Steroidal alkaloids are the main active components in many medicinal plants and exhibit diverse biological activities.Axillaridine A(AA)is a newly discovered steroidal alkaloid.However,whether AA could suppress osteoc...Steroidal alkaloids are the main active components in many medicinal plants and exhibit diverse biological activities.Axillaridine A(AA)is a newly discovered steroidal alkaloid.However,whether AA could suppress osteoclastogenesis and alleviate ovariectomy-induced bone loss in mice remains unknown.In vitro,AA significantly suppressed the receptor activator of nuclear factor-κB(NF-κB)ligand(RANKL)-induced osteoclast differentiation via downregulating the expression of osteoclastogenesis-related marker genes,proteins,and transcriptional regulators,including tartrate-resistant acid phosphatase(TRAP),c-Src,matrix metallopeptidase-9(MMP-9),cathepsin K,nuclear factor of activated T cells,cytoplasmic 1(NFATc1),and c-Fos.This was achieved by blocking RANKL-RANK interaction and inhibiting RANKL-mediated RANK signaling pathways,including NF-κB,AKT,and mitogen-activated protein kinases(MAPKs)in osteoclast precursors.In vivo,AA significantly inhibited the ovariectomized(OVX)-induced body weight gain and blood glucose increase in mice.AA did not adversely affect the histomorphologies,weights,and indices of the kidney and liver in OVX mice.AA effectively ameliorated bone loss in OVX mice by inhibiting osteoclastogenesis.AA significantly inhibited the serum levels of tartrate-resistant acid phosphatase 5b(TRACP-5b)and C-telopeptide of type I collagen(CTX-I).AA significantly inhibited the OVX-induced expression of osteoclastogenesis-related marker genes and proteins in the femur.In summary,AA alleviates ovariectomy-induced bone loss in mice by suppressing osteoclastogenesis via inhibition of RANKL-mediated RANK signaling pathways and could be potentially used for the prevention and treatment of osteoclastrelated diseases such as osteoporosis.展开更多
Amphibious vehicles are more prone to attitude instability compared to ships,making it crucial to develop effective methods for monitoring instability risks.However,large inclination events,which can lead to instabili...Amphibious vehicles are more prone to attitude instability compared to ships,making it crucial to develop effective methods for monitoring instability risks.However,large inclination events,which can lead to instability,occur frequently in both experimental and operational data.This infrequency causes events to be overlooked by existing prediction models,which lack the precision to accurately predict inclination attitudes in amphibious vehicles.To address this gap in predicting attitudes near extreme inclination points,this study introduces a novel loss function,termed generalized extreme value loss.Subsequently,a deep learning model for improved waterborne attitude prediction,termed iInformer,was developed using a Transformer-based approach.During the embedding phase,a text prototype is created based on the vehicle’s operation log data is constructed to help the model better understand the vehicle’s operating environment.Data segmentation techniques are used to highlight local data variation features.Furthermore,to mitigate issues related to poor convergence and slow training speeds caused by the extreme value loss function,a teacher forcing mechanism is integrated into the model,enhancing its convergence capabilities.Experimental results validate the effectiveness of the proposed method,demonstrating its ability to handle data imbalance challenges.Specifically,the model achieves over a 60%improvement in root mean square error under extreme value conditions,with significant improvements observed across additional metrics.展开更多
Guanting Reservoir, one of the drinking water supply sources of Beijing, suffers from water eutrophication. It is mainly supplied by Guishui River. Thus, to investigate the reasons of phosphorus （P） loss and improve...Guanting Reservoir, one of the drinking water supply sources of Beijing, suffers from water eutrophication. It is mainly supplied by Guishui River. Thus, to investigate the reasons of phosphorus （P） loss and improve the P management strategies in Guishui River watershed are important for the safety of drinking water in this region. In this study, a Revised Field P Ranking Scheme （PRS） was developed to reflect the field vulnerability of P loss at the field scale based on the Field PRS. In this new scheme, six factors are included, and each one was assigned a relative weight and a determination method. The affecting factors were classified into transport factors and source factors, and, the standards of environmental quality on surface water and soil erosion classification and degradation of the China were used in this scheme. By the new scheme, thirty-four fields in the Guishui River were categorized as ＂low＂, ＂medium＂ or ＂high＂ potential for P loss into the runoff. The results showed that the P loss risks of orchard and vegetable fields were higher than that of corn and soybean fields. The source factors were the main factors to affect P loss from the study area. In the study area, controlling P input and improving P usage efficiency are critical to decrease P loss. Based on the results, it was suggested that more attention should be paid on the fields of vegetable and orchard since they have extremely high usage rate of P and high soil test of P. Compared with P surplus by field measurements, the Revised Field PRS was more suitable for reflecting the characteristics of fields, and had higher potential capacity to identify critical source areas of P loss than PRS.展开更多
Coping with extreme climate events and its related climatic disasters caused by climate change has become a global issue and drew wide attention from scientists, policy-makers and public. This paper calculated the exp...Coping with extreme climate events and its related climatic disasters caused by climate change has become a global issue and drew wide attention from scientists, policy-makers and public. This paper calculated the expected annual multiple climatic hazards intensity index based on the results of nine climatic hazards including tropical cyclone, flood, landslide, storm surge, sand-dust storm, drought, heat wave, cold wave and wildfire. Then a vulnerability model involving the coping capacity indicator with mortality rate, affected population rate and GDP loss rate, was developed to estimate the expected annual affected population, mortality and GDP loss risks. The results showed that： countries with the highest risks are also the countries with large population or GDP. To substantially reduce the global total climatic hazards risks, these countries should reduce the exposure and improving the governance of integrated climatic risk; Without considering the total exposure, countries with the high mortality rate, affected population rate or GDP loss rate, which also have higher or lower coping capacity, such as the Philippines, Bangladesh and Vietnam, are the hotspots of the planning and strategy making for the climatic disaster risk reduction and should focus on promoting the coping capacity.展开更多
Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial spectrum.However,their use leads to irreversible hearing damage by causing apoptosis of hair cells as ...Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial spectrum.However,their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct target.In addition,the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon exposure.To investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides,we used a C57BL/6J mouse model treated with kanamycin.We found that the mice exhibited auditory deficits following the acute loss of outer hair cells.Spiral ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over time.Transcriptomic profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response,particularly those related to the NLRP3 inflammasome.Activation of the canonical pyroptotic pathway in spiral ganglion neurons was observed,accompanied by infiltration of macrophages and the release of proinflammatory cytokines.Pharmacological intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury model.These findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron degeneration.Inhibition of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.展开更多
Developing effective strategies to regulate graphene’s conduction loss and polarization has become a key to expanding its application in the electromagnetic wave absorption(EMWA)field.Based on the unique energy band ...Developing effective strategies to regulate graphene’s conduction loss and polarization has become a key to expanding its application in the electromagnetic wave absorption(EMWA)field.Based on the unique energy band structure of graphene,regulating its bandgap and electrical properties by introducing heteroatoms is considered a feasible solution.Herein,metal-nitrogen doping reduced graphene oxide(M–N-RGO)was prepared by embedding a series of single metal atoms M–N_(4) sites(M=Mn,Fe,Co,Ni,Cu,Zn,Nb,Cd,and Sn)in RGO using an N-coordination atom-assisted strategy.These composites had adjustable conductivity and polarization to optimize dielectric loss and impedance matching for efficient EMWA performance.The results showed that the minimum reflection loss(RL_(min))of Fe–N-RGO reaches−74.05 dB(2.0 mm)and the maximum effective absorption bandwidth(EAB_(max))is 7.05 GHz(1.89 mm)even with a low filler loading of only 1 wt%.Combined with X-ray absorption spectra(XAFS),atomic force microscopy,and density functional theory calculation analysis,the Fe–N_(4) can be used as the polarization center to increase dipole polarization,interface polarization and defect-induced polarization due to d-p orbital hybridization and structural distortion.Moreover,electron migration within the Fe further leads to conduction loss,thereby synergistically promoting energy attenuation.This study demonstrates the effectiveness of metal-nitrogen doping in regulating the graphene′s dielectric properties,which provides an important basis for further investigation of the loss mechanism.展开更多
Activity cliffs(ACs)are generally defined as pairs of similar compounds that only differ by a minor structural modification but exhibit a large difference in their binding affinity for a given target.ACs offer crucial...Activity cliffs(ACs)are generally defined as pairs of similar compounds that only differ by a minor structural modification but exhibit a large difference in their binding affinity for a given target.ACs offer crucial insights that aid medicinal chemists in optimizing molecular structures.Nonetheless,they also form a major source of prediction error in structure-activity relationship(SAR)models.To date,several studies have demonstrated that deep neural networks based on molecular images or graphs might need to be improved further in predicting the potency of ACs.In this paper,we integrated the triplet loss in face recognition with pre-training strategy to develop a prediction model ACtriplet,tailored for ACs.Through extensive comparison with multiple baseline models on 30 benchmark datasets,the results showed that ACtriplet was significantly better than those deep learning(DL)models without pretraining.In addition,we explored the effect of pre-training on data representation.Finally,the case study demonstrated that our model's interpretability module could explain the prediction results reasonably.In the dilemma that the amount of data could not be increased rapidly,this innovative framework would better make use of the existing data,which would propel the potential of DL in the early stage of drug discovery and optimization.展开更多
This editorial critically evaluates the application of foot reflexology as a treatment for sensorineural hearing loss(SNHL)in infants,as proposed in a case report published in the World of Clinical Cases.SNHL is a con...This editorial critically evaluates the application of foot reflexology as a treatment for sensorineural hearing loss(SNHL)in infants,as proposed in a case report published in the World of Clinical Cases.SNHL is a condition characterized by damage to the cochlea or the neural pathways that transmit auditory information to the brain.The etiology of SNHL is often complex,involving genetic mutations,prenatal factors,or perinatal insults.Reflexology,an alternative therapy involving the application of pressure to specific points on the feet,is based on the hypothesis that these points correspond to different organs and systems in the body,including the auditory system.However,the biological plausibility and clinical efficacy of foot reflexology in addressing SNHL lack empirical support.This editorial examines the pathophysiology of SNHL,assesses the clinical claims of reflexology practitioners,and emphasizes the necessity of evidence-based approaches in treating infant hearing loss.While complementary therapies may provide ancillary benefits,they should not supplant validated medical treatments in managing SNHL in infants.Further research is needed to evaluate the safety and efficacy of foot reflexology and other alternative therapies in pediatric audiology.展开更多
Hearing loss is the third leading cause of human disability.Age-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health burden.Noise-induced,ototox...Hearing loss is the third leading cause of human disability.Age-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health burden.Noise-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing loss.The etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental factors.Oxidative stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing loss.Short non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic response.Sensory hair cell death is a central histopathological finding in sensorineural hearing loss.As these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing loss.Ovid EMBASE,Ovid MEDLINE,Web of Science Core Collection,and ClinicalTrials.gov databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical trials.Registe red clinical trials known to the senior author we re also assessed.A total of 222studies were thus identified.After excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text screening.This resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative review.MiRNAs miR-34a and miR-29b levels increase with age in mice.These miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT1p53,and SIRT1/hypoxia-inducible factor 1-alpha signaling pathways resulting in increased apoptosis.Furthermore,hypoxia and oxidative stress had a similar adve rse apoptotic effect,which was inhibited by resve ratrol and a myocardial inhibitorassociated transcript,a miR-29b competing endogenous mRNA.Gentamicin reduced miR-182-5p levels and increased cochlear oxidative stress and cell death in mice-an effect that was corrected by inner ear stem cell-derived exosomes.There is ongoing work seeking to determine if these findings can be effectively translated to humans.展开更多
Gels and conductive polymer composites,including hydrogen bonds(HBs),have emerged as promising materials for electro-magnetic wave(EMW)absorption across various applications.However,the relationship between conduction...Gels and conductive polymer composites,including hydrogen bonds(HBs),have emerged as promising materials for electro-magnetic wave(EMW)absorption across various applications.However,the relationship between conduction loss in EMW-absorbing materials and charge transfer in HB remains to be fully understood.In this study,we developed a series of deep eutectic gels to fine-tune the quantity of HB by adjusting the molar ratio of choline chloride(ChCl)and ethylene glycol(EG).Owing to the unique properties of deep eutectic gels,the effects of magnetic loss and polarization loss on EMW attenuation can be disregarded.Our results indicate that the quantity of HB initially increases and then decreases with the introduction of EG,with HB-induced conductive loss following similar pat-terns.At a ChCl and EG molar ratio of 2.4,the gel labeled G22-CE2.4 exhibited the best EMW absorption performance,characterized by an effective absorption bandwidth of 8.50 GHz and a thickness of 2.54 mm.This superior performance is attributed to the synergistic ef-fects of excellent conductive loss and impedance matching generated by the optimal number of HB.This work elucidates the role of HB in dielectric loss for the first time and provides valuable insights into the optimal design of supramolecular polymer absorbers.展开更多
The application of organic fertilizers has become an increasingly popular practice in maize production to reduce thegaseous nitrogen(N) loss and soil degradation caused by inorganic fertilizers. Organic fertilizer pla...The application of organic fertilizers has become an increasingly popular practice in maize production to reduce thegaseous nitrogen(N) loss and soil degradation caused by inorganic fertilizers. Organic fertilizer plays a key rolein improving soil quality and stabilizing maize yields, but few studies have compared different substitution rates. Afield study was carried out in 2021 and 2022, based on a long-term trial initiated in 2016, which included five organicfertilizer N substitution rates with equal inputs of 200 kg N ha^(–1): 0% organic fertilizer(T1, 100% inorganic fertilizer),50.0% organic+50.0% inorganic fertilizer(T2), 37.5% organic+62.5% inorganic fertilizer(T3), 25.0% organic+75.0%inorganic fertilizer(T4), and 12.5% organic+87.5% inorganic fertilizer(T5), as well as a no fertilizer control(T6). Theresults of the two years showed that T3 and T1 had the highest grain yield and biomass, respectively, and there wasno significant difference between T1 and T3. Compared with T1, the 12.5, 25.0, 37.5, and 50.0% substitution rates in T5, T4, T3, and T2 significantly reduced total nitrogen losses(NH_(3), N_(2)O) by 8.3, 16.1, 18.7, and 27.0%, respectively.Nitrogen use efficiency(NUE) was higher in T5, T3, and T1, and there were no significant differences among them.Organic fertilizer substitution directly reduced NH_(3)volatilization and N_(2)O emission from farmland by lowering theammonium nitrogen and alkali-dissolved N contents and by increasing soil moisture. These substitution treatmentsreduced N_(2)O emissions indirectly by regulating the abundances of AOB and nirK-harboring genes by promotingsoil moisture. Specifically, the 37.5% organic fertilizer substitution reduces NH_(3)volatilization and N_(2)O emission from farmland by reducing the ammonium nitrogen and alkali-dissolved N contents and increasing moisture, which negatively regulate the abundance of AOB and nir K-harboring genes to reduce N_(2)O emissions indirectly in rainfed maize fields on the Loess Plateau of China.展开更多
Leaf turgor loss point has been recognized as an important plant physiological trait explaining a species’drought tolerance( π_(tlp)).Less is known about the variation of π_(tlp) in time and how seasonal or interan...Leaf turgor loss point has been recognized as an important plant physiological trait explaining a species’drought tolerance( π_(tlp)).Less is known about the variation of π_(tlp) in time and how seasonal or interannual differences in water availability are affecting π_(tlp) as a static trait.I monitored the seasonal variation of π_(tlp) during a drought year starting in early spring with juvenile leaves and assessed the interannual variation in π_(tlp) of fully matured leaves among years with diverting water availability for three temperate broad-leaved tree species.The largest seasonal changes in π_(tlp) occurred during leaf unfolding until leaves were fully developed and matured.After leaves matured,no significant changes occurred for the rest of the vegetation period.Interannual variation that could be related to water availability was only present in one of the three tree species.The results suggest that the investigated species have a rapid period of osmotic adjustment early in the growing season followed by a period of relative stability,when π_(tlp) can be considered as a static trait.展开更多
In the Internet era,recommendation systems play a crucial role in helping users find relevant information from large datasets.Class imbalance is known to severely affect data quality,and therefore reduce the performan...In the Internet era,recommendation systems play a crucial role in helping users find relevant information from large datasets.Class imbalance is known to severely affect data quality,and therefore reduce the performance of recommendation systems.Due to the imbalance,machine learning algorithms tend to classify inputs into the positive(majority)class every time to achieve high prediction accuracy.Imbalance can be categorized such as by features and classes,but most studies consider only class imbalance.In this paper,we propose a recommendation system that can integrate multiple networks to adapt to a large number of imbalanced features and can deal with highly skewed and imbalanced datasets through a loss function.We propose a loss aware feature attention mechanism(LAFAM)to solve the issue of feature imbalance.The network incorporates an attention mechanism and uses multiple sub-networks to classify and learn features.For better results,the network can learn the weights of sub-networks and assign higher weights to important features.We propose suppression loss to address class imbalance,which favors negative loss by penalizing positive loss,and pays more attention to sample points near the decision boundary.Experiments on two large-scale datasets verify that the performance of the proposed system is greatly improved compared to baseline methods.展开更多
During high-speed rotation,the surface of aeronautic spiral bevel gears will generate significant pressure and viscous forces,which will cause a certain amount of windage power loss and reduce the efficiency of the tr...During high-speed rotation,the surface of aeronautic spiral bevel gears will generate significant pressure and viscous forces,which will cause a certain amount of windage power loss and reduce the efficiency of the transmission system.Based on the computational fluid dynamics,this paper analyzes the windage power loss of a single spiral bevel gear and a spiral bevel gear pair under oil injection lubrication.In addition,the shroud is used to suppress gear windage loss,and the clearance size and opening angle of the designed shroud are optimized.Finally,by comparing and analyzing the experimental results,the following conclusions were obtained:(1)For a single gear,the speed is the most important factor affecting windage loss,followed by the hand of spiral,and rotation direction;(2)For gear pairs,under oil injection lubrication,the input speed has the greatest impact on windage power loss,followed by the influence of oil injection port speed,temperature and oil injection port pressure;(3)Installing a shroud is an effective method to reduce windage power loss;(4)In the pure air phase,the smaller the clearance between the shroud and the gear surface,and the smaller the radial direction between the shroud and the shaft,the better the effect of reducing windage;(5)In the two-phase flow of oil and gas,it is necessary to design oil drainage holes on the shroud to ensure the smooth discharge of lubricating oil and improve the drag reduction effect.展开更多
Foot reflexology is a non-invasive and safe complementary therapy that works by massaging the reflex zones of the feet and exerts systemic or whole-body regulation through meridian nerve conduction.This therapy is com...Foot reflexology is a non-invasive and safe complementary therapy that works by massaging the reflex zones of the feet and exerts systemic or whole-body regulation through meridian nerve conduction.This therapy is commonly used in the treatment of various conditions such as autism and Parkinson's disease.However,there is limited reporting on the use of foot reflexology therapy for infants with sensorineural hearing loss(SNHL).Currently,there is no definitive conclusion on how foot reflexology therapy can influence hearing.This editorial holds some guiding significance regarding this clinical issue.The aim is to present physiological evidence of how foot reflexology therapy can impact infants with SNHL,thereby enhancing clinician’s awareness of foot reflexology in treating infants with SNHL.展开更多
Hydrogen-enriched ironmaking presents a promising approach to mitigate coke consumption and carbon emission in blast furnace(BF)operations.This work investigated the relationship between the structural features of cok...Hydrogen-enriched ironmaking presents a promising approach to mitigate coke consumption and carbon emission in blast furnace(BF)operations.This work investigated the relationship between the structural features of cokes and their reactivity towards solution loss(SL),especially under hydrogen-enriched atmospheres.Six cokes were characterized,and their SL behaviors were examined under varying atmospheres to elucidate the effects of hydrogen enrichment.The results indicate that an increase in fixed carbon content leads to a decrease in the coke reactivity index(CRI)and an increase in coke strength after reaction(CSR),in the CO_(2) atmosphere,the CSR of coke increases from 35.76%−62.83%,while in the 90CO_(2)/10H_(2) atmosphere,the CSR of coke increases from 65.67%−84.09%.There is a good linear relationship between CRI and microcrystalline structure parameters of coke.Cokes with larger crystalline size,lower amorphous content,and smaller optical texture index(OTI)values show enhanced resistance to degradation and maintain structural integrity in BF.Kinetic analysis performed with the shifted-modified-random pore model(S-MRPM)reveals that alterations in pore structure and intrinsic mineral composition significantly influence the reaction rate.The introduction of a small amount of water vapor raises SL rates,whereas a minor addition of hydrogen(<10%)decelerates SL due to its incomplete conversion to water vapor and the reduced partial pressure of the gasifying agent.Thermodynamic calculations also indicate that the introduced hydrogen does not convert into the same fraction of water vapor.The shift from chemical reaction control to gas diffusion control as the rate-determining step with rising temperatures during SL process was confirmed,and the introduction of hydrogen does not notably alter SL behavior.This result demonstrated that introducing a small amount of hydrogen(<10%)can mitigate SL rates,thereby enhancing coke strength and reducing coke consumption and carbon emissions.展开更多
Early intervention for sensorineural hearing loss(SNHL)in childhood is crucial for auditory and language development.In recent years,innovative auditory stimulation techniques and speech therapy strategies,such as mid...Early intervention for sensorineural hearing loss(SNHL)in childhood is crucial for auditory and language development.In recent years,innovative auditory stimulation techniques and speech therapy strategies,such as middle ear implants,cochlear implants,auditory brainstem implants,and midbrain implants,have provided new avenues for improving patient outcomes.Additionally,basic research advancements in cell reprogramming and regeneration,stem cell therapy,and targeted drug delivery offer promising approaches to meet the individualized needs of children with SNHL.However,many challenges and unresolved issues remain in the treatment of SNHL.This article comments on the case report,which describes a female pediatric patient with SNHL who underwent foot reflexology which led to the normalization of hearing thresholds.Reflexology is considered to have potential benefits in physical rehabilitation,but its efficacy in hearing restoration requires further scientific validation through rigorous clinical trials and large-scale prospective studies.展开更多
基金supported by the grants from the National Natural Science Foundation of China(82404638)the Xingdian Talent Plan of Yunnan Province(XDYC-QNRC-2023-0427 and XDYC-YLXZ2022-0025)the Natural Science Foundation of Yunnan Province(202101BD070001-034,202101BD070001-049,202201AT070267,and 202201AU070183)。
文摘Steroidal alkaloids are the main active components in many medicinal plants and exhibit diverse biological activities.Axillaridine A(AA)is a newly discovered steroidal alkaloid.However,whether AA could suppress osteoclastogenesis and alleviate ovariectomy-induced bone loss in mice remains unknown.In vitro,AA significantly suppressed the receptor activator of nuclear factor-κB(NF-κB)ligand(RANKL)-induced osteoclast differentiation via downregulating the expression of osteoclastogenesis-related marker genes,proteins,and transcriptional regulators,including tartrate-resistant acid phosphatase(TRAP),c-Src,matrix metallopeptidase-9(MMP-9),cathepsin K,nuclear factor of activated T cells,cytoplasmic 1(NFATc1),and c-Fos.This was achieved by blocking RANKL-RANK interaction and inhibiting RANKL-mediated RANK signaling pathways,including NF-κB,AKT,and mitogen-activated protein kinases(MAPKs)in osteoclast precursors.In vivo,AA significantly inhibited the ovariectomized(OVX)-induced body weight gain and blood glucose increase in mice.AA did not adversely affect the histomorphologies,weights,and indices of the kidney and liver in OVX mice.AA effectively ameliorated bone loss in OVX mice by inhibiting osteoclastogenesis.AA significantly inhibited the serum levels of tartrate-resistant acid phosphatase 5b(TRACP-5b)and C-telopeptide of type I collagen(CTX-I).AA significantly inhibited the OVX-induced expression of osteoclastogenesis-related marker genes and proteins in the femur.In summary,AA alleviates ovariectomy-induced bone loss in mice by suppressing osteoclastogenesis via inhibition of RANKL-mediated RANK signaling pathways and could be potentially used for the prevention and treatment of osteoclastrelated diseases such as osteoporosis.
基金Supported by the National Defense Basic Scientific Research Program of China.
文摘Amphibious vehicles are more prone to attitude instability compared to ships,making it crucial to develop effective methods for monitoring instability risks.However,large inclination events,which can lead to instability,occur frequently in both experimental and operational data.This infrequency causes events to be overlooked by existing prediction models,which lack the precision to accurately predict inclination attitudes in amphibious vehicles.To address this gap in predicting attitudes near extreme inclination points,this study introduces a novel loss function,termed generalized extreme value loss.Subsequently,a deep learning model for improved waterborne attitude prediction,termed iInformer,was developed using a Transformer-based approach.During the embedding phase,a text prototype is created based on the vehicle’s operation log data is constructed to help the model better understand the vehicle’s operating environment.Data segmentation techniques are used to highlight local data variation features.Furthermore,to mitigate issues related to poor convergence and slow training speeds caused by the extreme value loss function,a teacher forcing mechanism is integrated into the model,enhancing its convergence capabilities.Experimental results validate the effectiveness of the proposed method,demonstrating its ability to handle data imbalance challenges.Specifically,the model achieves over a 60%improvement in root mean square error under extreme value conditions,with significant improvements observed across additional metrics.
基金Project supported by the National Basic Research Program of China(No.2005CB121107)the Innovation Research Group of National Basic Research Program of China(No.2005).
文摘Guanting Reservoir, one of the drinking water supply sources of Beijing, suffers from water eutrophication. It is mainly supplied by Guishui River. Thus, to investigate the reasons of phosphorus （P） loss and improve the P management strategies in Guishui River watershed are important for the safety of drinking water in this region. In this study, a Revised Field P Ranking Scheme （PRS） was developed to reflect the field vulnerability of P loss at the field scale based on the Field PRS. In this new scheme, six factors are included, and each one was assigned a relative weight and a determination method. The affecting factors were classified into transport factors and source factors, and, the standards of environmental quality on surface water and soil erosion classification and degradation of the China were used in this scheme. By the new scheme, thirty-four fields in the Guishui River were categorized as ＂low＂, ＂medium＂ or ＂high＂ potential for P loss into the runoff. The results showed that the P loss risks of orchard and vegetable fields were higher than that of corn and soybean fields. The source factors were the main factors to affect P loss from the study area. In the study area, controlling P input and improving P usage efficiency are critical to decrease P loss. Based on the results, it was suggested that more attention should be paid on the fields of vegetable and orchard since they have extremely high usage rate of P and high soil test of P. Compared with P surplus by field measurements, the Revised Field PRS was more suitable for reflecting the characteristics of fields, and had higher potential capacity to identify critical source areas of P loss than PRS.
基金The Innovative Research Group Project of National Natural Science Foundation of China,No.41321001The National Basic Research Program(973 Program),No.2012CB955404The Program for Introducing Talents of Disciplines to Universities funded by the Ministry of Education and State Administration of Foreign Experts Affairs,China,No.B08008
文摘Coping with extreme climate events and its related climatic disasters caused by climate change has become a global issue and drew wide attention from scientists, policy-makers and public. This paper calculated the expected annual multiple climatic hazards intensity index based on the results of nine climatic hazards including tropical cyclone, flood, landslide, storm surge, sand-dust storm, drought, heat wave, cold wave and wildfire. Then a vulnerability model involving the coping capacity indicator with mortality rate, affected population rate and GDP loss rate, was developed to estimate the expected annual affected population, mortality and GDP loss risks. The results showed that： countries with the highest risks are also the countries with large population or GDP. To substantially reduce the global total climatic hazards risks, these countries should reduce the exposure and improving the governance of integrated climatic risk; Without considering the total exposure, countries with the high mortality rate, affected population rate or GDP loss rate, which also have higher or lower coping capacity, such as the Philippines, Bangladesh and Vietnam, are the hotspots of the planning and strategy making for the climatic disaster risk reduction and should focus on promoting the coping capacity.
基金supported by the National Natural Science Foundation of China,Nos.81800919(to YX),82171140(to PW)the International Cooperation and Exchange of the National Natural Science Foundation of China,Nos.82020108008(to HS),81720108010(to SY).
文摘Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial spectrum.However,their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct target.In addition,the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon exposure.To investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides,we used a C57BL/6J mouse model treated with kanamycin.We found that the mice exhibited auditory deficits following the acute loss of outer hair cells.Spiral ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over time.Transcriptomic profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response,particularly those related to the NLRP3 inflammasome.Activation of the canonical pyroptotic pathway in spiral ganglion neurons was observed,accompanied by infiltration of macrophages and the release of proinflammatory cytokines.Pharmacological intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury model.These findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron degeneration.Inhibition of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.
基金supported by National Natural Science Foundation of China(NSFC 52432002,52372041,52302087)Heilongjiang Touyan Team Program,the Fundamental Research Funds for the Central Universities(Grant No.HIT.OCEF.2021003)the Shanghai Aerospace Science and Technology Innovation Fund(SAST2022-60).
文摘Developing effective strategies to regulate graphene’s conduction loss and polarization has become a key to expanding its application in the electromagnetic wave absorption(EMWA)field.Based on the unique energy band structure of graphene,regulating its bandgap and electrical properties by introducing heteroatoms is considered a feasible solution.Herein,metal-nitrogen doping reduced graphene oxide(M–N-RGO)was prepared by embedding a series of single metal atoms M–N_(4) sites(M=Mn,Fe,Co,Ni,Cu,Zn,Nb,Cd,and Sn)in RGO using an N-coordination atom-assisted strategy.These composites had adjustable conductivity and polarization to optimize dielectric loss and impedance matching for efficient EMWA performance.The results showed that the minimum reflection loss(RL_(min))of Fe–N-RGO reaches−74.05 dB(2.0 mm)and the maximum effective absorption bandwidth(EAB_(max))is 7.05 GHz(1.89 mm)even with a low filler loading of only 1 wt%.Combined with X-ray absorption spectra(XAFS),atomic force microscopy,and density functional theory calculation analysis,the Fe–N_(4) can be used as the polarization center to increase dipole polarization,interface polarization and defect-induced polarization due to d-p orbital hybridization and structural distortion.Moreover,electron migration within the Fe further leads to conduction loss,thereby synergistically promoting energy attenuation.This study demonstrates the effectiveness of metal-nitrogen doping in regulating the graphene′s dielectric properties,which provides an important basis for further investigation of the loss mechanism.
基金supported by the National Natural Science Foundation of China(Grant Nos.:U23A20530,82273858,and 82173746)the National Key Research and Development Programof China(Grant No.:2023YFF1204904)Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism(Shanghai Municipal Education Commission,China).
文摘Activity cliffs(ACs)are generally defined as pairs of similar compounds that only differ by a minor structural modification but exhibit a large difference in their binding affinity for a given target.ACs offer crucial insights that aid medicinal chemists in optimizing molecular structures.Nonetheless,they also form a major source of prediction error in structure-activity relationship(SAR)models.To date,several studies have demonstrated that deep neural networks based on molecular images or graphs might need to be improved further in predicting the potency of ACs.In this paper,we integrated the triplet loss in face recognition with pre-training strategy to develop a prediction model ACtriplet,tailored for ACs.Through extensive comparison with multiple baseline models on 30 benchmark datasets,the results showed that ACtriplet was significantly better than those deep learning(DL)models without pretraining.In addition,we explored the effect of pre-training on data representation.Finally,the case study demonstrated that our model's interpretability module could explain the prediction results reasonably.In the dilemma that the amount of data could not be increased rapidly,this innovative framework would better make use of the existing data,which would propel the potential of DL in the early stage of drug discovery and optimization.
文摘This editorial critically evaluates the application of foot reflexology as a treatment for sensorineural hearing loss(SNHL)in infants,as proposed in a case report published in the World of Clinical Cases.SNHL is a condition characterized by damage to the cochlea or the neural pathways that transmit auditory information to the brain.The etiology of SNHL is often complex,involving genetic mutations,prenatal factors,or perinatal insults.Reflexology,an alternative therapy involving the application of pressure to specific points on the feet,is based on the hypothesis that these points correspond to different organs and systems in the body,including the auditory system.However,the biological plausibility and clinical efficacy of foot reflexology in addressing SNHL lack empirical support.This editorial examines the pathophysiology of SNHL,assesses the clinical claims of reflexology practitioners,and emphasizes the necessity of evidence-based approaches in treating infant hearing loss.While complementary therapies may provide ancillary benefits,they should not supplant validated medical treatments in managing SNHL in infants.Further research is needed to evaluate the safety and efficacy of foot reflexology and other alternative therapies in pediatric audiology.
文摘Hearing loss is the third leading cause of human disability.Age-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health burden.Noise-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing loss.The etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental factors.Oxidative stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing loss.Short non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic response.Sensory hair cell death is a central histopathological finding in sensorineural hearing loss.As these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing loss.Ovid EMBASE,Ovid MEDLINE,Web of Science Core Collection,and ClinicalTrials.gov databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical trials.Registe red clinical trials known to the senior author we re also assessed.A total of 222studies were thus identified.After excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text screening.This resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative review.MiRNAs miR-34a and miR-29b levels increase with age in mice.These miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT1p53,and SIRT1/hypoxia-inducible factor 1-alpha signaling pathways resulting in increased apoptosis.Furthermore,hypoxia and oxidative stress had a similar adve rse apoptotic effect,which was inhibited by resve ratrol and a myocardial inhibitorassociated transcript,a miR-29b competing endogenous mRNA.Gentamicin reduced miR-182-5p levels and increased cochlear oxidative stress and cell death in mice-an effect that was corrected by inner ear stem cell-derived exosomes.There is ongoing work seeking to determine if these findings can be effectively translated to humans.
基金supported by the National Nat-ural Science Foundation of China(Nos.51872238,52074227,and 21806129)the Fundamental Research Funds for the Central Universities,China(Nos.3102018zy045 and 3102019AX11)+2 种基金the Guangdong Basic and Applied Basic Research Foundation,China(No.2024A1515010298)the Natural Science Basic Research Plan in Shaanxi Province of China(Nos.2017JQ5116 and 2020JM-118)the Key Laboratory of Icing and Anti/De-icing of CARDC(No.IADL20220401).
文摘Gels and conductive polymer composites,including hydrogen bonds(HBs),have emerged as promising materials for electro-magnetic wave(EMW)absorption across various applications.However,the relationship between conduction loss in EMW-absorbing materials and charge transfer in HB remains to be fully understood.In this study,we developed a series of deep eutectic gels to fine-tune the quantity of HB by adjusting the molar ratio of choline chloride(ChCl)and ethylene glycol(EG).Owing to the unique properties of deep eutectic gels,the effects of magnetic loss and polarization loss on EMW attenuation can be disregarded.Our results indicate that the quantity of HB initially increases and then decreases with the introduction of EG,with HB-induced conductive loss following similar pat-terns.At a ChCl and EG molar ratio of 2.4,the gel labeled G22-CE2.4 exhibited the best EMW absorption performance,characterized by an effective absorption bandwidth of 8.50 GHz and a thickness of 2.54 mm.This superior performance is attributed to the synergistic ef-fects of excellent conductive loss and impedance matching generated by the optimal number of HB.This work elucidates the role of HB in dielectric loss for the first time and provides valuable insights into the optimal design of supramolecular polymer absorbers.
基金supported by the State Key Laboratory of Arid Land Crop Science, Gansu Agricultural University,China (GSCS-2022-Z02)the National Key R&D Program of China (2022YFD1900300)+2 种基金the National Natural Science Foundation of China (32260549)the Innovation Group of Basic Research in Gansu Province, China (25JRRA807)the Major Special Research Projects in Gansu Province, China (22ZD6NA009)。
文摘The application of organic fertilizers has become an increasingly popular practice in maize production to reduce thegaseous nitrogen(N) loss and soil degradation caused by inorganic fertilizers. Organic fertilizer plays a key rolein improving soil quality and stabilizing maize yields, but few studies have compared different substitution rates. Afield study was carried out in 2021 and 2022, based on a long-term trial initiated in 2016, which included five organicfertilizer N substitution rates with equal inputs of 200 kg N ha^(–1): 0% organic fertilizer(T1, 100% inorganic fertilizer),50.0% organic+50.0% inorganic fertilizer(T2), 37.5% organic+62.5% inorganic fertilizer(T3), 25.0% organic+75.0%inorganic fertilizer(T4), and 12.5% organic+87.5% inorganic fertilizer(T5), as well as a no fertilizer control(T6). Theresults of the two years showed that T3 and T1 had the highest grain yield and biomass, respectively, and there wasno significant difference between T1 and T3. Compared with T1, the 12.5, 25.0, 37.5, and 50.0% substitution rates in T5, T4, T3, and T2 significantly reduced total nitrogen losses(NH_(3), N_(2)O) by 8.3, 16.1, 18.7, and 27.0%, respectively.Nitrogen use efficiency(NUE) was higher in T5, T3, and T1, and there were no significant differences among them.Organic fertilizer substitution directly reduced NH_(3)volatilization and N_(2)O emission from farmland by lowering theammonium nitrogen and alkali-dissolved N contents and by increasing soil moisture. These substitution treatmentsreduced N_(2)O emissions indirectly by regulating the abundances of AOB and nirK-harboring genes by promotingsoil moisture. Specifically, the 37.5% organic fertilizer substitution reduces NH_(3)volatilization and N_(2)O emission from farmland by reducing the ammonium nitrogen and alkali-dissolved N contents and increasing moisture, which negatively regulate the abundance of AOB and nir K-harboring genes to reduce N_(2)O emissions indirectly in rainfed maize fields on the Loess Plateau of China.
基金supported by the European Union as a mobility grant
文摘Leaf turgor loss point has been recognized as an important plant physiological trait explaining a species’drought tolerance( π_(tlp)).Less is known about the variation of π_(tlp) in time and how seasonal or interannual differences in water availability are affecting π_(tlp) as a static trait.I monitored the seasonal variation of π_(tlp) during a drought year starting in early spring with juvenile leaves and assessed the interannual variation in π_(tlp) of fully matured leaves among years with diverting water availability for three temperate broad-leaved tree species.The largest seasonal changes in π_(tlp) occurred during leaf unfolding until leaves were fully developed and matured.After leaves matured,no significant changes occurred for the rest of the vegetation period.Interannual variation that could be related to water availability was only present in one of the three tree species.The results suggest that the investigated species have a rapid period of osmotic adjustment early in the growing season followed by a period of relative stability,when π_(tlp) can be considered as a static trait.
基金supported by the National Key Research and Development Program of China(Grant numbers:2021YFF0901705,2021YFF0901700)the State Key Laboratory of Media Convergence and Communication,Communication University of China+1 种基金the Fundamental Research Funds for the Central Universitiesthe High-Quality and Cutting-Edge Disciplines Construction Project for Universities in Beijing(Internet Information,Communication University of China).
文摘In the Internet era,recommendation systems play a crucial role in helping users find relevant information from large datasets.Class imbalance is known to severely affect data quality,and therefore reduce the performance of recommendation systems.Due to the imbalance,machine learning algorithms tend to classify inputs into the positive(majority)class every time to achieve high prediction accuracy.Imbalance can be categorized such as by features and classes,but most studies consider only class imbalance.In this paper,we propose a recommendation system that can integrate multiple networks to adapt to a large number of imbalanced features and can deal with highly skewed and imbalanced datasets through a loss function.We propose a loss aware feature attention mechanism(LAFAM)to solve the issue of feature imbalance.The network incorporates an attention mechanism and uses multiple sub-networks to classify and learn features.For better results,the network can learn the weights of sub-networks and assign higher weights to important features.We propose suppression loss to address class imbalance,which favors negative loss by penalizing positive loss,and pays more attention to sample points near the decision boundary.Experiments on two large-scale datasets verify that the performance of the proposed system is greatly improved compared to baseline methods.
基金Supported by National Natural Science Foundation of China(Grant Nos.51175422,61973011)Shaanxi Provincial Natural Science Basic Research Plan of China(Grant No.2022JM-195)+1 种基金Fundamental Research Funds for the Central Universities of Chinathe Research Start-up Funds of Hangzhou International Innovation Institute of Beihang University(Grant No.2024KQ036)。
文摘During high-speed rotation,the surface of aeronautic spiral bevel gears will generate significant pressure and viscous forces,which will cause a certain amount of windage power loss and reduce the efficiency of the transmission system.Based on the computational fluid dynamics,this paper analyzes the windage power loss of a single spiral bevel gear and a spiral bevel gear pair under oil injection lubrication.In addition,the shroud is used to suppress gear windage loss,and the clearance size and opening angle of the designed shroud are optimized.Finally,by comparing and analyzing the experimental results,the following conclusions were obtained:(1)For a single gear,the speed is the most important factor affecting windage loss,followed by the hand of spiral,and rotation direction;(2)For gear pairs,under oil injection lubrication,the input speed has the greatest impact on windage power loss,followed by the influence of oil injection port speed,temperature and oil injection port pressure;(3)Installing a shroud is an effective method to reduce windage power loss;(4)In the pure air phase,the smaller the clearance between the shroud and the gear surface,and the smaller the radial direction between the shroud and the shaft,the better the effect of reducing windage;(5)In the two-phase flow of oil and gas,it is necessary to design oil drainage holes on the shroud to ensure the smooth discharge of lubricating oil and improve the drag reduction effect.
基金Supported by the Fundamental Research Funds for the Central Universities,No.2022CDJYGRH-004.
文摘Foot reflexology is a non-invasive and safe complementary therapy that works by massaging the reflex zones of the feet and exerts systemic or whole-body regulation through meridian nerve conduction.This therapy is commonly used in the treatment of various conditions such as autism and Parkinson's disease.However,there is limited reporting on the use of foot reflexology therapy for infants with sensorineural hearing loss(SNHL).Currently,there is no definitive conclusion on how foot reflexology therapy can influence hearing.This editorial holds some guiding significance regarding this clinical issue.The aim is to present physiological evidence of how foot reflexology therapy can impact infants with SNHL,thereby enhancing clinician’s awareness of foot reflexology in treating infants with SNHL.
基金supported by National Natural Science Foundation of China(22178002,22178001)Natural Science Foundation of Anhui Province(2308085Y19)Excellent Youth Research Project of Anhui Provincial Department of Education(2022AH030045).
文摘Hydrogen-enriched ironmaking presents a promising approach to mitigate coke consumption and carbon emission in blast furnace(BF)operations.This work investigated the relationship between the structural features of cokes and their reactivity towards solution loss(SL),especially under hydrogen-enriched atmospheres.Six cokes were characterized,and their SL behaviors were examined under varying atmospheres to elucidate the effects of hydrogen enrichment.The results indicate that an increase in fixed carbon content leads to a decrease in the coke reactivity index(CRI)and an increase in coke strength after reaction(CSR),in the CO_(2) atmosphere,the CSR of coke increases from 35.76%−62.83%,while in the 90CO_(2)/10H_(2) atmosphere,the CSR of coke increases from 65.67%−84.09%.There is a good linear relationship between CRI and microcrystalline structure parameters of coke.Cokes with larger crystalline size,lower amorphous content,and smaller optical texture index(OTI)values show enhanced resistance to degradation and maintain structural integrity in BF.Kinetic analysis performed with the shifted-modified-random pore model(S-MRPM)reveals that alterations in pore structure and intrinsic mineral composition significantly influence the reaction rate.The introduction of a small amount of water vapor raises SL rates,whereas a minor addition of hydrogen(<10%)decelerates SL due to its incomplete conversion to water vapor and the reduced partial pressure of the gasifying agent.Thermodynamic calculations also indicate that the introduced hydrogen does not convert into the same fraction of water vapor.The shift from chemical reaction control to gas diffusion control as the rate-determining step with rising temperatures during SL process was confirmed,and the introduction of hydrogen does not notably alter SL behavior.This result demonstrated that introducing a small amount of hydrogen(<10%)can mitigate SL rates,thereby enhancing coke strength and reducing coke consumption and carbon emissions.
文摘Early intervention for sensorineural hearing loss(SNHL)in childhood is crucial for auditory and language development.In recent years,innovative auditory stimulation techniques and speech therapy strategies,such as middle ear implants,cochlear implants,auditory brainstem implants,and midbrain implants,have provided new avenues for improving patient outcomes.Additionally,basic research advancements in cell reprogramming and regeneration,stem cell therapy,and targeted drug delivery offer promising approaches to meet the individualized needs of children with SNHL.However,many challenges and unresolved issues remain in the treatment of SNHL.This article comments on the case report,which describes a female pediatric patient with SNHL who underwent foot reflexology which led to the normalization of hearing thresholds.Reflexology is considered to have potential benefits in physical rehabilitation,but its efficacy in hearing restoration requires further scientific validation through rigorous clinical trials and large-scale prospective studies.
