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1.
ACS Chem Neurosci ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38775291

ABSTRACT

Mapping brain activities is necessary for understanding brain physiology and discovering new treatments for neurological disorders. Such efforts have greatly benefited from the advancement in technologies for analyzing neural activity with improving temporal or spatial resolution. Here, we constructed a multielectrode array based brain activity mapping (BAM) system capable of stabilizing and orienting zebrafish larvae for recording electroencephalogram (EEG) like local field potential (LFP) signals and brain-wide calcium dynamics in awake zebrafish. Particularly, we designed a zebrafish trap chip that integrates with an eight-by-eight surface electrode array, so that brain electrophysiology can be noninvasively recorded in an agarose-free and anesthetic-free format with a high temporal resolution of 40 µs, matching the capability typically achieved by invasive LFP recording. Benefiting from the specially designed hybrid system, we can also conduct calcium imaging directly on immobilized awake larval zebrafish, which further supplies us with high spatial resolution brain-wide activity data. All of these innovations reconcile the limitations of sole LFP recording or calcium imaging, emphasizing a synergy of combining electrical and optical modalities within one unified device for activity mapping across a whole vertebrate brain with both improved spatial and temporal resolutions. The compatibility with in vivo drug treatment further makes it suitable for pharmacology studies based on multimodal measurement of brain-wide physiology.

2.
Nat Commun ; 15(1): 4303, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773073

ABSTRACT

Uncontrollable zinc (Zn) plating and hydrogen evolution greatly undermine Zn anode reversibility. Previous electrolyte designs focus on suppressing H2O reactivity, however, the accumulation of alkaline byproducts during battery calendar aging and cycling still deteriorates the battery performance. Here, we present a direct strategy to tackle such problems using a strong Brønsted acid, bis(trifluoromethanesulfonyl)imide (HTFSI), as the electrolyte additive. This approach reformulates battery interfacial chemistry on both electrodes, suppresses continuous corrosion reactions and promotes uniform Zn deposition. The enrichment of hydrophobic TFSI- anions at the Zn|electrolyte interface creates an H2O-deficient micro-environment, thus inhibiting Zn corrosion reactions and inducing a ZnS-rich interphase. This highly acidic electrolyte demonstrates high Zn plating/stripping Coulombic efficiency up to 99.7% at 1 mA cm-2 ( > 99.8% under higher current density and areal capacity). Additionally, Zn | |ZnV6O9 full cells exhibit a high capacity retention of 76.8% after 2000 cycles.

3.
Sci Data ; 11(1): 531, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38782916

ABSTRACT

We present unprecedented datasets of current and future projected weather files for building simulations in 15 major cities distributed across 10 climate zones worldwide. The datasets include ambient air temperature, relative humidity, atmospheric pressure, direct and diffuse solar irradiance, and wind speed at hourly resolution, which are essential climate elements needed to undertake building simulations. The datasets contain typical and extreme weather years in the EnergyPlus weather file (EPW) format and multiyear projections in comma-separated value (CSV) format for three periods: historical (2001-2020), future mid-term (2041-2060), and future long-term (2081-2100). The datasets were generated from projections of one regional climate model, which were bias-corrected using multiyear observational data for each city. The methodology used makes the datasets among the first to incorporate complex changes in the future climate for the frequency, duration, and magnitude of extreme temperatures. These datasets, created within the IEA EBC Annex 80 "Resilient Cooling for Buildings", are ready to be used for different types of building adaptation and resilience studies to climate change and heatwaves.

4.
Genomics ; 116(3): 110859, 2024 May.
Article in English | MEDLINE | ID: mdl-38750703

ABSTRACT

Mitochondria play an important role in the energy production of plant cells through independent genetic systems. This study has aimed to assemble and annotate the functions of the mitochondrial (mt) genome of Luffa cylindrica. The mt genome of L. cylindrica contained two chromosomes with lengths of 380,879 bp and 67,982 bp, respectively. Seventy-seven genes including 39 protein-coding genes, 34 tRNA genes, 3 rRNA genes, and 1 pseudogene, were identified. About 90.63% of the codons ended with A or U bases, and 98.63% of monomers contained A/T, which contributed to the high A/T content (55.91%) of the complete mt genome. Six genes (ATP8, CCMFC, NAD4, RPL10, RPL5 and RPS4) showed positive selection. Phylogenetic analysis indicates that L. cylindrica is closely related to L. acutangula. The present results provide the mt genome of L. cylindrica, which may facilitate possible genetic variation, evolutionary, and molecular breeding studies of L. cylindrica.


Subject(s)
Genome, Mitochondrial , Luffa , Phylogeny , Luffa/genetics , RNA, Transfer/genetics , Genome, Plant , Plant Proteins/genetics , Plant Proteins/metabolism
5.
Ann Ital Chir ; 95(2): 206-212, 2024.
Article in English | MEDLINE | ID: mdl-38684500

ABSTRACT

OBJECTIVE: The incidence of deep vein thrombosis (DVT) after traumatic fracture is high, and DVT causes serious adverse effects on the postoperative recovery of patients. The purpose of this study was to explore the effect of coagulation-related indicators combined with vascular ultrasound measurements for the risk assessment of DVT after secondary traumatic fracture, and to provide a new method for predicting the occurrence of DVT. METHODS: The clinical data of patients with secondary traumatic fracture surgery in our hospital from January 2019 to January 2022 were retrospectively analyzed. The patients were divided into a non-DVT group and a DVT group according to whether DVT was indicated in the medical record system. The coagulation-related indices and vascular ultrasound measurements of the two groups were compared, and the risk factors for postoperative DVT were analyzed by bivariate correlation and multivariate logistic regression. RESULTS: According to the medical record system, 55 patients (47.41%) had DVT, and 61 patients (52.59%) did not have DVT. There was no significant difference in prothrombin time (PT) or activated partial thromboplastin time (APTT) between the two groups (p > 0.05). The thrombin time (TT) in the DVT group was lower than that in the non-DVT group. The levels of fibrinogen (FIB) and D-dimer (D-D) in the DVT group were higher than those in the non-DVT group (t = 2.766, 3.242, 2.649, p = 0.007, 0.002, 0.009). Spearman correlation analysis showed that peak systolic velocity (Vs), end-diastolic velocity (Vd), pulsatility index (PI), resistance index (RI), FIB, and D-D were positively correlated with the risk of DVT after secondary traumatic fracture surgery (r = 0.264, 0.656, 0.293, 0.276, 0.287, 0.251, p < 0.05). TT was negatively correlated with DVT risk after secondary traumatic fracture surgery (r = -0.249, p < 0.05). The measurements of peak systolic velocity (Vs), end diastolic velocity (Vd), pulsatility index (PI) and resistance index (RI) in the DVT group were higher than those in the non-DVT group (t = 2.663, 2.998, 3.135, 2.953, p = 0.009, 0.003, 0.002, 0.004). FIB, D-D, Vs, Vd, PI, and RI were independent risk factors for DVT after secondary traumatic fracture surgery (Odds Ratio (OR) = 1.483, 2.026, 2.208, 1.893, 1.820, 1.644, p < 0.05). TT index was an independent protective factor for DVT after secondary traumatic fracture surgery (OR = 0.868, p < 0.05). The sensitivity and specificity for prediction of DVT based on combined coagulation-related indicators and vascular ultrasound imaging measurements were higher than those of individual measurements (p < 0.05). CONCLUSIONS: Coagulation-related indicators and vascular ultrasound parameters can effectively predict the formation of DVT. Through the analysis of factors related to DVT formation, screening of high-risk patients for effective intervention may help to reduce the risk of DVT. Further verification in additional, large-scale clinical trials is advocated.


Subject(s)
Postoperative Complications , Venous Thrombosis , Humans , Venous Thrombosis/etiology , Venous Thrombosis/diagnostic imaging , Male , Female , Retrospective Studies , Postoperative Complications/etiology , Postoperative Complications/diagnostic imaging , Risk Assessment/methods , Middle Aged , Adult , Ultrasonography , Fractures, Bone/complications , Fractures, Bone/surgery , Risk Factors , Blood Coagulation , Aged , Fibrin Fibrinogen Degradation Products/analysis
6.
Clin Cancer Res ; 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38687583

ABSTRACT

PURPOSE: This phase II, multicenter, prospective, single-arm study aimed to evaluate the efficacy and safety of toripalimab plus bevacizumab in treating advanced hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Treatment-naïve patients with advanced HCC received toripalimab 240 mg plus bevacizumab 15 mg/kg every 3 weeks. Primary endpoints included safety and tolerability, and objective response rate (ORR) assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. RESULTS: Fifty-four patients were enrolled between Apr 17, 2020 and Dec 11, 2020. As assessed by the investigator according to RECIST v1.1, the ORR was 31.5% [95% confidence interval (CI), 19.5-45.6] and the lower bound of the 95% CI was above the pre-specified boundary of 10%. The independent review committee (IRC) assessed ORR according to modified RECIST (mRECIST) was 46.3% (95% CI, 32.6-60.4). The median progression-free survival were 8.5 months (95% CI, 5.5-11.0) and 9.8 months (95% CI, 5.6-not evaluable) assessed by the investigator according to RECIST v1.1 and IRC according to mRECIST criteria, respectively. The median overall survival (OS) was not reached, and the 12- and 24-month OS rates were 77.3% and 63.5%, respectively. Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 27 patients (50.0%). The most common TEAEs were proteinuria (59.3%), hypertension (38.9%), aspartate aminotransferase increased (33.3%), amylase increased (29.6%), platelet count decreased (27.8%), and bilirubin increased (27.8%). CONCLUSIONS: Toripalimab plus bevacizumab showed a favorable efficacy and safety profile, supporting further studies of this combination regimen as a first-line treatment of advanced HCC.

7.
Front Microbiol ; 15: 1352586, 2024.
Article in English | MEDLINE | ID: mdl-38596375

ABSTRACT

Introduction: Melatonin (MEL) is a crucial neuroendocrine hormone primarily produced by the pineal gland. Pinealectomy (PINX) has been performed on an endogenous MEL deficiency model to investigate the functions of pineal MEL and its relationship with various diseases. However, the effect of PINX on the gastrointestinal tract (GIT) MEL levels and gut microbiome in pigs has not been previously reported. Methods: By using a newly established pig PINX model, we detected the levels of MEL in the GIT by liquid chromatography-tandem mass spectrometry. In addition, we examined the effects of PINX on the expression of MEL synthesis enzymes, intestinal histomorphology, and the intestinal barrier. Furthermore, 16S rRNA sequencing was performed to analyze the colonic microbiome. Results: PINX reduced serum MEL levels but did not affect GIT MEL levels. Conversely, MEL supplementation increased MEL levels in the GIT and intestinal contents. Neither PINX nor MEL supplementation had any effect on weight gain, organ coefficient, serum biochemical indexes, or MEL synthetase arylalkylamine N-acetyltransferase (AANAT) expression in the duodenum, ileum, and colon. Furthermore, no significant differences were observed in the intestinal morphology or intestinal mucosal barrier function due to the treatments. Additionally, 16S rRNA sequencing revealed that PINX had no significant impact on the composition of the intestinal microbiota. Nevertheless, MEL supplementation decreased the abundance of Fibrobacterota and increased the abundance of Actinobacteriota, Desulfobacterota, and Chloroflexi. Conclusion: We demonstrated that synthesis of MEL in the GIT is independent of the pineal gland. PINX had no influence on intestinal MEL level and microbiota composition in pigs, while exogenous MEL alters the structure of the gut microbiota.

8.
Nat Commun ; 15(1): 3425, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38653984

ABSTRACT

While the monolayer sheet is well-established as a Mott-insulator with a finite energy gap, the insulating nature of bulk 1T-TaS2 crystals remains ambiguous due to their varying dimensionalities and alterable interlayer coupling. In this study, we present a unique approach to unlock the intertwined two-dimensional Mott-insulator and three-dimensional band-insulator states in bulk 1T-TaS2 crystals by structuring a laddering stack along the out-of-plane direction. Through modulating the interlayer coupling, the insulating nature can be switched between band-insulator and Mott-insulator mechanisms. Our findings demonstrate the duality of insulating nature in 1T-TaS2 crystals. By manipulating the translational degree of freedom in layered crystals, our discovery presents a promising strategy for exploring fascinating physics, independent of their dimensionality, thereby offering a "three-dimensional" control for the era of slidetronics.

9.
Lupus Sci Med ; 11(1)2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38599669

ABSTRACT

OBJECTIVE: Circadian rhythm disruption (CRD) has been associated with inflammation and immune disorders, but its role in SLE progression is unclear. We aimed to investigate the impact of circadian rhythms on immune function and inflammation and their contribution to SLE progression to lupus nephritis (LN). METHODS: This study retrospectively analysed the clinical characteristics and transcriptional profiles of 373 samples using bioinformatics and machine-learning methods. A flare risk score (FRS) was established to predict overall disease progression for patients with lupus. Mendelian randomisation was used to analyse the causal relationship between CRD and SLE progression. RESULTS: Abnormalities in the circadian pathway were detected in patients with SLE, and lower enrichment levels suggested a disease state (normalised enrichment score=0.6714, p=0.0062). The disruption of circadian rhythms was found to be closely linked to lupus flares, with the FRS showing a strong ability to predict disease progression (area under the curve (AUC) of 5-year prediction: 0.76). The accuracy of disease prediction was improved by using a prognostic nomogram based on FRS (AUC=0.77). Additionally, Mendelian randomisation analysis revealed an inverse causal relationship between CRD and SLE (OR 0.6284 (95% CI 0.3630 to 1.0881), p=0.0485) and a positive causal relationship with glomerular disorders (OR 0.0337 (95% CI 1.634e-3 to 6.934e-1), p=0.0280). CONCLUSION: Our study reveals that genetic characteristics arising from CRD can serve as biomarkers for predicting the exacerbation of SLE. This highlights the crucial impact of CRD on the progression of lupus.


Subject(s)
Lupus Erythematosus, Systemic , Lupus Nephritis , Humans , Disease Progression , Inflammation , Lupus Erythematosus, Systemic/complications , Lupus Nephritis/complications , Retrospective Studies , Mendelian Randomization Analysis
10.
Biomed Eng Online ; 23(1): 32, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38475784

ABSTRACT

PURPOSE: This study aimed to investigate the imaging repeatability of self-service fundus photography compared to traditional fundus photography performed by experienced operators. DESIGN: Prospective cross-sectional study. METHODS: In a community-based eye diseases screening site, we recruited 65 eyes (65 participants) from the resident population of Shanghai, China. All participants were devoid of cataract or any other conditions that could potentially compromise the quality of fundus imaging. Participants were categorized into fully self-service fundus photography or traditional fundus photography group. Image quantitative analysis software was used to extract clinically relevant indicators from the fundus images. Finally, a statistical analysis was performed to depict the imaging repeatability of fully self-service fundus photography. RESULTS: There was no statistical difference in the absolute differences, or the extents of variation of the indicators between the two groups. The extents of variation of all the measurement indicators, with the exception of the optic cup area, were below 10% in both groups. The Bland-Altman plots and multivariate analysis results were consistent with results mentioned above. CONCLUSIONS: The image repeatability of fully self-service fundus photography is comparable to that of traditional fundus photography performed by professionals, demonstrating promise in large-scale eye disease screening programs.


Subject(s)
Community Health Services , Glaucoma , Humans , Cross-Sectional Studies , Prospective Studies , China , Photography/methods , Fundus Oculi
11.
JACC Case Rep ; 29(6): 102253, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38549853

ABSTRACT

We present a unique case of left atrial (LA) dissection in a 46-year-old man following aortic dissection surgery. The LA dissection was attributed to coronary sinus catheter-related injury. This report highlights the importance of recognizing this rare complication and the crucial role of transesophageal echocardiography in its diagnosis. We discuss the pathogenesis, diagnostic criteria, and management strategies for LA dissection.

12.
Article in English | MEDLINE | ID: mdl-38479723

ABSTRACT

BACKGROUND: Anatomic and reverse total shoulder arthroplasty (TSA) are effective treatment options for end-stage glenohumeral osteoarthritis. However, consideration for pre-existing conditions must be taken into account. Factor V Leiden (FVL), the most common inherited thrombophilia, is one such condition that predisposes to a prothrombotic state and may affect perioperative and longer-term outcomes following TSA. METHODS: Adult patients undergoing primary TSA for osteoarthritis indication were identified in the 2010 through October 2021 PearlDiver M157 database. Patients with or without FVL were matched at a 1:4 ratio based on age, sex, and Elixhauser Comorbidity Index. Ninety-day adverse events and 5-year revision rates were assessed and compared with multivariable logistic regression and rank-log tests, respectively. Finally, the relative use and bleeding/clotting outcomes were assessed based on venous thromboembolic (VTE) prophylactic agents used, with categories defined as (1) warfarin, heparin, or direct oral anticoagulant (DOAC) or (2) aspirin/no prescription found. RESULTS: Of 104,258 TSA patients, FVL was identified for 283 (0.27%). Based on matching, 1081 patients without FVL and 272 patients with FVL were selected. Multivariable analyses demonstrated that those with FVL displayed independently greater odds ratios (ORs) of deep vein thrombosis (DVT, OR = 9.50, P < .0001), pulmonary embolism (PE, OR = 10.10, P < .0001), and pneumonia (OR = 2.43, P = .0019). Further, these events contributed to the increased odds of aggregated minor (OR = 1.95, P = .0001), serious (OR = 6.38, P < .0001), and all (OR = 3.51, P < .0001) adverse events. All other individual 90-day adverse events, as well as 5-year revision rates, were not different between the study groups. When compared to matched patients without FVL on the same anticoagulant agents, FVL patients on warfarin, heparin, or DOAC agents demonstrated lesser odds of 90-day DVT and PE (OR = 4.25, P < .0001, and OR = 2.54, P = .0065) than those on aspirin/no prescription found (OR = 7.64 and OR = 21.95, P < .0001 for both). Interestingly, those on VTE prophylactic agents were not at greater odds of bleeding complications (hematoma or transfusion). DISCUSSION AND CONCLUSIONS: TSA patients with FVL present a difficult challenge to shoulder reconstruction surgeons. The current study highlights the strong risk of VTE that was reduced but still significantly elevated for those with stronger classes of VTE chemoprophylaxis. Acknowledging this risk is important for surgical planning and patient counseling, but also noted was the reassurance of similar 5-year revision rates for those with vs. without FVL.

13.
Biochem Pharmacol ; 223: 116112, 2024 May.
Article in English | MEDLINE | ID: mdl-38458331

ABSTRACT

Glioblastoma (GBM) is the most common malignant glioma among brain tumors with low survival rate and high recurrence rate. Columbianadin (CBN) has pharmacological properties such as anti-inflammatory, analgesic, thrombogenesis-inhibiting and anti-tumor effects. However, it remains unknown that the effect of CBN on GBM cells and its underlying molecular mechanisms. In the present study, we found that CBN inhibited the growth and proliferation of GBM cells in a dose-dependent manner. Subsequently, we found that CBN arrested the cell cycle in G0/G1 phase and induced the apoptosis of GBM cells. In addition, CBN also inhibited the migration and invasion of GBM cells. Mechanistically, we chose network pharmacology approach by screening intersecting genes through targets of CBN in anti-GBM, performing PPI network construction followed by GO analysis and KEGG analysis to screen potential candidate signaling pathway, and found that phosphatidylinositol 3-kinase/Protein Kinase-B (PI3K/Akt) signaling pathway was a potential target signaling pathway of CBN in anti-GBM. As expected, CBN treatment indeed inhibited the PI3K/Akt signaling pathway in GBM cells. Furthermore, YS-49, an agonist of PI3K/Akt signaling, partially restored the anti-GBM effect of CBN. Finally, we found that CBN inhibited GBM growth in an orthotopic mouse model of GBM through inhibiting PI3K/Akt signaling pathway. Together, these results suggest that CBN has an anti-GBM effect by suppressing PI3K/Akt signaling pathway, and is a promising drug for treating GBM effectively.


Subject(s)
Coumarins , Glioblastoma , Proto-Oncogene Proteins c-akt , Animals , Mice , Proto-Oncogene Proteins c-akt/metabolism , Glioblastoma/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Cell Line, Tumor , Signal Transduction , Cell Proliferation
14.
Environ Res ; 251(Pt 2): 118644, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38485074

ABSTRACT

Tetracycline hydrochloride (TC) accumulates in large quantities in the water environment, causing a serious threat to human health and ecological environment safety. This research focused on developing cost-effective catalysts with high 2e- selectivity for electro-Fenton (EF) technology, a green pollution treatment method. Defective nitrogen-doped porous carbon (d-NPC) was prepared using the metal-organic framework as the precursor to achieve in-situ H2O2 production and self-decomposition into high activity ·OH for degradation of TC combined with Co2+/Co3+. The d-NPC produced 172.1 mg L-1 H2O2 within 120 min, and could degrade 96.4% of TC in EF system. The self-doped defects and graphite-nitrogen in d-NPC improved the oxygen reduction performance and increased the H2O2 yield, while pyridine nitrogen could catalyze H2O2 to generate ·OH. The possible pathway of TC degradation was also proposed. In this study, defective carbon materials were prepared by ball milling, which provided a new strategy for efficient in-situ H2O2 production and the degradation of pollutants.

15.
J Proteome Res ; 23(4): 1174-1187, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38427982

ABSTRACT

Protein homeostasis is essential for cyanobacteria to maintain proper cellular function under adverse and fluctuating conditions. The AAA+ superfamily of proteolytic complexes in cyanobacteria plays a critical role in this process, including ClpXP, which comprises a hexameric ATPase ClpX and a tetradecameric peptidase ClpP. Despite the physiological effects of ClpX on growth and photosynthesis, its potential substrates and underlying mechanisms in cyanobacteria remain unknown. In this study, we employed a streptavidin-biotin affinity pull-down assay coupled with label-free proteome quantitation to analyze the interactome of ClpX in the model cyanobacterium Synechocystis sp. PCC 6803 (hereafter Synechocystis). We identified 503 proteins as potential ClpX-binding targets, many of which had novel interactions. These ClpX-binding targets were found to be involved in various biological processes, with particular enrichment in metabolic processes and photosynthesis. Using protein-protein docking, GST pull-down, and biolayer interferometry assays, we confirmed the direct association of ClpX with the photosynthetic proteins, ferredoxin-NADP+ oxidoreductase (FNR) and phycocyanin subunit (CpcA). Subsequent functional investigations revealed that ClpX participates in the maintenance of FNR homeostasis and functionality in Synechocystis grown under different light conditions. Overall, our study provides a comprehensive understanding of the extensive functions regulated by ClpX in cyanobacteria to maintain protein homeostasis and adapt to environmental challenges.


Subject(s)
Photosynthesis , Synechocystis , Photosynthesis/genetics , Synechocystis/genetics , Synechocystis/metabolism , Adenosine Triphosphatases/genetics , Adenosine Triphosphatases/metabolism , Phycocyanin/metabolism
16.
Sci Rep ; 14(1): 7543, 2024 03 30.
Article in English | MEDLINE | ID: mdl-38555384

ABSTRACT

Lung cancer, specifically the histological subtype lung adenocarcinoma (LUAD), has the highest global occurrence and fatality rate. Extensive research has indicated that RNA alterations encompassing m6A, m5C, and m1A contribute actively to tumorigenesis, drug resistance, and immunotherapy responses in LUAD. Nevertheless, the absence of a dependable predictive model based on m6A/m5C/m1A-associated genes hinders accurately predicting the prognosis of patients diagnosed with LUAD. In this study, we collected patient data from The Cancer Genome Atlas (TCGA) and identified genes related to m6A/m5C/m1A modifications using the GeneCards database. The "ConsensusClusterPlus" R package was used to produce molecular subtypes by utilizing genes relevant to m6A/m5C/m1A identified through differential expression and univariate Cox analyses. An independent prognostic factor was identified by constructing a prognostic signature comprising six genes (SNHG12, PABPC1, IGF2BP1, FOXM1, CBFA2T3, and CASC8). Poor overall survival and elevated expression of human leukocyte antigens and immune checkpoints were correlated with higher risk scores. We examined the associations between the sets of genes regulated by m6A/m5C/m1A and the risk model, as well as the immune cell infiltration, using algorithms such as ESTIMATE, CIBERSORT, TIMER, ssGSEA, and exclusion (TIDE). Moreover, we compared tumor stemness indices (TSIs) by considering the molecular subtypes related to m6A/m5C/m1A and risk signatures. Analyses were performed based on the risk signature, including stratification, somatic mutation analysis, nomogram construction, chemotherapeutic response prediction, and small-molecule drug prediction. In summary, we developed a prognostic signature consisting of six genes that have the potential for prognostication in patients with LUAD and the design of personalized treatments that could provide new versions of personalized management for these patients.


Subject(s)
Adenine/analogs & derivatives , Adenocarcinoma of Lung , Lung Neoplasms , Humans , Prognosis , Adenocarcinoma of Lung/genetics , Lung Neoplasms/genetics , Nomograms
17.
Eur J Pharmacol ; 968: 176401, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38331340

ABSTRACT

Glioblastoma (GBM) is one of the most common intracranial primary malignancies with the highest mortality rate, and there is a lack of effective treatments. In this study, we examined the anti-GBM activity of Tenacissoside H (TH), an active component isolated from the traditional Chinese medicine Marsdenia tenacissima (Roxb.) Wight & Arn (MT), and investigated the potential mechanism. Firstly, we found that TH decreased the viability of GBM cells by inducing cell cycle arrest and apoptosis, and inhibited the migration of GBM cells. Furthermore, combined with the Gene Expression Omnibus database (GEO) and network pharmacology as well as molecular docking, TH was shown to inhibit GBM progression by directly regulating the PI3K/Akt/mTOR pathway, which was further validated in vitro. In addition, the selective PI3K agonist 740 y-p partially restored the inhibitory effects of TH on GBM cells. Finally, TH inhibited GBM progression in an orthotopic transplantation model by inactivating the PI3K/Akt/mTOR pathway in vivo. Conclusively, our results suggest that TH represses GBM progression by inhibiting the PI3K/Akt/mTOR signaling pathway in vitro and in vivo, and provides new insight for the treatment of GBM patients.


Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Glioblastoma/genetics , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Molecular Docking Simulation , Cell Line, Tumor , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Brain Neoplasms/genetics , Cell Proliferation
18.
ACS Omega ; 9(6): 7269, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38371812

ABSTRACT

[This corrects the article DOI: 10.1021/acsomega.3c04101.].

19.
Animals (Basel) ; 14(4)2024 Feb 17.
Article in English | MEDLINE | ID: mdl-38396614

ABSTRACT

Purebred Bamei piglets present problems, including slow growth, respiratory disease, and post-weaning stress. This study investigated the effects of Lactobacillus plantarum QP28-1- and Bacillus subtilis QB8-fermented feed supplementation on the growth performance, immunity, and intestinal microflora of Bamei piglets from Qinghai, China. A total of 48 purebred Bamei piglets (25 days; 6.8 ± 0.97 kg) were divided into the following four groups for a 28-day diet experiment: basal feed (CK); diet containing 10% Lactobacillus plantarum-fermented feed (L); diet containing 10% Bacillus subtilis-fermented feed (B); and diet containing a mixture of 5% Lactobacillus plantarum + 5% Bacillus subtilis-fermented feed (H). The daily weight gain and daily food intake of group H increased (p < 0.05), and the feed/weight gain ratios of the groups fed with fermented feed decreased more than that of the CK group. The levels of three immune factors, namely immunoglobulin (Ig)M, IgG, and interferon-γ, were higher (p < 0.05), whereas those of tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 were lower (p < 0.05) in the fermented feed groups than in the CK group. Total protein was higher (p < 0.05), while urea nitrogen, total cholesterol and triglycerides were lower (p < 0.05) in the mixed-fermented feed group than in the CK group. Analysis of the gut microbiota showed that the addition of fermented feed increased the α-diversity of the gut microbiota, increasing the abundances of probiotics including Lactobacillus, Muribaculaceae, Ruminococcaceae, Prevotellaceae, and Rikenellaceae. Additionally, correlation analysis demonstrated that several of these probiotic bacteria were closely related to serum immunity. In conclusion, fermented feed supplementation rebuilt the intestinal microbiota of Bamei piglets, thereby reducing the feed/weight ratio, improving feed intake, and enhancing immunity.

20.
J Mater Chem B ; 12(10): 2547-2558, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38358131

ABSTRACT

Monitoring active membrane cholesterol and lipid raft cholesterol in the inner leaflet of the plasma membrane is significant for understanding the membrane function and cellular physiopathological processes. Limited by existing methods, it is difficult to differentiate active membrane cholesterol and lipid raft cholesterol. A novel dual-monomer solvatochromic probe system (DSPS) that targets two types of cholesterol was developed. Acrylodan-BG/SNAP-D4 composed of SNAP-D4 cholesterol-recognizing monomers and solvatochromic acrylodan-BG-sensing monomers exhibits excellent cholesterol detecting properties in terms of selectivity, accuracy, convenience and economic benefits. Cell imaging revealed that lipid raft cholesterol emitted blue fluorescence, whereas active membrane cholesterol (which partially bobbed in aqueous cytosol) displayed green fluorescence; both the fluorescence emissions increased or decreased in a cholesterol-dependent manner. This system provides a new technology for the determination of two types of cholesterol, which is beneficial for the further study of membrane function, intracellular cholesterol trafficking, and cell signaling.


Subject(s)
2-Naphthylamine/analogs & derivatives , Cholesterol , Membrane Microdomains , Cell Membrane/metabolism , Cholesterol/metabolism , Membrane Microdomains/metabolism
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