Electrostimulation suppresses allograft rejection via promoting lymphatic regulatory T cell migration mediated by lymphotoxin - lymphotoxin receptor ß signaling.

Conventional immunosuppressants that suppress allograft rejection cause various side effects. Although regulatory T cells (Tregs) are essential for allograft survival, the limited efficacy of Treg therapy demands improvement. Thus, it is imperative to seek new approaches to enhancing Treg suppression. Low-intensity electrostimulation (ES) has been shown to exert antiinflammatory effects without causing major adverse reactions. However, it remains unknown whether and how ES regulates alloimmunity. Here, we found that regional ES delayed murine skin allograft rejection and promoted long-term allograft survival induced by an mTOR inhibitor, rapamycin. ES also extended islet allograft survival. Mechanistically, ES enhanced the expression of lymphotoxin α (LTα) on Tregs after transplantation. Blockade of lymphotoxin ß receptor-mediated nonclassical NFκB signaling suppressed lymphatic Treg migration and largely reversed the effects of ES on allograft survival. Moreover, ES failed to extend allograft survival when recipients lacked LTα/lymph nodes or if transferred Tregs lacked LTα. Therefore, ES promoted the lymphatic migration of CD4+Foxp3+ Tregs by upregulating their surface expression of LTα. Finally, ES augmented expression of LTα on murine or human Tregs, but not conventional T cells, while promoting their calcium influx in vitro. This ES-mediated upregulation of LTα relied on calcium influx. Thus, our findings have unveiled novel mechanisms underlying ES-mediated immunoregulation.

The neglected roles of adjacent natural ecosystems in maintaining bacterial diversity in agroecosystems.

A central aim of community ecology is to understand how local species diversity is shaped. Agricultural activities are reshaping and filtering soil biodiversity and communities; however, ecological processes that structure agricultural communities have often overlooked the role of the regional species pool, mainly owing to the lack of large datasets across several regions. Here, we conducted a soil survey of 941 plots of agricultural and adjacent natural ecosystems (e.g., forest, wetland, grassland, and desert) in 38 regions across diverse climatic and soil gradients to evaluate whether the regional species pool of soil microbes from adjacent natural ecosystems is important in shaping agricultural soil microbial diversity and completeness. Using a framework of multiscales community assembly, we revealed that the regional species pool was an important predictor of agricultural bacterial diversity and explained a unique variation that cannot be predicted by historical legacy, large-scale environmental factors, and local community assembly processes. Moreover, the species pool effects were associated with microbial dormancy potential, where taxa with higher dormancy potential exhibited stronger species pool effects. Bacterial diversity in regions with higher agricultural intensity was more influenced by species pool effects than that in regions with low intensity, indicating that the maintenance of agricultural biodiversity in high-intensity regions strongly depends on species present in the surrounding landscape. Models for community completeness indicated the positive effect of regional species pool, further implying the community unsaturation and increased potential in bacterial diversity of agricultural ecosystems. Overall, our study reveals the indubitable role of regional species pool from adjacent natural ecosystems in predicting bacterial diversity, which has useful implication for biodiversity management and conservation in agricultural systems.

Agricultural tillage practice and rhizosphere selection interactively drive the improvement of soybean plant biomass.

Rhizosphere microbes play key roles in plant growth and productivity in agricultural systems. One of the critical issues is revealing the interaction of agricultural management (M) and rhizosphere selection effects (R) on soil microbial communities, root exudates and plant productivity. Through a field management experiment, we found that bacteria were more sensitive to the M × R interaction effect than fungi, and the positive effect of rhizosphere bacterial diversity on plant biomass existed in the bacterial three two-tillage system. In addition, inoculation experiments demonstrated that the nitrogen cycle-related isolate Stenotrophomonas could promote plant growth and alter the activities of extracellular enzymes N-acetyl- d-glucosaminidase and leucine aminopeptidase in rhizosphere soil. Microbe-metabolites network analysis revealed that hubnodes Burkholderia-Caballeronia-Paraburkholderia and Pseudomonas were recruited by specific root metabolites under the M × R interaction effect, and the inoculation of 10 rhizosphere-matched isolates further proved that these microbes could promote the growth of soybean seedlings. Kyoto Encyclopaedia of Genes and Genomes pathway analysis indicated that the growth-promoting mechanisms of these beneficial genera were closely related to metabolic pathways such as amino acid metabolism, melatonin biosynthesis, aerobactin biosynthesis and so on. This study provides field observation and experimental evidence to reveal the close relationship between beneficial rhizosphere microbes and plant productivity under the M × R interaction effect.

Diagnostic value of IL-22, IL-23, and IL-17 for NK/T cell lymphoma.

NK/T cell lymphoma (NKTCL) is a common blood cancer, and early diagnosis of this disease is crucial. This study is aimed to investigate the roles of IL-17, IL-22 as well as IL-23 for the diagnosis of NKTCL. Sixty-five patients with NKTCL were included and the blood samples were collected, and sixty healthy objectives served as the controls. Serums of the patients and controls were collected. The expression levels of IL-17, IL-22, and IL-23 were examined using enzyme-linked immunosorbent (ELISA) assay. The receiver operator characteristic (ROC) curve was drawn for determining the potential diagnostic value of these cytokines. The serum levels of IL-17 (156.0 ± 67.75 pg/mL), IL-22 (39.98 ± 23.88 pg/mL), and IL-23 (43.05 ± 25.69 pg/mL) were all markedly increased in NKTCL patients (P<0.001); ROC analysis showed the serum level of IL-17, IL-22, and IL-23 could serve as the potential diagnostic biomarker for NKTCL with high sensitivity and specificity. The AUC of IL-17 was 0.9487 (95% confidence interval (CI), 0.9052 to 0.9922). Area under the curve (AUC) of IL-22 was 0.7321 (95% CI, 0.6449 to 0.8192). The AUC of IL-23 was 0.7885 (95% CI, 0.7070 to 0.8699). Our data indicated that IL-17, IL-22, and IL-23 were all increased in NKTCL and may function as potential diagnostic biomarkers for NKTCL.

Indigenous microbial community governs the survival of Escherichia coli O157:H7 in constructed wetlands.

The survival pattern of Escherichia coli O157:H7 (E. coli O157:H7) and its regulatory factors in natural environments have been widely studied. However, there is little information about the survival of E. coli O157:H7 in artificial environments, especially in wastewater treatment facilities. In this study, a contamination experiment was performed to explore the survival pattern of E. coli O157:H7 and its central control factors in two constructed wetlands (CWs) under different hydraulic loading rates (HLRs). The results showed that the survival time of E. coli O157:H7 was longer in the CW under the higher HLR. Substrate ammonium nitrogen and available phosphorus were the main factors that influenced the survival of E. coli O157:H7 in CWs. Despite the minimal effect of microbial α-diversity, some keystone taxa, such as Aeromonas, Selenomonas, and Paramecium, governed the survival of E. coli O157:H7. In addition, the prokaryotic community had a more significant impact on the survival of E. coli O157:H7 than the eukaryotic community. The biotic properties had a more substantial direct power on the survival of E. coli O157:H7 than the abiotic factors in CWs. Collectively, this study comprehensively disclosed the survival pattern of E. coli O157:H7 in CWs, which is an essential addition to the environmental behavior of E. coli O157:H7, providing a theoretical basis for the prevention and control of biological contamination in wastewater treatment processes.

Core phylotypes enhance the resistance of soil microbiome to environmental changes to maintain multifunctionality in agricultural ecosystems.

Agricultural ecosystems are facing increasing environmental changes. Revealing ecological stability of belowground organisms is key to developing management strategies that maintain agricultural ecosystem services in a changing world. Here, we collected soils from adjacent pairs of maize and rice fields along large spatial scale across Eastern and Southeast China to investigate the importance of core microbiota as a predictor of resistance of soil microbiome (e.g. bacteria, fungi and protist) to climate changes and nutrient fertilization, and their effect on multiple ecosystem functions, representing key services for crop growth and health in agro-ecosystems. Soil microbiome in maize soils exhibited stronger resistance than that in rice soils, by considering multiple aspects of the resistance index, for example, community, phylogenetic conservation and network complexity. Community resistance of soil microbiome showed a geographic pattern, with higher resistance at lower latitudes, suggesting their stronger resistance in warmer regions. Particularly, we highlighted the role of core phylotypes in enhancing the community resistance of soil microbiome, which was essential for the maintenance of multifunctionality in agricultural ecosystems. Our results represent a significant advance in linking core phylotypes to community resistance and ecosystem functions, and therefore forecasting agro-ecosystems dynamics in response to ongoing environmental changes. These suggest that core phylotypes should be considered a key factor in enhancing agricultural sustainability and crop productivity under global change scenarios.

Tug1 Acts on ERK12 Signaling Pathway to Aggravate Neuronal Damage after Acute Ischemic Stroke.

Approximately 85% of stroke patients suffer from ischemic stroke, which has a high incidence and difficult prognosis. It has become one of the leading causes of death in middle-aged and elderly people and seriously threatens human health. This study mainly considers the role of lncRNA tug 1 on the ERK 12 signaling pathway to enhance neuronal damage after acute ischemic stroke. In the experiment, the middle cerebral artery occlusion (MCAO) model was constructed using the thread embolization method. The real-time quantitative RT-CR method was used to detect the relative transcriptional activity of TG1, GAS5 and SM22a genes in tissues. The relative expression level of SM22a protein in tissues was detected by the immune-histochemical method. Twenty-four hours after cerebral infarction, the nerve function, cerebral infarction area and ERK1/2 protein expression level of cerebral cortex on the side of cerebral infarction were detected in each group. The experimental results showed that the successful animal behavior scores of the MCAO model in the normal saline control group and Pepstatin A interference group were 1 point 25, 2 points 17 and 3 points 18. The results show that lncRNA tug1 can enhance the neuronal damage of the ERK12 signaling pathway after acute ischemic stroke. lncRNATUGl plays an important role after OGD/RX and can accelerate cell apoptosis. If the expression of lncRNATUGl is inhibited, the number of apoptosis is significantly reduced.

A Novel Immunosuppressant, Luteolin, Modulates Alloimmunity and Suppresses Murine Allograft Rejection.

An allograft is rejected in the absence of any immunosuppressive treatment because of vigorous alloimmunity and thus requires extensive immunosuppression for its survival. Although there are many conventional immunosuppressants for clinical use, it is necessary to seek alternatives to existing drugs, especially in case of transplant patients with complicated conditions. Luteolin, a natural ingredient, exists in many plants. It exhibits multiple biological and pharmacological effects, including anti-inflammatory properties. In particular, luteolin has been shown to upregulate CD4+CD25+ regulatory T cells (Tregs) in the context of airway inflammation. However, it remains unknown whether luteolin regulates alloimmune responses. In this study, we demonstrated that luteolin significantly prolonged murine skin allograft survival, ameliorated cellular infiltration, and downregulated proinflammatory cytokine gene expression in skin allografts. Furthermore, luteolin increased the percentage of CD4+Foxp3+ Tregs while reducing frequency of mature dendritic cells and CD44highCD62Llow effector CD4+/CD8+ T cells posttransplantation. It also suppressed the proliferation of T cells and their production of cytokines IFN-γ and IL-17A in vitro while increasing IL-10 level in the supernatant. Moreover, luteolin promoted CD4+Foxp3+ Treg generation from CD4+CD25- T cells in vitro. Depleting Tregs largely, although not totally, reversed luteolin-mediated extension of allograft survival. More importantly, luteolin inhibited AKT/mTOR signaling in T cells. Thus, for the first time, to our knowledge, we found that luteolin is an emerging immunosuppressant as an mTOR inhibitor in allotransplantation. This finding could be important for the suppression of human allograft rejection, although it remains to be determined whether luteolin has an advantage over other conventional immunosuppressants in suppression of allograft rejection.

Divergent Co-occurrence Patterns and Assembly Processes Structure the Abundant and Rare Bacterial Communities in a Salt Marsh Ecosystem.

Understanding how species interaction and assembly processes structure the abundant and rare bacterial biospheres in soils is crucial for predicting how biodiversity influences ecosystem functioning. Here, we profiled the bacterial communities across a salt marsh ecosystem gradient to investigate the co-occurrence patterns across taxa and the relative influence of ecological processes mediating the assembly of the abundant and rare biospheres in soil. Our results revealed abundant taxa to be ubiquitous across all sites, whereas the distributions of the rare taxa were relatively more site specific. The α-diversity indices and ß-diversity of rare subcommunities were significantly higher than those of the abundant subcommunities. Besides, both the taxonomic and functional composition of soil bacterial communities differed significantly between the two biospheres. Furthermore, the influence of stochasticity differed in each subcommunity. In particular, stochastic processes were relatively more important in constraining the assembly of rare taxa. Co-occurrence network analysis revealed that a few abundant taxa occupy central nodes within the networks, possibly indicating crucial roles as keystone taxa. Collectively, these findings suggest that abundant and rare bacterial biospheres have distinct distributions underpinned by a dynamic interplay of ecological processes and taxon co-occurrence patterns.IMPORTANCE Estuarine salt marshes are highly productive ecosystems subjected to regular disturbances by hydrodynamic exchange. However, little is known about how distinct assembly processes and co-occurrence of taxa influence the structure of the abundant and rare bacterial biospheres in these soil systems. This study aims at unravelling these intricacies by studying a typical estuarine salt marsh located in Hangzhou Bay, China. Our study provides important pieces of evidence on the diverse distribution of rare and abundant bacterial biospheres. We show that a few abundant taxa are central nodes in species co-occurrence, potentially playing important roles as keystone species in the system. In addition, we highlight a dynamic interplay of assembly processes structuring these two subcommunities.

Bacterial Community Assembly in a Typical Estuarine Marsh with Multiple Environmental Gradients.

Bacterial communities play essential roles in estuarine marsh ecosystems, but the interplay of ecological processes underlying their community assembly is poorly understood. Here, we studied the sediment bacterial communities along a linear gradient extending from the water-land junction toward a high marsh, using 16S rRNA gene amplicon sequencing. Bacterial community compositions differed significantly between sediment transects. Physicochemical properties, particularly sediment nutrient levels (i.e., total nitrogen [TN] and available phosphorus [AP]), as well as sediment physical structure and pH (P < 0.05), were strongly associated with the overall community variations. In addition, the topological properties of bacterial cooccurrence networks varied with distance to the water-land junction. Both node- and network-level topological features revealed that the bacterial network of sediments farthest from the junction was less intense in complexity and interactions than other sediments. Phylogenetic null modeling analysis showed a progressive transition from stochastic to deterministic community assembly for the water-land junction sites toward the emerging terrestrial system. Taken together, data from this study provide a detailed outline of the distribution pattern of the sediment bacterial community across an estuarine marsh and inform the mechanisms and processes mediating bacterial community assembly in marsh soils.IMPORTANCE Salt marshes represent highly dynamic ecosystems where the atmosphere, continents, and the ocean interact. The bacterial distribution in this ecosystem is of great ecological concern, as it provides essential functions acting on ecosystem services. However, ecological processes mediating bacterial assembly are poorly understood for salt marshes, especially the ones located in estuaries. In this study, the distribution and assembly of bacterial communities in an estuarine marsh located in south Hangzhou Bay were investigated. The results revealed an intricate interplay between stochastic and deterministic processes mediating the assembly of bacterial communities in the studied gradient system. Collectively, our findings illustrate the main drivers of community assembly, taking into consideration changes in sediment abiotic variables and potential biotic interactions. Thus, we offer new insights into estuarine bacterial communities and illustrate the interplay of ecological processes shaping the assembly of bacterial communities in estuarine marsh ecosystems.

MiR-145-5p inhibits proliferation and inflammatory responses of RMC through regulating AKT/GSK pathway by targeting CXCL16.

The main pathological characteristics of chronic glomerulonephritis (CGN) are diffuse mesangial cells proliferation and inflammatory responses. Our previous studies have confirmed that miR-145-5p was abnormally elevated in CGN rats, but its mechanism remains unclear. Therefore, this study aimed to elucidate the mechanism of miR-145-5p in regulation of renal mesangial cells proliferation and inflammatory responses. In vivo study, the cationic bovine serum albumin (C-BSA)-induced CGN rat model was established, and the content of miR-145-5p in renal was examined by qRT-PCR, meanwhile, we also determined the renal function and inflammatory infiltrate. In vitro, the cell proliferation rate, cell cycle and inflammatory changes of rat mesangial cells (RMCs) were measured. Our results suggested that miR-145-5p extended the G0-G1 phase, shortened S phase, inhibited cell proliferation and suppressed inflammatory responses in RMCs. Moreover, miR-145-5p inhibited CXCL16 protein expression through binding the 3'-UTR of CXCL16, suppressed AKT/GSK signaling pathway, and decreased expression of inflammation related mRNAs, such as IL-1α, IL-2, IL-6, and TNF-α mRNAs. Further, locking CXCL16 alleviated inflammatory reactions and down-regulated AKT/GSK pathway in RMCs. Above all, we concluded that miR-145-5p inhibited proliferation and inflammatory responses of RMCs through regulation of AKT/GSK pathway by targeting CXCL16.

Mangiferin Attenuates Murine Lupus Nephritis by Inducing CD4+Foxp3+ Regulatory T Cells via Suppression of mTOR Signaling.

BACKGROUND/AIMS: Lupus nephritis (LN) is an autoimmune glomerulonephritis that frequently develops secondary to systemic lupus erythematosus. Patients with LN require extensive treatments with global immunosuppressive agents. However, long-term treatment with conventional immunosuppressants may cause various side effects. Therefore, it's important to seek alternative drugs for treating LN. Here we aimed to investigate the immunoregulatory effects of mangiferin (MG), an ingredient that was originally extracted from natural herbs, including Mangifera Indica Linn. and Rhizoma Anemarrhenae. METHODS: FasL-deficient B6/ gld mice were used as a spontaneous LN model. The serum anti-dsDNA Ab and creatinine levels were analyzed via ELISA. Renal histology and immunopathology were determined using H&E and PAS staining, immunofluorescence (IgG and C3), and IHC staining (CD3 and a-SMA). Cytokine gene expression was measured by RT-PCR assays while effector T cells and Tregs were enumerated by flow analysis. Finally, the proliferation and apoptosis of T cells were measured by CFSE staining and flow analysis while their mTOR signaling was detected through Western blotting. RESULTS: We found that administration of MG ameliorated LN in lupus-prone B6/gld mice by reducing the urinary protein and serum creatinine levels, diminishing T cell infiltration in kidneys and improving renal immunopathology. MG also significantly lowered the percentages of CD44highCD62Llow effector T cells in B6/gld mice. Importantly, treatments with MG augmented CD4+FoxP3+ Treg frequencies in spleens, lymph nodes and kidneys of B6/gld mice. It also induced CD4+FoxP3+ Tregs from CD3+ T cells in vitro and promoted Treg proliferation. Furthermore, it inhibited CD3+ T cell proliferation in vitro and suppressed their phosphorylation of mTOR and its downstream P70S6K. However, MG did not promote T cell apoptosis, implying that it is not cytotoxic. Depletion of CD4+CD25+FoxP3+ Tregs in B6/gld mice abrogated its therapeutic effects on LN. CONCLUSION: MG exerts a novel therapeutic effect on murine LN via upregulating CD4+FoxP3+ Tregs, downregulating mTOR/p70S6K pathway and improving renal immunopathology. It may be useful for treating LN in clinic.

Methotrexate and electrostimulation cooperate to alleviate the relapse of psoriasiform skin inflammation by suppressing memory T cells.

Methotrexate (MTX) is an immunosuppressant used to treat autoimmune diseases, including psoriasis. However, like other immunosuppressants, MTX alone does not prevent their recurrence. Electrostimulation (ES) has been utilized to treat some inflammatory disorders without any major side-effect. But it remains unknown if ES alone, or together with MTX, ameliorates autoimmune disease relapse: a sticky medical problem. In particular, the mechanisms underlying ES action remain unclear. The objective of this study was to determine an impact of ES and/or MTX on psoriasis relapse and their potential cooperation. We found that regional ES, but not MTX, ameliorated psoriasiform skin inflammation recurrence. Interestingly, treatment with both MTX and ES further prevented psoriasis recurrence compared to ES alone. Moreover, ES downregulated potassium channel Kv1.3 on T-cells and reduced CD4+/CD8+ effector memory (TEM) and CD8+ skin-resident memory T (TRM) cells, while ES plus MTX further decreased CD8+ TEM/TRM cells compared to ES alone. However, ES failed to further attenuate psoriasis recurrence or suppress T cell memory in Kv1.3-deficient mice, whereas lack of Kv1.3 itself ameliorated psoriasis relapse by shrinking T cell memory pool. Importantly, ES moderately inhibited T-cell proliferation in vitro. ES also reduced human CD8+ TRM cells and attenuated human skin lesions in humanized mice grafted with lesional skin from patients with recurrent psoriasis, with an enhanced efficacy in mice treated with both ES and MTX. Thus, ES and MTX cooperated to prevent psoriasis relapse by reducing T-cell memory via targeting potassium channel Kv1.3. Our studies may be implicated for treating human psoriasis.

Electroacupuncture and methotrexate cooperate to ameliorate psoriasiform skin inflammation by regulating the immune balance of Th17/Treg.

Psoriasis is an autoinflammatory dermatosis, while methotrexate (MTX) is an immunosuppressant used to treat psoriasis. However, conventional immunosuppressants may cause various side effects. Acupuncture has potential benefits in treating psoriasis based on its anti-inflammatory effects. However, the immune mechanisms underlying its effects remain unclear. In this study, imiquimod-induced psoriatic mice were used to investigate the effects and mechanisms of electroacupuncture (EA) and, in particular, its joint treatment with MTX. We found that treatment with either EA or MTX ameliorated psoriasiform skin lesions, improved skin pathology and reduced proinflammatory cytokines in the skin, while joint treatment with both EA and MTX further alleviated the skin lesions and inflammation compared to either one alone. Moreover, percentages of CD4+ IL-17A+ Th17 cells in the skin and lymph nodes were decreased by EA or MTX and further lowered by combined EA+MTX treatment. Similarly, EA or MTX also reduced their RORγt expression. On the contrary, CD4+ FoxP3+ Treg frequency in psoriatic mice was augmented by EA or MTX and further increased by the joint treatment. However, depleting Tregs mostly reversed the therapeutic effects of EA or EA plus MTX. Additionally, the phosphorylated NF-κB (p65) expression was suppressed by treatment with EA, MTX or better with EA+MTX. Meanwhile, the anti-inflammatory effects of EA plus MTX were offset by an NF-κB agonist. Thus, this study has revealed that EA cooperates with MTX to balance Th17/Treg responses and to ameliorate psoriasiform skin inflammation through suppressing NF-κB activation. Our findings may be implicated for treating human psoriasis.

The TOPK Inhibitor HI-TOPK-032 Enhances CAR T-cell Therapy of Hepatocellular Carcinoma by Upregulating Memory T Cells.

Chimeric antigen receptor (CAR) T cells are emerging as an effective antitumoral therapy. However, their therapeutic effects on solid tumors are limited because of their short survival time and the immunosuppressive tumor microenvironment. Memory T cells respond more vigorously and persist longer than their naïve/effector counterparts. Therefore, promoting CAR T-cell development into memory T cells could further enhance their antitumoral effects. HI-TOPK-032 is a T-LAK cell-originated protein kinase (TOPK)-specific inhibitor that moderately represses some types of tumors. However, it is unknown whether HI-TOPK-032 works on hepatocellular carcinoma (HCC) and whether it impacts antitumoral immunity. Using both subcutaneous and orthotopic xenograft tumor models of two human HCC cell lines, Huh-7 and HepG2, we found that HI-TOPK-032 significantly improved proliferation/persistence of CD8+ CAR T cells, as evidenced by an increase in CAR T-cell counts or frequency of Ki-67+CD8+ cells and a decrease in PD-1+LAG-3+TIM-3+CD8+ CAR T cells in vivo. Although HI-TOPK-032 did not significantly suppress HCC growth, it enhanced the capacity of CAR T cells to inhibit tumor growth. Moreover, HI-TOPK-032 augmented central memory CD8+ T cell (TCM) frequency while increasing eomesodermin expression in CD8+ CAR T cells in tumor-bearing mice. Moreover, it augmented CD8+ CAR TCM cells in vitro and reduced their expression of immune checkpoint molecules. Finally, HI-TOPK-032 inhibited mTOR activation in CAR T cells in vitro and in tumors, whereas overactivation of mTOR reversed the effects of HI-TOPK-032 on CD8+ TCM cells and tumor growth. Thus, our studies have revealed mechanisms underlying the antitumoral effects of HI-TOPK-032 while advancing CAR T-cell immunotherapy.

Smaller microorganisms outcompete larger ones in resistance and functional effects under disturbed agricultural ecosystems.

Body size is a key ecological trait of soil microorganisms related to their adaptation to environmental changes. In this study, we reveal that the smaller microorganisms show stronger community resistance than larger organisms in both maize and rice soil. Compared with larger organisms, smaller microorganisms have higher diversity and broader niche breadth to deploy survival strategies, because of which they are less affected by environmental selection and thus survive in complex and various kinds of environments. In addition, the strong correlation between smaller microorganisms and ecosystem functions reflects their greater metabolic flexibility and illustrates their significant roles in adaptation to continuously changing environments. This research highlights the importance of body size in maintaining stability of the soil microbiome and forecasting agroecosystem dynamics under environmental disturbances.

Zhen-Wu-Tang ameliorates lupus nephritis by diminishing renal tissue-resident memory CD8+ T cells via suppressing IL-15/STAT3 pathway.

Zhen-Wu-Tang (ZWT), a conventional herbal mixture, has been recommended for treating lupus nephritis (LN) in clinic. However, its mechanisms of action remain unknown. Here we aimed to define the immunological mechanisms underlying the effects of ZWT on LN and to determine whether it affects renal tissue-resident memory T (TRM) cells. Murine LN was induced by a single injection of pristane, while in vitro TRM cells differentiated with IL-15/TGF-ß. We found that ZWT or mycophenolate mofetil treatment significantly ameliorated kidney injury in LN mice by decreasing 24-h urine protein, Scr and anti-dsDNA Ab. ZWT also improved renal pathology and decreased IgG and C3 depositions. In addition, ZWT down-regulated renal Desmin expression. Moreover, it lowered the numbers of CD8+ TRM cells in kidney of mice with LN while decreasing their expression of TNF-α and IFN-γ. Consistent with in vivo results, ZWT-containing serum inhibited TRM cell differentiation induced by IL-15/TGF-ß in vitro. Mechanistically, it suppressed phosphorylation of STAT3 and CD122 （IL2/IL-15Rß）expression in CD8+ TRM cells. Importantly, ZWT reduced the number of total F4/80+CD11b+ and CD86+, but not CD206+, macrophages in the kidney of LN mice. Interestingly, ZWT suppressed IL-15 protein expression in macrophages in vivo and in vitro. Thus, we have provided the first evidence that ZWT decoction can be used to improve the outcome of LN by reducing CD8+ TRM cells via inhibition of IL-15/IL-15R /STAT3 signaling.

Land conversion to agriculture induces taxonomic homogenization of soil microbial communities globally.

Agriculture contributes to a decline in local species diversity and to above- and below-ground biotic homogenization. Here, we conduct a continental survey using 1185 soil samples and compare microbial communities from natural ecosystems (forest, grassland, and wetland) with converted agricultural land. We combine our continental survey results with a global meta-analysis of available sequencing data that cover more than 2400 samples across six continents. Our combined results demonstrate that land conversion to agricultural land results in taxonomic and functional homogenization of soil bacteria, mainly driven by the increase in the geographic ranges of taxa in croplands. We find that 20% of phylotypes are decreased and 23% are increased by land conversion, with croplands enriched in Chloroflexi, Gemmatimonadota, Planctomycetota, Myxcoccota and Latescibacterota. Although there is no significant difference in functional composition between natural ecosystems and agricultural land, functional genes involved in nitrogen fixation, phosphorus mineralization and transportation are depleted in cropland. Our results provide a global insight into the consequences of land-use change on soil microbial taxonomic and functional diversity.

Oligotrophic microbes are recruited to resist multiple global change factors in agricultural subsoils.

An increasing number of anthropogenic pressures can have negative effects on biodiversity and ecosystem functioning. However, our understanding of how soil microbial communities and functions in response to multiple global change factors (GCFs) is still incomplete, particularly in less frequently disturbed subsoils. In this study, we examined the impact of different levels of GCFs (0-9) on soil functions and bacterial communities in both topsoils (0-20 cm) and subsoils (20-40 cm) of an agricultural ecosystem, and characterized the intrinsic factors influencing community resistance based on microbial life history strategy. Our experimental results showed a decline in soil multifunctionality, bacterial diversity, and community resistance as the number of GCFs increased, with a more drastic reduction in community resistance of subsoils. Specifically, we observed a significantly positive relationship between the oligotroph/copiotroph ratio and community resistance in subsoils, which was also verified by the negative correlation between 16S rRNA operon (rrn) copy number and community resistance. Structural equation modeling further revealed the direct effects of community resistance in promoting the ecosystem functioning, regardless of top- and subsoils. Therefore, these results suggested that subsoils may recruit more oligotrophic microbes to enhance their originally weaker community resistance under multiple GCFs, which was essential for maintaining sustainable agroecological functions and services. Overall, our study represents a significant advance in linking microbial life history strategy to the resistance of belowground microbial community and functionality.