Aged microbiota exacerbates cardiac failure by PPARα/PGC1α pathway.

The dysbiosis of gut microbiota with aging has been extensively studied, revealing its substantial contribution to variety of diseases. However, the impact of aged microbiota in heart failure (HF) remains unclear. In this study, we employed the method of fecal microbiota transplantation (FMT) from aged donors to investigate its role in the context of HF. Our results demonstrate that FMT from aged donors alters the recipient's gut microbiota composition and abundance. Furthermore, FMT impairs cardiac function and physical activity in HF mice. Aged FMT induces metabolic alterations, leading to body weight gain, impaired glucose tolerance, increased respiratory exchange ratio, and enhanced fat accumulation. The epicardium of aged FMT recipients shows fat accumulation, accompanied by cardiomyocyte hypertrophy, cardiac fibrosis and increased cellular apoptosis. Mechanistically, aged FMT suppresses the PPARα/PGC1α signaling pathway in HF. Notably, activation of PPARα effectively rescues the metabolic changes and myocardial injury caused by aged FMT. In conclusion, our study emphasizes the role of the PPARα/PGC1α signaling pathway in aged FMT-mediated HF.

Hydrothermally Stimulated Molecular Interfaces for Augmented Electron Delocalization in Wet-Chemical Phosphorus Recovery from Incineration Ash of Sewage Sludge.

Wet-chemically recovering phosphorus (P) from sewage sludge incineration ash (SSIA) has already become a global initiative to address P deficit, but effectively isolating P from these accompanying metals (AMs) through adsorption in a SSIA-derived extract remains elusive. Here, we devised a hydrothermal stimulus-motivated thermodynamic and kinetic enhancement to gain anionic ethylenediaminetetraacetic acid (EDTA) molecular interfaces for AM enclosure to resolve this conundrum. A new dosage rule based on the EDTA coordination ratio with AMs was established for the first time. Upon hydrothermal extraction at 140 °C for 1 h, the P extraction efficiency reached 96.7% or higher for these obtained SSIA samples, and then exceptional P sequestration from these EDTA-chelated AMs was realized by the peculiar lanthanum (La)-based nanoadsorbent (having 188.86 mg P/g adsorbent at pH ∼ 3.0). Relevant theoretical calculations unraveled that these delocalized electrons of tetravalent EDTA molecules boosted the enclosure of liberated AMs, thereby entailing a substantially increased negative adsorption energy (-408.7 kcal/mol) of P in the form of H2PO4- through intruding lattice-edged carbonates to coordinate La with monodentate mononuclear over LaCO5(1 0 1). This work highlights the prospect of molecular adaptation of these common extractants in wet-chemical P recovery from various P-included wastes, further sustaining global P circularity.

Age-Related Gut Microbiota Transplantation Disrupts Myocardial Energy Homeostasis and Induces Oxidative Damage.

BACKGROUND: Aging-related energy homeostasis significantly affects normal heart function and disease development. The relationship between the gut microbiota and host energy metabolism has been well established. However, the influence of an aged microbiota on energy metabolism in the heart remains unclear. OBJECTIVE: The objective of this was to explore the effects of age-related microbiota composition on energy metabolism in the heart. METHODS: In this study, we used the fecal microbiota transplantation (FMT) method. The fecal microbiota from young (2-3 mo) and aged (18-22 mo) donor mice were transplanted into separate groups of young (2-3 mo) recipient mice. The analysis utilized whole 16S rRNA sequencing and plasma metabolomics to assess changes in the gut microbiota composition and metabolic potential. Energy changes were monitored by performing an oral glucose tolerance test, biochemical testing, body composition analysis, and metabolic cage measurements. Metabolic markers and markers of DNA damage were assessed in heart samples. RESULTS: FMT of an aged microbiota changed the composition of the recipient's gut microbiota, leading to an elevated Firmicutes-to-Bacteroidetes ratio. It also affected overall energy metabolism, resulting in elevated plasma glucose concentrations, impaired glucose tolerance, and epididymal fat accumulation. Notably, FMT of an aged microbiota increased the heart weight and promoted cardiac hypertrophy. Furthermore, there were significant associations between heart weight and cardiac hypertrophy indicators, epididymal fat weight, and fasting glucose concentrations. Mechanistically, FMT of an aged microbiota modulated the glucose metabolic pathway and induced myocardial oxidative damage. CONCLUSIONS: Our findings suggested that an aged microbiota can modulate metabolism and induce cardiac injury. This highlights the possible role of the gut microbiota in age-related metabolic disorders and cardiac dysfunction.

Exposure to triphenyltin impairs gut integrity, disturbs gut microbiota, and alters fecal metabolites.

Triphenyltin is an environmental contaminant widely used in antifouling paints and can cause toxicity in various organs in living organisms. However, its effects on intestinal function and the microbiome of the gut remain unknown. The objective of this study was to explore the intestinal toxicity of triphenyltin in mice by orally administering 0, 1.875, 3.75, and 7.5 mg/Kg to adult male mice for 8 weeks. Results showed that triphenyltin caused ileum tissue damage, induced oxidative stress, upregulated inflammation-related gene expression and increased serum tumor-necrosis factor α (TNF-α) levels in mice. Triphenyltin impaired ileum barrier function by downregulating Muc2, ZO-1, Occludin and their protein levels at 3.75 and 7.5 mg/Kg. TPT exposure led to partial inflammation and decreased mucin mRNA expression in the colon. Triphenyltin altered intestinal micro-ecological balance and fecal metabolome in mice. In conclusion, triphenyltin alters the mouse gut microbiota and fecal metabolome.

Roles of Human Gut Microbiota in Liver Cirrhosis Risk: A Two-Sample Mendelian Randomization Study.

BACKGROUND: Accumulating evidence suggests that alterations in gut microbiota composition and diversity are associated with liver cirrhosis. But whether gut microbiota promotes or hampers the genesis and development of liver cirrhosis remains vague. OBJECTIVES: This study aimed to establish a causal relationship between gut microbiota and the development of liver fibrosis and cirrhosis. To achieve this, we employed a 2-sample Mendelian randomization (MR) analysis utilizing genome-wide association study (GWAS) summary statistics. This approach enabled us to assess the potential impact of gut microbiota on liver cirrhosis. METHODS: The independent genetic instruments of gut microbiota were obtained from the MiBioGen (up to 18,340 participants), which is a large-scale genome-wide genotype and 16S fecal microbiome dataset. Cirrhosis data were derived from the FinnGen biobank analysis, which included 214,403 individuals of European ancestry (811 patients and 213,592 controls). To assess the causal relationship between gut microbiota and cirrhosis, we applied 4 different methods of MR analysis: the inverse-variance weighted method (IVW), the MR-Egger regression, the weighted median analysis (WME), and the weighted mode. Furthermore, sensitivity analyses were conducted to evaluate heterogeneity and horizontal pleiotropy. RESULTS: Results of MR analyses provided evidence of a causal association between 4 microbiota features and cirrhosis, including 2 family [Lachnosiraceae: odds ratio (OR): 1.82626178; 95% confidence interval (CI): 1.05208209, 3.17012532; P = 0.0323194; Lactobacillaceae : OR: 0.62897502; 95% CI: 0.42513162, 0.93055788; P = 0.02033345] and 2 genus [Butyricicoccus: OR: 0.41432215; 95% CI: 0.22716865, 0.75566257; P = 0.0040564; Lactobacillus: OR: 0.6663767; 95% CI: 0.45679511, 0.97211616; P = 0.03513627]. CONCLUSIONS: Our findings offered compelling evidence of a causal association between gut microbiota and cirrhosis in European population and identified specific bacteria taxa that may regulate the genesis and progression of liver fibrosis and cirrhosis, may offer a new direction for the treatment of cirrhosis.

Exploration of Converting Food Waste into Value-Added Products via Insect Pretreatment-Assisted Hydrothermal Catalysis.

The environmental burden of food waste (FW) disposal coupled with natural resource scarcity has aroused interest in FW valorization; however, transforming FW into valuable products remains a challenge because of its heterogeneous nature. In this study, a two-stage method involving black soldier fly (BSF)-based insect pretreatment and subsequent hydrothermal catalysis over a single-atom cerium-incorporated hydroxyapatite (Ce-HAP) was explored to convert FW into high added-value furfurals (furfural and 5-hydroxymethylfurfural). FW consisting of cereal, vegetables, meat, eggs, oil, and salt was initially degraded by BSF larvae to generate homogeneous BSF biomass, and then, crucial parameters impacting the conversion of BSF biomass into furfurals were investigated. Under the optimized conditions, 9.3 wt % yield of furfurals was attained, and repeated trials confirmed the recyclability of Ce-HAP. It was proved that the revenue of furfural production from FW by this two-stage method ranged from 3.14 to 584.4 USD/tonne. This study provides a potential technical orientation for FW resource utilization.

Morphology-Tailored Hydroxyapatite Nanocarrier for Rhizosphere-Targeted Phosphorus Delivery.

High hydrophilicity and soil fixation collectively hamper the delivery of phosphorus (P) released from conventional chemical phosphorus fertilizers (CPFs) to plant rhizosphere for efficient uptake. Here, a phosphorus nutrient nanocarrier (PNC) based on morphology-tailored nanohydroxyapatite (HAP) is constructed. By virtue of kinetic control of building blocks with designed calcium phosphate intermediates, rod-like and hexagonal prism-like PNCs are synthesized, both having satisfactory hydrophobicity (water contact angle of 105.4- 132.9°) and zeta potential (-17.43 to -58.4 mV at pH range from 3 to 13). Greenhouse experiments demonstrate that the P contents increase by up to 183% in maize rhizosphere and up to 16% in maize biomass when compared to the CPF. Due to the water potential gradient driven by photosynthesis and transpiration, both PNCs are stably transported to maize rhizosphere, and they are capable to counteract soil fixation prior to uptake by plant roots. Within the synergies of the HAP morphological characteristics and triggered phosphate starvation response, root anatomy confirms that two pathways are elucidated to enhance plant P replenishment from the PNCs. Together with structure tunability and facile synthesis, our results offer a new nanodelivery prototype to accommodate plant physiological traits by tailoring the morphology of HAP.

Complete genome sequence and probiotic properties of Lactococcus petauri LZys1 isolated from healthy human gut.

Introduction. Lactococcus petauri LZys1 (L. petauri LZys1) is a type of lactic acid bacteria (LAB), which was initially isolated from healthy human gut.Hypothesis/Gap Statement. It was previously anticipated that L. petauri LZys1 has potential characteristics of probiotic properties. The genetic structure and the regulation functions of L. petauri LZys1 need to be better revealed.Aim. The aim of this study was to detect the probiotic properties L. petauri LZys1 and to reveal the genome information related to its genetic adaptation and probiotic profiles.Methodology. Multiple in vitro experiments were carried out to evaluate its lactic acid-producing ability, resistance to pathogenic bacterial strains, auto-aggregation and co-aggregation ability, and so on. Additionally, complete genome sequencing, gene annotation, and probiotic associated gene analysis were performed.Results. The complete genome of L. petauri LZys1 comprised of 1 985 765 bp, with a DNA G+C content of 38.07 %, containing 50 tRNA, seven rRNA, and four sRNA. A total of 1931 genes were classified into six functional categories by Kyoto Encyclopaedia of Genes and Genomes (KEGG) database. The neighbour-joining phylogeny tree based on the whole genome of L. petauri LZys1 and other probiotics demonstrated that L. petauri LZys1 has a significant similarity to Lactococcus garvieae. The functional genes were detected to expound the molecular mechanism and biochemical processes of its potential probiotic properties, such as atpB gene.Conclusion. All the results described in this study, together with relevant information previously reported, made L. prtauri LZys1 a very interesting potential strain to be considered as a prominent candidate for probiotic use.

[Retracted] Generation and characterization of induced pluripotent stem cells from guinea pig fetal fibroblasts.

The authors wish to retract their article entitled "Generation and characterization of induced pluripotent stem cells from guinea pig fetal fibroblasts" published in Molecular Medicine Reports 15, 3690­3698, 2017. Following the publication of this article, the authors noted that the description of the reprogramming method and cell cultured conditions in the article was inconsistent with the experimental facts, due to their oversight and personnel issues in terms of who performed the experimental work and who wrote up the paper. Some of the experimental approaches were wrongly described in the Materials and methods section. Namely, the feeder cells which were used in this reprogramming were mouse embryonic fibroblasts, not guinea fibroblast cells, as was reported; the reprogramming medium contained 15% knockout serum replacement; the culture medium contained 10% ESC qualified fetal bovine serum and 10% knockout serum replacement; and 293T cells were transfected using the Quick Shuttle­293 system. Due to the authors' oversight, Figs 2A and C, and Fig. 3 on p. 3,694 do not match with the textual description. In view of these serious errors, which the authors are not able to rectify, they have requested that this article be retracted from the publication. All the named authors agree to this retraction. The authors regret any inconvenience to the readers that this retraction will cause.

Leukemia inhibitory factor regulates marmoset induced pluripotent stem cell proliferation via a PI3K/|Akt­dependent Tbx­3 activation pathway.

Leukemia inhibitory factor (LIF) is the most pleiotropic cytokine of the interleukin­6 family, and is widely used to establish and maintain pluripotent stem cells, particularly mouse pluripotent stem cells. However, no reports have fully elucidated the application of LIF in marmoset induced pluripotent stem cell (iPSC) culture, particularly the underlying mechanisms. To demonstrate the feasibility of the application of LIF to marmoset iPSCs, the present study assessed these cells in the presence of LIF. Cell proliferation was measured using MTT assay, cell apoptosis was determined by flow cytometric analysis of fluorescein isothiocyanate Annexin V staining and the differentially expressed genes were analysed using Digital Gene Expression (DGE) analysis. The altered expression of pluripotency­associated genes was confirmed by reverse transcription­quantitative polymerase chain reaction and western blot analysis. Furthermore, following treatment with LY294002, cell proliferation was measured by MTT assay and protein levels were confirmed by western blot analysis. The results showed that LIF significantly promoted the number of proliferating cells, but had no effect on apoptosis. Digital Gene Expression analysis was used to examine the differentially expressed genes of marmoset iPSCs in the presence of LIF. The results showed that the pluripotency­associated transcription factor­encoding gene T­box 3 (Tbx­3) was activated by LIF. Notably, LIF increased the levels of phosphorylated (p­)AKT and Tbx­3 in the marmoset iPSCs. Furthermore, pretreatment with LY294002, an inhibitor of phosphoinositide 3­kinase (PI3K), significantly impaired the LIF­induced upregulation of p­AKT and Tbx­3 in the marmoset iPSCs, suggesting that the PI3K/Akt signaling pathway is involved in this regulation. Taken together, the results suggested that LIF is effective in maintaining marmoset iPSCs in cultures, which is associated with the activation of Tbx­3 through regulation of the PI3K/Akt signaling pathway.

Human-induced pluripotent stem cell-derived macrophages and their immunological function in response to tuberculosis infection.

BACKGROUND: Induced pluripotent stem cells (iPS) represent an innovative source for the standardized in vitro generation of macrophages (Mφ). Mφ show great promise in disease pathogenesis, particularly tuberculosis. However, there is no information about human iPS-derived (hiPS) macrophages (hiPS-Mφ) in response to tuberculosis infection. METHODS: In the present study, macrophages derived from hiPS were established via embryoid body (EB) formation by using feeder-free culture conditions, and the human monocyte cell line THP-1 (THP-1-Mφ) was used as control. iPS-Mφ were characterized by using morphology, Giemsa staining, nonspecific esterase staining (α-NAE), phagocytosis, and surface phenotype. Additionally, after treatment with Bacillus Calmette-Guérin (BCG) for 24 h, cell apoptosis was detected by using an Annexin V-FITC Apoptosis Detection assay. The production of nitric oxide (NO), expression of tumor necrosis factor alpha (TNF-α), activity of apoptosis-related protein cysteine-3 (Caspase-3) and expression of B-cell lymphoma-2 (Bcl-2) were analyzed. RESULTS: With respect to morphology, surface phenotype, and function, the iPS-Mφ closely resembled their counterparts generated in vitro from a human monocyte cell line. iPS-Mφ exhibited the typically morphological characteristics of macrophages, such as round, oval, fusiform and irregular characteristics. The cells were Giemsa-stained-positive, α-NAE-positive, and possessed phagocytic ability. iPS-Mφ express high levels of CD14, CD11b, CD40, CD68, and major histocompatibility complex II (MHC-II). Moreover, with regard to the apoptotic rate, the production of NO, expression of TNF-α, and activity of Caspase-3 and Bcl-2, iPS-Mφ closely resemble that of their counterparts generated in vitro from human monocyte cell line in response to BCG infection. The rate of apoptosis of BCG-treated iPS-Mφ was 37.77 ± 7.94% compared to that of the untreated group at 4.97 ± 1.60% (P < 0.01) by using Annexin V-FITC Apoptosis Detection. Additionally, the rate of apoptosis of BCG-treated THP-1-Mφ was 37.1 ± 2.84% compared to that of the untreated group at 6.19 ± 1.68% (P < 0.001). The expression of TNF-α and the production of NO were significantly increased (P < 0.001), and the activity of Caspase-3 was increased. However, the expression of Bcl-2 was inhibited (P < 0.001). CONCLUSIONS: Our results demonstrate that Mφ derived from hiPS perform the immunological function in response to Bacillus Calmette-Guérin infection by undergoing apoptosis, increasing the production of NO and expression of TNF-α. Thus, our study may help to overcome the limitations of research into certain rare diseases due to the lack of adequate supply of disease-specific primary cells.

Generation and characterization of induced pluripotent stem cells from guinea pig fetal fibroblasts.

Induced pluripotent stem cells (iPS) represent an important tool to develop disease­modeling assays, drug testing assays and cell­based replacement therapies. The application of iPS in these fields requires the development of suitable animal models. Of the suitable species, guinea pigs are particularly important and offer significant advantages. Successful iPS generation has been accomplished in a number of species; however, it has not been reported in the guinea pig. The present study successfully generated iPS from guinea pigs (giPS) using single polycistronic virus transduction with mouse octamer­binding transcription factor 4 (Oct4), sex determining region Y­box 2 (Sox2), Kruppel­like factor 4 and c­Myc. The giPS cell lines were cultured in media containing leukemia inhibitory factor and guinea pig fibroblast cells were used as feeder cells. These cultures were expanded under feeder­free culture conditions using ESGRO Complete Plus Clonal Grade medium containing 15% fetal bovine serum on gelatin­coated dishes. The resultant cells had a normal karyotype, exhibited alkaline phosphatase activity and expressed the pluripotency markers Oct4, Sox2 and Nanog. The cells differentiated in vivo to form teratomas that contained all three germ layers of the tissue cells. The generation of giPS may facilitate future studies investigating the mechanisms underlying innate immunity, particularly for tuberculosis. These experiments provide proof of principle that iPS technology may be adapted to use the guinea pig as a model of human diseases.

Expression of FK506-binding protein 52 (FKBP52) in chorionic villi with early recurrent spontaneous abortion.

OBJECTIVE: To investigate the mRNA and protein expression of FK506-binding protein 52 (FKBP52) in the chorionic villi of patients with recurrent spontaneous abortion (RSA) and normal women during early pregnancy. METHODS: Fresh chorionic villus tissues were collected from 60 subjects. A total of 30 patients with a history of RSA were enrolled into the RSA group and 30 normal pregnant women were enrolled into the control group. The FKBP52 mRNA expression levels in chorionic villi of the RSA patients and healthy controls were measured via semiquantitative RT-PCR. The protein distribution and expression levels of FKBP52 in chorionic villi were analyzed through immunohistochemistry (IHC). The correlation between FKBP52 expression and RSA was analyzed. RESULTS: We demonstrated that FKBP52 mRNA is expressed in chorionic villi samples of normal pregnancy and RSA. RSA patients exhibited significantly lower FKBP52 gene expression levels compared with those in normal pregnancies (p < 0.05). FKBP52 immunoreactivity in chorionic villi was mainly observed in trophoblast cell cytoplasm. The FKBP52 protein expression levels in the chorionic villi of RSA patients was significantly lower than in normal women during pregnancy (p < 0.05). CONCLUSIONS: FKBP52 protein levels were decreased in the chorionic villi of RSA patients, which indicate that the decrease in FKBP52 may be associated with RSA. The low FKBP52 mRNA expression level, which is consistent with the IHC result, may affect embryonic development and even lead to abortion. FKBP52 may be involved in the pathogenesis of RSA and new therapies that increase the FKBP52 expression may help treat RSA.

An increase in vascular endothelial growth factor (VEGF) and VEGF soluble receptor-1 (sFlt-1) are associated with early recurrent spontaneous abortion.

Recurrent spontaneous abortion (RSA) is a health problem that affects approximately 1% to 5% reproductive age woman. Yet, in around half of these patients, the mechanism for RSA is unexplained. Recent studies have indicated that placental ischemia/hypoxia and endothelial dysfunction are important factors in miscarriage. Other studies have indicated that the level and expression of soluble FMS-like tyrosine kinase-1 (sFlt1) is increased under a hypoxic environment. However, decreased sFlt-1 in the maternal circulation during the first trimester has recently been proposed as a potential marker for identifying risk of pregnancy loss. In this prospective study clinical samples were obtained within a short time after the fetal death, protein expression and maternal serum levels of sFlt1 were assessed and compared to samples taken from those with normal pregnancies. Our results indicate that levels of VEGF and sFlt-1 are both increased in women during early pregnancy compared women that are not pregnant (p<0.05) indicating that VEGF and sFlt-1 are both associated with pregnancy. More importantly, we detected a significant (p<0.05) increase in sFlt1 and VEGF levels and expression in the RSA patients who suffered subsequent miscarriages compare to controls. These results demonstrate that there is likely a relationship between VEGF, sFlt-1 and RSA suggesting that the high levels and over expression of sFlt-1 and VEGF might be associated with the pathogenesis of RSA.

[Correlation of light rare earth elements in rats hair, blood and organs].

OBJECTIVE: To study the correlation of rare earth elements (REEs) in the rats' hair, blood and organs. METHODS: Based on the level of animal weights, 50 healthy male SD rats were randomly divided into five groups including control group and four Citrate REEs level groups (low, middle, high-I and high-II). Before the experiment, the hair of rats' back was eliminated. After the rats were fed for four weeks, the fresh hair of the rats was collected. Except the high-II group, the blood and organs of the others were collected. The high-II group was fed for other four weeks without Citrate REEs. At the end of eighth week, hair, blood and organs of the high-II group were collected. Determination of light REEs concentration in the rats' hair, blood, liver, spleen and bone by ICP-MS. RESULTS: The correlation coefficients of REEs concentration between hair and organs (such as liver, spleen and bone) were more than 0.5, while those of REEs concentration between blood and organs (such as liver spleen and bond) were less than 0.5. In the group H- Il, the Rees concentration in blood, hair, liver, spleen and bone were all decrease, and the REEs concentration of blood was close to that of the control groups. CONCLUSION: The concentrations of REEs in these organs were different. And hair was better than blood as a biomarker to reflect body exposure of REEs.

[Preliminary attempt at the speciation of 25-elements in the Chinese medicinal herbs].

OBJECTIVE: To make an attempt at the multi-element speciation in the Chinese medicinal herbs by determining the concentrations of 25 elements in different extraction solutions. METHOD: Firstly, five Chinese medicinal herbs (Buddleja officinalis, Dictamnus dasycarpus, Myristica fragrans, Albizia judibrissin and Inula japonica) from the same region of China were treated to obtain water-soluble phase, lipid-soluble phase and non-soluble phase by water extraction, organic solvent extraction and acid digestion, respectively. Secondly, Phytolacca acinosa, a Chinese medicinal herb collected from 9 regions of China, was extracted by 0% EtOH, 50% EtOH, 75% EtOH, 95% EtOH, respectively, referring the Chinese Pharmacopoeia. Finally, the concentrations of 25 elements, such as Be, Cr, Cu, Zn, Ge, Sr, Y, Mo, Cd, Tl, Pb and REEs, in the above three phases were determined by ICP-MS. RESULT: Under the optimal conditions, all the 25 elements could be determined with detection limits ranged from 0.003 to 0.71 ng x g(-1). The average recoveries of the elements in P. acinosa were 88% approximately 119%, with the relative standard deviations 1.7% approximately 13.3%. It was observed that the determined 25 elements distributed in all the water-soluble, lipid-soluble and non-soluble phases, indicating that the inorganic species, organicspecies, as well as the protein bound species were coexisted in the herbs. Big differences of the element extraction rates could be found by using different ethanol solutions. CONCLUSION: With the aid of the obtained results, we may increase the extraction of necessary elements while decrease that of the toxic elements from the herbs by choosing a suitable solvent during the drug production.