FBP1 inhibits NSCLC stemness by promoting ubiquitination of Notch1 intracellular domain and accelerating degradation.

The existence of cancer stem cells is widely acknowledged as the underlying cause for the challenging curability and high relapse rates observed in various tumor types, including non-small cell lung cancer (NSCLC). Despite extensive research on numerous therapeutic targets for NSCLC treatment, the strategies to effectively combat NSCLC stemness and achieve a definitive cure are still not well defined. The primary objective of this study was to examine the underlying mechanism through which Fructose-1,6-bisphosphatase 1 (FBP1), a gluconeogenic enzyme, functions as a tumor suppressor to regulate the stemness of NSCLC. Herein, we showed that overexpression of FBP1 led to a decrease in the proportion of CD133-positive cells, weakened tumorigenicity, and decreased expression of stemness factors. FBP1 inhibited the activation of Notch signaling, while it had no impact on the transcription level of Notch 1 intracellular domain (NICD1). Instead, FBP1 interacted with NICD1 and the E3 ubiquitin ligase FBXW7 to facilitate the degradation of NICD1 through the ubiquitin-proteasome pathway, which is independent of the metabolic enzymatic activity of FBP1. The aforementioned studies suggest that targeting the FBP1-FBXW7-NICD1 axis holds promise as a therapeutic approach for addressing the challenges of NSCLC recurrence and drug resistance.

Upregulation of CoQ shifts ferroptosis dependence from GPX4 to FSP1 in acquired radioresistance.

Acquired radioresistance is the primary contributor to treatment failure of radiotherapy, with ferroptosis is identified as a significant mechanism underlying cell death during radiotherapy. Although resistance to ferroptosis has been observed in both clinical samples of radioresistant cells and cell models, its mechanism remains unidentified. Herein, our investigation revealed that radioresistant cells exhibited greater tolerance to Glutathione Peroxidase 4 (GPX4) inhibitors and, conversely, increased sensitivity to ferroptosis suppressor protein 1 (FSP1) inhibitors compared to their sensitive counterparts. This observation suggested that FSP1 might play a dominant role in the development of radioresistance. Notably, the knockout of FSP1 demonstrated considerably superior efficacy in resensitizing cells to radiotherapy compared to the knockout of GPX4. To elucidate the driving force behind this functional shift, we conducted a metabolomic assay, which revealed an upregulation of Coenzyme Q (CoQ) synthesis and a downregulation of glutathione synthesis in the acquired radioresistance cells. Mechanistically, CoQ synthesis was found to be supported by aarF domain containing kinase 3-mediated phosphorylation of CoQ synthases, while the downregulation of Solute carrier family 7 member 11 led to decreased glutathione synthesis. Remarkably, our retrospective analysis of clinical response data further validated that the additional administration of statin during radiotherapy, which could impede CoQ production, effectively resensitized radioresistant cells to radiation. In summary, our findings demonstrate a dependency shift from GPX4 to FSP1 driven by altered metabolite synthesis during the acquisition of radioresistance. Moreover, we provide a promising therapeutic strategy for reversing radioresistance by inhibiting the FSP1-CoQ pathway.

Unrevealing Temporal Mechanoluminescence Behaviors at High Frequency via Piezoelectric Actuation.

Mechanoluminescence (ML) materials present widespread applications. Empirically, modulation for a given ML material is achieved by application of programmed mechanical actuation with different amplitude, repetition velocity and frequency. However, to date modulation on the ML is very limited within several to a few hundred hertz low-frequency actuation range, due to the paucity of high-frequency mechanical excitation apparatus. The universality of temporal behavior and frequency response is an important aspect of ML phenomena, and serves as the impetus for much of its applications. Here, we push the study on ML into high-frequency range (∼250 kHz) by combining with piezoelectric actuators. Two representative ML ZnS:Mn and ZnS:Cu, Al phosphors were chosen as the research objects. Time-resolved ML of ZnS:Mn and ZnS:Cu, Al shows unrevealed frequency-dependent saturation and quenching, which is associated with the dynamic processes of traps. From the point of applications, this study sets the cut-off frequency for ML sensing. Moreover, by in-situ tuning the strain frequency, ZnS:Mn exhibits reversible frequency-induced broad red-shift into near-infrared range. These findings offer keen insight into the photophysics nature of ML and also broaden the physical modulation of ML by locally adjusting the excitation frequency.

DSCC1 interacts with HSP90AB1 and promotes the progression of lung adenocarcinoma via regulating ER stress.

Lung cancer is a leading cause of cancer-related deaths, and the most common type is lung adenocarcinoma (LUAD). LUAD is frequently diagnosed in people who never smoked, patients are always diagnosed at advanced inoperable stages, and the prognosis is ultimately poor. Thus, there is an urgent need for the development of novel targeted therapeutics to suppress LUAD progression. In this study, we demonstrated that the expression of DNA replication and sister chromatid cohesion 1 (DSCC1) was higher in LUAD samples than normal tissues, and the overexpression of DSCC1 or its coexpressed genes were highly correlated with poor outcomes of LUAD patients, highlighting DSCC1 might be involved in LUAD progression. Furthermore, the expression of DSCC1 was positively correlated with multiple genetic mutations which drive cancer development, including TP53, TTN, CSMD, and etc. More importantly, DSCC1 could promote the cell proliferation, stemness, EMT, and metastatic potential of LUAD cells. In addition, DSCC1 interacted with HSP90AB1 and promoted the progression of LUAD via regulating ER stress. Meanwhile, DSCC1 expression negatively correlated with immune cell infiltration in lung cancer, and DSCC1 positively regulated the expression of PD-L1 in LUAD cells. Collectively, this study revealed that DSCC1 is a novel therapeutic target to treat LUAD and a biomarker for predicting the efficiency of PD-1/PD-L1 blockade treatment.

Integration of transcriptomic and proteomic analyses of Rhododendron chrysanthum Pall. in response to cold stress in the Changbai Mountains.

BACKGROUND: Cold stress is one of the abiotic stresses that affect plant growth and development, as well as life and geographical distribution important. For researching how plants react to low temperature stress, Rhododendron chrysanthum Pall. (R. chrysanthum) growing in Changbai Mountains of China is an essential study subject. METHODS AND RESULTS: R. chrysanthum was cold-treated at 4 °C for 12 h (cold-stress group-CS, and controls-CK), combined with transcriptomics (RNA-seq) and proteomics (iTRAQ) techniques, to investigate the response mechanisms of R. chrysanthum response to cold stress. Cold stress resulted in the discovery of 12,261 differentially expressed genes (DEGs) and 360 differentially expressed proteins (DEPs). Correlation of proteomic and transcriptome data, proteome regulation of distinct subcellular localization, and gene/protein functional groupings are all part of the investigation. CONCLUSIONS: The combined analysis showed that 6378 DEPs matched the corresponding DEGs when the control was compared with the cold-treated samples (CK vs CS). The analysis identified 54 DEGs-DEPs associated with cold stress. cold-tolerant DEGs-DEPs were enriched with hydrolase activity, acting on glycosyl bonds, carbon-oxygen lyase activity and ferric iron binding. Seven potential DEGs-DEPs with significant involvement in the cold stress response were identified by co-expression network analysis. These findings identify the synergistic effect of DEGs-DEPs as the key to improve the cold tolerance of R. chrysanthum and provide a theoretical basis for further studies on its cold resistance subsequently.

Agathis dammara Extract and its Monomer Araucarone Attenuate Abdominal Aortic Aneurysm in Mice.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a chronic vascular disease wherein the inflammation of vascular smooth muscle cells (VSMCs) plays a pivotal role in its development. Effectively mitigating AAA involves inhibiting VSMC inflammation. Agathis dammara (Lamb.) Rich, recognized for its robust anti-inflammatory and antioxidant attributes, has been employed as a traditional medicinal resource. Nonetheless, there is a dearth of information regarding the potential of Agathis dammara extract (AD) in attenuating AAA, specifically by diminishing vascular inflammation, notably VSMC inflammation. Furthermore, the active constituents of AD necessitate identification. AIM OF THE STUDY: This study sought to ascertain the efficacy of AD in reducing AAA, evaluate its impact on VSMC inflammation, and elucidate whether the monomer araucarone (AO) in AD acts as an active component against AAA. MATERIALS AND METHODS: The extraction of AD was conducted and subjected to analysis through High-Performance Liquid Chromatography (HPLC) and mass spectrometry. The isolation of the AO monomer followed, involving the determination of its content and purity. Subsequently, the effects of AD and AO on VSMC inflammation were assessed in vitro, encompassing an examination of inflammatory factors such as IL-6 and IL-18, as well as the activation of matrix metalloproteinase 9 (MMP9) in tumor necrosis factor-alpha (TNF-α)-stimulated VSMCs. To explore the inhibitory effects of AD/AO on AAA, C57BL/6J male mice were subjected to oral gavage (100 mg/kg) or intraperitoneal injection (50 mg/kg) of AD and AO in a porcine pancreatic elastase (PPE)-induced AAA model (14 days). This facilitated the observation of abdominal aorta dilatation, remodeling, elastic fiber disruption, and macrophage infiltration. Additionally, a three-day PPE mouse model was utilized to assess the effects of AD and AO (administered at 100 mg/kg via gavage) on acute inflammation and MMP9 expression in blood vessels. The mechanism by which AD/AO suppresses the inflammatory response was probed through the examination of NF-κB/NLRP3 pathway activation in VSMCs and aortas. RESULTS: Liquid Chromatography-Mass Spectrometry (LC-MS) revealed that AO constituted 15.36% of AD's content, with a purity of 96%. Subsequent pharmacological investigations of AO were conducted in parallel with AD. Both AD and AO exhibited the ability to inhibit TNF-α-induced VSMC inflammation and MMP production in vitro. Furthermore, both substances effectively prevented PPE-induced AAA in mice, whether administered through gavage or intraperitoneal injection, evidenced by decreased vascular diameter dilation, disruption of elastin fiber layers, and infiltration of inflammatory cells. In the three-day PPE mouse model, AD and AO mitigated the heightened expression of inflammatory factors and the elevated expression of MMP9 induced by PPE. The activation of the NF-κB/NLRP3 pathway in both VSMCs and aortas was significantly suppressed by treatment with AD or AO. CONCLUSIONS: Through suppressing NF-κB/NLRP3 pathway activation, AD effectively mitigates the inflammatory response in VSMCs, mitigates inflammation in aortas, prevents extracellular matrix degradation, and consequently impedes the progression of AAA. AO emerges as one of the active compounds in AD responsible for inhibiting VSMC inflammation and inhibiting AAA development.

Gratitude and psychological distress among first-year college students: The mediating roles of perceived social support and support provision.

Universities and colleges in the United States implemented remote learning and restrictions on in-person social events during the Fall 2020 academic semester. These changes and restrictions, in addition to the other numerous negative impacts of COVID-19, can exacerbate the already stressful transition from high school to college. This transition is a key developmental period during which the complexity of interpersonal relationships and the risk of internalizing symptoms such as anxiety and depression increase. As such, the present study examined dispositional gratitude as a protective factor against depressive symptoms and loneliness among a sample of first-year college students who began college during the peak of the COVID-19 pandemic. We also examined whether perceived social support and support provision mediated these relationships. Participants were 364 first-year college students who completed three online surveys during the 1st (T1), 7th (T2), and 14th (T3) weeks of the Fall 2020 academic semester. T1 gratitude was associated with lower T3 depressive symptoms and feelings of loneliness over time. These relationships were mediated by T2 perceived social support but not by T2 support provision. Implications of our findings are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Primary Ewing sarcoma/peripheral primitive neuroectodermal tumors in the cranial bone and mobile spine: what is the difference?

BACKGROUND: Primary Ewing sarcoma (ES)/peripheral primitive neuroectodermal tumors (pPNETs) are aggressive bone tumors that rarely occur in the axial skeleton, including the cranial bone and mobile spine. The purpose of this study was to investigate whether there were any differences in patient characteristics, treatment strategies, and outcomes between patients with ES/pPNETs of the cranial bone and those with ES/pPNETs of the mobile spine. METHODS: A retrospective study was performed on 33 patients with ES/pPNETs who had been surgically treated and pathologically confirmed at our institution between 2010 and 2020. Patient characteristics were compared using Fisher exact tests or independent t tests. Survival rates were estimated via Kaplan-Meier survival analysis and compared using log-rank tests. RESULTS: Thirteen patients had ES/pPNETs of the cranial bone (39.4%), while 20 patients had ES/pPNETs of the mobile spine (60.6%). Patients with ES/pPNETs of the cranial bone had a younger mean age (14.8 vs 22.6 years; p = 0.047) and longer mean disease duration (2.5 vs 1.9 months; p = 0.008) compared with those of patients with ES/pPNETs of the mobile spine. Kaplan-Meier analysis showed that gross total resection (GTR) and radiotherapy resulted in a longer median survival time. The overall survival rates and progression-free survival rates of patients with ES/pPNETs of the cranial bone versus those of the mobile spine were not significantly different (p = 0.386 and p = 0.368, respectively). CONCLUSIONS: Patients with ES/pPNETs of the cranial bone were younger compared to patients with ES/pPNETs of the mobile spine. There was no significant difference in the prognosis of patients with ES/pPNETs of the cranial bone versus those of the mobile spine. Taken together, our findings suggest that GTR and radiotherapy offer the best prognosis for improved long-term survival.

Minimally invasive transforaminal lumbar interbody fusion versus oblique lateral interbody fusion for lumbar degenerative disease: a meta-analysis.

BACKGROUND: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and oblique lateral interbody fusion (OLIF) are widely used in the treatment of lumbar degenerative diseases. In the present study, a meta-analysis was conducted to compare the clinical and radiographic efficacy of these two procedures. METHODS: A systematic literature review was performed, and the quality of retrieved studies was evaluated with the Newcastle-Ottawa Scale (NOS). Clinical outcomes, including operation time, intraoperative blood loss, improvement in Visual Analogue Scale (VAS), improvement in Oswestry Disability Index (ODI), Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) effectiveness rate and complications, in addition to radiographic outcomes, including restoration of disc height, disc angle, overall lumbar lordosis, fusion rate and subsidence, were extracted and input into a fixed or random effect model to compare the efficacy of MIS-TLIF and OLIF. RESULTS: Seven qualified studies were included. Clinically, OLIF resulted in less intraoperative blood loss and shorter operation time than MIS-TLIF. Improvement of VAS for leg pain was more obvious in the OLIF group (P < 0.0001), whereas improvement of VAS for back pain (P = 0.08) and ODI (P = 0.98) as well as JOABPEQ effectiveness rate (P = 0.18) were similar in the two groups. Radiographically, OLIF was more effective in restoring disc height (P = 0.01) and equivalent in improving the disc angle (P = 0.18) and lumbar lordosis (P = 0.48) compared with MIS-TLIF. The fusion rate (P = 0.11) was similar in both groups, while the subsidence was more severe in the MIS-TLIF group (P < 0.00001). CONCLUSIONS: The above evidence suggests that OLIF is associated with a shorter operation time (with supplementary fixation in the prone position) and less intraoperative blood loss than MIS-TLIF and can lead to better leg pain alleviation, disc height restoration and subsidence resistance. No differences regarding back pain relief, functional recovery, complications, disc angle restoration, lumbar lordosis restoration and fusion rate were found. However, due to the limited number of studies, our results should be confirmed with high-level studies to fully compare the therapeutic efficacy of MIS-TLIF and OLIF. TRIAL REGISTRATION: PROSPERO ID:  CRD42020201903 .

Parallel Connected Generative Adversarial Network with Quadratic Operation for SAR Image Generation and Application for Classification.

Thanks to the availability of large-scale data, deep Convolutional Neural Networks (CNNs) have witnessed success in various applications of computer vision. However, the performance of CNNs on Synthetic Aperture Radar (SAR) image classification is unsatisfactory due to the lack of well-labeled SAR data, as well as the differences in imaging mechanisms between SAR images and optical images. Therefore, this paper addresses the problem of SAR image classification by employing the Generative Adversarial Network (GAN) to produce more labeled SAR data. We propose special GANs for generating SAR images to be used in the training process. First, we incorporate the quadratic operation into the GAN, extending the convolution to make the discriminator better represent the SAR data; second, the statistical characteristics of SAR images are integrated into the GAN to make its value function more reasonable; finally, two types of parallel connected GANs are designed, one of which we call PWGAN, combining the Deep Convolutional GAN (DCGAN) and Wasserstein GAN with Gradient Penalty (WGAN-GP) together in the structure, and the other, which we call CNN-PGAN, applying a pre-trained CNN as a discriminator to the parallel GAN. Both PWGAN and CNN-PGAN consist of a number of discriminators and generators according to the number of target categories. Experimental results on the TerraSAR-X single polarization dataset demonstrate the effectiveness of the proposed method.

Exosomes originating from MSCs stimulated with TGF-ß and IFN-γ promote Treg differentiation.

Mesenchymal stem cells (MSCs) have been approved as a cellular drug for the treatment of a variety of immune-related diseases by the government of many countries'. Previous investigations, including ours, have shown that exosomes secreted by MSCs (MSC-ex) are one of the main factors responsible for the therapeutic effect of MSCs. However, the immune modulation activities and the contents of MSC-ex derived from cells under different incubation conditions differ dramatically. Therefore, the optimal way to ensure effectiveness is by identifying and preparing MSC-ex with confirmed potent immunosuppressive activity. The aim of this study was to investigate and analyze the composition and function of MSC-ex secreted by MSCs stimulated by different cytokines to obtain exosomes with more potent immunosuppressive activity. To achieve this aim, umbilical cord-derived MSCs were treated with PBS, TGF-ß, IFN-γ, or TGF-ß plus IFN-γ for 72 hr. Then, exosomes were isolated from the culture supernatants. Common exosome markers, such as CD9, CD63, and CD81, were detected and analyzed by FCM. At the same time, the TGF-ß, IFN-γ, IDO, and IL-10 content in exosomes was detected, and the influence of exosmes from defferent groups on the induction of mononuclear cell transformation into Tregs was analyzed via FCM. Our results show that the TGF-ß combined with IFN-γ exosome group more effectively promoted the transformation of mononuclear cells to Tregs, and the analysis showed that IDO may play an important role. This study might provide a novel strategy to treat GVHD as well as other immune-associated disorders.

Clinical and Biological Implications of Mutational Spectrum in Acute Myeloid Leukemia of FAB Subtypes M0 and M1.

BACKGROUND/AIMS: Acute myeloid leukemia (AML) of French-American-British (FAB) subtypes M0 and M1 are both poorly differentiated AML, but their mutational spectrum and molecular characteristics remain unknown. This study aimed to explore the mutational spectrum and prognostic factors of AML-M0 and M1. METHODS: Sixty-five AML patients derived from The Cancer Genome Atlas (TCGA) database were enrolled in this study. Whole-genome sequencing was performed to depict the mutational spectrum of each patient. Clinical characteristics at diagnosis, including peripheral blood (PB) white blood cell counts (WBC), blast percentages in PB and bone marrow (BM), FAB subtypes and the frequencies of known recurrent genetic mutations were described. Survival was estimated using the Kaplan-Meier methods and log-rank test. Univariate and multivariate Cox proportional hazard models were constructed for event-free survival (EFS) and overall survival (OS), using a limited backward elimination procedure. RESULTS: Forty-six patients had more than five recurrent genetic mutations. FLT3 had the highest mutation frequency (n=20, 31%), followed by NPM1 (n=18, 28%), DNMT3A (n=16, 25%), IDH1 (n=14, 22%), IDH2 (n=12, 18%), RUNX1 (n=11, 17%) and TET2 (n=7, 11%). Univariate analysis showed that age ≥60 years and TP53 mutations had adverse effect on EFS (P=0.015, P=0.036, respectively) and OS (P=0.003, P=0.004, respectively), WBC count ≥50×109/L and FLT3-ITD negatively affected EFS (P=0.003, P=0.034, respectively), whereas NPM1 mutations had favorable effect on OS (P=0.035) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) on EFS and OS (all P< 0.001). Multivariate analysis suggested that allo-HSCT and NPM1 mutations were independent favorable prognostic factors for EFS and OS (all P< 0.05), WBC count ≥50×109/L was an independent risk factor for EFS (P=0.002) and TP53 mutations for OS (P=0.043). CONCLUSIONS: Our study provided new insights into the mutational spectrum and molecular signatures of AML-M0 and M1. We proposed that FLT3-ITD, NPM1 and TP53 be identified as markers for risk stratification of AML-M0 and M1. Patients with AML-M0 and M1 would likely benefit from allo-HSCT.

A minicircuitry of microRNA-9-1 and RUNX1-RUNX1T1 contributes to leukemogenesis in t(8;21) acute myeloid leukemia.

MicroRNA-9-1(miR-9-1) plays an important role in the mechanism that regulates the lineage fate of differentiating hematopoietic cells. Recent studies have shown that miR-9-1 is downregulated in t (8; 21) AML. However, the pathogenic mechanisms underlying miR-9-1 downregulation and the RUNX1-RUNX1T1 fusion protein, generated from the translocation of t (8; 21) in AML, remain unclear. RUNX1-RUNX1T1 can induce leukemogenesis through resides in and functions as a stable RUNX1-RUNX1T1-containing transcription factor complex. In this study, we demonstrate that miR-9-1 expression increases significantly after the treatment of RUNX1-RUNX1T1 (+) AML cell lines with decitabine (a DNMT inhibitor) and trichostatin A (an HDAC inhibitor). In addition, we show that RUNX1-RUNX1T1 triggers the heterochromatic silencing of miR-9-1 by binding to RUNX1-binding sites in the promoter region of miR-9-1 and recruiting chromatin-remodeling enzymes, DNMTs, and HDACs, contributing to hypermethylation of miR-9-1 in t (8; 21) AML. Furthermore, because RUNX1, RUNX1T1, and RUNX1-RUNX1T1 are all regulated by miR-9-1, the silencing of miR-9-1 enhances the oncogenic activity of these genes. Besides, overexpression of miR-9-1 induces differentiation and inhibits proliferation in t (8; 21) AML cell lines. In conclusion, our results indicate a feedback circuitry involving miR-9-1 and RUNX1-RUNX1T1, contributing to leukemogenesis in RUNX1-RUNX1T1 (+) AML cell lines.

Artificially accelerating the reversal of desertification: cyanobacterial inoculation facilitates the succession of vegetation communities.

Desertification has been recognized as a global environmental problem, and one region experiencing ongoing desertification is the eastern edge of Qubqi Desert (Inner Mongolia). To investigate the facilitating effects of cyanobacterial inoculation technology on the desertification control along this steppe-desert transition region, artificial cyanobacterial crusts were constructed with two filamentous cyanobacteria 3 and 8 years ago combined with Salix planting. The results showed that no crusts formed after 3 years of fixation only with Salix planting, whereas after cyanobacterial inoculation, the crusts formed quickly and gradually succeed to moss crusts. During that course, topsoil environments were gradually improved, providing the necessary material basis for the regeneration of vascular plants. In this investigation, total 27 species of vascular plants had regenerated in the experimental region, mainly belonging to Asteraceae, Poaceae, Chenopodiaceae and Leguminosae. Using space time substitution, the dominant species along with the application of cyanobacterial inoculation technology succeeded from Agriophyllum squarrosum ultimately to Leymus chinensis. In addition, it was found that the shady side of the dunes is more conducive to crust development and succession of vegetation communities. Conclusively, our results indicate artificial cyanobacterial inoculation technology is an effective and desirable path for desertification control.

A rapid extraction and analysis method for the simultaneous determination of 26 bioflavonoids in Portulaca oleracea L.

INTRODUCTION: Portulaca oleracea L. (P. oleracea, purslane) is an edible plant that is widely distributed around the world, and flavonoids are its main bioactive constituents. Therefore, the detection of flavonoids is very important for a better understanding of its pharmacological actions and to monitor the product quality control of P. oleracea. OBJECTIVE: To develop a rapid method to extract and determine 26 bioflavonoids in P. oleracea, based on microwave extraction (MWE) and triple quadrupole-linear ion trap mass spectrometry. METHODS: The optimal conditions of MWE for the extraction of flavonoids from P. oleracea involved the use of methanol as the extraction solvent, a microwave power of 300 W, an extraction time of 450 s, and a solvent-to-solid ratio of 30 mL/g. The samples were analysed using an ultra-performance liquid chromatograph coupled with a triple quadrupole-linear ion trap mass spectrometer (UPLC-MS/MS) system. RESULTS: The calibration curves of all 26 analytes showed good linearity (r ≥ 0.999) and the intra- and interday precisions and repeatability were all within required limits. The mean recoveries measured at three concentrations were higher than 94.2%, with RSDs lower than 2.94% for the targets. CONCLUSION: The established MWE/UPLC-MS/MS method is a rapid and effective method for quality evaluation of P. oleracea from different production regions and different harvest periods.

The relationship between organizational climate and job satisfaction of kindergarten teachers: a chain mediation model of occupational stress and emotional labor.

Organizational climate has been shown to be an important factor associated with teachers' job satisfaction. However, the internal mechanism between them is unclear. The purpose of this study was to investigate whether the relationship between kindergarten organizational climate and kindergarten teachers' job satisfaction was affected by occupational stress and emotional labor. This study employed a questionnaire survey method to gather data from 1,091 kindergarten teachers nationwide. It conducted an analysis of the current status of kindergarten organizational climate and the job satisfaction of kindergarten teachers, elucidating the relationship between the two and the underlying mechanisms. Additionally, a chain mediation model was constructed. The findings indicated that: (1) organizational climate, kindergarten teachers' occupational stress and emotional labor all significantly predict kindergarten teachers' job satisfaction directly (2) organizational climate could indirectly influence kindergarten teachers' job satisfaction through three pathways: the separate mediating effect of occupational stress and emotional labor, and the chain mediating effect on both. The research findings highlight the significance of kindergarten organizational climate, occupational stress, and emotional labor in augmenting the job satisfaction of kindergarten teachers, offering valuable insights for the improvement of kindergarten teacher job satisfaction.

Less Acetabular Coverage Predicts the Failure of Core Decompression for Osteonecrosis of the Femoral Head: A Retrospective Cohort Study.

OBJECTIVE: It is unclear whether less acetabular coverage is associated with the failure of core decompression (CD) for osteonecrosis of the femoral head (ONFH). This study aimed to investigate the clinical outcomes of CD for ONFH with small- or medium-sized pre-collapse lesions, and determine what factors, especially acetabular anatomical parameters, predict the failure of CD. METHODS: Between January 2010 and December 2022, we retrospectively reviewed 269 consecutive CDs in 188 patients diagnosed with ONFH with small- or medium-sized pre-collapse lesions. The Kaplan-Meier method was used to evaluate the survival rate of CD for ONFH with progression of collapse or conversion to total hip arthroplasty (THA) as the endpoint. Univariate and multivariate logistic regression analyses were conducted to identify the potential risk factors for the failure of CD. Receiver operating characteristic (ROC) curve analysis was further performed with conversion to THA as the endpoint to determine the predictive value of these factors. RESULTS: The overall 5-year survival rate of CD for ONFH with small- or medium-sized pre-collapse lesions was 74.3% (95% confidence interval (CI) 69.0%-81.1%) with progression of collapse as the endpoint and 83.9% (95% CI 79.3%-88.7%) with conversion to THA as the endpoint. Univariate logistic regression analysis showed that bilateral affected hips was significantly associated with progression of collapse, and center-edge angle (CEA), sharp angle, acetabular head index (AHI), as well as acetabular depth ratio (ADR) were significantly associated with both progression of collapse and conversion to THA. Multivariate logistic regression analysis further indicated that CEA and AHI were independent risk factors for both progression of collapse and conversion to THA. ROC curve analysis with conversion to THA as the endpoint revealed that the cutoff values for CEA and AHI were 26.8° (sensitivity = 74.4%, specificity = 78.6%, area under the curve (AUC) = 0.809) and 79.8 (sensitivity = 78.4%, specificity = 73.8%, AUC = 0.818), respectively. CONCLUSIONS: CD showed satisfactory clinical outcomes for ONFH with small- or medium-sized pre-collapse lesions where less acetabular coverage with a CEA < 26.8° or AHI < 79.8 was identified as an independent risk factor for the failure of CD.

SPTBN2 suppresses ferroptosis in NSCLC cells by facilitating SLC7A11 membrane trafficking and localization.

The function of SLC7A11 in the process of ferroptosis is well-established, as it regulates the synthesis of glutathione (GSH), thereby influencing tumor development along with drug resistance in non-small cell lung cancer (NSCLC). However, the determinants governing SLC7A11's membrane trafficking and localization remain unknown. Our study identified SPTBN2 as a ferroptosis suppressor, enhancing NSCLC cells resistance to ferroptosis inducers. Mechanistically, SPTBN2, through its CH domain, interacted with SLC7A11 and connected it with the motor protein Arp1, thus facilitating the membrane localization of SLC7A11 - a prerequisite for its role as System Xc-, which mediates cystine uptake and GSH synthesis. Consequently, SPTBN2 suppressed ferroptosis through preserving the functional activity of System Xc- on the membrane. Moreover, Inhibiting SPTBN2 increased the sensitivity of NSCLC cells to cisplatin through ferroptosis induction, both in vitro and in vivo. Using Abrine as a potential SPTBN2 inhibitor, its efficacy in promoting ferroptosis and sensitizing NSCLC cells to cisplatin was validated. Collectively, SPTBN2 is a potential therapeutic target for addressing ferroptosis dysfunction and cisplatin resistance in NSCLC.

Transcriptome analysis reveals PRKCA as a potential therapeutic target for overcoming cisplatin resistance in lung cancer through ferroptosis.

Cisplatin-based chemotherapy is the current standard care for lung cancer patients; however, drug resistance frequently develops during treatment, thereby limiting therapeutic efficacy.The molecular mechanisms underlying cisplatin resistance remain elusive. In this study, we conducted an analysis of microarray data from the Gene Expression Omnibus (GEO) database under the accession numbers GSE21656, which encompassed expression profiling of cisplatin-resistant H460 (DDP-H460)and the parental cells (H460). Subsequently, we calculated the differentially expressed genes (DEGs) between DDP-H460 and H460. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs demonstrated significant impact on the Rap1, PI3K/AKT and MAPK signaling pathways. Moreover, protein and protein interaction (PPI) network analysis identified PRKCA, DET1, and UBE2N as hub genes that potentially contribute predominantly to cisplatin resistance. Ultimately, PRKCA was selected for validation due to its significant prognostic effect, which predicts unfavorable overall survival and disease-free survival in patients with lung cancer. Network analysis conducted on The Cancer Genome Atlas (TCGA) database revealed a strong gene-level correlation between PRKCA and TP53, CDKN2A, BYR2, TTN, KRAS, and PIK3CA; whereas at the protein level, it exhibited a high correlation with EGFR, Lck, Bcl2, and Syk. The in vitro experiments revealed that PRKCA was upregulated in the cisplatin-resistant A549 cells (DDP-A549), while knockdown of PRKCA increased DDP-A549 apoptosis upon cisplatin treatment. Moreover, we observed that PRKCA knockdown attenuated DDP-A549 proliferation, migration and invasion ability. Western blot analysis demonstrated that PRKCA knockdown downregulated phosphorylation of PI3K expression while upregulated the genes involved in ferroptosis signaling. In summary, our results elucidate the role of PRKCA in acquiring resistance to cisplatin and underscore its potential as a therapeutic target for cisplatin-resistant lung cancer.

Hydrogel-based immunoregulation of macrophages for tissue repair and regeneration.

The rational design of hydrogel materials to modulate the immune microenvironment has emerged as a pivotal approach in expediting tissue repair and regeneration. Within the immune microenvironment, an array of immune cells exists, with macrophages gaining prominence in the field of tissue repair and regeneration due to their roles in cytokine regulation to promote regeneration, maintain tissue homeostasis, and facilitate repair. Macrophages can be categorized into two types: classically activated M1 (pro-inflammatory) and alternatively activated M2 (anti-inflammatory and pro-repair). By regulating the physical and chemical properties of hydrogels, the phenotypic transformation and cell behavior of macrophages can be effectively controlled, thereby promoting tissue regeneration and repair. A full understanding of the interaction between hydrogels and macrophages can provide new ideas and methods for future tissue engineering and clinical treatment. Therefore, this paper reviews the effects of hydrogel components, hardness, pore size, and surface morphology on cell behaviors such as macrophage proliferation, migration, and phenotypic polarization, and explores the application of hydrogels based on macrophage immune regulation in skin, bone, cartilage, and nerve tissue repair. Finally, the challenges and future prospects of macrophage-based immunomodulatory hydrogels are discussed.