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1.
Acta Pharmacol Sin ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38839936

ABSTRACT

Cardiac fibrosis is a pathological scarring process that impairs cardiac function. N-acetyltransferase 10 (Nat10) is recently identified as the key enzyme for the N4-acetylcytidine (ac4C) modification of mRNAs. In this study, we investigated the role of Nat10 in cardiac fibrosis following myocardial infarction (MI) and the related mechanisms. MI was induced in mice by ligation of the left anterior descending coronary artery; cardiac function was assessed with echocardiography. We showed that both the mRNA and protein expression levels of Nat10 were significantly increased in the infarct zone and border zone 4 weeks post-MI, and the expression of Nat10 in cardiac fibroblasts was significantly higher compared with that in cardiomyocytes after MI. Fibroblast-specific overexpression of Nat10 promoted collagen deposition and induced cardiac systolic dysfunction post-MI in mice. Conversely, fibroblast-specific knockout of Nat10 markedly relieved cardiac function impairment and extracellular matrix remodeling following MI. We then conducted ac4C-RNA binding protein immunoprecipitation-sequencing (RIP-seq) in cardiac fibroblasts transfected with Nat10 siRNA, and revealed that angiomotin-like 1 (Amotl1), an upstream regulator of the Hippo signaling pathway, was the target gene of Nat10. We demonstrated that Nat10-mediated ac4C modification of Amotl1 increased its mRNA stability and translation in neonatal cardiac fibroblasts, thereby increasing the interaction of Amotl1 with yes-associated protein 1 (Yap) and facilitating Yap translocation into the nucleus. Intriguingly, silencing of Amotl1 or Yap, as well as treatment with verteporfin, a selective and potent Yap inhibitor, attenuated the Nat10 overexpression-induced proliferation of cardiac fibroblasts and prevented their differentiation into myofibroblasts in vitro. In conclusion, this study highlights Nat10 as a crucial regulator of myocardial fibrosis following MI injury through ac4C modification of upstream activators within the Hippo/Yap signaling pathway.

2.
Ageing Res Rev ; : 102363, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38838785

ABSTRACT

The basolateral amygdala (BLA) is the subregion of the amygdala located in the medial of the temporal lobe, which is connected with a wide range of brain regions to achieve diverse functions. Recently, an increasing number of studies have focused on the participation of the BLA in many neuropsychiatric disorders from the neural circuit perspective, aided by the rapid development of viral tracing methods and increasingly specific neural modulation technologies. However, how to translate this circuit-level preclinical intervention into clinical treatment using noninvasive or minor invasive manipulations to benefit patients struggling with neuropsychiatric disorders is still an inevitable question to be considered. In this review, we summarized the role of BLA-involved circuits in neuropsychiatric disorders including Alzheimer's disease, perioperative neurocognitive disorders, schizophrenia, anxiety disorders, depressive disorders, posttraumatic stress disorders, autism spectrum disorders, and pain-associative affective states and cognitive dysfunctions. Additionally, we provide insights into future directions and challenges for clinical translation.

3.
J Musculoskelet Neuronal Interact ; 24(2): 178-184, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38826000

ABSTRACT

OBJECTIVE: To investigate the effect of pericapsular nerve group (PENG) block combined with spinal anesthesia in the treatment of elderly patients with intertrochanteric fractures through "rapid diagnosis and treatment channel" PFNA internal fixation. METHODS: 52 elderly patients were randomly divided into the observation group (26 patients, PENG block combined with spinal anesthesia) and the control group (26 patients, spinal anesthesia alone). The general health, mean arterial pressure (MAP), and heart rate (HR) of both groups were compared at various stages: immediately before the administration of pain analgesia, during the positioning of spinal epidural anesthesia, at the beginning and end of the surgery, and 2 hours after surgery. Additionally, VAS scores at rest and during passive straight leg elevation by 15° were evaluated at 12 hours, 24 hours, 48 hours, 72 hours, and 7 days after surgery. RESULTS: The MAP and HR in the observation group under spinal anesthesia in the lateral position were lower than those in the control group (P < 0.05). Additionally, the VAS scores of the observation group during positioning and at 12 hours and 24 hours after surgery were lower than those in the control group under spinal epidural anesthesia (both P < 0.05). CONCLUSION: The application of ultrasound-guided PENG block combined with lumbar anesthesia can reduce pain when in lateral position, stabilize perioperative vital signs, and result in high satisfaction.


Subject(s)
Anesthesia, Spinal , Hip Fractures , Nerve Block , Humans , Anesthesia, Spinal/methods , Aged , Male , Female , Nerve Block/methods , Hip Fractures/surgery , Aged, 80 and over , Pain, Postoperative/prevention & control , Pain, Postoperative/drug therapy
4.
Insect Sci ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38831720

ABSTRACT

N6-methyladenosine (m6A) is the most prevalent modification in cellular RNA which orchestrates diverse physiological and pathological processes during stress response. However, the differential m6A modifications that cope with herbivore stress in resistant and susceptible crop varieties remain unclear. Here, we found that rice stem borer (RSB) larvae grew better on indica rice (e.g., MH63, IR64, Nanjing 11) than on japonica rice varieties (e.g., Nipponbare, Zhonghua 11, Xiushui 11). Then, transcriptome-wide m6A profiling of representative resistant (Nipponbare) and susceptible (MH63) rice varieties were performed using a nanopore direct RNA sequencing approach, to reveal variety-specific m6A modifications against RSB. Upon RSB infestation, m6A methylation occurred in actively expressed genes in Nipponbare and MH63, but the number of methylation sites decreased across rice chromosomes. Integrative analysis showed that m6A methylation levels were closely associated with transcriptional regulation. Genes involved in herbivorous resistance related to mitogen-activated protein kinase, jasmonic acid (JA), and terpenoid biosynthesis pathways, as well as JA-mediated trypsin protease inhibitors, were heavily methylated by m6A, and their expression was more pronounced in RSB-infested Nipponbare than in RSB-infested MH63, which may have contributed to RSB resistance in Nipponbare. Therefore, dynamics of m6A modifications act as the main regulatory strategy for expression of genes involved in plant-insect interactions, which is attributed to differential responses of resistant and susceptible rice varieties to RSB infestation. These findings could contribute to developing molecular breeding strategies for controlling herbivorous pests.

5.
Sci Rep ; 14(1): 12934, 2024 06 05.
Article in English | MEDLINE | ID: mdl-38839983

ABSTRACT

Osteosarcoma is a primary malignant tumor that commonly affects children and adolescents, with a poor prognosis. The existence of tumor heterogeneity leads to different molecular subtypes and survival outcomes. Recently, lipid metabolism has been identified as a critical characteristic of cancer. Therefore, our study aims to identify osteosarcoma's lipid metabolism molecular subtype and develop a signature for survival outcome prediction. Four multicenter cohorts-TARGET-OS, GSE21257, GSE39058, and GSE16091-were amalgamated into a unified Meta-Cohort. Through consensus clustering, novel molecular subtypes within Meta-Cohort patients were delineated. Subsequent feature selection processes, encompassing analyses of differentially expressed genes between subtypes, univariate Cox analysis, and StepAIC, were employed to pinpoint biomarkers related to lipid metabolism in TARGET-OS. We selected the most effective algorithm for constructing a Lipid Metabolism-Related Signature (LMRS) by utilizing four machine-learning algorithms reconfigured into ten unique combinations. This selection was based on achieving the highest concordance index (C-index) in the test cohort of GSE21257, GSE39058, and GSE16091. We identified two distinct lipid metabolism molecular subtypes in osteosarcoma patients, C1 and C2, with significantly different survival rates. C1 is characterized by increased cholesterol, fatty acid synthesis, and ketone metabolism. In contrast, C2 focuses on steroid hormone biosynthesis, arachidonic acid, and glycerolipid and linoleic acid metabolism. Feature selection in the TARGET-OS identified 12 lipid metabolism genes, leading to a model predicting osteosarcoma patient survival. The LMRS, based on the 12 identified genes, consistently accurately predicted prognosis across TARGET-OS, testing cohorts, and Meta-Cohort. Incorporating 12 published signatures, LMRS showed robust and significantly superior predictive capability. Our results offer a promising tool to enhance the clinical management of osteosarcoma, potentially leading to improved clinical outcomes.


Subject(s)
Bone Neoplasms , Lipid Metabolism , Machine Learning , Osteosarcoma , Osteosarcoma/genetics , Osteosarcoma/mortality , Osteosarcoma/metabolism , Osteosarcoma/pathology , Humans , Lipid Metabolism/genetics , Prognosis , Bone Neoplasms/genetics , Bone Neoplasms/mortality , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Female , Male , Gene Expression Regulation, Neoplastic , Adolescent , Gene Expression Profiling/methods , Child
6.
Lab Invest ; : 102090, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38830579

ABSTRACT

Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. Presently, the overall response rate to immunotherapy is low, and current methods for predicting the prognosis of GC are not optimal. Therefore, novel biomarkers with accuracy, efficiency, stability, performance ratio and wide clinical application are needed. Based on public data sets, the Chemotherapy Cohort and the Immunotherapy Cohort from Sun Yat-sen University Cancer Center, a series of bioinformatics analyses, such as differential expression analysis, survival analysis, drug sensitivity prediction, enrichment analysis, tumor immune dysfunction and exclusion (TIDE) analysis, single-sample gene set enrichment analysis (ssGSEA), stemness index calculation, immune cell infiltration analysis, were performed for screening and preliminary exploration. Immunohistochemical staining and in vitro experiments were performed for further verification. Overexpression of COX7A1 promoted the resistance of GC cells to Oxaliplatin. COX7A1 may induce immune escape by regulating the number of fibroblasts and their cellular communication with immune cells. In summary, measuring the expression levels of COX7A1 in the clinic may be useful to predict the prognosis of GC patients, the degree of chemotherapy resistance and the efficacy of immunotherapy.

7.
iScience ; 27(6): 109908, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38827397

ABSTRACT

Accurate detection of pathogens, particularly distinguishing between Gram-positive and Gram-negative bacteria, could improve disease treatment. Host gene expression can capture the immune system's response to infections caused by various pathogens. Here, we present a deep neural network model, bvnGPS2, which incorporates the attention mechanism based on a large-scale integrated host transcriptome dataset to precisely identify Gram-positive and Gram-negative bacterial infections as well as viral infections. We performed analysis of 4,949 blood samples across 40 cohorts from 10 countries using our previously designed omics data integration method, iPAGE, to select discriminant gene pairs and train the bvnGPS2. The performance of the model was evaluated on six independent cohorts comprising 374 samples. Overall, our deep neural network model shows robust capability to accurately identify specific infections, paving the way for precise medicine strategies in infection treatment and potentially also for identifying subtypes of other diseases.

9.
Front Oncol ; 14: 1345656, 2024.
Article in English | MEDLINE | ID: mdl-38725628

ABSTRACT

Background: Remimazolam is a new ultrashort-acting benzodiazepine for sedation and anesthesia. The effects of remimazolam and the mechanism by which it functions in cancer cells have not been determined. This research aimed to explore the mechanism of remimazolam action in colon cancer treatment, using bioinformatics analysis and in vitro experiments. Methods: Cell cycle progression, colony formation, self-renewal capacity, and apoptosis detection were performed in HCT8 cells treated with or without remimazolam. Transcriptome sequencing, Gene Ontology, Kyoto Encyclopedia of Genes and Genome, Protein-Protein Interaction, Gene Set Enrichment Analysis, Western blotting, and qPCR were performed to investigate the mechanism of action of remimazolam in HCT8 colon cancer cells. Results: Remimazolam promoted proliferation and cell-cycle progression of HCT8 cells. After remimazolam treatment, a total of 1,096 differentially expressed genes (DEGs) were identified: 673 genes were downregulated, and 423 genes were upregulated. The DEGs were enriched mainly in "DNA replication", "cell cycle", and "G1/S transition" related pathways. There were 15 DEGs verified by qPCR, and representative biomarkers were detected by Western Bloting. The remimazolam-mediated promotion of cell proliferation and cell cycle was reversed by G1T28, a CDK4/6 inhibitor. Conclusion: Remimazolam promoted cell-cycle progression and proliferation in HCT8 colon cancer cells, indicating that the long-term use of remimazolam has potential adverse effects in the anesthesia of patients with colon cancer.

10.
Angew Chem Int Ed Engl ; : e202404978, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38697945

ABSTRACT

Integrating aggregation-induced emission (AIE) into thermally activated delayed fluorescence (TADF) emitters holds great promise for the advancement of highly efficient organic light emitting diodes (OLEDs). Despite recent advancements, a thorough comprehension of the underlying mechanisms remains imperative for the practical application of such materials. In this work, we introduce a novel approach aimed at modulating the TADF process by manipulating dynamic processes in excited states through aggregation effect. Our findings reveal that aggregation not only enhances both prompt and delayed fluorescence simultaneously but also imposes constraints on molecular reorientation. This constraint reinforces spin-orbit coupling and reduces the energy gap between singlets and triplets. These insights deepen our understanding of the fundamental mechanisms governing the aggregation effect on TADF materials and provide valuable guidance for the design of high-efficiency photoluminescent materials.

11.
Jpn J Radiol ; 2024 May 03.
Article in English | MEDLINE | ID: mdl-38700623

ABSTRACT

PURPOSE: To explore the positive predictors of the clinical outcome in acute ischemic stroke (AIS) patients with anterior circulation large vessel occlusion (ACLVO) after endovascular mechanical thrombectomy (EMT) at a 90-day follow-up, and to establish a nomogram model to predict the clinical outcome. MATERIALS AND METHODS: AIS patients with ACLVO detected by multimodal Computed Tomography imaging who underwent EMT were collected. Patients were divided into the favorable and the unfavorable groups according to the 90-day modified Rankin Scale (mRS) score. Univariate and multivariate analyses were performed to investigate predictors of the favorable outcome (mRS of 0-2). A nomogram model for predicting the clinical outcome after EMT was drawn, and the receiver operating characteristic (ROC) curve was used to evaluate its predictive value. RESULTS: Totally 105 patients including 65 patients in the favorable group and 40 in the unfavorable group were enrolled. Multivariate logistic regression analysis showed that admission National Institute of Health Stroke scale (NIHSS) score [0.858 (95% CI 0.778-0.947)], ACLVO at M2 [20.023 (95% CI 2.204-181.907)] and infarct core (IC) volume [0.943 (95% CI 0.917-0.969)] was positively correlated with favorable outcome. The accuracy of the nomogram model in predicting the outcome was 0.923 (95% CI 0.870-0.976), with a cutoff value of 119.6 points. The area under the ROC curve was 0.848 (95% CI 0.780-0.917; sensitivity, 79.7%; specificity, 90.0%). CONCLUSION: A low Admission NIHSS score, ACLVO at M2, and a small IC volume were positive predictors for favorable outcome. The nomogram model may well predict the outcome in AIS patients with ACLVO after EMT.

12.
Natl Sci Rev ; 11(6): nwad262, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38715704

ABSTRACT

Surface electrons in axion insulators are endowed with a topological layer degree of freedom followed by exotic transport phenomena, e.g., the layer Hall effect. Here, we propose that such a layer degree of freedom can be manipulated in a dissipationless way based on the antiferromagnetic [Formula: see text] with tailored domain structure. This makes [Formula: see text] a versatile platform to exploit the 'layertronics' to encode, process and store information. Importantly, the layer filter, layer valve and layer reverser devices can be achieved using the layer-locked chiral domain wall modes. The dissipationless nature of the domain wall modes makes the performance of the layertronic devices superior to those in spintronics and valleytronics. Specifically, the layer reverser, a layer version of the Datta-Das transistor, also fills up the blank in designing the valley reverser in valleytronics. Our work sheds light on constructing new generation electronic devices with high performance and low-energy consumption in the framework of layertronics.

13.
Int J Genomics ; 2024: 2439396, 2024.
Article in English | MEDLINE | ID: mdl-38716378

ABSTRACT

Pod dehiscence brings much loss for modern agricultural production, and multiple pod dehiscence components have been identified in many plant species. However, the pod dehiscence regulation factors in soybean are limited. In this study, we investigate the function of GmDIR26, a close homologues gene of pod dehiscence genes GmPdh1, PvPdh1, and CaPdh1, in the regulation of pod dehiscence in soybean. The secondary and tertiary structure analysis reveals that GmDIR26 protein has a similar structure with GmPdh1, PvPdh1, and CaPdh1 proteins. Synteny analysis of soybean and chickpea genomes shows that the genomic region surrounding GmDIR26 and CaPdh1 might be evolved from the same ancestor, and these two genes might have similar function. GmDIR26 shows an increased expression pattern during pod development and reaches a peak at beginning seed stage. Meanwhile, GmDIR26 exhibits high expression levels in dorsal suture and pod wall, but low expression pattern in ventral suture. In addition, GmDIR26 shows higher expression levels in pod dehiscence genotype than that in pod indehiscence accessions. Overexpression of GmDIR26 in soybean increases pod dehiscence in transgenic plants, of which the lignin layer in inner sclerenchyma pods is thicker and looser. The expression levels of several pod dehiscence genes are altered. Our study provides important information for further modification of pod dehiscence resistance soybean and characterization of soybean pod dehiscence regulation network.

14.
Ultrasonics ; 141: 107332, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38718460

ABSTRACT

BACKGROUND: Stroke is the second leading cause of death across the globe. Early screening and risk detection could provide early intervention and possibly prevent its incidence. Imaging modalities, including 1D-Transcranial Doppler Ultrasound (1D-TCD) or Transcranial Color-code sonography (TCCS), could only provide low spatial resolution or 2D image information, respectively. Notably, 3D imaging modalities including CT have high radiation exposure, whereas MRI is expensive and cannot be adopted in patients with implanted devices. This study proposes an alternative imaging solution for reconstructing 3D Doppler ultrasound geared towards providing a screening tool for the 3D vessel structure of the brain. METHODS: The system comprises an ultrasound phased array attached to a servo motor, which can rotate 180˚ at a speed of 2˚/s. We extracted the color Doppler ROI from the image before reconstructing it into a 3D view using a customized pixel-based algorithm. Different vascular diameters, flow velocity, and depth were tested using a vascular phantom with a pumped flow to confirm the system for imaging blood flow. These variables were set to mimic the vessel diameter, flow speed, and depth of the Circle of Willis (CoW) during a transcranial screening. RESULTS AND CONCLUSIONS: The lower values of absolute error and ratio were found in the larger vascular channels, and vessel diameter overrepresentation was observed. Under different flow velocities, such diameter overrepresentation in the reconstructed flow did not change much; however, it did change with different depths. Meanwhile, the setting of the velocity scale and the color gain affected the dimension of reconstructed objectives. Moreover, we presented a 3D image of CoW from a subject to demonstrate its potential. The findings of this work can provide a good reference for further studies on the reconstruction of the CoW or other blood vessels using Doppler imaging.

15.
Front Microbiol ; 15: 1358222, 2024.
Article in English | MEDLINE | ID: mdl-38784797

ABSTRACT

Barkol Lake, a shrinking hypersaline lake situated in the northeast of Xinjiang, China, has experienced the exposure of its riverbed and the gradual drying up of its original sediment due to climate change and human activities, resulting in the formation of alkaline soils. These changes have correspondingly altered the physicochemical characteristics of the surrounding environment. Microorganisms play a crucial role, with special functioning involved in various nutrient cycling and energy transfer in saline lake environments. However, little is known about how the microbial community dynamics and metabolic functions in this shrinking saline lake relate to the degradation process. To address this knowledge gap, a cultivation-independent method of amplicon sequencing was used to identify and analyze the microbial community and its potential ecological functions in the sediment and degraded area. The microbial community diversity was found to be significantly lower in the degraded areas than in the sediment samples. The Pseudomonadota was dominant in Barkol Saline Lake. The abundance of Desulfobacterota and Bacillota in the degraded areas was lower than in the lake sediment, while Pseudomonadota, Acidobacteriota, and Actinobacteriota showed an opposite trend. The ßNTI showed that microbial community assembly was primarily associated with deterministic processes in Barkol Saline Lake ecosystems and stochastic processes at the boundary between sediment and degraded areas. Functional predictions showed that sulfur metabolism, particularly sulfate respiration, was much higher in sediment samples than in the degraded areas. Overall, these findings provided a possible perspective for us to understand how microorganisms adapt to extreme environments and their role in saline lakes under environmental change.

16.
Front Neurol ; 15: 1362061, 2024.
Article in English | MEDLINE | ID: mdl-38737351

ABSTRACT

Background: The efficacy and safety of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with whole-brain radiotherapy (WBRT) for treating brain metastases in non-small cell lung cancer patients remains to be determined. Methods: A systematic search was conducted using databases including PubMed, Embase, Web of Science, Cochrane, Wanfang, and China National Knowledge Infrastructure (CNKI), aiming to identify relevant clinical studies on the treatment of brain metastases originating from non-small cell lung cancer through the combination of EGFR-TKI and WBRT. Statistical analysis was performed utilizing Stata 17.0 software, covering clinical studies published until March 1, 2023. Results: This analysis incorporated 23 randomized controlled trials (RCTs), involving a total of 2,025 patients. Of these, 1,011 were allocated to the group receiving both EGFR-TKI and WBRT, while 1,014 were assigned to the WBRT alone group. The findings reveal that the combination of EGFR-TKI and WBRT significantly improves the intracranial objective remission rate (RR = 1.57, 95% CI: 1.42-1.74, p < 0.001), increases the intracranial disease control rate (RR = 1.30, 95% CI: 1.23-1.37, p < 0.001), and enhances the 1-year survival rate (RR = 1.48, 95% CI: 1.26-1.73, p < 0.001). Additionally, this combined treatment was associated with a significant survival advantage (RR = 1.48, 95% CI: 1.26-1.73, p < 0.001) and a reduced incidence of adverse effects (RR = 0.65, 95% CI: 0.51-0.83, p < 0.001), particularly with respect to nausea and vomiting (RR = 0.54, 95% CI: 0.37-0.81, p = 0.002) and myelosuppression (RR = 0.59, 95% CI: 0.40-0.87, p = 0.008). However, no statistically significant differences were observed for diarrhea (RR = 1.15, 95% CI: 0.82-1.62, p = 0.418), and skin rash (RR = 1.35, 95% CI: 0.88-2.07, p = 0.164). Conclusion: In contrast to WBRT alone, the combination of EGFR-TKI and WBRT significantly improves intracranial response, enhancing the objective response rate, disease control rate, and 1-year survival rate in NSCLC patients with brain metastases. Moreover, aside from mild cases of rash and diarrhea, there is no statistically significant increase in the incidence of additional adverse effects. Based on the comprehensive evidence collected, the use of third-generation EGFR-TKI combined with WBRT is recommended as the preferred treatment for NSCLC patients with brain metastases, offering superior management of metastatic brain lesions. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#, CRD42023415566.

17.
Int J Surg ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38759695

ABSTRACT

BACKGROUND: Cancer-associated fibroblasts (CAFs) are found in primary and advanced tumours. They are primarily involved in tumour progression through complex mechanisms with other types of cells in the tumour microenvironment. However, essential fibroblasts-related genes (FRG) in bladder cancer still need to be explored, and there is a shortage of an ideal predictive model or molecular subtype for the progression and immune therapeutic assessment for bladder cancer, especially muscular-invasive bladder cancer based on the FRG. MATERIALS AND METHODS: CAF-related genes of bladder cancer were identified by analyzing single-cell RNA sequence datasets, and bulk transcriptome datasets and gene signatures were used to characterize them. Then, ten types of machine learning algorithms were utilized to determine the hallmark FRG and construct the FRG index (FRGI) and subtypes. Further molecular subtypes combined with CD8+ T-cells were established to predict the prognosis and immune therapy response. RESULTS: 54 BLCA-related FRG were screened by large-scale scRNA-sequence datasets. The machine learning algorithm established a 3-genes FRG index (FRGI). High FRGI represented a worse outcome. Then, FRGI combined clinical variables to construct a nomogram, which shows high predictive performance for the prognosis of bladder cancer. Furthermore, the BLCA datasets were separated into two subtypes - fibroblast hot and cold types. In five independent BLCA cohorts, the fibroblast hot type showed worse outcomes than the cold type. Multiple cancer-related hallmark pathways are distinctively enriched in these two types. In addition, high FRGI or fibroblast hot type shows a worse immune therapeutic response. Then, four subtypes called CD8-FRG subtypes were established under the combination of FRG signature and activity of CD8+ T-cells, which turned out to be effective in predicting the prognosis and immune therapeutic response of bladder cancer in multiple independent datasets. Pathway enrichment analysis, multiple gene signatures, and epigenetic alteration characterize the CD8-FRG subtypes and provide a potential combination strategy method against bladder cancer. CONCLUSIONS: In summary, we established a novel FRGI and CD8-FRG subtype by large-scale datasets and organized analyses, which could accurately predict clinical outcomes and immune therapeutic response of BLCA after surgery.

18.
Article in English | MEDLINE | ID: mdl-38752993

ABSTRACT

Two novel bacterial strains, designated as SYSU D00823T and SYSU D00873T, were isolated from sandy soil of the Gurbantunggut Desert in Xinjiang, north-west China. SYSU D00823T and SYSU D00873T shared 99.0 % 16S rRNA gene sequence identity, and were both most closely related to Pedobacter xinjiangensis 12157T with 96.1 % and 96.0 % similarities, respectively. Phylogenetic and phylogenomic analyses revealed that the two isolates and P. xinjiangensis 12157T formed a separate distinct cluster in a stable subclade with the nearby species Pedobacter mongoliensis 1-32T, as well as the genera Pararcticibacter and Arcticibacter. Furthermore, P. mongoliensis 1-32T formed a separate deep-branching lineage and did not form a cluster with members of the genus Pedobacter. The average nucleotide identity and digital DNA-DNA hybridization values between SYSU D00823T and SYSU D00873T and related species were well below the thresholds for species delineation (<81.0 % and <24.0 %, respectively). The genomes of SYSU D00823T and SYSU D00873T were 6.19 and 6.43 Mbp in size with 40.4 % and 40.5 % DNA G+C contents, respectively. The predominant fatty acids (>10 %) of SYSU D00823T and SYSU D00873T were iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c). Menaquinone-7 was the only respiratory quinone. The major polar lipids were phosphatidylethanolamine, glycosphingolipid, aminoglycolipid/glycolipid, aminophospholipid and three or four unidentified polar lipids. These data indicated that strains SYSU D00823T and SYSU D00873T should be assigned to two novel species of a new genus within the family Sphingobacteriaceae, for which the names Desertivirga arenae gen. nov., sp. nov. and Desertivirga brevis sp. nov. are proposed. The type strains are SYSU D00823T (=CGMCC 1.18630T=MCCC 1K04973T=KCTC 82278T) and SYSU D00873T (=CGMCC 1.18629T=MCCC 1K04974T=KCTC 82281T), respectively. Accordingly, the reclassification of P. xinjiangensis as Desertivirga xinjiangensis comb. nov., and P. mongoliensis as Paradesertivirga mongoliensis gen. nov., comb. nov. are also proposed.


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Desert Climate , Fatty Acids , Pedobacter , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Soil Microbiology , Vitamin K 2 , RNA, Ribosomal, 16S/genetics , Pedobacter/genetics , Pedobacter/classification , Pedobacter/isolation & purification , Fatty Acids/chemistry , China , DNA, Bacterial/genetics , Vitamin K 2/analogs & derivatives , Nucleic Acid Hybridization
19.
J Am Chem Soc ; 146(19): 13391-13398, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38691098

ABSTRACT

Inverted p-i-n perovskite solar cells (PSCs) are easy to process but need improved interface characteristics with reduced energy loss to prevent efficiency drops when increasing the active photovoltaic area. Here, we report a series of poly ferrocenyl molecules that can modulate the perovskite surface enabling the construction of small- and large-area PSCs. We found that the perovskite-ferrocenyl interaction forms a hybrid complex with enhanced surface coordination strength and activated electronic states, leading to lower interfacial nonradiative recombination and charge transport resistance losses. The resulting PSCs achieve an enhanced efficiency of up to 26.08% for small-area devices and 24.51% for large-area devices (1.0208 cm2). Moreover, the large-area PSCs maintain >92% of the initial efficiency after 2000 h of continuous operation at the maximum power point under 1-sun illumination and 65 °C.

20.
Biochem Pharmacol ; 225: 116306, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38782076

ABSTRACT

Fibroblast growth factor 21 (FGF21) has promise for treating diabetes and its associated comorbidities. It has been found to reduce blood glucose in mice and humans; however, its underlying mechanism is not known. Here, the metabolic function of FGF21 in diabetes was investigated. Diabetic db/db mice received intraperitoneal injections of FGF21 for 28 days, the serum of each mouse was collected, and their metabolites were analyzed by untargeted metabolomics using UHPLC-MS/MS. It was found that FGF21 reduced blood glucose and oral glucose tolerance without causing hypoglycemia. Moreover, administration of FGF21 reduced the levels of TG and LDL levels while increasing those of HDL and adiponectin. Importantly, the levels of 45 metabolites, including amino acids and lipids, were significantly altered, suggesting their potential as biomarkers. We speculated that FGF21 may treat T2DM through the regulation of fatty acid biosynthesis, the TCA cycle, and vitamin digestion and absorption. These findings provide insight into the mechanism of FGF21 in diabetes and suggest its potential for treating diabetes.

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