Organic solvents-free and ambient-pressure drying melamine formaldehyde resin aerogels with homogeneous structures, outstanding mechanical strength and flame retardancy.

Atmospheric drying method for fabricating aerogels is considered the most promising way for casting aerogels on a large scale. However, the organic solvent exchange, remaining environmental pollution risk, is a crucial step in mitigating the impact of surface tension during the atmospheric drying process, especially for wet gel formed through the alkoxy-derived sol-gel process, such as melamine-formaldehyde resin (MF) aerogel. Herein, a tough polymer-assisted in situ polymerization was proposed to fabricate MF resin aerogel with a combination of mechanical toughness and strength, enabling it to withstand the capillary force during water evaporation. The monolithic MF resin aerogel through the sol-gel method can be directly prepared without additional network strengthening or organic solvent exchange. The resulting MF resin aerogel exhibits a homogeneous as well as hierarchical structure with macropores and mesopores (~6 µm and ~5 nm), high compressive modulus of 31.8 MPa, self-extinguishing property, and high-temperature thermal insulation with 97 % heat decrease for butane flame combustion. This work presents a straightforward and environmentally friendly method for fabricating MF resin aerogels with nanostructures and excellent performance in open conditions, exhibiting various applications.

Self-evolutionary recycling of flame-retardant polyurethane foam enabled by controllable catalytic cleavage.

Polyurethane (PU) foams, pivotal in modern life, face challenges suh as fire hazards and environmental waste burdens. The current reliance of PU on potentially ecotoxic halogen-/phosphorus-based flame retardants impedes large-scale material recycling. Here, our demonstrated controllable catalytic cracking strategy, using cesium salts, enables self-evolving recycling of flame-retardant PU. The incorporation of cesium citrates facilitates efficient urethane bond cleavage at low temperatures (160 °C), promoting effective recycling, while encouraging pyrolytic rearrangement of isocyanates into char at high temperatures (300 °C) for enhanced PU fire safety. Even in the absence of halogen/phosphorus components, this foam exhibits a substantial increase in ignition time (+258.8%) and a significant reduction in total smoke release (-79%). This flame-retardant foam can be easily recycled into high-quality polyol under mild conditions, 60 °C lower than that for the pure foam. Notably, the trace amounts of cesium gathered in recycled polyols stimulate the regenerated PU to undergo self-evolution, improving both flame-retardancy and mechanical properties. Our controllable catalytic cracking strategy paves the way for the self-evolutionary recycling of high-performance firefighting materials.

Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Population genomics and epigenomics of Spirodela polyrhiza provide insights into the evolution of facultative asexuality.

Many plants are facultatively asexual, balancing short-term benefits with long-term costs of asexuality. During range expansion, natural selection likely influences the genetic controls of asexuality in these organisms. However, evidence of natural selection driving asexuality is limited, and the evolutionary consequences of asexuality on the genomic and epigenomic diversity remain controversial. We analyzed population genomes and epigenomes of Spirodela polyrhiza, (L.) Schleid., a facultatively asexual plant that flowers rarely, revealing remarkably low genomic diversity and DNA methylation levels. Within species, demographic history and the frequency of asexual reproduction jointly determined intra-specific variations of genomic diversity and DNA methylation levels. Genome-wide scans revealed that genes associated with stress adaptations, flowering and embryogenesis were under positive selection. These data are consistent with the hypothesize that natural selection can shape the evolution of asexuality during habitat expansions, which alters genomic and epigenomic diversity levels.

Limit state equation and failure pressure prediction model of pipeline with complex loading.

Assessing failure pressure is critical in determining pipeline integrity. Current research primarily concerns the buckling performance of pressurized pipelines subjected to a bending load or axial compression force, with some also looking at the failure pressure of corroded pipelines. However, there is currently a lack of limit state models for pressurized pipelines with bending moments and axial forces. In this study, based on the unified yield criterion, we propose a limit state equation for steel pipes under various loads. The most common operating loads on buried pipelines are bending moment, internal pressure, and axial force. The proposed limit state equation for intact pipelines is based on a three-dimensional pipeline stress model with complex load coupling. Using failure data, we investigate the applicability of various yield criteria in assessing the failure pressure of pipelines with complex loads. We show that the evaluation model can be effectively used as a theoretical solution for assessing the failure pressure in such circumstances and for selecting appropriate yield criteria based on load condition differences.

Unveiling the intratumoral microbiota within cancer landscapes.

Recent advances in cancer research have unveiled a significant yet previously underappreciated aspect of oncology: the presence and role of intratumoral microbiota. These microbial residents, encompassing bacteria, fungi, and viruses within tumor tissues, have been found to exert considerable influence on tumor development, progression, and the efficacy of therapeutic interventions. This review aims to synthesize these groundbreaking discoveries, providing an integrated overview of the identification, characterization, and functional roles of intratumoral microbiota in cancer biology. We focus on elucidating the complex interactions between these microorganisms and the tumor microenvironment, highlighting their potential as novel biomarkers and therapeutic targets. The purpose of this review is to offer a comprehensive understanding of the microbial dimension in cancer, paving the way for innovative approaches in cancer diagnosis and treatment.

New Insights into Tetraplosphaeriaceae Based on Taxonomic Investigations of Bambusicolous Fungi and Freshwater Fungi.

Species within Tetraplosphaeriaceae have been frequently documented in recent years with the extensive investigations of microfungi along a latitudinal gradient from north to south in the Asian/Australian region. Both bamboo substrates and freshwater habitats serve as extensive reservoirs, hosting a rich diversity of fungi that exhibit broad geographical distributions. The most common fungi in these two environments are generally distributed in distinct families. However, our statistics have revealed an intriguingly distinct preference of Tetraplosphaeriaceae species for inhabiting both bamboo substrates and freshwater habitats. The genera Pseudotetraploa (100%) and Triplosphaeria (100%) exhibit a strong preference, followed by Shrungabeeja (71%) and Quadricrura (67%). Our taxonomic and phylogenetic study of microfungi in southern China have identified four additional novel species, viz., Aquatisphaeria bambusae sp. nov., Pseudotetraploa phyllostachydis sp. nov., Pseudotetraploa yangjiangensis sp. nov., and Tetraploa submersa sp. nov. from bamboo substrates and freshwater habitats. In addition, Aquatisphaeria thailandica has previously been documented from freshwater habitats in Thailand; however, we have once again isolated this species from decaying bamboo substrates in Guangdong, China. The new findings substantiate our hypothesis that the preference of Tetraplosphaeriaceae species for colonizing bamboo substrates and freshwater habitats will be more evident through more extensive investigations conducted in such environments.

Cuproptosis: unveiling a new frontier in cancer biology and therapeutics.

Copper plays vital roles in numerous cellular processes and its imbalance can lead to oxidative stress and dysfunction. Recent research has unveiled a unique form of copper-induced cell death, termed cuproptosis, which differs from known cell death mechanisms. This process involves the interaction of copper with lipoylated tricarboxylic acid cycle enzymes, causing protein aggregation and cell death. Recently, a growing number of studies have explored the link between cuproptosis and cancer development. This review comprehensively examines the systemic and cellular metabolism of copper, including tumor-related signaling pathways influenced by copper. It delves into the discovery and mechanisms of cuproptosis and its connection to various cancers. Additionally, the review suggests potential cancer treatments using copper ionophores that induce cuproptosis, in combination with small molecule drugs, for precision therapy in specific cancer types.

Bio-based phytic acid/amino acid complex coating for antimicrobial and flame-retardant cotton fabrics.

Here, a novel multifunctional coating containing bio-based phytic acid (PA), L-glutamic acid (L-Glu), and trimesoyl chloride (TMC) is constructed by a simple soaking strategy, giving cotton fabrics excellent flame retardancy, washability, and antibacterial properties. The coating layer on the cotton surface was prepared via the electrostatic and hydrogen bonding between PA and L-Glu, accompanied by the interface polymerization between PA, L-Glu, and TMC. Among them, the limiting oxygen index value of the treated cotton fabrics (C2 and C2-TMC) was as high as 40 %. During the vertical flammability test, both C2 and C2-TMC cotton showed self-extinguished behavior with a short damaged length (≤50 mm). Remarkably, the LOI of C2-TMC sustained a high value (30 %) even after 300 laundering cycles, maintaining its self-extinguishing behavior in the vertical combustion test. Additionally, in the cone calorimetry test, peak heat release rate and total heat release of treated cotton were lower than control cotton. Surprisingly, after 30 or 60 laundering cycles, the C2-TMC cotton exhibited excellent antibacterial activity against Escherichia coli, Staphylococcus aureus, and Candida albicans due to the continuous exposure of PA and L-Glu. Moreover, the coating layer on the cotton surface had little impact on the mechanical properties and feel of the fabric.

Emission of CO2 and its related carbonate system dynamics in a hotspot area during winter and summer: The Changjiang River estuary.

The carbonate chemistry in river-dominated marginal seas is highly heterogeneous, and there is ongoing debate regarding the definition of atmospheric CO2 source or sink. On this basis, we investigated the carbonate chemistry and air-sea CO2 fluxes in a hotspot estuarine area: the Changjiang Estuary during winter and summer. The spatial characteristics of the carbonate system were influenced by water mixing of three end-members in winter, including the Changjiang freshwater with low total alkalinity (TA) concentration, the less saline Yellow Sea Surface Water with high TA, and the saline East China Sea (ECS) offshore water with moderate TA. While in summer with increased river discharge, the carbonate system was regulated by simplified two end-member mixing between the Changjiang freshwater and the ECS offshore water. By performing the end-member mixing model on DIC variations in the river plume region, significant biological addition of DIC was found in winter with an estimation of -120 ± 113 µmol kg-1 caused by wintertime organic matter remineralization from terrestrial source. While this biological addition of DIC shifted to DIC removal due to biological production in summer supported by the increased nutrient loading from Changjiang River. The pCO2 dynamics in the river plume and the ECS offshore were both subjected to physical mixing of freshwater and seawater, whether in winter and summer. In the inner estuary without horizontal mixing, the pCO2 dynamics were mainly influenced by biological uptake in winter and temperature in summer. The inner estuary, the river plume, and the ECS offshore were sources of atmospheric CO2, with their contributions varying seasonally. The Changjiang runoff enhanced the inner estuary's role as a CO2 source in summer, while intensive biological uptake reduced the river plume's contribution.

[Synthesis and tissue distribution of bufadienolides in Bufo bufo gargarizans].

This study explored the biosynthesis of bufadienolides(BDs) in Bufo bufo gargarizans to solve the dilemma of the decreasing resources of B. bufo gargarizans and provide a theoretical basis for the sustainable utilization of the resources. Ultra-high performance liquid chromatography-Orbitrap-mass spectrometry(UHPLC-Orbitrap-MS) was employed to detect the synthesis sites of BDs in B. bufo gargarizans, and the results were verified by desorption electrospray ionization-mass spectrometry imaging(DESI-MSI) and homogenate incubation experiments. BDs in B. bufo gargarizans had the highest content in the liver and the highest concentration in the gallbladder, in addition to the parotid gland and skin, which suggested that the liver could synthesize BDs. The results of DESI-MSI also showed that BDs were mainly enriched in the liver rather than the immature parotid gland. The incubation experiment of liver homogenates demonstrated the liver of B. bufo gargarizans had the ability to synthesize BDs. This study showed that the liver was a major organ for the synthesis of BDs in B. bufo gargarizans during metamorphosis, development, and growth, which provided strong theoretical support for the biosynthesis of BDs and the sustainable utilization of B. bufo gargarizans resources.

Biomimetic Nanoporous Transparent Universal Fire-Resistant Coatings.

The inherent flammability of most polymeric materials poses a significant fire hazard, leading to substantial property damage and loss of life. A universal flame-retardant protective coating is considered as a promising strategy to mitigate such risks; however, simultaneously achieving high transparency of the coatings remains a great challenge. Here, inspired by the moth eye effect, we designed a nanoporous structure into a protective coating that leverages a hydrophilic-hydrophobic interactive assembly facilitated by phosphoric acid protonated amino siloxane. The coating demonstrates robust adhesion to a diverse range of substrates, including but not limited to fabrics, foams, paper, and wood. As expected, its moth-eye-inspired nanoporous structure conferred a high visible light transparency of >97% and water vapor transmittance of 96%. The synergistic effect among phosphorus (P), nitrogen (N), and silicon (Si) largely enhanced the char-forming ability and restricted the decomposition of the coated substrates, which successfully endowed the coating with high fire-fighting performance. More importantly, for both flexible and rigid substrates, the coated samples all possessed great mechanical properties. This work provides a new insight for the design of protective coatings, particularly focusing on achieving high transparency.

An endogenous promoter LpSUT2 discovered in duckweed: a promising transgenic tool for plants.

Promoters are one of the most critical elements in regulating gene expression. They are considered essential biotechnological tools for heterologous protein production. The one most widely used in plants is the 35S promoter from cauliflower mosaic virus. However, our study for the first time discovered the 35S promoter reduced the expression of exogenous proteins under increased antibiotic stress. We discovered an endogenous strong promoter from duckweed named LpSUT2 that keeps higher initiation activity under antibiotic stress. Stable transformation in duckweed showed that the gene expression of eGFP in the LpSUT2:eGFP was 1.76 times that of the 35S:eGFP at 100 mg.L-1 G418 and 6.18 times at 500 mg.L-1 G418. Notably, with the increase of G418 concentration, the gene expression and the fluorescence signal of eGFP in the 35S:eGFP were weakened, while the LpSUT2:eGFP only changed slightly. This is because, under high antibiotic stress, the 35S promoter was methylated, leading to the gene silencing of the eGFP gene. Meanwhile, the LpSUT2 promoter was not methylated and maintained high activity. This is a previously unknown mechanism that provides us with new insights into screening more stable promoters that are less affected by environmental stress. These outcomes suggest that the LpSUT2 promoter has a high capacity to initiate the expression of exogenous proteins. In conclusion, our study provides a promoter tool with potential application for plant genetic engineering and also provides new insights into screening promoters.

Congener-specific fate and impact of microcystins in the soil-earthworm system.

Microcystins (MCs) have a significant influence on aquatic ecosystems, but little is known about their terrestrial fate and impact. Here, we investigated the fate of two MCs (MC-LR and MC-RR) in the soil-earthworm system, with consideration of their congener-specific impact on earthworm health, soil bacteria, and soil metabolome. Although MCs had little acute lethal effect on earthworms, they caused obvious growth inhibition and setae rupture. Relative to MC-RR, MC-LR exhibited higher bioaccumulation and the resulting dermal lesions and deformation of longitudinal muscles. While the incorporation of both MCs into soils stimulated pathogenic bacteria and depressed oxidative stress tolerant bacteria, the response among soil nitrification and glutathione metabolism differed between the two congeners. The dissipation kinetics of MCs obeyed the first-order model. Earthworms stimulated soil N-cycling enzyme activities, increased the abundance of MC-degrading bacteria, and promoted bacterial metabolic functions related to glutathione metabolism, xenobiotics biodegradation, and metabolism of amino acids that comprise MCs, which accelerated the dissipation of MC-LR and MC-RR by 227% and 82%, respectively. These results provide evidence of significant congener differences in the terrestrial fate and impact of MCs, which will enable a better understanding of their role in mediating soil functions and ecosystem services.

Communication-Efficient Hybrid Federated Learning for E-Health With Horizontal and Vertical Data Partitioning.

Electronic healthcare (e-health) allows smart devices and medical institutions to collaboratively collect patients' data, which is trained by artificial intelligence (AI) technologies to help doctors make diagnosis. By allowing multiple devices to train models collaboratively, federated learning is a promising solution to address the communication and privacy issues in e-health. However, applying federated learning in e-health faces many challenges. First, medical data are both horizontally and vertically partitioned. Since single horizontal federated learning (HFL) or vertical federated learning (VFL) techniques cannot deal with both types of data partitioning, directly applying them may consume excessive communication cost due to transmitting a part of raw data when requiring high modeling accuracy. Second, a naive combination of HFL and VFL has limitations including low training efficiency, unsound convergence analysis, and lack of parameter tuning strategies. In this article, we provide a thorough study on an effective integration of HFL and VFL, to achieve communication efficiency and overcome the above limitations when data are both horizontally and vertically partitioned. Specifically, we propose a hybrid federated learning framework with one intermediate result exchange and two aggregation phases. Based on this framework, we develop a hybrid stochastic gradient descent (HSGD) algorithm to train models. Then, we theoretically analyze the convergence upper bound of the proposed algorithm. Using the convergence results, we design adaptive strategies to adjust the training parameters and shrink the size of transmitted data. The experimental results validate that the proposed HSGD algorithm can achieve the desired accuracy while reducing communication cost, and they also verify the effectiveness of the adaptive strategies.

Multiparametric MRI subregion radiomics for preoperative assessment of high-risk subregions in microsatellite instability of rectal cancer patients: A multicenter study.

BACKGROUND: Microsatellite instability (MSI) is associated with treatment response and prognosis in patients with rectal cancer (RC). However, intratumoral heterogeneity limits MSI testing in patients with RC. We developed a subregion radiomics model based on multiparametric magnetic resonance imaging (MRI) to preoperatively assess high-risk subregions with MSI and predict the MSI status of patients with RC. METHODS: This retrospective study included 475 patients (training cohort, 382; external test cohort, 93) with RC from two participating hospitals between April 2017 and June 2023. In the training cohort, subregion radiomic features were extracted from multiparametric MRI, which included T2-weighted, T1-weighted, diffusion-weighted, and contrast-enhanced T1-weighted imaging. MSI-related subregion radiomic features, classical radiomic features, and clinicoradiological variables were gathered to build five predictive models using logistic regression. Kaplan-Meier survival analysis was conducted to explore the prognostic information. RESULTS: Among the 475 patients (median age, 64 years [interquartile range, IQR: 55-70 years];304 men and 171 women), the prevalence of MSI was 11.16% (53/475). The subregion radiomics model outperformed the classical radiomics and clinicoradiological models in both training (area under the curve [AUC]=0.86, 0.72, and 0.59, respectively) and external test cohorts (AUC=0.83, 0.73, and 0.62, respectively). The subregion-clinicoradiological model combining clinicoradiological variables and subregion radiomic features performed the optimal, with AUCs of 0.87 and 0.85 in the training and external test cohorts, respectively. The 3-year disease-free survival rate of MSI groups predicted based on the model was higher than that of the predicted microsatellite stability (MSS) groups in both patient cohorts (training, P=0.032; external test, P=0.046). CONCLUSIONS: We developed and validated a model based on subregion radiomic features of multiparametric MRI to evaluate high-risk subregions with MSI and predict the MSI status of RC preoperatively, which may assist in individualized treatment decisions and positioning for biopsy.

Arbuscular Mycorrhizal Fungus Alleviates Charged Nanoplastic Stress in Host Plants via Enhanced Defense-Related Gene Expressions and Hyphal Capture.

Contamination of small-sized plastics is recognized as a factor of global change. Nanoplastics (NPs) can readily enter organisms and pose significant ecological risks. Arbuscular mycorrhizal (AM) fungi are the most ubiquitous and impactful plant symbiotic fungi, regulating essential ecological functions. Here, we first found that an AM fungus, Rhizophagus irregularis, increased lettuce shoot biomass by 25-100% when exposed to positively and negatively charged NPs vs control, although it did not increase that grown without NPs. The stress alleviation was attributed to the upregulation of gene expressions involving phytohormone signaling, cell wall metabolism, and oxidant scavenging. Using a root organ-fungus axenic growth system treated with fluorescence-labeled NPs, we subsequently revealed that the hyphae captured NPs and further delivered them to roots. NPs were observed at the hyphal cell walls, membranes, and spore walls. NPs mediated by the hyphae were localized at the root epidermis, cortex, and stele. Hyphal exudates aggregated positively charged NPs, thereby reducing their uptake due to NP aggregate formation (up to 5000 nm). This work demonstrates the critical roles of AM fungus in regulating NP behaviors and provides a potential strategy for NP risk mitigation in terrestrial ecosystems. Consequent NP-induced ecological impacts due to the affected AM fungi require further attention.

CAR T treatment beyond cancer: Hope for immunomodulatory therapy of non-cancerous diseases.

Engineering a patient's own T cells to accurately identify and eliminate cancer cells has effectively cured individuals afflicted with previously incurable hematologic cancers. These findings have stimulated research into employing chimeric antigen receptor (CAR) T therapy across various areas within the field of oncology. However, evidence from both clinical and preclinical investigations emphasize the broader potential of CAR T therapy, extending beyond oncology to address autoimmune disorders, persistent infections, cardiac fibrosis, age-related ailments and other conditions. Concurrently, the advent of novel technologies and platforms presents additional avenues for utilizing CAR T therapy in non-cancerous contexts. This review provides an overview of the rationale behind CAR T therapy, delineates ongoing challenges in its application to cancer treatment, summarizes recent findings in non-cancerous diseases, and engages in discourse regarding emerging technologies that bear relevance. The review delves into prospective applications of this therapeutic approach across a diverse range of scenarios. Lastly, the review underscores concerns related to precision and safety, while also outlining the envisioned trajectory for extending CAR T therapy beyond cancer treatment.

Tangshen Formula alleviates inflammatory injury against aged diabetic kidney disease through modulating gut microbiota composition and related amino acid metabolism.

Diabetic kidney disease (DKD) is leading causes and one of the fastest growing causes of chronic kidney disease worldwide, and leads to high morbidity and mortality. Emerging evidences have revealed gut microbiota dysbiosis and related metabolism dysfunction play a dominant role in DKD progression and treatment through modulating inflammation. Our previous studies showed that Tangshen Formula (TSF), a Chinese herbal prescription, exhibited anti-inflammatory effect on DKD, but underlying mechanism that involved gut microbiota and related metabolism in aged model remained obscure. Here, BTBR ob/ob mice were used to establish aged DKD model, and 16S rRNA sequence and untargeted metabolomic analyses were employed to investigate the correlation between colonic microbiota and serum metabolism. The aged ob/ob mice exhibited obvious glomerular and renal tubule injury and kidney function decline in kidney, while TSF treatment significantly attenuated these abnormalities. TSF also exhibited potent anti-inflammatory effect in aged ob/ob mice indicating by reduced proinflammatory factor IL-6 and TNF-α, MCP-1 and COX-2 in serum, kidney and intestine, which suggested the involvement of gut microbiota with TSF effect. The 16S rDNA sequencing of the colonic microbiome and untargeted serum metabolomics analysis revealed significant differences in gut microbiota structure and serum metabolomic profiles between WT and ob/ob mice. Notably, TSF treatment reshaped the structure of gut microbiota and corrected the disorder of metabolism especially tryptophan metabolism and arginine biosynthesis. TSF increased Anaeroplasma and Barnesiella genera and decreased Romboutsia, Akkermansia, and Collinsella genera, and further elevated tryptophan, 5-hydroxyindoleacetate, glutamic acid, aspartate and reduced 4-hydroxy-2-quinolinecarboxylic acid, indole-3-acetic acid, xanthurenic acid, glutamine. Further correlation analysis indicated that disturbed gut microbiota was linked to tryptophan metabolism and arginine biosynthesis to regulate inflammation in aged DKD. Our data revealed that TSF attenuated renal inflammation by modulating gut microbiota and related amino acid metabolism in aged DKD model, highlighting gut microbiota and related metabolism functioned as potential therapeutic target for DKD in elderly patients.

Multiomic study of the protective mechanism of Persicaria capitata (Buch.-Ham. ex D.Don) H.Gross against streptozotocin-induced diabetic nephropathy in Guizhou miniature pigs.

BACKGROUND: Persicaria capitata (Buch.-Ham. ex D.Don) H.Gross (P. capitata, PCB), a traditional drug of the Miao people in China, is potential traditional drug used for the treatment of diabetic nephropathy (DN). PURPOSE: The purpose of this study is to investigate the function of P. capitata and clarify its protective mechanism against DN. METHODS: We induced DN in the Guizhou miniature pig with injections of streptozotocin, and P. capitata was added to the pigs' diet to treat DN. In week 16, all the animals were slaughtered, samples were collected, and the relative DN indices were measured. 16S rRNA sequencing, metagenomics, metabolomics, RNA sequencing, and proteomics were used to explore the protective mechanism of P. capitata against DN. RESULTS: Dietary supplementation with P. capitata significantly reduced the extent of the disease, not only in term of the relative disease indices but also in hematoxylin-eosin-stained tissues. A multiomic analysis showed that two microbes (Clostridium baratii and Escherichia coli), five metabolites (oleic acid, linoleic acid, 4-phenylbutyric acid, 18-ß-glycyrrhetinic acid, and ergosterol peroxide), four proteins (ENTPD5, EPHX1, ARVCF and TREH), four important mRNAs (encoding ENTPD5, EPHX1, ARVCF, and TREH), six lncRNAs (TCONS_00024194, TCONS_00085825, TCONS_00006937, TCONS_00070981, TCONS_00074099, and TCONS_00097913), and two circRNAs (novel_circ_0001514 and novel_circ_0017507) are all involved in the protective mechanism of P. capitata against DN. CONCLUSIONS: Our results provide multidimensional theoretical support for the study and application of P. capitata.