Interannual evolution of the chemical composition,sources and processes of PM_(2.5)in Chengdu,China:Insights from observations in four winters

The air quality in China has improved significantly in the last decade and,correspondingly,the characteristics of PM_(2.5)have also changed.We studied the interannual variation of PM_(2.5)in Chengdu,one of the most heavily polluted megacities in southwest China,during the most polluted season(winter).Our results show that the mass concentrations of PM_(2.5)decreased significantly year-by-year,from 195.8±91.0μg/m~3in winter 2016 to 96.1±39.3μg/m^(3)in winter 2020.The mass concentrations of organic matter(OM),SO_()4^(2-),NH_(4)^(+)and NO_(3)^(-)decreased by 49.6%,57.1%,49.7% and 28.7%,respectively.The differential reduction in the concentrations of chemical components increased the contributions from secondary organic carbon and NO_(3)^(-)and there was a larger contribution from mobile sources.The contribution of OM and NO_(3)^(-)not only increased with increasing levels of pollution,but also increased year-by-year at the same level of pollution.Four sources of PM_(2.5)were identified:combustion sources,vehicular emissions,dust and secondary aerosols.Secondary aerosols made the highest contribution and increased year-by-year,from 40.6%in winter 2016 to 46.3% in winter 2020.By contrast,the contribution from combustion sources decreased from 14.4% to 8.7%.Our results show the effectiveness of earlier pollution reduction policies and emphasizes that priority should be given to key pollutants(e.g.,OM and NO_(3)^(-))and sources(secondary aerosols and vehicular emissions)in future policies for the reduction of pollution in Chengdu during the winter months.

Expression of Bmi-1 and EZH2 in tissues adjacent to human epithelial ovarian cancer cells of orthotopic implantation in nude mice

Objective This study investigated the feasibility of screening residual normal ovarian tissues based on the expression of Bmi-1 and EZH2 in tissues adjacent to orthotopic ovarian carcinomas in nude mice. Methods The human epithelial ovarian cancer cell line OVCAR3 was grown in subcutaneous tissues and the tumor tissues were orthotopically implanted. The expression levels of Bmi-1 and EZH2 were detected by immunohistochemical staining and RT-PCR in cancer tissues, proximal and remote tissues with respect to the cancer tissues, and normal ovarian tissues of nude mice.Results Thirty-five ovarian tissue samples with normal biopsy results were obtained from 40 cases of human epithelial ovarian cancer in the nude mice in which the tumor tissues were orthotopically implanted. Bmi-1 and EZH2 expression levels were lower in proximal paraneoplastic tissue samples than in cancer tissue samples(P < 0.05) and higher than in remote paraneoplastic tissue samples(P < 0.01). No significant difference was found in the expression levels of Bmi-1 and EZH2 using immunohistochemistry among residual normal ovarian tissues obtained from orthotopically implanted models that differed in severity. The expression of Bmi-1 and EZH2 was negative in 20 normal ovarian tissue samples.Conclusion The expression levels of Bmi-1 and EZH2 were reduced with increasing distance from the cancer tissues. Negative expression of these tumor-associated genes can be used as a standard for the screening of normal ovarian tissues adjacent to tumor tissues. Normal ovarian tissues can be obtained from the tissues adjacent to tumors.

Preliminary Study of Oxidative Stress in Human Hepatocellular Carcinoma and Adjacent Normal Liver Tissues

OBJECTIVE The antioxidative system in human hepatocellular carcinoma was investigated. METHODS The activities of cytosolic catalase (CAT), superoxide dismu-tase, glutathione peroxidase (GSH-Px), glutathione S-tranferase and levels of reduced glutathione, total protein thiols and malondialdehyde were assayed in 10 cases of hepatocellular carcinoma and adjacent normal liver. RESULTS Hepatoma tissues showed higher activities of CAT, GSH -Px and lower content of total antioxidative capacity compared to adjacent normal liver tissue (P<0.05). CONCLUSION These findings suggest that the antioxidative defense-related enzymes and antioxidants are largely regulated in hepatoma cells. However, the mechanism which is not clear requires further investigation.

Durable and enhanced immunity against SARS-CoV-2 elicited by manganese nanoadjuvant formulated subunit vaccine

Dear editor,Vaccines are the most efficient and effective means to prevent infectious diseases,but improving the long-term protective efficacy is still a major challenge in contemporary vaccine development.1 The waning immunity varies depending on the diversification of the pathogen and the number of booster doses.1 Strategies to overcome this warrant is using adjuvants that amplify the immune response,and drive the production of memory B and T cells or long-lived plasma cells that recognize the pathogen for durable protection.2–4 Although existing adjuvants have achieved promising results,research on generating durable protective immunity is lacking in promoting vaccine development and staying ahead of global pandemics such as coronavirus disease 2019(COVID-19).The precisely designed nanoadjuvants can enhance lymph node targeting and increase antigenpresenting cell(APCs)uptake,achieving the co-delivery of adjuvants and antigens and activating innate and adaptive immune responses.5 Previously,we reported a manganese nanoadjuvant(MnARK)and receptor-binding domain(RBD)monomer antigen formulated nanovaccine.6 MnARK transported antigens to lymph nodes,activated the STING pathway,elicited strong neutralizing abilities and increased immune memory T cell percentage against the infection of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).6 Regarding the long-term protection potential of MnARK for subunit vaccine development,we further explored the durable immune regulation abilities of MnARK to a SARS-CoV-2 RBD dimer antigen,which has been used in an approved COVID-19 subunit vaccine ZF2001 with aluminum adjuvant(alum).7,8 TEM result revealed that RBD dimer could interact with BSA on MnARK surface and epitope can be well preserved(Supplementary Fig.1a).The size and zeta potential of MnARK-RBD dimer nanovaccine was~58 nm and-14 mV,respectively(Supplementary Fig.1b,c).

Advancing intestinal organoid technology to decipher nano-intestine interactions and treat intestinal disease

With research burgeoning in nanoscience and nanotechnology,there is an urgent need to develop new biological models that can simulate native structure,function,and genetic properties of tissues to evaluate the adverse or beneficial effects of nanomaterials on a host.Among the current biological models,three-dimensional(3D)organoids have developed as powerful tools in the study of nanomaterial-biology(nano-bio)interactions,since these models can overcome many of the limitations of cell and animal models.A deep understanding of organoid techniques will facilitate the development of more efficient nanomedicines and further the fields of tissue engineering and personalized medicine.Herein,we summarize the recent progress in intestinal organoids culture systems with a focus on our understanding of the nature and influencing factors of intestinal organoid growth.We also discuss biomimetic extracellular matrices(ECMs)coupled with nanotechnology.In particular,we analyze the application prospects for intestinal organoids in investigating nano-intestine interactions.By integrating nanotechnology and organoid technology,this recently developed model will fill the gaps left due to the deficiencies of traditional cell and animal models,thus accelerating both our understanding of intestine-related nanotoxicity and the development of nanomedicines.

STING and TLR9 agonists synergistically enhance the immunogenicity of SARS-CoV-2 subunit vaccine

Vaccines that are reliable and efficacious are essential in the fight against the COVID-19 pandemic.In this study,we designed a dual-adjuvant system with two pathogen-associated molecular patterns(PAMPs),MnOx and CpG.This system can improve the retention of antigens at the injection site,facilitate pro-inflammatory cytokines secretion,further recruit and activate dendritic cells(DCs).As a result,antigens can be delivered to lymph nodes specifically,and adaptive immunity was strengthened.The immunized group showed an enhanced and broadened humoral and cellular immune response in systemic immunity and lung protection when combined with a tandem repeat-linked dimeric antigen version of the SARS-CoV-2 receptor binding domain(RBDdimer).Remarkably,even with a significant reduction in antigen dosage(three times lower)and a decrease in injection frequencies,our nanovaccine was able to produce the highest neutralizing antibody titers against various mutants.These titers were four-fold higher for the wild-type strain and two-fold higher for both the Beta and Omicron variants in comparison with those elicited by the Alum adjuvant group.In conclusion,our dual-adjuvant formulation presents a promising protein subunit-based candidate vaccine against SARS-CoV-2.

Engineered Nano−Bio Interfaces for Stem Cell Therapy

Engineered nanomaterials(ENMs)with different topographies provide effective nano−bio interfaces for controlling the differentiation of stem cells.The interaction of stem cells with nanoscale topographies and chemical cues in their microenvironment at the nano−bio interface can guide their fate.The use of nanotopographical cues,in particular nanorods,nanopillars,nanogrooves,nanofibers,and nanopits,as well as biochemical forces mediated factors,including growth factors,cytokines,and extracellular matrix proteins,can significantly impact stem cell differentiation.These factors were seen as very effective in determining the proliferation and spreading of stem cells.The specific outgrowth of stem cells can be decided with size variation of topographic nanomaterial along with variation in matrix stiffness and surface structure like a special arrangement.The precision chemistry enabled controlled design,synthesis,and chemical composition of ENMs can regulate stem cell behaviors.The parameters of size such as aspect ratio,diameter,and pore size of nanotopographic structures are the main factors for specific termination of stem cells.Protein corona nanoparticles(NPs)have shown a powerful facet in stem cell therapy,where combining specific proteins could facilitate a certain stem cell differentiation and cellular proliferation.Nano−bio reactions implicate the interaction between biological entities and nanoparticles,which can be used to tailor the stem cells’culmination.The ion release can also be a parameter to enhance cellular proliferation and to commit the early differentiation of stem cells.Further research is needed to fully understand the mechanisms underlying the interactions between engineered nano−bio interfaces and stem cells and to develop optimized regenerative medicine and tissue engineering designs.

整合照护对阿尔茨海默病患者长期管理的效果评价

目的探讨整合照护在阿尔茨海默病患者长期管理中的应用效果。方法对2016年3月—2018年3月入住杭州市福利中心的88例阿尔茨海默病患者,给予整合照护方法进行干预,主要包括照护人员课程培训、个案管理、环境布置、团体活动等。使用日常生活活动问卷(Activities of Daily Living Questionnaire,ADLQ)、Zarit照顾负担量表(Zarit Burden Interview,ZBI)和生存质量量表(Quality of Life,QOL),测量并比较干预前、干预3个月后以及6个月后的变化。结果干预3个月和6个月后,患者的ADLQ评分、QOL评分较干预前明显提高,同时患者ZBI评分较干预前明显减轻,差异具有统计学意义(ADLQ:49.32±10.99比52.74±9.31,QOL:16.73±6.16比30.18±4.61,ZBI:31.64±14.73比20.13±11.61;P<0.05)。结论整合照护可用于改善阿尔茨海默病患者的日常生活能力和生活质量,减轻照护人员负担,提高对阿尔茨海默病患者的护理水平。

卟啉–石墨炔衍生物的光热/光动力联合治疗

在本研究中,我们设计合成了两种卟啉修饰的新型石墨炔衍生物GDYO–TPP和GDY–TPP,它们在有机溶剂和水中具有良好的分散性及优异的生物相容性.研究发现GDYO–TPP和GDY–TPP不仅具有优异的光热转换性能,还具有优异的产生单线态氧能力,并可用于肿瘤的光热/光动力联合治疗,在动物体内表现出优异的肿瘤细胞生长抑制作用,且无毒副作用.进一步研究表明卟啉与石墨炔之间的高效电子转移使得共轭连接的GDY–TPP的光热/光动力联合治疗效果要优于非共轭连接的GDYO–TPP,实现了通过控制石墨炔中功能基团的键合方式对其光热/光动力联合治疗效果的调控,为设计新型功能石墨炔和光热/光动力联合治疗肿瘤提供了新思路.

Precise nanomedicine for intelligent therapy of cancer

Precise nanomedicine has been extensively explored for efficient cancer imaging and targeted cancer therapy, as evidenced by a few breakthroughs in their preclinical and clinical explorations. Here, we demonstrate the recent advances of intelligent cancer nanomedicine, and discuss the comprehensive understanding of their structure-function relationship for smart and efficient cancer nanomedicine including various imaging and therapeutic applications, as well as nanotoxicity. In particular, a few emerging strategies that have advanced cancer nanomedicine are also highlighted as the emerging focus such as tumor imprisonment, supramolecular chemotherapy, and DNA nanorobot. The challenge and outlook of some scientific and engineering issues are also discussed in future development. We wish to highlight these new progress of precise nanomedicine with the ultimate goal to inspire more successful explorations of intelligent nanoparticles for future clinical translations.

Smart CU1.75S nanocapsules with high and stable photothermal efficiency for NIR photo-triggered drug release

Thermosensitive 药交货系统(DDS ) 面对主要挑战，例如遥远、可重复的控制在 vivo 温度，尽管这些能增加药的治疗学的功效。处理这个问题，我们涂在红外线附近(NIR ) photothermal Cu 1.75 有 pH/thermos-sensitive 聚合物由的 S nanocrystals 在 situ 聚合。装载内容的 doxorubicine (纪录影片) 直到 40 wt.% ，与纪录影片在正常生理的条件下面正在被漏的不到 8.2 wt.%(pH = 7.4， 37 吗？

Coordination-responsive drug release inside gold nanorod @ metal-organic framework core-shell nanostructures for near-infrared-induced synergistic chemo-photothermal therapy

Multifunctional core-shell nanostructures formed by integration of distinct components have received wide attention as promising biological platforms in recent years. In this work, crystalline zeolitic imidazolate framework-8 （ZIF-8）, a typical metal-organic framework （MOF）, is coated onto single gold nanorod （AuNR） core for successful realization of synergistic photothermal and chemotherapy triggered by near-infrared （NIR） light. Impressivel）~ high doxorubicin hydrochloride （DOX） loading capacity followed by pH and NIR light dual stimuli-responsive DOX release can be easily implemented through formation and breakage of coordination bonds in the system. Moreover, under NIR laser irradiation at 808 nm, these novel AuNR@MOF core-shell nanostructures exhibit effective synergistic chemo-photothermal therapy both in vitro and in vivo, confirmed by cell treatment and tumor ablation via intravenous injection.

Protein corona in vivo: dynamic complement proteins-mediated opsonization and immune modulation

It has been well-established that blood biomolecules deposit on the surface of nanoparticles forming a protein rich layer,known as‘‘protein corona',which directly interacts with and is recognized by cells.These interactions play a critical role in affecting nanoparticle biological properties,including biodistribution[1],pathophysiology[2],and therapeutic efficacy[3].The compositions of protein corona undergo dynamic exchange in vivo and are

Direct site-specific treatment of skin cancer using doxorubicin-loaded nanofibrous membranes

Doxorubicin(DOX) is widely used in cancer therapy. However, its application is sometimes limited by its adverse cardiotoxicity and delivery pathways. In our study, we prepared a topical implantable delivery device for controlled drug release and site-specific treatment. The core region consisted of poly(lactic co-glycolic acid) and poly-caprolactone, whereas the shell region was composed of cross-linked gelatin.DOX was enclosed in the core region of a core-shell nanofiber obtained by electrospinning. This implantable delivery device was implanted on the top of the melanoma in a mouse model, which had shown a DOX-controlled release profile with sustained and sufficient local concentration against melanoma growth in mice with negligible side effects. Compared with the traditional intravenous administration,the implantable device allows precisely localized treatment and therefore can reduce the dose, decrease the injection frequency, and ensure antitumor efficacy associated with lower side effects to normal tissues. Using a coaxial electrospinning process, it is promising to deliver different hydrophobic or hydrophilic drugs for direct tumor site-specific therapy without large systemic doses and minimized systemic toxicity.

Toxicity of manufactured nanomaterials

Manufactured nanomaterials with unique properties have been extensively applied in various indus-trial,agricultural or medical fields.However,some of the properties have been identified to be closely related to nanomaterial toxicity.The"nano-paradox"has aroused concerns over the use and develop-ment of nanotechnology,which makes it difficult for regulatory agencies to regulate nanomaterials.The key to fulfilling proper nanomaterial regulation lies in the adequate understanding of the impact of nanomaterial properties on nano-bio interactions.To this end,we start the present work with a brief intro-duction to nano-bio interactions at different levels.Based on that,how key toxicity-associated properties of manufactured nanomaterials(i.e.,size,shape,chemical composition,surface properties,biocorona formation,agglomeration and/or aggregation state,and biodegradability)impact their toxicokinetics,cel-lular uptake,trafficking and responses,and toxicity mechanisms is deeply explored.Moreover,advanced analytical methods for studying nano-bio interactions are introduced.Furthermore,the current reg-ulatory and legislative frameworks for nanomaterial-containing products in different regions and/or countries are presented.Finally,we propose several challenges facing the nanotoxicology field and their possible solutions to shed light on the safety evaluation of nanomaterials.

Uptake of graphene enhanced the photophosphorylation performed by chloroplasts in rice plants

New and enhanced functions were potentially imparted to the plant organelles after interaction with nanoparticles.In this study,we found that∼44%and∼29%of the accumulated graphene in the rice leaves passively transported to the chloroplasts and thylakoid,respectively,significantly enhanced the fluorescence intensity of chloroplasts,and promoted about 2.4 times higher adenosine triphosphate production than that of controls.The enhancement of graphene on the photophosphorylation was ascribed to two reasons:One is that graphene facilitates the electron transfer process of photosystem II in thylakoid,and the other is that graphene protects the photosystem II against photo-bleaching by acting as a scavenger of reactive oxygen species.Overall,our work here confirmed that graphene translocating in the thylakoid promoted the photosynthetic activity of chloroplast in vivo and in vitro,providing new opportunities for designing biomimetic materials to enhance the solar energy conversion systems,especially for repairing or increasing the photosynthesis activity of the plants grown under stress environment.

Nano-bio interactions: the implication of size-dependent biological effects of nanomaterials

Due to their many advantageous properties,nanomaterials(NMs)have been utilized in diverse consumer goods,industrial products,and for therapeutic purposes.This situation leads to a constant risk of exposure and uptake by the human body,which are highly dependent on nanomaterial size.Consequently,an improved understanding of the interactions between different sizes of nanomaterials and biological systems is needed to design safer and more clinically relevant nano systems.We discuss the sizedependent effects of nanomaterials in living organisms.Upon entry into biological systems,nanomaterials can translocate biological barriers,distribute to various tissues and elicit different toxic effects on organs,based on their size and location.The association of nanomaterial size with physiological structures within organs determines the site of accumulation of nanoparticles.In general,nanomaterials smaller than 20 nm tend to accumulate in the kidney while nanomaterials between 20 and 100 nm preferentially deposit in the liver.After accumulating in organs,nanomaterials can induce inflammation,damage structural integrity and ultimately result in organ dysfunction,which helps better understand the size-dependent dynamic processes and toxicity of nanomaterials in organisms.The enhanced permeability and retention effect of nanomaterials and the utility of this phenomenon in tumor therapy are also highlighted.

Clathrin meets caveolae: fuse or not?

Eukaryotic cells use endocytosis to regulate the cellular signaling transduction by modulating the number of available receptors and their activity at the plasma membrane.In addition to the well-studied clathrin-dependent endocytic pathway,various clathrin-independent mechanisms have been identified.The canonical clathrin-dependent

Ferroxidase-like activity of Au nanorod/Pt nanodot structures and implications for cellular oxidative stress

铂 nanoparticles (NP ) 被报导模仿各种各样的抗氧化剂酶并且可以因此由减少反应的氧生产积极生物效果种类(ROS ) 层次。在这张手稿，我们报导磅 NP 由在金 nanorods (Au@Pt NDR ) 上扔铂 nanodots ferroxidase 作为酶模仿。Au@Pt NDR 显示出 pH 依赖的象 ferroxidase 一样活动并且在中立 pH 价值举办更高的活动。有人的房间线(肺腺癌 A549 和正常支气管的上皮的房间线 HBE ) 的 Cytotoxicity 结果证明 Au@Pt NDR 经由 endocytosis 和 translocate 被收起进房间进 endosome/lysosome。Au@Pt NDR 在比 0.15 n 低的 NDR 粒子集中有好 biocompatibility。然而，面对 H 2 O 2, lysosomelocated NDR 展出象 peroxidase 一样活动因此增加 cytotoxicity。面对 Fe 2+, ， NDR 的象 ferroxidase 一样活动由消费 H 2 O 2 。当在生物系统采用 Au@Pt NDR 时，彻底的考虑应该被给这行为。