Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer.

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

Effects of Individual Amino Acids on the Blood Circulation of Biosynthetic Protein Nanocages: Toward Guidance on Surface Engineering.

Protein nanocages (PNCs) hold great promise for developing multifunctional nanomedicines. Long blood circulation is a key requirement of PNCs for most in vivo application scenarios. In addition to the classical PEGylation strategy, short peptides with a specific sequence screened via phage display are also very effective in prolonging the blood half-life (t1/2 ) of PNCs. However, there is a lack of knowledge on how individual amino acids affect the circulation of PNCs. Here the effects of the 20 proteinogenic amino acids in the form of an X3 or X5 tag (X represents an amino acid) are explored on the pharmacokinetics of PNCs, which lead to the formation of a heatmap illustrating the extent of t1/2 prolongation by each proteinogenic amino acid. Significantly, oligo-lysine and oligo-arginine can effectively prolong the t1/2 of strongly negatively charged PNCs through charge neutralization, while oligo-cysteine can also do so, but via a different mechanism, mediating the covalent binding of PNCs with plasma albumin as a stealth material. These findings are extendible and offer guidance for surface-engineering biosynthetic PNCs and other nanoparticles.

Probing cell membrane integrity using a histone-targeting protein nanocage displaying precisely positioned fluorophores.

Cell membrane integrity is fundamental to the normal activities of cells and is involved in both acute and chronic pathologies. Here, we report a probe for analyzing cell membrane integrity developed from a 9 nm-sized protein nanocage named Dps via fluorophore conjugation with high spatial precision to avoid self-quenching. The probe cannot enter normal live cells but can accumulate in dead or live cells with damaged membranes, which, interestingly, leads to weak cytoplasmic and strong nuclear staining. This differential staining is found attributed to the high affinity of Dps for histones rather than DNA, providing a staining mechanism different from those of known membrane exclusion probes (MEPs). Moreover, the Dps nanoprobe is larger in size and thus applies a more stringent criterion for identifying severe membrane damage than currently available MEPs. This study shows the potential of Dps as a new bioimaging platform for biological and medical analyses. Electronic Supplementary Material: Supplementary material (Figs. S1-S12 including distance information between neighboring fluorophores on Dps, TEM images, MALDI-TOF analysis, fluorescence spectra, confocal images, gel retardation analysis, tissue staining, and additional data) is available in the online version of this article at 10.1007/s12274-022-4785-5.

Passive cancer targeting with a viral nanoparticle depends on the stage of tumorigenesis.

Tumor targeting with nanoparticles is a promising strategy for cancer diagnosis and treatment, especially for drug delivery to solid tumors. Previous studies mainly focused on nanoparticle design to improve their targeting efficiency, but few have investigated the impact of tumor progression stages on the targeting efficiency. Here, we used PEGylated viral nanoparticles (VNPs) of bacteriophage P22 to explore the relationship between targeting efficiency and tumor progression stages using a colorectal cancer model. We found an 8.1-fold increase in the accumulation of P22 VNPs systematically injected 7 days after tumor inoculation compared with those injected 21 days after tumor inoculation. Most tumor-targeted P22 VNPs were concentrated in tumor-associated macrophages in the tumor blood vessels, the density of which decreased with the progression of tumors. These results reveal that the tumor targeting efficiency of P22 VNPs decreased with tumor progression. These findings provide valuable information for not only the understanding of controversial observations regarding targeted cancer therapy in experimental and clinical studies but also the design of nanoparticle-based tumor targeting probes or therapeutics.

A ROS scavenging protein nanocage for in vitro and in vivo antioxidant treatment.

Elevated levels of reactive oxygen species (ROS) are implicated in the onset and progression of many diseases, e.g., virus infection, ischemic stroke and neurodegenerative diseases. ROS-scavenging nanomaterials have attracted particular interest. Here, we report the development of a natural protein nanocage named Dps for in vitro and in vivo antioxidant treatment by inhibiting the Fenton reaction, a critical step in ROS generation and interconversion. Systematic surface engineering enabled cell penetration, good colloidal stability, and facile purification of Dps. With its intrinsic ferroxidase activity consuming both H2O2 and Fe2+, Dps not only protects human cells from oxidative stress but also effectively alleviates ROS-induced inflammation in a mouse dermatitis model. The protection is triggered by elevated H2O2 and thereby, in principle, avoids ROS imbalances. Thus, Dps has potential as a new bionano platform for different purposes, such as antiaging, anti-inflammation and cosmetics.

The complete chloroplast genome sequence of Magnolia delavayi (Magnoliaceae), a rare ornamental and medical tree endemic to China.

Magnolia delavayi is a rare, famous ornamental and important medical tree endemic to China. Here, we assembled the complete chloroplast (cp) genome sequence of M. delavayi. Its length is 159,715 bp with four sub-regions: 87,906 bp of large single-copy region and 18,761 bp of small single-copy region are separated by two inverted repeats regions, each 26,524 bp. The genome contains 77 protein-coding genes, 6 rRNAs, and 29 tRNAs genes. Phylogenetic analysis of cp genome of M. delavayi with previously reported chloroplast genomes in Magnolia shows that M. delavayi is close to M. odoratissima with high bootstrap value.

Study on the Mechanism of Enhancement Effects of Astragalus complanatus Polysaccharides on the Proliferation of Meniscal Fibrochondrocyte Cells in Rabbits / 中国药房

OBJECTIVE：To study the mechanism of enhancement effects of Astragalus complanatus polysaccharides（ACP） on the proliferation of meniscal fibrochondrocytes cells in rabbits. METHODS ：The meniscal fibrochondrocytes cells were isolated from 1-month-old New Zealand white rabbits. The meniscal fibrochondrocytes cells were divided into normal control group （PBS）， positive control group （glucosamine sulfate ，10 mg/mL）and ACP high-dose，medium-dose and low-dose groups （40，20，10 mg/mL）. The morphology of meniscal fibrochondrocytes cells were observed under microscope. Cell proliferation rate was detected by MTT assay. Cell cycle was observed with flow cytometry. ELISA assay was used to detect relative expression of medium collagen type Ⅱ（Col Ⅱ）and alkaline phosphatase protein （ALP）in meniscal fibrochondrocytes cells. RT-qPCR and Western blotting assay were adopted to detect mRNA and protein expression of transforming growth factor β 1 （TGF-β 1） and bone morphogenetic protein 2（BMP-2）. RESULTS ：After cultured for 72 h，meniscal fibrochondrocytes cells were fused into a single layer，and most of them were slender type in appearance. Compared with normal control group ，the proliferation rate of meniscal fibrochondrocytes cells and the percentage of cells at G 1/G0 phase were decreased significantly in positive control group and ACP high-dose，medium-dose and low-dose groups （P＜0.05）；the percentage of cells at S phase ，protein expression of Col Ⅱ and ALP，mRNA and protein expression of TGF-β1 and BMP- 2 were increased significantly （P＜0.05）. Compared with positive control group，inhibitory rate of meniscal fibrochondrocytes cells proliferation and the percentage of cells at G 1/G0 phase were decreased significantly in ACP high-dose group （P＜0.05），while the percentage of cells at S phase ，protein expression of Col Ⅱ and ALP ， mRNA and protein expression of TGF-β1 and BMP- 2 were increased significantly （P＜0.05）. The inhibitory proliferation rate of meniscal fibrochondrocytes cells and the percentage of cells at G 1/G0 phase were increased significantly in ACP low-dose group （P＜ 0.05），while the percentage of cells at S phase ，protein expression of Col Ⅱ and ALP ，mRNA and protein expression of TGF-β1 and BMP- 2 were decreased significantly （P＜0.05）. There was no statistical significance in above indexes of ACP medium-dose group. CONCLUSIONS ：ACP can promote the proliferation of meniscal fibrochondrocytes cells ，reduce the percentage of cells at G1/G0 phase，promote cell transformation to S phase ；the mechanism of which may be related to up-regulating TGF-β1，BMP-2 mRNA and protein expression ，promoting Col Ⅱ and ALP protein expression enhancement.

Role of Surface RGD Patterns on Protein Nanocages in Tumor Targeting Revealed Using Precise Discrete Models.

The effectiveness of active targeting in cancer nanomedicine is becoming increasingly more debatable. Here, the role of the ligand functionalization patterns (number and distribution) on nanoparticle surfaces in tumor targeting is investigated using a 9 nm sized miniferritin protein nanocage, Dps modified with Arg-Gly-Asp (RGD) ligands whose functionalization patterns are precisely controlled. In vitro and in vivo experiments show that RGD modification endows Dps with tumor targeting capacity no matter what the surface pattern is. The tumor targeting of 2-ligand Dps, which is better than that of 1-ligand Dps, rivals or surpasses that of the 12- or 24-ligand Dps. The 12-ligand Dps with clustered RGD distribution shows 2.3 times the in vivo targeting efficiency of that with even distribution. The surface ligand pattern effects are correlated at least to receptor clustering and opsonization. This study provides insights into the understanding of the controversial findings on active tumor targeting in the literature and highlights the necessity of precise functionalization to achieve optimal active targeting in developing cancer nanomedicine.

Chemical constituents from Stellaria dichotoma and their anti-inflammatory activities / 中成药

AIM To study the chemical constituents from the Stellaria dichotoma L.var.lanceolata Bge and their anti-inflammatory activities.METHODS The 95％ ethnol extract from S.dichotoma was isolated and purified by silica,MCI,C18 prep-HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities were evaluated by LPS induced RAW264.7 inflammatory cell model.RESULTS Ten compounds were isolated and identified as 3-hydroxy-β-carboline (1),taraxacine A (2),1,2,3,4-tetrahydro-1,3,4-trioxo-β-carbo1ine (3),1-acetyl-β-carboline (4),arenarine A (5),arenarine B (6),diisobutyl-phthalate (7),dibutyl-phthalate (8),(z,z,z)-9,12,15-octadecatrienoic acid,methyl ester (9),tricin (10).Compounds 1-6 had stronger anti-inflammatory activities with the IC50 values of 4.79-9.34 μg/mL.CONCLUSION All the compounds are isolated from this plant for the first time.Their stronger anti-inflammatory activities are discovered for the first time.

Assessment of pollution and identification of sources of heavy metals in the sediments of Changshou Lake in a branch of the Three Gorges Reservoir.

To assess the heavy metal pollution in Changshou Lake, sediments were collected from nine sites at three periods (dry, normal, and wet) in 2013. The Hg, As, Cr, Cd, Pb, Cu, and Zn levels were then determined. The index of geoaccumulation (I geo) and the sediment pollution index (SPI) were applied to the sediment assessment, and Pearson's correlation analysis and factor analysis (FA) were performed to identify common pollution sources in the basin. The results showed that heavy metals presented significant spatial variations with Cr, Cd, Pb, Cu, Zn, Hg, and As concentrations of 29.66~42.58, 0.62~0.91, 24.91~37.96, 21.18~74.91, 41.65~86.86, 0.079~0.152, and 20.17~36.88 mg kg(-1), respectively, and no obvious variations were found among the different periods. The average contents of the metals followed the order Zn > Cu > Cr > Pb > As > Cd > Hg, which showed a high pollution in the sediments collected from open water and at the river mouth. The assessment results indicated that toxic heavy metals presented obvious pollution with I Hg of 0.64~1.36 (moderately polluted), I Cd of 1.66~2.22 (moderately to heavily polluted), and I As of 1.21~2.07 (moderately to heavily polluted). The heavy metal pollution states followed the order Cd > As > Hg > Cu > Pb > Zn > Cr, and the SPI showed that the sediment collected from open water area was more polluted than those obtained from the tributaries and the river mouth. Cr, Cd, Hg, Pb, Cu, As, and Zn were mainly attributed to sediment weathering with Hg, Pb, and Cu and partially due to domestic sewage from the upper reaches. These results indicate that the more attention should be paid to the inner loads of sediment in order to achieve improvements in reservoir water quality after the control of external pollution.