Spinal PTP1B Regulated NMDA Receptor-mediated Nociceptive Transmission and Peripheral Inflammation-induced Pain Sensitization.

Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of several pain-related substrates in spinal cord dorsal horn and are critically involved in the modification of pain transmission. The current study demonstrated that protein tyrosine phosphatase 1B (PTP1B), a unique endoplasmic reticulum-resident member of PTP family, displayed an activity-dependent increase in its protein expression and synaptic localization in spinal dorsal horn of adult male rats. PTP1B interacted with the Src Homology 3 (SH3) domain of Synapse-Associated Protein 102 (SAP102), one of the postsynaptic scaffolding proteins that anchored PTP1B at postsynaptic sites. The SAP102-tethered PTP1B augmented the synaptic transmission mediated specifically by GluN2B subunit-containing N-methyl-D-aspartate subtype glutamate receptors. Interference with PTP1B activity or disruption of its interaction with SAP102 attenuated GluN2B-mediated nociceptive transmission and ameliorated pain sensitization induced by intraplantar injection of Complete Freund's Adjuvant. These data suggested that the activity-dependent synaptic redistribution of PTP1B served as an important mechanism regulating GluN2B receptor activity and that manipulation of PTP1B synaptic targeting might represent an effective approach for the treatment of chronic inflammatory pain.

Impact of osteopenia and osteosarcopenia on the outcomes after surgery of hepatobiliary-pancreatic cancers.

Objective: The purpose of this study is to investigate potential associations between osteopenia, osteosarcopenia, and postoperative outcomes in patients with hepatobiliary-pancreatic cancer (HBPC). Methods: Three online databases, including Embase, PubMed, and the Cochrane Library, were thoroughly searched for literature describing the relationship between osteopenia, osteosarcopenia, and outcomes of surgical treatment of HBPC patients from the start of each database to September 29, 2023. The Newcastle-Ottawa Scale was used to rate the quality of the studies. Results: This analysis included a total of 16 articles with a combined patient cohort of 2,599 individuals. The results demonstrated that HBPC patients with osteopenia had significantly inferior OS (HR: 2.27, 95% CI: 1.70-3.03, p < 0.001) and RFS (HR: 1.96, 95% CI: 1.42-2.71, p < 0.001) compared to those without osteopenia. Subgroup analysis demonstrated that these findings were consistent across univariate and multivariate analyses, as well as hepatocellular carcinoma, biliary tract cancer, and pancreatic cancer. The risk of postoperative major complications was significantly higher in patients with osteopenia compared to those without osteopenia (OR: 1.66, 95% CI: 1.19-2.33, p < 0.001). Besides, we also found that the presence of osteosarcopenia in HBPC patients was significantly related to poorer OS (HR: 3.31, 95% CI: 2.00-5.48, p < 0.001) and PFS (HR: 2.50, 95% CI: 1.62-3.84, p < 0.001) in comparison to those without osteosarcopenia. Conclusion: Preoperative osteopenia and osteosarcopenia can predict poorer OS and RFS with HBPC after surgery.

PPM1F regulates ovarian cancer progression by affecting the dephosphorylation of ITGB1.

PPM1F has been shown to play diverse biological functions in the progression of multiple tumors. PPM1F controls the T788/T789 phosphorylation switch of ITGB1 and regulates integrin activity. However, the impacts of PPM1F and ITGB1 on ovarian cancer (OV) progression remain unclear. Whether there is such a regulatory relationship between PPM1F and ITGB1 in ovarian cancer has not been studied. Therefore, the purpose of this study is to elucidate the function and the mechanism of PPM1F in ovarian cancer. The expression level and the survival curve of PPM1F were analyzed by databases. Gain of function and loss of function were applied to explore the function of PPM1F in ovarian cancer. A tumor formation assay in nude mice showed that knockdown of PPM1F inhibited tumor formation. We tested the effect of PPM1F on ITGB1 dephosphorylation in ovarian cancer cells by co-immunoprecipitation and western blotting. Loss of function was applied to investigate the function of ITGB1 in ovarian cancer. ITGB1-mut overexpression promotes the progression of ovarian cancer. Rescue assays showed the promoting effect of ITGB1-wt on ovarian cancer is attenuated due to the dephosphorylation of ITGB1-wt by PPM1F. PPM1F and ITGB1 play an oncogene function in ovarian cancer. PPM1F regulates the phosphorylation of ITGB1, which affects the occurrence and development of ovarian cancer.

Altered Error Monitoring and Decreased Flanker Task Accuracy in Pediatric Obsessive-Compulsive Disorder.

The error-related negativity (ERN) and error positivity (Pe) are components of the event-related potential following an error that are potential mechanistic biomarkers of obsessive-compulsive disorder (OCD). The study examined the ERN, Pe, flanker task accuracy, and clinical measures in 105 OCD cases and 105 matched healthy controls (HC) ages 8-18 years. Higher flanker task accuracy in all participants was associated with an increased ERN amplitude and increased difference between Pe and correct positivity amplitudes (ΔPe). Compared to HC, OCD cases had an increased ERN but decreased ΔPe and flanker task accuracy. Those differences were also significant in tic-related and non-tic-related OCD cases compared to HC. A lower ΔPe was associated in cases with an earlier age at OCD symptom onset. The results support the hypothesis that OCD involves defects in an error monitoring system and suggest a reduced ΔPe may compromise error signaling and cause uncertainty about the correctness of a response.

The oncogenic role and regulatory mechanism of ACAA2 in human ovarian cancer.

Acetyl-CoAacyltransferase2 (ACAA2) is a key enzyme in the fatty acid oxidation pathway that catalyzes the final step of mitochondrial ß oxidation, which plays an important role in fatty acid metabolism. The expression of ACAA2 is closely related to the occurrence and malignant progression of tumors. However, the function of ACAA2 in ovarian cancer is unclear. The expression level and prognostic value of ACAA2 were analyzed by databases. Gain and loss of function were carried out to explore the function of ACAA2 in ovarian cancer. RNA-seq and bioinformatics methods were applied to illustrate the regulatory mechanism of ACAA2. ACAA2 overexpression promoted the growth, proliferation, migration, and invasion of ovarian cancer, and ACAA2 knockdown inhibited the malignant progression of ovarian cancer as well as the ability of subcutaneous tumor formation in nude mice. At the same time, we found that OGT can induce glycosylation modification of ACAA2 and regulate the karyoplasmic distribution of ACAA2. OGT plays a vital role in ovarian cancer as a function of oncogenes. In addition, through RNA-seq sequencing, we found that ACAA2 regulates the expression of DIXDC1. ACAA2 regulated the malignant progression of ovarian cancer through the WNT/ß-Catenin signaling pathway probably. ACAA2 is an oncogene in ovarian cancer and has the potential to be a target for ovarian cancer therapy.

A tripartite evolutionary game study of low-carbon innovation system from the perspective of dynamic subsidies and taxes.

Traditional manufacturing industry is in the early stages of transition to low-carbon innovative production, and is in urgent need of a low-carbon innovation system to achieve the goal of carbon neutrality. In order to realize the effective supervision of enterprise carbon emissions, this paper constructs a tripartite evolutionary game model among the corporate, government and public from the perspective of dynamic subsidies and taxes. The main results are as follows. First, the increase in government subsidies to a certain extent will help encourage companies to choose low-carbon innovative production strategies, but more subsidies are not always better. Excessive subsidies will increase the cost of government regulation and reduce the probability of government regulation. Second, the tripartite evolutionary game system does not converge under the static subsidies and taxes mechanism. But the system could quickly converges to the stable condition under dynamic subsidies and taxes. The stable point is the situation of corporate low-carbon innovation, government regulation, and public supervision. Third, the public intervention and supervision can effectively prevent the phenomenon of government misconduct and enterprises over-emission production. And the influence of public reward and punishment is more effective for the government than for enterprises.

Altered Error Monitoring and Decreased Flanker Task Accuracy in Pediatric Obsessive-Compulsive Disorder.

The error-related negativity (ERN) and error positivity (Pe) are components of the event-related potential following an error that are potential mechanistic biomarkers of obsessive-compulsive disorder (OCD). The study examined the ERN, Pe, flanker task accuracy, and clinical measures in 105 OCD cases and 105 matched healthy controls (HC), ages 8 to 18 years, with 21 cases having a tic disorder history. Higher flanker task accuracy in all participants was associated with an increased ERN amplitude and increased difference between Pe and correct positivity amplitudes (ΔPe). Compared to HC, OCD cases had an increased ERN but decreased flanker task accuracy and ΔPe. Those differences were also significant in tic-related and non-tic-related OCD cases compared to HC. A lower ΔPe was associated in OCD cases with an earlier age at OCD symptom onset. The results support the hypothesis that OCD involves defects in an error monitoring system and suggest a reduced ΔPe may compromise error signaling and cause uncertainty about the correctness of a response.

Sodium sulfite-driven Helicobacter pylori eradication: Unraveling oxygen dynamics through multi-omics investigation.

Due to the emergence and spread of multidrug resistance in Helicobacter pylori (H. pylori), its eradication has become difficult. Sodium sulfite (SS), a widely used food additive for ensuring food safety and storage, has been recognized as an effective nonbactericidal agent for H. pylori eradication. However, the mechanism by which H. pylori adapts and eventually succumbs under low- or no-oxygen conditions remains unknown. In this study, we aimed to evaluate the anti-H. pylori effect of SS and investigated the multiomics mechanism by which SS kills H. pylori. The results demonstrated that SS effectively eradicated H. pylori both in vitro and in vivo. H. pylori responds to the oxygen changes regulated by SS, downregulates the HcpE gene, which is responsible for redox homeostasis in bacteria, decreases the activities of enzymes related to oxidative stress, and disrupts the outer membrane structure, increasing susceptibility to oxidative stress. Furthermore, SS downregulates the content of cytochrome C in the microaerobic respiratory chain, leading to a sharp decrease in ATP synthesis. Consequently, the accumulation of triglycerides (TGs) in bacteria due to oxidative stress supports anaerobic respiration, meeting their energy requirements. The multifaceted death of H. pylori caused by SS does not result in drug resistance. Thus, screening of the redox homeostasis of HcpE as a new target for H. pylori infection treatment could lead to the development of a novel approach for H. pylori eradication therapy.

The oncogenic role and regulatory mechanism of PGK1 in human non-small cell lung cancer.

BACKGROUND: Phosphoglycerate kinase 1 (PGK1) is a metabolic enzyme that participates in various biological and pathological processes. Dysregulated PGK1 has been observed in numerous malignancies. However, whether and how PGK1 affects non-small cell lung cancer (NSCLC) is not yet fully elucidated. METHODS: Herein, the non-metabolic function of PGK1 in NSCLC was explored by integrating bioinformatics analyses, cellular experiments, and nude mouse xenograft models. The upstream regulators and downstream targets of PGK1 were examined using multiple techniques such as RNA sequencing, a dual-luciferase reporter assay, Co-immunoprecipitation, and Western blotting. RESULTS: We confirmed that PGK1 was upregulated in NSCLC and this upregulation was associated with poor prognosis. Further in vitro and in vivo experiments demonstrated the promoting effects of PGK1 on NSCLC cell growth and metastasis. Additionally, we discovered that PGK1 interacted with and could be O-GlcNAcylated by OGT. The inhibition of PGK1 O-GlcNAcylation through OGT silencing or mutation at the T255 O-GlcNAcylation site could weaken PGK1-mediated NSCLC cell proliferation, colony formation, migration, and invasion. We also found that a low miR-24-3p level led to an increase in OGT expression. Additionally, PGK1 exerted its oncogenic properties by augmenting ERK phosphorylation and MCM4 expression. CONCLUSIONS: PGK1 acted as a crucial mediator in controlling NSCLC progression. The miR-24-3p/OGT axis was responsible for PGK1 O-GlcNAcylation, and ERK/MCM4 were the downstream effectors of PGK1. It appears that PGK1 might be an attractive therapeutic target for the treatment of NSCLC.

A new step-wise surgical technique of knapsack-like uterine compression sutures for intractable postpartum hemorrhage in cesarean section.

BACKGROUND: Intractable postpartum hemorrhage (PPH) during cesarean section has been a significant concern for obstetricians. We aimed to explore the effectiveness and safety of a new type of uterine compression suture, the step-wise surgical technique of knapsack-like sutures for treating intractable PPH caused by uterine atony and placenta factors in cesarean section. METHODS: The step-wise surgical technique of knapsack-like sutures was established on the basis of the artful combination of vertical strap-like sutures and an annular suture-ligation technique. This novel surgical technique was applied to 34 patients diagnosed with PPH during cesarean section due to severe uterine atony and placental factors in our department. The hemostatic effects, clinical outcomes and follow-up visit results were all reviewed and analyzed. RESULTS: This new uterine compression suture successfully stopped bleeding in 33 patients, and the effective rate was 97.06%. Only 1 patient failed and was changed to use bilateral uterine arterial embolization and internal iliac artery embolization. The follow-up visits indicated that 33 patients restored menstruation except for 1 who was diagnosed with amenorrhea. The gynecological ultrasound tests of all the patients suggested good uterine involutions, and they had no obvious complaints such as hypogastralgia. CONCLUSIONS: This step-wise surgical technique of knapsack-like uterine compression sutures can compress the uterus completely. It is a technique that can conserve the uterus and fertility function without special equipment in caesarean section for PPH, with the characteristics of being safe, simple and stable (3 S) with rapid surgery, reliable hemostasis and resident doctor to operation (3R).