Decoding the nexus:branched-chain amino acids and their connection with sleep,circadian rhythms,and cardiometabolic health

The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other organs.Among these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral processes.Among the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of rapamycin.Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared transporter.Beyond their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy metabolism.Notably,they impact GABAergic neurons and the excitation/inhibition balance.The rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock control.The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood.Disturbed sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics.The mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies.In this context,the Drosophila model,though underutilized,holds promise in shedding new light on these mechanisms.Initial findings indicate its potential to introduce novel concepts,particularly in elucidating the intricate connections between the circadian clock,sleep/wake,and metabolism.Consequently,the use and transport of branched-chain amino acids emerge as critical components and orchestrators in the web of interactions across multiple organs throughout the sleep/wake cycle.They could represent one of the so far elusive mechanisms connecting sleep patterns to metabolic and cardiovascular health,paving the way for potential therapeutic interventions.

Increased excitatory amino acid transporter 2 levels in basolateral amygdala astrocytes mediate chronic stress–induced anxiety-like behavior

The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.

Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is well-documented.Nevertheless,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely understudied.The release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the penumbra.Our findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma concentrations.These amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate receptors.Blocking N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during hypoxia.It is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor activation.Thus,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain injury.Understanding these pathways co uld highlight new therapeutic targets to mitigate brain injury.

g-C_(3)N_(4)nanosheets coupled with CoSe_(2)as co-catalyst for efficient photooxidation of xylose to xylonic acid

Photocatalysis has emerged as an effective approach to sustainably convert biomass into value-added products.CoSe_(2)is a promising nonprecious,efficient cocatalyst for photooxidation,which can facilitate the separation of photogenerated electron–holes,increase the reaction rates,and enhance photocatalytic efficiency.In this work,we synthesized a stable and efficient photocatalysis system of CoSe_(2)/g-C_(3)N_(4)through attaching CoSe_(2)on g-C_(3)N_(4)sheets,with a yield of 50.12%for the selective photooxidation of xylose to xylonic acid.Under light illumination,the photogenerated electrons were prone to migrating from g-C_(3)N_(4)to CoSe_(2)due to the higher work function of CoSe_(2),resulting in the accelerated separation of photogenerated electron–holes and the promoted photooxidation.Herein,this study reveals the unique function of CoSe_(2),which can significantly promote oxygen adsorption,work as an electron sink and accelerate the generation of ·O_(2)^(-),thereby improving the selectivity toward xylonic acid over other by-products.This work provides useful insights into the design of selective photocatalysts by engineering g-C_(3)N_(4)for biomass high-value utilization.

Flotation separation of chalcopyrite from pyrite using mineral fulvic acid as selective depressant under weakly alkaline conditions

Mineral fulvic acid(MFA)was used as an eco-friendly pyrite depressant to recover chalcopyrite by flotation with the use of the butyl xanthate as a collector.Flotation experiments showed that MFA produced a stronger inhibition effect on pyrite than on chalcopyrite.The separation of chalcopyrite from pyrite was realized by introducing 150 mg/L MFA at a pulp pH of approximately 8.0.The copper grade,copper recovery,and separation efficiency were 28.03%,84.79%,and 71.66%,respectively.Surface adsorption tests,zeta potential determinations,and localized electrochemical impedance spectroscopy tests showed that more MFA adsorbed on pyrite than on chalcopyrite,which weakened the subsequent interactions between pyrite and the collector.Atomic force microscope imaging further confirmed the adsorption of MFA on pyrite,and X-ray photoelectron spectroscopy results indicated that hydrophilic Fe-based species on the pyrite surfaces increased after exposure of pyrite to MFA,thereby decreasing the floatability of pyrite.

Additive neurorestorative effects of exercise and docosahexaenoic acid intake in a mouse model of Parkinson’s disease

There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.

Leaching of WO_(3)from sulfuric acid converted product of scheelite in NH_(3)·H_(2)O−NH_(4)HCO_(3)solution

The leaching of sulfuric acid converted product of scheelite in NH_(3)·H_(2)O−NH_(4)HCO_(3)solution was systemically studied to improve sulfuric acid conversion−ammonium salts leaching technology route for ammonium paratungstate production.The results showed that the WO_(3)leaching efficiency was about 99%under optimal conditions of 350 r/min,liquid-to-solid ratio of 3 mL/g,1 mol/L NH_(4)HCO_(3),4 mol/L NH_(3)·H_(2)O,25℃,and 15 min.During the leaching,CaSO_(4)almost had no change and was still in a banding or rod-like shape in short leaching time,while conglobate CaCO_(3)was gradually formed on the CaSO_(4)surface.A secondary reaction might occur between CaSO_(4)and WO_(4)^(2−),which could be restrained by a certain amount of CO_(3)^(2−)in the solution.There was no CaCO_(3)phase determined by XRD in leaching residue of converted product for scheelite concentrate under optimal conditions,which was different from that for synthetic scheelite.The leaching process could be explained by neutralization reaction of H_(2)WO_(4)and solid transformation of CaSO_(4)in NH_(3)·H_(2)O−NH_(4)HCO_(3)solution.

Bile acid therapy for primary biliary cholangitis:Pathogenetic validation

Knowledge of the etiological and pathogenetic mechanisms of the development of any disease is essential for its treatment.Because the cause of primary biliary cholangitis(PBC),a chronic,slowly progressive cholestatic liver disease,is still unknown,treatment remains symptomatic.Knowledge of the physicochemical properties of various bile acids and the adaptive responses of cholangiocytes and hepatocytes to them has provided an important basis for the development of relatively effective drugs based on hydrophilic bile acids that can potentially slow the progression of the disease.Advances in the use of hydrophilic bile acids for the treatment of PBC are also associated with the discovery of pathogenetic mechanisms of the development of cholangiocyte damage and the appearance of the first signs of this disease.For 35 years,ursodeoxycholic acid(UDCA)has been the unique drug of choice for the treatment of patients with PBC.In recent years,the list of hydrophilic bile acids used to treat cholestatic liver diseases,including PBC,has expanded.In addition to UDCA,the use of obeticholic acid,tauroursodeoxycholic acid and norursodeoxycholic acid as drugs is discussed.The pathogenetic rationale for treatment of PBC with various bile acid drugs is discussed in this review.Emphasis is made on the mechanisms explaining the beneficial therapeutic effects and potential of each of the bile acid as a drug,based on the understanding of the pathogenesis of the initial stages of PBC.

Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke

It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke.Indeed,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue.Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently unclear.To simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke.We found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous acid.Further,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid hydrazide.Our results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation.However,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes.This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury.Lower levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-catenin.By transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear translocation.Altogether,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

Enhanced autophagic clearance of amyloid-βvia histone deacetylase 6-mediated V-ATPase assembly and lysosomal acidification protects against Alzheimer's disease in vitro and in vivo

Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque formation.Therefore,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's disease.Microtubule acetylation/deacetylation plays a central role in lysosomal acidification.Here,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's disease.Fu rthermore,we found that treatment with valproic acid markedly enhanced autophagy.promoted clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's disease.Our findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.

Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.

Concentration and retention of ascorbic acid,carotenoids,and sugars in fresh-cut lettuce in modified atmosphere packaging

Fresh-cut lettuce is widely used in ready-to-eat salads sold in modified atmosphere packages (MAP).Even in MAP,fresh-cut lettuce has short shelf life that results in loss of nutrients.Lettuce cultivars exhibit genetic variation for shelf life in MAP,but their variation for nutrient retention is not known.Fifty accessions were evaluated for initial content of ascorbic acid (AsA),carotenoids,and sugars and their retention in storage.Accessions with high content and/or good retention of one or more nutrients were identified.The romaine accession ‘Floricos’ had high levels of all the three nutrients.Accessions with relatively high retention of all the three nutrients were ‘Salinas 88’,‘Siskiyou’,‘Solar’,SM09A,‘Romance’,and ‘Green Towers’.Romaine cultivars,‘Balady Barrage’,‘Green Towers’,and ‘Darkland’ had relatively high initial levels of all tested nutrients and good rate of their retention.There was no clear correlation between initial AsA/carotene concentrations and their retention rates,suggesting that besides content,retention of nutrients should also be a breeding target in a lettuce nutritional improvement program.Statistical analyses with the Pearson's correlation coefficient determined a negative relationship between tissue deterioration(AUDePS) and retention of all tested nutrients[r of-0.52 (P<0.0001) for AsA,-0.27 (P<0.01) for total carotene,and-0.59 (P<0.0001) for total sugars],suggesting that an increase in tissue deterioration intensifies nutrient decay.Broad-sense heritability (H~2) across the experiments was0.15 for AsA,0.23 for total carotene,and 0.50 for total sugars.Identification of germplasm with high nutrient content,extended shelf life and good nutrient retention provides valuable information for the lettuce industry and associated breeding programs.

A review on global spatial distribution,sources and toxicity of perfluoroalkyl acid and prospect in the cryosphere

Perfluoroalkyl acid analogs(PFAAs)are a class of chemically stable environmentally persistent organic pollutants(POPs)that are difficult to degrade and have a strong capacity to accumulate in the human body.PFAAs have been found to be biotoxic to humans and have been detected in various environmental media,especially in the cryosphere at trace concentrations.The cryosphere,sensitively responds to climate change,plays a crucial role in the global water,carbon and energy cycles.However,researches on cryosphere PFAAs especially in Tibetan Plateau(TP)is limited.Therefore,we summarize the physicochemical properties,physiological toxicity,spatiotemporal distribution,sources,diffusion and migration pathways,as well as analysis and removal methods of PFAAs in the cryosphere regions.The results show that PFAAs pollutants are mainly produced and distributed in the more economically developed countries in Europe and the United States,as well as in East Asia,and PFAAs can be transported by atmospheric circulation and water cycle to remote regions including cryosphere regions.The current detection methods for PFAAs in cryosphere need to be further refined for increased accuracy and convenience.There is also a need to develop more effective removal methods that will reduce the environmental and human threats posed by these PFAAs.Finally,we propose key scientific questions for future research in cryosphere including PFAAs redistribution influenced by cryosphere changes,human activities,and the interaction of other spheres.

Effect of alpha-lipoic acid and Silybum marianum supplementation with a Mediterranean diet on metabolic dysfunction-associated steatosis

BACKGROUND The treatment of metabolic dysfunction-associated steatotic liver disease(MA-SLD)has focused on the control of comorbidities.Silybum marianum(SM)and alpha-lipoic acid(ALA)have shown antioxidant and adjuvant effects on the control of metabolic disorders.AIM To evaluate whether the SM-ALA formulation(LUDLEV®),in combination with the Mediterranean diet(MD),could improve MASLD-related liver injury.METHODS A randomized,double-blind clinical trial was conducted on patients with MA-SLD.Administration of SM-ALA plus MD(group A)vs placebo plus MD(group B)was compared for 24 weeks.At baseline and weeks 12 and 24,anthropometric measurements,metabolic parameters,and liver function were analyzed.Clinical effectiveness was evaluated through transient elastography.RESULTS Fifty patients aged 54±10 years were included,and the majority(74%)were female.Reduced visceral fat and umbilical circumference were reported in both groups,with significance in group A(P=0.045 and 0.003,respectively).The de-crease in controlled attenuation parameter was gradual and maintained at 12 and 24 weeks in group A(P=0.026),whereas in group B the decrease was greater at week 12 and remained unchanged at week 24(∆controlled attenuation parameter:-27 dB/m).Mild adverse effects were reported in 4 patients in group A(16%)and 4 patients in group B(16%),with no significant differences between groups(P=0.641).CONCLUSION SM-ALA(LUDLEV®)combined with the MD can promote the improvement of metabolic parameters,reducing visceral fat and hepatic steatosis in Mexican patients with MASLD.

Ascorbic acid alleviates reproductive toxicity of di-(2-ethyl hexyl) phthalate in female Wistar rats

Objective:To investigate the potential of ascorbic acid in mitigating reproductive toxicity induced by di-(2-ethyl hexyl)phthalate(DEHP)in female Wistar rats,focusing on oxidative stress,hormone levels,and gonadotropin receptors expression.Methods:Forty female Wistar rats[30 days old,weighing(60±10)g]were randomly divided into five groups(n=8 per group).Group 1 received corn oil(control).Groups 2 and 3 were administered DEHP at 10 and 100 mg/kg body weight(b.wt.),respectively.Groups 4 and 5 received DEHP at 10 and 100 mg/kg b.wt.,respectively,plus ascorbic acid 100 mg/kg b.wt..All treatments were given orally for 30 days.Blood and ovarian tissues were collected to assess serum reproductive hormones,gonadotropin receptor gene expression,oxidative stress markers,and apoptosis.Results:DEHP,particularly at the higher dose,significantly decreased hormone levels(follicle-stimulating hormone,luteinizing hormone,estradiol)and gonadotropin receptor gene expression(FSHR,LHR),while increasing oxidative stress and apoptosis.Co-treatment with ascorbic acid significantly improved these parameters,reducing oxidative stress and apoptosis,and restoring hormone levels and gonadotropin receptor expression.Histopathology revealed fewer atretic follicles and less disruption in ovarian structure in DEHP and ascorbic acid-treated groups compared to those treated with DEHP alone.Conclusions:Ascorbic acid demonstrates protective effects against DEHP-induced reproductive toxicity in female rats,likely through mitigating oxidative stress and normalizing hormone levels and ovarian function.

Glabridin and gymnemic acid alleviates choroid structural change and choriocapillaris impairment in diabetic rat’s eyes

BACKGROUND Small blood vessels in the eyes are more susceptible to injury,which can lead to complications.However,since diabetic retinopathy is often a serious clinical condition,most of this study focuses on the vascular system of the choroid.As part of this study,we looked at how gymnemic acid(from Gymnema sylvestre)and glabridin(from Glycyrrhiza glabra,or licorice)might help diabetic rats’choroid structural change and blood vessels.AIM To explore the effects of glabridin and gymnemic acid on the structural changes of the choroidal layer and choriocapillaris as well as the expression of vascular endothelial growth factor(VEGF)and cluster of differentiation(CD)31 in diabetic rat’s eye.METHODS The male Wistar rats were separated into five groups:The control group(control),the diabetic group(DM),the diabetic rats treated with glabridin 40 mg/kg body weight(DM+GB),the diabetic rats treated with gymnemic acid 400 mg/kg body weight(DM+GM),and the diabetic rats treated with glyburide 4 mg/kg body weight(DM+GR).RESULTS There was an increase in the thickness of both the choroid layer and the wall of the arteries in the DM.A decrease in vascularity and choroidal impairment was found in DM rats.After eight weeks of experimentation,the choroidal thickness increased,and the walls of choroid arteries.The choroidal thickness in the DM+GB was 15.69±1.54μm,DM+GM was 14.84±1.31,and DM+GR groups was 16.45±1.15 when compared with DM group(27.22±2.05),the walls thickness of choroid arteries in the DM+GB was 10.23±1.11,DM+GM was 10.41±1.44,and DM+GR was 9.80±1.78 when compared with DM group(16.35±5.01),The expression of VEGF and CD31 was lower compared to the DM group.CONCLUSION In diabetic choroidopathy,hyperglycemia and inflammation cause damage to the neurovascular unit and bloodretinal barrier.Anti-VEGF treatments can slow or reverse the progression of the disease.According to current research findings,glabridin and gymnemic acid can reduce damage to the choroid,which is a factor that can sometimes result in vision loss.

A vascular endothelial growth factor–loaded chitosan-hyaluronic acid hydrogel scaffold enhances the therapeutic effect of adipose-derived stem cells in the context of stroke

Adipose-derived stem cell,one type of mesenchymal stem cells,is a promising approach in treating ischemia-reperfusion injury caused by occlusion of the middle cerebral artery.However,its application has been limited by the complexities of the ischemic microenvironment.Hydrogel scaffolds,which are composed of hyaluronic acid and chitosan,exhibit excellent biocompatibility and biodegradability,making them promising candidates as cell carriers.Vascular endothelial growth factor is a crucial regulatory factor for stem cells.Both hyaluronic acid and chitosan have the potential to make the microenvironment more hospitable to transplanted stem cells,thereby enhancing the therapeutic effect of mesenchymal stem cell transplantation in the context of stroke.Here,we found that vascular endothelial growth factor significantly improved the activity and paracrine function of adipose-derived stem cells.Subsequently,we developed a chitosan-hyaluronic acid hydrogel scaffold that incorporated vascular endothelial growth factor and first injected the scaffold into an animal model of cerebral ischemiareperfusion injury.When loaded with adipose-derived stem cells,this vascular endothelial growth factor–loaded scaffold markedly reduced neuronal apoptosis caused by oxygen-glucose deprivation/reoxygenation and substantially restored mitochondrial membrane potential and axon morphology.Further in vivo experiments revealed that this vascular endothelial growth factor–loaded hydrogel scaffold facilitated the transplantation of adipose-derived stem cells,leading to a reduction in infarct volume and neuronal apoptosis in a rat model of stroke induced by transient middle cerebral artery occlusion.It also helped maintain mitochondrial integrity and axonal morphology,greatly improving rat motor function and angiogenesis.Therefore,utilizing a hydrogel scaffold loaded with vascular endothelial growth factor as a stem cell delivery system can mitigate the adverse effects of ischemic microenvironment on transplanted stem cells and enhance the therapeutic effect of stem cells in the context of stroke.

Recovery of Li, Ni, Co and Mn from spent lithium-ion batteries assisted by organic acids: Process optimization and leaching mechanism

The proper recycling of spent lithium-ion batteries(LIBs)can promote the recovery and utilization of valuable resources,while also negative environmental effects resulting from the presence of toxic and hazardous substances.In this study,a new environmentally friendly hydro-metallurgical process was proposed for leaching lithium(Li),nickel(Ni),cobalt(Co),and manganese(Mn)from spent LIBs using sulfuric acid with citric acid as a reductant.The effects of the concentration of sulfuric acid,the leaching temperature,the leaching time,the solid-liquid ratio,and the reducing agent dosage on the leaching behavior of the above elements were investigated.Key parameters were optimized using response surface methodology(RSM)to maximize the recovery of metals from spent LIBs.The maxim-um recovery efficiencies of Li,Ni,Co,and Mn can reach 99.08%,98.76%,98.33%,and 97.63%.under the optimized conditions(the sulfuric acid concentration was 1.16 mol/L,the citric acid dosage was 15wt%,the solid-liquid ratio was 40 g/L,and the temperature was 83℃ for 120 min),respectively.It was found that in the collaborative leaching process of sulfuric acid and citric acid,the citric acid initially provided strong reducing CO_(2)^(-),and the transition metal ions in the high state underwent a reduction reaction to produce transition metal ions in the low state.Additionally,citric acid can also act as a proton donor and chelate with lower-priced transition metal ions,thus speeding up the dissolution process.

A comparison study on structure-function relationship of polysaccharides obtained from sea buckthorn berries using different methods:antioxidant and bile acid-binding capacity

In this study,the structural characters,antioxidant activities and bile acid-binding ability of sea buckthorn polysaccharides(HRPs)obtained by the commonly used hot water(HRP-W),pressurized hot water(HRP-H),ultrasonic(HRP-U),acid(HRP-C)and alkali(HRP-A)assisted extraction methods were investigated.The results demonstrated that extraction methods had significant effects on extraction yield,monosaccharide composition,molecular weight,particle size,triple-helical structure,and surface morphology of HRPs except for the major linkage bands.Thermogravimetric analysis showed that HRP-U with filamentous reticular microstructure exhibited better thermal stability.The HRP-A with the lowest molecular weight and highest arabinose content possessed the best antioxidant activities.Moreover,the rheological analysis indicated that HRPs with higher galacturonic acid content and molecular weight showed higher viscosity and stronger crosslinking network(HRP-C,HRP-W and HRP-U),which exhibited stronger bile acid binding capacity.The present findings provide scientific evidence in the preparation technology of sea buckthorn polysaccharides with good antioxidant and bile acid binding capacity which are related to the structure affected by the extraction methods.

Selective leaching of lithium from spent lithium-ion batteries using sulfuric acid and oxalic acid

Traditional hydrometallurgical methods for recovering spent lithium-ion batteries(LIBs)involve acid leaching to simultaneously extract all valuable metals into the leachate.These methods usually are followed by a series of separation steps such as precipitation,extraction,and stripping to separate the individual valuable metals.In this study,we present a process for selectively leaching lithium through the synergistic effect of sulfuric and oxalic acids.Under optimal leaching conditions(leaching time of 1.5 h,leaching temperature of 70°C,liquid-solid ratio of 4 mL/g,oxalic acid ratio of 1.3,and sulfuric acid ratio of 1.3),the lithium leaching efficiency reached89.6%,and the leaching efficiencies of Ni,Co,and Mn were 12.8%,6.5%,and 21.7%.X-ray diffraction(XRD)and inductively coupled plasma optical emission spectrometer(ICP-OES)analyses showed that most of the Ni,Co,and Mn in the raw material remained as solid residue oxides and oxalates.This study offers a new approach to enriching the relevant theory for selectively recovering lithium from spent LIBs.