A thermally reversible injectable adhesive for intestinal tissue repair and anti-postoperative adhesion.

Intestine damage is an acute abdominal disease that usually requires emergency sealing. However, traditional surgical suture not only causes secondary damage to the injured tissue, but also results in adhesion with other tissues in the abdominal cavity. To this end, a thermally reversible injectable gelatin-based hydrogel adhesive (GTPC) is constructed by introducing transglutaminase (TGase) and proanthocyanidins (PCs) into a gelatin system. By reducing the catalytic activity of TGase, the density of covalent and hydrogen bond crosslinking in the hydrogel can be regulated to tune the sol-gel transition temperature of gelatin-based hydrogels above the physiological temperature (42 °C) without introducing any synthetic small molecules. The GTPC hydrogel exhibits good tissue adhesion, antioxidant, and antibacterial properties, which can effectively seal damaged intestinal tissues and regulate the microenvironment of the damaged site, promoting tissue repair and regeneration. Intriguingly, temperature-induced hydrogen bond disruption and reformation confer the hydrogel with asymmetric adhesion properties, preventing tissue adhesion when applied in vivo. Animal experiment outcomes reveal that the GTPC hydrogel can seal the damaged intestinal tissue firmly, accelerate tissue healing, and efficiently prevent postoperative adhesion.

Roflupram alleviates autophagy defects and reduces mutant hSOD1-induced motor neuron damage in cell and mouse models of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal and incurable disease involving motor neuron (MN) degeneration and is characterized by ongoing myasthenia and amyotrophia in adults. Most ALS patients die of respiratory muscle paralysis after an average of 3-5 years. Defective autophagy in MNs is considered an important trigger of ALS pathogenesis. Roflupram (ROF) was demonstrated to activate autophagy in microglial cells and exert protective effects against Parkinson's disease (PD) and Alzheimer's disease (AD). Therefore, our research aimed to investigate the efficacy and mechanism of ROF in treating ALS both in vivo and in vitro. We found that ROF could delay disease onset and prolong the survival of hSOD1-G93A transgenic mice. Moreover, ROF protected MNs in the anterior horn of the spinal cord, activated the AMPK/ULK1 signaling pathway, increased autophagic flow, and reduced SOD1 aggregation. In an NSC34 cell line stably transfected with hSOD1-G93A, ROF protected against cellular damage caused by hSOD1-G93A. Moreover, we have demonstrated that ROF inhibited gliosis in ALS model mice. Collectively, our study suggested that ROF is neuroprotective in ALS models and the AMPK/ULK1 signaling pathway is a potential therapeutic target in ALS, which increases autophagic flow and reduces SOD1 aggregation.

SPY1 inhibits neuronal ferroptosis in amyotrophic lateral sclerosis by reducing lipid peroxidation through regulation of GCH1 and TFR1.

Ferroptosis is an iron-dependent cell death with the accumulation of lipid peroxidation and dysfunction of antioxidant systems. As the critical regulator, glutathione peroxidase 4 (GPX4) has been demonstrated to be down-regulated in amyotrophic lateral sclerosis (ALS). However, the mechanism of ferroptosis in ALS remains unclear. In this research, bioinformatics analysis revealed a high correlation between ALS, ferroptosis, and Speedy/RINGO cell cycle regulator family member A (SPY1). Lipid peroxidation of ferroptosis in hSOD1G93A cells and mice was generated by TFR1-imported excess free iron, decreased GSH, mitochondrial membrane dysfunction, upregulated ALOX15, and inactivation of GCH1, GPX4. SPY1 is a "cyclin-like" protein that has been proved to enhance the viability of hSOD1G93A cells by inhibiting DNA damage. In our study, the decreased expression of SPY1 in ALS was resulted from unprecedented ubiquitination degradation mediated by MDM2 (a nuclear-localized E3 ubiquitin ligase). Further, SPY1 was identified as a novel ferroptosis suppressor via alleviating lipid peroxidation produced by dysregulated GCH1/BH4 axis (a resistance axis of ferroptosis) and transferrin receptor protein 1 (TFR1)-induced iron. Additionally, neuron-specific overexpression of SPY1 significantly delayed the occurrence and prolonged the survival in ALS transgenic mice through the above two pathways. These results suggest that SPY1 is a novel target for both ferroptosis and ALS.

Theta Oscillations and Source Connectivity During Complex Audiovisual Object Encoding in Working Memory.

Working memory is a limited capacity memory system that involves the short-term storage and processing of information. Neuroscientific studies of working memory have mostly focused on the essential roles of neural oscillations during item encoding from single sensory modalities (e.g., visual and auditory). However, the characteristics of neural oscillations during multisensory encoding in working memory are rarely studied. Our study investigated the oscillation characteristics of neural signals in scalp electrodes and mapped functional brain connectivity while participants encoded complex audiovisual objects in a working memory task. Experimental results showed that theta oscillations (4-8 Hz) were prominent and topographically distributed across multiple cortical regions, including prefrontal (e.g., superior frontal gyrus), parietal (e.g., precuneus), temporal (e.g., inferior temporal gyrus), and occipital (e.g., cuneus) cortices. Furthermore, neural connectivity at the theta oscillation frequency was significant in these cortical regions during audiovisual object encoding compared with single modality object encoding. These results suggest that local oscillations and interregional connectivity via theta activity play an important role during audiovisual object encoding and may contribute to the formation of working memory traces from multisensory items.

Military Career Adaptability Questionnaire in China: Development and Validation.

OBJECTIVE: To develop the Military Career Adaptability Questionnaire (MCAQ) in China and to test its reliability and validity. METHODS: In study 1, an open-ended questionnaire survey was conducted among 200 military personnel. Based on the empirical construction by military personnel of various branches, the dimensions of the MCAQ were constructed, and a preliminary questionnaire was prepared. In study 2, the questionnaire survey was conducted in 1,578 participants enrolled through stratified cluster sampling. They were randomly divided into two groups (n = 789). Sample 1 was used for item analysis and exploratory factor analysis, and sample 2 was used for confirmatory factor analysis and internal consistency testing. In sample 1, the participants were selected to test the test-retest reliability of the questionnaire at a 4 weeks interval. In sample 2, participants were selected to test criterion validity using the Psychological Capital Questionnaire and the Job Satisfaction Questionnaire. RESULTS: According to study 1, we obtained an initial 23-item MCAQ containing five dimensions (organization and fusion ability, communication ability, learning development ability, emotion regulation ability, and career transformation ability). After the exploratory factor analysis in study 2, 21 items contributing 72.17% of the total variance remained. Via the subsequent confirmatory factor analysis, the model was confirmed to have good fit indices [chi-square/degree of freedom (X 2/df) = 3.11, goodness of fit index (GFI) = 0.90, normed fit index (NFI) = 0.91, incremental fit index (IFI) = 0.94, tucker lewis index (TLI) = 0.93, comparative fit index (CFI) = 0.94, standardized root mean square residual (SRMR) = 0.07]. These five factors were significantly correlated with the total score of the MCAQ (r = 0.73-0.79, p < 0.01). The Cronbach α coefficient of the questionnaire was 0.92; the Cronbach α coefficients of the five factors were 0.89, 0.83, 0.88, 0.84, and 0.79, respectively, the test-retest reliability of the questionnaire was 0.93. CONCLUSION: The MCAQ developed in this study has a clear five-factor structure and good reliability and validity. It can be used to assess the career adaptability of military personnel to provide a theoretical basis for military vocational psychological education.

Psychometric Properties of the Short Form of the Fear of Cancer Recurrence Inventory (FCRI) in Chinese Breast Cancer Survivors.

Objective: Currently, fear of cancer recurrence (FCR) is emerging as an important issue for long-term breast cancer survivors and is associated with lower quality of life and functional impairment. Given that there is a dearth of research regarding the FCR of Chinese breast cancer survivors, this study investigated whether the short form of the Fear of Cancer Recurrence Inventory (FCRI) could detect high FCR and explored the level and characteristics of FCR in breast cancer survivors. Methods: Two hundred forty patients who had undergone successful breast cancer surgery in China submitted their survey through a website. The participants' demographic and medical data, level of FCR, anxiety, depression, and quality of life were assessed. Results: Two hundred seven patients with ages ranging from 19 to 60 years completed the questionnaires. The mean FCR score of the total sample was 18.39. A cutoff score of 12 or higher on the short form of the FCRI was optimal for the detection of high FCR with a sensitivity of 98.6% and a specificity of 35%, and the PPV (positive predictive values) and NPV (negative predictive values) were 44% and 98%, respectively. The area under the curve of the receiver operating characteristics (ROC) analysis was 83%. A total of 159 breast cancer survivors (76.81%) experienced high FCR levels (FCR score > 12), characterized by lower functional and overall health than survivors with a low FCR (P < 0.01). Conclusions: The short form of the FCRI is capable of detecting high FCR and is therefore able to assist Chinese breast cancer survivors in receiving appropriate care for reducing FCR.

Transcriptional Regulation Involved in Fear Memory Reconsolidation.

Memory reconsolidation has been demonstrated to offer a potential target period during which the fear memories underlying fear disorders can be disrupted. Reconsolidation is a labile stage that consolidated memories re-enter after memories are reactivated. Reactivated memories, induced by cues related to traumatic events, are susceptible to strengthening and weakening. Gene transcription regulation and protein synthesis have been suggested to be required for fear memory reconsolidation. Investigating the transcriptional regulation mechanisms underlying reconsolidation may provide a therapeutic method for the treatment of fear disorders such as post-traumatic stress disorder (PTSD). However, the therapeutic effect of treating a fear disorder through interfering with reconsolidation is still contradictory. In this review, we summarize several transcription factors that have been linked to fear memory reconsolidation and propose that transcription factors, as well as related signaling pathways can serve as targets for fear memory interventions. Then, we discuss the application of pharmacological and behavioral interventions during reconsolidation that may or not efficiently treat fear disorders.