Microstructure Evolution and Electrical Behaviors for High-Performance Cu2O/Zr-Doped ß-Ga2O3 Heterojunction Diodes.

Beta-gallium oxide (ß-Ga2O3) is emerging as a promising ultrawide band gap (UWBG) semiconductor, which is vital for high-power, high-frequency electronics and deep-UV optoelectronics. It is especially significant for flexible wearable electronics, enabling the fabrication of high-performance Ga2O3-based devices at low temperatures. However, the limited crystallinity and pronounced structural defects arising from the low-temperature deposition of Ga2O3 films significantly restrict the heterojunction interface quality and the relevant electrical performance of Ga2O3-based devices. In this work, cuprous oxide (Cu2O)/Zr-doped ß-Ga2O3 heterojunction diodes are fabricated by magnetron sputtering without intentional substrate heating, followed by an investigation into their microstructure and electrical behaviors. Zr doping can markedly enhance the Ga2O3 crystallinity at low substrate temperatures, transforming the amorphous structure of pristine Ga2O3 films into the crystallized ß phase. Moreover, crystalline ß-Ga2O3 facilitates the epitaxial growth of the Cu2O phase, suppressing the formation of detrimental secondary phase CuO at the heterojunction interface. Benefiting from the high-quality heterojunction interface, the Cu2O/Zr-doped ß-Ga2O3 heterojunction diode exhibits a near-ideal electrical behavior with a low ideality factor of 1.6. The consistent electrical parameters extracted from current-voltage (J-V) and capacitance-voltage (C-V) measurements also confirm the high quality of ß-Ga2O3. This work highlights the potential for the low-temperature production of high-quality ß-Ga2O3-based heterojunction devices through Zr doping.

Generating complex vectorial optical fields via surface lattice resonances.

Vectorial optical fields (VOFs) with extra degrees of freedom hold promise for many photonic applications. However, current methods to generate VOFs are either bulky in size or exhibit limited functionalities. Here, we demonstrate a tunable VOF generator by exciting plasmonic surface lattice resonances (SLRs) with axial symmetry. By meticulously arranging bilayer circular arrays with opposite handedness, we achieve a high Q-factor of 103 via just a few particles despite the general belief that too small array size suppresses the SLRs. This work presents tunable complex VOFs with distinct inhomogeneous spatial polarization distributions, which may enable various applications in integrated and polarization optics.

Photoinduced Lignin C α -C ß Bond Cleavage and Chemodivergent Functionalization via Iron Catalysis.

The photocatalytic conversion of lignin into value-added chemicals especially those functionalized molecules represent one of the most important strategies for sustainable and environmental-friendly development. Cleavage of C-C bonds in lignin under mild photocatalytic conditions for refining lignin into useful molecules is meaningful but challenging. Meanwhile, the assembly of diverse functional groups into active lignin fragments during the depolymerization is of great challenging. Herein, using cheap iron catalysts under visible light irradiation, the highly selective and efficient cleavage of Cα-Cß bond in lignin is realized via ligand-to-metal charge transfer (LMCT) and hydrogen atom transfer (HAT) processes. The subsequent divergent functionalization of generated lignin fragment-based radical intermediates enables an efficient formation of diverse functionalized molecules. This method is also effective for cleavage of Cα-Cß bond in native lignin, yielding two identified benzaldehyde monomers in a total yield of 8.7 wt%.

Distance and grid-like codes support the navigation of abstract social space in the human brain.

People form impressions about others during daily social encounters and infer personality traits from others' behaviors. Such trait inference is thought to rely on two universal dimensions: competence and warmth. These two dimensions can be used to construct a 'social cognitive map' organizing massive information obtained from social encounters efficiently. Originating from spatial cognition, the neural codes supporting the representation and navigation of spatial cognitive maps have been widely studied. Recent studies suggest similar neural mechanism subserves the map-like architecture in social cognition as well. Here we investigated how spatial codes operate beyond the physical environment and support the representation and navigation of social cognitive map. We designed a social value space defined by two dimensions of competence and warmth. Behaviorally, participants were able to navigate to a learned location from random starting locations in this abstract social space. At the neural level, we identified the representation of distance in the precuneus, fusiform gyrus, and middle occipital gyrus. We also found partial evidence of grid-like representation patterns in the medial prefrontal cortex and entorhinal cortex. Moreover, the intensity of grid-like response scaled with the performance of navigating in social space and social avoidance trait scores. Our findings suggest a neurocognitive mechanism by which social information can be organized into a structured representation, namely cognitive map and its relevance to social well-being.

When advisors do not know what is best for advisees: Uncertainty inhibits advice giving.

While seeking advice can be beneficial for advisees, advisors may not always possess the necessary knowledge to provide appropriate guidance. Poor-quality advice can mislead advisees rather than offering assistance. Despite the research interest in advisees, few studies have investigated advisors' psychological and behavioral responses, especially when they faced uncertainty regarding the optimal course of action for advisees. To fill this gap, we developed novel paradigms aiming at manipulating advisors' uncertainty, allowing for a systematic investigation of advisors' behavior, motivation, and emotion. Across four studies, we consistently found that advisors under uncertainty give less advice. Furthermore, we observed that uncertainty modulates advisors' motivation to influence, worry about harm to others, and/or sense of power. The motivation to influence and/or worry about harm to others can mediate the effect of uncertainty on advice giving. Besides, we identified nuanced distinctions in the effects of ambiguity and risk, two distinct types of uncertainty, on advisors' psychological processes. Our findings shed light on advisors' self-monitoring of the quality of their advice, thereby contributing to a deeper understanding of advisor-advisee communication from the perspective of advisors.

Photocatalytic Conversion of Lignin Models into Functionalized Aromatic Molecules Initiated by the Proton-Coupled Electron Transfer Process.

A mild and efficient method for lignin ß-O-4 cleavage and functionalization was achieved via photocatalysis. This protocol exhibits a broad scope of lignin models and excellent compatibility of functionalization reagents, constructing a series of functionalized lignin-based aromatic compounds. Highly selective formation of alkyl radical species through a proton-coupled electron transfer and ß-scission process provides the opportunity to form new C-C and C-N bonds by reaction with electrophilic reagents.

Safety and efficacy of tislelizumab plus chemotherapy as preoperative treatment in potentially resectable locally advanced non-small-cell lung cancer patients.

OBJECTIVES: Locally advanced non-small-cell lung cancer (LA-NSCLC) requires more preoperative regiments in the era of immunotherapy. Tislelizumab was approved for first-line treatment for advanced lung cancer, bringing hope for preoperative therapy in LA-NSCLC. The aim of this study was to investigate the safety and efficacy of preoperative tislelizumab plus chemotherapy in LA-NSCLC. METHODS: The medical records at the First Affiliated Hospital of Zhejiang University were examined retrospectively from September 2019 to June 2022 for this descriptive single-arm cohort study. Patients with LA-NSCLC were treated with tislelizumab plus platinum-based dual-drug regimens for 2-6 cycles and regular imaging assessments were performed every 1-2 cycles. Data including demographic characteristics, clinicopathological staging, adverse events and surgery-related details were recorded in specifically designed forms. RESULTS: Forty patients met the inclusion criteria of the study and 23 patients underwent curative intent surgeries. Significantly clinical and pathological downstaging was observed, with the objective response rate being 65.00%, leading to a major pathological remission (MPR) rate of 56.52% and a pathological complete remission (pCR) rate of 34.78%. Grade 3-4 treatment-related adverse events occurred in 4 patients and no perioperative death occurred. The 1-year progress-free survival rate and the 1-year overall survival rate were 85.0% and 90.0%, respectively. CONCLUSIONS: Tislelizumab plus chemotherapy as preoperative therapy demonstrates promising antitumour activity for potentially resectable LA-NSCLC with high MPR, pCR and acceptable toxicity and survival.

Imbedding Pd Nanoparticles into Porous In2O3 Structure for Enhanced Low-Concentration Methane Sensing.

Methane (CH4), as the main component of natural gas and coal mine gas, is widely used in daily life and industrial processes and its leakage always causes undesirable misadventures. Thus, the rapid detection of low concentration methane is quite necessary. However, due to its robust chemical stability resulting from the strong tetrahedral-symmetry structure, the methane molecules are usually chemically inert to the sensing layers in detectors, making the rapid and efficient alert a big challenge. In this work, palladium nanoparticles (Pd NPs) embedded indium oxide porous hollow tubes (In2O3 PHTs) were successfully synthesized using Pd@MIL-68 (In) MOFs as precursors. All In2O3-based samples derived from Pd@MIL-68 (In) MOFs inherited the morphology of the precursors and exhibited the feature of hexagonal hollow tubes with porous architecture. The gas-sensing performances to 5000 ppm CH4 were evaluated and it was found that Pd@In2O3-2 gave the best response (Ra/Rg = 23.2) at 370 °C, which was 15.5 times higher than that of pristine-In2O3 sensors. In addition, the sensing materials also showed superior selectivity against interfering gases and a rather short response/recovery time of 7 s/5 s. The enhancement in sensing performances of Pd@In2O3-2 could be attributed to the large surface area, rich porosity, abundant oxygen vacancies and the catalytic function of Pd NPs.

The Safety and Efficacy of Preoperative Immunotherapy Combined with Chemotherapy in Patients with Stage IIIA-IIIB Lung Squamous Cell Carcinoma.

OBJECTIVE: Data on preoperative immunotherapy combined with chemotherapy in potentially resectable lung squamous cell carcinoma (LUSC) remain scarce. This study was designed to investigate the safety and efficacy of preoperative immunotherapy and chemotherapy for stage IIIA-IIIB LUSC. METHODS: This study consecutively enrolled stage IIIA-IIIB LUSC who received preoperative immunotherapy combined with chemotherapy between January 2019 and July 2021. Patients received two to four cycles of immunotherapy combined with platinum-based doublet chemotherapy (platinum + paclitaxel) before surgery. Patients were assessed radiographically every one to two cycles until surgery. Postoperative pathological evaluation was also performed. Follow-up was performed until at least 3 months after surgery. RESULTS: Sixty-five patients with stage IIIA-IIIB LUSC were enrolled. The objective response rate was 78.46% (51/65), and no patients had progressive disease. Fifty-seven patients underwent surgery, and 55 patients achieved R0 resection. There were no perioperative deaths. The rate of pathological complete response (pCR) was 31.58% (18/57) and major pathological response was 68.42% (39/57). The incidence of grade 3 and 4 adverse reactions was 21.21 and 1.54%, respectively. CONCLUSION: Perioperative immunotherapy combined with chemotherapy followed by surgical resection for male patients with stage IIIA-IIIB LUSC was effective with a tolerable toxicity profile.

Heterogeneous Cu9S5/C nanocomposite fibers with adjustable electromagnetic parameters for efficient electromagnetic absorption.

One-dimensional carbon-based materials have emerged as promising electromagnetic wave absorption agents due to their outstanding conductivity, high stability, low weight, and easy availability. Properly optimizing their electromagnetic parameters is expected to further enhance the electromagnetic wave attenuation capacity. In this work, efficient Cu9S5/C nanocomposite fibers are prepared by a combined approach of electrospinning and subsequent carbonization-sulfurization processes. The Cu9S5 nanoparticles with size of ca. 100-200 nm were homogeneously embedded in fibrous carbon matrix with diameter of 300 nm. For electromagnetic wave absorption, the optimized composited nanofibers (Cu9S5/C-3) exhibited an extremely superb reflection loss of -65.4 dB (9.5 GHz, 2.7 mm) at a lower mass fraction (20 wt%). And the effective absorption bandwidth could be up to 4.1 GHz (8.0-12.1 GHz) with a matching thickness of 2.9 mm, covering the whole X-band. Electromagnetic wave attenuation mechanism investigation revealed that the performance enhancement originated from the synergy of various loss pathways, including interfacial polarization, dipole polarization, and conductive loss. The unique hierarchical structure from particle embedding, one-dimensional fiber, to three-dimensional network further amplified the performance advantages of each component. This work is anticipated to provide a feasible strategy to synthesize sulfide/carbon binary composite fibers for efficient electromagnetic wave absorption.

Evaluation of the safety and effectiveness of neoadjuvant combined chemoimmunotherapy in the treatment of locally advanced esophageal squamous cell carcinoma: a retrospective single-arm cohort study.

Background: Transforming potentially resectable advanced esophageal squamous cell carcinoma (ESCC) into resectable ESCC through preoperative induction therapy is an important component of ESCC comprehensive treatment. Immune checkpoint inhibitor (ICI) therapy has been shown to have significant effects in the treatment of advanced ESCC, but its role in the neoadjuvant treatment of potentially resectable ESCC is unclear. This study aims to investigate the safety and effectiveness of camrelizumab combined with chemotherapy in the neoadjuvant treatment of ESCC. Methods: We recruited consecutive patients with potentially resectable ESCC who received preoperative camrelizumab in combination with chemotherapy. Data including demographic data, clinicopathological characteristics, neoadjuvant treatment regimens, lesion changes observed by imaging, and surgical details were retrospectively collected through specially designed forms. Toxic effects of neoadjuvant therapy on hematology, gastrointestinal tract, liver, kidney, skin, and thyroid were also collected. Imaging assessments were performed every 1-2 treatment cycles. Follow-up is based on the patient's regular admission to the hospital for examination and treatment, at least 3 months after surgery. Results: A total of 66 patients with locally advanced ESCC were included in this study, including 8 patients with stage II, 29 patients with stage III, and 29 patients with stage IVA. The objective response rate (ORR) of the neoadjuvant immunotherapy combined with chemotherapy was 75.76% (50/66), and no one developed disease progression. A total of 60 patients underwent surgery, and the R0 resection rate was 98.3% (59/60). The pathological complete remission (pCR) rate and the major pathological response (MPR) rate was 6.7% (4/60) and 20% (12/60), respectively. There were 14 cases of treatment-related adverse reactions >3, but no perioperative deaths occurred. Conclusions: Neoadjuvant immunotherapy combined with chemotherapy followed by surgical resection may be an available treatment for patients with locally advanced ESCC.

Cortisol awakening response and testosterone jointly affect adolescents' theory of mind.

Adolescence is a critical period for the maturation of neurobiological processes and hormone secretion. Recent studies on the dual-hormone hypothesis have indicated that basal cortisol and testosterone jointly affect dominant and aggressive behavior among adolescents and adults. Whether this hypothesis applies to prosocial-related understanding of others' mental states remains unclear. The present study investigated associations between basal testosterone, basal cortisol (and cortisol awakening response [CAR]), and the cognitive/affective theory of mind (ToM) in 243 adolescents (67.9 % male, aged 14 to 17 years, Mage = 16.09, standard deviation = 0.62). Cognitive ToM (cToM) and affective ToM (aToM) were assessed with a cartoon story reasoning task: In the cToM condition, participants viewed a comic strip story and needed to predict what would happen based on a character's intentions, and in the aToM condition, they viewed a comic strip of two characters interacting and needed to think about what would make the protagonist feel better. The results showed that basal testosterone and basal cortisol did not interact with each other to affect the performance of ToM, either in terms of ToM accuracy or response speed. However, under the condition of low CAR, testosterone is associated with the fast performance of cToM, although the interaction of testosterone and CAR occurred only in female adolescents. Overall, our data provide new evidence for the dual-hormone hypothesis and further extend the hypothesis to social understanding.

Endophytic bacterial community diversity in two citrus cultivars with different citrus canker disease resistance.

The selective infection of Xanthomonas citri pv. citri (Xcc) to citrus cultivars is universally known, but the relationship between endophytic bacteria and the resistance of host variety to canker disease remains unclear. In this study, endophytic bacterial populations of two citrus cultivars-the resistant satsuma mandarin and the susceptible Newhall navel orange-were analyzed through high-throughput sequencing. The results showed that endophytic bacterial community of satsuma mandarin was more abundant than that of Newhall navel orange. In addition, bacterial abundance was the highest in the spring samples, followed by that in summer and winter samples, in both the varieties. In all samples, the predominant phyla were Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes; the major genera were Bacillus and Stenotrophomonas, and the main species was Bacillus subtilis. According to the analysis of the predominant bacteria in the two citrus cultivars, B. subtilis with potential antagonistic characteristics against Xcc existed universally in all samples. However, the susceptible Newhall navel oranges were abundant in Bacillus subtilis and had a relatively large number of canker-causing cooperative bacteria such as Stenotrophomonas. The results suggested that endophytic bacterial community of the two citrus cultivars had some differences based on the season or plant tissue, and these differences were mainly in the quantity of bacteria, affecting citrus canker disease occurrence. In conclusion, the differences in endophytic bacteria on citrus cultivars might be related to host resistance or susceptibility to citrus canker disease.

A model-based validation study of postoperative complications with considerations on operative timing.

BACKGROUND: Surgery is a highly technical procedure relying on high mental acuity and manual dexterity. The possibility that surgical outcomes and post-operative complications could be subject to influence by fatigue and/or circadian rhythms in surgeons has been investigated with inconsistent results. METHODS: We conducted a retrospective study to assess the significance of operative timing on classifying surgical complications using an interpretable machine learning approach. We trained various linear, generative as well as tree models on the surgical record data collected from a university-affiliated, tertiary teaching hospital in China by performing parameter tuning using grid search cross-validation for optimizing the F1 score. RESULTS: The results indicated that XGBoost was the best-performing model overall and its feature importance was shown to provide insight into possible timing-related associations with postoperative complications. We observed that the duration of surgery acted as the strongest indicator, and while surgery initiated at night (between 9 pm and 7 am) also ranked higher on the feature importance scale, it bore less significance than other factors such as the patient's age, gender, and type of surgery performed. CONCLUSIONS: We showed that surgical records could be used to demonstrate that operative timing might affect the occurrence of postoperative complications, but only in a relatively mild way while potentially entangling with multiple factors.

miRNA-146a-5p mitigates stress-induced premature senescence of D-galactose-induced primary thymic stromal cells.

Senescent thymic stromal cells (TSCs) producing senescence-associated secretory phenotype (SASP) may play a role at later phases of thymic involution. However, the etiology and mechanisms responsible for TSC senescence remain to be elucidated. In the present study, the effects of oxidative stress on TSCs and role of miRNA-146a-5p in stress-induced premature senescence (SIPS) were identified. D-galactose (D-gal) induced oxidative stress in primary TSCs and a limited cumulative oxidative stress induced premature senescence but not apoptosis of TSCs. miRNA-146a-5p overexpression can mitigate the SIPS by targeting tumor necrosis factor receptor-associated factor 6 (TRAF6) instead of increasing autophagy clearance. Furthermore, exogenous miRNA-146a-5p reversed the upregulation of chemokines including Cxcl5, pro-inflammatory cytokines, and antimicrobial peptides in TSCs with SIPS. In conclusion, the accumulated oxidative stress may be partially responsible for senescence in TSCs and modulation of miRNA-146a-5p may attenuate this process.

Label-free quantitative proteomics identifies transforming growth factor ß1 (TGF-ß1) as an inhibitor of adipogenic transformation in OP9-DL1 cells and primary thymic stromal cells.

BACKGROUND: Adipocyte accumulation is a predominant feature of age-related thymic involution, but the mechanisms responsible for thymic adipogenesis remain to be elucidated. The aim of this study was to identify key regulators in thymic adipogenesis. We used rosiglitazone, a potent peroxisome proliferator-activated receptor γ (PPARγ) agonist, to induce adipogenic differentiation of OP9-DL1 cells, and investigated the differentially expressed proteins during adipogenic differentiation by using label-free quantitative proteomics. Furthermore, the effects of transforming growth factor ß1 (TGF-ß1) on rosiglitazone-induced adipogenic differentiation of OP9-DL1 cells as well as the underlying mechanisms were also investigated. RESULTS: Proteomic analysis identified 139 proteins differed significantly in rosiglitazone-treated cells compared with dimethyl sulphoxide (DMSO)-treated cells. Rosiglitazone-induced adipogenic differentiation was inhibited by TGF-ß1 treatment in OP9-DL1 cells and primary thymic stromal cells. Real-time PCR analysis showed significant increases in PPARγ and fatty acid binding protein 4 mRNA levels in rosiglitazone-treated cells, which were inhibited by TGF-ß1 treatment. TGF-ß1 down-regulated PPARγ expression at both mRNA and protein levels in OP9-DL1 cells. Chromatin immunoprecipitation analysis demonstrated that TGF-ß1 enhanced the binding of Smad2/3 and histone deacetylase 1, but reduced the binding of H3K14ac to the promoter of PPARγ gene. TGF-ß1 partially reversed the inhibitory effects of rosiglitazone on the expression of Axin2 and ß-catenin protein levels. TGF-ß1 inhibited rosiglitazone-induced adipogenic transformation in OP9-DL1 cells by down-regulation of PPARγ and activation of the canonical Wnt/ß-catenin signaling pathway. CONCLUSION: Taken together, activation of TGF-ß pathway may serve as a useful strategy to prevent thymic adiposity in age-related thymic involution.

Human adipose­derived mesenchymal stem cells promote breast cancer MCF7 cell epithelial­mesenchymal transition by cross interacting with the TGF­ß/Smad and PI3K/AKT signaling pathways.

The influence and underlying mechanisms of human adipose­derived stem cells (Hu­ADSCs) on breast cancer cells in the tumor microenvironment remain unclear. Understanding the association between Hu­ADSCs and cancer cells may provide targets for breast cancer treatment and reference for the clinical application of stem cells. Therefore, a Hu­ADSC and breast cancer MCF7 cell coculture system was established to investigate the paracrine effects of Hu­ADSCs on MCF7 cell migration and invasion, in addition to the potential mechanism of action by reverse transcription­quantitative polymerase chain reaction and western blotting. Hu­ADSCs enhanced MCF7 cell migration and invasion by decreasing the expression of epithelial marker E­cadherin, and increasing the expression of interstitial marker N­cadherin and epithelial­mesenchymal transition (EMT) transcription factors in vitro. The EMT effect of cocultured MCF7 cells was inhibited with the addition of anti­transforming growth factor (TGF)­ß1 or phosphoinositide 3­kinase (PI3K) inhibitor LY294002, accompanied by a significant decrease in phosphorylated (p)­mothers against decapentaplegic homolog (Smad) and p­protein kinase B (AKT) expression. The data suggested that the paracrine effect of Hu­ADSCs in the tumor microenvironment promoted the EMT of MCF7 cells by cross interacting with the TGF­ß/Smad and PI3K/AKT pathways.

UC-MSCs affects apoptosis and proliferation of human lung adenocarcinoma A549 cells via PI3K/AKT signaling pathway / 中国肿瘤生物治疗杂志

@#Objective: To investigate the effects of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on apoptosis and proliferation of human lung adenocarcinoma A549 cells via PI3K/AKT signaling pathway, and to explore the mechanism. Methods: UCMSCs were isolated from human umbilical cord tissues by enzyme digestion method and cultured in vitro. The immunophenotypes of the obtained MSCs were identified by flow cytometry. The culture supernatant of UC-MSCs was collected to establish an indirect in vitro co-culture system of UC-MSCs conditioned medium and lung adenocarcinomaA549 cell line. Proliferation ofA549 cells was detected by CCK-8 assay; apoptosis ofA549 cells was determined byAnnexin V/PI double staining, and cell cycle distribution of tumor cells was determined by PI staining. The transcription levels of apoptosis and proliferation associated downstream genes in the PI3K/AKT pathway, such as CyclinD1, BAX and Bcl-2, were detected by quantitative polymerase chain reaction (qPCR). Moreover, Wb was utilized to detect the expression levels of PI3K/AKT pathway-related proteins. Results: The culture flask was filled with fibroblast-like cells, arranged in parallel, with spiral growth after three weeks of isolation and culture of human umbilical cord tissues. The flow cytometry results revealed that the MSC markers CD73, CD90 and CD105, but not CD45 and HLA-DR, were expressed on obtained cells.After indirect in vitro co-culture of UC-MSCs conditioned medium and lung adenocarcinoma A549 cells, the proliferation rate of A549 cells was significantly decreased; the apoptosis rate was significantly increased, and the cell cycle was obviously arrested at the G1 phase as compared with the control group (all P<0.01). The transcription levels of PI3K/AKT signaling pathway-related factors, CyclinD1 and Bcl-2 were down-regulated, and the transcription level of BAX was up-regulated (all P<0.01). The total AKT was not changed, but p-AKT protein expression was decreased in a dose-dependent manner inA549 cells cultured in UC-MSCs conditioned medium (P<0.01). Conclusion: UC-MSCs can affect the proliferation and the apoptosis of A549 cells, and arrest cells in G1 phase. The main mechanism is that UC-MSCs can inhibit the PI3K/AKT signaling pathway in A549 cells, providing an experimental basis for exploring the safety and effectiveness of clinical application of UC-MSCs.

Notch1 Inhibits Rosiglitazone-Induced Adipogenic Differentiation in Primary Thymic Stromal Cells.

Adipocyte deposition is believed to be a primary characteristic of age-related thymic involution. Herein, we cultured primary thymic stromal cells (TSCs), used rosiglitazone, a potent peroxisome proliferator-activated receptor γ (PPARγ) agonist, to induce adipogenic differentiation, and investigated the differentially expressed genes during adipogenic differentiation by using RNA-sequencing analysis. Furthermore, the effects of Notch1 on rosiglitazone-induced adipogenic differentiation of TSCs as well as the underlying mechanisms were also investigated. As a result, we identified a total of 1737 differentially expressed genes, among which 965 genes were up-regulated and 772 genes were down-regulated in rosiglitazone-treated cells compared with control cells. Gene ontology (GO) enrichment analysis showed that the GO terms were enriched in metabolic process, intracellular, and protein binding. Kyoto encyclopedia of genes and genomes (KEGG) analysis showed that a number of pathways, including ubiquitin mediated proteolysis, PPAR signaling pathway, and mammalian target of rapamycin (mTOR) signaling pathway were predominantly over-represented. Meanwhile, overexpression of Notch1 suppressed and inhibition of Notch1 promoted rosiglitazone-induced adipogenic differentiation in TSCs, and the pro-adipogenic effects of the Notch inhibitor DAPT were associated with the activation of autophagy. Taken together, our results suggest that Notch1 is a key regulator in thymic adipogenesis and may serve as a potential target to hinder thymic adiposity in age-related thymic involution.