Efficacy of targeted therapy in patients with non-small cell lung cancer harboring very rare mutations in EGFR exon 18.

Background: Somatic mutations in epidermal growth factor receptor (EGFR) exon 18 are classified as uncommon or rare mutations in non-small cell lung cancer (NSCLC), in this context, other than G719X or E709X exon 18 mutations are even more rare and heterogeneous. In such scenario, first line treatment options are still debated. The aim of this study was to investigate the response of NSCLC patients harboring very rare exon 18 mutations to EGFR tyrosine kinase inhibitors (EGFR-TKIs). Methods: This retrospective descriptive study included 105 patients with NSCLC harboring mutations in EGFR exon 18 diagnosed at West China Hospital. The clinical response to EGFR-TKIs was evaluated according to different classifications of mutations in 45 NSCLC patients: 39 harboring G719X or E709X mutations and 6 harboring very rare mutations in EGFR exon 18. Results: Among 105 patients, 84% (88/105) harbored rare mutations in EGFR exon 18, including G719X and E709X mutations. The remaining 16% (17/105) had very rare mutations in EGFR exon 18, including E709_710delinsX and G724S. For the subsequent efficacy analysis of EGFR-TKI in 45 NSCLC patients, patients harboring very rare mutations achieved a favorable disease control rate (DCR) of 100% and had a median progression-free survival (PFS) of 17.2 months, which was not significantly different compared to patients harboring G719X or E709X (P=0.59). Conclusions: EGFR-TKIs showed great efficacy in terms of responses and survival in patients harboring exon 18 EGFR rare mutations. This may justify the use of targeted therapies as a potential treatment strategy for these patients.

Isocentric fixed angle irradiation-based DRR: a novel approach to enhance x-ray and CT image registration.

Objective.Digitally reconstructed radiography (DRR) plays an important role in the registration of intraoperative x-ray and preoperative CT images. However, existing DRR algorithms often neglect the critical isocentric fixed angle irradiation (IFAI) principle in C-arm imaging, resulting in inaccurate simulation of x-ray images. This limitation degrades registration algorithms relying on DRR image libraries or employing DRR images (DRRs) to train neural network models. To address this issue, we propose a novel IFAI-based DRR method that accurately captures the true projection transformation during x-ray imaging of the human body.Approach.By strictly adhering to the IFAI principle and utilizing known parameters from intraoperative x-ray images paired with CT scans, our method successfully simulates the real projection transformation and generates DRRs that closely resemble actual x-ray images.Main result.Experimental results validate the effectiveness of our IFAI-based DRR method by successfully registering intraoperative x-ray images with preoperative CT images from multiple patients who underwent thoracic endovascular aortic procedures.Significance. The proposed IFAI-based DRR method enhances the quality of DRR images, significantly accelerates the construction of DRR image libraries, and thereby improves the performance of x-ray and CT image registration. Additionally, the method has the generality of registering CT and x-ray images generated by large C-arm devices.

Synergistic Cation-π Interactions and PEDOT-Based Protective Double-Layer for High Performance Zinc Anode.

Ensuring effective and controlled zinc ion transportation is crucial for functionality of the solid electrolyte interphase (SEI) and overall performance in zinc-based battery systems. Herein the first-ever demonstration of incorporate cation-π interactions are provided in the SEI to effectively facilitate uniform zinc ion flux. The artificial SEI design involves the immobilization of 4-amino-p-terphenyl (TPA), a strong amphiphilic cation-π interaction donor, as a monolayer onto a conductive poly(3,4-ethylenedioxythiophene) (PEDOT) matrix, which enable the establishment of a robust network of cation-π interactions. Through a carefully-designed interfacial polymerization process, a high-quality, large-area, robust is achieved, thin polymeric TPA/PEDOT (TP) film for the use of artificial SEI. Consequently, this interphase exhibits exceptional cycling stability with low overpotential and enables high reversibility of Zn plating/stripping. Symmetrical cells with TP/Zn electrodes can be cycled for more than 3200 hours at 1 mA cm-2 and 1 mAh cm-2 . And the asymmetric cells can cycle 3000 cycles stably with a high Coulomb efficiency of 99.78%. Also, under the extreme conditions of lean electrolyte and low N/P ratio, the battery with TP protective layer can still achieve ultra-stable cycle.

Immune checkpoint inhibitor plus chemotherapy as first-line treatment for non-small cell lung cancer with malignant pleural effusion: a retrospective multicenter study.

BACKGROUND: Immune checkpoint inhibitors (ICI) combined with chemotherapy are efficacious for treating advanced non-small cell lung cancer (NSCLC); however, the effectiveness of this approach in the malignant pleural effusion (MPE) population is unclear. This study evaluated ICI plus chemotherapy in NSCLC patients with MPE. METHODS: Patients from 3 centers in China with NSCLC and MPE who received ICI plus chemotherapy (ICI Plus Chemo) or chemotherapy alone (Chemo) between December 2014 and June 2023 were enrolled. Clinical outcomes and adverse events (AEs) were compared. RESULTS: Of 155 eligible patients, the median age was 61.0 years old. Males and never-smokers accounted for 73.5% and 39.4%, respectively. Fifty-seven and 98 patients received ICI Plus Chemo or Chemo, respectively. With a median study follow-up of 10.8 months, progression-free survival (PFS) was significantly longer with ICI Plus Chemo than with Chemo (median PFS: 7.4 versus 5.7 months; HR = 0.594 [95% CI: 0.403-0.874], P = 0.008). Median overall survival (OS) did not differ between groups (ICI Plus Chemo: 34.2 versus Chemo: 28.3 months; HR = 0.746 [95% CI: 0.420-1.325], P = 0.317). The most common grade 3 or worse AEs included decreased neutrophil count (3 [5.3%] patients in the ICI Plus Chemo group vs. 5 [5.1%] patients in the Chemo group) and decreased hemoglobin (3 [5.3%] versus 10 [10.2%]). CONCLUSIONS: In patients with untreated NSCLC with MPE, ICI plus chemotherapy resulted in significantly longer PFS than chemotherapy and had a manageable tolerability profile, but the effect on OS may be limited.

From antioxidant defense to genotoxicity: Deciphering the tissue-specific impact of AgNPs on marine clam Ruditapes philippinarum.

The escalating use of silver nanoparticles (AgNPs) across various sectors for their broad-spectrum antimicrobial capabilities, has raised concern over their potential ecotoxicological effects on aquatic life. This study explores the impact of AgNPs (50 µg/L) on the marine clam Ruditapes philippinarum, with a particular focus on its gills and digestive glands. We adopted an integrated approach that combined in vivo exposure, biochemical assays, and transcriptomic analysis to evaluate the toxicity of AgNPs. The results revealed substantial accumulation of AgNPs in the gills and digestive glands of R. philippinarum, resulting in oxidative stress and DNA damage, with the gills showing more severe oxidative damage. Transcriptomic analysis further highlights an adaptive up-regulation of peroxisome-related genes in the gills responding to AgNP-induxed oxidative stress. Additionally, there was a noteworthy enrichment of differentially expressed genes (DEGs) in key biological processes, including ion binding, NF-kappa B signaling and cytochrome P450-mediated metabolism of xenobiotics. These insights elucidate the toxicological mechanisms of AgNPs to R. philippinarum, emphasizing the gill as a potential sensitive organ for monitoring emerging nanopollutants. Overall, this study significantly advances our understanding of the mechanisms driving nanoparticle-induced stress responses in bivalves and lays the groundwork for future investigations into preventing and treating such pollutants in aquaculture.

Effect of different starting doses of FSH on laboratory and clinical outcomes in patients with moderate AMH level.

BACKGROUND: IVF and ICSI-ET are widely used ART for addressing infertility which have been developed and improved over the last four decades. COS is a crucial step in IVF/ICSI-ET, whereby medications stimulate the ovaries to produce multiple eggs. The success of the procedure depends on the number of eggs retrieved, and individualized ovarian stimulation protocols based on factors like age and ovarian reserve can optimize the chances of obtaining mature oocytes. The optimal starting dose of FSH at moderate AMH levels remains a topic of debate., tThis study aims to compare different starting doses of FSH in clinical outcomes by analyzing data from a single center. METHODS: This retrospective study collected clinical material from patients with moderate AMH levels at 1.2 ~ 4.5 ng/mL who received IVF/ICSI-ET under a follicular phase long protocol from July 2018 to December 2021 at Guiyang Maternal and Child Health Care Hospital, China. The patients' clinical data were retrieved from the hospital's software database and divided into two groups based on FSH starting dose, as follows: lower starting dose group: FSH ≤ 150 IU; and higher starting dose group: FSH > 150 IU. Multiple laboratory and clinical outcomes were compared between the two groups. RESULTS: A total of 1784 patients with moderate serum AMH levels who received IVF/ICSI-ET under a follicular phase long protocol were enrolled based on eligibility criteria. In the population with moderate AMH levels, a lower starting dose of FSH might have more benefit than a higher starting dose in numbers of follicles with diameters ≥ 14 mm and < 16 mm, ≥ 16 mm and < 18 mm, and ≥ 18 mm; numbers of retrieved oocytes, 2PNs, transferable embryos, high-quality embryos, and cleavage stage embryos transferred; and clinical pregnancy rate, intrauterine pregnancy rate, and parturition rate. Moreover, rFSH had a statistically significantly higher number of oocytes retrieved, number of 2PNs, and number of transferable embryos than that of patients who received uFSH. CONCLUSIONS: The starting dose of FSH in the moderate AMH population remains controversial and a higher starting dose may not lead to more benefit in laboratory and clinical outcomes.

Photocatalytic Hydrogen Production from Pure Water Using a IEF-11/g-C3N4 S-Scheme Heterojunction.

Construction of S-scheme heterojunction offers a promising way to enhance the photocatalytic performance of photocatalysts for converting solar energy into chemical energy. However, the photocatalytic H2 production in pure water without sacrificial agents is still a challenge. Herein, the IEF-11 with the best photocatalytic H2 production performance in MOFs and suitable band structure was selected and firstly constructed with g-C3N4 to obtain a S-scheme heterojunction for photocatalytic H2 production from pure water. As a result, the novel IEF-11/g-C3N4 heterojunction photocatalysts exhibited significantly improved photocatalytic H2 production performance in pure water without any sacrificial agent, with a rate of 576 µmol/g/h, which is about 8 times than that of g-C3N4 and 23 times of IEF-11. The novel IEF-11/g-C3N4 photocatalysts also had a photocatalytic H2 production rate of up to 92 µmol/g/h under visible light and a good photocatalytic stability. The improved performance can be attributed to the efficient separation of photogenerated charge carriers, faster charge transfer efficiency and longer photogenerated carrier lifetimes, which comes from the forming of S-scheme heterojunction in the IEF-11/g-C3N4 photocatalyst. This work is a promising guideline for obtaining MOF-based or g-C3N4-based photocatalysts with great photocatalytic water splitting performance.

Efficacy of bevacizumab through an indwelling pleural catheter in non-small cell lung cancer patients with symptomatic malignant pleural effusion.

BACKGROUND: Several studies have indicated that intrapleural infusion of bevacizumab is an effective treatment for non-small cell lung cancer (NSCLC) with malignant pleural effusion (MPE). However, the impact of bevacizumab administered through an indwelling pleural catheter (IPC) on the prognosis of these patients is unknown. METHODS: Consecutive advanced NSCLC patients with symptomatic MPE receiving an IPC alone or bevacizumab through an IPC were identified in a tertiary hospital. The patient characteristics and clinical outcomes were collected. RESULTS: A total of 149 patients were included, and the median age was 60.3 years. Males and nonsmokers accounted for 48.3% and 65.8%, respectively. A total of 69.8% (104/149) of patients harbored actionable mutations, including 92 EGFR-activating mutations, 11 ALK fusions, and 1 ROS1 fusion. A total of 81.9% (122/149) of patients received IPC alone, and 18.1% (27/149) received bevacizumab through an IPC. The incidence of spontaneous pleurodesis during the first 6 months was greater in the bevacizumab-treated group than in the IPC-treated group in the subgroup with actionable mutations (64.3% vs. 46.9%, P = 0.28). The median overall survival (OS) in patients with actionable mutations treated with bevacizumab through an IPC was 42.2 months, which was significantly longer than the 26.7 months in patients who received an IPC alone (P = 0.045). However, the median OS did not differ between the two arms in the subgroup without actionable mutations (10.8 vs. 41.0 months, P = 0.24). No significant difference between the bevacizumab through an IPC group and the IPC group was detected in the number of participants who had adverse events, either in patients with actionable mutations (14.3% vs. 8.4%; P = 0.42) or in patients without actionable mutations (16.7% vs. 12.8%; P = 1.00). CONCLUSIONS: Bevacizumab through an IPC resulted in a significantly improved prognosis for NSCLC patients with MPE and actionable mutations. However, patients without actionable mutations do not benefit from bevacizumab through IPC.

Musashi-2 potentiates colorectal cancer immune infiltration by regulating the post-translational modifications of HMGB1 to promote DCs maturation and migration.

Post-translational modifications (PTMs) of the non-histone protein high-mobility group protein B1 (HMGB1) are involved in modulating inflammation and immune responses. Recent studies have implicated that the RNA-binding protein (RBP) Musashi-2 (MSI2) regulates multiple critical biological metabolic and immunoregulatory functions. However, the precise role of MSI2 in regulating PTMs and tumor immunity in colorectal cancer (CRC) remains unclear. Here, we present data indicating that MSI2 potentiates CRC immunopathology in colitis-associated colon cancer (CAC) mouse models, cell lines and clinical specimens, specifically via HMGB1-mediated dendritic cell (DC) maturation and migration, further contributes to the infiltration of CD4+ and CD8+ T cells and inflammatory responses. Under stress conditions, MSI2 can exacerbate the production, nucleocytoplasmic transport and extracellular release of damage-associated molecular patterns (DAMPs)-HMGB1 in CRC cells. Mechanistically, MSI2 mainly enhances the disulfide HMGB1 production and protein translation via direct binding to nucleotides 1403-1409 in the HMGB1 3' UTR, and interacts with the cytoplasmic acetyltransferase P300 to upregulate its expression, further promoting the acetylation of K29 residue in HMGB1, thus leading to K29-HMGB1 nucleocytoplasmic translocation and extracellular release. Furthermore, blocking HMGB1 activity with glycyrrhizic acid (Gly) attenuates MSI2-mediated immunopathology and immune infiltration in CRC in vitro and in vivo. Collectively, this study suggests that MSI2 may improve the prognosis of CRC patients by reprogramming the tumor immune microenvironment (TIME) through HMGB1-mediated PTMs, which might be a novel therapeutic option for CRC immunotherapy.

Musashi-2 Deficiency Triggers Colorectal Cancer Ferroptosis by Downregulating the MAPK Signaling Cascade to Inhibit HSPB1 Phosphorylation.

BACKGROUND: Musashi-2 (MSI2) is a critical RNA-binding protein (RBP) whose ectopic expression drives the pathogenesis of various cancers. Accumulating evidence suggests that inducing ferroptosis of tumor cells can inhibit their malignant biological behavior as a promising therapeutic approach. However, it is unclear whether MSI2 regulates cell death in colorectal cancer (CRC), especially the underlying mechanisms and biological effects in CRC ferroptosis remain elusive. METHODS: Experimental methods including qRT‒PCR, immunofluorescence, flow cytometry, western blot, co-immunoprecipitation, CCK-8, colony formation assay, in vitro cell transwell migration and invasion assays, in vivo xenograft tumor experiments, liver and lung CRC metastasis models, CAC mice models, transmission electron microscopy, immunohistochemistry, histopathology, 4D label-free proteomics sequencing, bioinformatic and database analysis were used in this study. RESULTS: Here, we investigated that MSI2 was upregulated in CRC and positively correlated with ferroptosis inhibitor molecules. MSI2 deficiency suppressed CRC malignancy by inhibiting cell proliferation, viability, migration and invasion in vitro and in vivo; and MSI2 deficiency triggered CRC ferroptosis by changing the intracellular redox state (ROS levels and lipid peroxidation), erastin induced cell mortality and viability, iron homeostasis (intracellular total irons and ferrous irons), reduced glutathione (GSH) levels and mitochondrial injury. Mechanistically, through 4D-lable free proteomics analysis on SW620 stable cell lines, we demonstrated that MSI2 directly interacted with p-ERK and MSI2 knockdown downregulated the p-ERK/p38/MAPK axis signaling pathway, which further repressed MAPKAPK2 and HPSB1 phosphorylation, leading to decreased expression of PCNA and Ki67 and increased expression of ACSL4 in cancer cells. Furthermore, HSPB1 could rescue the phenotypes of MSI2 deficiency on CRC ferroptosis in vitro and in vivo. CONCLUSIONS: This study indicates that MSI2 deficiency suppresses the growth and survival of CRC cells and promotes ferroptosis by inactivating the MAPK signaling pathway to inhibit HSPB1 phosphorylation, which leads to downregulation of PCNA and Ki67 and upregulation of ACSL4 in cancer cells and subsequently induces redox imbalance, iron accumulation and mitochondrial shrinkage, ultimately triggering ferroptosis. Therefore, targeted inhibition of MSI2/MAPK/HSPB1 axis to promote ferroptosis might be a potential treatment strategy for CRC.

[Effect of Combined Application of an Enterobacter and Sulfur Fertilizer on Cadmium and Arsenic Accumulation in Rice].

The aim of this study was to explore the effects of different sulfur fertilizers combined with sulfate-reducing bacteria on the accumulation of cadmium and arsenic in rice and the formation of iron plaque under long-term flooding conditions and to provide a reference for the safe production of rice fields polluted by moderate and mild cadmium and arsenic. We adopted a pot experiment, selecting two sulfur fertilizers, sulfur and calcium sulfate, and Enterobacter M5 with sulfate-reducing ability, and designed six treatments of single application and combined application of different sulfur fertilizers and M5. The results showed that the combined application of calcium sulfate and M5(CM5) had the best effect on reducing available cadmium and arsenic in rice rhizosphere soil. The combined application of sulfur fertilizer or M5 could reduce the content of cadmium and inorganic arsenic in early season rice grains by 8%-51% and 42%-61%, respectively, under flooding conditions. The content of cadmium and inorganic arsenic in late rice grains decreased by 81%-92% and 41%-62%, respectively. The treatment of the combined application of sulfur and M5(SM5) and CM5 had the best effect on reducing cadmium and arsenic content in both early and late season rice grains. SM5 and CM5 could promote the adsorption of cadmium and arsenic by iron plaque, and the extracted cadmium and arsenic content of ACA in both treatments was significantly higher than that of CK. The extracted iron content of ACA in the CM5 treatment was also significantly higher than that of CK, which indicates that the combined application of calcium sulfate and M5 would promote the formation of iron plaque. The results showed that the combined application of sulfur fertilizer and M5 was better than single application in reducing the content of cadmium and arsenic in grains, whereas the combined application of calcium sulfate and M5 was the best and most stable method.

A scoring model based on clinical factors to predict postoperative moderate to severe acute respiratory distress syndrome in Stanford type A aortic dissection.

BACKGROUND: Postoperative acute respiratory distress syndrome (ARDS) after type A aortic dissection is common and has high mortality. However, it is not clear which patients are at high risk of ARDS and an early prediction model is deficient. METHODS: From May 2015 to December 2017, 594 acute Stanford type A aortic dissection (ATAAD) patients who underwent aortic surgery in Anzhen Hospital were enrolled in our study. We compared the early survival of MS-ARDS within 24 h by Kaplan-Meier curves and log-rank tests. The data were divided into a training set and a test set at a ratio of 7:3. We established two prediction models and tested their efficiency. RESULTS: The oxygenation index decreased significantly immediately and 24 h after TAAD surgery. A total of 363 patients (61.1%) suffered from moderate and severe hypoxemia within 4 h, and 243 patients (40.9%) suffered from MS-ARDS within 24 h after surgery. Patients with MS-ARDS had higher 30-day mortality than others (log-rank test: p-value <0.001). There were 30 variables associated with MS-ARDS after surgery. The XGboost model consisted of 30 variables. The logistic regression model (LRM) consisted of 11 variables. The mean accuracy of the XGBoost model was 70.7%, and that of the LRM was 80.0%. The AUCs of XGBoost and LRM were 0.764 and 0.797, respectively. CONCLUSION: Postoperative MS-ARDS significantly increased early mortality after TAAD surgery. The LRM model has higher accuracy, and the XGBoost model has higher specificity.

Small Things Make a Big Difference: Conductive Cross-Linking Sodium Alginate@MXene Binder Enables High-Volumetric-Capacity and High-Mass-Loading Li-S Battery.

Binders are crucial for maintaining the integrity of an electrode, and there is a growing need for integrating multiple desirable properties into the binder for high-energy batteries, yet significant challenges remain. Here, we successfully synthesized a new binder by cross-linking sodium alginate (SA) with MXene materials (Ti3C2Tx). Besides the improved adhesion and mechanical properties, the integrated SA@Ti3C2Tx binder demonstrates much improved electronic conductivity, which enables ruling out the fluffy conductive additive from the electrode component with enhanced volumetric capacity. When SA@Ti3C2Tx is used to fabricate sulfur (S) cathodes, the conductive-additive-free electrode demonstrates extremely high capacity (1422 mAh cm-3/24.5 mAh cm-2) under an S loading of 17.2 mg cm-2 for Li-S batteries. Impressively, the SA@Ti3C2Tx binder shows remarkable feasibility in other battery systems such as Na-S and LiFePO4 batteries. The proposed strategy of constructing a cross-linking conductive binder opens new possibilities for designing high-mass-loading electrodes with high volumetric capacity.

Introducing of Cu(I) in MOFs by In Situ Reduction with Ni as the Catalyst for Efficient Olefin/Paraffin Separation.

Olefins can be cracked to provide more low-carbon olefins than paraffins; therefore, separation of olefin/paraffin mixtures is essential for arranging hydrocarbon molecules for directed conversion. In this article, a simple approach for reducing copper atoms in Cu-BTC has been developed to improve olefin/paraffin adsorption capacity and selectivity. Considering that Cu-BTC shows adsorption benefits, its olefin/paraffin adsorption and separation performance were improved further by in situ reduction of Cu(II) to Cu(I) in Cu-BTC using ethanol as the reducing agent and nickel ions as the catalyst. The results revealed that during the reduction process, Cu ion conversion from tetra-ligand to diligand considerably increased their specific surface area, resulting in more active adsorption sites inside the modified sample. The ratio of Cu(I)/Cu(II) in the modified samples varied from 0.57 to 0.96. When Cu(II) of Cu-BTC was reduced to Cu(I), the adsorption capacities of 1-hexene increased from 145.97 to 243.65 mg/g, whereas n-hexane adsorption increased only slightly from 8.18 to 11.43 mg/g, resulting in an acceptable increase in selectivity from 17.84 to 21.32. Cu-BTC, due to its own Cu atoms, minimizes the substantial requirements for the synthesis process as well as the oxygen avoidance conditions for storage when monovalent copper is introduced, compared to other porous materials. Experimental results found that when Cu(I) was introduced, the Lewis acidic sites of the modified Cu-BTC material were increased, and Cu(I) has an electrical structure that makes it susceptible to both accepting and donating too many d electrons, resulting in a stronger adsorption of olefins containing π-electrons to them. Materials Studio simulation revealed that the isosteric heats of modified Cu-BTC increased by 2.7 kJ/mol, indicating that it has a stronger adsorption capacity for olefins.

Superior clinical outcomes in patients with non-small cell lung cancer harboring multiple ALK fusions treated with tyrosine kinase inhibitors.

Background: Patients with non-small cell lung cancer (NSCLC) harboring anaplastic lymphoma kinase (ALK) fusions may benefit from ALK-tyrosine kinase inhibitors (ALK-TKIs). However, few studies have analyzed the clinical outcome in patients harboring multiple ALK fusions, including double or triple ALK fusions. Here, our study aimed to analyze the impact of harboring multiple ALK fusions on the efficacy of receiving ALK-TKIs in NSCLC patients. Methods: A total of 125 patients with ALK-rearranged NSCLC detected by targeted capture DNA-based next-generation sequencing (NGS) at West China Hospital were enrolled. The literature on patients harboring multiple ALK fusions was systematically reviewed. The clinical response to ALK-TKIs was evaluated according to ALK fusion patterns in 62 patients: 56 from our center and 6 from the literature. Results: Among the 125 patients, a single canonical echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion was detected in 65.6% (82/125), a single non-EML4-ALK fusion was detected in 13.6% (17/125), and multiple ALK fusions were detected in 20.8% (26/125). Among the 62 patients with ALK fusion treated with ALK-TKIs, the median progression-free survival (PFS) was significantly longer in patients with multiple ALK fusions than in those with a single ALK fusion (26.9 vs. 11.2 months, P=0.009), irrespective of brain metastasis, type of TKI drug, and treatment lines. The multiple ALK fusion group also tended to have a longer overall survival (OS) (P=0.26). Multivariate Cox regression analysis revealed that harboring multiple ALK fusions had the potential to be an independent predictor of better PFS for ALK-positive NSCLC [hazard ratio (HR) =0.490; 95% confidence interval (CI): 0.229-1.049]. Conclusions: Harboring multiple ALK fusions could serve as an independent predictive marker of better clinical outcome for patients with NSCLC and ALK rearrangement who have received ALK-TKIs treatment.

Multiomics Analyses Reveal the Complexity of Interaction between Two Strains of Magnaporthe oryzae.

Plants growing in open environments are frequently coinfected by multiple strains of the same pathogen. However, few investigations have been carried out to reveal the outcomes and underlying mechanisms of such infections. This study aimed to observe the behaviors of two different strains under coinfection and cocultivation. We constructed an experimental system to study such interactions directly by labeling Magnaporthe oryzae strains with the green fluorescent proteins and mushroom cherry fluorescent protein to observe mixed strain behavior in vivo and in vitro. Moreover, multiomics analyses were conducted to explore the underlying mechanisms at the genomic, transcriptomic, and metabolomic levels. Our results revealed that coinfection with two strains can affect disease severity and that the more weakly virulent strain benefits from the coinfection system. We also found that amino acid variation might negatively influence such interactions at transcriptomic and metabolomic levels. In addition, we showed that the overexpression of a glutamine-related gene improved strain competitiveness during mixture cultivation. Collectively, our results provided experimental methods to analyze the interaction between two strains of M. oryzae and preliminarily explored the interacted mechanism of two strains under cocultivation through multiomics analyses.

Transition-Metal Single Atom Anchored on MoS2 for Enhancing Photocatalytic Hydrogen Production of g-C3N4 Photocatalysts.

Single-atom catalyst technology with near-100% atomic utilization and a well-defined coordination structure has provided new ideas for designing high-performance photocatalysts, which is also beneficial for reducing the usage of noble metal cocatalysts. Herein, a series of single-atomic MoS2-based cocatalysts where monoatomic Ru, Co, or Ni modify MoS2 (SA-MoS2) for enhancing the photocatalytic hydrogen production performance of g-C3N4 nanosheets (NSs) are rationally designed and synthesized. The 2D SA-MoS2/g-C3N4 photocatalysts with Ru, Co, or Ni single atoms show similar enhanced photocatalytic activity, and the optimized Ru1-MoS2/g-C3N4 photocatalyst has the highest hydrogen production rate of 11115 µmol/h/g, which is about 37 and 5 times higher than that of pure g-C3N4 and MoS2/g-C3N4 photocatalysts, respectively. Experimental and density functional theory calculation results reveal that the enhanced photocatalytic performance is mainly attributed to the synergistic effect and intimate interface between SA-MoS2 with well-defined coordination single-atomic structures and g-C3N4 NSs, which is conducive to the rapid interfacial charge transport, and the unique single-atomic structure of SA-MoS2 with modified electronic structure and appropriate hydrogen adsorption performance offers abundant reactive sites for enhancing the photocatalytic hydrogen production performance. This work provides new insight into improving the cocatalytic hydrogen production performance of MoS2 by a single-atomic strategy.

Quality of life in patients with cervical cancer between the Han nationality and ethnic minorities in the Yunnan Province of China.

BACKGROUND: Cervical cancer is the fourth most diagnosed cancer and the leading cause of cancer death, and it still poses a crippling threat to women's health. China launched the National Cervical Cancer Screening Program for Rural Women in 2009, and an increasing number of cervical cancer patients have been detected. Health-related quality of life is not only the end point of cancer research but is also related to socioeconomic and clinical factors and has received an increasing amount of attention. In light of the characteristics of the Yunnan nationality, we conducted cross-sectional research to assess and explore the health-related quality of life in both Han and ethnic minority patients. METHODS: A cross-sectional study was conducted from January 2020 to May 2021 at the Third Affiliated Hospital of Kunming University/Yunnan Cancer Hospital. Patients, including 100 Han patients and 100 ethnic minorities, were interviewed using the FACT-Cx questionnaire within 3 months of receiving treatment. RESULTS: Patients of Han ethnicity and ethnic minorities were comparable in both sociodemographic and clinical features. The total FACT-Cx scores were 139.38 ± 9.83 and 134.39 ± 13.63 in Han and ethnic minority patients, respectively (P < 0.05). Significant differences were shown in physical well-being, emotional well-being and the FACT-Cx subscale between the Han and ethnic minority groups. Independent predictors of the FACT-Cx scale were ethnicity, educational level, participation in the National Cervical Cancer Screening Program for Rural Areas (NCCSPRA) and clinical stage. CONCLUSIONS: The results of our study imply that the HRQOL of Han patients is better than that of ethnic minority patients. Thus, clinicians and related health workers should pay more attention to the HRQOL of cervical cancer patients, especially for ethnic minority patients, and provide psychosocial interventions as much as possible to improve their HRQOL. Policies should also aim to strengthen health education regarding cervical cancer and expand the coverage of the NCCSPRA among those who are ethnic minorities, are older and have low educational levels.

Enhanced Chemodynamic Therapy Mediated by a Tumor-Specific Catalyst in Synergy with Mitophagy Inhibition Improves the Efficacy for Endometrial Cancer.

Chemodynamic therapy (CDT) relies on the tumor microenvironment (e.g., high H2 O2 level) responsive Fenton-like reactions to produce hydroxyl radicals (·OH) against tumors. However, endogenous H2 O2 is insufficient for effective chemodynamic responses. An NAD(P)H: quinone oxidoreductase 1 (NQO1)high catalase (CAT)low therapeutic window for the use of NQO1 bioactive drug ß-lapachone (ß-Lap) is first identified in endometrial cancer (EC). Accompanied by NADH depletion, NQO1 catalyzes ß-Lap to produce excess H2 O2 and initiate oxidative stress, which selectively suppress NQO1high EC cell proliferation, induce DNA double-strand breaks, and promote apoptosis. Moreover, shRNA-mediated NQO1 knockdown or dicoumarol rescues NQO1high EC cells from ß-Lap-induced cytotoxicity. Arginine-glycine-aspartic acid (RGD)-functionalized iron-based metal-organic frameworks (MOF(Fe)) further promote the conversion of the accumulated H2 O2 into highly oxidative ·OH, which in turn, exacerbates the oxidative damage to RGD-positive target cells. Furthermore, mitophagy inhibition by Mdivi-1 blocks a powerful antioxidant defense approach, ultimately ensuring the anti-tumor efficacy of stepwise-amplified reactive oxygen species signals. The tumor growth inhibition rate (TGI) is about 85.92%. However, the TGI of MOF(Fe)-based synergistic antitumor therapy decreases to only 50.46% in NQO1-deficient KLE tumors. Tumor-specific chemotherapy and CDT-triggered therapeutic modality present unprecedented therapeutic benefits in treating NQO1high EC.