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"Gui, Jia"
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FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis
The role of Fat Mass and Obesity-associated protein （FTO） and its substrate N6-methyladenosine （m6A） in mRNA processing and adipogenesis remains largely unknown. We show that FTO expression and m6A levels are inversely correlated during adipogenesis. FTO depletion blocks differentiation and only catalytically active FTO restores adi- pogenesis. Transcriptome analyses in combination with m6A-seq revealed that gene expression and mRNA splicing of grouped genes are regulated by FTO. M6A is enriched in exonic regions flanking 5＇- and 3＇-splice sites, spatially over- lapping with mRNA splicing regulatory serine/arginine-rich （SR） protein exonic splicing enhancer binding regions. Enhanced levels of m6A in response to FTO depletion promotes the RNA binding ability of SRSF2 protein, leading to increased inclusion of target exons. FTO controls exonic splicing of adipogenie regulatory factor RUNX1T1 by regulating m6A levels around splice sites and thereby modulates differentiation. These findings provide compelling evidence that FTO-dependent m6A demethylation functions as a novel regulatory mechanism of RNA processing and plays a critical role in the regulation of adipogenesis.
Journal Article
Lamellar MXene: A novel 2D nanomaterial for electrochemical sensors
MXenes, as recently emerging lamellar two-dimensional (2D) materials of transition metal carbides and/or nitrides, have attracted intensive attention for various applications in sensors, catalysis, energy storage, and biomedicine owing to their fascinating and technologically useful properties. This review presents the current progress of MXene-based materials applied in the field of electrochemical sensors. Firstly, how synthetic strategies and surface modification affect the properties of MXene was emphasized. Secondly, MXene as an electrode material for constructing electrochemical sensors based on MXene nanocomposites, especially metal nanoparticles (MNPs)/MXene, conductive polymers (CPs)/MXene, and carbon materials/MXene nanocomposites, was well discussed. Finally, the challenges and outlooks in this field with possible solutions and future opportunities are discussed.Graphic abstract
Journal Article
Gender- and age-based differences in outcomes of mechanically ventilated ICU patients: a Chinese multicentre retrospective study
Background
Previous studies have suggested that the gender and/or age of a patient may influence the clinical outcomes of critically ill patients. Our aim was to determine whether there are gender- and age-based differences in clinical outcomes for mechanically ventilated patients in intensive care units (ICUs).
Methods
We performed a multicentre retrospective study involving adult patients who were admitted to the ICU and received at least 24 h of mechanical ventilation (MV). The patients were divided into two groups based on gender and, subsequently, further grouped based on gender and age < or ≥ 65 years. The primary outcome measure was hospital mortality.
Results
A total of 853 mechanically ventilated patients were evaluated. Of these patients, 63.2% were men and 61.5% were ≥ 65 years of age. The hospital mortality rate for men was significantly higher than that for women in the overall study population (
P
= 0.042), and this difference was most pronounced among elderly patients (age ≥ 65 years;
P
= 0.006). The durations of MV, ICU lengths of stay (LOS), and hospital LOS were significantly longer for men than for women among younger patients (
P
≤ 0.013) but not among elderly patients. Multivariate logistic regression analysis revealed that male gender was independently associated with hospital mortality among elderly patients but not among younger patients.
Conclusions
There were important gender- and age-based differences in the outcomes among mechanically ventilated ICU patients. The combination of male gender and advanced age is strongly associated with hospital mortality.
Journal Article
The lre‐miR159a‐LrGAMYB pathway mediates resistance to grey mould infection in Lilium regale
Grey mould is one of the most determinative factors of lily growth and plays a major role in limiting lily productivity. MicroRNA159 (miR159) is a highly conserved microRNA in plants, and participates in the regulation of plant development and stress responses. Our previous studies revealed that lre‐miR159a participates in the response of Lilium regale to Botrytis elliptica according to deep sequencing analyses; however, the response mechanism remains unknown. Here, lre‐miR159a and its target LrGAMYB gene were isolated from L. regale. Transgenic Arabidopsis overexpressing lre‐MIR159a exhibited larger leaves and smaller necrotic spots on inoculation with Botrytis than those of wild‐type and overexpressing LrGAMYB plants. The lre‐MIR159a overexpression also led to repressed expression of two targets of miR159, AtMYB33 and AtMYB65, and enhanced accumulation of hormone‐related genes, including AtPR1, AtPR2, AtNPR1, AtPDF1.2, and AtLOX for both the jasmonic acid and salicylic acid pathways. Moreover, lower levels of H2O2 and O2- were observed in lre‐MIR159a transgenic Arabidopsis, which reduced the damage from reactive oxygen species accumulation. Taken together, these results indicate that lre‐miR159a positively regulates resistance to grey mould by repressing the expression of its target LrGAMYB gene and activating a defence response. lre‐miR159a positively regulates resistance to grey mould by repressing the expression of its target LrGAMYB gene and activating a defence response in Lilium regale.
Journal Article
Parenchymal‐sparing versus extended hepatectomy for colorectal liver metastases: A systematic review and meta‐analysis
Aims To assess the safety and efficacy of parenchymal‐sparing hepatectomy (PSH) as a treatment of colorectal liver metastases (CLM). Methods A comprehensive medical literature search was performed. Perioperative and long‐term survival outcomes were pooled. Subgroup analysis and meta‐regression analysis were performed to identify potential sources of heterogeneity. Results A total of 18 studies comprising 7081 CLM patients were eligible for this study. The PSH was performed on 3974 (56.1%) patients. We found that the OS (overall survival; hazard ratio [HR] = 1.01, 95% confidence interval [CI]: 0.94‐1.08) and RFS (recurrence‐free survival; HR = 1.00, 95% CI: 0.94‐1.07) were comparable between non‐PSH and PSH group. The perioperative outcomes were better in PSH than in non‐PSH group. Non‐PSH group was significantly associated with longer operative time (standard mean difference [SMD] = 1.17, 95% CI: 0.33‐2.00), increased estimated blood loss (SMD = 1.36, 95% CI: 0.64‐2.07), higher intraoperative transfusion rate (risk ratio [RR] = 2.27, 95% CI: 1.60‐3.23), and more postoperative complications (RR = 1.39, 95% CI: 1.16‐1.66). Meta‐regression analyses revealed that no variable influenced the association between surgical types and the survival outcomes. Conclusions This study shows that PSH is associated with better perioperative outcomes without compromising oncological outcomes. Given the increasing incidence of hepatic parenchyma, the PSH treatment offers a greater opportunity of repeat resection for intrahepatic recurrent tumors. It should be considered as an effective surgical approach for CLM. The present study pooled outcomes of 18 studies to evaluate the safety and effectiveness of parenchymal‐sparing hepatectomy (PSH) for treating colorectal liver metastases (CLM). PSH is associated with potential better perioperative outcomes without compromising oncological outcomes. More future hepatic parenchymal will be preserved in the surgical process of PSH, it offers a greater opportunity of repeat resection for intrahepatic recurrent tumors. The PSH brings the treatment of CLM into personalized precision medicine era.
Journal Article
Unified Classification of Bacterial Colonies on Different Agar Media Based on Hyperspectral Imaging and Machine Learning
A universal method by considering different types of culture media can enable convenient classification of bacterial species. The study combined hyperspectral technology and versatile chemometric algorithms to achieve the rapid and non-destructive classification of three kinds of bacterial colonies (Escherichia coli, Staphylococcus aureus and Salmonella) cultured on three kinds of agar media (Luria–Bertani agar (LA), plate count agar (PA) and tryptone soy agar (TSA)). Based on the extracted spectral data, partial least squares discriminant analysis (PLS-DA) and support vector machine (SVM) were employed to established classification models. The parameters of SVM models were optimized by comparing genetic algorithm (GA), particle swarm optimization (PSO) and grasshopper optimization algorithm (GOA). The best classification model was GOA-SVM, where the overall correct classification rates (OCCRs) for calibration and prediction of the full-wavelength GOA-SVM model were 99.45% and 98.82%, respectively, and the Kappa coefficient for prediction was 0.98. For further investigation, the CARS, SPA and GA wavelength selection methods were used to establish GOA-SVM simplified model, where CARS-GOA-SVM was optimal in model accuracy and stability with the corresponding OCCRs for calibration and prediction and the Kappa coefficients of 99.45%, 98.73% and 0.98, respectively. The above results demonstrated that it was feasible to classify bacterial colonies on different agar media and the unified model provided a continent and accurate way for bacterial classification.
Journal Article
Effectiveness of Fenofibrate in Treatment-Naive Patients With Primary Biliary Cholangitis: A Randomized Clinical Trial
Primary biliary cholangitis (PBC) is a progressive autoimmune liver disease, and patients with inadequate response to ursodeoxycholic acid (UDCA) treatment show reduced long-term survival. Recent studies have shown that fenofibrate is an effective off-label therapy for PBC. However, prospective studies on biochemical response including the timing of fenofibrate administration are lacking. This study is aimed to evaluate the efficacy and safety of fenofibrate in UDCA treatment-naive patients with PBC.
A total of 117 treatment-naive patients with PBC were recruited from the Xijing Hospital for a 12-month randomized, parallel, and open-label clinical trial. Study participants were assigned to receive either UDCA standard dose (UDCA-only group) or fenofibrate at a daily dose of 200 mg in addition to UDCA (UDCA-Fenofibrate group).
The primary outcome was biochemical response percentage in patients according to the Barcelona criterion at 12 months. In the UDCA-Fenofibrate group, 81.4% (69.9%-92.9%) of patients achieved the primary outcome and 64.3% (51.9%-76.8%) in the UDCA-only group achieved the primary outcome ( P = 0.048). There was no difference between the 2 groups in noninvasive measures of liver fibrosis and biochemical markers other than alkaline phosphatase at 12 months. Creatinine and transaminases levels in the UDCA-Fenofibrate group increased within the first month, then returned to normal, and remained stable thereafter until the end of the study, even in patients with cirrhosis.
In this randomized clinical trial in treatment-naive patients with PBC, the combination of fenofibrate and UDCA resulted in a significantly higher biochemical response rate. Fenofibrate seemed to be well-tolerated in patients.
Journal Article
Megaelectronvolt electron acceleration driven by terahertz surface waves
Particles at relativistic energies form the basis of acceleration science. The emergence of terahertz-driven acceleration promises vastly smaller and cost-efficient accelerators; however, the field strength inside the acceleration structure has hitherto prevented the energy gain from reaching the megaelectronvolt range. Here we demonstrate an electron energy gain of up to 1.1 MeV and an effective acceleration gradient of up to 210 MV m−1 driven by terahertz surface waves, using their strong confinement to the waveguide and the fundamental transverse magnetic mode that is favourable for acceleration. The discrepancy in the velocity between the terahertz surface waves and electrons enables potential phase-space control, including temporal compression and spatial focusing. We expect these proof-of-principle results to enable the development of a tunable and highly efficient electron accelerator driven by terahertz surface waves for application in compact microscopy, radiation sources and cancer therapies.When near-infrared femtosecond laser pulses are focused onto a metal wire, relativistic electron acceleration is observed in the attached waveguide. An electron energy gain of 1.1 MeV and an effective acceleration gradient up to 210 MV m−1 are achieved using the laser-induced terahertz surface waves.
Journal Article
An efficient method for inducing multiple genotypes of tetraploids Lilium rosthornii Diels
Polyploids generally show strong environmental adaptation and diverse morphological variations. Therefore, polyploid induction is an important protocol for plant breeding. Lilium rosthornii is a wild lily species with high horticultural value and excellent disease resistance. In this study, seeds of L. rosthornii were subjected to polyploidy induction treatments to obtain multiple genotypes of tetraploids. Germinated seeds were immersed in two antimitotic agents at different concentrations for various times. In total, 199 tetraploid genotypes were obtained. The most efficient treatments of each agent were immersed in 0.05% colchicine for 36 h and in 0.01% oryzalin for 24 h; the induction rate of the former (27.78%) was significantly higher than that of the latter (22.22%). The swollen hypocotyl phenotype after colchicine and oryzalin treatments was strongly correlated with tetraploidy (0.989** and 0.975**, respectively), suggesting that this phenotype could serve as an early ploidy selection trait. The correlations were weaker between stomata length/density and tetraploidy (0.773** and 0.695**, respectively), implying that stomatal characters are affected by both the ploidy level and genotype. After several rounds subculture in vitro, the morphology and growth traits were not significantly different between diploids and tetraploids, but there were wider variations in these parameters in tetraploids than in diploids. After transplanting, the bulblet germination rate was higher in tetraploids than in diploids. The leaf phenotype did not differ between tetraploids and diploids initially, but the leaves of tetraploids became larger than those of diploids over time. Together, these suggest that tetraploids, may contribute diverse characteristics to lily breeding.Key messageMultiple genotypes of tetraploid Lilium rosthornii were induced by colchicine and oryzalin. Swollen hypocotyl was associated with polyploidy. Compared with diploids, tetraploids showed wider variations in morphological parameters.
Journal Article