQ A1924T to CS L was opposite in a [Ca2+]-dependent manner and its binding efficacy became smaller. The changes of the binding characteristics of IQ mutants to CS L would affect the regulation of Na V 1.5 channel, which may be related to LQT3 and BRS. • CS L could bind to Na V 1.5 channel IQ motif in a [CS L ]-dependent and [Ca2+]-dependent manner. • The binding sites of CS L to IQ motif were within the region of CS L that reprime the activity of Ca V 1.2 channel, L54-64. • LQTs-associated mutants, IQ Q1909R and IQ R1913H weakened the binding activity to CS L and the reaction rates were slower. • The binding characteristics of BRS-associated mutant, IQ A1924T , to CS L was reversed in the [Ca2+]-dependent manner. [ABSTRACT FROM AUTHOR]

Although diaphragmatic dysfunction is an important indicator of severity of illness and poor prognosis in ICU patients, there is no convenient and practical method to monitor diaphragmatic function. This study was designed to analyze diaphragmatic dynamic dysfunction by bedside ultrasound in septic patients and provide quantitative evidence to assess diaphragm function systematically. This prospective observational study was conducted from October 2019 to January 2021 in the Department of Respiratory and Critical Care Medicine. 74 patients suffered from sepsis were recruited and divided into two groups, sepsis group 1 (2 ≤ SOFA ≤ 5, n = 41) and sepsis group 2 (SOFA > 5, n = 33). 107 healthy volunteers were randomly recruited as the control group. In all participants, the diaphragmatic thickness and excursion were measured directly and the dynamic parameters including thickening fraction (TF), EQB/EDB, Contractile velocity, and area under diaphragmatic movement curve (AUDMC) were calculated by bedside ultrasound during quiet breathing (QB) and deep breathing (DB). Each parameter among three groups was analyzed separately by covariance analysis, which was adjusted by age, sex, body mass index, MAP, hypertension, and diabetes. First, contractile dysfunction occurred before diaphragmatic atrophy both in sepsis group 1 and sepsis group 2. Second, compared with the control group, the dynamic parameters showed significant decrease in sepsis group 1 and more obvious change in sepsis group 2, including TF, EQB/EDB. Third, the maximum contractile velocity decreased in sepsis group 1, reflecting the damage of intrinsic contraction efficiency accurately. Finally, per breathing AUDMC in two septic groups were lower than those in control group. However, per minute AUDMC was compensated by increasing respiratory rate in sepsis group 1, whereas it failed to be compensated which indicated gradual failure of diaphragm in sepsis group 2. Diaphragmatic ultrasound can be used to quantitatively evaluate the severity of sepsis patients whose contractile dysfunction occurred before diaphragmatic atrophy. As dynamic parameters, TF and EQB/EDB are early indicator associated with diaphragmatic injury. Furthermore, maximum contractile velocity can reflect intrinsic contraction efficiency accurately. AUDMC can evaluate diaphragmatic breathing effort and endurance to overcome resistance loads effectively. [ABSTRACT FROM AUTHOR]

Ischemic heart disease (IHD) is a condition where the heart muscle does not receive enough blood flow, leading to cardiac dysfunction. Restoring blood flow to the coronary artery is an effective clinical therapy for myocardial ischemia. This strategy helps lower the size of the myocardial infarction and improves the prognosis of patients. Nevertheless, if the disrupted blood flow to the heart muscle is restored within a specific timeframe, it leads to more severe harm to the previously deprived heart tissue. This condition is referred to as myocardial ischemia/reperfusion injury (MIRI). Until now, there is a dearth of efficacious strategies to prevent and manage MIRI. Hormones are specialized substances that are produced directly into the circulation by endocrine organs or tissues in humans and animals, and they have particular effects on the body. Hormonal medications utilize human or animal hormones as their active components, encompassing sex hormones, adrenaline medications, thyroid hormone medications, and others. While several studies have examined the preventive properties of different endocrine hormones, such as estrogen and hormone analogs, on myocardial injury caused by ischemia-reperfusion, there are other hormone analogs whose mechanisms of action remain unexplained and whose safety cannot be assured. The current study is on hormones and hormone medications, elucidating the mechanism of hormone pharmaceuticals and emphasizing the cardioprotective effects of different endocrine hormones. It aims to provide guidance for the therapeutic use of drugs and offer direction for the examination of MIRI in clinical therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Exopolysaccharides (EPSs) from halophilic Tetragenococcus halophilus were purified. • The structures and characteristics of EPSs were comprehensively elucidated. • EPSs might be explored as natural antioxidant agents. • EPSs had protective roles on other microbial cells. In this study, exopolysaccharides produced by Tetragenococcus halophilus were extracted and purified. Two fractions named EPS-1 and EPS-2 were obtained with average molecular weights of 2613.4 and 93.4 kDa, respectively. Analysis of the structures demonstrated that EPS-1 was mainly composed of galactose, glucose, mannose and glucuronic acid, and EPS-2 mostly consisted of glucose and mannose. 800 MHz nuclear magnetic resonance spectroscopy elucidated different and partial primary structures of EPS-1 and EPS-2. The microtopography was observed by atomic force microscope and scanning electron microscope. In addition, the two fractions exhibited antioxidant activities on DPPH, hydroxyl and ABTS•+ radicals. Furthermore, EPS-1 and EPS-2 could protect Lactococcus lactis against cryogenic and lyophilized stress. These results indicated that exopolysaccharides from T. halophilus in this study would have great potential in the application of food and pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Myocardial hypertrophy is a pathological feature of many heart diseases. This is a complex process involving all types of cells in the heart and interactions with circulating cells. This study is aimed at identifying the differentially expressed proteins (DEPs) in myocardial hypertrophy rats induced by isoprenaline (ISO) and treated with novel peptide Athycaltide-1 (ATH-1) and exploring the mechanism of its improvement. ITRAQ was performed to compare the three different heart states in control group, ISO group, and ATH-1 group. Pairwise comparison showed that there were 121 DEPs in ISO/control (96 upregulated and 25 downregulated), 47 DEPs in ATH-1/ISO (27 upregulated and 20 downregulated), and 116 DEPs in ATH-1/control (77 upregulated and 39 downregulated). Protein network analysis was then performed using the STRING software. Functional analysis revealed that Hspa1 protein, oxidative stress, and MAPK signaling pathway were significantly involved in the occurrence and development of myocardial hypertrophy, which was further validated by vivo model. It is proved that ATH-1 can reduce the expression of Hspa1 protein and the level of oxidative stress in hypertrophic myocardium and further inhibit the phosphorylation of p38 MAPK, JNK, and ERK1/2. [ABSTRACT FROM AUTHOR]

It is unclear why orexin-deficient animals, but not wild-type mice, show cataplexy. The current hypothesis predicts simultaneous excitation of cataplexy-inhibiting orexin neurons and cataplexy-inducing amygdala neurons. To test this hypothesis, we measured the activity of putative orexin neurons in orexin-knockout mice during cataplexy episodes using fiber photometry. We created two animal models of orexin-knockout mice with a GCaMP6 fluorescent indicator expressed in putative orexin neurons. We first prepared orexin-knockout mice crossed with transgenic mice carrying a tetracycline-controlled transactivator transgene under the control of the orexin promoter. TetO-GCaMP6 was then introduced into mice via an adeno-associated virus injection or natural crossing. The resulting two models showed restricted expression of GCaMP6 in the hypothalamus, where orexin neurons should be located, and showed excitation to an intruder stress that was similar to that observed in orexin-intact mice in our previous study. The activity of these putative orexin neurons increased immediately before the onset of cataplexy-like behavior but decreased (approximately − 20% of the baseline) during the cataplexy-like episode. We propose that the activity of orexin neurons during cataplexy is moderately inhibited by an unknown mechanism. The absence of cataplexy in wild-type mice may be explained by basal or residual activity-induced orexin release, and emotional stimulus-induced counter activation of orexin neurons may not be necessary. This study will serve as a basis for better treatment of cataplexy in narcolepsy patients. [ABSTRACT FROM AUTHOR]

Considering the increasingly strict motion precision requirements and repetitive task characteristics of magnetic levitation systems (MLSs) in the sophisticated industry, this article proposes a novel learning adaptive sliding mode control (LASMC) strategy for the MLS to achieve an excellent tracking performance. The LASMC scheme is obtained by combining adaptive sliding mode control (ASMC) and iterative learning control (ILC) terms in a parallel structure. ASMC can guarantee system stability and strong robustness, which employs an adaptive switching gain and parameter adaption algorithm. Even if the accurate disturbance bounds of MLS are not known, the ASMC item can also adjust the switching control gain online to ensure the stability and robustness of the system. Additionally, the ILC term can further improve the MLS performance for repetitive motion tasks without the accurate dynamics model. The asymptotic stability of the LASMC strategy is verified based on the Lyapunov theorem in the presence of unmodeled dynamics, disturbances, and saturation. Comparative experiments carried out on a maglev rotary table demonstrate that the proposed control strategy achieves excellent tracking accuracy and disturbance robustness in the practical MLS. The LASMC scheme provides a decent idea for the application of intelligent control technology in the controller design of MLSs. [ABSTRACT FROM AUTHOR]

In this work, Rosa roxburghii Tratt fruit polysaccharides (RPs) were extracted by ultrasound-assisted enzymatic method. The highest extraction yield of RPs was 4.78 ± 0.10 % under the optimal extraction conditions. Two purified fractions named RP1 and RP3 were obtained and systematically characterized by a combination strategy of FT-IR, monosaccharide composition, molecular weight distribution, methylation and 2D NMR spectroscopy analyses. Structural analysis showed that the main chain of RP1 was composed of rhamnogalacturonan type I (RG-I), while the side chains were rich in arabinogalactan and galactose. RP3 was composed of long homogalacturonan (HG) backbone interspersed with alternating sequences of RG-I domains, with galactose and arabinose side chains. RP1 and RP3 induced apoptosis of MCF-7 cells in a dose dependent manner in vitro especially for RP1, and had no effect on L929 cells. Furthermore, the possible anticancer mechanisms were revealed, and results suggested that RP1 induced apoptosis through ROS-dependent pathway and mitochondrial pathway. The results of this work not only provided an efficient extraction method and theoretical basis for the application of RPs, but also may contribute to develop novel functional foods or pharmaceutical products for the prevention and treatment of human breast cancer disease. [Display omitted] • The high yield of RPs was obtained by enzyme-assisted ultrasonic extraction. • The structures and morphologies of RP1 and RP3 were comprehensively elaborated. • RP1 and RP3 exhibited cytotoxicity against MCF-7 cells. • RP1 inhibited MCF-7 cells proliferation by inducing apoptosis in vitro. [ABSTRACT FROM AUTHOR]

Studies have confirmed that the intake of nonylphenol (NP) can increase nasal symptoms, eosinophils, and Th2 responses in allergic rhinitis (AR) mice. However, the molecular mechanism of NP exacerbating AR inflammatory response remains unclear. Recent data suggest that NOD-like receptor 3 (NLRP3) inflammasome-mediated pyroptosis contributes to AR development. To investigate the effects of NP on NLRP3 inflammasomes and pyroptosis, an AR mouse model induced by ovalbumin (OVA) was established and treated with 0.5 mg/kg/d NP every other day. Nasal symptoms were evaluated after the final OVA instillation. Mast cells and Eosinophils in the nasal mucosa were observed using toluidine blue and Sirius red staining, respectively. The levels of NLRP3, Caspase-1, ASC, phospho–nuclear factor kappa B (NF-κB) p65, interleukin (IL)-6, TNF-α, IL-18, GSDMD and IL-1β, were assessed by using immunohistochemical staining, ELISA, quantitative real-time PCR, or Western blot. Exposure to NP aggravates AR symptoms and promotes eosinophils, mast cells, and inflammatory factors release, along with significantly increased of NF–κB, NLRP3, Caspase-1, ASC, and GSDMD. It was concluded that NP exposure promotes NLRP3 inflammasome and GSDMD-mediated pyroptosis of the nasal mucosa. Targeted of NLRP3 and GSDMD-mediated pyroptosis may be a novel therapeutic strategy for AR exposed to NP. [ABSTRACT FROM AUTHOR]

Abstract: Water-soluble and luminescent ZnO quantum dots (QDs) capped by (3-aminopropyl) triethoxysilane (APTES) are environment-friendly with strong photoluminescence (max. wavelength: 530nm). Interestingly, it was found that the fluorescence could be quenched by dopamine (DA) directly. On the basis of above, a novel ZnO QDs based fluorescent probe has been successfully designed to detect DA with high selectivity and sensitivity. Moreover, the possible fluorescence quenching mechanism was proposed, which showed that the quenching effect may be caused by the electron transfer from ZnO QDs to oxidized dopamine–quinone. Under optimum conditions, the relative fluorescence intensity was linearly proportional to the concentration of DA within the range from 0.05 to 10μM, with the detection limit down to 12nM (n=3). Also, the selectivity experiment indicated the probe had a high selectivity for DA over a number of possible interfering species. Finally, this method was successfully used to detect DA in serum samples with quantitative recoveries (99–110%). With excellent selectivity and high sensitivity, it is believed that the ZnO QDs based fluorescent probe has a potential for the practical application in clinical analysis. [Copyright &y& Elsevier]

Acute lung injury (ALI) is a progressive inflammatory injury, and mesenchymal stem cells (MSCs) can be used to treat ALI. MSC-conditioned medium (MSC-CM) contains many cytokines, in which keratinocyte growth factor (KGF) is a soluble factor that plays a role in lung development. We aim to explore the protective effects of MSCs secreted KGF on ALI, and investigate the involvement of epithelial sodium channel (ENaC), which are important in alveolar fluid reabsorption. Both lipopolysaccharides (LPS)-induced mouse and alveolar organoid ALI models were established to confirm the potential therapeutic effect of MSCs secreted KGF. Meanwhile, the expression and regulation of ENaC were determined in alveolar type II epithelial (ATII) cells. The results demonstrated that MSC-CM and KGF could alleviate the extent of inflammation-related pulmonary edema in ALI mice, which was abrogated by a KGF neutralizing antibody. In an alveolar organoid ALI model, KGF in MSC-CM could improve the proliferation and decrease the differentiation of ATII cells. At the cellular level, the LPS-inhibited protein expression of ENaC could be reversed by KGF in MSC-CM. In addition, bioinformatics analysis and our experimental data provided the evidence that the NF-κB signaling pathway may be involved in the regulation of ENaC. Our research confirmed that the therapeutic effect of MSC-CM on edematous ALI was closely related to KGF, which may be involved in the proliferation and differentiation of ATII cells, as well as the upregulation of ENaC expression by the inhibition of NF-κB signaling pathway. [Display omitted] • MSC-CM and KGF had therapeutic effects on LPS-induced ALI model in mice. • KGF in MSC-CM could recover LPS-induced 3D alveolar organoid damage. • NF-κB signaling pathway may participate in the therapeutic effect of KGF in MSC-CM on ALI and the regulation of ENaC. [ABSTRACT FROM AUTHOR]

[Display omitted] • Hyperthermophilic composting (HC) accelerates the humification process. • Metabolic pathways of organic matter degradation are more abundant in HC. • Thermophilic bacteria and high temperature accelerate organic matter degradation. • The accelerated degradation of organic matter enhances the humification reaction. Hyperthermophilic composting (HC) has been widely recognized for the advantage of high treatment efficiency for organic wastes. However, the humification process is still unclear. In this study, the humification process of HC was investigated, compared to conventional composting (CK). The results showed that the highest composting temperature, organic matter degradation rate, and humification index in HC were 92.62 °C, 23.98%, and 1.59, while those in CK were 70.23 °C, 14.49 %, and 1.04, indicating HC accelerated humification process. Moreover, the results of metagenomic and untargeted metabolomic showed that the genes and metabolisms related to carbohydrate, lipid, amino acid, fatty acid, and nucleotide were more abundant in HC. Consequently, the metabolic pathways regarding organic matter degradation and microbial reproduction were enhanced in the high temperature stage of HC, further accelerating the humification reaction in the low temperature stage. This work contributes to the comprehension of the humification mechanism in HC. [ABSTRACT FROM AUTHOR]

Purpose: Bisphenol A (BPA) is found in many plastic products and is thus a common environmental endocrine disruptor. Plastic-related health problems, including allergic diseases, are attracting increasing attention. However, few experimental studies have explored the effect of BPA on allergic rhinitis (AR). We explore whether BPA was directly related to the allergic inflammation induced by ovalbumin (OVA) in AR mice.Methods: We first constructed OVA-induced mouse model, and after BPA administration, we evaluated nasal symptoms and measured the serum OVA-specific IgE levels by ELISA. Th2 and Treg-related cytokines of nasal mucosa were measured by cytometric bead array. Th2 and Treg-specific transcription factor levels were assayed by PCR. The proportions of CD3+CD4+IL-4+Th2 and CD4+Helios+Foxp3+ T cells (Tregs) in spleen tissue were determined by flow cytometry.Results: Compared to OVA-only-induced mice, BPA addition increased nasal symptoms and serum OVA-specific IgE levels. OVA and BPA coexposure significantly increased IL-4 and IL-13 protein levels compared to those after OVA exposure alone. BPA plus OVA tended to decrease the IL-10 protein levels compared to those after OVA alone. Coexposure to OVA and BPA significantly increased the GATA-3-encoding mRNA level, and decreased the levels of mRNAs encoding Foxp3 and Helios, compared to those after OVA exposure alone. BPA increased the Th2 cell proportion, and decreased that of Tregs, compared to the levels with OVA alone.Conclusion: BPA exerted negative effects by exacerbating AR allergic symptoms, increasing serum OVA-specific IgE levels, and compromising Th2 and Treg responses. [ABSTRACT FROM AUTHOR]

The pandemic SARS‐CoV‐2 has been reported in 123 countries with more than 5,000 patients died from it. However, the original and intermediate hosts of the virus remain unknown. In this study, 1,914 serum samples from 35 animal species were used for detection of SARS‐CoV‐2‐specific antibodies using double‐antigen sandwich ELISA after validating its specificity and sensitivity. The results showed that no SARS‐CoV‐2‐specific antibodies were detected in above samples which excluded the possibility of 35 animal species as intermediate host for SARS‐CoV‐2. More importantly, companion animals including pet dogs (including one dog the SARS‐CoV‐2 patient kept and two dogs which had close contact with it) and cats, street dogs and cats also showed serological negative to SARS‐CoV‐2, which relieved the public concerns for the pets as SARS‐CoV‐2 carriers. [ABSTRACT FROM AUTHOR]

Intracellular calcium is related to cardiac hypertrophy. The Ca V 1.2 channel and Ca2+/calmodulin-dependent protein kinase II (CaMKII) and CaM regulate the intracellular calcium content. However, the differences in CaMKII and CaM in cardiac hypertrophy are still conflicting and are worthy of studying as drug targets. Therefore, in this study, we aim to investigate the roles and mechanism of CaM and CaMKII on Ca V 1.2 in pathological myocardial hypertrophy. The results showed that ISO stimulation caused SD rat heart and cardiomyocyte hypertrophy. In vivo , the HW/BW, LVW/BW, cross-sectional area, fibrosis ratio and ANP expression were all increased. There were no differences in Ca V 1.2 channel expression in the in vivo model or the in vitro model, but the ISO stimulation induced channel activity, and the [Ca2+ i increased. The protein expression levels of CaMKII and p-CaMKII were all increased in the ISO group, but the CaM expression level decreased. AIP inhibited ANP, CaMKII and p-CaMKII expression, and ISO-induced [Ca2+ i increased. AIP also reduced HDAC4, p-HDAC and MEF2C expression. However, CMZ did not play a cardiac hypertrophy reversal role in vitro. In conclusion, we considered that compared with CaM, CaMKII may be a much more important drug target in cardiac hypertrophy reversal. • The expression of Ca V 1.2 did not change during cardiac hypertrophy. • In cardiac hypertrophy, the concentration of intracellular calcium increased. • In cardiac hypertrophy, the binding ability of CaMKII and Ca V 1.2 increased. • In cardiac hypertrophy, the binding ability of CaM and Ca V 1.2 decreased. • Compared with CaM, CaMKII may be a more important drug target in cardiac hypertrophy reversal. [ABSTRACT FROM AUTHOR]

Calmodulin (CaM) was reported to interact with PreIQ and IQ of Ca V 1.2 channels, but to date, no explicit binding sites of CaM were illustrated. Therefore, in the present study, we firstly used MOE (Molecular Operating Environment) for protein-protein docking and we found that the most likely residues of CaM that play an important role in the interface are concentrated in central linker region. Next we examined the binding properties of CaM and its mutants to PreIQ and IQ by GST pull-down assays. Here we confirmed that CaM binds to PreIQ and IQ in a concentration-dependent and [Ca2+-dependent manner. However, silencing the effect of N -lobe and C-lobe by mutating two Ca2+ binding sites of each lobe abolished [Ca2+-dependence of CaM binding, but could not influence the combination. And the mutant in central linker reduced the binding of CaM/PreIQ and CaM/IQ especially at low [Ca2+. We confirmed that N -lobe and C-lobe play vital role in sensing the change of Ca2+, and found that the central linker of CaM is involved in the binding of CaM to Ca V 1.2 channels in particular at low [Ca2+, not only participates in the combination with PreIQ, but also with IQ. • The most likely residues of CaM predicted by MOE are concentrated in central linker while docking against PreIQ and IQ. • CaM binding to PreIQ and IQ in a concentration-dependent and [Ca2+-dependent manner. • Mutant of EF-hands abolished [Ca2+-dependence of CaM binding but could not influence the combination with PreIQ and IQ. • Mutant of central linker significantly reduced the binding of CaM/PreIQ and CaM/IQ at low [Ca2+. [ABSTRACT FROM AUTHOR]

Glucosyltransferases (Gtfs), represented by GtfB and GtfC, are important virulence factors of Streptococcus mutans and the major etiologic pathogens of tooth decay. However, the individual roles of gtfB and gtfC in the initial attachment of S. mutans are not known. We used atomic force microscopy to explore the contribution of gtfB and gtfC, as well as enamel-surface roughness, on the initial attachment of S. mutans. Adhesion forces of four S. mutans strains (wild-type, ΔgtfB, ΔgtfC, and ΔgtfBC), onto etched enamel surfaces, were determined. Force curves showed that, with increasing etching time from 0 to 10 s, the forces of all strains increased accordingly with acid-exposure time, the adhesion forces of wild-type strains were significantly greater than those of mutant strains (p < .05), and the forces of the three mutants were similar (p < .05). When the etching time was increased from 10 to 30 s, difference in force between 20 and 30 s was not observed, and adhesion forces among ΔgtfB, ΔgtfC, and wild-type strains were not significantly different when the etching time was >20 s (p > .05). These data suggest that the roughness and morphology of enamel surfaces may have a significant influence upon the initial attachment of bacteria, and that gtfB and gtfC are essential for the adhesion activity of bacteria. Furthermore, gtfB seems to be more important than gtfC for bacterial-biofilm formation, and gtfB inactivation is an effective strategy to inhibit the virulence of cariogenic biofilms. [ABSTRACT FROM AUTHOR]

Happiness is key for both mental and physical well-being. To further understand the brain mechanisms involved, we utilized the cataplexy that occurs in narcoleptic animal models as a quantitative behavioral measure because it is triggered by actions associated with happiness, such as laughter in humans and palatable foods in mice. Here we report that the rostral part of the nucleus accumbens (NAc) shell is strongly activated during the beginning of chocolate-induced cataplexy in orexin neuron-ablated mice. We made a local lesion in the NAc using ibotenic acid and observed the animals' behavior. The number of cataplexy bouts was negatively correlated to the lesion size. We also examined the hedonic response to palatable food by measuring the number of tongue protrusions in response to presentation of honey, which was also found to be negatively correlated to the lesion size. Next, we used clozapine N-oxide to either activate or inactivate the NAc through viral DREADD expression. As expected, the number of cataplexy bouts increased with activation and decreased with inactivation, and saline control injections showed no changes. Hedonic response in the DREADD experiment varied and showed both increases and decreases across mice. These results demonstrated that the rostral part of the NAc plays a crucial role in triggering cataplexy and hedonic orofacial movements. Since the NAc is also implicated in motivated behavior, we propose that the NAc is one of the key brain structures involved in happiness and is a driving force for positive emotion-related behaviors. [ABSTRACT FROM AUTHOR]

Eighteen canine distemper virus (CDV) isolates were obtained from clinical samples in Henan province, China, between 2012 and 2016. These viruses could not be recognized by 1A4, a monoclonal antibody specific for the H protein of CDV vaccine strains. The complete haemagglutinin (H) genes of all 18 isolates were sequenced, and phylogenetic analysis showed that they segregated into two clusters within the Asia-1 genotype. Moreover, the H genes of four viruses were found to lack a potential N-glycosylation site at position 309, which is the most conserved site within the Asia-1 genotype of CDV, and a novel potential N-glycosylation site (amino acids 517–519) was found in strain HL013, which has not been reported previously. These results will help in achieving a better understanding of the evolution of CDV in China. [ABSTRACT FROM AUTHOR]

Pathological myocardial hypertrophy initially develops as an adaptive response to cardiac stress, which can be induced by many diseases. It is accompanied by adverse cardiovascular events, including heart failure, arrhythmias, and death. The purpose of this research was to explore the molecular mechanism of a novel peptide Athycaltide-1 (ATH-1) in the treatment of Ang II-induced pathological myocardial hypertrophy. In this study, the mRNA of Control group, Ang II group, ATH-1 group and Losartan group mice were sequenced by high-throughput sequencing technology. The results showed that the differentially expressed genes (DEGs) were significantly enriched in cell response to oxidative stress, regulation of reactive oxygen species metabolism and calmodulin binding. Then, the oxidation level of mouse hearts and H9c2 cardiomyocytes in each group and the expression of key proteins of CaMKII/HDAC/MEF2C and ERK1/2 signaling pathways were detected to preliminarily verify the positive effect of ATH-1. At the same time, the effect of ATH-1 was further determined by adding reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC) and CaMKII inhibitor AIP in vitro. The results showed that ATH-1 could significantly reduce the level of oxidative stress in hypertrophic cardiomyocytes and inhibiting the activation of CaMKII and ERK1/2. [ABSTRACT FROM AUTHOR]

Zygosaccharomyces rouxii has excellent fermentation performance and good tolerance to osmotic stress. Acetyl-CoA is a crucial intermediate precursor in the central carbon metabolic pathway of yeast. This study investigated the effect of engineering acetyl-CoA metabolism on the membrane functionality and stress tolerance of yeast. Firstly, exogenous supplementation of acetyl-CoA improved the biomass and the ability of unsaturated fatty acid synthesis of Z. rouxii under salt stress. Q-PCR results suggested that the gene ACSS (coding acetyl-CoA synthetase) was significantly up-expressed. Subsequently, the gene ACSS from Z. rouxii was transformed and heterologously expressed in S. cerevisiae. The recombinant cells exhibited better multiple stress (salt, acid, heat, and cold) tolerance, higher fatty acid contents, membrane integrity, and fluidity. Our findings may provide a suitable means to enhance the stress tolerance and fermentation efficiency of yeast under harsh fermentation environments. [Display omitted] • Exogenous acetyl-CoA improved the biomass of Z. rouxii under salt stress. • The gene ACSS was significantly up-expressed with the addition of acetyl-CoA. • The recombinant S. cerevisiae had better multiple stress tolerance. • The recombinant S. cerevisiae exhibited greater membrane functionality. [ABSTRACT FROM AUTHOR]

[Display omitted] • Electric heating increases composting temperature and promotes composting process. • The reproduction of thermophilic bacteria is enhanced by electric heating. • The least squares model is more accurate in predicting energy consumption ratio. • The energy consumption ratio is mainly affected by heating in the early stages. Composting with electric heating has attracted extensive attention for the advantage of high treatment efficiency for sludge. However, there are challenges in investigating how electric heating affects the composting process and how to reduce its energy consumption. This study investigated the effects of different electric heating methods on composting. The highest temperature, water content reduction, organic matter reduction, and weight reduction rate in group B6 (heating in the first and second stages) were 76.00° C, 16.76 %, 4.90 %, and 35.45 %, respectively, indicating that electric heating promoted water evaporation and organic matter degradation. In conclusion, electric heating promoted the sludge composting process and the heating method of group B6 was optimal for composting characteristics. This work contributes to the understanding of the mechanism of electric heating promoting composting process and providing theoretical support for the engineering application of composting with electric heating. [ABSTRACT FROM AUTHOR]

• The effects of BPA on ischemia/reperfusion (I/R) injured hearts were investigated. • BPA did not significantly affect coronary flow, and LDH or CK release in I/R hearts. • BPA inhibited the cardio-protective effects of 17β-oestradiol on LDH or CK release. Bisphenol A (BPA) is an environmental oestrogen or xenoestrogen (XEs). XEs represent a health risk due to their potential for endocrine disruption and ability to mimic estrogenic activity. The effects of BPA on isolated hearts under normal and ischemia/reperfusion (I/R) conditions were investigated for the first time, with a focus on the effects of BPA and 17β-oestradiol (E 2) co-administration on I/R injury. Our results indicated that BPA at 10−7 M and 10−5 M did not significantly affect heart rate (HR), coronary flow (CF), lactate dehydrogenase (LDH) or creatine kinase (CK) release in normal or I/R isolated hearts within the 90 min. However, E 2 exerted a protective effect against I/R injury, whereas, BPA inhibited the cardio-protective effects of E 2 on HR, CF, and LDH and CK release. Furthermore, BPA in combination with E 2 aggravated I/R injury by increasing infarct size and causing a more severe ultrastructural disruption as compared to treatment with E 2 alone. Based on our results, we conclude that BPA inhibits the cardio-protective effects of E 2 on I/R-injured hearts, despite not significantly affecting normal or I/R isolated hearts. [ABSTRACT FROM AUTHOR]

Pseudorabies virus (PRV) belongs to the Herpesviridae family, and is an important veterinary pathogen. Highly pathogenic PRV variants have caused severe epidemics in China since 2011, causing huge economic losses. To tackle the epidemics, we identified a panel of mouse monoclonal antibodies (mAbs) against PRV glycoprotein B (gB) that effectively block PRV infection. Among these 15 mAbs, fourteen of them block PRV entry in a complement-dependent manner. The remaining one, 1H1 mAb, however can directly neutralize the virus independent of complement and displays broad-spectrum neutralizing activities. We further determined the crystal structure of PRV gB and mapped the epitopes of these antibodies on the structure. Interestingly, all the complement-dependent neutralizing antibodies bind gB at the crown region (domain IV). In contrast, the epitope of 1H1 mAb is located at the bottom of domain I, which includes the fusion loops, indicating 1H1 mAb might neutralize the virus by interfering with the membrane fusion process. Our studies demonstrate that gB contains multiple B-cell epitopes in its crown and base regions and that antibodies targeting different epitopes block virus infection through different mechanisms. These findings would provide important clues for antiviral drug design and vaccine development. [ABSTRACT FROM AUTHOR]

Female BALB/c mice were immunized with a commercial PCV2 vaccine, and a monoclonal antibody (MAb) designated as 3H11 was achieved by hybridoma techniques. The MAb specifically reacted with Cap protein of PCV2, which has been identified by western blot. Immunoperoxidase monolayer assay results showed that 3H11 did not cross-react with PCV1-infected cells. Therefore, this work suggested that 3H11 could be a useful tool as a specific diagnostic reagent for PCV2 research. [ABSTRACT FROM AUTHOR]

Nonylphenol (NP) is one of the widely spread xenoestrogens (XEs) and is used in the production of industrial and consumer surfactants. In the present study, we examined the acute effects of NP on myocardial contractility to determine its rapid-response cardiac effects in the isolated heart. We also investigated the mechanism of action of NP by determining its effects on the L-type Ca 2+ channel (LTCC) currents ( I Ca-L ) in ventricular myocytes. Lower concentrations (10 −12 –10 −10 M) of NP increased cardiac contractility while higher concentrations (10 −8 –10 −6 M) exhibited opposite effects. These apparently opposing effects suggest that NP has biphasic concentration-dependent rapid effects on cardiac contractility. These non-monotonic changes in contractility correlated with the effects of NP on I Ca-L , indicating that ion channels, as rapidly responding membrane proteins, play a very important role in mediating the rapid-response effects of XEs. Further studies revealed that the G protein coupled receptor 30 (GPR30) mediates the effects of NP on LTCC at lower but not higher concentrations, implying that the differential involvement of GPR30 might be responsible for the non-monotonic effects of NP. [ABSTRACT FROM AUTHOR]

Astragaloside IV (AS-IV) is one of the main active ingredients of Astragalus membranaceus. This study is aimed to investigate AS-IV׳s effects on Ca 2+ channel activity of single cardiomyocytes and single Ca 2+ channels. Whole-cell Ca 2+ currents in freshly dissociated cardiomyocytes were measured using the whole-cell patch-clamp technique. Single Ca 2+ channel currents were examined in cell-attached patches and inside-out patches. In the whole-cell recording, AS-IV reduced the amplitude of l -type Ca 2+ currents ( I CaL ) in a concentration-dependent manner. Although AS-IV did not alter the steady-state activation curves, the voltage dependence of the current inactivation curves was negatively shifted by AS-IV in a concentration dependent manner. Consistent with the results of the whole-cell recording, in the inside-out configuration the ensemble average of single Ba 2+ current via l -type Ca 2+ channel was dose-dependently reduced by AS-IV. The reduction of unitary Ba 2+ current at 0.1 or 1 µM AS-IV was accounted for a decrease in the channel activity ( NPo ). In addition to the decrease in NPo , there was a reduction of Po without a change in channel number or an apparent change in single channel current. Furthermore, we found that the open-closed kinetics of the channel were affected by AS-IV. AS-IV induced the shift of l -type Ca 2+ channels from either brief openings (mode 1) or long-lasting openings (mode 2) to no active opening (mode 0). Our results suggest that AS-IV blocks the currents through Ca 2+ channels in guinea-pig ventricular myocytes by affecting the open-closed kinetics of l -type Ca 2+ channels to inhibit the channel activities. This study could provide theoretical basis for the drug exploiting of the monomer of Astragalus membranaceus . [ABSTRACT FROM AUTHOR]

Heart failure is a major global health concern. Noncoding RNAs (ncRNAs) are involved in physiological processes and in the pathogenesis of various diseases, including heart failure. ncRNAs have emerged as critical components of transcriptional regulatory pathways that govern cardiac development, stress response, signaling, and remodeling in cardiac pathology. Recently, studies of ncRNAs in cardiovascular disease have achieved significant development. Here, we discuss the roles of ncRNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) that modulate the cardiac hypertrophy and heart failure. [ABSTRACT FROM AUTHOR]

The present study examined the binding of the individual N- and C-lobes of calmodulin (CaM) to Cav1.2 at different Ca 2+ concentration ([Ca 2+ ]) from ≈ free to 2 mM, and found that they may bind to Cav1.2 Ca 2+ -dependently. In particular, using the patch-clamp technique, we confirmed that the N- or C-lobes can rescue the basal activity of Cav1.2 from run-down, demonstrating the functional relevance of the individual lobes. The data imply that at resting [Ca 2+ ], CaM may tether to the channel with its single lobe, leading to multiple CaM molecule binding to increase the grade of Ca 2+ -dependent regulation of Cav1.2. [ABSTRACT FROM AUTHOR]