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Abstract Plants can adapt to environmental changes by adjusting their functional traits and biomass allocation. The size and number of flowers are functional traits related to plant reproduction. Life history theory predicts that there is a trade‐off between flower size and number, and the trade‐off can potentially explain the adaptability of plants. Elevation gradients in mountains provide a unique opportunity to test how plants will respond to climate change. In this study, we tried to better explain the adaptability of the alpine plant Gentiana lawrencei var. farreri in response to climate change. We measured the flower size and number, individual size, and reproductive allocation of G. lawrencei var. farreri during the flowering period along an elevation gradient from 3200 to 4000 m, and explored their relationships using linear mixed‐effect models and the structural equation model. We found that with elevation increasing, individual size and flower number decreased and flower size increased, while reproductive allocation remained unchanged. Individual size positively affected flower number, but was not related to flower size; reproductive allocation positively affected flower size, but was not related to flower number; there is a clear trade‐off between flower size and number. We also found that elevation decreased flower number indirectly via directly reducing individual size. In sum, this study suggests that G. lawrencei var. farreri can adapt to alpine environments by the synergies or trade‐offs among individual size, reproductive allocation, flower size, and flower number. This study increases our understanding of the adaptation mechanisms of alpine plants to climate change in alpine environments.

Activating cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) holds great potential for cancer immunotherapy by eliciting type-I interferon (IFN-I) responses. Yet, current approaches to cGAS-STING activation rely on STING agonists, which suffer from difficult formulation, poor pharmacokinetics, and marginal clinical therapeutic efficacy. Here, we report nature-inspired oligonucleotide, Svg3, as a cGAS agonist for cGAS-STING activation in tumor combination immunotherapy. The hairpin-shaped Svg3 strongly binds to cGAS and enhances phase separation to form Svg3-cGAS liquid-like droplets. This results in cGAS-specific immunoactivation and robust IFN-I responses. Remarkably, Svg3 outperforms several state-of-the-art STING agonists in murine and human cells/tissues. Nanoparticle-delivered Svg3 reduces tumor immunosuppression and potentiates immune checkpoint blockade therapeutic efficacy of multiple syngeneic tumor models in wild-type mice, but in neither cGas−/− nor Sting−/− mice. Overall, these results demonstrate the great potential of Svg3 as a cGAS agonistic oligonucleotide for cancer combination immunotherapy.

Abstract Rheumatoid arthritis (RA) is a systemic autoimmune disease with pathogenic inflammation caused partly by excessive cell‐free DNA (cfDNA). Specifically, cfDNA is internalized into immune cells, such as macrophages in lymphoid tissues and joints, and activates pattern recognition receptors, including cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS), resulting in overly strong proinflammation. Here, nanomedicine‐in‐hydrogel (NiH) is reported that co‐delivers cGAS inhibitor RU.521 (RU) and cfDNA‐scavenging cationic nanoparticles (cNPs) to draining lymph nodes (LNs) for systemic immunosuppression in RA therapy. Upon subcutaneous injection, NiH prolongs LN retention of RU and cNPs, which pharmacologically inhibit cGAS and scavenged cfDNA, respectively, to inhibit proinflammation. NiH elicits systemic immunosuppression, repolarizes macrophages, increases fractions of immunosuppressive cells, and decreases fractions of CD4+ T cells and T helper 17 cells. Such skewed immune milieu allows NiH to significantly inhibit RA progression in collagen‐induced arthritis mice. These studies underscore the great potential of NiH for RA immunotherapy.

Abstract The tyre lateral force control is crucial to vehicle lateral stability. Vehicle side slip and out of control can be prevented effectively by observing accurately the lateral force. Thus, a novel quasi‐sliding mode observer (QSMO) is proposed. The algorithm adopts the longitudinal tyre force error as feedback considering vehicle parameter uncertainties and without a complex tyre model. First, the on‐line verification of the algorithm was carried out by dSPACE for using the experimental data of the real vehicle linear acceleration and deceleration conditions, and comparison of experimental output with different observation algorithms. Further, the simulation under emergency obstacle avoidance conditions and the double‐line shifting conditions were conducted to verify the accuracy of the algorithm respectively. Simulation results show that the percentage errors between the tyre lateral forces from the proposed QSMO and the actual data are less than 5.35%, and the prediction accuracy of the QSMO by 38.78% is higher than that of the conventional first‐order SMO (FSMO), which indicates that the QSMO is superior to the FSMO.

Nitrogen and phosphorus are important nutrient elements for plants and underground organisms. The nematode is an important part of the soil food web. Although many studies have explored the effects of fertilization on soil nematode community structure, little is known about the response mechanism of the nematode community to fertilization. In this study, we investigated the diversity and functional diversity of soil nematode communities, as well as soil physicochemical properties, root functional traits, and plant richness. We explored the response mechanism of soil nematode communities to nitrogen and phosphorus fertilizer. Nitrogen fertilizer increased the abundance and richness of bacterivorous nematodes, while phosphorus fertilizer decreased the total abundance of bacterivorous nematodes. Meanwhile, the diversity of the nematode community was significantly affected by soil physicochemical properties and plant root functional traits. Therefore, our study revealed the effects of nitrogen and phosphorus fertilizer on soil nematode community diversity and functional diversity. Exploring the response mechanism of soil nematode communities to fertilization interference provides further evidence for the role of nematodes in maintaining the function of subsurface ecosystems.

Abstract Immune checkpoint blockade (ICB) has significantly advanced cancer immunotherapy, yet its patient response rates are generally low. Vaccines, including immunostimulant‐adjuvanted peptide antigens, can improve ICB. The emerging neoantigens generated by cancer somatic mutations elicit cancer‐specific immunity for personalized immunotherapy; the novel cyclic dinucleotide (CDN) adjuvants activate stimulator of interferon genes (STING) for antitumor type I interferon (IFN‐I) responses. However, CDN/neoantigen vaccine development has been limited by the poor antigen/adjuvant codelivery. Here, pH‐responsive CDN/neoantigen codelivering nanovaccines (NVs) for ICB combination tumor immunotherapy are reported. pH‐responsive polymers are synthesized to be self‐assembled into multivesicular nanoparticles (NPs) at physiological pH and disassembled at acidic conditions. NPs with high CDN/antigen coloading are selected as NVs for CDN/antigen codelivery to antigen presenting cells (APCs) in immunomodulatory lymph nodes (LNs). In the acidic endosome of APCs, pH‐responsive NVs facilitate the vaccine release and escape into cytosol, where CDNs activate STING for IFN‐I responses and antigens are presented by major histocompatibility complex (MHC) for T‐cell priming. In mice, NVs elicit potent antigen‐specific CD8+ T‐cell responses with immune memory, and reduce multifaceted tumor immunosuppression. In syngeneic murine tumors, NVs show robust ICB combination therapeutic efficacy. Overall, these CDN/neoantigen‐codelivering NVs hold the potential for ICB combination tumor immunotherapy.

Global nitrogen eutrophication, which is disrupting the intimate plant–arbuscular mycorrhizal fungi (AMF) symbiosis, can alter the diversity and physiological functions of soil AMF greatly. However, shifts of beta diversity and the intrinsic patterns of AMF community dissimilarities in response to nitrogen addition remain unclear. Based on a 7-year nitrogen addition experiment in a Qinghai–Tibet Plateau alpine meadow, we detected the changes in soil AMF alpha diversity (richness and genus abundance) and the community composition beta diversity by partitioning the two components of Simpson and nestedness dissimilarities along (turnover) and within (variation) nitrogen addition treatments, and fitted with environmental factor dissimilarities. We found that nitrogen addition decreased AMF richness by decreasing the most dominant AMF genus of Glomus but increasing the abundance of the rare genera. The turnover of the AMF community overall beta diversity along the nitrogen addition gradients was induced by the increased nestedness dissimilarity, while the variation within treatments was explained by both increased Simpson and nestedness dissimilarities, which was significantly correlated with soil pH. Our study found both Simpson and nestedness dissimilarities worked on the AMF community dissimilarity after nitrogen addition and the significant variation within the same treatment, which would be important in the future for predicting global AMF or microbial diversity changes in response to nitrogen eutrophication.

Small GTPase is a kind of GTP-binding protein commonly found in eukaryotic cells. It plays an important role in cytoskeletal reorganization, cell polarity, cell cycle progression, gene expression and many other significant events in cells, such as the interaction with foreign particles. Therefore, it is of great scientific significance to understand the biological properties of small GTPases as well as the GTPase-nano interplay, since more and more nanomedicine are supposed to be used in biomedical field. However, there is no review in this aspect. This review summarizes the small GTPases in terms of the structure, biological function and its interaction with nanoparticles. We briefly introduced the various nanoparticles such as gold/silver nanoparticles, SWCNT, polymeric micelles and other nano delivery systems that interacted with different GTPases. These current nanoparticles exhibited different pharmacological effect modes and various target design concepts in the small GTPases study. This will help to elucidate the conclusion that the therapeutic strategy targeting small GTPases might be a new research direction. It is believed that the in-depth study on the functional mechanism of GTPases can provide insights for the design and study of nanomedicines. Keywords: Small GTPase, Nanoparticles, Ras, Rab, Rho

Cancer immunotherapy has shown great potential as witnessed by an increasing number of immuno-oncology drug approvals in the past few years. Meanwhile, the field of nucleic acid therapeutics has made significant advancement. Nucleic acid therapeutics, such as plasmids, antisense oligonucleotides (ASO), small interfering RNA (siRNA) and microRNA, messenger RNA (mRNA), immunomodulatory DNA/RNA, and gene-editing guide RNA (gRNA) are attractive due to their versatile abilities to alter the expression of target endogenous genes or even synthetic genes, and modulate the immune responses. These abilities can play vital roles in the development of novel immunotherapy strategies. However, limited by the intrinsic physicochemical properties such as negative charges, hydrophilicity, as well as susceptibility to enzymatic degradation, the delivery of nucleic acid therapeutics faces multiple challenges. It is therefore pivotal to develop drug delivery systems that can carry, protect, and specifically deliver and release nucleic acid therapeutics to target tissues and cells. In this review, we attempted to summarize recent advances in nucleic acid therapeutics and the delivery systems for these therapeutics in cancer immunotherapy.

It has been demonstrated that the interplay between negative and positive interactions simultaneously shapes community structure and composition. However, few studies have attempted to examine the effect of facilitation on compositional changes in communities through time. Additionally, due to the difficulties in collecting the long-term data, it would be useful to indicate the rate of temporal turnover using a readily obtainable metric. Using an individual-based model incorporating plant strategies, we examined the role of facilitation on the temporal turnover of communities located at different positions along an environmental gradient for three model scenarios: CM without facilitation; CFM-U, a unimodal relationship between facilitation and environmental severity; and CFM-L, a positively linear relationship between facilitation and environmental severity. Our results demonstrated that facilitation could increase, decrease or have no remarkable effect on temporal turnover. The specific outcome depended on the location of the focal community across the environmental gradient and the model employed. Compared with CM, the inclusion of positive interactions (i.e. CFM-U and CFM-L), at intermediate environmental stress levels (such as S = 0.7 and 0.8) resulted in lower Bray-Curtis similarity values; at other severity levels, facilitation slowed down (such as S = 0.3 and 0.4 at low to medium stress levels, and S = 0.9 at high stress levels) or had only a subtle effect (such as at S = 0.1) on temporal turnover. We also found that the coefficient of variation (CV) in species abundances and the rate of temporal variability showed a significant quadratic relationship. Our theoretical analysis contributes to the understanding of factors driving temporal turnover in biotic communities, and presents a potential metric (i.e. CV in species abundances) assessing the consequences of ongoing environmental change on community structure.

The relationship between species richness and evenness across communities remains an unsettled issue in ecology from both theoretical and empirical perspectives. As a result, we do not know the mechanisms that could generate a relationship between species richness and evenness, and how this responds to spatial scale. Here we examine the relationship between species richness(S) and evenness (Pielou's J' evenness) using a chronosequence of successional sub-alpine meadow communities in the eastern Qinghai-Tibetan Plateau. These meadows range from natural community (never farmed), to those that have been protected from agricultural exploitation for periods ranging from 1 to 10 years. A total of 30 sampling quadrats with size of 0.5 m×0.5 m were laid out along two transects at each meadow. Using correlation analyses we found a consistent negative correlation between S and J' in these communities along the successional gradient at the sampling scale of 0.5 m×0.5 m. We also explored the relationship between S and J' at different sampling scales (from 0.5 m×0.5 m to10 m×10 m) using properly measured ramet-mapped data of a10 m×10 m quadrat in the natural community. We found that S was negatively corrected with J' at the scales of 0.5 m×0.5 m to 2 m×2 m, but such a relationships disappeared at relative larger scales (≥2 m×4 m). When fitting different species abundance models combined with trait-specific methods, we found that niche preemption may be the determining mechanism of species evenness along the succession gradient. Considering all results together, we can conclude that such niche differentiation and spatial scale effects may help to explain the maintenance of high species richness in sub-alpine meadow communities.

The neutral assumption that individuals of either the same or different species share exactly the same birth, death, migration, and speciation probabilities is fundamental yet controversial to the neutral theory. Several theoretical studies have demonstrated that a slight difference in species per capita birth or death rates can have a profound consequence on species coexistence and community structure. Whether asymmetry in migration, a vital demographic parameter in the neutral model, plays an important role in community assembly still remains unknown. In this paper, we relaxed the ecological equivalence assumption of the neutral model by introducing differences into species regional dispersal ability. We investigated the effect of asymmetric dispersal on the neutral local community structure. We found that per capita asymmetric dispersal among species could reduce species richness of the local community and result in deviations of species abundance distributions from those predicted by the neutral model. But the effect was moderate compared with that of asymmetries in birth or death rates, unless very large asymmetries in dispersal were assumed. A large difference in species dispersal ability, if there is, can overwhelm the role of random drift and make local community dynamics deterministic. In this case, species with higher regional dispersal abilities tended to dominate in the local community. However, the species abundance distribution of the local community under asymmetric dispersal could be well fitted by the neutral model, but the neutral model generally underestimated the fundamental biodiversity number but overestimated the migration rate in such communities.

Aims: This study aims to comprehensively explore the decision‐making requirements of women contemplating vaginal birth after cesarean (VBAC). Design & Methods: A meta‐synthesis approach was employed for this study. Using an integrative methodology, we conducted a systematic assessment of women's experiences and needs related to VBAC decision‐making. A comprehensive search was conducted across The Cochrane Library, PubMed, EMBASE, Ovid Medline, SCOPUS, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, and Wan Fang databases to identify pertinent studies between 2000 and 2022. Furthermore, the reference lists of the included studies were thoroughly examined. Results: Fifteen studies were incorporated, from which seven themes emerged: emotional changes, preference for vaginal birth, unmet information needs, influences on decision‐making, decision‐making autonomy, aligning information provision with decision‐support needs, and the requirement for support systems. Two primary syntheses were constructed on the decision‐making process and the need for decision‐making aids, respectively. Conclusion: Women opting for VBAC experienced emotional shifts during their decision‐making process in pregnancy. There remains a need for an enhanced decision‐making tool to guide them in their choice. Recommendations for implementation in VBAC decision aids include facilitating women's involvement in decision‐making, satisfying their information needs, and delivering appropriate emotional support. [ABSTRACT FROM AUTHOR]

Understanding the changes in soil organic carbon (SOC) storage and chemical stabilization dynamics is important for accurately predicting ecosystem C sequestration and/or potential C loss, but the relevant information, especially for the intervention of environmental controls on grassland soil is limited in Tibetan plateau regions. Here we used a 9-year two-way factorial experiment involving warming with open top chambers (+1.80 °C in the daytime and +0.77 °C in the nighttime at the soil surface) and multilevel nitrogen (N) enrichment treatments (0, 5, 10, and 15 g m-2 year-1) in the Tibetan plateau to investigate the changes in SOC pool size and chemical structure. 9-year warming treatment significantly decreased SOC stock in the Tibetan grassland. We observed decreasing SOC concentrations which may be related to changes in the C degrading enzymes. Surprisingly, the SOC molecular structure remained unchanged in all N enrichment and warmed plots, suggesting that both treatments had affected all forms of SOC, from simple and complex polymeric in a similar way. Our results suggest that long-term warming stimulates soil C loss but no preference in SOC loss with different chemical structure. [ABSTRACT FROM AUTHOR]