Kangfuxin solution alleviates esophageal stenosis after endoscopic submucosal dissection:A natural ingredient strategy

BACKGROUND Esophageal stricture ranks among the most significant complications following endoscopic submucosal dissection(ESD).Excessive fibrotic repair is a typical pathological feature leading to stenosis after ESD.AIM To examine the effectiveness and underlying mechanism of Kangfuxin solution(KFX)in mitigating excessive fibrotic repair of the esophagus post-ESD.METHODS Pigs received KFX at 0.74 mL/kg/d for 21 days after esophageal full circumferential ESD.Endoscopic examinations occurred on days 7 and 21 post-ESD.In vitro,recombinant transforming growth factor(TGF)-β1(5 ng/mL)induced a fibrotic microenvironment in primary esophageal fibroblasts(pEsF).After 24 hours of KFX treatment(at 1.5%,1%,and 0.5%),expression ofα-smooth muscle actin-2(ACTA2),fibronectin(FN),and type collagen I was assessed.Profibrotic signaling was analyzed,including TGF-β1,Smad2/3,and phosphor-smad2/3(p-Smad2/3).RESULTS Compared to the Control group,the groups treated with KFX and prednisolone exhibited reduced esophageal stenosis,lower weight loss rates,and improved food tolerance 21 d after ESD.After treatment,Masson staining revealed thinner and less dense collagen fibers in the submucosal layer.Additionally,the expression of fibrotic effector molecules was notably inhibited.Mechanistically,KFX downregulated the transduction levels of fibrotic functional molecules such as TGF-β1,Smad2/3,and p-Smad2/3.In vitro,pEsF exposed to TGF-β1-induced fibrotic microenvironment displayed increased fibrotic activity,which was reversed by KFX treatment,leading to reduced activation of ACTA2,FN,and collagen I.The 1.5%KFX treatment group showed decreased expression of p-Smad 2/3 in TGF-β1-activated pEsF.CONCLUSION KFX showed promise as a therapeutic option for post-full circumferential esophageal ESD strictures,potentially by suppressing fibroblast fibrotic activity through modulation of the TGF-β1/Smads signaling pathway.

Impact of cattle density on the structure and natural regeneration of a turkey oak stand on an agrosilvopastoral farm in central Italy

On an agrosilvopastoral farm in central Italy where Maremmana cattle graze in Turkey oak forests,we evaluated the impact of different livestock densities on stand structure,tree diversity and natural regeneration in four types of grazed areas based on the grazing regime adopted:calf-grazed,high-intensity-grazed,low-intensity-grazed,ungrazed control.For each area,we set up three permanent circular plots(radius of 15 m)to survey the structural and dasometric characteristics of the overstorey,understorey,and regeneration layer.The results showed that grazing negatively affected the complexity of the forest structure and its potential to regenerate and maintain a high level of biodiversity.The differences in stand structure observed between the grazing areas were closely related to livestock density.The most sensitive components of the system were the understorey and the regeneration layers.Contrarily,the current grazing management did not affect the dominant tree structure or its composition.Our findings identified medium-term monitoring and regeneration management as the two significant aspects to consider when assessing sustainable livestock.New forests can be established by excluding graz-ing for about 20–25 years.

Stand dynamics of old-growth hemlock forests in central Bhutan are shaped by natural disturbances

Understanding how past disturbances have influenced the development of forests is critical for deciphering their current structure and composition and forecasting future changes.In this study,dendrochronological methods were applied to uncover the disturbance history of old-growth hemlock-dominated forests in central Bhutan.Analysis of tree-ring samples from two old-growth hemlock stands,located in two different topographic settings,identified the importance of gap-phase dynamics in facilitating recruitment and growth releases and producing complex,multi-aged structure s over time.One site showed evidence of a near stand-replacing disturbance in the late 1700s,while the other showed no evide nce of high-severity disturbance at any time over the last 400 years.At both sites low-to medium-severity disturbances,some of which appear to be associated with cyclones originating in the Bay of Bengal,dominated the disturbance regime.The hemlock stands exhibited a significant positive association between cyclone occurrence and growth release events and between recruitment pulses and growth release events.From 1800 to 1970 there was an increase in recruitment of angiosperm tree species at most sites and a corresponding decline in conifer recruitment.Over the past 50 years there has been little new recruitment;this may be due to light limitation in the understory from shade-tolerant angiosperms and bamboo in the lower strata of these stands.Significant variations in disturbance dynamics and recruitment were observed across the study sites,suggesting that other factors,such as topography and climate,may be influencing long-term stand development patterns.This study highlights the complex interplay between historical disturbance regimes and tree recruitment in shaping the age and size structures of old-growth hemlock forests in central Bhutan.It also provides new insights into the dynamics of these forests that can be used to support effective forest conservation and management in the future.

The Contribution of Hemispherical Photographs to Understand Natural Forest Regeneration in the AKAK Forest Area

Examining the contribution of hemispherical photographs in the understanding of Natural forest regeneration is very important in estimating the future forest structure, composition and to enforce conservation regulations. This study sets out to examine the interaction between stump sprouting, LAI, site and canopy openness for the entire AKAK forest area and for the logging compartments;2013, 2015 and 2017 respectively. 49 sprouted stump were identified randonly. 20 m × 20 m plots were demarcated along a canopy gaps for each sprouted stump, the plots were established in such a manner that the sprouted stumps will be in the middle. For each of the selected 49 sprouted stump, indirect measurements of canopy cover were performed in the 49 plots of 20 m × 20 m (0.04 ha), giving a total of 1.96 ha of land covered. Galaxy S3 smartphone with a built-in Infinix ZERO 4 fish-eye lens with 198˚ view angle equidistant projection was used to take photos. The fish-eye lens was mounted on the phone camera and photograph were taken at a fixed height of 1.3 m. Results revealed that, the combine Principal Component Factor Analysis (2013, 2015 and 2017) of the correlation matrix for Sprout, Years, LAI 4%, LAI 5%, Canopy and Site openness, shows that factor 1 explained 62.6% of total variance while factor 2 explained 17.9% together explain 80.05% Communalities. For the year 2013, 2015 and 2017 respectively shows that there is a very strong correlation (p p < 0.0005) between LAI4 and LAI5.

Diameter distribution of trees in natural stands managed on polycyclic cutting system

Diameter frequency distribution in a specific stand provides basic information for forest resources management. In this study, four probability models were applied to analyze diameter distribution of natural forests after selective cutting with different intensities （low intensity of 13.0% in volume, medium intensity of 29.1%, high intensity of 45.8%, and extra-high intensity of 67.1%） The results show that the skewness and kurtosis of the four models are positive except that of low intensity selective cutting, which suggest that the number of small-size trees dominate the stand. The more intensity of selective cutting, the wider range of diameter distributions. The diameter structure of selective cutting with low intensity met Weibull and Beta distributions; that of medium intensity met Weibull, negative exponential as well as Gamma distributions; that of high intensity cutting met Weibull and negative exponential distributions, but that of extra-high intensity could not meet any above model. Weibull distribution model fits better than others regarding the structure of diameter distribution in natural forests managed on polycyclic cutting system. The results will provide basic information for sustainable management for mixed natural stands managed on a polycyclic cutting system.

Considering and comparing regeneration in natural and man-made stands in northern Iran

In this study the regeneration diversity of Syahkal forests afforestated and natural stands in north of Iran was studied and compared from the point of view of evenness and diversity index. In order to accomplish this study two natural and man-made stands that almost are located in the same height above the sea level were chosen. The area of each stand was 30 ha and the inventory was done by the random-systematic method with a 5R land measurement （500 m2） selected. Also, in order to study the regeneration in the center of each sample piece 125 square meters micro plots were formed. The results show that regeneration diversity index in natural stands is more than that in man-made stands which in this case Mc-Arthur index with 2.41 has the most amount while Simpson index with 0.543 has the least amount. But the evenness indexes in man-made stands are more than that in natural stand which the main reason is the purity of the man-made stand.

Study on tracheid variation of Picea koraiensis (nakai) in natural stand and plantation

Tracheid characteristics ofPicea koraiensis from natural stand in Liangshui area and plantation in Mao'ershan area were studied. The results of variance analysis showed that the tracheid length, diameter, and thickness of tracheid wall were significant differences between the growth rings. All those characteristics tend to increase from heart-center to bark. In natural stand, it has positive correlation between the characteristics. In plantation, the tracheid length has positive correlation with the trachied diameter, while both the trachied length and the trachied diameter has negative correlation with the thickness of trachied wall. The tracheid length and diameter have no significant difference in growth between natural stand and plantations. The thickness of tracheid wall from the plantation is a little thicker than that from the natural stand before 15 years.

Biomimetic natural biomaterials for tissue engineering and regenerative medicine:new biosynthesis methods,recent advances,and emerging applications

Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering(TE)and regenerative medicine.In contrast to conventional biomaterials or synthetic materials,biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix(ECM).Additionally,such materials have mechanical adaptability,micro-structure interconnectivity,and inherent bioactivity,making them ideal for the design of living implants for specific applications in TE and regenerative medicine.This paper provides an overview for recent progress of biomimetic natural biomaterials(BNBMs),including advances in their preparation,functionality,potential applications and future challenges.We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM.Moreover,we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications.Finally,we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.

Genetic and epigenetic targets of natural dietary compounds as anti-Alzheimer's agents

Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinesterase activity,mitochondrial dysfunction,genotoxicity,and neuroinflammation are present in this syndrome,which leads to neurodegeneration.Neurodegenerative pathologies such as Alzheimer’s disease are considered late-onset diseases caused by the complex combination of genetic,epigenetic,and environmental factors.There are two main types of Alzheimer’s disease,known as familial Alzheimer’s disease(onset<65 years)and late-onset or sporadic Alzheimer’s disease(onset≥65 years).Patients with familial Alzheimer’s disease inherit the disease due to rare mutations on the amyloid precursor protein(APP),presenilin 1 and 2(PSEN1 and PSEN2)genes in an autosomaldominantly fashion with closely 100%penetrance.In contrast,a different picture seems to emerge for sporadic Alzheimer’s disease,which exhibits numerous non-Mendelian anomalies suggesting an epigenetic component in its etiology.Importantly,the fundamental pathophysiological mechanisms driving Alzheimer’s disease are interfaced with epigenetic dysregulation.However,the dynamic nature of epigenetics seems to open up new avenues and hope in regenerative neurogenesis to improve brain repair in Alzheimer’s disease or following injury or stroke in humans.In recent years,there has been an increase in interest in using natural products for the treatment of neurodegenerative illnesses such as Alzheimer’s disease.Through epigenetic mechanisms,such as DNA methylation,non-coding RNAs,histone modification,and chromatin conformation regulation,natural compounds appear to exert neuroprotective effects.While we do not purport to cover every in this work,we do attempt to illustrate how various phytochemical compounds regulate the epigenetic effects of a few Alzheimer’s disease-related genes.

Facile synthesis of hierarchical NaX zeolite from natural kaolinite for efficient Knoevenagel condensation

Zeolite catalysts have found extensive applications in the synthesis of various fine chemicals.However,the micropores of zeolites impose diffusion limitations on bulky molecules,greatly reducing the catalytic efficiency.Herein,we explore an economic and environmentally friendly method for synthesizing hierarchical NaX zeolite that exhibits improved catalytic performance in the Knoevenagel condensation reaction for producing the useful fine chemical 2-cyano-3-phenylacrylate.The synthesis was achieved via a low-temperature activation of kaolinite and subsequent in-situ transformation strategy without any template or seed.Systematic characterizations reveal that the synthesized NaX zeolite has both intercrystalline and intra-crystalline mesopores,smaller crystal size,and larger external specific surface area compared to commercial NaX zeolite.Detailed mechanism investigations show that the inter-crystalline mesopores are generated by stacking smaller crystals formed from in-situ crystallization of the depolymerized kaolinite,and the intra-crystalline mesopores are inherited from the pores in the depolymerized kaolinite.This synthesis strategy provides an energy-saving and effective way to construct hierarchical zeolites,which may gain wide applications in fine chemical manufacturing.

Natural Disaster Risk Monitoring for Immovable Cultural Relics Based on Digital Twin

Natural disaster risk monitoring is an important task for disaster prevention and reduction.In the case of immovable cultural relics,however,the feedback mechanism,risk factors,monitoring logic,and monitoring indicators of natural disaster risk monitoring are complex.How to achieve intelligent perception and monitoring of natural disaster risk for immovable cultural relics has always been a focus and a challenge for researchers.Based on the analysis of the concepts and issues related to the natural disaster risk of immovable cultural relics,this paper proposes a framework for natural disaster risk monitoring for immovable cultural relics based on the digital twin.This framework focuses on risk monitoring,including the physical entities of natural disaster risk for immovable cultural relics,monitoring indicators,and virtual entity construction.A platform for monitoring the natural disaster risk of immovable cultural relics is proposed.Using the Puzhou Ancient City Site as a test bed,the proposed concept can be used for monitoring the natural disaster risk of immovable cultural relics at different scales.

Hydrocarbon Generation Characteristics of Coal-measure Source Rocks and their Contribution to Natural Gas:A Case Study of Middle and Lower Jurassic Targets from the Southern Junggar Basin Margin

In order to study the hydrocarbon generation(HCGE)characteristics of coal-bearing basins,the coal-measure source rocks of the Middle Jurassic-Lower Jurassic(MLJ)of the piedmont thrust belt in the southern margin of the Junggar Basin in Northwest China are taken as research objects.More than 60 MLJ samples were collected from outcrops and wells.Total organic carbon(TOC),rock pyrolysis(Rock-Eval),organic petrological,vitrinite reflectance(%Ro),and hydrous pyrolysis were performed to analyze the relevant samples.The pyrolysis gases and liquid products were measured,and then the chemical composition,as well as carbon isotopes of the gases,were analyzed.The results indicate that the MLJ source rocks have the capacity for large-scale gas generation.In addition,for coal-measure source rocks,the heavier the carbon isotope of kerogen(δ^(13)C_(kerogen)),the lower the liquid hydrocarbon and hydrocarbon gas yield,and the easier it is to produce non-hydrocarbon gas.It is worth noting that when theδ^(13)C_(kerogen)in organic matter(OM)is relatively heavier,the fractionation of its products may become weaker in the evolutionary process.The vital contribution of the MLJ source rock to natural gas resources in the study area was further confirmed by comparing it with the Jurassic source gas.

Numerical analysis of downward progressive landslides in long natural slopes with sensitive clay

Landslides occurring in sensitive clay often result in widespread destruction,posing a significant risk to human lives and property due to the substantial decrease in undrained shear strength during deformation.Assessing the consequences of these landslides is challenging and necessitates robust numerical methods to comprehensively investigate their failure mechanisms.While studies have extensively explored upward progressive landslides in sensitive clays,understanding downward progressive cases remains limited.In this study,we utilised the nodal integration-based particle finite element method(NPFEM)with a nonlinear strain-softening model to analyse downward progressive landslides in sensitive clay on elongated slopes,induced by surcharge loads near the crest.We focused on elucidating the underlying failure mechanisms and evaluating the effects of different soil parameters and strainsoftening characteristics.The simulation results revealed the typical pattern for downward landslides,which typically start with a localised failure in proximity to the surcharge loads,followed by a combination of different types of failure mechanisms,including single flow slides,translational progressive landslides,progressive flow slides,and spread failures.Additionally,inclined shear bands occur within spread failures,often adopting distinctive ploughing patterns characterised by triangular shapes.The sensitive clay thickness at the base,the clay strength gradient,the sensitivity,and the softening rate significantly influence the failure mechanisms and the extent of diffused displacement.Remarkably,some of these effects mirror those observed in upward progressive landslides,underscoring the interconnectedness of these phenomena.This study contributes valuable insights into the complex dynamics of sensitive clay landslides,shedding light on the intricate interplay of factors governing their behaviour and progression.

Natural rubber latex as a potential additive for water-based drilling fluids

The environmental hazards and"carbon footprint"of oil and gas drilling can be significantly reduced by replacing traditional petroleum-based chemical additives with natural materials derived from plants and animals.This paper explored for the first time the interaction mechanism between natural rubber latex(NRL)and bentonite suspensions(BTs)through a series of characterization experiments,as well as the potential applications in water-based drilling fluids(WBDF).The gel viscoelasticity experiments showed that NRL could decrease the consistency coefficient(k)and flow index(n)of BTs,and enhance the shear thinning performance of BTs as pseudo-plastic fluids.In addition,0.5 w/v%NRL not only increased the critical yield stress and strengthened the structural strength between the bentonite particles,but also facilitated the compatibility of pressure loss and flow efficiency.The evaluation of colloidal stability and WBDF performance indicated that NRL particles could promote the hydration and charge stability on the surface of BTs particles,and optimize the particle size distribution and flow resistance of WBDF under the"intercalation-exfoliation-encapsulation"synergistic interaction.Moreover,NRL can improve the rheological properties of WBDF at high temperatures(<150.C),and form a dense blocking layer by bridging and sealing the pores and cracks of the filter cake,which ultimately reduces the permeability of the cake and the filtration loss of WBDF.

DNA G-Quadruplexes as Targets for Natural Product Drug Discovery

DNA guanine(G)-quadruplexes(G4s)are unique secondary structures formed by two or more stacked Gtetrads in G-rich DNA sequences.These structures have been found to play a crucial role in highly transcribed genes,especially in cancer-related oncogenes,making them attractive targets for cancer therapeutics.Significantly,targeting oncogene promoter G4 structures has emerged as a promising strategy to address the challenge of undruggable and drug-resistant proteins,such as MYC,BCL2,KRAS,and EGFR.Natural products have long been an important source of drug discovery,particularly in the fields of cancer and infectious diseases.Noteworthy progress has recently been made in the discovery of naturally occurring DNA G4-targeting drugs.Numerous DNA G4s,such as MYC-G4,BCL2-G4,KRAS-G4,PDGFR-b-G4,VEGF-G4,and telomeric-G4,have been identified as potential targets of natural products,including berberine,telomestatin,quindoline,sanguinarine,isaindigotone,and many others.Herein,we summarize and evaluate recent advancements in natural and nature-derived DNA G4 binders,focusing on understanding the structural recognition of DNA G4s by small molecules derived from nature.We also discuss the challenges and opportunities associated with developing drugs that target DNA G4s.

Models and form factors for stand volume estimation in natural forest ecosystems: a case study of Katarniaghat Wildlife Sanctuary (KGWS), Bahraich District, India

In view of the difficulties in stand volume estimation in natural forests, we derived real form factors and models for volume estimation in these types of forest ecosystems, using Katarniaghat Wildlife Sanctuary as a case study. Tree growth data were obtained for all trees （dbh 〉10 cm） in 4 plots （25 × 25 m） randomly located in each of three strata selected in the forest. The form factor calculated for the stand was 0.42 and a range of 0.42 0.57 was estimated for selected species （density 〉10）. The parameters of model variables were consistent with general growth trends of trees and each was statistically significant. There was no significant difference （p〉0.05） between the observed and predicted volumes for all models and there was very high correlation between observed and predicted volumes. The output of the performance statistics and the logical signs of the regression coefficients of the models demonstrated that they are useful for volume estimation with minimal error. Plotting the biases with respect to considerable regressor variables showed no meaningful and evident trend of bias values along with the independent variables. This showed that the models did not violate regression assumptions and there were no heteroscedacity or multiculnarity problems. We recommend use of the form factors and models in this ecosystem and in similar ones for stand and tree volume estimation.

Natural Silicate as a Solid Support for the Calix[4]Thiophosphorus Derivative for Removal Mercury (II), as Picrate from Water

Currently a technique widely used for gold extraction is mercury by amalgamation technique, the tailing produced pollutes water of all kinds, so it is necessary to develop a form of selective mitigation, for which it is necessary to use complexing agents based on calixarene functionalized with mercury sequestering agents. These are immobilized by adding supports based on natural silica to form polymers and make them insoluble in all types of solvents, so that they can be used as an extractor and at the same time regenerate to their original properties for continuous reuse.

Energy Design and Optimization of Greenhouse by Natural Convection

This study addresses the pressing need for energy-efficient greenhouse management by focusing on the innovative application of natural ventilation.The primary objective of this study is to evaluate various ventilation strategies to enhance energy efficiency and optimize crop production in agricultural greenhouses.Employing advanced numerical simulation tools,the study conducts a comprehensive assessment of natural ventilation’s effectiveness under real-world conditions.The results underscore the crucial role of the stack effect and strategic window positioning in greenhouse cooling,providing valuable insights for greenhouse designers.Our findings shed light on the significant benefits of optimized ventilation and also offer practical implications for improving greenhouse design,ensuring sustainable and efficient agricultural practices.The study demonstrated energy savings in cooling from November to April,with a maximum saving of 680 kWh in March,indicating the effectiveness of strategically positioning windows to leverage the stack effect.This approach enhances plant growth and reduces the need for costly cooling systems,thereby improving overall energy efficiency and lowering operational expenses.

Revealing High-Efficiency Natural Mycotoxin Antidotes in Zebrafish Model Screening Against Zearalenone-Induced Toxicity

Zearalenone(ZEA),a mycotoxin,poses a significant global hazard to human and animal health.Natural products(NPs)have shown promise for mitigating the adverse effects of ZEA owing to their diverse func-tional activities.However,the current challenge lies in the absence of an efficient strategy for systematic screening and identification of NPs that can effectively protect against ZEA-induced toxicity.This study describes a phenotype-based screening strategy for screening NP libraries and discovering more effective compounds to mitigate or counteract the adverse consequences of ZEA exposure in animals.Using this strategy,we initially identified 96 NPs and evaluated the potency and efficacy of two effective candidate compounds,fraxetin,and hydroxytyrosol,based on embryonic phenotype and locomotor activity using a scoring system and the TCMacro method.Furthermore,we performed transcriptome and proteinprotein interaction(PPI)network analyses to extract two mRNA signatures to query the Connectivity Map(CMap)database and predict NPs.The predicted NPs showed the potential to reverse the gene expression profiles associated with ZEA toxicity.Consequently,we further screened these compounds using our model,which indicated that hispidin,daphnetin,and riboflavin exhibit promising in vivo effi-cacy in zebrafish.Notably,throughout the process,fraxetin consistently stood out as the most promising NP.Biological pathway analysis and functional verification revealed that fraxetin completely reversed the toxic effects of ZEA at very low doses.This was achieved by repairing damaged cell apoptosis,modifying the cell cycle pathway,and preventing senescence induction,indicating good application potential.Overall,we demonstrated that this integration strategy can be successfully applied to effectively discover potential antidotes.

Effect of artificial natural light on the development of myopia among primary school-age children in China:a three-year longitudinal study

AIM:To assess the efficacy of artificial natural light in preventing incident myopia in primary school-age children.METHODS:This is a prospective,randomized control,intervention study.A total of 1840 students from 39 classes in 4 primary schools in Foshan participated in this study.The whole randomization method was adopted to include classes as a group according to 1:1 randomized control.Classrooms in the control group were illuminated by usual light,and classrooms in the intervention group were illuminated by artificial natural light.All students received uncorrected visual acuity and best-corrected visual acuity measurement,non-cycloplegic autorefraction,ocular biometric examination,slit lamp and strabismus examination.Three-year follow-up,the students underwent same procedures.Myopia was defined as spherical equivalent refraction≤-0.50 D and uncorrected visual acuity<20/20.RESULTS:There were 894 students in the control group and 946 students in the intervention group with a mean±SD age of 7.50±0.53y.The three-year cumulative incidence rate of myopia was 26.4%(207 incident cases among 784 eligible participants at baseline)in the control group and 21.2%(164 incident cases among 774 eligible participants at baseline)in the intervention group[difference of 5.2%(95%CI,3.7%to 10.1%);P=0.035].There was also a significant difference in the three-year change in spherical equivalent refraction for the control group(-0.81 D)compared with the intervention group[-0.63 D;difference of 0.18 D(95%CI,0.08 to 0.28 D);P<0.001].Elongation of axial length was significantly different between in the control group(0.77 mm)and the intervention group[0.72 mm;difference of 0.05 mm(95%CI,0.01 to 0.09 mm);P=0.003].CONCLUSION:Artificial natural light in the classroom of primary schools can result in reducing incidence rate of myopia during a period of three years.