A 1000-year high-resolution(～10 years) chironomid record from varved sediments of Sugan Lake,Qaidam Basin on the northern Tibetan Plateau,is presented.The chironomid assemblages are mainly composed of the relatively ...A 1000-year high-resolution(～10 years) chironomid record from varved sediments of Sugan Lake,Qaidam Basin on the northern Tibetan Plateau,is presented.The chironomid assemblages are mainly composed of the relatively high-saline-water taxa Psectrocladius barbimanus-type and Orthocladius/Cricotopus,and the relatively low-saline-water taxa Procladius and Psectrocladius sordidellus-type.Variations in the chironomid fauna and inferred salinities suggest that over the last millennium,the Sugan Lake catchment has alternated between contrasting climatic conditions,having a dry climate during the period 990―1550 AD,a relatively humid climate during the Little Ice Age(LIA)(1550―1840 AD),and a dry climate again from 1840 AD onwards.At the decadal to centennial scale,a wet event around 1200―1230 AD,interrupting the generally arid period(990―1550 AD),and a dry event around 1590―1700 AD,punctuating the generally humid period(1550―1840 AD),are clearly documented.Trends in the chironomid-based salinity time series indicate a highly unstable climate during the LIA when salinity fluctuations were of greater magnitude and higher frequency.The effective moisture evolution in the Sugan Lake catchment during the last millennium reconstructed by chironomid analysis is in broad agreement with previous palaeo-moisture data derived from other sites in arid Northwest China(ANC).The LIA,characterized by generally humid conditions over the west-erly-dominated ANC was distinctly different from that in monsoonal China,implying an "out-of-phase" relationship between moisture evolution in these two regions during the past 1000 years.展开更多
Fungi are an understudied,biotechnologically valuable group of organisms.Due to the immense range of habitats that fungi inhabit,and the consequent need to compete against a diverse array of other fungi,bacteria,and a...Fungi are an understudied,biotechnologically valuable group of organisms.Due to the immense range of habitats that fungi inhabit,and the consequent need to compete against a diverse array of other fungi,bacteria,and animals,fungi have developed numerous survival mechanisms.The unique attributes of fungi thus herald great promise for their application in biotechnology and industry.Moreover,fungi can be grown with relative ease,making production at scale viable.The search for fungal biodiversity,and the construction of a living fungi collection,both have incredible economic potential in locating organisms with novel industrial uses that will lead to novel products.This manuscript reviews fifty ways in which fungi can potentially be utilized as biotechnology.We provide notes and examples for each potential exploitation and give examples from our own work and the work of other notable researchers.We also provide a flow chart that can be used to convince funding bodies of the importance of fungi for biotechnological research and as potential products.Fungi have provided the world with penicillin,lovastatin,and other globally significant medicines,and they remain an untapped resource with enormous industrial potential.展开更多
The tumor suppressor p53 is a multifunctional, highly regulated, and promoter-specific transcriptional factor that is uniquely sensitive to DNA damage and cellular stress signaling. The mechanisms by which p53 directs...The tumor suppressor p53 is a multifunctional, highly regulated, and promoter-specific transcriptional factor that is uniquely sensitive to DNA damage and cellular stress signaling. The mechanisms by which p53 directs a damaged cell down either a cell growth arrest or an apoptotic pathway remain poorly understood. Evidence suggests that the in vivo functions of p53 seem to balance the cell-fate choice with the type and severity of damage that occurs. The concept of antirepression, or inhibition of factors that normally keep p53 at bay, may help explain the physiological mechanisms for p53 activation. These factors also provide novel chemotherapeutic targets for the reactivation of p53 in tumors harboring a wild-type copy of the gene.展开更多
Once thought to be a waste product of oxygen limited(anaerobic)metabolism,lactate is now known to form continuously under fully oxygenated(aerobic)conditions.Lactate shuttling between producer(driver)and consumer cell...Once thought to be a waste product of oxygen limited(anaerobic)metabolism,lactate is now known to form continuously under fully oxygenated(aerobic)conditions.Lactate shuttling between producer(driver)and consumer cells fulfills at least 3 purposes;lactate is:(1)a major energy source,(2)the major gluconeogenic precursor,and(3)a signaling molecule.The Lactate Shuttle theory is applicable to diverse fields such as sports nutrition and hydration,resuscitation from acidosis and Dengue,treatment of traumatic brain injury,maintenance of glycemia,reduction of inflammation,cardiac support in heart failure and following a myocardial infarction,and to improve cognition.Yet,dysregulated lactate shuttling disrupts metabolic flexibility,and worse,supports oncogenesis.Lactate production in cancer(the Warburg effect)is involved in all main sequela for carcinogenesis:angiogenesis,immune escape,cell migration,metastasis,and self-sufficient metabolism.The history of the tortuous path of discovery in lactate metabolism and shuttling was discussed in the 2019 American College of Sports Medicine Joseph B.Wolffe Lecture in Orlando,FL.展开更多
The treatment of pathological fractures of the femoral neck and trochanteric region secondary to benignlesions can be a challenge for orthopaedic surgeons because of the size and nature of the lesions, the resulting ...The treatment of pathological fractures of the femoral neck and trochanteric region secondary to benignlesions can be a challenge for orthopaedic surgeons because of the size and nature of the lesions, the resulting bony defect, the risk of recurrence, the possible associated deformities, and the risk of osteonecrosis. Numerous treatment modalities have been reported for the management of pathological fractures of the proximal femur secondary to benign lesions. An unsatisfactory outcome in 25% of patients and a complication rate of 45% have been observed.展开更多
The majority of pregnancy loss in ruminants occurs during the first three weeks after conception, particularly during the period of conceptus elongation that occurs prior to pregnancy recognition and implantation. Thi...The majority of pregnancy loss in ruminants occurs during the first three weeks after conception, particularly during the period of conceptus elongation that occurs prior to pregnancy recognition and implantation. This review integrates established and new information on the biological role of ovarian progesterone （P4）, prostaglandins （PGs）, interferon tau （IFNT） and cortisol in endometrial function and conceptus elongation. Progesterone is secreted by the ovarian corpus luteum （CL） and is the unequivocal hormone of pregnancy. Prostaglandins （PGs） and cortisol are produced by both the epithelial cells of the endometrium and the trophectoderm of the elongating conceptus. In contrast, IFNT is produced solely by the conceptus trophectoderm and is the maternal recognition of pregnancy signa that inhibits production of luteolytic pulses of PGF2α by the endometrium to maintain the CL and thus production of P4. Available results in sheep support the idea that the individual, interactive, and coordinated actions of P4, PGs, IFNT and cortisol regulate conceptus elongation and implantation by controlling expression of genes in the endometrium and/or trophectoderm. An increased knowledge of conceptus-endometrial interactions during early pregnancy in ruminants is necessary to understand and elucidate the causes of infertility and recurrent early pregnancy loss and provide new strategies to improve fertility and thus reproductive efficiency.展开更多
Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann c...Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be impaired.Recently,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such treatment.An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis.After initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and taurursodiol.The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function.We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in vitro.After a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered saline.None of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or changes in vital signs.Clinical lab ser展开更多
目的明确广西隆安县队列HBsAg无症状携带者感染的乙型肝炎病毒(hepatitis B virus,HBV)准种序列长期演化特征。方法收集9名广西隆安县队列HBsAg无症状携带者2004年、2007年、2013年、2019年或2020年4个不同时间点血清样本。酶联免疫吸...目的明确广西隆安县队列HBsAg无症状携带者感染的乙型肝炎病毒(hepatitis B virus,HBV)准种序列长期演化特征。方法收集9名广西隆安县队列HBsAg无症状携带者2004年、2007年、2013年、2019年或2020年4个不同时间点血清样本。酶联免疫吸附测定法检测HBV血清学标志物;聚合酶链式反应(polymerase chain reaction,PCR)荧光探针法检测HBV病毒载量;试剂盒提取HBV DNA;PCR法扩增HBV全基因组,进行二代测序;利用Mega等软件对所获得的序列进行生物信息学分析。结果共获得23份血清样本,309条全长基因准种序列,每份标本平均获得(0.18±0.07)G测序数据量。55.55%(5/9)的研究对象携带的HBV毒株基因型在长期进化过程中发生了基因型转换,PreS/S区系统进化树基因分型结果与全基因组分析结果完全一致;发现B/C、I/C重组体;各研究标本的Sn值范围为0~0.37,D值范围为0~0.11;共检出21种特殊单核苷酸/氨基酸突变位点(S区7种,X区2种,PreC区3种,BCP区9种)和6种缺失突变,发现多联突变组合形式,未发现任何耐药突变,77.8%(7/9)研究对象在2004年携带的HBV毒株发生了BCP区nt1762(A→T)/1764(G→A)双突变和PreC区1896位(G→A)点突变,HBV基因可在无抗病毒药物压力下由突变型可恢复为野生型和(或)野生型转变为突变型;HBV基因组进化率为2.03×10^(-5)~3.50×10^(-3)。结论在HBV自然感染进程中,HBV基因型和重组体、准种复杂性和多样性可随时间发生改变;HBV基因突变型和野生型可相互转换,一定程度上降低了利用基因型和相关突变来预测临床结局的价值;隆安县乙型肝炎表面抗原(hepatitis B surface antigen,HBsAg)无症状携带者HBV基因组进化率很高。展开更多
Objective:To investigate the role of red palm oil(RPO),rooibos tea extract(RTE)and their combined treatment(RPO+RTE)on antioxidant status in streptozotocin(STZ)-induced diabetic rats.Methods:Diabetes mellitus was indu...Objective:To investigate the role of red palm oil(RPO),rooibos tea extract(RTE)and their combined treatment(RPO+RTE)on antioxidant status in streptozotocin(STZ)-induced diabetic rats.Methods:Diabetes mellitus was induced by a single administration of streptozotocin(50 mg/kg)and the rats were treated for 7 weeks.Antioxidant enzymes[calalase(CAT),glutathione peroxidase(GPx),superoxide dismutase(SOD)],antioxidant capacity[trolox equivalence antioxidant capacity(TEAC),oxygen radical absorbance capacity(ORAC)]as well as total protein,albumin,globulin,total glutathione,conjugated diene and thiobarbituric acid reactive substances(TBARS)were investigated.Results:Treatment with RPO,RTE and RPO+RTE significantly(p>0.05)improved liver SOD and plasma ORAC in the diabetic rats.Similarly,diabetic rats treated with RTE and RPO+RTE enhanced liver GPx.A significant(P<0.05)increase in the plasma TBARS in the diabetic control group was observed when compared with the normal control group.Treatment of diabetic rats with RTE and RPO+RTE reduced plasma TBARS to a level not significantly different at P<0.05 from the normal control group.Conclusions:The results revealed the anti-oxidative potentials of red palm oil,rooibos and their combination in diabetic conditions and hence,they could be useful in the management of diabetes and its complications.展开更多
A detailed microstructural characterisation of the emerging weld-line grain structure,for bead-upon-plate welds in Ti-6Al-4V(Ti64)of differing plate thickness,was performed.The microstructure studied was formed during...A detailed microstructural characterisation of the emerging weld-line grain structure,for bead-upon-plate welds in Ti-6Al-4V(Ti64)of differing plate thickness,was performed.The microstructure studied was formed during both steady state and non-steady state sections within the weld path,with the non-steady state portion being taken from the end of the plate as the weld bead and heat source overhang the edge of the plate.This allows for the effects of welding process conditions on the microstructural evolution to be determined.The weld pool geometry and 3D tomography of the weld-induced defects have been investigated.Detailed characterisation of microstructure and texture for different welding parameters and for steady and non-steady states have been used to identify physical parameters for the microstructure predictions that are difficult to obtain otherwise.The different states significantly affect the weld crown shape and formation,weld toe,weld bead depth and width.However,the heat affected zone(HAZ)re-mains unchanged.Regarding the microstructural evolution,both the steady and non-steady states have similar microstructure and texture.No defects were observed in the steady state section of welds,but sub-surface spherical pores have been observed in the non-steady state section of a weld.Finite element modelling to simulate the thermal-metallurgical-mechanical fields within the steady and non-steady state sections of the welds was considered,and the cooling rates predicted within steady state and non-steady sections were interrogated to improve the theoretical understanding of the microstructure and defect formation differences in these Ti64 EB weld regions.展开更多
Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine,as interpreted by individual family physicians a...Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine,as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world.In‘Ⅳ:perspectives on practice—lenses of appreciation’,authors address the following themes:‘Relational connections in the doctor–patient partnership’,‘Feminism and family medicine’,‘Positive family medicine’,‘Mindful practice’,‘The new,old ethics of family medicine’,‘Public health,prevention and populations’,‘Information mastery in family medicine’and‘Clinical courage.’May readers nurture their curiosity through these essays.展开更多
Collagenase was isolated from fish waste (a mixture of haddock, herring, ground fish and flounder) using a Tris-buffer system. The proteins in the crude extract were precipitated using ammonium sulfate (40% - 80%) and...Collagenase was isolated from fish waste (a mixture of haddock, herring, ground fish and flounder) using a Tris-buffer system. The proteins in the crude extract were precipitated using ammonium sulfate (40% - 80%) and purified with gel-filtration chromatography using Sephadex G-100. The results showed that the collagenase enzyme was produced as a latent enzyme and was activated with bovine trypsin and potassium thiocyanate (KSCN). The enzyme activity was affected by pH and temperature. Optimal enzyme activities were found at 35?C and a pH of 7.5 when insoluble collagene type I was used as substrate and the liberated amino acids were measured in relation to L-leucine in the presence of ninhydrin. The enzyme activity was completely inhibited by the action of ethylenediaminetetraacetic acid (EDTA) suggesting that the collagenase enzyme isolated from the fish waste is a metalloproteinase enzyme requiring metal ions for enzyme activity. Dialysis against KSCN decreased the enzyme total activity and increased its specific activity. Sodium dodecyl sulphate polyacryla-mide gel electrophoresis (SDS-PAGE) indicated that the purified procollagenase enzyme have only one band at molecular weight of 50 kilodaltons (kDa). When the enzyme was cleaved with trypsin, it was found to consist of two subunits: a large unit with a molecular weight of 50 kDa and a small unit with a molecular weight of 10 kDa.展开更多
基金Supported by the Fund for Creative Research Groups,National Natural Science Foundation of China (Grant No. 40721061)Research Fund for the Doctoral Program of Higher Education (Grant No. 20060730003)
文摘A 1000-year high-resolution(～10 years) chironomid record from varved sediments of Sugan Lake,Qaidam Basin on the northern Tibetan Plateau,is presented.The chironomid assemblages are mainly composed of the relatively high-saline-water taxa Psectrocladius barbimanus-type and Orthocladius/Cricotopus,and the relatively low-saline-water taxa Procladius and Psectrocladius sordidellus-type.Variations in the chironomid fauna and inferred salinities suggest that over the last millennium,the Sugan Lake catchment has alternated between contrasting climatic conditions,having a dry climate during the period 990―1550 AD,a relatively humid climate during the Little Ice Age(LIA)(1550―1840 AD),and a dry climate again from 1840 AD onwards.At the decadal to centennial scale,a wet event around 1200―1230 AD,interrupting the generally arid period(990―1550 AD),and a dry event around 1590―1700 AD,punctuating the generally humid period(1550―1840 AD),are clearly documented.Trends in the chironomid-based salinity time series indicate a highly unstable climate during the LIA when salinity fluctuations were of greater magnitude and higher frequency.The effective moisture evolution in the Sugan Lake catchment during the last millennium reconstructed by chironomid analysis is in broad agreement with previous palaeo-moisture data derived from other sites in arid Northwest China(ANC).The LIA,characterized by generally humid conditions over the west-erly-dominated ANC was distinctly different from that in monsoonal China,implying an "out-of-phase" relationship between moisture evolution in these two regions during the past 1000 years.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences,Grant No.XDB31000000Naritsada Thongklang would like to thank Thailand research fund grants“Study of saprobic Agaricales in Thailand to find new industrial mushroom products”(Grant No.DBG6180015)+6 种基金Mae Fah Luang University grant“Optimal conditions for domestication and biological activities of selected species of Ganoderrma”(Grant No.621C1535)K.D.Hyde and Naritsada Thongklang would like to thanks to Thailand research fund grants“Domestication and bioactive evaluation of Thai Hymenopellis,Oudemansiella,Xerula and Volvariella species(basidiomycetes)”(Grant No.DBG6180033)K.D.Hyde thanks the financial support from the Visiting Professor grant at Chiang Mai University,Thailand and KIB.The authors acknowledge the contribution of M.M.Vasanthakumari,K.M.Manasa and P.Rajani,in various stages of preparation of the manuscript.Samantha C.Karunarathna thanks CAS President’s International Fellowship Initiative(PIFI)for funding his postdoctoral research(Number 2018PC0006)the National Science Foundation.Associate Professor R Jeewon thanks University of Mauritius for support.Binu C.Samarakoon offers her sincere gratitude to the“National Research Council of Thailand”(NRCT Grant No.256108A3070006)for the financial supportPeter E Mortimer would like to thank the National Science Foundation of China and the Chinese Academy of Sciences for financial support under the following Grants:41761144055,41771063,Y4ZK111B01M.Doilom would like to thank Chiang Mai University,the 5th batch of Postdoctoral Orientation Training Personnel in Yunnan Province and the 64th batch of China Postdoctoral Science Foundation.T.S.Suryanarayanan thanks the United States-India Educational Foundation(USIEF)New Delhi and the Fulbright Scholar Program(USA)for the award of a Fulbright-Nehru Senior Researcher grant to conduct research in the Department of Chemistry and Biochemistry,The Ohio State University,USA.Thanks to Research and Researchers for Industri
文摘Fungi are an understudied,biotechnologically valuable group of organisms.Due to the immense range of habitats that fungi inhabit,and the consequent need to compete against a diverse array of other fungi,bacteria,and animals,fungi have developed numerous survival mechanisms.The unique attributes of fungi thus herald great promise for their application in biotechnology and industry.Moreover,fungi can be grown with relative ease,making production at scale viable.The search for fungal biodiversity,and the construction of a living fungi collection,both have incredible economic potential in locating organisms with novel industrial uses that will lead to novel products.This manuscript reviews fifty ways in which fungi can potentially be utilized as biotechnology.We provide notes and examples for each potential exploitation and give examples from our own work and the work of other notable researchers.We also provide a flow chart that can be used to convince funding bodies of the importance of fungi for biotechnological research and as potential products.Fungi have provided the world with penicillin,lovastatin,and other globally significant medicines,and they remain an untapped resource with enormous industrial potential.
文摘The tumor suppressor p53 is a multifunctional, highly regulated, and promoter-specific transcriptional factor that is uniquely sensitive to DNA damage and cellular stress signaling. The mechanisms by which p53 directs a damaged cell down either a cell growth arrest or an apoptotic pathway remain poorly understood. Evidence suggests that the in vivo functions of p53 seem to balance the cell-fate choice with the type and severity of damage that occurs. The concept of antirepression, or inhibition of factors that normally keep p53 at bay, may help explain the physiological mechanisms for p53 activation. These factors also provide novel chemotherapeutic targets for the reactivation of p53 in tumors harboring a wild-type copy of the gene.
文摘Once thought to be a waste product of oxygen limited(anaerobic)metabolism,lactate is now known to form continuously under fully oxygenated(aerobic)conditions.Lactate shuttling between producer(driver)and consumer cells fulfills at least 3 purposes;lactate is:(1)a major energy source,(2)the major gluconeogenic precursor,and(3)a signaling molecule.The Lactate Shuttle theory is applicable to diverse fields such as sports nutrition and hydration,resuscitation from acidosis and Dengue,treatment of traumatic brain injury,maintenance of glycemia,reduction of inflammation,cardiac support in heart failure and following a myocardial infarction,and to improve cognition.Yet,dysregulated lactate shuttling disrupts metabolic flexibility,and worse,supports oncogenesis.Lactate production in cancer(the Warburg effect)is involved in all main sequela for carcinogenesis:angiogenesis,immune escape,cell migration,metastasis,and self-sufficient metabolism.The history of the tortuous path of discovery in lactate metabolism and shuttling was discussed in the 2019 American College of Sports Medicine Joseph B.Wolffe Lecture in Orlando,FL.
文摘The treatment of pathological fractures of the femoral neck and trochanteric region secondary to benignlesions can be a challenge for orthopaedic surgeons because of the size and nature of the lesions, the resulting bony defect, the risk of recurrence, the possible associated deformities, and the risk of osteonecrosis. Numerous treatment modalities have been reported for the management of pathological fractures of the proximal femur secondary to benign lesions. An unsatisfactory outcome in 25% of patients and a complication rate of 45% have been observed.
基金supported, in part, by AFRI competitive grants 2009 – 01722 and 2012-67015-30173 from the USDA National Institute of Food and Agriculture
文摘The majority of pregnancy loss in ruminants occurs during the first three weeks after conception, particularly during the period of conceptus elongation that occurs prior to pregnancy recognition and implantation. This review integrates established and new information on the biological role of ovarian progesterone （P4）, prostaglandins （PGs）, interferon tau （IFNT） and cortisol in endometrial function and conceptus elongation. Progesterone is secreted by the ovarian corpus luteum （CL） and is the unequivocal hormone of pregnancy. Prostaglandins （PGs） and cortisol are produced by both the epithelial cells of the endometrium and the trophectoderm of the elongating conceptus. In contrast, IFNT is produced solely by the conceptus trophectoderm and is the maternal recognition of pregnancy signa that inhibits production of luteolytic pulses of PGF2α by the endometrium to maintain the CL and thus production of P4. Available results in sheep support the idea that the individual, interactive, and coordinated actions of P4, PGs, IFNT and cortisol regulate conceptus elongation and implantation by controlling expression of genes in the endometrium and/or trophectoderm. An increased knowledge of conceptus-endometrial interactions during early pregnancy in ruminants is necessary to understand and elucidate the causes of infertility and recurrent early pregnancy loss and provide new strategies to improve fertility and thus reproductive efficiency.
基金support from the Miami Project to Cure Paralysis,the Buoniconti Fund,and the Interdisciplinary Stem Cell Institute(to AK,WDD,JDG,and ADL)the unconditional support of Dean Henri Ford of the Leonard M.Miller School of Medicine at the University of Miami.
文摘Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be impaired.Recently,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such treatment.An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis.After initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and taurursodiol.The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function.We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in vitro.After a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered saline.None of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or changes in vital signs.Clinical lab ser
文摘目的明确广西隆安县队列HBsAg无症状携带者感染的乙型肝炎病毒(hepatitis B virus,HBV)准种序列长期演化特征。方法收集9名广西隆安县队列HBsAg无症状携带者2004年、2007年、2013年、2019年或2020年4个不同时间点血清样本。酶联免疫吸附测定法检测HBV血清学标志物;聚合酶链式反应(polymerase chain reaction,PCR)荧光探针法检测HBV病毒载量;试剂盒提取HBV DNA;PCR法扩增HBV全基因组,进行二代测序;利用Mega等软件对所获得的序列进行生物信息学分析。结果共获得23份血清样本,309条全长基因准种序列,每份标本平均获得(0.18±0.07)G测序数据量。55.55%(5/9)的研究对象携带的HBV毒株基因型在长期进化过程中发生了基因型转换,PreS/S区系统进化树基因分型结果与全基因组分析结果完全一致;发现B/C、I/C重组体;各研究标本的Sn值范围为0~0.37,D值范围为0~0.11;共检出21种特殊单核苷酸/氨基酸突变位点(S区7种,X区2种,PreC区3种,BCP区9种)和6种缺失突变,发现多联突变组合形式,未发现任何耐药突变,77.8%(7/9)研究对象在2004年携带的HBV毒株发生了BCP区nt1762(A→T)/1764(G→A)双突变和PreC区1896位(G→A)点突变,HBV基因可在无抗病毒药物压力下由突变型可恢复为野生型和(或)野生型转变为突变型;HBV基因组进化率为2.03×10^(-5)~3.50×10^(-3)。结论在HBV自然感染进程中,HBV基因型和重组体、准种复杂性和多样性可随时间发生改变;HBV基因突变型和野生型可相互转换,一定程度上降低了利用基因型和相关突变来预测临床结局的价值;隆安县乙型肝炎表面抗原(hepatitis B surface antigen,HBsAg)无症状携带者HBV基因组进化率很高。
基金carried out through the funding Provided by CapePeninsula University of Technology,Bellville,South Africa(grant NO.NRF-CPUT/RJ24)
文摘Objective:To investigate the role of red palm oil(RPO),rooibos tea extract(RTE)and their combined treatment(RPO+RTE)on antioxidant status in streptozotocin(STZ)-induced diabetic rats.Methods:Diabetes mellitus was induced by a single administration of streptozotocin(50 mg/kg)and the rats were treated for 7 weeks.Antioxidant enzymes[calalase(CAT),glutathione peroxidase(GPx),superoxide dismutase(SOD)],antioxidant capacity[trolox equivalence antioxidant capacity(TEAC),oxygen radical absorbance capacity(ORAC)]as well as total protein,albumin,globulin,total glutathione,conjugated diene and thiobarbituric acid reactive substances(TBARS)were investigated.Results:Treatment with RPO,RTE and RPO+RTE significantly(p>0.05)improved liver SOD and plasma ORAC in the diabetic rats.Similarly,diabetic rats treated with RTE and RPO+RTE enhanced liver GPx.A significant(P<0.05)increase in the plasma TBARS in the diabetic control group was observed when compared with the normal control group.Treatment of diabetic rats with RTE and RPO+RTE reduced plasma TBARS to a level not significantly different at P<0.05 from the normal control group.Conclusions:The results revealed the anti-oxidative potentials of red palm oil,rooibos and their combination in diabetic conditions and hence,they could be useful in the management of diabetes and its complications.
基金support under the Manufacturing Portfolio collaborative project between Rolls-Royce plc,Partnership for Research in Simulation of Manufacturing and Materials (PRISM2),the University of Birmingham
文摘A detailed microstructural characterisation of the emerging weld-line grain structure,for bead-upon-plate welds in Ti-6Al-4V(Ti64)of differing plate thickness,was performed.The microstructure studied was formed during both steady state and non-steady state sections within the weld path,with the non-steady state portion being taken from the end of the plate as the weld bead and heat source overhang the edge of the plate.This allows for the effects of welding process conditions on the microstructural evolution to be determined.The weld pool geometry and 3D tomography of the weld-induced defects have been investigated.Detailed characterisation of microstructure and texture for different welding parameters and for steady and non-steady states have been used to identify physical parameters for the microstructure predictions that are difficult to obtain otherwise.The different states significantly affect the weld crown shape and formation,weld toe,weld bead depth and width.However,the heat affected zone(HAZ)re-mains unchanged.Regarding the microstructural evolution,both the steady and non-steady states have similar microstructure and texture.No defects were observed in the steady state section of welds,but sub-surface spherical pores have been observed in the non-steady state section of a weld.Finite element modelling to simulate the thermal-metallurgical-mechanical fields within the steady and non-steady state sections of the welds was considered,and the cooling rates predicted within steady state and non-steady sections were interrogated to improve the theoretical understanding of the microstructure and defect formation differences in these Ti64 EB weld regions.
文摘Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine,as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world.In‘Ⅳ:perspectives on practice—lenses of appreciation’,authors address the following themes:‘Relational connections in the doctor–patient partnership’,‘Feminism and family medicine’,‘Positive family medicine’,‘Mindful practice’,‘The new,old ethics of family medicine’,‘Public health,prevention and populations’,‘Information mastery in family medicine’and‘Clinical courage.’May readers nurture their curiosity through these essays.
文摘Collagenase was isolated from fish waste (a mixture of haddock, herring, ground fish and flounder) using a Tris-buffer system. The proteins in the crude extract were precipitated using ammonium sulfate (40% - 80%) and purified with gel-filtration chromatography using Sephadex G-100. The results showed that the collagenase enzyme was produced as a latent enzyme and was activated with bovine trypsin and potassium thiocyanate (KSCN). The enzyme activity was affected by pH and temperature. Optimal enzyme activities were found at 35?C and a pH of 7.5 when insoluble collagene type I was used as substrate and the liberated amino acids were measured in relation to L-leucine in the presence of ninhydrin. The enzyme activity was completely inhibited by the action of ethylenediaminetetraacetic acid (EDTA) suggesting that the collagenase enzyme isolated from the fish waste is a metalloproteinase enzyme requiring metal ions for enzyme activity. Dialysis against KSCN decreased the enzyme total activity and increased its specific activity. Sodium dodecyl sulphate polyacryla-mide gel electrophoresis (SDS-PAGE) indicated that the purified procollagenase enzyme have only one band at molecular weight of 50 kilodaltons (kDa). When the enzyme was cleaved with trypsin, it was found to consist of two subunits: a large unit with a molecular weight of 50 kDa and a small unit with a molecular weight of 10 kDa.
