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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease 被引量:4
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作者 Gabriela Seplovich Yazan Bouchi +8 位作者 Juan Pablo de Rivero Vaccari Jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy 《Neural Regeneration Research》 SCIE CAS 2025年第6期1644-1664,共21页
Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela ... Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline. 展开更多
关键词 Alzheimer's disease caspase-1 chronic traumatic encephalopathy INFLAMMASOMES neurodegeneration NEUROINFLAMMATION NLRP1 NLRP3 PYROPTOSIS TAUOPATHY traumatic brain injury
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Impact of coking plant to heavy metal characteristics in groundwater of surrounding areas:Spatial distribution,source apportionment and risk assessments 被引量:1
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作者 Congqing Wang Wanjun Wang +5 位作者 ChaoWang Shixing Ren Yingjun Wu Meicheng Wen Guiying Li Taicheng An 《Journal of Environmental Sciences》 2025年第3期688-698,共11页
Coking industry is a potential source of heavy metals(HMs)pollution.However,its impacts to the groundwater of surrounding residential areas have not been well understood.This study investigated the pollution character... Coking industry is a potential source of heavy metals(HMs)pollution.However,its impacts to the groundwater of surrounding residential areas have not been well understood.This study investigated the pollution characteristics and health risks of HMs in groundwater nearby a typical coking plant.Nine HMs including Fe,Zn,Mo,As,Cu,Ni,Cr,Pb and Cd were analyzed.The average concentration of total HMswas higher in the nearby area(244.27μg/L)than that of remote area away the coking plant(89.15μg/L).The spatial distribution of pollution indices including heavy metal pollution index(HPI),Nemerow index(NI)and contamination degree(CD),all demonstrated higher values at the nearby residential areas,suggesting coking activity could significantly impact the HMs distribution characteristics.Four sources of HMs were identified by Positive Matrix Factorization(PMF)model,which indicated coal washing and coking emission were the dominant sources,accounted for 40.4%,and 31.0%,respectively.Oral ingestionwas found to be the dominant exposure pathway with higher exposure dose to children than adults.Hazard quotient(HQ)values were below 1.0,suggesting negligible non-carcinogenic health risks,while potential carcinogenic risks were from Pb and Ni with cancer risk(CR)values>10−6.Monte Carlo simulation matched well with the calculated results with HMs concentrations to be the most sensitive parameters.This study provides insights into understanding how the industrial coking activities can impact the HMs pollution characteristics in groundwater,thus facilitating the implement of HMs regulation in coking industries. 展开更多
关键词 Coking industry Heavy metal GROUNDWATER Spatial distribution Source apportionment Monte Carlo simulation
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Functional central nervous system regeneration:Challenges from axons to circuits
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作者 Apolline Delaunay Mickael Le Boulc’h +1 位作者 Stephane Belin Homaira Nawabi 《Neural Regeneration Research》 2026年第5期1983-1984,共2页
The mature central nervous system(CNS,composed of the brain,spinal cord,olfactory and optic nerves)is unable to regenerate spontaneously after an insult,both in the cases of neurodegenerative diseases(for example Alzh... The mature central nervous system(CNS,composed of the brain,spinal cord,olfactory and optic nerves)is unable to regenerate spontaneously after an insult,both in the cases of neurodegenerative diseases(for example Alzheimer's or Parkinson's disease)or traumatic injuries(such as spinal cord lesions).In the last 20 years,the field has made significant progress in unlocking axon regrowth. 展开更多
关键词 parkinsons disease unlocking axon regrowth neurodegenerative diseases central nervous system cnscomposed functional regeneration axon regrowth spinal cord lesions central nervous system
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Neural network solution based on the minimum potential energy principle for static problems of structural mechanics
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作者 Jiamin QIAN Lincong CHEN J.Q.SUN 《Applied Mathematics and Mechanics(English Edition)》 2025年第6期1125-1142,共18页
This paper presents the variational physics-informed neural network(VPINN)as an effective tool for static structural analyses.One key innovation includes the construction of the neural network solution as an admissibl... This paper presents the variational physics-informed neural network(VPINN)as an effective tool for static structural analyses.One key innovation includes the construction of the neural network solution as an admissible function of the boundary-value problem(BVP),which satisfies all geometrical boundary conditions.We then prove that the admissible neural network solution also satisfies natural boundary conditions,and therefore all boundary conditions,when the stationarity condition of the variational principle is met.Numerical examples are presented to show the advantages and effectiveness of the VPINN in comparison with the physics-informed neural network(PINN).Another contribution of the work is the introduction of Gaussian approximation of the Dirac delta function,which significantly enhances the ability of neural networks to handle singularities,as demonstrated by the examples with concentrated support conditions and loadings.It is hoped that these structural examples are so convincing that engineers would adopt the VPINN method in their structural design practice. 展开更多
关键词 physics-informed neural network(PINN) variational physics-informed neural network(VPINN) structural statics admissible function Gaussian approximation
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Natural Tourism in Kosovo and the Potentials of the Dukagjin Region
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作者 Alberta Tahiri Anela Džogović +13 位作者 Idriz Kovaçi Thëllëza Latifi Sadrija Nora Draga Elvira Misini Ardiana Hyseni Selvije Lajqi Doresa Mulaj Fatbardha Shala Hyrije Bajramaj Kushtrim Agaj Flaka Muriqi Mimoza Mekuli Ismet Berisha Mendim Nimonaj 《Journal of Environmental & Earth Sciences》 2025年第3期274-285,共12页
This study aims to assess the potential of natural tourism in Kosovo,especially in the Dukagjin region as a case study.The main objective is to identify and analyze this region’s tourism potential to understand its i... This study aims to assess the potential of natural tourism in Kosovo,especially in the Dukagjin region as a case study.The main objective is to identify and analyze this region’s tourism potential to understand its impact and importance.180 respondents from the Dukagjin region participated in this study,and the quantitative method was used as a methodology.The measurement instrument consisted of 30 closed questions,which aimed to collect detailed information on the potential of natural tourism in this area.The study results showed that mountain,cultural,winter,healing,and rural tourism are especially important for developing the Dukagjin region.Furthermore,the analysis shows that 30%of the tourism potential is explained by rural tourism,underlining its importance in the local economy.Finally,the study’s findings are discussed,emphasizing their practical value for promoting and developing sustainable tourism in the region. 展开更多
关键词 Development Dukagjin Region Natural Tourism Rural Tourism Tourist Potentials Tourism Promotion
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Endoscopic full-thickness resection:A definitive solution for local complete resection of small rectal neuroendocrine neoplasms 被引量:1
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作者 Xiao-Long Zhang Yang-Yang Jiang +6 位作者 Ying-Ying Chang Yu-Li Sun Ying Zhou Yao-Hui Wang Xiao-Tan Dou Hui-Min Guo Ting-Sheng Ling 《World Journal of Gastroenterology》 2025年第10期51-61,共11页
BACKGROUND Recently,several endoscopic techniques have been used to improve the R0 resection rate of rectal neuroendocrine neoplasms(R-NENs).However,none of these methods can achieve 100%complete resection(CR),particu... BACKGROUND Recently,several endoscopic techniques have been used to improve the R0 resection rate of rectal neuroendocrine neoplasms(R-NENs).However,none of these methods can achieve 100%complete resection(CR),particularly in the vertical direction.Endoscopic full-thickness resection(EFTR)has proven to be an effective method for the treatment of submucosal tumors but is seldom utilized in the eradication of R-NENs.AIM To review cases of R-NENs removed using EFTR and to evaluate the safety and efficacy of this technique.METHODS This retrospective cohort study enrolled 160 patients with pathologically confirmed R-NENs,including 132 who underwent endoscopic submucosal dissection(ESD)and 28 who underwent EFTR.Lesions were categorized as<1 cm,1-2 cm,and>2 cm in size.CR rate,en bloc resection rate,operation time,and complications were evaluated.Subgroup analyses and follow-up were also performed.RESULTS EFTR achieved 100%CR rates for lesions<1 cm and 1-2 cm,compared with 67.0%and 50.0%,respectively,in the ESD group.En bloc resection and successful removal of the R-NENs were achieved in all patients.Meanwhile,EFTR showed performance comparable to ESD in terms of operation time,hospitalization cost,and postoperative adverse events,except for a one-day longer hospital stay.We also analyzed the invasion depth of R-NENs based on full-thickness specimens.The data showed that 80%of lesions(<1 cm)and 85.7%of lesions(1-2 cm)had invaded the SM3 level or deeper at the time of resection.For ESD specimens,46.6%(<1 cm)and 89.3%(1-2 cm)of lesions had infiltrated more than 2000μm beneath the muscularis mucosae.CONCLUSION EFTR has shown superior performance in the resection of small R-NENs compared with that of ESD. 展开更多
关键词 Endoscopic full-thickness resection Endoscopic submucosal dissection Rectal neuroendocrine neoplasms Complete resection Endoscopic technique
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The Impact of Public Investments on the Development of Sustainable Tourism in The Sharr Mountains Region
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作者 Alberta Tahiri Mimoza Luta 《Journal of Environmental & Earth Sciences》 2025年第1期457-470,共14页
The study aims to identify and analyze the perceptions and expectations of tourists regarding tourism development in the Sharr Mountains Region.In the Sharr Mountains Region,sustainable tourism is another opportunity ... The study aims to identify and analyze the perceptions and expectations of tourists regarding tourism development in the Sharr Mountains Region.In the Sharr Mountains Region,sustainable tourism is another opportunity for economic growth,cultural integrity,and environmental conservation.Public investments are vital in enhancing this investment as they help to develop infrastructure,promote businesses,and even promote environment-friendly activities.The research seeks to understand the relationship between public investments and investments in sustainable tourism in the Sharr Mountains region,focusing on the direct and indirect relational aspects of the economy,conservation,and the people.Key questions,address their expectations from public investment,infrastructure improvements,involvement of local authorities and the community,as well as concerns regarding the potential negative impact of tourism on the natural environment and local culture.The methodology of this study includes in-depth research through the quantitative method.Based on the results of data analysis,recommendations include improving tourism infrastructure,increasing awareness of environmental impact,and developing environmental education programs for tourists.Among the proposed actions is the improvement of cooperation between local authorities,the local community,and the private sector for the sustainable development of tourism in the Sharr Mountains Region.Finally,this study provides an essential contribution to the understanding of the expectations,evaluations,and impacts of tourists in this region,defining the key points of sustainable tourism development. 展开更多
关键词 Environmental Impact Local Community Local Authorities SUSTAINABILITY TOURISM
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Unwanted disorders and xenogeneic graft-versus-host disease in experimental immunodeficient mice:How to evaluate and how to report
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作者 Seyed Mostafa Monzavi Samad Muhammadnejad +2 位作者 Vahid Mansouri Hami Ashraf Naser Ahmadbeigi 《Animal Models and Experimental Medicine》 2025年第1期20-29,共10页
Human-derived tumor models are essential for preclinical development of new anti-cancer drug entities.Generating animal models bearing tumors of human origin,such as patient-derived or cell line-derived xenograft tumo... Human-derived tumor models are essential for preclinical development of new anti-cancer drug entities.Generating animal models bearing tumors of human origin,such as patient-derived or cell line-derived xenograft tumors,is dependent on immuno-deficient strains.Tumor-bearing immunodeficient mice are susceptible to develop-ing unwanted disorders primarily irrelevant to the tumor nature;and if get involved with such disorders,reliability of the study results will be undermined,inevitably con-founding the research in general.Therefore,a rigorous health surveillance and clinical monitoring system,along with the establishment of a strictly controlled barrier facility to maintain a pathogen-free state,are mandatory.Even if all pathogen control and biosafety measures are followed,there are various noninfectious disorders capable of causing tissue and multiorgan damage in immunodeficient animals.Therefore,the re-searchers should be aware of sentinel signs to carefully monitor and impartially report them.This review discusses clinical signs of common unwanted disorders in experi-mental immunodeficient mice,and how to examine and report them. 展开更多
关键词 animal models graft-versus-host disease health surveillance preclinical drug evaluation xenograft model antitumor assays
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Coupled effects of surface elasticity,couple stresses,and adhesion in nanocontact mechanics
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作者 Youxue BAN Xinyao YANG +1 位作者 Q.X.LI Changwen MI 《Applied Mathematics and Mechanics(English Edition)》 2025年第7期1237-1260,I0001,I0002,共26页
This paper investigates the adhesive nanocontact behavior of an elastic halfplane indented by a rigid cylindrical indenter,incorporating the simultaneous effects of surface elasticity,couple stresses,and adhesion.The ... This paper investigates the adhesive nanocontact behavior of an elastic halfplane indented by a rigid cylindrical indenter,incorporating the simultaneous effects of surface elasticity,couple stresses,and adhesion.The free surface of the half-plane is modeled by the Steigmann-Ogden surface elasticity theory,while the bulk material behavior is described by the classical couple-stress elasticity theory.The adhesion at the contact interface is characterized by the Maugis-Dugdale(MD)adhesive contact model.Building on the fundamental nonclassical Flamant solution,the governing equations and boundary conditions of the nanocontact problem are reformulated into a system of triple integral equations.These equations are solved numerically by the Gauss-Chebyshev quadratures in combination with an iterative algorithm.The validation against the existing literature confirms the accuracy and robustness of the proposed solution methodology.Comprehensive parametric studies are performed to elucidate the critical roles of surface elasticity and couple stresses in adhesive nanocontact.The numerical results provide insights into the complex interactions among surface,couple-stress,and adhesive effects.Specifically,the interplay between the surface and adhesive effects is predominantly competitive,while the interaction between the couple stresses and adhesion exhibits an intricate nature.The findings highlight the necessity of simultaneously considering surface elasticity,couple stresses,and adhesion in nanoindentation analyses to achieve accurate predictions of material responses. 展开更多
关键词 adhesive nanocontact Maugis-Dugdale(MD)adhesion Steigmann-Ogden surface effect classical couple-stress theory Gauss-Chebyshev quadrature
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Adult neurogenesis:a real hope or a delusion? 被引量:5
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作者 Ghulam Hussain Rabia Akram +5 位作者 Haseeb Anwar Faiqa Sajid Tehreem Iman Hyung Soo Han Chand Raza Jose-Luis Gonzalez De Aguilar 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第1期6-15,共10页
Adult neurogenesis,the process of creating new neurons,involves the coordinated division,migration,and differentiation of neural stem cells.This process is restricted to neurogenic niches located in two distinct areas... Adult neurogenesis,the process of creating new neurons,involves the coordinated division,migration,and differentiation of neural stem cells.This process is restricted to neurogenic niches located in two distinct areas of the brain:the subgranular zone of the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricle,where new neurons are generated and then migrate to the olfactory bulb.Neurogenesis has been thought to occur only during the embryonic and early postnatal stages and to decline with age due to a continuous depletion of neural stem cells.Interestingly,recent years have seen tremendous progress in our understanding of adult brain neurogenesis,bridging the knowledge gap between embryonic and adult neurogenesis.Here,we discuss the current status of adult brain neurogenesis in light of what we know about neural stem cells.In this notion,we talk about the importance of intra cellular signaling molecules in mobilizing endogenous neural stem cell prolife ration.Based on the current understanding,we can declare that these molecules play a role in targeting neurogenesis in the mature brain.However,to achieve this goal,we need to avoid the undesired proliferation of neural stem cells by controlling the necessary checkpoints,which can lead to tumorigenesis and prove to be a curse instead of a blessing or hope. 展开更多
关键词 adult neurogenesis AGING brain-derived neurotrophic factor dentate gyrus HIPPOCAMPUS neural stem cells neurotrophic factors NOTCH oxidative stress stem cells subgranular zone
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Effect of sodium content on the electrochemical performance of P2-Na_(2)Ni_(2)TeO_(6)layered oxide cathode for sodium-ion batteries
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作者 Iqra Moeez Ali Hussain Umar Bhatti +4 位作者 Min-Kyung Cho Dieky Susanto Muhammad Akbar Ghulam Ali Kyung Yoon Chung 《Carbon Energy》 2025年第2期109-120,共12页
Sodium-ion batteries(SIBs)employ P2-type layered transition metal oxides as promising cathode materials,primarily due to their abundant natural reserves and environmentally friendly characteristics.However,structural ... Sodium-ion batteries(SIBs)employ P2-type layered transition metal oxides as promising cathode materials,primarily due to their abundant natural reserves and environmentally friendly characteristics.However,structural instability and complex phase transitions during electrochemical cycling pose significant challenges to their practical applications.Employing cation substitution serves as a straightforward yet effective strategy for stabilizing the structure and improving the kinetics of the active material.In this study,we introduce a Ni-rich honeycomb-layered Na_(2+x)Ni_(2)TeO_(6)(NNTO)cathode material with variable sodium content(x=0,0.03,0.05,0.10).Physicochemical characterizations reveal that excess sodium content at the atomic scale modifies the surface and suppresses phase transitions,while preserving the crystal structure.This results in enhanced cyclic performance and improved electrochemical kinetics at room temperature.Furthermore,we investigate the performance of the NNTO cathode material containing 10%excess sodium at a relatively high temperature of 60℃,where it exhibits 71.6%capacity retention compared to 60%for the pristine.Overall,our results confirm that a preconstructed surface layer(induced by excess sodium)effectively safeguards the Ni-based cathode material from surface degradation and phase transitions during the electrochemical processes,thus exhibiting superior capacity retention relative to the pristine NNTO cathode.This study of the correlation between structure and performance can potentially be applied to the commercialization of SIBs. 展开更多
关键词 honeycomb structure layered oxides sodium content sodium-ion battery structure disorder
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Tamanu Oil in Acne Management: Potential Anti-Inflammatory and Wound-Healing Properties for Scar Reduction
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作者 Rachel Marciano Alexandra Loperfito +5 位作者 Maddie Moll Allison Liu Yuna Huh Nicole Werpachowski Kelly Frasier Julia Vinagolu-Baur 《Journal of Biomedical Science and Engineering》 2024年第10期185-193,共9页
Tamanu oil, derived from the nuts of Calophyllum inophyllum, has gained increasing attention for its potential in acne management due to its purported anti-inflammatory and wound-healing properties. This analysis eval... Tamanu oil, derived from the nuts of Calophyllum inophyllum, has gained increasing attention for its potential in acne management due to its purported anti-inflammatory and wound-healing properties. This analysis evaluates the efficacy of tamanu oil in acne treatment with a specific focus on its impact on inflammation and scar reduction. The novelty of this research lies in its comprehensive analysis of tamanu oil’s dual mechanism of action: reducing acne-related inflammation and promoting the healing of acne scars. Clinical trials and laboratory analyses were conducted to assess the oil’s effectiveness in diminishing erythema, swelling, and post-acne scarring compared to conventional treatments. Preliminary findings demonstrate that tamanu oil significantly reduces inflammation and accelerates wound healing, potentially offering a promising adjunct or alternative to standard acne therapies. Future research should aim to optimize formulation and application protocols, long-term effects, and comparative therapeutic efficacy with other anti-inflammatory agents. Tamanu oil offers a novel and effective approach to acne management, with potential advantages that go beyond inflammation reduction to include enhanced scar reduction, making it a subject that warrants further investigation. 展开更多
关键词 Tamanu Oil Calophyllum inophyllum Acne Management Anti-Inflammatory Properties Wound Healing Acne Scars Erythema Reduction Inflammation Reduction Scar Reduction Alternative Acne Therapies Natural Acne Treatments Dermatological Applications of Tamanu Oil
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Decoding the nexus:branched-chain amino acids and their connection with sleep,circadian rhythms,and cardiometabolic health 被引量:1
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作者 Hui Li Laurent Seugnet 《Neural Regeneration Research》 SCIE CAS 2025年第5期1350-1363,共14页
The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given th... The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other organs.Among these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral processes.Among the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of rapamycin.Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared transporter.Beyond their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy metabolism.Notably,they impact GABAergic neurons and the excitation/inhibition balance.The rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock control.The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood.Disturbed sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics.The mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies.In this context,the Drosophila model,though underutilized,holds promise in shedding new light on these mechanisms.Initial findings indicate its potential to introduce novel concepts,particularly in elucidating the intricate connections between the circadian clock,sleep/wake,and metabolism.Consequently,the use and transport of branched-chain amino acids emerge as critical components and orchestrators in the web of interactions across multiple organs throughout the sleep/wake cycle.They could represent one of the so far elusive mechanisms connecting sleep patterns to metabolic and cardiovascular health,paving the way for potential therapeutic interventions. 展开更多
关键词 branched-chain amino acids cardiovascular health circadian clock DROSOPHILA INSULIN metabolism SLEEP γ-aminobutyric acid
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Advances in Tumor Microenvironment and Immunotherapeutic Strategies for Hepatocellular Carcinoma
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作者 Jiahao Xue Jingchang Zhang +2 位作者 Gang Chen Liucui Chen Xinjun Lu 《Oncology Research》 2025年第9期2309-2329,共21页
Hepatocellular carcinoma(HCC)is a highly aggressive malignancy,largely driven by an immunosuppres-sive tumor microenvironment(TME)that facilitates tumor growth,immune escape,and resistance to therapy.Although immunoth... Hepatocellular carcinoma(HCC)is a highly aggressive malignancy,largely driven by an immunosuppres-sive tumor microenvironment(TME)that facilitates tumor growth,immune escape,and resistance to therapy.Although immunotherapy—particularly immune checkpoint inhibitors(ICIs)—has transformed the therapeutic landscape by restoring T cell-mediated anti-tumor responses,their clinical benefit as monotherapy remains suboptimal.This limitation is primarily attributed to immunosuppressive components within the TME,including tumor-associated macrophages,regulatory T cells(Tregs),and myeloid-derived suppressor cells(MDSCs).To address these challenges,combination strategies have been explored,such as dual checkpoint blockade targeting programmed cell death protein 1(PD-1),programmed death-ligand 1(PD-L1),and cytotoxic T-lymphocyte-associated antigen 4(CTLA-4),as well as synergistic use of ICIs with anti-angiogenic agents or TME-targeted interventions.These approaches have shown encouraging potential in enhancing immune efficacy.This review outlines the complex crosstalk between the TME and immunotherapeutic responses in HCC,emphasizing how combination regimens may overcome immune resistance.Furthermore,we discuss the remaining hurdles,including therapeutic resistance and immune-related adverse events,and propose future directions involving TME-associated biomarkers and individualized treatment strategies to improve patient outcomes. 展开更多
关键词 Hepatocellular carcinoma(HCC) tumor microenvironment(TME) IMMUNOTHERAPY immune checkpoint inhibitors(ICIs) combination therapy
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Promotion of symbiotic interaction between phagotrophic protists and beneficial bacteria,mediated via balancing of soil nutrients,reduces the incidence of watermelon Fusarium wilt
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作者 Yaoyao TONG Li WANG +7 位作者 Chuanfa WU Haoqing ZHANG Yangwu DENG Ming CHEN Xianqing ZHENG Weiguang LÜ Jianping CHEN Tida GE 《Pedosphere》 2025年第2期352-363,共12页
Elucidating the microbial mechanisms that trigger Fusarium wilt represents a key step in addressing the barriers to sustainable cropping.However,from the perspective of the complete microbiome,the integrated role of s... Elucidating the microbial mechanisms that trigger Fusarium wilt represents a key step in addressing the barriers to sustainable cropping.However,from the perspective of the complete microbiome,the integrated role of soil nutrients and microbial community in the fields with different rates of wilt disease remains unclear.In this study,we examined the potential interrelationships among the nutrients,bacteria,fungi,and protists in rhizospheric soils collected from the fields with watermelon cropping for 7 years at the Zhuanghang Experimental Station of Shanghai Academy of Agricultural Sciences,China.The soils collected were characterized by a high(HW,81.25%)or low(LW,6.25%)wilting rate.The HW soil was found to contain a higher abundance of Fusarium oxysporum(1.30-fold higher)than the LW soil,along with higher contents of available phosphorus(1.31-fold higher)and available potassium(2.39-fold higher).In addition,the interkingdom correlation between protists and bacteria in the HW soil was 2.08-fold higher than that in the LW soil.Furthermore,structural equation modeling revealed that an excess of soil available potassium enhanced the predation by potentially detrimental phagotrophic protists on potentially beneficial bacteria.In summary,our findings indicated that a balanced nutrient input and the interactions between protists(Cercomonas and Colpoda)and beneficial bacteria(Bacillus)played important roles in controlling the incidence of watermelon Fusarium wilt. 展开更多
关键词 continuous cropping co-occurrence network Fusarium oxysporum microbial community nitrogen limitation soil-borne pathogen
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High-fidelity Lumped-parameter Thermal Models for Assessing Cooling Techniques of PMSMs in EV Applications 被引量:2
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作者 Dawei Liang Zi Qiang Zhu Ankan Dey 《CES Transactions on Electrical Machines and Systems》 2025年第1期1-14,共14页
This paper presents a high-fidelity lumpedparameter(LP)thermal model(HF-LPTM)for permanent magnet synchronous machines(PMSMs)in electric vehicle(EV)applications,where various cooling techniques are considered,includin... This paper presents a high-fidelity lumpedparameter(LP)thermal model(HF-LPTM)for permanent magnet synchronous machines(PMSMs)in electric vehicle(EV)applications,where various cooling techniques are considered,including frame forced air/liquid cooling,oil jet cooling for endwinding,and rotor shaft cooling.To address the temperature misestimation in the LP thermal modelling due to assumptions of concentrated loss input and uniform heat flows,the developed HF-LPTM introduces two compensation thermal resistances for the winding and PM components,which are analytically derived from the multi-dimensional heat transfer equations and are robust against different load/thermal conditions.As validated by the finite element analysis method and experiments,the conventional LPTMs exhibit significant winding temperature deviations,while the proposed HF-LPTM can accurately predict both the midpoint and average temperatures.The developed HFLPTM is further used to assess the effectiveness of various cooling techniques under different scenarios,i.e.,steady-state thermal states under the rated load condition,and transient temperature profiles under city,freeway,and hybrid(city+freeway)driving cycles.Results indicate that no single cooling technique can maintain both winding and PM temperatures within safety limits.The combination of frame liquid cooling and oil jet cooling for end winding can sufficiently mitigate PMSM thermal stress in EV applications. 展开更多
关键词 Cooling techniques Electric vehicle Lumpedparameter thermal model Permanent magnet synchronous machines Thermal analysis Thermal management
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One-step preparation of biocompatible amphiphilic dimer nanoparticles with tunable particle morphology and surface property for interface stabilization and drug delivery
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作者 Xingqun Pu Rongrong Liu +9 位作者 Yuting Xie Chenjing Yang Jingyi Chen Baoling Guo Chun-Xia Zhao Peng Zhao Jian Ruan Fangfu Ye David A Weitz Dong Chen 《Chinese Chemical Letters》 2025年第3期345-350,共6页
Biocompatible amphiphilic nanoparticles(NPs)with tunable particle morphology and surface property are important for their applications as functional materials.However,previously developed methods to prepare amphiphili... Biocompatible amphiphilic nanoparticles(NPs)with tunable particle morphology and surface property are important for their applications as functional materials.However,previously developed methods to prepare amphiphilic NPs generally involve several steps,especially an additional step for surface modification,greatly hindering their largescale production and widespread applications.Here,a versatile one-step strategy is developed to prepare biocompatible amphiphilic dimer NPs with tunable particle morphology and surface property.The amphiphilic dimer NPs,which consist of a hydrophobic shellac bulb and a hydrophilic poly(lactic acid)(PLA)bulb with PLA-poly(ethylene glycol)(PEG)on the bulb surface,are prepared in a single step by controlled co-precipitation and self-assembly.Amphiphilic PLA-PEG/shellac dimer NPs demonstrate excellent tunability in particle morphology,thus showing good performances in controlling the interfacial curvature and emulsion type.In addition,temperatureresponsive PLA-poly(N-isopropyl acrylamide)(PNIPAM)/shellac dimer NPs are prepared following the same method and emulsions stabilized by them show temperature-triggered response.The applications of PLA-PEG-folic acid(FA)/shellac dimer NPs for drug delivery have also been demonstrated,which show a very good performance.The strategy of preparing the dimer NPs is green,scalable,facile and versatile,which provides a good platform for the design of dimer NPs with tunable particle morphology and surface property for diverse applications. 展开更多
关键词 Janus particle Amphiphilic particle Dimer particle Colloidal surfactant Pickering emulsion Drug delivery
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Patriarchal Apparatus:The Role of Media,University,and Athletic ISAs in the Nassar Abuse Case
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作者 A.Paige Frazier 《Journalism and Mass Communication》 2025年第4期209-215,共7页
The Larry Nassar scandal at Michigan State University is the worst and most widespread case of childhood sex abuse in this nation’s history to date,affecting over 150 young girls and women.This article asks:What were... The Larry Nassar scandal at Michigan State University is the worst and most widespread case of childhood sex abuse in this nation’s history to date,affecting over 150 young girls and women.This article asks:What were the structural and ideological mechanisms,policies,and practices that enabled this widespread abuse over a thirty-year period?Louis Althusser’s Marxist theory of Ideological State Apparatuses(and feminist responses to this theory)is useful in explaining how state-making institutions-media outlets,universities,athletic organizations,and family units-are not only produced and reproduced along class lines,but also with respect to gendered power dynamics.By examining the patriarchal nature of ISAs,one can begin to understand how Larry Nassar was for so long shielded from suspicion and criminal prosecution by the institutions that employed him. 展开更多
关键词 structural mechanisms ideological mechanisms feminist responses patriarchal nature criminal prosecution
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Metabolic Surgery: Concepts and New Classification
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作者 Paulo Reis Rizzo Esselin de Melo Victor Ramos Mussa Dib +34 位作者 Carlos Augusto Scussel Madalosso Chetan Parmar Omar Ghanem Miguel Ángel Carbajo Ricardo Zorron Amador García Ruiz de Gordejuela Caio Gustavo Gaspar de Aquino Luiz Alfredo Vieira d’Almeida Luciano Antozzi Rui Ribeiro Halit Eren Taskin Jorge Bravo López Christine Stier Patrick Noel José Sergio Verboonen Sotelo Laurent Abram Layani Ramon Vilallonga Puy Elinton Adami Chaim Helmuth Billy Carlos Eduardo Domene Paula Volpe Nilton Tokio Kawahara Augusto Cláudio de Almeida Tinoco Antelmo Sasso Fin Hiroji Okano Júnior Nicholas Tavares Kruel Giorgio Alfredo Pedroso Baretta Diogo Swain Kfouri Anna Carolina Hoff Fernando Reis Esselin Melo Thonya Cruz Braga Clayton Alencar Moreira Luis Poggi Almino Cardoso Ramos Antonio Torres 《Surgical Science》 2025年第2期87-109,共23页
Bariatric and metabolic surgeries have gained extensive popularity and trust due to their documented efficacy and safety in managing not only obesity but also associated comorbidities such as diabetes mellitus, hypert... Bariatric and metabolic surgeries have gained extensive popularity and trust due to their documented efficacy and safety in managing not only obesity but also associated comorbidities such as diabetes mellitus, hypertension, dyslipidemia, sleep apnea, and joint pain. Traditionally, bariatric surgeries have been categorized into hypoabsorptive, restrictive, or hybrid approaches. However, these classifications inadequately reflect the complex anatomical and physiological alterations associated with modern surgical methodologies. This paper explores the evolution of metabolic surgeries, emphasizing the integration of physiological concepts into classic procedures to provide more tailored and effective treatment options for obesity and its comorbidities. Finally, the proposal for a new classification based on current metabolic concepts will facilitate communication among patients, doctors, and healthcare professionals. Additionally, it will enable a more didactic and standardized approach to data collection for conducting studies and publications. 展开更多
关键词 Metabolic Surgery Bariatric Surgery OBESITY Physiological Concepts Gastrointestinal Procedures Transit Bipartition Long Common Channel Metabolically Functional Stomach Wide Anastomosis
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Concentration and retention of ascorbic acid,carotenoids,and sugars in fresh-cut lettuce in modified atmosphere packaging
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作者 Jinita Sthapit Kandel Ivan Simko +1 位作者 Ryan J.Hayes Beiquan Mou 《Horticultural Plant Journal》 2025年第1期303-313,共11页
Fresh-cut lettuce is widely used in ready-to-eat salads sold in modified atmosphere packages (MAP).Even in MAP,fresh-cut lettuce has short shelf life that results in loss of nutrients.Lettuce cultivars exhibit genetic... Fresh-cut lettuce is widely used in ready-to-eat salads sold in modified atmosphere packages (MAP).Even in MAP,fresh-cut lettuce has short shelf life that results in loss of nutrients.Lettuce cultivars exhibit genetic variation for shelf life in MAP,but their variation for nutrient retention is not known.Fifty accessions were evaluated for initial content of ascorbic acid (AsA),carotenoids,and sugars and their retention in storage.Accessions with high content and/or good retention of one or more nutrients were identified.The romaine accession ‘Floricos’ had high levels of all the three nutrients.Accessions with relatively high retention of all the three nutrients were ‘Salinas 88’,‘Siskiyou’,‘Solar’,SM09A,‘Romance’,and ‘Green Towers’.Romaine cultivars,‘Balady Barrage’,‘Green Towers’,and ‘Darkland’ had relatively high initial levels of all tested nutrients and good rate of their retention.There was no clear correlation between initial AsA/carotene concentrations and their retention rates,suggesting that besides content,retention of nutrients should also be a breeding target in a lettuce nutritional improvement program.Statistical analyses with the Pearson's correlation coefficient determined a negative relationship between tissue deterioration(AUDePS) and retention of all tested nutrients[r of-0.52 (P<0.0001) for AsA,-0.27 (P<0.01) for total carotene,and-0.59 (P<0.0001) for total sugars],suggesting that an increase in tissue deterioration intensifies nutrient decay.Broad-sense heritability (H^(2)) across the experiments was0.15 for AsA,0.23 for total carotene,and 0.50 for total sugars.Identification of germplasm with high nutrient content,extended shelf life and good nutrient retention provides valuable information for the lettuce industry and associated breeding programs. 展开更多
关键词 LETTUCE Shelf life Nutrient retention Ascorbic acid CAROTENE Sugars
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