Chimeric antigen receptors enable superior control of HIV replication by rapidly killing infected cells.

Engineered T cells hold great promise to become part of an effective HIV cure strategy, but it is currently unclear how best to redirect T cells to target HIV. To gain insight, we generated engineered T cells using lentiviral vectors encoding one of three distinct HIV-specific T cell receptors (TCRs) or a previously optimized HIV-targeting chimeric antigen receptor (CAR) and compared their functional capabilities. All engineered T cells had robust, antigen-specific polyfunctional cytokine profiles when mixed with artificial antigen-presenting cells. However, only the CAR T cells could potently control HIV replication. TCR affinity enhancement did not augment HIV control but did allow TCR T cells to recognize common HIV escape variants. Interestingly, either altering Nef activity or adding additional target epitopes into the HIV genome bolstered TCR T cell anti-HIV activity, but CAR T cells remained superior in their ability to control HIV replication. To better understand why CAR T cells control HIV replication better than TCR T cells, we performed a time course to determine when HIV-specific T cells were first able to activate Caspase 3 in HIV-infected targets. We demonstrated that CAR T cells recognized and killed HIV-infected targets more rapidly than TCR T cells, which correlates with their ability to control HIV replication. These studies suggest that the speed of target recognition and killing is a key determinant of whether engineered T cell therapies will be effective against infectious diseases.

Celastrol-Induced Nur77 Interaction with TRAF2 Alleviates Inflammation by Promoting Mitochondrial Ubiquitination and Autophagy.

Mitochondria play an integral role in cell death, autophagy, immunity, and inflammation. We previously showed that Nur77, an orphan nuclear receptor, induces apoptosis by targeting mitochondria. Here, we report that celastrol, a potent anti-inflammatory pentacyclic triterpene, binds Nur77 to inhibit inflammation and induce autophagy in a Nur77-dependent manner. Celastrol promotes Nur77 translocation from the nucleus to mitochondria, where it interacts with tumor necrosis factor receptor-associated factor 2 (TRAF2), a scaffold protein and E3 ubiquitin ligase important for inflammatory signaling. The interaction is mediated by an LxxLL motif in TRAF2 and results not only in the inhibition of TRAF2 ubiquitination but also in Lys63-linked Nur77 ubiquitination. Under inflammatory conditions, ubiquitinated Nur77 resides at mitochondria, rendering them sensitive to autophagy, an event involving Nur77 interaction with p62/SQSTM1. Together, our results identify Nur77 as a critical intracellular target for celastrol and unravel a mechanism of Nur77-dependent clearance of inflamed mitochondria to alleviate inflammation.

Alteration in neural oscillatory activity and phase-amplitude coupling after sleep deprivation: Evidence for impairment and compensation effects.

Insufficient sleep can significantly affect vigilance and increase slow-wave electroencephalographic power as homeostatic sleep pressure accumulates. Phase-amplitude coupling is involved in regulating the spatiotemporal integration of physiological processes. This study aimed to examine the functional associations of resting-state electroencephalographic power and delta/theta-gamma phase-amplitude coupling from the prefrontal cortex (PFC) to posterior regions with vigilance performance after sleep deprivation. Forty-six healthy adults underwent 24-hr sleep deprivation with resting-state electroencephalographic recordings, and vigilant attention was measured using the Psychomotor Vigilance Task. Power spectral and phase-amplitude coupling analyses were conducted, and correlation analysis was utilized to reveal the relationship between electroencephalographic patterns and changes in vigilance resulting from sleep deprivation. Sleep deprivation significantly declined vigilance performance, accompanied by increased resting-state electroencephalographic power in all bands and delta/theta-gamma phase-amplitude coupling. The increased theta activity in centro-parieto-occipital areas significantly correlated with decreased mean and slowest response speed. Conversely, the increased delta-low gamma and theta-high gamma phase-amplitude couplings negatively correlated with the deceleration of the fastest Psychomotor Vigilance Task reaction times. These findings suggest that sleep deprivation affects vigilance by altering electroencephalographic spectral power and information communication across frequency bands in different brain regions. The distinct effects of increased theta power and delta/theta-gamma phase-amplitude coupling might reflect the impairment and compensation of sleep deprivation on vigilance performance, respectively.

Reversible Acid-Base Long Persistent Luminescence Switch Based on Amino-Functionalized Metal-Organic Frameworks.

Metal-organic frameworks (MOFs) with long persistent luminescence (LPL) have attracted extensive research attention from researchers due to their potential applications in information encryption, anticounterfeiting technology, and security logic. In contrast to short-lived fluorescent materials, LPL materials offer a visible response that can be easily distinguished by the naked eye, thereby facilitating a much clearer visualization. However, there are few reports on functional LPL MOF materials as probes. In this article, two amino-functional LPL MOFs (VB4-2D and VB4-1D) were synthesized. They both exhibited adjustable fluorescence and phosphorescence from blue to green and from cyan to green, respectively. Notably, the MOFs emitted bright and adjustable LPL upon the removal of the different radiation sources. The basic amino functional groups in the MOFs exhibited acid and ammonia sensitivity, and fluorescence and phosphorescence emission intensities can be burst and restored in two atmospheres, respectively, which can be cycled multiple times. Furthermore, LPL intensity undergoes switching between two different conditions as well, which can be visually discerned by the naked eye, enabling visual sensing of volatiles by LPL. This combination of photoluminescence and the visual LPL switching behavior of acids and bases in functional MOFs may provide an effective avenue for stimulus response, anticounterfeiting, and encryption applications.

A wide-bandgap graphene-like structure C6BN with ultra-low dielectric constant.

This study introduces a new wide-bandgap graphene-like structure, denoted as C6BN, achieved by incorporating an eight-electron BN pair, substantially modifying its electronic properties. Utilizing extensive density functional calculations, we comprehensively analyzed the stability, electronic structure, mechanical properties, and optical-electrical characteristics of C6BN. Our investigations reveal the material's exceptional thermodynamic, mechanical, and dynamic stability. Notably, the calculated wide bandgap of 2.81 eV in C6BN, supported by analyses of energy levels, band structures, and density of states, positions it as a promising two-dimensional wide-bandgap semiconductor. Additionally, C6BN exhibits isotropic mechanical features, highlighting its inherent flexibility. Remarkably, our calculations indicate an ultra-low dielectric constant (k = 1.67) for C6BN, surpassing that of well-established third-generation semiconductors. Further exploration into the thermoelectric properties of C6BN demonstrates its promising performance, as evidenced by calculations of thermal conductivity (κ), power factor (P), and Seebeck coefficient (S). In summary, our findings underscore the significant potential of the proposed C6BN structure as a flexible two-dimensional material poised to drive future advancements in electronic and energy-related technologies.

Insight into the interaction of host-guest structures for pyrrole-based metal compounds and C70.

This study focuses on the recognition and isolation of fullerenes, which are crucial for further exploration of their physical and chemical properties. Our goal is to investigate the potential recognition of the D5h-C70 fullerene using crown-shaped metal compositions through density functional theory calculations. We assess the effectiveness of fullerene C70 recognition by studying the binding energy. Additionally, various analyses were conducted, including natural bond order charge analysis and reduced density gradient analysis, to understand the interaction mechanism between the host and guest molecules. These investigations provide valuable insights into the nature of the interaction and the stability of the host-guest system. To facilitate the release of the fullerene guest molecule, the vis-NIR spectra were simulated for the host-guest structures. This analysis offers guidance on the specific wavelengths that can be utilized to release the fullerene guest from the host-guest structures. Overall, this work proposes a new strategy for the effective recognition of various fullerene molecules and their subsequent release from host-guest systems. These findings could potentially be applied in assemblies involving fullerenes, advancing their practical applications.

Identification of seven hypoxia-related genes signature and risk score models for predicting prognosis for ovarian cancer.

Ovarian cancer (OC) is the most common malignant cancer in the female reproductive system. Hypoxia is an important part of tumor immune microenvironment (TIME), which is closely related to cancer progression and could significantly affect cancer metastasis and prognosis. However, the relationship between hypoxia and OC remained unclear. OCs were molecularly subtyped by consensus clustering analysis based on the expression characteristics of hypoxia-related genes. Kaplan-Meier (KM) survival was used to determine survival characteristics across subtypes. Immune infiltration analysis was performed by using Estimation of Stromal and Immune cells in Malignant Tumors using Expression data (ESTIMATE) and microenvironment cell populations-counter (MCP-Counter). Differential expression analysis was performed by using limma package. Next, univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were used to build a hypoxia-related risk score model (HYRS). Mutational analysis was applied to determine genomic variation across the HYRS groups. The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to compare the effectiveness of HYRS in immunotherapy prediction. We divided OC samples into two molecular subtypes (C1 and C2 subtypes) based on the expression signature of hypoxia genes. Compared with C1 subtype, there was a larger proportion of poor prognosis genotypes in the C2 subtype. And most immune cells scored higher in the C2 subtype. Next, we obtained a HYRS based on 7 genes. High HYRS group had a higher gene mutation rate, such as TP53. Moreover, HYRS performed better than TIDE in predicting immunotherapy effect. Combined with clinicopathological features, the nomogram showed that HYRS had the greatest impact on survival prediction and a strong robustness.

Long-term effects of Pfizer-BioNTech COVID-19 vaccinations on platelets.

There is a global concern about the safety of COVID-19 vaccines associated with platelet function. However, their long-term effects on overall platelet activity remain poorly understood. Here we address this problem by image-based single-cell profiling and temporal monitoring of circulating platelet aggregates in the blood of healthy human subjects, before and after they received multiple Pfizer-BioNTech (BNT162b2) vaccine doses over a time span of nearly 1 year. Results show no significant or persisting platelet aggregation trends following the vaccine doses, indicating that any effects of vaccinations on platelet turnover, platelet activation, platelet aggregation, and platelet-leukocyte interaction was insignificant.

Real-time intelligent classification of COVID-19 and thrombosis via massive image-based analysis of platelet aggregates.

Microvascular thrombosis is a typical symptom of COVID-19 and shows similarities to thrombosis. Using a microfluidic imaging flow cytometer, we measured the blood of 181 COVID-19 samples and 101 non-COVID-19 thrombosis samples, resulting in a total of 6.3 million bright-field images. We trained a convolutional neural network to distinguish single platelets, platelet aggregates, and white blood cells and performed classical image analysis for each subpopulation individually. Based on derived single-cell features for each population, we trained machine learning models for classification between COVID-19 and non-COVID-19 thrombosis, resulting in a patient testing accuracy of 75%. This result indicates that platelet formation differs between COVID-19 and non-COVID-19 thrombosis. All analysis steps were optimized for efficiency and implemented in an easy-to-use plugin for the image viewer napari, allowing the entire analysis to be performed within seconds on mid-range computers, which could be used for real-time diagnosis.

LINC01094 accelerates the metastasis of hepatocellular carcinoma via the miR-26b-3p/MDM4 axis.

To elucidate the role of LINC01094 in accelerating the metastatic potential of hepatocellular carcinoma (HCC) via the miR-26b-3p/MDM4 axis. Differential levels of LINC01094 in clinical samples of HCC and their influence on pathological indicators of recruited HCC patients were detected. Hep3B and SK-HEP-1 cell lines with stable knockdown of LINC01094 were generated by shRNA transfection, followed by detection of migration and invasion by Transwell and wound healing assay. Bioinformatic analysis, dual-luciferase reporter assay and rescue experiments were conducted to assess the interaction between LINC01094 and the miR-26b-3p/MDM4 axis. LINC01094 was upregulated in clinical samples of HCC and its level was linked to the incidences of lymphatic and distant metastasis of HCC patients. Knockdown of LINC01094 weakened migratory and invasive abilities in Hep3B and SK-HEP-1 cells. MiR-26b-3p was the downstream target of LINC01094, which was lowly expressed in HCC tissues and negatively correlated to the LINC01094 level. Moreover, MDM4 was the target gene of miR-26b-3p, which was highly expressed in HCC tissues and negatively correlated to the miR-26b-3p level. Rescue experiments showed that the knockdown of miR-26b-3p could reverse the inhibited metastasis in Hep3B and SK-HEP-1 cells with a stable knockdown of LINC01094. LINC01094 accelerates the metastasis of HCC via the miR-26b-3p/MDM4 axis, which is a potential biomarker and therapeutic target to be utilized in clinical practice.

Spatial distribution patterns across multiple microbial taxonomic groups.

Even in the vertical dimension, soil bacterial communities are spatially distributed in a distance-decay relationship (DDR). However, whether this pattern is universal among all soil microbial taxonomic groups, and how body size influences this distribution, remains elusive. Our study consisted of obtaining 140 soil samples from two adjacent ecosystems in the Yellow River Delta (YRD), both nontidal and tidal, and measuring the DDR between topsoil and subsoil for bacteria, archaea, fungi and protists (rhizaria). Our results showed that the entire community generally fitted the DDR patterns (P < 0.001), this was also true at the kingdom level (P < 0.001, with the exception of the fungal community), and for most individual phyla (47/75) in both ecosystems and with soil depth. Meanwhile, these results presented a general trend that the community turnover rate of nontidal soils was higher than tidal soils (P < 0.05), and that the rate of topsoil was also higher than that of subsoil (P < 0.05). Additionally, microbial spatial turnover rates displayed a negative relationship with body sizes in nontidal topsoil (R2 = 0.29, P = 0.009), suggesting that the smaller the body size of microorganisms, the stronger the spatial limitation was in this environment. However, in tidal soils, the body size effect was negligible, probably owing to the water's fluidity. Moreover, community assembly was judged to be deterministic, and heterogeneous selection played a dominant role in the different environments. Specifically, the spatial distance was much more influential, while the soil salinity in these ecosystems was the major environmental factor in selecting the distributions of microbial communities. Overall, this study revealed that microbial community compositions at different taxonomic levels followed relatively consistent distribution patterns and mechanisms in this coastal area.

Bioinspired polydopamine nanoparticles as efficient antioxidative and anti-inflammatory enhancers against UV-induced skin damage.

Excessive and prolonged ultraviolet radiation (UVR) exposure causes photodamage, photoaging, and photocarcinogenesis in human skin. Therefore, safe and effective sun protection is one of the most fundamental requirements. Living organisms tend to evolve various natural photoprotective mechanisms to avoid photodamage. Among them, melanin is the main functional component of the photoprotective system of human skin. Polydopamine (PDA) is synthesized as a mimic of natural melanin, however, its photoprotective efficiency and mechanism in protecting against skin damage and photoaging remain unclear. In this study, the novel sunscreen products based on melanin-inspired PDA nanoparticles (NPs) are rationally designed and prepared. We validate that PDA NPs sunscreen exhibits superior effects on photoprotection, which is achieved by the obstruction of epidermal hyperplasia, protection of the skin barrier, and resolution of inflammation. In addition, we find that PDA NPs are efficiently intake by keratinocytes, exhibiting robust ROS scavenging and DNA protection ability with minimal cytotoxicity. Intriguingly, PDA sunscreen has an influence on maintaining homeostasis of the dermis, displaying an anti-photoaging property. Taken together, the biocompatibility and full photoprotective properties of PDA sunscreen display superior performance to those of commercial sunscreen. This work provides new insights into the development of a melanin-mimicking material for sunscreens.

Selective reactivation of STING signaling to target Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a lethal skin cancer that metastasizes rapidly. Few effective treatments are available for patients with metastatic MCC. Poor intratumoral T cell infiltration and activation are major barriers that prevent MCC eradication by the immune system. However, the mechanisms that drive the immunologically restrictive tumor microenvironment remain poorly understood. In this study, we discovered that the innate immune regulator stimulator of IFN genes (STING) is completely silenced in MCCs. To reactivate STING in MCC, we developed an application of a human STING mutant, STINGS162A/G230I/Q266I, which we found to be readily stimulated by a mouse STING agonist, DMXAA. This STING molecule was efficiently delivered to MCC cells via an AAV vector. Introducing STINGS162A/G230I/Q266I expression and stimulating its activity by DMXAA in MCC cells reactivates their antitumor inflammatory cytokine/chemokine production. In response to MCC cells with restored STING, cocultured T cells expressing MCPyV-specific T cell receptors (TCRs) show increased cytokine production, migration toward tumor cells, and tumor cell killing. Our study therefore suggests that STING deficiency contributes to the immune suppressive nature of MCCs. More importantly, DMXAA stimulation of STINGS162A/G230I/Q266I causes robust cell death in MCCs as well as several other STING-silenced cancers. Because tumor antigens and DNA released by dying cancer cells have the potential to amplify innate immune response and activate antitumor adaptive responses, our finding indicates that targeted delivery and activation of STINGS162A/G230I/Q266I in tumor cells holds great therapeutic promise for the treatment of MCC and many other STING-deficient cancers.

Thermo-alkaline pretreatment of excess sludge: Effects of temperature on volatile fatty acids accumulation and microbial community.

In order to explore the role of thermal-alkaline pretreatment temperatures (TAPT) in sludge fermentation and the microbial characteristics, five groups (100, 120, 140, 160 °C and control group) were set up and the results showed that the increasing TAPT promoted the dissolution of soluble chemical oxygen demand (SCOD) and VFAs, but had slight influence on the release of NH4+-N and PO43--P. What's more, when it was 120 °C, the SCOD dissolution was comparable to that at 160 °C. Overall, 120 °C was the optimal condition, corresponding to the fact that the maximum release of SCOD was 8788.74 mg/L (2.63 times of the control group), the maximum dissolution of VFAs was 4596 mg/L (about 1.28 times of the control group). The trend of C/N was not significant. High-throughput sequencing showed that Firmicutes and Actinobacteriota were enriched with the temperature increasing, while Proteobacteria and Chloroflexi did not change significantly. Firmicutes was in a stable dominant position. Temperature conditions brought about significant changes in microbial interspecific interaction. Carbohydrate and amino acids had the highest metabolic abundance, especially at 120 °C group. The change rule of amino acid metabolism was similar to that of lipid metabolism, and the abundance of energy metabolism gradually increased with temperature. The protein metabolism was greatly affected by temperature. This study revealed the effect of microbial mechanism of TAPT on the sludge acid production efficiency.

ThePreparation of Electrospun PVDF/TBAC Multimorphology Nanofiber Membrane and Its Application in Direct Contact Membrane Distillation.

Microporous membrane with a hydrophobic surface, high porosity, and narrow pore size distribution is the ideal membrane distillation (MD) membrane. The electrospun membranes for MD are a new type and effective way to seawater desalination. Herein, a novel polyvinylidene fluoride (PVDF)/tetrabutylammonium chloride (TBAC) electrospun nanofiber membrane (ENMs) fabricated apply to for direct contact membrane distillation (DCMD). Combine with the spinning condition, the characteristic and content of TBAC significant effect on the multimorphology structure of nanofiber. Therefore, the porous structure and morphology of PVDF/TBAC ENMs can be well-designed by optimizing relative humidity and TBAC concentration in spinning process, three different structure nanofiber membranes are obtained. Lab-scale setup is used to test membrane separation performance. The result indicates that the ultrafine ENMs with 0.025 mol L-1 TBAC presented a steady water flux of about 20.6 L m-2 h-1 and a high-efficiency salt rejection rate of over 99%. PVDF/TBAC ENMs are expected to provide a solution for development of efficient water treatment membrane.

Discovering novel drug-supplement interactions using SuppKG generated from the biomedical literature.

OBJECTIVE: Develop a novel methodology to create a comprehensive knowledge graph (SuppKG) to represent a domain with limited coverage in the Unified Medical Language System (UMLS), specifically dietary supplement (DS) information for discovering drug-supplement interactions (DSI), by leveraging biomedical natural language processing (NLP) technologies and a DS domain terminology. MATERIALS AND METHODS: We created SemRepDS (an extension of an NLP tool, SemRep), capable of extracting semantic relations from abstracts by leveraging a DS-specific terminology (iDISK) containing 28,884 DS terms not found in the UMLS. PubMed abstracts were processed using SemRepDS to generate semantic relations, which were then filtered using a PubMedBERT model to remove incorrect relations before generating SuppKG. Two discovery pathways were applied to SuppKG to identify potential DSIs, which are then compared with an existing DSI database and also evaluated by medical professionals for mechanistic plausibility. RESULTS: SemRepDS returned 158.5% more DS entities and 206.9% more DS relations than SemRep. The fine-tuned PubMedBERT model (significantly outperformed other machine learning and BERT models) obtained an F1 score of 0.8605 and removed 43.86% of semantic relations, improving the precision of the relations by 26.4% over pre-filtering. SuppKG consists of 56,635 nodes and 595,222 directed edges with 2,928 DS-specific nodes and 164,738 edges. Manual review of findings identified 182 of 250 (72.8%) proposed DS-Gene-Drug and 77 of 100 (77%) proposed DS-Gene1-Function-Gene2-Drug pathways to be mechanistically plausible. DISCUSSION: With added DS terminology to the UMLS, SemRepDS has the capability to find more DS-specific semantic relationships from PubMed than SemRep. The utility of the resulting SuppKG was demonstrated using discovery patterns to find novel DSIs. CONCLUSION: For the domain with limited coverage in the traditional terminology (e.g., UMLS), we demonstrated an approach to leverage domain terminology and improve existing NLP tools to generate a more comprehensive knowledge graph for the downstream task. Even this study focuses on DSI, the method may be adapted to other domains.

Chemical Constituents of the Deep-Sea-Derived Penicillium citreonigrum MCCC 3A00169 and Their Antiproliferative Effects.

Six new citreoviridins (citreoviridins J-O, 1-6) and twenty-two known compounds (7-28) were isolated from the deep-sea-derived Penicillium citreonigrum MCCC 3A00169. The structures of the new compounds were determined by spectroscopic methods, including the HRESIMS, NMR, ECD calculations, and dimolybdenum tetraacetate-induced CD (ICD) experiments. Citreoviridins J-O (1-6) are diastereomers of 6,7-epoxycitreoviridin with different chiral centers at C-2-C-7. Pyrenocine A (7), terrein (14), and citreoviridin (20) significantly induced apoptosis for HeLa cells with IC50 values of 5.4 µM, 11.3 µM, and 0.7 µM, respectively. To be specific, pyrenocine A could induce S phase arrest, while terrein and citreoviridin could obviously induce G0-G1 phase arrest. Citreoviridin could inhibit mTOR activity in HeLa cells.

Effect of Nickel Ions on the Physiological and Transcriptional Responses to Carbon and Nitrogen Metabolism in Tomato Roots under Low Nitrogen Levels.

Nickel (Ni) is an essential trace element for plant growth and a component of the plant body that has many different functions in plants. Although it has been confirmed that nickel ions (Ni2+) havea certain regulatory effect on nitrogen (N) metabolism, there are not enough data to prove whether exogenous Ni2+ can increase the carbon (C) and N metabolism in the roots of tomato seedlingsunder low-nitrogen (LN) conditions. Therefore, through the present experiment, we revealed the key mechanism of Ni2+-mediated tomato root tolerance to LN levels. Tomato plants were cultured at two different N levels (7.66 and 0.383 mmol L-1) and two different Ni2+ levels (0 and 0.1 mg L-1 NiSO4 6H2O) under hydroponic conditions. After nine days, we collected roots for physiological, biochemical, and transcriptome sequencing analyses and found that the activities of N assimilation-related enzymes decreased at LN levels. In contrast, Ni2+ significantly increased the activities of N assimilation-related enzymes and increased the contents of nitrate (NO3-), ammonium (NH4+), and total amino acids. Through root transcriptomic analysis, 3738 differentially expressed genes (DEGs) were identified. DEGs related to C and N metabolism were downregulated after LN application. However, after Ni2+ treatment, PK, PDHB, GAPDH, NR, NiR, GS, GOGAT, and other DEGs related to C and N metabolism were significantly upregulated. In conclusion, our results suggest that Ni2+ can regulate the C and N metabolism pathways in tomato roots to alleviate the impact of LN levels.

Challenges and Opportunities of Using Adoptive T-Cell Therapy as Part of an HIV Cure Strategy.

HIV-infected individuals successfully controlling viral replication via antiretroviral therapy often have a compromised HIV-specific T-cell immune response due to the lack of CD4 T-cell help, viral escape, T-cell exhaustion, and reduction in numbers due to the withdrawal of cognate antigen. A successful HIV cure strategy will likely involve a durable and potent police force that can effectively recognize and eliminate remaining virus that may emerge decades after an individual undergoes an HIV cure regimen. T cells are ideally suited to serve in this role, but given the state of the HIV-specific T-cell response, it is unclear how to best restore HIV-specific T-cell activity prior initiation of a HIV cure strategy. Here, we review several strategies of generating HIV-specific T cells ex vivo that are currently being tested in the clinic and discuss how infused T cells can be part of an HIV cure strategy.

Warming reshaped the microbial hierarchical interactions.

Global warming may alter microbially mediated ecosystem functions through reshaping of microbial diversity and modified microbial interactions. Here, we examined the effects of 5-year experimental warming on different microbial hierarchical groups in a coastal nontidal soil ecosystem, including prokaryotes (i.e., bacteria and archaea), fungi, and Cercozoa, which is a widespread phylum of protists. Warming significantly altered the diversity and structure of prokaryotic and fungal communities in soil and additionally decreased the complexity of the prokaryotic network and fragmented the cercozoan network. By using the Inter-Domain Ecological Network approach, the cross-trophic interactions among prokaryotes, fungi, and Cercozoa were further investigated. Under warming, cercozoan-prokaryotic and fungal-prokaryotic bipartite networks were simplified, whereas the cercozoan-fungal network became slightly more complex. Despite simplification of the fungal-prokaryotic network, the strengthened synergistic interactions between saprotrophic fungi and certain prokaryotic groups, such as the Bacteroidetes, retained these phyla within the network under warming. In addition, the interactions within the fungal community were quite stable under warming conditions, which stabilized the interactions between fungi and prokaryotes or protists. Additionally, we found the microbial hierarchical interactions were affected by environmental stress (i.e., salinity and pH) and soil nutrients. Interestingly, the relevant microbial groups could respond to different soil properties under ambient conditions, whereas under warming these two groups tended to respond to similar soil properties, suggesting network hub species responded to certain environmental changes related to warming, and then transferred this response to their partners through trophic interactions. Finally, warming strengthened the network modules' negative association with soil organic matters through some fungal hub species, which might trigger soil carbon loss in this ecosystem. Our study provides new insights into the response and feedback of microbial hierarchical interactions under warming scenario.