Objective: Negative symptoms in schizophrenia indicate a poor prognosis. However, the mechanisms underlying the development of negative symptoms remain unclear. This study investigated the relationship between negative symptoms in schizophrenia and frontal alpha asymmetry (FAA). Methods: The study used a 32-channel electroencephalography to acquire alpha power in 4 target-paired sites in each patient. Regional alpha asymmetry was calculated based on the alpha power using EEGLAB Frontal Alpha Asymmetry Toolbox. Results: Sixty schizophrenia patients with predominant negative symptoms (PNS), 72 stabilized schizophrenia (SS) patients, and 73 healthy control (HC) participants were enrolled in this study. No significant differences were observed in FAA between the PNS and SS groups, although both groups exhibited reduced P3-P4 alpha asymmetry compared to HCs. A positive correlation was found between F7-F8 alpha asymmetry and illness duration. Additionally, a predictive model based on P3-P4 alpha asymmetry scores was able to differentiate schizophrenia patients from HCs, achieving a sensitivity of 71.2% and a specificity of 72.6%. Conclusion This study highlighted that parietal alpha asymmetry could serve as a valuable diagnostic tool for schizophrenia.

Objective: Negative symptoms in schizophrenia indicate a poor prognosis. However, the mechanisms underlying the development of negative symptoms remain unclear. This study investigated the relationship between negative symptoms in schizophrenia and frontal alpha asymmetry (FAA). Methods: The study used a 32-channel electroencephalography to acquire alpha power in 4 target-paired sites in each patient. Regional alpha asymmetry was calculated based on the alpha power using EEGLAB Frontal Alpha Asymmetry Toolbox. Results: Sixty schizophrenia patients with predominant negative symptoms (PNS), 72 stabilized schizophrenia (SS) patients, and 73 healthy control (HC) participants were enrolled in this study. No significant differences were observed in FAA between the PNS and SS groups, although both groups exhibited reduced P3-P4 alpha asymmetry compared to HCs. A positive correlation was found between F7-F8 alpha asymmetry and illness duration. Additionally, a predictive model based on P3-P4 alpha asymmetry scores was able to differentiate schizophrenia patients from HCs, achieving a sensitivity of 71.2% and a specificity of 72.6%. Conclusion This study highlighted that parietal alpha asymmetry could serve as a valuable diagnostic tool for schizophrenia.

Objective: Negative symptoms in schizophrenia indicate a poor prognosis. However, the mechanisms underlying the development of negative symptoms remain unclear. This study investigated the relationship between negative symptoms in schizophrenia and frontal alpha asymmetry (FAA). Methods: The study used a 32-channel electroencephalography to acquire alpha power in 4 target-paired sites in each patient. Regional alpha asymmetry was calculated based on the alpha power using EEGLAB Frontal Alpha Asymmetry Toolbox. Results: Sixty schizophrenia patients with predominant negative symptoms (PNS), 72 stabilized schizophrenia (SS) patients, and 73 healthy control (HC) participants were enrolled in this study. No significant differences were observed in FAA between the PNS and SS groups, although both groups exhibited reduced P3-P4 alpha asymmetry compared to HCs. A positive correlation was found between F7-F8 alpha asymmetry and illness duration. Additionally, a predictive model based on P3-P4 alpha asymmetry scores was able to differentiate schizophrenia patients from HCs, achieving a sensitivity of 71.2% and a specificity of 72.6%. Conclusion This study highlighted that parietal alpha asymmetry could serve as a valuable diagnostic tool for schizophrenia.

Objective: Negative symptoms in schizophrenia indicate a poor prognosis. However, the mechanisms underlying the development of negative symptoms remain unclear. This study investigated the relationship between negative symptoms in schizophrenia and frontal alpha asymmetry (FAA). Methods: The study used a 32-channel electroencephalography to acquire alpha power in 4 target-paired sites in each patient. Regional alpha asymmetry was calculated based on the alpha power using EEGLAB Frontal Alpha Asymmetry Toolbox. Results: Sixty schizophrenia patients with predominant negative symptoms (PNS), 72 stabilized schizophrenia (SS) patients, and 73 healthy control (HC) participants were enrolled in this study. No significant differences were observed in FAA between the PNS and SS groups, although both groups exhibited reduced P3-P4 alpha asymmetry compared to HCs. A positive correlation was found between F7-F8 alpha asymmetry and illness duration. Additionally, a predictive model based on P3-P4 alpha asymmetry scores was able to differentiate schizophrenia patients from HCs, achieving a sensitivity of 71.2% and a specificity of 72.6%. Conclusion This study highlighted that parietal alpha asymmetry could serve as a valuable diagnostic tool for schizophrenia.

Objective: Negative symptoms in schizophrenia indicate a poor prognosis. However, the mechanisms underlying the development of negative symptoms remain unclear. This study investigated the relationship between negative symptoms in schizophrenia and frontal alpha asymmetry (FAA). Methods: The study used a 32-channel electroencephalography to acquire alpha power in 4 target-paired sites in each patient. Regional alpha asymmetry was calculated based on the alpha power using EEGLAB Frontal Alpha Asymmetry Toolbox. Results: Sixty schizophrenia patients with predominant negative symptoms (PNS), 72 stabilized schizophrenia (SS) patients, and 73 healthy control (HC) participants were enrolled in this study. No significant differences were observed in FAA between the PNS and SS groups, although both groups exhibited reduced P3-P4 alpha asymmetry compared to HCs. A positive correlation was found between F7-F8 alpha asymmetry and illness duration. Additionally, a predictive model based on P3-P4 alpha asymmetry scores was able to differentiate schizophrenia patients from HCs, achieving a sensitivity of 71.2% and a specificity of 72.6%. Conclusion This study highlighted that parietal alpha asymmetry could serve as a valuable diagnostic tool for schizophrenia.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.

Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.

Objective To observe the clinical efficacy of modified Dahuang Fuzi Decoction following the therapy of unblocking bowels for the treatment of acute pancreatitis of pathogenic-cold accumulation and retention type.Methods A total of 78 patients with acute pancreatitis of pathogenic-cold accumulation and retention type were randomly divided into a study group and a control group,39 cases in each group.The control group was treated with conventional western medicine,and the study group was treated with oral use or nasogastric feeding of Dahuang Fuzi Decoction on the basis of treatment for the control group.The course of treatment covered seven days.The two groups were observed in the changes of serum pancreatic enzyme indicators of serum amylase and lipase,inflammatory factors of C-reactive protein(CRP),procalcitonin(PCT),interleukin-6(IL-6)and interleukin-8(IL-8),acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,and modified CT severity index(MCTSI)score before and after treatment.The time for abdominal pain relief,time for abdominal distension relief,and time for anal defecation were compared between the two groups.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)During the trial,there was one patient falling off separately from the study group and the control group,and 38 patients in each group were eventually included in the efficacy statistics.(2)After seven days of treatment,the total effective rate of the study group was 86.84％(33/38),and that of the control group was 78.95％(30/38).The intergroup comparison(tested by rank sum test)showed that the efficacy of the study group was significantly superior to that of the control group(P＜0.05).(3)After treatment,the serum levels of pancreatic enzyme indicators of amylase and lipase in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease of serum amylase and lipase levels in the study group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the serum levels of inflammatory factors of CRP,PCT,IL-6 and IL-8 in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease of serum CRP,PCT,IL-6 and IL-8 levels in the study group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the APACHE Ⅱ and MCTSI scores of the two groups were decreased compared with those before treatment(P＜0.05),and the decrease of APACHE Ⅱ and MCTSI scores in the study group was significantly superior to that in the control group(P＜0.05).(6)For the time of symptom relief,the time for abdominal pain relief,time for abdominal distension relief,and time for anal defecation in the study group were significantly shortened compared with those in the control group,and the differences were statistically significant(P＜0.05).(7)No obvious adverse reactions occurred in the two groups during the treatment,indicating high safety.Conclusion On the basis of conventional treatment,the use of modified Dahuang Fuzi Decoction following the therapy of unblocking bowels exerts certain efficacy for the treatment of patients with acute pancreatitis of pathogenic-cold accumulation and retention type.The therapy is effective on relieving the symptoms and signs of patients,and decreasing the level of serum pancreatic enzyme indicators and inflammatory factors.

R-spondin2 (Rspo2) is a member of protein family RSPOs, which can be coupled to receptor 4/5 (leucine-rich repeat-containing g protein-coupled receptor 4/5, LGR4/5), cell surface transmembrane E3 ubiquitin ligase ZNRF3/RNF43 (zinc and ring finger 3/ring finger protein 43), heparan sulfate proteoglycan (heparan sulfate proteoglycans, HSPGs) and the IQ motif (IQ gap 1) containing GTP enzyme activating protein 1, regulating the Wnt/β-catenin signaling pathway, which is the most widely studied signaling pathway and directly related to basic bone biology. Any problem in this pathway may have an impact on bone regulation. In recent years, it has been found that Rspo2 can act on osteoblast, osteoclast and chondrocytes through Wnt/β-catenin, and take part in occureace and development of some bone diseases such as ossification of the posterior longitudinal ligament (OPLL), osteoarthritis (OA) and rheumatoid arthritis (RA), so the study of Rspo2 may become a new therapeutic direction for bone-related diseases. Based on the latest research progress, this paper reviews the structure and main functions of Rspo2, the mechanism of Rspo2 regulating Wnt/β-catenin signaling pathway and its influence on skeletal system, in order to provide new ideas and ways for the prevention and treatment of bone-related diseases.