A cross sectional study of role of technology in health for middle-aged and older adults in Singapore.

Telemedicine has gained popularity due to the increasing use of technology in our lives. However, no studies have explored the demographic factors affecting acceptability, desirability and adherence (ADA) to telemedicine in Singapore. Our study aims to evaluate the level of ADA of telemedicine services within demographic factors and to explore the association of potential demographic factors with the degree of acceptability, desirability and adherence of telemedicine among older adults in Singapore. A cross-sectional study was conducted with Singapore citizens or permanent residents aged 40-99 years, who were able to provide informed consent. Interviewers conducted door-to-door surveys in 67 Blocks of Housing & Development Board flats in Singapore, offering a self-administered electronic questionnaire available in four languages. Random sampling without replacement determined the order of blocks, floors and units visited. The questionnaire utilised Qtelemediab scoring and covered sociodemographic data, usage of telemedicine, as well as ADA towards telemedicine. A total of 324 valid responses were analysed. Increased age was associated with a significant decrease across all three domains of ADA namely acceptability (ß = - 0.02, 95%CI - 0.03; - 0.02, p-value = 0.002), desirability (ß = - 0.02, 95%CI - 0.02; - 0.02, p-value < 0.001) and adherence (ß = - 0.02, 95%CI - 0.03; - 0.0.02, p-value < 0.001). Additionally, lower education was associated with a decrease in all domains of ADA. Conversely, employment and increased household income were associated with higher ADA scores across all three domains. These associations were independent of gender, chronic health conditions and smoking history. Older participants with lower income and lesser education demonstrated lower levels of acceptability, desirability and adherence towards telemedicine. Our study highlights the importance of considering these factors in the implementation and promotion of telemedicine solutions.

Combined effects of nitrogen limitation and overexpression of malic enzyme gene on lipid accumulation in Dunaliella parva.

Overexpression of Dunaliella parva (D. parva) malic enzyme (ME) gene (DpME) significantly increased DpME expression and ME enzyme activity in transgenic D. parva. Nitrogen limitation had an inhibitory effect on protein content, and DpME overexpression could improve protein content. Nitrogen limitation increased carbohydrate content, and Dunaliella parva overexpressing malic enzyme gene under nitrogen limitation (DpME-N-) group showed the lowest starch content among all groups. Dunaliella parva overexpressing malic enzyme gene under nitrogen sufficient condition (DpME) and DpME-N- groups showed considerably high mRNA levels of DpME. ME activity was significantly enhanced by DpME overexpression, and nitrogen limitation caused a smaller increase. DpME overexpression and nitrogen limitation obviously enhanced lipid accumulation, and DpME overexpression had more obvious effect. Compared with control (wild type), lipid content (68.97%) obviously increased in DpME-N- group. This study indicated that the combination of DpME overexpression and nitrogen limitation was favorable to the production of microalgae biodiesel.

The Voltage-Gated Calcium Channel α2δ Subunit in Neuropathic Pain.

Neuropathic pain (NP) is a chronic pain caused by injury or disease of the somatosensory nervous system, or it can be directly caused by disease. It often presents with clinical features like spontaneous pain, hyperalgesia, and dysesthesia. At present, voltage-gated calcium ion channels (VGCCs) are known to be closely related to the development of NP, especially the α2δ subunit. The α2δ subunit is a regulatory subunit of VGCCs. It exists mainly in the brain and peripheral nervous system, especially in nerve cells, and it plays a crucial part in regulating presynaptic and postsynaptic functions. Furthermore, the α2δ subunit influences neuronal excitation and pain signaling by promoting its expression and localization through binding to VGCC-related subunits. The α2δ subunit is widely used in the management of NP as a target of antiepileptic drugs gabapentin and pregabalin. Although drug therapy is one of the treatments for NP, its clinical application is limited due to the adverse reactions caused by drug therapy. Therefore, further research on the therapeutic target α2δ subunit is needed, and attempts are made to obtain an effective treatment for relieving NP without side effects. This review describes the current associated knowledge on the function of the α2δ subunit in perceiving and modulating NP.

Posterior approach to correct for focal plane offsets in lattice light-sheet structured illumination microscopy.

Significance: Lattice light-sheet structured illumination microscopy (latticeSIM) has proven highly effective in producing three-dimensional images with super resolution rapidly and with minimal photobleaching. However, due to the use of two separate objectives, sample-induced aberrations can result in an offset between the planes of excitation and detection, causing artifacts in the reconstructed images. Aim: We introduce a posterior approach to detect and correct the axial offset between the excitation and detection focal planes in latticeSIM and provide a method to minimize artifacts in the reconstructed images. Approach: We utilized the residual phase information within the overlap regions of the laterally shifted structured illumination microscopy information components in frequency space to retrieve the axial offset between the excitation and the detection focal planes in latticeSIM. Results: We validated our technique through simulations and experiments, encompassing a range of samples from fluorescent beads to subcellular structures of adherent cells. We also show that using transfer functions with the same axial offset as the one present during data acquisition results in reconstructed images with minimal artifacts and salvages otherwise unusable data. Conclusion: We envision that our method will be a valuable addition to restore image quality in latticeSIM datasets even for those acquired under non-ideal experimental conditions.

Gasdermin-E-mediated pyroptosis drives immune checkpoint inhibitor-associated myocarditis via cGAS-STING activation.

Immune checkpoint inhibitor (ICI)-induced myocarditis involves intensive immune/inflammation activation; however, its molecular basis is unclear. Here, we show that gasdermin-E (GSDME), a gasdermin family member, drives ICI-induced myocarditis. Pyroptosis mediated by GSDME, but not the canonical GSDMD, is activated in myocardial tissue of mice and cancer patients with ICI-induced myocarditis. Deficiency of GSDME in male mice alleviates ICI-induced cardiac infiltration of T cells, macrophages, and monocytes, as well as mitochondrial damage and inflammation. Restoration of GSDME expression specifically in cardiomyocytes, rather than myeloid cells, in GSDME-deficient mice reproduces ICI-induced myocarditis. Mechanistically, quantitative proteomics reveal that GSDME-dependent pyroptosis promotes cell death and mitochondrial DNA release, which in turn activates cGAS-STING signaling, triggering a robust interferon response and myocardial immune/inflammation activation. Pharmacological blockade of GSDME attenuates ICI-induced myocarditis and improves long-term survival in mice. Our findings may advance the understanding of ICI-induced myocarditis and suggest that targeting the GSDME-cGAS-STING-interferon axis may help prevent and manage ICI-associated myocarditis.

The causal effect of gut microbiota on hepatic encephalopathy: a mendelian randomization analysis.

BACKGROUND: There is growing evidence for a relationship between gut microbiota and hepatic encephalopathy (HE). However, the causal nature of the relationship between gut microbiota and HE has not been thoroughly investigated. METHOD: This study utilized the large-scale genome-wide association studies (GWAS) summary statistics to evaluate the causal association between gut microbiota and HE risk. Specifically, two-sample Mendelian randomization (MR) approach was used to identify the causal microbial taxa for HE. The inverse variance weighted (IVW) method was used as the primary MR analysis. Sensitive analyses were performed to validate the robustness of the results. RESULTS: The IVW method revealed that the genus Bifidobacterium (OR = 0.363, 95% CI: 0.139-0.943, P = 0.037), the family Bifidobacteriaceae (OR = 0.359, 95% CI: 0.133-0.950, P = 0.039), and the order Bifidobacteriales (OR = 0.359, 95% CI: 0.133-0.950, P = 0.039) were negatively associated with HE. However, no causal relationship was observed among them after the Bonferroni correction test. Neither heterogeneity nor horizontal pleiotropy was found in the sensitivity analysis. CONCLUSION: Our MR study demonstrated a potential causal association between Bifidobacterium, Bifidobacteriaceae, and Bifidobacteriales and HE. This finding may provide new therapeutic targets for patients at risk of HE in the future.

Investigating the impact of extreme weather events and related indicators on cardiometabolic multimorbidity.

BACKGROUND: The impact of weather on human health has been proven, but the impact of extreme weather events on cardiometabolic multimorbidity (CMM) needs to be urgently explored. OBJECTIVES: Investigating the impact of extreme temperature, relative humidity (RH), and laboratory testing parameters at admission on adverse events in CMM hospitalizations. DESIGNS: Time-stratified case-crossover design. METHODS: A distributional lag nonlinear model with a time-stratified case-crossover design was used to explore the nonlinear lagged association between environmental factors and CMM. Subsequently, unbalanced data were processed by 1:2 propensity score matching (PSM) and conditional logistic regression was employed to analyze the association between laboratory indicators and unplanned readmissions for CMM. Finally, the previously identified environmental factors and relevant laboratory indicators were incorporated into different machine learning models to predict the risk of unplanned readmission for CMM. RESULTS: There are nonlinear associations and hysteresis effects between temperature, RH and hospital admissions for a variety of CMM. In addition, the risk of admission is higher under low temperature and high RH conditions with the addition of particulate matter (PM, PM2.5 and PM10) and O3_8h. The risk is greater for females and adults aged 65 and older. Compared with first quartile (Q1), the fourth quartile (Q4) had a higher association between serum calcium (HR = 1.3632, 95% CI: 1.0732 ~ 1.7334), serum creatinine (HR = 1.7987, 95% CI: 1.3528 ~ 2.3958), fasting plasma glucose (HR = 1.2579, 95% CI: 1.0839 ~ 1.4770), aspartate aminotransferase/ alanine aminotransferase ratio (HR = 2.3131, 95% CI: 1.9844 ~ 2.6418), alanine aminotransferase (HR = 1.7687, 95% CI: 1.2388 ~ 2.2986), and gamma-glutamyltransferase (HR = 1.4951, 95% CI: 1.2551 ~ 1.7351) were independently and positively associated with unplanned readmission for CMM. However, serum total bilirubin and High-Density Lipoprotein (HDL) showed negative correlations. After incorporating environmental factors and their lagged terms, eXtreme Gradient Boosting (XGBoost) demonstrated a more prominent predictive performance for unplanned readmission of CMM patients, with an average area under the receiver operating characteristic curve (AUC) of 0.767 (95% CI:0.7486 ~ 0.7854). CONCLUSIONS: Extreme cold or wet weather is linked to worsened adverse health effects in female patients with CMM and in individuals aged 65 years and older. Moreover, meteorologic factors and environmental pollutants may elevate the likelihood of unplanned readmissions for CMM.

Flaxseed promotes productive performance through regulating gut microbiome in ducks.

BACKGROUND: Flaxseed has been widely used in animal diets to increase the omega-3 polyunsaturated fatty acid content in animal products and promote overall animal health, but little known about its effects on the productive performance and the mictobita of gut of laying duck. METHODS AND RESULTS: Jinding duck, a Chinese indigenous breed, was used in the study. The corn-soybean basal diet supplemented with 0, 2%, 3% 4% and 5% flaxseed were provided to Control, 2% Fla, 3% Fla, 4% Fla and 5% Fla groups for 53 days, respectively. Compared with Control group, groups fed with flaxseed diets showed higher egg production, egg mass, ovary weight and more preovulatory follicles. The Docosahexaenoic Acid content of egg was extremely significantly elevated by flaxseed diets (P < 0.01), and the albumen height and haugh unit were elevated, especially in 4% Fla and/or 5% Fla group (P < 0.05). Groups 4% Fla and 5% Fla had highest ileal villus height, jejunal and ileal crypt depth. Moreover, Flaxseed diets significantly increased the levels of IgG and IgM in all Fla groups (P < 0.01), while increased IgA levels except for in 3% Fla group (P < 0.05). The results of 16s rDNA sequencing showed that flaxseed diet altered the microbial composition of gut and reduced the diversity and evenness of gut microbial communities except for 5% Fla. The correlation analysis identified Blautia, Butyricicoccus and Subdoligranulum positively associated with egg production. Genera Fourinierella, Fusobacterium and Intestinimonas positively associated with ovary weight, haught unit and album height. And Mucispirillum positively associated with haugh unit and album height. CONCLUSION: This study has suggested that flaxseed play a positive role in productive performance, the overall or intestinal health of laying ducks.

Volatile and Nonvolatile Programmable Iontronic Memristor with Lithium Imbued TiOx for Neuromorphic Computing Applications.

We demonstrate a lithium (Li) imbued TiOx iontronic device that exhibits synapse-like short-term plasticity behavior without requiring a forming process beforehand or a compliance current during switching. A solid-state electrolyte lithium phosphorus oxynitride (LiPON) behaves as the ion source, and the embedding and releasing of Li ions inside the cathodic like TiOx renders volatile conductance responses from the device and offers a natural platform for hardware simulating neuron functionalities. Besides, these devices possess high uniformity and great endurance as no conductive filaments are present. Different short-term pulse-based phenomena, including paired pulse facilitation, post-tetanic potentiation, and spike rate-dependent plasticity, were observed with self-relaxation characteristics. Based on the voltage excitation period, the time scale of the volatile memory can be tuned. Temperature measurement reveals the ion displacement-induced conductance channels become frozen below 220 K. In addition, the volatile analog devices can be configured into nonvolatile memory units with multibit storage capabilities after an electroforming process. Therefore, on the same platform, we can configure volatile units as nonlinear dynamic reservoirs for performing neuromorphic training and the nonvolatile units as the weight storage layer. We proceed to use voice recognition as an example with the tunable time constant relationship and obtain 94.4% accuracy with a minimal training data set. Thus, this iontronic platform can effectively process and update temporal information for reservoir and neuromorphic computing paradigms.

Exploration of the mechanism of temperature influence on bitter taste of theacrine by activating human bitter taste receptor hTAS2R14.

Theacrine, a purine alkaloid derived from Camellia assamica var. kucha, has a distinct bitter taste. Our previous study found the lower recognition threshold of theacrine at 25 °C than 45 °C. This study aims to investigate the bitterness characterizations of theacrine at aforementioned temperatures and its taste perception mechanism. Sensory analysis exhibited higher bitterness intensity for theacrine at 25 °C than 45 °C. Subsequently, flow cytometry was performed to verify the above characterization at the cellular level. It revealed that theacrine could activated the bitter receptor hTAS2R14 and the calcium signal at 25 °C was higher than 45 °C. Ultimately, the interaction mechanism was studied by molecular dynamics simulations, indicating that the conformation of theacrine-hTAS2R14 had a higher binding capacity and better stability at 25 °C. Overall, temperature affected the binding of theacrine to the bitter receptor hTAS2R14, resulting in the stronger bitterness intensity of theacrine at 25 °C than 45 °C.

Study of the influence of macro-structure and micro-structure on the mechanical properties of stag beetle upper jaw.

Macrostructural control of stress distribution and microstructural influence on crack propagation is one of the strategies for obtaining high mechanical properties in stag beetle upper jaws. The maximum bending fracture force of the stag beetle upper jaw is approximately 154, 000 times the weight of the upper jaw. Here, we explore the macro and micro-structural characteristics of two stag beetle upper jaws and reveal the resulting differences in mechanical properties and enhancement mechanisms. At the macroscopic level, the elliptic and triangular cross-sections of the upper jaw of the two species of stag beetles have significant effects on the formation of cracks. The crack generated by the upper jaws with a triangular section grows slowly and deflects easily. At the microscopic level, the upper jaw of the two species is a chitin cross-layered structure, but the difference between the two adjacent fiber layers at 45° and 50° leads to different deflection paths of the cracks on the exoskeleton. The mechanical properties of the upper jaw of the two species of stag beetle were significantly different due to the interaction of macro-structure and micro-structure. In addition, a series of bionic samples with different cross-section geometries and different fiber cross angles were designed, and mechanical tests were carried out according to the macro-structure and micro-structure characteristics of the stag beetle upper jaw. The effects of cross-section geometry and fiber cross angle on the mechanical properties of bionic samples are compared and analyzed. This study provides new ideas for designing and optimizing highly loaded components in engineering. STATEMENT OF SIGNIFICANCE: The upper jaw of the stag beetle is composed of a complex arrangement of chitin and protein fibers, providing both rigidity and flexibility. This structure is designed to withstand various mechanical stresses, including impacts and bending forces, encountered during its burrowing activities and interactions with its environment. The study of the upper jaw of the stag beetle can provide an efficient structural design for engineering components that are subjected to high loads. Understanding the relationship between structure and mechanical properties in the stag beetle upper jaw holds significant implications for biomimetic design and engineering.

Single-cell tumor heterogeneity landscape of hepatocellular carcinoma: unraveling the pro-metastatic subtype and its interaction loop with fibroblasts.

BACKGROUND: Tumor heterogeneity presents a formidable challenge in understanding the mechanisms driving tumor progression and metastasis. The heterogeneity of hepatocellular carcinoma (HCC) in cellular level is not clear. METHODS: Integration analysis of single-cell RNA sequencing data and spatial transcriptomics data was performed. Multiple methods were applied to investigate the subtype of HCC tumor cells. The functional characteristics, translation factors, clinical implications and microenvironment associations of different subtypes of tumor cells were analyzed. The interaction of subtype and fibroblasts were analyzed. RESULTS: We established a heterogeneity landscape of HCC malignant cells by integrated 52 single-cell RNA sequencing data and 5 spatial transcriptomics data. We identified three subtypes in tumor cells, including ARG1+ metabolism subtype (Metab-subtype), TOP2A+ proliferation phenotype (Prol-phenotype), and S100A6+ pro-metastatic subtype (EMT-subtype). Enrichment analysis found that the three subtypes harbored different features, that is metabolism, proliferating, and epithelial-mesenchymal transition. Trajectory analysis revealed that both Metab-subtype and EMT-subtype originated from the Prol-phenotype. Translation factor analysis found that EMT-subtype showed exclusive activation of SMAD3 and TGF-ß signaling pathway. HCC dominated by EMT-subtype cells harbored an unfavorable prognosis and a deserted microenvironment. We uncovered a positive loop between tumor cells and fibroblasts mediated by SPP1-CD44 and CCN2/TGF-ß-TGFBR1 interaction pairs. Inhibiting CCN2 disrupted the loop, mitigated the transformation to EMT-subtype, and suppressed metastasis. CONCLUSION: By establishing a heterogeneity landscape of malignant cells, we identified a three-subtype classification in HCC. Among them, S100A6+ tumor cells play a crucial role in metastasis. Targeting the feedback loop between tumor cells and fibroblasts is a promising anti-metastatic strategy.

Neuronal double-stranded DNA accumulation induced by DNase II deficiency drives tau phosphorylation and neurodegeneration.

BACKGROUND: Deoxyribonuclease 2 (DNase II) plays a key role in clearing cytoplasmic double-stranded DNA (dsDNA). Deficiency of DNase II leads to DNA accumulation in the cytoplasm. Persistent dsDNA in neurons is an early pathological hallmark of senescence and neurodegenerative diseases including Alzheimer's disease (AD). However, it is not clear how DNase II and neuronal cytoplasmic dsDNA influence neuropathogenesis. Tau hyperphosphorylation is a key factor for the pathogenesis of AD. The effect of DNase II and neuronal cytoplasmic dsDNA on neuronal tau hyperphosphorylation remains unclarified. METHODS: The levels of neuronal DNase II and dsDNA in WT and Tau-P301S mice of different ages were measured by immunohistochemistry and immunolabeling, and the levels of DNase II in the plasma of AD patients were measured by ELISA. To investigate the impact of DNase II on tauopathy, the levels of phosphorylated tau, phosphokinase, phosphatase, synaptic proteins, gliosis and proinflammatory cytokines in the brains of neuronal DNase II-deficient WT mice, neuronal DNase II-deficient Tau-P301S mice and neuronal DNase II-overexpressing Tau-P301S mice were evaluated by immunolabeling, immunoblotting or ELISA. Cognitive performance was determined using the Morris water maze test, Y-maze test, novel object recognition test and open field test. RESULTS: The levels of DNase II were significantly decreased in the brains and the plasma of AD patients. DNase II also decreased age-dependently in the neurons of WT and Tau-P301S mice, along with increased dsDNA accumulation in the cytoplasm. The DNA accumulation induced by neuronal DNase II deficiency drove tau phosphorylation by upregulating cyclin-dependent-like kinase-5 (CDK5) and calcium/calmodulin activated protein kinase II (CaMKII) and downregulating phosphatase protein phosphatase 2A (PP2A). Moreover, DNase II knockdown induced and significantly exacerbated neuron loss, neuroinflammation and cognitive deficits in WT and Tau-P301S mice, respectively, while overexpression of neuronal DNase II exhibited therapeutic benefits. CONCLUSIONS: DNase II deficiency and cytoplasmic dsDNA accumulation can initiate tau phosphorylation, suggesting DNase II as a potential therapeutic target for tau-associated disorders.

P4HA2 promotes proliferation, invasion, and metastasis through regulation of the PI3K/AKT signaling pathway in oral squamous cell carcinoma.

Proline 4-hydroxylase 2 (P4HA2) is known for its hydroxylase activity, primarily involved in hydroxylating collagen precursors and promoting collagen cross-linking under physiological conditions. Although its overexpression influences a wide variety of malignant tumors' occurrence and development, its specific effects and mechanisms in oral squamous cell carcinoma (OSCC) remain unclear. This study focused on investigating the expression patterns, carcinogenic functions, and underlying mechanisms of P4HA2 in OSCC cells. Various databases, including TCGA, TIMER, UALCAN, GEPIA, and K-M plotter, along with paraffin-embedded samples, were used to ascertain P4HA2 expression in cancer and its correlation with clinicopathological features. P4HA2 knockdown and overexpression cell models were developed to assess its oncogenic roles and mechanisms. The results indicated that P4HA2 was overexpressed in OSCC and inversely correlated with patient survival. Knockdown of P4HA2 suppressed invasion, migration, and proliferation of OSCC cells both in vitro and in vivo, whereas overexpression of P4HA2 had the opposite effects. Mechanistically, the phosphorylation levels of the PI3K/AKT pathway were reduced following P4HA2 silencing. The study reveals that P4HA2 acts as a promising biomarker for predicting prognosis in OSCC and significantly affects metastasis, invasion, and proliferation of OSCC cells through the regulation of the PI3K/AKT signaling pathway.

Histamine H4 receptor and TRPV1 mediate itch induced by cadaverine, a metabolite of the microbiome.

Cadaverine is an endogenous metabolite produced by the gut microbiome with various activity in physiological and pathological conditions. However, whether cadaverine regulates pain or itch remains unclear. In this study, we first found that cadaverine may bind to histamine 4 receptor (H4R) with higher docking energy score using molecular docking simulations, suggesting cadaverine may act as an endogenous ligand for H4R. We subsequently found intradermal injection of cadaverine into the nape or cheek of mice induces a dose-dependent scratching response in mice, which was suppressed by a selective H4R antagonist JNJ-7777120, transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine and PLC inhibitor U73122, but not H1R antagonist or TRPA1 antagonist or TRPV4 antagonist. Consistently, cadaverine-induced itch was abolished in Trpv1-/- but not Trpa1-/- mice. Pharmacological analysis indicated that mast cells and opioid receptors were also involved in cadaverine-induced itch in mice. scRNA-Seq data analysis showed that H4R and TRPV1 are mainly co-expressed on NP2, NP3 and PEP1 DRG neurons. Calcium imaging analysis showed that cadaverine perfusion enhanced calcium influx in the dissociated dorsal root ganglion (DRG) neurons, which was suppressed by JNJ-7777120 and capsazepine, as well as in the DRG neurons from Trpv1-/- mice. Patch-clamp recordings found that cadaverine perfusion significantly increased the excitability of small diameter DRG neurons, and JNJ-7777120 abolished this effect, indicating involvement of H4R. Together, these results provide evidences that cadaverine is a novel endogenous pruritogens, which activates H4R/TRPV1 signaling pathways in the primary sensory neurons.

Mechanism and therapeutic potential of traditional Chinese medicine extracts in sepsis.

Sepsis is a complex syndrome characterized by multi-organ dysfunction, due to the presence of harmful microorganisms in blood which could cause mortality. Complications associated with sepsis involve multiple organ dysfunction. The pathogenesis of sepsis remains intricate, with limited treatment options and high mortality rates. Traditional Chinese medicine (TCM) has consistently demonstrated to have a potential on various disease management. Its complements include reduction of oxidative stress, inhibiting inflammatory pathways, regulating immune responses, and improving microcirculation. Traditional Chinese medicine can mitigate or even treat sepsis in a human system. This review examines progress on the use of TCM extracts for treating sepsis through different pharmacological action and its mechanisms. The potential targets of TCM extracts and active ingredients for the treatment of sepsis and its complications have been elucidated through molecular biology research, network pharmacology prediction, molecular docking analysis, and visualization analysis. Our aim is to provide a theoretical basis and empirical support for utilizing TCM in the treatment of sepsis and its complications while also serving as a reference for future research and development of sepsis drugs.

FTO mediates bisphenol F-induced blood-testis barrier impairment through regulating ferroptosis via YTHDF1/TfRc and YTHDF2/SLC7A11 signal axis.

Bisphenol F (BPF) has been extensively utilized in daily life, which brings new hazards to male reproductive health. However, the specific functional mechanism is still unclear. Both cell and animal models were utilized for exploring the role of RNA methylation and ferroptosis and its underlying mechanisms in male reproductive injury induced by BPF. In animal model, BPF severely destroyed the integrity of the blood-testis barrier (BTB) and induced ferroptosis. Furthermore, BPF significantly affected the barrier function of TM4 cells and promoted ferroptosis. Importantly, ChIP assays revealed that BPF inhibited AR transcriptional regulation of FTO and FTO expression was downregulated in TM4 cells. Overexpression of FTO prevented the impairment of BTB by inhibiting ferroptosis in TM4 cells. Mechanistically, FTO could significantly down-regulate the m6A modification level of TfRc and SLC7A11 mRNA through MeRIP experiment. RIP experiments showed that YTHDF1 can bind to TfRc mRNA and promote its translation while YTHDF2 could bind to SLC7A11 mRNA and reduce its mRNA stability. Therefore, our results suggest that FTO plays a key role in BPF induced male reproductive toxicity through YTHDF1-TfRc axis and YTHDF2-SLC7A11 axis and may provide new ideas and methods for the prevention and treatment of male reproductive diseases associated with environmental pollutants.

Entropy-Dominated Triplet Exciton Emission in Carbon Dots.

Phosphorescence in carbon dots (CDs) from triplet exciton radiative recombination at room temperature has achieved significant advancement. Confinement and nanoconfinement, serving as valuable techniques, are commonly utilized to brighten triplet exciton in CDs, thereby enhancing their phosphorescence. However, a comprehensive and universally applicable physical description of confinement-enhanced phosphorescence is still lacking, despite efforts to understand its underlying nature. In this study, the dominance of entropy is revealed in triplet exciton emission from CDs through the establishment of a microscopic vibration state model. CDs with varying entropy levels are studied, indicating that in a low entropy system, the multi-energy triplet exciton emission in CDs exhibits enhanced brightness, accompanied by a corresponding increase in their lifetimes. The product of lifetime and intensity in CDs serves as a descriptor for their phosphorescence properties. Moreover, an entropy-dependent information variation system based on the CDs is demonstrated. Specifically, in a low-entropy system, information is retained, whereas the corresponding information is erased in a high-entropy system. This work elucidates the underlying physical nature of confinement-enhanced triplet exciton emission, offering a deeper understanding of achieving ultralong phosphorescence in the future.

Three-dimensional dynamic homogenous modeling: The biomechanical influences of leg tissue stiffness on pressure performance of compression biomedical therapeutic textiles.

Patient compliance and therapeutic precision of compression textiles (CTs) are frequently limited by the inaccurate pressure distributions along biological bodies in physical-based compression therapy. Therefore, the biomechanical influences of physiological tissue material characteristics of lower extremities on compression generations of CTs need to be explored systematically to improve pressure management efficacy. In this study, we developed three-dimensional (3D) homogenous finite element (FE) CT-leg systems to qualitatively compare the pressure diversities along lower limbs with different biomaterial tissue properties under each external compression level. Simultaneously, through the obtained leg circumferential displacement, a contact analysis model was applied to quantitatively explore the impact mechanisms of soft leg indentations on the pressure performance of CTs. Based on the experimental validation study, the proposed FE systems could be efficiently utilized for compression performance prediction (error ratio: 7.45%). Through the biomechanical simulation and theoretical calculations, the tissue stiffness characteristics of applied bodies showed significant correlations (p < 0.05) with the body circumferential displacements but no correlations (p > 0.05) with pressure delivery differences of CTs. This study facilitates the pressure fit design principle and leg mannequin material selection guidance for the development and experimental assessment of CTs. It also provides effective simulation methods for pressure prediction and property parametric optimization of compression materials.

Primary large cell neuroendocrine carcinoma of the bladder: A case report.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) of the bladder is a rare non-urothelial tumor of the bladder. The treatment of LCNEC of the bladder is different from that of urothelial carcinoma (UC); therefore, early and accurate diagnosis is particularly important. As LCNEC of the bladder is rare and its clinical symptoms and radiographic features are similar to those of urothelial tumors, the clinical diagnosis of the disease remains challenging. CASE SUMMARY: We report a 72-year-old female patient who presented with gross hematuria for 3 mo. A solitary tumor located in the anterior wall of the bladder was found by cystoscopy. Pathological examination after biopsy suggested UC of the bladder in the absence of immunohistochemical assessment. The patient underwent partial cystectomy and was finally diagnosed with LCNEC (pT2bN0M0) based on the results of postoperative immunohistochemical examination. During the 10-mo follow-up, no signs of tumor recurrence or metastasis were found. CONCLUSION: Immunohistochemical examination is essential for diagnosing LCNEC of the bladder. Accurate diagnosis and multidisciplinary treatment in the early stage of the disease are crucial for improving the prognosis.