Parameters of peripheral blood cell have been shown as the potential predictors of erectile dysfunction(ED).To investigate the clinical significance of hematological parameters for predicting the risk of rapid ejacula...Parameters of peripheral blood cell have been shown as the potential predictors of erectile dysfunction(ED).To investigate the clinical significance of hematological parameters for predicting the risk of rapid ejaculation,we established a rat copulatory model on the basis of ejaculation distribution theory.Blood samples from different ejaculatory groups were collected for peripheral blood cell counts and serum serotonin(5-HT)tests.Meanwhile,the relationship between hematological parameters and ejaculatory behaviors was assessed.Final analysis included 11 rapid ejaculators,10 normal ejaculators,and 10 sluggish ejaculators whose complete data were available.The platelet(PLT)count in rapid ejaculators was significantly lower than that in normal and sluggish ejaculators,whereas the platelet distribution width(PDW)and mean platelet volume(MPV)were significantly greater in rapid ejaculators.Multivariate logistic regression analysis and receiver operating characteristic(ROC)curve analysis showed that the PLT was an independent protective factor for rapid ejaculation.Meanwhile,rapid ejaculators were found to have the lowest serum 5-HT compared to normal and sluggish ejaculators(P<0.001).Furthermore,there was a positive correlation between the PLT and serum 5-HT(r=0.662,P<0.001),indicating that the PLT could indirectly reflect the serum 5-HT concentration.In addition,we assessed the association between the PLT and ejaculatory parameters.There was a negative correlation between ejaculation frequency(EF)and the PLT(r=−0.595,P<0.001),whereas there was a positive correlation between ejaculation latency(EL)and the PLT(r=0.740,P<0.001).This study indicated that the PLT might be a useful and convenient diagnostic marker for predicting the risk of rapid ejaculation.展开更多
Orofacial clefts(OFCs),particularly cleft lip with or without cleft palate(CL/P)and cleft palate only(CPO),are among the most common birth defects in humans(Mossey et al.,2009;Dixon et al.,2011).The birth prevalence r...Orofacial clefts(OFCs),particularly cleft lip with or without cleft palate(CL/P)and cleft palate only(CPO),are among the most common birth defects in humans(Mossey et al.,2009;Dixon et al.,2011).The birth prevalence rate of OFCs in China is reported to be as high as 1.66 per thousand newborns.展开更多
Objective Autism spectrum disorder(ASD)is a neurodevelopmental condition characterized by difficulties with communication and social interaction,restricted and repetitive behaviors.Previous studies have indicated that...Objective Autism spectrum disorder(ASD)is a neurodevelopmental condition characterized by difficulties with communication and social interaction,restricted and repetitive behaviors.Previous studies have indicated that individuals with ASD exhibit early and lifelong attention deficits,which are closely related to the core symptoms of ASD.Basic visual attention processes may provide a critical foundation for their social communication and interaction abilities.Therefore,this study explores the behavior of children with ASD in capturing attention to changes in topological properties.Methods Our study recruited twenty-seven ASD children diagnosed by professional clinicians according to DSM-5 and twenty-eight typically developing(TD)age-matched controls.In an attention capture task,we recorded the saccadic behaviors of children with ASD and TD in response to topological change(TC)and non-topological change(nTC)stimuli.Saccadic reaction time(SRT),visual search time(VS),and first fixation dwell time(FFDT)were used as indicators of attentional bias.Pearson correlation tests between the clinical assessment scales and attentional bias were conducted.Results This study found that TD children had significantly faster SRT(P<0.05)and VS(P<0.05)for the TC stimuli compared to the nTC stimuli,while the children with ASD did not exhibit significant differences in either measure(P>0.05).Additionally,ASD children demonstrated significantly less attention towards the TC targets(measured by FFDT),in comparison to TD children(P<0.05).Furthermore,ASD children exhibited a significant negative linear correlation between their attentional bias(measured by VS)and their scores on the compulsive subscale(P<0.05).Conclusion The results suggest that children with ASD have difficulty shifting their attention to objects with topological changes during change detection.This atypical attention may affect the child’s cognitive and behavioral development,thereby impacting their social communication and interaction.In sum,our findings indicate that difficulties in attentional capture by TC may be a key feature of ASD.展开更多
BACKGROUND Exploring hypnotherapy's potential to modulate attention bias offers promising avenues for treating social anxiety disorder(SAD).AIM To determine if hypnotherapy can alleviate social anxiety by influenc...BACKGROUND Exploring hypnotherapy's potential to modulate attention bias offers promising avenues for treating social anxiety disorder(SAD).AIM To determine if hypnotherapy can alleviate social anxiety by influencing attention bias,specifically identifying the aspects of attention processes affected by hypnosis.METHODS In this study,69 SAD participants were divided into three groups based on their Liebowitz Social Anxiety Scale scores:Experimental group,control group,and baseline group.The experimental group(n=23)underwent six weekly hypnosis sessions,while the control(n=23)and baseline groups(n=23)received no treatment.To evaluate alterations in SAD severity and attention bias towards threatening stimuli following hypnotherapy,we employed a combination of self-report questionnaires,an odd-one-out task,and electroencephalography recordings.RESULTS The experimental group showed significant reductions in P1,N170,N2pc,and late positive potential(LPP)brain wave activities during attention sensitivity and disengagement conditions.This indicates that hypnotherapy modulates early-stage face processing and later-stage emotional evaluation of threat-related stimuli in SAD patients.CONCLUSION Our findings highlight P1,N170,N2pc,and LPP as key neural markers in SAD treatment.By identifying these neural markers influenced by hypnotherapy,we offer insight into the mechanisms by which this treatment modality impacts attentional processes,potentially easing SAD symptoms.展开更多
Precision therapy has become the preferred choice attributed to the optimal drug concentration in target sites,increased therapeutic efficacy,and reduced adverse effects.Over the past few years,sprayable or injectable...Precision therapy has become the preferred choice attributed to the optimal drug concentration in target sites,increased therapeutic efficacy,and reduced adverse effects.Over the past few years,sprayable or injectable thermosensitive hydrogels have exhibited high therapeutic potential.These can be applied as cell-growing scaffolds or drug-releasing reservoirs by simply mixing in a free-flowing sol phase at room temperature.Inspired by their unique properties,thermosensitive hydrogels have been widely applied as drug delivery and treatment platforms for precision medicine.In this review,the state-of-theart developments in thermosensitive hydrogels for precision therapy are investigated,which covers from the thermo-gelling mechanisms and main components to biomedical applications,including wound healing,anti-tumor activity,osteogenesis,and periodontal,sinonasal and ophthalmic diseases.The most promising applications and trends of thermosensitive hydrogels for precision therapy are also discussed in light of their unique features.展开更多
Psoriasis is caused by many factors and is characterized by excessive proliferation of the epidermis and erythema with silver scales on the surface of the skin and concomitant with a variety of diseases(Griffiths et a...Psoriasis is caused by many factors and is characterized by excessive proliferation of the epidermis and erythema with silver scales on the surface of the skin and concomitant with a variety of diseases(Griffiths et al., 2021). Despite the unclear aetiology,increasing evidence has demonstrated that genetic factors play key roles in the pathogenesis of psoriasis.展开更多
Oxidative stress,dysbiosis,and immune dysregulation have been confirmed to play pivotal roles in the complex pathogenesis of inflammatory bowel disease(IBD).Herein,we design copper ion-luteolin nanocomplexes(CuL NCs)t...Oxidative stress,dysbiosis,and immune dysregulation have been confirmed to play pivotal roles in the complex pathogenesis of inflammatory bowel disease(IBD).Herein,we design copper ion-luteolin nanocomplexes(CuL NCs)through a metal-polyphenol coordination strategy,which plays a multifaceted role in the amelioration of IBD.The fabricated CuL NCs function as therapeutic agents with exceptional antioxidant and anti-inflammatory capabilities because of their great stability and capacity to scavenge reactive oxygen species(ROS).It can effectively modulate the inflammatory microenvironment including facilitating the efficient reduction of pro-inflammatory cytokine levels,protecting intestinal epithelial cells,promoting mucosal barrier repair and regu-lating intestinal microbiota.In addition,CuL NCs have been found to enhance cellular antioxidant and anti-inflammatory capacities by regulating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1(Nrf2/HO-1)oxidative stress pathway and nuclear factor kappa B(NF-κB)signaling pathway,respectively.Notably,CuL NCs demonstrate significant prophylactic and therapeutic efficacy in mouse models with typical IBD,including ulcerative colitis(UC)and Crohn’s disease(CD).This study provides a new approach for building multifaceted therapeutic platforms for natural products to treat IBD.展开更多
UCNPs@AgBiS_(2) core-shell nanoparticles that AgBiS_(2) coated on the surface of upconversion nanoparticles (UCNPs) was successfully prepared through an ion exchange reaction. The photothermal conversion efficiency of...UCNPs@AgBiS_(2) core-shell nanoparticles that AgBiS_(2) coated on the surface of upconversion nanoparticles (UCNPs) was successfully prepared through an ion exchange reaction. The photothermal conversion efficiency of AgBiS_(2) can be improved from 14.7% to 45% due to the cross relaxation between Nd ions and AgBiS_(2). The doping concentration of Nd ions played a critical role in the production of reactive oxygen species (ROS) and enhanced the photothermal conversion efficiency. The NaYF4:Yb/Er/Nd@NaYF4:Nd nanoparticles endows strong upcon-version emissions when the doped concentration of Nd ions is 1% in the inner core, which excites the AgBiS_(2) shell to produce ROS for photodynamic therapy (PDT) of cancer cells. As a result, the as-prepared NaYF4:Yb/Er/ Nd@NaYF4:Nd@AgBiS_(2) core-shell nanoparticles showed combined photothermal/photodynamic therapy (PTT/ PDT) against malignant tumors. This work provides an alternative near-infrared light-active multimodal nano-structures for applications such as fighting against cancers.展开更多
Methicillin-resistant Staphylococcus aureus(MRSA)has become a rising clinical problem as its occurrence has increased due to the overuse and misuse of antibiotics.In this work,upconversion nanoparticles@AgBiS2 core–s...Methicillin-resistant Staphylococcus aureus(MRSA)has become a rising clinical problem as its occurrence has increased due to the overuse and misuse of antibiotics.In this work,upconversion nanoparticles@AgBiS2 core–shell were produced with enhanced photothermal transformation efficiency and ability to produce reactive oxygen species for synergistic photodynamic photothermal and photodynamic antibacterial performance.The nanoparticles exhibit good antibacterial effects in vitro and satisfactory therapeutic performance on healing MRSA-infected wounds in vivo experiments.RNA-sequencing technique has been used to investigate and reveal that photothermal–photodynamic therapy using the nanoparticles can interfere with metabolic processes such as galactose metabolism in MRSA bacteria,destroy the transport system on the surface of MRSA,and affect quorum sensing to hinder the formation of biofilms to achieve effective antibacterial efficacy.It was demonstrated that this work presents an alternative near-infrared photoactive multimodal nanostructure for antibacterial applications.展开更多
Oxidative stress that is induced by excessive reactive oxygen species(ROS)is considered to be a key pathophysiological mechanism of inflammatory bowel disease(IBD),and restoring redox homeostasis in the inflammatory r...Oxidative stress that is induced by excessive reactive oxygen species(ROS)is considered to be a key pathophysiological mechanism of inflammatory bowel disease(IBD),and restoring redox homeostasis in the inflammatory region by eliminating ROS is an effective way to treat IBD.Herein,ultrasmall Au_(25)nanoclusters(Au_(25)NCs)were synthesized using a simple improved protocol,which has good physiological stability and biosafety and can be noninvasively monitored by clinical computed tomography(CT)after oral administration.Au_(25)NCs can eliminate ROS such as ABTS radicals,superoxide free radicals(·O_(2)^(−)),and hydroxyl free radicals(·OH),upregulate the expression level of antioxidant enzymes,inhibit the expression of proinflammatory cytokines,and finally interrupt the inflammatory circuit of IBD to achieve the effective prevention and delayed treatment of IBD.This work will demonstrate the protective effect of Au_(25)NCs on IBD in living animals,which suggests a new nanomedicine strategy for IBD treatment.展开更多
Triple-negative breast cancer(TNBC)remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies.In this study,we introduce a“brake-release and accelerator-pressing”approach t...Triple-negative breast cancer(TNBC)remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies.In this study,we introduce a“brake-release and accelerator-pressing”approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles(Cu-PB)and the ferroptosis inducer sorafenib(SRF)for raised chemodynamic(CDT)/photothermal(PTT)combination therapy against TNBC.Upon transdermal insertion,the dissolving microneedles swiftly disintegrate and facilitate the release of SRF.Under gentle external light exposure,copper ions(Cu^(2+))and iron ions(Fe^(3+))were liberated from Cu-PB.The direct chelation of Cu^(2+)and the indirect suppression by SRF,collectively attenuate glutathione peroxidase 4(GPX4)enzymatic function,destabilizing the cellular redox equilibrium(referred to as the“brake-release”strategy).The release of Cu^(2+)and Fe^(3+)ions instigates a Fenton/Fenton-like reaction within tumor cells,further yielding hydroxyl radicals and elevating reactive oxygen species(ROS)concentrations(referred to as the“accelerator-pressing”strategy).This overwhelming ROS accumulation,coupled with the impaired clearance of resultant lipid peroxides(LPO),ultimately triggers a robust ferroptosis cell death response.In summary,this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC,implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.展开更多
The subgenual anterior cingulate cortex(sgACC)plays a central role in the pathophysiology of major depressive disorder(MDD).Its functional interactive profile with the left dorsal lateral prefrontal cortex(DLPFC)is as...The subgenual anterior cingulate cortex(sgACC)plays a central role in the pathophysiology of major depressive disorder(MDD).Its functional interactive profile with the left dorsal lateral prefrontal cortex(DLPFC)is associated with transcranial magnetic stimulation(TMS)treatment outcomes.Previous research on sgACC functional connectivity(FC)in MDD has yielded inconsistent results,partly due to small sample sizes and limited statistical power.Furthermore,calculating sgACC-FC to target TMS individually is challenging.We used a large multi-site cross-sectional sample(1660 patients with MDD vs.1341 healthy controls)from Phase Ⅱ of the Depression Imaging REsearch ConsorTium(DIRECT)to systematically delineate case-control difference maps of sgACC-FC.We explored the potential impact of group-level abnormality profiles on TMS target localization and clinical efficacy.Next,we developed an MDD big data-guided,individualized TMS targeting algorithm to integrate group-level statistical maps with individual-level brain activity to individually localize TMS targets.We found enhanced sgACCDLPFC FC in patients with MDD compared with healthy controls(HC).These group differences altered the position of the sgACC anti-correlation peak in the left DLPFC.We showed that the magnitude of case-control differences in the sgACC-FC was related to clinical improvement in two independent clinical samples.This targeting algorithm may generate targets demonstrating stronger associations with clinical efficiency than group-level targets.We reliably delineated MDD-related abnormalities of sgACC-FC profiles in a large,independently ascertained sample and demonstrated the potential impact of such casecontrol differences on FC-guided localization of TMS targets.展开更多
Bacterial infection hampers wound repair by impeding the healing process.Concurrently,inflammation at the wound site triggers the production of reactive oxygen species(ROS),causing oxidative stress and damage to prote...Bacterial infection hampers wound repair by impeding the healing process.Concurrently,inflammation at the wound site triggers the production of reactive oxygen species(ROS),causing oxidative stress and damage to proteins and cells.This can lead to chronic wounds,posing severe risks.Therefore,eliminating bacterial infection and reducing ROS levels are crucial for effective wound healing.Nanozymes,possessing enzyme-like catalytic activity,can convert endogenous substances into highly toxic substances,such as ROS,to combat bacteria and biofilms without inducing drug resistance.However,the current nanozyme model with single enzyme activity falls short of meeting the complex requirements of antimicrobial therapy.Thus,developing nanozymes with multiple enzymatic activities is essential.Herein,we engineered a novel metalloenzyme called Ru-procyanidin nanoparticles(Ru-PC NPs)with diverse enzymatic activities to aid wound healing and combat bacterial infections.Under acidic conditions,due to their glutathione(GSH)depletion and peroxidase(POD)-like activity,Ru-PC NPs combined with H2O2 exhibit excellent antibacterial effects.However,in a neutral environment,the Ru-PC NPs,with catalase(CAT)activity,decompose H2O2 to O2,alleviating hypoxia and ensuring a sufficient oxygen supply.Furthermore,Ru-PC NPs possess exceptional antioxidant capacity through their superior superoxide dismutase(SOD)enzyme activity,effectively scavenging excess ROS and reactive nitrogen species(RNS)in a neutral environment.This maintains the balance of the antioxidant system and prevents inflammation.Ru-PC NPs also promote the polarization of macrophages from M1 to M2,facilitating wound healing.More importantly,Ru-PC NPs show good biosafety with negligible toxicity.In vivo wound infection models have confirmed the efficacy of Ru-PC NPs in inhibiting bacterial infection and promoting wound healing.The focus of this work highlights the quadruple enzymatic activity of Ru-PC NPs and its potential to reduce inflammation and promote bacteria-infected wound healing.展开更多
Dear Editor,Acute Myeloid Leukemia(AML)patients are often found ineligible for aggressive standard chemotherapy in clinic because of old age and poor conditions.Current evidences suggest that targeted combination ther...Dear Editor,Acute Myeloid Leukemia(AML)patients are often found ineligible for aggressive standard chemotherapy in clinic because of old age and poor conditions.Current evidences suggest that targeted combination therapy might help these patients achieve a higher response rate with acceptable adverse events(AEs).^(1)Venetoclax(VEN),a selective small-molecule BCL2 inhibitor,combined with hypomethylating agent(HMA),such as azacytidine(AZA).展开更多
基金funded by the Research Foundation of Anhui Provincial Institute of Translational Medicine(No.2023zhyx-C94)the National Natural Science Foundation of China(No.82071637).
文摘Parameters of peripheral blood cell have been shown as the potential predictors of erectile dysfunction(ED).To investigate the clinical significance of hematological parameters for predicting the risk of rapid ejaculation,we established a rat copulatory model on the basis of ejaculation distribution theory.Blood samples from different ejaculatory groups were collected for peripheral blood cell counts and serum serotonin(5-HT)tests.Meanwhile,the relationship between hematological parameters and ejaculatory behaviors was assessed.Final analysis included 11 rapid ejaculators,10 normal ejaculators,and 10 sluggish ejaculators whose complete data were available.The platelet(PLT)count in rapid ejaculators was significantly lower than that in normal and sluggish ejaculators,whereas the platelet distribution width(PDW)and mean platelet volume(MPV)were significantly greater in rapid ejaculators.Multivariate logistic regression analysis and receiver operating characteristic(ROC)curve analysis showed that the PLT was an independent protective factor for rapid ejaculation.Meanwhile,rapid ejaculators were found to have the lowest serum 5-HT compared to normal and sluggish ejaculators(P<0.001).Furthermore,there was a positive correlation between the PLT and serum 5-HT(r=0.662,P<0.001),indicating that the PLT could indirectly reflect the serum 5-HT concentration.In addition,we assessed the association between the PLT and ejaculatory parameters.There was a negative correlation between ejaculation frequency(EF)and the PLT(r=−0.595,P<0.001),whereas there was a positive correlation between ejaculation latency(EL)and the PLT(r=0.740,P<0.001).This study indicated that the PLT might be a useful and convenient diagnostic marker for predicting the risk of rapid ejaculation.
基金funded by the National Natural Science Foundation of China(81970904 to MH,81970923 to ZB)Anhui Institute of Translational Medicine(ZHYX2020A005 to LS)+2 种基金the University Synergy Innovation Program of Anhui Province(GXXT-2020-064 to LS)Clinical medicine discipline construction project of Anhui Medical University(2021lcxk008 to LS)the National Key Research and Development Program(2016YFC1000505 to ZB)。
文摘Orofacial clefts(OFCs),particularly cleft lip with or without cleft palate(CL/P)and cleft palate only(CPO),are among the most common birth defects in humans(Mossey et al.,2009;Dixon et al.,2011).The birth prevalence rate of OFCs in China is reported to be as high as 1.66 per thousand newborns.
文摘Objective Autism spectrum disorder(ASD)is a neurodevelopmental condition characterized by difficulties with communication and social interaction,restricted and repetitive behaviors.Previous studies have indicated that individuals with ASD exhibit early and lifelong attention deficits,which are closely related to the core symptoms of ASD.Basic visual attention processes may provide a critical foundation for their social communication and interaction abilities.Therefore,this study explores the behavior of children with ASD in capturing attention to changes in topological properties.Methods Our study recruited twenty-seven ASD children diagnosed by professional clinicians according to DSM-5 and twenty-eight typically developing(TD)age-matched controls.In an attention capture task,we recorded the saccadic behaviors of children with ASD and TD in response to topological change(TC)and non-topological change(nTC)stimuli.Saccadic reaction time(SRT),visual search time(VS),and first fixation dwell time(FFDT)were used as indicators of attentional bias.Pearson correlation tests between the clinical assessment scales and attentional bias were conducted.Results This study found that TD children had significantly faster SRT(P<0.05)and VS(P<0.05)for the TC stimuli compared to the nTC stimuli,while the children with ASD did not exhibit significant differences in either measure(P>0.05).Additionally,ASD children demonstrated significantly less attention towards the TC targets(measured by FFDT),in comparison to TD children(P<0.05).Furthermore,ASD children exhibited a significant negative linear correlation between their attentional bias(measured by VS)and their scores on the compulsive subscale(P<0.05).Conclusion The results suggest that children with ASD have difficulty shifting their attention to objects with topological changes during change detection.This atypical attention may affect the child’s cognitive and behavioral development,thereby impacting their social communication and interaction.In sum,our findings indicate that difficulties in attentional capture by TC may be a key feature of ASD.
基金Supported by National Natural Science Foundation of China,No.82090034the Key Laboratory of Philosophy and Social Science of Anhui Province on Adolescent Mental Health and Crisis Intelligence Intervention,No.SYS2023B08the Anhui Natural Science Foundation,No.2023AH040086.
文摘BACKGROUND Exploring hypnotherapy's potential to modulate attention bias offers promising avenues for treating social anxiety disorder(SAD).AIM To determine if hypnotherapy can alleviate social anxiety by influencing attention bias,specifically identifying the aspects of attention processes affected by hypnosis.METHODS In this study,69 SAD participants were divided into three groups based on their Liebowitz Social Anxiety Scale scores:Experimental group,control group,and baseline group.The experimental group(n=23)underwent six weekly hypnosis sessions,while the control(n=23)and baseline groups(n=23)received no treatment.To evaluate alterations in SAD severity and attention bias towards threatening stimuli following hypnotherapy,we employed a combination of self-report questionnaires,an odd-one-out task,and electroencephalography recordings.RESULTS The experimental group showed significant reductions in P1,N170,N2pc,and late positive potential(LPP)brain wave activities during attention sensitivity and disengagement conditions.This indicates that hypnotherapy modulates early-stage face processing and later-stage emotional evaluation of threat-related stimuli in SAD patients.CONCLUSION Our findings highlight P1,N170,N2pc,and LPP as key neural markers in SAD treatment.By identifying these neural markers influenced by hypnotherapy,we offer insight into the mechanisms by which this treatment modality impacts attentional processes,potentially easing SAD symptoms.
基金financially supported by the National Natural Science Foundation of China(Grants 52172276)fund from Anhui Provincial Institute of Translational Medicine(2021zhyx-B15)。
文摘Precision therapy has become the preferred choice attributed to the optimal drug concentration in target sites,increased therapeutic efficacy,and reduced adverse effects.Over the past few years,sprayable or injectable thermosensitive hydrogels have exhibited high therapeutic potential.These can be applied as cell-growing scaffolds or drug-releasing reservoirs by simply mixing in a free-flowing sol phase at room temperature.Inspired by their unique properties,thermosensitive hydrogels have been widely applied as drug delivery and treatment platforms for precision medicine.In this review,the state-of-theart developments in thermosensitive hydrogels for precision therapy are investigated,which covers from the thermo-gelling mechanisms and main components to biomedical applications,including wound healing,anti-tumor activity,osteogenesis,and periodontal,sinonasal and ophthalmic diseases.The most promising applications and trends of thermosensitive hydrogels for precision therapy are also discussed in light of their unique features.
基金supported by grants from the National Natural Science Foundation of China(81972927,81773313)Anhui Institute of Translational Medicine(ZHYX2020A005)。
文摘Psoriasis is caused by many factors and is characterized by excessive proliferation of the epidermis and erythema with silver scales on the surface of the skin and concomitant with a variety of diseases(Griffiths et al., 2021). Despite the unclear aetiology,increasing evidence has demonstrated that genetic factors play key roles in the pathogenesis of psoriasis.
基金supported by the National Natural Science Foundation of China(Grants 82200610)the Natural Science Foundation of Hubei Province(2024AFB109)the Basic and Clinical Cooperative Research and Promotion Program of Anhui Medical University(2021xkjT027).
文摘Oxidative stress,dysbiosis,and immune dysregulation have been confirmed to play pivotal roles in the complex pathogenesis of inflammatory bowel disease(IBD).Herein,we design copper ion-luteolin nanocomplexes(CuL NCs)through a metal-polyphenol coordination strategy,which plays a multifaceted role in the amelioration of IBD.The fabricated CuL NCs function as therapeutic agents with exceptional antioxidant and anti-inflammatory capabilities because of their great stability and capacity to scavenge reactive oxygen species(ROS).It can effectively modulate the inflammatory microenvironment including facilitating the efficient reduction of pro-inflammatory cytokine levels,protecting intestinal epithelial cells,promoting mucosal barrier repair and regu-lating intestinal microbiota.In addition,CuL NCs have been found to enhance cellular antioxidant and anti-inflammatory capacities by regulating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1(Nrf2/HO-1)oxidative stress pathway and nuclear factor kappa B(NF-κB)signaling pathway,respectively.Notably,CuL NCs demonstrate significant prophylactic and therapeutic efficacy in mouse models with typical IBD,including ulcerative colitis(UC)and Crohn’s disease(CD).This study provides a new approach for building multifaceted therapeutic platforms for natural products to treat IBD.
基金This work was financially supported by the National Natural Science Foundation of China(Grants 52172276,U20A20379),research fund from Anhui Provincial Institute of Translational Medicine(2021zhyx-B15)Grants for Scientific Research of BSKY(No:XJ201933)from Anhui Medical University.Zhaoyou Chu,Tian Tian,and Zhenchao Tao contributed equally to this work.
文摘UCNPs@AgBiS_(2) core-shell nanoparticles that AgBiS_(2) coated on the surface of upconversion nanoparticles (UCNPs) was successfully prepared through an ion exchange reaction. The photothermal conversion efficiency of AgBiS_(2) can be improved from 14.7% to 45% due to the cross relaxation between Nd ions and AgBiS_(2). The doping concentration of Nd ions played a critical role in the production of reactive oxygen species (ROS) and enhanced the photothermal conversion efficiency. The NaYF4:Yb/Er/Nd@NaYF4:Nd nanoparticles endows strong upcon-version emissions when the doped concentration of Nd ions is 1% in the inner core, which excites the AgBiS_(2) shell to produce ROS for photodynamic therapy (PDT) of cancer cells. As a result, the as-prepared NaYF4:Yb/Er/ Nd@NaYF4:Nd@AgBiS_(2) core-shell nanoparticles showed combined photothermal/photodynamic therapy (PTT/ PDT) against malignant tumors. This work provides an alternative near-infrared light-active multimodal nano-structures for applications such as fighting against cancers.
基金supported by the National Natural Science Foundation of China(No.52172276).
文摘Methicillin-resistant Staphylococcus aureus(MRSA)has become a rising clinical problem as its occurrence has increased due to the overuse and misuse of antibiotics.In this work,upconversion nanoparticles@AgBiS2 core–shell were produced with enhanced photothermal transformation efficiency and ability to produce reactive oxygen species for synergistic photodynamic photothermal and photodynamic antibacterial performance.The nanoparticles exhibit good antibacterial effects in vitro and satisfactory therapeutic performance on healing MRSA-infected wounds in vivo experiments.RNA-sequencing technique has been used to investigate and reveal that photothermal–photodynamic therapy using the nanoparticles can interfere with metabolic processes such as galactose metabolism in MRSA bacteria,destroy the transport system on the surface of MRSA,and affect quorum sensing to hinder the formation of biofilms to achieve effective antibacterial efficacy.It was demonstrated that this work presents an alternative near-infrared photoactive multimodal nanostructure for antibacterial applications.
基金financially supported by the National Natural Science Foundation of China(82170572)research fund from Anhui Provincial Institute of Translational Medicine(2021zhyx-B15)Grants for Anhui Medical University Basic and Clinical Collaborative Research Promotion Program(2021xkjT027)from Anhui Medical University.
文摘Oxidative stress that is induced by excessive reactive oxygen species(ROS)is considered to be a key pathophysiological mechanism of inflammatory bowel disease(IBD),and restoring redox homeostasis in the inflammatory region by eliminating ROS is an effective way to treat IBD.Herein,ultrasmall Au_(25)nanoclusters(Au_(25)NCs)were synthesized using a simple improved protocol,which has good physiological stability and biosafety and can be noninvasively monitored by clinical computed tomography(CT)after oral administration.Au_(25)NCs can eliminate ROS such as ABTS radicals,superoxide free radicals(·O_(2)^(−)),and hydroxyl free radicals(·OH),upregulate the expression level of antioxidant enzymes,inhibit the expression of proinflammatory cytokines,and finally interrupt the inflammatory circuit of IBD to achieve the effective prevention and delayed treatment of IBD.This work will demonstrate the protective effect of Au_(25)NCs on IBD in living animals,which suggests a new nanomedicine strategy for IBD treatment.
基金financially supported by the Research Fund of Anhui Institute of Translational Medicine(2022zhyx-B02,China)the Distinguished Youth of Natural Science Research Projects in Anhui Province Universities(2024AH020005,China)+1 种基金the Anhui Provincial Natural Science Foundation(2208085Y24,China)Open Project of Key Laboratory of Science and Engineering for the Multi-modal Prevention and Control of Major Chronic Diseases,Ministry of Industry and Information Technology(MCD-2023-1-14,China).
文摘Triple-negative breast cancer(TNBC)remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies.In this study,we introduce a“brake-release and accelerator-pressing”approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles(Cu-PB)and the ferroptosis inducer sorafenib(SRF)for raised chemodynamic(CDT)/photothermal(PTT)combination therapy against TNBC.Upon transdermal insertion,the dissolving microneedles swiftly disintegrate and facilitate the release of SRF.Under gentle external light exposure,copper ions(Cu^(2+))and iron ions(Fe^(3+))were liberated from Cu-PB.The direct chelation of Cu^(2+)and the indirect suppression by SRF,collectively attenuate glutathione peroxidase 4(GPX4)enzymatic function,destabilizing the cellular redox equilibrium(referred to as the“brake-release”strategy).The release of Cu^(2+)and Fe^(3+)ions instigates a Fenton/Fenton-like reaction within tumor cells,further yielding hydroxyl radicals and elevating reactive oxygen species(ROS)concentrations(referred to as the“accelerator-pressing”strategy).This overwhelming ROS accumulation,coupled with the impaired clearance of resultant lipid peroxides(LPO),ultimately triggers a robust ferroptosis cell death response.In summary,this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC,implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.
基金the Beijing Nova Program of Science and Technology(20230484465)the Beijing Natural Science Foundation(J230040)+12 种基金the National Natural Science Foundation of China(82122035,81671774,81630031,and 32300933)the Sci-Tech Innovation 2030–Major Project of Brain Science and Braininspired Intelligence Technology(2021ZD0200600)the National Key R&D Program of China(2017YFC1309902)the Key Research Program of the Chinese Academy of Sciences(ZDBS-SSW-JSC006)the Scientific Foundation of Institute of Psychology,Chinese Academy of Sciences(E2CX4425YZ,E3CX1315,and Y9CX422005)the China Postdoctoral Science Foundation(2019M660847)the China National Postdoctoral Program for Innovative Talents(BX20200360)the Special Research Assistant Program of the Chinese Academy of Sciences(E2CX0624)the Key R&D Program of Sichuan Province(2023YFS0076)the Canadian Institutes of Health Research(CIHR),the National Institutes of Health–US(NIH)the Brain Canada Foundationthe Temerty Family through the Centre for Addiction and Mental Health(CAMH)Foundation and the Campbell Family Research Institutethe China Scholarship Council(202104910248)during a visit of Xiao Chen to the Centre for Addiction and Mental Health is acknowledged.
文摘The subgenual anterior cingulate cortex(sgACC)plays a central role in the pathophysiology of major depressive disorder(MDD).Its functional interactive profile with the left dorsal lateral prefrontal cortex(DLPFC)is associated with transcranial magnetic stimulation(TMS)treatment outcomes.Previous research on sgACC functional connectivity(FC)in MDD has yielded inconsistent results,partly due to small sample sizes and limited statistical power.Furthermore,calculating sgACC-FC to target TMS individually is challenging.We used a large multi-site cross-sectional sample(1660 patients with MDD vs.1341 healthy controls)from Phase Ⅱ of the Depression Imaging REsearch ConsorTium(DIRECT)to systematically delineate case-control difference maps of sgACC-FC.We explored the potential impact of group-level abnormality profiles on TMS target localization and clinical efficacy.Next,we developed an MDD big data-guided,individualized TMS targeting algorithm to integrate group-level statistical maps with individual-level brain activity to individually localize TMS targets.We found enhanced sgACCDLPFC FC in patients with MDD compared with healthy controls(HC).These group differences altered the position of the sgACC anti-correlation peak in the left DLPFC.We showed that the magnitude of case-control differences in the sgACC-FC was related to clinical improvement in two independent clinical samples.This targeting algorithm may generate targets demonstrating stronger associations with clinical efficiency than group-level targets.We reliably delineated MDD-related abnormalities of sgACC-FC profiles in a large,independently ascertained sample and demonstrated the potential impact of such casecontrol differences on FC-guided localization of TMS targets.
基金This work was supported by the National Natural Science Foundation of China(52202343,82172204,82372552,82372517)Anhui Key Research and Development Plan(grant No.202104j07020027,China)+2 种基金Anhui Province Natural Science Foundation(2208085QC81,China)Research Fund of Anhui Institute of Translational Medicine(2022zhyx-C01,China)the Basic and Clinical Cooperative Research and Promotion Program of Anhui Medical University(2021xkjT028,China).The authors would like to thank the Shiyanjia lab(www.shiyanjia.com)for their help in language polishing.
文摘Bacterial infection hampers wound repair by impeding the healing process.Concurrently,inflammation at the wound site triggers the production of reactive oxygen species(ROS),causing oxidative stress and damage to proteins and cells.This can lead to chronic wounds,posing severe risks.Therefore,eliminating bacterial infection and reducing ROS levels are crucial for effective wound healing.Nanozymes,possessing enzyme-like catalytic activity,can convert endogenous substances into highly toxic substances,such as ROS,to combat bacteria and biofilms without inducing drug resistance.However,the current nanozyme model with single enzyme activity falls short of meeting the complex requirements of antimicrobial therapy.Thus,developing nanozymes with multiple enzymatic activities is essential.Herein,we engineered a novel metalloenzyme called Ru-procyanidin nanoparticles(Ru-PC NPs)with diverse enzymatic activities to aid wound healing and combat bacterial infections.Under acidic conditions,due to their glutathione(GSH)depletion and peroxidase(POD)-like activity,Ru-PC NPs combined with H2O2 exhibit excellent antibacterial effects.However,in a neutral environment,the Ru-PC NPs,with catalase(CAT)activity,decompose H2O2 to O2,alleviating hypoxia and ensuring a sufficient oxygen supply.Furthermore,Ru-PC NPs possess exceptional antioxidant capacity through their superior superoxide dismutase(SOD)enzyme activity,effectively scavenging excess ROS and reactive nitrogen species(RNS)in a neutral environment.This maintains the balance of the antioxidant system and prevents inflammation.Ru-PC NPs also promote the polarization of macrophages from M1 to M2,facilitating wound healing.More importantly,Ru-PC NPs show good biosafety with negligible toxicity.In vivo wound infection models have confirmed the efficacy of Ru-PC NPs in inhibiting bacterial infection and promoting wound healing.The focus of this work highlights the quadruple enzymatic activity of Ru-PC NPs and its potential to reduce inflammation and promote bacteria-infected wound healing.
文摘Dear Editor,Acute Myeloid Leukemia(AML)patients are often found ineligible for aggressive standard chemotherapy in clinic because of old age and poor conditions.Current evidences suggest that targeted combination therapy might help these patients achieve a higher response rate with acceptable adverse events(AEs).^(1)Venetoclax(VEN),a selective small-molecule BCL2 inhibitor,combined with hypomethylating agent(HMA),such as azacytidine(AZA).
