Machine learning-based algorithm identifies key mitochondria-related genes in non-alcoholic steatohepatitis.

BACKGROUND: Evidence suggests that hepatocyte mitochondrial dysfunction leads to abnormal lipid metabolism, redox imbalance, and programmed cell death, driving the onset and progression of non-alcoholic steatohepatitis (NASH). Identifying hub mitochondrial genes linked to NASH may unveil potential therapeutic targets. METHODS: Mitochondrial hub genes implicated in NASH were identified via analysis using 134 algorithms. RESULTS: The Random Forest algorithm (RF), the most effective among the 134 algorithms, identified three genes: Aldo-keto reductase family 1 member B10 (AKR1B10), thymidylate synthase (TYMS), and triggering receptor expressed in myeloid cell 2 (TREM2). They were upregulated and positively associated with genes promoting inflammation, genes involved in lipid synthesis, fibrosis, and nonalcoholic steatohepatitis activity scores in patients with NASH. Moreover, using these three genes, patients with NASH were accurately categorized into cluster 1, exhibiting heightened disease severity, and cluster 2, distinguished by milder disease activity. CONCLUSION: These three genes are pivotal mitochondrial genes implicated in NASH progression.

Enhanced precision and efficiency in metabolic regulation: Compartmentalized metabolic engineering.

Metabolic engineering has witnessed remarkable advancements, enabling successful large-scale, cost-effective and efficient production of numerous compounds. However, the predominant expression of heterologous genes in the cytoplasm poses limitations, such as low substrate concentration, metabolic competition and product toxicity. To overcome these challenges, compartmentalized metabolic engineering allows the spatial separation of metabolic pathways for the efficient and precise production of target compounds. Compartmentalized metabolic engineering and its common strategies are comprehensively described in this study, where various membranous compartments and membraneless compartments have been used for compartmentalization and constructive progress has been made. Additionally, the challenges and future directions are discussed in depth. This review is dedicated to providing compartmentalized, precise and efficient methods for metabolic production, and provides valuable guidance for further development in the field of metabolic engineering.

Application of cold-adapted microbial agents in soil contaminate remediation: biodegradation mechanisms, case studies, and safety assessments.

The microbial agent technology has made significant progress in remediating nitro-aromatic compounds (NACs), such as p-nitrophenol, 2,4-dinitrophenol, and 2,4,6-Trinitrotoluene, in farmland soil over the past decade. However, there are still gaps in our understanding of the bioavailability and degradation mechanisms of these compounds in low-temperature environments. In this review, we provide a comprehensive summary of the strategies employed by cold-adapted microorganisms and elucidate the degradation pathways of NACs pollutants. To further analyze their metabolic mechanisms, we propose using mass balance to improve our understanding of biochemical processes and refine the degradation pathways through stoichiometry analysis. Additionally, we suggest employing 13C-metabolic flux analysis to track enzyme activity and intermediate products during bio-degradation processes with the aim of accelerating the remediation of nitro-aromatic compounds, particularly in cold regions. Through a comprehensive analysis of pollutant metabolic activities and a commitment to the 'One Health' approach, with an emphasis on selecting non-pathogenic strains, the environmental management strategies for soil remediation could be positioned to develop and implement safe and effective measure.

Stacking-dependent interlayer magnetic interactions in CrSe2.

Recently, CrSe2, a new ferromagnetic van der Waals two-dimensional material, was discovered to be highly stable under ambient conditions, making it an attractive candidate for fundamental research and potential device applications. Here, we study the interlayer interactions of bilayer CrSe2using first-principles calculations. We demonstrate that the interlayer interaction depends on the stacking structure. The AA and AB stackings exhibit antiferromagnetic (AFM) interlayer interactions, while the AC stacking exhibits ferromagnetic (FM) interlayer interaction. Furthermore, the interlayer interaction can be further tuned by tensile strain and charge doping. Specifically, under large tensile strain, most stacking structures exhibit FM interlayer interactions. Conversely, under heavy electron doping, all stacking structures exhibit AFM interlayer interactions. These findings are useful for designing spintronic devices based on CrSe2.

Integrative Dissection of Lignin Composition in Tartary Buckwheat Seed Hulls for Enhanced Dehulling Efficiency.

The rigid hull encasing Tartary buckwheat seeds necessitates a laborious dehulling process before flour milling, resulting in considerable nutrient loss. Investigation of lignin composition is pivotal in understanding the structural properties of tartary buckwheat seeds hulls, as lignin is key determinant of rigidity in plant cell walls, thus directly impacting the dehulling process. Here, the lignin composition of seed hulls from 274 Tartary buckwheat accessions is analyzed, unveiling a unique lignin chemotype primarily consisting of G lignin, a common feature in gymnosperms. Furthermore, the hardness of the seed hull showed a strong negative correlation with the S lignin content. Genome-wide detection of selective sweeps uncovered that genes governing the biosynthesis of S lignin, specifically two caffeic acid O-methyltransferases (COMTs) and one ferulate 5-hydroxylases, are selected during domestication. This likely contributed to the increased S lignin content and decreased hardness of seed hulls from more domesticated varieties. Genome-wide association studies identified robust associations between FtCOMT1 and the accumulation of S lignin in seed hull. Transgenic Arabidopsis comt1 plants expressing FtCOMT1 successfully reinstated S lignin content, confirming its conserved function across plant species. These findings provide valuable metabolic and genetic insights for the potential redesign of Tartary buckwheat seed hulls.

LRRC8A as a central mediator promotes colon cancer metastasis by regulating PIP5K1B/PIP2 pathway.

Colorectal cancer (CRC) has been the third most common malignancy and the second cause of cancer-related mortality. As the core of volume-sensitive chloride currents, leucine-rich repeat-containing 8A (LRRC8A) contributes to tumor progression but is not consistent, especially for whom the roles in colon carcinoma metastasis were not fully elucidated. Herein, LRRC8A proteins were found highly expressed in hematogenous metastasis from human colorectal cancer samples. The oxaliplatin-resistant HCT116 cells highly expressed LRRC8A, which was related to impaired proliferation and enhanced migration. The over-expressed LRRC8A slowed proliferation and increased migration ex vivo and in vivo. The elevated LRRC8A upregulated the focal adhesion, MAPK, AMPK, and chemokine signaling pathways via phosphorylation and dephosphorylation. Inhibition of LRRC8A impeded the TNF-α signaling cascade and TNF-α-induced migration. LRRC8A binding to PIP5K1B regulated the PIP2 formation, providing a platform for LRRC8A to mediate cell signaling transduction. Importantly, LRRC8A self-regulated its transcription via NF-κB1 and NF-κB2 pathways and the upregulation of NIK/NF-κB2/LRRC8A transcriptional axis was unfavorable for colon cancer patients. Collectively, our findings reveal that LRRC8A is a central mediator in mediating multiple signaling pathways to promote metastasis and targeting LRRC8A proteins could become a potential clinical biomarker-driven treatment strategy for colon cancer patients.

Exercise ameliorates lipid droplet metabolism disorder by the PLIN2-LIPA axis-mediated lipophagy in mouse model of non-alcoholic fatty liver disease.

Excessive hepatic lipid droplets (LDs) accumulation-induced lipid metabolism disorder contributes to the development of non-alcoholic fatty liver disease (NAFLD). Exercise is a promising therapeutic strategy for NAFLD. However, the mechanism by which exercise ameliorates NAFLD through regulating the catabolism of hepatic LDs remains unclear. In the present study, we investigated the effect of perilipin2 (PLIN2)-lysosomal acid lipase (LIPA) axis mediating exercise-triggered lipophagy in a high-fat diet (HFD)-induced NAFLD mouse model. Our results showed that exercise could reduce HFD-induced hepatic LDs accumulation and change the expression of lipolysis-related enzymes. Moreover, exercise upregulated the expression of microtubule associated protein 1 light chain 3 (LC3) and autophagy-related proteins, and downregulated sequestosome 1 (P62) expression and promoted autophagosomes formation. Interestingly, exercise downregulated PLIN2 expression, upregulated LIPA expression, and increased the activity of hepatic LIPA and serum levels of LIPA in the NAFLD mouse model. Further mechanistic studies demonstrated that adenosine monophosphate-activated protein kinase (AMPK) activator-5-Aminoimidazole-4-carboxamide ribonucleoside (AICAr) treatment significantly increased mRNA levels and protein expression of LIPA and LC3II and decreased levels of PLIN2 and P62 in palmitic acid (PA)-treated HepG2 cells. PLIN2 silencing and LIPA overexpression notably increased the mRNA level and protein expression of LC3II and decreased the mRNA level and protein expression of p62, respectively. In summary, our findings reveal novel insights into the effect of exercise on improving lipid droplet metabolism disorder in NAFLD. Enhancing the PLIN2-LIPA axis-mediated lipophagy may be one of the key mechanisms involved in NAFLD alleviation by exercise.

Long noncoding RNA KCNQ1OT1 aggravates cerebral infarction by regulating PTBT1/SIRT1 via miR-16-5p.

Cerebral infarction (CI) is one of the leading causes of disability and death. LncRNAs are key factors in CI progression. Herein, we studied the function of long noncoding RNA KCNQ1OT1 in CI patient plasma samples and in CI models. Quantitative real-time PCR and Western blotting tested gene and protein expressions. The interactions of KCNQ1OT1/PTBP1 and miR-16-5p were analyzed using dual-luciferase reporter and RNA immunoprecipitation assays; MTT assays measured cell viability. Cell migration and angiogenesis were tested by wound healing and tube formation assays. Pathological changes were analyzed by triphenyltetrazolium chloride and routine staining. We found that KCNQ1OT1 and PTBP1 were overexpressed and miR-16-5p was downregulated in CI patient plasma and in oxygen-glucose deprived (OGD) induced mouse brain microvascular endothelial (bEnd.3) cells. KCNQ1OT1 knockdown suppressed pro-inflammatory cytokine production and stimulated angiogenic responses in OGD-bEnd.3 cells. KCNQ1OT1 upregulated PTBP1 by sponging miR-16-5p. PTBP1 overexpression or miR-16-5p inhibition attenuated the effects of KCNQ1OT1 knockdown. PTBP1 silencing protected against OGD-bEnd.3 cell injury by enhancing SIRT1. KCNQ1OT1 silencing or miR-16-5p overexpression also alleviated ischemic injury in a mice middle cerebral artery occlusion model. Thus, KCNQ1OT1 silencing alleviates CI by regulating the miR-16-5p/PTBP1/SIRT1 pathway, providing a theoretical basis for novel therapeutic strategies targeting CI.

A New Potent Inhibitor against α-Glucosidase Based on an In Vitro Enzymatic Synthesis Approach.

Inhibiting the activity of intestinal α-glucosidase is considered an effective approach for treating type II diabetes mellitus (T2DM). In this study, we employed an in vitro enzymatic synthesis approach to synthesize four derivatives of natural products (NPs) for the discovery of therapeutic drugs for T2DM. Network pharmacology analysis revealed that the betulinic acid derivative P3 exerted its effects in the treatment of T2DM through multiple targets. Neuroactive ligand-receptor interaction and the calcium signaling pathway were identified as key signaling pathways involved in the therapeutic action of compound P3 in T2DM. The results of molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations indicate that compound P3 exhibits a more stable binding interaction and lower binding energy (-41.237 kcal/mol) with α-glucosidase compared to acarbose. In addition, compound P3 demonstrates excellent characteristics in various pharmacokinetic prediction models. Therefore, P3 holds promise as a lead compound for the development of drugs for T2DM and warrants further exploration. Finally, we performed site-directed mutagenesis to achieve targeted synthesis of betulinic acid derivative. This work demonstrates a practical strategy of discovering novel anti-hyperglycemic drugs from derivatives of NPs synthesized through in vitro enzymatic synthesis technology, providing potential insights into compound P3 as a lead compound for anti-hyperglycemic drug development.

Machine learning-based integration identifies the ferroptosis hub genes in nonalcoholic steatohepatitis.

BACKGROUND: Ferroptosis, is characterized by lipid peroxidation of fatty acids in the presence of iron ions, which leads to cell apoptosis. This leads to the disruption of metabolic pathways, ultimately resulting in liver dysfunction. Although ferroptosis is linked to nonalcoholic steatohepatitis (NASH), understanding the key ferroptosis-related genes (FRGs) involved in NASH remains incomplete. NASH may be targeted therapeutically by identifying the genes responsible for ferroptosis. METHODS: To identify ferroptosis-related genes and develop a ferroptosis-related signature (FeRS), 113 machine-learning algorithm combinations were used. RESULTS: The FeRS constructed using the Generalized Linear Model Boosting algorithm and Gradient Boosting Machine algorithms exhibited the best prediction performance for NASH. Eight FRGs, with ZFP36 identified by the algorithms as the most crucial, were incorporated into in FeRS. ZFP36 is significantly enriched in various immune cell types and exhibits significant positive correlations with most immune signatures. CONCLUSION: ZFP36 is a key FRG involved in NASH pathogenesis.

Microbial production and applications of ß-glucosidase-A review.

ß-Glucosidase exists in all areas of living organisms, and microbial ß-glucosidase has become the main source of its production because of its unique physicochemical properties and the advantages of high-yield production by fermentation. With the rise of the green circular economy, the production of enzymes through the fermentation of waste as the substrate has become a popular trend. Lignocellulosic biomass is an easily accessible and sustainable feedstock that exists in nature, and the production of biofuels from lignocellulosic biomass requires the involvement of ß-glucosidase. This review proposes ways to improve ß-glucosidase yield and catalytic efficiency. Optimization of growth conditions and purification strategies of enzymes can increase enzyme yield, and enzyme immobilization, genetic engineering, protein engineering, and whole-cell catalysis provide solutions to enhance the catalytic efficiency and activity of ß-glucosidase. Besides, the diversified industrial applications, challenges and prospects of ß-glucosidase are also described.

Mitochondrial VOLTAGE-DEPENDENT ANION CHANNEL 3 regulates stomatal closure by abscisic acid signaling.

In Arabidopsis (Arabidopsis thaliana), stomatal closure mediated by abscisic acid (ABA) is redundantly controlled by ABA receptor family proteins (PYRABACTIN RESISTANCE 1 [PYR1]/PYR1-LIKE [PYLs]) and subclass III SUCROSE NONFERMENTING 1 (SNF1)-RELATED PROTEIN KINASES 2 (SnRK2s). Among these proteins, the roles of PYR1, PYL2, and SnRK2.6 are more dominant. A recent discovery showed that ABA-induced accumulation of reactive oxygen species (ROS) in mitochondria promotes stomatal closure. By analyzing stomatal movements in an array of single and higher order mutants, we revealed that the mitochondrial protein VOLTAGE-DEPENDENT ANION CHANNEL 3 (VDAC3) jointly regulates ABA-mediated stomatal closure with a specialized set of PYLs and SnRK2s by affecting cellular and mitochondrial ROS accumulation. VDAC3 interacted with 9 PYLs and all 3 subclass III SnRK2s. Single mutation in VDAC3, PYLs (except PYR1 and PYL2), or SnRK2.2/2.3 had little effect on ABA-mediated stomatal closure. However, knocking out PYR1, PYL1/2/4/8, or SnRK2.2/2.3 in vdac3 mutants resulted in significantly delayed or attenuated ABA-mediated stomatal closure, despite the presence of other PYLs or SnRK2s conferring redundant functions. We found that cellular and mitochondrial accumulation of ROS induced by ABA was altered in vdac3pyl1 mutants. Moreover, H2O2 treatment restored ABA-induced stomatal closure in mutants with decreased stomatal sensitivity to ABA. Our work reveals that VDAC3 ensures redundant control of ABA-mediated stomatal closure by canonical ABA signaling components.

Autoclave-Induced Changes in the Physicochemical Properties and Antigen Adsorption of Aluminum Adjuvants.

Aluminum hydroxide adjuvants are widely used in human vaccines, such as diphtheria, tetanus, hepatitis A and hepatitis B vaccines. The adsorption of antigens on aluminum hydroxide adjuvants determines the immune boosting effect of vaccines, but it is not clear how changes in physicochemical properties resulting from the production and formulation processes affect the adsorption of aluminum hydroxide adjuvants with antigens. In this study, the commercial aluminum hydroxide adjuvant Alhydrogel® was pretreated by commonly used processes such as autoclaving and calcination, and the changes of aluminum hydroxide adjuvant in physicochemical properties during the treatment were then comprehensively characterized. The adsorption of ovalbumin (OVA) with treated Alhydrogel®, was also investigated, it was found that the decrease in specific surface area caused by the autoclaving process reduced the adsorptive capacity of the antigen, and the adsorptive strength of antigen was decreased only when the surface hydroxyl groups and chemically bound water of adjuvant were reduced by calcination. These findings help to optimize the production and formulation process of adjuvants for the rational regulation of antigen adsorption in vaccines.

Hypothalamic FTO promotes high-fat diet-induced leptin resistance in mice through increasing CX3CL1 expression.

Long-term consumption of a high-fat diet (HFD) disrupts energy homeostasis and leads to weight gain. The fat mass and obesity-associated (FTO) gene has been consistently identified to be associated with HFD-induced obesity. The hypothalamus is crucial for regulating energy balance, and HFD-induced hypothalamic leptin resistance contributes to obesity. FTO, an N6-methyladenosine (m6A) RNA methylation regulator, may be a key mediator of leptin resistance. However, the exact mechanisms remain unclear. Therefore, the present study aims to investigate the association between FTO and leptin resistance. After HFD or standard diet (SD) feeding in male mice for 22 weeks, m6A-sequencing and western blotting assays were used to identify target genes and assess protein level, and molecular interaction changes. CRISPR/Cas9 gene knockout system was employed to investigate the potential function of FTO in leptin resistance and obesity. Our data showed that chemokine (C-X3-C motif) ligand 1 (CX3CL1) was a direct downstream target of FTO-mediated m6A modification. Furthermore, upregulation of FTO/CX3CL1 and suppressor of cytokine signaling 3 (SOCS3) in the hypothalamus impaired leptin-signal transducer and activator of transcription 3 signaling, resulting in leptin resistance and obesity. Compared to wild-type (WT) mice, FTO deficiency in leptin receptor-expressing neurons of the hypothalamus significantly inhibited the upregulation of CX3CL1 and SOCS3, and partially ameliorating leptin resistance under HFD conditions. Our findings reveal that FTO involved in the hypothalamic leptin resistance and provides novel insight into the function of FTO in the contribution to hypothalamic leptin resistance and obesity.

Role of hierarchy structure on the mechanical adaptation of self-healing hydrogels under cyclic stretching.

Soft materials with mechanical adaptability have substantial potential for various applications in tissue engineering. Gaining a deep understanding of the structural evolution and adaptation dynamics of soft materials subjected to cyclic stretching gives insight into developing mechanically adaptive materials. Here, we investigate the effect of hierarchy structure on the mechanical adaptation of self-healing hydrogels under cyclic stretching training. A polyampholyte hydrogel, composed of hierarchical structures including ionic bonds, transient and permanent polymer networks, and bicontinuous hard/soft-phase networks, is adopted as a model. Conditions for effective training, mild overtraining, and fatal overtraining are demonstrated in soft materials. We further reveal that mesoscale hard/soft-phase networks dominate the long-term memory effect of training and play a crucial role in the asymmetric dynamics of compliance changes and the symmetric dynamics of hydrogel shape evolution. Our findings provide insights into the design of hierarchical structures for adaptive soft materials.

Aztreonam is a novel chemical inducer that promotes Agrobacteium transformation and lateral root development in soybean.

Agrobacterium-mediated soybean transformation is the simplest method of gene transfer. However, the low transformation due to the intractable nature of soybean genotypes hinders this process. The use of biochemicals (acetosyringone, cinnamic acid, flavonoids, etc.) plays an important role in increasing soybean transformation. These biochemicals induce chemotaxis and virulence gene activation during the infection process. Here we identified a biochemical, aztreonam (a monobactam), for high agrobacterium-mediated transformation in soybean. The soybean explants from three genotypes were inoculated with A. tumefaciens (GV3101) harboring the pMDC32 vector containing hpt or the GmUbi-35S-GUS vector containing the GUS gene during two separate events. High transient GUS expression was obtained during cotyledon explant culture on MS media supplemented with 2.5 mg/L aztreonam. The aztreonam-treated explants showed high efficiency in transient and stable transformation as compared to the untreated control. The transformation of aztreonam-treated explants during seed imbibition resulted in an average of 21.1% as compared to 13.2% in control by using the pMDC32 vector and 28.5 and 20.7% while using the GUS gene cassette, respectively. Based on these findings, the metabolic analysis of the explant after aztreonam treatment was assessed. The high accumulation of flavonoids was identified during an untargeted metabolic analysis. The quantification results showed a significantly high accumulation of the four compounds, i.e., genistein, apigenin, naringenin, and genistin, in cotyledon explants after 18 hours of aztreonam treatment. Alongside this, aztreonam also had some surprising effects on root elongation and lateral root formation when compared to indole-3-butyric acid (IBA). Our findings were limited to soybeans. However, the discovery of aztreonam and its effect on triggering flavonoids could lead to the potential role of aztreonam in the agrobacterium-mediated transformation of different crops.

VAMP726 from maize and Arabidopsis confers pollen resistance to heat and UV radiation by influencing lignin content of sporopollenin.

Sporopollenin in the pollen cell wall protects male gametophytes from stresses. Phenylpropanoid derivatives, including guaiacyl (G) lignin units, are known to be structural components of sporopollenin, but the exact composition of sporopollenin remains to be fully resolved. We analyzed the phenylpropanoid derivatives in sporopollenin from maize and Arabidopsis by thioacidolysis coupled with nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS). The NMR and GC-MS results confirmed the presence of p-hydroxyphenyl (H), G, and syringyl (S) lignin units in sporopollenin from maize and Arabidopsis. Strikingly, H units account for the majority of lignin monomers in sporopollenin from these species. We next performed a genome-wide association study to explore the genetic basis of maize sporopollenin composition and identified a vesicle-associated membrane protein (ZmVAMP726) that is strongly associated with lignin monomer composition of maize sporopollenin. Genetic manipulation of VAMP726 affected not only lignin monomer composition in sporopollenin but also pollen resistance to heat and UV radiation in maize and Arabidopsis, indicating that VAMP726 is functionally conserved in monocot and dicot plants. Our work provides new insight into the lignin monomers that serve as structural components of sporopollenin and characterizes VAMP726, which affects sporopollenin composition and stress resistance in pollen.

The differences of event-related potential components in patients with comorbid depression and anxiety, depression, or anxiety alone.

BACKGROUND: There was a high comorbidity rate of major depressive disorder (MDD) and generalized anxiety disorder (GAD), showing a poor prognosis and significant detrimental impact on functioning. The study aimed to find whether patients with comorbid GAD and MDD had some differences in cognitive functions from patients with MDD or GAD alone. METHODS: 360 adult patients were enrolled from inpatient department of psychiatry from 2020 to 2022. They were divided into three groups with 120 patients for each group: MDD, GAD, and MDD + GAD. All the patients completed psychological evaluation scales including patient health questionnaire-9 (PHQ-9) and 7-item generalized anxiety disorder (GAD-7). All the patients underwent examinations of auditory brainstem response and event-related potentials (ERPs). RESULTS: In MDD + GAD group, P3b latency was significantly longer than patients with MDD alone, and P300 reaction time was positively correlated with total score of GAD-7 and PHQ-9, and PHQ-9 total score was also significantly positively correlated with P2-P3b amplitude (all p < 0.05). In addition, MDD patients had significantly longer P300 reaction time and lower P2-P3b amplitude than the GAD group (p < 0.05). LIMITATIONS: It was a single-center and cross-sectional study, and we used self-report scales as assessment tools. CONCLUSIONS: Patients with MDD and GAD comorbidity might have a worse cognitive function than MDD patients, and the severity of cognitive impairments was positively correlated with the severity of anxiety and depression symptoms.

Hosts engineering and in vitro enzymatic synthesis for the discovery of novel natural products and their derivatives.

Novel natural products (NPs) and their derivatives are important sources for drug discovery, which have been broadly applied in the fields of agriculture, livestock, and medicine, making the synthesis of NPs and their derivatives necessarily important. In recent years, biosynthesis technology has received increasing attention due to its high efficiency in the synthesis of high value-added novel products and its advantages of green, environmental protection, and controllability. In this review, the technological advances of biosynthesis strategies in the discovery of novel NPs and their derivatives are outlined, with an emphasis on two areas of host engineering and in vitro enzymatic synthesis. In terms of hosts engineering, multiple microorganisms, including Streptomyces, Aspergillus, and Penicillium, have been used as the biosynthetic gene clusters (BGCs) provider and host strain for the expression of BGCs to discover new compounds over the past years. In addition, the use of in vitro enzymatic synthesis strategy to generate novel compounds such as triterpenoid saponins and flavonoids is also hereby described.

Shear wave elastography parameters adds prognostic value to adverse outcome in kidney transplantation recipients.

INTRODUCTION: The tissue stiffness of donor kidneys in transplantation may increase due to pathological changes such as glomerulosclerosis and interstitial fibrosis, and those changes associate worse outcomes in kidney transplantation recipients. Ultrasound elastography is a noninvasive imaging examination with the ability to quantitatively reflect tissue stiffness. Aim of this study was to evaluate the prognostic value of ultrasound elastography for adverse kidney outcome in kidney transplantation recipients. METHODS: Shear wave elastography (SWE) examinations were performed by two independent operators in kidney transplantation recipients. The primary outcome was a composite of kidney graft deterioration, all-cause re-hospitalization, and all-cause mortality. Survival analysis was calculated by Kaplan-Meier curves with the log-rank test and Cox regression analysis. RESULTS: A total of 161 patients (mean age 46 years, 63.4% men) were followed for a median of 20.1 months. 27 patients (16.77%) reached the primary endpoint. The mean and median tissue stiffness at the medulla (hazard ratio: 1.265 and 1.229, respectively), estimated glomerular filtration rate (eGFR), and serum albumin level were associated with the primary outcome in univariate Cox regression. Adding mean or median medulla SWE to a baseline model containing eGFR and albumin significantly improved its discrimination (C-statistics: 0.736 for the baseline, 0.766 and 0.772 for the model added mean and median medulla SWE, respectively). CONCLUSION: The medullary tissue stiffness of kidney allograft measured by shear wave elastography may provide incremental prognostic value to adverse outcomes in kidney transplantation recipients. Including SWE parameters in kidney transplantation recipients management could be considered to improve risk stratification.