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Abstract: A series of Cu-substituted LiNi0.5−x Cu x Mn1.5O4 (x =0, 0.03, 0.05 and 0.08) spinels have been synthesized using a sol–gel method. The results demonstrate that when x =0.05, the sample (LiNi0.45Cu0.05Mn1.5O4) exhibits the best electrochemical performance, achieving 124.5mAhg−1 and 115.0mAhg−1 at the discharge rates of 5C and 20C with the capacity retention of 97.7% and 95.7% after 150 cycles, respectively. Besides, the excellent cycle stability at 55°C has been demonstrated to retain 96.8% of the maximum attainable discharge capacity (127.3mAhg−1) at the discharge rate of 5C after 100 cycles. These data indicate that the LiNi0.45Cu0.05Mn1.5O4 cathode material has the real potential to be used for high power and high energy lithium ion battery in electric vehicle applications. [Copyright &y& Elsevier]

Abstract: Li3V2(PO4)3/C composite material has been firstly synthesized via a sol–gel method based on the composite chelating reagents of glycine and beta-cyclodextrin. The product is investigated by X-ray diffraction (XRD), scanning electron microscope (SEM), high-resolution transmission electron microscopy (HR-TEM) and electrochemical method. In the range of 3.0–4.3V, the LVP/C electrode presents excellent cyclic performance at high discharge rates. The largest capacities of 87.1, 89.9 and 74.5mAhg−1 are delivered at 0.9C charge and 35C discharge rates, 0.7C charge and 40C discharge rates, 0.6C charge and 50C discharge rates, respectively. 86.8%, 89.7% and 90.8% of the largest values are retained for the LVP/C electrode at the three discharge rates in the 500th, 300th and 250th cycles, respectively. The unexceptionable high-rate and cyclic performance is attributed to the existence of the composite carbon sources and the small particle size of the Li3V2(PO4)3/C. [Copyright &y& Elsevier]

Spike sorting is a fundamental process for decoding neural activity, involving preprocessing, spike detection, feature extraction, clustering, and validation. However, conventional spike sorting methods are highly fragmented, labor-intensive, and heavily reliant on expert manual curation, limiting their scalability and reproducibility. This challenge has become more pressing with advances in neural recording technology, such as high-density Neuropixels for large-scale neural recording or flexible electrodes for long-term stable recording over months to years. The volume and complexity of these datasets make manual curation infeasible, requiring an automated and scalable solution. Here, we introduce SpikeAgent, a multimodal large language model (LLM)-based AI agent that automates and standardizes the entire spike sorting pipeline. Unlike traditional approaches, SpikeAgent integrates multiple LLM backends, coding functions, and established algorithms, autonomously performing spike sorting with reasoning-based decision-making and real-time interaction with intermediate results. It generates interpretable reports, providing transparent justifications for each sorting decision, enhancing transparency and reliability. We benchmarked SpikeAgent against human experts across various neural recording technology, demonstrating its versatility and ability to achieve curation consistency that are equal to, or even higher than human experts. It also drastically reduces the expertise barrier and accelerates the curation and validation time by orders of magnitude. Moreover, it enables automated interpretability of the neural spiking data, which cannot be achieved by any conventional methods. SpikeAgent presents a paradigm shift in processing signals for neuroscience and brain-computer interfaces, while laying the ground for AI agent-augmented science across various domains.

Background: Cytomegalovirus (CMV) infection remains a critical cause of mortality after allogeneic hematopoietic stem cell transplantation, despite significant advancements in CMV prevention and treatment with the introduction and widespread use of letermovir. However, in China, due to limitations in the availability and cost of medications, some patients still face challenges in accessing letermovir. For this subset of the population, exploring the risk factors for CMV infection remains significant in predicting its occurrence., Methods: Therefore, a retrospective analysis was conducted on 88 haploidentical hematopoietic stem cell transplant recipients over 4 years., Results: Our study results indicate that chronic graft-versus-host disease (cGVHD) is an independent risk factor for CMV infection following haploidentical hematopoietic stem cell transplantation (Haplo-HSCT). Survival analysis reveals lower survival rates in the refractory CMV infection (RCI) group compared to the non-RCI group, with patients having lower viral loads demonstrating higher rates of seroconversion and improved survival under the same treatment regimen., Conclusion: Strengthening the monitoring of CMV-DNA in post-transplant patients, actively promoting hematopoietic recovery, preventing the occurrence of CMV infection, and controlling the development of CMV infection can lead to better survival outcomes for patients with aplastic anemia undergoing Haplo-HSCT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Feng, Zhang, Tan, Zhao, Hu, Chen, Wu, Yu, Wu, Ye and Liu.)

Aplastic anemia (AA) is a life-threatening bone marrow failure syndrome. The advent of next-generation sequencing (NGS) has shed light on the link between somatic mutations (SM) and the efficacy of immunosuppressive therapy (IST) in AA patients. However, the relationship between SM and hematopoietic stem cell transplantation (HSCT) has not been extensively explored. In this retrospective analysis, we examined 166 AA patients who received HSCT or IST at our institution between May 2019 and December 2023. NGS was conducted on 66 genes within bone marrow cells to investigate the correlation between SM and the prognosis and therapeutic response in AA patients, as well as to assess the impact of mutation types on HSCT outcomes. Clinical data were gathered from 166 AA patients, comprising 84 males and 82 females, with a median age of 32 years (ranging from 9 to 75 years). In our study, a total of 151 somatic mutations were identified across 84 patients (50.6%), with 42 patients (25.3%) presenting a single mutation and 26 patients (15.7%) harboring two mutations. The top five genes with the highest mutation frequency were BCOR/BCORL1 (12.6%), ASXL1 (8.6%), TET2 (6.6%), CEBPA (5.3%), and GATA2 (4.6%). We stratified patients into SM and No-SM groups based on the presence of mutations and further divided them into HSCT and IST groups to assess the influence of mutation types on treatment response and survival within and between these groups. The findings were as follows: 1.Patients in the HSCT group exhibited a higher treatment response (OR 85.9% vs. 68.4%, p < 0.05), although there was no significant difference in survival. 2.Patients with favorable mutations, such as PIGA and BCOR/BCORL1, experienced significantly improved response and survival compared to those with unfavorable mutations like ASXL1, DNMT3A, and TET2 (OR 93.7% vs. 72%, p < 0.05) (3-year OS 93.7% vs. 80%, p > 0.05). 3.The HSCT-Favorable group demonstrated superior response rates (OR 100% vs. 67.7%, p < 0.05) and longer survival (3-year OS 100% vs. 67.7%, p < 0.05) compared to the IST-Favorable group. This study underscores that AA patients carrying favorable mutations, particularly BCOR/BCORL1, tend to have a more robust response and better prognosis than those without mutations or those with unfavorable mutations, such as ASXL1/DNMT3A. These findings are especially pertinent to HSCT, highlighting the importance of NGS prior to initiating treatment., Competing Interests: Declarations. Ethics approval and consent to participate: The experimental protocol was established according to the ethical guidelines of the Helsinki Declaration and was approved by the Ethics Committee of The First Affiliated Hospital of Zhejiang Chinese Medical University. (approval number: 2024-KLS-290-01). Written informed consent was obtained from individual or guardian participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Electrocatalytic nitrate reduction (NO3RR) is a promising method for pollutant removal and ammonia synthesis and involves the transfer of eight electrons and nine protons. As such, the rational design of catalytic interfaces with enhanced mass transfer is crucial for achieving high ammonia yield rates and Faradaic efficiency (FE). In this work, we incorporated a Cu-bipyridine catalytic interface and fabricated crystalline 2D covalent organic framework films with significantly exposed catalytic sites, leading to improved FE and ammonia yield (FE = 92.7%, NH3 yield rate = 14.9 mg·h-1cm-2 in 0.5 M nitrate) compared to bulk catalysts and outperforming most reported NO3RR electrocatalysts. The film-like morphology enhances mass transfer across the Cu-bipyridine interface, resulting in superior catalytic performance. We confirmed the reaction pathway and mechanism through in-situ characterizations and theoretical calculations. The Cu sites act as primary centers for adsorption and activation, while the bipyridine sites facilitate water adsorption and dissociation, supplying sufficient H* and accelerating proton-coupled electron transfer kinetics. This study provides a viable strategy to enhance mass transfer at the catalytic interface through rational morphology control, boosting the intrinsic activity of catalysts in the NO3RR process., (© 2024 Wiley‐VCH GmbH.)

Recent advancements in flexible bioelectronics have enabled continuous, long-term stable interrogation and intervention of biological systems. However, effectively utilizing the interrogated data to modulate biological systems to achieve specific biomedical and biological goals remains a challenge. In this study, we introduce an AI-driven bioelectronics system that integrates tissue-like, flexible bioelectronics with cyber learning algorithms to create a long-term, real-time bidirectional b ioelectronic interface with o ptimized a daptive intelligent m odulation (BIO-AIM). When integrated with biological systems as an AI-cyborg system, BIO-AIM continuously adapts and optimizes stimulation parameters based on stable cell state mapping, allowing for real-time, closed-loop feedback through tissue-embedded flexible electrode arrays. Applied to human pluripotent stem cell-derived cardiac organoids, BIO-AIM identifies optimized stimulation conditions that accelerate functional maturation. The effectiveness of this approach is validated through enhanced extracellular spike waveforms, increased conduction velocity, and improved sarcomere organization, outperforming both fixed and no stimulation conditions.

Importance: Suicide is the third-leading cause of death among US adolescents. Environmental and lifestyle factors influence suicidal behavior and can inform risk classification, yet quantifying and incorporating them in risk assessment presents a significant challenge for reproducibility and clinical translation., Objective: To quantify the aggregate contribution of environmental and lifestyle factors to youth suicide attempt risk classification., Design, Setting, and Participants: This was a cohort study in 3 youth samples: 2 national longitudinal cohorts from the US and the UK and 1 clinical cohort from a tertiary pediatric US hospital. An exposome-wide association study (ExWAS) approach was used to identify risk and protective factors and compute aggregate exposomic scores. Logistic regression models were applied to test associations and model fit of exposomic scores with suicide attempts in independent data. Youth from the Adolescent Brain Cognitive Development (ABCD) study, the UK Millennium Cohort Study (MCS), and the Children's Hospital of Philadelphia emergency department (CHOP-ED) were included in the study., Exposures: A single-weighted exposomic score that sums significant risk and protective environmental/lifestyle factors., Main Outcome and Measure: Self-reported suicide attempt., Results: A total of 40 364 youth were included in this analysis: 11 564 from the ABCD study (3 waves of assessment; mean [SD] age, 12.0 [0.7] years; 6034 male [52.2%]; 344 attempted suicide [3.0%]; 1154 environmental/lifestyle factors were included in the ABCD study), 9000 from the MCS cohort (mean [SD] age, 17.2 [0.3] years; 4593 female [51.0%]; 661 attempted suicide [7.3%]; 2864 environmental/lifestyle factors were included in the MCS cohort), and 19 800 from the CHOP-ED cohort (mean [SD] age, 15.3 [1.5] years; 12 937 female [65.3%]; 2051 attempted suicide [10.4%]; 36 environmental/lifestyle factors were included in the CHOP-ED cohort). In the ABCD discovery subsample, ExWAS identified 99 risk and protective exposures significantly associated with suicide attempt. A single weighted exposomic score that sums significant risk and protective exposures was associated with suicide attempt in an independent ABCD testing subsample (odds ratio [OR], 2.2; 95% CI, 2.0-2.6; P < .001) and explained 17.6% of the variance (based on regression pseudo-R2) in suicide attempt over and above that explained by age, sex, race, and ethnicity (2.8%) and by family history of suicide (6.3%). Findings were consistent in the MCS and CHOP-ED cohorts (explaining 22.6% and 19.3% of the variance in suicide attempt, respectively) despite clinical, demographic, and exposure differences. In all cohorts, compared with youth at the median quintile of the exposomic score, youth at the top fifth quintile were substantially more likely to have made a suicide attempt (OR, 4.3; 95% CI, 2.6-7.2 in the ABCD study; OR, 3.8; 95% CI, 2.7-5.3 in the MCS cohort; OR, 5.8; 95% CI, 4.7-7.1 in the CHOP-ED cohort)., Conclusions and Relevance: Results suggest that exposomic scores of suicide attempt provided a generalizable method for risk classification that can be applied in diverse samples from clinical or population settings.

Introduction: Lymphangioleiomyomatosis (LAM) is a rare and progressive disorder that usually arises in the lung and almost exclusively affects women of childbearing age. In recent years, a number of molecules have been shown to be differentially expressed between patients with LAM and healthy control individuals, and some of these molecules, in addition to vascular endothelial growth factor D (VEGF-D), have the potential to be novel biomarkers., Areas Covered: This review summarizes the recent advances in omics research, including genomics, transcriptomics, proteomics, and metabolomics, in LAM biomarker discovery. It also retrieves the literature on LAM biomarkers studied by omics techniques in the last 10 years using PubMed and other retrieval tools., Expert Opinion: Further research on expanded sample sizes can be conducted to construct specific models to study the role of these molecules in the pathogenesis of LAM and clarify the underlying mechanisms involved. In the future, in terms of technology, the combination of various omics methods is expected to result in novel biomarker discovery.

Low levels of the indispensable trace element selenium (Se) can cause oxidative stress and disrupt environmental homeostasis in humans and animals. Selenoprotein S (Selenos), of which Se is a key component, is a member of the selenoprotein family involved in various biological processes. This study aimed to investigate whether low-level SELENOS gene expression can induce oxidative stress and decrease the antioxidative capacity of chondrocytes. Compared with control cells, SELENOS-knockdown ATDC5 cells showed substantially higher dihydroethidium, reactive oxygen species and malondialdehyde levels, and lower superoxide dismutase (SOD) expression. Knockout of the gene in C57BL/6 mice increased the 8-hydroxy-2-deoxyguanosine level considerably and decreased SOD expression in cartilages relative to the levels in wild-type mice. The results showed that the increased nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling mediated by low-level SELENOS expression was involved in oxidative damage. The proliferative zone of the cartilage growth plate of SELENOS-knockout mice was shortened, suggesting cartilage differentiation dysfunction. In conclusion, this study confirmed that low-level Selenos expression plays a role in oxidative stress in cartilages., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier GmbH. All rights reserved.)

There is growing recognition that earliest signs of autism need not clearly manifest in the first three years of life. To what extent is this variation in developmental trajectories associated with age at autism diagnosis? Does the genetic profile of autism vary with age at autism diagnosis? Using longitudinal data from four birth cohorts, we demonstrate that two different trajectories of socio-emotional behaviours are associated with age at diagnosis. We further demonstrate that the age at autism diagnosis is partly heritable (h 2 SNP = 0.12, s.e.m = 0.01), and is associated with two moderately correlated (r g = 0.38, s.e.m = 0.07) autism polygenic factors. One of these factors is associated with earlier diagnosis of autism, lower social and communication abilities in early childhood. The second factor is associated with later autism diagnosis, increased socio-emotional difficulties in adolescence, and has moderate to high positive genetic correlations with Attention-Deficit/Hyperactivity Disorder, mental health conditions, and trauma. Overall, our research identifies an axis of heterogeneity in autism, indexed by age at diagnosis, which partly explains heterogeneity in autism and the profiles of co-occurring neurodevelopmental and mental health profiles. Our findings have important implications for how we conceptualise autism and provide one model to explain some of the diversity within autism., Competing Interests: Ethics declarations ADB received speakers’ fee from Lundbeck. The authors declare no competing interests.

Although the first signs of autism are often observed as early as 18-36 months of age, there is a broad uncertainty regarding future development, and clinicians lack predictive tools to identify those who will later be diagnosed with co-occurring intellectual disability (ID). Here, we developed predictive models of ID in autistic children (n=5,633 from three cohorts), integrating different classes of genetic variants alongside developmental milestones. The integrated model yielded an AUC ROC=0.65, with this predictive performance cross-validated and generalised across cohorts. Positive predictive values reached up to 55%, accurately identifying 10% of ID cases. The ability to stratify the probabilities of ID using genetic variants was up to twofold greater in individuals with delayed milestones compared to those with typical development. These findings underscore the potential of models in neurodevelopmental medicine that integrate genomics and clinical observations to predict outcomes and target interventions.

Background: Although Hypertension (HTN) is considered to be a cardiovascular disease caused by multiple factors, the cause of it is still unknown. In this study, we aim to find out whether circulating immune cell characteristics have an impact on susceptibility to HTN., Methods: This study employed a comprehensive two-sample Mendelian randomization (MR) analysis to investigate the causal association between immune cell characteristics and HTN. Utilizing publicly accessible genetic data, we examined the causal relationship between HTN and the susceptibility to 731 immune cell signatures. To ensure the reliability and validity of the findings, a comprehensive sensitivity analysis was conducted to assess heterogeneity, confirm the robustness of the results and evaluate the presence of horizontal pleiotropy., Results: After FDR correction, immune phenotype had an effect on HTN. In our study, one immunophenotype was identified as being positively associated with HTN risk significance: HLA DR on CD33- HLA DR+. In addition, we examined 8 immune phenotype with no statistically significant effect of HTN, but it is worth mentioning that they had an unadjusted low P -value phenotype., Conclusions: Our MR study by genetic means demonstrated the close relationship between HTN and immune cells, thus providing guidance for future clinical prediction and subsequent treatment of HTN., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Zhang, Li, Wu and Li.)

The brain topology highly reflects the complex cognitive functions of the biological brain after million-years of evolution. Learning from these biological topologies is a smarter and easier way to achieve brain-like intelligence with features of efficiency, robustness, and flexibility. Here we proposed a brain topology-improved spiking neural network (BT-SNN) for efficient reinforcement learning. First, hundreds of biological topologies are generated and selected as subsets of the Allen mouse brain topology with the help of the Tanimoto hierarchical clustering algorithm, which has been widely used in analyzing key features of the brain connectome. Second, a few biological constraints are used to filter out three key topology candidates, including but not limited to the proportion of node functions (e.g., sensation, memory, and motor types) and network sparsity. Third, the network topology is integrated with the hybrid numerical solver-improved leaky-integrated and fire neurons. Fourth, the algorithm is then tuned with an evolutionary algorithm named adaptive random search instead of backpropagation to guide synaptic modifications without affecting raw key features of the topology. Fifth, under the test of four animal-survival-like RL tasks (i.e., dynamic controlling in Mujoco), the BT-SNN can achieve higher scores than not only counterpart SNN using random topology but also some classical ANNs (i.e., long-short-term memory and multi-layer perception). This result indicates that the research effort of incorporating biological topology and evolutionary learning rules has much in store for the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Wang, Zhang, Du, Zhang and Xu.)

Flexible electronics implanted during tissue formation enable chronic studies of tissue-wide electrophysiology. Here, we integrate tissue-like stretchable electronics during organogenesis of human stem cell-derived pancreatic islets, stably tracing single-cell extracellular spike bursting dynamics over months of functional maturation. Adapting spike sorting methods from neural studies reveals maturation-dependent electrical patterns of α and β-like (SC-α and β) cells, and their stimulus-coupled dynamics. We identified two major electrical states for both SC-α and β cells, distinguished by their glucose threshold for action potential firing. We find that improved hormone stimulation capacity during extended culture reflects increasing numbers of SC-α/β cells in low basal firing states, linked to energy and hormone metabolism gene upregulation. Continuous recording during further maturation by entrainment to daily feeding cycles reveals that circadian islet-level hormone secretion rhythms reflect sustained and coordinate oscillation of cell-level SC-α and β electrical activities. We find that this correlates with cell-cell communication and exocytic network induction, indicating a role for circadian rhythms in coordinating system-level stimulus-coupled responses. Cyborg islets thus reveal principles of electrical maturation that will be useful to build fully functional in vitro islets for research and therapeutic applications.

This article introduces a one-step extrusion-based fused deposition modeling (FDM) approach for the challenging separation of polypropylene (PP) and polyethylene terephthalate (PET) during recycling. A shear screw printer (SSP) with shear elements was designed, and it was compared to a conventional single-screw printer (CSP) to investigate the differences in print stability, degradation levels, tensile performance, molecular orientation, and crystallization when preparing recycled PP and recycled PET blends. Although the retention effect of the SSP screw slightly increases the degradation of the blended rPP/rPET, the strong shear (2.6 × 10 4 s -1 ) applied near the extrusion exit improves the blending efficiency. The SSP also enhances molecular orientation, modulus of the parts, and reduces performance fluctuations. Additionally, the SSP has the potential to simplify the recycling process, enabling the transformation of blended recycled materials into products with just one melt process.

Background and Aims: In the digital age, Internet addiction (IA) was deemed an epidemic and few treatments had been effectively developed for it. Here, we proposed a solution-focused group counseling (SFGC) as a potentially solution to reduce Internet addiction among college students. The present study examined the short- and long-term effect of a five-week solution-focused group counseling intervention on Internet addiction., Methods: Thirty-two participants were recruited and randomly assigned to either the experimental or control group, and twenty-six participants completed the whole intervention. The experimental group (n = 14) received the intervention, while control group (n = 12) did not. The revised version of the Chinese Internet Addiction Scale (CIAS-R), the Future Time Perspective, and resting-state EEG were administered pre-intervention, post-intervention, and at two follow-up tests (one month and six months after intervention)., Results: The results showed that the scores of the CIAS-R in the experimental group were significantly decreased after intervention, and these effects could be sustained for one month and six months follow-ups. Additionally, the intervention conducted an increase in future time perspective. EEG results further suggested that the alpha, beta, and gamma absolute power decreased after the intervention., Conclusion: These results from the pilot-study primarily suggested that solution-focused group counseling could be an effective intervention for Internet addiction.

Objective: The aim of this study was to observe the demographic and clinical characteristics of immunoglobulin (Ig) G4-related disease (IgG4-RD). We aimed to compare different treatment methods and to identify the risk factors for non-response and relapse after treatment., Methods: We performed a retrospective study of 201 IgG4-RD patients initially diagnosed and treated at the First Affiliated Hospital of China Medical University from January 2016 to December 2020. Patients' sex, age, clinical manifestations, baseline biochemical values, the number of organs involved, and the type of organ involvement were recorded. All patients received glucocorticoid (GC) monotherapy or GC + immunosuppressant combination therapy. The serum IgG4 concentration as well as the details of clinical response, relapse, and side effects were recorded at 1, 3, 6, and 12 months after treatment., Results: The incidence of IgG4-RD was primarily centered in the age group of 50-70 years old, and the proportion of affected male patients increased with age. The most common clinical symptom was swollen glands or eyes (42.79%). The rates of single- and double-organ involvement were 34.83% and 46.27%, respectively. The pancreas (45.77%) was the most frequently involved organ in cases of single-organ involvement, and the pancreas and biliary tract (45.12%) was the most common organ combination in cases of double-organ involvement. Correlation analysis showed that the number of organs involved was positively related to the serum IgG4 concentration (r = 0.161). The effective rate of GC monotherapy was 91.82%, the recurrence rate was 31.46%, and the incidence of adverse reactions was 36.77%. Meanwhile, the effective rate of GC + immunosuppressant combination therapy was 88.52%, the recurrence rate was 19.61%, and the adverse reaction rate was 41.00%. There were no statistically significant differences in response, recurrence, and adverse reactions. The overall response rate within 12 months was 90.64%. Age (< 50 years old) and aorta involvement were significantly associated with non-response. The overall recurrence rate within 12 months was 26.90%. Age (< 50 years old), low serum C4 concentration, a high number of involved organs, and lymph node involvement were significantly associated with recurrence., Conclusion: The clinical features vary among different age groups and according to gender. The number of organs involved in IgG4-RD is related to the serum IgG4 concentration. Age (< 50 years old), low serum C4 concentration, a high number of involved organs, and lymph node involvement are risk factors for recurrence., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Non-alcoholic fatty liver disease (NAFLD) is a complex disease that is considered as the next major health epidemic with alarmingly increasing global prevalence. To explore the pathogenesis of NAFLD, data from GSE118892 were analyzed. High mobility group AT-hook 2 (HMGA2), a member of the high mobility group family, is declined in liver tissues of NAFLD rats. However, its role in NAFLD remains unknown. This study attempted to identify the multiple roles of HMGA2 in NAFLD process. NAFLD was induced in rats using a high-fat diet (HFD). In vivo, HMGA2 knockdown using adenovirus system attenuated liver injury and liver lipid deposition, accompanied by decreased NAFLD score, increased liver function, and decreased CD36 and FAS, indicating the deceleration of NAFLD progression. Moreover, HMGA2 knockdown restrained liver inflammation by decreasing the expression of related inflammatory factors. Importantly, HMGA2 knockdown attenuated liver fibrosis via downregulating the expression of fibrous proteins, and inhibiting the activation of TGF-β1/SMAD signaling pathway. In vitro, HMGA2 knockdown relieved palmitic acid (PA)-induced hepatocyte injury and attenuated TGF-β1-induced liver fibrosis, consistent with in vivo findings. Strikingly, HMGA2 activated the transcription of SNAI2, which was evidenced by the dual luciferase assays. Moreover, HMGA2 knockdown largely downregulated SNAI2 levels. Indeed, SNAI2 overexpression effectively blocked the inhibitory effect of HMGA2 knockdown on NAFLD. Totally, our findings reveal that HMGA2 knockdown alleviates the progression of NAFLD by directly regulating the transcription of SNAI2. HMGA2 inhibition may emerge as a potential therapeutic target for NAFLD., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The prevalence of the Internet addiction disorder (IAD) has been on the rise, making it increasingly imperative to explore the neurophysiological markers of it. Using the whole-brain imaging approach of EEG microstate analysis, which treats multichannel EEG recordings as a series of quasi-steady states, similar as the resting-state networks found by fMRI, the present study aimed to investigate the specificity of the IAD in class C of the four canonical microstates. The existing EEG data of 40 participants (N = 20 for each group) was used, and correlation between the time parameters of microstate C and the performance of the Go/NoGo task was analyzed. Results suggested that the duration and coverage of class C were significantly reduced in the IAD group as compared to the healthy control (HC) group. Furthermore, the duration of class C had a significant inverse correlation with Go RTs in the IAD group. These results implied that class C might serve as a neurophysiological marker of IAD, helping to understand the underlying neural mechanism of inhibitory control in IAD., Competing Interests: Declaration of Competing Interest All the authors declare that there were no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Growing evidence suggests there is a bidirectional relationship between depression and obesity, which are associated with structural and functional brain abnormalities. However, the underlying neurobiological mechanisms subserving the foregoing associations have yet to be characterized. It is necessary to summarize the neuroplastic brain changes in relation to depression and obesity. We systematically searched articles from 1990 to November 2022 on databases including MEDLINE/PubMed, Web of Science, PsycINFO. Only neuroimaging studies within the scope of potential differences in brain function and structure in individuals with depression and obesity/ BMI changes were included. Twenty-four eligible studies were included in the review herein, consisting of 17 studies reporting changes in brain structure, 4 studies reporting abnormal brain function, and 3 studies reporting both changes in brain structure and function. Results indicated an interaction between depression and obesity on brain functions, and their influence on brain structure is both extensive and specific. Overall, reduced whole brain, intracranial, and gray matter volume (e.g. frontal, temporal gyri, thalamic, and hippocampal) and impaired white matter integrity was observed in persons with depression and obesity comorbidity. Additional evidence on resting state fMRI reveals select brain regions associated with cognitive control, emotion regulation, and reward functions. Due to the diversity of tasks in task fMRI, the distinct neural activation patterns are revealed separately. The bidirectional relationship between depression and obesity reflects different characteristics in brain structure and function. Longitudinal designs should be reinforced in follow-up studies., Competing Interests: Declaration of competing interest Dr. Roger McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, Atai Life Sciences. Dr. Roger McIntyre is a CEO of Braxia Scientific Corp. Kayla M. Teopiz has received personal fees from Braxia Scientific Corp. The other authors have no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), and ulcerative colitis (UC) are immune diseases of the digestive system. Some patients develop overlap syndrome, the presentation of two or more of the clinical, biochemical, immunological, and histological features of these conditions simultaneously or sequentially. The incidence of UC in PSC-AIH overlap syndrome is as high as 50%. In contrast, PSC-AIH overlap syndrome is rare in UC patients. However, because it has a low prevalence and has been studied in less detail, PSC is often misdiagnosed as primary biliary cholangitis (PBC) in its early stage. Herein, we reported a case of a 38-year-old male patient who presented to a clinician in 2014 with irregular bowel habits. A colonoscopy suggested UC. In 2016, the patient was found to have abnormal liver function and was diagnosed with PBC by pathology. He was treated with ursodeoxycholic acid (UDCA) but this had no effect on his liver function. Additional liver biopsies in 2018 indicated PBC-AIH overlap syndrome. The patient refused hormone therapy for personal reasons. Following UDCA monotherapy, his liver function remained abnormal. The patient was reexamined after repeated abnormal liver function tests and bowel symptoms. Systematic laboratory testing, imaging diagnosis, colonoscopy, liver biopsy, and various pathological examinations conducted in 2021 were used to diagnose the patient with PSC-AIH-UC overlap syndrome. He was treated with various drugs, including UDCA, methylprednisolone, mycophenolate mofetil, and mesalazine. His liver function improved significantly after treatment and follow-up is ongoing. Our case report highlights the need to raise awareness about rare and difficult-to-diagnose clinical disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Lin, Li, Guan, Li and Wang.)

Current biotechnologies can simultaneously measure multiple high-dimensional modalities (e.g., RNA, DNA accessibility, and protein) from the same cells. A combination of different analytical tasks (e.g., multi-modal integration and cross-modal analysis) is required to comprehensively understand such data, inferring how gene regulation drives biological diversity and functions. However, current analytical methods are designed to perform a single task, only providing a partial picture of the multi-modal data. Here, we present UnitedNet, an explainable multi-task deep neural network capable of integrating different tasks to analyze single-cell multi-modality data. Applied to various multi-modality datasets (e.g., Patch-seq, multiome ATAC + gene expression, and spatial transcriptomics), UnitedNet demonstrates similar or better accuracy in multi-modal integration and cross-modal prediction compared with state-of-the-art methods. Moreover, by dissecting the trained UnitedNet with the explainable machine learning algorithm, we can directly quantify the relationship between gene expression and other modalities with cell-type specificity. UnitedNet is a comprehensive end-to-end framework that could be broadly applicable to single-cell multi-modality biology. This framework has the potential to facilitate the discovery of cell-type-specific regulation kinetics across transcriptomics and other modalities., (© 2023. The Author(s).)

Background: Although immune microenvironment-related chemokines, extracellular matrix (ECM), and intrahepatic immune cells are reported to be highly involved in hepatitis B virus (HBV)-related diseases, their roles in diagnosis, prognosis, and drug sensitivity evaluation remain unclear. Here, we aimed to study their clinical use to provide a basis for precision medicine in hepatocellular carcinoma (HCC) via the amalgamation of artificial intelligence. Methods: High-throughput liver transcriptomes from Gene Expression Omnibus (GEO), NODE (https://www.bio.sino.org/node), the Cancer Genome Atlas (TCGA), and our in-house hepatocellular carcinoma patients were collected in this study. Core immunosignals that participated in the entire diseases course of hepatitis B were explored using the "Gene set variation analysis" R package. Using ROC curve analysis, the impact of core immunosignals and amino acid utilization related gene on hepatocellular carcinoma patient's clinical outcome were calculated. The utility of core immunosignals as a classifier for hepatocellular carcinoma tumor tissue was evaluated using explainable machine-learning methods. A novel deep residual neural network model based on immunosignals was constructed for the long-term overall survival (LS) analysis. In vivo drug sensitivity was calculated by the "oncoPredict" R package. Results: We identified nine genes comprising chemokines and ECM related to hepatitis B virus-induced inflammation and fibrosis as CLST signals. Moreover, CLST was co-enriched with activated CD4+ T cells bearing harmful factors (aCD4) during all stages of hepatitis B virus pathogenesis, which was also verified by our hepatocellular carcinoma data. Unexpectedly, we found that hepatitis B virus-hepatocellular carcinoma patients in the CLST high aCD4 high subgroup had the shortest overall survival (OS) and were characterized by a risk gene signature associated with amino acids utilization. Importantly, characteristic genes specific to CLST/aCD4 showed promising clinical relevance in identifying patients with early-stage hepatocellular carcinoma via explainable machine learning. In addition, the 5-year long-term overall survival of hepatocellular carcinoma patients can be effectively classified by CLST/aCD4 based GeneSet-ResNet model. Subgroups defined by CLST and aCD4 were significantly involved in the sensitivity of hepatitis B virus-hepatocellular carcinoma patients to chemotherapy treatments. Conclusion: CLST and aCD4 are hepatitis B virus pathogenesis-relevant immunosignals that are highly involved in hepatitis B virus-induced inflammation, fibrosis, and hepatocellular carcinoma. Gene set variation analysis derived immunogenomic signatures enabled efficient diagnostic and prognostic model construction. The clinical application of CLST and aCD4 as indicators would be beneficial for the precision management of hepatocellular carcinoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Zhao, Zhang, Zhao, Zhang, Chen and Dai.)

The substantial phenotypic heterogeneity in autism limits our understanding of its genetic etiology. To address this gap, here we investigated genetic differences between autistic individuals (n max  = 12,893) based on core and associated features of autism, co-occurring developmental disabilities and sex. We conducted a comprehensive factor analysis of core autism features in autistic individuals and identified six factors. Common genetic variants were associated with the core factors, but de novo variants were not. We found that higher autism polygenic scores (PGS) were associated with lower likelihood of co-occurring developmental disabilities in autistic individuals. Furthermore, in autistic individuals without co-occurring intellectual disability (ID), autism PGS are overinherited by autistic females compared to males. Finally, we observed higher SNP heritability for autistic males and for autistic individuals without ID. Deeper phenotypic characterization will be critical in determining how the complex underlying genetics shape cognition, behavior and co-occurring conditions in autism., (© 2022. The Author(s).)

Pancreatic neuroendocrine neoplasms (PNEN) are tumors that originate from neuroendocrine cells. Only about 1% patients are related to mutation of tuberous sclerosis complex gene. Here, we reported a rare case with involvement of multiple organs and space-occupying lesions. Initially, the patient was thought to have metastasis of a pancreatic tumor. However, the patient was diagnosed as pancreatic neuroendocrine tumors, liver perivascular epithelioid tumors, splenic hamartoma, and renal angiomyolipoma by pathological examination after surgery. We performed genetic mutation detection to identify that tuberous sclerosis complex 2 gene presented with a heterozygous variant. Tuberous sclerosis often presents with widespread tumors, but it is less common to present with pancreatic neuroendocrine tumors and liver perivascular tumors as highlighted in the case. So we analyzed the relationship between TSC gene mutations and related tumors. And we also reviewed the current molecular mechanisms and treatments for tuberous sclerosis complex., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Zhong, Lin, Li, Tian, Chang, Wang, Tong, Wang, Li, Jin, Huang, Wang, Cui, Guan and Li.)

Objective: To investigate the incidence and risk factors of gallbladder stones and polyps in individuals undergoing physical examinations in Liaoning province, China., Methods: This is a retrospective study of adults who underwent routine health examinations at Xikang Medical Center in Liaoning Province (Shenyang, Dandong, and Dalian) from 01/2016 to 12/2020. The routine health examination included anthropometry, blood tests, and liver ultrasound. Based on liver ultrasound results, patients were grouped into those with gallbladder stones, those with gallbladder polyps, those with both stones and polyps, and those with neither., Results: Of the 284,129 included subjects, 6,537 (2.30%) were diagnosed with gallbladder stones, and 18,873 (6.64%) were diagnosed with gallbladder polyps. The overall prevalence in Liaoning province increased each year, peaking in 2020. The prevalence of gallbladder stones was higher among females than males (2.39% vs. 2.23%, respectively), while the prevalence of gallbladder polyps was higher among males. The gallbladder polyp group had higher BMI, FBG, SBP, DBP, TG, TC, LDL-C, HDL-C, AST, ALP, GGT, BUN, Scr, SUA. Except for HDL-C, all factors were also higher in the gallbladder stone group. Patients with fatty liver had a higher prevalence of gallbladder stones and polyps than participants without fatty liver., Conclusion: The prevalence of gallbladder stones and polyps in Liaoning varies by sex, economic status of the city of residence, BMI, and metabolic indicators., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Guan, Tian and Li.)

IgG4-related disease is an immune-mediated chronic, systemic, and autoinflammatory disease that can affect various organs throughout the body. The most commonly affected areas are the pancreas and biliary system. Due to the diverse clinical manifestations of the disease, it affects widely distributed organs. Thus, it is often easy to misdiagnose or miss. The digestive tract is a rarely affected system, and most IgG4-related gastric diseases manifest as tumors detected by endoscopy. This article reports two special cases with IgG4-related disease involving atrophic gastritis and intestinal polyps to provide a more empirical and theoretical basis for clinical diagnosis and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Jin, Guan, Lin, Li and Li.)

The study of cellular complexity in the nervous system based on anatomy has shown more practical and objective advantages in morphology than other perspectives on molecular, physiological, and evolutionary aspects. However, morphology-based neuron type classification in the whole rat brain is challenging, given the significant number of neuron types, limited reconstructed neuron samples, and diverse data formats. Here, we report that different types of deep neural network modules may well process different kinds of features and that the integration of these submodules will show power on the representation and classification of neuron types. For SWC-format data, which are compressed but unstructured, we construct a tree-based recurrent neural network (Tree-RNN) module. For 2D or 3D slice-format data, which are structured but with large volumes of pixels, we construct a convolutional neural network (CNN) module. We also generate a virtually simulated dataset with two classes, reconstruct a CASIA rat-neuron dataset with 2.6 million neurons without labels, and select the NeuroMorpho-rat dataset with 35,000 neurons containing hierarchical labels. In the twelve-class classification task, the proposed model achieves state-of-the-art performance compared with other models, e.g., the CNN, RNN, and support vector machine based on hand-designed features.

A rechargeable aqueous Zn/Mn battery is a promising device for large-scale energy storage because of its abundant resources, low cost, and high safety. However, its application is plagued by a poor life cycle because of the electrochemical instability of MnO 2 in aqueous electrolytes. Here, an alkaline Zn-Na 0.44 MnO 2 dual-ion battery (denoted AZMDIB) is developed for the first time using Na 0.44 MnO 2 as the cathode, a zinc metal sheet as the anode, and a 6 M NaOH aqueous solution as the electrolyte. When the discharge cutoff voltage is lowered to 0.3 V (vs Zn/Zn 2+ ), the Na 0.44 MnO 2 cathode delivers a high capacity of 345.5 mA h g -1 but with a poor cycling performance. The charge-discharge mechanism and structural evolution of the Na 0.44 MnO 2 cathode in an extended potential window (1.95-0.3 V) are also explored. The Na 0.44 MnO 2 electrode experiences two different electrochemical processes: Na + ions insert/extract reversibly in the potential range of 1.95-1.1 V, and a phase transition occurs from Na 0.559 MnO 2 to Mn(OH) 2 below 1.1 V. The latter irreversible reaction is probably due to proton insertion, leading to a severe capacity fade. Nevertheless, in a narrower voltage range (2.0-1.1 V), the AZMDIB full cell exhibits a high reversible capacity (80.2 mA h g -1 at 0.5 C), high rate capability (32 mA h g -1 at 50 C), and excellent cycling stability (73% capacity retention over 1000 cycles at 10 C). Benefiting from the merits of environmental friendliness, cost-effectiveness, and high electrochemical performance, the rechargeable AZMDIB is a promising contender for grid-scale energy storage applications.

Decreasing particle size is an efficient strategy for improving the lithium storage properties of Li 3 V 2 (PO 4 ) 3 (LVP) due to a shorter transport distances of lithium ion and electrons. However, designing and synthesizing LVP nanocrystals (NCs) with sizes smaller than 30 nm remains a challenge. In this work, we developed a facile approach for the fabrication of the monodisperse LVP NCs through a robust high-temperature organic-phase method. The thermodynamics of the synthesis and the possible reaction mechanism were investigated. The results indicate that the organic-phase environment (at 320 °C) may not thermodynamically allow the crystallization of LVP. Nevertheless, oleic acid (OA) and oleylamine (OAm) are essential as capping agents to hinder the agglomeration and growth of the particles. Based on the thermodynamic need, calcination is essential to prepare LVP. The surface electronic conductivity of the LVP NCs was enhanced through a subsequent carbon-coating treatment. The optimum combination of reduction and carbon coating is very favorable for the kinetics of electron transfer and lithium ion diffusion. Therefore, the fabricated LVP@C NCs exhibit superior lithium storage properties with excellent rate capability (84 mA h g -1 at a rate of 20C) and perfect cyclic stability (96.2% capacity retention after 200 cycles at 5C), demonstrating their potential application in high-performance lithium-ion batteries., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Lithium-rich layered oxides are promising cathode candidates for the production of high-energy and high-power electronic devices with high specific capacity and high discharge voltage. However, unstable cycling performance, especially at high charge-recharge rate, is the most challenge issue which needs to be solved to foster the diffusion of these materials. In this paper, hierarchical platelike Li 1.2 Mn 0.54 Ni 0.13 Co 0.13 O 2 cathode materials were synthesized by a facile solvothermal method followed by calcination. Calcination time was found to be a key parameter to obtain pure layered oxide phase and tailor its hierarchical morphology. The Li-rich material consists of primary nanoparticles with exposed {010} planes assembled to form platelike layers which exhibit low resistance to Li + diffusion. In detail, the product by calcination at 900 °C for 12 h exhibits specific capacity of 228, 218, and 204 mA h g -1 at 200, 400, and 1000 mA g -1 , respectively, whereas after 100 cycles at 1000 mA g -1 rate of charge and recharge the specific capacity was retained by about 91%.