Purpose: Cotard’s syndrome, Alice in Wonderland Syndrome, and Catatonia are all rare psychiatric disorders that have relatively little research regarding their treatments. The aim of this article is to highlight any ...Purpose: Cotard’s syndrome, Alice in Wonderland Syndrome, and Catatonia are all rare psychiatric disorders that have relatively little research regarding their treatments. The aim of this article is to highlight any gaps in knowledge regarding represented demographics in these treatment studies, and to discuss the current and upcoming treatment options. Background: This literature review explores under-researched psychiatric conditions: Cotard’s syndrome, Alice in Wonderland syndrome, and Catatonic Schizophrenia. Understanding psychiatric disorders requires basic knowledge of brain anatomy. These conditions are often result of or associated with neurological issues, such as migraines or tumors. The brain has eight lobes, two of four kinds: frontal, parietal, occipital, and temporal lobes, which all govern different functions and abilities. Frontal lobes control judgment, decision-making, personality traits, and fine motor movements. Parietal lobes interpret pain and temperature, occipital lobes handle visual stimuli, and temporal lobes enable hearing. The pre-frontal cortex is associated with high intelligence, psychotic traits, and psychosis. The Broca’s Area in the frontal lobes controls expressive language. These areas and divisions of the brain contribute to the complexity of the psychiatric disorders discussed in this review. Introduction: Cotard’s syndrome is a psychiatric disorder characterized by delusions of being dead or not having certain limbs or organs. It is believed that there is a disconnect between their fusiform face area and the amygdala, causing a lack of familiarity between one’s mind and body. Alice in Wonderland Syndrome (AIWS) is another psychiatric disorder which is characterized by visual hallucinations, such as distorted perceptions of color, size, distance, and speed. The most common symptoms include micropsia and macropsia. Catatonia/Catatonic Schizophrenia is an uncommon type of schizophrenia. This type of schizophrenia is characterized by motor rigidity, verbal rigidity, the flat effect, psychomotor retardation, waxy flexibility, and overall negative symptoms. Thus, these people may come off as emotionally detached, and able to stay frozen in odd positions for periods on end. Treatments and Results: Cotard’s syndrome seemed to be most effectively treated by ECT (electroconvulsive therapy). Alice in Wonderland Syndrome (AIWS) had the highest positive responses to treatment by Valproate (an anti-epileptic drug), as well as intervention to treat the associated neurological conditions they had. Catatonia/Catatonic Schizophrenia seemed to be most effectively treated with a combination of benzodiazepines and ECT. Discussion and Demographics: In all 3 disorders, the Latino and African communities were underrepresented. There also seemed to be an underrepresentation of men in Cotard’s syndrome, and of women in Alice in Wonderland Syndrome. Japan and India seemed to have the highest density of treatment studies in all 3 disorders.展开更多
Diseases like Alzheimer’s and Parkinson’s diseases are defined by inflammation and the damage neurons undergo due to oxidative stress. A primary reactive oxygen species contributor in the central nervous system, NAD...Diseases like Alzheimer’s and Parkinson’s diseases are defined by inflammation and the damage neurons undergo due to oxidative stress. A primary reactive oxygen species contributor in the central nervous system, NADPH oxidase 4, is viewed as a potential therapeutic touchstone and indicative marker for these ailments. This in-depth review brings to light distinct features of NADPH oxidase 4, responsible for generating superoxide and hydrogen peroxide, emphasizing its pivotal role in activating glial cells, inciting inflammation, and disturbing neuronal functions. Significantly, malfunctioning astrocytes, forming the majority in the central nervous system, play a part in advancing neurodegenerative diseases, due to their reactive oxygen species and inflammatory factor secretion. Our study reveals that aiming at NADPH oxidase 4 within astrocytes could be a viable treatment pathway to reduce oxidative damage and halt neurodegenerative processes. Adjusting NADPH oxidase 4 activity might influence the neuroinflammatory cytokine levels, including myeloperoxidase and osteopontin, offering better prospects for conditions like Alzheimer’s disease and Parkinson’s disease. This review sheds light on the role of NADPH oxidase 4 in neural degeneration, emphasizing its drug target potential, and paving the path for novel treatment approaches to combat these severe conditions.展开更多
Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exoso...Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.展开更多
Polysurfacic tori or kideas are three-dimensional objects formed by rotating a regular polygon around a central axis. These toric shapes are referred to as “polysurfacic” because their characteristics, such as the n...Polysurfacic tori or kideas are three-dimensional objects formed by rotating a regular polygon around a central axis. These toric shapes are referred to as “polysurfacic” because their characteristics, such as the number of sides or surfaces separated by edges, can vary in a non-trivial manner depending on the degree of twisting during the revolution. We use the term “Kideas” to specifically denote these polysurfacic tori, and we represent the number of sides (referred to as “facets”) of the original polygon followed by a point, while the number of facets from which the torus is twisted during its revolution is indicated. We then explore the use of concave regular polygons to generate Kideas. We finally give acceleration for the algorithm for calculating the set of prime numbers.展开更多
Beginning with a 5D homogeneous universe [1], we have provided a plausible explanation of the self-rotation phenomenon of stellar objects previously with illustration of large number of star samples [2], via a 5D-4D p...Beginning with a 5D homogeneous universe [1], we have provided a plausible explanation of the self-rotation phenomenon of stellar objects previously with illustration of large number of star samples [2], via a 5D-4D projection. The origin of such rotation is the balance of the angular momenta of stars and that of positive and negative charged e-trino pairs, within a 3D ⊗1D?void of the stellar object, the existence of which is based on conservation/parity laws in physics if one starts with homogeneous 5D universe. While the in-phase e-trino pairs are proposed to be responsible for the generation of angular momentum, the anti-phase but oppositely charge pairs necessarily produce currents. In the 5D to 4D projection, one space variable in the 5D manifold was compacted to zero in most other 5D theories (including theories of Kaluza-Klein and Einstein [3] [4]). We have demonstrated, using the Fermat’s Last Theorem [5], that for validity of gauge invariance at the 4D-5D boundary, the 4th space variable in the 5D manifold is mapped into two current rings at both magnetic poles as required by Perelman entropy mapping;these loops are the origin of the dipolar magnetic field. One conclusion we draw is that there is no gravitational singularity, and hence no black holes in the universe, a result strongly supported by the recent discovery of many stars with masses well greater than 100 solar mass [6] [7] [8], without trace of phenomena observed (such as strong gamma and X ray emissions), which are supposed to be associated with black holes. We analyze the properties of such loop currents on the 4D-5D boundary, where Maxwell equations are valid. We derive explicit expressions for the dipolar fields over the whole temperature range. We then compare our prediction with measured surface magnetic fields of many stars. Since there is coupling in distribution between the in-phase and anti-phase pairs of e-trinos, the generated mag-netic field is directly related to the angular momentum, leading to the result that the magnetic field can be expressible in terms of only the mechanical variables (mass M, radius R, rotation period P)of a star, as if Maxwell equations are “hidden”. An explanation for the occurrence of this “un-expected result” is provided in Section (7.6). Therefore we provide satisfactory answers to a number of “mysteries” of magnetism in astrophysics such as the “Magnetic Bode’s Relation/Law” [9] and the experimental finding that B-P graph in the log-log plot is linear. Moreover, we have developed a new method for studying the relations among the data (M, R, P) during stellar evolution. Ten groups of stellar objects, effectively over 2000 samples are used in various parts of the analysis. We also explain the emergence of huge magnetic field in very old stars like White Dwarfs in terms of formation of 2D Semion state on stellar surface and release of magnetic flux as magnetic storms upon changing the 2D state back to 3D structure. Moreover, we provide an explanation, on the ground of the 5D theory, for the detection of extremely weak fields in Venus and Mars and the asymmetric distribution of magnetic field on the Martian surface. We predict the equatorial fields B of the newly discovered Trappist-1 star and the 6 nearest planets. The log B?−?log P graph for the 6 planets is linear and they satisfy the Magnetic Bode’s relation. Based on the above analysis, we have discovered several new laws of stellar magnetism, which are summarized in Section (7.6).展开更多
In this research we are going to define two new concepts: a) “The Potential of Events” (EP) and b) “The Catholic Information” (CI). The term CI derives from the ancient Greek language and declares all the Catholic...In this research we are going to define two new concepts: a) “The Potential of Events” (EP) and b) “The Catholic Information” (CI). The term CI derives from the ancient Greek language and declares all the Catholic (general) Logical Propositions (<img src="Edit_5f13a4a5-abc6-4bc5-9e4c-4ff981627b2a.png" width="33" height="21" alt="" />) which will true for every element of a set A. We will study the Riemann Hypothesis in two stages: a) By using the EP we will prove that the distribution of events e (even) and o (odd) of Square Free Numbers (SFN) on the axis Ax(N) of naturals is Heads-Tails (H-T) type. b) By using the CI we will explain the way that the distribution of prime numbers can be correlated with the non-trivial zeros of the function <em>ζ</em>(<em>s</em>) of Riemann. The Introduction and the Chapter 2 are necessary for understanding the solution. In the Chapter 3 we will present a simple method of forecasting in many very useful applications (e.g. financial, technological, medical, social, etc) developing a generalization of this new, proven here, theory which we finally apply to the solution of RH. The following Introduction as well the Results with the Discussion at the end shed light about the possibility of the proof of all the above. The article consists of 9 chapters that are numbered by 1, 2, …, 9.展开更多
INTRODUCTIONThe increased expression of ICAM-1 on a widerange of cells and in the sera of patients withmalignancies, chronic liver diseases andinflammation diseases has been described since thelate 1980s[1-22]. Recent...INTRODUCTIONThe increased expression of ICAM-1 on a widerange of cells and in the sera of patients withmalignancies, chronic liver diseases andinflammation diseases has been described since thelate 1980s[1-22]. Recently rapid progress in studieson expression of ICAM-1 in patients withhepatocellular carcinoma ( HCC ) have beenachieved, including clinical and experimentalresearches[23-31].展开更多
Huntington’s disease is a neurodegenerative disease caused by the expansion mutation of a cytosine-adenine-guanine triplet in the exon 1 of the HTT gene which is responsible for the production of the huntingtin (Htt)...Huntington’s disease is a neurodegenerative disease caused by the expansion mutation of a cytosine-adenine-guanine triplet in the exon 1 of the HTT gene which is responsible for the production of the huntingtin (Htt) protein. In physiological conditions, Htt is involved in many cellular processes such as cell signaling, transcriptional regulation, energy metabolism regulation, DNA maintenance, axonal trafficking, and antiapoptotic activity. When the genetic alteration is present, the production of a mutant version of Htt (mHtt) occurs, which is characterized by a plethora of pathogenic activities that, finally, lead to cell death. Among all the cells in which mHtt exerts its dangerous activity, the GABAergic Medium Spiny Neurons seem to be the most affected by the mHtt-induced excitotoxicity both in the cortex and in the striatum. However, as the neurodegeneration proceeds ahead the neuronal loss grows also in other brain areas such as the cerebellum, hypothalamus, thalamus, subthalamic nucleus, globus pallidus, and substantia nigra, determining the variety of symptoms that characterize Huntington’s disease. From a clinical point of view, Huntington’s disease is characterized by a wide spectrum of symptoms spanning from motor impairment to cognitive disorders and dementia. Huntington’s disease shows a prevalence of around 3.92 cases every 100,000 worldwide and an incidence of 0.48 new cases every 100,000/year. To date, there is no available cure for Huntington’s disease. Several treatments have been developed so far, aiming to reduce the severity of one or more symptoms to slow down the inexorable decline caused by the disease. In this context, the search for reliable strategies to target the different aspects of Huntington’s disease become of the utmost interest. In recent years, a variety of studies demonstrated the detrimental role of neuronal loss in Huntington’s disease condition highlighting how the replacement of lost cells would be a reasonable strategy to overcome the neurodegeneration. In this view, numerous have been the attempts in several preclinical models of Huntington’s disease to evaluate the feasibility of invasive and non-invasive approaches. Thus, the aim of this review is to offer an overview of the most appealing approaches spanning from stem cell-based cell therapy to extracellular vesicles such as exosomes in light of promoting neurogenesis, discussing the results obtained so far, their limits and the future perspectives regarding the neural regeneration in the context of Huntington’s disease.展开更多
α-Synuclein is a protein that mainly exists in the presynaptic terminals.Abnormal folding and accumulation of α-synuclein are found in several neurodegenerative diseases,including Parkinson’s disease.Aggregated and...α-Synuclein is a protein that mainly exists in the presynaptic terminals.Abnormal folding and accumulation of α-synuclein are found in several neurodegenerative diseases,including Parkinson’s disease.Aggregated and highly phospho rylated a-synuclein constitutes the main component of Lewy bodies in the brain,the pathological hallmark of Parkinson s disease.For decades,much attention has been focused on the accumulation of α-synuclein in the brain parenchyma rather than considering Parkinson s disease as a systemic disease.Recent evidence demonstrates that,at least in some patients,the initial α-synuclein pathology originates in the peripheral organs and spreads to the brain.Injection of α-synuclein preformed fibrils into the gastrointestinal tra ct trigge rs the gutto-brain propagation of α-synuclein pathology.However,whether α-synuclein pathology can occur spontaneously in peripheral organs independent of exogenous α-synuclein preformed fibrils or pathological α-synuclein leakage from the central nervous system remains under investigation.In this review,we aimed to summarize the role of peripheral α-synuclein pathology in the pathogenesis of Parkinson’s disease.We also discuss the pathways by which α-synuclein pathology spreads from the body to the brain.展开更多
Xinqiao Gully is located in the area of the 2008 Wenchuan M_(s)8.0 earthquake in Sichuan province,China.Based on the investigation of the 2023"6-26"Xinqiao Gully debris flow event,this study assessed the eff...Xinqiao Gully is located in the area of the 2008 Wenchuan M_(s)8.0 earthquake in Sichuan province,China.Based on the investigation of the 2023"6-26"Xinqiao Gully debris flow event,this study assessed the effectiveness of the debris flow control project and evaluated the debris flow hazards.Through field investigation and numerical simulation methods,the indicators of flow intensity reduction rate and storage capacity fullness were proposed to quantify the effectiveness of the engineering measures in the debris flow event.The simulation results show that the debris flow control project reduced the flow intensity by41.05%to 64.61%.The storage capacity of the dam decreases gradually from upstream to the mouth of the gully,thus effectively intercepting and controlling the debris flow.By evaluating the debris flow of different recurrence intervals,further measures are recommended for managing debris flow events.展开更多
In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of A...In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.展开更多
Neurodegenerative diseases are a group of disorders characterized by the progressive degeneration of neurons in the central or peripheral nervous system.Currently,there is no cure for neurodegenerative diseases and th...Neurodegenerative diseases are a group of disorders characterized by the progressive degeneration of neurons in the central or peripheral nervous system.Currently,there is no cure for neurodegenerative diseases and this means a heavy burden for patients and the health system worldwide.Therefore,it is necessary to find new therapeutic approaches,and antisense therapies offer this possibility,having the great advantage of not modifying cellular genome and potentially being safer.Many preclinical and clinical studies aim to test the safety and effectiveness of antisense therapies in the treatment of neurodegenerative diseases.The objective of this review is to summarize the recent advances in the development of these new technologies to treat the most common neurodegenerative diseases,with a focus on those antisense therapies that have already received the approval of the U.S.Food and Drug Administration.展开更多
Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s dis...Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.展开更多
We generalize the congruences of Friedmann-Tamarkine (1909), Lehmer (1938), and Ernvall-Metsänkyla (1991) on the sums of powers of integers weighted by powers of the Fermat quotients to the next Fermat quotient p...We generalize the congruences of Friedmann-Tamarkine (1909), Lehmer (1938), and Ernvall-Metsänkyla (1991) on the sums of powers of integers weighted by powers of the Fermat quotients to the next Fermat quotient power, namely to the third power of the Fermat quotient. Using this result and the Gessel identity (2005) combined with our past work (2021), we are able to relate residues of some truncated convolutions of Bernoulli numbers with some Ernvall-Metsänkyla residues to residues of some full convolutions of the same kind. We also establish some congruences concerning other related weighted sums of powers of integers when these sums are weighted by some analogs of the Teichmüller characters.展开更多
A century ago the classical physics couldn’t explain many atomic physical phenomena. Now the situation has changed. It’s because within the framework of classical physics with the help of Maxwell’s equations we can...A century ago the classical physics couldn’t explain many atomic physical phenomena. Now the situation has changed. It’s because within the framework of classical physics with the help of Maxwell’s equations we can derive Schrödinger’s equation, which is the foundation of quantum physics. The equations for energy, momentum, frequency and wavelength of the electromagnetic wave in the atom are derived using the model of atom by analogy with the transmission line. The action constant A0 = (μ0/ε0)1/2s02e2 is a key term in the above mentioned equations. Besides the other well-known constants, the only unknown constant in the last expression is a structural constant of the atom s0. We have found that the value of this constant is 8.277 56 and that it shows up as a link between macroscopic and atomic world. After calculating this constant we get the theory of atoms based on Maxwell’s and Lorentz equations only. This theory does not require knowledge of Planck’s constant h, which is replaced with theoretically derived action constant A0, while the replacement for the fine structure constant α-1 is theoretically derived expression 2s02 = 137.036. So, the structural constant s0 replaces both constants h and α. This paper also defines the stationary states of atoms and shows that the maximal atomic number is equal to Zmax = 137. The presented model of the atoms covers three of the four fundamental interactions, namely the electromagnetic, weak and strong interactions.展开更多
Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the pho...Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the phosphorylation and aggregation of tau protein.Among the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug development.The present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease.展开更多
Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have ...Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have on our aging population.Posture and gait control does not happen automatically,as previously believed,but rather requires continuous involvement of central nervous mechanisms.To effectively exert control over the body,the brain must integrate multiple streams of sensory information,including visual,vestibular,and somatosensory signals.The mechanisms which underpin the integration of these multisensory signals are the principal topic of the present work.Existing multisensory integration theories focus on how failure of cognitive processes thought to be involved in multisensory integration leads to falls in older adults.Insufficient emphasis,however,has been placed on specific contributions of individual sensory modalities to multisensory integration processes and cross-modal interactions that occur between the sensory modalities in relation to gait and balance.In the present work,we review the contributions of somatosensory,visual,and vestibular modalities,along with their multisensory intersections to gait and balance in older adults and patients with Parkinson’s disease.We also review evidence of vestibular contributions to multisensory temporal binding windows,previously shown to be highly pertinent to fall risk in older adults.Lastly,we relate multisensory vestibular mechanisms to potential neural substrates,both at the level of neurobiology(concerning positron emission tomography imaging)and at the level of electrophysiology(concerning electroencephalography).We hope that this integrative review,drawing influence across multiple subdisciplines of neuroscience,paves the way for novel research directions and therapeutic neuromodulatory approaches,to improve the lives of older adults and patients with neurodegenerative diseases.展开更多
Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic ...Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease.The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice.However,ethical issues and tumor formation were limitations of its clinical application.Induced pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell therapy.Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor formation.Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease.However,there are also ethical concerns and the risk of tumor formation that need to be addressed.This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical research.The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo reprogramming.These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.展开更多
BACKGROUND Meckel’s diverticulum is a common congenital malformation of the small intestine,with the three most common complications being obstruction,per-foration,and inflammation.To date,only a few cases have been ...BACKGROUND Meckel’s diverticulum is a common congenital malformation of the small intestine,with the three most common complications being obstruction,per-foration,and inflammation.To date,only a few cases have been reported world-wide.In children,the clinical symptoms are similar to appendicitis.As most of the imaging features are nonspecific,the preoperative diagnosis is not precise.In addition,the clinical characteristics are highly similar to pediatric acute appendicitis,thus special attention is necessary to distinguish Meckel’s diver-ticulum from pediatric appendicitis.Patients with poor disease control should undergo laparoscopic exploration to avoid serious complications,including intestinal necrosis,intestinal perforation and gastrointestinal bleeding.CASE SUMMARY This report presents three cases of appendicitis in children combined with intestinal obstruction,which was caused by fibrous bands(ligaments)arising from the top part of Meckel's diverticulum,diverticular perforation,and diver-ticular inflammation.All three patients,aged 11-12 years,had acute appendicitis as their initial clinical presentation.All were treated by laparoscopic surgery with a favorable outcome.A complete dataset including clinical presentation,dia-gnostic imaging,surgical information,and histopathologic findings was also provided.CONCLUSION Preoperative diagnosis of Meckel’s diverticulum and its complications is challenging because its clinical signs and complications are similar to those of appendicitis in children.Laparoscopy combined with laparotomy is useful for diagnosis and treatment.展开更多
A treat-to-target(T2T)approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease.The Selecting Therapeutic Targets in Inflammatory Bowel Disea...A treat-to-target(T2T)approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease.The Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)-II guidelines specify short,intermediate,and long-term treatment goals,documenting specific treatment targets to be achieved at each of these timepoints.Scheduled appraisal of Crohn’s disease activity against pre-defined treatment targets at these timepoints remains central to determining whether current therapy should be continued or modified.Consensus treatment targets in Crohn’s disease comprise combination clinical and patient-reported outcome remission,in conjunction with biomarker normalisation and endoscopic healing.Although the STRIDE-II guidelines endorse the pursuit of endoscopic healing,clinicians must consider that this may not always be appropriate,acceptable,or achievable in all patients.This underscores the need to engage patients at the outset in an effort to personalise care and individualise treatment targets.The use of non-invasive biomarkers such as faecal calprotectin in conjunction with cross-sectional imaging techniques,particularly intestinal ultrasound,holds great promise;as do emerging treatment targets such as transmural healing.Two randomised clinical trials,namely,CALM and STARDUST,have evaluated the efficacy of a T2T approach in achieving endoscopic endpoints in patients with Crohn’s disease.Findings from these studies reflect that patient subgroups and Crohn’s disease characteristics likely to benefit most from a T2T approach,remain to be clarified.Moreover,outside of clinical trials,data pertaining to the real-world effectiveness of a T2T approach remains scare,highlighting the need for pragmatic real-world studies.Despite the obvious promise of a T2T approach,a lack of guidance to support its integration into real-world clinical practice has the potential to limit its uptake.This highlights the need to describe strategies,processes,and models of care capable of supporting the integration and execution of a T2T approach in real-world clinical practice.Hence,this review seeks to examine the current and emerging literature to provide clinicians with practical guidance on how to incorporate the principles of T2T into routine clinical practice for the management of Crohn’s disease.展开更多
文摘Purpose: Cotard’s syndrome, Alice in Wonderland Syndrome, and Catatonia are all rare psychiatric disorders that have relatively little research regarding their treatments. The aim of this article is to highlight any gaps in knowledge regarding represented demographics in these treatment studies, and to discuss the current and upcoming treatment options. Background: This literature review explores under-researched psychiatric conditions: Cotard’s syndrome, Alice in Wonderland syndrome, and Catatonic Schizophrenia. Understanding psychiatric disorders requires basic knowledge of brain anatomy. These conditions are often result of or associated with neurological issues, such as migraines or tumors. The brain has eight lobes, two of four kinds: frontal, parietal, occipital, and temporal lobes, which all govern different functions and abilities. Frontal lobes control judgment, decision-making, personality traits, and fine motor movements. Parietal lobes interpret pain and temperature, occipital lobes handle visual stimuli, and temporal lobes enable hearing. The pre-frontal cortex is associated with high intelligence, psychotic traits, and psychosis. The Broca’s Area in the frontal lobes controls expressive language. These areas and divisions of the brain contribute to the complexity of the psychiatric disorders discussed in this review. Introduction: Cotard’s syndrome is a psychiatric disorder characterized by delusions of being dead or not having certain limbs or organs. It is believed that there is a disconnect between their fusiform face area and the amygdala, causing a lack of familiarity between one’s mind and body. Alice in Wonderland Syndrome (AIWS) is another psychiatric disorder which is characterized by visual hallucinations, such as distorted perceptions of color, size, distance, and speed. The most common symptoms include micropsia and macropsia. Catatonia/Catatonic Schizophrenia is an uncommon type of schizophrenia. This type of schizophrenia is characterized by motor rigidity, verbal rigidity, the flat effect, psychomotor retardation, waxy flexibility, and overall negative symptoms. Thus, these people may come off as emotionally detached, and able to stay frozen in odd positions for periods on end. Treatments and Results: Cotard’s syndrome seemed to be most effectively treated by ECT (electroconvulsive therapy). Alice in Wonderland Syndrome (AIWS) had the highest positive responses to treatment by Valproate (an anti-epileptic drug), as well as intervention to treat the associated neurological conditions they had. Catatonia/Catatonic Schizophrenia seemed to be most effectively treated with a combination of benzodiazepines and ECT. Discussion and Demographics: In all 3 disorders, the Latino and African communities were underrepresented. There also seemed to be an underrepresentation of men in Cotard’s syndrome, and of women in Alice in Wonderland Syndrome. Japan and India seemed to have the highest density of treatment studies in all 3 disorders.
基金supported by the National Research Foundation of the Republic of Korea 2018R1D1A3B07047960the Soonchunhyang University Research Fund(to SSY).
文摘Diseases like Alzheimer’s and Parkinson’s diseases are defined by inflammation and the damage neurons undergo due to oxidative stress. A primary reactive oxygen species contributor in the central nervous system, NADPH oxidase 4, is viewed as a potential therapeutic touchstone and indicative marker for these ailments. This in-depth review brings to light distinct features of NADPH oxidase 4, responsible for generating superoxide and hydrogen peroxide, emphasizing its pivotal role in activating glial cells, inciting inflammation, and disturbing neuronal functions. Significantly, malfunctioning astrocytes, forming the majority in the central nervous system, play a part in advancing neurodegenerative diseases, due to their reactive oxygen species and inflammatory factor secretion. Our study reveals that aiming at NADPH oxidase 4 within astrocytes could be a viable treatment pathway to reduce oxidative damage and halt neurodegenerative processes. Adjusting NADPH oxidase 4 activity might influence the neuroinflammatory cytokine levels, including myeloperoxidase and osteopontin, offering better prospects for conditions like Alzheimer’s disease and Parkinson’s disease. This review sheds light on the role of NADPH oxidase 4 in neural degeneration, emphasizing its drug target potential, and paving the path for novel treatment approaches to combat these severe conditions.
基金supported by grants from the Department of Science and Technology of Sichuan Province,Nos.2021ZYD0093(to LY),2022YFS0597(to LY),2021YJ0480(to YT),and 2022ZYD0076(to JY)。
文摘Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.
文摘Polysurfacic tori or kideas are three-dimensional objects formed by rotating a regular polygon around a central axis. These toric shapes are referred to as “polysurfacic” because their characteristics, such as the number of sides or surfaces separated by edges, can vary in a non-trivial manner depending on the degree of twisting during the revolution. We use the term “Kideas” to specifically denote these polysurfacic tori, and we represent the number of sides (referred to as “facets”) of the original polygon followed by a point, while the number of facets from which the torus is twisted during its revolution is indicated. We then explore the use of concave regular polygons to generate Kideas. We finally give acceleration for the algorithm for calculating the set of prime numbers.
文摘Beginning with a 5D homogeneous universe [1], we have provided a plausible explanation of the self-rotation phenomenon of stellar objects previously with illustration of large number of star samples [2], via a 5D-4D projection. The origin of such rotation is the balance of the angular momenta of stars and that of positive and negative charged e-trino pairs, within a 3D ⊗1D?void of the stellar object, the existence of which is based on conservation/parity laws in physics if one starts with homogeneous 5D universe. While the in-phase e-trino pairs are proposed to be responsible for the generation of angular momentum, the anti-phase but oppositely charge pairs necessarily produce currents. In the 5D to 4D projection, one space variable in the 5D manifold was compacted to zero in most other 5D theories (including theories of Kaluza-Klein and Einstein [3] [4]). We have demonstrated, using the Fermat’s Last Theorem [5], that for validity of gauge invariance at the 4D-5D boundary, the 4th space variable in the 5D manifold is mapped into two current rings at both magnetic poles as required by Perelman entropy mapping;these loops are the origin of the dipolar magnetic field. One conclusion we draw is that there is no gravitational singularity, and hence no black holes in the universe, a result strongly supported by the recent discovery of many stars with masses well greater than 100 solar mass [6] [7] [8], without trace of phenomena observed (such as strong gamma and X ray emissions), which are supposed to be associated with black holes. We analyze the properties of such loop currents on the 4D-5D boundary, where Maxwell equations are valid. We derive explicit expressions for the dipolar fields over the whole temperature range. We then compare our prediction with measured surface magnetic fields of many stars. Since there is coupling in distribution between the in-phase and anti-phase pairs of e-trinos, the generated mag-netic field is directly related to the angular momentum, leading to the result that the magnetic field can be expressible in terms of only the mechanical variables (mass M, radius R, rotation period P)of a star, as if Maxwell equations are “hidden”. An explanation for the occurrence of this “un-expected result” is provided in Section (7.6). Therefore we provide satisfactory answers to a number of “mysteries” of magnetism in astrophysics such as the “Magnetic Bode’s Relation/Law” [9] and the experimental finding that B-P graph in the log-log plot is linear. Moreover, we have developed a new method for studying the relations among the data (M, R, P) during stellar evolution. Ten groups of stellar objects, effectively over 2000 samples are used in various parts of the analysis. We also explain the emergence of huge magnetic field in very old stars like White Dwarfs in terms of formation of 2D Semion state on stellar surface and release of magnetic flux as magnetic storms upon changing the 2D state back to 3D structure. Moreover, we provide an explanation, on the ground of the 5D theory, for the detection of extremely weak fields in Venus and Mars and the asymmetric distribution of magnetic field on the Martian surface. We predict the equatorial fields B of the newly discovered Trappist-1 star and the 6 nearest planets. The log B?−?log P graph for the 6 planets is linear and they satisfy the Magnetic Bode’s relation. Based on the above analysis, we have discovered several new laws of stellar magnetism, which are summarized in Section (7.6).
文摘In this research we are going to define two new concepts: a) “The Potential of Events” (EP) and b) “The Catholic Information” (CI). The term CI derives from the ancient Greek language and declares all the Catholic (general) Logical Propositions (<img src="Edit_5f13a4a5-abc6-4bc5-9e4c-4ff981627b2a.png" width="33" height="21" alt="" />) which will true for every element of a set A. We will study the Riemann Hypothesis in two stages: a) By using the EP we will prove that the distribution of events e (even) and o (odd) of Square Free Numbers (SFN) on the axis Ax(N) of naturals is Heads-Tails (H-T) type. b) By using the CI we will explain the way that the distribution of prime numbers can be correlated with the non-trivial zeros of the function <em>ζ</em>(<em>s</em>) of Riemann. The Introduction and the Chapter 2 are necessary for understanding the solution. In the Chapter 3 we will present a simple method of forecasting in many very useful applications (e.g. financial, technological, medical, social, etc) developing a generalization of this new, proven here, theory which we finally apply to the solution of RH. The following Introduction as well the Results with the Discussion at the end shed light about the possibility of the proof of all the above. The article consists of 9 chapters that are numbered by 1, 2, …, 9.
基金Supported by the grant from the Guangxi ScienceTechnology Committee, No. 9811003
文摘INTRODUCTIONThe increased expression of ICAM-1 on a widerange of cells and in the sera of patients withmalignancies, chronic liver diseases andinflammation diseases has been described since thelate 1980s[1-22]. Recently rapid progress in studieson expression of ICAM-1 in patients withhepatocellular carcinoma ( HCC ) have beenachieved, including clinical and experimentalresearches[23-31].
文摘Huntington’s disease is a neurodegenerative disease caused by the expansion mutation of a cytosine-adenine-guanine triplet in the exon 1 of the HTT gene which is responsible for the production of the huntingtin (Htt) protein. In physiological conditions, Htt is involved in many cellular processes such as cell signaling, transcriptional regulation, energy metabolism regulation, DNA maintenance, axonal trafficking, and antiapoptotic activity. When the genetic alteration is present, the production of a mutant version of Htt (mHtt) occurs, which is characterized by a plethora of pathogenic activities that, finally, lead to cell death. Among all the cells in which mHtt exerts its dangerous activity, the GABAergic Medium Spiny Neurons seem to be the most affected by the mHtt-induced excitotoxicity both in the cortex and in the striatum. However, as the neurodegeneration proceeds ahead the neuronal loss grows also in other brain areas such as the cerebellum, hypothalamus, thalamus, subthalamic nucleus, globus pallidus, and substantia nigra, determining the variety of symptoms that characterize Huntington’s disease. From a clinical point of view, Huntington’s disease is characterized by a wide spectrum of symptoms spanning from motor impairment to cognitive disorders and dementia. Huntington’s disease shows a prevalence of around 3.92 cases every 100,000 worldwide and an incidence of 0.48 new cases every 100,000/year. To date, there is no available cure for Huntington’s disease. Several treatments have been developed so far, aiming to reduce the severity of one or more symptoms to slow down the inexorable decline caused by the disease. In this context, the search for reliable strategies to target the different aspects of Huntington’s disease become of the utmost interest. In recent years, a variety of studies demonstrated the detrimental role of neuronal loss in Huntington’s disease condition highlighting how the replacement of lost cells would be a reasonable strategy to overcome the neurodegeneration. In this view, numerous have been the attempts in several preclinical models of Huntington’s disease to evaluate the feasibility of invasive and non-invasive approaches. Thus, the aim of this review is to offer an overview of the most appealing approaches spanning from stem cell-based cell therapy to extracellular vesicles such as exosomes in light of promoting neurogenesis, discussing the results obtained so far, their limits and the future perspectives regarding the neural regeneration in the context of Huntington’s disease.
基金supported by the National Natural Science Foundation of China,Nos.82271447,81771382the National Key Research and Development Program of China,No.2019 YFE0115900the"New 20 Terms of Universities in Jinan,No.202228022 (all to ZZ)。
文摘α-Synuclein is a protein that mainly exists in the presynaptic terminals.Abnormal folding and accumulation of α-synuclein are found in several neurodegenerative diseases,including Parkinson’s disease.Aggregated and highly phospho rylated a-synuclein constitutes the main component of Lewy bodies in the brain,the pathological hallmark of Parkinson s disease.For decades,much attention has been focused on the accumulation of α-synuclein in the brain parenchyma rather than considering Parkinson s disease as a systemic disease.Recent evidence demonstrates that,at least in some patients,the initial α-synuclein pathology originates in the peripheral organs and spreads to the brain.Injection of α-synuclein preformed fibrils into the gastrointestinal tra ct trigge rs the gutto-brain propagation of α-synuclein pathology.However,whether α-synuclein pathology can occur spontaneously in peripheral organs independent of exogenous α-synuclein preformed fibrils or pathological α-synuclein leakage from the central nervous system remains under investigation.In this review,we aimed to summarize the role of peripheral α-synuclein pathology in the pathogenesis of Parkinson’s disease.We also discuss the pathways by which α-synuclein pathology spreads from the body to the brain.
基金supported by the project of the China Geological Survey(No.DD20221746)the National Natural Science Foundation of China(Grant Nos.41101086)。
文摘Xinqiao Gully is located in the area of the 2008 Wenchuan M_(s)8.0 earthquake in Sichuan province,China.Based on the investigation of the 2023"6-26"Xinqiao Gully debris flow event,this study assessed the effectiveness of the debris flow control project and evaluated the debris flow hazards.Through field investigation and numerical simulation methods,the indicators of flow intensity reduction rate and storage capacity fullness were proposed to quantify the effectiveness of the engineering measures in the debris flow event.The simulation results show that the debris flow control project reduced the flow intensity by41.05%to 64.61%.The storage capacity of the dam decreases gradually from upstream to the mouth of the gully,thus effectively intercepting and controlling the debris flow.By evaluating the debris flow of different recurrence intervals,further measures are recommended for managing debris flow events.
基金supported by STI2030-Major Projects,No.2021ZD 0201801(to JG)Shanxi Province Basic Research Program,No.20210302123429(to QS).
文摘In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.
基金supported by Association 2HE(Center for Human Health and Environment)by Regione Puglia-Grant Malattie Rare DUP n.246 of 2019(to CB).
文摘Neurodegenerative diseases are a group of disorders characterized by the progressive degeneration of neurons in the central or peripheral nervous system.Currently,there is no cure for neurodegenerative diseases and this means a heavy burden for patients and the health system worldwide.Therefore,it is necessary to find new therapeutic approaches,and antisense therapies offer this possibility,having the great advantage of not modifying cellular genome and potentially being safer.Many preclinical and clinical studies aim to test the safety and effectiveness of antisense therapies in the treatment of neurodegenerative diseases.The objective of this review is to summarize the recent advances in the development of these new technologies to treat the most common neurodegenerative diseases,with a focus on those antisense therapies that have already received the approval of the U.S.Food and Drug Administration.
基金supported in parts by the National Natural Science Foundation of China,Nos.82101501(to QF),and 82201589(to XH)。
文摘Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.
文摘We generalize the congruences of Friedmann-Tamarkine (1909), Lehmer (1938), and Ernvall-Metsänkyla (1991) on the sums of powers of integers weighted by powers of the Fermat quotients to the next Fermat quotient power, namely to the third power of the Fermat quotient. Using this result and the Gessel identity (2005) combined with our past work (2021), we are able to relate residues of some truncated convolutions of Bernoulli numbers with some Ernvall-Metsänkyla residues to residues of some full convolutions of the same kind. We also establish some congruences concerning other related weighted sums of powers of integers when these sums are weighted by some analogs of the Teichmüller characters.
文摘A century ago the classical physics couldn’t explain many atomic physical phenomena. Now the situation has changed. It’s because within the framework of classical physics with the help of Maxwell’s equations we can derive Schrödinger’s equation, which is the foundation of quantum physics. The equations for energy, momentum, frequency and wavelength of the electromagnetic wave in the atom are derived using the model of atom by analogy with the transmission line. The action constant A0 = (μ0/ε0)1/2s02e2 is a key term in the above mentioned equations. Besides the other well-known constants, the only unknown constant in the last expression is a structural constant of the atom s0. We have found that the value of this constant is 8.277 56 and that it shows up as a link between macroscopic and atomic world. After calculating this constant we get the theory of atoms based on Maxwell’s and Lorentz equations only. This theory does not require knowledge of Planck’s constant h, which is replaced with theoretically derived action constant A0, while the replacement for the fine structure constant α-1 is theoretically derived expression 2s02 = 137.036. So, the structural constant s0 replaces both constants h and α. This paper also defines the stationary states of atoms and shows that the maximal atomic number is equal to Zmax = 137. The presented model of the atoms covers three of the four fundamental interactions, namely the electromagnetic, weak and strong interactions.
基金supported by the European Regional Development Funds-European Union(ERDF-EU),FATZHEIMER project(EU-LAC HEALTH 2020,16/T010131 to FRdF),“Una manera de hacer Europa”Ministerio de Economía,Industria y Competitividad,Gobierno de Espa?a,Programa Estatal de Investigación,Desarrollo e Innovación Orientada a los Retos de la Sociedad(RTC2019-007329-1 to FRdF)+2 种基金Consejería de Economía,Conocimiento y Universidad,Junta de Andalucía,Plan Andaluz de Investigación,Desarrollo e Innovación(P18TP-5194 to FRdF)Instituto de Salud CarlosⅢ(DTS22/00021 to FRdF)DMV(FI20/00227)holds a“PFIS’’predoctoral contract from the National System of Health,EU-ERDF-Instituto de Salud CarlosⅢ。
文摘Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the phosphorylation and aggregation of tau protein.Among the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug development.The present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease.
文摘Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have on our aging population.Posture and gait control does not happen automatically,as previously believed,but rather requires continuous involvement of central nervous mechanisms.To effectively exert control over the body,the brain must integrate multiple streams of sensory information,including visual,vestibular,and somatosensory signals.The mechanisms which underpin the integration of these multisensory signals are the principal topic of the present work.Existing multisensory integration theories focus on how failure of cognitive processes thought to be involved in multisensory integration leads to falls in older adults.Insufficient emphasis,however,has been placed on specific contributions of individual sensory modalities to multisensory integration processes and cross-modal interactions that occur between the sensory modalities in relation to gait and balance.In the present work,we review the contributions of somatosensory,visual,and vestibular modalities,along with their multisensory intersections to gait and balance in older adults and patients with Parkinson’s disease.We also review evidence of vestibular contributions to multisensory temporal binding windows,previously shown to be highly pertinent to fall risk in older adults.Lastly,we relate multisensory vestibular mechanisms to potential neural substrates,both at the level of neurobiology(concerning positron emission tomography imaging)and at the level of electrophysiology(concerning electroencephalography).We hope that this integrative review,drawing influence across multiple subdisciplines of neuroscience,paves the way for novel research directions and therapeutic neuromodulatory approaches,to improve the lives of older adults and patients with neurodegenerative diseases.
基金supported by the National Natural Science Foundation of China,No.31960120Yunnan Science and Technology Talent and Platform Plan,No.202105AC160041(both to ZW).
文摘Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease.The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice.However,ethical issues and tumor formation were limitations of its clinical application.Induced pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell therapy.Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor formation.Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease.However,there are also ethical concerns and the risk of tumor formation that need to be addressed.This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical research.The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo reprogramming.These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.
文摘BACKGROUND Meckel’s diverticulum is a common congenital malformation of the small intestine,with the three most common complications being obstruction,per-foration,and inflammation.To date,only a few cases have been reported world-wide.In children,the clinical symptoms are similar to appendicitis.As most of the imaging features are nonspecific,the preoperative diagnosis is not precise.In addition,the clinical characteristics are highly similar to pediatric acute appendicitis,thus special attention is necessary to distinguish Meckel’s diver-ticulum from pediatric appendicitis.Patients with poor disease control should undergo laparoscopic exploration to avoid serious complications,including intestinal necrosis,intestinal perforation and gastrointestinal bleeding.CASE SUMMARY This report presents three cases of appendicitis in children combined with intestinal obstruction,which was caused by fibrous bands(ligaments)arising from the top part of Meckel's diverticulum,diverticular perforation,and diver-ticular inflammation.All three patients,aged 11-12 years,had acute appendicitis as their initial clinical presentation.All were treated by laparoscopic surgery with a favorable outcome.A complete dataset including clinical presentation,dia-gnostic imaging,surgical information,and histopathologic findings was also provided.CONCLUSION Preoperative diagnosis of Meckel’s diverticulum and its complications is challenging because its clinical signs and complications are similar to those of appendicitis in children.Laparoscopy combined with laparotomy is useful for diagnosis and treatment.
文摘A treat-to-target(T2T)approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease.The Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)-II guidelines specify short,intermediate,and long-term treatment goals,documenting specific treatment targets to be achieved at each of these timepoints.Scheduled appraisal of Crohn’s disease activity against pre-defined treatment targets at these timepoints remains central to determining whether current therapy should be continued or modified.Consensus treatment targets in Crohn’s disease comprise combination clinical and patient-reported outcome remission,in conjunction with biomarker normalisation and endoscopic healing.Although the STRIDE-II guidelines endorse the pursuit of endoscopic healing,clinicians must consider that this may not always be appropriate,acceptable,or achievable in all patients.This underscores the need to engage patients at the outset in an effort to personalise care and individualise treatment targets.The use of non-invasive biomarkers such as faecal calprotectin in conjunction with cross-sectional imaging techniques,particularly intestinal ultrasound,holds great promise;as do emerging treatment targets such as transmural healing.Two randomised clinical trials,namely,CALM and STARDUST,have evaluated the efficacy of a T2T approach in achieving endoscopic endpoints in patients with Crohn’s disease.Findings from these studies reflect that patient subgroups and Crohn’s disease characteristics likely to benefit most from a T2T approach,remain to be clarified.Moreover,outside of clinical trials,data pertaining to the real-world effectiveness of a T2T approach remains scare,highlighting the need for pragmatic real-world studies.Despite the obvious promise of a T2T approach,a lack of guidance to support its integration into real-world clinical practice has the potential to limit its uptake.This highlights the need to describe strategies,processes,and models of care capable of supporting the integration and execution of a T2T approach in real-world clinical practice.Hence,this review seeks to examine the current and emerging literature to provide clinicians with practical guidance on how to incorporate the principles of T2T into routine clinical practice for the management of Crohn’s disease.