Insight into Fructose-to-Sucrose Ratio as the Potential Target of Urinalysis in Bladder Cancer.

Bladder cancer usually has been diagnosed in elderly patients as it stays asymptomatic until it presents. Current detection methods for bladder cancer cannot be considered as an adequate screening strategy due to their high invasiveness and low sensitivity. However, there remains uncertainty about targets with high sensitivity and specificity for non-invasive bladder cancer examination. Our study aims to investigate the actionable non-invasive screening biomarkers in bladder cancer. Here, we employed scRNA-seq to explore the crucial biological processes for bladder cancer development. We then utilized bidirectional Mendelian randomization (MR) analysis to explore the bidirectional causal relationship between ATP-associated metabolites in urine and bladder cancer. Lastly, we used a BBN-induced mouse model of bladder cancer to validate the crucial gene identified by scRNA-seq and MR analysis. We found that (1) the ATP metabolism process plays a critical role in bladder cancer development; (2) there is a bidirectional and negative causal relationship between fructose-to-sucrose ratio in urine and the risk of bladder cancer; and (3) the higher expression of TPI1, a critical gene in the fructose metabolism pathway, was validated in BBN-induced bladder tumors. Our results reveal that fructose-to-sucrose ratio can serve as a potential target of urinalysis in bladder cancer.

The relationship between atmospheric particulate matter, leaf surface microstructure, and the phyllosphere microbial diversity of Ulmus L.

BACKGROUND: Plants can retain atmospheric particulate matter (PM) through their unique foliar microstructures, which has a profound impact on the phyllosphere microbial communities. Yet, the underlying mechanisms linking atmospheric particulate matter (PM) retention by foliar microstructures to variations in the phyllosphere microbial communities remain a mystery. In this study, we conducted a field experiment with ten Ulmus lines. A series of analytical techniques, including scanning electron microscopy, atomic force microscopy, and high-throughput amplicon sequencing, were applied to examine the relationship between foliar surface microstructures, PM retention, and phyllosphere microbial diversity of Ulmus L. RESULTS: We characterized the leaf microstructures across the ten Ulmus lines. Chun exhibited a highly undulated abaxial surface and dense stomatal distribution. Langya and Xingshan possessed dense abaxial trichomes, while Lieye, Zuiweng, and Daguo had sparsely distributed, short abaxial trichomes. Duomai, Qingyun, and Lang were characterized by sparse stomata and flat abaxial surfaces, whereas Jinye had sparsely distributed but extensive stomata. The mean leaf retention values for total suspended particulate (TSP), PM2.5, PM2.5-10, PM10-100, and PM> 100 were 135.76, 6.60, 20.10, 90.98, and 13.08 µg·cm- 2, respectively. Trichomes substantially contributed to PM2.5 retention, while larger undulations enhanced PM2.5-10 retention, as evidenced by positive correlations between PM2.5 and abaxial trichome density and between PM2.5-10 and the adaxial raw microroughness values. Phyllosphere microbial diversity patterns varied among lines, with bacteria dominated by Sediminibacterium and fungi by Mycosphaerella, Alternaria, and Cladosporium. Redundancy analysis confirmed that dense leaf trichomes facilitated the capture of PM2.5-associated fungi, while bacteria were less impacted by PM and struggled to adhere to leaf microstructures. Long and dense trichomes provided ideal microhabitats for retaining PM-borne microbes, as evidenced by positive feedback loops between PM2.5, trichome characteristics, and the relative abundances of microorganisms like Trichoderma and Aspergillus. CONCLUSIONS: Based on our findings, a three-factor network profile was constructed, which provides a foundation for further exploration into how different plants retain PM through foliar microstructures, thereby impacting phyllosphere microbial communities.

Concurrent Preimplantation Genetic Testing and Competence Assessment of Human Embryos by Transcriptome Sequencing.

Preimplantation genetic testing (PGT) can minimize the risk of birth defects. However, the accuracy and applicability of routine PGT is confounded by uneven genome coverage and high allele drop-out rate from existing single-cell whole genome amplification methods. Here, a method to diagnose genetic mutations and concurrently evaluate embryo competence by leveraging the abundant mRNA transcript copies present in trophectoderm cells is developed. The feasibility of the method is confirmed with 19 donated blastocysts. Next, the method is applied to 82 embryos from 26 families with monogenic defects for simultaneous mutation detection and competence assessment. The accuracy rate of direct mutation detection is up to 95%, which is significantly higher than DNA-based method. Meanwhile, this approach correctly predicted seven out of eight (87.5%) embryos that failed to implant. Of six embryos that are predicted to implant successfully, four met such expectations (66.7%). Notably, this method is superior at conditions for mutation detection that are challenging when using DNA-based PGT, such as when detecting pathogenic genes with a high de novo rate, multiple pseudogenes, or an abnormal expansion of CAG trinucleotide repeats. Taken together, this study establishes the feasibility of an RNA-based PGT that is also informative for assessing implantation competence.

Themis: advancing precision oncology through comprehensive molecular subtyping and optimization.

Recent advances in tumor molecular subtyping have revolutionized precision oncology, offering novel avenues for patient-specific treatment strategies. However, a comprehensive and independent comparison of these subtyping methodologies remains unexplored. This study introduces 'Themis' (Tumor HEterogeneity analysis on Molecular subtypIng System), an evaluation platform that encapsulates a few representative tumor molecular subtyping methods, including Stemness, Anoikis, Metabolism, and pathway-based classifications, utilizing 38 test datasets curated from The Cancer Genome Atlas (TCGA) and significant studies. Our self-designed quantitative analysis uncovers the relative strengths, limitations, and applicability of each method in different clinical contexts. Crucially, Themis serves as a vital tool in identifying the most appropriate subtyping methods for specific clinical scenarios. It also guides fine-tuning existing subtyping methods to achieve more accurate phenotype-associated results. To demonstrate the practical utility, we apply Themis to a breast cancer dataset, showcasing its efficacy in selecting the most suitable subtyping methods for personalized medicine in various clinical scenarios. This study bridges a crucial gap in cancer research and lays a foundation for future advancements in individualized cancer therapy and patient management.

Potential prognostic value of CSF-targeted proteomics across the Alzheimer's disease continuum.

BACKGROUND: Core biomarkers for Alzheimer's disease (AD), such as Aß42 and tau, have demonstrated high prognostic accuracy but do not fully capture the complex pathophysiology of AD. In this study, our objective was to identify novel cerebrospinal fluid (CSF) biomarkers using proteomics across the entire AD continuum to predict conversion to AD and explore their involvement in AD pathogenesis. METHODS: A cohort of 186 cognitively normal (CN), 127 subjective memory complaint (SMC), 79 early mild cognitive impairment (EMCI), 249 late MCI (LMCI), and 132 AD individuals was analyzed, with a follow-up period of over 3 years for non-AD participants. CSF 65 peptides, as well as hippocampal and entorhinal volumes were analyzed, and cognitive function was evaluated using the 13-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog 13). Cox proportional hazards models and mediation analysis were performed to investigate associations and causal relationships. RESULTS: During the follow-up, approximately one-fourth (146/580) of the non-AD participants progressed to AD. After adjusting for baseline diagnosis (CN to LMCI) and other variables, multivariable Cox regression analysis identified three peptides (VAELEDEK, VSFELFADK, and VVSSIEQK) as significant predictors of conversion to AD. Incorporating these three peptides into the initial model significantly improved the C-statistic from 0.82 to 0.85 for predicting AD conversion, surpassing the predictive ability of Aß42 and P-tau. Moreover, hippocampal and entorhinal volumes mediated 30.3-53.8% of the association between the three peptides and ADAS-Cog 13 scores. CONCLUSIONS: These findings underscore the potential of these three peptides as robust prognostic biomarker candidates for AD conversion across the entire AD continuum, with a mechanism involving the mediation of hippocampal and entorhinal volumes.

Risk factors, prognostic factors, and nomograms for synchronous brain metastases of solid tumors: a population-based study.

In previous literatures, we found that similar studies on the short-term prognosis of synchronous brain metastases (S-BM) from other systems are rare. Our aim was to evaluate the early mortality rate of patients with S-BM from the Surveillance, Epidemiology, and End Result (SEER) database and explore the risk factors for early mortality (≤ 1 year). We used Kaplan-Meier (KM) curves to evaluate early mortality in patients with S-BM from the SEER database. Logistic regression analyses were used to identify significant independent prognostic factors in patients with a follow-up time > 12 months. And the meaningful factors were used to construct a nomogram of overall early death. The receiver operating characteristic (ROC) curve was used to test the predictive ability of the model, while the decision curve analysis (DCA) curve was used to validate the clinical application ability of the model. A total of 47,284 patients were used for univariate and multivariate logistic regression analysis to screen variables to constructing a nomogram. In the all-cause early mortality specific model, the area under the ROC (AUC) curve of the training set was 0.764 (95% confidence interval (CI): 0.758-0.769), and the AUC of the validation set was 0.761 (95% CI: 0.752-0.770). The DCA calibration curves of the training set and validation set indicate that the 1-year early mortality rate predicted by this model is consistent with the actual situation. We found that the 1-year early mortality rate was 76.4%. We constructed a validated nomogram using these covariates to effectively predict 1-year early mortality in patients with S-BM. This nomogram can help clinical workers screen high-risk patients to develop more reasonable treatment plans.

Advances in 2,3-Dimethylmaleic Anhydride (DMMA)-Modified Nanocarriers in Drug Delivery Systems.

Cancer represents a significant threat to human health. The cells and tissues within the microenvironment of solid tumors exhibit complex and abnormal properties in comparison to healthy tissues. The efficacy of nanomedicines is inhibited by the presence of substantial and complex physical barriers in the tumor tissue. The latest generation of intelligent drug delivery systems, particularly nanomedicines capable of charge reversal, have shown promise in addressing this issue. These systems can transform their charge from negative to positive upon reaching the tumor site, thereby enhancing tumor penetration via transcytosis and promoting cell internalization by interacting with the negatively charged cell membranes. The modification of nanocarriers with 2,3-dimethylmaleic anhydride (DMMA) and its derivatives, which are responsive to weak acid stimulation, represents a significant advance in the field of charge-reversal nanomedicines. This review provides a comprehensive examination of the recent insights into DMMA-modified nanocarriers in drug delivery systems, with a particular focus on their potential in targeted therapeutics. It also discusses the synthesis of DMMA derivatives and their role in charge reversal, shell detachment, size shift, and ligand reactivation mechanisms, offering the prospect of a tailored, next-generation therapeutic approach to overcome the diverse challenges associated with cancer therapy.

External Guide Sequence Effectively Suppresses the Gene Expression and Replication of Herpes Simplex Virus 2.

Ribonuclease P (RNase P) complexed with an external guide sequence (EGS) represents a promising nucleic acid-based gene targeting approach for gene expression knock-down and modulation. The RNase P-EGS strategy is unique as an EGS can be designed to basepair any mRNA sequence and recruit intracellular RNase P for hydrolysis of the target mRNA. In this study, we provide the first direct evidence that the RNase P-based approach effectively blocks the gene expression and replication of herpes simplex virus 2 (HSV-2), the causative agent of genital herpes. We constructed EGSs to target the mRNA encoding HSV-2 single-stranded DNA binding protein ICP8, which is essential for viral DNA genome replication and growth. In HSV-2 infected cells expressing a functional EGS, ICP8 levels were reduced by 85%, and viral growth decreased by 3000 folds. On the contrary, ICP8 expression and viral growth exhibited no substantial differences between cells expressing no EGS and those expressing a disabled EGS with mutations precluding RNase P recognition. The anti-ICP8 EGS is specific in targeting ICP8 because it only affects ICP8 expression but does not affect the expression of the other viral immediate-early and early genes examined. This study shows the effective and specific anti-HSV-2 activity of the RNase P-EGS approach and demonstrates the potential of EGS RNAs for anti-HSV-2 applications.

Impact of Preoperative Neutrophil to Prealbumin Ratio Index (NPRI) on Short-Term Complications and Long-Term Prognosis in Patients Undergoing Laparoscopic Radical Surgery for Colorectal Cancer.

Objective: This study aims to evaluate the impact and predictive value of the preoperative NPRI on short-term complications and long-term prognosis in patients undergoing laparoscopic radical surgery for colorectal cCancer (CRC). Methods: A total of 302 eligible CRC patients were included, assessing five inflammation-and nutrition-related markers and various clinical features for their predictive impact on postoperative outcomes. Emphasis was on the novel indicator NPRI to elucidate its prognostic and predictive value for perioperative risks. Results: Multivariate logistic regression analysis identified a history of abdominal surgery, prolonged surgical duration, CEA levels ≥5 ng/mL, and NPRI ≥ 3.94 × 10-2 as independent risk factors for postoperative complications in CRC patients. The Clavien--Dindo complication grading system highlighted the close association between preoperative NPRI and both common and severe complications. Multivariate analysis also identified a history of abdominal surgery, tumor diameter ≥5 cm, poorly differentiated or undifferentiated tumors, and NPRI ≥ 2.87 × 10-2 as independent risk factors for shortened overall survival (OS). Additionally, a history of abdominal surgery, tumor maximum diameter ≥5 cm, tumor differentiation as poor/undifferentiated, NPRI ≥ 2.87 × 10-2, and TNM Stage III were determined as independent risk factors for shortened disease-free survival (DFS). Survival curve results showed significantly higher 5-year OS and DFS in the low NPRI group compared to the high NPRI group. The incorporation of NPRI into nomograms for OS and DFS, validated through calibration and decision curve analyses, attested to the excellent accuracy and practicality of these models. Conclusion: Preoperative NPRI independently predicts short-term complications and long-term prognosis in patients undergoing laparoscopic colorectal cancer surgery, enhancing predictive accuracy when incorporated into nomograms for patient survival.

Challenges and Coping Strategies in Transitioning From Caregiving to Widowhood: A Systematic Review.

Ninety-one percent of surviving spouses in the U.S. cared for their spouses before they died. This review explores the challenges of the transition from caregiving to widowhood and different coping strategies used by widowed spousal caregivers. A systematic review of literature on the transition from caregiving to widowhood was conducted using four major academic search engines. Overall, 280 articles were identified, with 22 meeting the inclusion criteria. Challenges for widowed caregivers included experiencing care burden, letting go of the caregiver role, grief, and triggers. Widowed caregivers' coping strategies included social support and services use, filling the time gap, finding spirituality, and engaging in unhealthy behaviors. Future research is needed to determine the efficacy of widowed caregivers' coping strategies. Concerted and collaborative action by health professionals, community organizations, and policymakers is needed to develop programs and other approaches to support widowed caregivers.

Financial train, health behaviors, and psychological well-being of family caregivers of older adults during the COVID-19 pandemic.

Objectives: This study aims to examine the change in financial strain, health behaviors, and psychological well-being of family caregivers of older adults during the COVID-19 pandemic and explore the differences in mental health outcomes by gender, race, and relationship status. Methods: Using the 2020 National Health and Aging Trends Study COVID-19 supplement, our sample included 2026 family caregivers of older adults. Structural equation modeling was conducted. Results: Caregivers with financial strain showed worse mental health than those with no financial strain. Female or adult children caregivers reported significantly less time walking, more financial strain, and a higher level of negative mental health outcomes compared to male or spouse caregivers; non-White caregivers reported greater positive mental health outcomes compared to White caregivers during the pandemic. Discussion: Health professionals should consider the financial and mental health impact of COVID-19 among family caregivers when designing and delivering caregiver support programs. Innovation: This study provides nationally representative estimates of several important health behaviors and health outcomes for caregivers of older adults during and after the COVID-19 pandemic, helping to fill the knowledge gap about the characteristics of caregivers whose health and well-being were most affected by the pandemic.

Nanoplastic toxicity induces metabolic shifts in Populus × euramericana cv. '74/76' revealed by multi-omics analysis.

There is increasing global concern regarding the pervasive issue of plastic pollution. We investigated the response of Populus × euramericana cv. '74/76' to nanoplastic toxicity via phenotypic, microanatomical, physiological, transcriptomic, and metabolomic approaches. Polystyrene nanoplastics (PS-NPs) were distributed throughout the test plants after the application of PS-NPs. Nanoplastics principally accumulated in the roots; minimal fractions were translocated to the leaves. In leaves, however, PS-NPs easily penetrated membranes and became concentrated in chloroplasts, causing thylakoid disintegration and chlorophyll degradation. Finally, oxidant damage from the influx of PS-NPs led to diminished photosynthesis, stunted growth, and etiolation and/or wilting. By integrating dual-omics data, we found that plants could counteract mild PS-NP-induced oxidative stress through the antioxidant enzyme system without initiating secondary metabolic defense mechanisms. In contrast, severe PS-NP treatments promoted a shift in metabolic pattern from primary metabolism to secondary metabolic defense mechanisms, an effect that was particularly pronounced during the upregulation of flavonoid biosynthesis. Our findings provide a useful framework from which to further clarify the roles of key biochemical pathways in plant responses to nanoplastic toxicity. Our work also supports the development of effective strategies to mitigate the environmental risks of nanoplastics by biologically immobilizing them in contaminated lands.

919 granules improve postpartum depression through the regulation of abnormal peripheral blood IL-1ß.

Postpartum depression (PPD) has a significant impact on the physical and mental health of mothers, potentially leading to symptoms such as low mood, fatigue, and decreased appetite. It may also affect the healthy growth of the infant. The onset of PPD is closely related to abnormalities in inflammation and the immune system. PPD patients exhibit abnormalities in the proportion of peripheral blood immune cells, along with an increase in pro-inflammatory cytokines. Excessive pro-inflammatory cytokines in peripheral blood can disrupt the blood-brain barrier (BBB) by activating astrocytes and reducing transendothelial electrical resistance (TEER), allowing peripheral immune cells or cytokines to enter the brain and trigger inflammation, ultimately leading to the onset of depression. In addition, PPD lacks safe and effective treatment medications. In this study, we collected peripheral blood from both healthy postpartum women and those with PPD, conducted single cell RNA sequencing (scRNA-seq), and used an in-house analytical tool scSTAR to reveal that PPD patients exhibit elevated proportions of peripheral blood cDC2 and Proliferation B cells, which are significantly correlated with IL-1ß. Additionally, animal experiments were designed to validate that 919 granules can improve PPD by modulating the levels of peripheral blood IL-1ß, providing a potential therapeutic mechanism for PPD treatment.

Diagnosis and management of urinary bladder paragangliomas: A Sino-American-European retrospective observational study.

OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.

Evaluation of bicyclist physiological response and visual attention in commercial vehicle loading zones.

INTRODUCTION: With growing freight operations throughout the world, there is a push for transportation systems to accommodate trucks during loading and unloading operations. Currently, many urban locations do not provide loading and unloading zones, which results in trucks parking in places that obstruct bicyclist's roadway infrastructure (e.g., bicycle lanes). METHOD: To understand the implications of these truck operations, a bicycle simulation experiment was designed to evaluate the impact of commercial vehicle loading and unloading activities on safe and efficient bicycle operations in a shared urban roadway environment. A fully counterbalanced, partially randomized, factorial design was chosen to explore three independent variables: commercial vehicle loading zone (CVLZ) sizes with three levels (i.e., no CVLZ, Min CVLZ, and Max CVLZ), courier position with three levels (i.e., no courier, behind the truck, beside the truck), and with and without loading accessories. Bicyclist's physiological response and eye tracking were used as performance measures. Data were obtained from 48 participants, resulting in 864 observations in 18 experimental scenarios using linear mixed-effects models (LMM). RESULTS: Results from the LMMs suggest that loading zone size and courier position had the greatest effect on bicyclist's physiological responses. Bicyclists had approximately two peaks-per-minute higher when riding in the condition that included no CVLZ and courier on the side compared to the base conditions (i.e., Max CVLZ and no courier). Additionally, when the courier was beside the truck, bicyclist's eye fixation durations (sec) were one (s) greater than when the courier was located behind the truck, indicating that bicyclists were more alert as they passed by the courier. The presence of accessories had the lowest influence on both bicyclists' physiological response and eye tracking measures. PRACTICAL APPLICATIONS: These findings could support better roadway and CVLZ design guidelines, which will allow our urban street system to operate more efficiently, safely, and reliable for all users.

A silver-mediated radical process of ß-keto sulfones for the synthesis of 2,3-diacyl furans.

A facile and efficient method for constructing 2,3-diacyl trisubstituted furans via a silver-mediated radical process of ß-keto sulfones is developed. The reaction mechanism has been carefully investigated, revealing that the transformation proceeds through a radical pathway, leading to moderate to good yields of desired products.

Somatostatin receptor subtype 2A expression and genetics in 184 paragangliomas: a single center retrospective observational study.

PURPOSE: Adrenal and extra-adrenal paragangliomas (PGLs) are a group of neuroendocrine tumors (NETs) with strong heterogeneity, which often express somatostatin receptor subtype 2 A (SSTR2A). However, the association between SSTR2A expression and genetic status of PGLs remains unclear. The purpose of the study was to identify whether various pathogenic variants (PVs) had an impact on SSTR2A expression in PGLs. METHODS: This retrospective study included 184 patients with pathologically confirmed PGLs. The immunohistochemical expression of SSTR2A were studied in 184 tumors and PVs were tested in 159 tumor samples. Clinical and genetic data were compared in SSTR2A positive and negative PGLs. RESULTS: SSTR2A was positive in 63.6% (117/184) of all tumors. PGLs with negative SSTR2A were more likely to be extra-adrenal (37.0% vs 18.0%; P = 0.005) and exhibited a considerably greater proportion of PVs (75.4% vs. 49.0%; P = 0.001) than those with positive SSTR2A. Compared to those without PVs, a higher proportion of PGLs with PVs in cluster 1B (P = 0.004) and cluster 2 (P = 0.004) genes, especially VHL (P = 0.009), FGFR1 (P = 0.010) and HRAS (P = 0.007), were SSTR2A negative. SSTR2A was positive in all tumors (4/4) with SDHx PVs and in 87.5% (7/8) of metastatic PGLs. CONCLUSIONS: SSTR2A negativity was correlated with extra-adrenal tumor location and PVs in cluster 1B and cluster 2 genes such as VHL, FGFR1 and HRAS. Immunohistochemistry of SSTR2A should be taken into consideration in the personalized management of PGLs.

Training to use smart tablets to access reliable online health information in older adults' post-pandemic: A focused pilot intervention study.

BACKGROUND: Older adults are becoming more accepting and interested in using digital technologies, but difficulties and barriers remain for accessing reliable health-related information. The purpose of this focused pilot intervention study was to: (1) understand older adults' firsthand experiences and challenges while using smart tablets post-COVID-19 pandemic, and (2) gather suggestions for age-appropriate training materials, preference of training materials, and resources to access reliable online health information. METHODS: A focused pilot intervention study that involved training older adults to use smart tablets followed by focus group of a convenience sample of 13 older adults (65-85 years old; 91.6% female) on their experiences of using smart tablets. RESULTS: Thematic analysis revealed three themes: tablets are convenient to access online information and older adults reported technical, security concerns, emotional and cognitive challenges regarding use of smart tablets. Older adults also requested one-on-one support, assistance, and topic specific learning for future training sessions. CONCLUSIONS: Future studies should focus on providing detailed, clear instructions at an acceptable pace for older adults.

Construction of functional neural network tissue combining CBD-NT3-modified linear-ordered collagen scaffold and TrkC-modified iPSC-derived neural stem cells for spinal cord injury repair.

Induced pluripotent stem cells (iPSCs) can be personalized and differentiated into neural stem cells (NSCs), thereby effectively providing a source of transplanted cells for spinal cord injury (SCI). To further improve the repair efficiency of SCI, we designed a functional neural network tissue based on TrkC-modified iPSC-derived NSCs and a CBD-NT3-modified linear-ordered collagen scaffold (LOCS). We confirmed that transplantation of this tissue regenerated neurons and synapses, improved the microenvironment of the injured area, enhanced remodeling of the extracellular matrix, and promoted functional recovery of the hind limbs in a rat SCI model with complete transection. RNA sequencing and metabolomic analyses also confirmed the repair effect of this tissue from multiple perspectives and revealed its potential mechanism for treating SCI. Together, we constructed a functional neural network tissue using human iPSCs-derived NSCs as seed cells based on the interaction of receptors and ligands for the first time. This tissue can effectively improve the therapeutic effect of SCI, thus confirming the feasibility of human iPSCs-derived NSCs and LOCS for SCI repair and providing a valuable direction for SCI research.