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.

The underlying mechanism of variety–water–nitrogen–stubble damage interactions on yield formation in ratoon rice with low stubble height under mechanized harvesting

Agronomic measures are the key to promote the sustainable development of ratoon rice by reducing the damage from mechanical crushing to the residual stubble of the main crop, thereby mitigating the impact on axillary bud sprouting and yield formation in ratoon rice. This study used widely recommended conventional rice Jiafuzhan and hybrid rice Yongyou 2640 as the test materials to conduct a four-factor block design field experiment in a greenhouse of the experimental farm of Fujian Agricultural and Forestry University, China from 2018 to 2019.The treatments included fertilization and no fertilization, alternate wetting and drying irrigation and continuous water flooding irrigation, and plots with and without artificial crushing damage on the rice stubble. At the same time, a 13C stable isotope in-situ detection technology was used to fertilize the pot experiment. The results showed significant interactions among varieties, water management, nitrogen application and stubble status.Relative to the long-term water flooding treatment, the treatment with sequential application of nitrogen fertilizer coupled with moderate field drought for root-vigor and tiller promotion before and after harvesting of the main crop, significantly improved the effective tillers from low position nodes. This in turn increased the effective panicles per plant and grains per panicle by reducing the influence of artificial crushing damage on rice stubble and achieving a high yield of the regenerated rice. Furthermore, the partitioning of 13C assimilates to the residual stubble and its axillary buds were significantly improved at the mature stage of the main crop, while the translocation rate to roots and rhizosphere soil was reduced at the later growth stage of ratooning season rice. This was triggered by the metabolism of hormones and polyamines at the stem base regulated by the interaction of water and fertilizer at this time. We therefore suggest that to achieve a high yield of ratoon rice with low stubble height under mechanized harvesting, the timely application of nitrogen fertilizer is fundamental,coupled with moderate field drying for root-vigor preservation and tiller promotion before and after the mechanical harvesting of the main crop.

To explore the mechanism of Yigong San anti-gastric cancer and immune regulation

BACKGROUND Yigong San(YGS)is a representative prescription for the treatment of digestive disorders,which has been used in clinic for more than 1000 years.However,the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear.AIM To explore the mechanism of YGS anti-gastric cancer and immune regulation.METHODS Firstly,collect the active ingredients and targets of YGS,and the differentially expressed genes of gastric cancer.Secondly,constructed a protein-protein interaction network between the targets of drugs and diseases,and screened hub genes.Then the clinical relevance,mutation and repair,tumor microenvironment and drug sensitivity of the hub gene were analyzed.Finally,molecular docking was used to verify the binding ability of YGS active ingredient and hub genes.RESULTS Firstly,obtained 55 common targets of gastric cancer and YGS.The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6,EGFR,MMP2,MMP9 and TGFB1 as the hub genes.The 5 hub genes were involved in gastric carcinogenesis,staging,typing and prognosis,and their mutations promote gastric cancer progression.Finally,molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets.CONCLUSION YGS has the effect of anti-gastric cancer and immune regulation.

Deep Insight of Design,Mechanism,and Cancer Theranostic Strategy of Nanozymes

Since the discovery of enzyme-like activity of Fe3O4 nanoparticles in 2007,nanozymes are becoming the promising substitutes for natural enzymes due to their advantages of high catalytic activity,low cost,mild reaction conditions,good stability,and suitable for large-scale production.Recently,with the cross fusion of nanomedicine and nanocatalysis,nanozyme-based theranostic strategies attract great attention,since the enzymatic reactions can be triggered in the tumor microenvironment to achieve good curative effect with substrate specificity and low side effects.Thus,various nanozymes have been developed and used for tumor therapy.In this review,more than 270 research articles are discussed systematically to present progress in the past five years.First,the discovery and development of nanozymes are summarized.Second,classification and catalytic mechanism of nanozymes are discussed.Third,activity prediction and rational design of nanozymes are focused by highlighting the methods of density functional theory,machine learning,biomimetic and chemical design.Then,synergistic theranostic strategy of nanozymes are introduced.Finally,current challenges and future prospects of nanozymes used for tumor theranostic are outlined,including selectivity,biosafety,repeatability and stability,in-depth catalytic mechanism,predicting and evaluating activities.

Recent research progress in the mechanism and suppression of fusion welding-induced liquation cracking of nickel based superalloys

Nickel-based superalloys are extensively used in the crucial hot-section components of industrial gas turbines,aeronautics,and astronautics because of their excellent mechanical properties and corrosion resistance at high temperatures.Fusion welding serves as an effective means for joining and repairing these alloys;however,fusion welding-induced liquation cracking has been a challenging issue.This paper comprehensively reviewed recent liquation cracking,discussing the formation mechanisms,cracking criteria,and remedies.In recent investigations,regulating material composition,changing the preweld heat treatment of the base metal,optimizing the welding process parameters,and applying auxiliary control methods are effective strategies for mitigating cracks.To promote the application of nickel-based superalloys,further research on the combination impact of multiple elements on cracking prevention and specific quantitative criteria for liquation cracking is necessary.

Preliminary discussion on the ignition mechanism of exploding foil initiators igniting boron potassium nitrate

Exploding foil initiator(EFI)is a kind of advanced device for initiating explosives,but its function is unstable when it comes to directly igniting pyrotechnics.To solve the problem,this research aims to reveal the ignition mechanism of EFIs directly igniting pyrotechnics.An oscilloscope,a photon Doppler velocimetry,and a plasma spectrum measurement system were employed to obtain information of electric characteristics,impact pressure,and plasma temperature.The results of the electric characteristics and the impact pressure were inconsistent with ignition results.The only thing that the ignition success tests had in common was that their plasma all had a relatively long period of high-temperature duration(HTD).It eventually concludes that the ignition mechanism in this research is the microconvection heat transfer rather than the shock initiation,which differs from that of exploding foil initiators detonating explosives.Furthermore,the methods for evaluating the ignition success of semiconductor bridge initiators are not entirely applicable to the tests mentioned in this paper.The HTD is the critical parameter for judging the ignition success,and it is influenced by two factors:the late time discharge and the energy of the electric explosion.The longer time of the late time discharge and the more energy of the electric explosion,the easier it is to expand the HTD,which improves the probability of the ignition success.

Unraveling the Fundamental Mechanism of Interface Conductive Network Influence on the Fast‑Charging Performance of SiO‑Based Anode for Lithium‑Ion Batteries

Progress in the fast charging of high-capacity silicon monoxide(SiO)-based anode is currently hindered by insufficient conductivity and notable volume expansion.The construction of an interface conductive network effectively addresses the aforementioned problems;however,the impact of its quality on lithium-ion transfer and structure durability is yet to be explored.Herein,the influence of an interface conductive network on ionic transport and mechanical stability under fast charging is explored for the first time.2D modeling simulation and Cryo-transmission electron microscopy precisely reveal the mitigation of interface polarization owing to a higher fraction of conductive inorganic species formation in bilayer solid electrolyte interphase is mainly responsible for a linear decrease in ionic diffusion energy barrier.Furthermore,atomic force microscopy and Raman shift exhibit substantial stress dissipation generated by a complete conductive network,which is critical to the linear reduction of electrode residual stress.This study provides insights into the rational design of optimized interface SiO-based anodes with reinforced fast-charging performance.

Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

Role of outdoor trees on pedestrian wind and thermal conditions around a pre-education building for sustainable energy management

Finding sustainable energy resources is essential to face the increasing energy demand.Trees are an important part of ancient architecture but are becoming rare in urban areas.Trees can control and tune the pedestrian-level wind velocity and thermal condition.In this study,a numerical investigation is employed to assess the role of trees planted in the windward direction of the building complex on the thermal and pedestrian wind velocity conditions around/inside a pre-education building located in the center of the complex.Compared to the previous studies(which considered only outside buildings),this work considers the effects of trees on microclimate change both inside/outside buildings.Effects of different parameters including the leaf area density and number of trees,number of rows,far-field velocity magnitude,and thermal condition around the main building are assessed.The results show that the flow velocity in the spacing between the first-row buildings is reduced by 30%-40% when the one-row trees with 2 m height are planted 15 m farther than the buildings.Furthermore,two rows of trees are more effective in higher velocities and reduce the maximum velocity by about 50%.The investigation shows that trees also could reduce the temperature by about 1℃around the building.

Debris flow runout behaviors considering the influences of densely populated buildings

Debris flows pose serious risks to communities in mountainous areas,often resulting in large losses of human life and property.The impeding presence of urban buildings often affects the runout behavior and deposition of debris flows.But the impact of different building densities and sizes on debris flow dynamics has yet to be quantified to guide urban planning in debris flow risk zones.This study focused on a debris flow that occurred in Zhouqu County,Gansu Province,China on August 7th,2010,which was catastrophic and destroyed many buildings.The FLO-2D software was used to simulate this debris flow in two scenarios,i.e.the presence and the absence of buildings,to obtain debris-flow intensity parameters.The developed model was then used to further analyze the influence of large buildings and narrow channels within the urban environment.The simulation results show that considering the presence of buildings in the simulation is essential for accurate assessment of debris flow intensity and deposition distribution.The layout of buildings in the upstream urban area,such as large buildings or parallel buildings which form narrow channels,can affect the flow velocity and depth of debris flow heading towards downstream buildings.To mitigate damage to downstream buildings,the relative spacing(d/a)between upstream and downstream buildings should not exceed a value of two and should ideally be even lower.These findings provide valuable insights for improving the resistance of mountainous cities to urban debris flows.

Deep tectonics and seismogenic mechanisms of the seismic source zone of the Jishishan M_(s)6.2 earthquake on December 18,2023,at the northeast margin of the Tibetan Plateau

On December 18,2023,an M_(s)6.2 earthquake occurred in Jishishan,Gansu Province,China.This earthquake happened in the eastern region of the Qilian Orogenic Belt,which is situated at the forefront of the NE margin of the Tibetan Plateau(i.e.,Qinghai-Tibet Plateau),encompassing a rhombic-shaped area that intersects the Qilian-Qaidam Basin,Alxa Block,Ordos Block,and South China Block.In this study,we analyzed the deep tectonic pattern of the Jishishan earthquake by incorporating data on the crustal thickness,velocity structure,global navigation satellite system(GNSS)strain field,and anisotropy.We discovered that the location of the earthquake was related to changes in the crustal structure.The results showed that the Jishishan M_(s)6.2 earthquake occurred in a unique position,with rapid changes in the crustal thickness,Vp/Vs,phase velocity,and S-wave velocity.The epicenter of the earthquake was situated at the transition zone between high and low velocities and was in proximity to a low-velocity region.Additionally,the source area is flanked by two high-velocity anomalies from the east and west.The principal compressive strain orientation near the Lajishan Fault is primarily in the NNE and NE directions,which align with the principal compressive stress direction in this region.In some areas of the Lajishan Fault,the principal compressive strain orientations show the NNW direction,consistent with the direction of the upper crustal fast-wave polarization from local earthquakes and the phase velocity azimuthal anisotropy.These features underscore the relationship between the occurrence of the Jishishan M_(s)6.2 earthquake and the deep inhomogeneous structure and deep tectonic characteristics.The NE margin of the Tibetan Plateau was thickened by crustal extension in the process of northeastward expansion,and the middle and lower crustal materials underwent structural deformation and may have been filled with salt-containing fluids during the extension process.The presence of this weak layer makes it easier for strong earthquakes to occur through the release of overlying rigid crustal stresses.However,it is unlikely that an earthquake of comparable or larger magnitude would occur in the short term(e.g.,in one year)at the Jishishan east margin fault.

Deterioration Reason and Improvement Measure of the Retarding Effect of Protein Retarder on Phosphorus Building Gypsum

The retarding effect of protein retarder on phosphorus building gypsum(PBG)and desulfurization building gypsum(DBG)was investigated,and the results show that protein retarder for DBG can effectively prolong the setting time and displays a better retarding effect,but for PBG shows a poor retarding effect.Furthermore,the deterioration reason of the retarding effect of protein retarder on PBG was investigated by measuring the pH value and the retarder concentration of the liquid phase from vacuum filtration of PBG slurry at different hydration time,and the measure to improve the retarding effect of protein retarding on PBG was suggested.The pH value of PBG slurry(<5.0)is lower than that of DBG slurry(7.8-8.5).After hydration for 5 min,the concentration of retarder in liquid phase of DBG slurry gradually decreases,but in liquid phase of PBG slurry continually increases,which results in the worse retarding effect of protein retarder on PBG.The liquid phase pH value of PBG slurry can be adjusted higher by sodium silicate,which is beneficial to improvement in the retarding effect of the retarder.By adding 1.0%of sodium silicate,the initial setting time of PBG was efficiently prolonged from 17 to 210 min,but little effect on the absolute dry flexural strength was observed.

Antagonism effect of residual S triggers the dual-path mechanism for water oxidation

Transition metal chalcogenides(TMCs)are recognized as pre-catalysts,and their(oxy)hydroxides derived from electrochemical reconstruction are the active species in the water oxidation.However,understanding the role of the residual chalcogen in the reconstructed layer is lacking in detail,and the corresponding catalytic mechanism remains controversial.Here,taking Cu_(1-x)Co_(x)S as a platform,we explore the regulating effect and existence form of the residual S doped into the reconstructive layer for oxygen evolution reaction(OER),where a dual-path OER mechanism is proposed.First-principles calculations and operando~(18)O isotopic labeling experiments jointly reveal that the residual S in the reconstructive layer of Cu_(1-x)Co_(x)S can wisely balance the adsorbate evolution mechanism(AEM)and lattice oxygen oxidation mechanism(LOM)by activating lattice oxygen and optimizing the adsorption/desorption behaviors at metal active sites,rather than change the reaction mechanism from AEM to LOM.Following such a dual-path OER mechanism,Cu_(0.4)Co_(0.6)S-derived Cu_(0.4)Co_(0.6)OSH not only overcomes the restriction of linear scaling relationship in AEM,but also avoids the structural collapse caused by lattice oxygen migration in LOM,so as to greatly reduce the OER potential and improved stability.

Obituary:Prof.Yun Zhang(1963-2023)-A scientist focused on toxins and their underlying mechanisms to decipher human diseases

Prof.Yun Zhang was born on 9 July 1963 in Kunming,Yunnan,China,during a tumultuous period which he often referenced.Throughout his life,he harbored a steadfast belief in using knowledge to unravel the mysteries of human diseases.His educational journey was marked by frequent changes in schools due to his parents’occupational relocations.However,despite these challenges,he consistently displayed diligence and was admitted to the East China University of Science and Technology,Shanghai,after completing high school in 1980.He remained an active and loyal member of the School of Biotechnology at the university.

Building the Capacity of Health Professionals in Monitoring and Evaluation in a Public Health Institution: Experience of the National Institute of Public Health (NIPH) of Côte d’Ivoire

Background: In the context of the fight against HIV, a lack of skills in monitoring and evaluating the personnel in charge of activities has been identified at the national level. It was the subject of a priority axis of the national plan for monitoring and evaluating the fight against HIV (2006-2010) that was aimed at strengthening the capacities of actors in this area. To increase the critical mass of competent human resources in the short term, the National Institute of Public Health (NIPH) of Côte d’Ivoire organized monitoring and evaluation training sessions for healthcare professionals from 2011 to 2016. Methods: A single case study with multiple levels of analysis was carried out, combining a qualitative survey and a literature review. An evaluation was carried out six months after each training session. In addition, the results of the pre- and post-tests and of the daily and final evaluations that accompanied the various training sessions were used to provide further information. The qualitative data collected were analyzed using INVIVO 15 software. Results: Some 89 health professionals (69% men and 31% women) working at the national level (51% at the central level, including 58% in health programs) and in development partner agencies (37%) participated in this capacity building program. Most participants were senior health managers (56%), data managers (23%), and statisticians and computer scientists (10%). Almost all the trainings were financed by 16 technical and financial partners (85%), mainly the MEASURE Evaluation project (27%). Conclusion: M&E training, despite all its imperfections, has made it possible to identify M&E training needs at the national level and to increase the critical mass of national skills and to have some culture in M&E.

The pathogenic mechanism of syndactyly type V identified in aHoxd13Q50R knock-in mice

Syndactyly type V (SDTY5) is an autosomal dominant extremity malformation characterized by fusion of the fourth and fifthmetacarpals. In the previous publication, we first identified a heterozygous missense mutation Q50R in homeobox domain (HD) ofHOXD13 in a large Chinese family with SDTY5. In order to substantiate the pathogenicity of the variant and elucidate the underlyingpathogenic mechanism causing limb malformation, transcription-activator-like effector nucleases (TALEN) was employed togenerate a Hoxd13Q50R mutant mouse. The mutant mice exhibited obvious limb malformations including slight brachydactyly andpartial syndactyly between digits 2-4 in the heterozygotes, and severe syndactyly, brachydactyly and polydactyly in homozygotes.Focusing on BMP2 and SHH/GREM1/AER-FGF epithelial mesenchymal (e-m) feedback, a crucial signal pathway for limbdevelopment, we found the ectopically expressed Shh, Grem1 and Fgf8 and down-regulated Bmp2 in the embryonic limb bud atE10.5 to E12.5. A transcriptome sequencing analysis was conducted on limb buds (LBs) at E11.5, revealing 31 genes that exhibitednotable disparities in mRNA level between the Hoxd13Q50R homozygotes and the wild-type. These genes are known to be involvedin various processes such as limb development, cell proliferation, migration, and apoptosis. Our findings indicate that the ectopicexpression of Shh and Fgf8, in conjunction with the down-regulation of Bmp2, results in a failure of patterning along both theanterior-posterior and proximal-distal axes, as well as a decrease in interdigital programmed cell death (PCD). This cascadeultimately leads to the development of syndactyly and brachydactyly in heterozygous mice, and severe limb malformations inhomozygous mice. These findings suggest that abnormal expression of SHH, FGF8, and BMP2 induced by HOXD13Q50R may beresponsible for the manifestation of human SDTY5.

Studies of an event-building algorithm of the readout system for the twin TPCs in HFRS

The High-energy Fragment Separator(HFRS),which is currently under construction,is a leading international radioactive beam device.Multiple sets of position-sensitive twin time projection chamber(TPC)detectors are distributed on HFRS for particle identification and beam monitoring.The twin TPCs'readout electronics system operates in a trigger-less mode due to its high counting rate,leading to a challenge of handling large amounts of data.To address this problem,we introduced an event-building algorithm.This algorithm employs a hierarchical processing strategy to compress data during transmission and aggregation.In addition,it reconstructs twin TPCs'events online and stores only the reconstructed particle information,which significantly reduces the burden on data transmission and storage resources.Simulation studies demonstrated that the algorithm accurately matches twin TPCs'events and reduces more than 98%of the data volume at a counting rate of 500 kHz/channel.

Progress in Resource Utilization of River Sediment in the Field of Building Materials

At present,there is a great demand for building materials in the market,and the market prospect of building materials is relatively considerable.Through studying the composition of river sediment and its resource utilization in the field of building materials,this paper expounds the current domestic scholars research on river sediment in building materials,and summarizes the current problems and challenges,so as to provide a reference for the sustainable development of river sediment in the field of building materials.

A Fine-grained Building Height Control Method for Heritage Areas from the Perspective of Visual Integrity

This study proposes a refined methodology for controlling building heights in heritage areas.In order to protect the visual integrity of the heritage area,buildings should not obstruct the view from important site points and viewpoints to the periphery.By calculating the building height thresholds that buildings should not obscure the view from each viewpoint,the results of which are weighted and superimposed,and the values are extracted to each building unit as a refined building height control guideline.This study takes the Zhoukoudian area as a case study,applies the refined building height control criterion to the Zhoukoudian Site,and relies on this refined criterion to assess the visual integrity of the Zhoukoudian area,so as to realize the scientific planning and monitoring of the Zhoukoudian area.The refined building height control method can be applied to building height planning and visual landscape protection in large heritage areas.

Composite Panels from the Combination of Rice Husk and Wood Chips with a Natural Resin Based on Tannins Reinforced with Sugar Cane Molasses Intended for Building Insulation: Physico-Mechanical and Thermal Properties

The objective of this work is to develop new biosourced insulating composites from rice husks and wood chips that can be used in the building sector. It appears from the properties of the precursors that rice chips and husks are materials which can have good thermal conductivity and therefore the combination of these precursors could make it possible to obtain panels with good insulating properties. With regard to environmental and climatic constraints, the composite panels formulated at various rates were tested and the physico-mechanical and thermal properties showed that it was essential to add a crosslinker in order to increase certain solicitation. an incorporation rate of 12% to 30% made it possible to obtain panels with low thermal conductivity, a low surface water absorption capacity and which gives the composite good thermal insulation and will find many applications in the construction and real estate sector. Finally, new solutions to improve the fire reaction of the insulation panels are tested which allows to identify suitable solutions for the developed composites. In view of the flame tests, the panels obtained are good and can effectively combat fire safety in public buildings.