p-Coumaric acid alleviates adriamycin-induced hepatotoxicity in rats

Objective:To evaluate the effect of p-coumaric acid against adriamycin-induced hepatotoxicity in rats.Methods:The rats were divided into 4 groups.The control group received solvent;the p-coumaric acid group was treated with 100 mg/kg of p-coumaric acid orally for five consecutive days;the adriamycin group was administered with a single dose of adriamycin(15 mg/kg,i.p.),and the p-coumaric acid+adriamycin group was given p-coumaric acid five days before adriamycin administration.Twenty-four hours after the last administration,blood samples were collected for biochemical analysis,and liver tissues were removed for histopathological and immunohistochemistrical studies.Moreover,the levels of tissue lipid peroxidation and enzyme activities of glutathione peroxidase,superoxide dismutase,and catalase in liver tissue were measured.Results:Treatment with p-coumaric acid protected the liver from the toxicity of adriamycin by attenuating the increase in alkaline phosphatase,alanine transaminase,aspartate transaminase,total bilirubin,total cholesterol,triglyceride,and low-density lipoprotein cholesterol and lessening the decrease in high-density lipoprotein cholesterol and albumin.p-Coumaric acid also raised the levels of glutathione peroxidase,superoxide dismutase,and catalase,as well as decreased lipid peroxidation in liver tissue and hepatic IL-1βexpression.Additionally,histopathological study confirmed the protective effect of p-coumaric acid against liver damage.Conclusions:p-Coumaric acid can alleviate adriamycin-induced hepatotoxicity.

Quantitative Extraction of p-Coumaric Acid and Ferulic Acid in Different Gramineous Materials and Structural Changes of Residual Alkali Lignin

Ferulic acid(FA)and p-coumaric acid(pCA)in bagasse,wheat straw,corn straw,and corncob were extracted by alkaline hydrolysis and characterized by gas chromatography(GC)and gas chromatography-mass spectrometry(GC-MS).It was found that the FA and most of the pCA in gramineous biomass could be dissociated and released after being treated with 1 M NaOH at 100℃for 4 h.The yields of pCA/FA in bagasse,wheat straw,corn straw,and corncob determined by GC-FID are 39.8/11.5,13.7/11.0,28.0/11.0,and 35.1/14.5 mg/g,respectively.The raw materials and the treated solid residues were characterized by gel-state 2D Heteronuclear Single Quantum Coherence Nuclear Magnetic Resonance(2D HSQC NMR).It was found that only a small amount of lignin was detected in the residue after alkali treatment,indicating that the alkali treatment conditions can effectively cleave the FA and pCA.Additionally,the lignin in the alkali solution was recovered and characterized by 2D HSQC NMR.The FA was not able to be detected by NMR,whereas a small amount of pCA remained in the alkali lignin.This study reveals the structural change of residual lignins during the quantitative isolation of FA and pCA,which is essential for the selective isolation of pCA/FA and valorization of residual alkali lignin.

Simultaneous determination of gallic acid and p-coumaric acid in rat plasma by UPLC-MS/MS and its application to a comparative pharmacokinetic study after oral administration of monomer compound and red wine extract

A rapid,sensitive and selective ultra high performance liquid chromatography-tandem mass spectrometry(UPLCMS/MS)method was developed and validated for simultaneous determination of gallic acid(GA)and p-coumaric acid(CA)in rat plasma.Plasma samples were extracted by methanol and separated on an ACQUITY UPLC BEH C18 column(1.7μm,100 mm×2.1 mm)using gradient elution consisting of acetonitrile–0.2%formic acid within a runtime of 4.0 min.The detection was performed in multiple reaction monitoring(MRM)mode with negative ionization.The linear range was 20–20000 ng/mL for both GA and CA,with lower limits of quantification of 20 ng/mL.Intra-day and inter-day precisions were within 5.4%and 10.0%,respectively and the accuracy(relative error,RE,%)was less than 7.2%and–4.9%,respectively.The mean absolute extraction recoveries of both analytes and IS from rat plasma were all more than 82.6%.The validated method was successfully applied to the comparative pharmacokinetic study of GA and CA in rat plasma after oral administration of GA and CA monomers and red wine extract,respectively.It was found that both the area under the curve(AUC)and t1/2 of the two constituents were remarkably increased for red wine extract group than that in monomer group,indicating the priority of intake of red wine to active component monomer.

Events associated with apoptotic effect of p-Coumaric acid in HCT-15 colon cancer cells

AIM:To investigate the events associated with the apoptotic effect of p-Coumaric acid,one of the phenolic components of honey,in human colorectal carcinoma(HCT-15)cells.METHODS:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltertazolium-bromide assay was performed to determine the antiproliferative effect of p-Coumaric acid against colon cancer cells.Colony forming assay was conducted to quantify the colony inhibition in HCT15 and HT 29 colon cancer cells after p-Coumaric acid treatment.Propidium Iodide staining of the HCT15 cells using flow cytometry was done to study the changes in the cell cycle of treated cells.Identification of apoptosis was done using scanning electron microscope and photomicrograph evaluation of HCT 15cells after exposing to p-Coumaric acid.Levels of reactive oxygen species(ROS)of HCT 15 cells exposed to p-Coumaric acid was evaluated using 2’,7’-dichlorfluorescein-diacetate.Mitochondrial membrane potential of HCT-15 was assessed using rhodamine-123 with the help of flow cytometry.Lipid layer breaks associated with p-Coumaric acid treatment was quantified using the dye merocyanine 540.Apoptosis was confirmed and quantified using flow cytometric analysis of HCT15 cells subjected to p-Coumaric acid treatment after staining with YO-PRO-1.RESULTS:Antiproliferative test showed p-Coumaric acid has an inhibitory effect on HCT 15 and HT 29 cells with an IC50(concentration for 50%inhibition)value of 1400 and 1600μmol/L respectively.Colony forming assay revealed the time-dependent inhibition of HCT 15 and HT 29 cells subjected to p-Coumaric acid treatment.Propidium iodide staining of treated HCT 15cells showed increasing accumulation of apoptotic cells(37.45±1.98 vs 1.07±1.01)at sub-G1phase of the cell cycle after p-Coumaric acid treatment.HCT-15 cells observed with photomicrograph and scanning electron microscope showed the signs of apoptosis like blebbing and shrinkage after p-Coumaric acid exposure.Evaluation of the lipid layer showed increasing lipid layer breaks was associated with the growth inhibition of p-Coumaric acid.A fall in mitochondrial membrane potential and increasing ROS generation was observed in the p-Coumaric acid treated cells.Further apoptosis evaluated by YO-PRO-1 staining also showed the timedependent increase of apoptotic cells after treatment.CONCLUSION:These results depicted that p-Coumaric acid inhibited the growth of colon cancer cells by inducing apoptosis through ROS-mitochondrial pathway.

p-Coumaric acid ameliorates ethanol-induced kidney injury by inhibiting inflammatory cytokine production and NF-κB signaling in rats

Objective: To examine the effects of p-coumaric acid on ethanol-induced kidney injury in Swiss Wistar rats.Methods: Ethanol(25% v/v) was used to induce nephrotoxicity in rats. p-Coumaric acid was orally administered at 50, 100, or 200 mg/kg body weight. The levels of oxidative parameters were determined; pro-inflammatory biomarkers were analyzed by Western blotting and apoptotic protein was analyzed by immunohistochemistry. Results: Ethanol treated rats showed decreased levels of antioxidants and aberrant production of pro-inflammatory cytokines(IL-6, IL1β, TNF-α), NF-κB activation and imbalance of proand anti-apoptotic proteins(Bcl-2, Bax, caspase 3). Meanwhile, p-coumaric acid restored antioxidant levels and decreased the levels of inflammatory cytokines, NF-κB, and proapoptotic proteins and increased Bcl-2 expression. Conclusions: p-Coumaric acid ameliorates ethanol-induced kidney injury by restoring antioxidant production and suppressing cellular apoptosis and inhibiting NF-κB expression.p-Coumaric acid should be further investigated as a promising candidate for ethanol-induced kidney toxicity.

Poly(p-coumaric acid)nanoparticles alleviate temporomandibular joint osteoarthritis by inhibiting chondrocyte ferroptosis

Oxidative stress and inflammation are key drivers of osteoarthritis(OA)pathogenesis and disease progression.Herein we report the synthesis of poly(p-coumaric)nanoparticles(PCA NPs)from p-courmaic acid(p-CA),a naturally occurring phytophenolic acid,to be a multifunctional and drug-free therapeutic for temporomandibular joint osteoarthritis(TMJOA).Compared to hyaluronic acid(HA)that is clinically given as viscosupplementation,PCA NPs exhibited long-term efficacy,superior anti-oxidant and anti-inflammatory properties in alleviating TMJOA and repairing the TMJ cartilage and subchondral bone in a rat model of TMJOA.Notably,TMJ repair mediated by PCA NPs could be attributed to their anti-oxidant and anti-inflammatory properties in enhancing cell proliferation and matrix synthesis,while reducing inflammation,oxidative stress,matrix degradation,and chondrocyte ferroptosis.Overall,our study demonstrates a multifunctional nanoparticle,synthesized from natural p-coumaric acid,that is stable and possess potent antioxidant,anti-inflammatory properties and ferroptosis inhibition,beneficial for treatment of TMJOA.

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.