Linear paired electrolysis of furfural to furoic acid at both anode and cathode in a multiple redox mediated system

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.

Microglia-mediated T cell infiltration drives neurodegeneration in tauopathy

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.

Immediate effects of scalp acupuncture with twirling reinforcing manipulation on hemiplegia following acute ischemic stroke: a hidden association study

Data mining has the potential to provide information for improving clinical acupuncture strategies by uncovering hidden rules between acupuncture manipulation and therapeutic effects in a data set. In this study, we performed acupuncture on 30 patients with hemiplegia due to acute ischemic stroke. All participants were pre-screened to ensure that they exhibited immediate responses to acupuncture. We used a twirling reinforcing acupuncture manipulation at the specific lines between the bilateral Baihui（GV20） and Taiyang（EX-HN5）. We collected neurologic deficit score, simplified Fugl-Meyer assessment score, muscle strength of the proximal and distal hemiplegic limbs, ratio of the maximal H-reflex to the maximal M-wave（Hmax/Mmax）, muscle tension at baseline and immediately after treatment, and the syndromes of traditional Chinese medicine at baseline. We then conducted data mining using an association algorithm and an artificial neural network backpropagation algorithm. We found that the twirling reinforcing manipulation had no obvious therapeutic difference in traditional Chinese medicine syndromes of ＂Deficiency and Excess＂. The change in the muscle strength of the upper distal and lower proximal limbs was one of the main factors affecting the immediate change in Fugl-Meyer scores. Additionally, we found a positive correlation between the muscle tension change of the upper limb and Hmax/Mmax immediate change, and both positive and negative correlations existed between the muscle tension change of the lower limb and immediate Hmax/Mmax change. Additionally, when the difference value of muscle tension for the upper and lower limbs was 〉 0 or 〈 0, the difference value of Hmax/Mmax was correspondingly positive or negative, indicating the scalp acupuncture has a bidirectional effect on muscle tension in hemiplegic limbs. Therefore, acupuncture with twirling reinforcing manipulation has distinct effects on acute ischemic stroke patients with different symptoms or stages of disease. Improved muscle tension in the upper and lower limbs, reflected by the variation in the Hmax/Mmax ratio, is crucial for recovery of motor function from hemiplegia.

Estrogen-mediated downregulation of HIF-1αsignaling in B lymphocytes influences postmenopausal bone loss

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.

Macrophage-derived small extracellular vesicles promote biomimetic mineralized collagen-mediated endogenous bone regeneration

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.

Human survival and immune mediated mitophagy in neuroplasticity disorders

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).

Angiogenesis in a 3D model containing adipose tissue stem cells and endothelial cells is mediated by canonical Wnt signaling

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.

Transcriptional Factor Snail Mediates Epithelial-Mesenchymal Transition in Human Bronchial Epithelial Cells Induced by Silica

Epithelial-mesenchymal transition （EMT） plays an important role in fibrotic diseases. We have previously showed that silica induces EMT in human bronchial epithelial cells （BECs）; however, the underlying mechanism of silica-induced EMT is poorly understood. In the present study, we investigated the role of Snail in silica-induced EMT in human BECs in vitro. Human BECs were treated with silica at various concentrations and incubation times. Then MTr assay, western blot, electrophoretic mobility shift assay （EMSA）, and small interfering RNA （siRNA） transfection were performed. We found that silica increased the expression and DNA binding activity of Snail in human BECs. SNAI silica-induced expression siRNA upregulated the siRNA inhibited the of Snail. Moreover, SNAI expression of epithelial marker E-cadherin, but attenuated the expression of mesenchymal marker a-smooth muscle actin and vimentin in silica-stimulated cells. These results suggest that Snail mediates the silica-induced EMT in human BECs.

LncRNA LUCAT1 Activation Mediated by theDown-regulation of DNMT1 Is Involved inCell Apoptosis Induced by PM2.5

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

Interleukin-17 mediates liver progenitor cell transformation into cancer stem cells through downregulation of miR-122

Objective:Cancer stem cells(CSCs)have been the focus of several studies because oftheir involvement in cancer initiation and progression.CSCs were identified in 28%to 50%of hepatocellular carcinomas(HCCs).The origin of CSCs is still unclear,but it has been recently suggested that CSCs could originate from the transformation of liver progenitor cells(LPCs)during chronic liver inflammation.

MYB41,MYB107,and MYC2 promote ABA-mediated primary fatty alcohol accumulation via activation of AchnFAR in wound suberization in kiwifruit

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.

Bone morphogenetic protein 7 mediates stem cells migration and angiogenesis:therapeutic potential for endogenous pulp regeneration

Pulp loss is accompanied by the functional impairment of defense,sensory,and nutrition supply.The approach based on endogenous stem cells is a potential strategy for pulp regeneration.However,endogenous stem cell sources,exogenous regenerative signals,and neovascularization are major difficulties for pulp regeneration based on endogenous stem cells.Therefore,the purpose of our research is to seek an effective cytokines delivery strategy and bioactive materials to reestablish an ideal regenerative microenvironment for pulp regeneration.In in vitro study,we investigated the effects of Wnt3a,transforming growth factor-beta 1,and bone morphogenetic protein 7(BMP7)on human dental pulp stem cells(h-DPSCs)and human umbilical vein endothelial cells.2D and 3D culture systems based on collagen gel,matrigel,and gelatin methacryloyl were fabricated to evaluate the morphology and viability of h-DPSCs.In in vivo study,an ectopic nude mouse model and an in situ beagle dog model were established to investigate the possibility of pulp regeneration by implanting collagen gel loading BMP7.We concluded that BMP7promoted the migration and odontogenic differentiation of h-DPSCs and vessel formation.Collagen gel maintained the cell adhesion,cell spreading,and cell viability of h-DPSCs in 2D or 3D culture.The transplantation of collagen gel loading BMP7 induced vascularized pulp-like tissue regeneration in vivo.The injectable approach based on collagen gel loading BMP7 might exert promising therapeutic application in endogenous pulp regeneration.

mpaired flow-mediated vasodilatation in Asian Indians with erectile dysfunction

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.

Seed-mediated synthesis of dendritic platinum nanostructures with high catalytic activity for aqueous-phase hydrogenation of acetophenone

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.

Acute liver failure secondary to acute antibody mediated rejection after compatible liver transplant: A case report

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.

REMOVAL OF ORGANIC POLLUTANTS USING TITANIUM DIOXIDE MEDIATED PHOTOCATALYTIC OXIDATION

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.

LEWIS ACID MEDIATED RING F OPENING-ACETYLATION OF STEROIDAL SAPOGENIN

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.

Glycosylation-independent binding to extracellular domains 11-13 of mannose-6-phosphate/insulin-like growth factor-2 receptor mediates the effects of soluble CREG on the phenotypic proliferation of vascular smooth muscle cells

Background The present study aimed to investigate the detailed mode and specific sites for their binding as well as the functional relevance of this binding in the phenotypic proliferation of vascular smooth muscle cells(SMCs). Methods CREG knocked-down SMCs were employed to evaluate the biological activity of wtCREG and mCREG.Expressions of SMC differentiation markers SM myosin heavy chain(SM-MHC),SM-actin,heavy caldesmon and myocardin were determined by Western blotting using specific antibodies. Cellular growth of SMCs was assessed by bromide dewuridine (BrdU) incorporation and cell cycle analysis on fluorescence-activated cell sorting(FACS).A solid-phase binding assay was used to study the binding of CREG to extracellular domains of M6P/IGF2R.The cellular co-localization of the two recombinant CREGs with M6P/IGF2R was detected on SMC surface by immunoprecipitation and immunofluorescence analysis.Results The molecular weight of wtCREG was around 30 kD while that of the mCREG was～25 kD.Treatment of wtCREG with PNGase F reduced its molecular weight from～30 kD to～25 kD,whereas PNGase F treatment had no effect on the molecular weight of mCREG.Both wtCREG and mCREG proteins enhanced SMC differentiation,inhibited BrdU incorporation,and arrested cell cycle progression when added to the culture medium.In CREG knocked-down SMCs,the amount of CREG detected by immunoblotting in M6P/IGF2R immunoprecipitates was significantly reduced when compared to normal cells.Both recombinant CREGs co-immunoprecipitated with M6P/IGF2R, although slightly reduced amount of the mutant CREG was detected in M6P/IGF2R immunoprecipitates.Immunostaining revealed that His-tagged CREGs co-localized with IGF2R on the cell surface in a glycosylation-independent manner.In vitro binding assay showed that CREGs bound to M6P/ IGF2R extracellular domains 7-10 and 11-13 in a glycosylation -dependent and -independent manner,respectively.Further blocking experiments using soluble M6P/IGF2R fragments and M6P/IGF2R neutralizing antibody indicated that the biological activities of recombinant CREGs in SMC growth and the up-regulation of SMC differentiation markers were all abolished by treatment with the M6P/IGF2R neutralizing antibody. However,although the growth inhibitory effect of wtCREG was nearly abolished by D7-10 or D11-13,the effect of mCREG was only reversed by Dll-13,indicating that the binding to domains 11-13 is required for CREG to modulate the proliferation of SMCs.Conclusions These data suggest that solubleCREG proteins can exert their biological function via binding to the extracellular domains 7-10 and 11-13 of cell surface M6P/IGF2R in both a glycosylation-dependent and -independent manner.

PRELIMINARY STUDY OF RETROVIRAL MEDIATED TRANSFER OF THE HUMAN mdr-1 GENE INTO MURINE AND HUMAN HEMATOPOIETIC STEM/PROGENITOR CELLS

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.

Mechanical tibial loading remotely suppresses brain tumors by dopamine-mediated downregulation of CCN4

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.