Microwave-Assisted Unidirectional Superconductivity in Al-InAs Nanowire-Al Junctions under Magnetic Fields.

Under certain symmetry-breaking conditions, a superconducting system exhibits asymmetric critical currents, dubbed the "superconducting diode effect." Recently, systems with the ideal superconducting diode efficiency or unidirectional superconductivity have received considerable interest. In this work, we report the study of Al-InAs nanowire-Al Josephson junctions under microwave irradiation and magnetic fields. We observe an enhancement of superconducting diode effect under microwave driving, featured by a horizontal offset of the zero-voltage step in the voltage-current characteristic that increases with microwave power. Devices reach the unidirectional superconductivity regime at sufficiently high driving amplitudes. The offset changes sign with the reversal of the magnetic field direction. Meanwhile, the offset magnitude exhibits a roughly linear response to the microwave power in dBm when both the power and the magnetic field are large. The signatures observed are reminiscent of a recent theoretical proposal using the resistively shunted junction (RSJ) model. However, the experimental results are not fully explained by the RSJ model, indicating a new mechanism for unidirectional superconductivity that is possibly related to nonequilibrium dynamics or dissipation in periodically driven superconducting systems.

Sn/InAs Josephson Junctions on Selective Area Grown Nanowires with in Situ Shadowed Superconductor Evaporation.

Superconductor-semiconductor nanowire hybrid structures are useful in fabricating devices for quantum information processing. While selective area growth (SAG) offers the flexibility to grow semiconductor nanowires in arbitrary geometries, in situ evaporation of superconductors ensures pristine superconductor-semiconductor interfaces, resulting in strong induced superconductivity in the semiconducting nanowire. In this work, we used high-aspect-ratio SiOx dielectric walls to in situ evaporate islands of superconductor tin on in-plane InAs SAG nanowires. Our technique enables customization in the designs of such hybrid nanostructures, while simultaneously performing the nanowire and superconductor growth without breaking vacuum. Using this technique, we grew super(S)-normal(N)-super(S), NS, and SNSNS junctions. We performed cryogenic electron transport measurements revealing the presence of gate and field tunable supercurrents. We further measured the superconducting gap and critical fields in the hybrid nanostructures and the crossover from 2e to 1e periodicity in the SNSNS junctions as a proof of the usability of these hybrid nanostructures.

Signatures of Andreev Blockade in a Double Quantum Dot Coupled to a Superconductor.

We investigate an electron transport blockade regime in which a spin triplet localized in the path of current is forbidden from entering a spin-singlet superconductor. To stabilize the triplet, a double quantum dot is created electrostatically near a superconducting Al lead in an InAs nanowire. The quantum dot closest to the normal lead exhibits Coulomb diamonds, and the dot closest to the superconducting lead exhibits Andreev bound states and an induced gap. The experimental observations compare favorably to a theoretical model of Andreev blockade, named so because the triplet double dot configuration suppresses Andreev reflections. Observed leakage currents can be accounted for by finite temperature. We observe the predicted quadruple level degeneracy points of high current and a periodic conductance pattern controlled by the occupation of the normal dot. Even-odd transport asymmetry is lifted with increased temperature and magnetic field. This blockade phenomenon can be used to study spin structure of superconductors. It may also find utility in quantum computing devices that use Andreev or Majorana states.

Cerebroventricular Injection of Pgk1 Attenuates MPTP-Induced Neuronal Toxicity in Dopaminergic Cells in Zebrafish Brain in a Glycolysis-Independent Manner.

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons. While extracellular Pgk1 (ePgk1) is reported to promote neurite outgrowth, it remains unclear if it can affect the survival of dopaminergic cells. To address this, we employed cerebroventricular microinjection (CVMI) to deliver Pgk1 into the brain of larvae and adult zebrafish treated with methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as a PD-like model. The number of dopamine-producing cells in ventral diencephalon clusters of Pgk1-injected, MPTP-treated embryos increased over that of MPTP-treated embryos. Swimming distances of Pgk1-injected, MPTP-treated larvae and adult zebrafish were much longer compared to MPTP-treated samples. The effect of injected Pgk1 on both dopamine-producing cells and locomotion was time- and dose-dependent. Indeed, injected Pgk1 could be detected, located on dopamine neurons. When the glycolytic mutant Pgk1, Pgk1-T378P, was injected into the brain of MPTP-treated zebrafish groups, the protective ability of dopaminergic neurons did not differ from that of normal Pgk1. Therefore, ePgk1 is functionally independent from intracellular Pgk1 serving as an energy supplier. Furthermore, when Pgk1 was added to the culture medium for culturing dopamine-like SH-SY5Y cells, it could reduce the ROS pathway and apoptosis caused by the neurotoxin MPP+. These results show that ePgk1 benefits the survival of dopamine-producing cells and decreases neurotoxin damage.

Correction to: Surgical treatment of traumatic distal anterior cerebral artery aneurysm: a report of nine cases from a single centre.

Incorrect family name of Dongsheng Guo.

Surgical treatment of traumatic distal anterior cerebral artery aneurysm: a report of nine cases from a single centre.

BACKGROUND: Traumatic distal anterior cerebral artery (dACA) aneurysm is rare and can be easily neglected and misdiagnosed in patients with trauma. The aim of this study was to explore the radiologic characteristics of and therapeutic strategies for traumatic dACA aneurysm and to improve our understanding of unusual complications after trauma. METHODS: The clinical data of nine cases of traumatic dACA aneurysm from our neurosurgical department from July 1, 2010, to July 1, 2018, were retrospectively analysed. RESULTS: All 9 patients had a history of brain trauma. The initial computed tomography scan immediately after trauma showed subarachnoid haemorrhage in 8 cases. Among these cases, delayed intracranial haemorrhage occurred in 7 cases. The average interval between injury and diagnosis was 13.67 ± 9.43 days. All 9 cases were confirmed as traumatic dACA aneurysm by computed tomography angiography (CTA) and/or digital subtraction angiography. According to Lehecka's classification system, traumatic dACA aneurysm located in the A3 and A4 segment was found in 3 and 6 cases, respectively. Surgical treatment was performed in 8 cases, including neck clipping, with or without wrapping in 3 cases, trapping in 4 cases, aneurysm excision and suturing in 1 case and conservative treatment in 1 case. Three patients required a ventriculoperitoneal shunt due to severe hydrocephalus. According to the Glasgow Outcome Scale scoring system, good recovery was achieved in 4 cases, moderate disability in 2 cases, severe disability in 1 case, and death in 2 cases. CONCLUSION: Traumatic dACA aneurysm is a rare complication of brain trauma. Delayed intracranial haemorrhage and the sudden deterioration of neurologic function were the typical characteristics in patients with traumatic dACA aneurysm. CTA is the first-line screening modality for patients who present with intracerebral haemorrhage in the corpus callosum after trauma, particularly for patients who are older, in a poorer or critical condition. When the aneurysm is located in the A4 segment or involves a small branch, surgical trapping is the preferred definitive therapy to prevent further growth and disastrous bleeding. Early diagnosis and prompt treatment could help to improve clinical outcomes.

Simultaneous transcatheter therapy for perimembranous ventricular septal defect combined with patent ductus arteriosus.

OBJECTIVE: This study aims to assess the clinical efficiency and safety of simultaneous transcatheter interventional treatment for perimembranous ventricular septal defect (pmVSD) combined with patent ductus arteriosus (PDA). METHODS: Twenty-five patients with pmVSD and PDA treated with simultaneous transcatheter interventions from April 2004 to December 2015 were included in this study. The mean age was 9.80 ± 8.14 years and the mean weight was 29.76 ± 14.82 Kg. Transthoracic echocardiography (TTE) and angiography were performed immediately after the procedure. Patients were re-examined by electrocardiogram, X-ray, and TTE at 2 days, 1 month, 3 months, and 6 months postoperatively. RESULTS: The interventional procedure was successfully performed in all 25 patients. No intraoperative complication was noted. TTE examination of the VSD and PDA immediately after the procedure showed no residual shunt and the occluder was well positioned. Among these patients, four patients showed electrocardiogram changes after the procedure that resolved after drug therapy. The cardiothoracic ratio, left atrial diameter, left ventricular end-systolic diameter, and left ventricular end-diastolic diameter recovered to normal in most patients at 6 months postoperatively. CONCLUSIONS: Simultaneously transcatheter interventional therapy is a safe and effective method for pmVSD combined with PDA.

Robust Grape Cluster Detection in a Vineyard by Combining the AdaBoost Framework and Multiple Color Components.

The automatic fruit detection and precision picking in unstructured environments was always a difficult and frontline problem in the harvesting robots field. To realize the accurate identification of grape clusters in a vineyard, an approach for the automatic detection of ripe grape by combining the AdaBoost framework and multiple color components was developed by using a simple vision sensor. This approach mainly included three steps: (1) the dataset of classifier training samples was obtained by capturing the images from grape planting scenes using a color digital camera, extracting the effective color components for grape clusters, and then constructing the corresponding linear classification models using the threshold method; (2) based on these linear models and the dataset, a strong classifier was constructed by using the AdaBoost framework; and (3) all the pixels of the captured images were classified by the strong classifier, the noise was eliminated by the region threshold method and morphological filtering, and the grape clusters were finally marked using the enclosing rectangle method. Nine hundred testing samples were used to verify the constructed strong classifier, and the classification accuracy reached up to 96.56%, higher than other linear classification models. Moreover, 200 images captured under three different illuminations in the vineyard were selected as the testing images on which the proposed approach was applied, and the average detection rate was as high as 93.74%. The experimental results show that the approach can partly restrain the influence of the complex background such as the weather condition, leaves and changing illumination.

Acute effects of Rho-kinase inhibitor fasudil on pulmonary arterial hypertension in patients with congenital heart defects.

BACKGROUND: We investigated the acute vasodilator effects of i.v. fasudil, a specific Rho-kinase inhibitor, on pulmonary circulation in patients with congenital heart defects (CHD) and severe pulmonary arterial hypertension (PAH). METHODS AND RESULTS: Thirty-five patients (34.23±12.10 years old) with CHD and severe PAH were consecutively enrolled. All patients underwent heart catheterization. At baseline and 30 min after initiation of i.v. fasudil, the following hemodynamic parameters were measured and calculated: right atrial pressure, pulmonary and systemic artery pressure (PAP and SAP), pulmonary and systemic vascular resistance, pulmonary-to-systemic blood pressure ratio (Pp/Ps), pulmonary-to-systemic blood flow ratio (Qp/Qs), cardiac index (CI) and artery oxygen saturation (SaO2). After fasudil treatment, marked decrease in mean PAP (mPAP), pulmonary vascular resistance (PVR), total pulmonary resistance, pulmonary-to-systemic vascular resistance ratio (Rp/Rs) and mean Pp/Ps (mPp/Ps) was found, while Qp/Qs increased significantly without affecting CI and SAP. mPAP, PVR, Rp/Rs and Qp/Qs tended to be improved more significantly in the post-tricuspid shunt group compared with the pre-tricuspid shunt group. CONCLUSIONS: Fasudil was well tolerated in patients with CHD and severe PAH, and significantly reduced PAP and PVR without affecting CI, SAP or SaO2.

3D PRINTING IN COMPLEX TIBIAL FRACTURE CLASSIFICATION & PLANNING.

Objective: Tibial plateau fractures are common intra-articular fractures that pose classification and treatment challenges for orthopedic surgeons. Objective: This study examines the value of 3D printing for classifying and planning surgery for complex tibial plateau fractures. Methods: We reviewed 54 complex tibial plateau fractures treated at our hospital from January 2017 to January 2019. Patients underwent preoperative spiral CT scans, with DICOM data processed using Mimics software. 3D printing technology created accurate 1:1 scale models of the fractures. These models helped subdivide the fractures into seven types based on the tibial plateau's geometric planes. Surgical approaches and simulated operations, including fracture reduction and plate placement, were planned using these models. Results: The 3D models accurately depicted the direction and extent of fracture displacement and plateau collapse. They facilitated the preoperative planning, allowing for precise reconstruction strategies and matching intraoperative details with the pre-printed models. Post-surgery, the anatomical structure of the tibial plateau was significantly improved in all 54 cases. Conclusion: 3D printing effectively aids in the classification and preoperative planning of complex tibial plateau fractures, enhancing surgical outcomes and anatomical restoration. Level of Evidence IV, Prospective Study.

Objetivo: As fraturas do planalto tibial são fraturas intra-articulares comuns de classificação e tratamento desafiadores aos cirurgiões ortopédicos. Objetivo: Este estudo investiga o uso de impressão 3D para classificar e planejar a cirurgia de fraturas complexas do planalto tibial. Métodos: 54 fraturas complexas do planalto tibial tratadas em nosso hospital de janeiro de 2017 a janeiro de 2019 foram revisadas. Os pacientes foram submetidos a tomografias computadorizadas em espiral pré-operatórias, com dados DICOM processados usando o software Mimics. A tecnologia de impressão 3D gerou modelos precisos em escala 1:1 das fraturas. Estes modelos ajudaram a subdividir as fraturas em sete tipos com base nos planos geométricos do planalto tibial. As abordagens cirúrgicas e as operações simuladas, incluindo a redução da fratura e a colocação de placa, foram planejadas utilizando estes modelos. Resultados: Os modelos 3D representaram com precisão a direção e a extensão da deslocação da fratura e do colapso do planalto. Os modelos facilitaram o planejamento pré-operatório, viabilizando estratégias de reconstrução precisas e a correspondência dos detalhes intraoperatórios com os modelos pré-impressos. Após a cirurgia, a estrutura anatômica do planalto tibial melhorou significativamente em todos os 54 casos. Conclusão: A impressão 3D ajuda na classificação e no planejamento pré-operatório de fraturas complexas do planalto tibial, melhorando os resultados cirúrgicos e a restauração anatômica. Nível de Evidência IV, Estudo Prospectivo.

Gate-defined quantum point contacts in a germanium quantum well.

We report an experimental study of quantum point contacts defined in a high-quality strained germanium quantum well with layered electric gates. At a zero magnetic field, we observed quantized conductance plateaus in units of 2e2/h. Bias-spectroscopy measurements reveal that the energy spacing between successive one-dimensional subbands ranges from 1.5 to 5 meV as a consequence of the small effective mass of the holes and the narrow gate constrictions. At finite magnetic fields perpendicular to the device plane, the edges of the conductance plateaus get split due to the Zeeman effect and Landé g factors were estimated to be ∼6.6 for the holes in the germanium quantum well. We demonstrate that all quantum point contacts in the same device have comparable performances, indicating a reliable and reproducible device fabrication process. Thus, our work lays a foundation for investigating multiple forefronts of physics in germanium-based quantum devices that require quantum point contacts as building blocks.

Bioactive fiber-reinforced hydrogel to tailor cell microenvironment for structural and functional regeneration of myotendinous junction.

Myotendinous junction (MTJ) injuries are prevalent in clinical practice, yet the treatment approaches are limited to surgical suturing and conservative therapy, exhibiting a high recurrence rate. Current research on MTJ tissue engineering is scarce and lacks in vivo evaluation of repair efficacy. Here, we developed a three-dimensional-printed bioactive fiber-reinforced hydrogel containing mesenchymal stem cells (MSCs) and Klotho for structural and functional MTJ regeneration. In a rat MTJ defect model, the bioactive fiber-reinforced hydrogel promoted the structural restoration of muscle, tendon, and muscle-tendon interface and enhanced the functional recovery of injured MTJ. In vivo proteomics and in vitro cell cultures elucidated the regenerative mechanisms of the bioactive fiber-reinforced hydrogel by modulating oxidative stress and inflammation, thus engineering an optimized microenvironment to support the survival and differentiation of transplanted MSCs and maintain the functional phenotype of resident cells within MTJ tissues, including tendon/muscle cells and macrophages. This strategy provides a promising treatment for MTJ injuries.

Low level of tumor necrosis factor α in tumor microenvironment maintains self-renewal of glioma stem cells by Vasorin-mediated glycolysis.

BACKGROUND: Self-renewal of glioma stem cells (GSCs) is responsible for glioblastoma (GBM) therapy-resistant and recurrence. Tumor necrosis factor α (TNFα) and TNF signaling pathway display an antitumor activity in preclinical models and in tumor patients. However, TNFα exhibits no significance for glioma clinical prognosis based on Glioma Genome Atlas database. This study aimed to explore whether TNFα of tumor microenvironment maintains self-renewal of GSCs and promotes worse prognosis in glioma patient. METHODS: Spatial transcriptomics, immunoblotting, sphere formation assay, extreme limiting dilution, and gene expression analysis were used to determine the role of TNFα on GSC's self-renewal. Mass spectrometry, RNA-sequencing detection, bioinformatic analyses, qRT-RNA, immunofluorescence, immunohistochemistry, single cell RNA sequencing, in vitro and in vivo models were used to uncover the mechanism of TNFα-induced GSC self-renewal. RESULTS: Low level of TNFα displays a promoting effect on GSC self-renewal and worse glioma prognosis. Mechanistically, Vasorin (VASN) mediated TNFα-induced self-renewal by potentiating glycolysis. Lactate produced by glycolysis inhibits the TNFα secretion of tumor-associated macrophages (TAMs) and maintains TNFα in a low level. CONCLUSIONS: TNFα-induced GSC self-renewal mediated by VASN provides a possible explanation for the failures of endogenous TNFα effect on GBM. Combination of targeting VASN and TNFα anti-tumor effect may be an effective approach for treating GBM.

Transgelin Promotes Glioblastoma Stem Cell Hypoxic Responses and Maintenance Through p53 Acetylation.

Glioblastoma (GBM) is a lethal cancer characterized by hypervascularity and necrosis associated with hypoxia. Here, it is found that hypoxia preferentially induces the actin-binding protein, Transgelin (TAGLN), in GBM stem cells (GSCs). Mechanistically, TAGLN regulates HIF1α transcription and stabilizes HDAC2 to deacetylate p53 and maintain GSC self-renewal. To translate these findings into preclinical therapeutic paradigm, it is found that sodium valproate (VPA) is a specific inhibitor of TAGLN/HDAC2 function, with augmented efficacy when combined with natural borneol (NB) in vivo. Thus, TAGLN promotes cancer stem cell survival in hypoxia and informs a novel therapeutic paradigm.

A 3D multifunctional bi-layer scaffold to regulate stem cell behaviors and promote osteochondral regeneration.

Osteochondral defect (OCD) regeneration remains a great challenge. Recently, multilayer scaffold simulating native osteochondral structures have aroused broad interest in osteochondral tissue engineering. Here, we developed a 3D multifunctional bi-layer scaffold composed of a kartogenin (KGN)-loaded GelMA hydrogel (GelMA/KGN) as an upper layer mimicking a cartilage-specific extracellular matrix and a hydroxyapatite (HA)-coated 3D printed polycaprolactone porous scaffold (PCL/HA) as a lower layer simulating subchondral bone. The bi-layer scaffolds were subsequently modified with tannic acid (TA) prime-coating and E7 peptide conjugation (PCL/HA-GelMA/KGN@TA/E7) to regulate endogenous stem cell behaviors and exert antioxidant activity for enhanced osteochondral regeneration. In vitro, the scaffolds could support cell attachment and proliferation, and enhance the chondrogenic and osteogenic differentiation capacity of bone marrow-derived mesenchymal stem cells (BMSCs) in a specific layer. Besides, the incorporation of TA/E7 significantly increased the biological activity of the bi-layer scaffolds including the pro-migratory effect, antioxidant activity, and the maintenance of cell viability against oxidative stress. In vivo, the developed bi-layer scaffolds enhanced the simultaneous regeneration of cartilage and subchondral bone when implanted into a rabbit OCD model through macroscopic, micro-CT, and histological evaluation. Taken together, these investigations demonstrated that the 3D multifunctional bi-layer scaffolds could provide a suitable microenvironment for endogenous stem cells, and promote in situ osteochondral regeneration, showing great potential for the clinical treatment of OCD.

Enhanced Cartilage and Subchondral Bone Repair Using Carbon Nanotube-Doped Peptide Hydrogel-Polycaprolactone Composite Scaffolds.

A carbon nanotube-doped octapeptide self-assembled hydrogel (FEK/C) and a hydrogel-based polycaprolactone PCL composite scaffold (FEK/C3-S) were developed for cartilage and subchondral bone repair. The composite scaffold demonstrated modulated microstructure, mechanical properties, and conductivity by adjusting CNT concentration. In vitro evaluations showed enhanced cell proliferation, adhesion, and migration of articular cartilage cells, osteoblasts, and bone marrow mesenchymal stem cells. The composite scaffold exhibited good biocompatibility, low haemolysis rate, and high protein absorption capacity. It also promoted osteogenesis and chondrogenesis, with increased mineralization, alkaline phosphatase (ALP) activity, and glycosaminoglycan (GAG) secretion. The composite scaffold facilitated accelerated cartilage and subchondral bone regeneration in a rabbit knee joint defect model. Histological analysis revealed improved cartilage tissue formation and increased subchondral bone density. Notably, the FEK/C3-S composite scaffold exhibited the most significant cartilage and subchondral bone formation. The FEK/C3-S composite scaffold holds great promise for cartilage and subchondral bone repair. It offers enhanced mechanical support, conductivity, and bioactivity, leading to improved tissue regeneration. These findings contribute to the advancement of regenerative strategies for challenging musculoskeletal tissue defects.

Silk-based hydrogel incorporated with metal-organic framework nanozymes for enhanced osteochondral regeneration.

Osteochondral defects (OCD) cannot be efficiently repaired due to the unique physical architecture and the pathological microenvironment including enhanced oxidative stress and inflammation. Conventional strategies, such as the control of implant microstructure or the introduction of growth factors, have limited functions failing to manage these complex environments. Here we developed a multifunctional silk-based hydrogel incorporated with metal-organic framework nanozymes (CuTA@SF) to provide a suitable microenvironment for enhanced OCD regeneration. The incorporation of CuTA nanozymes endowed the SF hydrogel with a uniform microstructure and elevated hydrophilicity. In vitro cultivation of mesenchymal stem cells (MSCs) and chondrocytes showed that CuTA@SF hydrogel accelerated cell proliferation and enhanced cell viability, as well as had antioxidant and antibacterial properties. Under the inflammatory environment with the stimulation of IL-1ß, CuTA@SF hydrogel still possessed the potential to promote MSC osteogenesis and deposition of cartilage-specific extracellular matrix (ECM). The proteomics analysis further confirmed that CuTA@SF hydrogel promoted cell proliferation and ECM synthesis. In the full-thickness OCD model of rabbit, CuTA@SF hydrogel displayed successfully in situ OCD regeneration, as evidenced by micro-CT, histology (HE, S/O, and toluidine blue staining) and immunohistochemistry (Col I and aggrecan immunostaining). Therefore, CuTA@SF hydrogel is a promising biomaterial targeted at the regeneration of OCD.

Glioma-derived LRIG3 interacts with NETO2 in tumor-associated macrophages to modulate microenvironment and suppress tumor growth.

Tumor-associated macrophages (TAMs) account for 30-50% of glioma microenvironment. The interaction between glioma tumor cells and TAMs can promote tumor progression, but the intrinsic mechanisms remain unclear. Herein, we reported that soluble LRIG3 (sLRIG3) derived from glioma tumor cells can block the M2 polarization of TAMs via interacting with NETO2, thus suppressing GBM malignant progression. The expression or activity of ADAM17 in glioma cells was positively correlated with the expression of sLRIG3 in cell supernatant. Soluble LRIG3 can suppress the M2-like polarity transformation of TAMs and inhibit the growth of tumor. High expression of LRIG3 predicts a good prognosis in patients with glioma. Mass spectrometry and Co-immunoprecipitation showed that sLRIG3 interacts with the CUB1 domain of NETO2 in TAMs. Silencing or knockout of NETO2 could block the effect of sLRIG3, which inhibited the M2-like polarity transformation of TAMs and promoted GBM tumor growth. However, overexpressing His-target NETO2 with CUB1 deletion mutation does not fully recover the suppressive effects of sLRIG3 on the TAM M2-polarization in NETO2-Knockout TAMs. Our study revealed vital molecular crosstalk between GBM tumor cells and TAMs. Glioma cells mediated the M2 polarization of TAM through the sLRIG3-NETO2 pathway and inhibited the progression of GBM, suggesting that sLRIG3-NETO2 may be a potential target for GBM treatment.

Silk Fibroin and Sericin Differentially Potentiate the Paracrine and Regenerative Functions of Stem Cells Through Multiomics Analysis.

Silk fibroin (SF) and sericin (SS), the two major proteins of silk, are attractive biomaterials with great potential in tissue engineering and regenerative medicine. However, their biochemical interactions with stem cells remain unclear. In this study, multiomics are employed to obtain a global view of the cellular processes and pathways of mesenchymal stem cells (MSCs) triggered by SF and SS to discern cell-biomaterial interactions at an in-depth, high-throughput molecular level. Integrated RNA sequencing and proteomic analysis confirm that SF and SS initiate widespread but distinct cellular responses and potentiate the paracrine functions of MSCs that regulate extracellular matrix deposition, angiogenesis, and immunomodulation through differentially activating the integrin/PI3K/Akt and glycolysis signaling pathways. These paracrine signals of MSCs stimulated by SF and SS effectively improve skin regeneration by regulating the behavior of multiple resident cells (fibroblasts, endothelial cells, and macrophages) in the skin wound microenvironment. Compared to SS, SF exhibits better immunomodulatory effects in vitro and in vivo, indicating its greater potential as a carrier material of MSCs for skin regeneration. This study provides comprehensive and reliable insights into the cellular interactions with SF and SS, enabling the future development of silk-based therapeutics for tissue engineering and stem cell therapy.

FAM129A promotes self-renewal and maintains invasive status via stabilizing the Notch intracellular domain in glioma stem cells.

BACKGROUND: Glioma stem cells (GSCs) are a subpopulation of tumor cells with self-renewal and tumorigenic capabilities in glioblastomas (GBMs). Diffuse infiltration of GSCs facilitates tumor progression and frustrates efforts at effective treatment. Further compounding this situation is the currently limited understanding of what drives GSC invasion. Here we comprehensively evaluated the significance of a novel invasion-related protein, Family with Sequence Similarity 129 Member A (FAM129A), in infiltrative GSCs. METHODS: Western blotting, immunohistochemistry, and gene expression analysis were used to quantify FAM129A in glioma specimens and cancer datasets. Overexpression and knockdown of FAM129A in GSCs were used to investigate its effects on tumor growth and invasion. RNA-seq, qRT-PCR, western blotting, and co-precipitation assays were used to investigate FAM129A signaling mechanisms. RESULTS: FAM129A is preferentially expressed in invasive frontiers. Targeting FAM129A impairs GSC invasion and self-renewal. Mechanistically, FAM129A acted as a positive regulator of Notch signaling by binding with the Notch1 intracellular domain (NICD1) and preventing its degradation. CONCLUSIONS: FAM129A and NICD1 provide a precise indicator for identifying tumor margins and aiding prognosis. Targeting them may provide a significantly therapeutic strategy for GSCs.