Exploring main soil drivers of vegetation succession in abandoned croplands of Minqin Oasis, China.

Background: The Minqin Oasis, which is located in Wuwei City, Gansu Province, China, faces a very serious land desertification problem, with about 94.5% of its total area desertified. Accordingly, it is crucial to implement ecological restoration policies such as cropland abandonment in this region. In abandoned croplands, abiotic factors such as soil properties may become more important than biotic factors in driving vegetation succession. However, the connections between soil properties and vegetation succession remain unclear. To fill this knowledge gap, this study investigated these connections to explore major factors that affected vegetation succession, which is meaningful to designing management measures to restore these degraded ecosystems. Methods: This study investigated seven 1-29-year-old abandoned croplands using the "space for time" method in Minqin Oasis. Vegetation succession was classified into different stages using a canonical correlation analysis (CCA) and two-way indicator species analysis (Twinspan). The link between soil properties and vegetation succession was analyzed using CCA. The primary factors shaping community patterns of vegetation succession were chosen by the "Forward selection" in CCA. The responses of dominant species to soil properties were analyzed using generalized additive models (GAMs). Results: Dominant species turnover occurred obviously after cropland abandonment. Vegetation succession can be classified into three stages (i.e., early, intermediate, and late successional stages) with markedly different community composition and diversity. The main drivers of vegetation succession among soil properties were soil salinity and saturated soil water content and they had led to different responses of the dominant species in early and late successional stages. During the development of vegetation succession, community composition became simpler, and species diversity decreased significantly, which was a type of regressive succession. Therefore, measures should be adopted to manage these degraded, abandoned croplands.

Carbon balance analysis of agricultural production systems in oasis areas.

China is the biggest emitter of greenhouse gases (GHGs) in the world, and agricultural GHG emission accounts for nearly a fifth of the total emission in China. To understand the carbon absorption and emission characteristics of agricultural production systems in those arid oasis areas, a typical representative city in northwestern China, Zhangye City, was selected for study.The emission factor method was used to analyze and calculate the characteristics of changing carbon emission dynamics in the whole agricultural production system in Zhangye city region (38,592 km2) from 2010 to 2021.The results revealed that carbon emissions during agricultural planting mainly come from fertilizers, which account for the highest proportion (47.9%) of total carbon emissions in agricultural planting. Animal enteric fermentation emissions from local livestock farming are the main contributor (86%) to GHG emissions. The annual average carbon absorption intensity is 4.4 t C-eq ha-1 for crop and 2.6 t C-eq ha-1 for the agricultural production system. The ratio of total carbon emissions from agricultural production to carbon sequestration of crops is 1:1.7. We find that the total carbon sequestration slightly exceeds its total carbon emissions in the study region, with an annual average of 41% for its sustainable development index. Carbon emissions of the agricultural production system in this oasis area are mainly driven by the livestock industry, mostly CH4 emissions from cattle raising.Reducing the local carbon emissions from the livestock industry, typically the cattle raising, will play a crucial role in reducing carbon emissions from this local agricultural production system and maintaining its net positive carbon balance.

An inulin-based glycovesicle for pathogen-targeted drug delivery to ameliorate salmonellosis.

The gut microbiota plays a significant role in the pathogenesis and remission of inflammatory bowel disease. However, conventional antibiotic therapies may alter microbial ecology and lead to dysbiosis of the gut microbiome, which greatly limits therapeutic efficacy. To address this challenge, novel nanomicelles that couple inulin with levofloxacin via disulfide bonds for the treatment of salmonellosis were developed in this study. Owing to their H2S-responsiveness, the nanomicelles can target the inflamed colon and rapidly release levofloxacin to selectively fight against enteric pathogens. Moreover, the embedded inulin can serve as prebiotic fiber to increase the amount of Bifidobacteria and Lactobacilli in mice with salmonellosis, thus maintaining the intestinal mechanical barrier and regulating the balance of the intestinal flora. Therefore, multifunctional nanomicelles had a better curative effect than pure levofloxacin on ameliorating inflammation in vivo. The pathogen-targeted glycovesicle represents a promising drug delivery platform to maximize the efficacy of antibacterial drugs for the treatment of inflammatory bowel disease.

Dendritic Polylysine with Paclitaxel and Triptolide Codelivery for Enhanced Cancer Ferroptosis through the Accumulation of ROS.

Recently, paclitaxel (PTX) was reported to increase intracellular lipid reactive oxygen species (ROS) levels, triggering cancer cell ferroptosis. Based on this, some efforts had been made to improve PTX treatment for non-small-cell lung cancer (NSCLC). Our previous studies demonstrated that triptolide (TPL) could improve the antitumor effect of PTX. Nevertheless, the poor solubility and side effects often limit the application of chemotherapy drugs. In this paper, we constructed a novel nanodrug delivery system (NDDS) chemosynthesis by PEGylated generation 3 (G3) dendritic polylysine coloaded with PTX and TPL (PTX-TPL-PEG-PLL, PTPP), which was endowed with the ability of tumor targeting and favorable solubility. In addition, we demonstrated that TPL could induce ROS generation by regulating the NF-κB signaling pathway to enhance the ferroptosis-induced effect of PTX. Besides, ferroptosis induced by PTPP could improve chemoresistance through inhibiting the level of P-gp, GPX4, and SLC7A11. Furthermore, we determined that ferroptosis may strengthen the immune response by increasing the expression of CD8+ T cells and IFN-γ+ cells while decreasing Treg cells. In general, PTPP may be a potential system for NSCLC treatment.

[Characteristics and Identification Priority Source of Heavy Metals Pollution in Farmland Soils in the Yellow River Basin].

Assessments of the soil environmental quality of farmland and pollution source apportionment are the foundation for ensuring national food security and agricultural sustainable development, as well as an important prerequisite for the pursuit to keep our lands clean. This study evaluated the characteristics of heavy metal pollution in farmland soils in the Yellow River Basin from 2000 to 2023, based on the data of heavy metal contents including As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn, using the geo-accumulation index method. Source apportionment was conducted by employing a positive matrix factorization (PMF) model. The probabilistic health risks were evaluated by coupling Monte Carlo simulation with a human health risk assessment model, and priority pollution sources and elements were identified. The results showed that:① the average content of all heavy metals in farmland soils within the study area was lower than the screening values specified in the soil environment quality risk control standard for soil contamination of agriculture land (GB 15618-2018) (pH>7.5). However, the contents of Cd, As, and Zn in the samples exceeded their screening values, with percentages of 21.69%, 5.56%, and 1.23%, respectively, with Cd having the highest rate of exceedance. ② Hg and Cd were moderately polluted, Cu and Pb were slightly polluted, and the other elements were not polluted. ③ The main sources of heavy metals in farmland soil were traffic-industrial sources, natural-agricultural sources, industrial-natural sources, and agricultural-industrial sources, with contribution rates of 37.04%, 26.69%, 21.72%, and 14.55%, respectively. ④ Heavy metals in farmland soil posed carcinogenic health risks to adults and children but did not have non-carcinogenic risks; As and Cd were priority control elements for human health risks, and industrial-natural sources and agricultural-industrial sources were priority control sources in the study area.

Multi-omics analysis reveals novel loci and a candidate regulatory gene of unsaturated fatty acids in soybean (Glycine max (L.) Merr).

BACKGROUND: Soybean is a major oil crop; the nutritional components of soybean oil are mainly controlled by unsaturated fatty acids (FA). Unsaturated FAs mainly include oleic acid (OA, 18:1), linoleic acid (LLA, 18:2), and linolenic acid (LNA, 18:3). The genetic architecture of unsaturated FAs in soybean seeds has not been fully elucidated, although many independent studies have been conducted. A 3 V multi-locus random single nucleotide polymorphism (SNP)-effect mixed linear model (3VmrMLM) was established to identify quantitative trait loci (QTLs) and QTL-by-environment interactions (QEIs) for complex traits. RESULTS: In this study, 194 soybean accessions with 36,981 SNPs were calculated using the 3VmrMLM model. As a result, 94 quantitative trait nucleotides (QTNs) and 19 QEIs were detected using single-environment (QTN) and multi-environment (QEI) methods. Three significant QEIs, namely rs4633292, rs39216169, and rs14264702, overlapped with a significant single-environment QTN. CONCLUSIONS: For QTNs and QEIs, further haplotype analysis of candidate genes revealed that the Glyma.03G040400 and Glyma.17G236700 genes were beneficial haplotypes that may be associated with unsaturated FAs. This result provides ideas for the identification of soybean lipid-related genes and provides insights for breeding high oil soybean varieties in the future.

MicroRNA-93 promotes the pathogenesis of glaucoma by inhibiting matrix metalloproteinases as well as up-regulating extracellular matrix and Rho/ROCK signaling pathways.

Objective: To investigate the effect and potential molecular mechanism of microRNA-93 (miR-93) on retinal ganglion cells (RGCs) apoptosis as well as retinal damage in acute glaucoma mice. Methods: RGCs apoptosis were induced by oxygen-glucose deprivation and reperfusion (OGD/R). The pro-apoptotic effect of miR-93 was evaluated by transfecting miR-93 mimics or miR-93 inhibitor into OGD/R-induced RGCs. The viability and apoptosis of RGCs were determined by MTT assay and flow cytometry. Mouse model of acute glaucoma were successfully induced via high intraocular pressure (IOP), and then these model animals were randomly divided into vehicle group, miR-93 mimics group or miR-93 inhibitor group (n = 10), using healthy mice as normal control. Histopathologic changes of retinal tissue were evaluated by Hematoxylin and Eosin (H&E) staining method. Moreover, cell counts of retinal ganglion cell layer and mean thickness of different layers were also determined. Quantitative real-time PCR (qPCR) and western blotting analysis were used to detect the mRNA and protein expression levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs) and Rho/ROCK signaling pathway. Results: miR-93 mimics significantly decreased or promoted the viability and apoptosis of OGD/R-induced RGCs, respectively. In addition, miR-93 mimics significantly exacerbated the degree of retinal tissue damage in mice with acute glaucoma, which was accompanied by a decrease in the number of ganglion cell layer (GCL) cells and the thickness of different tissue layers. Moreover, miR-93 mimics significantly increased IOP in mice with acute glaucoma. Significantly, miR-93 inhibitors significantly reversed the above changes. In addition, results of Western blot analysis showed that miR-93 mimics increased and decreased the expression of ECM-associated and MMP-associated proteins, respectively, by activating the Rho/ROCK signaling pathway. In contrast, miR-93 significantly decreased and increased the expression of ECM-associated and MMP-associated proteins, and suppressed the expression of Rho/ROCK signaling pathway-related proteins. Conclusion: miR-93 can promote the development of glaucoma by activating Rho/ROCK signaling pathway to mediate the accumulation of ECM-related proteins as well as the down-regulation of MMP-related proteins.

[Contamination Characteristics and Source Apportionment of Potentially Toxic Elements in Soil around the Coal-fired Power Plant Using APCS-MLR and PMF Models].

To investigate the characteristics and sources of potentially toxic elemental contamination in soils around the coal-fired power plant, we selected the soil around the Jingyuan power plant as the object of investigation. Thirty-six and 27 soil samples collected from the urban and farmland areas were analyzed for PTEs (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn), respectively. We employed the geoaccumulation index, single-factor pollution index, and improved Nemerow integrated pollution index to evaluate the contamination characteristics of PTEs, and combined correlation analysis with absolute principal component scores-multiple linear regression (APCS-MLR) and positive matrix factorization (PMF) receptor models were used to quantitatively analyze the pollution sources of PTEs. The results revealed that all the average concentrations of other soil metals around Jingyuan power plant exceeded their corresponding background values of Gansu Province, except for As, in agricultural soil, and Hg exhibited significant spatial non-homogeneity, and thus it was visibly affected by anthropogenic activities. The values of the single-factor pollution and geoaccumulation indices indicated that the soils of both sites were mainly contaminated with Cd, Cr, Ni, and Pb, and Hg contamination was reflected in wide areas for both sites. Additionally, the results of the improved Nemerow index demonstrated that the investigated soil was between moderately contaminated and heavily contaminated. Further, the comprehensive pollution degree of urban soil was higher than that of agricultural soil. Moreover, source apportionment revealed that PTEs in urban soil were derived from mixed sources of traffic activities and coal combustion, mixed sources of traffic activities and industrial and mining activities, and atmospheric deposition from industrial activities, with contribution rates of APCS-MLR of 35.2%, 25.1%, and 23.4%, respectively. The PMF contribution rates were 40.2%, 12.4%, and 47.7%, respectively. PTEs in agricultural soil were from one mixture source of industrial, mining, agricultural, and traffic sources, and the other mixed source was of traffic activities and coal combustion, with a APCS-MLR contribution rate of 40.3% and 35.9% and a contribution rate of PMF of 36.2% and 18.0%, respectively. In addition, another mixed source of agricultural activities and coal combustion was obtained using the PMF model, with a contribution rate of 48.5%.

Traditional Chinese Medicine formula Bu-Shen-Huo-Xue-Fang (BSHXF) protects nucleus pulposus cells against the inflammatory and oxidative stress-induced degenerative changes.

Degeneration of the intervertebral disc is primarily caused by the loss of nucleus pulposus cells (NPCs) and extracellular matrix (ECM) (IDD). Bu-Shen-Huo-Xue-Fang (BSHXF), a traditional Chinese medicine decoction, has been used to treat IDD in clinical; nevertheless, the active components and underlying molecular mechanisms remain unknown. BSHXF improved IL-1ß and H2O2 stimulation-induced injuries on NPCs by promoting cell viability, increasing ECM deposition, inhibiting cell senescence, and decreasing the levels of inflammatory factors. The active ingredients in BSHXF were identified by LC-MS/MS analysis; three active ingredients from the principal drugs, Aucubin, Tanshinol, and Tanshinone II A promoted NPC viability; and Aucubin and Tanshinol promoted NPC viability more. Aucubin and Tanshinol, respectively, improved H2O2 stimulation-induced injuries on NPCs by promoting cell viability, increasing ECM deposition, inhibiting cell senescence, and decreasing the levels of inflammatory factors. The activator of NF-κB and Wnt signaling pathways attenuated Aucubin and Tanshinol's protective effects by promoting ECM degradation and NPC senescence. Aucubin, Tanshinol, and Tanshinone II A were identified as the most potent compounds in BSHXF protection against degenerative changes in NPCs. The NF-κB and Wnt signaling pathways might be involved in the protective effects of Aucubin and Tanshinol against H2O2-induced degenerative changes.

Contamination, ecological-health risks, and sources of potentially toxic elements in road-dust sediments and soils of the largest urban riverfront scenic park in China.

Identifying the contamination and sources of potentially toxic elements (PTEs) in road-dust sediment (RDS) and the surrounding greenspace soil of urban environments and understanding their ecological-health risks are important for pollution management and public health. The contamination characteristics, ecological and probabilistic health risks, and source apportionment of eight PTEs (Cd, Pb, Cr, Cu, Ni, As, Zn, and Hg) in the Yellow River Custom Tourist Line of Lanzhou, which is the largest open urban riverfront scenic park in China, were investigated. The results showed that all the RDS PTE mean concentrations exceeded their soil background values, whereas for the surrounding greenspace soils, the concentrations of the PTEs, except for Cr and Ni, were also higher than their local background levels. Moreover, the RDS-soil system was mainly contaminated by Cd, Zn, Pb, Cu, and Hg to varying degrees, and the integrated ecological risks of PTEs in the RDS and soil were high and considerable at most sites, respectively. The probabilistic health risk assessment results demonstrated that the non-carcinogenic hazard risk for humans was negligible, but the total carcinogenic risks should be considered. Source apportionment using a positive matrix factorization model combined with multivariate statistical analyses revealed that Cr, Ni, and As in the RDS-soil system were from natural and industrial sources, Cd, Pb, Zn, Cu came from vehicle emissions and pesticide and fertilizer applications, and Hg was from natural and industrial sources and utilization of pesticides with fertilizers. This work provides scientific evidence for urban planning and human health protection in urban environments.

[Pollution Characteristics and Risk Assessment of Heavy Metals in Surface Dusts and Surrounding Green Land Soils from Yellow River Custom Tourist Line in Lanzhou].

In order to investigate the contamination levels of dust and its surrounding green land soil heavy metal pollution and potential ecological and health risks in the scenic areas of urban waterfront parks, the gardens, squares, and theme parks of the Yellow River Custom Tourist Line in Lanzhou were selected as the research area, using 27 dust samples and 26 soil samples from its surrounding green lands. The contamination characteristics and potential ecological risks of eight heavy metals (Cr, Ni, Cu, Zn, As, Cd, Hg, and Pb) were evaluated using the geo-accumulation index (Igeo), single-factor pollution index (Pi), Nemerow integrated pollution index (PN), and improved potential ecological risk index (RI). The human health risk assessment was also evaluated using the exposure risk model. The results showed that the average concentrations of the other heavy metals in the surface dusts were higher than the background values of Gansu Province and Lanzhou City, except that the As mean concentrations in the surface dusts and the surrounding green land soils were slightly lower than the Gansu Province background values. For its surrounding green land soils, the mean concentrations of the other heavy metals (Cu, Zn, Cd, Hg, and Pb) exceeded the soil background values of Gansu Province and Lanzhou City, whereas the Cr and Ni mean concentrations were lower than their corresponding soil background values of Gansu Province and Lanzhou City. The geo-accumulation and single-factor pollution indices demonstrated that a slight to moderate pollution of Cr, Cu, Zn, Cd, Hg, and Pb occurred in surface dusts, and Cu, Zn, Cd, Hg, and Pb appeared in varying degrees of contamination levels in its surrounding green land soils. The Nemerow integrated pollution index analysis manifested that the overall contamination status of the study areas was between slightly and heavily polluted. The potential ecological risk index suggested that Cd and Hg were recognized as significant pollutant elements and that the RI of the other heavy metals were all below 40, presenting slight ecological risk. The health risk assessment indicated that ingestion was the dominant exposure pathway for heavy metals from the surface dusts and the surrounding green land soils, and no carcinogenic and noncarcinogenic risks posed threats to adults and children.

[Spatial Distribution Characteristics and Source Analysis of Heavy Metals in Urban River Surface Sediments from the Lanzhou Reach of the Yellow River].

In order to investigate the contamination characteristics and potential sources of heavy metals from the urban river surface sediments in the Yellow River Basin, we selected the Lanzhou reach of the Yellow River as the object of investigation. A total of 46 surface sediment samples were collected along the Lanzhou reach of the Yellow River, and the contents of eight heavy metals, Cr, Ni, Cu, Zn, As, Cd, Hg, and Pb, were determined by using inductively coupled plasma mass spectrometry and an atomic fluorescence spectrometer. Contamination indexes including single factor pollution index (Pi) and geo-accumulation index (Igeo), together with the sediment pollution index (SPI), were used to assess heavy metal pollution characteristics and ecological risk levels in the urban river surface sediments of the Lanzhou reach of the Yellow River. Pearson's correlation analysis (CA), positive matrix factorization (PMF), and principal component analysis/absolute principal component score (PCA/APCS) were jointly employed to quantitatively analyze pollution sources of heavy metals. The results showed that the mean concentrations of the majority of heavy metals exceeded their corresponding background values of Gansu Province and Lanzhou City with the exception of As, and the spatial distribution of high concentrations of heavy metals was mainly concentrated in the corner of the river. Based on the single factor pollution and geo-accumulation indexes of the eight heavy metals, in the Lanzhou reach of the Yellow River, Cr was the dominant pollution element in the urban river surface sediments, followed by Cd and Ni. Additionally, the SPI values for the eight heavy metals in the surface sediments ranged from 0.48 to 8.56, presenting natural to low ecological risk level. Furthermore, source apportionment revealed that a mixture source of industrial and agricultural activities (77.6%) was the largest contributor of Cr, Ni, Zn, As, Cd, and Pb in the urban river surface sediments, followed by natural sources (11.4%) and a mixed source of industrial and traffic activities (11%).

Reprogrammed siTNFα/neutrophil cytopharmaceuticals targeting inflamed joints for rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe synovial inflammation and cartilage damage. Despite great progress in RA therapy, there still lacks the drugs to completely cure RA patients. Herein, we propose a reprogrammed neutrophil cytopharmaceuticals loading with TNFα-targeting-siRNA (siTNFα) as an alternative anti-inflammatory approach for RA treatment. The loaded siTNFα act as not only the gene therapeutics to inhibit TNFα production by macrophages in inflamed synovium, but also the editors to reprogram neutrophils to anti-inflammatory phenotypes. Leveraging the active tendency of neutrophils to inflammation, the reprogrammed siTNFα/neutrophil cytopharmaceuticals (siTNFα/TP/NEs) can rapidly migrate to the inflamed synovium, transfer the loaded siTNFα to macrophages followed by the significant reduction of TNFα expression, and circumvent the pro-inflammatory activity of neutrophils, thus leading to the alleviated synovial inflammation and improved cartilage protection. Our work provides a promising cytopharmaceutical for RA treatment, and puts forward a living neutrophil-based gene delivery platform.

Vitamin D receptor (VDR) mediates the quiescence of activated hepatic stellate cells (aHSCs) by regulating M2 macrophage exosomal smooth muscle cell-associated protein 5 (SMAP-5). / ç»´ç”Ÿç´ D受体（VDR）通过调节M2巨噬细胞外泌体SMAP-5介导肝星状细胞的静息.

An effective therapeutic regimen for hepatic fibrosis requires a deep understanding of the pathogenesis mechanism. Hepatic fibrosis is characterized by activated hepatic stellate cells (aHSCs) with an excessive production of extracellular matrix. Although promoted activation of HSCs by M2 macrophages has been demonstrated, the molecular mechanism involved remains ambiguous. Herein, we propose that the vitamin D receptor (VDR) involved in macrophage polarization may regulate the communication between macrophages and HSCs by changing the functions of exosomes. We confirm that activating the VDR can inhibit the effect of M2 macrophages on HSC activation. The exosomes derived from M2 macrophages can promote HSC activation, while stimulating VDR alters the protein profiles and reverses their roles in M2 macrophage exosomes. Smooth muscle cell-associated protein 5 (SMAP-5) was found to be the key effector protein in promoting HSC activation by regulating autophagy flux. Building on these results, we show that a combined treatment of a VDR agonist and a macrophage-targeted exosomal secretion inhibitor achieves an excellent anti-hepatic fibrosis effect. In this study, we aim to elucidate the association between VDR and macrophages in HSC activation. The results contribute to our understanding of the pathogenesis mechanism of hepatic fibrosis, and provide potential therapeutic targets for its treatment.

Real-time detection of T cell activation by visualizing TCR nanoclusters with a cholesterol derived aggregation-induced emission probe.

Successful T-cell based immunotherapy usually depends on the activation of T cells. Most of commonly used methods for assessing T cell activity rely on the antibody-based technology, which focus on detecting protein-centered activation markers, including CD25, cytokines and so on. However, these methods always involve tedious sample-preparation process, labor-consuming and costly, which could not be utilized in real-time detection. The T cell receptor (TCR) clustering is another kind of essential T cell activation marker on the membrane, which increases during the activation state of T cells. We herein developed a cholesterol derived aggregation-induced emission (AIE) fluorescent probe (R-TPE-PEG-Chol) for detecting T cell activation in real-time. Five probes were first designed and synthesized and among them COOH-TPE-PEG-Chol displayed the best imaging effects, which had no significant impact on the key physiological functions of T cells. In addition, we have proved that COOH-TPE-PEG-Chol was introduced onto the naïve T cell membrane in its molecularly dissolved form without fluorescent emission. While during T cell activation, the formation of TCR nanoclusters would induce aggregation of membrane cholesterol, which could provoke the fluorescence signal of the COOH-TPE-PEG-Chol due to the AIE characteristic. Moreover, the enhancement of the fluorescence intensity was positively related to the activation state of T cells. Our study demonstrated the concept of cholesterol-derived AIE fluorescent probes for deciphering the spatiotemporal arrangements of TCR on the membrane during T cell activation, and consequently provided a novel and complementary strategy for detecting T cell activation in real-time.

Sensitizing Tumors to Immune Checkpoint Blockage via STING Agonists Delivered by Tumor-Penetrating Neutrophil Cytopharmaceuticals.

Immune checkpoint inhibitors (ICIs) have displayed potential efficacy in triple-negative breast cancer (TNBC) treatment, while only a minority of patients benefit from ICI therapy currently. Although activation of the innate immune stimulator of interferon genes (STING) pathway potentiates antitumor immunity and thus sensitizes tumors to ICIs, the efficient tumor penetration of STING agonists remains critically challenging. Herein, we prepare a tumor-penetrating neotype neutrophil cytopharmaceutical (NEs@STING-Mal-NP) with liposomal STING agonists conjugating on the surface of neutrophils, which is different from the typical neutrophil cytopharmaceutical that loads drugs inside the neutrophils. We show NEs@STING-Mal-NP that inherit the merits of neutrophils including proactive tumor vascular extravasation and tissue penetration significantly boost the tumor penetration of STING agonists. Moreover, the backpacked liposomal STING agonists can be released in response to hyaluronidase rich in the tumor environment, leading to enhanced uptake by tumor-infiltrating immune cells and tumor cells. Thus, NEs@STING-Mal-NP effectively activate the STING pathway and reinvigorate the tumor environment through converting macrophages and neutrophils to antitumor phenotypes, promoting the maturation of dendritic cells, and enhancing the infiltration and tumoricidal ability of T cells. Specifically, this cytopharmaceutical displays a significant inhibition on tumor growth and prolongs the survival of TNBC-bearing mice when combined with ICIs. We demonstrate that neutrophils serve as promising vehicles for delivering STING agonists throughout solid tumors and the developed neutrophil cytopharmaceuticals with backpacked STING agonists exhibit huge potential in boosting the immunotherapy of ICIs.

Circ_0080940 Regulates miR-139-5p/CTGF Pathway to Promote the Proliferation, Migration, Extracellular Matrix Deposition of Human Tenon's Capsule Fibroblasts.

PURPOSE: Circular RNA (circRNA) has been identified as an important regulator for glaucoma progression. Our study aims to reveal the circ_0080940 roles in glaucoma progression. METHODS: Transforming growth factor ß1 (TGF-ß1) was used to treat human Tenon's capsule fibroblasts (HTFs) to mimic glaucoma cell models. Cell function was determined by cell counting kit 8 assay, EdU assay and wound healing assay. Protein levels were determined by western blot analysis. Quantitative real-time PCR was used to measure RNA expression. Dual-luciferase reporter assay was performed to evaluate RNA interaction. RESULTS: Our data confirmed that TGF-ß1 induced HTFs proliferation, migration and extracellular matrix (ECM) deposition. Circ_0080940 was highly expressed in glaucoma patients, and its knockdown inhibited TGF-ß1-induced proliferation, migration and ECM deposition in HTFs. Circ_0080940 sponged miR-139-5p, and anti-miR-139-5p revoked the effect of si-circ_0080940 on the biological functions of TGF-ß1-induced HTFs. CTGF was targeted by miR-139-5p, and overexpressed CTGF overturned the inhibition effect of miR-139-5p on the biological functions of TGF-ß1-induced HTFs. Furthermore, CTGF expression could be positively regulated by circ_0080940. CONCLUSION: To sum up, we confirmed that circ_0080940 contributed to glaucoma progression by miR-139-5p/CTGF axis.

Deterministic processes shape bacterial community assembly in a karst river across dry and wet seasons.

Karst rivers are particularly vulnerable to bacterial pollution because immigrations are easily diffused from the surrounding environments due to their strong hydraulic connectivity. However, the assembly mechanism in shaping riverine bacterial biogeography is still poorly understood, especially for an ecosystem in the karst area. Here, 16S rRNA genes were used to explore the spatiotemporal and biogeographical patterns of bacterial communities from the Chishui River in the dry and wet seasons, and explore the impact of external immigration on the assembly of water bacterial communities. Our results showed clear spatiotemporal patterns of bacterial communities with a more pronounced seasonal rather than spatial fluctuation, which appeared to be dependent on seasonal-related environmental factors (e.g., temperature and turbidity). The bacterial communities exhibited a significant (p < 0.05) distance-decay pattern in both seasons, and they had a stronger distance-decay relationship in the dry season than in the wet season. However, most of the biomarkers of different external immigrations did not show significant (p > 0.05) distance-decay patterns along the Chishui river, implying that the biomarkers could be used as indicators of external immigration (e.g., OTU_125 and OTU_536). Also, the tributaries were the main external immigration (20.44-83.68%) for the Chishui River, while other terrestrial immigration (e.g., livestock, the soil of the cropland, brewing wastewater treatment plant, and sewages) showed relatively little influence, which could be due to the hydrodynamic conditions (e.g., fragile rock-soil system and hydrological structure) of the karst river. Additionally, the assembly of water bacterial communities in the Chishui river was governed by more determinism (50.7-85.7%) than stochasticity (14.3-49.3%) in both the dry and wet seasons. We demonstrated that the bacterial community's substantial variations are largely shaped by deterministic processes, thereby providing a better understanding of spatiotemporal patterns and mechanisms of the bacterial community in karst river waters.

Distribution and correlation between antibiotic resistance genes and host-associated markers before and after swine fever in the longjiang watershed.

Antibiotic resistance genes (ARGs) are abundantly shed in feces. Thus, it is crucial to identify their host sources so that ARG pollution can be effectively mitigated and aquatic ecosystems can be properly conserved. Here, spatiotemporal variations and sources of ARGs in the Longjiang watershed of South China were investigated by linking them with microbial source tracker (MST) indicators. The most frequently detected ARGs (>90%) were sulI, sulII, blaTEM, tetW, ermF, and the mobile element intI1. Spatial distribution analyses showed that tributaries contributed significantly more sulI, sulII, and ermF contamination to the Longjiang watershed than the main channel. MST indicator analysis revealed that the Longjiang watershed was contaminated mainly by human fecal pollution. Livestock- and poultry-associated fecal pollution significantly declined after the swine fever outbreak. The occurrence of most ARGs is largely explained by human fecal pollution. In contrast, pig fecal pollution might account for the prevalence of tetO. Moreover, combined human-pig fecal pollution contributed to the observed blaNDM-1 distribution in the Longjiang watershed. Subsequent analysis of the characteristics of MST markers disclosed that the relatively lower specificities of BacHum and Rum-2-Bac may lead to inaccurate results of tracking ARG pollution source. The present study determined spatiotemporal variations and ARG origins in the Longjiang watershed by combining MST markers. It also underscored the necessity of using multiple MST markers simultaneously to identify and characterize ARG pollution sources accurately.