Preventive effect of Lactobacillus johnsonii YH1136 against uric acid accumulation and renal damages.

Background: Hyperuricemia (HUA) is a prevalent metabolic disorder whose development is associated with intestinal microbiota. Therefore, probiotics have emerged as a potential and safe approach for lowering uric acid (UA) levels. However, the underlying mechanisms of many effective probiotic strains remain unknown. Methods and results: C57BL/6 mice were randomly divided into two groups: control and model groups. The model group received 12 weeks of potassium oxonate. Through 16s sequencing we found that HUA resulted in a significant decrease in the total diversity of all intestinal segments. When each intestinal segment was analyzed individually, the reduction in diversity was only significant in the cecum and colon sections. RDA analysis showed that lactobacilli in the rat colon exhibited a strong correlation with model group, suggesting that Lactobacillus may play an important role in HUA. Consequently, the preventive effects of Lactobacillus johnsonii YH1136 against HUA were investigated. C57BL/6 mice were randomly divided into three groups: control, model and YH1136 groups. The results showed that administering Lactobacillus johnsonii YH1136 effectively reduced serum UA levels in vivo by inhibiting hepatic xanthine oxidase (XOD) activity and promoting renal ABCG2 transporter expression. Moreover, supplementation with Lactobacillus johnsonii YH1136 significantly ameliorated pathological damage in the kidney and liver, thereby reducing UA accumulation. Conclusion: Hyperuricemia is accompanied by an altered composition of multiple gut bacteria, of which Lactobacillus is a key genus. Lactobacillus johnsonii YH1136 may ameliorate renal involvement in HUA via the gut-kidney axis.

The impact of weight loss on renal function in individuals with obesity and type 2 diabetes: a comprehensive review.

Obesity and Type 2 Diabetes (T2D) are two highly prevalent diseases that exhibit a complex interplay between them. Obesity serves as a primary risk factor for the development of T2D, and conversely, individuals with T2D often exhibit comorbid obesity. Renal dysfunction emerges as a critical consequence of the convergence of obesity and Type 2 Diabetes, contributing significantly to the overall burden of complications associated with these conditions. Recognizing the profound implications of renal dysfunction in individuals contending with both obesity and Type 2 Diabetes, interventions targeting weight loss have gained prominence as potential therapeutic avenues. Weight loss not only addresses the primary risk factor of obesity but also holds the promise of mitigating the progression of Type 2 Diabetes and its associated renal complications. This comprehensive review aims to explore the impact of weight loss on renal function in individuals contending with the convergence of obesity and T2D.

Complete genome analysis of Bacillus velezensis TS5 and its potential as a probiotic strain in mice.

Introduction: In recent years, a large number of studies have shown that Bacillus velezensis has the potential as an animal feed additive, and its potential probiotic properties have been gradually explored. Methods: In this study, Illumina NovaSeq PE150 and Oxford Nanopore ONT sequencing platforms were used to sequence the genome of Bacillus velezensis TS5, a fiber-degrading strain isolated from Tibetan sheep. To further investigate the potential of B. velezensis TS5 as a probiotic strain, in vivo experiments were conducted using 40 five-week-old male specific pathogen-free C57BL/6J mice. The mice were randomly divided into four groups: high fiber diet control group (H group), high fiber diet probiotics group (HT group), low fiber diet control group (L group), and low fiber diet probiotics group (LT group). The H and HT groups were fed high-fiber diet (30%), while the L and LT groups were fed low-fiber diet (5%). The total bacteria amount in the vegetative forms of B. velezensis TS5 per mouse in the HT and LT groups was 1 × 109 CFU per day, mice in the H and L groups were given the same volume of sterile physiological saline daily by gavage, and the experiment period lasted for 8 weeks. Results: The complete genome sequencing results of B. velezensis TS5 showed that it contained 3,929,788 nucleotides with a GC content of 46.50%. The strain encoded 3,873 genes that partially related to stress resistance, adhesion, and antioxidants, as well as the production of secondary metabolites, digestive enzymes, and other beneficial nutrients. The genes of this bacterium were mainly involved in carbohydrate metabolism, amino acid metabolism, vitamin and cofactor metabolism, biological process, and molecular function, as revealed by KEGG and GO databases. The results of mouse tests showed that B. velezensis TS5 could improve intestinal digestive enzyme activity, liver antioxidant capacity, small intestine morphology, and cecum microbiota structure in mice. Conclusion: These findings confirmed the probiotic effects of B. velezensis TS5 isolated from Tibetan sheep feces and provided the theoretical basis for the clinical application and development of new feed additives.

Association Between Weight Change During Adulthood and Chronic Kidney Disease: Results from a National Survey 2011-2018.

Purpose: This study aimed to investigate the intricate relationship between weight change patterns and the onset of chronic kidney disease (CKD). Although obesity is recognized as a predisposing factor for CKD, the dynamics of weight fluctuation and its impact on CKD development are not well-defined. By analyzing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2011 to 2018, we sought to elucidate the association between weight trajectories and CKD risk. Patients and Methods: We included participants aged ≥40 years, employing body mass index (BMI) measurements at three life stages-baseline, age 25, and a decade preceding baseline-to categorize weight change patterns. Logistic regression was employed to evaluate the association of these patterns with CKD onset, adjusting for potential confounders. Results: The study encompassed 12,284 participants, with 2893 individuals diagnosed with CKD. Transitioning from normal weight to obesity and staying obese throughout adulthood were found to increase the risk of developing CKD. These associations remained consistent after adjusting for covariates but were statistically insignificant after adjusting for comorbidities. Notably, individuals transitioning from obesity to normal weight from age 25 to baseline and from 10 years before baseline to baseline demonstrated significant correlations with CKD but not between age 25 and 10 years before baseline. Conclusion: Obesity, weight gain throughout adulthood, and weight loss in middle-to-late adulthood are associated with an increased risk of CKD. This emphasizes the importance of long-term weight change patterns and maintaining a healthy weight throughout adulthood.

Update of the Pyrrolysyl-tRNA Synthetase/tRNAPyl Pair and Derivatives for Genetic Code Expansion.

The cotranslational incorporation of pyrrolysine (Pyl), the 22nd proteinogenic amino acid, into proteins in response to the UAG stop codon represents an outstanding example of natural genetic code expansion. Genetic encoding of Pyl is conducted by the pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNA, tRNAPyl. Owing to the high tolerance of PylRS toward diverse amino acid substrates and great orthogonality in various model organisms, the PylRS/tRNAPyl-derived pairs are ideal for genetic code expansion to insert noncanonical amino acids (ncAAs) into proteins of interest. Since the discovery of cellular components involved in the biosynthesis and genetic encoding of Pyl, synthetic biologists have been enthusiastic about engineering PylRS/tRNAPyl-derived pairs to rewrite the genetic code of living cells. Recently, considerable progress has been made in understanding the molecular phylogeny, biochemical properties, and structural features of the PylRS/tRNAPyl pair, guiding its further engineering and optimization. In this review, we cover the basic and updated knowledge of the PylRS/tRNAPyl pair's unique characteristics that make it an outstanding tool for reprogramming the genetic code. In addition, we summarize the recent efforts to create efficient and (mutually) orthogonal PylRS/tRNAPyl-derived pairs for incorporation of diverse ncAAs by genome mining, rational design, and advanced directed evolution methods.

The construction and optimization of engineered yeast chassis for efficient biosynthesis of 8-hydroxygeraniol.

Microbial production of monoterpenoid indole alkaloids (MIAs) provides a sustainable and eco-friendly means to obtain compounds with high pharmaceutical values. However, efficient biosynthesis of MIAs in heterologous microorganisms is hindered due to low supply of key precursors such as geraniol and its derivative 8-hydroxygeraniol catalyzed by geraniol 8-hydroxylase (G8H). In this study, we developed a facile evolution platform to screen strains with improved yield of geraniol by using the SCRaMbLE system embedded in the Sc2.0 synthetic yeast and confirmed the causal role of relevant genomic targets. Through genome mining, we identified several G8H enzymes that perform much better than the commonly used CrG8H for 8-hydroxygeraniol production in vivo. We further showed that the N-terminus of these G8H enzymes plays an important role in cellular activity by swapping experiments. Finally, the combination of the engineered chassis, optimized biosynthesis pathway, and utilization of G8H led to the final strain with more than 30-fold improvement in producing 8-hydroxygeraniol compared with the starting strain. Overall, this study will provide insights into the construction and optimization of yeast cells for efficient biosynthesis of 8-hydroxygeraniol and its derivatives.

The predictive effect of different machine learning algorithms for pressure injuries in hospitalized patients: A network meta-analyses.

Background: Pressure injury has always been a focus and difficulty of nursing. With the development of nursing informatization, a large amount of structured and unstructured data has been generated, and it is difficult for traditional methods to utilize these data. With the intersection of artificial intelligence and nursing, it has become a new trend to apply machine learning algorithms to build pressure injury prediction models to manage pressure injuries. However, there is no evidence on the effectiveness of the method and which of a large number of algorithms for machine learning is more applicable to pressure injuries. Objective: This review aims to systematically synthesize existing evidence to determine the effectiveness of applying machine learning algorithms for pressure injury management, to further evaluate and compare pressure injury prediction models constructed by numerous machine learning algorithms, and to derive evidence for the best algorithms for predicting and managing pressure injuries. Design: Systematic review and network meta-analysis. Methods: A systematic electronic search was conducted in the EBSCO, Embase, PubMed, and Web of Science databases. We included all retrospective diagnostic accuracy trials and prospective diagnostic accuracy trials constructing a predictive model by machine learning for pressure injuries up to December 2021. Two review authors independently selected relevant studies and extracted data using the Cochrane handbook for systematic reviews of diagnostic test accuracy. The network meta-analysis was conducted using statistical software R and STATA. The certainty of the evidence was rated using the QUADAS-2 tool. Result: Twenty-five clinical diagnostic trials with a total of 237397 participants were identified in this review. The results of our study revealed that pressure injury machine learning models can effectively predict these injuries. Combining the algorithms separately yields the main results: decision trees (sensitivity: 0.66, 95% CI: 0.42 to 0.84, specificity: 0.90, 95% CI: 0.78 to 0.96, diagnostic odds ratio [DOR]: 18, 95% CI: 7 to 49, AUC: 0.88, 95% CI: 0.85 to 0.91), logistic regression (sensitivity: 0.71, 95% CI: 0.60 to 0.80, specificity: 0.83, 95% CI: 0.75 to 0.89, DOR: 12, 95% CI: 9 to 17, AUC: 0.84, 95% CI: 0.81 to 0.87), neural networks (sensitivity: 0.73, 95% CI: 0.55 to 0.86, specificity: 0.78, 95% CI: 0.65 to 0.87, DOR: 9, 95% CI: 5 to 19, AUC: 0.82, 95% CI: 0.79 to 0.85), random forests (sensitivity: 0.72, 95% CI: 0.26 to 0.95, specificity: 0.96, 95% CI: 0.80 to 0.99, DOR: 56, 95% CI: 3 to 1258, AUC: 0.95, 95% CI: 0.93 to 0.97), support vector machines (sensitivity: 0.81, 95% CI: 0.69 to 0.90, specificity: 0.81, 95% CI: 0.59 to 0.93, DOR: 19, 95% CI: 6 to 54, AUC: 0.88, 95% CI: 0.85 to 0.90). According to the analysis of ROC and AUC values, random forest is the best algorithm for the prediction model of pressure injury. Conclusions: This review revealed that machine learning algorithms are generally effective in predicting pressure injuries, and after data merging, the random forest algorithm is the best algorithm for pressure injury prediction. Further well-designed diagnostic controlled trials are recommended to strengthen the current evidence. Registration number PROSPERO: CRD42021276993.

Systematic dissection of key factors governing recombination outcomes by GCE-SCRaMbLE.

With the completion of Sc2.0 chromosomes, synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE) becomes more critical for in-depth investigation of fundamental biological questions and screening of industrially valuable characteristics. Further applications, however, are hindered due to the lack of facile and tight regulation of the SCRaMbLE process, and limited understanding of key factors that may affect the rearrangement outcomes. Here we propose an approach to precisely regulate SCRaMbLE recombination in a dose-dependent manner using genetic code expansion (GCE) technology with low basal activity. By systematically analyzing 1380 derived strains and six yeast pools subjected to GCE-SCRaMbLE, we find that Cre enzyme abundance, genome ploidy and chromosome conformation play key roles in recombination frequencies and determine the SCRaMbLE outcomes. With these insights, the GCE-SCRaMbLE system will serve as a powerful tool in the future exploitation and optimization of the Sc2.0-related technologies.

The tRNA discriminator base defines the mutual orthogonality of two distinct pyrrolysyl-tRNA synthetase/tRNAPyl pairs in the same organism.

Site-specific incorporation of distinct non-canonical amino acids into proteins via genetic code expansion requires mutually orthogonal aminoacyl-tRNA synthetase/tRNA pairs. Pyrrolysyl-tRNA synthetase (PylRS)/tRNAPyl pairs are ideal for genetic code expansion and have been extensively engineered for developing mutually orthogonal pairs. Here, we identify two novel wild-type PylRS/tRNAPyl pairs simultaneously present in the deep-rooted extremely halophilic euryarchaeal methanogen Candidatus Methanohalarchaeum thermophilum HMET1, and show that both pairs are functional in the model halophilic archaeon Haloferax volcanii. These pairs consist of two different PylRS enzymes and two distinct tRNAs with dissimilar discriminator bases. Surprisingly, these two PylRS/tRNAPyl pairs display mutual orthogonality enabled by two unique features, the A73 discriminator base of tRNAPyl2 and a shorter motif 2 loop in PylRS2. In vivo translation experiments show that tRNAPyl2 charging by PylRS2 is defined by the enzyme's shortened motif 2 loop. Finally, we demonstrate that the two HMET1 PylRS/tRNAPyl pairs can simultaneously decode UAG and UAA codons for incorporation of two distinct noncanonical amino acids into protein. This example of a single base change in a tRNA leading to additional coding capacity suggests that the growth of the genetic code is not yet limited by the number of identity elements fitting into the tRNA structure.

A Combined Quantitative Evaluation Model for the Capability of Hyperspectral Imagery for Mineral Mapping.

To analyze the influence factors of hyperspectral remote sensing data processing, and quantitatively evaluate the application capability of hyperspectral data, a combined evaluation model based on the physical process of imaging and statistical analysis was proposed. The normalized average distance between different classes of ground cover is selected as the evaluation index. The proposed model considers the influence factors of the full radiation transmission process and processing algorithms. First- and second-order statistical characteristics (mean and covariance) were applied to calculate the changes for the imaging process based on the radiation energy transfer. The statistical analysis was combined with the remote sensing process and the application performance, which consists of the imaging system parameters and imaging conditions, by building the imaging system and processing models. The season (solar zenith angle), sensor parameters (ground sampling distance, modulation transfer function, spectral resolution, spectral response function, and signal to noise ratio), and number of features were considered in order to analyze the influence factors of the application capability level. Simulated and real data collected by Hymap in the Dongtianshan area (Xinjiang Province, China), were used to estimate the proposed model's performance in the application of mineral mapping. The predicted application capability of the proposed model is consistent with the theoretical analysis.

A GAMYB-like gene in tomato and its expression during seed germination.

To understand the function of the gibberellin (GA) transduction pathway during germination, the transcription factor gene GAMYB, which responds to the GA signal, has been studied in tomato (Solanum lycopersicum) seeds. This gene, called LeGAMYBL1 is present as a single copy, and is expressed in both the embryo and endosperm during seed germination in gib-1 mutant (non-GA producing) and wild-type (cv. Glamour) seeds. It is also expressed in young vegetative tissues. There is an 83% similarity in the amino acid sequence of the binding domain of the protein that is encoded by this tomato GAMYB-like gene when compared to that encoded by the GAMYB genes from barley, rice and Arabidopsis. In both mutant and wild-type intact tomato seeds, LeGAMYBL1 expression increases during germination, is upregulated by gibberellic acid (GA(3)), and declines thereafter. LeGAMYBL1 transcripts are also present in non-germinating gib-1 mutant seeds imbibed in water, and they are upregulated by GA(3) during promotion of germination. However, dissected gib-1 embryos complete germination when imbibed in either water or GA(3), with almost no difference in the amount of mRNA transcribed by the LeGAMYBL1 gene during this event. This is indicative that GA(3) is not required for the expression of the LeGAMYBL1 gene, which is likely necessary, but not sufficient, for germination to be completed, especially in the intact seed. The germination-inhibiting hormone abscisic acid does not influence expression of this gene. Expression of the LeGAMYB1 gene also occurs in the endosperm, but there is no correlation between its expression and GA-promoted expression of the cell-wall-degrading enzyme endo-beta-mannanase.

Hyperbaric oxygen attenuates apoptosis and decreases inflammation in an ischemic wound model.

The molecular mechanisms whereby hyperbaric oxygen (HBO) improves ischemic wound healing remain elusive. In this study, a rat model of wound ischemia was used to test the hypothesis that HBO enhances wound healing by modulating hypoxia-inducible factor-1alpha (HIF-1alpha) signaling. Male Sprague-Dawley rats underwent creation of a previously validated ischemic flap. Three groups underwent daily treatment: HBO (90 minutes, 2.4 atm); systemic administration of the free radical scavenger, N-acetylcysteine (NAC 150 mg kg(-1) intraperitoneal); control (neither HBO nor NAC). HBO treatment improved healing of the ischemic wounds. Analysis of ischemic wound tissue extracts demonstrated significantly reduced expression of HIF-1alpha, p53, and BNip3. Additionally, HBO increased expression of Bcl-2 while decreasing cleaved caspase-3. DNA fragmentation was abolished and the number of TUNEL-positive cells was reduced compared to the other groups. Vascular endothelial growth factor, cyclooxygenase-2, and neutrophil infiltration were reduced in ischemic wounds treated with HBO. These results indicate that HBO improves ischemic wound healing by downregulation of HIF-1alpha and subsequent target gene expression with attenuation of cell apoptosis and reduction of inflammation.

The emergence of embryos from hard seeds is related to the structure of the cell walls of the micropylar endosperm, and not to endo-beta-mannanase activity.

BACKGROUND AND AIMS: Seeds of carob, Chinese senna, date and fenugreek are hard due to thickened endosperm cell walls containing mannan polymers. How the radicle is able penetrate these thickened walls to complete seed germination is not clearly understood. The objective of this study was to determine if radicle emergence is related to the production of endo-beta-mannanase to weaken the mannan-rich cell walls of the surrounding endosperm region, and/or if the endosperm structure itself is such that it is weaker in the region through which the radicle must penetrate. METHODS: Activity of endo-beta-mannanase in the endosperm and embryo was measured using a gel assay during and following germination, and the structure of the endosperm in juxtaposition to the radicle, and surrounding the cotyledons was determined using fixation, sectioning and light microscopy. KEY RESULTS: The activity of endo-beta-mannanase, the major enzyme responsible for galactomannan cell wall weakening increased in activity only after emergence of the radicle from the seed. Thickened cell walls were present in the lateral endosperm in the hard-seeded species studied, but there was little to no thickening in the micropylar endosperm except in date seeds. In this species, a ring of thin cells was visible in the micropylar endosperm and surrounding an operculum which was pushed open by the expanding radicle to complete germination. CONCLUSIONS: The micropylar endosperm presents a lower physical constraint to the completion of germination than the lateral endosperm, and hence its structure is predisposed to permit radicle protrusion.