Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
2,687
result(s) for
"Zhang, Li-Zhen"
Sort by:
Screening of immune-related secretory proteins linking chronic kidney disease with calcific aortic valve disease based on comprehensive bioinformatics analysis and machine learning
Background
Chronic kidney disease (CKD) is one of the most significant cardiovascular risk factors, playing vital roles in various cardiovascular diseases such as calcific aortic valve disease (CAVD). We aim to explore the CKD-associated genes potentially involving CAVD pathogenesis, and to discover candidate biomarkers for the diagnosis of CKD with CAVD.
Methods
Three CAVD, one CKD-PBMC and one CKD-Kidney datasets of expression profiles were obtained from the GEO database. Firstly, to detect CAVD key genes and CKD-associated secretory proteins, differentially expressed analysis and WGCNA were carried out. Protein-protein interaction (PPI), functional enrichment and cMAP analyses were employed to reveal CKD-related pathogenic genes and underlying mechanisms in CKD-related CAVD as well as the potential drugs for CAVD treatment. Then, machine learning algorithms including LASSO regression and random forest were adopted for screening candidate biomarkers and constructing diagnostic nomogram for predicting CKD-related CAVD. Moreover, ROC curve, calibration curve and decision curve analyses were applied to evaluate the diagnostic performance of nomogram. Finally, the CIBERSORT algorithm was used to explore immune cell infiltration in CAVD.
Results
The integrated CAVD dataset identified 124 CAVD key genes by intersecting differential expression and WGCNA analyses. Totally 983 CKD-associated secretory proteins were screened by differential expression analysis of CKD-PBMC/Kidney datasets. PPI analysis identified two key modules containing 76 nodes, regarded as CKD-related pathogenic genes in CAVD, which were mostly enriched in inflammatory and immune regulation by enrichment analysis. The cMAP analysis exposed metyrapone as a more potential drug for CAVD treatment. 17 genes were overlapped between CAVD key genes and CKD-associated secretory proteins, and two hub genes were chosen as candidate biomarkers for developing nomogram with ideal diagnostic performance through machine learning. Furthermore, SLPI/MMP9 expression patterns were confirmed in our external cohort and the nomogram could serve as novel diagnosis models for distinguishing CAVD. Finally, immune cell infiltration results uncovered immune dysregulation in CAVD, and SLPI/MMP9 were significantly associated with invasive immune cells.
Conclusions
We revealed the inflammatory-immune pathways underlying CKD-related CAVD, and developed SLPI/MMP9-based CAVD diagnostic nomogram, which offered novel insights into future serum-based diagnosis and therapeutic intervention of CKD with CAVD.
Journal Article
Temporal dynamics of nutrient uptake by neighbouring plant species
Summary The productivity of species‐diverse plant assemblages strongly depends on the temporal dynamics of nutrient uptake by competing neighbouring plants. Our understanding, however, of how rates of nitrogen (N), phosphorous (P) and potassium (K) uptake might change through time between neighbouring plant species under field conditions is still very limited. Here, we specifically measure the temporal trajectories of N, P and K uptake by staple food plants such as wheat (Triticum aestivum L.), barley (Hordeum vulgare L.) and maize (Zea mays L.) when growing either in monocultures or in intercropping systems. We ask how (i) plant species combinations, (ii) N fertilization and (iii) film mulching might affect key indexes of N, P and K uptake over time. We fit logistic models to characterize the nutrient uptake trajectories. Maximum cumulative N, P and K uptake (kg ha−1) by wheat and barley were significantly greater in wheat–maize or barley–maize intercropping systems than in wheat or barley monocultures. Cumulative nutrient uptake by intercropped maize (either with wheat or with barley) was reduced by interspecific competition at early growth stages, but it increased rapidly after wheat and barley were harvested. Maximum cumulative N and P (but not K) uptake by intercropped maize were significantly higher than the uptake by monoculture maize, particularly when N fertilizer or film mulching was applied. Intercropping induced a significant temporal niche differentiation in maximum daily nutrient uptake rates (kg ha−1 day−1) between intercropped species. Fertilization had much stronger effects on maximum cumulative nutrient uptake of maize than that of wheat and barley. Mulching significantly increased the maximum cumulative nutrient uptake of maize and advanced the time to reach its maximum daily P and K uptake rates. Our study provides evidence of an important temporal niche differentiation mechanism (‘temporal complementarity’) in nutrient uptake rates between neighbouring plant species. A better understanding of temporal trajectories of interspecific nutrient uptake rates remains crucial if we want to maximize the nutrient‐use efficiency and sustain overyielding (i.e. high food production) in plant species‐diverse systems such as intercropping. Lay Summary
Journal Article
Pulmonary interleukin 1 beta/serum amyloid A3 axis promotes lung metastasis of hepatocellular carcinoma by facilitating the pre-metastatic niche formation
Background
Increasing evidence suggests a vital role of the pre-metastatic niche in the formation of distant metastasis of many cancers. However, how the pre-metastatic niche is formed and promotes pulmonary metastasis of hepatocellular carcinoma (HCC) remains unknown.
Methods
Orthotopic liver tumor models and RNA-Seq were used to identify dysregulated genes in the pre-metastatic lung.
Il1b
knockout (
Il1b
−/−
) mice and lentivirus-mediated gene knockdown/overexpression were utilized to demonstrate the role of interleukin 1 beta (IL-1β)/serum amyloid A3 (SAA3) in the pre-metastatic niche formation and pulmonary metastasis. The potential molecular mechanisms were investigated by RNA-Seq, real-time quantitative PCR (qPCR), western blotting, immunohistochemistry (IHC), flow cytometry, luciferase reporter assay, double immunofluorescent staining and H&E staining.
Results
Accumulation of myeloid cells and upregulation of IL-1β were observed in the pre-metastatic lung of orthotopic liver tumor models. Myeloid cells accumulation and pulmonary metastasis were suppressed in
Il1b
−/−
mice and Il1r1-silencing mice. Mechanistically, SAA3 and matrix metallopeptidase 9 (MMP9) were identified as potential downstream targets of IL-1β. Overexpression of SAA3 in the lungs of
Il1b
−/−
mice restored myeloid cells accumulation and pulmonary metastasis of the orthotopic HCC xenografts. Moreover, alveolar macrophages-derived IL-1β dramatically enhanced SAA3 expression in alveolar epithelial cells in an NF-κB dependent manner and increased MMP9 levels in an autocrine manner. Furthermore, SAA3 recruited myeloid cells to the lung without affecting the expression of MMP9 in myeloid cells.
Conclusions
Our study suggests a key role of pulmonary IL-1β and SAA3 in creating a permissive lung pre-metastatic niche by enhancing MMP9 expression and recruiting myeloid cells, respectively, thus promoting pulmonary metastasis of HCC.
Journal Article
Positive feedback regulation of lncRNA PVT1 and HIF2α contributes to clear cell renal cell carcinoma tumorigenesis and metastasis
Long noncoding RNAs (lncRNAs) have been reported to exert important roles in tumors, including clear cell renal cell carcinoma (ccRCC). PVT1 is an important oncogenic lncRNA which has critical effects on onset and development of various cancers, however, the underlying mechanism of PVT1 functioning in ccRCC remains largely unknown.
VHL
deficiency-induced HIF2α accumulation is one of the major factors for ccRCC. Here, we identified the potential molecular mechanism of PVT1 in promoting ccRCC development by stabilizing HIF2α. PVT1 was significantly upregulated in ccRCC tissues and high PVT1 expression was associated with poor prognosis of ccRCC patients. Both gain-of-function and loss-of function experiments revealed that PVT1 enhanced ccRCC cells proliferation, migration, and invasion and induced tumor angiogenesis in vitro and in vivo. Mechanistically, PVT1 interacted with HIF2α protein and enhanced its stability by protecting it from ubiquitination-dependent degradation, thereby exerting its biological significance. Meanwhile, HIF2α bound to the enhancer of PVT1 to transactivate its expression. Furthermore, HIF2α specific inhibitor could repress PVT1 expression and its oncogenic functions. Therefore, our study demonstrates that the PVT1/ HIF2α positive feedback loop involves in tumorigenesis and progression of ccRCC, which may be exploited for anticancer therapy.
Journal Article
A Comparison of RNA Interference via Injection and Feeding in Honey Bees
RNA interference (RNAi) has been used successfully to reduce target gene expression and induce specific phenotypes in several species. It has proved useful as a tool to investigate gene function and has the potential to manage pest populations and reduce disease pathogens. However, it is not known whether different administration methods are equally effective at interfering with genes in bees. Therefore, we compared the effects of feeding and injection of small interfering RNA (siRNA) on the messenger RNA (mRNA) levels of alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1), 4-coumarate-CoA ligase (4CL), and heat shock protein 70 (HSP70). Both feeding and injection of siRNA successfully knocked down the gene but feeding required more siRNA than the injection. Our results suggest that both feeding and injection of siRNA effectively interfere with brain genes in bees. The appropriateness of each method would depend on the situation.
Journal Article
Intraoperative protective ventilation with or without periodic lung recruitment manoeuvres on pulmonary complications after major abdominal surgery (REMAIN-1): protocol for a randomised controlled trial
IntroductionPostoperative pulmonary complications (PPCs) are frequent after abdominal surgery and significantly affect postoperative outcomes. Intraoperative protective ventilation (IPV) has been demonstrated to mitigate PPCs. However, the comparative effectiveness of two common IPV regimens—IPV with or without periodic lung recruitment manoeuvres (PLRM)—in preventing PPCs is unclear. This study aims to compare the effects of these two IPV regimens on PPCs.Methods and analysisThis study is a prospective, double-blinded, randomised controlled trial. A total of 1060 patients at intermediate or high risk for PPCs, scheduled to undergo major abdominal surgery, will be enrolled and randomly assigned to receive either an IPV with PLRM (intensive IPV group) or an IPV without PLRM (moderate IPV group). Patients assigned to the intensive IPV group will receive positive end-expiratory pressure (PEEP) of 6–10 cm H2O with lung recruitment manoeuvres performed every 30 min. Patients in the moderate IPV group will receive the same level of PEEP without lung recruitment manoeuvres. Both groups will receive a tidal volume of 7 mL/kg predicted body weight and an inspired oxygen fraction of 0.3–0.4. The primary outcome is respiratory failure within the first 7 postoperative days. Secondary outcomes include other PPCs, extrapulmonary complications, unplanned admissions to the intensive care unit, length of postoperative hospital stay and mortality from any cause.Ethics and disseminationThis protocol has been approved by the Ethics Committee of the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. The first participant was recruited on 9 October 2022, with an estimated completion date of 30 May 2025. The results of this trial are expected to be published in peer-reviewed journals.Trial registration numberNCT05556174.
Journal Article
Functional analysis of the nonstructural protein NSs of tomato zonate spot virus
Tomato zonate spot virus (TZSV), a member of the genus orthotospovirus , causes severe damage to vegetables and ornamental crops in southwest China. The NSs protein is an RNA silencing suppressor in various orthotospovirus like TZSV, but its mechanism and role in virus infection are poorly understood. Here, we observed that an NSs-GFP fusion protein was transiently expressed on the plasma membrane and Golgi bodies in Nicotiana benthamiana plants. The TZSV NSs gene was silenced and infiltrated into N . benthamiana and N . tabacum cv. K326. RT-qPCR and Indirect enzyme-linked immunosorbent assay (ID-ELISA) showed that the transcription and the protein expression of the NSs gene were inhibited by more than 90.00%, and the symptoms on silenced plants were alleviated. We also found that the expression of the Zingipain-2-like gene significantly decreased when the NSs gene was silenced, resulting in co-localization of the NSs-GFP and the Zingipain-2-like-mCherry fusion protein. The findings of this study provide new insights into the mechanism of silencing suppression by NSs, as well as its effect on systemic virus infection, and also support the theory of disease resistance breeding and control and prevention of TZSV in the field.
Journal Article
Open-lung strategies and mechanical power during protective ventilation for laparoscopic anterior resection: a randomised controlled trial
Higher intraoperative mechanical power (MP) is associated with increased postoperative pulmonary complications (PPCs). We hypothesised that periodic alveolar recruitment manoeuvres (PARM) alone, as an open-lung strategy for intraoperative protective ventilation, would reduce MP, thereby potentially mitigating PPCs. Seventy-five non-obese participants were equally allocated to either alveolar recruitment manoeuvres every 30 min alone (PARM group), or medium positive end-expiratory pressure (PEEP) of 6–8 cmH
2
O alone (PEEP group), or a combination of medium PEEP and PARM (combination group). As a result, the median (interquartile range, IQR) MP in the PARM group was lower than in the other groups (PARM, 4.34 [3.58–5.27]; PEEP, 6.47 [5.83–7.74]; combination, 6.32 [5.16–7.36] J min
−1
;
P
< 0.001). The median difference (95% confidence interval, 95% CI) of MP between the PARM and control group (combined PEEP and combination) was 2.05 (1.34–2.74) J min
−1
, with a significant reduction (32.2%,
P
< 0.001) in the PARM group. However, no clinical benefit (such as PPCs) was observed despite these physiological improvements. In conclusion, PARM alone as an open-lung strategy for protective ventilation leads to a 32.2% reduction in MP, compared with medium PEEP alone or a combination of PARM and medium PEEP. The association between PARM and PPCs warrant further investigations.
Journal Article
Full-Length Transcriptome Profile of Apis cerana Revealed by Nanopore Sequencing
The Asian honey bee (Apis cerana) plays a crucial role in providing abundant bee products and in maintaining ecological balance. Despite the availability of the genomic sequence of the Asian honey bee, its transcriptomic information remains largely incomplete. To address this issue, here we constructed three pooled RNA samples from the queen, drone, and worker bees of A. cerana and performed full-length RNA sequencing using Nanopore single-molecule sequencing technology. Ultimately, we obtained 160,811 full-length transcript sequences from 19,859 genes, with 141,189 being novel transcripts, of which 130,367 were functionally annotated. We detected 520, 324, and 1823 specifically expressed transcripts in the queen, worker, and drone bees, respectively. Furthermore, we identified 38,799 alternative splicing (AS) events from 5710 genes, 44,243 alternative polyadenylation (APA) sites from 1649 gene loci, 88,187 simple sequence repeats (SSRs), and 17,387 long noncoding RNAs (lncRNAs). Leveraging these transcripts as references, we identified 6672, 7795, and 6804 differentially expressed transcripts (DETs) in comparisons of queen ovaries vs drone testes, worker ovaries vs drone testes, and worker ovaries vs queen ovaries, respectively. Our research results provide a comprehensive set of reference transcript datasets for Apis cerana, offering important sequence information for further exploration of its gene functions.
Journal Article