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Cancer microbiota have recently been demonstrated in several cancer types. The microbiome enhances inflammation in the cancer microenvironment and affects the disease pathology by regulating tumourigenesis, cancer progression, and chemotherapy resistance. Hepatoblastoma (HB), the most common childhood malignant tumour, is a malignant embryonic tumour. However, the pathogenesis and molecular basis of HB remain poorly understood. In this study, to explore the existence and distribution of the microbiome in tumour tissues and adjacent non-tumour tissues of children with HB, we mainly performed 16S rDNA sequencing, and the results showed that the diversity and abundance of the microbiome in children with HB were significantly different between HB tumours and adjacent non-tumour tissues (p

Klebsiella pneumoniae is a common, conditionally pathogenic bacterium that often has a multidrug-resistant phenotype, leading to failure of antibiotic therapies. It can therefore induce serious diseases, including community-acquired pneumonia and bloodstream infections. As an emerging alternative to antibiotics, phages are considered key to solving the problem of drug-resistant bacterial infections. Here, we report a novel phage, pK3–24, that mainly targets ST447 K. pneumoniae. Phage pK3–24 is a T7-like short-tailed phage with a fast adsorption capacity that forms translucent plaques with halos on bacterial lawns. The optimal multiplicity of infection (MOI) is 0.01, and the average burst size is 50 PFU/mL. Phage pK3–24 shows environmental stability, surviving at below 50 °C and at pH values of 6–10. It has a double-stranded DNA genome of 40,327 bp and carries no antibiotic-resistance, virulence, or lysogeny genes. Phylogenetic analysis assigned phage pK3–24 to the genus Przondovirus as a new species. Phage pK3–24 inhibited the production of biofilm. Moreover, treatment with pK3–24 at doses with an MOI > 1 effectively reduced the mortality of Galleria mellonella larvae infected with ST447 K. pneumoniae.

We collected respiratory specimens from 128 pediatric patients diagnosed with pneumonia in Beijing in late 2023. Mycoplasma pneumoniae was detected in 77.3% (99/128) patients, with 36.4% (4/11), 82.9% (34/41), 80.3% (61/76) in children aged less than 3 years, 3–6 years, over 7 years, respectively. Mycoplasma pneumoniae (M. pneumoniae) was characterized using P1 gene typing, MLVA typing and sequencing of domain V of the 23S rRNA gene. P1 gene type 1 (P1-1; 76.1%, 54/71) and MLVA type 4-5-7-2 (73.7%, 73/99) were predominant. MLVA identified a new genotype: 3–4–6-2. Macrolide resistance-associated mutations were detected in 100% of samples, with A2063G accounting for 99% and A2064G for 1%. The positive rate of M. pneumoniae was higher compared to previous reports, especially in children less than 3 years, suggesting a M. pneumoniae epidemic showing a younger age trend occurred in late 2023 in Beijing, China. Higher proportions of macrolide-resistant M. pneumoniae, P1-1 and 4-5-7-2 genotype M. pneumoniae indicated increased macrolide resistance rate and genotyping shift phenomenon, which might be attributable to this epidemic. Additionally, complete clinical information from 73 M. pneumoniae pneumonia inpatients were analyzed. The incidence of severe M. pneumoniae pneumonia was 56.2% (41/73). Mycoplasma pneumoniae pneumonia patients exhibited longer duration of fever, with a median value of 10.0 days (IQR, 8.0–13.0), and higher incidence of complications (74.0%, 54/73). However, in this cohort, we found that the severity of M. pneumoniae pneumonia, co-infection, or complications were not associated with M. pneumoniae P1 gene or MLVA types. Clinicians should be aware that patients infected with macrolide-resistant M. pneumoniae exhibited more severe clinical presentations.

Abstract 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.

Abstract 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.

In this work, diamondoid metal-organic frameworks (MOFs) were efficiently prepared by sonochemical synthesis and grown on polyimide (PI), aiming to improve the anti-wear performance of the PI matrix. By introducing MOFs into the PI matrix, the free movement of PI molecular chains were restricted, and its hardness and elastic modulus were improved. It was found that the wear rate of the 3 wt.% MOFs/PI composites was reduced by 72.6% compared to pure PI at a load of 4 N after tribological testing by using a ball-on-disk tribometer. This can be attributed to the excellent load-bearing and shear resistance of the fourfold-interpenetrated diamondoid networks, in which the transition metal elements can favor the formation of transfer films. It is worth noting that the 3 wt.% MOFs/PI composites still exhibited great tribological properties under high loads or high speeds. The findings of the present study indicate that diamondoid metal-organic frameworks can be used as efficient modifiers to enhance the tribological properties of PI.

ABSTRACT Klebsiella pneumoniae is a well-known human nosocomial pathogen with an arsenal of virulence factors, including capsular polysaccharides (CPS), fimbriae, flagella, and lipopolysaccharides (LPS). Our previous study found that alcohol acted as an essential virulence factor for high-alcohol-producing K. pneumoniae (HiAlc Kpn). Integration host factor (IHF) is a nucleoid-associated protein that functions as a global virulence regulator in Escherichia coli. However, the regulatory role of IHF in K. pneumoniae remains unknown. In the present study, we found that deletion of ihfA or ihfB resulted in a slight defect in bacterial growth, a severe absence of biofilm formation and cytotoxicity, and a significant reduction in alcohol production. RNA sequencing differential gene expression analysis showed that compared with the wild-type control, the expression of many virulence factor genes was downregulated in ΔihfA and ΔihfB strains, such as those related to CPS (rcsA, galF, wzi, and iscR), LPS (rfbABCD), type I and type III fimbriae (fim and mrk operon), cellulose (bcs operon), iron transporter (feoABC, fhuA, fhuF, tonB, exbB, and exbD), quorum sensing (lsr operon and sdiA), type II secretion system (T2SS) and type VI secretion system (T6SS) (tssG, hcp, and gspE). Of these virulence factors, CPS, LPS, fimbriae, and cellulose are involved in biofilm formation. In addition, IHF could affect the alcohol production by regulating genes related to glucose intake (ptsG), pyruvate formate-lyase, alcohol dehydrogenase, and the tricarboxylic acid (TCA) cycle. Our data provided new insights into the importance of IHF in regulating the virulence of HiAlc Kpn. IMPORTANCE Klebsiella pneumoniae is a well-known human nosocomial pathogen that causes various infectious diseases, including urinary tract infections, hospital-acquired pneumonia, bacteremia, and liver abscesses. Our previous studies demonstrated that HiAlc Kpn mediated the development of nonalcoholic fatty liver disease by producing excess endogenous alcohol in vivo. However, the regulators regulating the expression of genes related to metabolism, biofilm formation, and virulence of HiAlc Kpn remain unclear. In this study, the regulator IHF was found to positively regulate biofilm formation and many virulence factors including CPS, LPS, type I and type III fimbriae, cellulose, iron transporter, AI-2 quorum sensing, T2SS, and T6SS in HiAlc Kpn. Furthermore, IHF positively regulated alcohol production in HiAlc Kpn. Our results suggested that IHF could be a potential drug target for treating various infectious diseases caused by K. pneumoniae. Hence, the regulation of different virulence factors by IHF in K. pneumoniae requires further investigation.

ABSTRACT This study aimed to develop a rapid and sensitive droplet digital PCR (ddPCR) assay for the specific detection of Klebsiella pneumoniae in fecal samples, and to evaluate its application in the clinic by comparison with real-time PCR assay and conventional microbial culture. Specific primers and a probe targeting the K. pneumoniae hemolysin (khe) gene were designed. Thirteen other pathogens were used to evaluate the specificity of the primers and probe. A recombinant plasmid containing the khe gene was constructed and used to assess the sensitivity, repeatability, and reproducibility of the ddPCR. Clinical fecal samples (n = 103) were collected and tested by the ddPCR, real-time PCR, and conventional microbial culture methods. The detection limit of ddPCR for K. pneumoniae was 1.1 copies/μL, about a 10-fold increase in sensitivity compared with real-time PCR. The ddPCR was negative for the 13 pathogens other than K. pneumoniae, confirming its high specificity. Clinical fecal samples gave a higher rate of positivity in the K. pneumoniae ddPCR assay than in analysis by real-time PCR or conventional culture. ddPCR also showed less inhibition by the inhibitor in fecal sample than real-time PCR. Thus, we established a sensitive and effective ddPCR-based assay method for K. pneumoniae. It could be a useful tool for K. pneumoniae detection in feces and may serve as a reliable method to identify causal pathogens and help guide treatment decisions. IMPORTANCE Klebsiella pneumoniae can cause a range of illnesses and has a high colonization rate in the human gut, making it crucial to develop an efficient method for detecting K. pneumoniae in fecal samples.

ABSTRACT High-alcohol-producing K. pneumoniae (HiAlc Kpn) causes nonalcoholic fatty liver disease (NAFLD) by producing excess endogenous alcohol in the gut of patients with NAFLD, using glucose as the main carbon source. The role of glucose in the response of HiAlc Kpn to environmental stresses such as antibiotics remains unclear. In this study, we found that glucose could enhance the resistance of HiAlc Kpn to polymyxins. First, glucose inhibited the expression of crp in HiAlc Kpn and promoted the increase of capsular polysaccharide (CPS), which promoted the drug resistance of HiAlc Kpn. Second, glucose maintained high ATP levels in HiAlc Kpn cells under the pressure of polymyxins, enhancing the resistance of the cells to the killing effect of antibiotics. Notably, the inhibition of CPS formation and the decrease of intracellular ATP levels could both effectively reverse glucose-induced polymyxins resistance. Our work demonstrated the mechanism by which glucose induces polymyxins resistance in HiAlc Kpn, thereby laying the foundation for developing effective treatments for NAFLD caused by HiAlc Kpn. IMPORTANCE HiAlc Kpn can use glucose to produce excess endogenous alcohol for promoting the development of NAFLD. Polymyxins are the last line of antibiotics and are commonly used to treat infections caused by carbapenem-resistant K. pneumoniae. In this study, we found that glucose increased bacterial resistance to polymyxins via increasing CPS and maintaining intracellular ATP; this increases the risk of failure to treat NAFLD caused by multidrug-resistant HiAlc Kpn infection. Further research revealed the important roles of glucose and the global regulator, CRP, in bacterial resistance and found that inhibiting CPS formation and decreasing intracellular ATP levels could effectively reverse glucose-induced polymyxins resistance. Our work reveals that glucose and the regulatory factor CRP can affect the resistance of bacteria to polymyxins, laying a foundation for the treatment of infections caused by multidrug-resistant bacteria.

Mycoplasma pneumoniae is a common causative pathogen of community-acquired pneumonia. An accurate and sensitive detection method is important for evaluating disease severity and treatment efficacy. Digital droplet PCR (ddPCR) is a competent method enabling the absolute quantification of DNA copy number with high precision and sensitivity. We established ddPCR for M. pneumoniae detection, using clinical specimens for validation, and this showed excellent specificity for M. pneumoniae. The limit of detection of ddPCR was 2.9 copies/reaction, while that for real-time PCR was 10.8 copies/reaction. In total, 178 clinical samples were used to evaluate the ddPCR assay, which correctly identified and differentiated 80 positive samples, whereas the real-time PCR tested 79 samples as positive. One sample that tested negative in real-time PCR was positive in ddPCR, with a bacterial load of three copies/test. For samples that tested positive in both methods, the cycle threshold of real-time PCR was highly correlated with the copy number of ddPCR. Bacterial loads in patients with severe M. pneumoniae pneumonia were significantly higher than those in patients with general M. pneumoniae pneumonia. The ddPCR showed that bacterial loads were significantly decreased after macrolide treatment, which could have reflected the treatment efficacy. The proposed ddPCR assay was sensitive and specific for the detection of M. pneumoniae. Quantitative monitoring of bacterial load in clinical samples could help clinicians to evaluate treatment efficacy.

ABSTRACT It has been known that high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) is one of causative agents of nonalcoholic fatty liver disease (NAFLD). However, how HiAlc Kpn promotes liver injury remains unclear. Recent findings suggest that DNA methylation might associate with the pathogenesis of NAFLD. Herein, the role of DNA methylation in HiAlc Kpn-induced liver injury was investigated. Murine models of NAFLD were established in C57BL/6N wild-type mice by gavaging HiAlc Kpn for 8 weeks. The liver injury was assessed based on the liver histopathology and biochemical indicators. In addition, DNA methylation in hepatic tissue was assessed by using dot bolt of 5-mC. RNA sequencing analysis and whole-genome bisulfite sequencing (WGBS) analysis were also performed. HiAlc Kpn significantly increased the activity of aspartate transaminase (AST), alanine transaminase (ALT), triglycerides (TGs), and glutathione (GSH), while hypomethylation was associated with liver injury in the experimental mice induced by HiAlc Kpn. The GO and KEGG pathway enrichment analysis of the transcriptome revealed that HiAlc Kpn induced fat metabolic disorders and DNA damage. The conjoint analysis of methylome and transcriptome showed that hypomethylation regulated related gene expression in signal pathways of lipid formation and circadian rhythm, including Rorα and Arntl1genes, which may be the dominant cause of NAFLD induced by HiAlc Kpn. Data suggest that DNA hypomethylation might play an important role in liver injury of NAFLD induced by HiAlc Kpn. Which possibly provides a new sight for understanding the mechanisms of NAFLD and selecting the potential therapeutic targets. IMPORTANCE High alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) is one of causative agents of nonalcoholic fatty liver disease (NAFLD) and could induce liver damage. DNA methylation, as a common epigenetic form following contact with an etiologic agent and pathogenesis, can affect chromosome stability and transcription. We conjointly analyzed DNA methylation and transcriptome levels in the established murine models to explore the potential mechanisms for further understanding the role of DNA methylation in the liver damage of HiAlc Kpn-induced NAFLD. The analysis of the DNA methylation landscape contributes to our understanding of the entire disease process, which might be crucial in developing treatment strategies.

IntroductionThe increased prevalence of non-alcoholic fatty liver disease (NAFLD) and sarcopenia among the elderly are facing a significant challenge to the world’s health systems. Our study aims to identify the coexpressed genes in NAFLD and sarcopenia patients.MethodsWe downloaded the transcriptome data of NAFLD tissue from patients, as well as muscle tissues from sarcopenia patients, from the GEO database in order to investigate the shared transcriptional regulation mechanisms between these two diseases. Then, focusing on the genes that were frequently expressed in these diseases, together with GSVA and WGCNA, we utilized a range of analysis methods to identify the main co-expressed genes in both diseases by taking intersections. We investigated these changes after learning that they mostly affected lipid metabolism and oxidative stress injury pathways.ResultsBy analyzing these genes and their interactions with transcription factors and proteins, we were able to identify 8 genes that share common patterns. From these 8 genes, we were possible to forecast potential future medicines. Our research raises the possibility of NAFLD and sarcopenia transcriptome regulatory pathways in aging populations.DiscussionIn conclusion, a complete transcription pattern mapping was carried out in order to identify the core genes, underlying biological mechanisms, and possible therapeutic targets that regulate aging in NAFLD and sarcopenia patients. It provides novel insights and proof in favor of decreasing the increased prevalence of sarcopenia in the elderly caused by NAFLD.

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.

Staphylococcus aureus is an opportunistic pathogen that shows a unique ability to quickly respond to a variety of antibiotics. The Crp/Fnr family transcriptional regulator ArcR controls expression of arginine deiminase pathway genes arcABDC, which enable the utilization of arginine as an energy source for cell growth under anaerobic conditions. However, ArcR shares low overall similarity with other Crp/Fnr family proteins, suggesting that they differ in the response to environmental stress. In this study, MIC and survival assays were performed to determine the role of ArcR in antibiotic resistance and tolerance. The results showed that deletion of arcR reduced tolerance of S.aureus to fluoroquinolone antibiotics, mainly through a defect in the response to oxidative stress. In ΔarcR mutant, the expression of the major catalase gene katA was downregulated, and katA overexpression restored bacterial resistance to oxidative stress and antibiotics. We showed that ArcR directly regulated katA transcription by binding to the promoter region of katA. Therefore, our results revealed the contribution of ArcR in bacterial tolerance to oxidative stress and subsequently to fluoroquinolones antibiotics. This study added our understanding on the role of Crp/Fnr family in bacterial susceptibility to antibiotics.

Nasal administration of Traditional Chinese medicine (TCM) has a long history of applications. With the gradual maturing of technology and pharmacological advances, nasal preparations of TCM have undergone significant changes. Nasal TCM formulations are used not only for treatment of pneumonia, asthma, sinusitis and allergic rhinitis but also Alzheimer's disease and Parkinson's disease, as antidepressants and antiepileptics, and in ischemia reperfusion. However, according to the analysis of nasal preparations of TCM currently on the market, most of them were compound preparations, which were used to treat allergic rhinitis (AR), common cold, headache and other local treatments, with a small range of diseases. At the same time, the dosage forms were mainly traditional dosage forms, aerosols and sprays, but there were no new dosage forms, which can not meet the clinical needs in terms of variety number, variety diversity and disease types. In this manuscript, we reviewed the development and applications of different nasal preparations of TCM from the aspects of nasal structure, origin, factors affecting absorption and common dosage forms, pharmacodynamics, targeting of nasal delivery and safety. In the near future, we expect that more nasal preparations of Chinese medicine with independent intellectual property rights will be marketed to meet the needs of clinical disease management.

Osteoporosis is a disease that impacts the elderly. Low estrogen is related to changes in DNA methylation and consequent alterations in gene expression, leading to a new direction in research related to the pathophysiology of osteoporosis. We constructed an Ovariectomized (OVX) mouse model in our study, and the mouse models had osteoporosis based on the phenotype and methylation levels in the mouse’s bone. Furthermore, the methylation level of the OVX mice was significantly changed compared to that of SHAM mice. Therefore, we performed genome-level analysis on the mouse model using transcriptome and Whole Genome Bisulfite Sequencing (WGBS) by combining the data of two omics and discovered that the changes in gene expression level caused by osteoporosis primarily focused on the decrease of bone and muscle development and the activation of the immune system. According to intersection analysis of methylation and transcriptome data, the differentially expressed genes and pathways are consistent with the differentially expressed methylation locations and regions. Further, the differentially expressed methylation sites were mainly concentrated in promoters, exons, and other critical functional regions of essential differentially expressed genes. This is also the primary cause of gene differential expression variations, indicating that estrogen deficiency might regulate gene expression by altering methylation modification, leading to osteoporosis. We demonstrated the clinical value of methylation modification research, and these findings would improve the current understanding of underlying molecular mechanisms of osteoporosis incidence and development and provide new ideas for early detection and treatment of osteoporosis.

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 T1/2 and Tmax of agarotetrol, isoliquiritigenin, and piperine (p > 0.05). There was a certain correlation between the increase in AUC0-t and the Cmax 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 Cmax and AUC0-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.

Mastering root distribution is essential for optimizing the root zone environment and for improving water use efficiency, especially for crops cultivated in greenhouses. Here, we set up two irrigation amount levels based on measurements of the cumulative 20 cm pan evaporation (Ep) (i.e., K0.9: 0.9 Ep; K0.5: 0.5 Ep), and three ventilation modes through opening the greenhouse vents at different locations (TR: open the roof vents only; TRS: open both the roof and south vents; TS: open the south vents only) to reveal the effects of the ventilation mode and irrigation amount on the root distribution of greenhouse tomato. Six treatments were designed in blocks with the ventilation mode as the main treatment and the irrigation amount as the vice treatment. On this basis, the normalized root length density (NRLD) model of six treatments was developed by considering air environment, soil water and temperature conditions, root length density (RLD) and yield. The results showed that air speed of the TRS was significantly higher than TR and TS (p < 0.01), and the air temperature and relative humidity under different ventilation showed the rule: TR > TS > TRS. There was a significant third-order polynomial function relationship between NRLD and soil depth, and the coefficient of the cubic term (R0) had a bivariate quadratic polynomial function relationship with irrigation amount and air speed (determination coefficient, R2 = 0.86). Root mean square errors of the simulated and measured value of NRLD under TR, TRS and TS were 0.20, 0.23 and 0.27 in 2020, and 0.31, 0.23 and 0.28 in 2021, respectively, normalized root mean squared errors were 15%, 17%, 20% in 2020, and 23%, 18% and 21% in 2021. The RLD distribution ratio from the ground surface to a one-quarter relative root depth was 74.1%, and 88.0% from the surface to a one-half relative root depth. The results of the yield showed that a better combination of ventilation and irrigation was recommended as TRS combined with K0.9.

Herb-induced liver injury (HILI) has become a great concern worldwide due to the widespread usage of herbal products. Among these products is Dictamni Cortex (DC), a well-known Traditional Chinese Medicine (TCM), widely used to treat chronic dermatosis. Dictamni Cortex has drawn increasing attention because of its hepatotoxicity caused by the hepatotoxic component, dictamnine. However, the potential hepatotoxicity mechanism of dictamnine remains unclear. Therefore, this study aimed to use the multi-omics approach (transcriptomic, metabolomic, and proteomic analyses) to identify genes, metabolites, and proteins expressions associated with dictamnine-induced hepatotoxicity. A study on mice revealed that a high dose of dictamnine significantly increases serum aspartate aminotransferase (AST) activity, total bilirubin (TBIL), and direct bilirubin (DBIL) levels, the relative liver weight and liver/brain weight ratio in female mice (P < 0.05 and P < 0.01), compared to the normal control group. Liver histologic analysis further revealed a high dose of dictamnine on female mice caused hepatocyte vesicular steatosis characterized by hepatocyte microvesicles around the liver lobules. The expressed genes, proteins, and metabolites exhibited strong associations with lipid metabolism disorder and oxidative stress. Dictamnine caused increased oxidative stress and early hepatic apoptosis via up-regulation of glutathione S transferase a1 (GSTA1) and Bax/Bcl-2 ratio and down-regulation of the antioxidative enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase 1 (GPx-1). Besides, the up-regulation of Acyl-CoA synthetase long-chain family member 4 (ACSL4) and down-regulation of acetyl-coa acetyltransferase 1 (ACAT1) and fatty acid binding protein 1 (FABP-1) proteins were linked to lipid metabolism disorder. In summary, dictamnine induces dose-dependent hepatotoxicity in mice, which impairs lipid metabolism and aggravates oxidative stress.

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.

While online gaming has become a choice for relaxation and entertainment in today’s digital age, Internet Gaming Disorder (IGD) has also become a widely concerning mental disorder. Nature connectedness has been found to effectively reduce addiction-related risks and alleviate symptoms of addictive behaviors. It is a relatively lacking but very important factor influencing psychological recovery and regulation in the digital society. This study aims to explore the relationship between nature connectedness and IGD, and the mediating roles of intolerance of uncertainty and desire thinking. A total of 571 young people voluntarily participated in the questionnaire survey. The results showed that: (1) nature connectedness was negatively correlated with IGD; (2) intolerance of uncertainty plays a mediating role between nature connectedness and IGD; and (3) intolerance of uncertainty and desire thinking plays a chain mediating role between nature connectedness and IGD. Analysis of the research results indicates that nature connectedness can effectively reduce IGD and reveal its mechanism of action. The findings provide new insights for the study and intervention of IGD in the digital age.

BackgroundThe left subclavian artery (LSA) can be intentionally covered by a stent graft to acquire adequate landing zones for a proximal entry tear near the LSA during thoracic endovascular aortic repair (TEVAR). The Castor single-branched stent graft is designed to treat type B aortic dissection (TBAD) to retain the LSA during TEVAR. This study investigates clinical outcomes, aortic remodeling, and abdominal aortic perfusion patterns after TEVAR with the novel Castor device.MethodsFrom November 2020 to June 2023, 29 patients with TBAD involving the LSA were treated with the Castor single-branched stent graft. In-hospital clinical outcome and aortic computed tomography angiography (CTA) data were analyzed. CTA was performed preoperatively and at follow-up to observe stent morphology; branch patency; endoleak; change in true lumen (TL), false lumen (FL), and transaortic diameters; and abdominal aortic branch perfusion pattern.ResultsThe technical success rate was 96.6%. One failure was that the branch section did not completely enter the LSA and the main body migrated distally. No in-hospital mortality, paraplegia, or stroke occurred. During follow-up, one type Ib endoleak, four distal new entry tears, and one recurrent type A dissection arose from a new entry tear at the ascending aorta, no stent migration was observed, and the branch patency rate was 100%. At the thoracic aorta, TL diameters significantly increased, FL diameters markedly decreased, and FL was partially or completely thrombosed in most patients at follow-up. At the abdominal aorta, we observed 33.3% of TL growth and 66.7% of TL stabilization or shrinkage. The initial TL ratio at iliac bifurcation negatively predicted abdominal TL growth after TEVAR with a cutoff of 21.0%. Of the 102 abdominal aortic branches, 94.1% of the branches showed no change in perfusion pattern, 3.9% of the branches had an increased TL perfusion, and 2.0% of the branches had an increased FL contribution.ConclusionThe Castor unibody single-branched stent graft offers an efficient endovascular treatment for TBAD involving the LSA. TEVAR with the Castor device effectively induced thoracic FL thrombosis and thoracic TL enlargement and resulted in abdominal TL growth when the initial TL ratio at iliac bifurcation is less than 21.0%. Abdominal aortic branch perfusion patterns remain relatively stable after TEVAR with the Castor stent graft.

Objective: To elucidate the key regulator responsible for autophagy and ferroptosis, and if specific pharmacological inhibitor of upregulated gene exerted the pro-autophagic and anti-ferroptotic effect on macrophage to alleviate the atherosclerosis. Methods: Autophagy and ferroptosis were evaluated in atherosclerotic lesions and THP-1 macrophages exposed to ox-LDL. Autophagy/ferroptosis-related differentially expressed genes (DEGs) in atherosclerosis were identified by bioinformatic analysis of GSE97210 dataset, and were validated in atherosclerotic cells and tissues. The efficacy and mechanism of pharmacological inhibition of the validated DEGs on alleviating atherosclerosis were explored in vivo and in vitro. Results: Atherosclerotic lesions were characterized by autophagy inhibition and ferroptosis activation in macrophages. The crosslink between autophagy and ferroptosis were demonstrated. Ox-LDL induced THP-1 macrophage foam cell formation, autophagy dysfunction, and ferroptosis occurrence. Rapamycin ameliorated and, conversely, erastin deteriorated the effect of ox-LDL on THP-1 macrophages. Eleven autophagy/ferroptosis-related DEGs were identified in atherosclerosis vs. normal. The up-regulated expression of HIF-1α was verified in atherosclerotic lesions and THP-1 macrophages induced by ox-LDL. HIF-1α inhibitor PX-478 restored autophagy function, depressed ferroptosis, and reduced lipid accumulation in ox-LDL induced THP-1 macrophage. Autophagy inhibitor 3-MA obviously abrogated the pro-autophagic, anti-ferroptotic, and anti-atherosclerotic effects of PX-478. PX-478 treatment down-regulated HIF-1α expression and reduced atherosclerotic plaques in the mice model. Conclusions: Autophagy is inhibited, ferroptosis is activated, and crosslink occurs between autophagy and ferroptosis during atherosclerosis. HIF-1α, an upregulated DEG between atherosclerosis and normal, co-regulates autophagy and ferroptosis. HIF-1α inhibitor PX-478 attenuates foam cell formation and lessens atherosclerosis by enhancing autophagy and depressing ferroptosis in macrophages.

ObjectiveTo monitor the radiological courses of symptomatic spontaneous isolated superior mesenteric artery dissection (SISMAD) after conservation, clarify the relationship between its morphological change and initial imaging classification, and identify these factors that affect dissection remodeling.MethodsEighty-nine conservative patients with SISMAD who underwent periodic follow-up of computed tomography angiography (CTA) were enrolled. Initial morphologic classification, imaging features and dissection remodeling were analyzed retrospectively. Logistic regression was used to identify predictors for remodeling. Receiver operating characteristics were performed for cutoff threshold.ResultsZerbib classification was adapted and initial CT appearance divided eighty-nine patients into: type I (15.7%), patent false lumen (FL) with both entry and re-entry; type II (37.1%), “cul-de-sac” shaped FL without re-entry; type III (27.0%), thrombosed FL with ulcer-like-projection (ULP); type IV (18%), intramural hematoma; type V (0%), dissecting aneurysm; and type VI (2.2%), total or partial occlusion of superior mesenteric artery (SMA). Follow-up CTA revealed complete remodeling (33.7%), partial remodeling (16.9%), no change (25.8%), type change (13.5%) and dissection progression (10.1%). There was no dissection-related mortality. Type I (92.9%) sustained patent FL and no angiographic change. Type II showed partial remodeling (42.4%), no change (27.3%) and dissection progression (27.3%), and the length of FL enhancement positively predicted dissection progression with the cutoff of 40.3 millimeters. Type III achieved complete remodeling (58.3%) or evolved into type II (41.7%), and the distance between SMA orifice and ULP negatively predicted type change with the cutoff of 23.5 millimeters. Type IV (87.5%) achieved complete remodeling due to hematoma absorption. One patient underwent stent placement for the evolution of ULP into an enlarged blind-ending FL 2 months after conservation.ConclusionAfter conservation, patent FL with a distal re-entry is no morphological change, FL thrombosis tends to be resolved, and the “cul-de-sac” shaped FL without re-entry is partially shortened, no change or progressively dilated. FL enhancement length ≥ 40.3 millimeters is a predictor for the blinding-end FL enlargement. Thrombosed FL with ULP evolves into a patent “cul-de-sac” shaped FL when the distance between SMA orifice to ULP is less than 23.5 millimeters. A careful follow-up is necessary for the lesions with demonstrated predictors.

Background: During the COVID-19 pandemic, depressive symptoms, a common emotional problem among adolescents, have become more prominent. Regarding the influencing factors of adolescent depressive symptoms, it is widely accepted that parents’ problematic cellphone use around the family (specifically parental phubbing) is a strong predictive factor for the development of depressive symptoms among adolescents. Notably, the COVID-19 pandemic caused a sharp increase in the number of individuals with depressive symptoms, and the negative consequences of parental phubbing and depressive symptoms might have been exacerbated. Accordingly, this study aimed to examine the association between parental phubbing and adolescent depressive symptoms as well as their underlying mechanism. Method: To test our hypotheses, we conducted an offline/online survey with 614 adolescents in Central China from May to June 2022, which corresponded to a period of strict lockdowns in some areas due to the outbreak of the Omicron variant. The participants completed a set of measures, including a technology interference questionnaire, a parent–child relationship scale, a self-concept clarity scale, and the depressive symptoms scale. Results: Parental phubbing was positively associated with adolescent depressive symptoms; the parent–child relationship and self-concept clarity could independently mediate this relationship; and the parent–child relationship and self-concept clarity were also serial mediators in this association. These findings extend previous research by highlighting the impact of parental technology use on their children and the underlying mechanism explaining adolescent depressive symptoms. They provide practical recommendations for parents to prioritize fostering a positive family environment and minimizing phubbing behaviors to enhance adolescent development, particularly in the context of the COVID-19 pandemic.

Objective. The homing of adipose-derived stem cells (ASCs) to infarcted myocardium, which is important for improved cardiac function, has been investigated previously, but with poor efficiency. Substantial improvements in engraftments are required to optimize ASC treatment. Stromal derived factor-1α (SDF-1α) is upregulated early after MI, and its endogenous receptor, chemokine receptor 4 (CXCR4), is pivotal in stem cell survival, migration, and engraftment. We examined whether CXCR4+ ASCs enhance their efficacy of migration and engraftment posttransplantation and improve heart function following myocardial infarction (MI). Methods and Results. CXCR4+ ASC subpopulations were sorted by fluorescence-activated cell sorting. CXCR4+ sorted ASCs exhibited the stronger cell viability, the faster proliferation rate, and the better migration capability in comparison with unfractionated ASCs. CXCR4+ sorted ASCs secreted a higher level of angiogenic growth factors including VEGF, HGF, and IGF-1 relative to unfractionated ASCs. Fewer apoptotic cells under oxygen-glucose deprivation were detected in CXCR4+ sorted ASCs than in unfractionated ASCs. Osteogenic and angiogenic differentiation were more pronounced in CXCR4+ sorted ASCs than in unfractionated ASCs. At 3 days after acute MI, rats were randomly allocated to receive intramyocardial injection of cell culture medium, CXCR4+ sorted ASCs, and unfractionated ASCs. Left ventricular function was assessed echocardiographically 4 weeks thereafter. Explanted hearts were then processed for the immunofluorescence detection of survived cells, quantification of angiogenesis, and cell engraftment. CXCR4+ sorted ASCs more obviously engrafted into infarcted myocardium, more markedly inhibited collagen remodeling, and more effectively improved heart function and promoted capillary formation than did unfractionated ASCs. Conclusion. CXCR4+ sorted ASCs are superior to unfractionated ASCs due to better viability, faster proliferation, more cytokine secretion, and stronger migration. CXCR4+ sorted ASCs provide better curative benefits on MI than do unfractionated ASCs and can be efficiently harvested and purified from adipose tissue, they may serve as a promising candidate for MI.

In recent years, the scarcity of pure water resources has received a lot of attention from society because of the increasing amount of pollution from industrial waste. It is very important to use low-cost adsorbents with high-adsorption performance to reduce water pollution. In this work, a gel adsorbent with a high-adsorption performance on methylene blue (MB) and Cu(II) was prepared from bamboo nanocellulose (BCNF) (derived from waste bamboo paper) and montmorillonite nanosheet (MMTNS) cross-linked by polyethyleneimine (PEI). The resulting gel adsorbent was characterized by Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (SEM), X-ray photoelectron spectroscopic (XPS), etc. The results indicated that the MB and Cu(II) adsorption capacities of the resulting gel adsorbent increased with the solution pH, contact time, initial concentration, and temperature before equilibrium. The adsorption processes of MB and Cu(II) fitted well with the fractal-like pseudo-second-order model. The maximal adsorption capacities on MB and Cu(II) calculated by the Sips model were 361.9 and 254.6 mg/g, respectively. The removal of MB and Cu(II) from aqueous solutions mainly included electrostatic attraction, ion exchange, hydrogen bonding interaction, etc. These results suggest that the resulting gel adsorbent is an ideal material for the removal of MB and Cu(II) from aqueous solutions.

Background: Thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD) induces false lumen (FL) thrombosis, promotes favorable aortic remodeling, and makes an impact on abdominal aortic branch perfusion patterns. However, little is known about the long-term fate of aortic remodeling and abdominal aortic branch perfusion after TEVAR for TBAD and the effect of FL thrombosis status on these changes.Materials and methods: Between January 2014 and May 2021, 59 enrolled patients with acute TBAD were treated with TEVAR and had post-operative or follow-up images. Pre-operative, post-operative, and latest follow-up CT angiography (CTA) data were analyzed for the largest diameter of true lumen (TL), FL, and transaorta and for the FL thrombosis status on the stented thoracic aorta, unstented thoracic aorta, and abdominal aorta. Abdominal aorta perfusion patterns were characterized.Results: The mean follow-up period was 17.1 months. In the stented thoracic aorta, average TL diameters increased, average FL diameters decreased, and average transaortic diameters did not change; 82.6% of the patients had either a stable or shrinking transaortic size and 87% of the patients achieved total FL thrombosis. In the unstented thoracic aorta, average TL diameters increased, transaortic growth and no changes occurred in 39.1 and 45.7% of the patients, respectively, and complete FL thrombosis was present in 50% of the patients. In the abdominal aorta, average FL and transaortic diameters increased, aorta was expanded in 52.2% of the patients, and FL remained patent in 65.2% of the patients. Of the 354 branches, 37 branches (10.5%) exhibited changes in perfusion patterns, 22 branches (6.2%) demonstrated an increased TL perfusion, and 15 branches (4.2%) had an increased FL contribution. Compared with patent or partially thrombosed FL, complete FL thrombosis was accompanied by a bigger decrease in FL diameters, a larger increase in TL diameters, and a higher percentage of abdominal branch TL perfusion.Conclusions: In majority of the patients, TEVAR stabilized the size of the stented thoracic aorta, namely TL expansion and FL obliteration. However, abdominal aortic FL remained patent FL, and it was expanded with the resultant transaortic growth over a long follow-up period. Abdominal aortic branch perfusion patterns remained largely stable after TEVAR. The failure to achieve FL thrombosis negatively affects the remodeling of a contagious abdominal aortic dissection.

In this research, the differences in protein and fatty acid composition among camel, cow and goat milks were analyzed by gel electrophoresis (GE) and gas chromatography (GC). The GE results showed that there were differences in the proportion of proteins in camel milk from different regions, and the production process had a significant effect on both camel milk protein and milk fat globule membrane protein composition. There were significant differences in protein composition among camel, cow and goat milks, and camel milk did not contain β-lacglobulin or αs1-casein, while cow and goat milks did not contain immunoglobulin G2 (IgG2) or IgG3. Therefore, GE could be used for the identification of camel milk mixed with cow or goat milk. The GC results showed that 31 fatty acids were detected in both camel and goat milks, and 29 fatty acids in cow milk. Camel milk contained fewer short-chain fatty acids than cow and goat milks, while the contents of most long-chain fatty acids were significantly higher than those in cow and goat milks. Principal component analysis (PCA) of the fatty acid composition data showed a clear separation of milks from different species and a clear discrimination between pure and adulterated camel milk. PCA can be used for the identification and analysis of fatty acids in camel milk mixed with cow milk and goat milk.

Klebsiella pneumoniae can enter a viable but nonculturable (VBNC) state to survive in unfavorable environments. Our research found that high-, medium-, and low-alcohol-producing K. pneumoniae strains are associated with nonalcoholic fatty liver disease. However, the presence of the three Kpn strains has not been reported in the VBNC state or during resuscitation. In this study, the effects of different strains, salt concentrations, oxygen concentrations, temperatures, and nutrients in K. pneumoniae VBNC state were evaluated. The results showed that high-alcohol-producing K. pneumoniae induced a slower VBNC state than medium-alcohol-producing K. pneumoniae, and low-alcohol-producing K. pneumoniae. A high-salt concentration and microoxygen environment accelerated the loss of culturability. Simultaneously, both real-time quantitative PCR and droplet digital PCR were developed to compare the quantitative comparison of three Kpn strain VBNC states by counting single-copy gene numbers. At 22°C or 37°C, the number of culturable cells decreased significantly from about 108 to 105-106 CFU/mL. In addition, imipenem, ciprofloxacin, polymyxin, and phiW14 inhibited cell resuscitation but could not kill VBNC-state cells. These results revealed that the different environments evaluated play different roles in the VBNC induction process, and new effective strategies for eliminating VBNC-state cells need to be further studied. These findings provide a better understanding of VBNC-state occurrence, maintenance, detection, and absolute quantification, as well as metabolic studies of resuscitation resistance and ethanol production. [ABSTRACT FROM AUTHOR]