Regeneration of the heart:f rom molecular mechanisms to clinical therapeutics

Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health burden.Military personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military medicine.So far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart regeneration.In the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury.Insights have emerged from studies in animal models and early clinical trials.Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease.In this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.

Hydrocarbon Generation Potential and Organic Matter Enrichment Mechanism of the Cambrian Marine Shale in the Tadong Low Uplift,Tarim Basin

Cambrian shales in China and elsewhere contain abundant oil and gas resources.However,due to its deep burial and limited outcrop,there has been relatively little research conducted on it.The Cambrian shale of the Tadong low uplift in the Tarim Basin of western China,specifically the Xidashan-Xishanbulake Formation(Fm.)and overlying Moheershan Fm.provide a case study through the use of organic petrology,mineralogy,organic and elemental geochemistry,with the aim of analyzing and exploring the hydrocarbon generation potential(PG)and organic matter(OM)enrichment mechanisms within these shale formations.The results indicate that:(1)the Cambrian shale of the Tadong low uplift exhibits relatively dispersed OM that consists of vitrinite-like macerals and solid bitumen.These formations have a higher content of quartz and are primarily composed of silica-based lithology;(2)shale samples from the Xidashan-Xishanbulake and Moheershan formations demonstrate high total organic carbon(TOC)and low pyrolytic hydrocarbon content(S_(2))content.The OM is predominantly typeⅠand typeⅡkerogens,indicating a high level of maturation in the wet gas period.These shales have undergone extensive hydrocarbon generation,showing characteristics of relatively poor PG;(3)the sedimentary environments of the Xidashan-Xishanbulake and Moheershan formations in the Tadong low uplift are similar.They were deposited in warm and humid climatic conditions,in oxygen-deficient environments,with stable terrigenous inputs,high paleoproductivity,high paleosalinity,weak water-holding capacity,and no significant hydrothermal activity;and(4)the relationship between TOC and the paleoproductivity parameter(P/Ti)is most significant in the Lower Cambrian Xidashan-Xishanbulake Fm.,whereas correlation with other indicators is not evident.This suggests a productivity-driven OM enrichment model,where input of landderived material was relatively small during the Middle Cambrian,and the ancient water exhibited lower salinity.A comprehensive pattern was formed under the combined control of paleoproductivity and preservation conditions.This study provides valuable guidance for oil and gas exploration in the Tarim Basin.

Enhancing Image Description Generation through Deep Reinforcement Learning:Fusing Multiple Visual Features and Reward Mechanisms

Image description task is the intersection of computer vision and natural language processing,and it has important prospects,including helping computers understand images and obtaining information for the visually impaired.This study presents an innovative approach employing deep reinforcement learning to enhance the accuracy of natural language descriptions of images.Our method focuses on refining the reward function in deep reinforcement learning,facilitating the generation of precise descriptions by aligning visual and textual features more closely.Our approach comprises three key architectures.Firstly,it utilizes Residual Network 101(ResNet-101)and Faster Region-based Convolutional Neural Network(Faster R-CNN)to extract average and local image features,respectively,followed by the implementation of a dual attention mechanism for intricate feature fusion.Secondly,the Transformer model is engaged to derive contextual semantic features from textual data.Finally,the generation of descriptive text is executed through a two-layer long short-term memory network(LSTM),directed by the value and reward functions.Compared with the image description method that relies on deep learning,the score of Bilingual Evaluation Understudy(BLEU-1)is 0.762,which is 1.6%higher,and the score of BLEU-4 is 0.299.Consensus-based Image Description Evaluation(CIDEr)scored 0.998,Recall-Oriented Understudy for Gisting Evaluation(ROUGE)scored 0.552,the latter improved by 0.36%.These results not only attest to the viability of our approach but also highlight its superiority in the realm of image description.Future research can explore the integration of our method with other artificial intelligence(AI)domains,such as emotional AI,to create more nuanced and context-aware systems.

Generation Mechanism and Social Impact of Knowledge in the Era of"New Quality Productivity"

The changes in knowledge forms in the era of"new quality productivity"are closely related to the development of society.With the rise of the Internet,"the world of dataism is coming".The traditional knowledge production model is undergoing fundamental changes in structure and nature.The most prominent change is that knowledge is becoming increasingly inseparable from data networks.The collaborative production of knowledge based on the Internet is becoming increasingly common,and Wikipedia is a prominent example of this.Wikipedia makes the networked production of knowledge possible by utilizing collective intelligence and data connectivity.Wiki users are commonly referred to as"wiki".This paper conducted interviews with 30 Wiki users and used content analysis to statistically analyze the interview records,in order to study the significance and value of the Wiki knowledge production model for online users,and to glimpse the impact of the knowledge structure changes in the era of"dataism"on social change.

Contribution of mechanical forces to structural synaptic plasticity:insights from 3D cellular motility mechanisms

Cells,tissues,and organs are constantly subjected to the action of mechanical forces from the extracellular environment-and the nervous system is no exception.Cell-intrinsic properties such as membrane lipid composition,abundance of mechanosensors,and cytoskeletal dynamics make cells more or less likely to sense these forces.Intrinsic and extrinsic cues are integrated by cells and this combined information determines the rate and dynamics of membrane protrusion growth or retraction(Yamada and Sixt,2019).Cell protrusions are extensions of the plasma membrane that play crucial roles in diverse contexts such as cell migration and neuronal synapse formation.In the nervous system,neurons are highly dynamic cells that can change the size and number of their pre-and postsynaptic elements(called synaptic boutons and dendritic spines,respectively),in response to changes in the levels of synaptic activity through a process called plasticity.Synaptic plasticity is a hallmark of the nervous system and is present throughout our lives,being required for functions like memory formation or the learning of new motor skills(Minegishi et al.,2023;Pillai and Franze,2024).

MET receptor tyrosine kinase promotes the generation of functional synapses in adult cortical circuits

Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse function.We have previously shown that MET receptor tyrosine kinase in the developing cortical circuits promotes dendritic growth and dendritic spine morphogenesis.To investigate whether enhancing MET in adult cortex has synapse regenerating potential,we created a knockin mouse line,in which the human MET gene expression and signaling can be turned on in adult(10–12 months)cortical neurons through doxycycline-containing chow.We found that similar to the developing brain,turning on MET signaling in the adult cortex activates small GTPases and increases spine density in prefrontal projection neurons.These findings are further corroborated by increased synaptic activity and transient generation of immature silent synapses.Prolonged MET signaling resulted in an increasedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-Daspartate(AMPA/NMDA)receptor current ratio,indicative of enhanced synaptic function and connectivity.Our data reveal that enhancing MET signaling could be an interventional approach to promote synaptogenesis and preserve functional connectivity in the adult brain.These findings may have implications for regenerative therapy in aging and neurodegeneration conditions.

Decoding molecular mechanisms:brain aging and Alzheimer's disease

The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.

Pyroptosis,ferroptosis,and autophagy in spinal cord injury:regulatory mechanisms and therapeutic targets

Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.

Generation of scale-free knowledge network with local world mechanism

In order to simulate the real growing process, a new type of knowledge network growth mechanism based on local world connectivity is constructed. By the mean-field method, theoretical prediction of the degree distribution of the knowledge network is given, which is verified by Matlab simulations. When the new added node＇s local world size is very small, the degree distribution of the knowledge network approximately has the property of scale-free. When the new added node＇s local world size is not very small, the degree distribution transforms from pure power-law to the power-law with an exponential tailing. And the scale-free index increases as the number of new added edges decreases and the tunable parameters increase. Finally, comparisons of some knowledge indices in knowledge networks generated by the local world mechanism and the global mechanism are given. In the long run, compared with the global mechanism, the local world mechanism leads the average knowledge levels to slower growth and brings homogenous phenomena.

Status of research on biogenic coalbed gas generation mechanisms

Biogenic coalbed gas,how it is generated and the geochemical characteristics of the gas are gaining global attention.The ways coalbed gas is generated,the status of research on the generation mechanism and the methods of differentiating between biogenic gasses are discussed.The generation of biogenic coalbed methane is consistent with anaerobic fermentation theory.Commercial biogenic coalbed gas reservoirs are mainly generated by the process of CO2 reduction.The substrates used by the microbes living in the coal include organic compounds,CO2,H2 and acetate.The production ratio and quantity of biogenic coalbed methane depend on the exposed surface area,the solubility and permeability of the coal and the microbial concentration in the coal seam.It is generally believed that biogenic coalbed gas has a value for δ13C1<-5.5%,C1/C1+>0.95.The H isotope ratio is controlled by both the environment and the generation mechanism:typically δD1<-20%.Biogenic methane formed by CO2 reduction has more δD1 than that formed by acetate fermentation.

Diversified roles of mineral transformation in controlling hydrocarbon generation process,mechanism,and pattern

Organic matter(OM)is intimately associated with minerals in clay-rich mudstones,leading to widespread organic-mineral interaction during hydrocarbon generation in argillaceous source rocks.What we are concerned is the effects of the different mineral properties on hydrocarbon generation process and mechanism during mineral transformation.In this way,pyrolysis experiments with smectite-octadecanoic acid complexes(Sm-OA and Ex-Sm-OA)were conducted to analyze correlation of mineralogy and pyrolysis behaviors.Based on organicmineral interaction,hydrocarbon generation process was divided into three phases.At 200–300℃,collapse of smectite led to desorption of OM,resulting in high yield of resin and slight increase in saturates.Subsequently,enhanced smectite illitization at 350–450℃was accompanied with large amounts of saturates and a mere gaseous hydrocarbon.Featured by neoformed plagioclase,ankerite,and illite,500C saw plenty of asphaltene and methane-rich gaseous hydrocarbons,revealing cracking reactions of OM.Noteworthy is that saturated and gaseous hydrocarbons in Ex-Sm-OA were considerably more than that in Sm-OA during second and third phases.Quantitative calculation of hydrogen revealed organic hydrogen provided by cross-linking of OM could not balance hydrogen consumed by cracking reactions,but supply of inorganic hydrogen ensured cracking could readily occur and consequently greatly promoted hydrocarbon generation.Further investigating characteristics of mineralogy and pyrolytic products,as well as effects of solid acidity on hydrocarbon generation,we concluded desorption of OM and decarboxylation promoted by Lewis acid were dominated at 200–300C,resulting in lowdegree hydrocarbon generation.While high yield of saturated and gaseous hydrocarbons in second and third phases,together with occurrence of ankerite,indicated predominance of decarboxylation and hydrogenation promoted by Lewis and Brønsted acid,respectively.Variations in organic-mineral interactions indicated(1)the controls of mineral transformation on hydrocarbon generation process and mechanism include desorption,decarboxylation,and hydrogenation reactions;(2)clay minerals acted as reactants evolving together with OM rather than catalysts.These findings are profoundly significant for understanding the hydrocarbon generation mechanisms,organic-inorganic interactions,and carbon cycle.

Mathematical Model and Geometrical Model of Double Pitch ZN-type Worm Gear Set Based on Generation Mechanism

The current researches on the tooth surface mathematical equations and the theory of gearing mainly pay attention to the ordinary type worm gear set（e.g., ZN, ZA, or ZK）. The research of forming mechanism and three-dimensional modeling method for the double pitch worm gear set is not enough. So there are some difficulties in mathematical model deducing and geometry modeling of double pitch ZN-type worm gear set based on generation mechanism. In order to establish the mathematical model and the precise geometric model of double pitch ZN-type worm gear set, the structural characteristics and generation mechanism of the double pitch ZN-type worm gear set are investigated. Mathematical model of the ZN-type worm gear set is derived based on its generation mechanism and the theory of gearing. According to the mathematical model of the worm gear set which has been developed, a geometry modeling method of the double pitch ZN-type worm and worm gear is presented. Furthermore, a geometrical precision calculate method is proposed to evaluate the geometrical quality of the double pitch worm gear set. As a result, the maximum error is less than 6′10–4 mm in magnitude, thus the model of the double pitch ZN-type worm gear set is available to meet the requirements of finite element analysis and engineering application. The derived mathematical model and the proposed geometrical modeling method are helpful to guiding the design, manufacture and contact analysis of the worm gear set.

EXPERIMENTAL INVESTIGATION ON GENERATION MECHANISM OF EXPLOSIVE STRESS WAVES

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Analysis on Physical Mechanism of Sound Generation inside Cavities Based on Acoustic Analogy Method

Analysis of coupling aerodynamics and acoustics are performed to investigate the self-sustained oscillation and aerodynamic noise in two-dimensional flow past a cavity with length to depth ratio of 2 at subsonic speeds. The large eddy simulation (LES) equations and integral formulation of Ffowcs-Williams and Hawings (FW-H) are solved for the cavity with same conditions as experiments. The obtained density-field agrees well with Krishnamurty’s experimental schlieren photograph, which simulates flow-field distributions and the direction of sound wave radiation. The simulated self-sustained oscillation modes inside the cavity agree with Rossiter’s and Heller’s predicated results, which indicate frequency characteristics are obtained. Moreover, the results indicate that the feedback mechanism that new shedding-vortexes induced by propagation of sound wave created by the impingement of the shedding-vortexes in the shear-layer and rear cavity face leads to self-sustained oscillation and high noise inside the cavity. The peak acoustic pressure occurs in the first oscillation mode and the most of sound energy focuses on the low-frequency region.

Hydrocarbon generation and storage mechanisms of deepwater shelf shales of Ordovician Wufeng Formation–Silurian Longmaxi Formation in Sichuan Basin, China

As the hydrocarbon generation and storage mechanisms of high quality shales of Upper Ordovician Wufeng Formation– Lower Silurian Longmaxi Formation remain unclear, based on geological conditions and experimental modelling of shale gas formation, the shale gas generation and accumulation mechanisms as well as their coupling relationships of deep-water shelf shales in Wufeng–Longmaxi Formation of Sichuan Basin were analyzed from petrology, mineralogy, and geochemistry. The high quality shales of Wufeng–Longmaxi Formation in Sichuan Basin are characterized by high thermal evolution, high hydrocarbon generation intensity, good material base, and good roof and floor conditions;the high quality deep-water shelf shale not only has high biogenic silicon content and organic carbon content, but also high porosity coupling. It is concluded that:(1) The shales had good preservation conditions and high retainment of crude oil in the early times, and the shale gas was mainly from cracking of crude oil.(2) The biogenic silicon(opal A) turned into crystal quartz in early times of burial diagenesis, lots of micro-size intergranular pores were produced in the same time;moreover, the biogenic silicon frame had high resistance to compaction, thus it provided the conditions not only for oil charge in the early stage, but also for formation and preservation of nanometer cellular-like pores, and was the key factor enabling the preservation of organic pores.(3) The high quality shale of Wufeng–Longmaxi Formation had high brittleness, strong homogeneity, siliceous intergranular micro-pores and nanometer organic pores, which were conducive to the formation of complicated fissure network connecting the siliceous intergranular nano-pores, and thus high and stable production of shale gas.

Characterization of Metal Oxide-modified Walnut-shell Activated Carbon and Its Application for Phosphine Adsorption: Equilibrium, Regeneration, and Mechanism Studies

We prepared a kind of metal oxide-modified walnut-shell activated carbon(MWAC) by KOH chemical activation method and used for PH_3 adsorption removal. Meanwhile, the PH_3 adsorption equilibrium was investigated experimentally and fitted by the Toth equation, and the isosteric heat of PH_3 adsorption was calculated by the Clausius-Clapeyron Equation. The exhausted MWAC was regenerated by water washing and air drying. Moreover, the properties of five different samples were characterized by N_2 adsorption isotherm, SEM/EDS, XPS, and FTIR. The results showed that the maximum PH_3 equilibrium adsorption capacity was 595.56 mg/g. The MWAC had an energetically heterogeneous surface due to values of isosteric heat of adsorption ranging from 43 to 90 kJ/mol. The regeneration method provided an effective way for both adsorption species recycling and exhausted carbon regeneration. The high removal efficiency and big equilibrium adsorption capacity for PH_3 adsorption on the MWAC were related to its large surface area and high oxidation activity in PH_3 adsorption-oxidation to H_3 PO_4 and P_2 O_5. Furthermore, a possible PH_3 adsorption mechanism was proposed.

Mechanism of generation of large(Ti,Nb,V)(C,N)-type precipitates in H13 + Nb tool steel

The characteristics and generation mechanism of（Ti,Nb,V）（C,N） precipitates larger than 2 μm in Nb-containing H13 bar steel were studied. The results show that two types of（Ti,Nb,V）（C,N） phases exist—a Ti-V-rich one and an Nb-rich one—in the form of single or complex precipitates. The sizes of the single Ti-V-rich（Ti,Nb,V）（C,N） precipitates are mostly within 5 to 10 μm, whereas the sizes of the single Nb-rich precipitates are mostly 2–5 μm. The complex precipitates are larger and contain an inner Ti-V-rich layer and an outer Nb-rich layer. The compositional distribution of（Ti,Nb,V）（C,N） is concentrated. The average composition of the single Ti-V-rich phase is（Ti_（0.511）V_（0.356）Nb_（0.133））（CxNy）, whereas that for the single Nb-rich phase is（Ti_（0.061）V_（0.263）Nb_（0.676））（C_xN_y）. The calculation results based on the Scheil–Gulliver model in the Thermo-Calc software combining with the thermal stability experiments show that the large phases precipitate during the solidification process. With the development of solidification, the Ti-V-rich phase precipitates first and becomes homogeneous during the subsequent temperature reduction and heat treatment processes. The Nb-rich phase appears later.

Consortium Chain Consensus Vulnerability and Chain Generation Mechanism

Effectively identifying and preventing the threat of Byzantine nodes to the security of distributed systems is a challenge in applying consortium chains.Therefore,this paper proposes a new consortium chain generation model,deeply analyzes the vulnerability of the consortium chain consensus based on the behavior of the nodes,and points out the effects of Byzantine node proportion and node state verification on the consensus process and system security.Furthermore,the normalized verification node aggregation index that represents the consensus ability of the consortium organization and the trust evaluation function of the verification node set is derived.When either of the two is lower than the threshold,the consortium institution or the verification node set members are dynamically adjusted.On this basis,an innovative consortium chain generation mechanism based on the Asynchronous Binary Byzantine Consensus Mechanism(ABBCM)is proposed.Based on the extended consortium chain consensus mechanism,a certain consensus value set can be combined into multiple proposals,which can realize crossdomain asynchronous message passing between multi-consortium chains without reducing the system’s security.In addition,experiments are carried out under four classical Byzantine Attack(BA)behaviors,BA1 to BA4.The results show that the proposed method can obtain better delay than the classical random Byzantine consensus algorithm Coin,effectively improving the consensus efficiency based on asynchronous message passing in the consortium chain and thus meeting the throughput of most Internet of Things(IoT)applications.

Formation mechanism of tight sandstone gas in areas of low hydrocarbon generation intensity: A case study of the Upper Paleozoic in north Tianhuan depression in Ordos Basin, NW China

The Upper Paleozoic in the north part of Tianhuan depression in the Ordos Basin,NW China has lower hydrocarbon generation intensity and complex gas-water relationship,the main factors controlling the formation of tight sandstone gas and the distribution of tight sandstone gas in the low hydrocarbon generation intensity area are studied.Through two-dimensional physical simulation experiment of hydrocarbon accumulation,analysis of reservoir micro-pore-throat hydrocarbon system and dissection of typical gas reservoirs,the evaluation models of gas injection pressure,reservoir physical property,and gas generation threshold were established to determine the features of tight gas reservoirs in low hydrocarbon intensity area:(1)at the burial depth of less than 3 000 m,the hydrocarbon generation intensity ofis high enough to maintain effective charging;(2)tight sandstone in large scale occurrence is conducive to accumulation of tight gas;(3)differences in reservoir physical property control the distribution of gas pool,for the channel sandstone reservoirs,ones with better physical properties generally concentrate in the middle of sandstone zone and local structural highs;ones with poor physical properties have low gas content generally.Based on the dissection of the gas reservoir in the north Tianhuan depression,the formation of tight gas reservoirs in low hydrocarbon generating intensity area are characterized by"long term continuous charging under hydrocarbon generation pressure,gas accumulation in large scale tight sandstone,pool control by difference in reservoir physical property,and local sweet spot",and the tight gas pools are distributed in discontinuous"sheets"on the plane.This understanding has been proved by expanding exploration of tight sandstone gas in the north Tianhuan depression.

Saline-Alkali(Mixed) Dust Storms and Their Main Generation Mechanism

The exposed surface of the dry salt lake basin contains a large number of extremely fine lightweight saline-alkali(mixed)dust and clay dust.It is extremely easy to dust and since saline-alkali lake is low-lying and its temperature