Tumor-associated macrophage (TAM) as an important component of tumor microenvironment (TME) are closely related with the occurrence, development, and metastasis of malignant tumors. TAMs are ...generally identified as two distinct functional populations in TME,
i.e.
, inflammatory/anti-tumorigenic (M1) and regenerative/pro-tumorigenic (M2) phenotype. Evidence suggests that occupation of the TME by M2-TAMs is closely related to the inactivation of anti-tumor immune cells such as T cells in TME. Recently, efforts have been made to reeducate TAMs from M2- to M1- phenotype to enhance cancer immunotherapy, and great progress has been made in realizing efficient modulation of TAMs using nanomedicines. To help readers better understand this emerging field, the potential TAM reeducation targets for potentiating cancer immunotherapy and the underlying mechanisms are summarized in this review. Moreover, the most recent advances in utilizing nanomedicine for the TAM immunomodulation for augmented cancer immunotherapy are introduced. Finally, we conclude with our perspectives on the future development in this field.
The multi-scale fiber and topological morphologies had been shown to influence cell mitogenesis and chemotaxis, direct cell differentiation, and induce constructive host tissue remodeling responses. ...To simulate multi-layer meshwork architecture of extracellular matrix and regulate cell behavior, we prepared different topological scaffolds, such as 3D printing fiber scaffolds, poly(lactic acid) (PLA) electrospun fiber scaffolds, 3D printing/knitted fabric composite scaffolds, and PLA electrospinning/knitted fabric composite scaffolds. The surface morphology, pore diameter, thickness, stress-strain curve, electrical current, and other properties were studied. The aim is to prepare multi-scale nano/micro fiber scaffolds with different topological morphologies and properties that can provide structural and mechanical support for potential tissue engineering applications.
Plants, as sessile organisms, uptake nutrients from the soil. Throughout their whole life cycle, they confront various external biotic and abiotic threats, encompassing harmful element toxicity, ...pathogen infection, and herbivore attack, posing risks to plant growth and production. Plants have evolved multifaceted mechanisms to cope with exogenous stress. The element defense hypothesis (EDH) theory elucidates that plants employ elements within their tissues to withstand various natural enemies. Notably, essential and non-essential trace metals and metalloids have been identified as active participants in plant defense mechanisms, especially in nanoparticle form. In this review, we compiled and synthetized recent advancements and robust evidence regarding the involvement of trace metals and metalloids in plant element defense against external stresses that include biotic stressors (such as drought, salinity, and heavy metal toxicity) and abiotic environmental stressors (such as pathogen invasion and herbivore attack). We discuss the mechanisms underlying the metals and metalloids involved in plant defense enhancement from physiological, biochemical, and molecular perspectives. By consolidating this information, this review enhances our understanding of how metals and metalloids contribute to plant element defense. Drawing on the current advances in plant elemental defense, we propose an application prospect of metals and metalloids in agricultural products to solve current issues, including soil pollution and production, for the sustainable development of agriculture. Although the studies focused on plant elemental defense have advanced, the precise mechanism under the plant defense response still needs further investigation.
•Polycarbonate greenhouse materials do not transmit UV-B or UV-A radiation.•Exclusion of UV-B and UV-A increased internode lengths and height of soybean.•Exclusion of UV-B only in a glasshouse ...increased soybean internode lengths slightly.•Elongated internodes are likely induced by gibberellic acid accumulation.•Soybean pod yield of cv. Maverick but not Williams-82 was increased by UV exclusion.
Soybean Glycine max (L.) Merr. cultivars Williams-82 and Maverick were grown in a polycarbonate greenhouse (P-GH), a glass greenhouse (G-GH), and outdoors during daytime (control) to investigate the effect of (i) exclusion of both ultraviolet B (UV-B, 280–320nm) and ultraviolet A (UV-A, 320–400nm), (ii) exclusion of UV-B only, and (iii) exposure to daytime solar UV radiation (09:00–17:00h local time daily). Both the P-GH and the G-GH were maintained at day/night air temperatures of 30/22°C. The purpose was to quantify the growth differences due to partial and total UV exclusion compared with the control. Exclusion of both UV-B and UV-A radiation caused elongated internodes on the plants, which resulted in greater plant height. Mean mainstem length of Williams-82 was 50.2cm for the control, but they were 45% and 237% greater for excluded UV-B radiation only and both excluded UV-B and UV-A radiation, respectively. Similarly, mean mainstem length of Maverick was 55.2cm for the control, but they were 52% and 198% greater for excluded UV-B only and both excluded UV-B and UV-A, respectively. There also was a slight increase in the number of nodes with increasing extent of UV radiation exclusion. The mean final V-stage of Williams-82 was 14.2 for the control, but they were 11% and 18% greater for excluded UV-B only and both excluded UV-B and UV-A, respectively. Likewise, the mean final V-stage of Maverick was 14.5 for the control, but they were 12% and 22% greater for excluded UV-B only and both excluded UV-B and UV-A, respectively. With exclusion of both UV-B and UV-A, pod yield for the Maverick cultivar was greater but this effect was not as clear for the Williams-82 cultivar. In summary, most of the total UV-exclusion effects were due to the exclusion of the UV-A radiation component. Finally, UV spectral transmission of greenhouse or controlled environment covering material should be considered before conducting research on plants, or producing plants commercially, that are sensitive to UV exclusion, such as certain grain legumes or horticultural crops.
Rhizosphere microorganisms play important ecological roles in promoting herb growth and producing abundant secondary metabolites. Studies on the rhizosphere microbes of traditional Chinese medicines ...(TCMs) are limited, especially on the genomic and metabolic levels. In this study, we reported the isolation and characterization of a
WLXQSS-4 strain from the rhizospheric soil of
Rupr. Genomic sequencing revealed an impressive total of 40 predicted biosynthetic gene clusters (BGCs), whereas metabolomic profiling revealed 13 secondary metabolites under current laboratory conditions. Particularly, medium screening activated the production of alloaureothin, whereas brominated and chlorinated pimprinine derivatives were identified through precursor-directed feeding. Moreover, antiproliferative activities against Hela and A549 cancer cell lines were observed for five compounds, of which two also elicited potent growth inhibition in
and
, respectively. Our results demonstrated the robust secondary metabolism of
WLXQSS-4, which may serve as a biocontrol agent upon further investigation.
In poplar cultivation, continuous cropping obstacles affect wood yield and soil-borne diseases, primarily due to structural changes in microbes and fungus infection. The bacterium
BJS-1-3 has strong ...antagonistic properties against pathogens that were isolated from the rhizosphere soil of poplars. Poplar rhizospheres were investigated for the effects of
BJS-1-3 on microbial communities. Three successive generations of soil were used to replant poplar seedlings. BJS-1-3 inoculated poplars were larger, had higher plant height and breast height diameter, and had a greater number of total and culturable bacteria than non-inoculated controls.
BJS-1-3 inoculated poplar rhizospheres were sequenced, utilizing the Illumina MiSeq platform to analyze changes in diversity and structure. The fungi abundance and diversity in the BJS-1-3 rhizosphere were significantly lower than in the control rhizosphere. In comparison to the control group,
sp. constituted 2.87% and 2.38% of the total bacterial community, while
sp. constituted 2.06% and 6.00% of the total fungal community. Among the potential benefits of
BJS-1-3 in poplar cultivation is that it enhances rhizosphere microbial community structure and facilitates the growth of trees.
Pyrotinib is a novel irreversible pan-HER tyrosine kinase inhibitor (TKI). However, real-world data of pyrotinib-containing therapy in human epidermal growth factor receptor 2 (HER2)-positive ...metastatic breast cancer (MBC) and developing brain metastases (BMs) are limited, and the genomic profile of this subpopulation is almost undefined.
Patients with BM of HER2-positive MBC (n = 35) treated with pyrotinib-containing therapy were enrolled in this analysis. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity profiles were evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) for disease progression were estimated using the Cox proportional hazards models. Targeted next-generation sequencing of 618 cancer-relevant genes was performed on plasma and primary breast tumors from patients with BM and without BM.
The median PFS time was 8.00 (95% CI, 5.98-10.017) months, and the median OS time was 23 (95% CI, 10.412-35.588) months. The ORR was 45.7%, and the DCR was 74.3%. In the Cox multivariate analysis, prior exposure to brain radiotherapy (HR = 3.268), received pyrotinib as third- or higher-line treatment (HR = 4.949), subtentorial brain metastasis (HR = 6.222), and both supratentorial and subtentorial brain metastases (HR = 5.863) were independently associated with increased risk of progression. The frequent grade 3-4 adverse event was increased direct bilirubin (14.3%), and two patients suffered from grade 3-4 diarrhea. In the exploratory genomic analysis, altered frequencies of FGFR3, CD276, CDC73, and EPHX1 were higher in the BM group. The consistency of mutated profiles of plasma and primary lesion in the BM group was significantly lower (30.4%
65.5%;
= 0.0038).
Pyrotinib-containing therapy shows favorable effectiveness and tolerable safety in patients with BM of HER2-positive MBC, particularly in a population that is brain radiotherapy-naïve, received pyrotinib as first- or second-line treatment, and developed supratentorial brain metastasis. In the exploratory genomic analysis, patients with BM showed distinct genomic features from patients without BM.
We combine photoemission electron microscopy and electromagnetic simulations to describe the surface plasmon polariton dynamics following interaction of an ultrafast optical pulse with a slit ...coupling structure in a silver film. Through analysis of interference phenomena that lead to photoelectron emission from the silver film, we establish the universal contributions of a nanoscale asperity to the scattered surface field. Our results reveal the important role of surface cylindrical waves within the slit in the excitation of surface plasmon.
Aberrant histone lysine methylation patterns that change chromatin structure can promote dysregulated gene transcription and disease progression. Diabetic conditions such as high glucose (HG) are ...known to alter key pathologic pathways. However, their impact on cellular histone lysine methylation is unknown. We hypothesized that chronic HG can induce aberrant changes in histone H3 lysine 4 and lysine 9 dimethylation (H3K4me2 and H3K9me2) within target cells. Chromatin immunoprecipitation linked to microarrays (ChIP-on-chip) is currently a widely used approach for acquiring genome-wide information on histone modifications. We adopted this approach to profile and compare the variations in H3K4me2 and H3K9me2 in human gene coding and CpG island regions in THP-1 monocytes cultured in normal glucose and HG. Subsequently, we identified key relevant candidate genes displaying differential changes in H3K4me2 and H3K9me2 in HG versus normal glucose and also validated them with follow-up conventional ChIPs. Relevance to human diabetes was demonstrated by noting that H3K9me2 at the coding and promoter regions of two candidate genes was significantly greater in blood monocytes of diabetic patients relative to normal controls similar to the THP-1 data. In addition, regular mRNA profiling with cDNA arrays revealed correlations between mRNA and H3K9me2 levels. These novel results show histone methylation variations, for the first time, under diabetic conditions at a genome-wide level.
Background and objectives
Malignant phyllodes tumor of the breast (MPTB) is a kind of rare tumor. Our objective was to investigate the role of adjuvant radiotherapy (RT) in MPTB patients.
Methods
...MPTB patients were identified in the Surveillance, Epidemiology and End Results (SEER) database. Kaplan–Meier curves and multivariable Cox proportional hazards analyses were conducted to determine the effect of adjuvant RT on MPTB patients. Propensity-score matching (PSM) method was used to balance the clinicopathological characteristics.
Results
A total of 1353 MPTB patients were included in our study and the median follow-up time was 99 months (range: 0–331 months). 16.7% (226) MPTB patients received adjuvant RT, of which 49.1% (111) received mastectomy and 50.9% (115) underwent breast conservation surgery (BCS). Patients receiving adjuvant RT were more likely to be white, with better differentiation and larger tumors (
p
< 0.05). Multivariate analysis showed that poorer tumor differentiation grade, larger tumor size, and lymph node metastasis were associated with reduced survival while BCS was a protective factor of disease-specific survival (DSS) (HR 0.297; 95% CI 0.184–0.480) and overall survival (OS) (HR 0.445; 95% CI 0.321–0.616). After PSM, survival curves showed patients did not achieve an improved OS or DSS from adjuvant RT (
p
> 0.05). In subgroup analysis, no subgroup benefited from adjuvant RT. Exploratory analysis showed a survival benefit trend from adjuvant RT in patients with tumor larger than 50 mm and undergoing BCS.
Conclusions
Among MPTB patients, adjuvant RT did not improve OS or DSS. In patients with tumor larger than 50 mm and receiving BCS, a survival benefit trend from adjuvant RT existed.