Progress,implications,and challenges in using humanized immune system mice in CAR-T therapy-Application evaluation and improvement

In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient mice.To better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor treat-ments.By exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and development.We believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient mice.The characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid substitution.Strategy study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development.

Establishment of a humanized ST6GAL1 mouse model for influenza research

Background:This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1.Methods:Humanized fragments,consisting of the endothelial cell-specific K18 promoter,human ST6GAL1-encoding gene,and luciferase gene,were microinjected into the fertilized eggs of mice.The manipulated embryos were transferred into the oviducts of pseudopregnant female mice.The offspring were identified using PCR.Mice exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation,and in vivo analysis was performed for screening.Expression of the humanized gene was tested by performing immunohistochemical(IHC)analysis.Hematologic and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were performed.Results:Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT ST6GAL1.Seven mice were identified as carrying copies of the humanized gene,and the in vivo analysis indicated that hST6GAL1gene expression in positive mice mirrored influenza virus infection characteristics.The IHC results revealed that hST6GAL1 was expressed in the lungs of humanized mice.Moreover,the hematologic and biochemical parameters of the positive mice were within the normal range.Conclusion:A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized.

Operation room nursing based on humanized nursing mode combined with nitric oxide on rehabilitation effect after lung surgery

BACKGROUND With advancements in the diagnosis and treatment of lung diseases,lung segment surgery has become increasingly common.Postoperative rehabilitation is critical for patient recovery,yet challenges such as complications and adverse outcomes persist.Incorporating humanized nursing modes and novel treatments like nitric oxide inhalation may enhance recovery and reduce postoperative complications.AIM To evaluate the effects of a humanized nursing mode combined with nitric oxide inhalation on the rehabilitation outcomes of patients undergoing lung surgery,focusing on pulmonary function,recovery speed,and overall treatment costs.METHODS A total of 79 patients who underwent lung surgery at a tertiary hospital from March 2021 to December 2021 were divided into a control group(n=39)receiving a routine nursing program and an experimental group(n=40)receiving additional humanized nursing interventions and atomized inhalation of nitric oxide.Key indicators were compared between the two groups alongside an analysis of treatment costs.RESULTS The experimental group demonstrated significant improvements in pulmonary function,reduced average recovery time,and lower total treatment costs compared to the control group.Moreover,the quality of life in the experimental group was significantly better in the 3 months post-surgery,indicating a more effective rehabilitation process.CONCLUSION The combination of humanized nursing mode and nitric oxide inhalation in postoperative care for lung surgery patients significantly enhances pulmonary rehabilitation outcomes,accelerates recovery,and reduces economic burden.This approach offers a promising reference for improving patient care and rehabilitation efficiency following lung surgery.

The Alienation of Nature in Emily Dickinson’s Poems through the Prism of Taoism

In the poems created by the renowned American poet Emily Dickinson,those related to nature constitute a considerable proportion.However,Dickinson’s attitude toward nature is,in fact,contradictory.On the one hand,Dickinson perceives nature as gentle and kind,akin to a mother.Nature is regarded as“heaven”and embodies harmony.On the other hand,nature possesses its own operational principles and harbors inherent cruelty.According to Dickinson,humans should refrain from excessive interference in the natural order.This article attempts to analyze the similarities in attitude towards nature between Dickinson’s poetry and Taoist philosophy.

Problems and Development Suggestions of Nature Education in Jiangxi Province

The forest coverage rate of Jiangxi Province ranks second in China.It has rich natural resources,a long history of ancient color culture and rich red culture.In the development of nature education,Jiangxi Province has great potential and advantages.This paper introduces the development conditions of nature education in Jiangxi Province,summarizes the problems existing in the development of nature education in Jiangxi Province from the aspects of the types of nature education and the construction of nature education base,such as simple content and single form,imperfect infrastructure and lack of professionals,and puts forward some suggestions on the development of nature education in Jiangxi Province.

《Nature》子刊:苏佳琪等开发基于牛奶的水凝胶,用作酒精中毒的解毒剂

近日,苏黎世联邦理工学院Raffaele Mezzenga、苏佳琪等人在《Nature》子刊《Nature Nanotechnology》上发表的一篇研究显示,该研究开发了一种口服的、基于牛奶蛋白的水凝胶——FeSA@FibBLG,或可作为急性酒精中毒的有效解毒剂,能够稳定耐受胃酸消化且持续显著降低酒精中毒小鼠血液中的酒精水平,同时避免额外积累有毒的乙醛,还可增强肝脏保护,并显著减轻肠道损伤和生态失调,强调了其作为酒精相关疾病的新疗法的潜力。

Nature’s Gift

NATURAL WONDERS IN CHINA AND AFRICA Qilian Mountains National Park Located in Northwest China’s Gansu and Qinghai provinces,Qilian Mountains National Park spans 50,200 square km,serving as a vital ecological security barrier and water source conservation area in west China.Established in 2017 to address ecosystem damage,intensive food chain protection and wildlife monitoring in the area began in early 2011.

Spatiotemporal Evolution of Ecological Quality in Alpine Freshwater Lake Nature Reserves in the Past 20 Years

The Caohai Nature Reserve is one of the three major plateau freshwater lakes in China.Since the 1950s,human activities such as land reclamation and population relocation have greatly damaged Caohai.A rapid evaluation of the spatiotemporal evolution trend of the ecological quality of the Caohai Nature Reserve is significant for the maintenance and construction of the ecosystem in this area.The research is based on the Google Earth Engine(GEE)remote sensing cloud computing platform.Landsat TM/OLI images from May to October in five time periods:2000-2002,2004-2006,2009-2011,2014-2016,and 2019-2021 were obtained to reconstruct the optimal cloud image set by averaging the images in each time period.By constructing four ecological indicators:Greenness(NDVI),Wetness(Wet),Hotness(LST),and Dryness(NDBSI),and using Principal Component Analysis(PCA)method to obtain the Remote Sensing Ecological Index(RSEI)for the corresponding years,the spatiotemporal variation of ecological quality in the Caohai Nature Reserve over 20 years was analyzed.The results indicate:①the mean value of RSEI increased from 0.460 in 2000-2002 to 0.772 in 2019-2021,a 67.83%increase,indicating a significant improvement in the ecological quality of the reserve over the 20 years;②from the perspective of functional zoning of the Caohai Nature Reserve,the ecological quality of the core area showed a degrading trend,while the ecological quality of the buffer zone and experimental zone significantly improved;③with the implementation of ecological restoration projects,the ecological quality of the reserve gradually recovered and improved from 2014 to 2021.The trend of RSEI value changes is well correlated with human interventions,indicating that the PCA-based RSEI model can be effectively used for ecological quality assessment in lake areas.

《Nature》:新开发的可穿戴超声贴片可连续、无创监测大脑血流

近日,一篇发表在《Nature》上的研究显示,研究人员开发出一种可穿戴超声贴片(wearable ultrasound patch),其可对大脑血流进行连续、无创的监测。该研究将贴片在36名健康志愿者身上进行了测试,以检验其测量脑部主要动脉血流速度(收缩期峰值、平均流速和舒张末期速度)的能力,发现测量结果与传统超声探头的测量结果非常吻合。

Research on the Application Effect of Humanized Nursing Management in Pediatric Rehabilitation Wards

Objective:To explore the application effect of humanized nursing management in pediatric rehabilitation wards.Methods:82 pediatric patients admitted to our hospital between January 2023 and January 2024 were randomly divided into a control group and an observation group.Among them,the control group was given routine care,while the observation group received humanized nursing management,and the clinical nursing effects and situations of the two groups of children were compared and analyzed.Results:After nursing,the observation group showed significantly better performance in intelligent Developmental Quotient(DQ)values(P<0.05).The clinical nursing satisfaction of the observation group was significantly better than that of the control group(χ^(2)=11.710,P<0.05).Conclusion:Humanized nursing management for patients in pediatric rehabilitation wards not only improves their recovery but also significantly enhances parental satisfaction,which is worth learning from and promoting in clinical settings.

Analysis of the Effect of Implementing Humanized Care Service in Severe ICU Patients

Objective:To analyze the effect of implementing humanized nursing service intervention for severe patients in the intensive care unit(ICU).Methods:A hundred severely ill ICU patients who were treated from January 2021 to December 2022 were selected and grouped into a control group and an observation group.The control group adopted routine nursing services and the observation group adopted humanized nursing services.The nursing outcome of the two groups was analyzed.Results:The nursing risk incidence of the observation group was lower than that of the control group(P<0.05).The scale of comfort and nursing satisfaction in the observation group was higher than those in the control group(P<0.05).Conclusion:The implementation of a humanized care service for ICU patients lowered nursing risk incidences and increased the physical comfort and nursing satisfaction of these patients.

《Nature》:科学家发现能驱动患者狼疮发生的两种细胞缺陷

近日,一篇发表在《Nature》上的研究显示,研究发现了一种特殊的分子缺陷或会促进系统性红斑狼疮的病理性免疫反应,同时揭示了逆转这一缺陷或有望逆转疾病。该研究中,研究人员报道了驱动狼疮发生的新通路,研究者表示,患者体内血液中的多种分子都会发生疾病相关的改变,最终,这些变化会导致芳香烃受体(aryl hydrocarbon receptor,AHR)所控制的通路激活不足,AHR能调节细胞对环境污染物、细菌或代谢产物的反应。

Application and Satisfaction Analysis of Humanized Quality Nursing Intervention in the Care of Patients with Critical Respiratory Failure

Objective:To implement humanized quality care in critical respiratory failure nursing,observe the effect,and analyze the satisfaction.Methods:80 patients with severe respiratory failure were divided into 40 cases per group(admitted from February 2022 to December 2023)by double-blind method,the control group performed routine care,and the observation group was given humanized quality care.Results:After the nursing care,two respiratory function indexes of the observation group were lower than those of the control group,and two pulmonary function indexes were higher than those of the control group(P<0.05);regarding the complication situation,the incidence rate of the observation group was lower(P<0.05);regarding the nursing care satisfaction situation,the observation group had a higher level of total satisfaction(P<0.05).Conclusion:The application of a humanized quality nursing intervention model in the care of critical respiratory failure can actively improve patients’respiratory status and lung function,reduce complications,and satisfy patients.

“Eternal Motion” as a “Form of Movement of a Special Nature” and the Main Condition for the Creation of the Universe

The article hypothesizes that DE and DM (UCM) are a “Form of Motion of a Special Nature”, where “Form of Motion” means “Eternal Motion” as the power of dynamics of different levels and varying degrees of self-sufficiency, and by “Special Nature”, gravitational and two other properties of matter, “tied” to the “Eternal Movement” and completely dependent on it. Carriers of key properties of a “Special Nature” have been established: “0”-DE particles and “3”-DM particles (UDM). The unity of their inherent “motionally-gravitational” properties and the peculiarity of the relationship between “motion” and “gravity” are revealed: the higher the intensity of “Eternal Motion”, the stronger the gravitational properties of matter are manifested (and vice versa). The relationship of “time” with the “vibration frequency” and the “mass” of photons with the “degree of bonding and deformation properties of the field” is shown. The maximum level of gravity has been determined, which allows Nature to successfully create the Universe: such a landmark is the proximity to the property of the Primary Source—the “pure graviton” of the OSP space, the most powerful “motionally-gravitational” particle of the Universe. The reasons for the emergence of such an identity of the gravitational properties of particles with the indicators of a “pure graviton” are established: for “0”-DE particles, this is the acquisition of the function of “freedom of movement”;for “3”-DM particles (UDM), the creation of a special structure—a “double field” (“Main” and “Small”). The presence in the “double field” of specific “tools” for the creation of the worlds of the Universe—gravitational “waves” gives rise to impulses (shocks) of varying intensity and shape. A list of functions performed by “waves” in the “Main” and “Small” fields has been compiled. The specific conditions for the formation of “UDM Streams”, their transformation into a “Vortex” and, under the influence of a powerful Initial Impulse (push), sending them to the “place” of the creation of galaxies, are shown. It is suggested that there is a “Cycle of Matter in Nature” in the closed structure of our Universe due to the “work” of “waves” and the functioning of special “factories” in the form of exotic space objects—Black holes.

Effects of humanized nursing care on negative emotions and complications in patients undergoing hysteromyoma surgery

BACKGROUND Uterine fibroids,are prevalent benign tumors affecting women of reproductive age.However,surgical treatment is often necessary for symptomatic hysteromyoma cases.This study examines the impact of humanized nursing care on reducing negative emotions and postoperative complications in patients receiving hysteromyoma surgery.AIM To investigate the impact of humanized nursing care on patients undergoing hysteromyoma surgery.METHODS Among patients who underwent hysteromyoma surgery at the Fudan University Affiliated Obstetrics and Gynecology Hospital,200 were randomly assigned to either the control group(n=100)or the humanized nursing care group(n=100).The control group received traditional nursing care,while the humanized nursing care group received a comprehensive care plan encompassing psychological support,pain management,and tailored rehabilitation programs.In addition,anxiety and depression levels were assessed using the hospital anxiety and depression scale preoperatively and postoperatively.Postoperative complications were evaluated during follow-up assessments and compared between both groups.RESULTS The humanized nursing care group demonstrated a significant decrease in anxiety and depression levels compared to the control group(P<0.05).The rate of postoperative complications,including infection,bleeding,and deep venous thrombosis,was also markedly lower in the humanized nursing care group(P<0.05).CONCLUSION Humanized nursing care can effectively alleviate negative emotions and reduce the incidence of postoperative complications in patients undergoing hysteromyoma surgery.This approach should be considered a crucial component of perioperative care for these patients.Further research may be needed to explore additional benefits and long-term outcomes of implementing humanized nursing care in this population.

Mushroomβ-glucan and polyphenol formulations as natural immunity boosters and balancers:nature of the application

Mushrooms are experiencing a kind of renaissance as a part of the contemporary human diet.These valuable organisms are more than food,they fit in perfectly as a novel market group known as nutra-mycoceuticals.Immune-balancing mushroom dietary fibers and secondary metabolites such as polyphenols are the main focus of the healthcare industry.Wellness and cosmetic companies are increasingly using mushroom extracts rich in these ingredients.This review considers the basic molecular immunomodulatory mechanisms of action of the most commonly used mushroom dietary fibers,β-glucans.The literature data on their bioavailability,metabolic transformations,preclinical and human clinical research,and safety are discussed.Immunomodulatory mechanisms of polyphenol ingredients are also considered.These molecules present great potential in the design of the new immunity balancer formulations according to their widespread structural diversity.Finally,we draw attention to the perspectives of modern trends in mushroom nutraceutical and cosmeceutical formulations to strengthen and balance immunity.

Characterization of genetic humanized mice with transgenic HLA DP401 or DRA but deficient in endogenous murine MHC classⅡgenes upon Staphylococcus aureus pneumonia

Background:Staphylococcus aureus can cause serious infections by secreting many superantigen exotoxins in“carrier”or“pathogenic”states.HLA DQ and HLA DR humanized mice have been used as a small animal model to study the role of two molecules during S.aureus infection.However,the contribution of HLA DP to S.aureus infection is unknown yet.Methods:In this study,we have produced HLA DP401 and HLA DRA0101 humanized mice by microinjection of C57BL/6J zygotes.Neo-floxed IAβ+/-mice were crossbred with Ella-Cre and further crossbred with HLA DP401 or HLA-DRA0101 humanized mice.After several rounds of traditional crossbreeding,we finally obtained HLA DP401-IAβ-/-and HLA DRA-IAβ-/-humanized mice,in which human DP401 or DRA0101 molecule was introduced into IAβ-/-mice deficient in endogenous murine MHC classⅡmolecules.A transnasal infection murine model of S.aureus pneumonia was induced in the humanized mice by administering 2×108CFU of S.aureus Newman dropwise into the nasal cavity.The immune responses and histopathology changes were further assessed in lungs in these infected mice.Results:We evaluated the local and systemic effects of S.aureus delivered intranasally in HLA DP401-IAβ-/-and HLA DRA-IAβ-/-transgenic mice.S.aureus Newman infection significantly increased the m RNA level of IL 12p40 in lungs in humanized mice.An increase in IFN-γand IL-6 protein was observed in HLA DRA-IAβ-/-mice.We observed a declining trend in the percentage of F4/80+macrophages in lungs in HLA DP401-IAβ-/-mice and a decreasing ratio of CD4+to CD8+T cells in lungs in IAβ-/-mice and HLA DP401-IAβ-/-mice.A decreasing ratio of Vβ3+to Vβ8+T cells was also found in the lymph node of IAβ-/-mice and HLA DP401-IAβ-/-mice.S.aureus Newman infection resulted in a weaker pathological injury in lungs in IAβ-/-genetic background mice.Conclusion:These humanized mice will be an invaluable mouse model to resolve the pathological mechanism of S.aureus pneumonia and study what role DP molecule plays in S.aureus infection.

Beyond Morality:Han Fei’s Unconventional Insights Into Human Nature

Han Fei presented a thought-provoking perspective on human nature and its implications for governance.Departing from traditional moral doctrines,Han Fei’s“non-moralistic”philosophy posited that human nature is inherently self-interested and driven by personal gain.In this paper,we explore Han Fei’s keen insights into human nature and its practical application in political governance.His emphasis on aligning political strategies with human inclinations,rather than relying solely on moral preaching,highlights the complexity and pragmatism of his approach.However,we also examine the limitations of his philosophy,particularly in disregarding individual differences and idealism.By striking a balance between political expediency and moral considerations,Han Fei’s ideas continue to resonate with contemporary discussions on governance and human behavior.This study calls for a reflective and cautious assessment of the implications of Han Fei’s“non-moralistic”thought in today’s society.

Human Rights Connotations and Its Legal Protection in the Harmonious Coexistence between Humans and Nature

Promoting the unity of human nature and sociality in practice is a fundamental path dependence for achieving people's well-rounded development.Within the context of harmonious coexistence between humans and nature,the practice of the unity of human nature and sociality is allowed to be truly implemented,and people's well-rounded development moves from possibility to reality.Strengthening the protection of human rights for people's well-rounded development in the harmonious coexistence between humans and nature not only requires the expansion of the connotations of environmental rights from“the right to a healthy environment”to“the right to a beautiful environment”,but also necessitates the formation of a collaborative framework between environmental rights and development rights.For legal responses to the expansion of the connotations of environmental rights,it is necessary to implement such expansions in environmental legislation,enhance the underlying principles,and make progress in the development of systematic environmental legislation simultaneously.Regarding the legal promotion of the synergy between environmental rights and development rights,it is essential to follow the guidance of the“Two Mountains Theory,”take the coordinated functions of environmental and traditional legal departments as the basis,and build a legal mechanism for the realization of the value of ecological products and services.

The Man Who Organized Nature: The Life of Linnaeus by Gunnar Broberg

GunnarBroberg(1942–2022),a professor of history ideas and sciences at the Lund University in Sweden,has assembled and summarized virtually all of the contemporary documents relating to the life of Carl Linnaeus(1707–1778).This is therefore a fact-laden and definitive personal biography of the founder of our systems of plant and animal taxonomy.Linnaeus’childhood included much time in nature that forever provided him an experience background for the huge amount of plant and animal species he would encounter.In his early days,his country was in an era of poverty where“hordes of starving,homeless people drifted along the roads in the years when the harvest failed.”Linnaeus himself“...could lie awake all night as he lacked the money for evening meals when he was a student.”He inserted paper into his shoes to cover the holes on which he walked.