As a new type of pollutant, microplastics have attracted increased attention because of their widespread and persistent existence in the water environment. In this study, we investigated one of the ...eight largest lakes in China—Wuliangsuhai Lake in Inner Mongolia. The microplastic concentration in Wuliangsuhai Lake ranges from 3.12 to 11.25 n/L. The different functional areas in Wuliangsuhai can be divided into four categories, namely effluent, fishing, intake and wetland areas. The highest microplastic concentration occurs in the intake area. The collected microplastics are divided into four types, i.e., fibers, pellets, fragments and films, of which fibers are the most abundant. Among the four functional areas of Wuliangsuhai Lake, the highest fiber concentration is observed in the fishing area. The microplastics in Wuliangsuhai Lake are mainly small size, and the microplastics smaller than 2 mm account for 98.2% of the total microplastics, while the microplastic size in the intake area is relatively large. Polystyrene and polyethylene are the main polymer types. Agricultural wastewater, domestic sewage and fishery discharge have the greatest impact on the microplastic distribution. This study reveals that the inland lakes in northern China are polluted by microplastics, which may cause potential harm to the surrounding environment.
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•Microplastics occurrence in Wuliangsuhai Lake were investigated.•The dominant microplastics were polystyrene fiber with 0–2 mm in size.•The discharge of human sewage and industrial wastewater were the main source of microplastics.•The spatial distribution of microplastics varies between different functional areas.
Microplastics (MPs) are less than 5 mm, and have significant implications for the environment. As a new type of environmental pollutant, MPs have increasingly attracted the attention of scientists ...and have led to marked increases in both public and political awareness. However, their distribution and fates in the terrestrial environment are limited. We investigated the distribution and characteristics of MPs in the agricultural soils of Shaanxi Province, a typical agricultural province in China. We found evidence that 100% of agricultural soils contained MPs. The concentration of MPs in the soil ranged from 1430 to 3410 items/kg. Fibers and small-sized particles (0–0.49 mm) were the predominant type and size, respectively. Polystyrene (PS), polyethylene (PE), polypropylene (PP), high-density polyethylene (HDPE), polyvinyl chloride (PVC) and polyethylene terephthalate (PET) particles were identified in agricultural soil. Furthermore, the abundance of microplastics in agricultural soil is closely related to the planting type of soil and climatic factors. The results from this study confirmed the presence of a high abundance of MPs in agricultural soil, and proved that agricultural activities might have caused MP contamination in soil.
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•Microplastics were investigated in agricultural soil of Shaanxi Province.•The concentration of MPs in the soil ranged from 1430 to 3410 items/kg.•Fiber and small size (0–0.5 mm) were the dominant type and size in soil samples.•The abundance of MPs in soil is related to the planting type and climatic factors.
In an era where the concept of green development is deeply rooted, magnesium (Mg) alloy as a light metal has a long-term development prospect in the process of energy saving, emission reduction and ...environmental improvement. However, anti-corrosion performance of Mg alloy is poor due to the high chemical activity and low equilibrium potential, which limits the development of Mg alloy products. Herein, three-dimensional mesopore hollow polypyrrole spheres (MHPS) were prepared, and the MHPS was inserted into the middle of the stacked hexagon boron nitride (h-BN) lamellae, which allowed the h-BN to be separated forming a further composite with abundant pore structure. Subsequently, the MHPS/h-BN-OH composite was uniformly sprayed on the Mg alloy surface via simple spraying method to form the superhydrophobic surface (SHS). Finally, the slippery liquid infused porous surface (SLIPS) was successfully fabricated by applying drops of silicone lubricant on the superhydrophobic coating surface. After a series of characterization and testing, the results showed that the stacking of h-BN lamellae was significantly reduced after h-BN was successfully embedded by MHPS. In addition, the fabricated SLIPS have excellent self-cleaning, mechanical stability, anti-icing and anti-corrosion properties. Therefore, the method of embedding polymer microspheres not only offers a new strategy for h-BN exfoliation, but also the successful prepared SLIPS largely retards the corrosion of Mg alloy while providing new ideas for the development of SLIPS.
Slippery liquid-infused porous surfaces with abundant pore structure have anti-corrosion, anti-contaminant mechanical stability and anti-icing properties.
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According to the latest evidence, the microbial metabolite Urolithin A (UA), known for its role in promoting cellular health, modulates CD8+ T cell‐mediated antitumor activity. However, the direct ...target protein of UA and its underlying mechanism remains unclear. Here, this research identifies ERK1/2 as the specific target crucial for UA‐mediated CD8+ T cell activation. Even at low doses, UA markedly enhances the persistence and effector functions of primary CD8+ cytotoxic T lymphocytes (CTLs) and human chimeric antigen receptor (CAR) T cells both in vitro and in vivo. Mechanistically, UA interacts directly with ERK1/2 kinases, enhancing their activation and subsequently facilitating T cell activation by engaging ULK1. The UA‐ERK1/2‐ULK1 axis promotes autophagic flux in CD8+ CTLs, enhancing cellular metabolism and maintaining reactive oxygen species (ROS) levels, as evidenced by increased oxygen consumption and extracellular acidification rates. UA‐treated CD8+ CTLs also display elevated ATP levels and enhanced spare respiratory capacity. Overall, UA activates ERK1/2, inducing autophagy and metabolic adaptation, showcasing its potential in tumor immunotherapy and interventions for diseases involving ERKs.
This study reports a new mechanism by which Urolithin A (UA) enhances the antitumor activity of primary CD8+ T and CAR T cells. UA directly binds and activates ERK1/2, further activating ULK1 to trigger autophagy and consequent metabolic adaption to maintain T cell fitness. These findings highlight the important role of UA‐ERK1/2‐ULK1 axis in tumor immunotherapy.
Abstract
Rosa rugosa
, commonly known as rugged rose, is a perennial ornamental shrub. It produces beautiful flowers with a mild fragrance and colorful seed pods. Unlike many other cultivated roses,
...R. rugosa
adapts to a wide range of habitat types and harsh environmental conditions such as salinity, alkaline, shade, drought, high humidity, and frigid temperatures. Here, we produced and analyzed a high-quality genome sequence for
R. rugosa
to understand its ecology, floral characteristics and evolution. PacBio HiFi reads were initially used to construct the draft genome of
R. rugosa
, and then Hi-C sequencing was applied to assemble the contigs into 7 chromosomes. We obtained a 382.6 Mb genome encoding 39,704 protein-coding genes. The genome of
R. rugosa
appears to be conserved with no additional whole-genome duplication after the gamma whole-genome triplication (WGT), which occurred ~100 million years ago in the ancestor of core eudicots. Based on a comparative analysis of the high-quality genome assembly of
R. rugosa
and other high-quality Rosaceae genomes, we found a unique large inverted segment in the Chinese rose
R. chinensis
and a retroposition in strawberry caused by post-WGT events. We also found that floral development- and stress response signaling-related gene modules were retained after the WGT. Two
MADS-box
genes involved in floral development and the stress-related transcription factors
DREB2A-INTERACTING PROTEIN 2
(
DRIP2
) and
PEPTIDE TRANSPORTER 3
(
PTR3
) were found to be positively selected in evolution, which may have contributed to the unique ability of this plant to adapt to harsh environments. In summary, the high-quality genome sequence of
R. rugosa
provides a map for genetic studies and molecular breeding of this plant and enables comparative genomic studies of
Rosa
in the near future.
The spatial organization of immune cells within the tumor microenvironment (TME) largely determines the anti-tumor immunity and also highly predicts tumor progression and therapeutic response. Tim-3 ...is a well-accepted immune checkpoint and plays multifaceted immunoregulatory roles via interaction with distinct Tim-3 ligands (Tim-3L), showing great potential as an immunotherapy target. However, the cell sociology mediated by Tim-3/Tim-3L and their contribution to tumor development remains elusive. Here, we analyzed the spatial distribution of Tim-3/Tim-3L in TME using multiplex fluorescence staining and revealed that despite the increased Tim-3 expression in various tumor-infiltrated lymphocytes, Tim-3+CD4+ cells were more accumulated in parenchymal/tumor region compared with stromal region and exhibited more close association with patient survival. Strikingly, CD4 T cells surrounding Tim-3L+ cells expressed higher Tim-3 than other cells in cancerous tissues. In vivo studies confirmed that depletion of CD4 T cells completely abrogated the inhibition of tumor growth and metastasis, as well as the functional improvement of CD8 T and NK, mediated by Tim-3 blockade, which was further validated in peripheral lymphocytes from patients with hepatocellular carcinoma. In conclusion, our findings unravel the importance of CD4 T cells in Tim-3/Tim-3L-mediated immunosuppression and provide new thoughts for Tim-3 targeted cancer immunotherapy.
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The authors analyzed the cell sociology mediated by Tim-3/Tim-3L and their contribution to tumor development. They unraveled the close association of Tim-3+CD4 T cells with Tim-3L-expressing cells in TME and their significance with patient prognosis. Functionally, CD4 T cells are critical for Tim-3/Tim-3L-mediated immunosuppression in TME.
To explore whether the paraventricular nucleus (PVN) participates in regulation of the anti-myocardial ischemia-reperfusion injury (MIRI) effect of electroacupuncture (EA) and whether this is ...achieved through the PVN-interposed nucleus (IN) neural pathway.
The modeling method of myocardial ischemia reperfusion injury was achieved by ligating the left anterior descending coronary artery in Sprague-Dawley rats. We used the Powerlab multi-channel physiological recorder system to record electro-cardiograms and analyze the changes in ST segment displacement; 2,3,5-Triphenyltetrazolium chloride staining was used to observe the percentage of myocardial infarction areas. Detecting cardiac troponin I (cTnI), lactate dehydrogenase (LDH) in serum was done with an enzyme-linked immunosorbent assay kit. Morphological changes in the myocardium were detected in each group with hematoxylin-eosin staining of paraffin sections. Detection of c-fos protein expression in the PVN of the hypothalamus was done with the immune-ofluorescence method. The Plexon multi-channel acquisition system recorded PVN neuron discharges and local field potentials in each group of rats. Offline Sorter software was used for cluster analysis. Neuro Explorer software was used to perform autocorrelation, raster and frequency characteristics and spectral energy analysis of neuron signals in each group.
Compared with the MIRI model group, the areas of myocardial infarction in the EA group were significantly reduced; the expression of cTnI, LDH in serum was decreased significantly. The firing frequency of pyramidal cells in the PVN was significantly increased and the spectrum energy map showed energy was reduced, c-fos expression in PVN was reduced, this indicated that neuronal activity in the PVN participates in the effect of EA improving myocardial injury. In addition, we used the kainic acid method to lesion the IN and observed that the effect of EA was weakened. For example, the area of myocardial infarction of lesion IN + EA group in rats was significantly increased compared with that resulting from EA group, the expression of cTnI, LDH in serum was significantly increased, the firing frequency of pyramidal cells in the PVN was significantly reduced. A spectral energy diagram shows that the energy after damage was higher than that of EA group. At the same time, the expression of c-fos in the PVN increased again.
Our results indicated that the PVN-IN nerve pathway may participate as an effective pathway of EA to improve the effect of myocardial injury.
T cell immunoglobulin and mucin-containing molecule 3 (Tim-3), expressed in dysfunctional and exhausted T cells, has been widely acknowledged as a promising immune checkpoint target for tumor ...immunotherapy. Here, using a strategy combining virtual and functional screening, we identified a compound named ML-T7 that targets the FG-CC' cleft of Tim-3, a highly conserved binding site of phosphatidylserine (PtdSer) and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). ML-T7 enhanced the survival and antitumor activity of primary CD8
cytotoxic T lymphocytes (CTLs) and human chimeric antigen receptor (CAR) T cells and reduced their exhaustion in vitro and in vivo. In addition, ML-T7 promoted NK cells' killing activity and DC antigen-presenting capacity, consistent with the reported activity of Tim-3. ML-T7 strengthened DCs' functions through both Tim-3 and Tim-4, which is consistent with the fact that Tim-4 contains a similar FG-CC' loop. Intraperitoneal dosing of ML-T7 showed comparable tumor inhibitory effects to the Tim-3 blocking antibody. ML-T7 reduced syngeneic tumor progression in both wild-type and Tim-3 humanized mice and alleviated the immunosuppressive microenvironment. Furthermore, combined ML-T7 and anti-PD-1 therapy had greater therapeutic efficacy than monotherapy in mice, supporting further development of ML-T7 for tumor immunotherapy. Our study demonstrates a potential small molecule for selectively blocking Tim-3 and warrants further study.
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