Risk factors for benign paroxysmal positional vertigo and construction of a nomogram predictive model.

BACKGROUND: To analyze the risk factors for benign paroxysmal positional vertigo (BPPV) and to construct a predictive nomogram model. METHODS: In this retrospective study, 312 participants were enrolled, including 164 BPPV patients and 148 healthy subjects without BPPV. Risk predictors for BPPV were identified using univariate and multivariate analyses, and a clinical nomogram was constructed. The predictive accuracy was assessed by unadjusted concordance index (C-index) and calibration plot. RESULTS: Univariate and multivariate regression analysis identified stroke (95% CI, 0.575-5.954; P=0.022), hyperlipidemia (95% CI, 0.471-4.647; P=0.003), chronic suppurative otitis media (95% CI, 1.222-45.528; P=0.005), cervical spondylosis (95% CI, 1.232-3.017; P=0.005), and osteoporosis (95% CI, 1.130-3.071; P=0.001) were the independent risk factors for BPPV. These risk factors were used to construct a clinical predictive nomogram. The regression equation was: logit (P) = -6.820 + 0.450 * stroke + hyperlipidemia * 0.312 + chronic suppurative otitis media * 0.499 + cervical spondylosis * 0.916 + osteoporosis * 0.628. The calibration curves demonstrated excellent accuracy of the predictive nomogram. Decision curve analysis showed that the predictive model is clinically applicable when the threshold probability was between 20% and 60%. CONCLUSIONS: Stroke, hyperlipidemia, chronic suppurative otitis media, cervical spondylosis and osteoporosis are independent risk predictors for BPPV. The developed nomogram is useful in predicting the risk of BPPV.

Accumulation of DNA G-quadruplex in mitochondrial genome hallmarks mesenchymal senescence.

Searching for biomarkers of senescence remains necessary and challenging. Reliable and detectable biomarkers can indicate the senescence condition of individuals, the need for intervention in a population, and the effectiveness of that intervention in controlling or delaying senescence progression and senescence-associated diseases. Therefore, it is of great importance to fulfill the unmet requisites of senescence biomarkers especially when faced with the growing global senescence nowadays. Here, we established that DNA G-quadruplex (G4) in mitochondrial genome was a reliable hallmark for mesenchymal senescence. Via developing a versatile and efficient mitochondrial G4 (mtG4) probe we revealed that in multiple types of senescence, including chronologically healthy senescence, progeria, and replicative senescence, mtG4 hallmarked aged mesenchymal stem cells. Furthermore, we revealed the underlying mechanisms by which accumulated mtG4, specifically within respiratory chain complex (RCC) I and IV loci, repressed mitochondrial genome transcription, finally impairing mitochondrial respiration and causing mitochondrial dysfunction. Our findings endowed researchers with the visible senescence biomarker based on mitochondrial genome and furthermore revealed the role of mtG4 in inhibiting RCC genes transcription to induce senescence-associated mitochondrial dysfunction. These findings depicted the crucial roles of mtG4 in predicting and controlling mesenchymal senescence.

Diffusive metasurfaces based on transverse magnetized ferrite for reduction of radar cross section.

Diffusive metasurfaces have attracted a great deal of interest in recent years for their promising radar cross section reduction ability. In this work, we proposed a methodology for designing non-tunable and tunable diffusive metasurfaces with transverse magnetized ferrite (TMF). The metasurfaces are two-dimensional arrays configured by metal plates and TMFs backed by metal plates, where the TMFs are functioned as perfect magnetic conductor and magnetic absorbers in lossless and lossy cases, respectively. The designed tunable metasurface allows for control of the operating frequency by adjusting the biased magnetic field, while the non-tunable version provides a wider operation band. This paper demonstrates that the ferrite-based metasurface have exotic stealth performance at microwave frequencies and offers a new approach to design stealth structures.

Reprogramming of 3D genome structure underlying HSPC development in zebrafish.

BACKGROUND: Development of hematopoietic stem and progenitor cells (HSPC) is a multi-staged complex process that conserved between zebrafish and mammals. Understanding the mechanism underlying HSPC development is a holy grail of hematopoietic biology, which is helpful for HSPC clinical application. Chromatin conformation plays important roles in transcriptional regulation and cell fate decision; however, its dynamic and role in HSPC development is poorly investigated. METHODS: We performed chromatin structure and multi-omics dissection across different stages of HSPC developmental trajectory in zebrafish for the first time, including Hi-C, RNA-seq, ATAC-seq, H3K4me3 and H3K27ac ChIP-seq. RESULTS: The chromatin organization of zebrafish HSPC resemble mammalian cells with similar hierarchical structure. We revealed the multi-scale reorganization of chromatin structure and its influence on transcriptional regulation and transition of cell fate during HSPC development. Nascent HSPC is featured by loose conformation with obscure structure at all layers. Notably, PU.1 was identified as a potential factor mediating formation of promoter-involved loops and regulating gene expression of HSPC. CONCLUSIONS: Our results provided a global view of chromatin structure dynamics associated with development of zebrafish HSPC and discovered key transcription factors involved in HSPC chromatin interactions, which will provide new insights into the epigenetic regulatory mechanisms underlying vertebrate HSPC fate decision.

Genome-wide identification and mining elite allele variation of the Monoacylglycerol lipase (MAGL) gene family in upland cotton (Gossypium hirsutum L.).

BACKGROUND: Monoacylglycerol lipase (MAGL) genes belong to the alpha/beta hydrolase superfamily, catalyze the terminal step of triglyceride (TAG) hydrolysis, converting monoacylglycerol (MAG) into free fatty acids and glycerol. RESULTS: In this study, 30 MAGL genes in upland cotton have been identified, which have been classified into eight subgroups. The duplication of GhMAGL genes in upland cotton was predominantly influenced by segmental duplication events, as revealed through synteny analysis. Furthermore, all GhMAGL genes were found to contain light-responsive elements. Through comprehensive association and haplotype analyses using resequencing data from 355 cotton accessions, GhMAGL3 and GhMAGL6 were detected as key genes related to lipid hydrolysis processes, suggesting a negative regulatory effect. CONCLUSIONS: In summary, MAGL has never been studied in upland cotton previously. This study provides the genetic mechanism foundation for the discover of new genes involved in lipid metabolism to improve cottonseed oil content, which will provide a strategic avenue for marker-assisted breeding aimed at incorporating desirable traits into cultivated cotton varieties.

Central obesity may affect bone development in adolescents: association between abdominal obesity index ABSI and adolescent bone mineral density.

PURPOSE: Previous studies have suggested that obesity defined by body mass index(BMI) is a protective factor for bone mineral density(BMD), but have overlooked the potential influence of different types of obesity. This study aims to evaluate the correlation between abdominal obesity index A Body Shape Index(ABSI) and adolescent bone density, and analyze the relationship between abdominal obesity and bone metabolism. METHODS: A total of 1557 adolescent participants were included in NHANES from 2007 to 2018. Calculate the ABSI using a specific formula that takes into account waist circumference and BMI. A weighted multiple linear regression model is used to evaluate the linear correlation between ABSI and BMD. Forest plots are used to analyze the correlations between subgroups, and cubic splines are limited to evaluate the nonlinear correlations and saturation effects between ABSI and BMD. RESULTS: After adjusting for confounding factors, there was a significant linear correlation (P < 0.01) between ABSI and femoral BMD, both as a continuous variable and an ordered categorical variable. The restrictive cubic spline curve indicates a significant nonlinear correlation and saturation effect between adolescent ABSI and BMD. CONCLUSION: Research has shown a significant negative correlation between ABSI and BMD at the four detection sites of the femur, and this correlation may vary slightly due to age, race, family income, and different detection sites. The research results indicate that compared to overall body weight, fat distribution and content may be more closely related to bone metabolism.

Epigenetically Rewiring Metabolic Genes via SIRT6 Orchestrates MSC Fate Determination.

SIRT6 owns versatile types of enzymatic activities as a multitasking protein, including ribosyltransferase and deacetylase ones. To investigate the epigenetic regulations of SIRT6 on MSC fate determination via histone deacetylation, we utilized allosteric small molecules specifically controlling its histone 3 deacetylation activities. Results showed that enhanced deacetylation of SIRT6 promoted the ossific lineage commitment of MSC and finally achieved anabolic effects on hard tissues. Mechanistically, H3K9ac and H3K56ac, governed by SIRT6, in MSC orchestrated the transcriptions of crucial metabolic genes, mediating MSC fate determination. Most importantly, our data evidenced that modulating the epigenetic regulations of SIRT6, specifically via enhancing its deacetylation of H3K9ac and H3K56ac, was a promising choice to treat bone loss diseases and promote dentine regeneration. In this study, we revealed the specific roles of SIRT6's histone modification in MSC fate determination. These findings endow us with insights on SIRT6 and the promising therapeutic choices through SIRT6's epigenetic functions for hard tissues regeneration.

Composite water value: A way forward to balance the development and protection of transboundary lakes.

Transboundary lakes are shared by multiple administrative regions. The key to balance the development and protection of transboundary lakes is to properly measure the value of water resources. Most of previous studies on the measurement of lake water resources value have not fully considered the ecosystem service function. This paper proposes a new concept "composite water value" to measure the value of transboundary lakes by integrating the external runoff value and the internal runoff value of water resources. The study constructs a composite water value measurement system for transboundary lakes, further analyzes its influencing factors,and applies the system to the case of Nansi Lake, a representative transboundary lake in eastern China. The results show that: (1) The composite water value of lakes is influenced by various factors, including industrial structure, water withdrawal, and water use methods, which impact the external runoff water value; meanwhile, the composite water quality and fluctuations in lake level are closely associated with the internal runoff water value. From 2008 to 2021, the average annual composite water value of Nansi Lake was 39.628 billion yuan, exhibiting a "rising-falling-fluctuating rising" trend due to pollution control policies, reduced precipitation, and enhanced water-saving technologies successively. (2) From a long-term perspective, it is necessary to focus on the internal runoff water use value of lakes. The internal runoff water value of Nansi Lake has been over 75% of the composite water value, and flood storage and water conservation are important manifestations of its ecosystem service value. (3) The external runoff water value of lake is closely related to the internal runoff water value, and relevant departments need to consider the balance between the water withdrawal of multiple cities along the lake and the retained water volume of the lake to achieve the maximum benefit of composite water value.

Gut microorganisms of Locusta migratoria in various life stages and its possible influence on cellulose digestibility.

Locusta migratoria is an important phytophagous pest, and its gut microbial communities play an important role in cellulose degradation. In this study, the gut microbial and cellulose digestibility dynamics of Locusta migratoria were jointly analyzed using high-throughput sequencing and anthrone colorimetry. The results showed that the gut microbial diversity and cellulose digestibility across life stages were dynamically changing. The species richness of gut bacteria was significantly higher in eggs than in larvae and imago, the species richness and cellulose digestibility of gut bacteria were significantly higher in early larvae (first and second instars) than in late larvae (third to fifth instars), and the diversity of gut bacteria and cellulose digestibility were significantly higher in imago than in late larvae. There is a correlation between the dynamics of gut bacterial communities and cellulose digestibility. Enterobacter, Lactococcus, and Pseudomonas are the most abundant genera throughout all life stages. Six strains of highly efficient cellulolytic bacteria were screened, which were dominant gut bacteria. Carboxymethyl cellulase activity (CMCA) and filter paper activity (FPA) experiments revealed that Pseudomonas had the highest cellulase enzyme activity. This study provides a new way for the screening of cellulolytic bacteria and lays the foundation for developing insects with significant biomass into cellulose-degrading bioreactors. IMPORTANCE: Cellulose is the most abundant and cheapest renewable resource in nature, but its degradation is difficult, so finding efficient cellulose degradation methods is an urgent challenge. Locusta migratoria is a large group of agricultural pests, and the large number of microorganisms that inhabit their intestinal tracts play an important role in cellulose degradation. We analyzed the dynamics of Locusta migratoria gut microbial communities and cellulose digestibility using a combination of high-throughput sequencing technology and anthrone colorimetry. The results revealed that the gut microbial diversity and cellulose digestibility were dynamically changed at different life stages. In addition, we explored the intestinal bacterial community of Locusta migratoria across life stages and its correlation with cellulose digestibility. The dominant bacterial genera at different life stages of Locusta migratoria were uncovered and their carboxymethyl cellulase activity (CMCA) and filter paper activity (FPA) were determined. This study provides a new avenue for screening cellulolytic bacteria and lays the foundation for developing insects with significant biomass into cellulose-degrading bioreactors.

High throughput identification of carbonyl compounds in natural organic matter by directional derivatization combined with ultra-high resolution mass spectrometry.

Carbonyl compounds are important components of natural organic matter (NOM) with high reactivity, so that play a pivotal role in the dynamic transformation of NOM. However, due to the lack of effective analytical methods, our understanding on the molecular composition of these carbonyl compounds is still limited. Here, we developed a high-throughput screening method to detect carbonyl molecules in complex NOM samples by combining chemical derivatization with electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR-MS). In six different types of dissolved organic matter (DOM) samples tested in this study, 20-30 % of detected molecules contained at least one carbonyl group, with relative abundance accounted for 45-70 %. These carbonyl molecules displayed lower unsaturation level, lower molecular weight, and higher oxidation degree compared to non-carbonyl molecules. More importantly, the measured abundances of carbonyl molecules were consistent with the results of 13C nuclear magnetic resonance (NMR) analysis. Based on this method, we found that carbonyl molecules can be produced at DOM-ferrihydrite interface, thus playing a role in shaping the molecular diversity of DOM. This method has broad application prospects in screening carbonyl compounds from complex mixtures, and the same strategy can be used to directional identification of molecules with other functional groups as well.

Population pharmacokinetics and CD20 binding dynamics for mosunetuzumab in relapsed/refractory B-cell non-Hodgkin lymphoma.

Mosunetuzumab (Mosun) is a CD20xCD3 T-cell engaging bispecific antibody that redirects T cells to eliminate malignant B cells. The approved step-up dose regimen of 1/2/60/30 mg IV is designed to mitigate cytokine release syndrome (CRS) and maximize efficacy in early cycles. A population pharmacokinetic (popPK) model was developed from 439 patients with relapsed/refractory B-Cell Non-Hodgkin lymphoma receiving Mosun IV monotherapy, including fixed dosing (0.05-2.8 mg IV every 3 weeks (q3w)) and Cycle 1 step-up dosing groups (0.4/1/2.8-1/2/60/30 mg IV q3w). Prior to Mosun treatment, ~50% of patients had residual levels of anti-CD20 drugs (e.g., rituximab or obinutuzumab) from prior treatment. CD20 receptor binding dynamics and rituximab/obinutuzumab PK were incorporated into the model to calculate the Mosun CD20 receptor occupancy percentage (RO%) over time. A two-compartment model with time-dependent clearance (CL) best described the data. The typical patient had an initial CL of 1.08 L/day, transitioning to a steady-state CL of 0.584 L/day. Statistically relevant covariates on PK parameters included body weight, albumin, sex, tumor burden, and baseline anti-CD20 drug concentration; no covariate was found to have a clinically relevant impact on exposure at the approved dose. Mosun CD20 RO% was highly variable, attributed to the large variability in residual baseline anti-CD20 drug concentration (median = 10 µg/mL). The 60 mg loading doses increased Mosun CD20 RO% in Cycle 1, providing efficacious exposures in the presence of the competing anti-CD20 drugs. PopPK model simulations, investigating Mosun dose delays, informed treatment resumption protocols to ensure CRS mitigation.

The alteration of the structure and macroscopic mechanical response of porcine patellar tendon by elastase digestion.

Background: The treatment of patellar tendon injury has always been an unsolved problem, and mechanical characterization is very important for its repair and reconstruction. Elastin is a contributor to mechanics, but it is not clear how it affects the elasticity, viscoelastic properties, and structure of patellar tendon. Methods: The patellar tendons from six fresh adult experimental pigs were used in this study and they were made into 77 samples. The patellar tendon was specifically degraded by elastase, and the regional mechanical response and structural changes were investigated by: (1) Based on the previous study of elastase treatment conditions, the biochemical quantification of collagen, glycosaminoglycan and total protein was carried out; (2) The patellar tendon was divided into the proximal, central, and distal regions, and then the axial tensile test and stress relaxation test were performed before and after phosphate-buffered saline (PBS) or elastase treatment; (3) The dynamic constitutive model was established by the obtained mechanical data; (4) The structural relationship between elastin and collagen fibers was analyzed by two-photon microscopy and histology. Results: There was no statistical difference in mechanics between patellar tendon regions. Compared with those before elastase treatment, the low tensile modulus decreased by 75%-80%, the high tensile modulus decreased by 38%-47%, and the transition strain was prolonged after treatment. For viscoelastic behavior, the stress relaxation increased, the initial slope increased by 55%, the saturation slope increased by 44%, and the transition time increased by 25% after enzyme treatment. Elastin degradation made the collagen fibers of patellar tendon become disordered and looser, and the fiber wavelength increased significantly. Conclusion: The results of this study show that elastin plays an important role in the mechanical properties and fiber structure stability of patellar tendon, which supplements the structure-function relationship information of patellar tendon. The established constitutive model is of great significance to the prediction, repair and replacement of patellar tendon injury. In addition, human patellar tendon has a higher elastin content, so the results of this study can provide supporting information on the natural properties of tendon elastin degradation and guide the development of artificial patellar tendon biomaterials.

Pulmonary Arterial Anatomical Patterns: a Classification Scheme Based on Lobectomy and 3D-CTBA.

PURPOSE: Preoperative evaluation of pulmonary vascular and tracheal routes and variations is of great importance to the surgeon. Three-dimensional computed tomography bronchography and angiography (3D-CTBA) has evolved in recent years with the optimization of 3D reconstruction techniques and artificial intelligence. We aim to apply CT angiography and Exoview 3D reconstruction technology to assess patients' pulmonary arterial tree and its anatomical variants and to try to summarize a set of anatomical typing of the pulmonary arterial tree that is relatively easy and conducive to promoting teaching based on surgical habits of lobectomy. METHODS: A total of 358 patients hospitalized in the Department of Thoracic Surgery of the First Affiliated Hospital of Soochow University between July 2020 and August 2021 were included in this study. We carefully analyzed the site of emanation, alignment, and number of branches of the pulmonary artery according to a uniform classification method in conjunction with the two-dimensional CT images and transformed them into 3D reconstruction models. RESULTS: Different types of pulmonary artery were observed in 358 cases. We evaluated the complete pulmonary artery tree and counted the number and frequency of major arteries of the pulmonary based on the surgical habits of anatomical lobectomy. CONCLUSION: The 3D-CTBA technique enables us to adequately assess the anatomy of the pulmonary arteries. Moreover, we provide a practical classification scheme of pulmonary arterial anatomical patterns based on lobectomy and 3D-CTBA. Our data can be used by clinicians in the teaching of pulmonary artery anatomy and the preoperative preparation for anatomical lobectomy.

The Establishment of Calvarial Suture-Bony Composite Defects in Rats: A Standardized Model for Suture-Regenerative Therapy Investigation.

Large-scale calvarial defects often coincide with cranial suture disruption, leading to impairments in calvarial defect restoration and skull development (the latter occurs in the developing cranium). However, the lack of a standardized model hinders progress in investigating suture-regenerative therapies and poses challenges for conducting comparative analyses across distinct studies. To address this issue, the current protocol describes the detailed modeling process of calvarial suture-bony composite defects in rats. The model was generated by drilling full-thickness rectangular holes measuring 4.5 mm × 2 mm across the coronal sutures. The rats were euthanized, and the cranium samples were harvested postoperatively at day 0, week 2, week 6, and week 12. µCT results from samples collected immediately post-surgery confirmed the successful establishment of the suture-bony composite defect, involving the removal of the coronal suture and the adjacent bone tissues. Data from the 6th and 12th postoperative weeks demonstrated a natural healing tendency for the defect to close. Histological staining further validated this trend by showing increased mineralized fibers and new bone at the defect center. These findings indicate progressive suture fusion over time following calvarial defects, underscoring the significance of therapeutic interventions for suture regeneration. We anticipate that this protocol will facilitate the development of suture-regenerative therapies, offering fresh insights into the functional restoration of calvarial defects and reducing adverse outcomes associated with suture loss.

Characteristic volatile components analysis of Camelina sativa (L.) Crantz by GC-MS and their antibacterial and antioxidant activities.

Camelina sativa (L.) Crantz is an oilseed plant common in Europe and Asia. This study used the gas chromatography-mass spectrometry (GC-MS) to examine the differences in the aroma on the basis of extraction method such as water distillation extraction (CSPW), Solid-phase microextraction (CSPM) and subcritical extraction (CSPS). Antibacterial test was evaluated by the microdilution method against Salmonella typhimurium, Streptococcus pneumoniae, Escherichia coli, Strepococcus pyogenens, Staphylococcus aureus, and antioxidant activity was determined through DPPH free radical, hydroxyl free radical, and superoxide anion radical scavenging capacity activity. The result revealed that three extraction methods were distinct from each other based on their volatile compounds. Sixty-one volatiles of diverse chemical nature were identified and quantified. The volatile components contain thioether, aldehydes, alcohols, ketones, acids, esters, alkene, alkanes, amide, and furan compounds. The volatile components of Camelina sativa (L.) Crantz have good antibacterial and antioxidant activities. Furthermore, this work provides reference methods for detecting novel volatile organic compounds in plants and products.

Design, synthesis, and structure-activity relationship study of novel plinabulin derivatives as anti-tumor agents based on the co-crystal structure.

Plinabulin, a 2, 5-diketopiperazine-type tubulin inhibitor derived from marine natural products, is currently undergoing Phase III clinical trials for the treatment of non-small cell lung cancer (NSCLC) and chemotherapy-induced neutropenia (CIN). To obtain novel 2, 5-diketopiperazine derivatives with higher biological activity, we designed and synthesized two series of 37 plinabulin derivatives at the C-ring, based on the co-crystal structure of compound 1 and tubulin. Their structures were characterized using NMR and HRMS. All compounds were screened in vitro using the lung cancer cell line NCI-H460 using the MTT method, and the compounds with better activity were further screened in BxPC-3 and HT-29 cells. The compounds 16c (IC50 = 2.0, NCI-H460; IC50 = 1.2 nM, BxPC-3; IC50 = 1.97 nM, HT-29) and 26r (IC50 = 0.96, NCI-H460; IC50 = 0.66 nM, BxPC-3; IC50 = 0.61 nM, HT-29) had the best activity. The cytotoxic activity of compound 26r against various tumor cell lines occurred at less than 1 nM.

Causal association of gastroesophageal reflux disease on irritable bowel syndrome: a two-sample Mendelian randomization study.

Background: Recently, observational studies have reported that gastroesophageal reflux disease (GERD) is commonly associated with irritable bowel syndrome (IBS), but the causal relationship is unclear. Methods: We conducted a two-sample Mendelian randomization study using summary data from genome-wide association studies (GWASs) to explore a causal relationship between GERD (N cases = 129,080) and IBS (N cases = 4,605) of European ancestry. Furthermore, the inverse-variance weighted (IVW) method and a series of sensitivity analyses were used to assess the accuracy and confidence of our results. Results: We found a significant association of GERD with IBS (NSNP = 74; OR: 1.375; 95% CI: 1.164-1.624; p < 0.001). Reverse MR analysis showed no evidence of a causal association for IBS with GERD (NSNP = 6; OR: 0.996; 95% CI: 0.960-1.034; p = 0.845). Conclusion: This study provides evidence that the presence of GERD increases the risk of developing IBS, and it is observed from the reverse MR results that IBS did not increase the risk of GERD.

Investigating the Immunogenic Cell Death-Dependent Subtypes and Prognostic Signature of Triple-Negative Breast Cancer.

Recently, immunotherapy has emerged as a promising and effective method for treating triple-negative breast cancer (TNBC). However, challenges still persist. Immunogenic cell death (ICD) is considered a prospective treatment and potential combinational treatment strategy as it induces an anti-tumor immune response by presenting the antigenic epitopes of dead cells. Nevertheless, the ICD process in TNBC and its impact on disease progression and the response to immunotherapy are not well understood. In this study, we observed dysregulation of the ICD process and verified the altered expression of prognostic ICD genes in TNBC through quantitative real-time polymerase chain reaction (qRT-PCR) analysis. To investigate the potential role of the ICD process in TNBC progression, we determined the ICD-dependent subtypes, and two were identified. Analysis of their distinct tumor immune microenvironment (TIME) and cancer hallmark features revealed that Cluster 1 and 2 corresponded to the immune "cold" and "hot" phenotypes, respectively. In addition, we constructed the prognostic signature ICD score of TNBC patients and demonstrated its clinical independence and generalizability. The ICD score could also serve as a potential biomarker for immune checkpoint blockade and may aid in the identification of targeted effective agents for individualized clinical strategies. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00133-x.

Transcriptomic and cellular decoding of scaffolds-induced suture mesenchyme regeneration.

Precise orchestration of cell fate determination underlies the success of scaffold-based skeletal regeneration. Despite extensive studies on mineralized parenchymal tissue rebuilding, regenerating and maintaining undifferentiated mesenchyme within calvarial bone remain very challenging with limited advances yet. Current knowledge has evidenced the indispensability of rebuilding suture mesenchymal stem cell niches to avoid severe brain or even systematic damage. But to date, the absence of promising therapeutic biomaterials/scaffolds remains. The reason lies in the shortage of fundamental knowledge and methodological evidence to understand the cellular fate regulations of scaffolds. To address these issues, in this study, we systematically investigated the cellular fate determinations and transcriptomic mechanisms by distinct types of commonly used calvarial scaffolds. Our data elucidated the natural processes without scaffold transplantation and demonstrated how different scaffolds altered in vivo cellular responses. A feasible scaffold, polylactic acid electrospinning membrane (PLA), was next identified to precisely control mesenchymal ingrowth and self-renewal to rebuild non-osteogenic suture-like tissue at the defect center, meanwhile supporting proper osteointegration with defect bony edges. Especially, transcriptome analysis and cellular mechanisms underlying the well-orchestrated cell fate determination of PLA were deciphered. This study for the first time cellularly decoded the fate regulations of scaffolds in suture-bony composite defect healing, offering clinicians potential choices for regenerating such complicated injuries.