Explore the vast range of titles available.

Our previous studies have shown that high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn ) in the intestinal microbiome could be one of the causes of non-alcoholic fatty liver disease (NAFLD). Considering antimicrobial resistance of K. pneumoniae and dysbacteriosis caused by antibiotics, phage therapy might have potential in treatment of HiAlc Kpn -induced NAFLD, because of the specificity targeting the bacteria. Here, we clarified the effectiveness of phage therapy in male mice with HiAlc Kpn -induced steatohepatitis. Comprehensive investigations including transcriptomes and metabolomes revealed that treatment with HiAlc Kpn -specific phage was able to alleviate steatohepatitis caused by HiAlc Kpn , including hepatic dysfunction and expression of cytokines and lipogenic genes. In contrast, such treatment did not cause significantly pathological changes, either in functions of liver and kidney, or in components of gut microbiota. In addition to reducing alcohol attack, phage therapy also regulated inflammation, and lipid and carbohydrate metabolism. Our data suggest that phage therapy targeting gut microbiota is an alternative to antibiotics, with potential efficacy and safety, at least in HiAlc Kpn -caused NAFLD. Previous studies have shown that high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn ) in the intestinal microbiome could be one of the causes of non-alcoholic fatty liver disease (NAFLD). Here, the authors show the effectiveness of phage in mice with HiAlc Kpn -induced NAFLD indicating phage therapy targeting gut microbiota may be an alternative to antibiotics, with potential efficacy and safety.

Crop evapotranspiration estimation is a key parameter for achieving functional irrigation systems. However, ET is difficult to directly measure, so an ideal solution was to develop a simulation model to obtain ET. There are many ways to calculate ET, most of which use models based on the Penman–Monteith equation, but they are often inaccurate when applied to greenhouse crop evapotranspiration. The use of machine learning models to predict ET has gradually increased, but research into their application for greenhouse crops is relatively rare. We used experimental data for three years (2019–2021) to model the effects on ET of eight meteorological factors (net solar radiation (Rn), mean temperature (Ta), minimum temperature (Tamin), maximum temperature (Tamax), relative humidity (RH), minimum relative humidity (RHmin), maximum relative humidity (RHmax), and wind speed (V)) using a greenhouse drip irrigated tomato crop ET prediction model (XGBR-ET) that was based on XGBoost regression (XGBR). The model was compared with seven other common regression models (linear regression (LR), support vector regression (SVR), K neighbors regression (KNR), random forest regression (RFR), AdaBoost regression (ABR), bagging regression (BR), and gradient boosting regression (GBR)). The results showed that Rn, Ta, and Tamax were positively correlated with ET, and that Tamin, RH, RHmin, RHmax, and V were negatively correlated with ET. Rn had the greatest correlation with ET (r = 0.89), and V had the least correlation with ET (r = 0.43). The eight models were ordered, in terms of prediction accuracy, XGBR-ET > GBR-ET > SVR-ET > ABR-ET > BR-ET > LR-ET > KNR-ET > RFR-ET. The statistical indicators mean square error (0.032), root mean square error (0.163), mean absolute error (0.132), mean absolute percentage error (4.47%), and coefficient of determination (0.981) of XGBR-ET showed that XGBR-ET modeled daily ET for greenhouse tomatoes well. The parameters of the XGBR-ET model were ablated to show that the order of importance of meteorological factors on XGBR-ET was Rn > RH > RHmin> Tamax> RHmax> Tamin> Ta> V. Selecting Rn, RH, RHmin, Tamax, and Tamin as model input variables using XGBR ensured the prediction accuracy of the model (mean square error 0.047). This study has value as a reference for the simplification of the calculation of evapotranspiration for drip irrigated greenhouse tomato crops using a novel application of machine learning as a basis for an effective irrigation program.

In recent years, several drugs have been withdrawn from use by regulatory bodies owing to hepatotoxicity; therefore, studies on drug-induced liver injury (DILI) are being actively pursued. Most studies evaluating DILI use rats or mice as animal models to determine drug toxicity; however, the toxicity of a drug can vary between rats or mice. These inconsistencies in in vivo studies among different animal models affect the extrapolation of experimental results to humans. Thus, it is particularly important to choose the most suitable animal model to determine drug hepatotoxicity owing to the genomic differences between rats and mice resulting from evolution. In this study, genome-wide transcriptome analysis was used to explore hepatotoxicity caused by differences in species. Our findings provide the preclinical basis to further study the mechanisms of drug hepatotoxicity and aid in the selection of animal models to determine drug safety. We used murine models (Sprague-Dawley and Wistar rats, ICR and Kunming mice) in this study and by using transcriptome sequencing with the differentially expressed genes in rat and mouse livers as the entry point, we explored the mechanism of oxidative stress and the difference in gene expression in the lipid-metabolism pathway between rats and mice. The clinically established hepatotoxic drugs, fructus psoraleae and acetaminophen were used to validate our study. Using pathological studies, we confirmed that oxidative stress in mice was more serious than that in rats, and that Kunming mice were more suited for the study of oxidative stress-related DILI. The validity of our findings was further verified based on gene expression. Thus, our study could serve as a valuable reference for the evaluation of potential preclinical hepatotoxicity. Moreover, it could be used in the prediction and early diagnosis of drug-induced liver injury caused by traditional Chinese medicine or synthetic drugs, thereby providing a new avenue for drug-toxicity studies.

Aldehyde dehydrogenase 2 ( Aldh2 ) Glu504Lys mutation, common in East Asians, is linked to various alcohol-related pathologies, notably fatty liver disease. Recent findings suggest that high ethanol-producing Klebsiella pneumoniae (HiAlc Kpn ) exacerbates liver injury in non-alcoholic fatty liver disease (NAFLD). Our study investigated the combined effects of Aldh2 deficiency and HiAlc Kpn on NAFLD liver injury, transcriptome analyses to unearth potential mechanisms and therapeutic targets. In our controlled experiment with Aldh2 -deficient mice, we induced fatty liver via alcohol and HiAlc Kpn gavage, followed by comprehensive analyses to detect gene expression and epigenetic changes. The results showed that Aldh2 -deficient mice were particularly vulnerable to ethanol and HiAlc Kpn , with notable gene expression changes in key metabolic and liver injury pathways. Our analysis identified crucial differentially expressed genes (DEGs) and pathways, highlighting the significant roles of genes like Cyp8b1 , Cyp7a1 , and Ugt2b1 in liver metabolism and suggesting them as therapeutic targets. The study underscores the impact of Aldh2 deficiency and HiAlc Kpn on NAFLD progression, revealing potential therapeutic strategies. Despite these insights, further research is needed to clarify the systemic effects on aldehyde metabolism and the full implications of Aldh2 deficiency and HiAlc Kpn in liver injury.

The adenoids and tonsils are important immune organs of the nasopharynx that often become hypertrophic in childhood because of recurrent pathogen infection. However, the differences in the immune microenvironment of adenoid hypertrophy (AH) and tonsil hypertrophy (TH) are unclear. Here, we show the epidemiological characteristics and peripheral blood cell indices of 1209 pediatric patients (1–15 years old) diagnosed with AH, and find that AH is often accompanied by TH and characterized by specific changes in immune cell types. Single-cell RNA sequencing analysis show that 12 paired AH and TH samples contain large numbers of B, T cells and some exhausted effector memory CD4 + T cells. Compared with matched TH, AH have more naïve B cells and regulatory CD4 + T cells and less plasma B cells. Weaker antigen presentation and more significant immunosuppression are also observed in AH. In contrast, the number and cytotoxicity of cytotoxic CD8 + T cells decrease with AH grade. These findings will help our understanding of the immune response to nasopharyngeal infection. Adenoids and tonsils in children can become hypertrophic because of multiple infections. Here the authors use single cell transcriptomics to assess the immune cell composition of these hypertrophic organs and find B, T and NK cells and exhausted memory CD4 T cells indicating immune changes in these organs associated with respiratory infection.

Background Klebsiella aerogenes can cause ventilator-associated pneumonia by forming biofilms, and it is frequently associated with multidrug resistance. Phages are good antibiotic alternatives with unique advantages. There has been a lack of phage therapeutic explorations, kinetic studies, and interaction mechanism research targeting K. aerogenes . Methods Plaque assay, transmission electron microscopy and whole-genome sequencing were used to determine the biology, morphology, and genomic characteristics of the phage. A mouse pneumonia model was constructed by intratracheal/endobronchial delivery of K. aerogenes to assess the therapeutic effect of phage in vivo. Bioinformatics analysis and a prokaryotic protein expression system were used to predict and identify a novel capsule depolymerase. Confocal laser scanning microscopy, Galleria mellonella larvae infection models and other experiments were performed to clarify the function of the capsule depolymerase. Results A novel lytic phage (pK4-26) was isolated from hospital sewage. It was typical of the Podoviridae family and exhibited serotype specificity, high lytic activity, and high environmental adaptability. The whole genome is 40,234 bp in length and contains 49 coding domain sequences. Genomic data show that the phage does not carry antibiotic resistance, virulence, or lysogenic genes. The phage effectively lysed K. aerogenes in vivo, reducing mortality and alleviating pneumonia without promoting obvious side effects. A novel phage-derived depolymerase was predicted and proven to be able to digest the capsule, remove biofilms, reduce bacterial virulence, and sensitize the bacteria to serum killing. Conclusions The phage pK4-26 is a good antibiotic alternative and can effectively relieve pneumonia caused by multidrug-resistant K. aerogenes . It carries a depolymerase that removes biofilms, reduces virulence, and improves intrinsic immune sensitivity.

The improvement of the simulation accuracy of crop models in different greenhouse environments would be better applied to the automation management of greenhouse cultivation. Tomatoes under drip irrigation in a greenhouse were taken as the research object, and the cumulative evaporation capacity (Ep) of the 20 cm standard evaporation dish was taken as the basis for irrigation. Three treatments were set up in the experiment: high water treatment without mulch (NM-0.9 Ep), high water treatment with mulch (M-0.9 Ep), and low water treatment with mulch (M-0.5 Ep). AquaCrop and DSSAT models were used to simulate the canopy coverage, soil water content, biomass, and yield of the tomatoes. Data from 2020 were used to correct the model, and simulation results from 2021 were analyzed in this paper. The results showed that: (1) Of the two crop models, the simulation accuracy of the greenhouse tomato canopy coverage kCC was higher, and the root mean square errors were less than 6.8% (AquaCrop model) and 8.5% (DSSAT model); (2) The AquaCrop model could accurately simulate soil water change under high water treatments, while the DSSAT model was more suitable for the conditions without mulch; (3) The relative error RE of simulated and observed values for biomass B, yield Y, and water use efficiency WUE in the AquaCrop model were less than 2.0%, 2.3%, and 9.0%, respectively, while those of the DSSAT model were less than 4.7%, 7.6%, and 10.4%, respectively; (4) Considering the simulation results of each index comprehensively, the AquaCrop model was superior to the DSSAT model; subsequently, the former was used to predict 16 different water and film coating treatments (S1–S16). It was found that the greenhouse tomato yield and WUE were the highest under S7 (0.8 Ep), at 8.201 t/ha and 2.79 kg/m3, respectively.

Bacterial infections caused by multidrug-resistant (MDR) gram-negative strains carrying the mobile colistin resistance gene mcr-1 are serious threats to world public health due to the lack of effective treatments. Inhibition of the ATP synthase makes bacteria such as Staphylococcus aureus and Klebsiella pneumoniae more sensitive to polymyxin. This provides new strategies for treating infections caused by polymyxins-resistant bacteria carrying mcr-1 . Six mcr-1 -positive strains were isolated from clinical samples, and all were identified as Escherichia coli . Here we investigated several ATP synthase inhibitors, N , N ’-dicyclohexylcarbodiimide (DCCD), resveratrol, and piceatannol, for their antibacterial effects against the mcr-1 -positive strains combined with polymyxin B (POL). Checkerboard assay, time-kill assay, biofilm inhibition and eradication assay indicated the significant synergistic effect of ATP synthase inhibitors/POL combination in vitro. Meanwhile, mouse infection model experiment was also performed, showing a 5 log 10 reduction of the pathogen after treatment with the resveratrol/POL combination. Moreover, adding adenosine disodium triphosphate (Na 2 ATP) could inhibit the antibacterial effect of the ATP synthase inhibitors/POL combination. In conclusion, our study confirmed that inhibition of ATP production could increase the susceptibility of bacteria carrying mcr-1 to polymyxins. This provides a new strategy against polymyxins-resistant bacteria infection.

Capsular polysaccharides are critical virulence factors of Klebsiella pneumoniae, enabling the bacterium to evade host immune recognition and exacerbate infection. Phage-derived depolymerases, which specifically degrade these capsular polysaccharides, are increasingly recognized as a highly promising strategy for the treatment of bacterial infections. In the present study, we isolated and characterized a lytic Klebsiella pneumoniae phage, named phiTH1, and sequenced its genome. The K30-type capsular polysaccharide was identified as the receptor for phiTH1 infection. A tail fiber protein with a pectate lyase domain, Dop5, was then recognized as a potential K30-type depolymerase. Therefore, the recombinant protein Dop5 was expressed in Escherichia coli and purified, and its in vitro capsular depolymerase activity was demonstrated. Further, by using a murine aspiration pneumonia model induced by K30-type Klebsiella pneumoniae TH1, we found that Dop5 protected 80% of mice from lethal challenge with Klebsiella pneumoniae. After Dop5 treatment, the pathological damage in multiple organs of mice was alleviated, the bacterial load was reduced, and serum levels of inflammatory cytokines and complement C3 decreased, along with a significant reduction in the pathological score of the lungs. Hence, this study revealed the potential of the depolymerase Dop5 for the treatment of Klebsiella pneumoniae infections.

Tibetan medicine is one of the oldest traditional medicine systems in the world. Taking the Ruyi Zhenbao tablet (RYZB) as an example, which is a widely used classic oral Tibetan medicine, this article discusses the pharmacokinetics of single administration and long-term treatment and analyzed its metabolic properties and tissue distribution in vivo . After single administration, blood samples were collected before administration and at different time points after administration in different groups of rats. In the study of long-term treatment effects, blood samples were collected from the animals in each group on days 1, 15, and 30 and on day 15 after withdrawal. The results showed that after a single administration, the dose change had no significant effect on the T 1/2 and T max of agarotetrol, isoliquiritigenin, and piperine ( p > 0.05). There was a certain correlation between the increase in AUC 0-t and the C max of agarotetrol, isoliquiritigenin, piperine, and the increase in dosage, with a dose range of 0.225–0.900 g/kg. There were no significant differences in C max and AUC 0-t of ferulic acid at different doses ( p > 0.05). Meanwhile, there was no significant sex-based difference in the pharmacokinetic parameters of these four components in rats. After long-term administration, the distribution agarotetrol in various tissues of rats was kidney > liver > heart > brain; the tissue distribution in low- and medium-dose groups of isoliquiritigenin was liver > kidney > heart > brain, and in the high-dose group, kidney > liver > heart > brain. The tissue distribution of piperine in each dose group was liver > kidney > heart > brain, and that of ferulic acid in each dose group was kidney > liver > heart > brain. Through the establishment of the previously developed methodology, the pharmacokinetic properties of RYZB were analyzed after a single administration and long-term administration. Our findings confirmed this approach for the exploration and establishment of a pharmacokinetic evaluation of Tibetan medicine, to support its guiding role in clinical application, but also to accelerate research into Tibetan medicine theory and medicine and to provide a solid foundation for the translation of Tibetan medicine throughout the world.