In this paper, incised valley filling deposits, which formed an important pathway system for long-distance hydrocarbon migration, are discussed in detail based on core and logging data. The sequence SQy23 of the Creta...In this paper, incised valley filling deposits, which formed an important pathway system for long-distance hydrocarbon migration, are discussed in detail based on core and logging data. The sequence SQy23 of the Cretaceous Yaojia Formation is the main hydrocarbon-bearing layer in the Fulaerji Oilfield. The hydrocarbon source of the oilfield is the Qijia-Gulong Sag which is about 80 km away from the Fulaerji Oilfield. The transport layer of long-distance hydrocarbon migration is the overlapped sandstone complex which fills the incised valley. The incised valley developed during the depositional period from the late Qingshankou Formation to the early Yaojia Formation of Cretaceous (SQqna-SQy0 was about 70 km long and 20 km wide, and extended in the NW-SE direction. The overlapped filling of the incised valley mainly occurred in the expanding system tract of the third-order sequence SQy23 (ESTy23). Towards the basin, incised valley filling deposits overlapped on the delta developed in the early period, and towards the basin margin, incised valley filling deposits were covered by the shore-shallow lacustrine sandy beach bar developed in the maximum flooding period. All of the delta, the incised valley filling and the shore-shallow sandy beach bar are sandstone-rich, and have high porosity and permeability, and can form an effective hydrocarbon migration and accumulation system. Deltaic sand bodies collected and pumped hydrocarbon from the active source, incised valley filling depositional system completed the long-distance hydrocarbon migration, and lithological traps of shore-shallow lacustrine sandy beach bar accumulated hydrocarbon. The incised valley filling sequences are multi-cycle: an integrated shortterm filling cycle was developed on the erosion surface, and the sequences upward were mud-gravel stone, medium-fine sandstone containing terrigenous gravels and muddy pebbles with cross bedding, silty mudstone with ripple bedding, and mudstone. The incised valley filling deposits are characterized by a strong heterogeneity and the main hydrocarbon migration pathway is the medium-fine sandstone interval.展开更多
Research on the distribution of mantle CO_(2)should involve comprehensive analysis from CO_(2)source to accumulation.The crust-mantle pathway system is the key controlling factor of the distribution of mantle CO_(2),b...Research on the distribution of mantle CO_(2)should involve comprehensive analysis from CO_(2)source to accumulation.The crust-mantle pathway system is the key controlling factor of the distribution of mantle CO_(2),but has received little attention.The pathway system and controlling factors of CO_(2)distribution in the Bohai Sea are analyzed using data on fault styles and information on the mantle and lithosphere.The relation between volcanic rocks and the distribution of mantle CO_(2)is reassessed using age data for CO_(2)accumulations.The distribution of mantle CO_(2)is controlled by uplift of the asthenosphere and upper mantle,magma conduits in the mantle and fault systems in the crust.Uplifted regions of the asthenosphere are accumulation areas for CO_(2).The area with uplift of the Moho exhibits accumulation of mantle CO_(2)at depth.CO_(2)was mainly derived from vertical migration through the upper mantle and lower crust.The fault style in the upper crust controls the distance of horizontal migration and the locations of CO_(2)concentrations.The distribution of mantle CO_(2)and volcanic rocks are not the same,but both probably followed the same pathways sometimes.Mantle CO_(2)in the Bohai Sea is concentrated in the Bozhong sag and the surrounding area,particularly in a trap that formed before 5.1 Ma and is connected to crustal faults(the Bozhang faults)and lithospheric faults(the Tanlu faults).展开更多
The presented research illustrates the applicability and productiveness of the systematic literature review methodology, a non-empirical methodology in the geological sciences, particularly volcanology. The systematic...The presented research illustrates the applicability and productiveness of the systematic literature review methodology, a non-empirical methodology in the geological sciences, particularly volcanology. The systematic literature review methodology is a replicable, rigorous, and transparent methodology for synthesizing existing literature to answer questions on a specific topic. The synthesis allows for knowledge consolidation, such as identifying knowledge gaps. In our illustration of this methodology, we focused on the expanding knowledge about the magma pathway at Mount Cameroon, one of Africa’s active volcanoes. Our synthesis of the relevant international geoscience research literature is based on the framework of knowledge about the magma pathway beneath a typical basaltic volcano. The framework has three primary components: magma supply, storage, and transport to erupting vents. Across these components is a total of twelve secondary components. The result is a previously non-existent and fragmented overall understanding of the magma pathway at Mount Cameroon. The gaps in the understanding (such as in the magma supply rates, timescales of chamber processes, and magma ascent rates) may be addressed in future research. Another key implication of the presented research lies in the proof of concept of the systematic literature review methodology as an applicable qualitative research methodology in the study of volcanoes.展开更多
A critical unaddressed problem in Parkinson’s disease is the lack of therapy that slows or hampers neurodegeneration.While medications effectively manage symptoms,they offer no long-term benefit because they fail to ...A critical unaddressed problem in Parkinson’s disease is the lack of therapy that slows or hampers neurodegeneration.While medications effectively manage symptoms,they offer no long-term benefit because they fail to address the underlying neuronal loss.This highlights that the elusive goals of halting progression and restoring damaged neurons limit the long-term impact of current approaches.Recent clinical trials using gene therapy have demonstrated the safety of various vector delivery systems,dosages,and transgenes expressed in the central nervous system,signifying tangible and substantial progress in applying gene therapy as a promising Parkinson’s disease treatment.Intriguingly,at diagnosis,many dopamine neurons remain in the substantia nigra,offering a potential window for recovery and survival.We propose that modulating these surviving dopamine neurons and axons in the substantia nigra and striatum using gene therapy offers a potentially more impactful therapeutic approach for future research.Moreover,innovative gene therapies that focus on preserving the remaining elements may have significant potential for enhancing long-term outcomes and the quality of life for patients with Parkinson’s disease.In this review,we provide a perspective on how gene therapy can protect vulnerable elements in the substantia nigra and striatum,offering a novel approach to addressing Parkinson’s disease at its core.展开更多
The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enh...The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut–brain axis.The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites,which activates the vagus nerve and modulates the immune and neuroendocrine systems.Conversely,alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota,creating a dynamic network of microbial-host interactions.This reciprocal regulation affects neurodevelopment,neurotransmitter control,and behavioral traits,thus playing a role in the modulation of neurological diseases.The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation,mitochondrial dysfunction,abnormal energy metabolism,microglial activation,oxidative stress,and neurotransmitter release,which collectively influence the onset and progression of neurological diseases.This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway,along with its implications for potential therapeutic interventions in neurological diseases.Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders.This can be achieved through various methods such as dietary modifications,probiotic supplements,Chinese herbal extracts,combinations of Chinese herbs,and innovative dosage forms.These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.展开更多
Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-b...Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this condition.Dopamine is a crucial catecholaminergic neurotransmitter in the human body.Dopamine-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical manifestations.Howeve r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive impairment.This review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related drugs.The aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.展开更多
Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways...Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle function.The process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle function.Muscle contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular junction.Within muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate force.Regulation of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction coupling.The development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as myogenesis.Myogenic regulators coordinate the diffe rentiation of myoblasts into mature muscle fibers.Signaling pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient availability.Seve ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal muscle.Therapeutic interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular pathways.Other molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling pathway.In recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular junction.In fact,research in the last few years now suggests that these two signaling pathways are interconnected and that they jointly control physiological and pathophysiological processes in muscle fibers.In this review,we will summarize and discuss the data on these two pathways,focusing on their concerted action next to their contribution to skeletal muscle biology.However,an in-depth discussion of the noncanonical Wnt pathway,the fibro/a dipogenic precursors,or the mechanosensory aspects of these pathways is not the focus of this review.展开更多
The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically revie...The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.展开更多
Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal sur...Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.展开更多
Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage.The expression of the C-C motif chemokine ligand...Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage.The expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after injury.Recent studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for treatment.This review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord injury.Additionally,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted drugs.Nevertheless,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.展开更多
Rho-associated kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase RhoA. The Rho/ROCK pathway is closely related to the pathogenesis of several central nervous syst...Rho-associated kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase RhoA. The Rho/ROCK pathway is closely related to the pathogenesis of several central nervous system (CNS) disorders, and involved in many aspects of neuronal functions including neurite outgrowth and retraction. In the adult CNS, the damaged neuron regeneration is very difficult due to the presence of myelin-associated axon growth inhibitors such as Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (Omgp), etc. The effects of these axon growth inhibitors are reversed by blocking the Rho/ROCK pathway 47 vitro, and the inhibition of Rho/ROCK pathway can promote axon regeneration and functional recovery in the injured CNS in viva In addition, the therapeutic effects of the Rho/ROCK inhibitors have also been demonstrated in some animal models and the Rho/ROCK pathway becomes an attractive target for the development of drugs for treating CNS disorders. In this review, we summarized on the effect of the Rho and the downstream factor ROCK in neural regeneration, and the potential therapeutic effect of Rho/ROCK inhibitors in the survival and axonal regeneration of retinal ganglion cell was also discussed.展开更多
To characterize effects of plant roots on preferential flow(PF),we measured root length density(RLD)and root biomass(RB) in Jiufeng National Forest Park,Beijing,China.Comparisons were made for RLD and RB between...To characterize effects of plant roots on preferential flow(PF),we measured root length density(RLD)and root biomass(RB) in Jiufeng National Forest Park,Beijing,China.Comparisons were made for RLD and RB between soil preferential pathways and soil matrices.RLD and RB declined with the increasing soil depth(0–10,10–20,20–30,30–40,40–50,50–60 cm) in all experimental plots.RLD was greater in soil preferential pathways than in the surrounding soil matrix and was 69.5,75.0 and72.2 % for plant roots of diameter(d) /1,1 / d / 3 and3 / d / 5 mm,respectively.Fine root systems had the most pivotal influence on soil preferential flow in this forest ecosystem.In all experimental plots,RB content was the sum of RB from soil preferential pathways and the soil matrix in each soil depth.With respect to 6 soil depth gradient(0–10,10–20,20–30,30–40,40–50,50–60 cm) in each plot,the number of soil depth gradient that RB content was greater in soil preferential pathways than in the soil matrix was characterized,and the proportion was68.2 % in all plots.展开更多
An active stereo vision system based on a model of neural pathways of human binocular motor system is proposed. With this model, it is guaranteed that the two cameras of the active stereo vision system can keep their ...An active stereo vision system based on a model of neural pathways of human binocular motor system is proposed. With this model, it is guaranteed that the two cameras of the active stereo vision system can keep their lines of sight fixed on the same target object during smooth pursuit. This feature is very important for active stereo vision systems, since not only 3D reconstruction needs the two cameras have an overlapping field of vision, but also it can facilitate the 3D reconstruction algorithm. To evaluate the effectiveness of the proposed method, some software simulations are done to demonstrate the same target tracking characteristic in a virtual environment apt to mistracking easily. Here, mistracking means two eyes track two different objects separately. Then the proposed method is implemented in our active stereo vision system to perform real tracking task in a laboratory scene where several persons walk self-determining. Before the proposed model is implemented in the system, mistracking occurred frequently. After it is enabled, mistracking never occurred. The result shows that the vision system based on neural pathways of human binocular motor system can reliably avoid mistracking.展开更多
Neural degeneration is a very complicated process. In spite of all the advancements in the molecular chemistry, there are many unknown aspects of the phenomena of neurodegeneration which need to be put together. It is...Neural degeneration is a very complicated process. In spite of all the advancements in the molecular chemistry, there are many unknown aspects of the phenomena of neurodegeneration which need to be put together. It is a common sequela of the conditions of niacin deficiency. Neural degeneration in Pellagra manifests as chromatolysis mainly in pyramidal followed by other neurons and glial cells. However, there is a gross lack of understanding of biochemi- cal mechanisms of neurodegeneration in niacin deficiency states. Because of the necessity of niacin or its amide derivative NAD in a number of biochemical pathways, it is understandable that several of these pathways may be involved in the common outcome of neural degener- ation. Here, we highlight five pathways that could be involved in the neuraldegeneration for which evidence has accumulated through several studies. These pathways are: 1) the trypto- phan-kyneurenic acid pathway, 2) the mitochondrial ATP generation related pathways, 3) the poly (ADP-ibose) polymerase (PARP) pathway, 4) the BDNF-TRKB Axis abnormalities, 5) the genetic influences of niacin deficiency.展开更多
In this study,the hypothesis that Wnt/β-catenin pathway is involved in the arterial calcification by regulating the osteoprotegerin(OPG)/receptor activator of NF-κB ligand(RANKL)system was tested.Theβ-catenin expre...In this study,the hypothesis that Wnt/β-catenin pathway is involved in the arterial calcification by regulating the osteoprotegerin(OPG)/receptor activator of NF-κB ligand(RANKL)system was tested.Theβ-catenin expression was measured in the warfarin-induced calcified arteries and the osteoblast-like cells differentiating from smooth muscle cells(SMCs)by immunohistochemistry and Western blotting.The Wnt/β-catenin pathway was activated or inhibited by lithium chloride(LiCl)or dickkopf 1(DKK1)in vitro and in vivo.Then the calcification level was determined by von Kossa staining,Ca^2+content assay,and alkaline phosphatase(ALP)activity assay.The expression levels of osteocalcin,OPG and RANKL were detected by Western blotting or real-time PCR.The results showed that in calcified arteries and OBL cells,the activation of Wnt/β-catenin pathway significantly enhanced the calcification as evidenced by increased von Kossa stains,Ca^2+contcnts,ALP activities,and osteocalcin expression levels(P<0.05),and it promoted the RANKL expression(P<0.05),but slightly affected the OPG expression.These results indicated that the activation of Wnt/β-catenin pathway worsens the arterial calcification,probably by promoting the RANKL expression.展开更多
Computational systems biology approaches provide insights to understand complex molecular phenomena in living systems. Such understanding demands the need to systematically interrogate and review existing literature t...Computational systems biology approaches provide insights to understand complex molecular phenomena in living systems. Such understanding demands the need to systematically interrogate and review existing literature to refine and distil key molecular pathways. This paper explores a methodological process to identify key molecular pathways from systematic bioinformatics literature review. This process is used to identify molecular pathways for a ubiquitous molecular process in all plant biological systems: C1 metabolism and formaldehyde detoxification, specific to maize. The C1 metabolism is essential for all organisms to provide one-carbon units for methylation and other types of modifications, as well as for nucleic acid, amino acid, and other biomolecule syntheses. Formaldehyde is a toxic one-carbon molecule which is produced endogenously and found in the environment, and whose detoxification is an important part of C1 metabolism. This systematic review involves a five-part process: 1) framing of the research question;2) literature collection based on a parallel search strategy;3) relevant study selection based on search refinement;4) molecular pathway identification;and 5) integration of key molecular pathway mechanisms to yield a well-defined set molecular systems associated with a particular biochemical function. Findings from this systematic review produced three main molecular systems: a) methionine biosynthesis;b) the methylation cycle;and c) formaldehyde detoxification. Specific insights from the resulting molecular pathways indicate that normal C1 metabolism involves the transfer of a carbon group from serine through a folate-mediated pathway to methionine, and eventually the methylation of a biomolecule. In photosynthetic tissues, C1 metabolism often proceeds in reverse towards serine biosynthesis and formate oxidation. C1 metabolism, in maize, appears to be present in the developing embryo and endosperm indicating that these cells are vulnerable to perturbations in formaldehyde detoxification. These insights demonstrate the value of a systematic bioinformatics literature review process from a broad spectrum of domain literature to specific and relevant molecular pathways.展开更多
While SlPti5 has been shown to play a crucial role in the regulation of antagonistic genes in Solanum lycopersicum and Arabidopsis against pathogen infection,there have been no comprehensive studies on the effects of ...While SlPti5 has been shown to play a crucial role in the regulation of antagonistic genes in Solanum lycopersicum and Arabidopsis against pathogen infection,there have been no comprehensive studies on the effects of SlPti5 on the regulatory response mechanism of reactive oxygen species(ROS) system and hormone pathways during growth and disease resistance of tomato plants.Here,we investigated the function of SlPti5 in the defense response of tomato against Botrytis cinerea utilizing a virus-induced gene silencing(VIGS)-based system.Expression profile analysis showed that SlPti5 was significantly induced upon B.cinerea infection,with high expression levels in the leaves and fruit of tomato.VIGS-based silencing of SlPti5 inhibited early vegetative growth,increased the plant’s susceptibility to infection,promoted the development of ROS,affected the expression of genes involved in the ROS scavenging system,and attenuated the expression of genes associated with pathogenesis and the ethylene/jasmonic acid signaling pathways.In sum,our data demonstrated that SlPti5 stimulates the immune response of tomato plant to Botrytis cinerea infection by involving the ethylene(ET)-and jasmonic acid(JA)-mediated pathways and modulating the expression of some key pathogenesis-related(PR) genes.展开更多
AIM: To evaluate effect of hypertension on retinal ganglion cell(RGC) apoptosis, intraocular pressure(IOP),and the activation of endothelin-1(ET-1) signaling pathway in central retinal artery(CRA) in rats.MET...AIM: To evaluate effect of hypertension on retinal ganglion cell(RGC) apoptosis, intraocular pressure(IOP),and the activation of endothelin-1(ET-1) signaling pathway in central retinal artery(CRA) in rats.METHODS: The experimental study was performed on20 male Sprague Dawley rats that were divided into control group, and hypertension groups. The hypertension was induced by subcutaneous deoxycorticoacetate(DOCA)10 mg/kg twice a week and administered 0.9% Na Cl solution daily for 2, 6, and 10 wk. Blood pressure(BP) was measured using animal BP analyzer. IOP was measured by handheld tonometry. Retinal tissue preparations by paraffin blocks were made after enucleation. The expression of ET-1, e NOS, ET-1 receptor A(ETRA), ET-1receptor B(ETRB), and phosphorylated myosin light chain kinase(MLCK), and caldesmon(Ca D) in CRA and RGC apoptosis were evaluated through immunofluorescent staining method then observed using laser scanning confocal microscopy. RESULTS: BP significantly increased in all of the hypertension groups compared to control(P =0.001).Peak IOP elevation(7.78±4.14 mm Hg) and RGC apoptosis(576.15±33.28 Au) occurred on 2wk of hypertension. ET-1expression(1238.6±55.1 Au) and e NOS expression(2814.2±70.7 Au) were found highest in 2wk of hypertension,although the ratio of ET-1/e NOS decreased since 2wk.ETRAreached peak expression in 10 wk of hypertension(1219.4 ±6.3 Au), while ETRBsignificantly increased only in 2 weeks group(1069.2 ±9.6 Au). The highest MLCK expression(1190.09±58.32 Au), Ca D(1670.28±18.36 Au)were also found in 2wk of hypertension.CONCLUSION: Hypertension effects to activation of ET-1 signaling pathway significantly in CRA, elevation of IOP, and RGC apoptosis. The highest value was achieved at 2wk, which is the development phase of hypertension.展开更多
<strong>Background:</strong> Clinical pathways are effective in reducing healthcare cost and standardizing management protocol for diseases and conditions. However, there are no standardized pathways for a...<strong>Background:</strong> Clinical pathways are effective in reducing healthcare cost and standardizing management protocol for diseases and conditions. However, there are no standardized pathways for appendicitis. This study aims to determine whether implementation of a standardized clinical pathway for managing appendicitis may lead to improved patient care. <strong>Materials and Methods:</strong> We searched for articles published in PubMed, MEDLINE, and Cochrane library between 1974 and 2015. Thirty-seven papers published in English that met inclusion criteria were included and analyzed in this review. A total of 37 studies met inclusion criteria and were analyzed for the purpose of this study. <strong>Results:</strong> A clear definition for appendicitis pathway was observed in 30 articles. Appendicitis was diagnosed based on clinical and laboratory findings;however, 34% of the studies included radiological investigations. Sixteen studies provided clear definitions for discharge criteria. Time of follow-up (5 - 28 days) was reported in 10 studies. Operative time was the most commonly used outcome measure. The mean length of stay for non-complicated appendicitis was 1.3 days, and 6.26 days for complicated appendicitis. Most of the studies concluded that the accuracy of a clinical pathway for appendicitis diagnosis can be achieved by assessing the incidence of a normal appendix. The mean cost for patient care was $4874.14 (SAR 18,278.03). <strong>Conclusion:</strong> There was no standardized definition for appendicitis clinical pathway components. Studies suggested that establishing a clinical pathway for appendicitis improves the outcome and minimizes the cost.展开更多
BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which...BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which is indicated for the treatment of liver cancer.However,its impact on the liver cancer tumor microenvironment,particularly on tumor-associated macrophages(TAMs),is not well understood.AIM To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/β-catenin pathway modulation.METHODS This study identified the active components of CB using UPLC-Q-TOF-MS,evaluated its anti-neoplastic effects in a nude mouse model,and elucidated the underlying mechanisms via network pharmacology,transcriptomics,and molecular docking.In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs,and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis.RESULTS This study identified 22 active components in CB,11 of which were detected in the bloodstream.Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth.An integrated approach employing network pharmacology,transcriptomics,and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization.In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/β-catenin pathway activation.The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001,confirming its pathway specificity.CONCLUSION This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/β-catenin pathway,contributing to the suppression of liver cancer growth.展开更多
文摘In this paper, incised valley filling deposits, which formed an important pathway system for long-distance hydrocarbon migration, are discussed in detail based on core and logging data. The sequence SQy23 of the Cretaceous Yaojia Formation is the main hydrocarbon-bearing layer in the Fulaerji Oilfield. The hydrocarbon source of the oilfield is the Qijia-Gulong Sag which is about 80 km away from the Fulaerji Oilfield. The transport layer of long-distance hydrocarbon migration is the overlapped sandstone complex which fills the incised valley. The incised valley developed during the depositional period from the late Qingshankou Formation to the early Yaojia Formation of Cretaceous (SQqna-SQy0 was about 70 km long and 20 km wide, and extended in the NW-SE direction. The overlapped filling of the incised valley mainly occurred in the expanding system tract of the third-order sequence SQy23 (ESTy23). Towards the basin, incised valley filling deposits overlapped on the delta developed in the early period, and towards the basin margin, incised valley filling deposits were covered by the shore-shallow lacustrine sandy beach bar developed in the maximum flooding period. All of the delta, the incised valley filling and the shore-shallow sandy beach bar are sandstone-rich, and have high porosity and permeability, and can form an effective hydrocarbon migration and accumulation system. Deltaic sand bodies collected and pumped hydrocarbon from the active source, incised valley filling depositional system completed the long-distance hydrocarbon migration, and lithological traps of shore-shallow lacustrine sandy beach bar accumulated hydrocarbon. The incised valley filling sequences are multi-cycle: an integrated shortterm filling cycle was developed on the erosion surface, and the sequences upward were mud-gravel stone, medium-fine sandstone containing terrigenous gravels and muddy pebbles with cross bedding, silty mudstone with ripple bedding, and mudstone. The incised valley filling deposits are characterized by a strong heterogeneity and the main hydrocarbon migration pathway is the medium-fine sandstone interval.
基金supported by the Major Program of the National Natural Science Foundation of China(41790453)the Natural Science Foundation of Jilin Province(20170101001JC)+1 种基金the National Natural Science Foundation of China(41472304)the National Science and Technology Major Project of the Ministry of Science and Technology of China(2016ZX05026-004-001)。
文摘Research on the distribution of mantle CO_(2)should involve comprehensive analysis from CO_(2)source to accumulation.The crust-mantle pathway system is the key controlling factor of the distribution of mantle CO_(2),but has received little attention.The pathway system and controlling factors of CO_(2)distribution in the Bohai Sea are analyzed using data on fault styles and information on the mantle and lithosphere.The relation between volcanic rocks and the distribution of mantle CO_(2)is reassessed using age data for CO_(2)accumulations.The distribution of mantle CO_(2)is controlled by uplift of the asthenosphere and upper mantle,magma conduits in the mantle and fault systems in the crust.Uplifted regions of the asthenosphere are accumulation areas for CO_(2).The area with uplift of the Moho exhibits accumulation of mantle CO_(2)at depth.CO_(2)was mainly derived from vertical migration through the upper mantle and lower crust.The fault style in the upper crust controls the distance of horizontal migration and the locations of CO_(2)concentrations.The distribution of mantle CO_(2)and volcanic rocks are not the same,but both probably followed the same pathways sometimes.Mantle CO_(2)in the Bohai Sea is concentrated in the Bozhong sag and the surrounding area,particularly in a trap that formed before 5.1 Ma and is connected to crustal faults(the Bozhang faults)and lithospheric faults(the Tanlu faults).
文摘The presented research illustrates the applicability and productiveness of the systematic literature review methodology, a non-empirical methodology in the geological sciences, particularly volcanology. The systematic literature review methodology is a replicable, rigorous, and transparent methodology for synthesizing existing literature to answer questions on a specific topic. The synthesis allows for knowledge consolidation, such as identifying knowledge gaps. In our illustration of this methodology, we focused on the expanding knowledge about the magma pathway at Mount Cameroon, one of Africa’s active volcanoes. Our synthesis of the relevant international geoscience research literature is based on the framework of knowledge about the magma pathway beneath a typical basaltic volcano. The framework has three primary components: magma supply, storage, and transport to erupting vents. Across these components is a total of twelve secondary components. The result is a previously non-existent and fragmented overall understanding of the magma pathway at Mount Cameroon. The gaps in the understanding (such as in the magma supply rates, timescales of chamber processes, and magma ascent rates) may be addressed in future research. Another key implication of the presented research lies in the proof of concept of the systematic literature review methodology as an applicable qualitative research methodology in the study of volcanoes.
基金supported by the National Research Foundation of Korea(RS-2023-00245298)the Korea Healthcare Technology R&D(HI21C1795)grants,funded by the Korean government(to SRK).
文摘A critical unaddressed problem in Parkinson’s disease is the lack of therapy that slows or hampers neurodegeneration.While medications effectively manage symptoms,they offer no long-term benefit because they fail to address the underlying neuronal loss.This highlights that the elusive goals of halting progression and restoring damaged neurons limit the long-term impact of current approaches.Recent clinical trials using gene therapy have demonstrated the safety of various vector delivery systems,dosages,and transgenes expressed in the central nervous system,signifying tangible and substantial progress in applying gene therapy as a promising Parkinson’s disease treatment.Intriguingly,at diagnosis,many dopamine neurons remain in the substantia nigra,offering a potential window for recovery and survival.We propose that modulating these surviving dopamine neurons and axons in the substantia nigra and striatum using gene therapy offers a potentially more impactful therapeutic approach for future research.Moreover,innovative gene therapies that focus on preserving the remaining elements may have significant potential for enhancing long-term outcomes and the quality of life for patients with Parkinson’s disease.In this review,we provide a perspective on how gene therapy can protect vulnerable elements in the substantia nigra and striatum,offering a novel approach to addressing Parkinson’s disease at its core.
基金supported by the National Natural Science Foundation of China,No.82003965the Science and Technology Research Project of Sichuan Provincial Administration of Traditional Chinese Medicine,No.2024MS167(to LH)+2 种基金the Xinglin Scholar Program of Chengdu University of Traditional Chinese Medicine,No.QJRC2022033(to LH)the Improvement Plan for the'Xinglin Scholar'Scientific Research Talent Program at Chengdu University of Traditional Chinese Medicine,No.XKTD2023002(to LH)the 2023 National Project of the College Students'Innovation and Entrepreneurship Training Program at Chengdu University of Traditional Chinese Medicine,No.202310633028(to FD)。
文摘The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut–brain axis.The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites,which activates the vagus nerve and modulates the immune and neuroendocrine systems.Conversely,alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota,creating a dynamic network of microbial-host interactions.This reciprocal regulation affects neurodevelopment,neurotransmitter control,and behavioral traits,thus playing a role in the modulation of neurological diseases.The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation,mitochondrial dysfunction,abnormal energy metabolism,microglial activation,oxidative stress,and neurotransmitter release,which collectively influence the onset and progression of neurological diseases.This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway,along with its implications for potential therapeutic interventions in neurological diseases.Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders.This can be achieved through various methods such as dietary modifications,probiotic supplements,Chinese herbal extracts,combinations of Chinese herbs,and innovative dosage forms.These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.
文摘Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this condition.Dopamine is a crucial catecholaminergic neurotransmitter in the human body.Dopamine-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical manifestations.Howeve r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive impairment.This review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related drugs.The aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.
基金supported by the German Research Council(Deutsche Forschungsgemeinschaft,HA3309/3-1/2,HA3309/6-1,HA3309/7-1)。
文摘Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle function.The process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle function.Muscle contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular junction.Within muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate force.Regulation of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction coupling.The development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as myogenesis.Myogenic regulators coordinate the diffe rentiation of myoblasts into mature muscle fibers.Signaling pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient availability.Seve ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal muscle.Therapeutic interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular pathways.Other molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling pathway.In recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular junction.In fact,research in the last few years now suggests that these two signaling pathways are interconnected and that they jointly control physiological and pathophysiological processes in muscle fibers.In this review,we will summarize and discuss the data on these two pathways,focusing on their concerted action next to their contribution to skeletal muscle biology.However,an in-depth discussion of the noncanonical Wnt pathway,the fibro/a dipogenic precursors,or the mechanosensory aspects of these pathways is not the focus of this review.
基金supported by Yuan Du Scholars,Clinical Research Center of Affiliated Hospital of Shandong Second Medical University,No.2022WYFYLCYJ02Weifang Key Laboratory,Weifang Science and Technology Development Plan Project Medical Category,No.2022YX093.
文摘The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.
基金supported by the National Natural Science Foundation of China(Youth Science Fund Project),No.81901292(to GC)the National Key Research and Development Program of China,No.2021YFC2502100(to GC)the National Natural Science Foundation of China,No.82071183(to ZZ).
文摘Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.
基金supported by the National Natural Science Foundation of China(Key Program),No.11932013the National Natural Science Foundation of China(General Program),No.82272255+2 种基金Armed Police Force High-Level Science and Technology Personnel ProjectThe Armed Police Force Focuses on Supporting Scientific and Technological Innovation TeamsKey Project of Tianjin Science and Technology Plan,No.20JCZDJC00570(all to XC)。
文摘Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage.The expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after injury.Recent studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for treatment.This review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord injury.Additionally,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted drugs.Nevertheless,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.
基金Supported by National Nature Science Foundation of China (No.81070728)Shanghai "Science and Technology Innovation Action Plan" Basic Research Key Project,China (No.11JC1407700 and 11 JC1407701)+1 种基金Shanghai Nature Science Foundation, China (No.08ZR1413900)Shanghai Leading Academic Discipline Project, China(No.S30205)
文摘Rho-associated kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase RhoA. The Rho/ROCK pathway is closely related to the pathogenesis of several central nervous system (CNS) disorders, and involved in many aspects of neuronal functions including neurite outgrowth and retraction. In the adult CNS, the damaged neuron regeneration is very difficult due to the presence of myelin-associated axon growth inhibitors such as Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (Omgp), etc. The effects of these axon growth inhibitors are reversed by blocking the Rho/ROCK pathway 47 vitro, and the inhibition of Rho/ROCK pathway can promote axon regeneration and functional recovery in the injured CNS in viva In addition, the therapeutic effects of the Rho/ROCK inhibitors have also been demonstrated in some animal models and the Rho/ROCK pathway becomes an attractive target for the development of drugs for treating CNS disorders. In this review, we summarized on the effect of the Rho and the downstream factor ROCK in neural regeneration, and the potential therapeutic effect of Rho/ROCK inhibitors in the survival and axonal regeneration of retinal ganglion cell was also discussed.
基金supported by a grant from the Natural Science Foundation of China(41271044)
文摘To characterize effects of plant roots on preferential flow(PF),we measured root length density(RLD)and root biomass(RB) in Jiufeng National Forest Park,Beijing,China.Comparisons were made for RLD and RB between soil preferential pathways and soil matrices.RLD and RB declined with the increasing soil depth(0–10,10–20,20–30,30–40,40–50,50–60 cm) in all experimental plots.RLD was greater in soil preferential pathways than in the surrounding soil matrix and was 69.5,75.0 and72.2 % for plant roots of diameter(d) /1,1 / d / 3 and3 / d / 5 mm,respectively.Fine root systems had the most pivotal influence on soil preferential flow in this forest ecosystem.In all experimental plots,RB content was the sum of RB from soil preferential pathways and the soil matrix in each soil depth.With respect to 6 soil depth gradient(0–10,10–20,20–30,30–40,40–50,50–60 cm) in each plot,the number of soil depth gradient that RB content was greater in soil preferential pathways than in the soil matrix was characterized,and the proportion was68.2 % in all plots.
文摘An active stereo vision system based on a model of neural pathways of human binocular motor system is proposed. With this model, it is guaranteed that the two cameras of the active stereo vision system can keep their lines of sight fixed on the same target object during smooth pursuit. This feature is very important for active stereo vision systems, since not only 3D reconstruction needs the two cameras have an overlapping field of vision, but also it can facilitate the 3D reconstruction algorithm. To evaluate the effectiveness of the proposed method, some software simulations are done to demonstrate the same target tracking characteristic in a virtual environment apt to mistracking easily. Here, mistracking means two eyes track two different objects separately. Then the proposed method is implemented in our active stereo vision system to perform real tracking task in a laboratory scene where several persons walk self-determining. Before the proposed model is implemented in the system, mistracking occurred frequently. After it is enabled, mistracking never occurred. The result shows that the vision system based on neural pathways of human binocular motor system can reliably avoid mistracking.
文摘Neural degeneration is a very complicated process. In spite of all the advancements in the molecular chemistry, there are many unknown aspects of the phenomena of neurodegeneration which need to be put together. It is a common sequela of the conditions of niacin deficiency. Neural degeneration in Pellagra manifests as chromatolysis mainly in pyramidal followed by other neurons and glial cells. However, there is a gross lack of understanding of biochemi- cal mechanisms of neurodegeneration in niacin deficiency states. Because of the necessity of niacin or its amide derivative NAD in a number of biochemical pathways, it is understandable that several of these pathways may be involved in the common outcome of neural degener- ation. Here, we highlight five pathways that could be involved in the neuraldegeneration for which evidence has accumulated through several studies. These pathways are: 1) the trypto- phan-kyneurenic acid pathway, 2) the mitochondrial ATP generation related pathways, 3) the poly (ADP-ibose) polymerase (PARP) pathway, 4) the BDNF-TRKB Axis abnormalities, 5) the genetic influences of niacin deficiency.
文摘In this study,the hypothesis that Wnt/β-catenin pathway is involved in the arterial calcification by regulating the osteoprotegerin(OPG)/receptor activator of NF-κB ligand(RANKL)system was tested.Theβ-catenin expression was measured in the warfarin-induced calcified arteries and the osteoblast-like cells differentiating from smooth muscle cells(SMCs)by immunohistochemistry and Western blotting.The Wnt/β-catenin pathway was activated or inhibited by lithium chloride(LiCl)or dickkopf 1(DKK1)in vitro and in vivo.Then the calcification level was determined by von Kossa staining,Ca^2+content assay,and alkaline phosphatase(ALP)activity assay.The expression levels of osteocalcin,OPG and RANKL were detected by Western blotting or real-time PCR.The results showed that in calcified arteries and OBL cells,the activation of Wnt/β-catenin pathway significantly enhanced the calcification as evidenced by increased von Kossa stains,Ca^2+contcnts,ALP activities,and osteocalcin expression levels(P<0.05),and it promoted the RANKL expression(P<0.05),but slightly affected the OPG expression.These results indicated that the activation of Wnt/β-catenin pathway worsens the arterial calcification,probably by promoting the RANKL expression.
文摘Computational systems biology approaches provide insights to understand complex molecular phenomena in living systems. Such understanding demands the need to systematically interrogate and review existing literature to refine and distil key molecular pathways. This paper explores a methodological process to identify key molecular pathways from systematic bioinformatics literature review. This process is used to identify molecular pathways for a ubiquitous molecular process in all plant biological systems: C1 metabolism and formaldehyde detoxification, specific to maize. The C1 metabolism is essential for all organisms to provide one-carbon units for methylation and other types of modifications, as well as for nucleic acid, amino acid, and other biomolecule syntheses. Formaldehyde is a toxic one-carbon molecule which is produced endogenously and found in the environment, and whose detoxification is an important part of C1 metabolism. This systematic review involves a five-part process: 1) framing of the research question;2) literature collection based on a parallel search strategy;3) relevant study selection based on search refinement;4) molecular pathway identification;and 5) integration of key molecular pathway mechanisms to yield a well-defined set molecular systems associated with a particular biochemical function. Findings from this systematic review produced three main molecular systems: a) methionine biosynthesis;b) the methylation cycle;and c) formaldehyde detoxification. Specific insights from the resulting molecular pathways indicate that normal C1 metabolism involves the transfer of a carbon group from serine through a folate-mediated pathway to methionine, and eventually the methylation of a biomolecule. In photosynthetic tissues, C1 metabolism often proceeds in reverse towards serine biosynthesis and formate oxidation. C1 metabolism, in maize, appears to be present in the developing embryo and endosperm indicating that these cells are vulnerable to perturbations in formaldehyde detoxification. These insights demonstrate the value of a systematic bioinformatics literature review process from a broad spectrum of domain literature to specific and relevant molecular pathways.
基金supported by the National Key Technology R&D Program of China (2016YFD0401201)the National Natural Science Foundation of China (31801602 and 31571897)+1 种基金the Project of Tianjin Education Commission Scientific Research Plan, China (2018KJ094)the National Science and Technology Major Project of China (2018ZX10101003-002-004)。
文摘While SlPti5 has been shown to play a crucial role in the regulation of antagonistic genes in Solanum lycopersicum and Arabidopsis against pathogen infection,there have been no comprehensive studies on the effects of SlPti5 on the regulatory response mechanism of reactive oxygen species(ROS) system and hormone pathways during growth and disease resistance of tomato plants.Here,we investigated the function of SlPti5 in the defense response of tomato against Botrytis cinerea utilizing a virus-induced gene silencing(VIGS)-based system.Expression profile analysis showed that SlPti5 was significantly induced upon B.cinerea infection,with high expression levels in the leaves and fruit of tomato.VIGS-based silencing of SlPti5 inhibited early vegetative growth,increased the plant’s susceptibility to infection,promoted the development of ROS,affected the expression of genes involved in the ROS scavenging system,and attenuated the expression of genes associated with pathogenesis and the ethylene/jasmonic acid signaling pathways.In sum,our data demonstrated that SlPti5 stimulates the immune response of tomato plant to Botrytis cinerea infection by involving the ethylene(ET)-and jasmonic acid(JA)-mediated pathways and modulating the expression of some key pathogenesis-related(PR) genes.
基金Foundation:Directorate General of Higher Education(DGHE),National Education Ministry Republic of Indonesia
文摘AIM: To evaluate effect of hypertension on retinal ganglion cell(RGC) apoptosis, intraocular pressure(IOP),and the activation of endothelin-1(ET-1) signaling pathway in central retinal artery(CRA) in rats.METHODS: The experimental study was performed on20 male Sprague Dawley rats that were divided into control group, and hypertension groups. The hypertension was induced by subcutaneous deoxycorticoacetate(DOCA)10 mg/kg twice a week and administered 0.9% Na Cl solution daily for 2, 6, and 10 wk. Blood pressure(BP) was measured using animal BP analyzer. IOP was measured by handheld tonometry. Retinal tissue preparations by paraffin blocks were made after enucleation. The expression of ET-1, e NOS, ET-1 receptor A(ETRA), ET-1receptor B(ETRB), and phosphorylated myosin light chain kinase(MLCK), and caldesmon(Ca D) in CRA and RGC apoptosis were evaluated through immunofluorescent staining method then observed using laser scanning confocal microscopy. RESULTS: BP significantly increased in all of the hypertension groups compared to control(P =0.001).Peak IOP elevation(7.78±4.14 mm Hg) and RGC apoptosis(576.15±33.28 Au) occurred on 2wk of hypertension. ET-1expression(1238.6±55.1 Au) and e NOS expression(2814.2±70.7 Au) were found highest in 2wk of hypertension,although the ratio of ET-1/e NOS decreased since 2wk.ETRAreached peak expression in 10 wk of hypertension(1219.4 ±6.3 Au), while ETRBsignificantly increased only in 2 weeks group(1069.2 ±9.6 Au). The highest MLCK expression(1190.09±58.32 Au), Ca D(1670.28±18.36 Au)were also found in 2wk of hypertension.CONCLUSION: Hypertension effects to activation of ET-1 signaling pathway significantly in CRA, elevation of IOP, and RGC apoptosis. The highest value was achieved at 2wk, which is the development phase of hypertension.
文摘<strong>Background:</strong> Clinical pathways are effective in reducing healthcare cost and standardizing management protocol for diseases and conditions. However, there are no standardized pathways for appendicitis. This study aims to determine whether implementation of a standardized clinical pathway for managing appendicitis may lead to improved patient care. <strong>Materials and Methods:</strong> We searched for articles published in PubMed, MEDLINE, and Cochrane library between 1974 and 2015. Thirty-seven papers published in English that met inclusion criteria were included and analyzed in this review. A total of 37 studies met inclusion criteria and were analyzed for the purpose of this study. <strong>Results:</strong> A clear definition for appendicitis pathway was observed in 30 articles. Appendicitis was diagnosed based on clinical and laboratory findings;however, 34% of the studies included radiological investigations. Sixteen studies provided clear definitions for discharge criteria. Time of follow-up (5 - 28 days) was reported in 10 studies. Operative time was the most commonly used outcome measure. The mean length of stay for non-complicated appendicitis was 1.3 days, and 6.26 days for complicated appendicitis. Most of the studies concluded that the accuracy of a clinical pathway for appendicitis diagnosis can be achieved by assessing the incidence of a normal appendix. The mean cost for patient care was $4874.14 (SAR 18,278.03). <strong>Conclusion:</strong> There was no standardized definition for appendicitis clinical pathway components. Studies suggested that establishing a clinical pathway for appendicitis improves the outcome and minimizes the cost.
基金Supported by National Natural Science Foundation of China,No.82074450Education Department of Hunan Province,No.21A0243,No.21B0374,No.22B0397,and No.22B0392+2 种基金Research Project of"Academician Liu Liang Workstation"of Hunan University of Traditional Chinese Medicine,No.21YS003Hunan Administration of Traditional Chinese Medicine,No.B2023001 and No.B2023009Hunan Provincial Natural Science Foundation of China,No.2023JJ40481。
文摘BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which is indicated for the treatment of liver cancer.However,its impact on the liver cancer tumor microenvironment,particularly on tumor-associated macrophages(TAMs),is not well understood.AIM To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/β-catenin pathway modulation.METHODS This study identified the active components of CB using UPLC-Q-TOF-MS,evaluated its anti-neoplastic effects in a nude mouse model,and elucidated the underlying mechanisms via network pharmacology,transcriptomics,and molecular docking.In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs,and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis.RESULTS This study identified 22 active components in CB,11 of which were detected in the bloodstream.Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth.An integrated approach employing network pharmacology,transcriptomics,and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization.In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/β-catenin pathway activation.The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001,confirming its pathway specificity.CONCLUSION This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/β-catenin pathway,contributing to the suppression of liver cancer growth.