Serial mediation effect of physical activity and sleep quality between dietary behaviour and depression symptoms: A nationwide cross-sectional survey.

Background: Substantial studies have revealed the potential mechanisms underlying the link between dietary behaviour and depression symptoms. This study investigated the relationship between depression symptoms and dietary behaviour, physical activity, and sleep quality in a nationwide sample of Chinese residents. Methods: A total of 18 819 Chinese Residents completed the dietary behaviour, patient health questionnaire, international physical activity questionnaire, and Pittsburgh sleep quality index. We used the Hayes' serial mediation model to investigate the correlation between the variables. Results: Among the participants, 85.5% were aged between 18 and 59, 41.2% were male, and 73.8% were urban residents. There is a negative correlation between dietary behaviour and physical activity (r = -0.038, P < 0.001), while there is a positive correlation with depression symptoms (r = 0.238, P < 0.001) and sleep quality (r = 0.115, P < 0.001). Additionally, depression shows a positive correlation with physical activity (r = 0.024, P < 0.001) and sleep quality (r = 0.298, P < 0.001), while there is a negative correlation between physical activity and sleep quality (r = -0.035, P < 0.001). Dietary behaviour was found to be connected with depression symptoms via three mediation pathways: (1) physical activity (B = -0.003, 95% confidence interval (CI) = -0.016, -0.007), (2) sleep quality (B = 0.034, 95% CI = 0.126, 0.164), and (3) physical activity and sleep quality (B = 0.001, 95% CI = 0.001, 0.003). Conclusions: These findings highlight the significance of psychological and physical factors in exploring the mechanisms through which dietary behaviour is related to depression symptoms. Overall, this study showed the important role of lifestyle factors in depression symptoms, suggesting that appropriate dietary behaviours, appropriate physical activity, and good sleep quality are necessary for the avoidance or improvement of depression symptoms.

Generation of a human induced pluripotent stem cell line (FDCHi012-A) from a patient with DYRK1A-related intellectual disability syndrome carrying DYRK1A mutation (c.1024G > T).

DYRK1A haploinsufficiency causes a neurodevelopmental syndrome termed DYRK1A-related intellectual disability syndrome which is associated with a range of symptoms including microcephaly, epileptic seizures, and autism spectrum disorder. Here, we generated an induced Pluripotent Stem Cell (iPSC) line with a de novo missense mutation (DYRKIA c.1024G > T) from the peripheral blood mononuclear cells of a patient with DYRK1A-related intellectual disability syndrome. This iPSC line showed normal karyotype, exhibited pluripotency, and has three embryonic germ layers differentiation capacity. This iPSC line will be of great use in investigating the disease mechanisms and drug screening for patients with DYRK1A-related intellectual disability syndrome.

Electrospun silk fibroin/fibrin vascular scaffold with superior mechanical properties and biocompatibility for applications in tissue engineering.

Electrospun scaffolds play important roles in the fields of regenerative medicine and vascular tissue engineering. The aim of the research described here was to develop a vascular scaffold that mimics the structural and functional properties of natural vascular scaffolding. The mechanical properties of artificial vascular tissue represent a key issue for successful transplantation in small diameter engineering blood vessels. We blended silk fibroin (SF) and fibrin to fabricate a composite scaffold using electrospinning to overcome the shortcomings of fibrin with respect to its mechanical properties. Subsequently, we then carefully investigated the morphological, mechanical properties, hydrophilicity, hemocompatibility, degradation, cytocompatibility and biocompatibility of the SF/fibrin (0:100), SF/fibrin (15:85), SF/fibrin (25:75), and SF/fibrin (35:65) scaffolds. Based on these in vitro results, we implanted SF/fibrin (25:75) vascular scaffold subcutaneously and analyzed its in vivo degradation and histocompatibility. The fiber structure of the SF/fibrin hybrid scaffold was smooth and uniform, and its fiber diameters were relatively small. Compared with the fibrin scaffold, the SF/fibrin scaffold clearly displayed increased mechanical strength, but the hydrophilicity weakened correspondingly. All of the SF/fibrin scaffolds showed excellent blood compatibility and appropriate biodegradation rates. The SF/fibrin (25:75) scaffold increased the proliferation and adhesion of MSCs. The results of animal experiments confirmed that the degradation of the SF/fibrin (25:75) scaffold was faster than that of the SF scaffold and effectively promoted tissue regeneration and cell infiltration. All in all, the SF/fibrin (25:75) electrospun scaffold displayed balanced and controllable biomechanical properties, degradability, and good cell compatibility. Thus, this scaffold proved to be an ideal candidate material for artificial blood vessels.

Abnormalities of the Serum proteomic in thrombosis after CVC catheterization in patients with end-stage renal disease.

INTRODUCTION: This study utilized serum proteomics with tandem mass tags (TMT) to investigate potential biomarkers associated with femoral central venous catheter (CVC) thrombosis in endstage kidney disease (ESKD) patients. TMT proteomics analysis on serum samples was conducted to identify proteins with distinct expression levels that may be linked to thrombosis. The findings have important implications for enhancing anticoagulant procedures, catheter closure techniques, and determining optimal intervention timing for post-catheterization dialysis. METHODS: Thirty ESKD patients with CVC receiving hemodialysis between May 2021 and October 2022 at the First Affiliated Hospital of Chengdu Medical College were included in the study, and grouped according to vascular color Doppler ultrasound results, including 23 patients in the thrombo-positive group and 7 patients in the thrombo-negative group. Selection criteria were: 1) Patients with ESKD candidate for hemodialysis initiation; 2) no dialysis access has been placed previously, and CVC needs to be inserted as a temporary access; 3) patients volunteered to participate in this clinical study. Clinical data, blood tests, coagulation function, and biochemical parameters were collected and analyzed on the 14th day after catheterization. Color ultrasonography was conducted on the same day to categorize patients into two groups: those with thrombus-positive results and those with thrombus-negative results. RESULTS: TMT proteomics analysis identified twenty-eight differently expressed proteins, including 16 upregulated and 12 downregulated proteins. Enrichment analysis demonstrated nine proteins that were significantly enriched in four pathways within the thrombus-positive group after CVC insertion. Enzyme-linked immunosorbent assay (ELISA) test confirmed the TMT proteomics findings, specifically highlighting significant differences in human plasma kallikrein B1 (KLKB1) and angiopoietin-like protein 3 (ANGPTL3) levels on the 14th day after CVC insertion. Additionally, KLKB1, fibrinogen (FIB), D-dimer, and fibrinogen degradation products (FDP) levels were significantly elevated, while ANGPTL3 levels were decreased on the 14th day after CVC insertion in the thrombus-positive ESKD patient group. CONCLUSION: Monitoring coagulation status post-CVC catheterization and evaluating potential biomarkers like KLKB1 and ANGPTL3 can contribute to the development of personalized treatment plans, improving the quality of hemodialysis and the overall quality of life for ESKD patients.  DOI: 10.52547/ijkd.7671.

Medical Personnel Behavior Preferences for Providing mHealth Service in China: A Discrete Choice Experiment.

Purpose: This study aims to investigate factors affecting medical personnel behavioral preferences for providing mHealth in China, so as to provide decision-making basis for mHealth providers and managers to encourage more doctors to participate in mHealth service delivery. Methods: Typical case sampling techniques were applied in a hospital setting to conduct a discrete choice experimental questionnaire survey of doctors (n=216) concerning mHealth preferences between July and October 2022. A conditional logit model was used to assess medical personnel preferences for each attribute and level of mHealth services. Results: Length of service, information security, subjects of treatment and financial compensation all have a significant effect on medical staff's preference for providing mHealth services (p < 0.05). In terms of service duration and financial compensation, medical staff preferred mHealth services that provided shorter service duration and higher financial compensation; in terms of information security, medical staff preferred mHealth services with confidentiality of diagnostic and therapeutic information compared to information disclosure; and in terms of treatment targets, medical staff preferred the general population compared to key populations, such as pregnant women, the elderly, infants and children. Conclusion: The preference of medical professionals to provide mHealth services is affected by a variety of factors. By enhancing the confidentiality of information in mHealth services, providing more options for service recipients, increasing their financial compensation, and shortening the duration of the service or increasing the number of service hours that can be adjusted can guide improvement of mHealth services and promoting of its adoption among medical professionals.

Social Participation: A Strategy to Manage Depression in Disabled Populations.

This study aimed to investigate whether social participation (SP) can decrease depressive symptom severity in disabled older adults. A total of 5,937 disabled participants (4877, 1970, 219, and 8 participants responding 1, 2, 3, 4 times, respectively), obtained from the China Health and Retirement Longitudinal Study, were enrolled in our analysis. Based on pooled Ordinary Least Square regressions, SP was associated with decreased depressive symptom severity, and this association was significant in recreational activities and interacting with friends. For brain-disabled respondents, the association was not significant. SP is effective in decreasing depressive symptom severity in disabled older populations. Diversified activities and targeted interventions should be applied to specified older disabled populations to prevent depression.

Correlations between depressives symptom severity and social participation (SP) among disable older adults were measured in a Chinese context.Pooled Ordinary Least Square regression were used to explore the impact of SP on depressives symptom severity in older populations with disabilities.Social participation, including recreational activities and interacting with friends, was associated with decreased depressives symptom severity in disabled middle-aged and older adults.The impact of SP on depressives symptom severity was not significant for older adults with brain disabilities.

Comprehensive spatiotemporal mapping of single-cell lineages in developing mouse brain by CRISPR-based barcoding.

A fundamental interest in developmental neuroscience lies in the ability to map the complete single-cell lineages within the brain. To this end, we developed a CRISPR editing-based lineage-specific tracing (CREST) method for clonal tracing in Cre mice. We then used two complementary strategies based on CREST to map single-cell lineages in developing mouse ventral midbrain (vMB). By applying snapshotting CREST (snapCREST), we constructed a spatiotemporal lineage landscape of developing vMB and identified six progenitor archetypes that could represent the principal clonal fates of individual vMB progenitors and three distinct clonal lineages in the floor plate that specified glutamatergic, dopaminergic or both neurons. We further created pandaCREST (progenitor and derivative associating CREST) to associate the transcriptomes of progenitor cells in vivo with their differentiation potentials. We identified multiple origins of dopaminergic neurons and demonstrated that a transcriptome-defined progenitor type comprises heterogeneous progenitors, each with distinct clonal fates and molecular signatures. Therefore, the CREST method and strategies allow comprehensive single-cell lineage analysis that could offer new insights into the molecular programs underlying neural specification.

Comprehensive analysis of the prognosis and immune effect of the oncogenic protein Four Jointed Box 1.

Background: The Four Jointed Box 1 (FJX1) gene has been implicated in the upregulation of various cancers, highlighting its crucial role in oncology and immunity. In order to better understand the biological function of FJX1 and identify new immunotherapy targets for cancer, we conducted a comprehensive analysis of this gene. Methods: We analyzed the expression profiles and prognostic value of FJX1 using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). Copy number alterations (CNAs), mutations, and DNA methylation were analyzed through cBioPortal. The Immune Cell Abundance Identifier (ImmuCellAI) was used to examine the correlation between FJX1 expression and immune cell infiltration. The relationship between FJX1 expression and immune-related genes and immunosuppressive pathway-related genes was analyzed using The Tumor Immune Estimation Resource version 2 (TIMER2). Tumor mutational burden (TMB) and microsatellite instability (MSI) were obtained from TCGA pan-cancer data. The effect of immunotherapy and the IC50 were assessed using IMvigor210CoreBiologies and Genomics For Drug Sensitivity in Cancer (GDSC). Finally, we evaluated the impact of FJX1 on colon cancer cell proliferation and migration through in vitro functional experiments. Results: Our study indicated that FJX1 expression was high in most cancers and was significantly associated with poor prognosis. High FJX1 expression was also linked to significant alterations in CNA, DNA methylation, TMB, and MSI. Positive correlations were found between FJX1 expression and tumor-associated macrophages (TAMs) and with immune-related genes such as TGFB1 and IL-10 and immunosuppressive pathway-related genes such as TGFB1 and WNT1. On the other hand, FJX1 expression showed a negative relationship with CD8+ T cells. Furthermore, high FJX1 expression led to reduced effectiveness of immunotherapy and drug resistance. In colon cancer cells, FJX1 knockdown was found to decrease cell proliferation and migration. Conclusion: Our research findings demonstrate that FJX1 is a new prognostic factor with a significant role in tumor immunity. Our results highlight the importance of further exploring the potential of targeting FJX1 as a therapeutic strategy in cancer.

Quercetin prevents the ferroptosis of OPCs by inhibiting the Id2/transferrin pathway.

Spinal cord injury (SCI) is a destructive neurological disorder that causes impaired mobility, sensory, and autonomic dysfunctions. The loss of oligodendrocyte progenitor cells (OPCs), which can differentiate into mature oligodendrocytes and re-myelinate damaged axons, is related to poorer recovery for SCI patients. However, inhibiting OPCs loss has always been a difficult problem to overcome. In this study, we demonstrated the anti-ferroptosis effects of quercetin as a mechanism in erastin-induced OPC ferroptosis. Quercetin ameliorated erastin-induced ferroptosis in OPCs, as indicated by decreased iron concentration, reactive oxygen species (ROS) production, and increased content of glutathione (GSH) as well as more normal mitochondria morphology. Compared with erastin-induced OPCs, the myelin basic protein (MBP)-positive myelin and NF200-positive axonal was remarkably increased in quercetin-treated OPCs. Furthermore, quercetin ameliorated the erastin-induced ferroptosis as well as the myelin and axon loss of OPCs by downregulating transferrin. Transfected OPCs with transferrin overexpression plasmids significantly abrogated the protective role of quercetin in OPC ferroptosis. Using ChIP-qPCR, a direct interaction of transferrin with its upstream gene Id2 was found. The overexpression of Id2 reversed the effect of quercetin on OPC ferroptosis. In vivo study found that quercetin greatly decreased the area of injury, and enhanced the BBB score after SCI. Furthermore, in the SCI model, quercetin significantly downregulated Id2 and transferrin expression, while significantly up-regulated GPX4 and PTGS2 expression. In conclusion, quercetin prevents the ferroptosis of OPCs by inhibiting the Id2/transferrin pathway. These findings highlight quercetin as an anti-ferroptosis agent for the treatment or prevention of spinal cord injury.

Encapsulation of Silicon Nano Powders via Electrospinning as Lithium Ion Battery Anode Materials.

Silicon-containing polyester from tetramethoxysilane, ethylene glycol, and o-Phthalic anhydride were used as encapsulating materials for silicon nano powders (SiNP) via electrospinning, with Polyacrylonitrile (PAN) as spinning additives. In the correct quantities, SiNP could be well encapsulated in nano fibers (200-400 nm) using scanning electron microscopy (SEM). The encapsulating materials were then carbonized to a Si-O-C material at 755 °C (Si@C-SiNF-5 and Si@C-SiNF-10, with different SiNP content). Fiber structure and SiNP crystalline structure were reserved even after high-temperature treatment, as SEM and X-ray diffraction (XRD) verified. When used as lithium ion battery (LIB) anode materials, the cycling stability of SiNPs increased after encapsulation. The capacity of SiNPs decreased to ~10 mAh/g within 30 cycles, while those from Si@C-SiNF-5 and Si@C-SiNF-10 remained over 500 mAh/g at the 30th cycle. We also found that adequate SiNP content is necessary for good encapsulation and better cycling stability. In the anode from Si@C-SiNF-10 in which SiNPs were not well encapsulated, fibers were broken and pulverized as SEM confirmed; thus, its cycling stability is poorer than that from Si@C-SiNF-5.

Mapping of clonal lineages across developmental stages in human neural differentiation.

The cell lineages across developmental stages remain to be elucidated. Here, we developed single-cell split barcoding (SISBAR) that allows clonal tracking of single-cell transcriptomes across stages in an in vitro model of human ventral midbrain-hindbrain differentiation. We developed "potential-spective" and "origin-spective" analyses to investigate the cross-stage lineage relationships and mapped a multi-level clonal lineage landscape depicting the whole differentiation process. We uncovered many previously uncharacterized converging and diverging trajectories. Furthermore, we demonstrate that a transcriptome-defined cell type can arise from distinct lineages that leave molecular imprints on their progenies, and the multilineage fates of a progenitor cell-type represent the collective results of distinct rather than similar clonal fates of individual progenitors, each with distinct molecular signatures. Specifically, we uncovered a ventral midbrain progenitor cluster as the common clonal origin of midbrain dopaminergic (mDA) neurons, midbrain glutamatergic neurons, and vascular and leptomeningeal cells and identified a surface marker that can improve graft outcomes.

Modeling congenital brain malformations with brain organoids: a narrative review.

Background and Objective: During embryonic development, the dysregulation of the proliferation and differentiation of neuronal progenitors triggers congenital brain malformations. These malformations are common causes of morbidity and mortality in patients younger than 2 years old. Animal models have provided considerable insights into the etiology of diseases that cause congenital brain malformations. However, the interspecies differences in brain structure limit the ability to transfer these insights directly to studies of humans. In recent years, brain organoids generated from human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs) using a 3-dimensional (3D) culture system have been used to resemble the structure and function of a developing human brain. Therefore, we aimed to summarize the different congenital brain malformations that have been modeled by organoids and discuss the ability of this model to reveal the cellular and molecular mechanisms of congenital brain malformations. Methods: A comprehensive search was performed using PubMed and Web of Science's Core Collection for literature published from July 1, 2000 to July 1, 2022. Keywords included terms related to brain organoids and congenital brain malformations, as well as names of individual malformations. Key Content and Findings: The self-assembled 3D aggregates have been used to recapitulate structural malformations of human brains, such as microcephaly, macrocephaly, lissencephaly (LIS), and periventricular nodular heterotopia (PH). The use of disease-specific brain organoids has revealed unprecedented details of mechanisms that cause congenital brain malformations. Conclusions: This review summarizes the establishment and development of brain organoid technologies and provides an overview of their applications in modeling congenital brain malformations. Although several hurdles still need to be overcome, using brain organoids has greatly expanded our ability to reveal the pathogenesis of congenital brain malformations. Compared with existing methods, the combination with cutting-edge technologies enables a more accurate diagnosis and development of increasingly personalized targeted therapy for patients with congenital brain diseases.

Functional reconstruction of the basal ganglia neural circuit by human striatal neurons in hypoxic-ischaemic injured brain.

Perinatal hypoxic-ischaemic encephalopathy is the leading cause of neonatal death and permanent neurological deficits, while the basal ganglia is one of the major nuclei that is selectively and greatly affected in the brains of hypoxic-ischaemic encephalopathy patients, especially in severe cases. Human embryonic stem cell-derived neurons have shown great potential in different types of brain disorders in adults. However, it remains unknown whether and how grafted human embryonic stem cell-derived neurons can repair immature brains with hypoxic-ischaemic encephalopathy. Here, by administrating genetically labelled human embryonic stem cell-derived striatal neural progenitors into the ipsilateral striatum of hypoxic-ischaemic encephalopathy-injured mice, we found that the grafted cells gradually matured into GABA spiny projection neurons morphologically and electrophysiologically, and significantly rescued the area loss of hypoxic-ischaemic encephalopathy-injured brains. Intriguingly, using immunohistochemical staining combined with enhanced ascorbate peroxidase-based immunoelectron microscopy and rabies virus-mediated trans-synaptic tracing, we show that the grafts start to extend axonal projections to the endogenous target areas (globus pallidus externa, globus pallidus internus, substantia nigra), form synapses with host striatal, globus pallidus and nigra neurons, and receive extensive and stable synaptic inputs as early as 2 months post-transplantation. Importantly, we further demonstrated functional neural circuits re-established between the grafted neurons and host cortical, striatal and substantial nigra neurons at 3-6 months post-transplantation in the hypoxic-ischaemic encephalopathy-injured brain by optogenetics combined with electrophysiological recording. Finally, the transplanted striatal spiny projection neurons but not spinal GABA neurons restored the motor defects of hypoxic-ischaemic encephalopathy, which were reversed by clozapine-N-oxide-based inhibition of graft function. These findings demonstrate anatomical and functional reconstruction of the basal ganglia neural circuit including multiple loops by striatal spiny projection neurons in hypoxic-ischaemic encephalopathy-injured immature brains, which raises the possibility of such a cell replacement therapeutic strategy for hypoxic-ischaemic encephalopathy in neonates.

Generation of a human iPSC line (FDCHi009-A) from a patient with CHARGE syndrome carrying a novel CHD7 mutation (c.2939 T > C).

CHARGE syndrome (OMIM 214800) is an autosomal dominant disease with coloboma, heart defects, atresia of choanae and retardation of growth and/or development, etc. CHD7 mutation is the major known pathogenic cause in patients with CHARGE syndrome. A human iPSC line with a novel heterozygous mutation (CHD7 c.2939 T > C) was constructed from peripheral blood mononuclear cells of a patient with CHARGE syndrome. The iPSC line showed normal karyotype, highly expressed pluripotency markers, and had differentiation potential of three germ layers. This iPSC line provides a useful model to study the underlying mechanisms and drug screening of CHARGE syndrome.

Fast generation of forebrain oligodendrocyte spheroids from human embryonic stem cells by transcription factors.

Oligodendrocyte spheroids (OL-spheroids) containing oligodendrocytes and neurons provide an accessible system to dissect demyelinating diseases and test therapeutic treatment. However, generation of human OL-spheroids is still technically challenging and time-consuming until now. Here, we presented evidence that overexpression of SOX10 and OLIG2 (SO) in human embryonic stem cells (hESCs)-derived ventral forebrain neural progenitors is sufficient to produce forebrain pre-oligodendrocytes (pre-OLs) and mature oligodendrocytes (OLs) within 20-40 days. More importantly, optimizing this procedure by overexpression of SO in ventral forebrain spheroids, we successfully generated OL-spheroids with pre-OLs, mature OLs, and neurons 40 days after OL-induction. We further demonstrated oligodendrocyte-neuron interactions and obvious axon myelination in OL-spheroids. Finally, over 30% cells developed into mature oligodendrocytes with forebrain identity and myelinate axons in mouse brain 3 months after transplantation. This study provides a strategy to generate forebrain OL-spheroids rapidly and efficiently which would facilitate development of new therapeutics for demyelinating disorders.

Association of depression symptoms and sleep quality with state-trait anxiety in medical university students in Anhui Province, China: a mediation analysis.

BACKGROUND: The prevalence of depression symptoms among medical students is particularly high, and it has increased during the COVID-19 epidemic. Sleep quality and state-trait anxiety are risk factors for depression, but no study has yet investigated the mediating role of state-trait anxiety in the relationship between poor sleep quality and depression symptoms in medical students. This study aims to investigate the relationship among depression symptoms, sleep quality and state-trait anxiety in medical university students in Anhui Province. METHODS: This was a cross-sectional survey of 1227 students' online questionnaires collected from four medical universities in Anhui Province using a convenience sampling method. We measured respondents' sleep quality, state-trait anxiety, and depression symptoms using three scales: the Pittsburgh Sleep Quality Index (PSQI), the State-Trait Anxiety Inventory (STAI) and the Self-rating Depression Scale (SDS). We analysed the mediating role of STAI scores on the association between PSQI scores and SDS scores through the Sobel-Goodman Mediation Test while controlling for covariates. P < 0.05 was considered statistically significant. RESULTS: A total of 74.33% (912) and 41.40% (518) of the respondents reported suffering from poor sleep quality and depression symptoms. Sleep quality, state-trait anxiety, and depression symptoms were positively associated with each other (ß = 0.381 ~ 0.775, P < 0.001). State-trait anxiety partially mediated the association between sleep quality and depression symptoms (Sobel test Z = 15.090, P < 0.001), and this mediating variable accounted for 83.79% of the association when adjusting for potential confounders. Subgroup analysis further revealed that STAI scores partially mediated the association between PSQI scores and SDS scores in females and rural students and fully mediated the association between PSQI scores and SDS scores in males and urban students. CONCLUSIONS: This study found that sleep quality and state-trait anxiety have a significant predictive effect on depression symptoms. State-trait anxiety mediated the relationship between sleep quality and depression symptoms, with a more complex mechanism observed among rural and female medical students. Multiple pathways of intervention should be adopted, such as encouraging students to self-adjust, providing professional psychological intervention and timely monitoring, enriching extracurricular activities, and making changes in policies regarding long shifts and working hours.

MACC1 Promotes the Progression and Is a Novel Biomarker for Predicting Immunotherapy Response in Colorectal Cancer.

Aims: As one of the most prevalent malignant diseases in the world, the mechanisms of metastasis in colon cancer are poorly understood. The aim of this study was to investigate the role of the HGF/c-MET axis in the proliferation and metastasis in colon cancer. Methods: The effect of MACC1 on cell proliferation and metastasis was analyzed through a series of in vitro experiments. The role of MACC1 in cancer cells was demonstrated by overexpression and silencing of MACC1 in gain or loss function experiments. To investigate the relationship between MACC1 and c-MET/HGF, we detected c-MET protein expression by disrupting with or overexpressing MACC1. The bioinformatics analysis was used to investigate the correlation between MACC1 and c-MET, and the c-MET expression after the interference of HGF with MACC1 was determined. Subsequently, the function of c-MET was verified in colon cancer cells by a series of experiments. The mouse tumor transplantation model experiment is most suitable in vivo. Results: The results indicated that the overexpression of MACC1 could accelerate proliferation and facilitate metastasis in colon cancer cell lines. Furthermore, c-MET was determined to be the downstream regulator of MACC1. The addition of HGF could stimulate the expression of MACC1. With further exploration, we proved that c-MET is downstream of MACC1 in colon cancer and that overexpression of c-MET in colon cancer enhances cell proliferation and migration capability. At last, MACC1 expression level negatively correlates with the infiltration levels and several immune checkpoint biomarkers. High MACC1 expression has a lower response rate with ICIs in COAD. Conclusions: We found that, under the regulation of the MACC1/HGF/c-MET axis, the proliferation and metastasis of colorectal cancer are increased by MACC1, which can be a novel biomarker for predicting ICIs response in colorectal cancer. Our findings provide a new idea for the targeted treatment of colorectal cancer.

Human midbrain dopaminergic neuronal differentiation markers predict cell therapy outcomes in a Parkinson's disease model.

Human pluripotent stem cell-based (hPSC-based) replacement therapy holds great promise for the treatment of Parkinson's disease (PD). However, the heterogeneity of hPSC-derived donor cells and the low yield of midbrain dopaminergic (mDA) neurons after transplantation hinder its broad clinical application. Here, we have characterized the single-cell molecular landscape during mDA neuron differentiation. We found that this process recapitulated the development of multiple but adjacent fetal brain regions including the ventral midbrain, the isthmus, and the ventral hindbrain, resulting in a heterogenous donor cell population. We reconstructed the differentiation trajectory of the mDA lineage and identified calsyntenin 2 (CLSTN2) and protein tyrosine phosphatase receptor type O (PTPRO) as specific surface markers of mDA progenitors, which were predictive of mDA neuron differentiation and could facilitate high enrichment of mDA neurons (up to 80%) following progenitor cell sorting and transplantation. Marker-sorted progenitors exhibited higher therapeutic potency in correcting motor deficits of PD mice. Different marker-sorted grafts had a strikingly consistent cellular composition, in which mDA neurons were enriched, while off-target neuron types were mostly depleted, suggesting stable graft outcomes. Our study provides a better understanding of cellular heterogeneity during mDA neuron differentiation and establishes a strategy to generate highly purified donor cells to achieve stable and predictable therapeutic outcomes, raising the prospect of hPSC-based PD cell replacement therapies.

Combination of Body Mass Index and Fasting Blood Glucose Improved Predictive Value of New-Onset Prediabetes or Diabetes After Acute Pancreatitis: A Retrospective Cohort Study.

OBJECTIVES: We sought to evaluate whether combining body mass index (BMI) and fasting blood glucose (FBG) can refine the predictive value of new-onset prediabetes/diabetes after acute pancreatitis (NODAP). METHODS: In this retrospective cohort study, we used Kaplan-Meier analysis to compare differences in the NODAP rate among 492 patients with different BMI or FBG levels, or with the combination of these 2 factors mentioned above. RESULTS: In all, 153 of 492 (31.1%) eligible patients finally developed NODAP. According to univariate and multivariate analyses, BMI (hazard ratio, 2.075; 95% confidence interval, 1.408-3.060; P < 0.001) and FBG (hazard ratio, 2.544; 95% confidence interval, 1.748-3.710; P < 0.001) were important predictors of the incidence of NODAP. Subsequently, we divided 492 eligible patients into 3 groups according to the median BMI and FBG values, and found that the NODAP rate in the high-risk group was significantly higher than that in the medium-risk group ( P = 0.018) or the low-risk group ( P < 0.001). CONCLUSIONS: Body mass index and FBG are independent predictors of NODAP. The combination of BMI and FBG can refine the prediction of NODAP and identify candidates for clinical prevention.

Glucose hydrothermal encapsulation of carbonized silicone polyester to prepare anode materials for lithium batteries with improved cycle stability.

A silicon polyester (Si-PET) was synthesized with ethylene glycol and phthalic anhydride, and then it was carbonized and hydrothermally coated with glucose. The formed SiO x with layered graphene as the 3D network had an amorphous carbon layer. The graphene oxide (rGO) after carbothermal reduction was completely retained in SiO x , which improved the conductivity of the SiO x anode material. SiO x were encapsulated with a flexible amorphous carbon layer on the surface, which can not only improve the electrical performance, but also effectively relieve the huge volume changes of the compound. Further, the key point is that, the solid electrolyte interphase (SEI) film was mainly formed on the surface carbon layer. This would keep a stable SEI film during volume pulverization, and result in a good cycle stability. The SiO x /C-rGO material maintained a reversible capacity of 660 mA h g-1 at a current density of 100 mA g-1 for 100 cycles, a reversible capacity of 469.7 mA h g-1 at a current density of 200 mA g-1 for 300 cycles. The Coulomb efficiency was maintained at 98% except for the first cycle. After long cycling, the electrode expansion was 16%, which was much lower than those of silicon based materials. Therefore, this article provides a cheap, simple, and commercially valuable anode material for lithium batteries.