Heat stress induces calcium dyshomeostasis to subsequent cognitive impairment through ERS-mediated apoptosis via SERCA/PERK/eIF2α pathway.

Heat exposure is an environmental stressor that has been associated with cognitive impairment. However, the neural mechanisms that underlie this phenomenon have yet to be extensively investigated. The Morris water maze test was utilized to assess cognitive performance. RNA sequencing was employed to discover the primary regulators and pathological pathways involved in cognitive impairment caused by heat. Before heat exposure in vivo and in vitro, activation of the sarco/endoplasmic reticulum (SR/ER) calcium (Ca2+)-ATPase (SERCA) was achieved by CDN1163. Hematoxylin-Eosin, Nissl staining, calcium imaging, transmission electron microscopy, western blot, and immunofluorescence were utilized to visualize histological changes, intracellular calcium levels, endoplasmic reticulum stress (ERS) markers, apoptosis, and synaptic proteins alterations. Heat stress (HS) significantly induced cognitive decline and neuronal damage in mice. By the transcriptome sequencing between control (n = 5) and heat stress (n = 5) mice in hippocampal tissues, we identified a reduction in the expression of the atp2a gene encoding SERCA, accompanied by a corresponding decrease in its protein level. Consequently, this dysregulation resulted in an excessive accumulation of intracellular calcium ions. Furthermore, HS exposure also activated ERS and apoptosis, as evidenced by the upregulation of p-PERK, p-eIF2α, CHOP, and caspase-3. Consistently, a reduction in postsynaptic density protein 95 (PSD95) and synaptophysin (SYN) expressions indicated modifications in synaptic function. Notably, the impacts on neurons caused by HS were found to be mitigated by CDN1163 treatment both in vivo and in vitro. Additionally, SERCA-mediated ERS-induced apoptosis was attenuated by GSK2606414 treatment via inhibiting PERK-eIF2α-CHOP axis that not only curtailed the level of caspase-3 but also elevated the levels of PSD95 and SYN. These findings highlight the significant impact of heat stress on cognitive impairment, and further elucidate the underlying mechanism involving SERCA/PERK/eIF2α pathway.

Construction of synthetic anti-fouling consortia: fouling control effects and polysaccharide degradation mechanisms.

The physical states and chemical components of bulk sludge determine the occurrence and development of membrane fouling in membrane bioreactors. Thus, regulation of sludge suspensions can provide new strategies for fouling control. In this study, we used "top-down" enrichment to construct a synthetic anti-fouling consortium (SAC) from bio-cake and evaluate its roles in preventing membrane fouling. The SAC was identified as Massilia-dominated and could almost wholly degrade the alginate solution (1,000 mg/L) within 72 h. Two-dimensional Fourier transformation infrared correlation spectroscopy (2D-FTIR-CoS) analysis demonstrated that the SAC induced the breakage of glycosidic bond in alginates. The co-cultivation of sludge with a low dosage of SAC (ranging from 0 to 1%) led to significant fouling mitigation, increased sludge floc size, and decreased unified membrane fouling index value (0.55 ± 0.06 and 0.11 ± 0.05). FTIR spectra and X-ray spectroscopy analyses demonstrated that the addition of SAC decreased the abundance of the O-acetylation of polysaccharides in extracellular polymeric substances. Secondary derivatives analysis of amide I spectra suggested a strong reduction in the α-helix/(ß-sheet + random coil) ratio in the presence of SAC, which was expected to enhance cell aggregation. Additionally, the extracellular secretions of SAC could both inhibit biofilm formation and strongly disperse the existing biofilm strongly during the biofilm incubation tests. In summary, this study illustrates the feasibility and benefits of using SAC for fouling control and provides a new strategy for fouling control.

Colorful Conductive Threads for Wearable Electronics: Transparent Cu-Ag Nanonets.

Electronic textiles have been regarded as the basic building blocks for constructing a new generation of wearable electronics. However, the electronization of textiles often changes their original properties such as color, softness, glossiness, or flexibility. Here a rapid room-temperature fabrication method toward conductive colorful threads and fabrics with Ag-coated Cu (Cu-Ag) nanonets is demonstrated. Cu-Ag core-shell nanowires are produced through a one-pot synthesis followed by electroless deposition. According to the balance of draining and entraining forces, a fast dip-withdraw process in a volatile solution is developed to tightly wrap Cu-Ag nanonets onto the fibers of thread. The modified threads are not only conductive, but they also retain their original features with enhanced mechanical stability and dry-wash durability. Furthermore, various e-textile devices are fabricated such as a fabric heater, touch screen gloves, a wearable real-time temperature sensor, and warm fabrics against infrared thermal dissipation. These high quality and colorful conductive textiles will provide powerful materials for promoting next-generation applications in wearable electronics.

A solution-processed octahedral nano-blocks structure CaIn2S4film for UV/vis photodetection.

A novel CaIn2S4with three-dimensional octahedral nano-blocks (ONBs) are successfully synthesized on fluorine-doped tin oxide (FTO) substrate by a simple hydrothermal method. The CaIn2S4ONBs are uniform grown and scattered on the whole FTO substrate with high regular and symmetric morphology as well as average diagonal length of about 600 nm. Based on the as-synthesized CaIn2S4ONBs, a photodetector (PD) is fabricated. Satisfyingly, it is found that the CaIn2S4ONBs PD achieves a broad-band response ranging from ultraviolet (UV) to visible ( vis) light at zero bias voltage. It is also significant that the CaIn2S4ONBs PD enables a fast response, in which the rise time and decay time are less than 0.15 and 0.2 s, respectively. Furthermore, the morphological evolution of the CaIn2S4ONBs and plausible UV/vis detection mechanism of the CaIn2S4ONBs PD are discussed.

Development and validation of a triplex assay to study an antibody cocktail against Ebola virus in cynomolgus serum.

Background: To support the rapid development of an antibody cocktail against Ebola virus and avoid unnecessary exposure to infectious environments, an automatic and fast turnover triplex assay was developed using Simoa® (Quanterix Corporation, MA, USA). Materials & methods: A robust triplex assay was developed and validated for simultaneous quantification of the antibody cocktail against Ebola virus in cynomolgus serum. Results: The assay had a quantitation range of 78.1-5000 ng/ml. The intra- and interassay precisions (%CV) were within 11.4 and 13.9%, and the accuracies (%RE) were within -10.8 to 6.8%, respectively. Cross-reactivity was evaluated, and the results met the acceptance criteria. Conclusion: The assay was successfully applied to a pharmacokinetics study following a single-dose intravenous administration of 10 mg/kg the antibody cocktail against Ebola virus to cynomolgus monkeys.

Dihydromyricetin prevents obesity-induced slow-twitch-fiber reduction partially via FLCN/FNIP1/AMPK pathway.

Obesity is often accompanied by decreases in the proportion of skeletal muscle slow-twitch fibers and insulin sensitivity. Increased plasma non-esterified fatty acids (NEFA) levels are responsible for obesity-associated insulin resistance. Palmitate, one of the most elevated plasma NEFA in obesity, has been recognized as the principle inducer of insulin resistance. The present study showed that increased plasma NEFA levels were negatively linked to slow-twitch fiber proportion and insulin sensitivity, while slow-twitch fiber proportion was positively correlated to insulin sensitivity in high fat diet (HFD)-fed and ob/ob mice. Dihydromyricetin (DHM) intervention increased slow-twitch fiber proportion and improved insulin resistance. In cultured C2C12 myotubes, palmitate treatment resulted in decrease of slow-twitch fiber specific Myh7 expression and insulin resistance, concomitant with folliculin (FLCN) and folliculin-interacting protein 1 (FNIP1) expression increase, AMP-activated protein kinase (AMPK) inactivation and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression decrease. Those palmitate-induced effects could be blocked by knock-down of FLCN expression or DHM intervention. Meanwhile, the protective effects of DHM were alleviated by over-expression of FLCN. In addition, the changes in AMPK activity and expression of FLCN and FNIP1 in vivo were consistent with those occurring in vitro. These findings suggest that DHM treatment prevents palmitate-induced slow-twitch fibers decrease partially via FLCN-FNIP1-AMPK pathway thereby improving insulin resistance in obesity.

Dihydromyricetin Improves Hypobaric Hypoxia-Induced Memory Impairment via Modulation of SIRT3 Signaling.

Inadequate oxygen availability-for instance at high altitudes-leads to hippocampal neurodegeneration and memory impairment. Although oxidative stress is one factor, the mechanism underlying the effects of hypobaric hypoxia (HH) are unclear, and effective strategies for preventing the resultant damage to the brain are limited. In the present study, we demonstrate that ingesting dihydromyricetin (DM) protects against memory impairment in adult rats subjected to HH for 7 days, equivalent to an altitude of 5000 m above sea level. Moreover, DM treatment stimulated mitochondrial biogenesis and improved mitochondrial morphology and function, suppressed the generation of reactive oxygen species, and reduced lipid peroxidation in the hippocampus. In HT-22 cells exposed to hypoxic conditions, the neuroprotective effects of DM were shown to be exerted via attenuation of oxidative stress through sirtuin 3-induced forkhead box O3 deacetylation.

Dihydromyricetin stimulates irisin secretion partially via the PGC-1α pathway.

Irisin, derived from FNDC5, is an exercise-induced myokine that can stimulate the 'browning' of white adipose tissue, which is regulated by peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α). Dihydromyricetin (DHM), a natural flavonoid, exerts its activities through PGC-1α activation. Here, we explored whether DHM could mimic the effects of exercise on irisin secretion. DHM administration increased circulating irisin in rats and humans. Notably, the serum irisin level had a greater correlation to the level of circulating DHM than to the amount of exercise. DHM treatment upregulated PGC-1α and FNDC5 expression, enhanced energy metabolism, as evidenced by NMR-based metabonomics analysis, and partially abolished the suppressive effects of Pgc-1α siRNA on FNDC5 expression. These results suggest that DHM can stimulate irisin secretion partially via the PGC-1α pathway. As a potent exercise mimetic, DHM is expected to benefit patients suffering from metabolic diseases, especially those who cannot undergo rigorous exercise.

Protective effects of myricetin on acute hypoxia-induced exercise intolerance and mitochondrial impairments in rats.

PURPOSE: Exercise tolerance is impaired in hypoxia. The aim of this study was to evaluate the effects of myricetin, a dietary flavonoid compound widely found in fruits and vegetables, on acute hypoxia-induced exercise intolerance in vivo and in vitro. METHODS: Male rats were administered myricetin or vehicle for 7 days and subsequently spent 24 hours at a barometric pressure equivalent to 5000 m. Exercise capacity was then assessed through the run-to-fatigue procedure, and mitochondrial morphology in skeletal muscle cells was observed by transmission electron microscopy (TEM). The enzymatic activities of electron transfer complexes were analyzed using an enzyme-linked immuno-sorbent assay (ELISA). mtDNA was quantified by real-time-PCR. Mitochondrial membrane potential was measured by JC-1 staining. Protein expression was detected through western blotting, immunohistochemistry, and immunofluorescence. RESULTS: Myricetin supplementation significantly prevented the decline of run-to-fatigue time of rats in hypoxia, and attenuated acute hypoxia-induced mitochondrial impairment in skeletal muscle cells in vivo and in vitro by maintaining mitochondrial structure, mtDNA content, mitochondrial membrane potential, and activities of the respiratory chain complexes. Further studies showed that myricetin maintained mitochondrial biogenesis in skeletal muscle cells under hypoxic conditions by up-regulating the expressions of mitochondrial biogenesis-related regulators, in addition, AMP-activated protein kinase(AMPK) plays a crucial role in this process. CONCLUSIONS: Myricetin may have important applications for improving physical performance under hypoxic environment, which may be attributed to the protective effect against mitochondrial impairment by maintaining mitochondrial biogenesis.

Supplementation of Superfine Powder Prepared from Chaenomeles speciosa Fruit Increases Endurance Capacity in Rats via Antioxidant and Nrf2/ARE Signaling Pathway.

Chaenomeles speciosa fruit is a traditional herb medicine widely used in China. In this study, superfine powder of C. speciosa fruit (SCE), ground by supersonic nitrogen airflow at -140°C, was investigated to assess its in vitro antioxidant activity and in vivo antiphysical fatigue activity. SCE was homogenous (d < 10 µm) and rich in antioxidants like polyphenols, saponins, oleanolic acid, ursolic acid, ascorbic acid, and SOD. According to the in vitro experiments, SCE displayed promising antioxidant activity with powerful FARP, SC-DPPH, and SC-SAR activities. According to the in vivo experiments, rats supplemented with SCE had prolonged exhaustive swimming time (57%) compared to the nonsupplemented rats. Meanwhile, compared to the nonsupplemented rats, the SCE-supplemented rats had higher levels of blood glucose and liver and muscular glycogen and lower levels of LA and BUN. Lower MDA, higher antioxidant enzymes (SOD, CAT, and GSH-Px) activities, and upregulated Nrf2/ARE mediated antioxidant enzymes (HO-1, Trx, GCLM, and GCLC) expression were also detected in the supplemented group. This study indicates that SCE is a potent antioxidant and antifatigue agent, and SCE could be a promising raw material for the food and pharmaceutical industries.