EPPK1 as a Prognostic Biomarker in Type I Endometrial Cancer and Its Correlation with Immune Infiltration.

Purpose: Approximately 20% of patients with type I endometrial cancer (EC) of the uterus experience recurrence and metastasis. However, existing data do not provide sufficient evidence for the utility of protein levels as prognostic biomarkers in type I EC. This study aims to determine whether epiplakin1 (EPPK1) and progesterone receptor (PR) play a role in the recurrence and metastasis of type I EC. Methods: Following the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) for assessing the quality of biomarker research results, a retrospective analysis was conducted on clinical information and tissue samples of type I EC patients. Protein expression data and clinical data for type I EC were downloaded from The Cancer Proteome Atlas (TCPA) database. We utilized the Kaplan-Meier (K-M) method and Cox proportional hazards regression analyses to evaluate whether epiplakin1 (EPPK1), progesterone receptor (PR) and certain clinical parameters can serve as independent prognostic factors. The Immune Cell Abundance Identifier (ImmuCellAI) and Cancer Immunome Atlas (TCIA) were employed to predict responses to immunotherapy. Immunohistochemistry was carried out to assess the expression of EPPK1 in type I EC. Results: Type I EC patients with high EPPK1 and low PR expression had higher International Federation of Gynecology and Obstetrics (FIGO) stage, recurrence, and metastasis rates. Furthermore, EPPK1 was identified as an independent prognostic factor, and low expression of EPPK1 was predominantly observed in the POLE ultramutated (POLEmut) group, indicating a favorable prognosis. Additionally, the high EPPK1 expression group had a lower Immune Prognostic Score (IPS), suggesting that the high-expression group may not benefit from immune checkpoint inhibitors. Conclusion: High expression of EPPK1 is an independent prognostic factor in type I EC patients with low PR expression. It can identify a subgroup of patients at high risk of recurrence. A more aggressive treatment approach is recommended for these patients.

Effect of acupuncture for temporomandibular disorders: a randomized clinical trial.

BACKGROUND: Temporomandibular disorders (TMD) is the leading cause of pain and disability among frequently occurring facial pain and the second leading cause of musculoskeletal conditions. AIM: We examined whether acupuncture could alleviate pain intensity in patients with temporomandibular disorders (TMD). DESIGN AND METHODS: Sixty participants with TMD were randomly assigned (ratio 1:1) to receive three acupuncture or sham acupuncture sessions weekly for 4 weeks. The primary outcome was the change in the mean weekly pain intensity from baseline to week 4. Secondary and exploratory outcomes included proportion of participants with ≥30% or ≥ 50% reduction in pain intensity, change in jaw opening and movement, graded chronic pain scale, jaw functional limitations scale-20-item, Depression, Anxiety and Stress Scales-21, Pittsburgh sleep quality index at week 4 and 8, and the pressure pain threshold and surface electromyography at week 4. RESULTS AND CONCLUSION: The acupuncture group showed significantly reduced pain intensity compared to the sham group at week 4 (-1.49, 95% confidence interval [CI]: -2.32 to -0.65; P < 0.001) and week 8 (-1.23, 95% CI: -2.11 to -0.54; P = 0.001). Acupuncture's effectiveness surpassed sham's at 4 weeks and lasted 8 weeks. Participants in the acupuncture group experienced significantly greater improvements in the 30% and 50% response rate, jaw opening and movement, GCPS, JFLS-20, DASS-21 and PSQI than those in the sham acupuncture group. There were no significant between-group differences in PPT and sEMG. In summary, acupuncture provided marked pain relief and improvement in physical and emotional function for patients with TMD compared with sham acupuncture.

Inhibition of circDGKZ ameliorates myocardial ischemia/reperfusion injury by targeting miR-345-5p/TLR4.

AIMS: This study aims to explore the molecular mechanism of circular RNAs' (circRNAs) potential involvement in myocardial ischaemia-reperfusion injury (MIRI). METHODS AND RESULTS: Differently expressed genes in myocardial infarction (MI) were identified by screening the GEO database. Serum was collected from MI patients and healthy volunteers (n = 5 for each group). AC16 cells were cultured and exposed to hypoxia/reperfusion (H/R) treatment for the cell experiments. Then candidate genes were validated in human serum and the H/R model. Quantitative real-time PCR and western blot were used to detect expression of key molecules such as circDGKZ, miR-345-5p, and Toll-like receptor 4 (TLR4), as well as pyroptosis markers such as NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), ASC, C-caspase1, interleukin (IL)-1ß, and IL-18. CircDGKZ was positively correlated in human serum (P < 0.05) and in AC16 cells (P < 0.01). Knockdown of circDGKZ inhibited cardiomyocyte pyroptosis and the TLR4/nuclear factor kappa B (NF-κB) signalling pathway (all P < 0.05). A luciferase assay was used to detect the molecule interaction. MiR-345-5p was regulated by circDGKZ and regulated TLR4 in cardiomyocytes both through direct interaction (P < 0.01). The stability and distribution of circRNA or linear RNA were examined by subcellular localization and RNA decay assays. CircDGKZ was stably expressed in cardiomyocytes and mainly distributed in the cytoplasm (P < 0.01). Knockdown of circDGKZ also promoted the degradation of NLRP3 by inducing autophagy (P < 0.05). MIRI rat models were constructed (n = 5 for each group), and the cellular results were further confirmed in rat models (P < 0.05). CONCLUSIONS: Knockdown of circDGKZ interrupted pyroptosis and induced autophagy of cardiomyocytes via regulating miR-345-5p/TLR4/NF-κB.

Distinct roles of excitatory and inhibitory neurons in the medial prefrontal cortex in the expression and reconsolidation of methamphetamine-associated memory in male mice.

Methamphetamine, a commonly abused drug, is known for its high relapse rate. The persistence of addictive memories associated with methamphetamine poses a significant challenge in preventing relapse. Memory retrieval and subsequent reconsolidation provide an opportunity to disrupt addictive memories. However, the key node in the brain network involved in methamphetamine-associated memory retrieval has not been clearly defined. In this study, using the conditioned place preference in male mice, whole brain c-FOS mapping and functional connectivity analysis, together with chemogenetic manipulations of neural circuits, we identified the medial prefrontal cortex (mPFC) as a critical hub that integrates inputs from the retrosplenial cortex and the ventral tegmental area to support both the expression and reconsolidation of methamphetamine-associated memory during its retrieval. Surprisingly, with further cell-type specific analysis and manipulation, we also observed that methamphetamine-associated memory retrieval activated inhibitory neurons in the mPFC to facilitate memory reconsolidation, while suppressing excitatory neurons to aid memory expression. These findings provide novel insights into the neural circuits and cellular mechanisms involved in the retrieval process of addictive memories. They suggest that targeting the balance between excitation and inhibition in the mPFC during memory retrieval could be a promising treatment strategy to prevent relapse in methamphetamine addiction.

Precise Helium Sieving from Hydrogen Using Fluorine-Decorated Carbon Hollow Fiber Membranes.

Separating helium (He) and hydrogen (H2), two gases that are extremely similar in molecular size and condensation properties, presents a formidable challenge in the helium industry. The development of membranes capable of precisely differentiating between these gases is crucial for achieving large-scale, energy-efficient He/H2 separation. However, the limited selectivity of current membranes has hindered their practical application. In this study, we propose a novel approach to overcome this challenge by engineering submicroporous membranes through the fluorination of partially carbonized hollow fibers. We demonstrate that the fluorine substitution on the inner rim of the micropore walls within the carbon hollow fibers enables tunability of the microporous architecture. Furthermore, it enhances interactions between H2 molecules and the micropore walls through the polarization and hydrogen bonding induced by C-F bonds, resulting in simultaneous improvements in both He/H2 diffusivity and solubility selectivities. The fluorinated HFM-550-F-1min membrane exhibits exceptional mixed-gas separation performance, with a binary mixed-gas He/H2 selectivity of 10.5 and a ternary mixed-gas He/(H2+CO2) selectivity of 20.8, at 40 bar feed pressure and 35 oC, surpassing all previously reported polymer-based gas separation membranes, and remarkable plasticization resistance and long-term continuous stability over 30 days.

GSDMD protects intestinal epithelial cells against bacterial infections through its N-terminal activity impacting intestinal immune homeostasis.

The intestinal mucosal barrier serves as a vital guardian for gut health, maintaining a delicate equilibrium between gut microbiota and host immune homeostasis. Recent studies have found the intricate roles of Gasdermin D (GSDMD), a key executioner of pyroptosis downstream of the inflammasome, within the intestine, including controlling colitis in intestinal macrophage and the regulatory function in goblet cell mucus secretion. Thus, the exact role and nature of GSDMD's regulatory function in maintaining intestinal immune homeostasis and defending against pathogens remain elucidation. Here, we uncover that GSDMD plays a key role in defending against intestinal Citrobacter rodentium infection, with high expression in intestinal epithelial and lamina propria myeloid cells. Our results show that GSDMD specifically acts in intestinal epithelial cells to fight the infection, independently of its effects on antimicrobial peptides or mucin secretion. Instead, the resistance is mediated through GSDMD's N-terminal fragments, highlighting its importance in intestinal immunity. However, the specific underlying mechanism of GSDMD N-terminal activity in protection against intestinal bacterial infections still needs further study to clarify in the future.

Machine learning model for prediction of permanent stoma after anterior resection of rectal cancer: A multicenter study.

BACKGROUND: The conversion from a temporary to a permanent stoma (PS) following rectal cancer surgery significantly impacts the quality of life of patients. However, there is currently a lack of practical preoperative tools to predict PS formation. The purpose of this study is to establish a preoperative predictive model for PS using machine learning algorithms to guide clinical practice. METHODS: In this retrospective study, we analyzed clinical data from a total of 655 patients who underwent anterior resection for rectal cancer, with 552 patients from one medical center and 103 from another. Through machine learning algorithms, five predictive models were developed, and each was thoroughly evaluated for predictive performance. The model with superior predictive accuracy underwent additional validation using both an independent testing cohort and the external validation cohort. The Shapley Additive exPlanations (SHAP) approach was employed to elucidate the predictive factors influencing the model, providing an in-depth visual analysis of its decision-making process. RESULTS: Eight variables were selected for the construction of the model. The support vector machine (SVM) model exhibited superior predictive performance in the training set, evidenced by an AUC of 0.854 (95 % CI:0.803-0.904). This performance was corroborated in both the testing set and external validation set, where the model demonstrated an AUC of 0.851 (95%CI:0.748-0.954) and 0.815 (95%CI:0.710-0.919), respectively, indicating its efficacy in identifying the PS. CONCLUSIONS: The model(https://yangsu2023.shinyapps.io/psrisk/) indicated robust predictive performance in identifying PS after anterior resection for rectal cancer, potentially guiding surgeons in the preoperative stratification of patients, thus informing individualized treatment plans and improving patient outcomes.

Career adaptability among new oncology nurses: A longitudinal exploration.

AIM: This study aims to explore the longitudinal predictive effect of self-awareness on career adaptability in new nurses at a tumor specialty hospital and the mediating mechanisms of work readiness and transition shock. BACKGROUND: Career adaptability is crucial for the personal development of nurses and also intricately linked to the retention rates among newcomers in oncology nursing. Inadequate career adaptability contributes to higher turnover, which in turn exacerbates the shortage of qualified nursing personnel in this field. There is a pressing need for dedicated research and interventions that support new nurses, especially in specialized areas like oncology, to promote their well-being and career advancement. Comprehending these challenges is essential for devising effective strategies that will retain nursing talent and ensure the sustainability of a robust healthcare workforce. METHODS: Longitudinal data from four follow-up surveys were collected from 248 new clinical nurses at the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College. Mediation analyses using R 4.1.2 were conducted to examine the pathways between self-awareness, work readiness, transition shock, and career adaptability. CONCLUSIONS: Self-awareness not only directly predicts career adaptability but also influences it through the bidirectional and chained mediating pathways of work readiness and transition shock. IMPLICATIONS FOR NURSING AND HEALTH POLICY: These findings equip nursing managers with flexible strategies to foster and enhance nurses' career adaptability, providing targeted support as nurses assimilate into their clinical roles. This not only strengthens workforce stability but also mitigates turnover, ultimately reinforcing the healthcare workforce.

Pressure stabilizes ferrous iron in bridgmanite under hydrous deep lower mantle conditions.

Earth's lower mantle is a potential water reservoir. The physical and chemical properties of the region are in part controlled by the Fe3+/ΣFe ratio and total iron content in bridgmanite. However, the water effect on the chemistry of bridgmanite remains unclear. We carry out laser-heated diamond anvil cell experiments under hydrous conditions and observe dominant Fe2+ in bridgmanite (Mg, Fe)SiO3 above 105 GPa under the normal geotherm conditions corresponding to depth > 2300 km, whereas Fe3+-rich bridgmanite is obtained at lower pressures. We further observe FeO in coexistence with hydrous NiAs-type SiO2 under similar conditions, indicating that the stability of ferrous iron is a combined result of H2O effect and high pressure. The stability of ferrous iron in bridgmanite under hydrous conditions would provide an explanation for the nature of the low-shear-velocity anomalies in the deep lower mantle. In addition, entrainment from a hydrous dense layer may influence mantle plume dynamics and contribute to variations in the redox conditions of the mantle.

PRDM14 extinction enables the initiation of trophoblast stem cell formation.

Trophoblast stem cells (TSCs) can be chemically converted from embryonic stem cells (ESCs) in vitro. Although several transcription factors (TFs) have been recognized as essential for TSC formation, it remains unclear how differentiation cues link elimination of stemness with the establishment of TSC identity. Here, we show that PRDM14, a critical pluripotent circuitry component, is reduced during the formation of TSCs. The reduction is further shown to be due to the activation of Wnt/ß-catenin signaling. The extinction of PRDM14 results in the erasure of H3K27me3 marks and chromatin opening in the gene loci of TSC TFs, including GATA3 and TFAP2C, which enables their expression and thus the initiation of the TSC formation process. Accordingly, PRDM14 reduction is proposed here as a critical event that couples elimination of stemness with the initiation of TSC formation. The present study provides novel insights into how induction signals initiate TSC formation.

Natural history of depression up to 18 years after stroke: a population-based South London Stroke Register study.

Background: Current evidence on the long-term natural history of post-stroke depression (PSD) is limited. We aim to determine the prevalence, incidence, duration and recurrence rates of depression to 18-years after stroke and assess differences by onset-time and depression severity. Methods: Data were from the South London Stroke Register (1995-2019, N = 6641 at registration). Depression was defined using the Hospital Anxiety and Depression scale (scores > 7 = depression) at 3-months, then annually to 18-years after stroke. We compared early- (3-months post-stroke) vs late-onset depression (1-year) and initial mild (HADS scores > 7) vs severe depression (scores > 10). Findings: 3864 patients were assessed for depression at any time-points during the follow-up (male:55.4% (2141), median age: 68.0 (20.4)), with the number ranging from 2293 at 1-year to 145 at 18-years after stroke. Prevalence of PSD ranged from 31.3% (28.9-33.8) to 41.5% (33.6-49.3). The cumulative incidence of depression was 59.4% (95% CI 57.8-60.9), of which 87.9% (86.5-89.2) occurred within 5-years after stroke. Of patients with incident PSD at 3-months after stroke, 46.6% (42.1-51.2) recovered after 1 year. Among those recovered, 66.7% (58.0-74.5) experienced recurrent depression and 94.4% (87.5-98.2) of recurrences occurred within 5-years since recovery. Similar estimates were observed in patients with PSD at 1-year. 34.3% (27.9-41.1) of patients with severe depression had recovered at the next time-point, compared to 56.7% (50.5-62.8) with mild depression. Recurrence rate at 1-year after recovery was higher in patients with severe depression (52.9% (35.1-70.2)) compared to mild depression (23.5% (14.1-35.4)) (difference: 29.4% (7.6-51.2), p = 0.003). Interpretation: Long-term depressive status may be established by 5-years post-onset. Early- and late-onset depression presented similar natural history, while severe depression had a longer duration and quicker recurrence than mild depression. These estimates were limited to alive patients completing the depression assessment, who tended to have less severe stroke than excluded patients, so may be underestimated and not generalizable to all stroke survivors. Funding: National Institute for Health and Care Research (NIHR202339).

Mechanism of action of Taohong Siwu decoction in the alleviation of primary dysmenorrhea.

Background: As one of the most common gynecological disorders, PD significantly impacts the quality of life for women. TSD, a well-known traditional Chinese medical prescription, has gained popularity for its use in treating gynecological cold coagulation and blood stasis syndromes such as PD. However, the lack of comprehensive data hinders our understanding of its molecular mechanism. Purpose: The objective of the present study is to investigate the therapeutic effects of TSD on PD and elucidate its plausible mechanism. Methods: HPLC was employed to confirm the presence of the principal metabolites of TSD. The rat model of PD was induced by OT exposure following IWM and EB pretreatment, and subsequently treated with TSD via gastric gavage. The effects and potential mechanisms of TSD on PD rats were explored, encompassing general behavior, morphological alterations in the uterus and ovaries, biochemical indicators in the uterus and serum, and levels of proteins related to the PI3K/AKT signaling pathway. Results: Gallic acid, hydroxysafflower yellow A, albiflorin, paeoniflorin, and ferulic acid were determined to be the primary active metabolites of TSD. The pharmacological studies yielded results indicating the successful establishment of the PD model in rats. Additionally, TSD demonstrated its ability to protect PD rats by ameliorating general behavior, mitigating pathological damage to uterine and ovarian tissues, and modulating the expression levels of correlated factors (PGE2, PGF2α, Ca2+, TXB2, IL-6, TNF-α, NO, and COX-2) as well as p-PI3K/PI3K and p-AKT/AKT proteins. Conclusion: TSD exhibited protective effects against PD in rats through its interaction with multiple targets including P13K/AKT signaling pathway, indicating that TSD holds therapeutic potential for PD treatment and providing evidence supporting the rational utilization of TSD.

Research on the Effectiveness of the Training of Nosocomial Infection Control Specialist Nurses under the Background of the New Crown Epidemic Based on Competence-based Theory.

Background: Coronavirus disease 2019 is highly contagious and has the potential to cause nosocomial infections, has placed a strong pressure on worldwide healthcare systems over the last years. Nosocomial infection has many influencing factors, among which the unreasonable operation of nurses accounts for 30.0%-50.0%. Therefore, strengthening the professional skill training of nurses is of great significance in reducing the nosocomial infection rate. Objective: This research aimed to explore the effectiveness of the training of nosocomial infection control on the competencies of specialist nurses under the background of the new crown epidemic based on competency-based theory. Design: This was a retrospective study. Setting: This study was performed in Dongfang Hospital, Affiliated to Tongji University. Participants: A total of 84 key nurses, each of them recommended by one department from June 2020 to June 2021, were chosen as study subjects, and they could actively participate in the training. Interventions: Nurses received systematic and standardized training based on competency-based theory under the background of coronavirus disease 2019, including focus group meeting, training of core emergency capability, teaching training and contingency plan for COVID-19 infection. Primary Outcome Measures: (1) core competence (2) job fit (3) core emergency response for major infectious diseases, and (4) nurses' satisfaction. All these primary outcomes can reflect the competencies of specialist nurses after training. Results: The scores in critical thinking and scientific research, clinical nursing, ethics and legal practice, professional development, education consulting and professional knowledge, professional skills, comprehensive quality, and professional ability of nurses training were higher than those before (P = .000). After training, the scores in relevant matters needing attention (international rescue, bioterrorist attacks, and infectious disease emergencies after natural disasters), filling in the People's Republic of China Infectious Disease Report Card, and the scope of reporting infectious disease emergencies were all higher than before (P = .000). All nurses had relatively high satisfaction with the curriculum setting and assessment form, with satisfaction of 100.0%, followed by training duration, with satisfaction of 92.86%. Conclusion: Under the background of coronavirus disease 2019, based on competence-based theory, training of nosocomial infection control specialist nurses could improve their core competence, job fit, and core emergency response capabilities, with high satisfaction. Under the background of the normalization of the prevention and control of the novel coronavirus pneumonia epidemic, the training model based on competence-based theory of nurses is worth promoting.

Experimental Virtual Distillation of Entanglement and Coherence.

Noise is, in general, inevitable and detrimental to practical and useful quantum communication and computation. Under the resource theory framework, resource distillation serves as a generic tool to overcome the effect of noise. Yet, conventional resource distillation protocols generally require operations on multiple copies of resource states, and strong limitations exist that restrict their practical utilities. Recently, by relaxing the setting of resource distillation to only approximating the measurement statistics instead of the quantum state, a resource-frugal protocol, "virtual resource distillation," is proposed, which allows more effective distillation of noisy resources. Here, we report its experimental implementation on a photonic quantum system for the distillation of quantum coherence (up to dimension four) and bipartite entanglement. We show the virtual distillation of the maximal superposed state of dimension four from the state of dimension two, an impossible task in conventional coherence distillation. Furthermore, we demonstrate the virtual distillation of entanglement with operations acting only on a single copy of the noisy Einstein-Podolsky-Rosen (EPR) pair and showcase the quantum teleportation task using the virtually distilled EPR pair with a significantly improved fidelity of the teleported state. These results illustrate the feasibility of the virtual resource distillation method and pave the way for accurate manipulation of quantum resources with noisy quantum hardware.

Genome-wide detections for runs of homozygosity and selective signatures reveal novel candidate genes under domestication in chickens.

BACKGROUND: Indigenous chickens were developed through a combination of natural and artificial selection; essentially, changes in genomes led to the formation of these modern breeds via admixture events. However, their confusing genetic backgrounds include a genomic footprint regulating complex traits, which is not conducive to modern animal breeding. RESULTS: To better evaluate the candidate regions under domestication in indigenous chickens, we considered both runs of homozygosity (ROHs) and selective signatures in 13 indigenous chickens. The genomes of Silkie feather chickens presented the highest heterozygosity, whereas the highest inbreeding status and ROH number were found in Luhua chickens. Short ROH (< 1 Mb), were the principal type in all chickens. A total of 291 ROH islands were detected, and QTLdb mapping results indicated that body weight and carcass traits were the most important traits. An ROH on chromosome 2 covering VSTM2A gene was detected in 12 populations. Combined analysis with the Tajima's D index revealed that 18 genes (e.g., VSTM2A, BBOX1, and RYR2) were under selection and covered by ROH islands. Transcriptional analysis results showed that RYR2 and BBOX1 were specifically expressed in the heart and muscle tissue, respectively. CONCLUSION: Based on genome-wide scanning for ROH and selective signatures, we evaluated the genomic characteristics and detected significant candidate genes covered by ROH islands and selective signatures. The findings in this study facilitated the understanding of genetic diversity and provided valuable insights for chicken breeding and conservation strategies.

Low energy-consumption oriented membrane fouling control strategy in anaerobic fluidized membrane bioreactor.

Anaerobic fluidized membrane bioreactors (AFMBR) has attracted growing interest as an emerging wastewater treatment technology towards energy recovery from wastewater. AFMBR combines the advantages of anaerobic digestion and membrane bioreactors and shows great potential in overcoming limiting factors such as membrane fouling and low efficiency in treating low-strength wastewater such as domestic sewage. In AFMBR, the fluidized media performs significant role in reducing the membrane fouling, as well as improving the anaerobic microbial activity of AFMBRs. Despite extensive research aimed at mitigating membrane fouling in AFMBR, there has yet to emerge a comprehensive review focusing on strategies for controlling membrane fouling with an emphasis on low energy consumption. Thus, this work overviews the recent progress of AFMBR by summarizing the factors of membrane fouling and energy consumption in AFMBR, and provides targeted in-depth analysis of energy consumption related to membrane fouling control. Additionally, future development directions for AFMBR are also outlooked, and further promotion of AFMBR engineering application is expected. By shedding light on the relationship between energy consumption and membrane fouling control, this review offers a useful information for developing new AFMBR processes with an improved efficiency, low membrane fouling and low energy consumption, and encourages more research efforts and technological advancements in the domain of AFMBR.

SAH is a major metabolic sensor mediating worsening metabolic crosstalk in metabolic syndrome.

In this study, we observed worsening metabolic crosstalk in mouse models with concomitant metabolic disorders such as hyperhomocysteinemia (HHcy), hyperlipidemia, and hyperglycemia and in human coronary artery disease by analyzing metabolic profiles. We found that HHcy worsening is most sensitive to other metabolic disorders. To identify metabolic genes and metabolites responsible for the worsening metabolic crosstalk, we examined mRNA levels of 324 metabolic genes in Hcy, glucose-related and lipid metabolic systems. We examined Hcy-metabolites (Hcy, SAH and SAM) by LS-ESI-MS/MS in 6 organs (heart, liver, brain, lung, spleen, and kidney) from C57BL/6J mice. Through linear regression analysis of Hcy-metabolites and metabolic gene mRNA levels, we discovered that SAH-responsive genes were responsible for most metabolic changes and all metabolic crosstalk mediated by Serine, Taurine, and G3P. SAH-responsive genes worsen glucose metabolism and cause upper glycolysis activation and lower glycolysis suppression, indicative of the accumulation of glucose/glycogen and G3P, Serine synthesis inhibition, and ATP depletion. Insufficient Serine due to negative correlation of PHGDH with SAH concentration may inhibit the folate cycle and transsulfurarion pathway and consequential reduced antioxidant power, including glutathione, taurine, NADPH, and NAD+. Additionally, we identified SAH-activated pathological TG loop as the consequence of increased fatty acid (FA) uptake, FA ß-oxidation and Ac-CoA production along with lysosomal damage. We concluded that HHcy is most responsive to other metabolic changes in concomitant metabolic disorders and mediates worsening metabolic crosstalk mainly via SAH-responsive genes, that organ-specific Hcy metabolism determines organ-specific worsening metabolic reprogramming, and that SAH, acetyl-CoA, Serine and Taurine are critical metabolites mediating worsening metabolic crosstalk, redox disturbance, hypomethylation and hyperacetylation linking worsening metabolic reprogramming in metabolic syndrome.

The crosstalk between cell death and pregnancy related diseases: A narrative review.

Programmed cell death is intricately linked to various physiological phenomena such as growth, development, and metabolism, as well as the proper function of the pancreatic ß cell and the migration and invasion of trophoblast cells in the placenta during pregnancy. Traditional and recently identified programmed cell death include apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis. In addition to cancer and degenerative diseases, abnormal activation of cell death has also been implicated in pregnancy related diseases like preeclampsia, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, fetal growth restriction, and recurrent miscarriage. Excessive or insufficient cell death and pregnancy related diseases may be mutually determined, ultimately resulting in adverse pregnancy outcomes. In this review, we systematically describe the characteristics and mechanisms underlying several types of cell death and their roles in pregnancy related diseases. Moreover, we discuss potential therapeutic strategies that target cell death signaling pathways for pregnancy related diseases, hoping that more meaningful treatments will be applied in clinical practice in the future.

Pleiotropic Role of Endoplasmic Reticulum Stress in the Protection of Psoralidin against Sepsis-associated encephalopathy.

Sepsis-associated encephalopathy (SAE) is a severe complication that affects the central nervous system and is a leading cause of increased morbidity and mortality in intensive care units. Psoralidin (PSO), a coumarin compound isolated from the traditional Chinese medicine Psoralea corylifolia L., can penetrate the blood-brain barrier and has various pharmacological activities, including anti-inflammation, anti-oxidation and anti-depression. This study aims to explore whether PSO alleviates SAE and delved into the underlying mechanisms. We found that PSO treatment significantly reduced sepsis scores, aspartate transaminase (AST) and aspartate transaminase (LDH), while increased anal temperature and neurological scores in CLP-injured mice. Moreover, PSO treatment ameliorated sepsis-associated cognitive impairment, mood, anxiety disorders, inhibited inflammatory responses, as well as improved endoplasmic reticulum stress (ERS). These results were also validated in vitro experiments, PSO treatment reduced ROS, inflammation response, and improved ERS in LPS-injured N2a cells. Importantly, tunicamycin (TUN), as ERS agonist, significantly reversed the protective effect of PSO on LPS-injured N2a cells, as evidenced by increased expression levels of IL-6, NLRP3, CHOP, and ATF6. Likewise, ATF6 overexpression also reversed the protective effect of PSO. In conclusion, these results confirmed that PSO has a protective effect on SAE, which was largely attributed to neuroinflammation and ERS. These findings provide new insight into the neuroprotective role of PSO and suggest that PSO is a new therapeutic intervention of SAE.