Inhibition of HDAC activity directly reprograms murine embryonic stem cells to trophoblast stem cells.

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.

Eye movement intervention facilitates concurrent perception and memory processing.

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.

Mean Blood Glucose Level During ICU Hospitalization is a Strong Predictor of the Mortality of COVID-19.

Objective: To investigate the potential prognostic value of mean blood glucose (MBG) in hospital for prognosis of COVID-19 adult patients in the intensive unit care unit (ICU). Methods: A single-site and retrospective study enrolled 107 patients diagnosed as COVID-19 from department of critical care medicine in the Second Xiangya Hospital between October 2022 and June 2023. Demographic information including glucose during ICU hospitalization, comorbidity, clinical data, types of medications and treatment, and clinical outcome were collected. The multivariate logistic and cox regression was used to explore the relationship between blood glucose changes and clinical outcomes of COVID-19 during ICU stay. Results: In total, 107 adult patients confirmed with COVID-19 were included. Multivariate logistic regression results showed an increase in MBG was associated with ICU mortality rate. Compared with normal glucose group (MBG <= 7.8 mmol/L), the risk of ICU mortality, 7-day mortality and 28-day mortality from COVID-19 were significantly increased in high glucose group (MBG >7.8mmol/L). Conclusion: MBG level during ICU hospitalization was strongly correlated to all-cause mortality and co-infection in COVID-19 patients. These findings further emphasize the importance of overall glucose management in severe cases of COVID-19.

Biclustering analysis on tree-shaped time-series single cell gene expression data of Caenorhabditis elegans.

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.

Ion Velocity Map Imaging Study of the Reactive Collisions between Carbon Dioxide and Helium Ion.

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.

Seroprevalence of IgG antibodies against pertussis toxin in the Chinese population: A systematic review and meta-analysis.

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.

Differences in metabolomic profiles between Black and White women in the U.S.: Analyses from two prospective cohorts.

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.

An elastic single crystal composed of one-dimensional chiral coordination polymers.

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.

Quantitative evaluation of the impact of indoor relative humidity on deposition of aerosols generated during tooth grinding in a real-world clinical setting.

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.

The temporal trends of prevalence and years lived with disability of anaemia in China, Japan, and South Korea, from 1990 to 2021: Results from the Global Burden of Disease Study 2021.

Background: Studies have shown that the disease burden of anaemia varies globally, yet they have not yet determined its exact extent in East Asian countries specifically. We thus aimed to investigate the prevalence and years lived with disability (YLDs) due to anaemia from 1990 to 2021 in China, Japan, and South Korea. Methods: We extracted the prevalence and YLDs with their age-standardised rates (ASRs) in China, Japan, and South Korea from the Global Burden of Disease Study 2021, stratified by sex, age, and causes. We then examined the temporal trend of anaemia burden from 1990 to 2021 using joinpoint analysis and the association of anaemia burden with the Human Development Index and Universal Health Index through Spearman's correlation analysis. Results: In 2021, anaemia affected 136 million people in China (95% uncertainty interval (UI) = 131, 141), with ASRs of prevalence of 8.9% (95% UI = 8.6, 9.3), and accounted for 3.0 million YLDs (95% UI = 2.0, 4.4). It affected 13.6 million people in Japan (95% UI = 11.8, 16.0), with ASRs of prevalence of 7.4% (95% UI = 6.1, 9.0), and caused 181 thousand YLDs (95% UI = 108, 282). It also affected 2.7 million individuals in South Korea (95% UI = 2.4, 3.0), with ASRs of prevalence of 5.2% (95% UI = 4.6, 5.7), and led to 34 thousand YLDs (95% UI = 22, 55). We observed a significant gender discrepancy in the anaemia burden in these three countries, with the prevalence and YLD rates in women being almost twice as high as those in men. Moreover, the peak age of the anaemia burden shifted toward higher age groups in all three countries, particularly in Japan. Chronic kidney disease was responsible for a growing share of anaemia cases and YLDs, especially in adults aged more than 60 years in Japan and South Korea. Haemoglobinopathies were another noticeable cause of anaemia in China, though dietary iron deficiency remained the leading cause. Both socioeconomic development and essential health service coverage showed negative associations with the anaemia burden in the three countries in the past three decades, though with differential patterns. Conclusions: Anaemia remains a major public health issue in China, Japan, and South Korea; targeted surveillance and interventions are recommended for high-risk populations and cause-specific anaemia.

The MnO2/GelMA Composite Hydrogels Improve the ROS Microenvironment of Annulus Fibrosus Cells by Promoting the Antioxidant and Autophagy through the SIRT1/NRF2 Pathway.

Intervertebral disc degeneration (IVDD) is a worldwide disease that causes low back pain and reduces quality of life. Biotherapeutic strategies based on tissue engineering alternatives, such as intervertebral disc scaffolds, supplemented by drug-targeted therapy have brought new hope for IVDD. In this study, to explore the role and mechanism of MnO2/GelMA composite hydrogels in alleviating IVDD, we prepared composite hydrogels with MnO2 and methacrylate gelatin (GelMA) and characterized them using compression testing and transmission electron microscopy (TEM). Annulus fibrosus cells (AFCs) were cultured in the composite hydrogels to verify biocompatibility by live/dead and cytoskeleton staining. Cell viability assays and a reactive oxygen species (ROS) probe were used to analyze the protective effect of the composite hydrogels under oxidative damage. To explore the mechanism of improving the microenvironment, we detected the expression levels of antioxidant and autophagy-related genes and proteins by qPCR and Western blotting. We found that the MnO2/GelMA composite hydrogels exhibited excellent biocompatibility and a porous structure, which promoted cell proliferation. The addition of MnO2 nanoparticles to GelMA cleared ROS in AFCs and induced the expression of antioxidant and cellular autophagy through the common SIRT1/NRF2 pathway. Therefore, the MnO2/GelMA composite hydrogels, which can improve the disc microenvironment through scavenging intracellular ROS and resisting oxidative damage, have great application prospects in the treatment of IVDD.

Pd-Catalyzed Enantioselective Desymmetrizing 1,7-Enyne Cycloisomerization of Alkyne-Tethered Cyclopentenes.

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.

Prevalence and risk of nonalcoholic fatty liver disease among adult psoriatic patients: A systematic review, meta-analysis, and trial sequential analysis.

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.

Eagle-Eye Inspired Meta-Device for Phase Imaging.

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.

Contribution of FOS in neutrophils to venous thromboembolism via miR-144 based on bioinformatic prediction and validation.

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.

miR-449a disturbs atherosclerotic plaque stability in streptozotocin and high-fat diet-induced diabetic mice by targeting CEACAM1.

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.

IL21 inhibits miR-361-5p to promote MAP3K9 and further aggravate the progression of shoulder arthritis.

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.

Direct Observation of Anionic Yields from the Liquid-Vapor Interface by Electron Irradiation.

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.

m6A demethylation of FOSL1 mRNA protects hepatoma cells against necrosis under glucose deprivation.

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.

Hypoxia enhances autophagy level of human sperms.

The relationship between oxygen sensing and autophagy in human sperms was explored in this study. Health semen and asthenozoospermia (astheno) semen were incubated with hypoxia-inducible factor-1α (HIF-1α) interferents, i.e., lificiguat (YC-1) or cobalt chloride (CoCl2), respectively. Label-free quantitative proteomic technology was used to identify the differentially expressed proteins in human semen under the hypoxia condition. Selected proteins were detected with ELISA. It was found that the autophagy levels of sperm in the YC-1 + health group or CoCl2 + astheno group increased while the vitality decreased. A total of 17, 34 and 35 differentially expressed proteins were observed in the Astheno group, the YC-1 + health group and the CoCl2 + astheno group, respectively. These proteins were primarily associated with protein processing in endoplasmic reticulum, Th17 cell differentiation, progesterone-mediated oocyte maturation, glycolysis/gluconeogenesis, HIF-1 signaling pathway, biosynthesis of amino acids, and carbon metabolism. The expression levels of protein HIF-1α, LC3B, histone H4, cathepsin L and ENO1 changed significantly in the groups. The study suggests that hypoxia can increase sperm autophagy level and reduce their vitality through HIF-1 signaling pathway and glycolysis/gluconeogenesis signaling pathway. Furthermore, proteins histone H4, cathepsin L, glutathione synthetase and ENO1 are proposed as potential biomarkers of autophagy and vitality in asthenozoospermia sperm.