Fasting mimicking diet extends lifespan and improves intestinal and cognitive health.

Caloric restriction is an effective means of extending a healthy lifespan. Fasting mimicking diet (FMD) is a growing pattern of caloric restriction. We found that FMD significantly prolonged the lifespan of prematurely aging mice. In naturally aging mice, FMD improved cognitive and intestinal health. Through a series of behavioral experiments, we found that FMD relieved anxiety and enhanced cognition in aged mice. In the intestine, the FMD cycles enhanced the barrier function, reduced senescence markers, and maintained T cell naïve-memory balance in the lamina propria mucosa. To further explore the causes of immune alterations, we examined changes in the stool microbiota using 16S rRNA sequencing. We found that FMD remodeled gut bacterial composition and significantly expanded the abundance of Lactobacillus johnsonii. Our research revealed that FMD has in-depth investigative value as an anti-aging intervention for extending longevity and improving cognition, intestinal function, and gut microbiota composition.

Microbial metabolite enhances immunotherapy efficacy by modulating T cell stemness in pan-cancer.

The immune checkpoint blockade (ICB) response in human cancers is closely linked to the gut microbiota. Here, we report that the abundance of commensal Lactobacillus johnsonii is positively correlated with the responsiveness of ICB. Supplementation with Lactobacillus johnsonii or tryptophan-derived metabolite indole-3-propionic acid (IPA) enhances the efficacy of CD8+ T cell-mediated αPD-1 immunotherapy. Mechanistically, Lactobacillus johnsonii collaborates with Clostridium sporogenes to produce IPA. IPA modulates the stemness program of CD8+ T cells and facilitates the generation of progenitor exhausted CD8+ T cells (Tpex) by increasing H3K27 acetylation at the super-enhancer region of Tcf7. IPA improves ICB responsiveness at the pan-cancer level, including melanoma, breast cancer, and colorectal cancer. Collectively, our findings identify a microbial metabolite-immune regulatory pathway and suggest a potential microbial-based adjuvant approach to improve the responsiveness of immunotherapy.

L-arginine metabolism ameliorates age-related cognitive impairment by Amuc_1100-mediated gut homeostasis maintaining.

Aging-induced cognitive impairment is associated with a loss of metabolic homeostasis and plasticity. An emerging idea is that targeting key metabolites is sufficient to impact the function of other organisms. Therefore, more metabolism-targeted therapeutic intervention is needed to improve cognitive impairment. We first conducted untargeted metabolomic analyses and 16S rRNA to identify the aging-associated metabolic adaption and intestinal microbiome change. Untargeted metabolomic analyses of plasma revealed L-arginine metabolic homeostasis was altered during the aging process. Impaired L-arginine metabolic homeostasis was associated with low abundance of intestinal Akkermansia muciniphila (AKK) colonization in mice. Long-term supplementation of AKK outer membranes protein-Amuc_1100, rescued the L-arginine level and restored cognitive impairment in aging mice. Mechanically, Amuc_1100 acted directly as a source of L-arginine and enriched the L-arginine-producing bacteria. In aged brain, Amuc_1100 promoted the superoxide dismutase to alleviated oxidation stress, and increased nitric oxide, derivatives of L-arginine, to improve synaptic plasticity. Meanwhile, L-arginine repaired lipopolysaccharide-induced intestinal barrier damage and promoted growth of colon organoid. Our findings indicated that aging-related cognitive impairment was closely associated with the disorders of L-arginine metabolism. AKK-derived Amuc_1100, as a potential postbiotic, targeting the L-arginine metabolism, might provide a promising therapeutic strategy to maintain the intestinal homeostasis and cognitive function in aging.

Design and implementation of mechanical property testing equipment for thoracic aortic stent grafts.

The mechanical properties of the stent graft are important factors influencing the outcome of TEVAR treatment and the occurrence of postoperative complications. The aim of this study is to improve and design a mechanical performance testing equipment for thoracic aortic stent grafts. The mechanical performance testing equipment consists of a radial force testing equipment of the stent graft designed by the wire compression grip method and a dynamic straightening force testing device with stable and controllable test conditions and continuously variable test angles. By constructing the testing equipment to physically measure the stent specimen, the experimental results reflect the trend of change and the simulation results are basically consistent, i.e. the mechanical properties of the thoracic aortic stent designed in this study is feasible and the measured data are valid. The testing equipment can provide the basis and reference direction for the quality testing of stent graft products, optimisation of mechanical properties of stent grafts and R&D innovation.

Heat-inactivated Bifidobacterium adolescentis ameliorates colon senescence through Paneth-like-cell-mediated stem cell activation.

Declined numbers and weakened functions of intestinal stem cells (ISCs) impair the integrity of the intestinal epithelium during aging. However, the impact of intestinal microbiota on ISCs in this process is unclear. Here, using premature aging mice (telomerase RNA component knockout, Terc-/-), natural aging mice, and in vitro colonoid models, we explore how heat-inactivated Bifidobacterium adolescentis (B. adolescentis) affects colon senescence. We find that B. adolescentis could mitigate colonic senescence-related changes by enhancing intestinal integrity and stimulating the regeneration of Lgr5+ ISCs via Wnt/ß-catenin signaling. Furthermore, we uncover the involvement of Paneth-like cells (PLCs) within the colonic stem-cell-supporting niche in the B. adolescentis-induced ISC regeneration. In addition, we identify soluble polysaccharides (SPS) as potential effective components of B. adolescentis. Overall, our findings reveal the role of heat-inactivated B. adolescentis in maintaining the ISCs regeneration and intestinal barrier, and propose a microbiota target for ameliorating colon senescence.

Strengthening Ni-Coated CNT/Mg Composites by Optimizing the CNT Content.

The dispersion of carbon nanotubes (CNTs) is the bottleneck in CNT-reinforced metal matrix composites. In this work, CNT/Mg composites were prepared by grinding Mg powder and then dispersing CNTs via ball milling and hot pressing. The uniform distribution of Ni-coated CNTs in the matrix was achieved by optimizing the content of CNTs. Scanning electron microscope, high-resolution transmission electron microscopy and X-ray diffraction, optical microscopy, and compression tests were employed. With the CNT content being less than 1%, the CNTs can be evenly distributed in CNT/Mg composites, resulting in a sharp increase in strength. However, with the higher CNT content, the CNTs gradually cluster, leading decreased fracture strain and strength. Furthermore, the coated Ni in the CNTs reacts with the magnesium matrix and completely transforms into Mg2Ni, significantly enhancing the interface bonding. This strong interface bonding and the diffusely distributed Mg2Ni in the matrix significantly strengthen the CNT/Mg composite.

Strengthening and Toughening CNTs/Mg Composites by OpTimizing the Grinding Time of Magnesium Powder.

In this paper, CNT/Mg composites with high compressive properties were prepared by using Ni-plated CNT and pure magnesium powder as raw materials through the grinding of magnesium powder, ball-milling mixing and hot-pressing sintering. The effect of grinding time for finer magnesium powder on the microstructure and properties of the final composites was studied mainly by SEM, XRD, HRTEM and compression tests. The results show that with the prolongation of milling time, the magnesium particle size decreases gradually and the CNT dispersion becomes more uniform. Moreover, the nickel layer on the surface of CNT reacts with highly active broken magnesium powder in the sintering process to generate MgNi2 intermediate alloy, which significantly improves interface bonding. The strength and fracture strain of composites are significantly increased by the combined action of the uniform distribution of CNTs and strong interface bonding from the MgNi2 phase. The compressive strength, yield strength and fracture strain of the composites, prepared with a 60 h grinding of magnesium powder, reached 268%, 272% and 279% of those in composites without the grinding of magnesium powder.

Nitrogen loadings affect trophic structure in stream food webs on the Tibetan Plateau, China.

Anthropogenic activities, such as agricultural and industrial development, have increased nutrient inputs into waterways, which affect trophic interactions and the flow of energy through food webs in the aquatic ecosystems. However, the responses of food web structure and function to specific anthropogenic stressors in the alpine stream systems remain unclear. Here, we studied the stream food webs in the Lhasa River on the Tibetan Plateau, China. We measured the isotopic ratios (δ13C and δ15N) of macroinvertebrate and fish functional feeding groups (FFGs) and their basal resources in the streams. Dietary contributions of basal resources to consumers and food web metrics including trophic length, diversity, and redundancy were used to quantify changes in stream food webs in response to anthropogenic disturbance. Dietary analysis showed that allochthonous resources contributed more than autochthonous resources to macroinvertebrate primary consumers regardless of the disturbance intensity in the adjacent land areas. Anthropogenic activities increased the δ15N values in epilithic algae and isotopic variation in basal resources and fish but reduced the trophic length and redundancy (i.e., fewer species or taxon at each trophic level) in food webs. Additionally, the total nitrogen concentration in waters was the most important environmental variable affecting trophic diversity and redundancy. Therefore, the reduction of nitrogen inputs into streams is critical for sustainable river management and biodiversity conservation in the streams on the Tibetan Plateau.

Comparison of Corrosion Performance of Extruded and Forged WE43 Mg Alloy.

Adjusting the microstructure through the deformation process is one of the ways to improve the properties of Mg alloys. Most studies have focused on the influence of the microstructure after deformation treatment on the mechanical properties of Mg alloys. In this paper, extruded and forged Mg-Gd-Y-Nd-Zr alloys were selected to investigate the corrosion performance of two deformed magnesium alloys immersed in 0.6 M NaCl solution using a hydrogen evolution test, a weight loss test, an immersion experiment, and an electrochemical test. The results showed that WE43 alloys undergoing different deformation treatments presented different microstructures, which led to different corrosion behaviors and corrosion resistance. The extruded WE43 alloy showed uniform corrosion, while the forged WE43 alloy suffered severe local galvanic corrosion. Meanwhile, the corrosion rate of the forged WE43 alloy was about four times faster than that of the extruded WE43 alloy.

Novel long non-coding RNA CYB561-5 promotes aerobic glycolysis and tumorigenesis by interacting with basigin in non-small cell lung cancer.

Abnormally expressed long non-coding RNAs (lncRNAs) have been recognized as potential diagnostic biomarkers or therapeutic targets in non-small cell lung cancer (NSCLC). The role of the novel lnc-CYB561-5 in NSCLC and its specific biological activity remain unknown. In this study, lncRNAs highly expressed in NSCLC tissue samples compared with paired adjacent normal tissue samples and atypical adenomatous hyperplasia were identified by RNA-seq analysis. Lnc-CYB561-5 is highly expressed in human NSCLC and is associated with a poor prognosis in lung adenocarcinoma. In vivo, downregulation of lnc-CYB561-5 significantly decreases tumour growth and metastasis. In vitro, lnc-CYB561-5 knockdown treatment inhibits cell migration, invasion and proliferation ability, as well as glycolysis rates. In addition, RNA pulldown and RNA immunoprecipitation (RIP) assays show that basigin (Bsg) protein interacts with lnc-CYB561-5. Overall, this study demonstrates that lnc-CYB561-5 is an oncogene in NSCLC, which is involved in the regulation of cell proliferation and metastasis. Lnc-CYB561-5 interacts with Bsg to promote the expression of Hk2 and Pfk1 and further lead to metabolic reprogramming of NSCLC cells.

Physiological effects induced by aluminium and fluoride stress in tall fescue (Festuca arundinacea Schreb).

Aluminium (Al) and fluoride (F) are phytotoxic elements that can inhibit plant growth and development. Al3+ and F- can react with each other to form complexes in the soil which will induce alteration of toxicity of single element. However, the mechanisms of plant response to aluminium fluoride induced toxicity are not very clear. In the present study, tall fescue (Festuca arundinacea Schreb) cultivar 'Houndog 5' was treated by 0, 0.4, 4, 20 mg·L-1 Al2(SO4)3 and 0, 0.5, 5 mg·L-1 NaF, respectively. After 25 days of treatment, leaf samples were collected for physiological evaluation. The results showed that several forms of Al-OH and Al-F complexes such as Al(OH)2+, AlOH2+, Al(OH)3, Al(OH)4-, Al2(OH)24+, Al3(OH)45+, AlF2+, AlF2+, AlF3 and AlF4- were formed in Al3+ and F- combined solution. The nutrient uptake including Al, P and K were improved by Al3+ and F-. Under Al3+ stress, the MDA (malondialdehyde) content and EL (electrolyte leakage) dramatically increased after high concentration of F- treatment, while relative low concentration of F induced decrease of MDA content and EL. On the contrary, chlorophyll content decreased significantly after high concentration of F treatment. The photosynthesis efficiency parameters, including φP0 (Fv/Fm), δR0 and PIABS, decreased remarkably after high concentration of Al and F treatment. However, L-band incresed after high concentration of Al3+ and F- treatment. The results of correlation analysis showed that MDA content and EL negatively correlated with other indexes, and Al-F complex significantly correlated with MDA, Pro and EL but negatively correlated with Chl and φP0. These results suggested that low concentration of F could alleviate the damage induced by Al stress in tall fescue, but high concentration of Al and F combined solution had negative effects on the growth and development of tall fescue.

The Aged Intestine: Performance and Rejuvenation.

Owing to the growing elderly population, age-related problems are gaining increasing attention from the scientific community. With senescence, the intestine undergoes a spectrum of changes and infirmities that are likely the causes of overall aging. Therefore, identification of the aged intestine and the search for novel strategies to rescue it, are required. Although progress has been made in research on some components of the aged intestine, such as intestinal stem cells, the comprehensive understanding of intestinal aging is still limited, and this restricts the in-depth search for efficient strategies. In this concise review, we discuss several aspects of intestinal aging. More emphasis is placed on the appraisal of current and potential strategies to alleviate intestinal aging, as well as future targets to rejuvenate the aged intestine.

Polymodal Functionality of C. elegans OLL Neurons in Mechanosensation and Thermosensation.

Sensory modalities are important for survival but the molecular mechanisms remain challenging due to the polymodal functionality of sensory neurons. Here, we report the C. elegans outer labial lateral (OLL) sensilla sensory neurons respond to touch and cold. Mechanosensation of OLL neurons resulted in cell-autonomous mechanically-evoked Ca2+ transients and rapidly-adapting mechanoreceptor currents with a very short latency. Mechanotransduction of OLL neurons might be carried by a novel Na+ conductance channel, which is insensitive to amiloride. The bona fide mechano-gated Na+-selective degenerin/epithelial Na+ channels, TRP-4, TMC, and Piezo proteins are not involved in this mechanosensation. Interestingly, OLL neurons also mediated cold but not warm responses in a cell-autonomous manner. We further showed that the cold response of OLL neurons is not mediated by the cold receptor TRPA-1 or the temperature-sensitive glutamate receptor GLR-3. Thus, we propose the polymodal functionality of OLL neurons in mechanosensation and cold sensation.

Bifidobacterium adolescentis regulates catalase activity and host metabolism and improves healthspan and lifespan in multiple species.

To identify candidate bacteria associated with aging, we performed fecal microbiota sequencing in young, middle-aged and older adults, and found lower Bifidobacterium adolescentis abundance in older individuals aged ≥60 years. Dietary supplementation of B. adolescentis improved osteoporosis and neurodegeneration in a mouse model of premature aging (Terc-/-) and increased healthspan and lifespan in Drosophila melanogaster and Caenorhabditis elegans. B. adolescentis supplementation increased the activity of the catalase (CAT) enzyme in skeletal muscle and brain tissue from Terc-/- mice, and suppressed cellular senescence in mouse embryonic fibroblasts. Transgenic deletion of catalase (ctl-2) in C. elegans abolished the effects of B. adolescentis on the lifespan and healthspan. B. adolescentis feeding also led to changes in oxidative stress-associated metabolites in Terc-/- mouse feces. These results suggest a role for B. adolescentis in improving the healthspan and lifespan through the regulation of CAT activity and host metabolism.

Transcriptomic analysis of short-term heat stress response in Pinellia ternata provided novel insights into the improved thermotolerance by spermidine and melatonin.

Heat stress has been a major environmental factor limiting the growth and development of Pinellia ternata which is an important Chinese traditional medicine. It has been reported that spermidine (SPD) and melatonin (MLT) play pivotal roles in modulating heat stress response (HSR). However, the roles of SPD and MLT in HSR of P. ternata, and the potential mechanism is still unknown. Here, exogenous SPD and MLT treatments alleviated heat-induced damages in P. ternata, which was supported by the increased chlorophyll content, OJIP curve, and relative water content, and the decreased malondialdehyde and electrolyte leakage. Then, RNA sequencing between CK (control) and Heat (1 h of heat treatment) was conducted to analyze how genes were in response to short-term heat stress in P. ternata. A total of 14,243 (7870 up- and 6373 down-regulated) unigenes were differentially expressed after 1 h of heat treatment. Bioinformatics analysis revealed heat-responsive genes mainly included heat shock proteins (HSPs), ribosomal proteins, ROS-scavenging enzymes, genes involved in calcium signaling, hormone signaling transduction, photosynthesis, pathogen resistance, and transcription factors such as heat stress transcription factors (HSFs), NACs, WRKYs, and bZIPs. Among them, PtABI5, PtNAC042, PtZIP17, PtSOD1, PtHSF30, PtHSFB2b, PtERF095, PtWRKY75, PtGST1, PtHSP23.2, PtHSP70, and PtLHC1 were significantly regulated by SPD or MLT treatment with same or different trends under heat stress condition, indicating that exogenous application of MLT and SPD might enhance heat tolerance in P. ternata through regulating these genes but may with different regulatory patterns. These findings contributed to the identification of potential genes involved in short-term HSR and the improved thermotolerance by MLT and SPD in P. ternata, which provided important clues for improving thermotolerance of P. ternata.

Dietary type 2 resistant starch improves systemic inflammation and intestinal permeability by modulating microbiota and metabolites in aged mice on high-fat diet.

Type 2 resistant starch (RS2) is a fermentable dietary fiber conferring health benefits. We investigated the effects of RS2 on host, gut microbiota, and metabolites in aged mice on high-fat diet. In eighteen-month old mice randomly assigned to control, high-fat (HF), or high-fat+20% RS2 (HFRS) diet for 16 weeks, RS2 reversed the weight gain and hepatic steatosis induced by high-fat diet. Serum and fecal LPS, colonic IL-2 and hepatic IL-4 mRNA expressions decreased while colonic mucin 2 mRNA and protein expressions increased in the HFRS compared to the HF and the control group. 16s rRNA sequencing of fecal microbial DNA demonstrated that RS2 decreased the abundance of pathogen taxa associated with obesity, inflammation, and aging including Desulfovibrio (Proteobacteria phylum), Ruminiclostridium 9, Lachnoclostridium, Helicobacteria, Oscillibacter, Alistipes, Peptococcus, and Rikenella. Additionally, RS2 increased the colonic butyric acid by 2.6-fold while decreasing the isobutyric and isovaleric acid levels by half compared to the HF group. Functional analyses based on Clusters of Orthologous Groups showed that RS2 increased carbohydrate while decreasing amino acid metabolism. These findings demonstrate that RS2 can reverse weight gain, hepatic steatosis, inflammation, and increased intestinal permeability in aged mice on high-fat diet mediated by changes in gut microbiome and metabolites.

Salt-Induced Damage is Alleviated by Short-Term Pre-Cold Treatment in Bermudagrass (Cynodon dactylon).

Excess salinity is a major environmental stress that limits growth and development of plants. Improving salt stress tolerance of plants is important in order to enhance land utilization and crop yield. Cold priming has been reported to trigger the protective processes in plants that increase their stress tolerance. Bermudagrass (Cynodon dactylon) is one of the most widely used turfgrass species around the world. However, the effect of cold priming on salt tolerance of bermudagrass is largely unknown. In the present study, wild bermudagrass was pre-treated with 4 °C for 6 h before 150 mM NaCl treatment for one week. The results showed that the cell membrane stability, ion homeostasis and photosynthesis process which are usually negatively affected by salt stress in bermudagrass were alleviated by short-term pre-cold treatment. Additionally, the gene expression profile also corresponded to the change of physiological indexes in bermudagrass. The results suggest that cold priming plays a positive role in improving salt stress tolerance of bermudagrass.

High developmental pluripotency­associated 4 expression promotes cell proliferation and glycolysis, and predicts poor prognosis in non­small­cell lung cancer.

The developmental pluripotency­associated 4 (Dppa4) gene serves critical roles in cell self­renewal, as well as in cancer development and progression. However, the regulatory role of Dppa4 in non­small­cell lung cancer (NSCLC) and its underlying mechanisms remain elusive. The aim of the present study was to investigate the biological function of Dppa4 in NSCLC and its underlying mechanism of action. Dppa4 expression was measured in NSCLC tissue samples and cell lines, and its effect on cell proliferation and the expression of glycolytic enzymes was determined. In addition, the underlying mechanisms of Dppa4­induced alterations in glycolysis were analyzed. Univariate and multivariate analyses were also performed to analyze the prognostic significance of clinicopathological characteristics. Dppa4 was found to be highly expressed in NSCLC tissues and cell lines. Furthermore, it was observed that Dppa4 was correlated with the degree of tumor differentiation and TNM stage. Univariate and multivariate analyses identified Dppa4 expression and clinical stage as prognostic factors for NSCLC patients. Kaplan­Meier analysis further revealed that patients with lower Dppa4 expression exhibited a better prognosis. In NSCLC cells, Dppa4 knockdown inhibited cell proliferation, while Dppa4 overexpression enhanced cell proliferation, which was likely mediated by glycolysis promotion. Dppa4 knockdown had no evident effect on the majority of enzymes examined; however, glucose transporter type 4 (GLUT­4) and pyruvate kinase isozyme M2 were significantly upregulated, and hexokinase II (HK­II) and lactate dehydrogenase B (LDHB) were downregulated following Dppa4 knockdown. By contrast, Dppa4 overexpression resulted in downregulation of GLUT­4, and upregulation of HK­II, enolase and LDHB, whereas it had no effect on other enzymes. Since the most evident effect was observed on LDHB, further functional experiments demonstrated that this enzyme reversed the promoting effects of Dppa4 in NSCLC. In conclusion, Dppa4 promotes NSCLC progression, partly through glycolysis by LDHB. Thus, the Dppa4­LDHB axis critically contributes to glycolysis in NSCLC cells, thereby promoting NSCLC development and progression.

Reductive cleavage of inert aryl C-O bonds to produce arenes.

Reductive cleavage of the aryl C-O bonds in various phenolic compounds and aryl ethers was achieved using LiAlH4 combined with KOtBu and without any other catalysts or additives, solely producing arenes in high yields.

Synthesis of metalloporphyrin-based conjugated microporous polymer spheres directed by bipyridine-type ligands.

Zinc porphyrin (TP-Zn)-based conjugated microporous polymer (Zn-CMP) spheres were obtained via Sonagashira-Hagihara cross coupling reactions between 5,10,15,20-tetrakis(4-ethynylphenyl)porphyrin-Zn(II) and brominated monomers directed by bidentate bipyridine (BP)-type ligands for the first time, and the sphere diameters could be adjusted from 320 to 740 nm. The coordination between BP and TP-Zn was proved to be the key to forming spheres.