●Multiple evanescent white dot syndrome(MEWDS)is a rare fundus disease,characterized by acute vision loss and visual field defects.Many previous studies have explained the possible pathogenesis and clinical features ...●Multiple evanescent white dot syndrome(MEWDS)is a rare fundus disease,characterized by acute vision loss and visual field defects.Many previous studies have explained the possible pathogenesis and clinical features of primary MEWDS.However,as the number of reported cases increases,secondary MEWDS occurs in other related retinal diseases and injuries,exhibiting some special characteristics.The associated retinal diseases include multifocal choroiditis/punctate inner choroidopathy(MFC/PIC),acute zonal occult outer retinopathy,best vitelliform macular dystrophy,pseudoxanthoma elasticum,and ocular toxoplasmosis.The related retinal injury is laser photocoagulation,surgery,and trauma.Although primary MEWDS often have a self-limiting course,secondary MEWDS may require treatment in some cases,according to the severity of concomitant diseases and complications.Notably,MEWDS secondary to MFC/PIC that is prone to forming choroidal neovascularization and focal choroidal excavation,needs positive treatment with corticosteroids.The possible underlying pathogenesis of secondary MEWDS is the exposure of choroidal antigen after the disruption of Bruch’s membrane.The MEWDS-related features in secondary MEWDS are still evanescent under most circumstances.Its prognosis and treatment depend on the severity of complications.Current studies propose that the etiology is associated with immune factors,including viral infection,inflammation in choroid and Bruch’s membrane,and antigen exposure caused by retinal and/or choroidal insults.More pathogenic studies should be conducted in the future.Accurate diagnosis for secondary MEWDS could benefit patients in aspects of management and prognosis.展开更多
In the last two years,a new seve re acute res piratory syndrome coronavirus(SARS-CoV)infection has spread worldwide leading to the death of millions.Va ccination represents the key factor in the global strategy agains...In the last two years,a new seve re acute res piratory syndrome coronavirus(SARS-CoV)infection has spread worldwide leading to the death of millions.Va ccination represents the key factor in the global strategy against this pandemic,but it also poses several problems,especially for vulnerable people such as patients with multiple scle rosis.In this review,we have briefly summarized the main findings of the safety,efficacy,and acceptability of Coronavirus Disease 2019(COVID-19)vaccination fo r multiple sclerosis patients.Although the acceptability of COVID-19 vaccines has progressively increased in the last year,a small but significant part of patients with multiple sclerosis still has relevant concerns about vaccination that make them hesitant about receiving the COVID-19 vaccine.Overall,available data suggest that the COVID-19 vaccination is safe and effective in multiple scle rosis patients,even though some pharmacological treatments such as anti-CD20 therapies or sphingosine I-phosphate receptor modulato rs can reduce the immune response to vaccination.Accordingly,COVID-19 vaccination should be strongly recommended for people with multiple scle rosis and,in patients treated with anti-CD20 therapies and sphingosine I-phosphate receptor modulato rs,and clinicians should evaluate the appropriate timing for vaccine administration.Further studies are necessary to understand the role of cellular immunity in COVID-19 vaccination and the possible usefulness of booster jabs.On the other hand,it is mandatory to learn more about the reasons why people refuse vaccination.This would help to design a more effective communication campaign aimed at increasing vaccination coverage among vulnerable people.展开更多
Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow d...Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.展开更多
BACKGROUND Lung cancer is a common disease with high mortality,and psychological support is very important in the diagnosis and treatment of postoperative patients with cancer pain.AIM To explore the application effec...BACKGROUND Lung cancer is a common disease with high mortality,and psychological support is very important in the diagnosis and treatment of postoperative patients with cancer pain.AIM To explore the application effect of the narrative nursing method in postoperative lung cancer patients in the intensive care unit.METHODS A total of 120 patients diagnosed with lung cancer and experiencing cancer-related pain were randomly allocated into two groups:an observation group and a control group,each consisting of 60 cases.The control group was given routine analgesic and psychological care,while the research group applied the five-step narrative nursing method based on routine care,comparing the visual analogue scale scores,sleep status,anxiety and depression status,and quality of life of the two groups of patients before and after the intervention.RESULTS The pain scores,anxiety scores,and depression scores of the study group were lower than those of the control group after the intervention using the narrative nursing method,and the difference was statistically significant(P<0.05).CONCLUSION Using narrative nursing methods to intervene in patients with lung cancer combined with cancerous pain can help patients to correctly recognize their disease,adjust their mentality,establish confidence,alleviate patients'subjective pain feelings,and improve their adverse emotions.展开更多
The fatigue damage caused by flow-induced vibration(FIV)is one of the major concerns for multiple cylindrical structures in many engineering applications.The FIV suppression is of great importance for the security of ...The fatigue damage caused by flow-induced vibration(FIV)is one of the major concerns for multiple cylindrical structures in many engineering applications.The FIV suppression is of great importance for the security of many cylindrical structures.Many active and passive control methods have been employed for the vibration suppression of an isolated cylinder undergoing vortex-induced vibrations(VIV).The FIV suppression methods are mainly extended to the multiple cylinders from the vibration control of the isolated cylinder.Due to the mutual interference between the multiple cylinders,the FIV mechanism is more complex than the VIV mechanism,which makes a great challenge for the FIV suppression.Some efforts have been devoted to vibration suppression of multiple cylinder systems undergoing FIV over the past two decades.The control methods,such as helical strakes,splitter plates,control rods and flexible sheets,are not always effective,depending on many influence factors,such as the spacing ratio,the arrangement geometrical shape,the flow velocity and the parameters of the vibration control devices.The FIV response,hydrodynamic features and wake patterns of the multiple cylinders equipped with vibration control devices are reviewed and summarized.The FIV suppression efficiency of the vibration control methods are analyzed and compared considering different influence factors.Further research on the FIV suppression of multiple cylinders is suggested to provide insight for the development of FIV control methods and promote engineering applications of FIV control methods.展开更多
BACKGROUND Multiple endocrine neoplasia type 2(MEN2)is a rare,autosomal dominant endocrine disease.Currently,the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis.Once an RET carrier is detected,fam...BACKGROUND Multiple endocrine neoplasia type 2(MEN2)is a rare,autosomal dominant endocrine disease.Currently,the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis.Once an RET carrier is detected,family members should be screened to enable early detection of medullary thyroid carcinoma,pheochromocytoma,and hyperparatitity.Among these,medullary thyroid carcinoma is the main factor responsible for patient mortality.Accordingly,delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners.CASE SUMMARY Herein,we present RET proto-oncogene mutations,clinical characteristics,and treatment strategies in a family with MEN2A.A family study was conducted on patients diagnosed with MEN2A.DNA was extracted from the peripheral blood of family members,and first-generation exon sequencing of the RET protooncogene was conducted.The C634Y mutation was identified in three family members spanning three generations.Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas.A 9-yearold child harboring the gene mutation was diagnosed with medullary thyroid carcinoma.Surgical resection of the tumors was performed.All family members were advised to undergo complete genetic testing related to the C634Y mutation,and the corresponding treatments administered based on test results and associated clinical guidelines.CONCLUSION Advancements in MEN2A research are important for familial management,assessment of medullary thyroid cancer invasive risk,and deciding surgical timing.展开更多
MgH_(2) is considered one of the most promising hydrogen storage materials because of its safety,high efficiency,high hydrogen storage quantity and low cost characteristics.But some shortcomings are still existed:high...MgH_(2) is considered one of the most promising hydrogen storage materials because of its safety,high efficiency,high hydrogen storage quantity and low cost characteristics.But some shortcomings are still existed:high operating temperature and poor hydrogen absorption dynamics,which limit its application.Porous Ni_(3)ZnC_(0.7)/Ni loaded carbon nanotubes microspheres(NZC/Ni@CNT)is prepared by facile filtration and calcination method.Then the different amount of NZC/Ni@CNT(2.5,5.0 and 7.5 wt%)is added to the MgH_(2) by ball milling.Among the three samples with different amount of NZC/Ni@CNT(2.5,5.0 and 7.5 wt%),the MgH_(2)-5 wt%NZC/Ni@CNT composite exhibits the best hydrogen storage performances.After testing,the MgH_(2)-5 wt%NZC/Ni@CNT begins to release hydrogen at around 110℃ and hydrogen absorption capacity reaches 2.34 wt%H_(2) at 80℃ within 60 min.Moreover,the composite can release about 5.36 wt%H_(2) at 300℃.In addition,hydrogen absorption and desorption activation energies of the MgH_(2)-5 wt%NZC/Ni@CNT composite are reduced to 37.28 and 84.22 KJ/mol H_(2),respectively.The in situ generated Mg_(2)NiH_(4)/Mg_(2)Ni can serve as a"hydrogen pump"that plays the main role in providing more activation sites and hydrogen diffusion channels which promotes H_(2) dissociation during hydrogen absorption process.In addition,the evenly dispersed Zn and MgZn2 in Mg and MgH_(2) could provide sites for Mg/MgH_(2) nucleation and hydrogen diffusion channel.This attempt clearly proved that the bimetallic carbide Ni_(3)ZnC_(0.7) is a effective additive for the hydrogen storage performances modification of MgH_(2),and the facile synthesis of the Ni_(3)ZnC_(0.7)/Ni@CNT can provide directions of better designing high performance carbide catalysts for improving MgH_(2).展开更多
The hybrid carrier(HC)system rooted in the carrier fusion concept is gradually garnering attention.In this paper,we study the extended hybrid carrier(EHC)multiple access scheme to ensure reliable wireless communicatio...The hybrid carrier(HC)system rooted in the carrier fusion concept is gradually garnering attention.In this paper,we study the extended hybrid carrier(EHC)multiple access scheme to ensure reliable wireless communication.By employing the EHC modulation,a power layered multiplexing framework is realized,which exhibits enhanced interference suppression capability owing to the more uniform energy distribution design.The implementation method and advantage mechanism are explicated respectively for the uplink and downlink,and the performance analysis under varying channel conditions is provided.In addition,considering the connectivity demand,we explore the non-orthogonal multiple access(NOMA)method of the EHC system and develop the EHC sparse code multiple access scheme.The proposed scheme melds the energy spread superiority of EHC with the access capacity of NOMA,facilitating superior support for massive connectivity in high mobility environments.Simulation results have verified the feasibility and advantages of the proposed scheme.Compared with existing HC multiple access schemes,the proposed scheme exhibits robust bit error rate performance and can better guarantee multiple access performance in complex scenarios of nextgeneration communications.展开更多
The effects of various contaminants in the electrolytic refinement of indium were investigated using a glow discharge mass spectrometer(GDMS).The effects of several factors such as the indium ion(In3+)concentration,th...The effects of various contaminants in the electrolytic refinement of indium were investigated using a glow discharge mass spectrometer(GDMS).The effects of several factors such as the indium ion(In3+)concentration,the sodium chloride(NaCl)concentration,the current density,the gelatin concentration,the pH,and the electrode distance,were examined.Significant variations in impurity levels concerning gelatin concentration were observed.Both the gelatin and In3+concentration were moderately positively correlated with the Pb content.The Sb concentration was associated positively with the NaCl concentration,while the Ti concentration had an adverse correlation with the NaCl concentration.The Bi element content was positively linked to the electrode distance.As the current density increased,Cu,Pb,and Bi impurities initially rose and then eventually declined.Notably,a critical current density of 45 A·m^(-2) was identified in this behavior.展开更多
Cultural symbols,a manifestation of cities’cultural resources,are not only signs that frame concepts but also forms that express meanings.Exploring the international communication of cities from the perspective of sy...Cultural symbols,a manifestation of cities’cultural resources,are not only signs that frame concepts but also forms that express meanings.Exploring the international communication of cities from the perspective of symbols,this paper analyzes in depth how cities create their cultural symbols in the dynamic process of international communication in an era of symbol-based digital media,and how they develop their narratives and explain meanings through the dissemination of symbols when telling their stories to international audiences,thus enhancing the efficiency and effectiveness of their international communication efforts.展开更多
Introduction: Infections are additional factors of morbidity and mortality in multiple myeloma (MM), and the current recommendation is antibiotic prophylaxis. In sub-Saharan Africa, few data on infectious complication...Introduction: Infections are additional factors of morbidity and mortality in multiple myeloma (MM), and the current recommendation is antibiotic prophylaxis. In sub-Saharan Africa, few data on infectious complications of MM are available. We aim to describe the microbiological features of infections in MM, and their impact on survival in Senegalese patients. Methods: A retrospective (January 2005-January 2022), analytic, multicenter study on infections in patients followed for MM (IMWG criteria) in Senegalese clinical hematology services. The socio-epidemiological, diagnostic, microbiological, evolutionary and survival aspects were analyzed. Results: The study included 106 patients with multiple myeloma who had an infection at admission or during the treatment. Ten patients have the comorbidity (hypertension, lupus, type 2 diabetes). These patients had 136 infectious events identified at diagnosis (79.2%) or during chemotherapy (20.8%). The sites of infection are lung (42.6%), urinary (29.4%), dermatological (6.6%), digestive (5.2%), osteoarticular (4.4%), ear, nose and throat (3.7%), central nervous system (1.5%), or without site. We recorded 26.4% of patients with multi-site infections. The causal pathogens are bacteria (Gram-negative bacilli: 22.1%;Gram positive bacilli: 9.5%, Mycobacterium tuberculosis: 13.3%), parasitique (plasmodium falciparum 6.6%), viruses (SARS-COV2: 2.9%, VZV: 2.2%) and fungal (2.9%). Survival was reduced in patients who had an infection at the time of multiple myeloma diagnosis (p: 0.189) and those who had multiple infectious foci (p: 0.011). Conclusion: Infections in multiple myeloma are more frequent at diagnosis. The germs are varied and mostly bacteria, particularly gram-negative bacteria, and Kochs bacillus. Our study reveals that multiple infectious foci are a poor prognosis factor. It is necessary to evaluate the infectious risk early, and to adopt an antibiotic prophylaxis based on our tropical environment.展开更多
Magnetic reconnection processes in three-dimensional(3D)complex field configurations have been investigated in different magneto-plasma systems in space,laboratory,and astrophysical systems.Two-dimensional(2D)features...Magnetic reconnection processes in three-dimensional(3D)complex field configurations have been investigated in different magneto-plasma systems in space,laboratory,and astrophysical systems.Two-dimensional(2D)features of magnetic reconnection have been well developed and applied successfully to systems with symmetrical property,such as toroidal fusion plasmas and laboratory experiments with an axial symmetry.But in asymmetric systems,the 3D features are inevitably different from those in the 2D case.Magnetic reconnection structures in multiple celestial body systems,particularly star-planet-Moon systems,bring fresh insights to the understanding of the 3D geometry of reconnection.Thus,we take magnetic reconnection in an ancient solar-lunar terrestrial magneto-plasma system as an example by using its crucial parameters approximately estimated already and also some specific applications in pathways for energy and matter transports among Earth,ancient Moon,and the interplanetary magnetic field(IMF).Then,magnetic reconnection of the ancient lunar-terrestrial magnetospheres with the IMF is investigated numerically in this work.In a 3D simulation for the Earth-Moon-IMF system,topological features of complex magnetic reconnection configurations and dynamical characteristics of magnetic reconnection processes are studied.It is found that a coupled lunar-terrestrial magnetosphere is formed,and under various IMF orientations,multiple X-points emerge at distinct locations,showing three typical magnetic reconnection structures in such a geometry,i.e.,the X-line,the triple current sheets,and the A-B null pairs.The results can conduce to further understanding of reconnection physics in 3D for plasmas in complex magnetic configurations,and also a possible mechanism for energy and matters transport in evolutions of similar astrophysical systems.展开更多
Spatial narrative,as a unique literary narrative technique,focuses on advancing the plot and shaping characters through meticulous portrayal of space,providing readers with rich visual and perceptual experiences.This ...Spatial narrative,as a unique literary narrative technique,focuses on advancing the plot and shaping characters through meticulous portrayal of space,providing readers with rich visual and perceptual experiences.This paper examines the spatial narrative utilized in Jin Yucheng’s novel,Flowers of Shanghai.Through an in-depth analysis of the spatial narrative techniques in the novel,this paper asserts that such an exploration has far-reaching consequences in broadening research perspectives and fostering interdisciplinary collaborations between literature and geography.Furthermore,the paper explores the unique aspects of narrative perspective,narrative structure,and narrative time in Flowers of Shanghai,and how these elements perfectly combine with spatial narrative to create a fascinating literary world for readers.The aim of this study is to deeply explore the artistic value and literary charm of the novel through a comprehensive interpretation of the spatial narrative in Flowers of Shanghai.展开更多
Multiple myeloma(MM)is a hematologic malignancy notorious for its high relapse rate and development of drug resistance,in which cell adhesion-mediated drug resistance plays a critical role.This study integrated four R...Multiple myeloma(MM)is a hematologic malignancy notorious for its high relapse rate and development of drug resistance,in which cell adhesion-mediated drug resistance plays a critical role.This study integrated four RNA sequencing datasets(CoMMpass,GSE136337,GSE9782,and GSE2658)and focused on analyzing 1706 adhesionrelated genes.Rigorous univariate Cox regression analysis identified 18 key prognosis-related genes,including KIF14,TROAP,FLNA,MSN,LGALS1,PECAM1,and ALCAM,which demonstrated the strongest associations with poor overall survival(OS)in MM patients.To comprehensively evaluate the impact of cell adhesion on MM prognosis,an adhesion-related risk score(ARRS)model was constructed using Lasso Cox regression analysis.The ARRS model emerged as an independent prognostic factor for predicting OS.Furthermore,our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs,protein kinase inhibitors,and drugs targeting the PI3K/Akt/mTOR signaling pathway.Nevertheless,we identified promising drug candidates,such as tirofiban,pirenzepine,erlotinib,and bosutinib,which exhibit potential in reversing this resistance.In vitro,experiments employing NCIH929,RPMI8226,and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate drugs.By employing siRNA-mediated knockdown of the key ARRS model gene KIF14,we observed suppressed proliferation of NCIH929 cells,along with decreased adhesion to BMSCs and fibronectin.This study presents compelling evidence establishing cell adhesion as a significant prognostic factor in MM.Additionally,potential molecular mechanisms underlying adhesion-related resistance are proposed,along with viable strategies to overcome such resistance.These findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM.展开更多
Let X={X(t)∈R^(d),t∈R^(N)}be a centered space-time anisotropic Gaussian field with indices H=(H_(1),…,H_(N))∈(0,1)~N,where the components X_(i)(i=1,…,d)of X are independent,and the canonical metric√(E(X_(i)(t)-X...Let X={X(t)∈R^(d),t∈R^(N)}be a centered space-time anisotropic Gaussian field with indices H=(H_(1),…,H_(N))∈(0,1)~N,where the components X_(i)(i=1,…,d)of X are independent,and the canonical metric√(E(X_(i)(t)-X_(i)(s))^(2))^(1/2)(i=1,…,d)is commensurate with■for s=(s_(1),…,s_(N)),t=(t_(1),…,t_(N))∈R~N,α_(i)∈(0,1],and with the continuous functionγ(·)satisfying certain conditions.First,the upper and lower bounds of the hitting probabilities of X can be derived from the corresponding generalized Hausdorff measure and capacity,which are based on the kernel functions depending explicitly onγ(·).Furthermore,the multiple intersections of the sample paths of two independent centered space-time anisotropic Gaussian fields with different distributions are considered.Our results extend the corresponding results for anisotropic Gaussian fields to a large class of space-time anisotropic Gaussian fields.展开更多
The paper develops a multiple matching attenuation method based on extended filtering in the curvelet domain,which combines the traditional Wiener filtering method with the matching attenuation method in curvelet doma...The paper develops a multiple matching attenuation method based on extended filtering in the curvelet domain,which combines the traditional Wiener filtering method with the matching attenuation method in curvelet domain.Firstly,the method uses the predicted multiple data to generate the Hilbert transform records,time derivative records and time derivative records of Hilbert transform.Then,the above records are transformed into the curvelet domain and multiple matching attenuation based on least squares extended filtering is performed.Finally,the attenuation results are transformed back into the time-space domain.Tests on the model data and field data show that the method proposed in the paper effectively suppress the multiples while preserving the primaries well.Furthermore,it has higher accuracy in eliminating multiple reflections,which is more suitable for the multiple attenuation tasks in the areas with complex structures compared to the time-space domain extended filtering method and the conventional curvelet transform method.展开更多
BACKGROUND Multiple acyl-CoA dehydrogenase deficiency(MADD)is a disease of rare autosomal recessive disorder.There are three types of MADD.Type I is a neonatalonset form with congenital anomalies.Type II is a neonatal...BACKGROUND Multiple acyl-CoA dehydrogenase deficiency(MADD)is a disease of rare autosomal recessive disorder.There are three types of MADD.Type I is a neonatalonset form with congenital anomalies.Type II is a neonatal-onset form without congenital anomalies.Type III is considered to a milder form and usually responds to riboflavin.However,late-onset form could also be fatal and not responsive to treatments.CASE SUMMARY We report a severe case of a young man with onset type III MADD induced by drugs and strenuous exercise characterized by rhabdomyolysis and liver dysfunction.Urine analysis indicated 12 out of 70 kinds of organic acids like glutaric acid-2 were detected.Serum analysis in genetic metabolic diseases revealed 24 out of 43 tested items were abnormal,revealing the elevation of several acylcarnitines and the reduction of carnitine in the patient.By next generation sequencing technology for gene sequencing related to fatty acid oxidation and carnitine cycle defects,a rare ETFDH gene variant was identified:NM_004453:4:C.1448C>T(p.Pro483 Leu).The patient was diagnosed with lateonset GAII.He was not responsive to riboflavin and progressively worsened into multiple organ failure that finally led to death.CONCLUSION Type III MADD can also be fatal and not responsive to treatments.展开更多
Multiple myeloma(MM)is the second most prevalent hematological malignancy.Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy.This study addressed these limitations th...Multiple myeloma(MM)is the second most prevalent hematological malignancy.Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy.This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy,which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes,termed T-PB@M.The results from our investigations highlight the considerable bone affinity of T-PB@M,both in vitro and in vivo.Additionally,this material demonstrated a capability for drug release triggered by low pH conditions.Moreover,T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose)polymerase 1(PARP1)-Caspase-3-B-cell lymphoma-2(Bcl-2)pathway in MM cells.Notably,T-PB@M preferentially targeted bone-involved sites,thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice.Therefore,this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.展开更多
Multiple myeloma(MM)is a plasma cell malignancy and remains incurable as it lacks effective curative approaches;thus,novel therapeutic strategies are desperately needed.The study aimed to explore the therapeutic role ...Multiple myeloma(MM)is a plasma cell malignancy and remains incurable as it lacks effective curative approaches;thus,novel therapeutic strategies are desperately needed.The study aimed to explore the therapeutic role of dihydromyricetin(DHM)in MM and explore its mechanisms.Human MM and normal plasma samples,human MM cell lines,and normal plasma cells were used for in vitro experiments.Cell counting kit-8(CCK-8),flow cytometry,and trans-well assays were performed for the assessment of cell viability,apoptosis,migration,and invasion,respectively.Quantitative real-time polymerase chain reaction(qRT-PCR)was employed to assess the mRNA expression of signal transducer and activator of transcription 1(STAT1)and retinoic acid-inducible gene I(RIG-I).Western blotting was employed to assess E-cadherin,N-cadherin,signal transducer,STAT1,p-STAT1,and RIG-I protein expression.A tumor xenograft model was used for in vivo experiments.Here,dihydromyricetin(DHM)dose-dependently restrained viability,apoptosis,migration,and invasion,and facilitated apoptosis of U266 cells.After DHM treatment,the Ecadherin level was increased and the N-cadherin level was decreased in U266 and RPMI-8226 cells,suggesting the inhibitory effects of DHM on epithelial-mesenchymal transition(EMT)in MM.Besides,the levels of p-STAT1/STAT1 and RIG-I were down-regulated in MM.However,the STAT1 inhibitor fludarabine undid the suppressive effect of DMH on the malignant characteristics of U266 cells.Also,DHM inhibited MM tumor growth and EMT,and activated STAT1/RIG-I pathway in vivo.Collectively,this study first revealed that DHM can restrain EMT and tumor growth in MM by activating STAT1/RIG-I signaling,which provides a novel drug for the treatment of MM.展开更多
Implementing a new energy-saving electrochemical synthesis system with high commercial value is a strategy of the sustainable development for upgrading the bulk chemicals preparation technology in the future.Here,we r...Implementing a new energy-saving electrochemical synthesis system with high commercial value is a strategy of the sustainable development for upgrading the bulk chemicals preparation technology in the future.Here,we report a multiple redox-mediated linear paired electrolysis system,combining the hydrogen peroxide mediated cathode process with the I2 mediated anode process,and realize the conversion of furfural to furoic acid in both side of the dividedflow cell simultaneously.By reasonably controlling the cathode potential,the undesired water splitting reaction and furfural reduction side reactions are avoided.Under the galvanostatic electrolysis,the two-mediated electrode processes have good compatibility,which reduce the energy consumption by about 22%while improving the electronic efficiency by about 125%.This system provides a green electrochemical synthesis route with commercial prospects.展开更多
基金Supported by the National Natural Science Foundation of China(No.82171073No.82101147).
文摘●Multiple evanescent white dot syndrome(MEWDS)is a rare fundus disease,characterized by acute vision loss and visual field defects.Many previous studies have explained the possible pathogenesis and clinical features of primary MEWDS.However,as the number of reported cases increases,secondary MEWDS occurs in other related retinal diseases and injuries,exhibiting some special characteristics.The associated retinal diseases include multifocal choroiditis/punctate inner choroidopathy(MFC/PIC),acute zonal occult outer retinopathy,best vitelliform macular dystrophy,pseudoxanthoma elasticum,and ocular toxoplasmosis.The related retinal injury is laser photocoagulation,surgery,and trauma.Although primary MEWDS often have a self-limiting course,secondary MEWDS may require treatment in some cases,according to the severity of concomitant diseases and complications.Notably,MEWDS secondary to MFC/PIC that is prone to forming choroidal neovascularization and focal choroidal excavation,needs positive treatment with corticosteroids.The possible underlying pathogenesis of secondary MEWDS is the exposure of choroidal antigen after the disruption of Bruch’s membrane.The MEWDS-related features in secondary MEWDS are still evanescent under most circumstances.Its prognosis and treatment depend on the severity of complications.Current studies propose that the etiology is associated with immune factors,including viral infection,inflammation in choroid and Bruch’s membrane,and antigen exposure caused by retinal and/or choroidal insults.More pathogenic studies should be conducted in the future.Accurate diagnosis for secondary MEWDS could benefit patients in aspects of management and prognosis.
基金FC has received travel grants from Biogen,Merck,Sanofi-Genzyme,Rocheresearch grants from Merck。
文摘In the last two years,a new seve re acute res piratory syndrome coronavirus(SARS-CoV)infection has spread worldwide leading to the death of millions.Va ccination represents the key factor in the global strategy against this pandemic,but it also poses several problems,especially for vulnerable people such as patients with multiple scle rosis.In this review,we have briefly summarized the main findings of the safety,efficacy,and acceptability of Coronavirus Disease 2019(COVID-19)vaccination fo r multiple sclerosis patients.Although the acceptability of COVID-19 vaccines has progressively increased in the last year,a small but significant part of patients with multiple sclerosis still has relevant concerns about vaccination that make them hesitant about receiving the COVID-19 vaccine.Overall,available data suggest that the COVID-19 vaccination is safe and effective in multiple scle rosis patients,even though some pharmacological treatments such as anti-CD20 therapies or sphingosine I-phosphate receptor modulato rs can reduce the immune response to vaccination.Accordingly,COVID-19 vaccination should be strongly recommended for people with multiple scle rosis and,in patients treated with anti-CD20 therapies and sphingosine I-phosphate receptor modulato rs,and clinicians should evaluate the appropriate timing for vaccine administration.Further studies are necessary to understand the role of cellular immunity in COVID-19 vaccination and the possible usefulness of booster jabs.On the other hand,it is mandatory to learn more about the reasons why people refuse vaccination.This would help to design a more effective communication campaign aimed at increasing vaccination coverage among vulnerable people.
文摘Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.
文摘BACKGROUND Lung cancer is a common disease with high mortality,and psychological support is very important in the diagnosis and treatment of postoperative patients with cancer pain.AIM To explore the application effect of the narrative nursing method in postoperative lung cancer patients in the intensive care unit.METHODS A total of 120 patients diagnosed with lung cancer and experiencing cancer-related pain were randomly allocated into two groups:an observation group and a control group,each consisting of 60 cases.The control group was given routine analgesic and psychological care,while the research group applied the five-step narrative nursing method based on routine care,comparing the visual analogue scale scores,sleep status,anxiety and depression status,and quality of life of the two groups of patients before and after the intervention.RESULTS The pain scores,anxiety scores,and depression scores of the study group were lower than those of the control group after the intervention using the narrative nursing method,and the difference was statistically significant(P<0.05).CONCLUSION Using narrative nursing methods to intervene in patients with lung cancer combined with cancerous pain can help patients to correctly recognize their disease,adjust their mentality,establish confidence,alleviate patients'subjective pain feelings,and improve their adverse emotions.
基金financially supported by the National Natural Science Foundation of China(Grant Nos.U2106223,51979193,52301352)。
文摘The fatigue damage caused by flow-induced vibration(FIV)is one of the major concerns for multiple cylindrical structures in many engineering applications.The FIV suppression is of great importance for the security of many cylindrical structures.Many active and passive control methods have been employed for the vibration suppression of an isolated cylinder undergoing vortex-induced vibrations(VIV).The FIV suppression methods are mainly extended to the multiple cylinders from the vibration control of the isolated cylinder.Due to the mutual interference between the multiple cylinders,the FIV mechanism is more complex than the VIV mechanism,which makes a great challenge for the FIV suppression.Some efforts have been devoted to vibration suppression of multiple cylinder systems undergoing FIV over the past two decades.The control methods,such as helical strakes,splitter plates,control rods and flexible sheets,are not always effective,depending on many influence factors,such as the spacing ratio,the arrangement geometrical shape,the flow velocity and the parameters of the vibration control devices.The FIV response,hydrodynamic features and wake patterns of the multiple cylinders equipped with vibration control devices are reviewed and summarized.The FIV suppression efficiency of the vibration control methods are analyzed and compared considering different influence factors.Further research on the FIV suppression of multiple cylinders is suggested to provide insight for the development of FIV control methods and promote engineering applications of FIV control methods.
基金Supported by The Finance Bureau of Dongguan City,Guangdong Province.
文摘BACKGROUND Multiple endocrine neoplasia type 2(MEN2)is a rare,autosomal dominant endocrine disease.Currently,the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis.Once an RET carrier is detected,family members should be screened to enable early detection of medullary thyroid carcinoma,pheochromocytoma,and hyperparatitity.Among these,medullary thyroid carcinoma is the main factor responsible for patient mortality.Accordingly,delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners.CASE SUMMARY Herein,we present RET proto-oncogene mutations,clinical characteristics,and treatment strategies in a family with MEN2A.A family study was conducted on patients diagnosed with MEN2A.DNA was extracted from the peripheral blood of family members,and first-generation exon sequencing of the RET protooncogene was conducted.The C634Y mutation was identified in three family members spanning three generations.Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas.A 9-yearold child harboring the gene mutation was diagnosed with medullary thyroid carcinoma.Surgical resection of the tumors was performed.All family members were advised to undergo complete genetic testing related to the C634Y mutation,and the corresponding treatments administered based on test results and associated clinical guidelines.CONCLUSION Advancements in MEN2A research are important for familial management,assessment of medullary thyroid cancer invasive risk,and deciding surgical timing.
基金supported by research programs of National Natural Science Foundation of China(52101274,51731002)Natural Science Foundation of Shandong Province(No.ZR2020QE011)Youth Top Talent Foundation of Yantai University(2219008).
文摘MgH_(2) is considered one of the most promising hydrogen storage materials because of its safety,high efficiency,high hydrogen storage quantity and low cost characteristics.But some shortcomings are still existed:high operating temperature and poor hydrogen absorption dynamics,which limit its application.Porous Ni_(3)ZnC_(0.7)/Ni loaded carbon nanotubes microspheres(NZC/Ni@CNT)is prepared by facile filtration and calcination method.Then the different amount of NZC/Ni@CNT(2.5,5.0 and 7.5 wt%)is added to the MgH_(2) by ball milling.Among the three samples with different amount of NZC/Ni@CNT(2.5,5.0 and 7.5 wt%),the MgH_(2)-5 wt%NZC/Ni@CNT composite exhibits the best hydrogen storage performances.After testing,the MgH_(2)-5 wt%NZC/Ni@CNT begins to release hydrogen at around 110℃ and hydrogen absorption capacity reaches 2.34 wt%H_(2) at 80℃ within 60 min.Moreover,the composite can release about 5.36 wt%H_(2) at 300℃.In addition,hydrogen absorption and desorption activation energies of the MgH_(2)-5 wt%NZC/Ni@CNT composite are reduced to 37.28 and 84.22 KJ/mol H_(2),respectively.The in situ generated Mg_(2)NiH_(4)/Mg_(2)Ni can serve as a"hydrogen pump"that plays the main role in providing more activation sites and hydrogen diffusion channels which promotes H_(2) dissociation during hydrogen absorption process.In addition,the evenly dispersed Zn and MgZn2 in Mg and MgH_(2) could provide sites for Mg/MgH_(2) nucleation and hydrogen diffusion channel.This attempt clearly proved that the bimetallic carbide Ni_(3)ZnC_(0.7) is a effective additive for the hydrogen storage performances modification of MgH_(2),and the facile synthesis of the Ni_(3)ZnC_(0.7)/Ni@CNT can provide directions of better designing high performance carbide catalysts for improving MgH_(2).
基金supported in part by the National Natural Science Foundation of China under Grant U23A20278in part by the National Natural Science Foundation of China under Grant 62171151in part by the Fundamental Research Funds for the Central Universities under Grant HIT.OCEF.2021012。
文摘The hybrid carrier(HC)system rooted in the carrier fusion concept is gradually garnering attention.In this paper,we study the extended hybrid carrier(EHC)multiple access scheme to ensure reliable wireless communication.By employing the EHC modulation,a power layered multiplexing framework is realized,which exhibits enhanced interference suppression capability owing to the more uniform energy distribution design.The implementation method and advantage mechanism are explicated respectively for the uplink and downlink,and the performance analysis under varying channel conditions is provided.In addition,considering the connectivity demand,we explore the non-orthogonal multiple access(NOMA)method of the EHC system and develop the EHC sparse code multiple access scheme.The proposed scheme melds the energy spread superiority of EHC with the access capacity of NOMA,facilitating superior support for massive connectivity in high mobility environments.Simulation results have verified the feasibility and advantages of the proposed scheme.Compared with existing HC multiple access schemes,the proposed scheme exhibits robust bit error rate performance and can better guarantee multiple access performance in complex scenarios of nextgeneration communications.
基金supported by the National Natural Science Foundation of China(52074180)the Science and Technology Major Project of Yunnan Province(202302AB080020)+2 种基金the Independent Research Project of State Key Laboratory of Advanced Special Steel,Shanghai Key Laboratory of Advanced Ferrometallurgy,Shanghai University(SKLASS 2023-Z07)the Science and Technology Commission of Shanghai Municipality(19DZ2270200)the Program for Professor of Special Appointment(Eastern Scholar)at SIHL,Shanghai Sailing Program(19YF1416500).
文摘The effects of various contaminants in the electrolytic refinement of indium were investigated using a glow discharge mass spectrometer(GDMS).The effects of several factors such as the indium ion(In3+)concentration,the sodium chloride(NaCl)concentration,the current density,the gelatin concentration,the pH,and the electrode distance,were examined.Significant variations in impurity levels concerning gelatin concentration were observed.Both the gelatin and In3+concentration were moderately positively correlated with the Pb content.The Sb concentration was associated positively with the NaCl concentration,while the Ti concentration had an adverse correlation with the NaCl concentration.The Bi element content was positively linked to the electrode distance.As the current density increased,Cu,Pb,and Bi impurities initially rose and then eventually declined.Notably,a critical current density of 45 A·m^(-2) was identified in this behavior.
文摘Cultural symbols,a manifestation of cities’cultural resources,are not only signs that frame concepts but also forms that express meanings.Exploring the international communication of cities from the perspective of symbols,this paper analyzes in depth how cities create their cultural symbols in the dynamic process of international communication in an era of symbol-based digital media,and how they develop their narratives and explain meanings through the dissemination of symbols when telling their stories to international audiences,thus enhancing the efficiency and effectiveness of their international communication efforts.
文摘Introduction: Infections are additional factors of morbidity and mortality in multiple myeloma (MM), and the current recommendation is antibiotic prophylaxis. In sub-Saharan Africa, few data on infectious complications of MM are available. We aim to describe the microbiological features of infections in MM, and their impact on survival in Senegalese patients. Methods: A retrospective (January 2005-January 2022), analytic, multicenter study on infections in patients followed for MM (IMWG criteria) in Senegalese clinical hematology services. The socio-epidemiological, diagnostic, microbiological, evolutionary and survival aspects were analyzed. Results: The study included 106 patients with multiple myeloma who had an infection at admission or during the treatment. Ten patients have the comorbidity (hypertension, lupus, type 2 diabetes). These patients had 136 infectious events identified at diagnosis (79.2%) or during chemotherapy (20.8%). The sites of infection are lung (42.6%), urinary (29.4%), dermatological (6.6%), digestive (5.2%), osteoarticular (4.4%), ear, nose and throat (3.7%), central nervous system (1.5%), or without site. We recorded 26.4% of patients with multi-site infections. The causal pathogens are bacteria (Gram-negative bacilli: 22.1%;Gram positive bacilli: 9.5%, Mycobacterium tuberculosis: 13.3%), parasitique (plasmodium falciparum 6.6%), viruses (SARS-COV2: 2.9%, VZV: 2.2%) and fungal (2.9%). Survival was reduced in patients who had an infection at the time of multiple myeloma diagnosis (p: 0.189) and those who had multiple infectious foci (p: 0.011). Conclusion: Infections in multiple myeloma are more frequent at diagnosis. The germs are varied and mostly bacteria, particularly gram-negative bacteria, and Kochs bacillus. Our study reveals that multiple infectious foci are a poor prognosis factor. It is necessary to evaluate the infectious risk early, and to adopt an antibiotic prophylaxis based on our tropical environment.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11975087,42261134533,and 42011530086)the National Magnetic Confinement Fusion Energy Research and Development Program of China(Grant No.2022YFE03190400)the Heilongjiang Touyan Innovation Team Program,China.
文摘Magnetic reconnection processes in three-dimensional(3D)complex field configurations have been investigated in different magneto-plasma systems in space,laboratory,and astrophysical systems.Two-dimensional(2D)features of magnetic reconnection have been well developed and applied successfully to systems with symmetrical property,such as toroidal fusion plasmas and laboratory experiments with an axial symmetry.But in asymmetric systems,the 3D features are inevitably different from those in the 2D case.Magnetic reconnection structures in multiple celestial body systems,particularly star-planet-Moon systems,bring fresh insights to the understanding of the 3D geometry of reconnection.Thus,we take magnetic reconnection in an ancient solar-lunar terrestrial magneto-plasma system as an example by using its crucial parameters approximately estimated already and also some specific applications in pathways for energy and matter transports among Earth,ancient Moon,and the interplanetary magnetic field(IMF).Then,magnetic reconnection of the ancient lunar-terrestrial magnetospheres with the IMF is investigated numerically in this work.In a 3D simulation for the Earth-Moon-IMF system,topological features of complex magnetic reconnection configurations and dynamical characteristics of magnetic reconnection processes are studied.It is found that a coupled lunar-terrestrial magnetosphere is formed,and under various IMF orientations,multiple X-points emerge at distinct locations,showing three typical magnetic reconnection structures in such a geometry,i.e.,the X-line,the triple current sheets,and the A-B null pairs.The results can conduce to further understanding of reconnection physics in 3D for plasmas in complex magnetic configurations,and also a possible mechanism for energy and matters transport in evolutions of similar astrophysical systems.
文摘Spatial narrative,as a unique literary narrative technique,focuses on advancing the plot and shaping characters through meticulous portrayal of space,providing readers with rich visual and perceptual experiences.This paper examines the spatial narrative utilized in Jin Yucheng’s novel,Flowers of Shanghai.Through an in-depth analysis of the spatial narrative techniques in the novel,this paper asserts that such an exploration has far-reaching consequences in broadening research perspectives and fostering interdisciplinary collaborations between literature and geography.Furthermore,the paper explores the unique aspects of narrative perspective,narrative structure,and narrative time in Flowers of Shanghai,and how these elements perfectly combine with spatial narrative to create a fascinating literary world for readers.The aim of this study is to deeply explore the artistic value and literary charm of the novel through a comprehensive interpretation of the spatial narrative in Flowers of Shanghai.
基金supported by Incubation Program for Clinical Trials(No.19HXFH030)Achievement Transformation Project(No.CGZH21001)+4 种基金1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYJC21007)Translational Research Grant of NCRCH(No.2021WWB03),Chengdu Science and Technology Program(No.2022-YF05-01444-SN)Key Research and Development Program of Sichuan Province(No.2023YFS0031)Post-Doctor Research Project,West China Hospital,Sichuan University(No.2023HXBH111)National Key Research and Development Program of China(Nos.2022YFC2502600,2022YFC2502603).
文摘Multiple myeloma(MM)is a hematologic malignancy notorious for its high relapse rate and development of drug resistance,in which cell adhesion-mediated drug resistance plays a critical role.This study integrated four RNA sequencing datasets(CoMMpass,GSE136337,GSE9782,and GSE2658)and focused on analyzing 1706 adhesionrelated genes.Rigorous univariate Cox regression analysis identified 18 key prognosis-related genes,including KIF14,TROAP,FLNA,MSN,LGALS1,PECAM1,and ALCAM,which demonstrated the strongest associations with poor overall survival(OS)in MM patients.To comprehensively evaluate the impact of cell adhesion on MM prognosis,an adhesion-related risk score(ARRS)model was constructed using Lasso Cox regression analysis.The ARRS model emerged as an independent prognostic factor for predicting OS.Furthermore,our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs,protein kinase inhibitors,and drugs targeting the PI3K/Akt/mTOR signaling pathway.Nevertheless,we identified promising drug candidates,such as tirofiban,pirenzepine,erlotinib,and bosutinib,which exhibit potential in reversing this resistance.In vitro,experiments employing NCIH929,RPMI8226,and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate drugs.By employing siRNA-mediated knockdown of the key ARRS model gene KIF14,we observed suppressed proliferation of NCIH929 cells,along with decreased adhesion to BMSCs and fibronectin.This study presents compelling evidence establishing cell adhesion as a significant prognostic factor in MM.Additionally,potential molecular mechanisms underlying adhesion-related resistance are proposed,along with viable strategies to overcome such resistance.These findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM.
基金supported by the National Natural Science Foundation of China(12371150,11971432)the Natural Science Foundation of Zhejiang Province(LY21G010003)+2 种基金the Management Project of"Digital+"Discipline Construction of Zhejiang Gongshang University(SZJ2022A012,SZJ2022B017)the Characteristic&Preponderant Discipline of Key Construction Universities in Zhejiang Province(Zhejiang Gongshang University-Statistics)the Scientific Research Projects of Universities in Anhui Province(2022AH050955)。
文摘Let X={X(t)∈R^(d),t∈R^(N)}be a centered space-time anisotropic Gaussian field with indices H=(H_(1),…,H_(N))∈(0,1)~N,where the components X_(i)(i=1,…,d)of X are independent,and the canonical metric√(E(X_(i)(t)-X_(i)(s))^(2))^(1/2)(i=1,…,d)is commensurate with■for s=(s_(1),…,s_(N)),t=(t_(1),…,t_(N))∈R~N,α_(i)∈(0,1],and with the continuous functionγ(·)satisfying certain conditions.First,the upper and lower bounds of the hitting probabilities of X can be derived from the corresponding generalized Hausdorff measure and capacity,which are based on the kernel functions depending explicitly onγ(·).Furthermore,the multiple intersections of the sample paths of two independent centered space-time anisotropic Gaussian fields with different distributions are considered.Our results extend the corresponding results for anisotropic Gaussian fields to a large class of space-time anisotropic Gaussian fields.
基金funded by the Wenhai Program of the ST Fund of Laoshan Laboratory (No.202204803)the National Natural Science Foundation of China (Nos.42074138,42206195)+1 种基金the National Key R&D Program of China (No.2022YFC2803501)the Research Project of the China National Petroleum Corporation (No.2021ZG02)。
文摘The paper develops a multiple matching attenuation method based on extended filtering in the curvelet domain,which combines the traditional Wiener filtering method with the matching attenuation method in curvelet domain.Firstly,the method uses the predicted multiple data to generate the Hilbert transform records,time derivative records and time derivative records of Hilbert transform.Then,the above records are transformed into the curvelet domain and multiple matching attenuation based on least squares extended filtering is performed.Finally,the attenuation results are transformed back into the time-space domain.Tests on the model data and field data show that the method proposed in the paper effectively suppress the multiples while preserving the primaries well.Furthermore,it has higher accuracy in eliminating multiple reflections,which is more suitable for the multiple attenuation tasks in the areas with complex structures compared to the time-space domain extended filtering method and the conventional curvelet transform method.
文摘BACKGROUND Multiple acyl-CoA dehydrogenase deficiency(MADD)is a disease of rare autosomal recessive disorder.There are three types of MADD.Type I is a neonatalonset form with congenital anomalies.Type II is a neonatal-onset form without congenital anomalies.Type III is considered to a milder form and usually responds to riboflavin.However,late-onset form could also be fatal and not responsive to treatments.CASE SUMMARY We report a severe case of a young man with onset type III MADD induced by drugs and strenuous exercise characterized by rhabdomyolysis and liver dysfunction.Urine analysis indicated 12 out of 70 kinds of organic acids like glutaric acid-2 were detected.Serum analysis in genetic metabolic diseases revealed 24 out of 43 tested items were abnormal,revealing the elevation of several acylcarnitines and the reduction of carnitine in the patient.By next generation sequencing technology for gene sequencing related to fatty acid oxidation and carnitine cycle defects,a rare ETFDH gene variant was identified:NM_004453:4:C.1448C>T(p.Pro483 Leu).The patient was diagnosed with lateonset GAII.He was not responsive to riboflavin and progressively worsened into multiple organ failure that finally led to death.CONCLUSION Type III MADD can also be fatal and not responsive to treatments.
基金supported by the National Natural Science Foundation of China(52073145 and 82004081)the Jiangsu Talent Professor Program,Jiangsu Innovation Project of Graduate Student(KYCX23-2192)+1 种基金the National Natural Science Foundation of Nanjing University of Chinese Medicine(NZY82004081)the Special Grants of China Postdoctoral Science Foundation(2021T140792).
文摘Multiple myeloma(MM)is the second most prevalent hematological malignancy.Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy.This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy,which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes,termed T-PB@M.The results from our investigations highlight the considerable bone affinity of T-PB@M,both in vitro and in vivo.Additionally,this material demonstrated a capability for drug release triggered by low pH conditions.Moreover,T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose)polymerase 1(PARP1)-Caspase-3-B-cell lymphoma-2(Bcl-2)pathway in MM cells.Notably,T-PB@M preferentially targeted bone-involved sites,thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice.Therefore,this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.
基金The authors disclosed receipt of the following financial support for the research,authorship,and/or publication of this article:This work was supported by Mechanism of Dihydromyricetin Inhibiting Multiple Myeloma Growth and Epithelial Mesenchymal Transition by Regulating STAT1/RIG-I Pathway(Grant Number 2022KY094).
文摘Multiple myeloma(MM)is a plasma cell malignancy and remains incurable as it lacks effective curative approaches;thus,novel therapeutic strategies are desperately needed.The study aimed to explore the therapeutic role of dihydromyricetin(DHM)in MM and explore its mechanisms.Human MM and normal plasma samples,human MM cell lines,and normal plasma cells were used for in vitro experiments.Cell counting kit-8(CCK-8),flow cytometry,and trans-well assays were performed for the assessment of cell viability,apoptosis,migration,and invasion,respectively.Quantitative real-time polymerase chain reaction(qRT-PCR)was employed to assess the mRNA expression of signal transducer and activator of transcription 1(STAT1)and retinoic acid-inducible gene I(RIG-I).Western blotting was employed to assess E-cadherin,N-cadherin,signal transducer,STAT1,p-STAT1,and RIG-I protein expression.A tumor xenograft model was used for in vivo experiments.Here,dihydromyricetin(DHM)dose-dependently restrained viability,apoptosis,migration,and invasion,and facilitated apoptosis of U266 cells.After DHM treatment,the Ecadherin level was increased and the N-cadherin level was decreased in U266 and RPMI-8226 cells,suggesting the inhibitory effects of DHM on epithelial-mesenchymal transition(EMT)in MM.Besides,the levels of p-STAT1/STAT1 and RIG-I were down-regulated in MM.However,the STAT1 inhibitor fludarabine undid the suppressive effect of DMH on the malignant characteristics of U266 cells.Also,DHM inhibited MM tumor growth and EMT,and activated STAT1/RIG-I pathway in vivo.Collectively,this study first revealed that DHM can restrain EMT and tumor growth in MM by activating STAT1/RIG-I signaling,which provides a novel drug for the treatment of MM.
基金This study is supported by the National Key Research and Development Program of China(2017YFB0307500).
文摘Implementing a new energy-saving electrochemical synthesis system with high commercial value is a strategy of the sustainable development for upgrading the bulk chemicals preparation technology in the future.Here,we report a multiple redox-mediated linear paired electrolysis system,combining the hydrogen peroxide mediated cathode process with the I2 mediated anode process,and realize the conversion of furfural to furoic acid in both side of the dividedflow cell simultaneously.By reasonably controlling the cathode potential,the undesired water splitting reaction and furfural reduction side reactions are avoided.Under the galvanostatic electrolysis,the two-mediated electrode processes have good compatibility,which reduce the energy consumption by about 22%while improving the electronic efficiency by about 125%.This system provides a green electrochemical synthesis route with commercial prospects.