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Chirality is a widespread phenomenon in nature and in living organisms and plays an important role in living systems. The sensitive discrimination of chiral molecular enantiomers remains a challenge in the fields of chemistry and biology. Establishing a simple, fast, and efficient strategy to discriminate the spatial configuration of chiral molecular enantiomers is of great significance. Chiral perovskite nanocrystals (PNCs) have attracted much attention because of their excellent optical activity. However, it is a challenge to prepare perovskites with both chiral and fluorescence properties for chiral sensing. In this work, we synthesized two chiral fluorescent perovskite nanocrystal assembly (PNA) enantiomers by using l- or d-phenylalanine (Phe) as chiral ligands. PNA exhibited good fluorescence recognition for l- and d-proline (Pro). Homochiral interaction led to fluorescence enhancement, while heterochiral interaction led to fluorescence quenching, and there is a good linear relationship between the fluorescence changing rate and l- or d-Pro concentration. Mechanism studies show that homochiral interaction-induced fluorescence enhancement is attributed to the disassembly of chiral PNA, while no disassembly of chiral PNA was found in heterochiral interaction-induced fluorescence quenching, which is attributed to the substitution of Phe on the surface of chiral PNA by heterochiral Pro. This work suggests that chiral perovskite can be used for chiral fluorescence sensing; it will inspire the development of chiral nanomaterials and chiral optical sensors.
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BACKGROUND: Gliomas are the deadliest malignant tumors of the adult central nervous system. We previously discovered that beta2-microglobulin (B2M) is abnormally upregulated in glioma tissues and that it exerts a range of oncogenic effects. Besides its tissue presence, serum B2M levels serve as biomarkers for various diseases. This study aimed to explore whether serum B2M levels can be used in the diagnosis and prognosis of gliomas. METHODS: Medical records from 246 glioma patients were retrospectively analyzed. The relationship between preoperative serum B2M levels and clinicopathological features was examined. Kaplan-Meier analysis, alongside uni- and multivariate Cox regression, assessed the association between B2M levels, systemic inflammatory markers, and glioma patient prognosis. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic significance of these biomarkers specifically for glioblastoma (GBM). RESULTS: Patients with malignant gliomas exhibited elevated preoperative serum B2M levels. Glioma patients with high serum B2M levels experienced shorter survival times. Multivariate Cox analysis determined the relationship between B2M levels (hazard ratio = 1.92, 95% confidence interval: 1.05-3.50, P = 0.034) and the overall survival of glioma patients. B2M demonstrated superior discriminatory power in distinguishing between GBM and non-GBM compared to inflammation indicators. Moreover, postoperative serum B2M levels were lower than preoperative levels in the majority of glioma patients. CONCLUSIONS: High preoperative serum B2M levels correlated with malignant glioma and a poor prognosis. Serum B2M shows promise as a novel biomarker for predicting patient prognosis and reflecting the therapeutic response.
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Biomarcadores de Tumor , Neoplasias Encefálicas , Glioma , Microglobulina beta-2 , Humanos , Microglobulina beta-2/sangre , Femenino , Masculino , Persona de Mediana Edad , Pronóstico , Biomarcadores de Tumor/sangre , Glioma/sangre , Glioma/mortalidad , Glioma/patología , Glioma/diagnóstico , Estudios Retrospectivos , Adulto , Neoplasias Encefálicas/sangre , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/diagnóstico , Anciano , Curva ROC , Estimación de Kaplan-Meier , Índice de Severidad de la EnfermedadRESUMEN
Central nervous system (CNS) disorders represent the leading cause of disability and the second leading cause of death worldwide, and impose a substantial economic burden on society. In recent years, emerging evidence has found that beta2 -microglobulin (B2M), a subunit of major histocompatibility complex class I (MHC-I) molecules, plays a crucial role in the development and progression in certain CNS diseases. On the one hand, intracellular B2M was abnormally upregulated in brain tumors and regulated tumor microenvironments and progression. On the other hand, soluble B2M was also elevated and involved in pathological stages in CNS diseases. Targeted B2M therapy has shown promising outcomes in specific CNS diseases. In this review, we provide a comprehensive summary and discussion of recent advances in understanding the pathological processes involving B2M in CNS diseases (e.g., Alzheimer's disease, aging, stroke, HIV-related dementia, glioma, and primary central nervous system lymphoma).
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Enfermedades del Sistema Nervioso Central , Microglobulina beta-2 , Humanos , Microglobulina beta-2/metabolismo , Enfermedades del Sistema Nervioso Central/metabolismo , Enfermedades del Sistema Nervioso Central/patología , AnimalesRESUMEN
OBJECTIVE: PM2.5 is closed linked to asthma exacerbation. The Notch1 pathway acts as an important pathway, ultimately inducing T-helper cells that express GATA3 and its corresponding Th2 cytokines. The regulatory effects of miR-139-5p on the Notch1 pathway have been indicated in cancer. However, studies on miR-139-5p have not applied asthma-related models. The role of miR-139-5p and its regulatory effects on the Notch1-GATA3 pathway in asthma exacerbation induced by acute PM2.5 exposure has not been elucidated. We hypothesize that acute PM2.5 exposure induces asthma exacerbation by regulating the expression of miR-139-5p and activating the Notch1-GATA3 pathway. METHODS: We first employed Diseased Human Bronchial Epithelial Cells-Asthma cells to establish an in vitro model of acute exposure to PM2.5, and explored the relationship between the different concentrations and durations of acute PM2.5 exposure and the activation of Notch1-GATA3 pathway. We investigated the protein and mRNA expression changes of Notch1, upstream Jagged1, downstream GATA3, as well as the regulatory effect of miR-139-5p involved in it. RESULTS: The miR-139-5p expression increased within 24 h of PM2.5 exposure. However, if PM2.5 exposure was sustained, miR-139-5p expression turned to decrease, accompanied by upregulations of the mRNA and protein expression of Notch1-GATA3 pathway. Overexpression of miR-139-5p blocked Notch1-GATA3 pathway activation induced by acute PM2.5 exposure. CONCLUSION: Acute PM2.5 exposure can activate Notch1-GATA3 pathway in asthma bronchial epithelial cells model, which might be involved in PM2.5-induced asthma exacerbation. miR-139-5p has a potential protective role of inhibiting PM2.5-induced asthma airway inflammation by targeting Notch1.
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Asma , Bronquios , Células Epiteliales , Factor de Transcripción GATA3 , MicroARNs , Material Particulado , Receptor Notch1 , MicroARNs/metabolismo , MicroARNs/genética , Humanos , Asma/genética , Asma/metabolismo , Asma/inducido químicamente , Receptor Notch1/metabolismo , Receptor Notch1/genética , Factor de Transcripción GATA3/metabolismo , Factor de Transcripción GATA3/genética , Material Particulado/efectos adversos , Células Epiteliales/metabolismo , Bronquios/citología , Transducción de Señal , Proteína Jagged-1/genética , Proteína Jagged-1/metabolismo , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/toxicidadRESUMEN
BACKGROUND: Depression and anxiety have been found prevalent during all phases of the COVID-19 pandemic. In late December 2022, almost all COVID-19 control measures were lifted in China, leading to a surge in COVID-19 infections. The public's perceived risk and fear of COVID-19 would be increased. This study aims to examine the prevalence of depression and anxiety in the Chinese general population and explores the mediating role of fear of COVID-19 between COVID-19 perceived risk and depression/anxiety and the moderating role of resilience between fear of COVID-19 and depression/anxiety. METHODS: A cross-sectional online survey was conducted in Wenzhou, China, immediately following almost all COVID-19 control measures lifted. The 9-item Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), the COVID-19 Risk Perception Scale, the Fear of COVID-19 Scale, and the Connor-Davidson Resilience Scale (CD-RISC) were used to evaluate depression, anxiety, COVID-19 perceived risk, fear of COVID-19, and resilience, respectively. Structural Equation Modeling (SEM) with Maximum Likelihood (ML) estimator and adjusted for significant background factors was performed to test the moderated mediation. Data obtained from 935 participants were analyzed. RESULTS: The prevalence of moderate to severe depression and anxiety was 23.7% and 9.5%, respectively. The present study revealed positive associations among COVID-19 perceived risk, fear of COVID-19 and depression/anxiety, and negative associations between resilience and fear of COVID-19/depression/anxiety. Fear of COVID-19 partially mediated the association between COVID-19 perceived risk and depression/anxiety. Furthermore, resilience significantly moderated the association between fear of COVID-19 and depression/anxiety. Two moderated mediation models were constructed. CONCLUSION: Depression and anxiety were prevalent among Chinese adults during the final phase of the pandemic in China. The significant mediation role of fear of COVID-19 implies that reducing fear of COVID-19 may effectively alleviate depression and anxiety symptoms. Moreover, enhancing public resilience during an epidemic crisis is crucial for promoting mental health.
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COVID-19 , Pruebas Psicológicas , Resiliencia Psicológica , Adulto , Humanos , Estudios Transversales , Salud Mental , Pandemias , COVID-19/epidemiología , MiedoRESUMEN
BACKGROUND: A considerable number of individuals infected with COVID-19 experience residual symptoms after the acute phase. However, the correlation between residual symptoms and psychological distress and underlying mechanisms are scarcely studied. We aim to explore the association between residual symptoms of COVID-19 and psychological distress, specifically depression, anxiety, and fear of COVID-19, and examine the role of risk perception and intolerance of uncertainty in the association. METHODS: A cross-sectional survey was conducted by online questionnaire-based approach in mid-January 2023. Self-reported demographic characteristics, COVID-19-related information, and residual symptoms were collected. Depression, anxiety, fear, risk perception and intolerance of uncertainty were evaluated using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Fear of COVID-19 Scale (FCV-19S), COVID-19 Risk Perception Scale and Intolerance of Uncertainty Scale-12 (IUS-12), respectively. Linear regression analyses were conducted to explore the associations. A moderated mediation model was then constructed to examine the role of risk perception of COVID-19 and intolerance of uncertainty in the association between residual symptoms and psychological distress. RESULTS: 1735 participants effectively completed the survey. 34.9% of the patients experienced residual symptoms after acute phase of COVID-19. Psychological distress was markedly increased by COVID-19 infection, while residual symptoms had a significant impact on psychological distress (Ps < 0.001), including depression (ß = 0.23), anxiety (ß = 0.21), and fear of COVID-19 (ß = 0.14). Risk perception served as a mediator between residual symptoms and all forms of psychological distress, while intolerance of uncertainty moderated the effect of risk perception on depression and anxiety. CONCLUSION: A considerable proportion of patients experience residual symptoms after acute phase of COVID-19, which have a significant impact on psychological distress. Risk perception and intolerance of uncertainty play a moderated-mediation role in the association between residual symptoms and depression/anxiety. It highly suggests that effective treatment for residual symptoms, maintaining appropriate risk perception and improving intolerance of uncertainty are critical strategies to alleviate COVID-19 infection-associated psychological distress.
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COVID-19 , Distrés Psicológico , Humanos , Estudios Transversales , Incertidumbre , Depresión/psicología , Ansiedad/psicología , PercepciónRESUMEN
BACKGROUND: Photodynamic therapy (PDT) is a relatively safe and highly selectivity antitumor treatment, which might be increasingly used as a supplement to conventional therapies. A clinical overview and detailed comparison of how to select patients and lesions for PDT in different scenarios are urgently needed to provide a basis for clinical treatment. SUMMARY: This review demonstrates the highlights and obstacles of applying PDT for lung cancer and underlines points worth considering when planning to initiate PDT. The aim was to make out the appropriate selection and help PDT develop efficacy and precision through a better understanding of its clinical use. KEY MESSAGES: Increasing evidence supports the feasibility and safety of PDT in the treatment of non-small cell lung cancer. It is important to recognize the factors that influence the efficacy of PDT to develop individualized management strategies and implement well-designed procedures. These important issues should be worth considering in the present and further research.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Fotoquimioterapia , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Fotoquimioterapia/métodosRESUMEN
Introduction Previous meta-analyses have explored the diagnostic accuracy and safety of computed tomography-guided percutaneous lung biopsy of ground-glass opacities (GGOs). However, no research has investigated the role of nonsurgical biopsies (including transbronchial approaches). Additionally, studies reporting the diagnostic accuracy of GGOs with different characteristics are scarce, with no quantitative assessment published to date. We performed a systematic review to explore the diagnostic accuracy and safety of nonsurgical biopsy for diagnosing GGOs, especially those with higher ground-glass component and smaller nodule sizes. Methods A thorough literature search of four databases was performed to compile studies evaluating both or either of the diagnostic accuracy and complications of nonsurgical biopsy for GGOs. A bivariate random-effects model and random-effect model were utilized for data synthesis. The methodological quality of the studies was assessed according to the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Results Nineteen eligible studies with a total of 1,379 biopsy-sampled lesions were analyzed, of which 1,124 were confirmed to be malignant. Nonsurgical biopsy reported a pooled sensitivity of 0.89, a specificity of 0.99, and negative predictive value (NPV) of 60.3%. The overall sensitivity, specificity, and NPV of nonsurgical biopsy for diagnosing GGOs according to GGO component were 0.90, 0.99, and 77.2% in pure GGOs; 0.87, 0.99, and 67.2% in GG-predominant lesions; and 0.89, 1.00 and 44.1% in solid-predominant lesions, respectively. Additionally, the diagnostic sensitivity was better in lesions ≥ 20 mm than in small lesions (0.95 vs 0.88). Factors that contributed to higher sensitivity were the use of coaxial needle system and CT fluoroscopy, but not the needle gauge. The summary sensitivity of core needle biopsy (CNB) was not significantly higher than fine needle aspiration (FNA) (0.92 vs 0.84; P = 0.42); however, we found an increased incidence of hemorrhage in CNB compared with FNA (60.9% vs 14.2%; P = 0.012). Conclusion Nonsurgical biopsy for diagnosing GGOs shows high sensitivity and specificity with an acceptably low risk of complications. However, negative biopsy results are unreliable in excluding malignancy, necessitating resampling or subsequent follow-up. The applicability of our study is limited due to significant heterogeneity, indirect comparisons, and the paucity of data on bronchoscopic approaches, restricting the generalizability of our findings to patients requiring transbronchial biopsies. Trial Registry: PROSPERO; No.: CRD42023429977; URL: www.crd.york.ac.uk/PROSPERO/).
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Lead-based perovskites are highly susceptible to environmental influences, and their application in analytical chemistry, especially in aqueous solution, has been reported rarely. All-inorganic lead-free metal halide perovskites have been considered as a substitute for lead-based perovskites. Herein, a Cs2RbTbCl6 perovskite microcrystal (PMCs), which emits strong yellow-green fluorescence with a maximum emission wavelength at 547 nm, was for the first time synthesized and characterized. The Cs2RbTbCl6 PMCs could be well dispersed in N,N-dimethylacetamide (DMF), and its fluorescence could be significantly enhanced by the addition of norfloxacin (NOR) in the aqueous solution. We found that the Cs2RbTbCl6 PMCs can be used as fluorescent probes (excitation, 365 nm; emission, 547 nm) to selectively detect NOR in a concentration range from 10.0 to 200.0 µM with the limit of detection (LOD) being 0.04 µM. The Cs2RbTbCl6 PMCs could also be adsorbed on filter paper to fabricate as a fluorescent test paper for visual detection of NOR under 365-nm ultraviolet (UV) lamp irradiation. The proposed method has the potential to establish a new analytical method to visualize the detection of NOR in aqueous environments and also promotes the application of all-inorganic lead-free perovskites for analytical detection in aqueous environments.
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BACKGROUND: Photodynamic therapy (PDT) is a promising interventional treatment approach that contributes to antitumor immunity. It has been reported that PDT can enhance the effectiveness of immune checkpoint inhibitors (ICIs), but its mechanism is yet unclear. Herein, we implemented bioinformatics analysis to detect common pathways and potential biomarkers in non-small cell lung cancer (NSCLC), PDT, and NSCLC immunotherapy to investigate potential links between PDT, immunotherapy and NSCLC, and their clinical impact. METHODS: Differentially expressed genes in NSCLC- and NSCLC immunotherapy-related data in the GEO database were intersected with PDT-related genes in the GeneCards database to obtain candidate genes and shared pathways. Enrichment analysis and protein-protein interaction were established to identify key genes in functionally enriched pathways. The expression profiles and the prognostic significance of key genes were depicted. RESULTS: Bioinformatics analysis showed that HIF-1α was screened as a prognostic gene in hypoxia, HIF-1, and PD-L1-related signaling pathways, which was associated with clinical response in NSCLC patients after PDT and immunotherapy. In vivo experiments showed that PDT could inhibit tumor growth and upregulate HIF-1α and PD-L1 expressions in NSCLC tissues with a positive correlation, which might influence the blocking activity of ICIs on the HIF-1, and PD-L1-related signaling pathways. CONCLUSIONS: PDT might improve the clinical response of ICIs by upregulating tumor HIF-1α and PD-L1 expressions in NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Fotoquimioterapia , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Relevancia Clínica , Antígeno B7-H1/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genéticaRESUMEN
We herein present a nickel-catalyzed cross-coupling reaction of aryl halides and nitriles with imidazolium salts. A series of 2-arylated imidazoles could be obtained in moderate to good yields through inert C-N bond cleavage. The imidazolium salt in this reaction acts as both a coupling partner and N-heterocyclic carbene (NHC) ligand precursor. Mechanistic studies reveal that consecutive steps of migratory insertion of the NHC into the aryl C-Ni bond and ß-C elimination might be involved in the proposed reaction mechanism.
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BACKGROUND: Xanthomatosis, a metabolic disorder causing yellow growths (xanthomas), poses challenges in lipid metabolism. This case study introduces the first documented instance within China's Yi population, emphasizing the need to explore dietary habits and treatment strategies tailored to this specific community. CASE SUMMARY: Xanthomatosis is a metabolic disorder where lipid metabolism goes awry, resulting in the development of yellowish growths called xanthomas. A male patient, 47 years of age, from China's Yi population, who is obese, visited our dermatology clinic complaining of widespread, non-painful rashes that have been present for two weeks. The patient works as a chef and has a diet that frequently includes oily and greasy foods. This case represents the initial documentation of xanthomatosis within the Yi population in China, offering a theoretical foundation for understanding dietary patterns and treatment options specific to the Yi community. CONCLUSION: The first report of xanthomatosis in the Yi population in China lays a theoretical foundation for understanding Yi dietary patterns and treatment.
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Lead halide perovskite nanocrystals (PNCs) have attracted intense attention due to their excellent optoelectronic properties. In this work, a series of water-stable CsPb(Br/I)3PNCs fluorescent probes were prepared using an anion exchange method. It was found that the PNCs probes could be used to detect ascorbic acid (AA) in water, and interestingly, the FL spectra of the PNCs probes can be adjusted by controlling the concentration of KI in anion exchange to improve the detection selectivity of AA. The high sensitivity and selectivity make CsPb(Br/I)3PNCs an ideal material for AA sensing. The concentration of AA can be linearly measured in the range from 0.01 to 50µM, with a detection limit of 4.2 nM. The reason for the enhanced FL of CsPb(Br/I)3PNCs was studied, and it is considered that AA causes the aggregation of CsPb(Br/I)3PNCs. This strategy of improving the selectivity of the probe to the substrate by adjusting the spectrum will significantly expand the application of PNCs in the field of analysis and detection.
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In this paper, we designed and synthesized a two-dimensional fluorescent covalent organic framework (TAPB-DMTP-COF) for the precise determination of H2O content in methanol. The COF was synthesized using two typical monomers by grinding method, which significantly reduced the synthesis time. By adjusting the pH value of the COF suspension to 4.0, the portion of the COF material structure is disrupted, thereby mitigating π-π stacking and resolving the aggregation-caused quenching (ACQ) effect. Consequently, the non-fluorescent TAPB-DMTP-COF exhibited blue-purple fluorescence emission in methanol. At the same time, it is observed that in the presence of H2O, there is a red shift in the maximum fluorescence emission peak of TAPB-DMTP-COF, which correlates with the H2O content within a specific range. Notably, this redshift demonstrates a linear relationship with H2O content from 4% to 80% in methanol. Our work presents novel insights for efficient analysis and detection of H2O content in methanol and could be used for H2O detection in other organic solvents.
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CONTEXT: Supplemental methotrexate (MTX) may affect the clinical course of Graves' disease (GD). OBJECTIVE: Evaluate efficacy of add-on MTX on medical treatment in GD. DESIGN: Prospective, open-label, randomized supplementation controlled trial. SETTING: Academic endocrine outpatient clinic. PATIENTS: One hundred and fifty-three untreated hyperthyroid patients with GD. INTERVENTION: Patients received MTX 10 mg/d with methimazole (MMI) or MMI only. MTX and MMI were discontinued at months 12-18 in euthyroid patients. MAIN OUTCOME MEASURES: Discontinuation rate at months 18 in each group. RESULTS: In the MTX with MMI group, the discontinuation rate was higher than the MMI group at months 15-18 (50.0 vs. 33.3%, P=0.043, 95% CI 1.020 to 3.922; and 55.6 vs 38.9%, P=0.045, 95%CI 1.011 to 3.815, respectively). The decrease in TRAb levels in the MTX with MMI group was significant from baseline to months 6 compared to the MMI alone group [MTX+MMI 67.22% (43.12-80.32), MMI 54.85% (33.18-73.76), P= 0.039) and became more significant from months 9 [MTX+MMI 77.79% (62.27-88.18), MMI 69.55% (50.50-83.22), P= 0.035] to months 18 (P < 0.01 in 15-18 months). A statistically significant difference between the levels of TRAb in the MTX with MMI group and the MMI group at 9-18 months. There were no significant differences in the levels of FT3, FT4 and TSH between two groups. No serious drug-related adverse events were observed in both groups(P=0.771). CONCLUSIONS: Supplemental MTX with MMI resulted in higher discontinuation rate and improvement in decreased TRAb levels to homeostatic levels faster than methimazole treatment alone at months 12-18.
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Exopolysaccharide produced by lactic acid bacteria has various functions. In the present study, one anti-oxidant polysaccharide fraction, namely S1-EPS, was extracted and purified from Pediococcus acidilactici S1, and its structure and its potential effect on the gel properties of fat substitute meat mince were investigated. The results showed that S1-EPS, one of homogeneous polysaccharides, was mainly composed of Gal, Glc, and Man in molar ratio of 7.61: 15.25: 77.13 and molecular weight of 46.975â¯kDa. The backbone of EPS-S1 contained â2,6)-α-D-Manp-(1âï¼â2)-α-D-Manp-(1â,â3)-α-D-Glcp-(1â¯ââ¯and a small amount ofâ6)-ß-D-Manp-(1â. The linkages of branches in EPS-S1 were mainly composed of α-D-Manp-(1â attached to a sugar residue â2,6)-α-D-Manp-(1âO-2 or ß-D-Galp-(1â attached to a sugar residue â2,6)-α-D-Manp-(1âO-6. Furthermore, as S1-EPS increased, the meat minced gel pores decreased, and the surface became smooth. A remarkable inhibitory effect on the lipid oxidation of meat minced gel was found as S1-EPS concentration increased. Overall, S1-EPS was found to have substantial potential in low-fat meat products by serving as a natural, anti-oxidant, and functional additive.
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Sustitutos de Grasa , Pediococcus acidilactici , Polisacáridos Bacterianos , Polisacáridos Bacterianos/química , Pediococcus acidilactici/metabolismo , Pediococcus acidilactici/química , Sustitutos de Grasa/química , Peso Molecular , Antioxidantes/química , Antioxidantes/farmacología , Geles/química , Productos de la Carne/microbiologíaRESUMEN
BACKGROUND: Lymph node ratio (LNR) was demonstrated to play a crucial role in the prognosis of many tumors. However, research concerning the prognostic value of LNR in postoperative gastric neuroendocrine neoplasm (NEN) patients was limited. AIM: To explore the prognostic value of LNR in postoperative gastric NEN patients and to combine LNR to develop prognostic models. METHODS: A total of 286 patients from the Surveillance, Epidemiology, and End Results database were divided into the training set and validation set at a ratio of 8:2. 92 patients from the First Affiliated Hospital of Soochow University in China were designated as a test set. Cox regression analysis was used to explore the relationship between LNR and disease-specific survival (DSS) of gastric NEN patients. Random survival forest (RSF) algorithm and Cox proportional hazards (CoxPH) analysis were applied to develop models to predict DSS respectively, and compared with the 8th edition American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging. RESULTS: Multivariate analyses indicated that LNR was an independent prognostic factor for postoperative gastric NEN patients and a higher LNR was accompanied by a higher risk of death. The RSF model exhibited the best performance in predicting DSS, with the C-index in the test set being 0.769 [95% confidence interval (CI): 0.691-0.846] outperforming the CoxPH model (0.744, 95%CI: 0.665-0.822) and the 8th edition AJCC TNM staging (0.723, 95%CI: 0.613-0.833). The calibration curves and decision curve analysis (DCA) demonstrated the RSF model had good calibration and clinical benefits. Furthermore, the RSF model could perform risk stratification and individual prognosis prediction effectively. CONCLUSION: A higher LNR indicated a lower DSS in postoperative gastric NEN patients. The RSF model outperformed the CoxPH model and the 8th edition AJCC TNM staging in the test set, showing potential in clinical practice.
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The minimization of irreversible active lithium loss stands as a pivotal concern in rechargeable lithium batteries, particularly in the context of grid-storage applications, where achieving the utmost energy density over prolonged cycling is imperative to meet stringent demands, notably in terms of life cost. Departing from conventional methodologies advocating electrode prelithiation and/or electrolyte additives, a new paradigm is proposed here: the integration of a designer lithium reservoir (DLR) featuring lithium orthosilicate (Li4SiO4) and elemental sulfur. This approach concurrently addresses active lithium consumption through solid electrolyte interphase (SEI) formation and mitigates minor yet continuous parasitic reactions at the electrode/electrolyte interface during extended cycling. The remarkable synergy between the Li-ion conductive Li4SiO4 and the SEI-favorable elemental sulfur enables customizable compensation kinetics for active lithium loss throughout continuous cycling. The introduction of a minute quantity of DLR (3 wt% Li4SiO4@S) yields outstanding cycling stability in a prototype pouch cell (graphite||LiFePO4) with an ampere-hour-level capacity (≈2.3 Ah), demonstrating remarkable capacity retention (≈95%) even after 3000 cycles. This utilization of a DLR is poised to expedite the development of enduring lithium batteries for grid-storage applications and stimulate the design of practical, implantable rechargeable batteries based on related cell chemistries.
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BACKGROUND: Heat shock protein A4 (HSPA4) belongs to molecular chaperone protein family which plays important roles within variable cellular activities, including cancer initiation and progression. However, the prognostic and immunological significance of HSPA4 in lung adenocarcinoma (LUAD) has not been revealed yet. AIM: To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD. METHODS: We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database. The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test. Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors, including HSPA4, in LUAD. Gene set enrichment analysis (GSEA) was conducted to identify the key signaling pathways associated with HSPA4. The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis (ssGSEA). RESULTS: Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage, advanced pathologic stage, progression disease status of primary therapy outcome and female subgroups with LUAD. In addition, increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival. GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response, particularly through diminishing the function of cytotoxicity cells and CD8 T cells. The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells, while a negative correlation was observed with cytotoxic cell infiltration levels. CONCLUSION: Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.