Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied fo...Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.展开更多
As one of the latest research hotspots in the field of artificial intelligence,AI-generated content(AIGC)can create virtual teaching scenarios,such as those involving educational digital humans,through content creatio...As one of the latest research hotspots in the field of artificial intelligence,AI-generated content(AIGC)can create virtual teaching scenarios,such as those involving educational digital humans,through content creation.This integration of AI and education is a product that will profoundly change the form of online education and the learning experience.Currently,most courses for educational digital humans still rely on traditional educational models and face many problems in practice.Based on an overview of AIGC technology and its application in micro-course production,this paper analyzes the current status of micro-courses for educational digital humans.It proposes the application of AIGC technology and educational digital humans in micro-course production,namely,using AIGC technology to drive the transformation of micro-courses for educational digital humans towards intelligence,thereby improving education quality and efficiency.展开更多
The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cereb...The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.展开更多
Human spinal cord organoids(hSCOs)offer a promising platform to study neurotrauma by addressing many limitations of traditional research models.These organoids provide access to human-specific physiological and geneti...Human spinal cord organoids(hSCOs)offer a promising platform to study neurotrauma by addressing many limitations of traditional research models.These organoids provide access to human-specific physiological and genetic mechanisms and can be derived from an individual's somatic cells(e.g.,blood or skin).This enables patient-specific paradigms for precision neurotrauma research,pa rticula rly relevant to the over 300,000 people in the United States living with chronic effects of spinal cord injury(SCI).展开更多
Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after inju...Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.展开更多
BACKGROUND Donor-specific antibodies(DSAs)against human leukocyte antigen(HLA)-DQ are increasingly recognized as major contributors to antibody-mediated rejection(AMR)and graft failure in kidney transplantation.Howeve...BACKGROUND Donor-specific antibodies(DSAs)against human leukocyte antigen(HLA)-DQ are increasingly recognized as major contributors to antibody-mediated rejection(AMR)and graft failure in kidney transplantation.However,their clinical impact remains understudied in Morocco.AIM To evaluate the presence and implications of anti-HLA-DQ DSAs in Moroccan kidney transplant recipients.METHODS We retrospectively analyzed the immunological profiles and clinical outcomes of kidney transplant recipients screened for anti-HLA antibodies between 2015 and 2020,who developed anti-HLA-DQ DSAs either before or after transplantation.Anti-HLA antibodies were identified using Luminex®single antigen bead technology,and clinical follow-up included graft function assessment,biopsy interpretation,and evaluation of immunosuppression.RESULTS In the pre-transplant group(n=6 with confirmed donor typing),patients with low to moderate median fluorescence intensity(MFI)anti-HLA-DQ DSAs(MFI 561-1581)underwent successful transplantation and maintained stable graft function under optimized immunosuppression.In contrast,in the post-transplant group(n=6 with confirmed donor typing),the emergence of de novo anti-HLA-DQ DSAs was consistently associated with AMR,with MFI values reaching up to 19473,with biopsy-proven AMR in 5 of 6 cases and suspicion of AMR in 1 case.Two representative cases are detailed to illustrate the clinical impact of DQ DSAs:one patient developed high-level anti-DQB1*02 de novo DSA(MFI 12029)with persistent AMR after 5 years,while another developed anti-DQA1*05:01 de novo DSA after an early AMR episode but maintained stable graft function after 5 years(creatinine 1.48 mg/dL).CONCLUSION Our findings underscore the clinical significance of anti-HLA-DQ DSAs in Moroccan kidney transplant recipients.While preformed DSAs with low immunogenicity may permit successful transplantation,de novo DSAs strongly correlate with AMR.Proactive monitoring,including routine DSA screening and HLA-DQ typing,could improve graft outcomes by enabling early intervention and better donor selection.展开更多
Parkinson’s disease(PD)is the second most common neurodegenerative disorder.The progressive degeneration of dopamine(DA)producing neurons in the midbrain is the pathological hallmark,which leads to debilitating motor...Parkinson’s disease(PD)is the second most common neurodegenerative disorder.The progressive degeneration of dopamine(DA)producing neurons in the midbrain is the pathological hallmark,which leads to debilitating motor symptoms,including tremors,rigidity,and bradykinesia.Drug treatments,such as levodopa,provide symptomatic relief.However,they do not halt disease progression,and their effectiveness diminishes over time(reviewed in Poewe et al.,2017).展开更多
Intrathecal administration of human umbilical cord mesenchymal stem cells may be a promising approach for the treatment of stroke,but its safety,effectiveness,and mechanism remain to be elucidated.In this study,good m...Intrathecal administration of human umbilical cord mesenchymal stem cells may be a promising approach for the treatment of stroke,but its safety,effectiveness,and mechanism remain to be elucidated.In this study,good manufacturing practice-grade human umbilical cord mesenchymal stem cells(5×105 and 1×106 cells)and saline were administered by cerebellomedullary cistern injection 72 hours after stroke induced by middle cerebral artery occlusion in rats.The results showed(1)no significant difference in mortality or general conditions among the three groups.There was no abnormal differentiation or tumor formation in various organs of rats in any group.(2)Compared with saline-treated animals,those treated with human umbilical cord mesenchymal stem cells showed significant functional recovery and reduced infarct volume,with no significant differences between different human umbilical cord mesenchymal stem cell doses.(3)Human umbilical cord mesenchymal stem cells were found in the ischemic brain after 14 and 28 days of follow-up,and the number of positive cells significantly decreased over time.(4)Neuronal nuclei expression in the human umbilical cord mesenchymal stem cell group was greater than that in the saline group,while glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 expression levels decreased.(5)Human umbilical cord mesenchymal stem cell treatment increased the number of CD31+microvessels and doublecortin-positive cells after ischemic stroke.Human umbilical cord mesenchymal stem cells also upregulated the expression of CD31+/Ki67+.(6)At 14 days after intrathecal administration,brain-derived neurotrophic factor expression in the peri-infarct area and the concentrations of brain-derived neurotrophic factor in the cerebrospinal fluid in both human umbilical cord mesenchymal stem cell groups were significantly greater than those in the saline group and persisted until the 28th day.Taken together,these results indicate that the intrathecal administration of human umbilical cord mesenchymal stem cells via cerebellomedullary cistern injection is safe and effective for the treatment of ischemic stroke in rats.The mechanisms may include alleviating the local inflammatory response in the peri-infarct region,promoting neurogenesis and angiogenesis,and enhancing the production of neurotrophic factors.展开更多
Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological s...Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.展开更多
Understanding the interactions between humans and nature in the Anthropocene is central to the quest for both human wellbeing and global sustainability.However,the time-space compression,long range interactions,and re...Understanding the interactions between humans and nature in the Anthropocene is central to the quest for both human wellbeing and global sustainability.However,the time-space compression,long range interactions,and reconstruction of socio-economic structures at the global scale all pose great challenges to the traditional analytical frameworks of human-nature systems.In this paper,we extend the connotation of coupled human and natural systems(CHANS)and their four dimensions—space,time,appearance,and organization,and propose a novel framework:“Coupled Human and Natural Cube”(CHNC)to explain the coupling mechanism between humans and the natural environment.Our proposition is inspired by theories based on the human-earth areal system,telecoupling framework,planetary urbanization,and perspectives from complexity science.We systematically introduce the concept,connotation,evolution rules,and analytical dimensions of the CHNC.Notably there exist various“coupling lines”in the CHNC,connecting different systems and elements at multiple scales and forming a large,nested,interconnected,organic system.The rotation of the CHNC represents spatiotemporal nonlinear fluctuations in CHANS in different regions.As a system continually exchanges energy with the environment,a critical phase transition occurs when fluctuations reach a certain threshold,leading to emergent behavior of the system.The CHNC has four dimensions—pericoupling and telecoupling,syncoupling and lagcoupling,apparent coupling and hidden coupling,and intra-organization coupling and inter-organizational coupling.We mainly focus on the theoretical connotation,research methods,and typical cases of telecoupling,lagcoupling,hidden coupling,and inter-organizational coupling,and put forward a human-nature coupling matrix to integrate multiple dimensions.In summary,the CHNC provides a more comprehensive and systematic research paradigm for understanding the evolution and coupling mechanism of the human-nature system,which expands the analytical dimension of CHANS.The CHNC also provides a theoretical support for formulating regional,sustainable development policies for human wellbeing.展开更多
Although spermatozoa are formed during spermatogenesis in the testis, testicular spermatozoa are immature and cannot swim or fertilize. These critical spermatozoal functions are acquired in the epididymis where a spec...Although spermatozoa are formed during spermatogenesis in the testis, testicular spermatozoa are immature and cannot swim or fertilize. These critical spermatozoal functions are acquired in the epididymis where a specific luminal environment is created by the blood-epididymal barrier; proteins secreted by epididymal principal cells bind to maturing spermatozoa and regulate the maturational process of the spermatozoa. In the epididymis, epithelial cell-cell interactions are mediated by adhering junctions, necessary for cell adhesion, and by tight junctions, which form the blood-epididymal barrier. The regulation of these cellular junctions is thought to represent a key determinant in the process of sperm maturation within the epididymis. Tight junctions between adjacent principal cells permit the formation of a specific microenvironment in the lumen of the epididymis that is essential for sperm maturation. Although we have made significant progress in understanding epididymal function and the blood-epididymal barrier, using animal models, there is limited information on the human epididymis. If we are to understand the normal and pathological conditions attributable to human epididymal function, we must clearly establish the physiological, cellular and molecular regulation of the human epididymis, develop tools to characterize these functions and develop clinical strategies that will use epididymal functions to improve treatment of infertility. （Asian J Androl 2007 July; 9： 463- 475）展开更多
Simultaneous co-firing of the levator palpebrae （LP） and pterygoid muscles were recorded in Marcus Gann Syndrome （MGS） patients in early clinical studies. ＂Release hypothesis＂ proposed an intrinsic masticatory o...Simultaneous co-firing of the levator palpebrae （LP） and pterygoid muscles were recorded in Marcus Gann Syndrome （MGS） patients in early clinical studies. ＂Release hypothesis＂ proposed an intrinsic masticatory oculo- motor neural circuit and this kind circuit, which, however, has been observed only in amphibian. On the other hand, congenital miswiring hypothesis has overwhelmed other interpretations. However, the same phenomenon visualized in MGS cases was unveiled in human subjects without any sign of congenital oculomotor disorder. To further study co-firing of the upper eyelid and jaw muscles, we applied non-invasive EMG recording of the upper eyelid and ipsilateral masseter muscle belly in nine healthy volunteers. LP activity was determined initially by looking upward and active retraction of upper eyelid with head fixed. Then, dual channel inputs from upper eyelid and masseter muscle was recorded during tooth occlusion motivated by isometric masseter muscle contraction without jaw and face moving. The EMG recorded from upper eyelid when the subjects retracted eyelid with head fixed exhibited the same pattern as that collected during tooth occlusion, but the pattern was completely different from EMG of active eye closure. This reflects tooth occlusion evoked LP activity. Then, simultaneous co-firing of the LP and masseter muscle was recorded simultaneously during tooth occlusion without jaw movement. Finally, the aforemen- tioned co-firing was recorded when the subjects conducted rhythmic occlusion and synchronous EMG from both muscles was acquired. In conclusions, humans may also have an intrinsic masticatory oculomotor circuit and release hypothesis may apply, at least, to some cases of MGS.展开更多
Microalgae has been consumed in human diet for thousands of years.It is an under-exploited crop for production of dietary foods.Microalgae cultivation does not compete with land and resources required for traditional ...Microalgae has been consumed in human diet for thousands of years.It is an under-exploited crop for production of dietary foods.Microalgae cultivation does not compete with land and resources required for traditional crops and has a superior yield compared to terrestrial crops.Its high protein content has exhibited a huge potential to meet the dietary requirements of growing population.Apart from being a source of protein,presence of various bio-active components in microalgae provide an added health benefit.This review describes various microalgal sources of proteins and other bio-active components.One of the heavily studied group of bio-active components are pigments due to their anticarcenogenic,antioxidative and antihypertensive properties.Compared to various plant and floral species,microalgae contain higher amounts of pigments.Microalgal derived proteins have complete Essential Amino Acids(EAA)profiles and their protein content is higher than conventional sources such as meat,poultry and dairy products.However,microalgal based functional foods have not flooded the market.The lack of awareness coupled with scarce incentives for producers result in under-exploitation of microalgal potential.Application of microalgal derived components as dietary and nutraceutical supplements is discussed comprehensively.展开更多
Semen analysis(SA)remains the cornerstone of male infertility evaluation and should ideally be performed by an accredited andrology laboratory or in vitro fertilization(IVF)clinics based on the standards defined by th...Semen analysis(SA)remains the cornerstone of male infertility evaluation and should ideally be performed by an accredited andrology laboratory or in vitro fertilization(IVF)clinics based on the standards defined by the World Health Organization(WHO)for the Examination and Processing of Human Semen and in accordance with the International Organization for Standardization’s Basic Semen Examination on Specification and Test Methods.展开更多
1.Introduction The real question is not whether machines think but whether men do.Burrhus Frederic Skineer Dedicated manufacturing systems are fading out as future manufacturing(i.e.,Industry 4.0[1])demands ultra-flex...1.Introduction The real question is not whether machines think but whether men do.Burrhus Frederic Skineer Dedicated manufacturing systems are fading out as future manufacturing(i.e.,Industry 4.0[1])demands ultra-flexible smart manufacturing systems that can self-adapt to production process changes resulting from the varied batch sizes of personalized products[2–4].The manufacturing shop-floor can become an unstructured environment where manufacturing systems and processes change their configurations dynamically via adaptive near-real-time decision-making.One emerging trend to make manufacturing flexible and reconfigurable is to introduce collaborative machines that work alongside humans with high productivity[5-7].展开更多
In November 2019,one of the first approved human trials of the gene-editing technology“CRISPR”reported dramatically positive results in each of the two initial patients given a single round of therapy[1].Both patien...In November 2019,one of the first approved human trials of the gene-editing technology“CRISPR”reported dramatically positive results in each of the two initial patients given a single round of therapy[1].Both patients suffered from a painful,life-threatening,inherited blood disease and had received an infusion of billions of their own hematopoietic stem cells.These precursor blood cells had been altered with CRISPR to produce disease-free blood cells.展开更多
At some future time, each person alive today will be either an ancestor of everyone or an ancestor of no one. If the global population were unstructured by geography, race, religion and other factors, the time to futu...At some future time, each person alive today will be either an ancestor of everyone or an ancestor of no one. If the global population were unstructured by geography, race, religion and other factors, the time to future common ancestry for present-day humans would be between 33 and 66 generations, or about 1000 - 2000 years. In a structured population, migration and intermarriage are the necessary conditions for global common ancestry. Simulation of random and hierarchical migration models, shows that time to future global ancestry is generally less than triple, and often less than twice, that required for an unstructured population. The models suggest that someone alive today will become a common ancestor of the entire world population by about 5000 CE, or sooner;and that all current humans who are destined to become global common ancestors will be so by about 8000 CE, or sooner. At which time, everybody then alive will have the exact same genealogical ancestors from the present day.展开更多
Humanity is in the grip of another pandemic beyond coronavirus disease(COVID).Although it is not spreading as rapidly as the viral pandemic,it is insidious and probably presents a greater threat in the long run.Throug...Humanity is in the grip of another pandemic beyond coronavirus disease(COVID).Although it is not spreading as rapidly as the viral pandemic,it is insidious and probably presents a greater threat in the long run.Through the large-scale use of antibiotics,we have driven the emergence of antimicrobial resistance(AMR)in bacteria,and these resistant bacteria are increasing in number and prevalence,threatening our ability to treat common infections and reducing our opportunities to use other life-saving treatments such as chemotherapy and surgery.A recent study showed that bacterial AMR was associated with nearly 5 million deaths in2019,with about 1.3 million being directly attributable to resistance[1].These numbers are likely to increase.展开更多
Objective The current outbreak of Zika virus(ZIKV)poses a severe threat to human health.Two ZIKV strains were isolated from mosquitoes collected from the Dejiang prefecture in China in 2016,which was the first isolati...Objective The current outbreak of Zika virus(ZIKV)poses a severe threat to human health.Two ZIKV strains were isolated from mosquitoes collected from the Dejiang prefecture in China in 2016,which was the first isolation of ZIKV in nature in China.Methods In this study,serum samples were collected from 366 healthy individuals and 104 animals from Dejiang prefecture in 2017,and the plaque reduction neutralization test(PRNT)was used to evaluate the seroprevalence of ZIKV.Results None of the 366 residents from whom the samples were collected were seropositive for ZIKV.None of the 11 pigs from whom the samples were collected were seropositive for ZIKV,while 1 of 63(1.59%)chickens and 2 of 30(6.67%)sheep were seropositive for ZIKV.Conclusions The extremely low seropositivity rate of ZIKV antibodies in animals in the Dejiang prefecture,Guizhou province in this study indicates that ZIKV can infect animals;however,there is a low risk of ZIKV circulating in the local population.展开更多
There are an accumulating number of identified gene mutations that cause infertility in humans. Most of the known gene mutations impair normal puberty and subsequently cause infertility by either hypothalamic /pituita...There are an accumulating number of identified gene mutations that cause infertility in humans. Most of the known gene mutations impair normal puberty and subsequently cause infertility by either hypothalamic /pituitary deficiency of important tropic factors to the gonad or by gonadal genes.展开更多
文摘Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.
文摘As one of the latest research hotspots in the field of artificial intelligence,AI-generated content(AIGC)can create virtual teaching scenarios,such as those involving educational digital humans,through content creation.This integration of AI and education is a product that will profoundly change the form of online education and the learning experience.Currently,most courses for educational digital humans still rely on traditional educational models and face many problems in practice.Based on an overview of AIGC technology and its application in micro-course production,this paper analyzes the current status of micro-courses for educational digital humans.It proposes the application of AIGC technology and educational digital humans in micro-course production,namely,using AIGC technology to drive the transformation of micro-courses for educational digital humans towards intelligence,thereby improving education quality and efficiency.
基金supported by the Grant PID2021-126715OB-IOO financed by MCIN/AEI/10.13039/501100011033 and"ERDFA way of making Europe"by the Grant PI22CⅢ/00055 funded by Instituto de Salud CarlosⅢ(ISCⅢ)+6 种基金the UFIECPY 398/19(PEJ2018-004965) grant to RGS funded by AEI(Spain)the UFIECPY-396/19(PEJ2018-004961)grant financed by MCIN (Spain)FI23CⅢ/00003 grant funded by ISCⅢ-PFIS Spain) to PMMthe UFIECPY 328/22 (PEJ-2021-TL/BMD-21001) grant to LM financed by CAM (Spain)the grant by CAPES (Coordination for the Improvement of Higher Education Personnel)through the PDSE program (Programa de Doutorado Sanduiche no Exterior)to VSCG financed by MEC (Brazil)
文摘The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.
基金supported by the Belle Carnell Regenerative Neurorehabilitation Fundthe National Institutes of Health(R01NS113935 to CKF)。
文摘Human spinal cord organoids(hSCOs)offer a promising platform to study neurotrauma by addressing many limitations of traditional research models.These organoids provide access to human-specific physiological and genetic mechanisms and can be derived from an individual's somatic cells(e.g.,blood or skin).This enables patient-specific paradigms for precision neurotrauma research,pa rticula rly relevant to the over 300,000 people in the United States living with chronic effects of spinal cord injury(SCI).
文摘Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.
基金Supported by the National Science and Technology Research Center(Morocco)“PhD-Associate Scholarship-PASS”Program,No.88UH2C2023.
文摘BACKGROUND Donor-specific antibodies(DSAs)against human leukocyte antigen(HLA)-DQ are increasingly recognized as major contributors to antibody-mediated rejection(AMR)and graft failure in kidney transplantation.However,their clinical impact remains understudied in Morocco.AIM To evaluate the presence and implications of anti-HLA-DQ DSAs in Moroccan kidney transplant recipients.METHODS We retrospectively analyzed the immunological profiles and clinical outcomes of kidney transplant recipients screened for anti-HLA antibodies between 2015 and 2020,who developed anti-HLA-DQ DSAs either before or after transplantation.Anti-HLA antibodies were identified using Luminex®single antigen bead technology,and clinical follow-up included graft function assessment,biopsy interpretation,and evaluation of immunosuppression.RESULTS In the pre-transplant group(n=6 with confirmed donor typing),patients with low to moderate median fluorescence intensity(MFI)anti-HLA-DQ DSAs(MFI 561-1581)underwent successful transplantation and maintained stable graft function under optimized immunosuppression.In contrast,in the post-transplant group(n=6 with confirmed donor typing),the emergence of de novo anti-HLA-DQ DSAs was consistently associated with AMR,with MFI values reaching up to 19473,with biopsy-proven AMR in 5 of 6 cases and suspicion of AMR in 1 case.Two representative cases are detailed to illustrate the clinical impact of DQ DSAs:one patient developed high-level anti-DQB1*02 de novo DSA(MFI 12029)with persistent AMR after 5 years,while another developed anti-DQA1*05:01 de novo DSA after an early AMR episode but maintained stable graft function after 5 years(creatinine 1.48 mg/dL).CONCLUSION Our findings underscore the clinical significance of anti-HLA-DQ DSAs in Moroccan kidney transplant recipients.While preformed DSAs with low immunogenicity may permit successful transplantation,de novo DSAs strongly correlate with AMR.Proactive monitoring,including routine DSA screening and HLA-DQ typing,could improve graft outcomes by enabling early intervention and better donor selection.
基金supported by the DGIST start-up funds from the Ministry of Science and ICT(2024010330)a National Research Foundation of Korea(NRF)grant funded by the Korea Government(MSIT)(No.RS-2024-00351442)(to TWK).
文摘Parkinson’s disease(PD)is the second most common neurodegenerative disorder.The progressive degeneration of dopamine(DA)producing neurons in the midbrain is the pathological hallmark,which leads to debilitating motor symptoms,including tremors,rigidity,and bradykinesia.Drug treatments,such as levodopa,provide symptomatic relief.However,they do not halt disease progression,and their effectiveness diminishes over time(reviewed in Poewe et al.,2017).
基金supported by the Medicine-Engineering Interdisciplinary Project of Sun Yat-sen Memorial Hospital,China,No.YXYGRH202203(to YW)Key-Area Research and Development Program of Guangdong Province,China,No.2023B1111050003(to HC)Guangzhou Science and Technology Talent Project of China,No.201909020006(to HC).
文摘Intrathecal administration of human umbilical cord mesenchymal stem cells may be a promising approach for the treatment of stroke,but its safety,effectiveness,and mechanism remain to be elucidated.In this study,good manufacturing practice-grade human umbilical cord mesenchymal stem cells(5×105 and 1×106 cells)and saline were administered by cerebellomedullary cistern injection 72 hours after stroke induced by middle cerebral artery occlusion in rats.The results showed(1)no significant difference in mortality or general conditions among the three groups.There was no abnormal differentiation or tumor formation in various organs of rats in any group.(2)Compared with saline-treated animals,those treated with human umbilical cord mesenchymal stem cells showed significant functional recovery and reduced infarct volume,with no significant differences between different human umbilical cord mesenchymal stem cell doses.(3)Human umbilical cord mesenchymal stem cells were found in the ischemic brain after 14 and 28 days of follow-up,and the number of positive cells significantly decreased over time.(4)Neuronal nuclei expression in the human umbilical cord mesenchymal stem cell group was greater than that in the saline group,while glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 expression levels decreased.(5)Human umbilical cord mesenchymal stem cell treatment increased the number of CD31+microvessels and doublecortin-positive cells after ischemic stroke.Human umbilical cord mesenchymal stem cells also upregulated the expression of CD31+/Ki67+.(6)At 14 days after intrathecal administration,brain-derived neurotrophic factor expression in the peri-infarct area and the concentrations of brain-derived neurotrophic factor in the cerebrospinal fluid in both human umbilical cord mesenchymal stem cell groups were significantly greater than those in the saline group and persisted until the 28th day.Taken together,these results indicate that the intrathecal administration of human umbilical cord mesenchymal stem cells via cerebellomedullary cistern injection is safe and effective for the treatment of ischemic stroke in rats.The mechanisms may include alleviating the local inflammatory response in the peri-infarct region,promoting neurogenesis and angiogenesis,and enhancing the production of neurotrophic factors.
基金supported by Deutsche Forschungsgemeinschaft,German Research Foundation grant GA 654/13-2 to OG.
文摘Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.
基金Program of the National Natural Science Foundation of China,No.41590842,No.41801164China Postdoctoral Science Foundation,No.2018M630196。
文摘Understanding the interactions between humans and nature in the Anthropocene is central to the quest for both human wellbeing and global sustainability.However,the time-space compression,long range interactions,and reconstruction of socio-economic structures at the global scale all pose great challenges to the traditional analytical frameworks of human-nature systems.In this paper,we extend the connotation of coupled human and natural systems(CHANS)and their four dimensions—space,time,appearance,and organization,and propose a novel framework:“Coupled Human and Natural Cube”(CHNC)to explain the coupling mechanism between humans and the natural environment.Our proposition is inspired by theories based on the human-earth areal system,telecoupling framework,planetary urbanization,and perspectives from complexity science.We systematically introduce the concept,connotation,evolution rules,and analytical dimensions of the CHNC.Notably there exist various“coupling lines”in the CHNC,connecting different systems and elements at multiple scales and forming a large,nested,interconnected,organic system.The rotation of the CHNC represents spatiotemporal nonlinear fluctuations in CHANS in different regions.As a system continually exchanges energy with the environment,a critical phase transition occurs when fluctuations reach a certain threshold,leading to emergent behavior of the system.The CHNC has four dimensions—pericoupling and telecoupling,syncoupling and lagcoupling,apparent coupling and hidden coupling,and intra-organization coupling and inter-organizational coupling.We mainly focus on the theoretical connotation,research methods,and typical cases of telecoupling,lagcoupling,hidden coupling,and inter-organizational coupling,and put forward a human-nature coupling matrix to integrate multiple dimensions.In summary,the CHNC provides a more comprehensive and systematic research paradigm for understanding the evolution and coupling mechanism of the human-nature system,which expands the analytical dimension of CHANS.The CHNC also provides a theoretical support for formulating regional,sustainable development policies for human wellbeing.
文摘Although spermatozoa are formed during spermatogenesis in the testis, testicular spermatozoa are immature and cannot swim or fertilize. These critical spermatozoal functions are acquired in the epididymis where a specific luminal environment is created by the blood-epididymal barrier; proteins secreted by epididymal principal cells bind to maturing spermatozoa and regulate the maturational process of the spermatozoa. In the epididymis, epithelial cell-cell interactions are mediated by adhering junctions, necessary for cell adhesion, and by tight junctions, which form the blood-epididymal barrier. The regulation of these cellular junctions is thought to represent a key determinant in the process of sperm maturation within the epididymis. Tight junctions between adjacent principal cells permit the formation of a specific microenvironment in the lumen of the epididymis that is essential for sperm maturation. Although we have made significant progress in understanding epididymal function and the blood-epididymal barrier, using animal models, there is limited information on the human epididymis. If we are to understand the normal and pathological conditions attributable to human epididymal function, we must clearly establish the physiological, cellular and molecular regulation of the human epididymis, develop tools to characterize these functions and develop clinical strategies that will use epididymal functions to improve treatment of infertility. （Asian J Androl 2007 July; 9： 463- 475）
基金partially supported by Natural Sciences Research Funding 2006C225 and 2009K01-74 from Shaanxi Province
文摘Simultaneous co-firing of the levator palpebrae （LP） and pterygoid muscles were recorded in Marcus Gann Syndrome （MGS） patients in early clinical studies. ＂Release hypothesis＂ proposed an intrinsic masticatory oculo- motor neural circuit and this kind circuit, which, however, has been observed only in amphibian. On the other hand, congenital miswiring hypothesis has overwhelmed other interpretations. However, the same phenomenon visualized in MGS cases was unveiled in human subjects without any sign of congenital oculomotor disorder. To further study co-firing of the upper eyelid and jaw muscles, we applied non-invasive EMG recording of the upper eyelid and ipsilateral masseter muscle belly in nine healthy volunteers. LP activity was determined initially by looking upward and active retraction of upper eyelid with head fixed. Then, dual channel inputs from upper eyelid and masseter muscle was recorded during tooth occlusion motivated by isometric masseter muscle contraction without jaw and face moving. The EMG recorded from upper eyelid when the subjects retracted eyelid with head fixed exhibited the same pattern as that collected during tooth occlusion, but the pattern was completely different from EMG of active eye closure. This reflects tooth occlusion evoked LP activity. Then, simultaneous co-firing of the LP and masseter muscle was recorded simultaneously during tooth occlusion without jaw movement. Finally, the aforemen- tioned co-firing was recorded when the subjects conducted rhythmic occlusion and synchronous EMG from both muscles was acquired. In conclusions, humans may also have an intrinsic masticatory oculomotor circuit and release hypothesis may apply, at least, to some cases of MGS.
基金the Fundamental Research Grant Scheme,Malaysia[FRGS/1/2015/SG05/UNIM/03/1]the Ministry of Science and Technology,Malaysia[MOSTI02-02-12-SF0256]+1 种基金the Prototype Research Grant Scheme,Malaysia[PRGS/2/2015/SG05/UNIM/03/1]International Cooperation Seeds Funding of Nanjing Agricultural University(Grant number:2018-AH-04).
文摘Microalgae has been consumed in human diet for thousands of years.It is an under-exploited crop for production of dietary foods.Microalgae cultivation does not compete with land and resources required for traditional crops and has a superior yield compared to terrestrial crops.Its high protein content has exhibited a huge potential to meet the dietary requirements of growing population.Apart from being a source of protein,presence of various bio-active components in microalgae provide an added health benefit.This review describes various microalgal sources of proteins and other bio-active components.One of the heavily studied group of bio-active components are pigments due to their anticarcenogenic,antioxidative and antihypertensive properties.Compared to various plant and floral species,microalgae contain higher amounts of pigments.Microalgal derived proteins have complete Essential Amino Acids(EAA)profiles and their protein content is higher than conventional sources such as meat,poultry and dairy products.However,microalgal based functional foods have not flooded the market.The lack of awareness coupled with scarce incentives for producers result in under-exploitation of microalgal potential.Application of microalgal derived components as dietary and nutraceutical supplements is discussed comprehensively.
文摘Semen analysis(SA)remains the cornerstone of male infertility evaluation and should ideally be performed by an accredited andrology laboratory or in vitro fertilization(IVF)clinics based on the standards defined by the World Health Organization(WHO)for the Examination and Processing of Human Semen and in accordance with the International Organization for Standardization’s Basic Semen Examination on Specification and Test Methods.
基金supported by grants from The University of Auckland FRDF New Staff Research Fund(3720540).
文摘1.Introduction The real question is not whether machines think but whether men do.Burrhus Frederic Skineer Dedicated manufacturing systems are fading out as future manufacturing(i.e.,Industry 4.0[1])demands ultra-flexible smart manufacturing systems that can self-adapt to production process changes resulting from the varied batch sizes of personalized products[2–4].The manufacturing shop-floor can become an unstructured environment where manufacturing systems and processes change their configurations dynamically via adaptive near-real-time decision-making.One emerging trend to make manufacturing flexible and reconfigurable is to introduce collaborative machines that work alongside humans with high productivity[5-7].
文摘In November 2019,one of the first approved human trials of the gene-editing technology“CRISPR”reported dramatically positive results in each of the two initial patients given a single round of therapy[1].Both patients suffered from a painful,life-threatening,inherited blood disease and had received an infusion of billions of their own hematopoietic stem cells.These precursor blood cells had been altered with CRISPR to produce disease-free blood cells.
文摘At some future time, each person alive today will be either an ancestor of everyone or an ancestor of no one. If the global population were unstructured by geography, race, religion and other factors, the time to future common ancestry for present-day humans would be between 33 and 66 generations, or about 1000 - 2000 years. In a structured population, migration and intermarriage are the necessary conditions for global common ancestry. Simulation of random and hierarchical migration models, shows that time to future global ancestry is generally less than triple, and often less than twice, that required for an unstructured population. The models suggest that someone alive today will become a common ancestor of the entire world population by about 5000 CE, or sooner;and that all current humans who are destined to become global common ancestors will be so by about 8000 CE, or sooner. At which time, everybody then alive will have the exact same genealogical ancestors from the present day.
文摘Humanity is in the grip of another pandemic beyond coronavirus disease(COVID).Although it is not spreading as rapidly as the viral pandemic,it is insidious and probably presents a greater threat in the long run.Through the large-scale use of antibiotics,we have driven the emergence of antimicrobial resistance(AMR)in bacteria,and these resistant bacteria are increasing in number and prevalence,threatening our ability to treat common infections and reducing our opportunities to use other life-saving treatments such as chemotherapy and surgery.A recent study showed that bacterial AMR was associated with nearly 5 million deaths in2019,with about 1.3 million being directly attributable to resistance[1].These numbers are likely to increase.
基金supported by the National Science and Technology Major Project [2018ZX10713-002,2017ZX10104001,2018ZX10711001]National key research and development project [2017YFC1200505,2016YFC1200905]the Development Grant of State Key Laboratory of Infectious Disease Prevention and Control [2015SKLID505,2014SKLID103]
文摘Objective The current outbreak of Zika virus(ZIKV)poses a severe threat to human health.Two ZIKV strains were isolated from mosquitoes collected from the Dejiang prefecture in China in 2016,which was the first isolation of ZIKV in nature in China.Methods In this study,serum samples were collected from 366 healthy individuals and 104 animals from Dejiang prefecture in 2017,and the plaque reduction neutralization test(PRNT)was used to evaluate the seroprevalence of ZIKV.Results None of the 366 residents from whom the samples were collected were seropositive for ZIKV.None of the 11 pigs from whom the samples were collected were seropositive for ZIKV,while 1 of 63(1.59%)chickens and 2 of 30(6.67%)sheep were seropositive for ZIKV.Conclusions The extremely low seropositivity rate of ZIKV antibodies in animals in the Dejiang prefecture,Guizhou province in this study indicates that ZIKV can infect animals;however,there is a low risk of ZIKV circulating in the local population.
文摘There are an accumulating number of identified gene mutations that cause infertility in humans. Most of the known gene mutations impair normal puberty and subsequently cause infertility by either hypothalamic /pituitary deficiency of important tropic factors to the gonad or by gonadal genes.
