This study utilises linear-scaling density functional theory(DFT)and develops a new machine-learning potential for carbon and nitrogen(GAP-CN),based on the carbon potential(GAP20),to investigate the interaction betwee...This study utilises linear-scaling density functional theory(DFT)and develops a new machine-learning potential for carbon and nitrogen(GAP-CN),based on the carbon potential(GAP20),to investigate the interaction between carbon self-interstitials and nitrogen-vacancy(NV)centres in diamond,focusing on their excited states and diffusion behaviour.From the simulated excited states,‘Bright’,‘Spike’,and‘Dark’defect configurations are classified based on their absorption spectrum features.Furthermore,machine learning molecular dynamics simulation provides insight into the possible diffusion mechanism of Ci and NV,showing that Ci can diffuse away or recombine with NV.The study yields new insight into the formation of NV defects in diamond for quantum technology applications.展开更多
Cerebral small vessel disease encompasses a group of neurological disorders characterized by injury to small blood vessels,often leading to stroke and dementia.Due to its diverse etiologies and complex pathological me...Cerebral small vessel disease encompasses a group of neurological disorders characterized by injury to small blood vessels,often leading to stroke and dementia.Due to its diverse etiologies and complex pathological mechanisms,preventing and treating cerebral small vessel vasculopathy is challenging.Recent studies have shown that the glymphatic system plays a crucial role in interstitial solute clearance and the maintenance of brain homeostasis.Increasing evidence also suggests that dysfunction in glymphatic clearance is a key factor in the progression of cerebral small vessel disease.This review begins with a comprehensive introduction to the structure,function,and driving factors of the glymphatic system,highlighting its essential role in brain waste clearance.Afterwards,cerebral small vessel disease was reviewed from the perspective of the glymphatic system,after which the mechanisms underlying their correlation were summarized.Glymphatic dysfunction may lead to the accumulation of metabolic waste in the brain,thereby exacerbating the pathological processes associated with cerebral small vessel disease.The review also discussed the direct evidence of glymphatic dysfunction in patients and animal models exhibiting two subtypes of cerebral small vessel disease:arteriolosclerosis-related cerebral small vessel disease and amyloid-related cerebral small vessel disease.Diffusion tensor image analysis along the perivascular space is an important non-invasive tool for assessing the clearance function of the glymphatic system.However,the effectiveness of its parameters needs to be enhanced.Among various nervous system diseases,including cerebral small vessel disease,glymphatic failure may be a common final pathway toward dementia.Overall,this review summarizes prevention and treatment strategies that target glymphatic drainage and will offer valuable insight for developing novel treatments for cerebral small vessel disease.展开更多
The excessive buildup of neurotoxicα-synuclein plays a pivotal role in the pathogenesis of Parkinson's disease,highlighting the urgent need for innovative therapeutic strategies to promoteα-synuclein clearance,p...The excessive buildup of neurotoxicα-synuclein plays a pivotal role in the pathogenesis of Parkinson's disease,highlighting the urgent need for innovative therapeutic strategies to promoteα-synuclein clearance,particularly given the current lack of disease-modifying treatments.The glymphatic system,a recently identified perivascular fluid transport network,is crucial for clearing neurotoxic proteins.This review aims to synthesize current knowledge on the role of the glymphatic system inα-synuclein clearance and its implications for the pathology of Parkinson's disease while emphasizing potential therapeutic strategies and areas for future research.The review begins with an overview of the glymphatic system and details its anatomical structure and physiological functions that facilitate cerebrospinal fluid circulation and waste clearance.It summarizes emerging evidence from neuroimaging and experimental studies that highlight the close correlation between the glymphatic system and clinical symptom severity in patients with Parkinson's disease,as well as the effect of glymphatic dysfunction onα-synuclein accumulation in Parkinson's disease models.Subsequently,the review summarizes the mechanisms of glymphatic system impairment in Parkinson's disease,including sleep disturbances,aquaporin-4 impairment,and mitochondrial dysfunction,all of which diminish glymphatic system efficiency.This creates a vicious cycle that exacerbatesα-synuclein accumulation and worsens Parkinson's disease.The therapeutic perspectives section outlines strategies for enhancing glymphatic activity,such as improving sleep quality and pharmacologically targeting aquaporin-4 or its subcellular localization.Promising interventions include deep brain stimulation,melatonin supplementation,γ-aminobutyric acid modulation,and non-invasive methods(such as exercise and bright-light therapy),multisensoryγstimulation,and ultrasound therapy.Moreover,identifying neuroimaging biomarkers to assess glymphatic flow as an indicator ofα-synuclein burden could refine Parkinson's disease diagnosis and track disease progression.In conclusion,the review highlights the critical role of the glymphatic system inα-synuclein clearance and its potential as a therapeutic target in Parkinson's disease.It advocates for further research to elucidate the specific mechanisms by which the glymphatic system clears misfoldedα-synuclein and the development of imaging biomarkers to monitor glymphatic activity in patients with Parkinson's disease.Findings from this review suggest that enhancing glymphatic clearance is a promising strategy for reducingα-synuclein deposits and mitigating the progression of Parkinson's disease.展开更多
Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease that extends beyond joint inflammation,affecting pulmonary and metabolic pathways.Interstitial lung disease(ILD)is one of its most serious extra-articul...Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease that extends beyond joint inflammation,affecting pulmonary and metabolic pathways.Interstitial lung disease(ILD)is one of its most serious extra-articular complications,while type 2 diabetes mellitus(T2DM)frequently coexists with RA and may exacerbate inflammatory and fibrotic processes.This editorial discusses the study by Sutton et al,the largest population-based analysis to date exploring the link between T2DM and ILD in patients with RA,and reflects on its mechanistic and clinical implications.In a nationwide cohort of more than 120000 hospitalized RA patients,Sutton et al demonstrated that the coexistence of T2DM nearly doubles the odds of developing ILD(odds ratio=2.02;95%confidence interval:1.84-2.22),with additional increases in pulmonary hypertension,pneumothorax,and length of stay.These findings reinforce the concept of a metabolic-pulmonary-autoimmune axis,in which chronic inflammation promotes insulin resistance and metabolic dysfunction,while hyperglycaemia and advanced glycation end-products amplify oxidative stress and fibrogenesis.This reciprocal interaction may induce a self-perpetuating cycle of“metaflammation”,fibrosis,and organ damage.Conclusion:Recognizing diabetes as a silent amplifier of RA-associated ILD redefines the interface between rheumatology,pulmonology,and endocrinology.Early detection and integrated management of metabolic and pulmonary comorbidities should be prioritized,while future studies must determine whether optimizing glycemic control can attenuate pulmonary fibrosis and improve longterm outcomes.展开更多
Metal-support interaction(MSI) is crucial for fine-tuning the active-site structure of supported catalysts and enhancing performance.Here,we present an ammonia-directed reactive gas-metal-support interaction(RGMSI),in...Metal-support interaction(MSI) is crucial for fine-tuning the active-site structure of supported catalysts and enhancing performance.Here,we present an ammonia-directed reactive gas-metal-support interaction(RGMSI),in which NH_(3) reduces ZnO and assembles an anti-perovskite Ni_(3)ZnN structure with interstitial nitrogen,significantly boosting hydrogenation efficiency.Nitrogen incorporation expands the lattice parameter,increasing the(111) lattice spacing from 2.04Å in Ni to 2.18Å in Ni_(3)ZnN,with an extended Ni-Ni interatomic distance from 2.49Å to 2.65Å.Additionally,Ni-N coordination shifts the d-band center downward and induces electron deficiency in Ni via charge transfer.These modifications optimize reactant adsorption on the tailored Ni_(3)ZnN structure compared to Ni,leading to a remarkable increase in 1,3-butadiene hydrogenation selectivity from 30.0 % to 92.9 %,along with an enhanced TOF from 0.067 s^(-1) to 0.079 s^(-1).These findings highlight RGMSI as a versatile and effective strategy for designing supported metal catalysts,offering new insights into selective hydrogenation catalysis.展开更多
High-pressure electrides,characterized by the presence of interstitial quasi-atoms(ISQs),possess unique electronic structures and physical properties,such as diverse dimensions of electride states exhibiting different...High-pressure electrides,characterized by the presence of interstitial quasi-atoms(ISQs),possess unique electronic structures and physical properties,such as diverse dimensions of electride states exhibiting different superconductivity,which has attracted significant attention.Here,we report a new electron-deficient type of electride Li_(4)Al and identify its phase transition progress with pressurization,where the internal driving force behind phase transitions,bonding characteristics,and superconducting behaviors have been revealed based on first-principles density functional theory.Through analysis of the bonding properties of electride Li_(4)Al,we demonstrate that the ISQs exhibiting increasingly covalent characteristics between Al ions play a critical role in driving the phase transition.Our electron–phonon coupling calculations indicate that all phases exhibit superconducting behaviors.Importantly,we prove that the ISQs behave as free electrons and demonstrate that the factor governing T_(c) is primarily derived from Li-p-hybridized electronic states with ISQ compositions.These electronic states are scattered by low-frequency phonons arising from mixed vibrations of Li and Al affected by ISQs to enhance electron–phonon coupling.Our study largely expands the research scope of electrides,provides new insight for understanding phase transitions,and elucidates the effects of ISQs on superconducting behavior.展开更多
The metallic Ni catalyst suffers from strong binding with the*CO intermediate,resulting in poisoning of the catalyst surface.It is feasible to facilitate the generation of CO by alleviating the binding strength of the...The metallic Ni catalyst suffers from strong binding with the*CO intermediate,resulting in poisoning of the catalyst surface.It is feasible to facilitate the generation of CO by alleviating the binding strength of the*CO intermediate on the Ni metal surface through a lattice expansion strategy.Here,Ni_(3)ZnC_(0.7)@C with lattice expansion was synthesized by co-doping with Zn and interstitial C through high-temperature pyrolysis.Structural characterization confirms that the lattice of Ni_(3)ZnC_(0.7)expands by 5.47%compared to Ni due to the co-doping of Zn and interstitial C.The Ni_(3)ZnC_(0.7)@C possesses excellent catalytic performance with Faradaic efficiency(FE)of CO exceeding 90%over a wide potential range from−0.8 to−1.4 V versus reversible hydrogen electrode(vs.RHE)with a peak FECO of 96.6%at−1.0 V vs.RHE.In membrane electrode assembly(MEA)testing,Ni_(3)ZnC_(0.7)@C achieves a FECO of 81.4%at the industrial-level current density of 400 mA cm^(−2).In situ attenuated total reflection surface-enhanced infrared absorption spectroscopy(ATR-SEIRAS)and density functional theory(DFT)calculations reveal that the co-introduction of Zn and interstitial C in the Ni crystal can significantly promote the desorption of*CO intermediate,which facilitates the generation of CO.This study demonstrates a viable way for designing efficient transition metal catalysts for CO_(2)electroreduction through lattice strain engineering.展开更多
Bacterial infection is a major threat to global public health,and can cause serious diseases such as bacterial skin infection and foodborne diseases.It is essential to develop a new method to rapidly diagnose clinical...Bacterial infection is a major threat to global public health,and can cause serious diseases such as bacterial skin infection and foodborne diseases.It is essential to develop a new method to rapidly diagnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time.In this work,we developed a 4-mercaptophenylboronic acid gold nanoparticles(4-MPBA-AuNPs)-functionalized hydrogel microneedle(MPBA-H-MN)for bacteria detection in skin interstitial fluid.MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min.Surface enhanced Raman spectroscopy(SERS)detection was then performed and combined with machine learning technology to distinguish and identify a variety of bacteria.Overall,the capture efficiency of this method exceeded 50%.In the concentration range of 1×10_(7) to 1×10^(10) colony-forming units/mL(CFU/mL),the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration.Using random forest(RF)-based machine learning,bacteria were effectively distinguished with an accuracy of 97.87%.In addition,the harmless disposal of used MNs by photothermal ablation was convenient,environmentally friendly,and inexpensive.This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.展开更多
BACKGROUND This study investigates the impact of type 2 diabetes mellitus(T2DM)on the risk of interstitial lung disease(ILD)and its subtypes in patients with rheumatoid arthritis(RA).RA is often complicated by ILD.T2D...BACKGROUND This study investigates the impact of type 2 diabetes mellitus(T2DM)on the risk of interstitial lung disease(ILD)and its subtypes in patients with rheumatoid arthritis(RA).RA is often complicated by ILD.T2DM has systemic proinflam-matory effects,but its impact on RA-related ILD is unclear.This research aims to elucidate the interplay between these conditions to inform clinical management and patient care strategies.AIM To determine if RA patients with T2DM have a higher occurrence of ILD compar-ed to RA patients without T2DM.METHODS We conducted a retrospective cohort study using the 2019-2020 National Inpa-tient Sample.Adult RA patients with and without T2DM were identified via International Classification of Diseases,10th Revision(ICD-10)codes.Propensity score matching(1:1)balanced 15+confounders.Logistic regression assessed the association of T2DM with ILD(overall and by subtype)and secondary outcomes(acute respiratory distress syndrome,pneumothorax,pleural effusion,pulmonary hypertension).Missing data were excluded.ILD subtypes were included based on ICD-10 codes and case count.RESULTS Among 199380 RA inpatients,ILD was more common in those with T2DM(2.25%)vs without(1.11%).After matching(n=121046),ILD remained higher in RA+T2DM[odds ratio(OR)=2.02,95%CI:1.84-2.22,P<0.001],with an absolute risk increase of about 1.14%.T2DM was associated with higher odds of ILD subtypes including usual interstitial pneumonia(OR=3.20)and non-specific interstitial pneumonia(OR=3.50).Other subtypes showed elevated ORs;eosinophilic pneumonia showed an inverse association(OR=0.23).PAH and pneumo-thorax were also more common in RA+T2DM(OR=1.40 and 1.85,respectively).Acute respiratory distress syn-drome and pleural effusion rates did not differ by T2DM status.Rare subtype findings should be interpreted cautiously.CONCLUSION T2DM increases ILD risk in RA and is linked to higher rates of pulmonary hypertension and pneumothorax,suggesting a role in exacerbating RA-related lung complications.展开更多
The past decade has witnessed the rapid increasement in power conversion efficiency of perovskite solar cells(PSCs).However,serious ion migration hampers their operational stability.Although dopants composed of varied...The past decade has witnessed the rapid increasement in power conversion efficiency of perovskite solar cells(PSCs).However,serious ion migration hampers their operational stability.Although dopants composed of varied cations and anions are introduced into perovskite to suppress ion migration,the impact of cations or anions is not individually explored,which hinders the evaluation of different cations and further application of doping strategy.Here we report that a special group of sulfonic anions(like CF_(3)SO_(3)^(-))successfully introduce alkaline earth ions(like Ca^(2+))into perovskite lattice compared to its halide counterparts.Furthermore,with effective crystallization regulation and defect passivation of sulfonic anions,perovskite with Ca(CF_(3)SO_(3))_(2)shows reduced PbI2 residue and metallic Pb0 defects;thereby,corresponding PSCs show an enhanced PCE of 24.95%.Finally by comparing the properties of perovskite with Ca(CF_(3)SO_(3))_(2)and FACF_(3)SO_(3),we found that doped Ca^(2+)significantly suppressed halide migration with an activation energy of 1.246 eV which accounts for the improved operational stability of Ca(CF_(3)SO_(3))_(2-)doped PSCs,while no obvious impact of Ca^(2+)on trap density is observed.Combining the benefits of cations and anions,this study presents an effective method to decouple the effects of cations and anions and fabricate efficient and stable PSCs.展开更多
1.Introduction.Ni-Mn-X(X=Ga,In,Sn,or Sb)Heusler alloys have versatile properties[1-4],such as shape memory effect[1],superelastic-ity[5],magnetocaloric effect[3],elastocaloric effect[6],and even multicaloric effect[7]...1.Introduction.Ni-Mn-X(X=Ga,In,Sn,or Sb)Heusler alloys have versatile properties[1-4],such as shape memory effect[1],superelastic-ity[5],magnetocaloric effect[3],elastocaloric effect[6],and even multicaloric effect[7],that indicate their potential for use in actu-ators,sensors,micropumps,energy harvesters,and solid-state re-frigeration[8-10].Among the alloys,Ni-Mn-Sn-based alloys are environment-friendly and cost-effective[6,7,11],and hence,they have received widespread attention.展开更多
Objective:To evaluate the predictive value of the neutrophil⁃to⁃lymphocyte ratio(NLR)and the systemic immune⁃inflammation index(SII)in predicting patients with anti⁃melanoma differentiation⁃associated gene 5⁃positive(...Objective:To evaluate the predictive value of the neutrophil⁃to⁃lymphocyte ratio(NLR)and the systemic immune⁃inflammation index(SII)in predicting patients with anti⁃melanoma differentiation⁃associated gene 5⁃positive(anti⁃MDA5+)dermatomyositis(DM)develop into the rapidly progressive interstitial lung disease(RPILD).Methods:We retrospectively analyzed the clinical and laboratory data of 124 anti⁃MDA5+DM patients from the First Affiliated Hospital of Nanjing Medical University between March 2019 and September 2023.We identified independent risk factors associated with the development and mortality of RPILD with the Cox regression analysis,and determined the optimal cut⁃off values for predicting adverse outcomes with the receiver operating characteristic(ROC)curve analysis.Results:Among the 124 patients,36 patients(29.03%)developed RPILD,and 39 patients(31.45%)died during the follow⁃up period.The results of multivariate Cox regression analysis showed that the elevated NLR was an independent risk factor for RPILD development,while the elevated SII expression was independently associated with the increased mortality of RPILD.Based on the ROC curve analysis,NLR>6.12 was a predictor for RPILD,and SII>875.79 was associated with increased mortality risk of RPILD.Conclusion:Both NLR and SII are accessible,cost⁃effective,and reliable prognostic indicators for the prognosis of patients with anti⁃MDA5^(+)DM,providing a valuable guidance for clinical management and risk stratification of the disease.展开更多
The bone marrow microenvironment is critical for the maintenance and functionality of stem/progenitor cells,which are essential for bone development and regeneration.However,the composition and potential use of bone m...The bone marrow microenvironment is critical for the maintenance and functionality of stem/progenitor cells,which are essential for bone development and regeneration.However,the composition and potential use of bone marrow interstitial fluid have not been well explored.In this study,we report the role of neonatal bovine bone marrow interstitial fluid(NBIF)in enhancing the bone regeneration capacity of human bone marrow mesenchymal stem cells(hBMSCs).Unlike adult bovine bone marrow interstitial fluid(ABIF),NBIF-fed hBMSCs exhibit enhanced self-renewal and osteogenic potential and bone marrow homing ability,along with transcriptome changes as compared to hBMSCs cultured in standard fetal bovine serum(FBS)supplemented medium.Mass spectrometry analysis reveals that multiple secreted factors associated with tissue repair and bone development are enriched in NBIF compared to FBS and ABIF.The combined use of NBIF-enriched Nerve Growth Factor(NGF),Lactoferrin(LTF),and High Mobility Group Protein B1(HMGB1),together with Insulin-Like Growth Factor 1(IGF1)for culturing hBMSCs in the presence of FBS can enhance osteogenic potential and bone marrow homing ability,mimicking NBIF's effects.These findings highlight the role of interstitial fluid in the bone marrow microenvironment and its potential to optimize stem cell-based therapies.展开更多
Objective:To assess whether there is a correlation between CT scan severity score and pulmonary function in Interstitial Lung Disease,and provide a more reliable basis for clinical diagnosis and treatment.Materials an...Objective:To assess whether there is a correlation between CT scan severity score and pulmonary function in Interstitial Lung Disease,and provide a more reliable basis for clinical diagnosis and treatment.Materials and Methods:Sixty patients with clinical diagnosis of Interstitial Lung Disease(ILD)were collected,and chest CT and pulmonary function tests were performed at the same time.Here DLCO%and FEV1%were used as the pulmonary function indexes.The severity of the patients was assessed by CT scores as mild(range,1~10),moderate(range 11~20),and severe(range 21~30).Correlation analysis was carried out between CT score and pulmonary function index,and the lung function parameters of patients at three grades were compared between groups and pairwise among the means.Results:As per the CT severity classification,there were 13 mild cases,31 moderate cases,and 16 severe cases.CT score was negatively correlated with DLCO%and FEV1%.R value was-0.814 and-0.797,respectively;The comparison of the mean value of DLCO%and FEV1%among the three groups and the pairings of the mean value of DLCO%and FEV1%were statistically significant.Conclusion:There was good correlation between CT score of ILD and the pulmonary function index.The pulmonary function index of patients with different CT severity grading was statistically significant,which can provide a new basis for the clinical evaluation and diagnosis of the disease.展开更多
BACKGROUND Most non-small cell lung cancer patients have epidermal growth factor receptor(EGFR)activating mutations,such as exon 19 deletion and exon 21 replacement mutations.Osimertinib is a third-generation EGFR-tyr...BACKGROUND Most non-small cell lung cancer patients have epidermal growth factor receptor(EGFR)activating mutations,such as exon 19 deletion and exon 21 replacement mutations.Osimertinib is a third-generation EGFR-tyrosine kinase inhibitors ap-proved for the treatment of lung cancer patients carrying EGFR activating mu-tations.Osimertinib-induced interstitial lung disease(ILD)is a rare and poten-tially fatal pulmonary toxic manifestation of drug therapy.At present,there is no international consensus on the risks and treatment of the osimertinib-induced ILD.CASE SUMMARY We report a case of a 56-year-old woman who was diagnosed with lung adenocar-cinoma with lung hilum,mediastinal lymph nodes and brain metastases(T4N3-M1c stage IVB).The patient received targeted treatment with osimertinib after radiotherapy and chemotherapy.But she developed ILD after osimertinib treat-ment.Following active symptomatic treatment and hormone treatment,the lung injury alleviated.The patient was retreated with furmonertinib combined with prednisone and did not experience ILD again.So far,she has survived for 14 months without disease progression.CONCLUSION Retreatment with furmonertinib under prednisone could be considered as an effective therapeutic option after risk-benefit assessment for EGFR-mutant lung adenocarcinoma patients.展开更多
Interstitial alloying has emerged as a powerful strategy to tune microstructure and microproperties of high-entropy alloys(HEAs) due to the strong interaction of interstitials with constituent elements and crystal def...Interstitial alloying has emerged as a powerful strategy to tune microstructure and microproperties of high-entropy alloys(HEAs) due to the strong interaction of interstitials with constituent elements and crystal defects,which enables the development of advanced alloys with superior mechanical and functional properties. The paper reviews the latest progress in the atomic-scale understanding of the effects of various interstitials, including carbon, boron, nitrogen, oxygen, and hydrogen, on the microstructure, stability, mechanical properties, and deformation behavior of HEAs. Emphases are placed on the in-depth insights on the interaction of interstitials with constituent elements and crystal defects, such as vacancies,stacking faults, and grain boundaries. Key parameters for rapid prediction of intrinsic properties of HEAs are also discussed. Finally, we highlight some unsolved issues and provide perspectives for future research directions.展开更多
Dermatomyositis(DM)is an idiopathic inflammatory myopathy characterized by prominent skin lesions,muscle weakness,and clinically heterogeneous systemic manifestations.Among patients with DM,the male-to-female ratio is...Dermatomyositis(DM)is an idiopathic inflammatory myopathy characterized by prominent skin lesions,muscle weakness,and clinically heterogeneous systemic manifestations.Among patients with DM,the male-to-female ratio is 2:1.Juvenile dermatomyositis(JDM)is most prevalent between the ages of 4 and 14 years,while adult-onset dermatomyositis typically occurs between the ages of 40 and 60 years.In a population-based study conducted in Olmsted County,Minnesota,USA,the risk of DM was found to increase with age across different age groups stratified by decade.The incidence rate of DM in individuals aged≥80 years was 3.2 per 100,000 person-years.Dermatomyositis in elderly patients is characterized by unique clinical manifestations,pathogenic mechanisms,and therapeutic approaches.However,discussions regarding geriatric dermatomyositis are currently limited.Therefore,this article aims to review the epidemiology,clinical features,histopathology,and pathogenesis of dermatomyositis,with a particular focus on the unique clinical characteristics of geriatric dermatomyositis.展开更多
BACKGROUND We previously identified miR-10b-5p as a key regulator of gastrointestinal(GI)motility through its essential role in the development and function of interstitial cells of Cajal(ICC),the pacemaker cells of t...BACKGROUND We previously identified miR-10b-5p as a key regulator of gastrointestinal(GI)motility through its essential role in the development and function of interstitial cells of Cajal(ICC),the pacemaker cells of the gut.Loss of miR-10b-5p in ICC im-pairs intestinal motility and contributes to constipation,a common condition in the elderly.Notably,miR-10b-5p is co-expressed with its paralog,miR-10a-5p,in ICC.AIM To investigate the roles of miR-10a-5p and miR-10b-5p in age-associated intestinal dysmotility and assess the therapeutic potential of restoring their expression.METHODS We employed aged mice,mir-10a and mir-10b single and double knockout(KO)models,and human plasma and colon samples across age groups.GI and colonic transit,ICC network integrity,and expression levels of miR-10a/b-5p were eva-luated.Additionally,we tested whether treatment with their microRNA mimics could restore GI motility in aged mice.RESULTS Aged mice exhibited delayed GI and colonic transit,reduced fecal output,and diminished expression of miR-10a-5p and miR-10b-5p,which peaked during late embryonic and early postnatal stages and declined with age.This decline para-lleled ICC network deterioration in the colon.All KO models exhibited impaired motility and ICC loss,with mir-10a KO mice displaying more severe phenotypes than mir-10b KO mice.Double KO mice demonstrated growth retardation and reduced survival,with homozygous mutants living only up to 3 months.Treatment of aged mice with miR-10a-5p and miR-10b-5p mimics encapsu-lated in jetPEI significantly improved GI and colonic motility.Successful delivery to the gut,including the colon,was confirmed.In human samples,both miR-10a/b-5p and KIT expression decreased with age.CONCLUSION miR-10a-5p and miR-10b-5p are essential for ICC maintenance and colonic motility,and their age-related decline contributes to GI dysmotility in both mice and humans.Restoring their levels offers a promising therapeutic stra-tegy for treating age-related constipation and other motility disorders.展开更多
Interstitial lung diseases(ILD)encompass a diverse group of over 200 chronic pulmonary disorders characterized by varying degrees of inflammation and fibrosis,which can lead to severe respiratory impairment.Lung trans...Interstitial lung diseases(ILD)encompass a diverse group of over 200 chronic pulmonary disorders characterized by varying degrees of inflammation and fibrosis,which can lead to severe respiratory impairment.Lung transplantation offers a crucial therapeutic option for patients with advanced ILD,extending survival and improving quality of life.This review explores optimal management strategies in both the pre-and post-transplant phases to enhance patient outcomes.Comprehensive pre-transplant evaluation,including pulmonary function testing,imaging,and comorbidity assessment,is critical for determining transplant eligibility and timing.Post-transplant care must focus on preventing complications such as primary graft dysfunction and chronic lung allograft dysfunction,managed through tailored immunosuppression and proactive monitoring.Recent advancements in diagnostic techniques and therapeutic approaches,including emerging technologies like ex vivo lung perfusion and precision medicine,promise to further improve outcomes.The ultimate goal is to establish an evidencebased,multidisciplinary framework for optimizing ILD management and lung transplantation.展开更多
BACKGROUND The high mortality rate and recurrence/metastasis remain major challenges in the clinical management of gastric cancer(GC)patients.To optimize treatment stratification and management,there is an urgent need...BACKGROUND The high mortality rate and recurrence/metastasis remain major challenges in the clinical management of gastric cancer(GC)patients.To optimize treatment stratification and management,there is an urgent need for efficient and non-invasive biomarkers.A meta-analysis on the prognostic role of circulating tumor cells(CTCs)in GC revealed a strong association between CTCs and patient prognosis.Among CTC subtypes,Interstitial CTCs(I-CTCs)exhibited the strongest invasiveness.This study innovatively investigated the expression profile of I-CTCs in advanced GC patients to evaluate their clinical utility.AIM To evaluate the clinical utility of I-CTCs as a non-invasive prognostic biomarker in advanced GC.To investigate the correlation between I-CTC count thresholds and chemotherapy efficacy in advanced GC patients.To establish the potential of preoperative I-CTC profiling for optimizing treatment stratification and postoperative surveillance.METHODS This study retrospectively analyzed 59 patients with advanced GC treated at the General Surgery Clinical Medical Center of Gansu Provincial Hospital between October 2019 and October 2020.The expression levels of I-CTCs were measured,and patient survival was monitored.The receiver operating characteristic curve was plotted to determine the optimal cut-off value for I-CTCs expression levels.Based on this cut-off value,59 GC patients were grouped into positive and negative groups.The differences in clinicopathological characteristics between the two groups were analyzed.Patient survival was follow-up and recorded until October 2022.Plotting survival curves and performing univariate and multifactorial analyses of patient prognostic factors.The Kaplan-Meier method and Cox regression model were used,respectively.RESULTS A total of 59 patients were included in this study,and receiver operating characteristic curve analysis showed that the best cut-off value for I-CTCs was 5,with an area under the curve of 0.8356(95%CI:0.7122-0.9590).The I-CTC count of≥5 defines the positive group,while counts<5 are classified as the negative group.Positive I-CTCs correlated with the degree of tumor differentiation and disease progression(P<0.05).16 of 59 patients received neoadjuvant chemotherapy.There were divided into progressive disease and disease control groups based on response to neoadjuvant chemotherapy.Patients in the I-CTCs-negative group had longer overall survival and disease-free survival than those in the positive group(P<0.05).Multifactorial analysis revealed that I-CTCs positivity(HR=13.323,95%CI:1.675-105.962,P=0.014)was an independent risk factor for survival in patients with advanced GC.CONCLUSION In patients with advanced GC,an I-CTC count of≥5 is associated with both poor prognosis and reduced chemotherapy efficacy.I-CTCs may serve as a valuable preoperative biomarker for predicting the prognosis of advanced GC.展开更多
基金the use of the University of Oxford Advanced Research Computing(ARC)facility in carrying out this work(https://doi.org/10.5281/zenodo.22558).Additionally,we acknowledge the use of NQIT computing nodes and the Quantum Computing and Simulation Hub.J.C.A.P.acknowledges the support of St.Edmund Hall,University of Oxford,through the Cooksey Early Career Teaching and Research Fellowship,and the embedded CSE programme of the ARCHER UK National Supercomputing Service.We extend our thanks to Yuxing Zhou for valuable suggestions on ML potential training,to Xingrui Cheng for providing experimental data,and to Jacx Chan for offering meaningful insights for this work.
文摘This study utilises linear-scaling density functional theory(DFT)and develops a new machine-learning potential for carbon and nitrogen(GAP-CN),based on the carbon potential(GAP20),to investigate the interaction between carbon self-interstitials and nitrogen-vacancy(NV)centres in diamond,focusing on their excited states and diffusion behaviour.From the simulated excited states,‘Bright’,‘Spike’,and‘Dark’defect configurations are classified based on their absorption spectrum features.Furthermore,machine learning molecular dynamics simulation provides insight into the possible diffusion mechanism of Ci and NV,showing that Ci can diffuse away or recombine with NV.The study yields new insight into the formation of NV defects in diamond for quantum technology applications.
基金supported by the National Natural Science Foundation of China,No.82274304(to YH)the Major Clinical Study Projects of Shanghai Shenkang Hospital Development Center,No.SHDC2020CR2046B(to YH)Shanghai Municipal Health Commission Talent Plan,No.2022LJ010(to YH).
文摘Cerebral small vessel disease encompasses a group of neurological disorders characterized by injury to small blood vessels,often leading to stroke and dementia.Due to its diverse etiologies and complex pathological mechanisms,preventing and treating cerebral small vessel vasculopathy is challenging.Recent studies have shown that the glymphatic system plays a crucial role in interstitial solute clearance and the maintenance of brain homeostasis.Increasing evidence also suggests that dysfunction in glymphatic clearance is a key factor in the progression of cerebral small vessel disease.This review begins with a comprehensive introduction to the structure,function,and driving factors of the glymphatic system,highlighting its essential role in brain waste clearance.Afterwards,cerebral small vessel disease was reviewed from the perspective of the glymphatic system,after which the mechanisms underlying their correlation were summarized.Glymphatic dysfunction may lead to the accumulation of metabolic waste in the brain,thereby exacerbating the pathological processes associated with cerebral small vessel disease.The review also discussed the direct evidence of glymphatic dysfunction in patients and animal models exhibiting two subtypes of cerebral small vessel disease:arteriolosclerosis-related cerebral small vessel disease and amyloid-related cerebral small vessel disease.Diffusion tensor image analysis along the perivascular space is an important non-invasive tool for assessing the clearance function of the glymphatic system.However,the effectiveness of its parameters needs to be enhanced.Among various nervous system diseases,including cerebral small vessel disease,glymphatic failure may be a common final pathway toward dementia.Overall,this review summarizes prevention and treatment strategies that target glymphatic drainage and will offer valuable insight for developing novel treatments for cerebral small vessel disease.
基金supported by the National Natural Science Foundation of China,No.81971031(to ZL)the National Key Research and Development Program of China,No.2022YFE0210100(to JFC)+7 种基金the National Natural Science Foundation of China(Original Exploration Project),No.82151308(to JFC)the National Natural Science Foundation of China(Research Fund for International Senior Scientists),No.82150710558(to JFC)Science&Technology Initiative STI2030-Major Projects,No.2021ZD0203400(to JFC)Key Research and Development Program of Zhejiang Province,No.2023C03079(to JFC)Scientific Research Starting Foundation of Oujiang Laboratory(Zhejiang Laboratory for Regenerative Medicine,Vision and Brain Health),No.OJQDSP2022007(to JFC)Project of State Key Laboratory of Ophthalmology,Optometry and Visual Science,Wenzhou Medical University,No.J01-20190101(to JFC)Scientific Research Starting Foundation of Wenzhou Medical University,No.QTJ12003(to JFC)Department of Science and Technology of Zhejiang Province,No.2023ZY1011(to JFC)。
文摘The excessive buildup of neurotoxicα-synuclein plays a pivotal role in the pathogenesis of Parkinson's disease,highlighting the urgent need for innovative therapeutic strategies to promoteα-synuclein clearance,particularly given the current lack of disease-modifying treatments.The glymphatic system,a recently identified perivascular fluid transport network,is crucial for clearing neurotoxic proteins.This review aims to synthesize current knowledge on the role of the glymphatic system inα-synuclein clearance and its implications for the pathology of Parkinson's disease while emphasizing potential therapeutic strategies and areas for future research.The review begins with an overview of the glymphatic system and details its anatomical structure and physiological functions that facilitate cerebrospinal fluid circulation and waste clearance.It summarizes emerging evidence from neuroimaging and experimental studies that highlight the close correlation between the glymphatic system and clinical symptom severity in patients with Parkinson's disease,as well as the effect of glymphatic dysfunction onα-synuclein accumulation in Parkinson's disease models.Subsequently,the review summarizes the mechanisms of glymphatic system impairment in Parkinson's disease,including sleep disturbances,aquaporin-4 impairment,and mitochondrial dysfunction,all of which diminish glymphatic system efficiency.This creates a vicious cycle that exacerbatesα-synuclein accumulation and worsens Parkinson's disease.The therapeutic perspectives section outlines strategies for enhancing glymphatic activity,such as improving sleep quality and pharmacologically targeting aquaporin-4 or its subcellular localization.Promising interventions include deep brain stimulation,melatonin supplementation,γ-aminobutyric acid modulation,and non-invasive methods(such as exercise and bright-light therapy),multisensoryγstimulation,and ultrasound therapy.Moreover,identifying neuroimaging biomarkers to assess glymphatic flow as an indicator ofα-synuclein burden could refine Parkinson's disease diagnosis and track disease progression.In conclusion,the review highlights the critical role of the glymphatic system inα-synuclein clearance and its potential as a therapeutic target in Parkinson's disease.It advocates for further research to elucidate the specific mechanisms by which the glymphatic system clears misfoldedα-synuclein and the development of imaging biomarkers to monitor glymphatic activity in patients with Parkinson's disease.Findings from this review suggest that enhancing glymphatic clearance is a promising strategy for reducingα-synuclein deposits and mitigating the progression of Parkinson's disease.
文摘Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease that extends beyond joint inflammation,affecting pulmonary and metabolic pathways.Interstitial lung disease(ILD)is one of its most serious extra-articular complications,while type 2 diabetes mellitus(T2DM)frequently coexists with RA and may exacerbate inflammatory and fibrotic processes.This editorial discusses the study by Sutton et al,the largest population-based analysis to date exploring the link between T2DM and ILD in patients with RA,and reflects on its mechanistic and clinical implications.In a nationwide cohort of more than 120000 hospitalized RA patients,Sutton et al demonstrated that the coexistence of T2DM nearly doubles the odds of developing ILD(odds ratio=2.02;95%confidence interval:1.84-2.22),with additional increases in pulmonary hypertension,pneumothorax,and length of stay.These findings reinforce the concept of a metabolic-pulmonary-autoimmune axis,in which chronic inflammation promotes insulin resistance and metabolic dysfunction,while hyperglycaemia and advanced glycation end-products amplify oxidative stress and fibrogenesis.This reciprocal interaction may induce a self-perpetuating cycle of“metaflammation”,fibrosis,and organ damage.Conclusion:Recognizing diabetes as a silent amplifier of RA-associated ILD redefines the interface between rheumatology,pulmonology,and endocrinology.Early detection and integrated management of metabolic and pulmonary comorbidities should be prioritized,while future studies must determine whether optimizing glycemic control can attenuate pulmonary fibrosis and improve longterm outcomes.
基金the financial support provided by the National Natural Science Foundation of China (Nos.22072164,22472180,22002173)Energy Revolution S&T Program of Yulin Innovation Institute of Clean Energy (No.E411030705)+2 种基金Natural Science Foundation of Liaoning Province (No.2022-MS004)China Postdoctoral Science Foundation (No.2020M680999)the Research Fund of Shenyang National Laboratory for Materials Science。
文摘Metal-support interaction(MSI) is crucial for fine-tuning the active-site structure of supported catalysts and enhancing performance.Here,we present an ammonia-directed reactive gas-metal-support interaction(RGMSI),in which NH_(3) reduces ZnO and assembles an anti-perovskite Ni_(3)ZnN structure with interstitial nitrogen,significantly boosting hydrogenation efficiency.Nitrogen incorporation expands the lattice parameter,increasing the(111) lattice spacing from 2.04Å in Ni to 2.18Å in Ni_(3)ZnN,with an extended Ni-Ni interatomic distance from 2.49Å to 2.65Å.Additionally,Ni-N coordination shifts the d-band center downward and induces electron deficiency in Ni via charge transfer.These modifications optimize reactant adsorption on the tailored Ni_(3)ZnN structure compared to Ni,leading to a remarkable increase in 1,3-butadiene hydrogenation selectivity from 30.0 % to 92.9 %,along with an enhanced TOF from 0.067 s^(-1) to 0.079 s^(-1).These findings highlight RGMSI as a versatile and effective strategy for designing supported metal catalysts,offering new insights into selective hydrogenation catalysis.
基金supported by the National Key Research and Development Program of China (Grant Nos.2023YFA1406200 and 2022YFA-1405500)the National Natural Science Foundation of China (Grant Nos.12304021 and 52072188)+3 种基金Zhejiang Provincial Natural Science Foundation of China (Grant Nos.LQ23A040004 and MS26A040028)Natural Science Foundation of Ningbo (Grant Nos.2022J091 and ZX2025001430)the Program for Science and Technology Innovation Team in Zhejiang (Grant No.2021R01004)the Program for Changjiang Scholars and Innovative Research Team in University (Grant No.IRT_15R23)。
文摘High-pressure electrides,characterized by the presence of interstitial quasi-atoms(ISQs),possess unique electronic structures and physical properties,such as diverse dimensions of electride states exhibiting different superconductivity,which has attracted significant attention.Here,we report a new electron-deficient type of electride Li_(4)Al and identify its phase transition progress with pressurization,where the internal driving force behind phase transitions,bonding characteristics,and superconducting behaviors have been revealed based on first-principles density functional theory.Through analysis of the bonding properties of electride Li_(4)Al,we demonstrate that the ISQs exhibiting increasingly covalent characteristics between Al ions play a critical role in driving the phase transition.Our electron–phonon coupling calculations indicate that all phases exhibit superconducting behaviors.Importantly,we prove that the ISQs behave as free electrons and demonstrate that the factor governing T_(c) is primarily derived from Li-p-hybridized electronic states with ISQ compositions.These electronic states are scattered by low-frequency phonons arising from mixed vibrations of Li and Al affected by ISQs to enhance electron–phonon coupling.Our study largely expands the research scope of electrides,provides new insight for understanding phase transitions,and elucidates the effects of ISQs on superconducting behavior.
基金financial support from the National Natural Science Foundation of China(No.22478278,22308246)the Central Government Guides the Local Science and Technology Development Special Fund(No.YDZJSX20231A015)the Fundamental Research Program of Shanxi Province(No.202203021212266).
文摘The metallic Ni catalyst suffers from strong binding with the*CO intermediate,resulting in poisoning of the catalyst surface.It is feasible to facilitate the generation of CO by alleviating the binding strength of the*CO intermediate on the Ni metal surface through a lattice expansion strategy.Here,Ni_(3)ZnC_(0.7)@C with lattice expansion was synthesized by co-doping with Zn and interstitial C through high-temperature pyrolysis.Structural characterization confirms that the lattice of Ni_(3)ZnC_(0.7)expands by 5.47%compared to Ni due to the co-doping of Zn and interstitial C.The Ni_(3)ZnC_(0.7)@C possesses excellent catalytic performance with Faradaic efficiency(FE)of CO exceeding 90%over a wide potential range from−0.8 to−1.4 V versus reversible hydrogen electrode(vs.RHE)with a peak FECO of 96.6%at−1.0 V vs.RHE.In membrane electrode assembly(MEA)testing,Ni_(3)ZnC_(0.7)@C achieves a FECO of 81.4%at the industrial-level current density of 400 mA cm^(−2).In situ attenuated total reflection surface-enhanced infrared absorption spectroscopy(ATR-SEIRAS)and density functional theory(DFT)calculations reveal that the co-introduction of Zn and interstitial C in the Ni crystal can significantly promote the desorption of*CO intermediate,which facilitates the generation of CO.This study demonstrates a viable way for designing efficient transition metal catalysts for CO_(2)electroreduction through lattice strain engineering.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82204340,82173954,and 82073815)the Natural Science Foundation of Jiangsu Province,China(Grant No.:BK20221048)+1 种基金the Jiangsu Funding Program for Excellent Postdoctoral Talent,China(Grant No.:2022ZB295)Key Laboratory Project of Quality Control of Chinese Herbal Medicines and Decoction Pieces,Gansu Institute for Drug Control,China(Grant No.:2024GSMPA-KL02).
文摘Bacterial infection is a major threat to global public health,and can cause serious diseases such as bacterial skin infection and foodborne diseases.It is essential to develop a new method to rapidly diagnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time.In this work,we developed a 4-mercaptophenylboronic acid gold nanoparticles(4-MPBA-AuNPs)-functionalized hydrogel microneedle(MPBA-H-MN)for bacteria detection in skin interstitial fluid.MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min.Surface enhanced Raman spectroscopy(SERS)detection was then performed and combined with machine learning technology to distinguish and identify a variety of bacteria.Overall,the capture efficiency of this method exceeded 50%.In the concentration range of 1×10_(7) to 1×10^(10) colony-forming units/mL(CFU/mL),the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration.Using random forest(RF)-based machine learning,bacteria were effectively distinguished with an accuracy of 97.87%.In addition,the harmless disposal of used MNs by photothermal ablation was convenient,environmentally friendly,and inexpensive.This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.
文摘BACKGROUND This study investigates the impact of type 2 diabetes mellitus(T2DM)on the risk of interstitial lung disease(ILD)and its subtypes in patients with rheumatoid arthritis(RA).RA is often complicated by ILD.T2DM has systemic proinflam-matory effects,but its impact on RA-related ILD is unclear.This research aims to elucidate the interplay between these conditions to inform clinical management and patient care strategies.AIM To determine if RA patients with T2DM have a higher occurrence of ILD compar-ed to RA patients without T2DM.METHODS We conducted a retrospective cohort study using the 2019-2020 National Inpa-tient Sample.Adult RA patients with and without T2DM were identified via International Classification of Diseases,10th Revision(ICD-10)codes.Propensity score matching(1:1)balanced 15+confounders.Logistic regression assessed the association of T2DM with ILD(overall and by subtype)and secondary outcomes(acute respiratory distress syndrome,pneumothorax,pleural effusion,pulmonary hypertension).Missing data were excluded.ILD subtypes were included based on ICD-10 codes and case count.RESULTS Among 199380 RA inpatients,ILD was more common in those with T2DM(2.25%)vs without(1.11%).After matching(n=121046),ILD remained higher in RA+T2DM[odds ratio(OR)=2.02,95%CI:1.84-2.22,P<0.001],with an absolute risk increase of about 1.14%.T2DM was associated with higher odds of ILD subtypes including usual interstitial pneumonia(OR=3.20)and non-specific interstitial pneumonia(OR=3.50).Other subtypes showed elevated ORs;eosinophilic pneumonia showed an inverse association(OR=0.23).PAH and pneumo-thorax were also more common in RA+T2DM(OR=1.40 and 1.85,respectively).Acute respiratory distress syn-drome and pleural effusion rates did not differ by T2DM status.Rare subtype findings should be interpreted cautiously.CONCLUSION T2DM increases ILD risk in RA and is linked to higher rates of pulmonary hypertension and pneumothorax,suggesting a role in exacerbating RA-related lung complications.
基金support from the National Key Research and Development Program of China(No.2022YFE0137400)the National Natural Science Foundation of China(Grant No.62274040).
文摘The past decade has witnessed the rapid increasement in power conversion efficiency of perovskite solar cells(PSCs).However,serious ion migration hampers their operational stability.Although dopants composed of varied cations and anions are introduced into perovskite to suppress ion migration,the impact of cations or anions is not individually explored,which hinders the evaluation of different cations and further application of doping strategy.Here we report that a special group of sulfonic anions(like CF_(3)SO_(3)^(-))successfully introduce alkaline earth ions(like Ca^(2+))into perovskite lattice compared to its halide counterparts.Furthermore,with effective crystallization regulation and defect passivation of sulfonic anions,perovskite with Ca(CF_(3)SO_(3))_(2)shows reduced PbI2 residue and metallic Pb0 defects;thereby,corresponding PSCs show an enhanced PCE of 24.95%.Finally by comparing the properties of perovskite with Ca(CF_(3)SO_(3))_(2)and FACF_(3)SO_(3),we found that doped Ca^(2+)significantly suppressed halide migration with an activation energy of 1.246 eV which accounts for the improved operational stability of Ca(CF_(3)SO_(3))_(2-)doped PSCs,while no obvious impact of Ca^(2+)on trap density is observed.Combining the benefits of cations and anions,this study presents an effective method to decouple the effects of cations and anions and fabricate efficient and stable PSCs.
基金supported by the National Key R&D Pro-gram of China(No.2022YFB3805701)National Natural Science Foundation of China(NSFC)(No.52371182,51701052,52192592,52192593)+1 种基金Young Elite Scientists Sponsorship Program by CAST(No.2019QNRC001)the Heilongjiang Touyan Innovation Team Program.
文摘1.Introduction.Ni-Mn-X(X=Ga,In,Sn,or Sb)Heusler alloys have versatile properties[1-4],such as shape memory effect[1],superelastic-ity[5],magnetocaloric effect[3],elastocaloric effect[6],and even multicaloric effect[7],that indicate their potential for use in actu-ators,sensors,micropumps,energy harvesters,and solid-state re-frigeration[8-10].Among the alloys,Ni-Mn-Sn-based alloys are environment-friendly and cost-effective[6,7,11],and hence,they have received widespread attention.
文摘Objective:To evaluate the predictive value of the neutrophil⁃to⁃lymphocyte ratio(NLR)and the systemic immune⁃inflammation index(SII)in predicting patients with anti⁃melanoma differentiation⁃associated gene 5⁃positive(anti⁃MDA5+)dermatomyositis(DM)develop into the rapidly progressive interstitial lung disease(RPILD).Methods:We retrospectively analyzed the clinical and laboratory data of 124 anti⁃MDA5+DM patients from the First Affiliated Hospital of Nanjing Medical University between March 2019 and September 2023.We identified independent risk factors associated with the development and mortality of RPILD with the Cox regression analysis,and determined the optimal cut⁃off values for predicting adverse outcomes with the receiver operating characteristic(ROC)curve analysis.Results:Among the 124 patients,36 patients(29.03%)developed RPILD,and 39 patients(31.45%)died during the follow⁃up period.The results of multivariate Cox regression analysis showed that the elevated NLR was an independent risk factor for RPILD development,while the elevated SII expression was independently associated with the increased mortality of RPILD.Based on the ROC curve analysis,NLR>6.12 was a predictor for RPILD,and SII>875.79 was associated with increased mortality risk of RPILD.Conclusion:Both NLR and SII are accessible,cost⁃effective,and reliable prognostic indicators for the prognosis of patients with anti⁃MDA5^(+)DM,providing a valuable guidance for clinical management and risk stratification of the disease.
基金financially supported by the Guangzhou National Laboratory(grant#GZNL2025C02022,A.M.#QNPG2317,J.Z.)partially by the National Natural Science Foundation of China(31988101)。
文摘The bone marrow microenvironment is critical for the maintenance and functionality of stem/progenitor cells,which are essential for bone development and regeneration.However,the composition and potential use of bone marrow interstitial fluid have not been well explored.In this study,we report the role of neonatal bovine bone marrow interstitial fluid(NBIF)in enhancing the bone regeneration capacity of human bone marrow mesenchymal stem cells(hBMSCs).Unlike adult bovine bone marrow interstitial fluid(ABIF),NBIF-fed hBMSCs exhibit enhanced self-renewal and osteogenic potential and bone marrow homing ability,along with transcriptome changes as compared to hBMSCs cultured in standard fetal bovine serum(FBS)supplemented medium.Mass spectrometry analysis reveals that multiple secreted factors associated with tissue repair and bone development are enriched in NBIF compared to FBS and ABIF.The combined use of NBIF-enriched Nerve Growth Factor(NGF),Lactoferrin(LTF),and High Mobility Group Protein B1(HMGB1),together with Insulin-Like Growth Factor 1(IGF1)for culturing hBMSCs in the presence of FBS can enhance osteogenic potential and bone marrow homing ability,mimicking NBIF's effects.These findings highlight the role of interstitial fluid in the bone marrow microenvironment and its potential to optimize stem cell-based therapies.
基金providing by the Shenzhen City Nanshan District Science and Technology Plan Project(Medical and Health Category)(Grant No.2018073)。
文摘Objective:To assess whether there is a correlation between CT scan severity score and pulmonary function in Interstitial Lung Disease,and provide a more reliable basis for clinical diagnosis and treatment.Materials and Methods:Sixty patients with clinical diagnosis of Interstitial Lung Disease(ILD)were collected,and chest CT and pulmonary function tests were performed at the same time.Here DLCO%and FEV1%were used as the pulmonary function indexes.The severity of the patients was assessed by CT scores as mild(range,1~10),moderate(range 11~20),and severe(range 21~30).Correlation analysis was carried out between CT score and pulmonary function index,and the lung function parameters of patients at three grades were compared between groups and pairwise among the means.Results:As per the CT severity classification,there were 13 mild cases,31 moderate cases,and 16 severe cases.CT score was negatively correlated with DLCO%and FEV1%.R value was-0.814 and-0.797,respectively;The comparison of the mean value of DLCO%and FEV1%among the three groups and the pairings of the mean value of DLCO%and FEV1%were statistically significant.Conclusion:There was good correlation between CT score of ILD and the pulmonary function index.The pulmonary function index of patients with different CT severity grading was statistically significant,which can provide a new basis for the clinical evaluation and diagnosis of the disease.
基金Supported by Guangxi Guilin Science and Technology Fund,No.20190218-7-6.
文摘BACKGROUND Most non-small cell lung cancer patients have epidermal growth factor receptor(EGFR)activating mutations,such as exon 19 deletion and exon 21 replacement mutations.Osimertinib is a third-generation EGFR-tyrosine kinase inhibitors ap-proved for the treatment of lung cancer patients carrying EGFR activating mu-tations.Osimertinib-induced interstitial lung disease(ILD)is a rare and poten-tially fatal pulmonary toxic manifestation of drug therapy.At present,there is no international consensus on the risks and treatment of the osimertinib-induced ILD.CASE SUMMARY We report a case of a 56-year-old woman who was diagnosed with lung adenocar-cinoma with lung hilum,mediastinal lymph nodes and brain metastases(T4N3-M1c stage IVB).The patient received targeted treatment with osimertinib after radiotherapy and chemotherapy.But she developed ILD after osimertinib treat-ment.Following active symptomatic treatment and hormone treatment,the lung injury alleviated.The patient was retreated with furmonertinib combined with prednisone and did not experience ILD again.So far,she has survived for 14 months without disease progression.CONCLUSION Retreatment with furmonertinib under prednisone could be considered as an effective therapeutic option after risk-benefit assessment for EGFR-mutant lung adenocarcinoma patients.
基金the financial support from National Natural Science Foundation of China(No.52171162)Research Grants Council of Hong Kong(Nos.15202824,15227121,C5002-24Y,C1017D21GF,and C1020D21GF)+4 种基金Shenzhen Science and Technology Program(No.JCYJ20210324142203009)the Research Institute for Advanced Manufacturing Fund(No.P0046108)PolyU Fund(Nos.P0044243 and P0043467)Guangdong Science and Technology Innovation Foundation(No.2023A1515240061)Open access funding provided by The Hong Kong Polytechnic University
文摘Interstitial alloying has emerged as a powerful strategy to tune microstructure and microproperties of high-entropy alloys(HEAs) due to the strong interaction of interstitials with constituent elements and crystal defects,which enables the development of advanced alloys with superior mechanical and functional properties. The paper reviews the latest progress in the atomic-scale understanding of the effects of various interstitials, including carbon, boron, nitrogen, oxygen, and hydrogen, on the microstructure, stability, mechanical properties, and deformation behavior of HEAs. Emphases are placed on the in-depth insights on the interaction of interstitials with constituent elements and crystal defects, such as vacancies,stacking faults, and grain boundaries. Key parameters for rapid prediction of intrinsic properties of HEAs are also discussed. Finally, we highlight some unsolved issues and provide perspectives for future research directions.
文摘Dermatomyositis(DM)is an idiopathic inflammatory myopathy characterized by prominent skin lesions,muscle weakness,and clinically heterogeneous systemic manifestations.Among patients with DM,the male-to-female ratio is 2:1.Juvenile dermatomyositis(JDM)is most prevalent between the ages of 4 and 14 years,while adult-onset dermatomyositis typically occurs between the ages of 40 and 60 years.In a population-based study conducted in Olmsted County,Minnesota,USA,the risk of DM was found to increase with age across different age groups stratified by decade.The incidence rate of DM in individuals aged≥80 years was 3.2 per 100,000 person-years.Dermatomyositis in elderly patients is characterized by unique clinical manifestations,pathogenic mechanisms,and therapeutic approaches.However,discussions regarding geriatric dermatomyositis are currently limited.Therefore,this article aims to review the epidemiology,clinical features,histopathology,and pathogenesis of dermatomyositis,with a particular focus on the unique clinical characteristics of geriatric dermatomyositis.
基金Supported by National Institutes of Health Grants,No.R01DK103055(to Ro S)RosVivo Therapeutics,No.AWD-01-00003158(to Ro S)the National Research Foundation of Korea Grant Funded by the Korean Government(MSIT),No.NRF-2021R1C1C2006743(to Kim MS)and No.NRF-2021R1A2C1095311(to Lee MY).
文摘BACKGROUND We previously identified miR-10b-5p as a key regulator of gastrointestinal(GI)motility through its essential role in the development and function of interstitial cells of Cajal(ICC),the pacemaker cells of the gut.Loss of miR-10b-5p in ICC im-pairs intestinal motility and contributes to constipation,a common condition in the elderly.Notably,miR-10b-5p is co-expressed with its paralog,miR-10a-5p,in ICC.AIM To investigate the roles of miR-10a-5p and miR-10b-5p in age-associated intestinal dysmotility and assess the therapeutic potential of restoring their expression.METHODS We employed aged mice,mir-10a and mir-10b single and double knockout(KO)models,and human plasma and colon samples across age groups.GI and colonic transit,ICC network integrity,and expression levels of miR-10a/b-5p were eva-luated.Additionally,we tested whether treatment with their microRNA mimics could restore GI motility in aged mice.RESULTS Aged mice exhibited delayed GI and colonic transit,reduced fecal output,and diminished expression of miR-10a-5p and miR-10b-5p,which peaked during late embryonic and early postnatal stages and declined with age.This decline para-lleled ICC network deterioration in the colon.All KO models exhibited impaired motility and ICC loss,with mir-10a KO mice displaying more severe phenotypes than mir-10b KO mice.Double KO mice demonstrated growth retardation and reduced survival,with homozygous mutants living only up to 3 months.Treatment of aged mice with miR-10a-5p and miR-10b-5p mimics encapsu-lated in jetPEI significantly improved GI and colonic motility.Successful delivery to the gut,including the colon,was confirmed.In human samples,both miR-10a/b-5p and KIT expression decreased with age.CONCLUSION miR-10a-5p and miR-10b-5p are essential for ICC maintenance and colonic motility,and their age-related decline contributes to GI dysmotility in both mice and humans.Restoring their levels offers a promising therapeutic stra-tegy for treating age-related constipation and other motility disorders.
文摘Interstitial lung diseases(ILD)encompass a diverse group of over 200 chronic pulmonary disorders characterized by varying degrees of inflammation and fibrosis,which can lead to severe respiratory impairment.Lung transplantation offers a crucial therapeutic option for patients with advanced ILD,extending survival and improving quality of life.This review explores optimal management strategies in both the pre-and post-transplant phases to enhance patient outcomes.Comprehensive pre-transplant evaluation,including pulmonary function testing,imaging,and comorbidity assessment,is critical for determining transplant eligibility and timing.Post-transplant care must focus on preventing complications such as primary graft dysfunction and chronic lung allograft dysfunction,managed through tailored immunosuppression and proactive monitoring.Recent advancements in diagnostic techniques and therapeutic approaches,including emerging technologies like ex vivo lung perfusion and precision medicine,promise to further improve outcomes.The ultimate goal is to establish an evidencebased,multidisciplinary framework for optimizing ILD management and lung transplantation.
基金Supported by China Postdoctoral Science Foundation,No.2024M751334.
文摘BACKGROUND The high mortality rate and recurrence/metastasis remain major challenges in the clinical management of gastric cancer(GC)patients.To optimize treatment stratification and management,there is an urgent need for efficient and non-invasive biomarkers.A meta-analysis on the prognostic role of circulating tumor cells(CTCs)in GC revealed a strong association between CTCs and patient prognosis.Among CTC subtypes,Interstitial CTCs(I-CTCs)exhibited the strongest invasiveness.This study innovatively investigated the expression profile of I-CTCs in advanced GC patients to evaluate their clinical utility.AIM To evaluate the clinical utility of I-CTCs as a non-invasive prognostic biomarker in advanced GC.To investigate the correlation between I-CTC count thresholds and chemotherapy efficacy in advanced GC patients.To establish the potential of preoperative I-CTC profiling for optimizing treatment stratification and postoperative surveillance.METHODS This study retrospectively analyzed 59 patients with advanced GC treated at the General Surgery Clinical Medical Center of Gansu Provincial Hospital between October 2019 and October 2020.The expression levels of I-CTCs were measured,and patient survival was monitored.The receiver operating characteristic curve was plotted to determine the optimal cut-off value for I-CTCs expression levels.Based on this cut-off value,59 GC patients were grouped into positive and negative groups.The differences in clinicopathological characteristics between the two groups were analyzed.Patient survival was follow-up and recorded until October 2022.Plotting survival curves and performing univariate and multifactorial analyses of patient prognostic factors.The Kaplan-Meier method and Cox regression model were used,respectively.RESULTS A total of 59 patients were included in this study,and receiver operating characteristic curve analysis showed that the best cut-off value for I-CTCs was 5,with an area under the curve of 0.8356(95%CI:0.7122-0.9590).The I-CTC count of≥5 defines the positive group,while counts<5 are classified as the negative group.Positive I-CTCs correlated with the degree of tumor differentiation and disease progression(P<0.05).16 of 59 patients received neoadjuvant chemotherapy.There were divided into progressive disease and disease control groups based on response to neoadjuvant chemotherapy.Patients in the I-CTCs-negative group had longer overall survival and disease-free survival than those in the positive group(P<0.05).Multifactorial analysis revealed that I-CTCs positivity(HR=13.323,95%CI:1.675-105.962,P=0.014)was an independent risk factor for survival in patients with advanced GC.CONCLUSION In patients with advanced GC,an I-CTC count of≥5 is associated with both poor prognosis and reduced chemotherapy efficacy.I-CTCs may serve as a valuable preoperative biomarker for predicting the prognosis of advanced GC.
