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.

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).

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

Particulate matter （PM）, which is a greatenvironmental concern, has been classified as aGroup 1 human carcinogen by the InternationalAgency for Research on Cancer （IARC）.Epidemiological and experimental studies haveindicated that chronic exposure to PM, especiallyPM2.5 （particles with an aerodynamic diameter lessthan 2.5 μm） may lead to an increase in lung cancerincidence.

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

ＰＲＥＬＩＭＩＮＡＲＹＳＴＵＤＹＯＦＲＥＴＲＯＶＩＲＡＬＭＥＤＩＡＴＥＤＴＲＡＮＳＦＥＲＯＦＴＨＥＨＵＭＡＮｍｄｒ１ＧＥＮＥＩＮＴＯＭＵＲＩＮＥＡＮＤＨＵＭＡＮＨＥＭＡＴＯＰＯＩＥＴＩＣＳＴＥＭ／ＰＲＯＧＥＮＩＴＯＲＣＥＬＬＳＦｅｎｇＫａｉ冯凯Ｐｅ...

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.

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.

SEQUENCE STUDY AND RETROVIRUS MEDIATED GENE TRANSFER IN MAMMALIAN CELL SYSTEMS OF HUMAN INTERLEUKIN 2 cDNA

Interleukin 2 (IL- 2) is a T cell growth factor. In the present study, human IL- 2 cDNA was cloned from total RNA of activated tonsillar mononuclear cells (TMNC) following reverse transcription and PCR amplification using a pair of synthesized primers. DNA sequence analysis demonstrated that the IL- 2 cDNA cloned from the Chinese tonsil donor is identical with the data reported so far, reflecting the high structural conservation of this gene. The human IL- 2 cDNA was inserted into XM6 to construct a recombinant retroviral expression vector XM6-IL2, having human IL-2 cDNA driven by the 5’ LTR of MMLV. This vector was successfully passaged through ψ 2 and PA317 cells to yield high producer lines of ecotropic and amphotroplc infectious viruses. The murine myeloma cell line SP2/0 after being infected by retrovirus released from high titer PA317 constitutlvely secreted IL- 2 activity into the culture medium when assayed for T cell proliferative capacity. Activated human T cells are also exposed to the

Positive Q-Value Neutron Transfer Mediated Sub-Barrier Fusion Reactions

Positive Q-value neutron transfer mediated sub-barrier fusion reactions are studied with an empirical coupled channels model, which takes into account neutron rearrangement related only to the dynamical matching condition with no free parameters. Fusion cross sections of collision systems ^(32)S+^(90,94,96)Zr are calculated and analyzed.Logarithmic residual enhancement(LRE) is proposed to evaluate the discrepancy between calculated results and experimental data. The experimental data can be described well with this model for the first time as a whole,while the LRE analysis shows that there are still theoretical systematic deviations.

Highlighted multi-modifications of enzymes:a novel succinylation mediated by histone acetyltransferase 1 in tumors

Histone acetyltransferase 1 serves as a succinyl transferase in tumors Protein post-translational modification(PTM)as an important research field has attracted increasing attention.Recently,our group has reported that histone acetyltransferase 1(HAT1)succinylated histones and non-histones and promoted tumorigenesis1.HAT1 plays a role in different biological processes,including cell cycle progression,glucose metabolism,histone production,and DNA damage repair2.We found that HAT1 succinylated histone H3 on K122.For a non-histone,HAT1 catalyzed the succinylation of phosphoglycerate mutase 1(PGAM1)on K99 to increase its enzyme activity,promoting glycolysis in cancer cells.Functionally,HAT1-mediated succinylation contributed to tumorigenesis.Our finding provided new insight into the mechanism of how a histone acetyltransferase HAT1 modulated succinylation during cancer development.

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.

Triple hit to the kidney-dual pathological crescentic glomerulonephritis and diffuse proliferative immune complexmediated glomerulonephritis: A case report

BACKGROUND Anti-glomerular basement membrane(GBM)disease is a rare rapidly progressive glomerulonephritis,frequently associated with alveolar hemorrhage in the lungs and involving the kidney by crescentic glomerulonephritis.It has been described in association with other glomerulonephritides[such as anti-neutrophilic antibody(ANCA)-glomerulonephritis,membranous nephropathy,and immunoglobulin(Ig)A nephropathy].CASE SUMMARY Herein we present an unusual case of concurrent anti-GBM disease,ANCAassociated crescentic glomerulonephritis and diffuse proliferative immune complex mediated glomerulonephritis with predominant staining for IgA and C3 by immunofluorescence.The patient is a 46-year-old Caucasian male who presented to the emergency department with acute onset of flank pain and was found to have high serum creatinine levels of 15 mg/dL,proteinuria,and hematuria.He rapidly deteriorated and became anuric.He was found to have high anti-GBM antibodies titers(151 units)and high anti-neutrophil cytoplasmic-ANCA.Despite prompt and early treatment,the patient’s condition worsened,and he succumbed to his illness.CONCLUSION Our case emphasizes the importance of a renal biopsy in anti-GBM disease,even in the presence of positive serum anti-GBM antibodies,to identify other potential causes of rapidly progressive glomerulonephritis.The challenge in treating such cases lies in the different therapy modalities.

A Patient with Post Infectious Immune Mediated Neuropathy (Miller Fisher Syndrome)

The Miller Fisher variant is an uncommon but well known syndrome being described as a triad of areflexia, ataxia and complex ophthalmoplegia. It is characterized by antibodies against myelin that affects peripheral nerves, extraocular muscles and Schwann cells. Anti-ganglioside antibodies have been recognized in disease pathogenesis and decreasing antibody production is the mainstay of treatment. The course is usually benign with improvement after immunomodulation. This case report describes the approach to a patient suspected of having a demyelinating disorder. It delineates the subsets of immune mediated neuropathies in evaluating the diagnosis and emphasizes the need for early therapeutic intervention in achieving a good clinical outcome.

Long-term liver allograft fibrosis:A review with emphasis on idiopathic post-transplant hepatitis and chronic antibody mediated rejection

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.

<i>Agrobacterium</i>-Mediated Transformation of Mexican Lime (<i>Citrus aurantifolia</i>Swingle) Using Optimized Systems for Epicotyls and Cotyledons

Transgenic Mexican lime (Citrus aurantifolia Swingle) was produced through two explant sources, each using systems previously optimized for each source. One used epicotyls segments, which was the predominant explant for transgenic Citrus production following co-cultivation with Agrobacterium, and has a well-established protocol. The other procedure used embryo cotyledons from mature seeds, which was developed in our lab as an alternative for stable Citrus transformation. Cotyledon transformation and regeneration protocols were optimized by comparing variables in culture medium composition on shoot regeneration and four parameters in transient transformation. The optimized protocols were compared, and frequency of regeneration, frequency of transgenic plant-recovery and stable transformation efficiency indicated the superiority of the cotyledon protocol for Agrobacterium-mediated genetic transformation in Mexican lime. The tissue choice resulted in marked improvement in shoot regeneration (14.1% of explants producing shoots in epicotyls;55.8% in cotyledons), stable transformation frequency (11.4% of epicotyls explants;40.2% in cotyledons), and frequency of transgenic plant-recovery (37.9% in epicotyl explants;92.6% in cotyledons). Thus, easy availability of explants using embryo cotyledons from mature seeds, technical simplicity, shortening of transformation time-course, and higher transformation and regeneration frequencies makes this new system an attractive alternative over the previously published Citrus transformation protocols. In the course of this project, we generated Mexican lime with a Recombinase Mediated Exchange Cassette landing pad, which was designed for stacking transgenes.

Screening microRNA expression profile in patients with acute T cell mediated rejection after kidney transplantation

Objective:To explore the expression profile of miRNA in peripheral blood of patients with acute T cell mediated rejection after kidney transplantation.Method:4 patients with acute T cell mediated rejection(TCMR)after kidney transplantation were collected as experimental group.Meanwhile,4 patients under stable condition after kidney transplantation were collected as control group.The elbow blood was taken from two groups.The next generation sequencing was used to study miRNA libraries.Then,they were analyzed of variance by R language software.Results:14 miRNAs were differently expressed in the experimental group and control group,including 5 up-regulated miRNAs(P<0.05)and 9 down-regulated miRNAs(P<0.05).Conclusions:Peripheral blood miRNAs expression variations might be ideal biomarkers and reveal mechanisms for acute TCMR.

Deubiquitinase USP28 inhibits ubiquitin ligase KLHL2-mediated uridine-cytidine kinase 1 degradation and confers sensitivity to 5'-azacytidine-resistant human leukemia cells

Resistance to the chemotherapeutic drug 5'-azacytidine(5'-AZA)is a major obstacle in the treatment of patients with acute myeloid leukemia(AML).The uridine-cytidine kinase 1(UCK1)has an established role in activating 5'-AZA and its protein level is significantly downregulated in patients resistant to the drug.However,the underlying molecular mechanism for the reduced UCK1 expression remains to be elucidated.We demonstrated that the ubiquitin E3 ligase KLHL2 interacted with UCK1 and mediated its polyubiquitination at the K81 residue and degradation.We showed that deubiquitinase USP28 antagonized KLHL2-mediated polyubiquitylation of UCK1.We also provided evidence that ATM-mediated phosphorylation of USP28 resulted in its disassociation from KLHL2 and UCK1 destabilization.Conversely,UCK1 phosphorylation by 5'-AZA-activated ATM enhanced the KLHL2-UCK1 complex formation,Importantly,silencing KLHL2 or USP28 overexpression not only inhibited AML cell proliferation but also sensitized AML cells to 5'-AZA-induced apoptosis in vitro and in vivo.These results were no longer observed in USP28-deficient cells.