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1.
Cancer Discov ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38975897

ABSTRACT

Resistance to inactive state-selective RASG12C inhibitors frequently entails accumulation of RASGTP, rendering effective inhibition of active RAS potentially desirable. Here, we evaluated the anti-tumor activity of the RAS(ON) multi-selective tri-complex inhibitor RMC-7977 and dissected mechanisms of response and tolerance in KRASG12C-mutant NSCLC. Broad-spectrum, reversible RASGTP inhibition with or without concurrent covalent targeting of active RASG12C yielded superior and differentiated antitumor activity across diverse co-mutational KRASG12C-mutant NSCLC mouse models of primary or acquired RASG12C(ON) or (OFF) inhibitor resistance. Interrogation of time-resolved single cell transcriptional responses established an in vivo atlas of multi-modal acute and chronic RAS pathway inhibition in the NSCLC ecosystem and uncovered a regenerative mucinous transcriptional program that supports long-term tumor cell persistence. In patients with advanced KRASG12C-mutant NSCLC, the presence of mucinous histological features portended poor response to sotorasib or adagrasib. Our results have potential implications for personalized medicine and the development of rational RAS inhibitor-anchored therapeutic strategies.

2.
Angew Chem Int Ed Engl ; : e202411219, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39020249

ABSTRACT

Two-dimensional organic-inorganic hybrid perovskites ( OIHPs) with alternating structure of the organic and inorganic layers have a natural quantum well structure. The difference of dielectric constants between organic and inorganic layers in this structure results in the enhancement of dielectric confinement effect, which exhibits a large exciton binding energy and hinders the separation of electron-hole pairs. Herein, a strategy to reduce the dielectric confinement effect by narrowing the dielectric difference between organic amine molecule and [PbBr6]4- octahedron is put forward. The Ethanolamine (EOA) contains hydroxyl groups, resulting in the positive and negative charge centers of O and H non-overlapping,which generated a larger polarity and dielectric constant. The reduced dielectric constant produces a smaller exciton binding energy (71.03 meV) of (C2H7NO)2PbBr4 ((EOA)2PbBr4) than (C8H11N)2PbBr4 ((PEA)2PbBr4 (156.07 meV), and promotes the dissociation of electrons and holes. The increasing of lifetime of photogenerated carrier in (EOA)2PbBr4 are proved by femtosecond transient absorption spectra. DFT calculations have also indicated that the small energy shift of the total density of states (DOS) between the C/H/N and the Pb/Br in (EOA)2PbBr4 favors the separation of electrons and holes. In addition, this work demonstrates the application of (PEA)2PbBr4 and (EOA)2PbBr4 in the field of photocatalytic CO2 reduction.

3.
bioRxiv ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38979334

ABSTRACT

Accumulating evidence suggests that the tumor immune microenvironment (TIME) significantly influences the response to immunotherapy, yet this complex relationship remains elusive. To address this issue, we developed TimiGP-Response (TIME Illustration based on Gene Pairing designed for immunotherapy Response), a computational framework leveraging single-cell and bulk transcriptomic data, along with response information, to construct cell-cell interaction networks associated with responders and estimate the role of immune cells in treatment response. This framework was showcased in triple-negative breast cancer treated with immune checkpoint inhibitors targeting the PD-1:PD-L1 interaction, and orthogonally validated with imaging mass cytometry. As a result, we identified CD8+ GZMB+ T cells associated with responders and its interaction with regulatory T cells emerged as a potential feature for selecting patients who may benefit from these therapies. Subsequently, we analyzed 3,410 patients with seven cancer types (melanoma, non-small cell lung cancer, renal cell carcinoma, metastatic urothelial carcinoma, hepatocellular carcinoma, breast cancer, and esophageal cancer) treated with various immunotherapies and combination therapies, as well as several chemo- and targeted therapies as controls. Using TimiGP-Response, we depicted the pan-cancer immune landscape associated with immunotherapy response at different resolutions. At the TIME level, CD8 T cells and CD4 memory T cells were associated with responders, while anti-inflammatory (M2) macrophages and mast cells were linked to non-responders across most cancer types and datasets. Given that T cells are the primary targets of these immunotherapies and our TIME analysis highlights their importance in response to treatment, we portrayed the pan-caner landscape on 40 T cell subtypes. Notably, CD8+ and CD4+ GZMK+ effector memory T cells emerged as crucial across all cancer types and treatments, while IL-17-producing CD8+ T cells were top candidates associated with immunotherapy non-responders. In summary, this study provides a computational method to study the association between TIME and response across the pan-cancer immune landscape, offering resources and insights into immune cell interactions and their impact on treatment efficacy.

4.
Article in English | MEDLINE | ID: mdl-38992888

ABSTRACT

BACKGROUND: The impact of sodium-glucose cotransporter 2 (SGLT2) inhibitors on the postoperative recurrence of atrial fibrillation (AF) in patients with persistent AF undergoing an initial radiofrequency ablation is not yet established. The objective of this study is to assess the impact of SGLT2 inhibitors on the recurrence of AF after radiofrequency ablation in patients with type 2 diabetes complicated persistent AF. METHODS: A total of 182 patients with type 2 diabetes and persistent AF, who underwent their first radiofrequency ablation for AF at our center, were enrolled and divided into two groups: the SGLT2 inhibitor group and the non-SGLT2 inhibitor group. The main outcome of the follow-up was the postoperative recurrence of AF. RESULTS: A total of 49 participants experienced AF recurrence. The use of SGLT2 inhibitors in patients with type 2 diabetes who underwent AF ablation was associated with a significantly lower risk of AF recurrence (adjusted hazard ratio: 0.65; 95% confidence interval: 0.28-0.83; p < .01). CONCLUSIONS: The use of SGLT2 inhibitors is associated with a decreased risk of arrhythmia recurrence after AF ablation in patients with type 2 diabetes complicated with persistent AF.

5.
Front Immunol ; 15: 1410250, 2024.
Article in English | MEDLINE | ID: mdl-38979408

ABSTRACT

Nasopharyngeal carcinoma with bone marrow metastasis presents a rare and challenging clinical scenario associated with exceedingly poor prognosis. While standard treatment regimens offer limited efficacy and tolerability in such cases, individualized approaches are increasingly necessary. We present the case of a 64-year-old male diagnosed with recurrent nonkeratinizing undifferentiated nasopharyngeal carcinoma with extensive bone marrow metastasis (rTxN0M1). Treatment was initiated with immunotherapy-based combination therapy, consisting of pembrolizumab and low-dose cisplatin, which resulted in an initial response. Subsequently, there was a transition to standard-dose nab-paclitaxel-cisplatin chemotherapy in combination with pembrolizumab, followed by maintenance therapy with pembrolizumab plus fruquintinib. The patient achieved a sustained response with renormalization of tumor markers, imaging findings, and bone biopsies, resulting in complete remission. This case highlights the successful management of nasopharyngeal carcinoma with extensive bone marrow metastasis through an individualized treatment approach incorporating immunotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Bone Marrow Neoplasms , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , Male , Middle Aged , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/pathology , Bone Marrow Neoplasms/secondary , Bone Marrow Neoplasms/therapy , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Immunotherapy/methods , Remission Induction , Paclitaxel/administration & dosage , Paclitaxel/therapeutic use , Treatment Outcome , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Albumins
6.
Cancer Innov ; 3(3): e112, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38947760

ABSTRACT

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subtype of non-small cell lung cancer (NSCLC), characterized by the presence of epithelial and sarcoma-like components. The molecular and immune landscape of PSC has not been well defined. Methods: Multiomics profiling of 21 pairs of PSCs with matched normal lung tissues was performed through targeted high-depth DNA panel, whole-exome, and RNA sequencing. We describe molecular and immune features that define subgroups of PSC with disparate genomic and immunogenic features as well as distinct clinical outcomes. Results: In total, 27 canonical cancer gene mutations were identified, with TP53 the most frequently mutated gene, followed by KRAS. Interestingly, most TP53 and KRAS mutations were earlier genomic events mapped to the trunks of the tumors, suggesting branching evolution in most PSC tumors. We identified two distinct molecular subtypes of PSC, driven primarily by immune infiltration and signaling. The Immune High (IM-H) subtype was associated with superior survival, highlighting the impact of immune infiltration on the biological and clinical features of localized PSCs. Conclusions: We provided detailed insight into the mutational landscape of PSC and identified two molecular subtypes associated with prognosis. IM-H tumors were associated with favorable recurrence-free survival and overall survival, highlighting the importance of tumor immune infiltration in the biological and clinical features of PSCs.

7.
Int Immunopharmacol ; 138: 112533, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38924868

ABSTRACT

BACKGROUND: Hepatic ischemia-reperfusion (IR) injury is a major complication of liver transplantation and gravely affects patient prognosis. Icaritin (ICT), the primary plasma metabolite of icariin (ICA), plays a critical role in anti-inflammatory and immunomodulatory processes. However, the role of ICT in hepatic IR injury remains largely undefined. In this study, we aimed to elucidate the role of ICT in hepatic IR injury. METHODS: We established hepatic IR injury models in animals, as well as an oxygen-glucose deprivation/reperfusion (OGD/R) cell model. Liver injury in vivo was assessed by measuring serum alanine aminotransferase (ALT) levels, necrotic areas by liver histology and local hepatic inflammatory responses. For in vitro analyses, we implemented flow-cytometric and western blot analyses, transmission electron microscopy, and an mRFP-GFP-LC3 adenovirus reporter assay to assess the effects of ICT on OGD/R injury in AML12 and THLE-2 cell lines. Signaling pathways were explored in vitro and in vivo to identify possible mechanisms underlying ICT action in hepatic IR injury. RESULTS: Compared to the mouse model group, ICT preconditioning considerably protected the liver against IR stress, and diminished the levels of necrosis/apoptosis and inflammation-related cytokines. In additional studies, ICT treatment dramatically boosted the expression ratios of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR proteins in hepatic cells following OGD/R damage. We also applied LY294002 (a PI3K inhibitor) and RAPA (rapamycin, an mTOR inhibitor), which blocked the protective effects of ICT in hepatocytes subjected to OGD/R. CONCLUSION: This study indicates that ICT attenuates ischemia-reperfusion injury by exerting anti-inflammation, anti-oxidative stress, and anti-autophagy effects, as demonstrated in mouse livers. We thus posit that ICT could have therapeutic potential for the treatment of hepatic IR injury.

8.
Drug Resist Updat ; 76: 101114, 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38924995

ABSTRACT

Therapy resistance poses a significant obstacle to effective cancer treatment. Recent insights into cell plasticity as a new paradigm for understanding resistance to treatment: as cancer progresses, cancer cells experience phenotypic and molecular alterations, corporately known as cell plasticity. These alterations are caused by microenvironment factors, stochastic genetic and epigenetic changes, and/or selective pressure engendered by treatment, resulting in tumor heterogeneity and therapy resistance. Increasing evidence suggests that cancer cells display remarkable intrinsic plasticity and reversibly adapt to dynamic microenvironment conditions. Dynamic interactions between cell states and with the surrounding microenvironment form a flexible tumor ecosystem, which is able to quickly adapt to external pressure, especially treatment. Here, this review delineates the formation of cancer cell plasticity (CCP) as well as its manipulation of cancer escape from treatment. Furthermore, the intrinsic and extrinsic mechanisms driving CCP that promote the development of therapy resistance is summarized. Novel treatment strategies, e.g., inhibiting or reversing CCP is also proposed. Moreover, the review discusses the multiple lines of ongoing clinical trials globally aimed at ameliorating therapy resistance. Such advances provide directions for the development of new treatment modalities and combination therapies against CCP in the context of therapy resistance.

9.
J Zhejiang Univ Sci B ; 25(6): 451-470, 2024 Jun 15.
Article in English, Chinese | MEDLINE | ID: mdl-38910492

ABSTRACT

Interferon regulatory factor 1 (IRF-1) is a member of the IRF family. It is the first transcription factor to be identified that could bind to the interferon-stimulated response element (ISRE) on the target gene and displays crucial roles in the interferon-induced signals and pathways. IRF-1, as an important medium, has all of the advantages of full cell cycle regulation, cell death signaling transduction, and reinforcing immune surveillance, which are well documented. Current studies indicate that IRF-1 is of vital importance to the occurrence and evolution of multifarious liver diseases, including but not limited to inhibiting the replication of the hepatitis virus (A/B/C/E), alleviating the progression of liver fibrosis, and aggravating hepatic ischemia-reperfusion injury (HIRI). The tumor suppression of IRF-1 is related to the clinical characteristics of liver cancer patients, which makes it a potential indicator for predicting the prognosis and recurrence of liver cancer; additionally, the latest studies have revealed other effects of IRF-1 such as protection against alcoholic/non-alcoholic fatty liver disease (AFLD/NAFLD), cholangiocarcinoma suppression, and uncommon traits in other liver diseases that had previously received little attention. Intriguingly, several compounds and drugs have featured a protective function in specific liver disease models in which there is significant involvement of the IRF-1 signal. In this paper, we hope to propose a prospective research basis upon which to help decipher translational medicine applications of IRF-1 in liver disease treatment.


Subject(s)
Interferon Regulatory Factor-1 , Liver Diseases , Liver Neoplasms , Interferon Regulatory Factor-1/metabolism , Interferon Regulatory Factor-1/genetics , Humans , Liver Diseases/metabolism , Animals , Liver Neoplasms/metabolism , Signal Transduction , Liver Cirrhosis/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Reperfusion Injury , Cholangiocarcinoma/metabolism
10.
MedComm (2020) ; 5(6): e604, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38840771

ABSTRACT

Tumor mutational burden (TMB) and T-cell receptor (TCR) might predict the response to immunotherapy in patients with non-small cell lung cancer (NSCLC). However, the predictive value of the combination of TMB and TCR was not clear. Targeted DNA and TCR sequencing were performed on tumor biopsy specimens. We combined TMB and TCR diversity into a TMB-and-TCR (TMR) score using logistic regression. In total, 38 patients with advanced NSCLC were divided into a discovery set (n = 17) and validation set (n = 21). A higher TMR score was associated with better response and longer progression-free survival to immunotherapy in both the discovery set and validation set. The performance of TMR score was confirmed in the two external validation cohorts of 225 NSCLC patients and 306 NSCLC patients. Tumors with higher TMR scores were more likely to combine with LRP1B gene mutation (p = 0.027) and top 1% CDR3 sequences (p = 0.001). Furthermore, LRP1B allele frequency was negatively correlated with the top 1% CDR3 sequences (r = -0.55, p = 0.033) and positively correlated with tumor shrinkage (r = 0.68, p = 0.007). The TMR score could serve as a potential predictive biomarker for the response to immunotherapy in advanced NSCLC.

11.
Res Sq ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38826463

ABSTRACT

Traditional feature dimension reduction methods have been widely used to uncover biological patterns or structures within individual spatial transcriptomics data. However, these methods are designed to yield feature representations that emphasize patterns or structures with dominant high variance, such as the normal tissue spatial pattern in a precancer setting. Consequently, they may inadvertently overlook patterns of interest that are potentially masked by these high-variance structures. Herein we present our graph contrastive feature representation method called CoCo-ST (Comparing and Contrasting Spatial Transcriptomics) to overcome this limitation. By incorporating a background data set representing normal tissue, this approach enhances the identification of interesting patterns in a target data set representing precancerous tissue. Simultaneously, it mitigates the influence of dominant common patterns shared by the background and target data sets. This enables discerning biologically relevant features crucial for capturing tissue-specific patterns, a capability we showcased through the analysis of serial mouse precancerous lung tissue samples.

12.
Cell Mol Life Sci ; 81(1): 282, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38943031

ABSTRACT

Cetuximab resistance has been a major challenge for head and neck squamous cell carcinoma (HNSCC) patients receiving targeted therapy. However, the mechanism that causes cetuximab resistance, especially microRNA (miRNA) regulation, remains unclear. Growing evidence suggests that miRNAs may act as "nuclear activating miRNAs" for targeting promoter regions or enhancers related to target genes. This study elucidates a novel mechanism underlying cetuximab resistance in HNSCC involving the nuclear activation of KDM7A transcription via miR-451a. Herein, small RNA sequencing, quantitative real-time polymerase chain reaction (qRT‒PCR) and fluorescence in situ hybridization (FISH) results provided compelling evidence of miR-451a nuclear enrichment in response to cetuximab treatment. Chromatin isolation via RNA purification, microarray analysis, and bioinformatic analysis revealed that miR-451a interacts with an enhancer region in KDM7A, activating its expression and further facilitating cetuximab resistance. It has also been demonstrated that the activation of KDM7A by nuclear miR-451a is induced by cetuximab treatment and is AGO2 dependent. Logistic regression analyses of 87 HNSCC samples indicated the significance of miR-451a and KDM7A in the development of cetuximab resistance. These discoveries support the potential of miR-451a and KDM7A as valuable biomarkers for cetuximab resistance and emphasize the function of nuclear-activating miRNAs.


Subject(s)
Cetuximab , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms , MicroRNAs , Squamous Cell Carcinoma of Head and Neck , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Cetuximab/pharmacology , Drug Resistance, Neoplasm/genetics , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/metabolism , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic/drug effects , Jumonji Domain-Containing Histone Demethylases/genetics , Jumonji Domain-Containing Histone Demethylases/metabolism , Argonaute Proteins/genetics , Argonaute Proteins/metabolism , Animals , Mice , Cell Nucleus/metabolism , Cell Nucleus/genetics , Female , Mice, Nude
13.
bioRxiv ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38915535

ABSTRACT

Introduction: Racial and ethnic disparities in the presentation and outcomes of lung cancer are widely known. To evaluate potential factors contributing to these observations, we measured systemic immune parameters in Black and White patients with lung cancer. Methods: Patients scheduled to receive cancer immunotherapy were enrolled in a multi-institutional prospective biospecimen collection registry. Clinical and demographic information were obtained from electronic medical records. Pre-treatment peripheral blood samples were collected and analyzed for cytokines using a multiplex panel and for immune cell populations using mass cytometry. Differences between Black and White patients were determined and corrected for multiple comparisons. Results: A total of 187 patients with non-small cell lung cancer (Black, 19; White, 168) were included in the analysis. There were no significant differences in baseline characteristics between Black and White patients. Compared to White patients, Black patients had significantly lower levels of CCL23 and CCL27, and significantly higher levels of CCL8, CXCL1, CCL26, CCL25, CCL1, IL-1 b, CXCL16, and IFN-γ (all P <0.05, FDR<0.1). Black patients also exhibited greater populations of non-classical CD16+ monocytes, NKT-like cells, CD4+ cells, CD38+ monocytes, and CD57+ gamma delta T cells (all P <0.05). Conclusions: Black and White patients with lung cancer exhibit several differences in immune parameters, with Black patients exhibiting greater levels of numerous pro-inflammatory cytokines and cell populations. The etiology and clinical significance of these differences warrant further evaluation.

14.
Nat Commun ; 15(1): 4807, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38839799

ABSTRACT

Constructing S-scheme heterojunctions proves proficient in achieving the spatial separation of potent photogenerated charge carriers for their participation in photoreactions. Nonetheless, the restricted contact areas between two phases within S-scheme heterostructures lead to inefficient interfacial charge transport, resulting in low photocatalytic efficiency from a kinetic perspective. Here, In2O3/Nb2O5 S-scheme heterojunctions are fabricated through a straightforward one-step electrospinning technique, enabling intimate contact between the two phases and thereby fostering ultrafast interfacial electron transfer (<10 ps), as analyzed via femtosecond transient absorption spectroscopy. As a result, powerful photo-electrons and holes accumulate in the Nb2O5 conduction band and In2O3 valence band, respectively, exhibiting extended long lifetimes and facilitating their involvement in subsequent photoreactions. Combined with the efficient chemisorption and activation of stable CO2 on the Nb2O5, the resulting In2O3/Nb2O5 hybrid nanofibers demonstrate improved photocatalytic performance for CO2 conversion.

15.
Poult Sci ; 103(8): 103939, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38909507

ABSTRACT

As a highly infectious and contagious pathogen in chickens, infectious bronchitis virus (IBV) is currently grouped into nine genotypes (GI to GIX). However, the classification of serotypes of IBV is still not clear. In this study, 270 field strains of IBV were isolated from dead or diseased chicken flocks in eastern and southern China during January 2021 to April 2023. These isolated IBV strains could be classified into 2 genotypes, GI (including 5 lineages GI-1, GI-13, GI-19, GI-22, and GI-28) and GVI based on the complete S1 sequence. Further analysis showed that the GI-19, GI-13, GI-22, GI-28, and GVI were the dominant genotypes with the proportions of 61.48, 8.89, 8.89, 7.78, and 8.89% respectively, and the homology of S1 protein of these isolates ranged from 86.85 to 100% in GI-19, 92.22 to 100% in GI-13, 83.1 to 100% in GI-22, 94.81 to 100% in GI-28 and 90.0 to 99.8% in GVI, respectively. Moreover, cross-neutralization test with sera revealed that these isolates in GI-19 lineage could be classified into at least 3 serotypes according to the antigenic relationship. In addition, structure assay using PyMOL indicated that one mutation such as S120 in receptor binding site (RBD) of GI-19 might alter the antigenicity and conformation of S protein of IBV. Overall, our data demonstrate that not only multiple genotypes, but also multiple serotypes in a single genotype or lineage have been co-circulated in eastern and southern China, providing novel insights into the molecular evolution of the antigenicity of IBV and highlighting the significance of the selection of the dominant isolate for vaccine development in IBV endemic region.

16.
J Thorac Oncol ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38866326

ABSTRACT

INTRODUCTION: Germline mutations driving lung cancer have been infrequently reported in the literature, with EGFR T790M being a known germline mutation identified in 1% of NSCLCs. Typically, a somatic EGFR mutation is acquired to develop lung adenocarcinoma. Osimertinib has become a standard-of-care treatment for EGFR T790M-positive lung cancer. METHODS: We perform a retrospective analysis through the Lung Cancer Moon Shot GEMINI database at the University of Texas MD Anderson Cancer Center. Of the patients that underwent cell-free DNA analysis, germline mutations were identified by those with high variant allelic fraction approximating 50%, followed by further confirmation on genetic testing. RESULTS: We identified 22 patients with germline EGFR mutations, with the majority harboring an EGFR T790M mutation (95.5%) and an EGFR L858R somatic mutation (50%). Notably, most patients were female (86.4%), non-smokers (81.8%), white (86.4%), had a family history of lung cancer (59.1%), and stage IV at diagnosis (72.7%). A distinct radiographic pattern of small multifocal ground-glass pulmonary nodules was observed in the majority of our cohort (72.7%). Among the 18 with advanced-stage NSCLC, 12 patients (66.7%) were treated with first-line osimertinib, demonstrating a median progression-free survival (PFS) of 16.9 months (95% confidence interval [CI]: 6.3-not reached [NR]). Others were treated with first-line afatinib (11.1%) or chemotherapy (22.2%). Among the 17 patients treated with osimertinib (in first or second-line), median PFS was 20.4 months (95% CI: 6.3-NR) and median overall survival was 82.0 months (95% CI: 28.4-NR). CONCLUSIONS: Based on our institutional cohort, NSCLC driven by EGFR germline mutations occurs more frequently in non-smoking, white females with multi-focal pulmonary nodules radiographically. Osimertinib for advanced germline EGFR-mutated NSCLC renders similar PFS compared to somatic T790M EGFR-mutated NSCLC.

17.
Front Psychiatry ; 15: 1282742, 2024.
Article in English | MEDLINE | ID: mdl-38887725

ABSTRACT

Background: Increasing evidence suggests a correlation between intestinal microbiota and the gut-brain axis; however, the causal relationship between gut microbiota and postpartum depression (PPD) remains unclear. Methods: In this study, a two-sample Mendelian randomization (MR) design was employed to analyze the GWAS data of gut microorganisms from the Mibiogen database and PPD data from the UK biobank. Various statistical methods, including inverse variance weighted, MR-Egger, weighted median, weighted model, and MR-PRESSO, were utilized to investigate the causal relationship between gut microbiota and PPD. Additionally, sensitivity analysis was conducted to assess the robustness of the findings. Results: Through MR analysis, it was found that phylum Actinobacteria (P=0.014, OR=0.971, 95% CI=0.948-0.994) and genus Holdemanella (P=0.023, OR=0.979, 95% CI=0.961-0.997) have protective effects on PPD, while the other two unknown genera, genus Unknown Ids 2001 (P=0.025, OR=0.972,95% CI=0.947-0.996), and genus Unknown Ids 2755 (P=0.012, OR=0.977, 95% CI=0.959-0.995) also has a protective effect on PPD. The sensitivity analysis results indicate that there is no heterogeneity or horizontal pleiotropy. Conclusion: This study has identified a causal association between Actinomycetota, Holdemanella, and PDD through MR analysis. These findings offer significant contributions to the development of personalized treatment approaches for PPD, encompassing interventions such as dietary modifications or microbiome interventions.

18.
Langmuir ; 40(24): 12632-12640, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38832432

ABSTRACT

The poor compatibility with nonpolar lubricant still hinders the application of carbon dots (CDs) in lubrication. In addition, research proves that the existence of ionic structure and active groups on CDs are conducive to their lubricity. In order to obtain the ionic structures and good oil compatibility synchronously, a kind of ionic nitrogen-doped CDs (NCDs) was synthesized via the alkylation of nitrogen in NCDs and anion exchange. The new material could exhibit good tribological performance as poly alpha olefins (PAO4) additives with low addition. Moreover, an ionic liquid, [N44HH][DEHP], with the same anion was chosen as a comparison to investigate the role of NCD cations. The surface analyses demonstrate that NCD cations and phosphate ester anions adsorb on the friction interface to play a synergistic lubrication role during the friction process, which could generate a superior carbon-based tribofilm.

19.
Adv Mater ; : e2406460, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38837488

ABSTRACT

Solar fuel synthesis is intriguing because solar energy is abundant and this method compensates for its intermittency. However, most photocatalysts can only absorb UV-to-visible light, while near-infrared (NIR) light remains unexploited. Surprisingly, the charge transfer between ZnO and CuInS2 quantum dots (QDs) can transform a NIR-inactive ZnO into a NIR-active composite. This strong response is attributed to the increased concentration of free charge carriers in the p-type semiconductor at the interface after the charge migration between ZnO and CuInS2, enhancing the localized surface plasmon resonance (LSPR) effect and the NIR response of CuInS2. As a paradigm, this ZnO/CuInS2 heterojunction is used for H2O2 production coupled with glycerin oxidation and demonstrates supreme performance, corroborating the importance of NIR response and efficient charge transfer. Mechanistic studies through contact potential difference (CPD), Hall effect test, and finite element method (FEM) calculation allow for the direct correlation between the NIR response and charge transfer. This approach bypasses the general light response issues, thereby stepping forward to the ambitious goal of harnessing the entire solar spectrum.

20.
Front Public Health ; 12: 1349169, 2024.
Article in English | MEDLINE | ID: mdl-38855450

ABSTRACT

Introduction: Mild traumatic brain injury (mTBI) is a prevalent health issue with significant effects on patients' lives. Understanding and attitudes toward mTBI among patients and their families can influence management and outcomes. This study aimed to assess knowledge and attitudes toward mTBI in these groups. Methods: A cross-sectional study was conducted at Zhejiang Hospital from July 1, 2023, to September 30, 2023. Patients with mTBI and their family members participated. Data were collected via an online questionnaire covering demographic information and mTBI knowledge and attitudes. Knowledge scores ranged from 0 to 20 and attitude scores from 8 to 40. Multivariate logistic regression identified factors influencing these scores. Results: A total of 573 valid questionnaires were analyzed (289 males, 50.44%; 284 females, 49.56%). Among respondents, 258 (45.03%) had experienced a concussion. Mean knowledge and attitude scores were 11.00 ± 2.75 and 27.78 ± 4.07, respectively. Monthly per capita income of 5,000-10,000 RMB was negatively associated with knowledge and attitude scores (ß = 0.160, 95% CI: [3.245 to 0.210], P = 0.026). Middle school education decreased the likelihood of positive attitudes toward mTBI (OR = 0.378, 95% CI: [0.1630.874], P = 0.023). mTBI due to falls was associated with increased likelihood of positive attitudes (OR = 3.588, 95% CI: [1.274-10.111], P = 0.016). Discussion: Significant gaps in knowledge and attitudes toward mTBI exist among patients and their families, influenced by income and education levels. Personal experience with mTBI from falls correlates with more positive attitudes. These findings highlight the need for targeted educational interventions to improve understanding and attitudes, ultimately enhancing patient care and management. Comprehensive, accessible mTBI education is crucial for fostering positive attitudes and better knowledge among patients and their families.


Subject(s)
Family , Health Knowledge, Attitudes, Practice , Humans , Female , Male , Cross-Sectional Studies , Adult , Middle Aged , Surveys and Questionnaires , Family/psychology , China , Brain Concussion/psychology , Aged , Young Adult , Adolescent
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