Case Report: A successful outcome of nadroparin calcium therapy for cerebral venous sinus thrombosis in a child with acute lymphoblastic leukemia.

Background: The appearance of cerebral venous sinus thrombosis (CVST) in childhood acute lymphocytic leukemia (ALL) is a rare life-threatening disease that can cause significant morbidity, neurological sequelae, and potentially poor outcomes. Case presentation: We present the case of a 13-year-old boy with ALL who developed CVST and intrinsic hemorrhage approximately 30 days after receiving chemotherapy with vincristine, dexamethasone, daunorubicin, and pegylated-asparaginase (PEG-Asp). He complained of a severe headache and then developed a generalized seizure at night. T1- and T2-weighted magnetic resonance imaging (MRI) and cerebral magnetic resonance venography sequences revealed superior sagittal sinus thrombosis and intrinsic hemorrhagic changes in the bilateral frontoparietal lobes. He received nadroparin calcium as the anticoagulant treatment and was switched to Erwinia asparaginase (Erwinia Asp) rather than PEG-Asp. Oxcarbazepine and clonazepam were started with good seizure control. Intrathecal treatment was delayed until 1 month later. Anticoagulation treatment was stopped for 24 h before and 6 h after lumbar puncture. Platelet transfusion was administered to ensure the platelet count remained at >50 × 109/L. Oral acetazolamide (500-1,000 mg, daily) was administered to relieve headache and reduce intracranial pressure. Three months later, brain MRI showed a complete resolution of or significant improvement in the filling defect. Nadroparin calcium was administered for 1 week after switching to Erwinia Asp to prevent clot recurrence. He completed the 6-month chemotherapy and is doing well with no neurological sequelae and no recurrence of bleeding or thrombosis. Conclusions: Nadroparin calcium therapy appears to be safe and effective for pediatric CVST with ALL. The reintroduction of Erwinia Asp should be accompanied by anticoagulant therapy with nadroparin calcium.

Radiofrequency vs Steroid Injections for Spinal Facet and Sacroiliac Joint Pain: A Systematic Review and Meta-Analysis.

Purpose: Pain management for spinal facet joint (SFJ) and sacroiliac joint (SIJ) pain is challenging, often requiring interventions like radiofrequency ablation (RFA) or corticosteroid injections (CI). This study aims to assess and compare the effectiveness of CI and RFA in treating SFJ and SIJ pain. We combine these treatments due to their shared pathophysiology, similar therapeutic interventions, and the necessity for an integrated approach to spinal pain management. Patients and methods: Literature search from PubMed, Scopus, CENTRAL and Google Scholar for published studies upto 31st December 2023, and reporting data of patients who were treated using CI of RFA for SFJ and SIJ pain. Pooled standardized mean difference (SMD) with a 95% Confidence Interval (CI) was calculated. Results: Our meta-analysis incorporated thirteen studies. Overall, patients, treated with CI had a higher pain intensity score compared to patients treated with RFA (SMD=0.92; 95% CI: 0.19 to 1.65) at 3 months, and at 6 months (SMD=1.53; 95% CI: 0.66 to 2.40) after the treatment. No significant association was reported at 12 months (SMD=1.47; 95% CI: -0.03 to 2.97). Subgroup analysis based on joint types revealed increased pain intensity scores in patients who were treated with CI for SIJ (SMD=1.25; 95% CI: 0.39 to 2.11) and SFJ (SMD=1.33; 95% CI: 0.09 to 2.57) pain. A negative but not significant effect was detected in patients, treated with CI for cervical joint pain (SMD=-0.40; 95% CI: -0.90 to 0.10). Patients treated with CI exhibited higher functional disability score compared to patients treated with RFA at 3 months (SMD=1.28; 95% CI: 0.20 to 2.35) post-treatment. Conclusion: This study suggests that RFA may offer superior pain relief with longer duration compared to steroid injections for spinal facet and sacroiliac joint pain. Decision regarding specific interventions should be individualized and consider patient preferences, clinical context, and potential risks.

Molecular serotyping of diarrheagenic Escherichia coli with a MeltArray assay reveals distinct correlation between serotype and pathotype.

Diarrheagenic Escherichia coli serotypes are associated with various clinical syndromes, yet the precise correlation between serotype and pathotype remains unclear. A major barrier to such studies is the reliance on antisera-based serotyping, which is culture-dependent, low-throughput, and cost-ineffective. We have established a highly multiplex PCR-based serotyping assay, termed the MeltArray E. coli serotyping (EST) assay, capable of identifying 163 O-antigen-encoding genes and 53 H-antigen-encoding genes of E. coli. The assay successfully identified serotypes directly from both simulated and real fecal samples, as demonstrated through spike-in validation experiments and a retrospective study. In a multi-province study involving 637 E. coli strains, it revealed that the five major diarrheagenic pathotypes have distinct serotype compositions. Notably, it differentiated 257 Shigella isolates into four major Shigella species, distinguishing them from enteroinvasive E. coli based on their distinct serotype profiles. The assay's universality was further corroborated by in silico analysis of whole-genome sequences from the EnteroBase. We conclude that the MeltArray EST assay represents a paradigm-shifting tool for molecular serotyping of E. coli, with potential routine applications for comprehensive serotype analysis, disease diagnosis, and outbreak detection.

Isolation, purification, characterization and stability analysis of melanin pigment from Mesona chinensis.

In this study, the isolation and purification of melanin pigment from Mesona chinensis (MCM) were conducted, and the structural characterization and stability evaluation of MCM were performed. The results indicate that MCM is consistent with the spectral features of catechins and polyphenols, identified the stretching vibrations of functional groups such as OH, CH, CO, and CO. It is inferred that the structure of MCM is consistent with that of theophylline and it is mainly composed of phenolic acids, terpenoids, and organic acids. Stability evaluations indicate that MCM exhibits stability under white light, ultraviolet (UV) light, neutral, and alkaline environments, and it shows low sensitivity to reducing agents.

Comparison of long-term changes in the effective optical zone following SMILE and FS-LASIK for moderate and high myopia.

BACKGROUND: Visual quality after corneal refractive surgery is linked to the postoperative effective optical zone (EOZ). This study aims to compare long-term changes in the EOZ following small incision lenticule extraction (SMILE) and femtosecond laser-assisted in-situ keratomileusis (FS-LASIK) for moderate and high myopia. METHODS: This study included 42 patients (72 eyes) who underwent either SMILE (36 eyes) or FS-LASIK (36 eyes). A custom software program based on the tangential curvature difference map of the Pentacam HR (Oculus Optikgeräte GmbH) was used to define the EOZ at 3 and 7 years postoperatively. The EOZ, its chronological changes compared to the programmed optical zone (POZ), and the corneal wavefront aberrations following SMILE and FS-LASIK were analyzed. Correlations between the EOZ changes and relevant parameters were evaluated. RESULTS: Three years postoperatively, EOZ following SMILE and FS-LASIK were 5.13 ± 0.27 mm and 4.70 ± 0.24 mm (P < 0.001), respectively. Seven years postoperatively, EOZ following SMILE and FS-LASIK decreased to 5.03 ± 0.28 mm and 4.63 ± 0.23 mm (P < 0.001), respectively. At postoperative 7 years, the percentages of EOZ/POZ were negatively correlated with Q-value changes (ß = -5.120, P = 0.009) following SMILE and positively correlated with the cylinder correction (ß = 1.184, P = 0.004) following FS-LASIK. The induced spherical aberrations in the SMILE group were less than those in the FS-LASIK group (P < 0.05) and were negatively correlated with the EOZ/POZ (ß = -16.653, P < 0.001). CONCLUSIONS: The EOZ following SMILE was larger than that following FS-LASIK in the long postoperative term for moderate and high myopia. Furthermore, a continual reduction in the EOZ was noted after both surgical modalities.

Immunogenicity and safety of Vero cell culture-derived Japanese encephalitis vaccine: a phase 3 study in Chinese infants.

BACKGROUND: Japanese encephalitis (JE) is a severe infectious disease of the central nervous system. Vaccination with Vero cell culture-derived vaccines may effectively reduce JE incidence. RESEARCH DESIGN AND METHODS: In this single-center, randomized, blinded, positive-controlled clinical trial in China involving 600 healthy infants aged 6-11 months, participants were divided into experimental and control groups administered JEV-PI and JEV-LI, respectively. Antibody titers were determined after 0- and 7-day immunization schedules. A booster dose followed 12 months later. RESULTS: After primary vaccination and before booster vaccination, the positive conversion rate, geometric mean titer (GMT), and geometric mean increase (GMI) of JEV-PI-neutralizing antibodies exceeded those of JEV-LI. After booster immunization, the GMT and GMI of JEV-PI were higher than those of JEV-LI. After primary immunization, the local, systemic, and overall adverse reactions were of grades 1 and 2, with a low incidence of grade 3. After booster immunization, these differences were mainly grades 1 and 2, with no differences between JEV-PI and JEV-LI. CONCLUSION: JEV-PI is a promising vaccine as infants acquired long-lasting and highly neutralizing immune antibodies after inoculation with JEV-PI. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry (https://www.chictr.org.cn/showproj.html?proj = 203130; registration number: ChiCTR2300074692; registration date: 14/08/2023).

Vibrational study of CO, O2, and H2 Adsorbed on the CoCrFeNi (110) High Entropy Alloy Surface.

The vibrational properties of CO, O2, and H2 molecularly or dissociatively adsorbed on a CoCrFeNi(110) surface have been probed using high-resolution energy loss spectroscopy (HREELS) and modeled using density functional theory (DFT) calculations. Large (∼20 mm3) single-crystal, quaternary face-centered cubic CoCrFeNi was synthesized via a modified Czochralski technique. We show strong evidence that CO adsorbs primarily on bridge and on-top sites in compositionally varied local environments, which reflect the random, multielemental surface composition inherent in a high entropy alloy. A variation of adsorption sites is also found with oxygen, which exhibits two broad groups of modes. Comparison to previous photoemission and theoretical studies suggests that the higher energy modes consist primarily of local CrO x species, while the lower energy modes are due to oxygen atoms adsorbed on other metal sites. Unlike CO and O2, HREELS upon H2 adsorption shows only two much narrower modes and is consistent with atomic adsorption on 3-fold hollow sites. The hypothesized adsorption sites for all three species are directly corroborated by our DFT calculations.

Association of dietary fiber intake with epileptic seizures in U.S. adults: A Population-base study of 13,277 participants.

OBJECTIVE: Epilepsy, a neurological disorder, is identified by the presence of recurrent seizures. We aimed to detect dietary fiber intake and its association with epilepsy prevalence in U.S. adults. METHODS: This cross-sectional study obtained data from the 2013-2018 National Health and Nutrition Examination Survey database. Univariate and multivariate logistic regression models were employed to estimate the association between dietary fiber intake and epilepsy prevalence. The restricted cubic spline (RCS) model was also applied to investigate the dose-response relationships between dietary fiber intake and epileptic seizure events(ESEs). RESULTS: Our final sample included 13,277 NHANES participants, with the average prevalence of ESEs being 1.09 % (145/13277). After adjusting for all confounding factors, the third quartile of dietary fiber intake levels remained significantly associated with a decreased risk of ESEs[odds ratios (OR) 0.54,95 % confidence interval (CI) 0.33-0.88, P = 0.014)] compared to the first quartile. Higher fiber intake indicated a stable negative association with ESEs in the multivariate logistic regression analysis, weighted generalized additive model. A nonlinear dose-response relationship was observed between dietary fiber intake levels and decreased ESEs risk (P for overall=0.017, P for nonlinear=0.155). Interaction tests showed no significant effect of demographic and disease status on the association between dietary fiber intake and ESEs. CONCLUSION: In this cross-sectional study, people with a high dietary fiber intake were at a reduced risk of ESEs. However, further prospective studies are needed to investigate the effect of dietary fiber intake in epilepsy events and to determine causality.

Dehydration drives damage in the freezing of brittle hydrogels.

It is widely known that freezing breaks soft, wet materials. However, the mechanism underlying this damage is still not clear. To understand this process, we freeze model, brittle hydrogel samples, while observing the growth of ice-filled cracks that break these apart. We show that damage is not caused by the expansion of water upon freezing or the growth of ice-filled cavities in the hydrogel that exert pressure on the surrounding material. Instead, local ice growth dehydrates the adjacent hydrogel, leading to drying-induced fracture. This dehydration is driven by the process of cryosuction, whereby undercooled ice sucks nearby water toward itself, feeding ice growth. Our results highlight the strong analogy between freezing damage and desiccation cracking, which we anticipate being useful for developing an understanding of both topics. Our results should also give useful insights into a wide range of freezing processes, including cryopreservation, food science, and frost heave.

Unlocking the intricacies: Exploring the complex interplay between platelets and ovarian cancer.

Ovarian cancer, an aggressive malignancy of the female reproductive tract, is frequently linked to an elevated risk of thrombotic events. This association is manifested by a pronounced rise in platelet counts and activation levels. Current research firmly supports the pivotal role of platelets in the oncogenic processes of ovarian cancer, influencing tumor cell proliferation and metastasis. Platelets influence these processes through direct interactions with tumor cells or by secreting cytokines and growth factors that enhance tumor growth, angiogenesis, and metastasis. This review aims to thoroughly dissect the interactions between platelets and ovarian cancer cells, emphasizing their combined role in tumor progression and associated thrombotic events. Additionally, it summarizes therapeutic strategies targeting platelet-cancer interface which show significant promise. Such approaches could not only be effective in managing the primary ovarian tumor but also play a pivotal role in preventing metastasis and attenuating thrombotic complications associated with ovarian cancer.

Preparation and Research on Mechanical Properties of Eco-Friendly Geopolymer Grouting Cementitious Materials Based on Industrial Solid Wastes.

Red mud (RM), a hazardous solid waste generated in the alumina production process, of which the mineral composition is mainly hematite, is unable to be applied directly in the cement industry due to its high alkalinity. With the rise of geopolymers, RM-based grouting materials play an essential role in disaster prevention and underground engineering. To adequately reduce the land-based stockpiling of solid wastes, ultrafine calcium oxide, red mud, and slag were utilized as the main raw materials to prepare geopolymers, the C-R-S (calcium oxide-red mud-slag) grouting cementitious materials. The direct impact of red mud addition on the setting time, fluidity, water secretion, mechanical properties, and rheological properties of C-R-S were also investigated. In addition, a scanning electron microscope (SEM), X-ray diffraction (XRD), three-dimensional CT (3D-CT), Fourier transform infrared spectroscopy (FT-IR), and other characterization techniques were used to analyze the microstructure and polymerization mechanism. The related results reveal that the increase in red mud addition leads to an enhanced setting time, and the C-R-S-40 grouting cementitious material (40% red mud addition) exhibits the best fluidity of 27.5 cm, the lowest water secretion rate of 5.7%, and a high mechanical strength of 57.7 MPa. The C-R-S polymer grout conforms to the Herschel-Bulkley model, and the fitted value of R2 is above 0.99. All analyses confirm that the preparation process of C-R-S grouting cementitious material not only substantially improves the utilization rate of red mud, but also provides a theoretical basis for the high-volume application of red mud in the field of grouting.

Approaches for Lynch syndrome screening and characteristics of subtypes with mismatch repair deficiency in patients with colorectal carcinoma.

To evaluate different Lynch syndrome (LS) screening approaches and establish an efficient and sensitive strategy are critical for clinical practice. In total, 583 patients with colorectal carcinoma (CRC) at Fudan University Shanghai Cancer Center were enrolled. Patient samples were examined by immunohistochemistry (IHC) and next-generation sequencing (NGS), and MLH1 promoter hypermethylation (MPH) was detected in MLH1-deficient cases. Germline genetic testing was performed in cases with deleterious variants and large genomic rearrangements (LGRs) of tumor MMR genes were detected in cases with dMMR or MSI-H cases with no MMR germline variants. Our results showed that triage with IHC and followed by BRAF/MLH1 methylation testing (Strategy 1) identified 93.3% (70/75) of LS cases. IHC followed by germline NGS (Strategy 2) or direct tumor NGS (Strategy 3) both identified 98.7% (74/75) of LS cases. The proportion of LGRs in LS cases was 16.0% (12/75), while 84.0% (63/75) showed SNV/Indel. The average cost per patient was ¥6010.81, ¥6058.48, and ¥8029.98 for Strategy 1, Strategy 2 and Strategy 3, respectively. The average time spent on different strategies was 4.74 days (Strategy 1), 4.89 days (Strategy 2), and 14.50 days (Strategy 3) per patient, respectively. LS and Lynch-like syndrome (LLS) were associated with an earlier onset age than MPH. In conclusion, we compared different workflows for LS screening and IHC plus germline NGS is recommended for LS screening when taking sensitivity, time, and cost into account. Moreover, multiplex ligation-dependent probe amplification made up for the shortcoming of NGS and should be incorporated into routine screening.

Nursing students' work readiness and its influencing factors before participating in a nurse residency program: a multicenter cross-sectional study.

Background: Studies have shown that work readiness is closely related to nurses' role adaptation, career development, and patient safety. However, we know little about the nursing students' work readiness and its influencing factors before participating in a nurse residency program, and whether factors have changed from before. Aim: (1) To investigate the work readiness of nursing students ready to engage in a nurse residency program; (2) to identify the factors affecting the nursing students' work readiness and the associations between emotional intelligence and work readiness; and (3) to discuss the changes of factors affecting nursing students' work readiness. Design: An online, multicenter cross-sectional study. Methods: 878 nursing students from eight tertiary hospitals in Chongqing, China were recruited. The online investigation used the General Information Questionnaire, the Nursing Students' Work Readiness Scale, and the Emotional Intelligence scale. The data were analyzed using IBM SPSS V23.0. Results: 768 valid questionnaires were included in this study. The nurses obtained a work readiness score of 277.08 ± 44.39 and an emotional intelligence score of 89.57 ± 13.89. Univariate analysis revealed that the following factors affected work readiness: age, sex, family support for becoming a nurse, voluntary choice of nursing major, previous experience as a student cadre, scholarship recipient status, willingness to engage in nursing work during the COVID-19 pandemic and confidence in clinical nursing practice. Frequent incidents of violence, poor salary for nurses for the nurse residency program, and low social acceptance were the top three reasons for decreased confidence in clinical nursing among nursing students. Furthermore, multiple linear regression analysis indicated that age, voluntary choice of nursing major, student leadership experience, confidence in clinical nursing work, self-emotion, and emotional application significantly influenced nurses' work readiness. Conclusion: Clinical instructors and administrators should dynamically assess nurses' work readiness, prioritize individuals aged ≤23, who have chosen the nursing profession involuntarily, lack prior experience as student cadres, and exhibit low confidence in clinical nursing work. This focus will enhance their emotional self-management skills and ability to apply emotions effectively, improving their work readiness and training efficacy.

Causal associations between severe COVID-19 and diseases of seven organs: a proteome-wide mendelian randomization study.

The coronavirus disease 2019 (COVID-19) pandemic poses an enormous threat to public health worldwide. Many retrospective studies and case reports to date have shown associations between severe COVID-19 and diseases of multi-organs. However, the research on the causal mechanisms behind this phenomenon is neither extensive nor comprehensive. We conducted a proteome-wide Mendelian randomization (MR) study using summary statistics from a Genome-Wide Association Studies (GWAS) of severe COVID-19 and diseases related to seven organs: lung, spleen, liver, heart, kidney, testis, and thyroid, based on the European ancestry. The primary analytical method used is the radial inverse variance-weighted (radial IVW) method, supplemented with the inverse variance-weighted (IVW), weighted-median (WM), MR-Egger methods. Our findings have confirmed the association between severe COVID-19 and multiple organ-related diseases, such as Hypothyroidism, strict autoimmune (HTCBSA), Thyroid disorders (TD), and Graves' disease (GD). And we have also identified certain proteins that are associated with organ-related diseases, such as Superoxide Dismutase 2 (SOD2) and TEK Receptor Tyrosine Kinase (TEK), which are also considered potential drug targets. Phenotype scanning and sensitivity analyses were implemented to consolidate the results for Mendelian randomization. This study provides a compelling foundation for investigating COVID-19 caused diseases in future studies.

Angelicin improves osteoporosis in ovariectomized rats by reducing ROS production in osteoclasts through regulation of the KAT6A/Nrf2 signalling pathway.

BACKGROUND: Angelicin, which is found in Psoralea, can help prevent osteoporosis by stopping osteoclast formation, although the precise mechanism remains unclear. METHODS: We evaluated the effect of angelicin on the oxidative stress level of osteoclasts using ovariectomized osteoporosis model rats and RAW264.7 cells. Changes in the bone mass of the femur were investigated using H&E staining and micro-CT. ROS content was investigated by DHE fluorescence labelling. Osteoclast-related genes and proteins were examined for expression using Western blotting, immunohistochemistry, tartrate-resistant acid phosphatase staining, and real-time quantitative PCR. The influence of angelicin on osteoclast development was also evaluated using the MTT assay, double luciferin assay, chromatin immunoprecipitation, immunoprecipitation and KAT6A siRNA transfection. RESULTS: Rats treated with angelicin had considerably higher bone mineral density and fewer osteoclasts. Angelicin prevented RAW264.7 cells from differentiating into osteoclasts in vitro when stimulated by RANKL. Experiments revealed reduced ROS levels and significantly upregulated intracellular KAT6A, HO-1, and Nrf2 following angelicin treatment. The expression of genes unique to osteoclasts, such as MMP9 and NFATc1, was also downregulated. Finally, KAT6A siRNA transfection increased intracellular ROS levels while decreasing KAT6A, Nrf2, and HO-1 protein expression in osteoclasts. However, in the absence of KAT6A siRNA transfection, angelicin greatly counteracted this effect in osteoclasts. CONCLUSIONS: Angelicin increased the expression of KAT6A. This enhanced KAT6A expression helps to activate the Nrf2/HO-1 antioxidant stress system and decrease ROS levels in osteoclasts, thus inhibiting oxidative stress levels and osteoclast formation.

On the role of disjoining pressure in nanofluid-assisted enhanced oil recovery: a mini-review.

Nanofluid application in enhanced oil recovery (EOR) recently emerged and garnered significant attention within the field. Nanofluids possess unique properties of reducing oil-water interfacial tension, stabilizing emulsions, altering rock surface wettability, and enhancing disjoining pressure between crude oil and rock surfaces, therefore have potential for the oil recovery process. This review provides an in-depth exploration of various aspects related to nanofluids in EOR. Different types of nanofluids are presented with their preparation methods and representative properties. More importantly, the disjoining pressure, a key physical concept in nanofluid-assisted EOR, is introduced and discussed in terms of the mechanism of oil displacement and measurement methods. Further understanding the role of disjoining pressure in nanofluid-assisted oil displacement is necessary for the development and application of effective nanofluids for EOR.

Atractylodes macrocephala Koidz. and Cuscuta chinensis Lam. extract relieves insulin resistance via PI3K/Akt signalling in diabetic Drosophila.

Background and aim: Type-2 diabetes mellitus (T2DM) is mainly characterized by insulin resistance (IR) induced by hyperglycaemia and insufficient insulin secretion. We employed a diabetic fly model to examine the effect and molecular mechanism of Atractylodes macrocephala Koidz. and Cuscuta chinensis Lam. (AMK-CCL) extract as traditional Chinese medicine in treating IR and T2DM. Experimental procedure: The contents of the active ingredients (rhamnose, xylose, mannose, and hyperoside) in AMK-CCL extract were determined by high-performance liquid chromatography. Wild-type (Cg-GAL4/+) or diabetic (Cg > InRK1409A) Drosophila flies were divided into the control group or metformin group and AMK-CCL (0.0125, 0.025, 0.05, 0.1 g/ml) groups. Food intake, haemolymph glucose and trehalose, protein, weight, triglycerides (TAG), and glycogen were measured to assess glycolipid metabolism. Phosphatidylinositol-3-kinase (PI3K)/Akt signalling was detected using fluorescent reporters [tGPH, Drosophila forkhead box O (dFoxO)-green fluorescent protein (GFP), Glut1-GFP, 2-NBDG] in vivo. Glut1/3 mRNA levels and Akt phosphorylation levels were detected by quantitative polymerase chain reaction and western blotting, respectively, in vitro. Results: AMK-CCL extract contained 0.038 % rhamnose, 0.017 % xylose, 0.69 % mannose, and 0.039 % hyperoside. AMK-CCL at 0.0125 g/mL significantly suppressed the increase in circulating glucose, and the decrease in body weight, TAG, and glycogen contents of diabetic flies. AMK-CCL improved PI3K activity, Akt phosphorylation, Glut1/3 expression, and glucose uptake in diabetic flies, and also rescued diabetes-induced dFoxO nuclear localisation. Conclusions: These findings indicate that AMK-CCL extract ameliorates IR-induced diabetes via the PI3K/Akt signalling pathway, providing an experimental basis for clinical treatment.

Fabrication of heterocellular spheroids with controllable core-shell structure using inertial focusing effect for scaffold-free 3D cell culture models.

Three-dimensional (3D) cell culture models capable of emulating the biological functions of natural tissues are pivotal in tissue engineering and regenerative medicine. Despite progress, the fabrication ofin vitroheterocellular models that mimic the intricate structures of natural tissues remains a significant challenge. In this study, we introduce a novel, scaffold-free approach leveraging the inertial focusing effect in rotating hanging droplets for the reliable production of heterocellular spheroids with controllable core-shell structures. Our method offers precise control over the core-shell spheroid's size and geometry by adjusting the cell suspension density and droplet morphology. We successfully applied this technique to create hair follicle organoids, integrating dermal papilla cells within the core and epidermal cells in the shell, thereby achieving markedly enhanced hair inducibility compared to mixed-structure models. Furthermore, we have developed melanoma tumor spheroids that accurately mimic the dynamic interactions between tumor and stromal cells, showing increased invasion capabilities and altered expressions of cellular adhesion molecules and proteolytic enzymes. These findings underscore the critical role of cellular spatial organization in replicating tissue functionalityin vitro. Our method represents a significant advancement towards generating heterocellular spheroids with well-defined architectures, offering broad implications for biological research and applications in tissue engineering.