Neoadjuvant immunotherapy based on PD-1/L1 inhibitors for gastrointestinal tumors: a review of the rationale and clinical advances.

The landscape of current tumor treatment has been revolutionized by the advent of immunotherapy based on PD-1/PD-L1 inhibitors. Leveraging its capacity to mobilize systemic antitumor immunity, which is primarily mediated by T cells, there is growing exploration and expansion of its potential value in various stages of clinical tumor treatment. Neoadjuvant immunotherapy induces a robust immune response against tumors prior to surgery, effectively facilitating tumor volume reduction, early eradication or suppression of tumor cell activity, and control of potential metastatic spread, to improve curative surgical resection rates, and prevent tumor recurrence. This review delineates the theoretical basis of neoadjuvant immunotherapy from preclinical research evidence, discusses specific challenges in clinical application, and provides a comprehensive overview of clinical research progress in neoadjuvant immunotherapy for gastrointestinal tumors. These findings suggest that neoadjuvant immunotherapy has the potential to ameliorate immunosuppressive states and enhance cytotoxic T cell function while preserving lymphatic drainage in the preoperative period. However, further investigations are needed on specific treatment regimens, suitable patient populations, and measurable endpoints. Despite numerous studies demonstrating the promising efficacy and manageable adverse events of neoadjuvant immunotherapy in gastrointestinal tumors, the availability of high-quality randomized controlled trials is limited, which highlights the necessity for further research.

Reforestation of Cunninghamia lanceolata changes the relative abundances of important prokaryotic families in soil.

Over the past decades, many forests have been converted to monoculture plantations, which might affect the soil microbial communities that are responsible for governing the soil biogeochemical processes. Understanding how reforestation efforts alter soil prokaryotic microbial communities will therefore inform forest management. In this study, the prokaryotic communities were comparatively investigated in a secondary Chinese fir forest (original) and a reforested Chinese fir plantation (reforested from a secondary Chinese fir forest) in Southern China. The results showed that reforestation changed the structure of the prokaryotic community: the relative abundances of important prokaryotic families in soil. This might be caused by the altered soil pH and organic matter content after reforestation. Soil profile layer depth was an important factor as the upper layers had a higher diversity of prokaryotes than the lower ones (p < 0.05). The composition of the prokaryotic community presented a seasonality characteristic. In addition, the results showed that the dominant phylum was Acidobacteria (58.86%) with Koribacteraceae (15.38%) as the dominant family in the secondary Chinese fir forest and the reforested plantation. Furthermore, soil organic matter, total N, hydrolyzable N, and NH4+-N were positively correlated with prokaryotic diversity (p < 0.05). Also, organic matter and NO3--N were positively correlated to prokaryotic abundance (p < 0.05). This study demonstrated that re-forest transformation altered soil properties, which lead to the changes in microbial composition. The changes in microbial community might in turn influence biogeochemical processes and the environmental variables. The study could contribute to forest management and policy-making.

Strong Invasive Mechanism of Wedelia trilobata via Growth and Physiological Traits under Nitrogen Stress Condition.

Nitrogen (N) is one of the most crucial elements for plant growth. However, a deficiency of N affects plant growth and development. Wedelia trilobata is a notorious invasive plant species that exhibits superior tolerance to adapt to environmental stresses. Yet, research on the growth and antioxidant defensive system of invasive Wedelia under low N stress, which could contribute to understanding invasion mechanisms, is still limited. Therefore, this study aims to investigate and compare the tolerance capability of invasive and native Wedelia under low and normal N conditions. Native and invasive Wedelia species were grown in normal and low-N conditions using a hydroponic nutrient solution for 8 weeks to assess the photosynthetic parameters, antioxidant activity, and localization of reactive oxygen species (ROS). The growth and biomass of W. trilobata were significantly (p < 0.05) higher than W. chinensis under low N. The leaves of W. trilobata resulted in a significant increase in chlorophyll a, chlorophyll b, and total chlorophyll content by 40.2, 56.2, and 46%, respectively, compared with W. chinensis. W. trilobata significantly enhanced antioxidant defense systems through catalase, peroxidase, and superoxide dismutase by 18.6%, 20%, and 36.3%, respectively, providing a positive response to oxidative stress caused by low N. The PCA analysis showed that W. trilobata was 95.3% correlated with physiological traits by Dim1 (79.1%) and Dim2 (16.3%). This study provides positive feedback on W. trilobata with respect to its comprehensive invasion mechanism to improve agricultural systems via eco-friendly approaches in N deficit conditions, thereby contributing to the reclamation of barren land.

Mutation status of the KMT2 family associated with immune checkpoint inhibitors (ICIs) therapy and implicating diverse tumor microenvironments.

Mounting evidence suggests a strong association between tumor immunity and epigenetic regulation. The histone-lysine N-methyltransferase 2 (KMT2) family plays a crucial role in the methylation of histone H3 at lysine 4. By influencing chromatin structure and DNA accessibility, this modification serves as a key regulator of tumor progression and immune tolerance across various tumors. These findings highlight the potential significance of the KMT2 family in determining response to immune checkpoint inhibitor (ICI) therapy, which warrants further exploration. In this study, we integrated four ICI-treated cohorts (n = 2069) across 10 cancer types and The Cancer Genome Atlas pan-cancer cohort and conducted a comprehensive clinical and bioinformatic analysis. Our study indicated that patients with KMT2 family gene mutations benefited more from ICI therapy in terms of overall survival (P < 0.001, hazard ratio [HR] = 0.733 [95% confidence interval (CI): 0.632-0.850]), progression-free survival (P = 0.002, HR = 0.669 [95% CI: 0.518-0.864]), durable clinical benefit (P < 0.001, 54.1% vs. 32.6%), and objective response rate (P < 0.001, 40.6% vs. 22.0%). Through a comprehensive analysis of the tumor microenvironment across different KMT2 mutation statuses, we observed that tumors harboring the KMT2 mutation exhibited enhanced immunogenicity, increased infiltration of immune cells, and higher levels of immune cell cytotoxicity, suggesting a propensity towards a "hot tumor" phenotype. Therefore, our study indicates a potential association between KMT2 mutations and a more favorable response to ICI therapy and implicates different tumor microenvironments associated with ICI therapy response.

Targeting proteasomal deubiquitinases USP14 and UCHL5 with b-AP15 reduces 5-fluorouracil resistance in colorectal cancer cells.

5-Fluorouracil (5-FU) is the first-line treatment for colorectal cancer (CRC) patients, but the development of acquired resistance to 5-FU remains a big challenge. Deubiquitinases play a key role in the protein degradation pathway, which is involved in cancer development and chemotherapy resistance. In this study, we investigated the effects of targeted inhibition of the proteasomal deubiquitinases USP14 and UCHL5 on the development of CRC and resistance to 5-FU. By analyzing GEO datasets, we found that the mRNA expression levels of USP14 and UCHL5 in CRC tissues were significantly increased, and negatively correlated with the survival of CRC patients. Knockdown of both USP14 and UCHL5 led to increased 5-FU sensitivity in 5-FU-resistant CRC cell lines (RKO-R and HCT-15R), whereas overexpression of USP14 and UCHL5 in 5-FU-sensitive CRC cells decreased 5-FU sensitivity. B-AP15, a specific inhibitor of USP14 and UCHL5, (1-5 µM) dose-dependently inhibited the viability of RKO, RKO-R, HCT-15, and HCT-15R cells. Furthermore, treatment with b-AP15 reduced the malignant phenotype of CRC cells including cell proliferation and migration, and induced cell death in both 5-FU-sensitive and 5-FU-resistant CRC cells by impairing proteasome function and increasing reactive oxygen species (ROS) production. In addition, b-AP15 inhibited the activation of NF-κB pathway, suppressing cell proliferation. In 5-FU-sensitive and 5-FU-resistant CRC xenografts nude mice, administration of b-AP15 (8 mg·kg-1·d-1, intraperitoneal injection) effectively suppressed the growth of both types of tumors. These results demonstrate that USP14 and UCHL5 play an important role in the development of CRC and resistance to 5-FU. Targeting USP14 and UCHL5 with b-AP15 may represent a promising therapeutic strategy for the treatment of CRC.

Dose dependent effect of nitrogen on the phyto extractability of Cd in metal contaminated soil using Wedelia trilobata.

Cadmium (Cd) is one of the toxic heavy metal that negatively affect plant growth and compromise food safety for human consumption. Nitrogen (N) is an essential macronutrient for plant growth and development. It may enhance Cd tolerance of invasive plant species by maintaining biochemical and physiological characteristics during phytoextraction of Cd. A comparative study was conducted to evaluate the phenotypical and physiological responses of invasive W. trilobata and native W. chinensis under low Cd (10 µM) and high Cd (80 µM) stress, along with different N levels (i.e., normal 91.05 mg kg-1 and low 0.9105 mg kg-1). Under low-N and Cd stress, the growth of leaves, stem and roots in W. trilobata was significantly increased by 35-23%, 25-28%, and 35-35%, respectively, compared to W. chinensis. Wedelia trilobata exhibited heightened antioxidant activities of catalase and peroxidase were significantly increased under Cd stress to alleviate oxidative stress. Similarly, flavonoid content was significantly increased by 40-50% in W. trilobata to promote Cd tolerance via activation of the secondary metabolites. An adverse effect of Cd in the leaves of W. chinensis was further verified by a novel hyperspectral imaging technology in the form of normalized differential vegetation index (NDVI) and photochemical reflectance index (PRI) compared to W. trilobata. Additionally, W. trilobata increased the Cd tolerance by regulating Cd accumulation in the shoots and roots, bolstering its potential for phytoextraction potential. This study demonstrated that W. trilobata positively responds to Cd with enhanced growth and antioxidant capabilities, providing a new platform for phytoremediation in agricultural lands to protect the environment from heavy metals pollution.

Clonal integration can promote the growth and spread of Alternanthera philoxeroides in cadmium-contaminated environments.

Clonal plants are able to support the growth of their ramets in stressful environments via clonal integration between the ramets. However, it remains unclear whether the developmental status of stressed ramets affects the role of clonal integration. Here, we explored the effects of clonal integration at both the ramet level and the whole clonal fragment level when the apical ramets (younger) and basal ramets (older) were subjected to different concentrations of cadmium contamination. We grew pairs of ramets of Alternanthera philoxeroides, which were connected or disconnected by stolon between them. The apical and basal ramets were either uncontaminated or individually subjected to Cd contamination at concentrations of 5 mg kg-1 and 50 mg kg-1, respectively. Our results showed that clonal integration significantly promoted the growth of apical ramets subjected to Cd contamination. More importantly, under high Cd treatment, clonal integration also had a significant positive effect on the fitness of the whole clonal fragments. However, clonal integration did not affect plant growth when basal ramets were subjected to Cd contamination. Our study reveals the influence of the developmental status of stressed ramets on the role of clonal integration in heterogeneous heavy metal stress environments, suggesting that clonal integration may facilitate the spread of A. philoxeroides in Cd-contaminated habitats.

A method for quantifying relative competitive advantage and the combined effect of co-invasion for two invasive plants.

Image 1.

Invasive clonal plants possess greater capacity for division of labor than natives in high patch contrast environments.

Invasion success of clonal plants is closely related to their unique clonal life history, and clonal division of labor is a crucial clonal trait. However, so far, it is unclear whether invasive alien clonal species generally possess a greater capacity for division of labor than native species and whether this pattern is affected by environmental conditions. To test whether patch contrast affects the differences in the capacity for division of labor between invasive alien and native clonal plants, we selected five pairs of exotic invasive and native clonal plant species that are congeneric and co-occurring in China as experimental materials. We grew the clonal fragment pairs of these invasive and native plants under high, low, or no contrast of reciprocal patchiness of light and nutrient, respectively, with ramet connections either severed (division of labor prevented) or kept intact (division of labor allowed). The results showed that connection significantly decreased the proportion of biomass allocated to roots in distal (younger) ramets, whereas it increased in proximal (older) ramets of all studied plants under high -contrast treatments. This clear pattern strongly indicated the occurrence of division of labor. Furthermore, the connection had a more pronounced effect on the pattern of biomass allocation of invasive alien plants, resulting in a greater increase in biomass for invasive alien plants compared to native plants. These findings suggest that the invasive alien plants possess a greater capacity for division of labor, which may confer a competitive advantage to them over natives, thus facilitating their invasion success in some heterogeneous habitats such as forest edges where light and soil nutrients show a high negative correlation.

Invasive Plant Alternanthera philoxeroides Benefits More Competition Advantage from Rhizosphere Bacteria Regardless of the Host Source.

The rhizosphere plays a vital role in the exchange of materials in the soil-plant ecosystem, and rhizosphere microorganisms are crucial for plant growth and development. In this study, we isolated two strains of Pantoea rhizosphere bacteria separately from invasive Alternanthera philoxeroides and native A. sessilis. We conducted a control experiment to test the effects of these bacteria on the growth and competition of the two plant species using sterile seedlings. Our findings showed that the rhizobacteria strain isolated from A. sessilis significantly promoted the growth of invasive A. philoxeroides in monoculture compared to native A. sessilis. Both strains significantly enhanced the growth and competitiveness of invasive A. philoxeroides under competition conditions, regardless of their host source. Our study suggests that rhizosphere bacteria, including those from different host sources, can contribute to the invasion of A. philoxeroides by significantly enhancing its competitiveness.

Plant growth promoting rhizobacteria and biochar production from Parthenium hysterophorus enhance seed germination and productivity in barley under drought stress.

Drought stress can significantly affect plant growth and development. Biochar (BC) and plant growth-promoting rhizobacteria (PGPR) have been found to increase plant fertility and development under drought conditions. The single effects of BC and PGPR in different plant species have been widely reported under abiotic stress. However, there have been relatively few studies on the positive role of PGPR, BC, and their combination in barley (Hordeum vulgare L.). Therefore, the current study investigated the effects of BC from Parthenium hysterophorus, drought tolerant PGPR (Serratia odorifera), and the combination of BC + PGPR on the growth, physiology, and biochemical traits of barley plants under drought stress for two weeks. A total of 15 pots were used under five treatments. Each pot of 4 kg soil comprised the control (T0, 90% water), drought stress alone (T1, 30% water), 35 mL PGPR/kg soil (T2, 30% water), 2.5%/kg soil BC (T3, 30% water), and a combination of BC and PGPR (T4, 30% water). Combined PGPR and BC strongly mitigated the negative effects of drought by improving the shoot length (37.03%), fresh biomass (52%), dry biomass (62.5%), and seed germination (40%) compared to the control. The PGPR + BC amendment treatment enhanced physiological traits, such as chlorophyll a (27.9%), chlorophyll b (35.3%), and total chlorophyll (31.1%), compared to the control. Similarly, the synergistic role of PGPR and BC significantly (p< 0.05) enhanced the antioxidant enzyme activity including peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) to alleviate the toxicity of ROS. The physicochemical properties (N, K, P, and EL) of the soils were also enhanced by (85%, 33%, 52%, and 58%) respectively, under the BC + PGPR treatment compared to the control and drought stress alone. The findings of this study have suggested that the addition of BC, PGPR, and a combination of both will improve the soil fertility, productivity, and antioxidant defense systems of barley under drought stress. Therefore, BC from the invasive plant P. hysterophorus and PGPR can be applied to water-deficient areas to improve barley crop production.

Current Status and Influencing Factors of Readiness for Discharge of Elderly Patients with Chronic Obstructive Pulmonary Disease.

Objective: Readiness for hospital discharge is an important indicator of patients' transition from illness to health and can predict rehabilitation and prognosis. Identifying factors that influence readiness for discharge is crucial for developing effective nursing interventions. Therefore, this study aims to investigate the current status of discharge readiness and its influencing factors in elderly patients with chronic obstructive pulmonary disease (COPD). Methods: A total of 311 elderly inpatients diagnosed with COPD were enrolled in this investigation at a tertiary hospital in Chengdu between December 2021 and June 2022. Questionnaires were designed to collect general information, disease-related information, and responses to the Readiness for Hospital Discharge Scale (RHDS) and the Quality of Discharge Teaching Scale (QDTS). Univariate and multivariate linear regression analyses were employed to further analyze factors related to discharge readiness and the correlation between discharge readiness and the quality of discharge guidance. Results: The total score of discharge readiness of elderly COPD patients was 77.72 ± 11.86 with a mean score of 6.48 ± 0.19 for each item. The quality of discharge instructions was 110.54 ± 15.66, with a mean score of 6.12 ± 0.15 for each item. Discharge preparation was positively correlated with the quality of discharge guidance. Multivariate analysis showed that marital status, admission mode, length of stay in hospital, Classification of Severity of Airflow Limitation, mMRC classification, number of medications taken with discharge, presence of inhalers in medication orders, mode of home oxygen therapy, and quality of discharge guidance were independent factors of discharge readiness in elderly COPD patients (P < 0.05). Conclusion: Both discharge readiness and the quality of discharge guidance for elderly COPD patients in China are currently suboptimal and need further improvement. The survey findings provide valuable insights that can guide future management practices and interventions aimed at improving discharge readiness.

A Green Approach Used for Heavy Metals 'Phytoremediation' Via Invasive Plant Species to Mitigate Environmental Pollution: A Review.

Heavy metals (HMs) normally occur in nature and are rapidly released into ecosystems by anthropogenic activities, leading to a series of threats to plant productivity as well as human health. Phytoremediation is a clean, eco-friendly, and cost-effective method for reducing soil toxicity, particularly in weedy plants (invasive plant species (IPS)). This method provides a favorable tool for HM hyperaccumulation using invasive plants. Improving the phytoremediation strategy requires a profound knowledge of HM uptake and translocation as well as the development of resistance or tolerance to HMs. This review describes a comprehensive mechanism of uptake and translocation of HMs and their subsequent detoxification with the IPS via phytoremediation. Additionally, the improvement of phytoremediation through advanced biotechnological strategies, including genetic engineering, nanoparticles, microorganisms, CRISPR-Cas9, and protein basis, is discussed. In summary, this appraisal will provide a new platform for the uptake, translocation, and detoxification of HMs via the phytoremediation process of the IPS.

"Dark under the lamp": ecological equity of urban agglomeration from the perspective of natural capital in China.

Although equity is an important aspect of sustainable development, equity research has mainly focused on income and economics while paying insufficient attention to ecological equity. Therefore, aiming to improve our understanding of equity and promote environmental protection, this study introduced natural capital to measure regional ecological equity and analyze its driving factors. Based on ecological footprint (EF) and ecosystem service value (ESV), we constructed evaluation indexes and drew an "ecological Lorentz curve bundle" to analyze ecological equity in the Jing-Jin-Ji urban agglomeration (JUA) from 2009 to 2020. The results showed that economic development in JUA resulted in the severe depletion of natural capital, especially biological and energy resources, and the supply and demand of natural capital was in a low-level equilibrium state. Based on JUA's population base, natural capital utilization in the region had exceeded ecological equity, and the Gini coefficient of EF based on population was close to the international warning value of 0.4. Although economic development in JUA has promoted economic equity, it has also led to environmental inequity. Large cities such as Beijing and Tianjin, as well as industrial cities such as Tangshan and Handan, have had the greatest effects on ecological equity. Moreover, the excessive consumption of natural capital stock and energy-dependent industrial structures threaten ecological equity.

Both Adaptability and Endophytic Bacteria Are Linked to the Functional Traits in the Invasive Clonal Plant Wedelia trilobata.

The role of the interactions between endophytes and host plants is unclear in invasive plants from different geographical latitudes. In this study, we aimed to explore the relationship between endophytic microbes and the functional traits of the invasive plant Wedelia trilobata. We explored the relationship between endophytes and the clonal growth traits of the invasive clonal plant Wedelia trilobata from different geographical latitudes using high-throughput sequencing technology and a common garden-planting experiment. We found that: (1) Different W. trilobata populations had similar endophytic fungi but different endophytic bacteria. However, no latitudinal variation pattern of the overall microbial community was found; (2) plant clonal growth performance (i.e., spacer length) was significantly correlated with endophytic bacterial diversity but not fungal diversity; and (3) the latitudinal variation pattern of the plant clonal growth performance of W. trilobata populations was found in pre-cultivated (i.e., wild) individuals but disappeared in post-cultivated W. trilobata. Our results suggest both environmental adaptability and the endophytic bacterial community are linked to the functional traits of the invasive clonal plant W. trilobata, and these functional traits tend to increase its invasiveness, which may enhance its invasion success.

A systemic review and meta-analysis comparing the ability of diagnostic of the third heart sound and left ventricular ejection fraction in heart failure.

Objective: This study aimed to compare the sensitivity and specificity of diagnosis between the third heart sound (S3) and left ventricular ejection fraction (LVEF) in heart failure (HF). Methods: Relevant studies were searched in PubMed, SinoMed, China National Knowledge Infrastructure, and the Cochrane Trial Register until February 20, 2022. The sensitivity, specificity, likelihood ratio (LR), and diagnostic odds ratio (DOR) were pooled. The symmetric receiver operator characteristic curve (SROC) and Fagan's nomogram were drawn. The source of heterogeneity was explored by meta-regression and subgroup analysis. Results: A total of 19 studies, involving 5,614 participants, were included. The combined sensitivity of S3 was 0.23 [95% confidence interval (CI) (0.15-0.33), specificity was 0.94 [95% CI (0.82-0.98)], area under the SROC curve was 0.49, and the DOR was 4.55; while the sensitivity of LVEF was 0.70 [95% CI (0.53-0.83)], specificity was 0.79 [95% CI (0.75-0.82)], area under the SROC curve was 0.79, and the DOR was 8.64. No publication bias was detected in Deeks' funnel plot. The prospective design, partial verification bias, and blind contributed to the heterogeneity in specificity, while adequate description of study participants contributed to the heterogeneity in sensitivity. In Fagan's nomogram, the post-test probability was 48% when the pre-test probability was set as 20%, while in LVEF, the post-test probability was 45% when the pre-test probability was set as 20%. Conclusion: The use of S3 alone presented lower sensitivity in diagnosing HF compared with LVEF, whereas it was useful in early pathological assessment.

Clonal functional traits favor the invasive success of alien plants into native communities.

Functional traits are frequently proposed to determine the invasiveness of alien species. However, few empirical studies have directly manipulated functional traits and tested their importance in the invasion success of alien species into native plant communities, particularly under global change. We manipulated clonal integration (a key clonal functional trait) of four alien clonal plants by severing inter-ramet connections or keeping them intact and simulated their invasion into native plant communities with two levels of species diversity, population density and nutrient availability. High community diversity and density impeded the invasion success of the alien clonal plants. Clonal integration of the alien plants promoted their invasion success, particularly in the low-density communities associated with low species diversity or nutrient addition, which resulted in a negative correlation between the performance of alien plants and native communities, as expected under global change. Thus, clonal integration can favor the invasion success of alien clonal plants into degraded resident communities with a high degree of disturbance and eutrophication. Our findings confirm the role of clonal functional traits in facilitating alien plant invasions into native plant communities and suggest that clonal functional traits should be considered to efficiently restore degraded communities heavily invaded by alien clonal plants.

Pathogen resistance in Sphagneticola trilobata (Singapore daisy): molecular associations and differentially expressed genes in response to disease from a widespread fungus.

Understanding the molecular associations underlying pathogen resistance in invasive plant species is likely to provide useful insights into the effective control of alien plants, thereby facilitating the conservation of native biodiversity. In the current study, we investigated pathogen resistance in an invasive clonal plant, Sphagneticola trilobata, at the molecular level. Sphagneticola trilobata (i.e., Singapore daisy) is a noxious weed that affects both terrestrial and aquatic ecosystems, and is less affected by pathogens in the wild than co-occurring native species. We used Illumina sequencing to investigate the transcriptome of S. trilobata following infection by a globally distributed generalist pathogen (Rhizoctonia solani). RNA was extracted from leaves of inoculated and un-inoculated control plants, and a draft transcriptome of S. trilobata was generated to examine the molecular response of this species following infection. We obtained a total of 49,961,014 (94.3%) clean reads for control (un-inoculated plants) and 54,182,844 (94.5%) for the infected treatment (inoculated with R. solani). Our analyses facilitated the discovery of 117,768 de novo assembled contigs and 78,916 unigenes. Of these, we identified 3506 differentially expressed genes and 60 hormones associated with pathogen resistance. Numerous genes, including candidate genes, were associated with plant-pathogen interactions and stress response in S. trilobata. Many recognitions, signaling, and defense genes were differentially regulated between treatments, which were confirmed by qRT-PCR. Overall, our findings improve our understanding of the genes and molecular associations involved in plant defense of a rapidly spreading invasive clonal weed, and serve as a valuable resource for further work on mechanism of disease resistance and managing invasive plants.

STING1 in sepsis: Mechanisms, functions, and implications.

Sepsis is a life-threatening clinical syndrome and one of the most challenging health problems in the world. Pathologically, sepsis and septic shock are caused by a dysregulated host immune response to infection, which can eventually lead to multiple organ failure and even death. As an adaptor transporter between the endoplasmic reticulum and Golgi apparatus, stimulator of interferon response cGAMP interactor 1 (STING1, also known as STING or TMEM173) has been found to play a vital role at the intersection of innate immunity, inflammation, autophagy, and cell death in response to invading microbial pathogens or endogenous host damage. There is ample evidence that impaired STING1, through its immune and non-immune functions, is involved in the pathological process of sepsis. In this review, we discuss the regulation and function of the STING1 pathway in sepsis and highlight it as a suitable drug target for the treatment of lethal infection.

Soil Microbe-Mediated N:P Stoichiometric Effects on Solidago canadensis Performance Depend on Nutrient Levels.

Both soil microbes and soil N:P ratios can affect plant growth, but it is unclear whether they can interact to alter plant growth and whether such an interactive effect depends on nutrient levels. Here, we tested the hypothesis that soil microbes can ameliorate the negative effects of nutrient imbalance caused by low or high N:P ratios on plant growth and that such an ameliorative effect of soil microbes depends on nutrient supply levels. We grew individuals of six populations of the clonal plant Solidago canadensis at three N:P ratios (low (1.7), intermediate (15), and high (135)), under two nutrient levels (low versus high) and in the presence versus absence of soil microbes. The presence of soil microbes significantly increased biomass of S. canadensis at all three N:P ratios and under both nutrient levels. Under the low-nutrient level, biomass, height, and leaf number of S. canadensis did not differ significantly among the three N:P ratio treatments in the absence of soil microbes, but they were higher at the high than at the low and the intermediate N:P ratio in the presence of soil microbes. Under the high-nutrient level, by contrast, biomass, height, and leaf number of S. canadensis were significantly higher at the low than at the high and the intermediate N:P ratio in the absence of soil microbes, but increased with increasing the N:P ratio in the presence of soil microbes. In the presence of soil microbes, number of ramets (asexual individuals) and the accumulation of N and P in plants were significantly higher at the high than at the low and the intermediate N:P ratio under both nutrient levels, whereas in the absence of soil microbes, they did not differ significantly among the three N:P ratio regardless of the nutrient levels. Our results provide empirical evidence that soil microbes can alter effects of N:P ratios on plant performance and that such an effect depends on nutrient availability. Soil microbes may, therefore, play a role in modulating ecosystem functions such as productivity and carbon and nutrient cycling via modulating nutrient imbalance caused by low and high N:P ratios.