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Xiao-Meng Xie,1 Sha Sha,1 Hong Cai,2 Xinyu Liu,1 Isadora Jiang,3 Ling Zhang,1 Gang Wang1 1The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders Beijing Anding Hospital & the Advanced Innovation Center for Human Brain Protection, Capital Medical University, School of Mental Health, Beijing, People’s Republic of China; 2Unit of Medical Psychology and Behavior Medicine, School of Public Health, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3Bellarmine College of Liberal Arts, Loyola Marymount University, Los Angeles, CA, USACorrespondence: Gang Wang, Beijing Anding Hospital, Beijing, People’s Republic of China, Email gangwangdoc@gmail.comBackground: Major depressive disorder (MDD) becomes one of the psychiatric disorders characteristic of a combination of cognitive, emotional, and somatic symptoms. Additionally, cognitive impairment has the most significant impact on functional results. However, the evaluation of cognitive level is still based on various subjective questionnaires as there is no objective standard assessment yet. This research focuses on resting-state alpha activity to identify cognition in MDD patients using electroencephalography (EEG) signals.Methods: Ninety-two subjects were recruited: 44 patients with MDD and 48 healthy individuals as controls. Functional outcome and cognition were assessed using standardized instruments, and the EEG resting state signal of open and closed eyes was recorded. The comparison and correlation of cognitive levels with alpha power in the bilateral frontal region, bilateral central region, bilateral occipital region, and middle line was evaluated.Results: The relative alpha power in MDD group was significantly lower than that in the control group (P < 0.05). Through correlation analysis, it was shown that the bilateral frontal and occipital alpha power of MDD patients in the closed-eyes state was positively correlated with information processing rate, verbal learning, working memory, and attention retention. The alpha power of the bilateral frontal region in the open-eyes state was positively correlated with information processing rate, working memory, and attention retention (P < 0.05).Conclusion: The research indicates that the changes in frontal and occipital alpha activities may be a promising neurophysiological indicator of cognitive level to diagnose and treat response prediction.Keywords: major depressive disorder, MDD, EEG, alpha power, cognition impairment

Sumei Sha,1,&ast; Haitao Shi,1,&ast; Jie Wu,2,&ast; Ming Zhang,3 Bin Qin,1 Longbao Yang,1 Xin Liu1 1Department of Gastroenterology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Pathology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Respiratory, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Liu, Department of Gastroenterology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710004, People’s Republic of China, Email docliuxin126@xjtu.edu.cnIntroduction: Patients with inflammatory bowel disease are at high risk for opportunistic infections, and fungal infections are relatively uncommon among various infections.Case: This case is the first reported ulcerative colitis accompanied with Cryptococcus neoformans infection after infliximab treatment. In the course of the disease, the patients had a variety of opportunistic infections, including viruses, fungi and bacteria.Conclusion: This case highlights the importance of paying continued attention to opportunistic infections for patients with inflammatory bowel disease.Keywords: ulcerative colitis, Cryptococcus neoformans pneumonia, cytomegalovirus infection, clostridium difficile infection, biological agents, case report

Hong Cai,1– 3,&ast; Yan-jie Zhao,1– 3,&ast; Xiaomeng Xing,4,&ast; Tengfei Tian,4,&ast; Wang Qian,4 Sixiang Liang,4 Zhe Wang,4 Teris Cheung,5 Zhaohui Su,6 Yi-Lang Tang,7,8 Chee H Ng,9 Sha Sha,4 Yu-Tao Xiang1– 3 1Unit of Psychiatry, Department of Public Health and Medicinal Administration, & Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macao Special Administrative Region, People’s Republic of China; 2Centre for Cognitive and Brain Sciences, University of Macau, Macao Special Administrative Region, People’s Republic of China; 3Institute of Advanced Studies in Humanities and Social Sciences, University of Macau, Macao Special Administrative Region, People’s Republic of China; 4The National Clinical Research Center for Mental Disorder & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital & the Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China; 5School of Nursing, Hong Kong Polytechnic University, Hong Kong Special Administrative Region, People’s Republic of China; 6School of Public Health, Southeast University, Nanjing, China, Nanjing, People’s Republic of China; 7Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA; 8Atlanta VA Medical Center, Decatur, GA, USA; 9Department of Psychiatry, The Melbourne Clinic and St Vincent’s Hospital, University of Melbourne, Richmond, Victoria, Australia&ast;These authors contributed equally to this workCorrespondence: Sha Sha, The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders Beijing Anding Hospital & the Advanced Innovation Center for Human Brain Protection, Capital Medical University, School of Mental Health, Beijing, People’s Republic of China, Email sarahbon@163.com Chee H Ng, Department of Psychiatry, The Melbourne Clinic and St Vincent’s Hospital, University of Melbourne, Richmond, Victoria, Australia, Email cng@unimelb.edu.auBackground: A high proportion of clinicians experienced common anxiety, insomnia and depression during the COVID-19 pandemic. This study examined the item-level association of comorbid anxiety and insomnia symptoms among clinicians who suffered from depressive symptoms during the late stage of the COVID-19 pandemic using network analysis (NA).Methods: Clinicians with depressive symptoms (with a Patients Health Questionnaire (PHQ-9) total score of 5 and above) were included in this study. Anxiety and insomnia symptoms were measured using the Generalized Anxiety Disorder Scale - 7-item (GAD-7) and Insomnia Severity Index (ISI), respectively. Network analysis was conducted to investigate the network structure, central symptoms, bridge symptoms, and network stability of these disturbances. Expected influence (EI) was used to measure the centrality of index.Results: Altogether, 1729 clinicians were included in this study. The mean age was 37.1 [standard deviation (SD)=8.04 years], while the mean PHQ-9 total score was 8.42 (SD=3.33), mean GAD-7 total score was 6.45 (SD=3.13) and mean ISI total score was 8.23 (SD=5.26). Of these clinicians, the prevalence of comorbid anxiety symptoms (GAD-7≥ 5) was 76.8% (95% CI 74.82– 78.80%), while the prevalence of comorbid insomnia symptoms (ISI≥ 8) was 43.8% (95% CI: 41.50– 46.18%). NA revealed that nodes ISI7 (“Interference with daytime functioning”) (EI=1.18), ISI4 (“Sleep dissatisfaction”) (EI=1.08) and ISI5 (“Noticeability of sleep problem by others”) (EI=1.07) were the most central (influential) symptoms in the network model of comorbid anxiety and insomnia symptoms in clinicians. Bridge symptoms included nodes PHQ3 (“Sleep”) (bridge EI=0.55) and PHQ4 (“Fatigue”) (bridge EI=0.49). Gender did not significantly influence the network structure, but “having the experience of caring for COVID-19 patients” significantly influenced the network structure.Conclusion: Central symptoms and key bridge symptoms identified in this NA should be targeted in the treatment and preventive measures for clinicians suffering from comorbid anxiety, insomnia and depressive symptoms during the late stage of the COVID-19 pandemic.Keywords: depression, anxiety, sleep, network analysis, health personnel

Biling Jiang,1,&ast; Yamin Zhang,1,&ast; Yuce Li,2 Yu Chen,2 Shanshan Sha,1 Liang Zhao,1 Danqi Li,1 Jingjing Wen,1 Jiajia Lan,1 Yuchen Lou,1 Hua Su,3 Chun Zhang,3 Jintao Zhu,2 Juan Tao1 1Hubei Engineering Research Center of Skin Disease Theranostics and Health, Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, People’s Republic of China; 2Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, HUST, Wuhan, People’s Republic of China; 3Department of Nephrology, Union Hospital, Tongji Medical College, HUST, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan Tao; Jintao Zhu, Email tjhappy@126.com; jtzhu@mail.hust.edu.cnBackground: Mycophenolate mofetil (MMF), for which the bioactive metabolite is mycophenolic acid (MPA), is a frequently used immunosuppressant for systemic lupus erythematosus (SLE). However, its short half-life and poor biodistribution into cells and tissues hinder its clinical efficacy. Our dextran mycophenolate-based nanoparticles (MPA@Dex-MPA NPs) have greatly improved the pharmacokinetics of MMF/MPA. We here tested the therapeutic efficacy of MPA@Dex-MPA NPs against SLE and investigated the underlying mechanism.Methods: The tissue and immune cell biodistributions of MPA@Dex-MPA NPs were traced using live fluorescence imaging system and flow cytometry, respectively. Serological proinflammatory mediators and kidney damage were detected to assess the efficacy of MPA@Dex-MPA NPs treatments of MRL/lpr lupus-prone mice. Immune cell changes in the kidney and spleen were further analyzed post-treatment via flow cytometry. Bone marrow-derived macrophages were used to investigate the potential mechanism.Results: MPA@Dex-MPA NPs exhibited superior therapeutic efficacy and safety in the MRL/lpr mice using significantly lower administration dosage (one-fifth) and frequency (once/3 days) compared to MMF/MPA used in ordinary practice. The overall prognosis of the mice was improved as they showed lower levels of serological proinflammatory mediators. Moreover, kidney injury was alleviated with reduced pathological signs and decreased urine protein-creatinine ratio. Further investigations of the underlying mechanism revealed a preferential penetration and persistent retention of MPA@Dex-MPA NPs in the spleen and kidney, where they were mostly phagocytosed by macrophages. The macrophages were found to be polarized towards a CD206+ M2-like phenotype, with a downregulation of surface CD80 and CD40, and reduced TNF-α production in the spleen and kidney and in vitro. The expansion of T cells was also significantly inhibited in these two organs.Conclusion: Our research improved the efficacy of MPA for MRL/lpr mice through synthesizing MPA@Dex-MPA NPs to enhance its tissue biodistribution and explored the possible mechanism, providing a promising strategy for SLE therapy.Graphical Abstract: Keywords: mycophenolate, nanoparticles, macrophage polarization, tissue damage, systemic lupus erythematosus

Wei Bai,1– 3,&ast; Yanjie Zhao,1– 3,&ast; Fengrong An,4,&ast; Qinge Zhang,4,&ast; Sha Sha,4,&ast; Teris Cheung,5 Calvin Pak-Wing Cheng,6 Chee H Ng,7 Yu-Tao Xiang1– 3 1Unit of Psychiatry, Department of Public Health and Medicinal Administration, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macao SAR, People’s Republic of China; 2Centre for Cognitive and Brain Sciences, University of Macau, Macao SAR, People’s Republic of China; 3Institute of Advanced Studies in Humanities and Social Sciences, University of Macau, Macao SAR, People’s Republic of China; 4The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders Beijing Anding Hospital & the Advanced Innovation Center for Human Brain Protection, Capital Medical University, School of Mental Health, Beijing, People’s Republic of China; 5School of Nursing, Hong Kong Polytechnic University, Hong Kong SAR, People’s Republic of China; 6Department of Psychiatry, University of Hong Kong, Hong Kong SAR, People’s Republic of China; 7Department of Psychiatry, The Melbourne Clinic and St Vincent’s Hospital, University of Melbourne, Richmond, VIC, Australia&ast;These authors contributed equally to this workCorrespondence: Yu-Tao XiangFaculty of Health Sciences, University of Macau, 1/F, Building E12, Avenida da Universidade, Taipa, Macao SAR, People’s Republic of ChinaTel +853 8822-4223Fax +853 2288-2314Email xyutly@gmail.comChee H NgDepartment of Psychiatry, The Melbourne Clinic and St Vincent’s Hospital, University of Melbourne, Richmond, VIC, AustraliaEmail cng@unimelb.edu.auPurpose: The coronavirus disease 2019 (COVID-19) pandemic is associated with increased risk of insomnia symptoms (insomnia hereafter) in health-care professionals. Network analysis is a novel approach in linking mechanisms at the symptom level. The aim of this study was to characterize the insomnia network structure in mental health professionals during the COVID-19 pandemic.Patients and Methods: A total of 10,516 mental health professionals were recruited from psychiatric hospitals or psychiatric units of general hospitals nationwide between March 15 and March 20, 2020. Insomnia was assessed with the insomnia severity index (ISI). Centrality index (ie, strength) was used to identify symptoms central to the network. The stability of network was examined using a case-dropping bootstrap procedure. The network structures between different genders were also compared.Results: The overall network model showed that the item ISI7 (interference with daytime functioning) was the most central symptom in mental health professionals with the highest strength. The network was robust in stability and accuracy tests. The item ISI4 (sleep dissatisfaction) was connected to the two main clusters of insomnia symptoms (ie, the cluster of nocturnal and daytime symptoms). No significant gender network difference was found.Conclusion: Interference with daytime functioning was the most central symptom, suggesting that it may be an important treatment outcome measure for insomnia. Appropriate treatments, such as stimulus control techniques, cognitive behavioral therapy and relaxation training, could be developed. Moreover, addressing sleep satisfaction in treatment could simultaneously ameliorate daytime and nocturnal symptoms.Keywords: sleep, insomnia, SARS-CoV-2, COVID-19, physicians

The pathogenesis of acute myeloid leukemia (AML) involves serial acquisition of mutations controlling several cellular processes, requiring combination therapies affecting key downstream survival nodes in order to treat the disease effectively. The BCL2 selective inhibitor venetoclax has potent anti-leukemia efficacy; however, resistance can occur due to its inability to inhibit MCL1, which is stabilized by the MAPK pathway. In this study, we aimed to determine the anti-leukemia efficacy of concomitant targeting of the BCL2 and MAPK pathways by venetoclax and the MEK1/2 inhibitor cobimetinib, respectively. The combination demonstrated synergy in seven of 11 AML cell lines, including those resistant to single agents, and showed growth-inhibitory activity in over 60% of primary samples from patients with diverse genetic alterations. The combination markedly impaired leukemia progenitor functions, while maintaining normal progenitors. Mass cytometry data revealed that BCL2 protein is enriched in leukemia stem/progenitor cells, primarily in venetoclax-sensitive samples, and that cobimetinib suppressed cytokine-induced pERK and pS6 signaling pathways. Through proteomic profiling studies, we identified several pathways inhibited downstream of MAPK that contribute to the synergy of the combination. In OCI-AML3 cells, the combination downregulated MCL1 protein levels and disrupted both BCL2:BIM and MCL1:BIM complexes, releasing BIM to induce cell death. RNA sequencing identified several enriched pathways, including MYC, mTORC1, and p53 in cells sensitive to the drug combination. In vivo, the venetoclax-cobimetinib combination reduced leukemia burden in xenograft models using genetically engineered OCI-AML3 and MOLM13 cells. Our data thus provide a rationale for combinatorial blockade of MEK and BCL2 pathways in AML.

BACKGROUND AND PURPOSE: In vivo MR imaging and postmortem neuropathologic studies have demonstrated elevated iron concentration and atrophy within the striatum of patients with Huntington disease, implicating neuronal loss and iron accumulation in the pathogenesis of this neurodegenerative disorder. We used 7T MR imaging to determine whether quantitative phase, a measurement that reflects both iron content and tissue microstructure, is altered in subjects with premanifest Huntington disease. MATERIALS AND METHODS: Local field shift, calculated from 7T MR phase images, was quantified in 13 subjects with premanifest Huntington disease and 13 age- and sex-matched controls. All participants underwent 3T and 7T MR imaging, including volumetric T1 and 7T gradient recalled-echo sequences. Local field shift maps were created from 7T phase data and registered to caudate ROIs automatically parcellated from the 3T T1 images. Huntington disease-specific disease burden and neurocognitive and motor evaluations were also performed and compared with local field shift. RESULTS: Subjects with premanifest Huntington disease had smaller caudate volume and higher local field shift than controls. A significant correlation between these measurements was not detected, and prediction accuracy for disease state improved with inclusion of both variables. A positive correlation between local field shift and genetic disease burden was also found, and there was a trend toward significant correlations between local field shift and neurocognitive tests of working memory and executive function. CONCLUSIONS: Subjects with premanifest Huntington disease exhibit differences in 7T MR imaging phase within the caudate nuclei that correlate with genetic disease burden and trend with neurocognitive assessments. Ultra-high-field MR imaging of quantitative phase may be a useful approach for monitoring neurodegeneration in premanifest Huntington disease.

In this work, the influence of Mn and Ca doping on the microstructure and mechanical properties of Mg–3Zn, Mg–3Zn-0.5Mn, and Mg–3Zn-0.5Mn-1.2Ca alloys is systematically investigated. The addition of Mn elements is shown to exert no obvious effect on the microstructure of as-cast, as-homogenized, and extruded Mg–3Zn alloys. In contrast, the introduction of Ca into the extruded Mg–3Zn-0.5Mn alloy promotes the formation of nano-sized compounds and enhances grain refinement compared to the other two alloys. The extruded Mg–3Zn-0.5Mn alloy exhibits the higher yield strength (YS, 155 MPa) and ultimate tensile strength (UTS, 183 MPa) but the lower elongation (13%) than the extruded Mg–3Zn alloy (YS of 130 MPa, UTS of 175 MPa, and elongation of 25%). The improved strength of the extruded Mg–3Zn-0.5Mn alloy is mainly attributed to the refined grains, while both the lack of twinning deformation and strong texture result in ductility loss. The most optimal combination of strength and ductility is achieved in an extruded Mg–3Zn-0.5Mn-1.2Ca alloy (YS of 180 MPa, UTS of 250 MPa, and elongation of 26%). This suggests that fine grains and high volume fraction of nano-sized MgZn2 compounds contribute mainly to the strength of Mg–3Zn-0.5Mn-1.2Ca alloy. Although the grain refinement also facilitates the suppression of twinning in the extruded Mg–3Zn-0.5Mn-1.2Ca alloy, the weak texture and fine homogeneous grains are conducive to the high ductility.

Interventions to mitigate the negative impact of stress on college students through resilience-building strategies are attracting considerable interest; however, there has been little discussion regarding the strategies college students readily use to build their resilience. This study (1) describes and identifies patterns of college students’ resilience-promoting behaviors and (2) examines the relationships of resilience-promoting strategies with trait resilience and well-being.

Abstract This study aims to understand the connectivity characteristics of construction land during the spatial evolution of historic urban areas. The complex network analysis method is employed to examine the evolution of the spatial structure of construction land in the four periods of the Changsha historic urban area. The results indicate that the spatial network morphology of construction land follows a repeated development pattern resembling a cluster–mother–child relationship. Additionally, the vulnerability in the evolution of land use spatial relationships is very low, while the overall stability of the land use network structure decreases. The spatial equilibrium of land use shows a downwards trend, the accessibility of land where existing cultural relics and historic sites are located is generally moderate to low, and some plots require improvement. In the evolution of connectivity in the construction land of historic urban areas, the main development challenges are the uneven growth caused by imbalanced land value influenced by capital and the need to balance the preservation of land use patterns with improved accessibility to cultural relics and historic sites. Therefore, it is highly important to dynamically detect and optimize the network structure of construction land to protect and develop historic urban areas.

Purposes The economic dispatch of Integrated Energy Systems (IES) is a key research topic of energy technology reform, inherently a complex Mixed-Integer Nonlinear Programming problem. Traditional optimization methods have high computational complexity and struggle to adapt to the source-load uncertainty in IES coupled with renewable energy systems. Utilizing Deep Reinforcement Learning to decompose and accelerate the original problem enhances the efficiency of the IES economic dispatch model. Methods To address these issues, in this paper, an IES optimization dispatch framework based on an improved Proximal Policy Optimization (PPO) algorithm is proposed. The PPO algorithm is used to approximate some variables of the nonlinear constraints in the original model, converting them into linear constraints to speed up the solution. Findings The effectiveness and efficiency of this method over others are validated through case studies, predicting significant computational advantages in large-scale IES optimization problems.

Abstract The potential brain mechanism underlying resilience to socially transferred allodynia remains unknown. Here, we utilize a well-established socially transferred allodynia paradigm to segregate male mice into pain-susceptible and pain-resilient subgroups. Brain screening results show that ventral tegmental area glutamatergic neurons are selectively activated in pain-resilient mice as compared to control and pain-susceptible mice. Chemogenetic manipulations demonstrate that activation and inhibition of ventral tegmental area glutamatergic neurons bi-directionally regulate resilience to socially transferred allodynia. Moreover, ventral tegmental area glutamatergic neurons that project specifically to the nucleus accumbens shell and lateral habenula regulate the development and maintenance of the pain-resilient phenotype, respectively. Together, we establish an approach to explore individual variations in pain response and identify ventral tegmental area glutamatergic neurons and related downstream circuits as critical targets for resilience to socially transferred allodynia and the development of conceptually innovative analgesics.

Abstract Toll-like receptor 9 (TLR9) recognizes bacterial, viral and self DNA and play an important role in immunity and inflammation. However, the role of TLR9 in obesity is less well-studied. Here, we generate B-cell-specific Tlr9-deficient (Tlr9 fl/fl /Cd19Cre +/- , KO) B6 mice and model obesity using a high-fat diet. Compared with control mice, B-cell-specific-Tlr9-deficient mice exhibited increased fat tissue inflammation, weight gain, and impaired glucose and insulin tolerance. Furthermore, the frequencies of IL-10-producing-B cells and marginal zone B cells were reduced, and those of follicular and germinal center B cells were increased. This was associated with increased frequencies of IFNγ-producing-T cells and increased follicular helper cells. In addition, gut microbiota from the KO mice induced a pro-inflammatory state leading to immunological and metabolic dysregulation when transferred to germ-free mice. Using 16 S rRNA gene sequencing, we identify altered gut microbial communities including reduced Lachnospiraceae, which may play a role in altered metabolism in KO mice. We identify an important network involving Tlr9, Irf4 and Il-10 interconnecting metabolic homeostasis, with the function of B and T cells, and gut microbiota in obesity.

Healthcare workers’ (HCWs) attitudes toward vaccine greatly influences individuals’ vaccine acceptance rate. Research in high-income countries identified five key person-level factors for vaccine hesitancy. Perception of vaccine were different in low-income or developing country, and the reason for vaccine hesitancy might not be the same as that in developed countries. This study assesses HCWs parents’ attitude toward their child getting COVID-19 vaccine and the potential influencing factors in HCWs living in Gaza Strip.

Abstract Background The popularity of e-cigarettes is on the rise among current cigarette users. Therefore, there are concerns about their health implications. This study examined the impact of health-related social media use on e-cigarette use among current cigarette users. It assesses the mediating influence of online anti-tobacco messages and the moderating role of the harm perception of e-cigarettes. Methods This study was focused on 563 current cigarette users from the 2022 Health Information National Trends Survey (HINTS). Three tasks were performed: (1) assessing the direct and indirect impacts of health-related social media use on e-cigarette use among current cigarette users, (2) exploring the mediating role of exposure to online anti-tobacco messages, and (3) examining the moderating influence of e-cigarette harm perception on the path from anti-tobacco messages to e-cigarette use. Results Health-related social media use was positively associated with current cigarette users’ e-cigarette use directly (bp = 0.183, p

Abstract Background Oxidative stress (OS) plays a major role in the progress of hypoxic‐ischemic brain damage (HIBD). This study aimed to investigate OS‐related genes and their underlying molecular mechanisms in neonatal HIBD. Methods Microarray data sets were acquired from the Gene Expression Omnibus (GEO) database to screen the differentially expressed genes (DEGs) between control samples and HIBD samples. OS‐related genes were drawn from GeneCards and OS‐DEGs in HIBD were obtained by intersecting with the DEGs. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were conducted to determine the underlying mechanisms and functions of OS‐DEGs in HIBD. Moreover, the hub genes were screened using the protein−protein interaction network and identified in the GSE144456 data set. CIBERSORT was then performed to evaluate the expression of immunocytes in each sample and perform a correlation analysis of the optimal OS‐DEGs and immunocytes. Finally, quantitative reverse transcription polymerase chain reaction (RT‐qPCR) and immunohistochemistry were performed to validate the expression levels of the optimal OS‐DEGs. Results In total, 93 OS‐DEGs were identified. GO, KEGG, and GSEA enrichment analyses indicated that these genes were predominantly enriched in OS and inflammation. Four OS‐related biomarker genes (Jun, Fos, Tlr2, and Atf3) were identified and verified. CIBERSORT analysis revealed the dysregulation of six types of immune cells in the HIBD group. Moreover, 47 drugs that might target four OS‐related biomarker genes were screened. Eventually, RT‐qPCR and immunohistochemistry results for rat samples further validated the expression levels of Fos, Tlr2, and Atf3. Conclusions Fos, Tlr2 and Atf3 are potential OS‐related biomarkers of HIBD progression. The mechanisms of OS are associated with those of neonatal HIBD.

Summary: Liquid-liquid phase separation (LLPS) mediated by G3BP1/2 proteins and non-translating mRNAs mediates stress granule (SG) assembly. We investigated the phylogenetic evolution of G3BP orthologs from unicellular yeast to mammals and identified both conserved and divergent features. The modular domain organization of G3BP orthologs is generally conserved. However, invertebrate orthologs displayed reduced capacity for SG assembly in human cells compared to vertebrate orthologs. We demonstrated that the protein-interaction network facilitated by the NTF2L domain is a crucial determinant of this specificity. The evolution of the G3BP1 network coincided with its exploitation by certain viruses, as evident from the interaction between viral proteins and G3BP orthologs in insects and vertebrates. We revealed the importance and divergence of the G3BP interaction network in human SG formation. Leveraging this network, we established a 7-component in vitro SG reconstitution system for quantitative studies. These findings highlight the significance of G3BP network divergence in the evolution of biological processes.

Abstract The aim of this study is to compare ecologically-valid measure (the Cambridge Prospective Memory Test, CAMPROMPT) and laboratory measure (eye-tracking paradigm) in assessing prospective memory (PM) in individuals with schizophrenia spectrum disorders (SSDs). In addition, eye-tracking indices are used to examine the relationship between PM and other cognitive domains in SSDs patients. Initially, the study sample was formed by 32 SSDs patients and 32 healthy control subjects (HCs) who were matched in sociodemographic profile and the performance on CAMPROMPT. An eye-tracking paradigm was employed to examine the differences in PM accuracy and key cognitive processes (e.g., cue monitoring) between the two groups. Additional 31 patients were then recruited to investigate the relationship between PM cue monitoring, other cognitive functions, and the severity of clinical symptoms within the SSDs group. The monitoring of PM cue was reflected in total fixation time and total fixation counts for distractor words. Cognitive functions were assessed using the Chinese version of the MATRICS Consensus Cognitive Battery (MCCB). The Positive and Negative Syndrome Scale (PANSS) was applied to assess psychopathology. SSDs patients exhibited fewer total fixation counts for distractor words and lower PM accuracy compared to HCs, even though they were priori matched on CAMPROMPT. Correlation analysis within the SSDs group (63 cases) indicated a negative correlation between PM accuracy and PANSS total score, and a positive correlation with working memory and attention/vigilance. Regression analysis within the SSDs group revealed that higher visual learning and lower PANSS total scores independently predicted more total fixation counts on distractor words. Impairment in cue monitoring is a critical factor in the PM deficits in SSDs. The eye-tracking laboratory paradigm has advantages over the ecologically-valid measurement in identifying the failure of cue detection, making it a more sensitive tool for PM deficits in patients with SSDs.

Abstract Objective Placenta accreta spectrum disorder (PAS) is a serious obstetric complication associated with significant maternal morbidity and mortality. Prophylactic balloon occlusion (PBO), as an intravascular interventional therapies, has emerged as a potential management strategy for controlling massive hemorrhage in patients with PAS. However, current evidence about the clinical application of PBO in PAS patients are still controversial. This study aimed to evaluate the effectiveness and safety of PBO in the management of PAS. Methods A retrospective cohort study including PAS patients underwent cesarean delivery was conducted in a tertiary hospital from January 2015 to March 2022. Included PAS patients were further divided into balloon and control groups by whether PBO was performed. Groups were compared for demographic characteristics, intraoperative and postoperative parameters, maternal and neonatal outcomes, PBO-related complication and follow up outcomes. Additionally, multivariate-logistic regression analysis was performed to determine the definitive associations between PBO and risk of massive hemorrhage and hysterectomy. Results A total of 285 PAS patients met the inclusion criteria were included, of which 57 PAS patients underwent PBO (PBO group) and 228 women performed cesarean section (CS) without PBO (control group). Irrespective of the differences of baseline characteristics between the two groups, PBO intervention did not reduce the blood loss, hysterectomy rate and postoperative hospital stay, but it prolonged the operation time and increased the cost of hospitalization (All P 0.05). In particular, patients undergoing PBO were more likely to develop the venous thrombosis postoperatively (P = 0.001). However, multivariate logistic regression analysis showed that PBO significantly decreased the risk of massive hemorrhage (OR 0.289, 95%CI:0.109–0.766, P = 0.013). The grade of PAS and MRI with S2 invasion were the significant risk factors affecting massive hemorrhage(OR:6.232 and OR:5.380, P