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
Bisphosphonate-related osteonecrosis of jaw(BRONJ)is characterized by impaired osteogenic differentiation of orofacial bone marrow stromal cells(BMSCs).Corin has recently been demonstrated to act as a key regulator in...Bisphosphonate-related osteonecrosis of jaw(BRONJ)is characterized by impaired osteogenic differentiation of orofacial bone marrow stromal cells(BMSCs).Corin has recently been demonstrated to act as a key regulator in bone development and orthopedic disorders.However,the role of corin in BRONJ-related BMSCs dysfunction remains unclarified.A m6A epitranscriptomic microarray study from our group shows that the CORIN gene is significantly upregulated and m6A hypermethylated during orofacial BMSCs osteogenic differentiation.Corin knockdown inhibits BMSCs osteogenic differentiation,whereas corin overexpression or soluble corin(sCorin)exerts a promotion effect.Furthermore,corin expression is negatively regulated by bisphosphonates(BPs).Corin overexpression or sCorin reverses BPs-impaired BMSCs differentiation ability.Mechanistically,we find altered expression of phos-ERK in corin knockdown/overexpression BMSCs and BMSCs under sCorin stimulation.PD98059(a selective ERK inhibitor)blocks the corin-mediated promotion effect.With regard to the high methylation level of corin during osteogenic differentiation,we apply a non-selective m6A methylase inhibitor,Cycloleucine,which also blocks the corin-mediated promotion effect.Furthermore,we demonstrate that METTL7A modulates corin m6A modification and reverses BPs-impaired BMSCs function,indicating that METTL7A regulates corin expression and thus contributes to orofacial BMSCs differentiation ability.To conclude,our study reveals that corin reverses BPs-induced BMSCs dysfunction,and METTL7A-mediated corin m6A modification underlies corin promotion of osteogenic differentiation via the ERK pathway.We hope this brings new insights into future clinical treatments for BRONJ.展开更多
Extracellular deposition of amyloid-βas neuritic plaques and intracellular accumulation of hyperphosphorylated,aggregated tau as neurofibrillary tangles are two of the characteristic hallmarks of Alzheimer's dise...Extracellular deposition of amyloid-βas neuritic plaques and intracellular accumulation of hyperphosphorylated,aggregated tau as neurofibrillary tangles are two of the characteristic hallmarks of Alzheimer's disease1,2.The regional progression of brain atrophy in Alzheimer's disease highly correlates with tau accumulation but not amyloid deposition3-5,and the mechanisms of tau-mediated neurodegeneration remain elusive.展开更多
The anther-smut Microbotryum violaceum ( Brandenburger and Schvinn) G. Deml. and Oberw.) causes a systematic infection of its host Silene dioica ( L.) Clairv., resulting in sterility and production of teliospores (dis...The anther-smut Microbotryum violaceum ( Brandenburger and Schvinn) G. Deml. and Oberw.) causes a systematic infection of its host Silene dioica ( L.) Clairv., resulting in sterility and production of teliospores (dispersal propagules) in flowers. These spores are transmitted to healthy plants mainly by flower visitors. The behavioral responses of flower visitors to a variation in floral characters are not only likely to affect rates of pollen export/import, but also the rate of spore deposition and probability of disease. In a transplantation experiment, using plants from four different populations, we tested for correlation between variation in female floral morphology and patterns of spore and pollen deposition, and a resulting risk of disease. The source populations in this experiment were located on four islands in Skeppsvik archipelago in northern Sweden, and represented a gradient of disease incidence from completely healthy ( Island 1), low incidence ( Island 2) to high incidences ( Islands 3 and 4) of disease. Fifty plants from each population were transplanted to the center, of the population on Island 4. There were significant differences among the transplants in floral characters, i.e. corolla size, style length and ovule number. Plants from the non-diseased population had larger flowers and longer styles than plants from the highly diseased populations. Numbers of pollen grains and spores deposited on flowers were strongly and positively correlated. We found that plants originating from the non-diseased population captured approximately 4 times more pollen and 9 times more spores, per flower than die individuals from the resident population (Island 4, population 4). The incidences of disease among plants, from the four populations differed significantly, and was 37%, 20%, 18% and 0 for populations 1, 2, 3 and 4 respectively. In a survey of ten populations we found a significant negative correlation between the mean style length ( positively correlated with corolla size and ovule number) among healthy plants and incidence of disease in these populations. The potentiality for pathogen-pollinator mediated selection oil floral characters; and consequences for gone flow between populations of Silene dioica are discussed.展开更多
The genetic transformation was achieved by pollen_mediated approach on maize ( Zea mays L.) inbred lines Tai 9101 and Zong 31. Plasmid DNA of pGLⅡ_RC_1 was mixed with fresh pollen of maize inbreds in sucrose ...The genetic transformation was achieved by pollen_mediated approach on maize ( Zea mays L.) inbred lines Tai 9101 and Zong 31. Plasmid DNA of pGLⅡ_RC_1 was mixed with fresh pollen of maize inbreds in sucrose solution. The pollens were treated by ultrasonication and collected, pollinated on silks of maize ears. Transformants were confirmed by dot blot hybridization, PCR amplification and PCR_Southern blot hybridization. The pollen_mediated transformation approach could circumvent the tedious tissue culture procedures like in particle bombardment and Agrobacterium infection, etc. This approach is simple, easy to operate, and could be widely used in practice.展开更多
In the bone marrow, B cells and bone-resorbing osteoclasts colocalize and form a specific microenvironment. How B cells functionally influence osteoclasts and bone architecture is poorly understood. Using genetically ...In the bone marrow, B cells and bone-resorbing osteoclasts colocalize and form a specific microenvironment. How B cells functionally influence osteoclasts and bone architecture is poorly understood. Using genetically modified mice and highthroughput analyses, we demonstrate that prolonged HIF-1α signaling in B cells leads to enhanced RANKL production and osteoclast formation. In addition, deletion of HIF-1α in B cells prevents estrogen deficiency-induced bone loss in mice.Mechanistically, estrogen controls HIF-1α protein stabilization through HSP70-mediated degradation in bone marrow B cells.The stabilization of HIF-1α protein in HSP70-deficient bone marrow B cells promotes RANKL production and osteoclastogenesis.Induction of HSP70 expression by geranylgeranylacetone(GGA) administration alleviates ovariectomy-induced osteoporosis.Moreover, RANKL gene expression has a positive correlation with HIF1 A expression in human B cells. In conclusion, HIF-1αsignaling in B cells is crucial for the control of osteoclastogenesis, and the HSP70/HIF-1α axis may serve as a new therapeutic target for osteoporosis.展开更多
Macrophages play an important role in material-related immune responses and bone formation,but the functionality of macrophage-derived extracellular vesicles(EVs)in material-mediated bone regeneration is still unclear...Macrophages play an important role in material-related immune responses and bone formation,but the functionality of macrophage-derived extracellular vesicles(EVs)in material-mediated bone regeneration is still unclear.Here,we evaluated intracellular communication through small extracellular vesicles(sEVs)and its effects on endogenous bone regeneration mediated by biomimetic intrafibrillarly mineralized collagen(IMC).After implantation in the bone defect area,IMC generated more neobone and recruited more mesenchymal stem cells(MSCs)than did extrafibrillarly mineralized collagen(EMC).More CD63+CD90+and CD63+CD163+cells were detected in the defect area in the IMC group than in the EMC group.To determine the functional roles of sEVs,extracellular vesicles from macrophages cultured on different mineralized collagen were isolated,and they showed no morphological differences.However,macrophage-derived sEVs in the IMC group showed an enhanced Young’s modulus and exerted beneficial effects on the osteogenic differentiation of bone marrow MSCs by increasing the expression of the osteoblastic differentiation markers BMP2,BGLAP,COL1,and OSX and calcium nodule formation.Mechanistically,sEVs from IMC-treated macrophages facilitated MSC osteogenesis through the BMP2/Smad5 pathway,and blocking sEV secretion with GW4869 significantly impaired MSC proliferative,immunomodulative and osteogenic potential.Taken together,these findings show that macrophage-derived sEVs may serve as an emerging functional tool in biomaterial-mediated endogenous bone regeneration.展开更多
Dear editors,Neurodegenerative diseases are now associated with the global obesity and diabetes epidemic in the developing and developed world.Neurodegenerative diseases are a heterogeneous group of disorders with com...Dear editors,Neurodegenerative diseases are now associated with the global obesity and diabetes epidemic in the developing and developed world.Neurodegenerative diseases are a heterogeneous group of disorders with complex factors such as neurohumoral,endocrine and environmental factors involved in induction of these neurodegenerative diseases.The future of science and medicine in neurodegenerative diseases is now dependent on nutritional genomics with insulin resistance a major factor in the induction of neurodegenerative diseases.Nutritional genomics now involves the anti-aging gene Sirtuin 1(Sirt 1)that is important to the prevention of insulin resistance with its critical involvement in the immune system(Martins,2018a,b).Sirt 1 inactivation leads to toxic immune reactions connected to the acceleration of neuron death in various communities.Appetite control with relevance to immunometabolism has become of critical importance to the treatment of neurodegeneration(Figure 1).Nutritional diets activate the heat shock gene Sirt 1 to prevent the increase in heat shock proteins connected to autoimmune disease,mitophagy(Martins,2018a,b)and irreversible programmed cell death in global populations(Figure 1).展开更多
Adipose-derived stromal cells （ASCs） have gained great attention in regenerative medicine. Progress in our understanding of adult neovascularization further suggests the potential of ASCs in promoting vascular regen...Adipose-derived stromal cells （ASCs） have gained great attention in regenerative medicine. Progress in our understanding of adult neovascularization further suggests the potential of ASCs in promoting vascular regeneration, although the specific cues that stimulate their angiogenic behavior remain controversial In this study, we established a three-dimensional （3D） angiogenesis model by co-culturing ASCs and endothelial cells （ECs） in collagen gel and found that ASC-EC-instructed angiogenesis was regulated by the canonical Wnt pathway. Furthermore, the angiogenesis that occurred in implants collected after injections of our collagen gel- based 3D angiogenesis model into nude mice was confirmed to be functional and also regulated by the canonical Wnt pathway. Wnt regulation of angiogenesis involving changes in vessel length, vessel density, vessel sprout, and connection numbers occurred in our system. Wnt signaling was then shown to regulate ASC- mediated paracrine signaling during angiogenesis through the nuclear translocation of β-catenin after its cytoplasmic accumulation in both ASCs and ECs. This translocation enhanced the expression of nuclear cofactor Lef-1 and cyclin D1 and activated the angiogenic transcription of vascular endothelial growth factor A （VEGFA）, basic fibroblast growth factor （bFGF）, and insulin-like growth factor 1 （IGF-1）. The angiogenesis process in the 3D collagen model appeared to follow canonical Wnt signaling, and this model can help us understand the importance of the canonical Wnt pathway in the use of ASCs in vascular regeneration.展开更多
Particulate matter （PM）, which is a great environmental concern, has been classified as a Group 1 human carcinogen by the International Agency for Research on Cancer （IARC）;.Epidemiological and experimental studie...Particulate matter （PM）, which is a great environmental concern, has been classified as a Group 1 human carcinogen by the International Agency for Research on Cancer （IARC）;.Epidemiological and experimental studies have indicated that chronic exposure to PM, especially PM;(particles with an aerodynamic diameter less than展开更多
Liver transplantation(LT)is a life-saving surgical procedure and the current standard of care for most patients with end stage liver disease.With improvements in organ preservation techniques,perioperative care,and im...Liver transplantation(LT)is a life-saving surgical procedure and the current standard of care for most patients with end stage liver disease.With improvements in organ preservation techniques,perioperative care,and immunosuppression,there is better patient and graft survival following LT,and assessment of the liver allograft in long-term survivors is becoming increasingly important.Recurrent or de novo viral or autoimmune injury remains the most common causes of chronic hepatitis and fibrosis following liver transplantation in adults.However,no obvious cause can be identified in many adults with controlled recurrent disease and the majority of pediatric LT recipients,as they have been transplanted for non-recurrent liver diseases.Serial surveillance liver biopsies post LT have been evaluated in several adult and pediatric centers to identify long-term pathological changes.Pathological findings are frequently present in liver biopsies obtained after a year post LT.The significance of these findings is uncertain as many of these are seen in protocol liver biopsies from patients with clinically good allograft function and normal liver chemistry parameters.This narrative review summaries the factors predisposing to long-term liver allograft fibrosis,highlighting the putative role of idiopathic post-LT hepatitis and chronic antibody mediated rejection in its pathogenesis.展开更多
Mechanical loading to the bone is known to be beneficial for bone homeostasis and for suppressing tumor-induced osteolysis in the loaded bone.However,whether loading to a weight-bearing hind limb can inhibit distant t...Mechanical loading to the bone is known to be beneficial for bone homeostasis and for suppressing tumor-induced osteolysis in the loaded bone.However,whether loading to a weight-bearing hind limb can inhibit distant tumor growth in the brain is unknown.We examined the possibility of bone-to-brain mechanotransduction using a mouse model of a brain tumor by focusing on the response to Lrp5-mediated Wnt signaling and dopamine in tumor cells.The results revealed that loading the tibia with elevated levels of tyrosine hydroxylase,a rate-limiting enzyme in dopamine synthesis,markedly reduced the progression of the brain tumors.The simultaneous application of fluphenazine(FP),an antipsychotic dopamine modulator,enhanced tumor suppression.Dopamine and FP exerted antitumor effects through the dopamine receptors DRD1 and DRD2,respectively.Notably,dopamine downregulated Lrp5 via DRD1 in tumor cells.A cytokine array analysis revealed that the reduction in CCN4 was critical for loading-driven,dopamine-mediated tumor suppression.The silencing of Lrp5 reduced CCN4,and the administration of CCN4 elevated oncogenic genes such as MMP9,Runx2,and Snail.In summary,this study demonstrates that mechanical loading regulates dopaminergic signaling and remotely suppresses brain tumors by inhibiting the Lrp5-CCN4 axis via DRD1,indicating the possibility of developing an adjuvant bone-mediated loading therapy.展开更多
To investigate the characteristics of multidrugresistance and transplantation of modified stem/ progenitor cells by multidrugresistant gene (mdr1 gene), we established PA317/MDR1 cell line which producing retroviruse...To investigate the characteristics of multidrugresistance and transplantation of modified stem/ progenitor cells by multidrugresistant gene (mdr1 gene), we established PA317/MDR1 cell line which producing retroviruses by transfecting the retroviral vector PHaMDR1/A into packging cell line PA317 by Lipofectin. The virus titer of the supernatants was 1.2×105 cfu/ml. We transfected the murine hematopietic cells collected from 5FU pretreated mice and they showed the ability to reconstitute the longterm hematopoiesis of preirradiated mice. After 4 months, both of bone marrow cells and peripheral blood cells of transplanted mice still contained mdr1 gene. We also transfered mdr1 gene into human bone marrow CD34+ cells selected by using magnetic cell sorting system. PCR analysis showed that transduced CD34+ cells maintained the mdr1 cDNA. A fraction of CFUGM originated from transfected CD34+ cells had the charactor of resistance to Taxol. It is indicated that mdr1 gene can be transduced into murine and human stem/proginitor cells through retroviral mediated gene transfer and it protects the transfected cells from cytotoxic drugs.展开更多
Endothelial dysfunction is the postulated link between coronary artery disease （CAD） and erectile dysfunction （ED）. Brachial artery flow-mediated vasodilatation （FMD） is a non-invasive surrogate marker for endot...Endothelial dysfunction is the postulated link between coronary artery disease （CAD） and erectile dysfunction （ED）. Brachial artery flow-mediated vasodilatation （FMD） is a non-invasive surrogate marker for endothelial function assessment. Despite Asian Indians representing a considerable global CAD burden, data on FMD and ED in these patients are lacking. Of the 225 patients undergoing coronary angiography, 72% had ED （assessed using the International Index of Erectile Function （IIEF-5） questionnaire）; ED was moderate to severe in 61% of the patients. ED patients had a higher incidence of severe and diffuse angiographic CAD, a greater number of coronary vessels involved and a lower mean brachial artery FMD （6.40%±4.60% vs. 9.10%±4.87%, P〈0.001） compared to non-ED patients. A progressive reduction in FMD was noted with increasing severity of ED. Impaired FMD （ ≤ 5.5%） was twice as common in ED patients （52% vs. 24% without ED）. Patients with impaired FMD had higher ED prevalence （85% vs. 62%） and lower mean I IEF-5 scores compared to those with normal FMD. Impaired FMD was a significant ED predictor independent of other risk factors （odds ratio, 2.33; 95% confidence interval： 0.59-9.23; P=0.03）. An inverse correlation between FMD and ED severity was observed （r=-0.22; P=0.004）. ED is common among Asian Indians with angiographically documented CAD. Patients with ED have impaired FMD independent of other risk factors, suggesting that endothelial dysfunction is the underlying pathophysiology. Urologists and cardiologists need to be aware of the association between ED, CAD and endothelial dysfunction.展开更多
The recyclable and stable ZnFe_(2)O_(4) small particle decorated one‐dimensional perylene diimide(PDI)S‐scheme heterojunction(1D PDI/ZnFe_(2)O_(4))is prepared by the hydrochloric acid‐mediated(HCl‐mediated)strateg...The recyclable and stable ZnFe_(2)O_(4) small particle decorated one‐dimensional perylene diimide(PDI)S‐scheme heterojunction(1D PDI/ZnFe_(2)O_(4))is prepared by the hydrochloric acid‐mediated(HCl‐mediated)strategy,interestingly,the morphology of the 1D PDI/ZnFe_(2)O_(4) can also be effectively regulated by HCl‐mediated process,the existence of HCl can regulate PDI into a uniform rod structure,while the co‐existence of HCl and PDI can limit ZnFe_(2)O_(4) to become the uniform small particles.More importantly,based on the 1D rod structure of PDI and the small size effect of ZnFe_(2)O_(4),carriers can migrate to the surface more easily,which can improve the photocatalytic activity.Meanwhile,due to the appropriate energy level structure,the S‐scheme heterojunction structure is formed between PDI and ZnFe_(2)O_(4),which eliminates meaningless photo‐generated charge carriers through recombination and introduces strong redox to further enhance the photodegradation effect,thereby,1D PDI/ZnFe_(2)O_(4) exhibits excellent photocatalytic ability,under the visible light irradiation,the degradation rate of tetracycline(TC)with 1D PDI/ZnFe_(2)O_(4)(66.67%)is 9.18 times that with PDI(7.26%)and 9.73 times that with ZnFe_(2)O_(4)(6.85%).This work proposes new ideas for the assembly of magnetic organic‐inorganic S‐scheme heterojunction photocatalysts.展开更多
Wound damage triggers the accumulation of abscisic acid(ABA),which induces the expression of a large number of genes involved in wound suberization in plants.Fatty acyl-CoA reductase(FAR)catalyzes the generation of pr...Wound damage triggers the accumulation of abscisic acid(ABA),which induces the expression of a large number of genes involved in wound suberization in plants.Fatty acyl-CoA reductase(FAR)catalyzes the generation of primary fatty alcohols by the reduction of fatty acids in suberin biosynthesis.However,the regulatory effects of transcription factors(TFs)on AchnFAR in response to ABA are unexplored.In this study,kiwifruit AchnFAR displayed a biological function analogous to that of FAR in transiently overexpressed tobacco(Nicotiana benthamiana)leaves.The positive role of TFs,including AchnMYB41,AchnMYB107,and AchnMYC2,in the regulation of AchnFAR was identified.The three TFs could individually bind to the AchnFAR promoter to activate gene transcription in yeast one-hybrid and dualluciferase assays.Transient overexpression of TFs in tobacco leaves resulted in the upregulation of aliphatic synthesis genes(including FAR)and the increase in aliphatics,including primary alcohols,α,ω-diacids,ω-hydroxyacids,and fatty acids.Moreover,exogenous ABA treatment elevated TF-mediated AchnFAR expression and the accumulation of primary alcohols.Conversely,fluridone,an inhibitor of ABA biosynthesis,suppressed the expression of AchnFAR and TF genes and reduced the formation of primary alcohols.The results indicate that AchnMYB41,AchnMYB107,and AchnMYC2 activate AchnFAR transcription to promote ABA-mediated primary alcohol formation in wound suberization in kiwifruit.展开更多
This work reports a facile and efficient seed-mediated method for the synthesis of dendritic platinum （Pt） nanoparticles （NPs） at low temperatures of 55-60 ℃ in water, using L-ascorbic acid as a reducing agent an...This work reports a facile and efficient seed-mediated method for the synthesis of dendritic platinum （Pt） nanoparticles （NPs） at low temperatures of 55-60 ℃ in water, using L-ascorbic acid as a reducing agent and sodium citrate as a capping agent. It is found that the dendritic Pt NPs （10-150 nm） are composed of tiny Pt nanocrystals, which nucleate and grow through the introduced smaller Pt seeds with diameters of 3-5 nm. Further investigation shows that the dendritic Pt nanostructures display excellent catalytic performance in an aqueous-phase aromatic ketone hydrogenation reaction, including： （i） acetophenone conversion rate of 〉 90%, with smaller dendritic Pt NPs （10-46 nm） offering a higher conversion efficiency; （ii） high chemoselectivity toward carbonyl group （90.6%-91.5%）, e.g., the selectivity to l-phenylethanol is -90.1% with nearly 100% acetophenone conversion for 10 nm dendritic Pt NPs within 60 rain, under mild reaction conditions （20 ℃, 1.5 bar H2 pressure, and 1.5 tool% catalyst）. The high catalytic activity, selectivity and stability of the dendritic Pt nanostructures under the organic solvent-free conditions make them promising for many potential applications in green catalytic conversion of hydrophilic biomass derived compounds.展开更多
BACKGROUND The liver has traditionally been regarded as resistant to antibody-mediated rejection(AMR).AMR in liver transplants is a field in its infancy compared to kidney and lung transplants.In our case we present a...BACKGROUND The liver has traditionally been regarded as resistant to antibody-mediated rejection(AMR).AMR in liver transplants is a field in its infancy compared to kidney and lung transplants.In our case we present a patient with alpha-1-antitrypsin disease who underwent ABO compatible liver transplant complicated by acute liver failure(ALF)with evidence of antibody mediated rejection on allograft biopsy and elevated serum donor-specific antibodies(DSA).This case highlights the need for further investigations and heightened awareness for timely diagnosis.CASE SUMMARY A 56 year-old woman with alpha-1-antitrypsin disease underwent ABO compatible liver transplant from a deceased donor.The recipient MELD at the time of transplant was 28.The flow cytometric crossmatches were noted to be positive for T and B lymphocytes.The patient had an uneventful recovery postoperatively.Starting on postoperative day 5 the patient developed fevers,elevated liver function tests,distributive shock,renal failure,and hepatic encephalopathy.She went into ALF with evidence of antibody mediated rejection with portal inflammation,bile duct injury,endothelitis,and extensive centrizonal necrosis,and C4d staining on allograft biopsy and elevated DSA.Despite various interventions including plasmapheresis and immunomodulating therapy,she continued to deteriorate.She was relisted and successfully underwent liver retransplantation.CONCLUSION This very rare case highlights AMR as the cause of ALF following liver transplant requiring retransplantation.展开更多
A simple and effective method of removing polluted organics in water is reported here.Titanium dioxide is a catalyst in photo-oxidation of monocrotophos.The mechanism of photocatalytic oxidation and the kinetics of th...A simple and effective method of removing polluted organics in water is reported here.Titanium dioxide is a catalyst in photo-oxidation of monocrotophos.The mechanism of photocatalytic oxidation and the kinetics of the reaction were studied. This same principle also leads to the construction of instrument of PTR-FIA analysis for monitoring organic phosphorus and phosphate in water.展开更多
Treatment of steroidal sapogenin diosgenin 1 with Lewis acid ethereal trifluoroborane in acetic anhydride at room temperature afforded a new type of pseudosapugenin 23, 26-diacetyl-△22(23)- pseudo-sapogenin 3 and its...Treatment of steroidal sapogenin diosgenin 1 with Lewis acid ethereal trifluoroborane in acetic anhydride at room temperature afforded a new type of pseudosapugenin 23, 26-diacetyl-△22(23)- pseudo-sapogenin 3 and its C-20 isomer 4 in 54% and 19% yield respectively.The possible mechanism was also suggested.展开更多
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.
基金supported by grants from the National Natural Science Foundation of China(82130028 to Z.P.F.)National Key Research and Development Program(2022YFA1104401)+1 种基金CAMS Innovation Fund for Medical Sciences(2019-I2M-5-031 to Z.P.F.)grants from Innovation Research Team Project of Beijing Stomatological Hospital,Capital Medical University(NO.CXTD202204 to Z.P.F.).
文摘Bisphosphonate-related osteonecrosis of jaw(BRONJ)is characterized by impaired osteogenic differentiation of orofacial bone marrow stromal cells(BMSCs).Corin has recently been demonstrated to act as a key regulator in bone development and orthopedic disorders.However,the role of corin in BRONJ-related BMSCs dysfunction remains unclarified.A m6A epitranscriptomic microarray study from our group shows that the CORIN gene is significantly upregulated and m6A hypermethylated during orofacial BMSCs osteogenic differentiation.Corin knockdown inhibits BMSCs osteogenic differentiation,whereas corin overexpression or soluble corin(sCorin)exerts a promotion effect.Furthermore,corin expression is negatively regulated by bisphosphonates(BPs).Corin overexpression or sCorin reverses BPs-impaired BMSCs differentiation ability.Mechanistically,we find altered expression of phos-ERK in corin knockdown/overexpression BMSCs and BMSCs under sCorin stimulation.PD98059(a selective ERK inhibitor)blocks the corin-mediated promotion effect.With regard to the high methylation level of corin during osteogenic differentiation,we apply a non-selective m6A methylase inhibitor,Cycloleucine,which also blocks the corin-mediated promotion effect.Furthermore,we demonstrate that METTL7A modulates corin m6A modification and reverses BPs-impaired BMSCs function,indicating that METTL7A regulates corin expression and thus contributes to orofacial BMSCs differentiation ability.To conclude,our study reveals that corin reverses BPs-induced BMSCs dysfunction,and METTL7A-mediated corin m6A modification underlies corin promotion of osteogenic differentiation via the ERK pathway.We hope this brings new insights into future clinical treatments for BRONJ.
文摘Extracellular deposition of amyloid-βas neuritic plaques and intracellular accumulation of hyperphosphorylated,aggregated tau as neurofibrillary tangles are two of the characteristic hallmarks of Alzheimer's disease1,2.The regional progression of brain atrophy in Alzheimer's disease highly correlates with tau accumulation but not amyloid deposition3-5,and the mechanisms of tau-mediated neurodegeneration remain elusive.
文摘The anther-smut Microbotryum violaceum ( Brandenburger and Schvinn) G. Deml. and Oberw.) causes a systematic infection of its host Silene dioica ( L.) Clairv., resulting in sterility and production of teliospores (dispersal propagules) in flowers. These spores are transmitted to healthy plants mainly by flower visitors. The behavioral responses of flower visitors to a variation in floral characters are not only likely to affect rates of pollen export/import, but also the rate of spore deposition and probability of disease. In a transplantation experiment, using plants from four different populations, we tested for correlation between variation in female floral morphology and patterns of spore and pollen deposition, and a resulting risk of disease. The source populations in this experiment were located on four islands in Skeppsvik archipelago in northern Sweden, and represented a gradient of disease incidence from completely healthy ( Island 1), low incidence ( Island 2) to high incidences ( Islands 3 and 4) of disease. Fifty plants from each population were transplanted to the center, of the population on Island 4. There were significant differences among the transplants in floral characters, i.e. corolla size, style length and ovule number. Plants from the non-diseased population had larger flowers and longer styles than plants from the highly diseased populations. Numbers of pollen grains and spores deposited on flowers were strongly and positively correlated. We found that plants originating from the non-diseased population captured approximately 4 times more pollen and 9 times more spores, per flower than die individuals from the resident population (Island 4, population 4). The incidences of disease among plants, from the four populations differed significantly, and was 37%, 20%, 18% and 0 for populations 1, 2, 3 and 4 respectively. In a survey of ten populations we found a significant negative correlation between the mean style length ( positively correlated with corolla size and ovule number) among healthy plants and incidence of disease in these populations. The potentiality for pathogen-pollinator mediated selection oil floral characters; and consequences for gone flow between populations of Silene dioica are discussed.
文摘The genetic transformation was achieved by pollen_mediated approach on maize ( Zea mays L.) inbred lines Tai 9101 and Zong 31. Plasmid DNA of pGLⅡ_RC_1 was mixed with fresh pollen of maize inbreds in sucrose solution. The pollens were treated by ultrasonication and collected, pollinated on silks of maize ears. Transformants were confirmed by dot blot hybridization, PCR amplification and PCR_Southern blot hybridization. The pollen_mediated transformation approach could circumvent the tedious tissue culture procedures like in particle bombardment and Agrobacterium infection, etc. This approach is simple, easy to operate, and could be widely used in practice.
文摘In the bone marrow, B cells and bone-resorbing osteoclasts colocalize and form a specific microenvironment. How B cells functionally influence osteoclasts and bone architecture is poorly understood. Using genetically modified mice and highthroughput analyses, we demonstrate that prolonged HIF-1α signaling in B cells leads to enhanced RANKL production and osteoclast formation. In addition, deletion of HIF-1α in B cells prevents estrogen deficiency-induced bone loss in mice.Mechanistically, estrogen controls HIF-1α protein stabilization through HSP70-mediated degradation in bone marrow B cells.The stabilization of HIF-1α protein in HSP70-deficient bone marrow B cells promotes RANKL production and osteoclastogenesis.Induction of HSP70 expression by geranylgeranylacetone(GGA) administration alleviates ovariectomy-induced osteoporosis.Moreover, RANKL gene expression has a positive correlation with HIF1 A expression in human B cells. In conclusion, HIF-1αsignaling in B cells is crucial for the control of osteoclastogenesis, and the HSP70/HIF-1α axis may serve as a new therapeutic target for osteoporosis.
基金This work was supported by the Projects of the National Natural Science Foundations of China(No.81970901 to N.J.and No.81871492 to Y.L.)the Ten Thousand Talents Program(Y.L.)the Beijing Municipal Natural Science Foundation(No.L182005 to Y.L.).
文摘Macrophages play an important role in material-related immune responses and bone formation,but the functionality of macrophage-derived extracellular vesicles(EVs)in material-mediated bone regeneration is still unclear.Here,we evaluated intracellular communication through small extracellular vesicles(sEVs)and its effects on endogenous bone regeneration mediated by biomimetic intrafibrillarly mineralized collagen(IMC).After implantation in the bone defect area,IMC generated more neobone and recruited more mesenchymal stem cells(MSCs)than did extrafibrillarly mineralized collagen(EMC).More CD63+CD90+and CD63+CD163+cells were detected in the defect area in the IMC group than in the EMC group.To determine the functional roles of sEVs,extracellular vesicles from macrophages cultured on different mineralized collagen were isolated,and they showed no morphological differences.However,macrophage-derived sEVs in the IMC group showed an enhanced Young’s modulus and exerted beneficial effects on the osteogenic differentiation of bone marrow MSCs by increasing the expression of the osteoblastic differentiation markers BMP2,BGLAP,COL1,and OSX and calcium nodule formation.Mechanistically,sEVs from IMC-treated macrophages facilitated MSC osteogenesis through the BMP2/Smad5 pathway,and blocking sEV secretion with GW4869 significantly impaired MSC proliferative,immunomodulative and osteogenic potential.Taken together,these findings show that macrophage-derived sEVs may serve as an emerging functional tool in biomaterial-mediated endogenous bone regeneration.
基金supported by grants from Edith Cowan Universitythe McCusker Alzheimer’s Research Foundationthe National Health and Medical Research Council
文摘Dear editors,Neurodegenerative diseases are now associated with the global obesity and diabetes epidemic in the developing and developed world.Neurodegenerative diseases are a heterogeneous group of disorders with complex factors such as neurohumoral,endocrine and environmental factors involved in induction of these neurodegenerative diseases.The future of science and medicine in neurodegenerative diseases is now dependent on nutritional genomics with insulin resistance a major factor in the induction of neurodegenerative diseases.Nutritional genomics now involves the anti-aging gene Sirtuin 1(Sirt 1)that is important to the prevention of insulin resistance with its critical involvement in the immune system(Martins,2018a,b).Sirt 1 inactivation leads to toxic immune reactions connected to the acceleration of neuron death in various communities.Appetite control with relevance to immunometabolism has become of critical importance to the treatment of neurodegeneration(Figure 1).Nutritional diets activate the heat shock gene Sirt 1 to prevent the increase in heat shock proteins connected to autoimmune disease,mitophagy(Martins,2018a,b)and irreversible programmed cell death in global populations(Figure 1).
基金funded by the National Natural Science Foundation of China(81771125,81471803,81671031)the Sichuan Province Youth Science and Technology Innovation Team(2014TD0001)
文摘Adipose-derived stromal cells （ASCs） have gained great attention in regenerative medicine. Progress in our understanding of adult neovascularization further suggests the potential of ASCs in promoting vascular regeneration, although the specific cues that stimulate their angiogenic behavior remain controversial In this study, we established a three-dimensional （3D） angiogenesis model by co-culturing ASCs and endothelial cells （ECs） in collagen gel and found that ASC-EC-instructed angiogenesis was regulated by the canonical Wnt pathway. Furthermore, the angiogenesis that occurred in implants collected after injections of our collagen gel- based 3D angiogenesis model into nude mice was confirmed to be functional and also regulated by the canonical Wnt pathway. Wnt regulation of angiogenesis involving changes in vessel length, vessel density, vessel sprout, and connection numbers occurred in our system. Wnt signaling was then shown to regulate ASC- mediated paracrine signaling during angiogenesis through the nuclear translocation of β-catenin after its cytoplasmic accumulation in both ASCs and ECs. This translocation enhanced the expression of nuclear cofactor Lef-1 and cyclin D1 and activated the angiogenic transcription of vascular endothelial growth factor A （VEGFA）, basic fibroblast growth factor （bFGF）, and insulin-like growth factor 1 （IGF-1）. The angiogenesis process in the 3D collagen model appeared to follow canonical Wnt signaling, and this model can help us understand the importance of the canonical Wnt pathway in the use of ASCs in vascular regeneration.
基金supported by the National Natural Science Foundation of China[81202231 to LLH]the Medical Scientific Research Funding of Guangdong Province,China[A2018225 to LLH]+1 种基金the College Students Cultivate Special Science and Technology Innovation from Education Department of Guangdong Province,China[pdjh2016a0212]the Project for Creative Talent of Guangdong Education Department[2014KQNCX102]
文摘Particulate matter （PM）, which is a great environmental concern, has been classified as a Group 1 human carcinogen by the International Agency for Research on Cancer （IARC）;.Epidemiological and experimental studies have indicated that chronic exposure to PM, especially PM;(particles with an aerodynamic diameter less than
文摘Liver transplantation(LT)is a life-saving surgical procedure and the current standard of care for most patients with end stage liver disease.With improvements in organ preservation techniques,perioperative care,and immunosuppression,there is better patient and graft survival following LT,and assessment of the liver allograft in long-term survivors is becoming increasingly important.Recurrent or de novo viral or autoimmune injury remains the most common causes of chronic hepatitis and fibrosis following liver transplantation in adults.However,no obvious cause can be identified in many adults with controlled recurrent disease and the majority of pediatric LT recipients,as they have been transplanted for non-recurrent liver diseases.Serial surveillance liver biopsies post LT have been evaluated in several adult and pediatric centers to identify long-term pathological changes.Pathological findings are frequently present in liver biopsies obtained after a year post LT.The significance of these findings is uncertain as many of these are seen in protocol liver biopsies from patients with clinically good allograft function and normal liver chemistry parameters.This narrative review summaries the factors predisposing to long-term liver allograft fibrosis,highlighting the putative role of idiopathic post-LT hepatitis and chronic antibody mediated rejection in its pathogenesis.
基金supported in part by funds from the NIH(R01 AR052144 and R03 CA238555 to H.Y.).
文摘Mechanical loading to the bone is known to be beneficial for bone homeostasis and for suppressing tumor-induced osteolysis in the loaded bone.However,whether loading to a weight-bearing hind limb can inhibit distant tumor growth in the brain is unknown.We examined the possibility of bone-to-brain mechanotransduction using a mouse model of a brain tumor by focusing on the response to Lrp5-mediated Wnt signaling and dopamine in tumor cells.The results revealed that loading the tibia with elevated levels of tyrosine hydroxylase,a rate-limiting enzyme in dopamine synthesis,markedly reduced the progression of the brain tumors.The simultaneous application of fluphenazine(FP),an antipsychotic dopamine modulator,enhanced tumor suppression.Dopamine and FP exerted antitumor effects through the dopamine receptors DRD1 and DRD2,respectively.Notably,dopamine downregulated Lrp5 via DRD1 in tumor cells.A cytokine array analysis revealed that the reduction in CCN4 was critical for loading-driven,dopamine-mediated tumor suppression.The silencing of Lrp5 reduced CCN4,and the administration of CCN4 elevated oncogenic genes such as MMP9,Runx2,and Snail.In summary,this study demonstrates that mechanical loading regulates dopaminergic signaling and remotely suppresses brain tumors by inhibiting the Lrp5-CCN4 axis via DRD1,indicating the possibility of developing an adjuvant bone-mediated loading therapy.
文摘To investigate the characteristics of multidrugresistance and transplantation of modified stem/ progenitor cells by multidrugresistant gene (mdr1 gene), we established PA317/MDR1 cell line which producing retroviruses by transfecting the retroviral vector PHaMDR1/A into packging cell line PA317 by Lipofectin. The virus titer of the supernatants was 1.2×105 cfu/ml. We transfected the murine hematopietic cells collected from 5FU pretreated mice and they showed the ability to reconstitute the longterm hematopoiesis of preirradiated mice. After 4 months, both of bone marrow cells and peripheral blood cells of transplanted mice still contained mdr1 gene. We also transfered mdr1 gene into human bone marrow CD34+ cells selected by using magnetic cell sorting system. PCR analysis showed that transduced CD34+ cells maintained the mdr1 cDNA. A fraction of CFUGM originated from transfected CD34+ cells had the charactor of resistance to Taxol. It is indicated that mdr1 gene can be transduced into murine and human stem/proginitor cells through retroviral mediated gene transfer and it protects the transfected cells from cytotoxic drugs.
文摘Endothelial dysfunction is the postulated link between coronary artery disease （CAD） and erectile dysfunction （ED）. Brachial artery flow-mediated vasodilatation （FMD） is a non-invasive surrogate marker for endothelial function assessment. Despite Asian Indians representing a considerable global CAD burden, data on FMD and ED in these patients are lacking. Of the 225 patients undergoing coronary angiography, 72% had ED （assessed using the International Index of Erectile Function （IIEF-5） questionnaire）; ED was moderate to severe in 61% of the patients. ED patients had a higher incidence of severe and diffuse angiographic CAD, a greater number of coronary vessels involved and a lower mean brachial artery FMD （6.40%±4.60% vs. 9.10%±4.87%, P〈0.001） compared to non-ED patients. A progressive reduction in FMD was noted with increasing severity of ED. Impaired FMD （ ≤ 5.5%） was twice as common in ED patients （52% vs. 24% without ED）. Patients with impaired FMD had higher ED prevalence （85% vs. 62%） and lower mean I IEF-5 scores compared to those with normal FMD. Impaired FMD was a significant ED predictor independent of other risk factors （odds ratio, 2.33; 95% confidence interval： 0.59-9.23; P=0.03）. An inverse correlation between FMD and ED severity was observed （r=-0.22; P=0.004）. ED is common among Asian Indians with angiographically documented CAD. Patients with ED have impaired FMD independent of other risk factors, suggesting that endothelial dysfunction is the underlying pathophysiology. Urologists and cardiologists need to be aware of the association between ED, CAD and endothelial dysfunction.
文摘The recyclable and stable ZnFe_(2)O_(4) small particle decorated one‐dimensional perylene diimide(PDI)S‐scheme heterojunction(1D PDI/ZnFe_(2)O_(4))is prepared by the hydrochloric acid‐mediated(HCl‐mediated)strategy,interestingly,the morphology of the 1D PDI/ZnFe_(2)O_(4) can also be effectively regulated by HCl‐mediated process,the existence of HCl can regulate PDI into a uniform rod structure,while the co‐existence of HCl and PDI can limit ZnFe_(2)O_(4) to become the uniform small particles.More importantly,based on the 1D rod structure of PDI and the small size effect of ZnFe_(2)O_(4),carriers can migrate to the surface more easily,which can improve the photocatalytic activity.Meanwhile,due to the appropriate energy level structure,the S‐scheme heterojunction structure is formed between PDI and ZnFe_(2)O_(4),which eliminates meaningless photo‐generated charge carriers through recombination and introduces strong redox to further enhance the photodegradation effect,thereby,1D PDI/ZnFe_(2)O_(4) exhibits excellent photocatalytic ability,under the visible light irradiation,the degradation rate of tetracycline(TC)with 1D PDI/ZnFe_(2)O_(4)(66.67%)is 9.18 times that with PDI(7.26%)and 9.73 times that with ZnFe_(2)O_(4)(6.85%).This work proposes new ideas for the assembly of magnetic organic‐inorganic S‐scheme heterojunction photocatalysts.
基金supported by the National Natural Science Foundation of China(Nos.31772365 and 31972468)the National Key Research and Development Program of China(No.2018YFD0401303).
文摘Wound damage triggers the accumulation of abscisic acid(ABA),which induces the expression of a large number of genes involved in wound suberization in plants.Fatty acyl-CoA reductase(FAR)catalyzes the generation of primary fatty alcohols by the reduction of fatty acids in suberin biosynthesis.However,the regulatory effects of transcription factors(TFs)on AchnFAR in response to ABA are unexplored.In this study,kiwifruit AchnFAR displayed a biological function analogous to that of FAR in transiently overexpressed tobacco(Nicotiana benthamiana)leaves.The positive role of TFs,including AchnMYB41,AchnMYB107,and AchnMYC2,in the regulation of AchnFAR was identified.The three TFs could individually bind to the AchnFAR promoter to activate gene transcription in yeast one-hybrid and dualluciferase assays.Transient overexpression of TFs in tobacco leaves resulted in the upregulation of aliphatic synthesis genes(including FAR)and the increase in aliphatics,including primary alcohols,α,ω-diacids,ω-hydroxyacids,and fatty acids.Moreover,exogenous ABA treatment elevated TF-mediated AchnFAR expression and the accumulation of primary alcohols.Conversely,fluridone,an inhibitor of ABA biosynthesis,suppressed the expression of AchnFAR and TF genes and reduced the formation of primary alcohols.The results indicate that AchnMYB41,AchnMYB107,and AchnMYC2 activate AchnFAR transcription to promote ABA-mediated primary alcohol formation in wound suberization in kiwifruit.
基金the financial support of the Australian Research Council (ARC) projectsUSyd Early Career Researcher Scheme+2 种基金Major Equipment Schemethe scholarships provided by China Scholarship Council (CSC)the Commonwealth Scientific and Industrial Research Organization (CSIRO) OCE Top-up Scholarship
文摘This work reports a facile and efficient seed-mediated method for the synthesis of dendritic platinum （Pt） nanoparticles （NPs） at low temperatures of 55-60 ℃ in water, using L-ascorbic acid as a reducing agent and sodium citrate as a capping agent. It is found that the dendritic Pt NPs （10-150 nm） are composed of tiny Pt nanocrystals, which nucleate and grow through the introduced smaller Pt seeds with diameters of 3-5 nm. Further investigation shows that the dendritic Pt nanostructures display excellent catalytic performance in an aqueous-phase aromatic ketone hydrogenation reaction, including： （i） acetophenone conversion rate of 〉 90%, with smaller dendritic Pt NPs （10-46 nm） offering a higher conversion efficiency; （ii） high chemoselectivity toward carbonyl group （90.6%-91.5%）, e.g., the selectivity to l-phenylethanol is -90.1% with nearly 100% acetophenone conversion for 10 nm dendritic Pt NPs within 60 rain, under mild reaction conditions （20 ℃, 1.5 bar H2 pressure, and 1.5 tool% catalyst）. The high catalytic activity, selectivity and stability of the dendritic Pt nanostructures under the organic solvent-free conditions make them promising for many potential applications in green catalytic conversion of hydrophilic biomass derived compounds.
基金Corresponding author:Lena Sibulesky,MD,Associate Professor,Surgeon,Department of Surgery,University of Washington Medical Center,UWMC 1959 NE Pacific St,Box 356410 Seattle,Seattle,WA 98195,United States.lenasi@uw.edu。
文摘BACKGROUND The liver has traditionally been regarded as resistant to antibody-mediated rejection(AMR).AMR in liver transplants is a field in its infancy compared to kidney and lung transplants.In our case we present a patient with alpha-1-antitrypsin disease who underwent ABO compatible liver transplant complicated by acute liver failure(ALF)with evidence of antibody mediated rejection on allograft biopsy and elevated serum donor-specific antibodies(DSA).This case highlights the need for further investigations and heightened awareness for timely diagnosis.CASE SUMMARY A 56 year-old woman with alpha-1-antitrypsin disease underwent ABO compatible liver transplant from a deceased donor.The recipient MELD at the time of transplant was 28.The flow cytometric crossmatches were noted to be positive for T and B lymphocytes.The patient had an uneventful recovery postoperatively.Starting on postoperative day 5 the patient developed fevers,elevated liver function tests,distributive shock,renal failure,and hepatic encephalopathy.She went into ALF with evidence of antibody mediated rejection with portal inflammation,bile duct injury,endothelitis,and extensive centrizonal necrosis,and C4d staining on allograft biopsy and elevated DSA.Despite various interventions including plasmapheresis and immunomodulating therapy,she continued to deteriorate.She was relisted and successfully underwent liver retransplantation.CONCLUSION This very rare case highlights AMR as the cause of ALF following liver transplant requiring retransplantation.
文摘A simple and effective method of removing polluted organics in water is reported here.Titanium dioxide is a catalyst in photo-oxidation of monocrotophos.The mechanism of photocatalytic oxidation and the kinetics of the reaction were studied. This same principle also leads to the construction of instrument of PTR-FIA analysis for monitoring organic phosphorus and phosphate in water.
文摘Treatment of steroidal sapogenin diosgenin 1 with Lewis acid ethereal trifluoroborane in acetic anhydride at room temperature afforded a new type of pseudosapugenin 23, 26-diacetyl-△22(23)- pseudo-sapogenin 3 and its C-20 isomer 4 in 54% and 19% yield respectively.The possible mechanism was also suggested.
