The mechanisms for the regulation of synaptic dopamine (DA) include its release from presynaptic vesicles, its interaction with post-synaptic and pre-synaptic DA receptors, the reuptake of DA, via dopamine transport...The mechanisms for the regulation of synaptic dopamine (DA) include its release from presynaptic vesicles, its interaction with post-synaptic and pre-synaptic DA receptors, the reuptake of DA, via dopamine transporter (DAT), the diffusion of DA and its metabolism by mono-amine oxidase (MAO) and cate- chol-O-methyl transferase (COMT). DA controls complex and specialized functions including, movements, behavior, mood, perception, reward, and more recently, neurogenesis (Popolo et al., 2004; Reimer et al., 2013) and neuroregeneration (Hoglinger et al., 2004; Yang et al., 2008). These functions are varied and of high fidelity. Movement, as an example, requires regulatory mechanisms for initiating, stopping, slowing-down speed- ing-up, changing directions, for governing the relentless urges to move in the young and sedentariness in the old as well as in motor-freezing, catalepsy, tremor and stereotypy.展开更多
Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangle...Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the brain.The NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and aggregation.Because NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines.Here,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau phosphorylation.Using biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons.In primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis present.In the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical neurons.Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses.We also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced responses.These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in neurons.Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.展开更多
With plenty of popular and effective ternary organic solar cells(OSCs)construction strategies proposed and applied,its power conversion efficiencies(PCEs)have come to a new level of over 19%in single-junction devices....With plenty of popular and effective ternary organic solar cells(OSCs)construction strategies proposed and applied,its power conversion efficiencies(PCEs)have come to a new level of over 19%in single-junction devices.However,previous studies are heavily based in chloroform(CF)leaving behind substantial knowledge deficiencies in understanding the influence of solvent choice when introducing a third component.Herein,we present a case where a newly designed asymmetric small molecular acceptor using fluoro-methoxylated end-group modification strategy,named BTP-BO-3FO with enlarged bandgap,brings different morphological evolution and performance improvement effect on host system PM6:BTP-eC9,processed by CF and ortho-xylene(o-XY).With detailed analyses supported by a series of experiments,the best PCE of 19.24%for green solvent-processed OSCs is found to be a fruit of finely tuned crystalline ordering and general aggregation motif,which furthermore nourishes a favorable charge generation and recombination behavior.Likewise,over 19%PCE can be achieved by replacing spin-coating with blade coating for active layer deposition.This work focuses on understanding the commonly met yet frequently ignored issues when building ternary blends to demonstrate cutting-edge device performance,hence,will be instructive to other ternary OSC works in the future.展开更多
Maillard reaction(MR)is a non-enzymatic browning reaction commonly seen in food processing,which occurs between reducing sugars and compounds with amino groups.Despite certain advantages based on Maillard reaction pro...Maillard reaction(MR)is a non-enzymatic browning reaction commonly seen in food processing,which occurs between reducing sugars and compounds with amino groups.Despite certain advantages based on Maillard reaction products(MRPs)found in some food for health and storage application have appeared,however,the MR occurring in human physiological environment can produce advanced glycation end products(AGEs)by non-enzymatic modification of macromolecules such as proteins,lipids and nucleic acid,which could change the structure and functional activity of the molecules themselves.In this review,we take AGEs as our main object,on the one hand,discuss physiologic aging,that is,age-dependent covalent cross-linking and modification of proteins such as collagen that occur in eyes and skin containing connective tissue.On the other hand,pathological aging associated with autoimmune and inflammatory diseases,neurodegenerative diseases,diabetes and diabetic nephropathy,cardiovascular diseases and bone degenerative diseases have been mainly proposed.Based on the series of adverse effects of accelerated aging and disease pathologies caused by MRPs,the possible harm caused by some MR can be slowed down or inhibited by artificial drug intervention,dietary pattern and lifestyle control.It also stimulates people's curiosity to continue to explore the potential link between the MR and human aging and health,which should be paid more attention to for the development of life sciences.展开更多
Soluble receptor for advanced glycation end products(sRAGE)acts as a decoy sequestering of RAGE ligands,thus preventing the activation of the ligand-RAGE axis linking human diseases.However,the molecular mechanisms un...Soluble receptor for advanced glycation end products(sRAGE)acts as a decoy sequestering of RAGE ligands,thus preventing the activation of the ligand-RAGE axis linking human diseases.However,the molecular mechanisms underlying sRAGE remain unclear.In this study,THP-1 monocytes were cultured in normal glucose(NG,5.5 mmol/L)and high glucose(HG,15 mmol/L)to investigate the effects of diabetesrelevant glucose concentrations on sRAGE and interleukin-1β(IL-1β)secretion.The modulatory effects of epigallocatechin gallate(EGCG)in response to HG challenge were also evaluated.HG enhanced intracellular reactive oxygen species(ROS)generation and RAGE expression.The secretion of sRAGE,including esRAGE and cRAGE,was reduced under HG conditions,together with the downregulation of a disintegrin and metallopeptidase 10(ADAM10)and nuclear factor erythroid 2-related factor 2(Nrf2)nuclear translocation.Mechanistically,the HG effects were counteracted by siRAGE and exacerbated by siNrf2.Chromatin immunoprecipitation results showed that Nrf2 binding to the ADAM10 promoter and HG interfered with this binding.Our data reinforce the notion that RAGE and Nrf2 might be sRAGE-regulating factors.Under HG conditions,the treatment of EGCG reduced ROS generation and RAGE activation.EGCG-stimulated cRAGE release was likely caused by the upregulation of the Nrf2-ADAM10 pathway.EGCG inhibited HG-mediated NLRP3 inflammasome activation at least partly by stimulating sRAGE,thereby reducing IL-1βrelease.展开更多
Phenazine-based non-fullerene acceptors(NFAs)have demonstrated great potential in improving the power conversion efficiency(PCE)of organic solar cells(OSCs).Halogenation is known to be an effective strategy for increa...Phenazine-based non-fullerene acceptors(NFAs)have demonstrated great potential in improving the power conversion efficiency(PCE)of organic solar cells(OSCs).Halogenation is known to be an effective strategy for increasing optical absorption,refining energy levels,and improving molecular packing in organic semiconductors.Herein,a series of NFAs(Pz IC-4H,Pz IC-4F,Pz IC-4Cl,Pz IC-2Br)with phenazine as the central core and with/without halogen-substituted(dicyanomethylidene)-indan-1-one(IC)as the electron-accepting end group were synthesized,and the effect of end group matched phenazine central unit on the photovoltaic performance was systematically studied.Synergetic photophysical and morphological analyses revealed that the PM6:Pz IC-4F blend involves efficient exciton dissociation,higher charge collection and transfer rates,better crystallinity,and optimal phase separation.Therefore,OSCs based on PM6:Pz IC-4F as the active layer exhibited a PCE of 16.48%with an open circuit voltage(Voc)and energy loss of 0.880 V and 0.53 e V,respectively.Accordingly,this work demonstrated a promising approach by designing phenazine-based NFAs for achieving high-performance OSCs.展开更多
Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeu...Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA repair.Among the elements that lead to DDP resistance,O^(6)-methylguanine(O^(6)-MG)-DNA-methyltransferase(MGMT),a DNA-repair enzyme,performs a quintessential role.In this study,we clarify the significant involvement of MGMT in conferring DDP resistance in CRC,elucidating the underlying mechanism of the regulatory actions of MGMT.A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study,and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in vivo.Conversely,in cancer cells,MGMT overexpression abolishes their sensitivity to DDP treatment.Mechanistically,the interaction between MGMT and cyclin dependent kinase 1(CDK1)inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of CDK1.Meanwhile,to achieve nonhomologous end joining,MGMT interacts with XRCC6 to resist chemotherapy drugs.Our transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation,and several Wnt inhibitors can repress drug-resistant cells.In summary,our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.展开更多
Glycation of proteins and DNA forms advanced glycation end products(AGEs)causing cell and tissue dysfunction and subsequent various chronic diseases,in particular,metabolic and age-related diseases.Targeted AGE inhibi...Glycation of proteins and DNA forms advanced glycation end products(AGEs)causing cell and tissue dysfunction and subsequent various chronic diseases,in particular,metabolic and age-related diseases.Targeted AGE inhibition includes scavengers of reactive carbonyl species(RCS)such as methylglyoxal(MG),glyoxalase-1 enhancers,Nrf2/ARE pathway activators,AGE/RAGE formation inhibitors and other antiglycatng agents.Citrus flavonoids have demonstrated antioxidant and anti-inflammatory effects and are also found to be effective antiglycating agents.Herein,we reviewed the up to date progress of the antiglycation effects of citrus flavonoids and associated mechanisms.Major citrus flavonoids,hesperedin and its aglycone,hesperetin,inhibited glycation by scavenging MG forming mono-or di-flavonoid adducts with MG,enhanced the activity of glyoxase-1,activated Akt/Nrf2 signal pathway while inhibiting AGE/RAGE/NF-κB pathway,reduced the formation of Nε-(carboxylmethyl)lysine(CML)and pentosidine,inhibited aldol reductase activity and decreased the levels of fructosamine.The antiglycating activity and mechanisms of other flavonoids was also summarized in this review.In conclusion,citrus flavonoids possess effective antiglycating activity via different mechanisms,yet there are many challenging questions remaining to be studied in the near future such as in vivo testing and human study of citrus flavonoids for efficacy,effectiveness and adverse effects of citrus flavonoids as a functional food in managing high levels of AGEs and controlling AGE-induced chronic diseases,diabetic complications in particular.展开更多
Combining the detached eddy simulation(DES)method and Ffowcs Williams-Hawkings(FW-H)equation,the effect of bogie cavity end wall inclination on the flow field and aerodynamic noise in the bogie region is numerically s...Combining the detached eddy simulation(DES)method and Ffowcs Williams-Hawkings(FW-H)equation,the effect of bogie cavity end wall inclination on the flow field and aerodynamic noise in the bogie region is numerically studied.First,the simulation is conducted based on a simplified cavity-bogie model,including five cases with different inclination angles of the front and rear walls of the cavity.By comparing and analyzing the flow field and acoustic results of the five cases,the influence of the regularity and mechanism of the bogie cavity end wall inclination on the flow field and the aerodynamic noise of the bogie region are revealed.Then,the noise reduction strategy determined by the results of the simplified cavity-bogie model is applied to a three-car marshaling train model to verify its effectiveness when applied to the real train.The results reveal that the forward inclination of the cavity front wall enlarges the influence area of shear vortex structures formed at the leading edge of the cavity and intensifies the interaction between the vortex structures and the front wheelset,frontmotor,and front gearbox,resulting in the increase of the aerodynamic noise generated by the bogie itself.The backward inclination of the cavity rear wall is conducive to guiding the vortex structures flow out of the cavity and weakening the interaction between the shear vortex structures and the cavity rear wall,leading to the reduction of the aerodynamic noise generated by the bogie cavity.Inclining the rear end wall of the foremost bogie cavity of the head car is a feasible aerodynamic noise reduction measure for high-speed trains.展开更多
Cemented and mechanically clamped types of end fittings(fitting-C and fitting-M)are commonly used in transformer bushings.During the Luding Ms 6.8 earthquake that occurred in China on September 5,2022,all transformer ...Cemented and mechanically clamped types of end fittings(fitting-C and fitting-M)are commonly used in transformer bushings.During the Luding Ms 6.8 earthquake that occurred in China on September 5,2022,all transformer bushings with the two types of end fittings in a 500 kV substation were damaged.Post-earthquake field investigations were conducted,and the failures of the two types of bushings were compared.Two elementary simulation models of the transformer-bushing systems were developed to simulate the engineering failures,and further compute their seismic responses for comparison.The results indicate that the hitch lugs of the connection flange are structurally harmful to seismic resistance.Fitting-M can decrease the bending stiffness of the bushing due to the flexible sealing rubber gasket.Since it provides a more flexible connection that dissipates energy,the peak accelerations and relative displacements at the top of the bushing are significantly lower than those of the bushing with fitting-C.Compared with fitting-C,fitting-M transfers the high-stress areas from the connection flange to the root of the porcelain,so the latter becomes the most vulnerable component.Fitting-M increases the failure risk of the low-strength porcelain,indicating the unsuitability of applying it in high-intensity fortification regions.展开更多
Design and synthesis of superior cost-effective non-fullerene acceptors(NFAs)are still big challenges for facilitating the commercialization of organic solar cells(OSCs),yet to be realized.Herein,two medium bandgap fu...Design and synthesis of superior cost-effective non-fullerene acceptors(NFAs)are still big challenges for facilitating the commercialization of organic solar cells(OSCs),yet to be realized.Herein,two medium bandgap fully non-fused ring electron acceptors(NFREAs,medium bandgap,i,e.,1,3-1,8 eV),namely PTR-2Cl and PTR-4Cl are synthesized with only four steps by using intramolecular noncovalent interaction central core,structured alkyl side chain orientation linking units and flanking with different electron-withdrawing end group.Among them,PTR-4C1 exhibits increased average electrostatic potential(ESP)difference with polymer donor,enhanced crystallinity and compactπ-πstacking compared with the control molecule PTR-2CI.As a result,the PTR-4Cl-based OSC achieved an impressive power conversion efficiency(PCE)of 14.72%,with a much higher open-circuit voltage(V_(OC))of 0.953 V and significantly improved fill factor(FF)of 0.758,demonstrating one of the best acceptor material in the top-performing fully NFREA-based OSCs with both high PCE and V_(OC).Notably,PTR-4Cl-based cells maintain a good T_80lifetime of its initial PCE after over 936 h under a continuous thermal annealing treatment and over1300 h T_(80)lifetime without encapsulation.This work provides a cost-effective design strategy for NFREAs on obtaining high V_(OC),efficient exciton dissociation,and ordered molecular packing and thus high-efficiency and stable OSCs.展开更多
Non-enzymatic glycation reaction in food can produce diet-derived advanced glycation end products(dAGEs),which have potential health risks.Thus,it is of great significance to find efficient substances to improve the n...Non-enzymatic glycation reaction in food can produce diet-derived advanced glycation end products(dAGEs),which have potential health risks.Thus,it is of great significance to find efficient substances to improve the negative effects induced by dAGEs on human health.This study investigated the intervening effects of peanut skin procyanidins(PSP)on the dAGEs-induced oxidative stress and systemic inflammation in experimental mice model.Results showed that the accumulation of AGEs in serum,liver,and kidney was significantly increased after mice were fed dAGEs(P<0.05).The expression of advanced glycation product receptor(RAGE)was also significantly increased in liver and kidney(P<0.05).PSP could not only effectively reduce the accumulation of AGEs in serum,liver and kidney of mice,but also reduce the expression of RAGE in liver and kidney of mice.And the levels of pro-inflammatory cytokines interleukin-6(IL-6),tumor necrosis factor(TNF-α),and IL-1βin serum of mice were significantly decreased(P<0.05),while the levels of antiinflammatory factor IL-10 were increased,and the inflammatory injury in mice was improved.In addition,the levels of superoxide dismutase(SOD),glutathione(GSH),catalase(CAT)in liver and kidney of mice were increased(P<0.05),and the level of malondialdehyde(MDA)was decreased(P<0.05),which enhanced the antioxidant capacity of mice in vivo,and improved the oxidative damage of liver and kidney.Molecular docking technique was used to confirm that the parent compound of procyanidins and its main metabolites,such as 3-hydroxyphenylacetic acid,could interact with RAGE,which might inhibit the activation of nuclear transcription factor(NF-κB),and ultimately reduce oxidative stress and inflammation in mice.展开更多
Designing novel nonfullerene acceptors(NFAs)is of vital importance for the development of organic solar cells(OSC).Modification on the side chain and end group are two powerful tools to construct efficient NFAs.Here,b...Designing novel nonfullerene acceptors(NFAs)is of vital importance for the development of organic solar cells(OSC).Modification on the side chain and end group are two powerful tools to construct efficient NFAs.Here,based on the high-performance L8BO,we selected 3-ethylheptyl to substitute the inner chain of 2-ethylhexyl,obtaining the backbone of BON3.Then we introduced different halogen atoms of fluorine and chlorine on 2-(3-oxo-2,3-dihydro-1Hinden-1-ylidene)malononitrile end group(EG)to construct efficient NFAs named BON3-F and BON3-Cl,respectively.Polymer donor D18 was chosen to combine with two novel NFAs to construct OSC devices.Impressively,D18:BON3-Cl-based device shows a remarkable power conversion efficiency(PCE)of 18.57%,with a high open-circuit voltage(V_(OC))of 0.907 V and an excellent fill factor(FF)of 80.44%,which is one of the highest binary PCE of devices based on D18 as the donor.However,BON3-F-based device shows a relatively lower PCE of 17.79%with a decreased FF of 79.05%.The better photovoltaic performance is mainly attributed to the red-shifted absorption,higher electron and hole mobilities,reduced charge recombination,and enhanced molecular packing in the D18:BON3-Cl films.Also,we performed stability tests on two binary systems;the D18:BON3-Cl and D18:BON3-F devices maintain 88.1%and 85.5%of their initial efficiencies after 169 h of storage at 85°C in an N2-filled glove box,respectively.Our work demonstrates the importance of selecting halogen atoms on EG and provides an efficient binary system of D18:BON3-Cl for further improvement of PCE.展开更多
BACKGROUND Type 2 diabetes mellitus(T2DM)is a metabolic disease of impaired glucose utilization.Uncontrolled high sugar levels lead to advanced glycation end products(AGEs),which affects several metabolic pathways by ...BACKGROUND Type 2 diabetes mellitus(T2DM)is a metabolic disease of impaired glucose utilization.Uncontrolled high sugar levels lead to advanced glycation end products(AGEs),which affects several metabolic pathways by its receptor of advanced glycation end products(RAGE)and causes diabetic complication.MiRNAs are small RNA molecules which regulate genes linked to diabetes and affect AGEs pathogenesis,and target tissues,influencing health and disease processes.AIM To explore miRNA roles in T2DM's metabolic pathways for potential therapeutic and diagnostic advancements in diabetes complications.METHODS We systematically searched the electronic database PubMed using keywords.We included free,full-length research articles that evaluate the role of miRNAs in T2DM and its complications,focusing on genetic and molecular disease mechanisms.After assessing the full-length papers of the shortlisted articles,we included 12 research articles.RESULTS Several types of miRNAs are linked in metabolic pathways which are affected by AGE/RAGE axis in T2DM and its complications.miR-96-5p,miR-7-5p,miR-132,has_circ_0071106,miR-143,miR-21,miR-145-5p,and more are associated with various aspects of T2DM,including disease risk,diagnostic markers,complications,and gene regulation.CONCLUSION Targeting the AGE/RAGE axis,with a focus on miRNA regulation,holds promise for managing T2DM and its complications.MiRNAs have therapeutic potential as they can influence the metabolic pathways affected by AGEs and RAGE,potentially reducing inflammation,oxidative stress,and vascular complications.Additionally,miRNAs may serve as early diagnostic biomarkers for T2DM.Further research in this area may lead to innovative therapeutic strategies for diabetes and its associated complications.展开更多
Objective To determine the factors that contribute to the survival of elderly individuals diagnosed with brain glioma and develop a prognostic nomogram.Methods Data from elderly individuals(age≥65 years)histologicall...Objective To determine the factors that contribute to the survival of elderly individuals diagnosed with brain glioma and develop a prognostic nomogram.Methods Data from elderly individuals(age≥65 years)histologically diagnosed with brain glioma were sourced from the Surveillance,Epidemiology,and End Results(SEER)database.The dataset was randomly divided into a training cohort and an internal validation cohort at a 6:4 ratio.Additionally,data obtained from Tangdu Hospital constituted an external validation cohort for the study.The identification of independent prognostic factors was achieved through the least absolute shrinkage and selection operator(LASSO)and multivariate Cox regression analysis,enabling the construction of a nomogram.Model performance was evaluated using C-index,ROC curves,calibration plot and decision curve analysis(DCA).Results A cohort of 20483 elderly glioma patients was selected from the SEER database.Five prognostic factors(age,marital status,histological type,stage,and treatment)were found to significantly impact overall survival(OS)and cancer-specific survival(CSS),with tumor location emerging as a sixth variable independently linked to CSS.Subsequently,nomogram models were developed to predict the probabilities of survival at 6,12,and 24 months.The assessment findings from the validation queue indicate a that the model exhibited strong performance.Conclusion Our nomograms serve as valuable prognostic tools for assessing the survival probability of elderly glioma patients.They can potentially assist in risk stratification and clinical decision-making.展开更多
Background:Information on the possibility of drawing up Advance Directives(AD)is a necessity,and represents a major medical,ethical,and legal challenge.The difficulties are numerous,both organizational and cultural,an...Background:Information on the possibility of drawing up Advance Directives(AD)is a necessity,and represents a major medical,ethical,and legal challenge.The difficulties are numerous,both organizational and cultural,and this is also true in the context of oncology,where ADs(and more broadly,advanced palliative care)are of critical importance.As an eminently sensitive subject,dealing with ADs(and therefore with end-of-life issues)requires both societal and medical/health-care acculturation.An institutional approach has therefore been developed,to deploy information tools,training professionals,and formalize the collection of AD.Such an approach cannot be implemented without an assessment not only of its objective results but also above all of its psychological effects,on both users(patients,family caregivers)and professionals.Methods:This longitudinal study,based on a mixed-method,interdisciplinary approach,will assess the impact of this information dissemination on AD,in terms of both potential positive and negative effects,using validated measurement methods.Thus,this study follows the 5 criteria of the RE-AIM model,designed to analyze the interest and impact of a device intended for users of the healthcare system;we will use a mixed methodology,relying on both a quantitative component(counting the number of people benefiting from the scheme,and those requesting support in drawing up their DA...,administering questionnaires),as well as a qualitative component(focus groups)which will enable us to study the subjective experiences of users,their relatives and the professionals involved in the scheme.Results:The results of this study will make it possible to determine the effects of this system of assistance in the drafting of ADs,which is currently being promoted by the legislator,but which is struggling to be implemented.展开更多
Current treatment strategies for diabetic retinopathy(DR),an eye condition that can lead to blindness,have mainly focused on proliferative DR,including vitreous injection,retinal photocoagulation,and vitrectomy.Vitreo...Current treatment strategies for diabetic retinopathy(DR),an eye condition that can lead to blindness,have mainly focused on proliferative DR,including vitreous injection,retinal photocoagulation,and vitrectomy.Vitreous injections mainly depend on anti-vascular endothelial growth factor therapy.In this editorial,we comment on the article by Sun et al.We focus specifically on the mechanisms of the protective effect of genipin on the retina.Genipin is a gardenia extract used in traditional Chinese medicine(TCM).In their study,the authors suggest that controlling advanced glycosylation by the intraocular injection of genipin may be a strategy for preventing retinopathy.The innovative use of a Chinese medicine extract injected into the eye to achieve a curative effect has attracted our attention.Although TCM is effective in treating DR,the topical application of DR,especially intraocular injections,is not yet feasible.Herein,we present a brief analysis of effective Chinese medicines for the treatment of DR.The effectiveness of local injections of TCM applied directly into the eyes holds promise as an effective treatment approach for DR.展开更多
The article presents data on the study of phenological phases of blackberries in the Samarkand region in 2022-2023. The influence of differing in weather conditions, especially at the beginning and end of the growing ...The article presents data on the study of phenological phases of blackberries in the Samarkand region in 2022-2023. The influence of differing in weather conditions, especially at the beginning and end of the growing season, on the timing of onset and duration of the main phenophases of the plant is analyzed. The objects of the study were 4 varieties of different genetic and ecological-geographical origin of foreign selection: Brazos, Jumbo, Thornfree and Karaka Black. Phenological observations were carried out according to the classical methodology developed for this crop in Russia. The timing of all phenophases was significantly dependent on the temperature conditions of the growing season: in the year with a higher sum of average daily temperatures, the corresponding phenophases occurred earlier. According to preliminary data, the climatic indicators of the vegetation period of this region allow for the cultivation of blackberries of the main morphological groups (erect, semi-erect, trailing) and different ripening periods.展开更多
The Advanced Glycation End Products(AGE)binding with its receptor can increase reactive oxygen species(ROS)generation through specific signaling mediators.The effect of superoxide(O2-)and O2-mediated ROS and reactive ...The Advanced Glycation End Products(AGE)binding with its receptor can increase reactive oxygen species(ROS)generation through specific signaling mediators.The effect of superoxide(O2-)and O2-mediated ROS and reactive nitrogen species depends on their concentration and location of formation.Nitric oxide(NO)has anti-inflammatory and anticoagulant properties and a vasodilation effect,but NO can be deactivated by reacting with O_(2)^(-).This reaction between NO and O2-produces the potent oxidant ONOO−.Therefore,ONOO-'s regulatory role in AGEs in diabetic cardiovascular complications must considered as a regulator of cardiovascular complications in diabetes.展开更多
BACKGROUND Radicular cyst is a lesion of odontogenic origin that arises from epithelial remains due to periapical periodontitis caused by inflammatory reactions generated at the apex of affected teeth with infected or...BACKGROUND Radicular cyst is a lesion of odontogenic origin that arises from epithelial remains due to periapical periodontitis caused by inflammatory reactions generated at the apex of affected teeth with infected or necrotic pulps.The therapeutic mana gement of radicular cysts is controversial.There is only one case report of enucleation of a radicular cyst managed with microsurgery and apicoectomy,but without the use of the guided tissue regeneration(GTR)technique in the same surgical procedure.The present clinical case describes the management of a radicular cyst with microsurgical approach,performance of an apicoectomy of the tooth associated with the entity,application of GTR technique,use of a resorbable membrane of type I bovine collagen,and bovine xenograft.CASE SUMMARY A 68-year-old patient presented with a radicular cyst from an upper lateral incisor.The microsurgical management used was aimed at enucleating the chemical membrane,performing apicoectomy of the tooth along with careful and precise retrograde filling,and implementing GTR technique using a resorbable collagen membrane and bovine xenograft.The diagnosis of radicular cyst was confirmed using histopathological analysis.The patient underwent follow-up evaluations at 10 and 30 d postoperatively.At 4 months postoperative evaluation,she remained asymptomatic,and radiographs showed significant periapical healing with adequate bone formation.CONCLUSION These results suggest that microsurgical management using the GTR technique with collagen membrane and xenograft,contributes to bone regeneration.展开更多
文摘The mechanisms for the regulation of synaptic dopamine (DA) include its release from presynaptic vesicles, its interaction with post-synaptic and pre-synaptic DA receptors, the reuptake of DA, via dopamine transporter (DAT), the diffusion of DA and its metabolism by mono-amine oxidase (MAO) and cate- chol-O-methyl transferase (COMT). DA controls complex and specialized functions including, movements, behavior, mood, perception, reward, and more recently, neurogenesis (Popolo et al., 2004; Reimer et al., 2013) and neuroregeneration (Hoglinger et al., 2004; Yang et al., 2008). These functions are varied and of high fidelity. Movement, as an example, requires regulatory mechanisms for initiating, stopping, slowing-down speed- ing-up, changing directions, for governing the relentless urges to move in the young and sedentariness in the old as well as in motor-freezing, catalepsy, tremor and stereotypy.
基金supported by a grant from Key Laboratory of Alzheimer's Disease of Zhejiang Province,Institute of Aging,Wenzhou Medical University,No.ZJAD-2021002(to ZW)。
文摘Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the brain.The NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and aggregation.Because NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines.Here,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau phosphorylation.Using biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons.In primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis present.In the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical neurons.Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses.We also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced responses.These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in neurons.Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.
基金R.Ma thanks the support from PolyU Distinguished Postdoc Fellowship(1-YW4C)Z.Luo thanks the National Natural Science Foundation of China(NSFC,No.22309119)+7 种基金J.Wu thanks the Guangdong government and the Guangzhou government for funding(2021QN02C110)the Guangzhou Municipal Science and Technology Project(No.2023A03J0097 and 2023A03J0003)H.Yan appreciates the support from the National Key Research and Development Program of China(No.2019YFA0705900)funded by MOST,the Basic and Applied Research Major Program of Guangdong Province(No.2019B030302007)the Shen Zhen Technology and Innovation Commission through(Shenzhen Fundamental Research Program,JCYJ20200109140801751)the Hong Kong Research Grants Council(research fellow scheme RFS2021-6S05,RIF project R6021-18,CRF project C6023‐19G,GRF project 16310019,16310020,16309221,and 16309822)Hong Kong Innovation and Technology Commission(ITC‐CNERC14SC01)Foshan‐HKUST(Project NO.FSUST19‐CAT0202)Zhongshan Municipal Bureau of Science and Technology(NO.ZSST20SC02)and Tencent Xplorer Prize。
文摘With plenty of popular and effective ternary organic solar cells(OSCs)construction strategies proposed and applied,its power conversion efficiencies(PCEs)have come to a new level of over 19%in single-junction devices.However,previous studies are heavily based in chloroform(CF)leaving behind substantial knowledge deficiencies in understanding the influence of solvent choice when introducing a third component.Herein,we present a case where a newly designed asymmetric small molecular acceptor using fluoro-methoxylated end-group modification strategy,named BTP-BO-3FO with enlarged bandgap,brings different morphological evolution and performance improvement effect on host system PM6:BTP-eC9,processed by CF and ortho-xylene(o-XY).With detailed analyses supported by a series of experiments,the best PCE of 19.24%for green solvent-processed OSCs is found to be a fruit of finely tuned crystalline ordering and general aggregation motif,which furthermore nourishes a favorable charge generation and recombination behavior.Likewise,over 19%PCE can be achieved by replacing spin-coating with blade coating for active layer deposition.This work focuses on understanding the commonly met yet frequently ignored issues when building ternary blends to demonstrate cutting-edge device performance,hence,will be instructive to other ternary OSC works in the future.
基金financially supported by grants from the National Natural Science Foundation of China (82170873,81871095)the National Natural Science Foundation of China (81974503)the Tsinghua University Spring Breeze Fund (20211080005)。
文摘Maillard reaction(MR)is a non-enzymatic browning reaction commonly seen in food processing,which occurs between reducing sugars and compounds with amino groups.Despite certain advantages based on Maillard reaction products(MRPs)found in some food for health and storage application have appeared,however,the MR occurring in human physiological environment can produce advanced glycation end products(AGEs)by non-enzymatic modification of macromolecules such as proteins,lipids and nucleic acid,which could change the structure and functional activity of the molecules themselves.In this review,we take AGEs as our main object,on the one hand,discuss physiologic aging,that is,age-dependent covalent cross-linking and modification of proteins such as collagen that occur in eyes and skin containing connective tissue.On the other hand,pathological aging associated with autoimmune and inflammatory diseases,neurodegenerative diseases,diabetes and diabetic nephropathy,cardiovascular diseases and bone degenerative diseases have been mainly proposed.Based on the series of adverse effects of accelerated aging and disease pathologies caused by MRPs,the possible harm caused by some MR can be slowed down or inhibited by artificial drug intervention,dietary pattern and lifestyle control.It also stimulates people's curiosity to continue to explore the potential link between the MR and human aging and health,which should be paid more attention to for the development of life sciences.
文摘Soluble receptor for advanced glycation end products(sRAGE)acts as a decoy sequestering of RAGE ligands,thus preventing the activation of the ligand-RAGE axis linking human diseases.However,the molecular mechanisms underlying sRAGE remain unclear.In this study,THP-1 monocytes were cultured in normal glucose(NG,5.5 mmol/L)and high glucose(HG,15 mmol/L)to investigate the effects of diabetesrelevant glucose concentrations on sRAGE and interleukin-1β(IL-1β)secretion.The modulatory effects of epigallocatechin gallate(EGCG)in response to HG challenge were also evaluated.HG enhanced intracellular reactive oxygen species(ROS)generation and RAGE expression.The secretion of sRAGE,including esRAGE and cRAGE,was reduced under HG conditions,together with the downregulation of a disintegrin and metallopeptidase 10(ADAM10)and nuclear factor erythroid 2-related factor 2(Nrf2)nuclear translocation.Mechanistically,the HG effects were counteracted by siRAGE and exacerbated by siNrf2.Chromatin immunoprecipitation results showed that Nrf2 binding to the ADAM10 promoter and HG interfered with this binding.Our data reinforce the notion that RAGE and Nrf2 might be sRAGE-regulating factors.Under HG conditions,the treatment of EGCG reduced ROS generation and RAGE activation.EGCG-stimulated cRAGE release was likely caused by the upregulation of the Nrf2-ADAM10 pathway.EGCG inhibited HG-mediated NLRP3 inflammasome activation at least partly by stimulating sRAGE,thereby reducing IL-1βrelease.
基金financially supported by the National Natural Science Foundation of China (22279152,U21A20331)the National Science Fund for Distinguished Young Scholars (21925506)+1 种基金the Ningbo key scientific and technological project (2022Z117)the Ningbo Natural Science Foundation (2021J192)。
文摘Phenazine-based non-fullerene acceptors(NFAs)have demonstrated great potential in improving the power conversion efficiency(PCE)of organic solar cells(OSCs).Halogenation is known to be an effective strategy for increasing optical absorption,refining energy levels,and improving molecular packing in organic semiconductors.Herein,a series of NFAs(Pz IC-4H,Pz IC-4F,Pz IC-4Cl,Pz IC-2Br)with phenazine as the central core and with/without halogen-substituted(dicyanomethylidene)-indan-1-one(IC)as the electron-accepting end group were synthesized,and the effect of end group matched phenazine central unit on the photovoltaic performance was systematically studied.Synergetic photophysical and morphological analyses revealed that the PM6:Pz IC-4F blend involves efficient exciton dissociation,higher charge collection and transfer rates,better crystallinity,and optimal phase separation.Therefore,OSCs based on PM6:Pz IC-4F as the active layer exhibited a PCE of 16.48%with an open circuit voltage(Voc)and energy loss of 0.880 V and 0.53 e V,respectively.Accordingly,this work demonstrated a promising approach by designing phenazine-based NFAs for achieving high-performance OSCs.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.:82003807,82173394)the Shaanxi Province Science Foundation,China(Grant No.:2023-GHZD-19)+1 种基金the Medical Foundation-Clinical Integration Program of Xi'an Jiaotong University,China(Grant No.:YXJLRH2022043)the Xi'an Jiaotong University Free Exploration and Innovation-Teacher Project Foundation,China(Grant No.:xzy012023104).
文摘Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA repair.Among the elements that lead to DDP resistance,O^(6)-methylguanine(O^(6)-MG)-DNA-methyltransferase(MGMT),a DNA-repair enzyme,performs a quintessential role.In this study,we clarify the significant involvement of MGMT in conferring DDP resistance in CRC,elucidating the underlying mechanism of the regulatory actions of MGMT.A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study,and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in vivo.Conversely,in cancer cells,MGMT overexpression abolishes their sensitivity to DDP treatment.Mechanistically,the interaction between MGMT and cyclin dependent kinase 1(CDK1)inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of CDK1.Meanwhile,to achieve nonhomologous end joining,MGMT interacts with XRCC6 to resist chemotherapy drugs.Our transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation,and several Wnt inhibitors can repress drug-resistant cells.In summary,our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.
基金support from the High Level Scientific Research Cultivation Project of Huanggang Normal University(202108504)from the National Natural Science Foundation of China(31571832)。
文摘Glycation of proteins and DNA forms advanced glycation end products(AGEs)causing cell and tissue dysfunction and subsequent various chronic diseases,in particular,metabolic and age-related diseases.Targeted AGE inhibition includes scavengers of reactive carbonyl species(RCS)such as methylglyoxal(MG),glyoxalase-1 enhancers,Nrf2/ARE pathway activators,AGE/RAGE formation inhibitors and other antiglycatng agents.Citrus flavonoids have demonstrated antioxidant and anti-inflammatory effects and are also found to be effective antiglycating agents.Herein,we reviewed the up to date progress of the antiglycation effects of citrus flavonoids and associated mechanisms.Major citrus flavonoids,hesperedin and its aglycone,hesperetin,inhibited glycation by scavenging MG forming mono-or di-flavonoid adducts with MG,enhanced the activity of glyoxase-1,activated Akt/Nrf2 signal pathway while inhibiting AGE/RAGE/NF-κB pathway,reduced the formation of Nε-(carboxylmethyl)lysine(CML)and pentosidine,inhibited aldol reductase activity and decreased the levels of fructosamine.The antiglycating activity and mechanisms of other flavonoids was also summarized in this review.In conclusion,citrus flavonoids possess effective antiglycating activity via different mechanisms,yet there are many challenging questions remaining to be studied in the near future such as in vivo testing and human study of citrus flavonoids for efficacy,effectiveness and adverse effects of citrus flavonoids as a functional food in managing high levels of AGEs and controlling AGE-induced chronic diseases,diabetic complications in particular.
基金supported by National Natural Science Foundation of China(12172308)National Key Research and Development Program of China(2020YFA0710902).
文摘Combining the detached eddy simulation(DES)method and Ffowcs Williams-Hawkings(FW-H)equation,the effect of bogie cavity end wall inclination on the flow field and aerodynamic noise in the bogie region is numerically studied.First,the simulation is conducted based on a simplified cavity-bogie model,including five cases with different inclination angles of the front and rear walls of the cavity.By comparing and analyzing the flow field and acoustic results of the five cases,the influence of the regularity and mechanism of the bogie cavity end wall inclination on the flow field and the aerodynamic noise of the bogie region are revealed.Then,the noise reduction strategy determined by the results of the simplified cavity-bogie model is applied to a three-car marshaling train model to verify its effectiveness when applied to the real train.The results reveal that the forward inclination of the cavity front wall enlarges the influence area of shear vortex structures formed at the leading edge of the cavity and intensifies the interaction between the vortex structures and the front wheelset,frontmotor,and front gearbox,resulting in the increase of the aerodynamic noise generated by the bogie itself.The backward inclination of the cavity rear wall is conducive to guiding the vortex structures flow out of the cavity and weakening the interaction between the shear vortex structures and the cavity rear wall,leading to the reduction of the aerodynamic noise generated by the bogie cavity.Inclining the rear end wall of the foremost bogie cavity of the head car is a feasible aerodynamic noise reduction measure for high-speed trains.
基金National Natural Science Foundation of China under Grant No.51878508。
文摘Cemented and mechanically clamped types of end fittings(fitting-C and fitting-M)are commonly used in transformer bushings.During the Luding Ms 6.8 earthquake that occurred in China on September 5,2022,all transformer bushings with the two types of end fittings in a 500 kV substation were damaged.Post-earthquake field investigations were conducted,and the failures of the two types of bushings were compared.Two elementary simulation models of the transformer-bushing systems were developed to simulate the engineering failures,and further compute their seismic responses for comparison.The results indicate that the hitch lugs of the connection flange are structurally harmful to seismic resistance.Fitting-M can decrease the bending stiffness of the bushing due to the flexible sealing rubber gasket.Since it provides a more flexible connection that dissipates energy,the peak accelerations and relative displacements at the top of the bushing are significantly lower than those of the bushing with fitting-C.Compared with fitting-C,fitting-M transfers the high-stress areas from the connection flange to the root of the porcelain,so the latter becomes the most vulnerable component.Fitting-M increases the failure risk of the low-strength porcelain,indicating the unsuitability of applying it in high-intensity fortification regions.
基金the financial support by Hong Kong Scholar program(XJ2021-038)Young Talent Fund of Xi’an Association for Science and Technology(959202313080)+6 种基金the Natural Science Foundation Research Project of Shaanxi Province(2022JM-269)the Postgraduate Innovation and Practical Ability Training Program of Xi’an Shiyou University(YCS21212144)the National Natural Science Foundation of China(52103221,52172048,12175298)the Shandong Provincial Natural Science Foundation(ZR2021QB179,ZR2021QB024,ZR2021ZD06)the Guangdong Natural Science Foundation of China(2023A1515012323,2023A1515010943)the National Key Research and Development Program of China(2022YFB4200400)funded by MOSTthe Fundamental Research Funds of Shandong University。
文摘Design and synthesis of superior cost-effective non-fullerene acceptors(NFAs)are still big challenges for facilitating the commercialization of organic solar cells(OSCs),yet to be realized.Herein,two medium bandgap fully non-fused ring electron acceptors(NFREAs,medium bandgap,i,e.,1,3-1,8 eV),namely PTR-2Cl and PTR-4Cl are synthesized with only four steps by using intramolecular noncovalent interaction central core,structured alkyl side chain orientation linking units and flanking with different electron-withdrawing end group.Among them,PTR-4C1 exhibits increased average electrostatic potential(ESP)difference with polymer donor,enhanced crystallinity and compactπ-πstacking compared with the control molecule PTR-2CI.As a result,the PTR-4Cl-based OSC achieved an impressive power conversion efficiency(PCE)of 14.72%,with a much higher open-circuit voltage(V_(OC))of 0.953 V and significantly improved fill factor(FF)of 0.758,demonstrating one of the best acceptor material in the top-performing fully NFREA-based OSCs with both high PCE and V_(OC).Notably,PTR-4Cl-based cells maintain a good T_80lifetime of its initial PCE after over 936 h under a continuous thermal annealing treatment and over1300 h T_(80)lifetime without encapsulation.This work provides a cost-effective design strategy for NFREAs on obtaining high V_(OC),efficient exciton dissociation,and ordered molecular packing and thus high-efficiency and stable OSCs.
基金supported by the Doctoral Science Foundation of Shanxi Agricultural University(2023BQ34)Shanxi Province Work Award Fund Research Project(SXBYKY2022116).
文摘Non-enzymatic glycation reaction in food can produce diet-derived advanced glycation end products(dAGEs),which have potential health risks.Thus,it is of great significance to find efficient substances to improve the negative effects induced by dAGEs on human health.This study investigated the intervening effects of peanut skin procyanidins(PSP)on the dAGEs-induced oxidative stress and systemic inflammation in experimental mice model.Results showed that the accumulation of AGEs in serum,liver,and kidney was significantly increased after mice were fed dAGEs(P<0.05).The expression of advanced glycation product receptor(RAGE)was also significantly increased in liver and kidney(P<0.05).PSP could not only effectively reduce the accumulation of AGEs in serum,liver and kidney of mice,but also reduce the expression of RAGE in liver and kidney of mice.And the levels of pro-inflammatory cytokines interleukin-6(IL-6),tumor necrosis factor(TNF-α),and IL-1βin serum of mice were significantly decreased(P<0.05),while the levels of antiinflammatory factor IL-10 were increased,and the inflammatory injury in mice was improved.In addition,the levels of superoxide dismutase(SOD),glutathione(GSH),catalase(CAT)in liver and kidney of mice were increased(P<0.05),and the level of malondialdehyde(MDA)was decreased(P<0.05),which enhanced the antioxidant capacity of mice in vivo,and improved the oxidative damage of liver and kidney.Molecular docking technique was used to confirm that the parent compound of procyanidins and its main metabolites,such as 3-hydroxyphenylacetic acid,could interact with RAGE,which might inhibit the activation of nuclear transcription factor(NF-κB),and ultimately reduce oxidative stress and inflammation in mice.
基金supported by the National Natural Science Foundation of China(No.U21A20331)the National Science Fund for Distinguished Young Scholars(No.21925506)+3 种基金Zhejiang Provincial Natural Science Foundation of China(No.LQ22E030013)Ningbo Key Scientific and Technological Project(2022Z117)Ningbo Public Welfare Science and Technology Planning Project(2021S149)ZBTI Scientific Research Innovation Team(KYTD202105).
文摘Designing novel nonfullerene acceptors(NFAs)is of vital importance for the development of organic solar cells(OSC).Modification on the side chain and end group are two powerful tools to construct efficient NFAs.Here,based on the high-performance L8BO,we selected 3-ethylheptyl to substitute the inner chain of 2-ethylhexyl,obtaining the backbone of BON3.Then we introduced different halogen atoms of fluorine and chlorine on 2-(3-oxo-2,3-dihydro-1Hinden-1-ylidene)malononitrile end group(EG)to construct efficient NFAs named BON3-F and BON3-Cl,respectively.Polymer donor D18 was chosen to combine with two novel NFAs to construct OSC devices.Impressively,D18:BON3-Cl-based device shows a remarkable power conversion efficiency(PCE)of 18.57%,with a high open-circuit voltage(V_(OC))of 0.907 V and an excellent fill factor(FF)of 80.44%,which is one of the highest binary PCE of devices based on D18 as the donor.However,BON3-F-based device shows a relatively lower PCE of 17.79%with a decreased FF of 79.05%.The better photovoltaic performance is mainly attributed to the red-shifted absorption,higher electron and hole mobilities,reduced charge recombination,and enhanced molecular packing in the D18:BON3-Cl films.Also,we performed stability tests on two binary systems;the D18:BON3-Cl and D18:BON3-F devices maintain 88.1%and 85.5%of their initial efficiencies after 169 h of storage at 85°C in an N2-filled glove box,respectively.Our work demonstrates the importance of selecting halogen atoms on EG and provides an efficient binary system of D18:BON3-Cl for further improvement of PCE.
文摘BACKGROUND Type 2 diabetes mellitus(T2DM)is a metabolic disease of impaired glucose utilization.Uncontrolled high sugar levels lead to advanced glycation end products(AGEs),which affects several metabolic pathways by its receptor of advanced glycation end products(RAGE)and causes diabetic complication.MiRNAs are small RNA molecules which regulate genes linked to diabetes and affect AGEs pathogenesis,and target tissues,influencing health and disease processes.AIM To explore miRNA roles in T2DM's metabolic pathways for potential therapeutic and diagnostic advancements in diabetes complications.METHODS We systematically searched the electronic database PubMed using keywords.We included free,full-length research articles that evaluate the role of miRNAs in T2DM and its complications,focusing on genetic and molecular disease mechanisms.After assessing the full-length papers of the shortlisted articles,we included 12 research articles.RESULTS Several types of miRNAs are linked in metabolic pathways which are affected by AGE/RAGE axis in T2DM and its complications.miR-96-5p,miR-7-5p,miR-132,has_circ_0071106,miR-143,miR-21,miR-145-5p,and more are associated with various aspects of T2DM,including disease risk,diagnostic markers,complications,and gene regulation.CONCLUSION Targeting the AGE/RAGE axis,with a focus on miRNA regulation,holds promise for managing T2DM and its complications.MiRNAs have therapeutic potential as they can influence the metabolic pathways affected by AGEs and RAGE,potentially reducing inflammation,oxidative stress,and vascular complications.Additionally,miRNAs may serve as early diagnostic biomarkers for T2DM.Further research in this area may lead to innovative therapeutic strategies for diabetes and its associated complications.
基金supported by the Fund for Distinguished Young Scientists of the Department of Science and Technology of Shaanxi Province(No.2023-JC-JQ-68).
文摘Objective To determine the factors that contribute to the survival of elderly individuals diagnosed with brain glioma and develop a prognostic nomogram.Methods Data from elderly individuals(age≥65 years)histologically diagnosed with brain glioma were sourced from the Surveillance,Epidemiology,and End Results(SEER)database.The dataset was randomly divided into a training cohort and an internal validation cohort at a 6:4 ratio.Additionally,data obtained from Tangdu Hospital constituted an external validation cohort for the study.The identification of independent prognostic factors was achieved through the least absolute shrinkage and selection operator(LASSO)and multivariate Cox regression analysis,enabling the construction of a nomogram.Model performance was evaluated using C-index,ROC curves,calibration plot and decision curve analysis(DCA).Results A cohort of 20483 elderly glioma patients was selected from the SEER database.Five prognostic factors(age,marital status,histological type,stage,and treatment)were found to significantly impact overall survival(OS)and cancer-specific survival(CSS),with tumor location emerging as a sixth variable independently linked to CSS.Subsequently,nomogram models were developed to predict the probabilities of survival at 6,12,and 24 months.The assessment findings from the validation queue indicate a that the model exhibited strong performance.Conclusion Our nomograms serve as valuable prognostic tools for assessing the survival probability of elderly glioma patients.They can potentially assist in risk stratification and clinical decision-making.
文摘Background:Information on the possibility of drawing up Advance Directives(AD)is a necessity,and represents a major medical,ethical,and legal challenge.The difficulties are numerous,both organizational and cultural,and this is also true in the context of oncology,where ADs(and more broadly,advanced palliative care)are of critical importance.As an eminently sensitive subject,dealing with ADs(and therefore with end-of-life issues)requires both societal and medical/health-care acculturation.An institutional approach has therefore been developed,to deploy information tools,training professionals,and formalize the collection of AD.Such an approach cannot be implemented without an assessment not only of its objective results but also above all of its psychological effects,on both users(patients,family caregivers)and professionals.Methods:This longitudinal study,based on a mixed-method,interdisciplinary approach,will assess the impact of this information dissemination on AD,in terms of both potential positive and negative effects,using validated measurement methods.Thus,this study follows the 5 criteria of the RE-AIM model,designed to analyze the interest and impact of a device intended for users of the healthcare system;we will use a mixed methodology,relying on both a quantitative component(counting the number of people benefiting from the scheme,and those requesting support in drawing up their DA...,administering questionnaires),as well as a qualitative component(focus groups)which will enable us to study the subjective experiences of users,their relatives and the professionals involved in the scheme.Results:The results of this study will make it possible to determine the effects of this system of assistance in the drafting of ADs,which is currently being promoted by the legislator,but which is struggling to be implemented.
基金Supported by National Natural Science Foundation of China,No.82104862Scientific Research Project Foundation of Zhejiang Chinese Medical University,No.2023FSYYZZ01 and No.2023RCZXZK49.
文摘Current treatment strategies for diabetic retinopathy(DR),an eye condition that can lead to blindness,have mainly focused on proliferative DR,including vitreous injection,retinal photocoagulation,and vitrectomy.Vitreous injections mainly depend on anti-vascular endothelial growth factor therapy.In this editorial,we comment on the article by Sun et al.We focus specifically on the mechanisms of the protective effect of genipin on the retina.Genipin is a gardenia extract used in traditional Chinese medicine(TCM).In their study,the authors suggest that controlling advanced glycosylation by the intraocular injection of genipin may be a strategy for preventing retinopathy.The innovative use of a Chinese medicine extract injected into the eye to achieve a curative effect has attracted our attention.Although TCM is effective in treating DR,the topical application of DR,especially intraocular injections,is not yet feasible.Herein,we present a brief analysis of effective Chinese medicines for the treatment of DR.The effectiveness of local injections of TCM applied directly into the eyes holds promise as an effective treatment approach for DR.
文摘The article presents data on the study of phenological phases of blackberries in the Samarkand region in 2022-2023. The influence of differing in weather conditions, especially at the beginning and end of the growing season, on the timing of onset and duration of the main phenophases of the plant is analyzed. The objects of the study were 4 varieties of different genetic and ecological-geographical origin of foreign selection: Brazos, Jumbo, Thornfree and Karaka Black. Phenological observations were carried out according to the classical methodology developed for this crop in Russia. The timing of all phenophases was significantly dependent on the temperature conditions of the growing season: in the year with a higher sum of average daily temperatures, the corresponding phenophases occurred earlier. According to preliminary data, the climatic indicators of the vegetation period of this region allow for the cultivation of blackberries of the main morphological groups (erect, semi-erect, trailing) and different ripening periods.
文摘The Advanced Glycation End Products(AGE)binding with its receptor can increase reactive oxygen species(ROS)generation through specific signaling mediators.The effect of superoxide(O2-)and O2-mediated ROS and reactive nitrogen species depends on their concentration and location of formation.Nitric oxide(NO)has anti-inflammatory and anticoagulant properties and a vasodilation effect,but NO can be deactivated by reacting with O_(2)^(-).This reaction between NO and O2-produces the potent oxidant ONOO−.Therefore,ONOO-'s regulatory role in AGEs in diabetic cardiovascular complications must considered as a regulator of cardiovascular complications in diabetes.
文摘BACKGROUND Radicular cyst is a lesion of odontogenic origin that arises from epithelial remains due to periapical periodontitis caused by inflammatory reactions generated at the apex of affected teeth with infected or necrotic pulps.The therapeutic mana gement of radicular cysts is controversial.There is only one case report of enucleation of a radicular cyst managed with microsurgery and apicoectomy,but without the use of the guided tissue regeneration(GTR)technique in the same surgical procedure.The present clinical case describes the management of a radicular cyst with microsurgical approach,performance of an apicoectomy of the tooth associated with the entity,application of GTR technique,use of a resorbable membrane of type I bovine collagen,and bovine xenograft.CASE SUMMARY A 68-year-old patient presented with a radicular cyst from an upper lateral incisor.The microsurgical management used was aimed at enucleating the chemical membrane,performing apicoectomy of the tooth along with careful and precise retrograde filling,and implementing GTR technique using a resorbable collagen membrane and bovine xenograft.The diagnosis of radicular cyst was confirmed using histopathological analysis.The patient underwent follow-up evaluations at 10 and 30 d postoperatively.At 4 months postoperative evaluation,she remained asymptomatic,and radiographs showed significant periapical healing with adequate bone formation.CONCLUSION These results suggest that microsurgical management using the GTR technique with collagen membrane and xenograft,contributes to bone regeneration.