Based on the data of daily precipitation in 11 national ground meteorological observation stations in Jining City from 1981 to 2020,the interdecadal variation,intensity,range and spatial distribution of rainstorms in ...Based on the data of daily precipitation in 11 national ground meteorological observation stations in Jining City from 1981 to 2020,the interdecadal variation,intensity,range and spatial distribution of rainstorms in Jining City were analyzed.The results show that the number of rainstorm days and the total amount of rainstorms in Jining City had significant changes among different decades.There was a continuous upward trend from the 1980s to the early 21 st century and a decrease after the early 21 st century.Rainstorms had distinct seasonal characteristics.They were mainly concentrated in summer,especially in July and August.In terms of spatial distribution,the frequency and intensity of rainstorms in the southeastern regions were significantly higher than those in the northwestern regions.The above results can provide a scientific basis for flood control and disaster reduction in Jining City.展开更多
Based on the observation data of meteorological observation stations in Jining City during 1970-2024,MK mutation test and principal component analysis(PCA)were used to study the evolution characteristics of urban heat...Based on the observation data of meteorological observation stations in Jining City during 1970-2024,MK mutation test and principal component analysis(PCA)were used to study the evolution characteristics of urban heat island intensity(UHII)and the contribution rate of various influencing factors in Jining City over the past 55 years.The results show that from 1970 to 2024,the UHII in Jining City generally rose at a rate of 0.1℃/10 a.On the interannual scale,the correlation between temperature and UHII was most significantly positive.On the seasonal scale,there was a strong negative correlation between wind speed and UHII.PCA reveals that temperature had a significant positive impact on the increase of UHII in Jining City.展开更多
[ Objective] The study aimed to discuss the characteristics of atmospheric environmental pollution in Jining City. Methed] Based on the environmental monitoring data and synchronous meteorological data in 2006 -2010 ...[ Objective] The study aimed to discuss the characteristics of atmospheric environmental pollution in Jining City. Methed] Based on the environmental monitoring data and synchronous meteorological data in 2006 -2010 in Jining City, the distribution regularity of main atmospheric pol- lutants in this city was studied by the method of statistical analysis. [ Result] There were obvious spatial and temporal distribution of atmospheric pollutants in Jining City during 2006 -2010 under the comprehensive effects of meteorological conditions and pollution source emission. That is, at- mospheric pollution was serious in winter but slight in summer, and it was severe in the morning and evening. The load coefficients of SO2, NO2 and PM10 in the atmosphere showed an increasing trend from 2006 to 2010, and their concentrations had close relations with wind direction and ve- locity, urban heat island effect, and motor vehicle quantity. [ Conclusion] This research has important practical significance to the control of atmos- pheric pollution in Jining City.展开更多
Co-assembling chiral molecules with achiral compounds via non-covalent interactions like areneperfluoroarene(AP) interactions offers an effective approach for fabricating chiral functional materials.Herein,chiral mole...Co-assembling chiral molecules with achiral compounds via non-covalent interactions like areneperfluoroarene(AP) interactions offers an effective approach for fabricating chiral functional materials.Herein,chiral molecules L/D-PF1 and L/D-PF2 with pyrene groups were synthesized and its chiroptical properties upon co-assembly with achiral compound octafluoronaphthalene(OFN) through AP interaction were systemically studied.The co-assembly of L/D-PF1/OFN and L/D-PF2/OFN exhibited distinct chiroptical properties such as circular dichroism(CD) and circularly polarized luminescence(CPL) signals.Chirality transfer from the chirality center of L/D-PF1 and L/D-PF2 to the achiral OFN and chiral amplification were successfully achieved.Besides,no significant CPL signal was observed in the self-assembly of L/DPF1 or L/D-PF2 while co-assembly with OFN exhibited obvious CPL amplification induced by AP interaction.Notably,a reversal CD signal and CPL signal could be observed in L/D-PF2/OFN when the molar ratio changed from 1:1 to 1:2 while not found in L/D-PF1/OFN,indicating that that minor structural changes of molecules could cause large changes in assembly.In addition,a series of computational calculations were conducted to verify the AP interaction between L-PF1/L-PF2 and OFN.This work demonstrated that arene-perfluoroarene interaction could drive chiral transfer,chiral amplification and chiral inversion and provided a new method for the preparation of chiroptical materials.展开更多
Internal structural defects in engineering rock masses vary in size,exhibit complex shapes,and are unevenly distributed.Dominant fractures within a rock mass often play a critical to its mechanical behavior,directly a...Internal structural defects in engineering rock masses vary in size,exhibit complex shapes,and are unevenly distributed.Dominant fractures within a rock mass often play a critical to its mechanical behavior,directly affecting the macromechanical properties and failure modes.These fractures affect the instability and failure of the surrounding rock,significantlyimpacting the overall stability of engineering structures.Herein,sand-powder three-dimensional(3D)printing technology was used to prepare rock-like specimens with internal fracture networks.Triaxial compression testing,post-failure fracture mapping,and fractal dimension analysis of the fracture surfaces were conducted to investigate the effects of dominant fracture angles on the strength and deformation of rocks with internal fracture networks under triaxial stress.The results indicate that the dominant fracture angle has a pronounced effect on the mechanical behavior of rock.With increasing angle,both compressive strength and elastic modulus exhibit an initial decline followed by an increase.Moreover,higher confiningpressure significantlyimproves the compressive strength of fractured rock.This enhancement weakens as the confiningpressure further increases.Moreover,with increasing confiningpressure,the differences between the maximum and minimum values of elastic moduli and lateral strain ratios in fractured rock gradually decrease.Thus,the impact of the dominant fracture angle on rock mass deformation decreases with increasing confiningpressure.This research elucidates the effects of dominant fracture angles on the mechanical and failure properties of complex fractured rock masses and the influenceof the confiningpressure on these relationships.It provides valuable theoretical insights and practical guidance for stability analyses in engineering rock masses.展开更多
Objectives:This study aimed to determine the role and mechanism underlying migration and invasion inhibitory protein(MIIP)modulation in M2 macrophages within the tumor microenvironment and the potential of targeting t...Objectives:This study aimed to determine the role and mechanism underlying migration and invasion inhibitory protein(MIIP)modulation in M2 macrophages within the tumor microenvironment and the potential of targeting the MIIP-stimulator of interferon genes(STING)pathway in colorectal cancer(CRC)therapy.Methods:MIIP expression was analyzed for associations with the STING pathway and M2 macrophage infiltration using public datasets and clinical CRC samples.CRC cells were genetically modified using lentiviral vectors to overexpress or silence MIIP and STING.The interactions of genetically modified CRC cells with macrophages were studied in co-culture systems.Techniques,including immunofluorescence staining,RT‒qPCR,western blot,ELISA,flow cytometry,and Transwell migration and invasion assays,were used to evaluate the crosstalk between CRC cells and macrophages.An orthotopic mouse CRC model was developed to study the effects of MIIP on M2 macrophage polarization and tumor metastasis through the STING-NFκB2-IL10 axis.The therapeutic significance of a STING antagonist was also assessed in vivo.Results:Analyses of The Cancer Genome Atlas(TCGA)cohort and our CRC cohort revealed low MIIP expression is associated with STING pathway activation,increased M2 macrophage infiltration,and poor clinical outcomes.The results of functional experiments demonstrated that MIIP inhibits IL10 production via the STING-TRAF3-NFκB2 axis in CRC cells,suppressing M2 macrophage polarization in co-culture systems.Conversely,M2 macrophages promoted CRC cell migration and invasion in an IL10-dependent manner.In vitro and in vivo studies confirmed that the MIIP-mediated feedback loop between CRC cells and macrophages depends on the STING-NFκB2-IL10 axis.Furthermore,inhibition of STING expression in a mouse model reduced M2 macrophage polarization and tumor metastasis.Conclusions:This study established MIIP as a crucial regulator of macrophage polarization in the CRC tumor microenvironment,providing new insights into the role in suppressing CRC progression and immune-tumor crosstalk.These findings highlight the potential of targeting the STING pathway as a therapeutic strategy for CRC patients who respond poorly to immune checkpoint inhibitors.展开更多
Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(P...Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(PC)remain not fully explored.The study aimed to explore how gut metabolites regulate death-ligand 1(PD-L1)blockade via exosomes and boost immune checkpoint inhibitors(ICIs)in PC.Methods:We recruited 70 PC patients to set up into five subgroups.The integrated multi-omics analysis was performed.In parallel,we validated the function of gut microbiome-associated metabolites on PD-L1 production and immunotherapy treatment efficacy in PC cell lines and transgenic adenocarcinoma of the mouse prostate(TRAMP)models.Results:We identified two metabolites,16(R)-Hydroxyeicosatetraenoic acid(16(R)-HETE)and 6-Keto-Prostaglandin E1(6-Keto-PGE1),that positively correlated with the plasma exosomal PD-L1 levels.The in vitro experiments found that both 16(R)-HETE and 6-Keto-PGE1 can enhance PD-L1 expression at the mRNA,protein,and exosome levels in both human and mouse PC cell lines,which were also validated in vivo based on subcutaneous mouse models.Both metabolites significantly promoted the anti-PD-L1 efficacy against PC in situ on a TRAMP mouse model.Conclusions:Targeting the“gut-tumor metabolic axis”is a promising strategy to improve the efficacy of immune checkpoint inhibitors in tumors.展开更多
Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular...Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.展开更多
BACKGROUND Middle meningeal artery embolization(MMAE)is emerging as a promising treatment for chronic subdural hematoma(CSDH),serving both as an adjunct to surgery and as a primary therapeutic option depending on pati...BACKGROUND Middle meningeal artery embolization(MMAE)is emerging as a promising treatment for chronic subdural hematoma(CSDH),serving both as an adjunct to surgery and as a primary therapeutic option depending on patient presentation.Due to its low recurrence rate and minimal complications,MMAE has gained increasing acceptance among clinicians in recent years.This report presents a case of diplopia following MMAE due to the presence of a potential anastomotic artery,aiming to enhance awareness of this complication.CASE SUMMARY A 60-year-old male patient presented with a headache following head trauma,and cranial computed tomography revealed a left-sided CSDH.The patient underwent left MMAE;however,polyvinyl alcohol particles inadvertently flowed into the lacrimal artery through an anastomotic artery,resulting in diplopia due to impaired abduction of the left eye.The diplopia resolved by postoperative day 40.The patient’s headache resolved by postoperative day 7,and the hematoma completely resolved by postoperative day 108.CONCLUSION Potential anastomotic arteries in the middle meningeal artery(MMA)can lead to serious complications.Superselective angiography of the MMA or its branches prior to embolization is essential.Performing embolization distal to potential anastomotic sites can reduce risks,and the presence of an anastomosis may warrant coil embolization or termination of the procedure.展开更多
BACKGROUND The pathophysiology of diabetic kidney disease(DKD)is complex.Interfering with the processes of pyroptosis and fibrosis is an effective strategy for slowing DKD progression.Previous studies have revealed th...BACKGROUND The pathophysiology of diabetic kidney disease(DKD)is complex.Interfering with the processes of pyroptosis and fibrosis is an effective strategy for slowing DKD progression.Previous studies have revealed that nuclear receptor subfamily 4 group A member 1(NR4A1)may serve as a novel pathogenic element in DKD;however,the specific mechanism by which it contributes to pyroptosis and fibrosis in DKD is unknown.AIM To investigate the role of NR4A1 in renal pyroptosis and fibrosis in DKD and possible molecular mechanisms.METHODS Streptozotocin 60 mg/kg was injected intraperitoneally to establish a rat model of DKD.Typically,45 mmol/L glucose[high glucose(HG)]was used to activate HK-2 cells to mimic the DKD model in vitro.HK-2 cells were transfected with NR4A1 siRNA to silence NR4A1.RESULTS NR4A1 was elevated in renal tissues of DKD rats and HG-stimulated HK-2 cells.Concurrently,NOD-like receptor protein 3(NLRP3)and phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)pathways were triggered,and pyroptosis and expression of fibrosis-linked elements was increased in vivo and in vitro.These alterations were significantly reversed via NR4A1 silencing.CONCLUSION Inhibition of NR4A1 mitigated pyroptosis and fibrosis via suppressing NLRP3 activation and the PI3K/AKT pathway in HG-activated HK-2 cells.展开更多
Background:This study investigated the relationship between meteorological factors and daily outpatient visits to rabies post-exposure prophylaxis clinics to inform animal injury prevention strategies.Methods:Daily ou...Background:This study investigated the relationship between meteorological factors and daily outpatient visits to rabies post-exposure prophylaxis clinics to inform animal injury prevention strategies.Methods:Daily outpatient visit data from rabies post-exposure prophylaxis clinics in Jinan and corresponding meteorological data were collected from January 1,2020,to December 31,2022.A generalized additive model was used to quantitatively assess the relationship between these factors.A total of 202,010 patients visited these clinics during this period.Results:Daily mean,maximum,and minimum temperatures,and relative humidity were positively associated with outpatient visits.A 1°C increase in mean,maximum,and minimum temperatures corresponded to increases in daily visits of 1.65%(95%Confidence Interval(CI):1.55–1.76),1.59%(95%CI:1.50–1.69),and 1.27%(95%CI:1.17–1.36)respectively.Each 1%increase in relative humidity was associated with a 0.18%(95%CI:0.15–0.20)increase in visits.Mean pressure was negatively associated with outpatient visits,the outpatient visits decreased by 0.91%(95%CI:−1.71 to−0.11)for every 1 kPa increased in mean pressure.Conclusion:The change of meteorological factors will lead to the increase of outpatient visits in rabies exposure treatment clinic.展开更多
To address the challenges posed by high reaction temperatures and the slow kinetics of Mg-based alloys with high hydrogen storage density,Mg−RE−TM(RE=rare earth,TM=metallic element)alloys have been extensively researc...To address the challenges posed by high reaction temperatures and the slow kinetics of Mg-based alloys with high hydrogen storage density,Mg−RE−TM(RE=rare earth,TM=metallic element)alloys have been extensively researched and hold great promise.In this study,a series of Mg−RE−TM based Mg_(90)Y_(2)Ce_(2)Ni_(3)Al_(3-x)Sc_(x)(x=0,0.3,0.6,0.9,1.2)alloys were prepared.The addition of Sc element has been found to enhance the activation and kinetic properties of the alloy.Compared with the significant differences in the first four dehydrogenation curves of the Sc0 sample,the first activated dehydrogenation curve of the Sc1.2 alloy overlaps with the fully activated dehydrogenation curve.The dehydrogenation activation energy decreased from 96.56 kJ/mol in the Sc0 alloy to 63.69 kJ/mol in the Sc0.9 alloy.Through analysis of the microstructure,phase composition,and hydrogen absorption and desorption kinetics of the alloy,the mechanisms for improving the hydrogen storage properties of the alloy were elucidated.The nucleation-growth-impingement Avrami model was employed to accurately simulate the hydrogen storage kinetics.The results showed that stage II was prolonged and accelerated at high temperature,and the growth rate and hydrogen storage of stage I were increased at low temperature in hydrogen absorption.Microstructure analysis revealed the presence of Mg,CeMg_(12),Mg_(47)Y,and YNi_(2)Al_(3) phases in the Sc0 sample.Upon the addition of Sc element,a new phase,ScNiAl,was formed,and the coarse grain size of the main phase was significantly refined.This refinement provides faster diffusion channels for hydrogen atoms,accelerating the phase transition between Mg alloys and hydrides.The microstructure changes explain the improved activation properties,effective hydrogen absorption and desorption capacity,and kinetic properties of the Mg-based samples.展开更多
Rare earth(RE)elements have been successfully utilized in solid-state hydrogen storage as hydrogen-absorbing elements with excellent hydrogen storage properties in terms of safety and efficiency.RE-Mg-based hydrogen s...Rare earth(RE)elements have been successfully utilized in solid-state hydrogen storage as hydrogen-absorbing elements with excellent hydrogen storage properties in terms of safety and efficiency.RE-Mg-based hydrogen storage materials with high magnesium content are considered to be one of the most promising hydrogen storage materials for application due to their high mass/volume hydrogen storage density,moderate required hydrogen pressure,good reversibility,non-toxicity,and harmlessness.Furthermore,RE-Mg-based materials with low magnesium content and superlattice structure show great potential for application in the field of solid-state hydrogen storage.They are also widely used as anode materials for nickel-metal hydride batteries.In this paper,we comprehensively summarized and evaluated the organization and hydrogen storage properties of different RE-Mg system alloys(Mg-RE,Mg-RE-TM(TM=transition metals),and superlattice-type RE-Mg-TM)and the catalytic effect and mechanisms of catalysts on RE-Mg system alloys.The interactions between the types of RE elements,the contents of RE elements,the crystal structures,and the catalysts with the microstructure morphology and hydrogen storage properties of RE-Mg-based hydrogen storage alloys were established.The intrinsic mechanisms between microstructure morphology,phase structure,phase composition,and hydrogen storage properties of alloys with different RE-Mg-based systems were elucidated.By comparing the differences and characteristics between the organizational structures and hydrogen storage properties of different RE-Mg systems,a feasible idea and solution for the rational design and development of RE-Mg-based alloys with high hydrogen storage capacity,low cost,and fast hydrogen absorption and desorption kinetics was proposed.展开更多
Myeloblastosis(MYB)transcription factors,particularly those in the R2R3 MYB subclass,are pivotal in plant growth,development,and environmental stress responses.As one of the largest transcription factor families in pl...Myeloblastosis(MYB)transcription factors,particularly those in the R2R3 MYB subclass,are pivotal in plant growth,development,and environmental stress responses.As one of the largest transcription factor families in plants,the MYB family significantly regulates plant secondary metabolism,including the biosynthetic pathways for phenylpropanoids,which are crucial for stress resistance.This review presents a comprehensive overview of MYB transcription factor classification and their regulatory mechanisms in plant metabolism and stress responses.We discuss the roles of MYB transcription factors in biotic stress resistance,such as defense against pathogens and pests,and in abiotic stress tolerance,including responses to drought and salinity.Special attention is given to the interactions of R2R3 MYB with other transcription factors and co-repressors,focusing on how these synergistic or antagonistic relationships modulate physiological processes.The multifunctional role of R2R3 MYBs in stress responses positions them as promising targets for enhancing crop resilience through genetic breeding.Furthermore,this review highlights potential applications of MYB transcription factors in developing stress-resistant crops and their utility in plant resistant breeding programs.展开更多
Objective To explore the sequential effects of hypoxic exercising on miR-27/PPARγand lipid metabolism targetgene and protein expression levels in the obesity rats’liver.Methods 13-week-old male diet-induced obesity ...Objective To explore the sequential effects of hypoxic exercising on miR-27/PPARγand lipid metabolism targetgene and protein expression levels in the obesity rats’liver.Methods 13-week-old male diet-induced obesity rats were randomlydivided into three groups(n=10):normal oxygen concentration quiet group(N),hypoxia quiet group(H),hypoxic exercise group(HE).Exercise training on the horizontal animal treadmill for 1 h/d,5 d/week for a total of 4 week,and the intensity of horizontaltreadmill training was 20 m/min(hypoxic concentration was 13.6%).Comparison of the weights of perirenal fat and epididymal fat in rats across different groups and calculation of Lee’s index based on body weight and body length of rats in each group were done.And the serum concentrations of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),high-densitylipoprotein cholesterol(HDL-C)levels were detected.RT-PCR and Western Blot were used to detect the levels of miR-27,PPARγ,CYP7A1 and CD36.Results Hypoxic exercise decreased the expression levels of miR-27 in the obese rats’liver,however,theexpression level of PPARγwas gradually increased.The expression levels of miR-27 in HE group were significantly lower than Ngroup(P<0.05).The expression levels of PPARγmRNA in N group were significantly lower than H group(P<0.05),especially lowerthan HE group(P<0.01).The protein expression of PPARγprotein in N group was significantly lower than that other groups(P<0.01).The expression of lipid metabolism-related genes and proteins increased in the obese rats’liver.The expression of CYP7A1mRNA in N group was significantly lower than H group(P<0.05),especially lower than HE group(P<0.01).The expression ofCYP7A1 protein in the obese rats’liver in N group was extremely lower than H group and HE group(P<0.01).The proteinexpression of CD36 in N group was significantly lower than that in HE group(P<0.05).Hypoxia exercise improved the relatedphysiological and biochemical indexes of lipid metabolism disorder.The perirenal fat weight of obese rats in HE group wasextremely lower than N group and H group(P<0.01),and the perirenal fat weight in N group was significantly higher than H group(P<0.05).The epididymal fat weight in N group was significantly higher than H group(P<0.05),and extremely higher than HEgroup(P<0.01).The Lee’s index in HE group was extremely lower than N group and H group(P<0.01).The serum concentration ofTC in obese rats in HE group was extremely lower than N group and H group(P<0.01).The serum concentration of TG in HE groupwas extremely lower than N group and H group(P<0.01).The serum concentration of LDL-C in N group was extremely higher thanHE group(P<0.01).The serum concentration of HDL-C in N group was extremely lower than H group(P<0.01).Conclusion Hypoxiaand hypoxia exercise may negatively regulate the levels of PPARγby inhibiting miR-27 in the obese rats’liver,thereby affecting theexpression of downstream target genes CYP7A1 and CD36,and promoting cholesterol,fatty acid oxidation and HDL-C transport inthe liver,and ultimately the lipid levels in obese rats were improved.The effect of hypoxia exercise on improving blood lipid isbetter than simple hypoxia intervention.展开更多
Objective:Early predicting response before neoadjuvant chemotherapy(NAC)is crucial for personalized treatment plans for locally advanced breast cancer patients.We aim to develop a multi-task model using multiscale who...Objective:Early predicting response before neoadjuvant chemotherapy(NAC)is crucial for personalized treatment plans for locally advanced breast cancer patients.We aim to develop a multi-task model using multiscale whole slide images(WSIs)features to predict the response to breast cancer NAC more finely.Methods:This work collected 1,670 whole slide images for training and validation sets,internal testing sets,external testing sets,and prospective testing sets of the weakly-supervised deep learning-based multi-task model(DLMM)in predicting treatment response and pCR to NAC.Our approach models two-by-two feature interactions across scales by employing concatenate fusion of single-scale feature representations,and controls the expressiveness of each representation via a gating-based attention mechanism.Results:In the retrospective analysis,DLMM exhibited excellent predictive performance for the prediction of treatment response,with area under the receiver operating characteristic curves(AUCs)of 0.869[95%confidence interval(95%CI):0.806−0.933]in the internal testing set and 0.841(95%CI:0.814−0.867)in the external testing sets.For the pCR prediction task,DLMM reached AUCs of 0.865(95%CI:0.763−0.964)in the internal testing and 0.821(95%CI:0.763−0.878)in the pooled external testing set.In the prospective testing study,DLMM also demonstrated favorable predictive performance,with AUCs of 0.829(95%CI:0.754−0.903)and 0.821(95%CI:0.692−0.949)in treatment response and pCR prediction,respectively.DLMM significantly outperformed the baseline models in all testing sets(P<0.05).Heatmaps were employed to interpret the decision-making basis of the model.Furthermore,it was discovered that high DLMM scores were associated with immune-related pathways and cells in the microenvironment during biological basis exploration.Conclusions:The DLMM represents a valuable tool that aids clinicians in selecting personalized treatment strategies for breast cancer patients.展开更多
Parkinson's disease(PD)is a common clinical nervous system disease,which seriously affects the health of middle—aged and elderly people.The current treatment for Parkinson's disease is only aimed at alleviati...Parkinson's disease(PD)is a common clinical nervous system disease,which seriously affects the health of middle—aged and elderly people.The current treatment for Parkinson's disease is only aimed at alleviating early symptoms.Curcumin(CUR)is a natural product,which has been widely used in anti—in—flammation,anticancer,and other fields.However,the potential mechanism of CUR in treating PD is currently unclear.The corresponding genes of CUR were harvested from the TCMSP,SwissTargetPrediction,SuperPred,PharmMapper,and SEA.Meanwhile,genes associated with PD were adopted from OMIM,TTD,DrugBank,MalaCards,and GeneCards databases.Through Gene Ontology(GO)and Kyoto Encyclopaedia of Genes and Genomes(KEGG)pathway enrichment analyses,therapeutic targeting KEGG pathways and functions were further collected.Then,STRING was used to generate the protein—protein interaction(PPI)network.The"drug—targets—disease"network was built by Cystoscope.Finally,the binding between CUR and core targets of PD was identified via molecular docking technology.The network pharmacology analysis revealed 65 potential targets related to the treatment of PD with CUR.The 10 core targets are CYP3A4,GSK3B,CYP19A1,CHEK1,COMT,CYP2A6,CYP2C19,HSD17B1,NFE2L2,and AHR.Moreover,KEGG enrichment analysis found that it was closely related to metabolic pathways,glycosaminoglycan degradation,steroid hormone biosynthesis,etc.The molecular docking results revealed that CUR had a strong binding ability with the PD target protein.In vitro experiments have shown that CUR can significantly improve oxidative damage caused by rotenone intervention in PD SHSY5Y cells and upregulate the level of key antioxidant pathway proteins Nrf2 and AHR.In a word,CUR may have therapeutic effects on PD through multitarget and multi—pathway,which provide a scientificbasis for further elaborating the mechanism of CUR in the treatment of PD.展开更多
BACKGROUND Immunoglobulin G4(IgG4)-related disease(IgG4-RD),a relatively rare immunemediated chronic inflammatory condition characterized by fibrosis,is capable of affecting multiple organs and systems.Epidemiological...BACKGROUND Immunoglobulin G4(IgG4)-related disease(IgG4-RD),a relatively rare immunemediated chronic inflammatory condition characterized by fibrosis,is capable of affecting multiple organs and systems.Epidemiologically,the disease predominantly affects middle-aged and older men in Asian populations,whereas it shows a female predominance in the corresponding age group in the United States.In IgG4-RD,affected tissues and organs may exhibit diffuse or localized swelling,mimicking neoplastic lesions.IgG4-related cholecystitis(IgG4-CC)represents a manifestation involving the gallbladder,with isolated gallbladder involvement without other organ lesions being exceptionally uncommon.CASE SUMMARY A 53-year-old man was admitted to the hospital with abdominal pain.Preoperative evaluations could not exclude gallbladder carcinoma,and surgical intervention was required.Based on intraoperative findings,postoperative pathology,and postoperative serum IgG4 levels,a diagnosis of IgG4-CC was considered.After glucocorticoid therapy,the patient’s general condition substantially improved.CONCLUSION For patients present with space-occupying lesions of the gallbladder,IgG4-RD should be included in the differential diagnosis.展开更多
The compelling case report by Xie et al,published in a renowned medical journal,is an excellent example of meticulous clinical evaluation,comprehensive labo-ratory testing,advanced imaging,and genetic analysis.The aut...The compelling case report by Xie et al,published in a renowned medical journal,is an excellent example of meticulous clinical evaluation,comprehensive labo-ratory testing,advanced imaging,and genetic analysis.The authors identified novel compound heterozygous mutations in the hemojuvelin gene of a patient diagnosed with juvenile hemochromatosis.They suggested that long-term,strategic phlebotomy might offer a novel therapeutic strategy for severe juvenile hemochromatosis,challenging the traditional treatment paradigms.展开更多
Background:VPS37A(VPS37A subunit of ESCRT-I),a component of the ESCRT-I(endosomal sorting complex required for transport I)complex,mediates vesicular trafficking through sorting endocytic ubiquitinated cargos into mul...Background:VPS37A(VPS37A subunit of ESCRT-I),a component of the ESCRT-I(endosomal sorting complex required for transport I)complex,mediates vesicular trafficking through sorting endocytic ubiquitinated cargos into multivesicular bodies(MVBs).Although accumulating evidence indicates that VPS37A deficiency occurs in numerous malignancies and exerts tumor-suppressive effects during cancer progression,its functional significance in colorectal cancer(CRC)pathogenesis remains poorly characterized.Therefore,this study aims to further investigate the functional and molecular mechanisms by which VPS37A downregulation contributes to malignant biological phenotypes in CRC,with a specific focus on how its dysregulation affects cell death pathways.Methods:Multi-omics analysis of TCGA,GEO,and CPTAC cohorts identified VPS37A as a downregulated tumor suppressor gene in CRC.The prognostic relevance of VPS37A was validated in two clinical cohorts(Cohorts 1 and 2)using immunohistochemistry.Functional assays in VPS37A-overexpressing CRC cells and xenografts assessed proliferation,cell cycle progression,and stress-induced cell death.RNA sequencing,nuclear factor kappa-B(NF-κB)luciferase reporter assays,and lysosomal inhibition experiments elucidated the mechanisms underlying tumor necrosis factor receptor 1(TNFR1)degradation.Results:VPS37A is significantly downregulated in advanced-stage CRC and independently predicts poor survival.Functionally,VPS37A overexpression suppresses proliferation and induces G2/M arrest in vitro,while reducing xenograft growth.Under metabolic stress(glucose deprivation/galactose adaptation),VPS37A triggers cell death via apoptosis,necroptosis,and ferroptosis.Mechanistically,VPS37A redirects TNFR1 to lysosomal degradation,suppressing NF-κB nuclear translocation and transcriptional activity.Conclusion:VPS37A deficiency drives CRC progression by sustaining TNFR1/NF-κB signaling under metabolic stress.Restoring VPS37A activity promotes TNFR1 degradation,offering a therapeutic strategy to counteract NF-κB-mediated treatment resistance in CRC.展开更多
基金the Project of Jining Meteorological Bureau(2023JNZL09).
文摘Based on the data of daily precipitation in 11 national ground meteorological observation stations in Jining City from 1981 to 2020,the interdecadal variation,intensity,range and spatial distribution of rainstorms in Jining City were analyzed.The results show that the number of rainstorm days and the total amount of rainstorms in Jining City had significant changes among different decades.There was a continuous upward trend from the 1980s to the early 21 st century and a decrease after the early 21 st century.Rainstorms had distinct seasonal characteristics.They were mainly concentrated in summer,especially in July and August.In terms of spatial distribution,the frequency and intensity of rainstorms in the southeastern regions were significantly higher than those in the northwestern regions.The above results can provide a scientific basis for flood control and disaster reduction in Jining City.
基金Supported by the Project of Jining Meteorological Bureau(2024JNZL08).
文摘Based on the observation data of meteorological observation stations in Jining City during 1970-2024,MK mutation test and principal component analysis(PCA)were used to study the evolution characteristics of urban heat island intensity(UHII)and the contribution rate of various influencing factors in Jining City over the past 55 years.The results show that from 1970 to 2024,the UHII in Jining City generally rose at a rate of 0.1℃/10 a.On the interannual scale,the correlation between temperature and UHII was most significantly positive.On the seasonal scale,there was a strong negative correlation between wind speed and UHII.PCA reveals that temperature had a significant positive impact on the increase of UHII in Jining City.
文摘[ Objective] The study aimed to discuss the characteristics of atmospheric environmental pollution in Jining City. Methed] Based on the environmental monitoring data and synchronous meteorological data in 2006 -2010 in Jining City, the distribution regularity of main atmospheric pol- lutants in this city was studied by the method of statistical analysis. [ Result] There were obvious spatial and temporal distribution of atmospheric pollutants in Jining City during 2006 -2010 under the comprehensive effects of meteorological conditions and pollution source emission. That is, at- mospheric pollution was serious in winter but slight in summer, and it was severe in the morning and evening. The load coefficients of SO2, NO2 and PM10 in the atmosphere showed an increasing trend from 2006 to 2010, and their concentrations had close relations with wind direction and ve- locity, urban heat island effect, and motor vehicle quantity. [ Conclusion] This research has important practical significance to the control of atmos- pheric pollution in Jining City.
基金financially supported by the National Natural Science Foundation of China (Nos.22171165 and 22371170)Natural Science Foundation of Shandong Province (No.ZR2022MB080)Scientific and Technological Frontiers in Project of Henan Province(No.242102110192)。
文摘Co-assembling chiral molecules with achiral compounds via non-covalent interactions like areneperfluoroarene(AP) interactions offers an effective approach for fabricating chiral functional materials.Herein,chiral molecules L/D-PF1 and L/D-PF2 with pyrene groups were synthesized and its chiroptical properties upon co-assembly with achiral compound octafluoronaphthalene(OFN) through AP interaction were systemically studied.The co-assembly of L/D-PF1/OFN and L/D-PF2/OFN exhibited distinct chiroptical properties such as circular dichroism(CD) and circularly polarized luminescence(CPL) signals.Chirality transfer from the chirality center of L/D-PF1 and L/D-PF2 to the achiral OFN and chiral amplification were successfully achieved.Besides,no significant CPL signal was observed in the self-assembly of L/DPF1 or L/D-PF2 while co-assembly with OFN exhibited obvious CPL amplification induced by AP interaction.Notably,a reversal CD signal and CPL signal could be observed in L/D-PF2/OFN when the molar ratio changed from 1:1 to 1:2 while not found in L/D-PF1/OFN,indicating that that minor structural changes of molecules could cause large changes in assembly.In addition,a series of computational calculations were conducted to verify the AP interaction between L-PF1/L-PF2 and OFN.This work demonstrated that arene-perfluoroarene interaction could drive chiral transfer,chiral amplification and chiral inversion and provided a new method for the preparation of chiroptical materials.
基金supported by the National Key Research and Development Program Young Scientist Project(Grant No.2024YFC2911000)the National Natural Science Foundation of China(Grant No.52474103)the Major Basic Research Project of the Natural Science Foundation of Shandong Province(Grant No.ZR2024ZD22).
文摘Internal structural defects in engineering rock masses vary in size,exhibit complex shapes,and are unevenly distributed.Dominant fractures within a rock mass often play a critical to its mechanical behavior,directly affecting the macromechanical properties and failure modes.These fractures affect the instability and failure of the surrounding rock,significantlyimpacting the overall stability of engineering structures.Herein,sand-powder three-dimensional(3D)printing technology was used to prepare rock-like specimens with internal fracture networks.Triaxial compression testing,post-failure fracture mapping,and fractal dimension analysis of the fracture surfaces were conducted to investigate the effects of dominant fracture angles on the strength and deformation of rocks with internal fracture networks under triaxial stress.The results indicate that the dominant fracture angle has a pronounced effect on the mechanical behavior of rock.With increasing angle,both compressive strength and elastic modulus exhibit an initial decline followed by an increase.Moreover,higher confiningpressure significantlyimproves the compressive strength of fractured rock.This enhancement weakens as the confiningpressure further increases.Moreover,with increasing confiningpressure,the differences between the maximum and minimum values of elastic moduli and lateral strain ratios in fractured rock gradually decrease.Thus,the impact of the dominant fracture angle on rock mass deformation decreases with increasing confiningpressure.This research elucidates the effects of dominant fracture angles on the mechanical and failure properties of complex fractured rock masses and the influenceof the confiningpressure on these relationships.It provides valuable theoretical insights and practical guidance for stability analyses in engineering rock masses.
文摘Objectives:This study aimed to determine the role and mechanism underlying migration and invasion inhibitory protein(MIIP)modulation in M2 macrophages within the tumor microenvironment and the potential of targeting the MIIP-stimulator of interferon genes(STING)pathway in colorectal cancer(CRC)therapy.Methods:MIIP expression was analyzed for associations with the STING pathway and M2 macrophage infiltration using public datasets and clinical CRC samples.CRC cells were genetically modified using lentiviral vectors to overexpress or silence MIIP and STING.The interactions of genetically modified CRC cells with macrophages were studied in co-culture systems.Techniques,including immunofluorescence staining,RT‒qPCR,western blot,ELISA,flow cytometry,and Transwell migration and invasion assays,were used to evaluate the crosstalk between CRC cells and macrophages.An orthotopic mouse CRC model was developed to study the effects of MIIP on M2 macrophage polarization and tumor metastasis through the STING-NFκB2-IL10 axis.The therapeutic significance of a STING antagonist was also assessed in vivo.Results:Analyses of The Cancer Genome Atlas(TCGA)cohort and our CRC cohort revealed low MIIP expression is associated with STING pathway activation,increased M2 macrophage infiltration,and poor clinical outcomes.The results of functional experiments demonstrated that MIIP inhibits IL10 production via the STING-TRAF3-NFκB2 axis in CRC cells,suppressing M2 macrophage polarization in co-culture systems.Conversely,M2 macrophages promoted CRC cell migration and invasion in an IL10-dependent manner.In vitro and in vivo studies confirmed that the MIIP-mediated feedback loop between CRC cells and macrophages depends on the STING-NFκB2-IL10 axis.Furthermore,inhibition of STING expression in a mouse model reduced M2 macrophage polarization and tumor metastasis.Conclusions:This study established MIIP as a crucial regulator of macrophage polarization in the CRC tumor microenvironment,providing new insights into the role in suppressing CRC progression and immune-tumor crosstalk.These findings highlight the potential of targeting the STING pathway as a therapeutic strategy for CRC patients who respond poorly to immune checkpoint inhibitors.
基金supported by Tianjian advanced biomedical laboratory key research and development projectHenan Province Natural Science Foundation(Grant Number 242300421283)Major Science and Technology Project of Henan Province(221100310200)。
文摘Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(PC)remain not fully explored.The study aimed to explore how gut metabolites regulate death-ligand 1(PD-L1)blockade via exosomes and boost immune checkpoint inhibitors(ICIs)in PC.Methods:We recruited 70 PC patients to set up into five subgroups.The integrated multi-omics analysis was performed.In parallel,we validated the function of gut microbiome-associated metabolites on PD-L1 production and immunotherapy treatment efficacy in PC cell lines and transgenic adenocarcinoma of the mouse prostate(TRAMP)models.Results:We identified two metabolites,16(R)-Hydroxyeicosatetraenoic acid(16(R)-HETE)and 6-Keto-Prostaglandin E1(6-Keto-PGE1),that positively correlated with the plasma exosomal PD-L1 levels.The in vitro experiments found that both 16(R)-HETE and 6-Keto-PGE1 can enhance PD-L1 expression at the mRNA,protein,and exosome levels in both human and mouse PC cell lines,which were also validated in vivo based on subcutaneous mouse models.Both metabolites significantly promoted the anti-PD-L1 efficacy against PC in situ on a TRAMP mouse model.Conclusions:Targeting the“gut-tumor metabolic axis”is a promising strategy to improve the efficacy of immune checkpoint inhibitors in tumors.
基金supported by the National Natural Science Foundation of China,No.82101340(to FJ).
文摘Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.
文摘BACKGROUND Middle meningeal artery embolization(MMAE)is emerging as a promising treatment for chronic subdural hematoma(CSDH),serving both as an adjunct to surgery and as a primary therapeutic option depending on patient presentation.Due to its low recurrence rate and minimal complications,MMAE has gained increasing acceptance among clinicians in recent years.This report presents a case of diplopia following MMAE due to the presence of a potential anastomotic artery,aiming to enhance awareness of this complication.CASE SUMMARY A 60-year-old male patient presented with a headache following head trauma,and cranial computed tomography revealed a left-sided CSDH.The patient underwent left MMAE;however,polyvinyl alcohol particles inadvertently flowed into the lacrimal artery through an anastomotic artery,resulting in diplopia due to impaired abduction of the left eye.The diplopia resolved by postoperative day 40.The patient’s headache resolved by postoperative day 7,and the hematoma completely resolved by postoperative day 108.CONCLUSION Potential anastomotic arteries in the middle meningeal artery(MMA)can lead to serious complications.Superselective angiography of the MMA or its branches prior to embolization is essential.Performing embolization distal to potential anastomotic sites can reduce risks,and the presence of an anastomosis may warrant coil embolization or termination of the procedure.
基金Supported by Research Fund for Academician Lin He New Medicine,No.JYHL2022FMS02.
文摘BACKGROUND The pathophysiology of diabetic kidney disease(DKD)is complex.Interfering with the processes of pyroptosis and fibrosis is an effective strategy for slowing DKD progression.Previous studies have revealed that nuclear receptor subfamily 4 group A member 1(NR4A1)may serve as a novel pathogenic element in DKD;however,the specific mechanism by which it contributes to pyroptosis and fibrosis in DKD is unknown.AIM To investigate the role of NR4A1 in renal pyroptosis and fibrosis in DKD and possible molecular mechanisms.METHODS Streptozotocin 60 mg/kg was injected intraperitoneally to establish a rat model of DKD.Typically,45 mmol/L glucose[high glucose(HG)]was used to activate HK-2 cells to mimic the DKD model in vitro.HK-2 cells were transfected with NR4A1 siRNA to silence NR4A1.RESULTS NR4A1 was elevated in renal tissues of DKD rats and HG-stimulated HK-2 cells.Concurrently,NOD-like receptor protein 3(NLRP3)and phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)pathways were triggered,and pyroptosis and expression of fibrosis-linked elements was increased in vivo and in vitro.These alterations were significantly reversed via NR4A1 silencing.CONCLUSION Inhibition of NR4A1 mitigated pyroptosis and fibrosis via suppressing NLRP3 activation and the PI3K/AKT pathway in HG-activated HK-2 cells.
基金supported by Chinese Association of Preventive Medicine-Vaccine and Immunization Youth Talent Support Project(CPMAQT-YM0314)Shandong medical and health science and technology development plan project(202012050267)Shandong Center for Disease Control and Prevention-Youth Innovation Fund Project(QC-202301).
文摘Background:This study investigated the relationship between meteorological factors and daily outpatient visits to rabies post-exposure prophylaxis clinics to inform animal injury prevention strategies.Methods:Daily outpatient visit data from rabies post-exposure prophylaxis clinics in Jinan and corresponding meteorological data were collected from January 1,2020,to December 31,2022.A generalized additive model was used to quantitatively assess the relationship between these factors.A total of 202,010 patients visited these clinics during this period.Results:Daily mean,maximum,and minimum temperatures,and relative humidity were positively associated with outpatient visits.A 1°C increase in mean,maximum,and minimum temperatures corresponded to increases in daily visits of 1.65%(95%Confidence Interval(CI):1.55–1.76),1.59%(95%CI:1.50–1.69),and 1.27%(95%CI:1.17–1.36)respectively.Each 1%increase in relative humidity was associated with a 0.18%(95%CI:0.15–0.20)increase in visits.Mean pressure was negatively associated with outpatient visits,the outpatient visits decreased by 0.91%(95%CI:−1.71 to−0.11)for every 1 kPa increased in mean pressure.Conclusion:The change of meteorological factors will lead to the increase of outpatient visits in rabies exposure treatment clinic.
基金National Natural Science Foundation of China(51871125)the Major Programs of Central Iron and Steel Research Institute(No.23020230ZD)for financial support of the work.
文摘To address the challenges posed by high reaction temperatures and the slow kinetics of Mg-based alloys with high hydrogen storage density,Mg−RE−TM(RE=rare earth,TM=metallic element)alloys have been extensively researched and hold great promise.In this study,a series of Mg−RE−TM based Mg_(90)Y_(2)Ce_(2)Ni_(3)Al_(3-x)Sc_(x)(x=0,0.3,0.6,0.9,1.2)alloys were prepared.The addition of Sc element has been found to enhance the activation and kinetic properties of the alloy.Compared with the significant differences in the first four dehydrogenation curves of the Sc0 sample,the first activated dehydrogenation curve of the Sc1.2 alloy overlaps with the fully activated dehydrogenation curve.The dehydrogenation activation energy decreased from 96.56 kJ/mol in the Sc0 alloy to 63.69 kJ/mol in the Sc0.9 alloy.Through analysis of the microstructure,phase composition,and hydrogen absorption and desorption kinetics of the alloy,the mechanisms for improving the hydrogen storage properties of the alloy were elucidated.The nucleation-growth-impingement Avrami model was employed to accurately simulate the hydrogen storage kinetics.The results showed that stage II was prolonged and accelerated at high temperature,and the growth rate and hydrogen storage of stage I were increased at low temperature in hydrogen absorption.Microstructure analysis revealed the presence of Mg,CeMg_(12),Mg_(47)Y,and YNi_(2)Al_(3) phases in the Sc0 sample.Upon the addition of Sc element,a new phase,ScNiAl,was formed,and the coarse grain size of the main phase was significantly refined.This refinement provides faster diffusion channels for hydrogen atoms,accelerating the phase transition between Mg alloys and hydrides.The microstructure changes explain the improved activation properties,effective hydrogen absorption and desorption capacity,and kinetic properties of the Mg-based samples.
基金supported by the National Natural Science Foundation of China(51871125)the Major Programs of Central Iron and Steel Research Institute(No.23020230ZD).
文摘Rare earth(RE)elements have been successfully utilized in solid-state hydrogen storage as hydrogen-absorbing elements with excellent hydrogen storage properties in terms of safety and efficiency.RE-Mg-based hydrogen storage materials with high magnesium content are considered to be one of the most promising hydrogen storage materials for application due to their high mass/volume hydrogen storage density,moderate required hydrogen pressure,good reversibility,non-toxicity,and harmlessness.Furthermore,RE-Mg-based materials with low magnesium content and superlattice structure show great potential for application in the field of solid-state hydrogen storage.They are also widely used as anode materials for nickel-metal hydride batteries.In this paper,we comprehensively summarized and evaluated the organization and hydrogen storage properties of different RE-Mg system alloys(Mg-RE,Mg-RE-TM(TM=transition metals),and superlattice-type RE-Mg-TM)and the catalytic effect and mechanisms of catalysts on RE-Mg system alloys.The interactions between the types of RE elements,the contents of RE elements,the crystal structures,and the catalysts with the microstructure morphology and hydrogen storage properties of RE-Mg-based hydrogen storage alloys were established.The intrinsic mechanisms between microstructure morphology,phase structure,phase composition,and hydrogen storage properties of alloys with different RE-Mg-based systems were elucidated.By comparing the differences and characteristics between the organizational structures and hydrogen storage properties of different RE-Mg systems,a feasible idea and solution for the rational design and development of RE-Mg-based alloys with high hydrogen storage capacity,low cost,and fast hydrogen absorption and desorption kinetics was proposed.
基金supported by the Faculty Startup Fund from Jining Medical University,the Shandong Provincial Natural Science Foundation,China(Grant No.ZR2023QC309)the National Natural Science Foundation of China(Grant No.32102236)。
文摘Myeloblastosis(MYB)transcription factors,particularly those in the R2R3 MYB subclass,are pivotal in plant growth,development,and environmental stress responses.As one of the largest transcription factor families in plants,the MYB family significantly regulates plant secondary metabolism,including the biosynthetic pathways for phenylpropanoids,which are crucial for stress resistance.This review presents a comprehensive overview of MYB transcription factor classification and their regulatory mechanisms in plant metabolism and stress responses.We discuss the roles of MYB transcription factors in biotic stress resistance,such as defense against pathogens and pests,and in abiotic stress tolerance,including responses to drought and salinity.Special attention is given to the interactions of R2R3 MYB with other transcription factors and co-repressors,focusing on how these synergistic or antagonistic relationships modulate physiological processes.The multifunctional role of R2R3 MYBs in stress responses positions them as promising targets for enhancing crop resilience through genetic breeding.Furthermore,this review highlights potential applications of MYB transcription factors in developing stress-resistant crops and their utility in plant resistant breeding programs.
文摘Objective To explore the sequential effects of hypoxic exercising on miR-27/PPARγand lipid metabolism targetgene and protein expression levels in the obesity rats’liver.Methods 13-week-old male diet-induced obesity rats were randomlydivided into three groups(n=10):normal oxygen concentration quiet group(N),hypoxia quiet group(H),hypoxic exercise group(HE).Exercise training on the horizontal animal treadmill for 1 h/d,5 d/week for a total of 4 week,and the intensity of horizontaltreadmill training was 20 m/min(hypoxic concentration was 13.6%).Comparison of the weights of perirenal fat and epididymal fat in rats across different groups and calculation of Lee’s index based on body weight and body length of rats in each group were done.And the serum concentrations of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),high-densitylipoprotein cholesterol(HDL-C)levels were detected.RT-PCR and Western Blot were used to detect the levels of miR-27,PPARγ,CYP7A1 and CD36.Results Hypoxic exercise decreased the expression levels of miR-27 in the obese rats’liver,however,theexpression level of PPARγwas gradually increased.The expression levels of miR-27 in HE group were significantly lower than Ngroup(P<0.05).The expression levels of PPARγmRNA in N group were significantly lower than H group(P<0.05),especially lowerthan HE group(P<0.01).The protein expression of PPARγprotein in N group was significantly lower than that other groups(P<0.01).The expression of lipid metabolism-related genes and proteins increased in the obese rats’liver.The expression of CYP7A1mRNA in N group was significantly lower than H group(P<0.05),especially lower than HE group(P<0.01).The expression ofCYP7A1 protein in the obese rats’liver in N group was extremely lower than H group and HE group(P<0.01).The proteinexpression of CD36 in N group was significantly lower than that in HE group(P<0.05).Hypoxia exercise improved the relatedphysiological and biochemical indexes of lipid metabolism disorder.The perirenal fat weight of obese rats in HE group wasextremely lower than N group and H group(P<0.01),and the perirenal fat weight in N group was significantly higher than H group(P<0.05).The epididymal fat weight in N group was significantly higher than H group(P<0.05),and extremely higher than HEgroup(P<0.01).The Lee’s index in HE group was extremely lower than N group and H group(P<0.01).The serum concentration ofTC in obese rats in HE group was extremely lower than N group and H group(P<0.01).The serum concentration of TG in HE groupwas extremely lower than N group and H group(P<0.01).The serum concentration of LDL-C in N group was extremely higher thanHE group(P<0.01).The serum concentration of HDL-C in N group was extremely lower than H group(P<0.01).Conclusion Hypoxiaand hypoxia exercise may negatively regulate the levels of PPARγby inhibiting miR-27 in the obese rats’liver,thereby affecting theexpression of downstream target genes CYP7A1 and CD36,and promoting cholesterol,fatty acid oxidation and HDL-C transport inthe liver,and ultimately the lipid levels in obese rats were improved.The effect of hypoxia exercise on improving blood lipid isbetter than simple hypoxia intervention.
基金supported by the National Natural Science Foundation of China(No.82371933)the National Natural Science Foundation of Shandong Province of China(No.ZR2021MH120)+1 种基金the Taishan Scholars Project(No.tsqn202211378)the Shandong Provincial Natural Science Foundation for Excellent Young Scholars(No.ZR2024YQ075).
文摘Objective:Early predicting response before neoadjuvant chemotherapy(NAC)is crucial for personalized treatment plans for locally advanced breast cancer patients.We aim to develop a multi-task model using multiscale whole slide images(WSIs)features to predict the response to breast cancer NAC more finely.Methods:This work collected 1,670 whole slide images for training and validation sets,internal testing sets,external testing sets,and prospective testing sets of the weakly-supervised deep learning-based multi-task model(DLMM)in predicting treatment response and pCR to NAC.Our approach models two-by-two feature interactions across scales by employing concatenate fusion of single-scale feature representations,and controls the expressiveness of each representation via a gating-based attention mechanism.Results:In the retrospective analysis,DLMM exhibited excellent predictive performance for the prediction of treatment response,with area under the receiver operating characteristic curves(AUCs)of 0.869[95%confidence interval(95%CI):0.806−0.933]in the internal testing set and 0.841(95%CI:0.814−0.867)in the external testing sets.For the pCR prediction task,DLMM reached AUCs of 0.865(95%CI:0.763−0.964)in the internal testing and 0.821(95%CI:0.763−0.878)in the pooled external testing set.In the prospective testing study,DLMM also demonstrated favorable predictive performance,with AUCs of 0.829(95%CI:0.754−0.903)and 0.821(95%CI:0.692−0.949)in treatment response and pCR prediction,respectively.DLMM significantly outperformed the baseline models in all testing sets(P<0.05).Heatmaps were employed to interpret the decision-making basis of the model.Furthermore,it was discovered that high DLMM scores were associated with immune-related pathways and cells in the microenvironment during biological basis exploration.Conclusions:The DLMM represents a valuable tool that aids clinicians in selecting personalized treatment strategies for breast cancer patients.
基金Supported by Shandong Natural Science Foundation General Project(ZR2022MH197)。
文摘Parkinson's disease(PD)is a common clinical nervous system disease,which seriously affects the health of middle—aged and elderly people.The current treatment for Parkinson's disease is only aimed at alleviating early symptoms.Curcumin(CUR)is a natural product,which has been widely used in anti—in—flammation,anticancer,and other fields.However,the potential mechanism of CUR in treating PD is currently unclear.The corresponding genes of CUR were harvested from the TCMSP,SwissTargetPrediction,SuperPred,PharmMapper,and SEA.Meanwhile,genes associated with PD were adopted from OMIM,TTD,DrugBank,MalaCards,and GeneCards databases.Through Gene Ontology(GO)and Kyoto Encyclopaedia of Genes and Genomes(KEGG)pathway enrichment analyses,therapeutic targeting KEGG pathways and functions were further collected.Then,STRING was used to generate the protein—protein interaction(PPI)network.The"drug—targets—disease"network was built by Cystoscope.Finally,the binding between CUR and core targets of PD was identified via molecular docking technology.The network pharmacology analysis revealed 65 potential targets related to the treatment of PD with CUR.The 10 core targets are CYP3A4,GSK3B,CYP19A1,CHEK1,COMT,CYP2A6,CYP2C19,HSD17B1,NFE2L2,and AHR.Moreover,KEGG enrichment analysis found that it was closely related to metabolic pathways,glycosaminoglycan degradation,steroid hormone biosynthesis,etc.The molecular docking results revealed that CUR had a strong binding ability with the PD target protein.In vitro experiments have shown that CUR can significantly improve oxidative damage caused by rotenone intervention in PD SHSY5Y cells and upregulate the level of key antioxidant pathway proteins Nrf2 and AHR.In a word,CUR may have therapeutic effects on PD through multitarget and multi—pathway,which provide a scientificbasis for further elaborating the mechanism of CUR in the treatment of PD.
基金Supported by the National Natural Science Foundation of Shandong Province,No.ZR2019QH008.
文摘BACKGROUND Immunoglobulin G4(IgG4)-related disease(IgG4-RD),a relatively rare immunemediated chronic inflammatory condition characterized by fibrosis,is capable of affecting multiple organs and systems.Epidemiologically,the disease predominantly affects middle-aged and older men in Asian populations,whereas it shows a female predominance in the corresponding age group in the United States.In IgG4-RD,affected tissues and organs may exhibit diffuse or localized swelling,mimicking neoplastic lesions.IgG4-related cholecystitis(IgG4-CC)represents a manifestation involving the gallbladder,with isolated gallbladder involvement without other organ lesions being exceptionally uncommon.CASE SUMMARY A 53-year-old man was admitted to the hospital with abdominal pain.Preoperative evaluations could not exclude gallbladder carcinoma,and surgical intervention was required.Based on intraoperative findings,postoperative pathology,and postoperative serum IgG4 levels,a diagnosis of IgG4-CC was considered.After glucocorticoid therapy,the patient’s general condition substantially improved.CONCLUSION For patients present with space-occupying lesions of the gallbladder,IgG4-RD should be included in the differential diagnosis.
文摘The compelling case report by Xie et al,published in a renowned medical journal,is an excellent example of meticulous clinical evaluation,comprehensive labo-ratory testing,advanced imaging,and genetic analysis.The authors identified novel compound heterozygous mutations in the hemojuvelin gene of a patient diagnosed with juvenile hemochromatosis.They suggested that long-term,strategic phlebotomy might offer a novel therapeutic strategy for severe juvenile hemochromatosis,challenging the traditional treatment paradigms.
基金funded by the National Natural Science Foundation of China(81902815,81802786)the Natural Science Foundation of Shandong Province(ZR2023MH011,ZR2019BH044,ZR2018BH025).
文摘Background:VPS37A(VPS37A subunit of ESCRT-I),a component of the ESCRT-I(endosomal sorting complex required for transport I)complex,mediates vesicular trafficking through sorting endocytic ubiquitinated cargos into multivesicular bodies(MVBs).Although accumulating evidence indicates that VPS37A deficiency occurs in numerous malignancies and exerts tumor-suppressive effects during cancer progression,its functional significance in colorectal cancer(CRC)pathogenesis remains poorly characterized.Therefore,this study aims to further investigate the functional and molecular mechanisms by which VPS37A downregulation contributes to malignant biological phenotypes in CRC,with a specific focus on how its dysregulation affects cell death pathways.Methods:Multi-omics analysis of TCGA,GEO,and CPTAC cohorts identified VPS37A as a downregulated tumor suppressor gene in CRC.The prognostic relevance of VPS37A was validated in two clinical cohorts(Cohorts 1 and 2)using immunohistochemistry.Functional assays in VPS37A-overexpressing CRC cells and xenografts assessed proliferation,cell cycle progression,and stress-induced cell death.RNA sequencing,nuclear factor kappa-B(NF-κB)luciferase reporter assays,and lysosomal inhibition experiments elucidated the mechanisms underlying tumor necrosis factor receptor 1(TNFR1)degradation.Results:VPS37A is significantly downregulated in advanced-stage CRC and independently predicts poor survival.Functionally,VPS37A overexpression suppresses proliferation and induces G2/M arrest in vitro,while reducing xenograft growth.Under metabolic stress(glucose deprivation/galactose adaptation),VPS37A triggers cell death via apoptosis,necroptosis,and ferroptosis.Mechanistically,VPS37A redirects TNFR1 to lysosomal degradation,suppressing NF-κB nuclear translocation and transcriptional activity.Conclusion:VPS37A deficiency drives CRC progression by sustaining TNFR1/NF-κB signaling under metabolic stress.Restoring VPS37A activity promotes TNFR1 degradation,offering a therapeutic strategy to counteract NF-κB-mediated treatment resistance in CRC.
