Alcohol solvent effect on the self-assembly behaviors of lignin oligomers

The interactions between lignin oligomers and solvents determine the behaviors of lignin oligomers self-assembling into uniform lignin nanoparticles(LNPs).Herein,several alcohol solvents,which readily interact with the lignin oligomers,were adopted to study their effects during solvent shifting process for LNPs’production.The lignin oligomers with widely distributed molecular weight and abundant guaiacyl units were extracted from wood waste(mainly consists of pine wood),exerting outstanding self-assembly capability.Uniform and spherical LNPs were generated in H_(2)O-n-propanol cosolvent,whereas irregular LNPs were obtained in H_(2)O-methanol cosolvent.The unsatisfactory self-assembly performance of the lignin oligomers in H_(2)O-methanol cosolvent could be attributed to two aspects.On one hand,for the initial dissolution state,the distinguishing Hansen solubility parameter and polarity between methanol solvent and lignin oligomers resulted in the poor dispersion of the lignin oligomers.On the other hand,strong hydrogen bonds between methanol solvent and lignin oligomers during solvent shifting process,hindered the interactions among the lignin oligomers for self-assembly.

Single-cell and spatial heterogeneity landscapes of mature epicardial cells

Tbx18,Wt1,and Tcf21 have been identified as epicardial markers during the early embryonic stage.However,the gene markers of mature epicardial cells remain unclear.Single-cell transcriptomic analysis was performed with the Seurat,Monocle,and CellphoneDB packages in R software with standard procedures.Spatial transcriptomics was performed on chilled Visium Tissue Optimization Slides(10x Genomics)and Visium Spatial Gene Expression Slides(10x Genomics).Spatial transcriptomics analysis was performed with Space Ranger software and R software.Immunofluorescence,whole-mount RNA in situ hybridization and X-gal staining were performed to validate the analysis results.Spatial transcriptomics analysis revealed distinct transcriptional profiles and functions between epicardial tissue and non-epicardial tissue.Several gene markers specific to postnatal epicardial tissue were identified,including Msln,C3,Efemp1,and Upk3b.Single-cell transcriptomic analysis revealed that cardiac cells from wildtype mouse hearts(from embryonic day 9.5 to postnatal day 9)could be categorized into six major cell types,which included epicardial cells.Throughout epicardial development,Wt1,Tbx18,and Upk3b were consistently expressed,whereas genes including Msln,C3,and Efemp1 exhibited increased expression during the mature stages of development.Pseudotime analysis further revealed two epicardial cell fates during maturation.Moreover,Upk3b,Msln,Efemp1,and C3 positive epicardial cells were enriched in extracellular matrix signaling.Our results suggested Upk3b,Efemp1,Msln,C3,and other genes were mature epicardium markers.Extracellular matrix signaling was found to play a critical role in the mature epicardium,thus suggesting potential therapeutic targets for heart regeneration in future clinical practice.

From oral formulations to drug-eluting implants:using 3D and 4D printing to develop drug delivery systems and personalized medicine

Since the start of the Precision Medicine Initiative by the United States of America in 2015,interest in personalized medicine has grown extensively.In short,personalized medicine is a term that describes medical treatment that is tuned to the individual.One possible way to realize personalized medicine is 3D printing.When using materials that can be tuned upon stimulation,4D printing is established.In recent years,many studies have been exploring a new field that combines 3D and 4D printing with therapeutics.This has resulted in many concepts of pharmaceutical devices and formulations that can be printed and,possibly,tailored to an individual.Moreover,the first 3D printed drug,Spritam®,has already found its way to the clinic.This review gives an overview of various 3D and 4D printing techniques and their applications in the pharmaceutical field as drug delivery systems and personalized medicine.

Deep diving in the PACIFIC:Practical issues in stage III non-small cell lung cancer to avoid shipwreck

After publication of the PACIFIC trial results,immune checkpoint inhibitor-based immunotherapy was included in the treatment algorithm of locally advanced non-small cell lung cancer(NSCLC).The PACIFIC trial demonstrated that 12 mo of durvalumab consolidation therapy after radical-intent platinum doublet chemotherapy with concomitant radiotherapy improved both progression-free survival and overall survival in patients with unresectable stage III NSCLC.This is the first treatment in decades to successfully improve survival in this clinical setting,with manageable toxicity and without deterioration in quality of life.The integration of durvalumab in the management of locally advanced NSCLC accentuates the need for multidisciplinary,coordinated decision-making among lung cancer specialists,bringing new challenges and controversies as well as important changes in clinical work routines.The aim of the present article is to review—from a practical,multidisciplinary perspective—the findings and implications of the PACIFIC trial.We evaluate the immunobiological basis of durvalumab as well as practical aspects related to programmed cell death ligand 1 determination.In addition,we comprehensively assess the efficacy and toxicity data from the PACIFIC trial and discuss the controversies and practical aspects of incorporating durvalumab into routine clinical practice.Finally,we discuss unresolved questions and future challenges.In short,the present document aims to provide clinicians with a practical guide for the application of the PACIFIC regimen in routine clinical practice.

Long-COVID-19: the persisting imprint of SARS-CoV-2 infections on the innate immune system

In a recent Cell publication,Cheong et al.uncover how COVID-19 causes IL-6 induced epigenetic reprogramming of human immune stem cells,which causes lasting alterations in the composition and response characteristics of circulating immune cells.1 The study provides important insights into the mechanisms by which SARSCoV-2 infections impact the human immune system and is an important hook into unraveling the mechanisms of post-acute sequelae of COVID-19(PASC)commonly referred to as longCOVID.

A novel in vitro prognostic model of bladder cancer based on urine-derived living tumor cells

Bladder cancer(BLCA)remains a difficult malignancy to manage because of its high recurrence,intense follow-up,and invasive diagnostic and treatment techniques.Immune checkpoint inhibitors(ICIs)have forged a new direction for the treatment of BLCA,but it is currently challenging to predict whether an individual patient will be sensitive to ICIs.We collected 43 urine/tumor samples from BLCA patients for primary bladder cancer cells(BCCs)culturing using our previously reported BCC culture platform.We used flow cytometry(FCM)to measure the expression levels of Programmed Death-Ligand 1(PD-L1)on BCCs before and after interferon-gamma(IFN-γ)treatment and found that PD-L1 expression and the sensitivities to IFN-γvaried among patients.RNA-sequencing,western blotting,and programmed death-1(PD-1)binding assays confirmed that the BCC FCM-based PD-L1 detection platform(BC-PD-L1)was reliable and was not hindered by the glycosylation of PD-L1.In the subsequent retrospective study,we found that IFN-γ-stimulated PD-L1(sPD-L1)expression on BCCs detected by BC-PD-L1 could predict the prognosis of BLCA patients.Importantly,the prognostic value was similar or even better in urine-derived BC-PD-L1(UBC-PD-L1).Transcriptome analysis showed that BCCs with high sPD-L1 tended to enrich genes associated with the collagen-containing extracellular matrix,cell–cell adhesion,and positive regulation of the immune system.In addition,the UBC-PD-L1 also exhibited predictive value for ICI response in BLCA patients.In conclusion,as a novel personalized urine-detection method,UBC-PD-L1 may provide a rapid,accurate,and non-invasive tool for monitoring tumor progression,predicting therapeutic responses,and helping improve BLCA clinical treatment in future.

Integrative multi-omics and drug-response characterization of patient-derived prostate cancer primary cells

Prostate cancer(PCa)is the second most prevalent malignancy in males across the world.A greater knowledge of the relationship between protein abundance and drug responses would benefit precision treatment for PCa.Herein,we establish 35 Chinese PCa primary cell models to capture specific characteristics among PCa patients,including gene mutations,mRNA/protein/surface protein distributions,and pharmaceutical responses.The multi-omics analyses identify Anterior Gradient 2(AGR2)as a pre-operative prognostic biomarker in PCa.Through the drug library screening,we describe crizotinib as a selective compound for malignant PCa primary cells.We further perform the pharmacoproteome analysis and identify 14,372 significant protein-drug correlations.Surprisingly,the diminished AGR2 enhances the inhibition activity of crizotinib via ALK/c-MET-AKT axis activation which is validated by PC3 and xenograft model.Our integrated multi-omics approach yields a comprehensive understanding of PCa biomarkers and pharmacological responses,allowing for more precise diagnosis and therapies.

Specific pupylation as IDEntity reporter(SPIDER)for the identification of protein-biomolecule interactions

Protein-biomolecule interactions play pivotal roles in almost all biological processes.For a biomolecule of interest,the identification of the interacting protein(s)is essential.For this need,although many assays are available,highly robust and reliable methods are always desired.By combining a substrate-based proximity labeling activity from the pupylation pathway of Mycobacterium tuberculosis and the streptavidin(SA)-biotin system,we developed the Specific Pupylation as IDEntity Reporter(SPIDER)method for identifying protein-biomolecule interactions.Using SPIDER,we validated the interactions between the known binding proteins of protein,DNA,RNA,and small molecule.We successfully applied SPIDER to construct the global protein interactome for m^(6)A and m RNA,identified a variety of uncharacterized m^(6)A binding proteins,and validated SRSF7 as a potential m^(6)A reader.We globally identified the binding proteins for lenalidomide and Cob B.Moreover,we identified SARS-CoV-2-specific receptors on the cell membrane.Overall,SPIDER is powerful and highly accessible for the study of proteinbiomolecule interactions.

三维表面活性剂-石墨烯复合阴极界面材料在有机太阳能电池中的应用

低沸点绿色溶剂中分散石墨烯可广泛应用于涂料、导电油墨、电池、电子产品和太阳能电池等领域.研究发现,在乙醇溶液中,两种三维阴极界面材料POSSFN和ADMAFN分散石墨烯的浓度可达到0.97–1.18 mg mL^-1,通过计算得知这两种材料在石墨烯表面具有较大的吸附能.通过ESR、Raman、SKPM和XPS等测试手段证实,POSSFN侧链上的氨基能够与石墨烯发生n-掺杂作用;而AD-MAFN与石墨烯之间能够形成偶极相互作用.两种三维界面修饰-石墨烯复合材料(POSSFN-G和ADMAFN-G)均可作为阴极界面修饰材料应用于有机太阳能电池中,并使基于PM6:Y6光活性层的有机太阳能电池的能量转换效率(PCE)提高到了15.9%–16.1%,其中基于存在偶极相互作用的复合材料ADMAFN-G阴极修饰层的有机太阳能电池的PCE达到16.11%;使用存在n-掺杂作用的POSSFN-G阴极修饰层的器件,在厚膜状态下依然可获得较高的能量转换效率.

Single-wall carbon nanotube-containing cathode interfacial materials for high performance organic solar cells

Water/alcohol soluble cathode interfacial materials(CIMs)are playing important roles in optoelectronic devices such as organic light emitting diodes,perovskite solar cells and organic solar cells(OSCs).Herein,n-doped solution-processable single-wall carbon nanotubes(SWCNTs)-containing CIMs for OSCs are developed by dispersing SWCNTs to the typical CIMs perylene diimide(PDI)derivatives PDIN and PDINO.The Raman and X-ray photoelectron spectroscopy(XPS)measurement results illustrate the ndoped behavior of SWCNTs by PDIN/PDINO in the blend CIMs.The blended and n-doped SWCNTs can tune the work function and enhance the conductivity of the PDI-derivative/SWCNT(PDI-CNT)composite CIMs,and the composite CIMs can regulate and down-shift the work function of cathode,reduce the charge recombination,improve the charge extraction rate and enhance photovoltaic performance of the OSCs.High power conversion efficiency(PCE)of 17.1%and 17.7%are obtained for the OSCs based on PM6:Y6 and ternary PM6:Y6:PC_(71) BM respectively with the PDI-CNTcomposites CIMs.These results indicate that the ndoped SWCNT-containing composites,like other n-doped nanomaterials such as zero dimensional fullerenes and two dimensional graphenes,are excellent CIMs for OSCs and could find potential applications in other optoelectronic devices.

Blockading a new NSCLC immunosuppressive target by pluripotent autologous tumor vaccines magnifies sequential immunotherapy

The presence of multiple immunosuppressive targets and insufficient activation and infiltration of cytotoxic T lymphocytes(CTLs)allow tumor cells to escape immune surveillance and disable anti-PD-1/PD-L1 immunotherapy.Nanobiotechnology-engineered autologous tumor vaccines(ATVs)that were camouflaged by tumor cell membrane(TCM)were designed to activate and facilitate CTLs infiltration for killing the unprotected lung tumor cells,consequently realizing the sequential immunotherapy.PDE5 was firstly screened out as a new immunosuppressive target of lung cancer in clinical practice.Immediately afterwards,phosphodiesterase-5(PDE5)and programmed cell death 1 ligand 1(PD-L1)dual-target co-inhibition was proposed to unfreeze the immunosuppressive microenvironment of NSCLC.Systematic studies validated that this ATVs-unlocked sequential immunotherapy after co-encapsulating PDE5 inhibitor and NO donor(i.e.,L-arginine)exerted robust anti-tumor effects through increasing inducible nitric oxide synthase(iNOS)expression,blockading PDE5 pathway and activating systematic immune responses,which synergistically eradicated local and abscopal lung cancers in either orthotopic or subcutaneous models.The pluripotent ATVs that enable PDE5 inhibition and sequential immunotherapy provide a new avenue to mitigate immunosuppressive microenvironment and magnify anti-PD-1/PD-L1 immunotherapy.