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1.
Cancer Immunol Immunother ; 73(8): 140, 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38833011

OBJECTIVES: To investigate the feasibility and potential clinical value of local consolidative therapy (LCT) in PD-1/PD-L1 inhibitor-treated metastatic non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: PD-1/PD-L1 inhibitor-treated metastatic NSCLC patients with measurable disease in three academic centers were screened and those with adequate follow-up were included. Oligo-residual disease (ORD) was defined as residual tumors limited to three organs and five lesions evaluated at the best response among patients with partial response or stable disease after PD-1/PD-L1 inhibitors. Oligometastatic and multiple-metastatic disease (OMD/MMD) were similarly classified at baseline. Locoregional interventions, administered after effective treatment of PD-1/PD-L1 inhibitors and before initial disease progression, were defined as LCT. Patterns of initial progressive disease (PD) were classified as involving only residual sites (RP), only new sites (NP), or a combination of both (BP). RESULTS: Among the 698 patients included, ORD was documented in 73 (47.1%) of 155 patients with baseline OMD and 60 (11.0%) of 543 patients with baseline MMD. With a median follow-up of 31.0 (range, 6.0-53.0) months, 108 patients with ORD developed initial PD, with RP, NP, and BP occurring in 51 (47%), 23 (21.3%), and 34 (31.5%), respectively. Among the 133 patients with ORD, those receiving LCT (n = 43) had longer progression-free survival (HR = 0.58, 95% CI 0.40-0.85, p = 0.01) and overall survival (HR = 0.49, 95% CI 0.30-0.79, p < 0.0001). CONCLUSION: ORD occurs with a clinically relevant frequency among PD-1/PD-L1 inhibitor-treated metastatic NSCLC patients and LCT may provide extra survival benefits in those with ORD.


Carcinoma, Non-Small-Cell Lung , Immune Checkpoint Inhibitors , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/mortality , Male , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Female , Middle Aged , Aged , Immune Checkpoint Inhibitors/therapeutic use , Adult , Neoplasm, Residual , B7-H1 Antigen/antagonists & inhibitors , Aged, 80 and over , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Incidence , Neoplasm Metastasis , Follow-Up Studies , Retrospective Studies
2.
Am J Hypertens ; 2024 Jun 03.
Article En | MEDLINE | ID: mdl-38828480

BACKGROUND: This study aims to explore the association between a healthy lifestyle and abnormal ambulatory blood pressure (ABP) in Chinese youths. METHODS: A school-based sample of 1,296 college students was investigated. A lifestyle score was calculated by synthesizing five lifestyle factors, including smoking, alcohol consumption, diet, physical activity, and sleeping. The total score ranged from 0 to 5, with a higher score indicating a healthier lifestyle. This score was then divided into three categories representing low adherence to a healthy lifestyle (0-2), medium adherence (3), and high adherence (4-5). Abnormal 24-hour blood pressure (BP) was defined as systolic BP (SBP) ≥ 130 mmHg and/or diastolic BP (DBP) ≥ 80 mmHg. Abnormal daytime BP was determined as daytime SBP ≥ 135 mmHg and/or DBP ≥ 85 mmHg, while abnormal nighttime BP was characterized as nighttime SBP ≥ 120 mmHg and/or DBP ≥ 70 mmHg. We assessed the associations using the binomial regression model. RESULTS: Mean age was 18.81 years, and 74.5% were women. The prevalence of abnormal 24-hour BP, daytime BP, and nighttime BP are 4.2%, 3.7%, and 9.0%, respectively. We found that participants with high level of adherence to a healthy lifestyle had a significantly lower prevalence of abnormal 24-hour BP [prevalence ratios (PR) = 0.15, 95% CI: 0.05, 0.48] and abnormal daytime BP (PR = 0.16, 95%CI: 0.05, 0.52), when compared to those with low level of adherence and after adjusting for the potential covariates. CONCLUSIONS: A healthier lifestyle is associated with better ambulatory BP profile among youths.

3.
Inorg Chem ; 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38833379

We report the first room-temperature synthesis of ternary CdTeSe magic-size clusters (MSCs) that have mainly the surface ligand oleate (OA). The MSCs display sharp optical absorption peaking at ∼399 nm and are thus referred to as MSC-399. They are made from prenucleation-stage samples of binary CdTe and CdSe, which are prepared by two reactions in 1-octadecene (ODE) of cadmium oleate (Cd(OA)2) and tri-n-octylphosphine chalcogenide (ETOP, E = Te and Se) at 25 °C for 120 min and 80 °C for 15 min, respectively. When the two binary samples are mixed at room temperature and dispersed in a mixture of toluene (Tol) and octylamine (OTA), the CdTeSe MSC-399 develops. Also, when the CdSe sample is added to CdTe MSC-371 in a dispersion, the transformation from CdTe MSC-371 to CdTeSe MSC-399 is seen. We propose that the MSCs develop from their precursor compounds (PCs) that are relatively transparent in optical absorption, such as CdTeSe MSC-399 from CdTeSe PC-399 and CdTe MSC-371 from CdTe PC-371. The formation of CdTeSe PC-399 undergoes monomer substitution and not anion exchange, which is the reaction of CdTe PC-371 and the CdSe monomer to produce CdTeSe PC-399 and the CdTe monomer. Our study provides evidence of monomer substitution for the transformation from binary CdTe to ternary CdTeSe PCs.

4.
Oncol Lett ; 28(1): 334, 2024 Jul.
Article En | MEDLINE | ID: mdl-38827568

Despite advances in treatment and diagnosis, the prognosis of patients with esophageal squamous cell carcinoma (ESCC) remains poor. MicroRNAs (miRNAs/miRs) are associated with prognosis in esophageal cancer, indicating that they may help guide treatment decisions. The aim of the present study was to explore exosomal miR-185 as a candidate prognostic biomarker and therapeutic target in ESCC, to investigate its biological function and clinical significance, and to ascertain the applicability of circulating exosomal miR-185 for the development of targeted drugs for ESCC treatment. A GeneChip miRNA array was used to compare exosomal miRNA expression in ESCC cell lines under hypoxia with those under normoxia. Exosomal miR-185 expression was then confirmed by reverse transcription-quantitative PCR. Patient background and prognosis were compared between high and low miR-185 expression groups. Functional analyses were performed to evaluate the antitumor effects of miR-185 in ESCC cells. Global Gene Set Enrichment Analysis of The Cancer Genome Atlas data was also performed, and differentially expressed exosomal miRNAs under hypoxia were identified compared to those under normoxia. Hypoxia markedly decreased the expression of exosomal miR-185 in KYSE-960 and T.Tn cell culture media. Overexpression of miR-185 suppressed the migration, invasion and colony-forming abilities of ESCC lines, and also suppressed cell cycle progression and promoted apoptosis after cisplatin treatment. Notably, high miR-185 expression was associated with signaling pathways related to cell death, DNA damage and p53. Furthermore, circulating exosomal miR-185 levels were associated with cN and cStage, and could predict progression-free survival and disease-specific survival of patients with ESCC after initial treatment. In conclusion, miR-185 holds potential as a prognostic biomarker and therapeutic target in ESCC.

5.
Dev Cell ; 2024 May 28.
Article En | MEDLINE | ID: mdl-38823394

Embryonic stem cells (ESCs) can differentiate into all cell types of the embryonic germ layers. ESCs can also generate totipotent 2C-like cells and trophectodermal cells. However, these latter transitions occur at low frequency due to epigenetic barriers, the nature of which is not fully understood. Here, we show that treating mouse ESCs with sodium butyrate (NaB) increases the population of 2C-like cells and enables direct reprogramming of ESCs into trophoblast stem cells (TSCs) without a transition through a 2C-like state. Mechanistically, NaB inhibits histone deacetylase activities in the LSD1-HDAC1/2 corepressor complex. This increases acetylation levels in the regulatory regions of both 2C- and TSC-specific genes, promoting their expression. In addition, NaB-treated cells acquire the capacity to generate blastocyst-like structures that can develop beyond the implantation stage in vitro and form deciduae in vivo. These results identify how epigenetics restrict the totipotent and trophectoderm fate in mouse ESCs.

6.
J Cell Mol Med ; 28(11): e18370, 2024 Jun.
Article En | MEDLINE | ID: mdl-38818568

The Finkel-Biskis-Jinkins Osteosarcoma (c-Fos; encoded by FOS) plays an important role in several cardiovascular diseases, including atherosclerosis and stroke. However, the relationship between FOS and venous thromboembolism (VTE) remains unknown. We identified differentially expressed genes in Gene Expression Omnibus dataset, GSE48000, comprising VTE patients and healthy individuals, and analysed them using CIBERSORT and weighted co-expression network analysis (WGCNA). FOS and CD46 expressions were significantly downregulated (FOS p = 2.26E-05, CD64 p = 8.83E-05) and strongly linked to neutrophil activity in VTE. We used GSE19151 and performed PCR to confirm that FOS and CD46 had diagnostic potential for VTE; however, only FOS showed differential expression by PCR and ELISA in whole blood samples. Moreover, we found that hsa-miR-144 which regulates FOS expression was significantly upregulated in VTE. Furthermore, FOS expression was significantly downregulated in neutrophils of VTE patients (p = 0.03). RNA sequencing performed on whole blood samples of VTE patients showed that FOS exerted its effects in VTE via the leptin-mediated adipokine signalling pathway. Our results suggest that FOS and related genes or proteins can outperform traditional clinical markers and may be used as diagnostic biomarkers for VTE.


Computational Biology , MicroRNAs , Neutrophils , Proto-Oncogene Proteins c-fos , Venous Thromboembolism , Humans , MicroRNAs/genetics , MicroRNAs/blood , MicroRNAs/metabolism , Neutrophils/metabolism , Venous Thromboembolism/genetics , Venous Thromboembolism/metabolism , Venous Thromboembolism/blood , Computational Biology/methods , Proto-Oncogene Proteins c-fos/genetics , Proto-Oncogene Proteins c-fos/metabolism , Gene Expression Regulation , Male , Gene Expression Profiling , Gene Regulatory Networks , Female , Biomarkers/blood , Biomarkers/metabolism
7.
Clin Oral Investig ; 28(5): 292, 2024 May 02.
Article En | MEDLINE | ID: mdl-38693418

OBJECTIVES: Exposure to aerosol particles generated from tooth grinding has a negative impact on the health of dental personnel. The aim of this study was to quantitatively analyze the impact of indoor relative humidity (IRH) on the deposition of these suspended particles in a well-controlled dental environment. MATERIALS AND METHODS: In this study, a humidity control system was employed to effectively regulate and maintain indoor relative humidity (IRH). A novel computer-assisted numerical control system was developed to pre-treat the molar specimens, and accurately simulate clinical tooth grinding procedures. Each procedure was performed in triplicate, with an online real-time particle counter (ORPC; TR-8301, TongrenCo.) measuring aerosol production. All testing devices were controlled remotely. The data obtained were statistically analyzed using descriptive statistics and non-parametric tests (Kruskal-Wallis/ Dunn's post hoc test with Bonferroni correction, p < 0.05). RESULTS: The findings showed that with increasing IRH, the maximum peak concentration of aerosol particles decreased by 397% from 6.51 × 107 particles/m3 at 30% to 1.64 × 107 particles/m3 at 80%. The Kruskal-Wallis test results indicated a statistically significant effect of IRH on the aerosol increment (p < 0.05). CONCLUSIONS: Increasing the IRH level can effectively promote the deposition of aerosol particles, with a return to baseline within 15 min after reaching 60% or above. CLINICAL RELEVANCE: Our study suggested that maintaining IRH above 70% during the cleaning process, allowing natural recovery to ambient humidity levels within 15 min after cleaning, and taking basic precautions, may lead to an adequate reduction in the possible health risks of aerosol contamination.


Aerosols , Air Pollution, Indoor , Humidity , Humans , Air Pollution, Indoor/analysis
8.
Aging (Albany NY) ; 16(9): 7915-7927, 2024 May 07.
Article En | MEDLINE | ID: mdl-38728237

OBJECTIVE: This research aimed to explore IL-21/miR-361-5p/MAP3K9 expression in shoulder arthritis and identify its regulatory pathways. METHODS: We established a rat shoulder arthritis model, then quantified IL21 and miR-361-5p in synovial fluid using ELISA and monitored the arthritis development. Additionally, IL21's effect on miR-361-5p levels in cultured human chondrocytes (HC-a) was assessed. Chondrocyte cell cycle status and apoptosis were measured via flow cytometry. Interactions between miR-361-5p and MAP3K9 were confirmed through dual-luciferase reporting and bioinformatic scrutiny. Protein levels of MAP3K9, p-ERK1/2, p-NF-κB, MMP1, and MMP9 were analyzed by Western blots. RESULTS: IL21 levels were elevated, while miR-361-5p was reduced in the synovial fluid from arthritic rats compared to healthy rats. IL21 was shown to suppress miR-361-5p in chondrocytes leading to hindered cell proliferation and increased apoptosis. Western blots indicated that miR-361-5p curbed MAP3K9 expression, reducing MMP activity by attenuating the ERK1/2/NF-κB pathway in chondrocytes. CONCLUSION: IL21 upregulation and miR-361-5p downregulation characterize shoulder arthritis, resulting in MAP3K9 overexpression. This chain of molecular events boosts MMP expression in chondrocytes and exacerbates the condition's progression.


Chondrocytes , MAP Kinase Kinase Kinases , MicroRNAs , Animals , Humans , Male , Rats , Apoptosis/genetics , Cell Proliferation/genetics , Chondrocytes/metabolism , Disease Progression , Interleukins/metabolism , Interleukins/genetics , MAP Kinase Kinase Kinases/metabolism , MAP Kinase Kinase Kinases/genetics , MicroRNAs/metabolism , MicroRNAs/genetics , Rats, Sprague-Dawley
9.
J Phys Chem Lett ; 15(21): 5607-5611, 2024 May 30.
Article En | MEDLINE | ID: mdl-38758196

Dissociative electron attachment (DEA) is widely believed to play a high-profile role in ionizing radiation damages of bioorganic molecules, and its fundamentals are mainly learned from the gas-phase studies. However, the DEA process in aqueous solution is still in debate. Here we provide experimental evidence about the DEA processes of liquid methanol by using electron-impact-time-delayed mass spectrometry. In contrast to the gas- and solid-phase DEAs, methoxide ion CH3O- is the predominant product from the liquid interface. Furthermore, this anion can be produced with both the primary low-energy electrons and the inelastically scattered and secondary low-energy electrons. On the contrary, the primary low-energy electrons in the liquid bulk are more likely to be solvated, rather than directly participating in the DEA process. Our study provides new insights into radiation chemistry, particularly of bioorganic relevance.

10.
Cereb Cortex ; 34(5)2024 May 02.
Article En | MEDLINE | ID: mdl-38725291

A widely used psychotherapeutic treatment for post-traumatic stress disorder (PTSD) involves performing bilateral eye movement (EM) during trauma memory retrieval. However, how this treatment-described as eye movement desensitization and reprocessing (EMDR)-alleviates trauma-related symptoms is unclear. While conventional theories suggest that bilateral EM interferes with concurrently retrieved trauma memories by taxing the limited working memory resources, here, we propose that bilateral EM actually facilitates information processing. In two EEG experiments, we replicated the bilateral EM procedure of EMDR, having participants engaging in continuous bilateral EM or receiving bilateral sensory stimulation (BS) as a control while retrieving short- or long-term memory. During EM or BS, we presented bystander images or memory cues to probe neural representations of perceptual and memory information. Multivariate pattern analysis of the EEG signals revealed that bilateral EM enhanced neural representations of simultaneously processed perceptual and memory information. This enhancement was accompanied by heightened visual responses and increased neural excitability in the occipital region. Furthermore, bilateral EM increased information transmission from the occipital to the frontoparietal region, indicating facilitated information transition from low-level perceptual representation to high-level memory representation. These findings argue for theories that emphasize information facilitation rather than disruption in the EMDR treatment.


Electroencephalography , Eye Movement Desensitization Reprocessing , Humans , Female , Male , Young Adult , Adult , Eye Movement Desensitization Reprocessing/methods , Eye Movements/physiology , Stress Disorders, Post-Traumatic/physiopathology , Stress Disorders, Post-Traumatic/therapy , Stress Disorders, Post-Traumatic/psychology , Visual Perception/physiology , Memory/physiology , Brain/physiology , Photic Stimulation/methods , Memory, Short-Term/physiology
11.
Diabetol Metab Syndr ; 16(1): 98, 2024 May 08.
Article En | MEDLINE | ID: mdl-38715117

BACKGROUND: Emerging evidence indicates carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is involved in the development of atherosclerosis (AS). However, the roles and functions of CEACAM1 in AS remain unknown. Therefore, this study aims to investigate the roles and molecular functions of CEACAM1 in AS. METHODS: We constructed a diabetes mellitus (DM) + high-fat diet (HFD) mouse model based on the streptozotocin (STZ)-induced apolipoprotein E-knockdown (ApopE-/-) mouse to investigate the roles and regulatory mechanism of miR-449a/CEACAM1 axis. The mRNA expression and protein levels in this study were examined using quantity PCR, western blot, immunofluorescence (IF), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry (IHC), respectively. And the lipid deposition and collagen content were detected using Oil Red O and Sirius Red staining. Cell apoptosis, migration, invasion, and tuber formation were detected by Annexin-V FITC/PI, wound healing, transwell, and tuber formation assays, respectively. The relationship between miR-449a and CEACAM1 was determined by a dual-luciferase reporter gene assay. RESULTS: miR-449a and MMP-9 were upregulated, and CEACAM1 was downregulated in the DM + HFD MOUSE model. Upregulation of CEACAM1 promoted atherosclerotic plaque stability and inhibited inflammation in the DM + HFD mouse model. And miR-449a directly targeted CEACAM1. Besides, miR-449a interacted with CEACAM1 to regulate atherosclerotic plaque stability and inflammation in DM-associated AS mice. In vitro, the rescue experiments showed miR-449a interacted with CEACAM1 to affect apoptosis, migration, invasion, and tuber formation ability in high glucose (HG)-induced HUVECs. CONCLUSION: These results demonstrated that miR-449a promoted plaque instability and inflammation in DM and HFD-induced mice by targeting CEACAM1.

12.
Hum Vaccin Immunother ; 20(1): 2341454, 2024 Dec 31.
Article En | MEDLINE | ID: mdl-38695296

Pertussis is a vaccine-preventable infectious disease; however, data on pertussis antibody levels in a nationwide population are still limited in China. We aimed to pool the seropositivity rates of IgG antibodies against pertussis toxin (PT-IgG) across the country. We systematically searched PubMed, Web of Science, Embase, and the China National Knowledge Infrastructure Database for studies published between January 1, 2010, and June 30, 2023. Studies reporting the seroprevalence of PT-IgG among a healthy Chinese population were included. Pooled estimates were obtained using random-effects meta-analyzes. The meta-analysis included 39 studies (47,778 participants) reporting anti-PT IgG seropositivity rates. The pooled rate for all ages was 7.06% (95% CI, 5.50%-9.07%). Subgroup analyzes showed rates ranging from 6.36% to 12.50% across different age groups. This meta-analysis indicated a low anti-PT IgG seropositivity rate in the Chinese population, particularly among school-aged children and young adults. This finding underscores the urgent need to refine immunization strategies.


Antibodies, Bacterial , Immunoglobulin G , Pertussis Toxin , Whooping Cough , Humans , Seroepidemiologic Studies , Pertussis Toxin/immunology , Immunoglobulin G/blood , Whooping Cough/epidemiology , Whooping Cough/immunology , Whooping Cough/prevention & control , China/epidemiology , Antibodies, Bacterial/blood , Child , Adult , Young Adult , Adolescent , Child, Preschool , Middle Aged , Pertussis Vaccine/immunology , Pertussis Vaccine/administration & dosage , East Asian People
13.
Eur J Epidemiol ; 2024 May 04.
Article En | MEDLINE | ID: mdl-38703248

There is growing interest in incorporating metabolomics into public health practice. However, Black women are under-represented in many metabolomics studies. If metabolomic profiles differ between Black and White women, this under-representation may exacerbate existing Black-White health disparities. We therefore aimed to estimate metabolomic differences between Black and White women in the U.S. We leveraged data from two prospective cohorts: the Nurses' Health Study (NHS; n = 2077) and Women's Health Initiative (WHI; n = 2128). The WHI served as the replication cohort. Plasma metabolites (n = 334) were measured via liquid chromatography-tandem mass spectrometry. Observed metabolomic differences were estimated using linear regression and metabolite set enrichment analyses. Residual metabolomic differences in a hypothetical population in which the distributions of 14 risk factors were equalized across racial groups were estimated using inverse odds ratio weighting. In the NHS, Black-White differences were observed for most metabolites (75 metabolites with observed differences ≥ |0.50| standard deviations). Black women had lower average levels than White women for most metabolites (e.g., for N6, N6-dimethlylysine, mean Black-White difference = - 0.98 standard deviations; 95% CI: - 1.11, - 0.84). In metabolite set enrichment analyses, Black women had lower levels of triglycerides, phosphatidylcholines, lysophosphatidylethanolamines, phosphatidylethanolamines, and organoheterocyclic compounds, but higher levels of phosphatidylethanolamine plasmalogens, phosphatidylcholine plasmalogens, cholesteryl esters, and carnitines. In a hypothetical population in which distributions of 14 risk factors were equalized, Black-White metabolomic differences persisted. Most results replicated in the WHI (88% of 272 metabolites available for replication). Substantial differences in metabolomic profiles exist between Black and White women. Future studies should prioritize racial representation.

14.
BMC Bioinformatics ; 25(1): 183, 2024 May 09.
Article En | MEDLINE | ID: mdl-38724908

BACKGROUND: In recent years, gene clustering analysis has become a widely used tool for studying gene functions, efficiently categorizing genes with similar expression patterns to aid in identifying gene functions. Caenorhabditis elegans is commonly used in embryonic research due to its consistent cell lineage from fertilized egg to adulthood. Biologists use 4D confocal imaging to observe gene expression dynamics at the single-cell level. However, on one hand, the observed tree-shaped time-series datasets have characteristics such as non-pairwise data points between different individuals. On the other hand, the influence of cell type heterogeneity should also be considered during clustering, aiming to obtain more biologically significant clustering results. RESULTS: A biclustering model is proposed for tree-shaped single-cell gene expression data of Caenorhabditis elegans. Detailedly, a tree-shaped piecewise polynomial function is first employed to fit non-pairwise gene expression time series data. Then, four factors are considered in the objective function, including Pearson correlation coefficients capturing gene correlations, p-values from the Kolmogorov-Smirnov test measuring the similarity between cells, as well as gene expression size and bicluster overlapping size. After that, Genetic Algorithm is utilized to optimize the function. CONCLUSION: The results on the small-scale dataset analysis validate the feasibility and effectiveness of our model and are superior to existing classical biclustering models. Besides, gene enrichment analysis is employed to assess the results on the complete real dataset analysis, confirming that the discovered biclustering results hold significant biological relevance.


Caenorhabditis elegans , Single-Cell Analysis , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Animals , Single-Cell Analysis/methods , Cluster Analysis , Gene Expression Profiling/methods , Algorithms
15.
J Phys Chem A ; 128(19): 3821-3829, 2024 May 16.
Article En | MEDLINE | ID: mdl-38714336

The reactive collision between He+ and CO2 plays an important role in substance evolutions of the planetary CO2-rich atmosphere. Using a three-dimensional ion velocity map imaging technique, we investigate the low-energy ion-molecule reactions He+ + CO2 → He + CO2+/He + CO+ + O/He + CO + O+. The velocity images of the products CO+ and O+ of dissociative charge-exchange reactions are distinctly different from those of charge-exchange product CO2+. The remarkable features of stereodynamics are observed in the dissociative charge-exchange reaction and are attributed to the spatial alignment of the initially random target CO2 during the He+ approach. Branching ratios of different channels of dissociative charge exchange are further obtained with the Doppler kinematics model, indicating a high preference for the energy-resonant channel.

16.
Cell Death Differ ; 2024 May 18.
Article En | MEDLINE | ID: mdl-38762597

Stress-adaptive mechanisms enabling cancer cells to survive under glucose deprivation remain elusive. N6-methyladenosine (m6A) modification plays important roles in determining cancer cell fate and cellular stress response to nutrient deficiency. However, whether m6A modification functions in the regulation of cancer cell survival under glucose deprivation is unknown. Here, we found that glucose deprivation reduced m6A modification levels. Increasing m6A modification resulted in increased hepatoma cell necrosis under glucose deprivation, whereas decreasing m6A modification had an opposite effect. Integrated m6A-seq and RNA-seq revealed potential targets of m6A modification under glucose deprivation, including the transcription factor FOSL1; further, glucose deprivation upregulated FOSL1 by inhibiting FOSL1 mRNA decay in an m6A-YTHDF2-dependent manner through reducing m6A modification in its exon1 and 5'-UTR regions. Functionally, FOSL1 protected hepatoma cells against glucose deprivation-induced necrosis in vitro and in vivo. Mechanistically, FOSL1 transcriptionally repressed ATF3 by binding to its promoter. Meanwhile, ATF3 and MAFF interacted via their leucine zipper domains to form a heterodimer, which competed with NRF2 for binding to antioxidant response elements in the promoters of NRF2 target genes, thereby inhibiting their transcription. Consequently, FOSL1 reduced the formation of the ATF3-MAFF heterodimer, thereby enhancing NRF2 transcriptional activity and the antioxidant capacity of glucose-deprived-hepatoma cells. Thus, FOSL1 alleviated the necrosis-inducing effect of glucose deprivation-induced reactive oxygen species accumulation. Collectively, our study uncovers the protective role of m6A-FOSL1-ATF3 axis in hepatoma cell necrosis under glucose deprivation, and may provide new targets for cancer therapy.

17.
Medicine (Baltimore) ; 103(18): e38007, 2024 May 03.
Article En | MEDLINE | ID: mdl-38701269

BACKGROUND: This systematic review and meta-analysis aimed to report the evaluation of the prevalence and risk of nonalcoholic fatty liver disease (NAFLD) among adult psoriatic patients in a systematic review and meta-analysis. METHODS: A comprehensive search was conducted across 4 databases of PubMed, Scopus, Cochrane Library, and Web of Science to collect relevant studies until November 30, 2023, without any restrictions for finding observational studies. The comprehensive meta-analysis version 3.0 software was used to calculate effect sizes, showing the event rate (ER), odds ratio (OR), and a 95% confidence interval (CI) to evaluate NAFLD risk or prevalence in psoriatic patients and controls or psoriatic patients alone. The quality scoring was performed by 1 author based on the Newcastle-Ottawa Scale tool. Publication bias, meta-regression analysis, and sensitivity analyses were performed. Additionally, Trial Sequential Analysis (TSA) was performed using TSA software. RESULTS: A total of 581 records were identified among the databases and electronic sources. At last, 41 studies involving 607,781 individuals were included in the meta-analysis. The pooled ER of NAFLD among psoriatic patients was 29.5% (95%CI: 19.6%-41.7%) and I2 = 99.79%. The pooled OR of NAFLD in psoriatic patients compared to controls was 1.685 (95%CI: 1.382-2.055; P < .001) and I2 = 87.96%. CONCLUSIONS: The study found a significant link between psoriasis and NAFLD, with psoriatic patients having a higher chance of developing NAFLD compared to the controls. The study calls for regular NAFLD screening in psoriatic patients to prevent liver complications.


Non-alcoholic Fatty Liver Disease , Psoriasis , Humans , Non-alcoholic Fatty Liver Disease/epidemiology , Psoriasis/epidemiology , Psoriasis/complications , Prevalence , Adult , Risk Factors
18.
Org Lett ; 26(20): 4400-4405, 2024 May 24.
Article En | MEDLINE | ID: mdl-38735050

An enantioselective Pd-catalyzed intramolecular desymmetrizing cycloisomerization of N-(cyclopent-3-en-1-yl)propiolamides has been developed by employing a new chiral phosphoramidite ligand. A series of structurally unique bridged azabicycles are achieved in moderate to excellent yields with good E/Z selectivity and high enantioselectivity. Synthetic transformations are conducted to demonstrate the practical utility of this reaction.

19.
Adv Mater ; : e2402751, 2024 May 30.
Article En | MEDLINE | ID: mdl-38816897

The dual-focus vision observed in eagles' eyes is an intriguing phenomenon that has long captivated scientists. Inspired by this natural occurrence, our research introduces a novel bifocal meta-device incorporating a polarized camera capable of simultaneously capturing images for two different polarizations with slightly different focal distances. This innovative approach facilitates the concurrent acquisition of underfocused and overfocused images in a single snapshot, enabling the effective extraction of quantitative phase information from the object using the transport of intensity equation. Experimental demonstrations showcase the application of quantitative phase imaging to artificial objects and human embryonic kidney cells, particularly emphasizing the meta-device's relevance in dynamic scenarios such as laser-induced ablation in human embryonic kidney cells. Moreover, it provides a solution for the quantification during the dynamic process at the cellular level. Notably, the proposed eagle-eye inspired meta-device for phase imaging (EIMPI), due to its simplicity and compact nature, holds promise for significant applications in fields such as endoscopy and headsets, where a lightweight and compact setup is essential. This article is protected by copyright. All rights reserved.

20.
Dalton Trans ; 53(21): 8905-8909, 2024 May 28.
Article En | MEDLINE | ID: mdl-38757356

A single crystal composed of one-dimensional coordinated polymers, [CdCl2(1-methyl-2-pyridone)]n, has been synthesized and characterized. This compound exhibits outstanding elastic bending due to the molecular spring nature of the CdCl2 coordination framework and weak intermolecular interactions between the coordination chains. Owing to the helical arrangement of organic ligands surrounding the coordination structure, the compound crystallizes in a chiral space group. As a result, it displays compelling circular dichroism spectra and second harmonic generation properties.

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