Glycolysis-Mediated Activation of v-ATPase by Nicotinamide Mononucleotide Ameliorates Lipid-Induced Cardiomyopathy by Repressing the CD36-TLR4 Axis.

BACKGROUND: Chronic overconsumption of lipids followed by their excessive accumulation in the heart leads to cardiomyopathy. The cause of lipid-induced cardiomyopathy involves a pivotal role for the proton-pump vacuolar-type H+-ATPase (v-ATPase), which acidifies endosomes, and for lipid-transporter CD36, which is stored in acidified endosomes. During lipid overexposure, an increased influx of lipids into cardiomyocytes is sensed by v-ATPase, which then disassembles, causing endosomal de-acidification and expulsion of stored CD36 from the endosomes toward the sarcolemma. Once at the sarcolemma, CD36 not only increases lipid uptake but also interacts with inflammatory receptor TLR4 (Toll-like receptor 4), together resulting in lipid-induced insulin resistance, inflammation, fibrosis, and cardiac dysfunction. Strategies inducing v-ATPase reassembly, that is, to achieve CD36 reinternalization, may correct these maladaptive alterations. For this, we used NAD+ (nicotinamide adenine dinucleotide)-precursor nicotinamide mononucleotide (NMN), inducing v-ATPase reassembly by stimulating glycolytic enzymes to bind to v-ATPase. METHODS: Rats/mice on cardiomyopathy-inducing high-fat diets were supplemented with NMN and for comparison with a cocktail of lysine/leucine/arginine (mTORC1 [mechanistic target of rapamycin complex 1]-mediated v-ATPase reassembly). We used the following methods: RNA sequencing, mRNA/protein expression analysis, immunofluorescence microscopy, (co)immunoprecipitation/proximity ligation assay (v-ATPase assembly), myocellular uptake of [3H]chloroquine (endosomal pH), and [14C]palmitate, targeted lipidomics, and echocardiography. To confirm the involvement of v-ATPase in the beneficial effects of both supplementations, mTORC1/v-ATPase inhibitors (rapamycin/bafilomycin A1) were administered. Additionally, 2 heart-specific v-ATPase-knockout mouse models (subunits V1G1/V0d2) were subjected to these measurements. Mechanisms were confirmed in pharmacologically/genetically manipulated cardiomyocyte models of lipid overload. RESULTS: NMN successfully preserved endosomal acidification during myocardial lipid overload by maintaining v-ATPase activity and subsequently prevented CD36-mediated lipid accumulation, CD36-TLR4 interaction toward inflammation, fibrosis, cardiac dysfunction, and whole-body insulin resistance. Lipidomics revealed C18:1-enriched diacylglycerols as lipid class prominently increased by high-fat diet and subsequently reversed/preserved by lysine/leucine/arginine/NMN treatment. Studies with mTORC1/v-ATPase inhibitors and heart-specific v-ATPase-knockout mice further confirmed the pivotal roles of v-ATPase in these beneficial actions. CONCLUSION: NMN preserves heart function during lipid overload by preventing v-ATPase disassembly.

Mycoplasma invasion into host cells: An integrated model of infection strategy.

Mycoplasma belong to the genus Mollicutes and are notable for their small genome sizes (500-1300 kb) and limited biosynthetic capabilities. They exhibit pathogenicity by invading various cell types to survive as intracellular pathogens. Adhesion is a crucial prerequisite for successful invasion and is orchestrated by the interplay between mycoplasma surface adhesins and specific receptors on the host cell membrane. Invasion relies heavily on clathrin- and caveolae-mediated internalization, accompanied by multiple activated kinases, cytoskeletal rearrangement, and a myriad of morphological alterations, such as membrane invagination, nuclear hypertrophy and aggregation, cytoplasmic edema, and vacuolization. Once mycoplasma successfully invade host cells, they establish resilient sanctuaries in vesicles, cytoplasm, perinuclear regions, and the nucleus, wherein specific environmental conditions favor long-term survival. Although lysosomal degradation and autophagy can eliminate most invading mycoplasmas, some viable bacteria can be released into the extracellular environment via exocytosis, a crucial factor in the prolonging infection persistence. This review explores the intricate mechanisms by which mycoplasma invades host cells and perpetuates their elusive survival, with the aim of highlighting the challenge of eradicating this enigmatic bacterium.

Treponema pallidum lipoprotein Tp0768 promotes the migration and adhesion of THP-1 cells to vascular endothelial cells through stress of the endoplasmic reticulum and the NF-κB/HIF-1α pathway.

Endothelial cell injury is a key factor in the spread of infection and pathogenicity of Treponema pallidum. The migration and adhesion reaction mediated by T. pallidum lipoprotein plays an important role. This study aimed to systematically explore the migration and adhesion effect of T. pallidum lipoprotein Tp0768 and its molecular mechanism. Stimulating vascular endothelial cells with Tp0768 increased the expression of ICAM-1, MCP-1, and IL-8. Moreover, it promoted the migration and adhesion of THP-1 cells to vascular endothelial cells. Our results revealed that Tp0768 promoted the THP-1 cells migrating and adhering to vascular endothelial cells by the PERK and IRE-1α pathways of endoplasmic reticulum (ER) stress. We further demonstrated that the inhibition of the NF-κB pathway and the downregulation of hypoxia-inducible factor 1 alpha (HIF-1α) reduced the mRNA levels of ICAM-1, MCP-1, and IL-8 induced by Tp0768. Also, the adhesion rate of THP-1 cells to endothelial cells decreased. After inhibiting ER stress, NF-κB p65 nuclear translocation was weakened, and the mRNA level of HIF-1α was also significantly downregulated. Our results indicated that T. pallidum lipoprotein Tp0768 promoted the migration and adhesion of THP-1 cells to vascular endothelial cells through ER stress and NF-κB/HIF-1α pathway.

Beyond Conventional Enhancements: Self-Organization of a Buffer Material on Tin Oxide as a Game-Changer for Improving the Performance of Inverted Organic Solar Cells.

Inverted organic solar cells (OSCs) have garnered significant interest due to their remarkable stability. In this study, the efficiency and stability of inverted OSCs are enhanced via the in situ self-organization (SO) of an interfacial modification material Phen-NaDPO onto tin oxide (SnO2). During the device fabrication, Phen-NaDPO is spin-coated with the active materials all together on SnO2. Driven by the interactions with SnO2 and the thermodynamic forces due to its high surface energy and the convection flow, Phen-NaDPO spontaneously migrates to the SnO2 interface, resulting in the formation of an in situ modification layer on SnO2. This self-organization of Phen-NaDPO not only effectively reduces the work function of SnO2, but also enhances the ordered molecular stacking and manipulates the vertical morphology of the active layer, which suppress the surface trap-assisted recombination and minimize the charge extraction. As a result, the SO devices based on PM6:Y6 exhibit significantly improved photovoltaic performance with an enhanced power conversion efficiency of 17.62%. Moreover, the stability of the SO device is also improved. Furthermore, the SO ternary devices based on PM6:D18:L8-BO achieved an impressive PCE of 18.87%, standing as one of the highest values for single-junction inverted organic solar cells to date.

Molecular mechanisms of aging and anti-aging strategies.

Aging is a complex and multifaceted process involving a variety of interrelated molecular mechanisms and cellular systems. Phenotypically, the biological aging process is accompanied by a gradual loss of cellular function and the systemic deterioration of multiple tissues, resulting in susceptibility to aging-related diseases. Emerging evidence suggests that aging is closely associated with telomere attrition, DNA damage, mitochondrial dysfunction, loss of nicotinamide adenine dinucleotide levels, impaired macro-autophagy, stem cell exhaustion, inflammation, loss of protein balance, deregulated nutrient sensing, altered intercellular communication, and dysbiosis. These age-related changes may be alleviated by intervention strategies, such as calorie restriction, improved sleep quality, enhanced physical activity, and targeted longevity genes. In this review, we summarise the key historical progress in the exploration of important causes of aging and anti-aging strategies in recent decades, which provides a basis for further understanding of the reversibility of aging phenotypes, the application prospect of synthetic biotechnology in anti-aging therapy is also prospected.

Computer-aided designing of a novel multi­epitope DNA vaccine against severe fever with thrombocytopenia syndrome virus.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (Dabie bandavirus), which has become a substantial risk to public health. No specific treatment is available now, that calls for an effective vaccine. Given this, we aimed to develop a multi-epitope DNA vaccine through the help of bioinformatics. The final DNA vaccine was inserted into a special plasmid vector pVAX1, consisting of CD8+ T cell epitopes, CD4+ T cell epitopes and B cell epitopes (six epitopes each) screened from four genome-encoded proteins--nuclear protein (NP), glycoprotein (GP), RNA-dependent RNA polymerase (RdRp), as well as nonstructural protein (NSs). To ascertain if the predicted structure would be stable and successful in preventing infection, an immunological simulation was run on it. In conclusion, we designed a multi-epitope DNA vaccine that is expected to be effective against Dabie bandavirus, but in vivo trials are needed to verify this claim.

Microbial creation of ß-Nicotinamide mononucleotide and its regulation of lipid metabolism in the liver of high-fat diet mice.

ß-Nicotinamide mononucleotide (NMN) is a biologically active nucleotide that regulates the physiological metabolism of the body by rapidly increasing nicotinamide adenine dinucleotide (NAD+). To determine the safety and biological activity of NMN resources, we constructed a recombinant strain of P. pastoris that heterologously expresses nicotinamide-phosphate ribosyltransferase (NAMPT), and subsequently catalyzed and purified the expressed product to obtain NMN. Consequently, this study established a high-fat diet (HFD) obese model to investigate the lipid-lowering activity of NMN. The findings showed that NMN supplementation directly increased the NAD+ levels, and reduced HFD-induced liver injury and lipid deposition. NMN treatment significantly decreased total cholesterol (TC) and triglyceride (TG) in serum and liver, as well as alanine aminotransferase (ALT) and insulin levels in serum (p < .05 or p < .01). In conclusion, this study combined synthetic biology with nutritional evaluation to confirm that P. pastoris-generated NMN modulated lipid metabolism in HFD mice, offering a theoretical framework and evidence for the application of microbially created NMN.

Study on the role of CCM3 gene and lead exposure induced neurotoxicity through neurovascular units.

This study aimed to determine the toxic effects of vascular CCM3 gene deficiency and lead (Pb) exposure on the nervous system. Lentiviral transfection was performed to generate a stable strain of brain microvascular endothelial cells with low CCM3 expression. MTT assay assessed the survival rate of cells exposed to Pb, determining the dose and duration of Pb exposure in vitro. Proteomic analysis was performed on the differentially expressed proteins in bEnd3 and HT22 cells and flow cytometry was used to detect cell apoptosis. Finally, urine samples from pregnant and postpartum women were subjected to ICP-MS to detect Pb levels and HPLC to detect neurotransmitter metabolites. Based on the proteomic analysis of bEnd3 (CCM3-/-) cells co-cultured with HT22 cells, it was determined that HT22 cells and CCM3 genes interfered with bEnd3 cell differential proteins,2 including apoptosis and ferroptosis pathways. Electron microscopy observation, ICP-MS iron ion loading detection, and WB determination of protein GPX4 expression confirmed that HT22 cells undergo apoptosis, while bEnd3 cells undergo multiple pathways of iron death and apoptosis regulation. Furthermore, a linear regression model showed the interaction between maternal urine Pb levels, the rs9818496 site of the CCM3 SNP in peripheral blood DNA, and the concentration of the neurotransmitter metabolite 5-HIAA in maternal urine (F=4.198, P < 0.05). bEnd3 cells with CCM3 gene deficiency can induce HT22 cell apoptosis through iron death and apoptosis pathways under Pb exposure in a combined cell culture Pb exposure model, and CCM3 gene deficiency in endothelial cells and Pb exposure interacts with neural cell HT22. Epidemiological studies on maternal and newborn infants further confirmed the interaction between urine Pb levels in mothers and the SNP rs9818496 site of the CCM3 gene in peripheral blood DNA.

Paeoniflorin loaded liposomes modified with glycyrrhetinic acid for liver-targeting: preparation, characterization, and pharmacokinetic study.

OBJECTIVE: To enhance the retention times and therapeutic efficacy of paeoniflorin (PF), a liver-targeted drug delivery system has been developed using glycyrrhetinic acid (GA) as a ligand. SIGNIFICANCE: The development and optimization of GA-modified PF liposomes (GPLs) have shown promising potential for targeted delivery to the liver, opening up new possibilities for liver disease treatment. METHODS: This study aimed to identify the best prescriptions using single-factor experiments and response surface methodology. The formulation morphology was determined using transmission electron microscopy. Tissue distribution was observed through in vivo imaging, and pharmacokinetic studies were conducted. RESULTS: The results indicated that GPLs, prepared using the thin film dispersion method and response surface optimization, exhibited well-dispersed and uniformly sized particles. The in vitro release rate of GPLs was slower compared to PF monomers, suggesting a sustained release effect. The liver-targeting ability of GA resulted in stronger fluorescence signals in the liver for targeted liposomes compared to non-targeted liposomes. Furthermore, pharmacokinetic studies demonstrated that GPLs significantly prolonged the residence time of PF in the bloodstream, thereby contributing to prolonged efficacy. CONCLUSION: These findings suggest that GPLs are more effective than PF monomers in terms of controlling drug release and delivering drugs to specific targets, highlighting the potential of PF as a liver-protective drug.

Construction and validation of a nomogram for predicting fear of falling related activity restrictions in community-dwelling older adults.

Fear of falling related activity restrictions are widespread among older adults, leading to several adverse effects. Given these consequences, there is an urgent need for a comprehensive assessment tool that integrates various risk factors to predict the likelihood of older adults experiencing such activity restrictions. This cross-sectional study investigated fear of falling related activity restrictions and its influencing factors, simultaneously constructed and validated a nomogram among older adults residing in the communities in China. The model includes variables like age, gender, self-rated health, past year injurious falls, gait stability, anxiety, and cognitive impairment. It showed an AUC of 0.892. Internal validation had an AUC of 0.893, and external validation had an AUC of 0.939. Calibration curve showed good fit, and decision curve showed high clinical benefits. It's an intuitive tool for medical professionals to identify older adults at high risk of activity restrictions due to fear of falling.

Revealing the Influence of Electron Migration Inside Polymer Electrolyte on Li+ Transport and Interphase Reconfiguration for Li Metal Batteries.

The development of highly producible and interfacial compatible in situ polymerized electrolytes for solid-state lithium metal batteries (SSLMBs) have been plagued by insufficient transport kinetics and uncontrollable dendrite propagation. Herein, we seek to explore a rationally designed nanofiber architecture to balance all the criteria of SSLMBs, in which La0.6Sr0.4CoO3-δ (LSC) enriched with high valence-state Co species and oxygen vacancies is developed as electronically conductive nanofillers embedded within ZnO/Zn3N2-functionalized polyimide (Zn-PI) nanofiber framework for the first time, to establish Li+ transport highways for poly vinylene carbonate (PVC) electrolyte and eliminate nonuniform Li deposits. Revealed by characterization and theoretical calculation under electric field, the positive-negative electrical dipole layer in LSC derived from electron migration between Co and O atoms aids in accelerating Li+ diffusion kinetics through densified electric field around filler particle, featuring a remarkable ionic conductivity of 1.50 mS cm-1 at 25 °C and a high Li+ transference number of 0.91 without the risk of electron leakage. Integrating with the preferential sacrifice of ZnO/Zn3N2 on PI nanofiber upon immediate detection of dendritic Li, which takes part in reconfiguring hierarchical SEI chemistry dominated by LixNy/Li-Zn alloy inner layer and LiF outer layer, SSLMBs are further endowed with prolonged cycling lifespan and exceptional rate capability.

In Situ Constructing Robust and Highly Conductive Solid Electrolyte with Tailored Interfacial Chemistry for Durable Li Metal Batteries.

Employing nanofiber framework for in situ polymerized solid-state lithium metal batteries (SSLMBs) is impeded by the insufficient Li+ transport properties and severe dendritic Li growth. Both critical issues originate from the shortage of Li+ conduction highways and nonuniform Li+ flux, as randomly-scattered nanofiber backbone is highly prone to slippage during battery assembly. Herein, a robust fabric of Li0.33 La0.56 Ce0.06 Ti0.94 O3-δ /polyacrylonitrile framework (p-LLCTO/PAN) with inbuilt Li+ transport channels and high interfacial Li+ flux is reported to manipulate the critical current density of SSLMBs. Upon the merits of defective LLCTO fillers, TFSI- confinement and linear alignment of Li+ conduction pathways are realized inside 1D p-LLCTO/PAN tunnels, enabling remarkable ionic conductivity of 1.21 mS cm-1 (26 °C) and tLi+ of 0.93 for in situ polymerized polyvinylene carbonate (PVC) electrolyte. Specifically, molecular reinforcement protocol on PAN framework further rearranges the Li+ highway distribution on Li metal and alters Li dendrite nucleation pattern, boosting a homogeneous Li deposition behavior with favorable SEI interface chemistry. Accordingly, excellent capacity retention of 76.7% over 1000 cycles at 2 C for Li||LiFePO4 battery and 76.2% over 500 cycles at 1 C for Li||LiNi0.5 Co0.2 Mn0.3 O2 battery are delivered by p-LLCTO/PAN/PVC electrolyte, presenting feasible route in overcoming the bottleneck of dendrite penetration in in situ polymerized SSLMBs.

HBV covalently closed circular DNA minichromosomes in distinct epigenetic transcriptional states differ in their vulnerability to damage.

BACKGROUND AND AIMS: HBV covalently closed circular DNA (cccDNA) is a major obstacle for a cure of chronic hepatitis B. Accumulating evidence suggests that epigenetic modifications regulate the transcriptional activity of cccDNA minichromosomes. However, it remains unclear how the epigenetic state of cccDNA affects its stability. APPROACHES AND RESULTS: By using HBV infection cell models and in vitro and in vivo recombinant cccDNA (rcccDNA) and HBVcircle models, the reduction rate of HBV cccDNA and the efficacy of apolipoprotein B mRNA editing enzyme catalytic subunit 3A (APOBEC3A)-mediated and CRISPR/CRISPR-associated 9 (Cas9)-mediated cccDNA targeting were compared between cccDNAs with distinct transcriptional activities. Interferon-α treatment and hepatitis B x protein (HBx) deletion were applied as two strategies for cccDNA repression. Chromatin immunoprecipitation and micrococcal nuclease assays were performed to determine the epigenetic pattern of cccDNA. HBV cccDNA levels remained stable in nondividing hepatocytes; however, they were significantly reduced during cell division, and the reduction rate was similar between cccDNAs in transcriptionally active and transcriptionally repressed states. Strikingly, HBV rcccDNA without HBx expression exhibited a significantly longer persistence in mice. The cccDNA with low transcriptional activity exhibited an epigenetically inactive pattern and was more difficult to access by APOBEC3A and engineered CRISPR-Cas9. The epigenetic regulator activating cccDNA increased its vulnerability to APOBEC3A. CONCLUSIONS: HBV cccDNA minichromosomes in distinct epigenetic transcriptional states showed a similar reduction rate during cell division but significantly differed in their accessibility and vulnerability to targeted nucleases and antiviral agents. Epigenetic sensitization of cccDNA makes it more susceptible to damage and may potentially contribute to an HBV cure.

Investigation of the immune escape mechanism of Treponema pallidum.

BACKGROUND: Syphilis is a chronic sexually transmitted disease caused by Treponema pallidum subspecies pallidum (T. pallidum), which is a public health problem that seriously affects human health worldwide. T. pallidum is characterized by early transmission and immune escape and is therefore termed an "invisible pathogen". METHODS: This review systematically summarizes the host's innate and adaptive immune responses to T. pallidum infection as well as the escape mechanisms of T. pallidum. PURPOSE: To lay the foundation for assessing the pathogenic mechanism and the systematic prevention and treatment of syphilis. CONCLUSION: The immune escape mechanism of T. pallidum plays an important role in its survival. Exploring the occurrence and development of these mechanisms has laid the foundation for the development of syphilis vaccine.

TLR2 mediates autophagy through ERK signaling pathway in Chlamydia psittaci CPSIT_p7 protein-stimulated RAW264.7 cells.

Chlamydia psittaci is a zoonotic pathogen found in birds and humans. Macrophages, major components of the innate immune system, can resist chlamydial infections and trigger adaptive immune responses. However, the molecular mechanisms underlying the action of macrophages against C. psittaci infection are not well understood. This study investigated the roles and mechanisms of plasmid-encoded protein CPSIT_p7 of C. psittaci in regulating autophagy in RAW264.7 cells. The results demonstrated that stimulation of RAW264.7 with C. psittaci plasmid protein CPSIT_p7 induced the expressions of the autophagy signaling primary regulators LC3 and Beclin1, which could also significantly induce the phosphorylation levels of ERK, JNK, p38, and Akt. Next, siRNA knockdown of TLR2 resulted in significant downregulation of CPSIT_p7-triggered autophagy in RAW264.7 cells. Moreover, the extracellular regulated protein kinase (ERK) inhibitor PD98059 markedly reduced autophagy in CPSIT_p7-stimulated macrophages. In summary, these results indicated that TLR2 plays an essential role in the induction of autophagy through the ERK signaling pathway in CPSIT_p7-stimulated RAW264.7 cells.

Consumption in Non-Pastoral Regions Drove Three-Quarters of Forage-Livestock Conflicts in China.

Forage-livestock conflict (FLC) is a major anthropogenic cause of rangeland degradation. It poses tremendous threats to the environment owing to its adverse impacts on carbon sequestration, water supply and regulation, and biodiversity conservation. Existing policy interventions focus on the in situ FLCs induced by local production activities but overlook the role of consumption activities in driving FLCs. Here, we investigate the spatiotemporal variations in China's FLCs and the domestic final consumers at the county level by combining remote sensing data and multi-regional input-output model. Results show that during 2005-2015, China's pastoralism induced an average of 82 million tons of FLCs per year. Domestic final demand was responsible for 85-93% of the FLCs in China. There was spatiotemporal heterogeneity in domestic consumption driving China's FLCs. In particular, the final demand of non-pastoral regions was responsible for around three-quarters (74-79%) of the total FLCs throughout the decade. The rangeland-based livestock raising, agricultural and sideline product processing, and catering sectors are important demand-side drivers. These findings can support targeted demand-side strategies and interregional cooperation to reduce China's FLCs, thus mitigating rangeland degradation.

Cognitive Aging: How the Brain Ages?

Cognitive aging refers to the cognitive changes or functional decline that comes with age. The relation between aging and functional declines involves various aspects of cognition, including memory, attention, processing speed, and executive function. In this chapter, we have introduced several dimensions about cognitive aging trajectories. Meanwhile, we have reviewed the history of the study of cognitive aging and expatiated two trends that are particularly noteworthy in the effort to elucidate the process of aging. One is that the differences between components of mental abilities have become gradually specified. The other one is a growing interest in the neural process, which relates changes in the brain structure to age-related changes in cognition. Lastly, as the basis of cognitive function, brain structures and functions change during aging, and these changes are reflected in a corresponding decline in cognitive function. We have discussed the patterns of reorganization of various structural and functional aging processes of the brain and their relationship with cognitive function.

dCas9-Based PDGFR-ß Activation ADSCs Accelerate Wound Healing in Diabetic Mice through Angiogenesis and ECM Remodeling.

The chronic wound represents a serious disease characterized by a failure to heal damaged skin and surrounding soft tissue. Mesenchymal stem cells (MSCs) derived from adipose tissue (ADSCs) are a promising therapeutic strategy, but their heterogeneity may result in varying or insufficient therapeutic capabilities. In this study, we discovered that all ADSCs populations expressed platelet-derived growth factor receptor ß (PDGFR-ß), while the expression level decreased dynamically with passages. Thus, using a CRISPRa-based system, we endogenously overexpressed PDGFR-ß in ADSCs. Moreover, a series of in vivo and in vitro experiments were conducted to determine the functional changes in PDGFR-ß activation ADSCs (AC-ADSCs) and to investigate the underlying mechanisms. With the activation of PDGFR-ß, AC-ADSCs exhibited enhanced migration, survival, and paracrine capacity relative to control ADSCs (CON-ADSCs). In addition, the secretion components of AC-ADSCs contained more pro-angiogenic factors and extracellular matrix-associated molecules, which promoted the function of endothelial cells (ECs) in vitro. Additionally, in in vivo transplantation experiments, the AC-ADSCs transplantation group demonstrated improved wound healing rates, stronger collagen deposition, and angiogenesis. Consequently, our findings revealed that PDGFR-ß overexpression enhanced the migration, survival, and paracrine capacity of ADSCs and improved therapeutic effects after transplantation to diabetic mice.

Discovering the effect of co-fermentation involving Saccharomyces cerevisiae and Schizosaccharomyces pombe on the sensory quality improvement of mandarin wine based on metabolites and transcriptomic profiles.

BACKGROUND: Mandarin wine has high added value, which can extend the industry chain of mandarins with excellent economic results. However, innovative fermentation methods are urgently needed to improve the typical taste and flavor characteristics of mandarin wine. In this study, the effect and underlying mechanism of co-fermentation with Saccharomyces cerevisiae and Schizosaccharomyces pombe on the characteristics of mandarin wine were investigated based on integrated metabolomic and transcriptomic analyses. RESULTS: In comparison with fermentation with only S. cerevisiae, the mandarin wine produced from co-fermentation with S. cerevisiae and Sc. pombe had a higher pH value, lower malic acid content, and more abundant free amino acids, resulting in better sensory evaluation scores. The introduction of Sc. pombe extended the stage of alcoholic fermentation and enhanced the richness and diversity of volatile compounds, especially floral and fruity aroma compounds, including ethyl hexanoate, ethyl caprylate, ethyl enanthate, 1-heptanol, and phenylethyl alcohol. he significantly differential metabolites and varying genes were mainly found in pathways of glycolysis, pyruvate metabolism, the citrate cycle, and amino acid metabolism. CONCLUSION: Co-fermentation with S. cerevisiae and Sc. pombe showed advantages in producing distinctive taste and flavor of mandarin wine in comparison with fermentation with only S. cerevisiae. This study can inspire new co-fermentation strategies to improve the sensory quality of mandarin wine. © 2023 Society of Chemical Industry.

Executive and motor function in children with autism spectrum disorder.

The purpose of this study was to investigate the relationship between executive function, mainly attention and impulse control, and motor function impairment in children with ASD. Fifteen children with ASD (ages 8-14 years) were examined on their executive function using the Conners continuous performance test-3 and motor function using the movement assessment battery for children-2 (MABC-2). It was found that children with ASD were delayed on executive and motor function. This means that those effects were also observed in male children with Autism Spectrum Disorder (ASD) who had similar characteristics as the participants in the study. This study may have practical implications in the relationship between executive function and motor performance in children with ASD and for clinicians and educators working with children with ASD. Furthermore, the findings suggest that variability in reaction time may be a useful predictor of motor skill performance in children with ASD and may reflect underlying difficulties in executive function and future research is suggested.