Research on the mechanism of Guanyu Zhixie Granule in intervening gastric ulcers in rats based on network pharmacology and multi-omics.

Objective: Guanyu Zhixie Granule (GYZXG) is a traditional Chinese medicine compound with definite efficacy in intervening in gastric ulcers (GUs). However, the effect mechanisms on GU are still unclear. This study aimed to explore its mechanism against GU based on amalgamated strategies. Methods: The comprehensive chemical characterization of the active compounds of GYZXG was conducted using UHPLC-Q/TOF-MS. Based on these results, key targets and action mechanisms were predicted through network pharmacology. GU was then induced in rats using anhydrous ethanol (1 mL/200 g). The intervention effects of GYZXG on GU were evaluated by measuring the inhibition rate of GU, conducting HE staining, and assessing the levels of IL-6, TNF-α, IL-10, IL-4, Pepsin (PP), and epidermal growth factor (EGF). Real-time quantitative PCR (RT-qPCR) was used to verify the mRNA levels of key targets and pathways. Metabolomics, combined with 16S rRNA sequencing, was used to investigate and confirm the action mechanism of GYZXG on GU. The correlation analysis between differential gut microbiota and differential metabolites was conducted using the spearman method. Results: For the first time, the results showed that nine active ingredients and sixteen targets were confirmed to intervene in GU when using GYZXG. Compared with the model group, GYZXG was found to increase the ulcer inhibition rate in the GYZXG-M group (p < 0.05), reduce the levels of IL-6, TNF-α, PP in gastric tissue, and increase the levels of IL-10, IL-4, and EGF. GYZXG could intervene in GU by regulating serum metabolites such as Glycocholic acid, Epinephrine, Ascorbic acid, and Linoleic acid, and by influencing bile secretion, the HIF-1 signaling pathway, and adipocyte catabolism. Additionally, GYZXG could intervene in GU by altering the gut microbiota diversity and modulating the relative abundance of Bacteroidetes, Bacteroides, Verrucomicrobia, Akkermansia, and Ruminococcus. The differential gut microbiota was strongly associated with serum differential metabolites. KEGG enrichment analysis indicated a significant role of the HIF-1 signaling pathway in GYZXG's intervention on GU. The changes in metabolites within metabolic pathways and the alterations in RELA, HIF1A, and EGF mRNA levels in RT-qPCR experiments provide further confirmation of this result. Conclusion: GYZXG can intervene in GU induced by anhydrous ethanol in rats by regulating gut microbiota and metabolic disorders, providing a theoretical basis for its use in GU intervention.

Combining Mefloquine with an Mcl-1 Inhibitor as a Novel Therapeutic Strategy for the Treatment of Nasopharyngeal Carcinoma.

Considering the established pharmacokinetics and toxicity profiles, drug repurposing has emerged as an alternative therapeutic approach for treating cancer. Mefloquine has previously demonstrated inhibitory effects on multiple cancer types. This study aims to explore the impact of mefloquine on nasopharyngeal carcinoma (NPC). We found that mefloquine, at pharmacologically achievable concentrations, displayed anti-NPC activity while sparing normal counterparts. Mefloquine inhibits proliferation and induces death by reducing the levels of Cyclin A2, Bcl-2, and Bcl-xL. Intriguingly, we observed an increase in the levels of the anti-apoptotic protein Mcl-1. Mefloquine exerts its effects on NPC cells by inducing lysosomal-mediated ROS production, and the heightened expression of Mcl-1 is a consequence of ROS generation in mefloquine-treated NPC cells. The combination of an Mcl-1 inhibitor with mefloquine synergistically inhibits NPC growth in mice without causing substantial toxicity. These findings demonstrate the effectiveness and limited toxicity of mefloquine as a monotherapy and in combination with an Mcl-1 inhibitor. Our research underscores the promise of the mefloquine and Mcl-1 inhibitor combination as a potential treatment for NPC. Additionally, the elevation of Mcl-1 is a compensatory response in cells exposed to oxidative stress, offering a potential target to overcome resistance induced by pro-oxidant therapies.

Shaoyao decoction improves damp-heat colitis by activating the AHR/IL-22/STAT3 pathway through tryptophan metabolism driven by gut microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: The efficacy of Shaoyao Decoction (SYD), a traditional Chinese medicine prescription, in treating damp-heat colitis is established, but its underlying mechanism remains to be elucidated. AIM OF THE STUDY: Our study aims to investigate the effect and mechanism of action of SYD in treating damp-heat colitis. MATERIALS AND METHODS: A mouse model of damp-heat colitis was induced and treated with SYD via gavage for seven days. The therapeutic efficacy of SYD was assessed through clinical indicators and histopathological examinations. The inflammatory factors and oxidative stress parameters were detected by ELISA and biochemical kits. We also analyzed alterations in the gut microbiome via 16 S rRNA gene sequencing and quantified serum indole derivatives using targeted tryptophan metabolomics. Western blotting and immunofluorescence were used to detect the expressions of AHR, CYP1A1, STAT3 and tight junction (TJ) proteins. The ELISA kit was utilized to detect the content of antibacterial peptides (Reg3ß and Reg3γ) in colon. The immunohistochemistry was employed to detect the expressions of proliferating cell nuclear antigen (PCNA) protein. RESULTS: SYD effectively alleviated symptoms in mice with damp-heat colitis, including body weight loss, shortened colon, elevated DAI, enlarged spleen, and damage to the intestinal mucosa. SYD notably reduced IL-6, TNF-α, IL-1ß and MDA levels in colon tissues, while increasing IL-10 and T-AOC levels. Furthermore, SYD mitigated gut microbiota disturbance, restored microbial tryptophan metabolite production (such as IA, IAA, and IAld), notably increased the protein levels of AHR, CYP1A1 and p-STAT3 in colon tissue, and elevated the IL-22 level. Moreover, the expression levels of Reg3ß, Reg3γ, occludin, ZO-1 and PCNA were increased in SYD group. CONCLUSION: Our study showed that SYD ameliorates damp-heat colitis by restructuring gut microbiota structure, enhancing the metabolism of tryptophan associated with gut microbiota to activate the AHR/IL-22/STAT3 pathway, thereby recovering damaged intestinal mucosa. This research offers novel insights into the therapeutic mechanisms of SYD on damp-heat colitis.

Analyzing ozone formation sensitivity in a typical industrial city in China: Implications for effective source control in the chemical transition regime.

Volatile organic compounds (VOCs) play a major role in O3 formation in urban environments. However, the complexity in the emissions of VOCs and nitrogen oxides (NOx) in industrial cities has made it challenging to identify the key factors influencing O3 formation. This study used observation-based-model (OBM) to analyze O3 sensitivities to VOCs and NOx during summer in a typical industrial city in China. The OBM model results were coupled with a receptor model to analyze the sources of O3. Higher concentrations of O3 precursors were observed during polluted periods indicating that precursor accumulation contributed to the higher maxima of the net ozone formation rate and HOx concentrations. Analyses of ROx· budgets and relative incremental reactivity (RIR) indicated that O3 production is in a chemical transition regime and was sensitive to both VOCs and NOx. Results from Positive Matrix Factorization (PMF) analysis indicated that gasoline vehicle emissions, industrial processes, and coal combustion were major sources of O3 precursors. The sensitivities of O3 production to these sources depend on if both VOC and NOx sensitivities are considered. If only VOCs sensitivity is considered, in contrast, the contribution of anthropogenic sources to O3 production was significantly underestimated. This study highlights the importance of accounting for both VOCs and NOx sensitivities when O3 chemistry is in a transition regime in O3 production attribution studies.

TIMELESS promotes reprogramming of glucose metabolism in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC), the predominant malignancy of the oral cavity, is characterized by high incidence and low survival rates. Emerging evidence suggests a link between circadian rhythm disruptions and cancer development. The circadian gene TIMELESS, known for its specific expression in various tumors, has not been extensively studied in the context of OSCC. This study aims to explore the influence of TIMELESS on OSCC, focusing on cell growth and metabolic alterations. METHODS: We analyzed TIMELESS expression in OSCC using western blot, immunohistochemistry, qRT-PCR, and data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE). The role of TIMELESS in OSCC was examined through clone formation, MTS, cell cycle, and EdU assays, alongside subcutaneous tumor growth experiments in nude mice. We also assessed the metabolic impact of TIMELESS by measuring glucose uptake, lactate production, oxygen consumption, and medium pH, and investigated its effect on key metabolic proteins including silent information regulator 1 (SIRT1), hexokinase 2 (HK2), pyruvate kinase isozyme type M2 (PKM2), recombinant lactate dehydrogenase A (LDHA) and glucose transporter-1 (GLUT1). RESULTS: Elevated TIMELESS expression in OSCC tissues and cell lines was observed, correlating with reduced patient survival. TIMELESS overexpression enhanced OSCC cell proliferation, increased glycolytic activity (glucose uptake and lactate production), and suppressed oxidative phosphorylation (evidenced by reduced oxygen consumption and altered pH levels). Conversely, TIMELESS knockdown inhibited these cellular and metabolic processes, an effect mirrored by manipulating SIRT1 levels. Additionally, SIRT1 was positively associated with TIMELESS expression. The expression of SIRT1, HK2, PKM2, LDHA and GLUT1 increased with the overexpression of TIMELESS levels and decreased with the knockdown of TIMELESS. CONCLUSION: TIMELESS exacerbates OSCC progression by modulating cellular proliferation and metabolic pathways, specifically by enhancing glycolysis and reducing oxidative phosphorylation, largely mediated through the SIRT1 pathway. This highlights TIMELESS as a potential target for OSCC therapeutic strategies.

Evolution of dislocation substructures in metals via high-strain-rate nanoindentation.

Deformation at high strain rates often results in high stresses on many engineering materials, potentially leading to catastrophic failure without proper design. High-strain-rate mechanical testing is thus needed to improve the design of future structural materials for a wide range of applications. Although several high-strain-rate mechanical testing techniques have been developed to provide a fundamental understanding of material responses and microstructural evolution under high-strain-rate deformation conditions, these tests are often very time consuming and costly. In this work, we utilize a high-strain-rate nanoindentation testing technique and system in combination with transmission electron microscopy to reveal the deformation mechanisms and dislocation substructures that evolve in pure metals from low (10-2 s-1) to very high indentation strain rates (104 s-1), using face-centered cubic aluminum and body-centered cubic molybdenum as model materials. The results help to establish the conditions under which micro- and macro-scale tests can be compared with validity and also provide a promising pathway that could lead to accelerated high-strain-rate testing at substantially reduced costs.

Real-time computer-generated integral imaging light field displays: revisiting the point retracing rendering method from a signal processing perspective.

Integral imaging light field displays (InIm-LFDs) can provide realistic 3D images by showing an elemental image array (EIA) under a lens array. However, it is always challenging to computationally generate an EIA in real-time with entry-level computing hardware because the current practice that projects many viewpoints to the EIA induces heavy computations. This study discards the viewpoint-based strategy, revisits the early point retracing rendering method, and proposes that InIm-LFDs and regular 2D displays share two similar signal processing phases: sampling and reconstructing. An InIm-LFD is demonstrated to create a finite number of static voxels for signal sampling. Each voxel is invariantly formed by homogeneous pixels for signal reconstructing. We obtain the static voxel-pixel mapping through arbitrarily accurate raytracing in advance and store it as a lookup table (LUT). Our EIA rendering method first resamples input 3D data with the pre-defined voxels and then assigns every voxel's value to its homogeneous pixels through the LUT. As a result, the proposed method reduces the computational complexity by several orders of magnitude. The experimental rendering speed is as fast as 7 to 10 ms for a full-HD EIA frame on an entry-level laptop. Finally, considering a voxel may not be perfectly integrated by its homogeneous pixels, called the sampling error, the proposed and conventional viewpoint-based methods are analyzed in the Fourier domain. We prove that even with severe sampling errors, the two methods negligibly differ in the output signal's frequency spectrum. We expect the proposed method to break the long-standing tradeoff between rendering speed, accuracy, and system complexity for computer-generated integral imaging.

Compact dual-focal augmented reality head-up display using a single picture generation unit with polarization multiplexing.

The augmented reality head-up display (AR-HUD) attracts increasing attention. It features multiple focal planes to display basic and AR information, as well as a wider field of view (FOV). Using two picture generation units (PGUs) to create dual-focal AR-HUDs leads to expanded size, increased cost, and reduced reliability. Thus, we previously proposed an improved solution by dividing one PGU into two partitions that were separately imaged into two virtual images with an optical relay system. However, the resolution of the PGU was halved for either virtual image. Regarding the drawbacks, this paper proposes a dual-focal AR-HUD using one PGU and one freeform mirror. Either virtual image utilizes the full resolution of the PGU through polarization-multiplexing. By performing optical design optimization, high image quality, except for the distortion, is achieved in an eyebox of 130 by 60 mm for far (10 m, 13° by 4°) and near (2.5 m, 10° by 1°) images. Next, we propose a distortion correction method by directly inputting the distorted but clear images acquired in the design stage into the real HUD with an inversed optical path. The proposed optical architecture enables a compact system volume of 9.5 L, close to traditional single-focal HUDs. Finally, we build an AR-HUD prototype, where a polarizing reflective film and a twisted nematic liquid crystal cell achieve polarization-multiplexing. The expected image quality of the two virtual images is experimentally verified.

Lonicerae Japonicae Caulis: a review of its research progress of active metabolites and pharmacological effects.

Lonicerae Japonicae Caulis is the aboveground stem part of the Lonicera Japonica Thunb, which belongs to the medicine food homology species in China. It has the effects of clearing away heat, toxic material, dredging wind and unblocking collaterals. Modern research shows that it contains various active metabolites and a wide range of pharmacological effects, which is of great research and clinical application value. It mainly contains organic acids, volatile oils, flavonoids, triterpenes, triterpene saponins and other active metabolites. Its pharmacological effects mainly include anti-inflammatory, antibacterial, antitumor, antioxidant, and repairing bone and soft tissue. Based on the literature reports in recent years, the active metabolites, pharmacological effects and mechanisms of Lonicerae Japonicae Caulis were sorted out and summarized. It lays a foundation for explaining the efficacy material basis and application value of Lonicerae Japonicae Caulis. It aims to provide a reference for the in-depth research, development and utilization of Lonicerae Japonicae Caulis.

Heteroatom-boron-heteroatom-doped π-conjugated systems: structures, synthesis and photofunctional properties.

The potency of heteroatom-doping in reshaping optoelectronic properties arises from the distinct electronegativity variations between heteroatoms and carbon atoms. By incorporating two heteroatoms with differing electronegativities (e.g., B = N), not only is the architectural coherence of π-conjugated systems retained, but also dipolar traits are introduced, accompanied by unique intermolecular interactions absent in their all-carbon analogs. Another burgeoning doping strategy, featuring the heteroatom-boron-heteroatom motif (X-B-X, where X = N, O), has captured growing attention. This configuration's coexistence of the boron-heteroatom unit and an isolated heteroatom stimulates mutual modulation in the dipole of the boron-heteroatom unit and the heteroatom's electronegativity. In this Feature article, we present an encompassing survey of XBX-doped π-conjugated systems, elucidating how the integration of the X-B-X unit induces transformative structural and property changes within π-conjugated systems.

EGCG-LYS Fibrils-Mediated CircMAP2K2 Silencing Decreases the Proliferation and Metastasis Ability of Gastric Cancer Cells in Vitro and in Vivo.

Aberrant expression of circular RNAs (circRNAs) has been reported to play an important biological regulatory role in gastric cancer (GC). For the purpose of silencing cancer-related genes, a new approach for cancer treatment using nanocarriers to deliver siRNA has been proposed. In this study, abundantly expressed circMAP2K2 (hsa_circRNA_102415) is identified in GC cells. CircMAP2K2 regulates the PCBP1/GPX1 axis through proteasome-mediated degradation, which further mediates the activation of the AKT/GSK3ß/epithelial-to-mesenchymal transition (EMT) signaling pathway and enhances the proliferation and metastatic ability of GC cells. To establish novel GC treatment, epigallocatechin-3-gallate-lysozyme (EGCG-LYS) fibrils are synthesized, and in vitro experiments demonstrate that EGCG-LYS has a higher siRNA delivery efficiency than Lipofectamine 2000 (lipo2000), which effectively silences the expression of circMAP2K2. Further studies show that EGCG-LYS carrying siRNA can successfully achieve lysosome escape, which allows it to be located in the cytoplasm to achieve post-transcriptional gene silencing. In addition, EGCG-LYS carrying si-circMAP2K2 has good circulating stability, excellent biosafety and antitumor ability in vivo. The EGCG-LYS fibrils delivery system provides a new tool and approach for the treatment of GC.

FeS as excellent co-activator driving nano calcium peroxide oxidation for contaminants degradation: Performance and mechanisms.

In this study, ferrous sulfide (FeS) was introduced to nano calcium peroxide (nCP)/Fe(III) system to facilitate the generation of Fe(II), more than 90% of naphthalene (NAP) could be removed at a wide pH range of 3-9. As a heterogeneous reductant, FeS could mitigate competitive reactions with reactive oxygen species (ROS), which favored the NAP degradation. As evidenced by scavenging experiments, HO• was the major ROS contributing to NAP degradation. The role of sulfur species (S2-, SO32-, and S2O32-) in nCP/Fe(III) system was investigated with S2O32- showing the preferable reactivity in Fe(III) reduction. In addition, the surface-bound HO• and surface Fe(II) were detected and the role of them on NAP degradation was revealed and concluded that both dissolved and surface Fe(II) contributed to NAP degradation, whereas surface-bound HO• was not superior to solution HO• in degrading NAP. Furthermore, nCP/Fe(III)/FeS system showed high feasibility to different solution matrixes and various types of water as well as the broad-spectrum reactivity to other toxic organic pollutants, exhibiting promise for practical application to remediate complex contaminants.

[Revealing Driving Factors of Urban O3 Based on Explainable Machine Learning].

Driven by precursor emissions, meteorological conditions, and other factors, atmospheric ozone (O3) has become the main pollutant affecting urban air quality in summer. The current deductive models driven by physical and chemical mechanisms require a large number of parameters for the analysis of O3 pollution, and the calculation timeliness is poor. The data-driven inductive models are efficient but have problems such as poor explanation. In this study, an explainable model of data-driven Correlation-ML-SHAP was established to reveal the strongly correlated influencing factors of O3 concentration. Additionally, the machine learning ML module coupled with the explainable SHAP module was used to calculate the contributions of driving factors to O3 concentration, so as to realize the quantitative analysis of driving factors. The O3 pollution process in the summer of 2021 in Jincheng City was used as an example to carry out the application research. The results showed that the Correlation-ML-SHAP model could reveal and use strong driving factors to simulate O3 concentration and quantify influence contribution, and the ML module used the XGBoost model to achieve the best simulation accuracy. Air temperature, solar radiation, relative humidity, and precursor emission level were the strong driving factors of O3 pollution in Jincheng City in summer 2021, and the contribution weights were 32.1%, 21.3%, 16.5%, and 15.6%. The contribution weights of air temperature, solar radiation, and precursor emission level increased by 3.4%, 1.2%, and 1.2% on polluted days, respectively, and the contribution weights of precursor emission level rose to third place on polluted days. Each driving factor had a nonlinear interaction effect on O3 concentration. When the air temperature exceeded 24℃, or the relative humidity was lower than 70%, there was a 94.9% and 94.1% probability of positive contribution to O3 pollution, respectively. Under such meteorological conditions, ρ(NO2) exceeded 9 µg·m-3, or ρ(CO) exceeded 0.7 mg·m-3, and there was a 94.9% and 99.3% probability of positive contribution to O3 pollution, respectively. The southeast wind speed was lower than 5.8 m·s-1, or the south wind speed was lower than 5.3 m·s-1, both of which contributed positively to O3 pollution. The model quantitatively analyzed the influence contribution of various driving factors on urban O3 concentration, which could provide a basis for the prevention and control of urban atmospheric O3 pollution in summer.

Multiple Helicenes Defected by Heteroatoms and Heptagons with Narrow Emissions and Superior Photoluminescence Quantum Yields.

The incorporation of heteroatoms and/or heptagons as the defects into helicenes expands the variety of chiroptical materials with novel properties. However, it is still challenging to construct novel boron-doped heptagon-containing helicenes with high photoluminescence quantum yields (PLQYs) and narrow full-width-at-half-maximum (FWHM) values. We report an efficient and scalable synthesis of a quadruple helicene 4Cz-NBN with two nitrogen-boron-nitrogen (NBN) units and a double helicene 4Cz-NBN-P1 bearing two NBN-doped heptagons, the latter could be formed via a two-fold Scholl reaction of the former. The helicenes 4Cz-NBN and 4Cz-NBN-P1 exhibit excellent PLQYs up to 99 % and 65 % with narrow FWHM of 24 nm and 22 nm, respectively. The emission wavelengths are tunable via stepwise titration experiments of 4Cz-NBN-P1 toward fluoride, enabling distinguished circularly polarized luminescence (CPL) from green, orange (4Cz-NBN-P1-F1) to yellow (trans/cis-4Cz-NBN-P1-F2) with near-unity PLQYs and broader circular dichroism (CD) ranges. The five structures of the aforementioned four helicenes were confirmed by single crystal X-ray diffraction analysis. This work provides a novel design strategy for construction of non-benzenoid multiple helicenes exhibiting narrow emissions with superior PLQYs.

Fast shadow casting algorithm in analytical polygon-based computer-generated holography.

Shadow casting is essential in computer graphics, which can significantly enhance the reality of rendered images. However, shadow casting is rarely studied in polygon-based computer-generated holography (CGH) because state-of-art triangle-based occlusion handling methods are too complicated for shadow casting and unfeasible for complex mutual occlusion handling. We proposed a novel drawing method based on the analytical polygon-based CGH framework and achieved Z-buffer-based occlusion handling instead of the traditional Painter's algorithm. We also achieved shadow casting for parallel and point light sources. Our framework can be generalized to N-edge polygon (N-gon) rendering and accelerated using CUDA hardware, by which the rendering speed can be significantly enhanced.

Exosomal circSPIRE1 mediates glycosylation of E-cadherin to suppress metastasis of renal cell carcinoma.

Metastasis is the main cause of mortality in renal cell carcinoma (RCC). Circular RNAs (circRNAs) involvement in RCC metastasis has been described, although the underlying mechanisms remain unknown. We evaluated recurring lung-metastasis cases using patient-derived xenograft models and isolated a highly metastatic clone. CircSPIRE1 was identified as a metastasis-inhibiting circRNA in clinical cohort and xenograft models. Mechanistically, circSPIRE1 suppressed mesenchymal state through regulating ELAV like RNA binding protein 1-mRNA binding, and upregulating polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) and KH domain RNA binding protein (QKI) expression. GALNT3 promoted glycosylation and cytomembrane localization of E-cadherin. QKI formed a positive feedback loop to enhance circSPIRE1 expression. Meanwhile, exosomal circSPIRE1 suppressed angiogenesis and vessel permeability. Our work reveals a non-canonical route for circRNAs in RCC to suppress metastasis. Furthermore, a nanomedicine consisting of circSPIRE1 plasmid suppressed metastasis formation. In conclusion, circSPIRE1 may be a predictor of metastasis and a potential therapeutic target of metastatic RCC.

Universal cover-time distributions of random motion in bounded granular gases.

The exhaustive random exploration of a complex domain is a fundamental issue in many natural, social, and engineering systems. The key characterizing quantity is the cover time, which is the time to visit every site in the system. One prototypical experimental platform is the confined granular gas, where the random motion of granular particles mimics the wandering of random walkers in a confined region. Here, we investigate the cover-time distribution of the random motion of tracer particles in granular gases confined in four containers to account for different boundary and angle effects and examine whether the cover time of the heterogeneous random motion of the granular gases can be rescaled into the universal Gumbel distribution according to a recent theory [Dong et al., arXiv:2210.05122 (2022)]. It is found that for long cover times, the experimental results are in full accord, while for short cover times, the agreement is reasonable, with noticeable deviations that can be attributed to spatial correlations of the sites in the covering process. Our results, thus, call for further theoretical investigations in order to take into full account these nonideal issues.

Drought-induced recruitment of specific root-associated bacteria enhances adaptation of alfalfa to drought stress.

Drought is a major abiotic stress that threatens crop production. Soil microbiomes are thought to play a role in enhancing plant adaptation to various stresses. However, it remains unclear whether soil microbiomes play a key role when plants are challenged by drought and whether different varieties are enriched with specific bacteria at the rhizosphere. In this study, we measured changes in growth phenotypes, physiological and biochemical characteristics of drought-tolerant alfalfa (AH) and drought-sensitive (QS) under sterilized and unsterilized soil conditions with adequate watering and with drought stress, and analyzed the rhizosphere bacterial community composition and changes using 16S rRNA high-throughput sequencing. We observed that the unsterilized treatment significantly improved the growth, and physiological and biochemical characteristics of alfalfa seedlings under drought stress compared to the sterilized treatment. Under drought stress, the fresh and dry weight of seedlings increased by 35.24, 29.04, and 11.64%, 2.74% for unsterilized AH and QS, respectively, compared to sterilized treatments. The improvement was greater for AH than for QS. AH and QS recruited different rhizosphere bacteria when challenged by drought. Interestingly, under well-watered conditions, the AH rhizosphere was already rich in drought-tolerant bacterial communities, mainly Proteobacteria and Bacteroidetes, whereas these bacteria started to increase only when QS was subjected to drought. When drought stress was applied, AH was enriched with more drought-tolerant bacteria, mainly Acidobacteria, while the enrichment was weaker in QS rhizosphere. Therefore, the increase in drought tolerance of the drought-tolerant variety AH was greater than that of the drought-sensitive variety QS. Overall, this study confirmed the key role of drought-induced rhizosphere bacteria in improving the adaptation of alfalfa to drought stress, and clarified that this process is significantly related to the variety (genotype). The results of this study provide a basis for improving drought tolerance in alfalfa by regulating the rhizosphere microbiome.

Universal cover-time distribution of heterogeneous random walks.

The cover-time problem, i.e., the time to visit every site in a system, is one of the key issues of random walks with wide applications in natural, social, and engineered systems. Addressing the full distribution of cover times for random walk on complex structures has been a long-standing challenge and has attracted persistent efforts. Usually it is assumed that the random walk is noncompact, to facilitate theoretical treatments by neglecting the correlations between visits. The known results are essentially limited to noncompact and homogeneous systems, where different sites are on an equal footing and have identical or close mean first-passage times, such as random walks on a torus. In contrast, realistic random walks are prevailingly heterogeneous with diversified mean first-passage times. Does a universal distribution still exist? Here, by considering the most general situations of noncompact random walks, we uncover a generalized rescaling relation for the cover time, exploiting the diversified mean first-passage times that have not been accounted for before. This allows us to concretely establish a universal distribution of the rescaled cover times for heterogeneous noncompact random walks, which turns out to be the Gumbel universality class that is ubiquitous for a large family of extreme value statistics. Our analysis is based on the transfer matrix framework, which is generic in that, besides heterogeneity, it is also robust against biased protocols, directed links, and self-connecting loops. The finding is corroborated with extensive numerical simulations of diverse heterogeneous noncompact random walks on both model and realistic topological structures. Our technical ingredient may be exploited for other extreme value or ergodicity problems with nonidentical distributions.

UWB Localization Based on Improved Robust Adaptive Cubature Kalman Filter.

Aiming at the problems of Non-Line-of-Sight (NLOS) observation errors and inaccurate kinematic model in ultra-wideband (UWB) systems, this paper proposed an improved robust adaptive cubature Kalman filter (IRACKF). Robust and adaptive filtering can weaken the influence of observed outliers and kinematic model errors on filtering, respectively. However, their application conditions are different, and improper use may reduce positioning accuracy. Therefore, this paper designed a sliding window recognition scheme based on polynomial fitting, which can process the observation data in real-time to identify error types. Simulation and experimental results indicate that compared to the robust CKF, adaptive CKF, and robust adaptive CKF, the IRACKF algorithm reduces the position error by 38.0%, 45.1%, and 25.3%, respectively. The proposed IRACKF algorithm significantly improves the positioning accuracy and stability of the UWB system.