RESUMO
Molecularly imprinted polymers (MIPs) have been widely studied in environmental protection and food industry, owing to their excellent specific recognition and structural stability. However, MIPs prepared by conventional methods suffer from low adsorption capacity and slow mass transfer rate. To date, the combination of electrostatic spinning technology and molecular imprinting technology has been proposed to prepare molecularly imprinted membranes (MIMs) with specific recognition capability, and has shown great attraction in the separation and detection of food additives, as well as the extraction and release of active ingredients. In recent years, MIPs and electrostatic spinning technologies have been investigated and evaluated. However, there is no review of electrostatically spun MIMs for food field. In this review, we focus on the fabrication methods and applications of electrostatically spun MIMs in the food, discuss the challenges in practical food applications, and emphasize the promising applications of electrostatically spun MIMs in food field.
RESUMO
Universal coatings with versatile surface adhesion, good mechanochemical robustness, and the capacity for secondary modification are of great scientific interest. However, incorporating these advantages into a system is still a great challenge. Here, we report a series of catechol-decorated polyallylamines (CPAs), denoted as pseudo-Mytilus edulis foot protein 5 (pseudo-Mefp-5), that mimic not only the catechol and amine groups but also the backbone of Mefp-5. CPAs can fabricate highly adhesive, robust, multifunctional polyCPA (PCPA) coatings based on synergetic catechol-polyamine chemistry as universal building blocks. Due to the interpenetrating entangled network architectures, these coatings exhibit high chemical robustness against harsh conditions (HCl, pH 1; NaOH, pH 14; H2O2, 30%), good mechanical robustness, and wear resistance. In addition, PCPA coatings provide abundant grafting sites, enabling the fabrication of various functional surfaces through secondary modification. Furthermore, the versatility, multifaceted robustness, and scalability of PCPA coatings indicate their great potential for surface engineering, especially for withstanding harsh conditions in multipurpose biomedical applications.
RESUMO
Cyclin D1 has been recognized as an oncogene due to its abnormal upregulation in different types of cancers. Here, we demonstrated that cyclin D1 is SUMOylated, and we identified Itch as a specific E3 ligase recognizing SUMOylated cyclin D1 and mediating SUMO-induced ubiquitination and proteasome degradation of cyclin D1. We generated cyclin D1 mutant mice with mutations in the SUMOylation site, phosphorylation site, or both sites of cyclin D1, and found that double mutant mice developed a Mantle cell lymphoma (MCL)-like phenotype. We showed that arsenic trioxide (ATO) enhances cyclin D1 SUMOylation-mediated degradation through inhibition of cyclin D1 deSUMOylation enzymes, leading to MCL cell apoptosis. Treatment of severe combined immunodeficiency (SCID) mice grafted with MCL cells with ATO resulted in a significant reduction in tumor growth. In this study, we provide novel insights into the mechanisms of MCL tumor development and cyclin D1 regulation and discover a new strategy for MCL treatment.
RESUMO
BACKGROUND: Antiangiogenic treatment and immunochemotherapy effectively treat patients with advanced esophageal cancer. However, there remains a dearth of studies concerning neoadjuvant therapy for resectable esophageal cancer. METHODS: The study focused on patients with T2-4NxM0 resectable esophageal carcinoma. Neoadjuvant treatment involved administering anlotinib (10 mg orally, once a day, 2 weeks on and 1 week off) for antiangiogenesis and sintilimab (200 mg) and chemotherapy for three cycles. Surgical treatment was performed 4-6 weeks after the last chemotherapy cycle was completed. The primary endpoints assessed were pathological complete response (pCR) and safety. RESULTS: Out of the 34 screened patients, 17 were successfully enrolled in the study, and 14 completed the entire treatment process. The pCR was 35.3% (6/17). However, two patients experienced mortality. The occurring rate of grade 3 or higher complications after the surgery was 78.6% (11/14) according to Clavien-Dindo classification. Specifically, anastomotic leakage was observed in 57.1% (8/14) of the patients. CONCLUSION: Compared to neoadjuvant chemotherapy, the current regimen demonstrated improved pCR. However, it did not show significant improvement compared to immunochemotherapy. It is essential to exercise caution when using this treatment approach in patients with esophageal cancer as it might increase postoperative complications, especially anastomotic leakage.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Esofágicas , Indóis , Terapia Neoadjuvante , Quinolinas , Humanos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Masculino , Terapia Neoadjuvante/métodos , Quinolinas/uso terapêutico , Quinolinas/administração & dosagem , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Indóis/uso terapêutico , Indóis/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , AdultoRESUMO
OBJECTIVE: To evaluate the effectiveness of oral probiotic supplements in patients undergoing immune checkpoint inhibitors (ICIs) for the treatment of advanced lung cancer. METHODS: This prospective real-world study enrolled patients with advanced lung cancer who were receiving ICIs as part of their treatment. The patients were divided into 2 groups: Group OPS received oral probiotic supplements along with ICIs, while Group C did not. The primary endpoint was progression-free survival (PFS). The secondary outcome measure was the objective response rate (ORR). RESULTS: A total of 253 patients were included in the study, with 71 patients in Group OPS and 182 patients in the control group (Group C). No significant differences were observed in the median PFS between the 2 groups for all patients. However, for small cell lung cancer (SCLC) patients, the median PFS was significantly better in the Group OPS compared to the Group C (11.1 months vs 7.0 months, P = .049). No significant differences were observed in median PFS for the non-small cell lung cancer (NSCLC) cohort between the 2 groups, but a trend towards better median PFS in Group OPS was noticed (16.5 months vs 12.3 months, P = .56). The ORR for the entire cohort was 58.0%. CONCLUSION: Oral probiotics supplements in combination with ICIs included regimen may improve the outcome in patients with advanced SCLC. The above points should be proved by further study.
This study examined whether the addition of oral probiotic supplements to ICIs could enhance the treatment of advanced lung cancer. A total of 253 patients with advanced lung cancer were involved in the study, with some receiving probiotics in combination with ICIs and others not. The findings revealed that patients with SCLC who took probiotics had significantly better PFS compared to those who did not. Additionally, there was a tendency towards enhanced PFS in NSCLC patients who received probiotics. In conclusion, the study indicates that incorporating oral probiotics with ICIs may lead to better outcomes for patients with advanced SCLC, although further research is necessary to validate these results.This real world study explores whether oral probiotic supplements along with immune checkpoint inhibitors (ICIs) can help treat advanced lung cancer. The study included 253 patients with advanced lung cancer receiving ICIs treatment, part of them taking probiotics along with ICIs. The results showed that patients with small cell lung cancer (SCLC) who took probiotics had better progression-free survival (PFS) compared to those who didn't. There was also a trend towards better PFS in non-small cell lung cancer (NSCLC) patients who took probiotics. Overall, the study suggests that taking oral probiotics along with ICIs may improve outcomes for patients with advanced SCLC, but more research is needed to confirm these findings.
Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Probióticos , Humanos , Probióticos/administração & dosagem , Probióticos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/mortalidade , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Idoso , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/administração & dosagem , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/terapia , Carcinoma de Pequenas Células do Pulmão/patologia , Administração Oral , Suplementos Nutricionais , Intervalo Livre de Progressão , Terapias Complementares/métodos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , AdultoRESUMO
Bone secretory proteins, termed osteokines, regulate bone metabolism and whole-body homeostasis. However, fundamental questions as to what the bona fide osteokines and their cellular sources are and how they are regulated remain unclear. In this study, we analyzed bone and extraskeletal tissues, osteoblast (OB) conditioned media, bone marrow supernatant (BMS), and serum, for basal osteokines and those responsive to aging and mechanical loading/unloading. We identified 375 candidate osteokines and their changes in response to aging and mechanical dynamics by integrating data from RNA-seq, scRNA-seq, and proteomic approaches. Furthermore, we analyzed their cellular sources in the bone and inter-organ communication facilitated by them (bone-brain, liver, and aorta). Notably, we discovered that senescent OBs secrete fatty-acid-binding protein 3 to propagate senescence toward vascular smooth muscle cells (VSMCs). Taken together, we identified previously unknown candidate osteokines and established a dynamic regulatory network among them, thus providing valuable resources to further investigate their systemic roles.
Assuntos
Osteoblastos , Animais , Osteoblastos/metabolismo , Osteoblastos/citologia , Camundongos , Osso e Ossos/metabolismo , Proteômica , Camundongos Endogâmicos C57BL , Masculino , Envelhecimento/metabolismo , Humanos , Senescência Celular , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citologia , MultiômicaRESUMO
BACKGROUND: Ultra-performance Liquid Chromatography-tandem Mass Spectrometry (UPLC-MS/MS) is widely used for concentration detection of many Tyrosine Kinase Inhibitors (TKIs), including afatinib, crizotinib, and osimertinib. In order to analyze whether pralsetinib takes effect in Rearranged during Transfection (RET)-positive patients with central nervous system metastasis, we aimed to develop a method for the detection of pralsetinib concentrations in human plasma and Cerebrospinal Fluid (CSF) by UPLC-MS/MS. METHODS: The method was developed using the external standard method, and method validation included precision, accuracy, stability, extraction recovery, and matrix effect. Working solutions were all obtained based on stock solutions of pralsetinib of 1mg/mL. The plasma/CSF samples were precipitated by acetonitrile for protein precipitation and then separated on an ACQUITY UPLC HSS T3 column (2.1×100 mm, 1.8 µm) with a gradient elution using 0.1% formic acid (solution A) and acetonitrile (solution B) as mobile phases at a flow rate of 0.4 mL/min. The tandem mass spectrometry was performed by a triple quadrupole linear ion trap mass spectrometry system (QTRAPTM 6500+) with an electrospray ion (ESI) source and Analyst 1.7.2 data acquisition system. Data were collected in Multiple Reaction Monitoring (MRM) and positive ionization mode. RESULTS: A good linear relationship of pralsetinib in both plasma and CSF was successfully established, and the calibration ranges were found to be 1.0-64.0 µg/mL and 50.0ng/mL-12.8 µg/mL for pralsetinib in the plasma and CSF, respectively. Validation was performed, including calibration assessment, selectivity, precision, accuracy, matrix effect, extraction recovery, and stability, and all results have been found to be acceptable. The method has been successfully applied to pralsetinib concentration detection in a clinical sample, and the concentrations have been found to be 475 ng/mL and 61.55 µg/mL in the CSF and plasma, respectively. CONCLUSION: We have developed a quick and effective method for concentration detection in both plasma and CSF, and it can be applied for drug monitoring in clinical practice. The method can also provide a reference for further optimization.
Assuntos
Monitoramento de Medicamentos , Espectrometria de Massas em Tandem , Humanos , Monitoramento de Medicamentos/métodos , Cromatografia Líquida de Alta Pressão , Antineoplásicos/sangue , Antineoplásicos/líquido cefalorraquidiano , Pirróis/líquido cefalorraquidiano , Pirróis/sangue , Pirróis/química , Estrutura Molecular , Inibidores de Proteínas Quinases/líquido cefalorraquidiano , Inibidores de Proteínas Quinases/sangue , Inibidores de Proteínas Quinases/química , Espectrometria de Massa com Cromatografia Líquida , Pirazóis , Piridinas , PirimidinasRESUMO
BACKGROUND: Class and social disadvantage have long been identified as significant factors in the etiology and epidemiology of psychosis. Few studies have explicitly examined the impact of intersecting social disadvantage on long-term employment and financial independence. METHODS: We applied latent class analysis (LCA) to 20-year longitudinal data from participants with affective and non-affective psychosis (n = 256) within the Chicago Longitudinal Research. LCA groups were modeled using multiple indicators of pre-morbid disadvantage (parental social class, educational attainment, race, gender, and work and social functioning prior to psychosis onset). The comparative longitudinal work and financial functioning of LCA groups were then examined. RESULTS: We identified three distinct latent classes: one comprised entirely of White participants, with the highest parental class and highest levels of educational attainment; a second predominantly working-class group, with equal numbers of Black and White participants; and a third with the lowest parental social class, lowest levels of education and a mix of Black and White participants. The latter, our highest social disadvantage group experienced significantly poorer employment and financial outcomes at all time-points, controlling for diagnosis, symptoms, and hospitalizations prior to baseline. Contrary to our hypotheses, on most measures, the two less disadvantaged groups did not significantly differ from each other. CONCLUSIONS: Our analyses add to a growing literature on the impact of multiple forms of social disadvantage on long-term functional trajectories, underscoring the importance of proactive attention to sociostructural disadvantage early in treatment, and the development and evaluation of interventions designed to mitigate ongoing social stratification.
RESUMO
Osteoarthritis (OA) is the most prevalent disorder of synovial joint affecting multiple joints. In the past decade, we have witnessed conceptual switch of OA pathogenesis from a 'wear and tear' disease to a disease affecting entire joint. Extensive studies have been conducted to understand the underlying mechanisms of OA using genetic mouse models and ex vivo joint tissues derived from individuals with OA. These studies revealed that multiple signalling pathways are involved in OA development, including the canonical Wnt/ß-catenin signalling and its interaction with other signalling pathways, such as transforming growth factor ß (TGF-ß), bone morphogenic protein (BMP), Indian Hedgehog (Ihh), nuclear factor κB (NF-κB), fibroblast growth factor (FGF), and Notch. The identification of signalling interaction and underlying mechanisms are currently underway and the specific molecule(s) and key signalling pathway(s) playing a decisive role in OA development need to be evaluated. This review will focus on recent progresses in understanding of the critical role of Wnt/ß-catenin signalling in OA pathogenesis and interaction of ß-catenin with other pathways, such as TGF-ß, BMP, Notch, Ihh, NF-κB, and FGF. Understanding of these novel insights into the interaction of ß-catenin with other pathways and its integration into a complex gene regulatory network during OA development will help us identify the key signalling pathway of OA pathogenesis leading to the discovery of novel therapeutic strategies for OA intervention.
Assuntos
Osteoartrite , Transdução de Sinais , beta Catenina , Humanos , Osteoartrite/metabolismo , Osteoartrite/patologia , Animais , beta Catenina/metabolismo , Via de Sinalização Wnt , NF-kappa B/metabolismo , Proteínas Hedgehog/metabolismo , Proteínas Morfogenéticas Ósseas/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
This study aims to determine the molecular mechanisms and analgesic effects of transient receptor potential vanilloid 1 (TRPV1) in the treatments of osteoarthritis (OA) and rheumatoid arthritis (RA). We summarize and analyse current studies regarding the biological functions and mechanisms of TRPV1 in arthritis. We search and analyse the related literature in Google Scholar, Web of Science and PubMed databases from inception to September 2023 through the multi-combination of keywords like 'TRPV1', 'ion channel', 'osteoarthritis', 'rheumatoid arthritis' and 'pain'. TRPV1 plays a crucial role in regulating downstream gene expression and maintaining cellular function and homeostasis, especially in chondrocytes, synovial fibroblasts, macrophages and osteoclasts. In addition, TRPV1 is located in sensory nerve endings and plays an important role in nerve sensitization, defunctionalization or central sensitization. TRPV1 is a non-selective cation channel protein. Extensive evidence in recent years has established the significant involvement of TRPV1 in the development of arthritis pain and inflammation, positioning it as a promising therapeutic target for arthritis. TRPV1 likely represents a feasible therapeutic target for the treatment of OA and RA.
Assuntos
Antineoplásicos , Artrite Reumatoide , Osteoartrite , Humanos , Artrite Reumatoide/tratamento farmacológico , Condrócitos , Inflamação/tratamento farmacológico , Osteoartrite/tratamento farmacológicoRESUMO
The prediction of optical properties dominated by light scattering in particulate media composed of high-concentration and polydisperse particles is greatly important in various optical applications. However, the accuracy and efficiency of light propagation simulations are still limited by the huge computational burden and complex interactions between dense and polydisperse particles. Here, we proposed a new optimization strategy that can effectively and accurately predict optical properties based on Monte Carlo simulation with particle size and dependent scattering corrections. Both the scattering parameters of particles and the experimental reflectance spectrum are fully examined for verification. Furthermore, using the weighted solar reflectance of particulate media as a representative optical property, both numerical simulations and experiments confirm the superiority and universality of the proposed optimization approach in a variety of materials systems. Moreover, our work can guide the design of particulate media with specific optical features insightfully and will be applicable in many fields involving multiparticle scattering.
RESUMO
Conventional Ti-based implants are vulnerable to postsurgical infection and improving the antibacterial efficiency without compromising the osteogenic ability is one of the key issues in bone implant design. Although zinc oxide (ZnO) nanorods grown on Ti substrates hydrothermally can improve the antibacterial properties, but cannot meet the stringent requirements of bone implants, as rapid degradation of ZnO and uncontrolled leaching of Zn2+ are detrimental to peri-implant cells and tissues. To solve these problems, a lattice-damage-free method is adopted to modify the ZnO nanorods with thin calcium phosphate (CaP) shells. The Ca and P ions from the CaP shells diffuse thermally into the ZnO lattice to prevent the ZnO nanorods from rapid degradation and ensure the sustained release of Zn2+ ions as well. Furthermore, the designed heterostructural nanorods not only induce the osteogenic performances of MC3T3-E1 cells but also exhibit excellent antibacterial ability against S. aureus and E. coli bacteria via physical penetration. In vivo studies also reveal that hybrid Ti-ZnO@CaP5 can not only eradicates bacteria in contact, but also provides sufficient biocompatibility without causing excessive inflammation response. Our study provides insights into the design of multifunctional biomaterials for bone implants. STATEMENT OF SIGNIFICANCE: ⢠A lattice-damage-free method is adopted to modify the ZnO nanorods with thin calcium phosphate (CaP) shells. ⢠The dynamic process of Ca and P diffusion into the ZnO lattice is analyzed by experimental verification and theoretical calculation. ⢠The degradation rate of ZnO nanorods is significantly decreased after CaP deposition. ⢠The ZnO nanorods after CaP deposition can not only sterilize bacteria in contact via physical penetration, but also provide sufficient biocompatibility and osteogenic capability without causing excessive inflammation response..
Assuntos
Infecções Bacterianas , Óxido de Zinco , Humanos , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Osteogênese , Cálcio/farmacologia , Titânio/farmacologia , Staphylococcus aureus , Escherichia coli , Antibacterianos/farmacologia , Antibacterianos/química , Bactérias , Fosfatos de Cálcio/farmacologia , Íons/farmacologia , InflamaçãoRESUMO
Although aging has traditionally been viewed as the most important risk factor for osteoarthritis (OA), an increasing amount of epidemiological evidence has highlighted the association between metabolic abnormalities and OA, particularly in younger individuals. Metabolic abnormalities, such as obesity and type II diabetes, are strongly linked to OA, and they affect both weight-bearing and non-weight-bearing joints, thus suggesting that the pathogenesis of OA is more complicated than the mechanical stress induced by overweight. This review aims to explore the recent advances in research on the relationship between metabolic abnormalities and OA risk, including the impact of abnormal glucose and lipid metabolism, the potential pathogenesis and targeted therapeutic strategies.
Assuntos
Diabetes Mellitus Tipo 2 , Osteoartrite , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Osteoartrite/epidemiologia , Obesidade/complicações , Fatores de Risco , Metabolismo dos LipídeosRESUMO
Cyclin D1 is a key regulator of cell cycle progression, which forms a complex with CDK4/6 to regulate G1/S transition during cell cycle progression. Cyclin D1 has been recognized as an oncogene since it was upregulated in several different types of cancers. It is known that the post-translational regulation of cyclin D1 is controlled by ubiquitination/proteasome degradation system in a phosphorylation-dependent manner. Several cullin-associated F-box E3 ligases have been shown to regulate cyclin D1 degradation; however, it is not known if additional cullin-associated E3 ligases participate in the regulation of cyclin D1 protein stability. In this study, we have screened an siRNA library containing siRNAs specific for 154 ligase subunits, including F-box, SOCS, BTB-containing proteins, and DDB proteins. We found that multiple cullin-associated E3 ligases regulate cyclin D1 activity, including Keap1, DDB2, and WSB2. We found that these E3 ligases interact with cyclin D1, regulate cyclin D1 ubiquitination and proteasome degradation in a phosphorylation-dependent manner. These E3 ligases also control cell cycle progression and cell proliferation through regulation of cyclin D1 protein stability. Our study provides novel insights into the regulatory mechanisms of cyclin D1 protein stability and function.
Assuntos
Proteínas Culina , Proteínas F-Box , Proteínas Culina/genética , Proteínas Culina/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas F-Box/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estabilidade ProteicaRESUMO
The multivalency of bioligands in living systems brings inspiration for not only the discovery of biological mechanisms but also the design of extracellular matrix (ECM)-mimicking biomaterials. However, designing controllable multivalency construction strategies is still challenging. Herein, we synthesized a series of well-defined multivalent antimicrobial peptide polymers (mAMPs) by clicking ligand molecules onto polymers prepared by reversible addition-fragmentation chain transfer polymerization. The multiple cationic ligands in the mAMPs could enhance the local disturbance of the anionic phospholipid layer of the bacterial membrane through multivalent binding, leading to amplification of the bactericidal effect. In addition to multivalency-enhanced antibacterial activity, mAMPs also enable multivalency-assisted hydrogel fabrication with an ECM-like dynamic structure. The resultant hydrogel with self-healing and injectable properties could be successfully employed as an antibacterial biomaterial scaffold to treat infected skin wounds. The multivalency construction strategy presented in this work provides new ideas for the biomimetic design of highly active and dynamic biomaterials for tissue repair and regeneration.
RESUMO
Sulfur dioxide (SO2) is a common atmospheric pollutant. Currently, most of the detection methods are based on chemical reactions and optical absorption principles. However, these methods have some limitations in their detection range and accuracy, especially in complex environments. In this work, sulfur dioxide was absorbed by an ionic liquid, and a new electrochemical sensor based on 3D-rGO/CB was developed for electrochemical detection. Specifically, carbon black (CB) nanoparticles were incorporated with graphene oxide (GO) sheets using spray drying technology to form a highly porous and interconnected 3D-GO/CB microsphere structure. Then, the 3D-rGO/CB/GCE electrochemical sensor was fabricated by electrochemical reduction of the composite material onto a glassy carbon electrode (GCE) surface and used to detect sulfur dioxide in ionic liquids. The results demonstrated that the sensor had excellent conductivity and mass transfer preferable performance catalytic activity for SO2 in ionic liquids, and a linear detection range of 100-3500 ppm. Besides, the detection limit was 52.3 ppm (S/N = 3). Moreover, it had high selectivity, stability, and repeatability. This work significantly contributed to the development of advanced electrochemical sensors with improved performance for detecting SO2 in ionic liquids and has a potential application prospect in the field of electrochemical gas detection.
RESUMO
BACKGROUND: This study aimed to investigate the prospects of using chemotherapy in combination with atezolizumab in the neoadjuvant or conversion treatment of small cell lung cancer (SCLC). METHODS: Prior to surgery, untreated patients with limited-stage SCLC received three cycles of neoadjuvant or conversion atezolizumab combined with chemotherapy of etoposide and platinum. The primary endpoint of the trial was pathological complete response (pCR) in the per-protocol (PP) cohort. In addition, safety was assessed based on treatment-related adverse events (AEs) and postoperative complications. RESULTS: Overall, 13 of 17 patients (including 14 males and 3 females) underwent surgery. In the PP cohort, pCR and major pathological response were observed in 8 (8/13, 61.5%) and 12 (12/13, 92.3%) patients, respectively. According to the intention-to-treat (ITT) analysis, the pCR and major pathological response in the ITT cohort were 47.1% (8/17) and 70.6% (12/17), respectively. In addition, an overall response rate of 100% was recorded in the PP cohort. Moreover, 15 (15/17, 88.2%) patients and 1 (1/17, 5.9%) in the ITT cohort attained partial remission (PR), and complete remission, respectively, with an overall response rate of 94.1%. The median overall survival of the patients of pCR and the median event-free survival of the patients on surgery had not achieved. However, the median overall survival of the patients of non-pCR was 18.2 months and the median event-free survival of the nonsurgical patients was 9.5 months. During the neoadjuvant treatment, the incidence of grade 3 or higher AEs was 58.8% (10/17). Additionally, three patients (17.6%) developed immune-related adverse event (grades 1-2). CONCLUSION: In patients with SCLC, neoadjuvant or conversion atezolizumab combined with chemotherapy significantly improved pCR with manageable AEs. Therefore, this regimen may be considered a safe and effective treatment for SCLC.
Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Feminino , Masculino , Humanos , Terapia Neoadjuvante , Estudos de Coortes , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
The fundamental mechanism of solar absorbance during the phase-change process is investigated in ABO3 perovskites based on first-principles predictions. A Gaussian-like relationship between the solar absorbance and band gaps is established, which follows the Shockley-Queisser limiting efficiency. For ABO3 perovskites with bandgaps of Eg > 3.5 eV, a low solar absorbance is obtained, whereas a high solar absorbance is obtained for ABO3 perovskites, with band gaps ranging from 0.25 to 2.2 eV. The relationship between the orbital character of the density of states (DOS) and the absorption spectra reveals that ABO3 perovskites with magnetic (strongly interacting) and distorted crystal structures always exhibit a higher solar absorptivity. In contrast, non-magnetic and cubic ABO3 perovskites always exhibit a lower solar absorptivity. Moreover, the tunable solar absorptivity always undergoes a phase change from cubic to large distorted crystal structures in ABO3 perovskites with strong interactions. These results can be attributed to a rich structural, electronic, and magnetic phase diagram resulting from the strong interplay between the lattice, spin, and orbital degrees of freedom, which induce highly tunable optical characteristics in the phase-change process. The findings presented in this study are critical for the development of ABO3 perovskite-based smart thermal control materials in the spacecraft field.
RESUMO
Glucocorticoid (GC)-induced osteoporosis is the most common secondary cause of osteoporosis, resulting in fractures and significant morbidity. In this issue of Cell Metabolism, Liu et al. reveal that in response to GCs, bone marrow adipocytes (BMAds) undergo rapid cellular senescence, triggering secondary senescence in bone marrow and causing bone deterioration.