Assessment of efficacy and safety of MET tyrosine kinase inhibitors in non-small-cell lung cancer patients with MET alterations.

Background: While targeted therapy has become the standard treatment for certain non-small-cell lung cancer (NSCLC) patients with gene mutation positivity, there remains a lack of enough reports of the efficacy of mesenchymal-epithelial transition (MET) alterations in the real world. Objectives: We aimed to explore the efficacy and toxicity of targeted therapy in NSCLC patients with different types of MET alterations and hope to provide more clinical medication guidance. Design: Designed different subgroups to compare the efficacy and safety of targeted therapy in NSCLC patients with MET alterations. Methods: We conducted analyses on the efficacy and safety of mesenchymal-epithelial transition factor-tyrosine kinase inhibitor (MET-TKI) therapy in NSCLC patients with MET alterations. Tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors version 1.1 criteria, and both progression-free survival (PFS) and overall survival were determined using the Kaplan-Meier method. Results: Our study encompassed 116 NSCLC patients with MET alterations, including MET ex14 skipping mutation (n = 50), MET primary amplification (amp) (n = 25), and secondary amp (n = 41). Among treated patients, 34 achieved a partial response, while 52 exhibited stable disease. The overall response rate for the entire cohort was 29.31%, with a disease control rate of 74.14%. A significant difference was observed in the median PFS among patients with MET ex14 skipping mutation, MET primary amplification (amp), and secondary amp (10.4 versus 6.6 versus 4.5 months, p = 0.002). In all, 69 patients experienced drug-related adverse effects, with the most common being peripheral edema (35.34%), nausea and vomiting (21.55%), and fatigue (10.34%). In total, 29 patients (25%) encountered drug-related adverse reactions of grade 3 or higher. Conclusion: MET-TKI therapy works better for MET ex14 skipping mutation than other types of MET gene alteration. In the two MET amplified groups, the secondary amp was less effective. This study may provide more research support for the treatment of these patients.

Phytohabitans maris sp. nov., isolated from marine sediment.

A novel actinobacterium, strain ZYX-F-186T, was isolated from marine sediment sampled on Yongxing Island, Hainan Province, PR China. Based on the results of 16S rRNA gene sequence analysis, strain ZYX-F-186T belongs to the genus Phytohabitans, with high similarity to Phytohabitans kaempferiae KK1-3T (98.3 %), Phytohabitans rumicis K11-0047T (98.1 %), Phytohabitans flavus K09-0627T (98.1 %), Phytohabitans houttuyneae K11-0057T (97.9 %), Phytohabitans suffuscus K07-0523T (97.7 %), and Phytohabitans aurantiacus RD004123T (97.7 %). Phylogenetic analysis of 16S rRNA gene sequences showed that the strain formed a single subclade in the genus Phytohabitans. The novel isolate contained meso-diaminopimelic acid, d-glutamic acid, glycine, d-alanine, and l-lysine in the cell wall. The whole-cell sugars were xylose, arabinose, ribose, and rhamnose. The predominant menaquinones were MK-9(H8), MK-9(H6), and MK-9(H4). The characteristic phospholipids were phosphatidylethanolamine, phosphatidylinositol, phosphatidylmethylethanolamine, phosphatidylglycerol, and an unknown phospholipid. The major fatty acids (>5 %) were iso-C16 : 0, anteiso-C17 : 0, and iso-C18 : 0. Genome sequencing showed a DNA G+C content of 71.9 mol%. Low average nucleotide identity, digital DNA-DNA hybridization, and average amino acid identity values demonstrated that strain ZYX-F-186T could be readily distinguished from its closely related species. Based on its phylogenetic, chemotaxonomic, and physiological characteristics, strain ZYX-F-186T represents a novel species of the genus Phytohabitans, for which the name Phytohabitans maris sp. nov. is proposed. The type strain is ZYX-F-186T (=CGMCC 4.8025T=CCTCC AA 2023025T=JCM 36507T).

Predicted Fracture Tendency of Naturally Occurring Aluminum Surface Coatings under Tensile Loading.

Naturally occurring coatings on aluminum metal, such as its oxide or hydroxide, serve to protect the material from corrosion. Understanding the conditions under which these coatings mechanically fail is therefore expected to be an important aspect of predictive models for aluminum component lifetimes. To this end, we develop and apply a molecular dynamics (MD) modeling framework for conducting tension tests that is capable of isolating factors governing the mechanical strength as a function of coating chemistry, defect morphology, and variables associated with the loading path. We consider two representative materials, including γ-Al2O3 and γ-Al(OH)3 (i.e., oxide and hydroxide), both of which form readily as aluminum surface coatings. Our results indicate that defects have a significant bearing on the strength of aluminum oxide, with grain boundaries serving to reduce the strain at failure from εzz = 0.300 to 0.219, relative to perfect single crystal. Our simulations also predict that porosity lowers the elastic stiffness and yield strength of the oxide. Relative to perfect crystal, we find porosity factors of 5%, 10% and 20% decrease the yield stress by 26%, 36% and 53%, respectively. MD predicts that perfect hydroxide and oxide single crystal have respective strains at failure of 0.08 and 0.31 under tensile uniaxial strain loading, and that the corresponding yield stresses are respectively 1.6 and 11.1 GPa. These data indicate that the hydroxide is substantially more susceptible to mechanical failure than the oxide. Our results, coupled with literature findings that indicate hot and humid conditions favor formation of hydroxide and defective oxide coatings, indicate the potential for a complicated dependence of aluminum corrosion susceptibility and stress corrosion cracking on aging history.

An 18F-FDG-PET/CT-based radiomics signature for estimating malignance probability of solitary pulmonary nodule.

BACKGROUND: Some solitary pulmonary nodules (SPNs) as early manifestations of lung cancer, it is difficult to determine its nature, which brings great trouble to clinical diagnosis and treatment. Radiomics can deeply explore the essence of images and provide clinical decision support for clinicians. The purpose of our study was to explore the effect of positron emission tomography (PET) with 2-deoxy-2-[fluorine-18] fluoro-d-glucose integrated with computed tomography (CT; 18F-FDG-PET/CT) combined with radiomics for predicting probability of malignancy of SPNs. METHODS: We retrospectively enrolled 190 patients with SPNs confirmed by pathology from January 2013 to December 2019 in our hospital. SPNs were benign in 69 patients and malignant in 121 patients. Patients were randomly divided into a training or testing group at a ratio of 7:3. Three-dimensional regions of interest (ROIs) were manually outlined on PET and CT images, and radiomics features were extracted. Synthetic minority oversampling technique (SMOTE) method was used to balance benign and malignant samples to a ratio of 1:1. In the training group, least absolute shrinkage and selection operator (LASSO) regression analyses and Spearman correlation analyses were used to select the strongest radiomics features. Three models including PET model, CT model, and joint model were constructed using multivariate logistic regression analysis. Receiver operating characteristic (ROC) curves, calibration curves, and decision curves were plotted to evaluate diagnostic efficiency, calibration degree, and clinical usefulness of all models in training and testing groups. RESULTS: The estimative effectiveness of the joint model was superior to the CT or PET model alone in the training and testing groups. For the joint model, CT model, and PET model, area under the ROC curve was 0.929, 0.819, 0.833 in the training group, and 0.844, 0.759, 0.748 in the testing group, respectively. Calibration and decision curves showed good fit and clinical usefulness for the joint model in both training and testing groups. CONCLUSION: Radiomics models constructed by combining PET and CT radiomics features are valuable for distinguishing benign and malignant SPNs. The combined effect is superior to qualitative diagnoses with CT or PET radiomics models alone.

High-Speed Electro-Optic Modulators Based on Thin-Film Lithium Niobate.

Electro-optic modulators (EOMs) are pivotal in bridging electrical and optical domains, essential for diverse applications including optical communication, microwave signal processing, sensing, and quantum technologies. However, achieving the trifecta of high-density integration, cost-effectiveness, and superior performance remains challenging within established integrated photonics platforms. Enter thin-film lithium niobate (LN), a recent standout with its inherent electro-optic (EO) efficiency, proven industrial performance, durability, and rapid fabrication advancements. This platform inherits material advantages from traditional bulk LN devices while offering a reduced footprint, wider bandwidths, and lower power requirements. Despite its recent introduction, commercial thin-film LN wafers already rival or surpass established alternatives like silicon and indium phosphide, benefitting from decades of research. In this review, we delve into the foundational principles and technical innovations driving state-of-the-art LN modulator demonstrations, exploring various methodologies, their strengths, and challenges. Furthermore, we outline pathways for further enhancing LN modulators and anticipate exciting prospects for larger-scale LN EO circuits beyond singular components. By elucidating the current landscape and future directions, we highlight the transformative potential of thin-film LN technology in advancing electro-optic modulation and integrated photonics.

Co-occurring EGFR p.E709X mutation Mediates Primary Resistance to the Third-generation EGFR-TKIs in EGFR p.G719X-mutant Patients with Advanced NSCLC.

PURPOSE: Current NCCN guidelines recommend afatinib or osimertinib as the preferred first-line treatment strategy for patients with advanced NSCLC harboring EGFR p.G719X mutation. However, in the absence of head-to-head trials comparing afatinib with osimertinib in EGFR p.G719X mutant patients, it is unclear which regimen is the preferred treatment option. EXPERIMENTAL DESIGN: A large cohort of 4228 treatment-naïve patients with lung cancer who underwent targeted NGS testing was screened for EGFR p.G719X mutation. A multicenter cohort involving 68 EGFR p.G719X-mutant patients with advanced NSCLC and NGS profiling was retrospectively enrolled to evaluate clinical responses to afatinib(n=37) and the third-generation EGFR-TKIs(n=31). Ba/F3 cells stably expressing the EGFR p.G719A mutation were created to investigate the response to EGFR-TKIs in vitro. RESULTS: Concurrent EGFR p.E709X mutations, being the most frequent co-occurring EGFR mutation in EGFR p.G719X-mutant NSCLC(~30%), exerted a detrimental effect on outcomes in patients treated with third-generation EGFR-TKI(G719X/E709X vs. G719X; ORR:0.00% vs. 47.62%, P<0.001; mPFS:7.18 vs. 14.2 months, P=0.04; respectively). Conversely, no significant difference was found in the treatment efficacy of afatinib between EGFR p.G719X/E709X and EGFR p.G719X patients(G719X/E709X vs. G719X; ORR:71.43% vs. 56.67%, P=0.99; mPFS:14.7 vs. 15.8 months, P=0.69; respectively). In vitro experiments elucidated a resistant drug sensitivity and poor inhibition of EGFR phosphorylation in Ba/F3 cells expressing EGFR p.G719A/E709K mutation upon the third-generation EGFR-TKIs treatment. CONCLUSION: Co-occurring EGFR p.E709X mutation mediates primary resistance to the third-generation EGFR-TKIs in EGFR p.G719X-mutant patients but remained sensitive to afatinib. A personalized treatment strategy should be undertaken based on the co-existing EGFR p.E709X mutation status.

Clinical characteristics and prognostic implications of immune-related hepatitis in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors: a retrospective study.

Background: With the widespread use of immune checkpoint inhibitors (ICIs), patients inevitably experience immune-related adverse events (irAEs). Therefore, the study was conducted on the clinical characteristics and outcomes of patients with non-small cell lung cancer (NSCLC) with immune-related hepatitis (ir-hepatitis). Methods: We identified patients with advanced NSCLC who developed ir-hepatitis after immunotherapy between June 2016 and December 2022. Their irAEs were categorized according to the Common Terminology Criteria for Adverse Events version 4.03 (CTCAE 4.03). Kaplan-Meier curves and log-rank tests were used to analyze survival. Results: A total of 35 patients were enrolled in the study. The numbers of mild (grade 1-2) and severe (grade 3-4) ir-hepatitis cases were 13 (grade 1, 3; grade 2, 10) and 22 (grade 3, 17; grade 4, 5), respectively. The median onset time of ir-hepatitis was 1.6 months. The median progression-free survival (mPFS) was 8.3 months. PFS differed between patients with early ir-hepatitis developing within two treatment cycles and those with ir-hepatitis developing more than two treatment cycles (5.5 vs. 12.7 months, P=0.004). Patients with severe rather than mild ir-hepatitis tended to poorer PFS survival (5.8 vs. 11.2 months, P=0.130). The appearance of ir-hepatitis within two treatment cycles (P=0.002) and higher severity grades of ir-hepatitis (P=0.005) were independent risk factors for PFS. Conclusions: Early and severe ir-hepatitis are associated with worse survival benefits, which still required more basic and perspective studies.

Exploration of efficacy of different therapy regimens for advanced NSCLC patients with KRAS mutation in the first-line treatment.

PURPOSE: The treatment of the advanced non-small cell lung cancer (NSCLC) with KRAS mutation has been closely paid more attention. The aim of this study is to investigate the efficacy of different first-line regimens in advanced KRAS-mutated non-small cell lung cancer. METHODS: In our retrospective study, we collected patients with advanced NSCLC with KRAS mutation in Zhejiang Cancer Hospital between January 2015 and May 2023. We analyzed the benefit of different first-line therapy according to theraputic methods and the differential effect of the same treatment method among KRAS-mutated subtypes. We divided the patients into group A (A1, chemotherapy alone; A2, immunotherapy alone) and group B (B1, chemotherapy plus immunotherapy; B2, chemotherapy combined with antiangiogenic therapy; B3, chemotherapy combined with immunotherapy plus antiangiogenic therapy). The Kaplan-Meier survival curve was used to reflect the PFS and OS of different methods. The objective response rate (ORR) and the disease control rate (DCR) were used to evaluated the response. RESULTS: We enrolled 227 patients including eighty-two with KRAS G12C mutation. The ORR and DCR of first-line treatment in the overall population were 32.2% and 80.6% respectively. The median PFS was 6.7 months and the median OS was 17.4 months for the overall population. The PFS of the Group B was significantly better than that of the Group A (7.7 months vs 5.4 months, P = 0.003), while no significant difference in OS was observed (19.4 months vs 15.0 months, P = 0.077). In the Group B, chemotherapy combined immunotherapy with antiangiogenic therapy showed better PFS than chemotherapy plus immunotherapy (14.1 months vs 7.7 months, P = 0.049), and OS also showed that tendency of difference (31.9 months vs 19.3 months, P = 0.158). There was no statistically significant difference between KRAS G12C and non-G12C mutation according to first-line treatment methods, whereas patients with TP53 co-mutation showed a better survival benefit (OS, 23.7 vs 12.5 months, P = 0.023). CONCLUSION: In the first-line treatment, combination regimen has advantages over single regimen. Among them, chemotherapy combined with immunotherapy plus antiangiogenic therapy can achieve significant efficacy benefits.

High-enhancement photoluminescence of monolayer MoS2 in hybrid plasmonic systems.

Monolayer molybdenum disulfide (M o S 2) has a weak light-matter interaction due to ultrathin thickness, which limits its potential application in lasing action. In this study, we propose a hybrid structure consisting of a nanocavity and Au nanoparticles to enhance the photon emission efficiency of monolayer M o S 2. Numerical simulations show that photoluminescence (PL) emission is significantly enhanced by introducing localized surface plasmon resonance (LSPR) to the proposed structure. Furthermore, an exciton energy band system is proposed to elucidate the physical mechanism of the PL process. By optimizing the spacer thickness, a high Purcell enhancement factor of 95 can be achieved. The results provided by this work pave the way to improve the PL efficiency of two-dimensional (2D) material, which constitutes a significant step towards the development of nanodevices such as nanolasers and sensors.

Secure ECDSA SRAM-PUF Based on Universal Single/Double Scalar Multiplication Architecture.

Physically unclonable functions (PUFs) are crucial for enhancing cybersecurity by providing unique, intrinsic identifiers for electronic devices, thus ensuring their authenticity and preventing unauthorized cloning. The SRAM-PUF, characterized by its simple structure and ease of implementation in various scenarios, has gained widespread usage. The soft-decision Reed-Muller (RM) code, an error correction code, is commonly employed in these designs. This paper introduces the design of an RM code soft-decision attack algorithm to reveal its potential security risks. To address this problem, we propose a soft-decision SRAM-PUF structure based on the elliptic curve digital signature algorithm (ECDSA). To improve the processing speed of the proposed secure SRAM-PUF, we propose a custom ECDSA scheme. Further, we also propose a universal architecture for the critical operations in ECDSA, elliptic curve scalar multiplication (ECSM), and elliptic curve double scalar multiplication (ECDSM) based on the differential addition chain (DAC). For ECSMs, iterations can be performed directly; for ECDSMs, a two-dimensional DAC is constructed through precomputation, followed by iterations. Moreover, due to the high similarity of ECSM and ECDSM data paths, this universal architecture saves hardware resources. Our design is implemented on a field-programmable gate array (FPGA) and an application-specific integrated circuit (ASIC) using a Xilinx Virtex-7 and an TSMC 40 nm process. Compared to existing research, our design exhibits a lower bit error rate (2.7×10-10) and better area-time performance (3902 slices, 6.615 µs ECDSM latency).

Efficacy and safety analysis of immunotherapy in non-small cell lung cancer patients with MET alterations.

BACKGROUND: Mesenchymal epithelial transition factor (MET) is a rare oncologic driver gene, and information on immunotherapy for non-small cell lung cancer (NSCLC) patients with this driver gene is limited. Here we evaluate the efficacy and safety of immune checkpoint inhibitors (ICI) under different therapeutic regimen for NSCLC patients with MET alterations. METHODS: From June 2019 to December 2023, we assessed the efficacy and toxicity of ICIs in 42 NSCLC patients with MET alterations. Survival curves were plotted using the Kaplan-Meier method and the Cox proportional hazards model applied for univariate and multivariate analyses. We assessed the size of target lesion according to RECIST v1.1, and objective response rate (ORR) was defined as the sum of complete response (CR) and partial response (PR), disease control rate (DCR) as the sum of CR, PR, and disease stable. RESULTS: A total of 42 NSCLC patients with MET alterations were included in this retrospective study, 10 was MET 14 skipping mutation and 32 was MET amplification. The ORR for ICI treatment was 30.95% and the DCR was 71.43%. Median progression-free survival (mPFS) and median overall survival (OS) were 4.40 and 13.97 months, respectively. There exists statistical differences between the mPFS of ICI monotherapy and combine ICI therapy (2.8 vs 7.8 months, p = 0.022). The incidence of drug-related adverse reactions was 47.62%, mainly bone marrow suppression (14.28%), immune-related pneumonia (7.14%), and liver function impairment (7.14%), and six patients (14.28%) experiencing grade 3 or above adverse events. CONCLUSION: NSCLC patients with MET alterations can benefit from immunotherapy, especially the patients treated by combined ICI therapy. However, special attention should be paid to the occurrence of grade 3/4 adverse reactions while using the combined ICI therapy.

Androgen loss weakens anti-tumor immunity and accelerates brain tumor growth.

Many cancers, including glioblastoma (GBM), have a male-biased sex difference in incidence and outcome. The underlying reasons for this sex bias are unclear but likely involve differences in tumor cell state and immune response. This effect is further amplified by sex hormones, including androgens, which have been shown to inhibit anti-tumor T cell immunity. Here, we show that androgens drive anti-tumor immunity in brain tumors, in contrast to its effect in other tumor types. Upon castration, tumor growth was accelerated with attenuated T cell function in GBM and brain tumor models, but the opposite was observed when tumors were located outside the brain. Activity of the hypothalamus-pituitary-adrenal gland (HPA) axis was increased in castrated mice, particularly in those with brain tumors. Blockade of glucocorticoid receptors reversed the accelerated tumor growth in castrated mice, indicating that the effect of castration was mediated by elevated glucocorticoid signaling. Furthermore, this mechanism was not GBM specific, but brain specific, as hyperactivation of the HPA axis was observed with intracranial implantation of non-GBM tumors in the brain. Together, our findings establish that brain tumors drive distinct endocrine-mediated mechanisms in the androgen-deprived setting and highlight the importance of organ-specific effects on anti-tumor immunity.

Targeting the intracellular neurexin interactome by in vivo proximity ligation.

In a recent study, Profes, Tiroumalechetty, and colleagues used the in vivo proximity ligation technique TurboID to scrupulously characterize the interactome of the intracellular domain (ICD) of neurexin, revealing that this domain may be involved in presynaptic actin assembly by interacting with actin-associated proteins.

Tunable double notch filter on a thin-film lithium niobate platform.

Tunable optical filters at the chip scale play a crucial role in fulfilling the need for reconfigurability in channel routing, optical switching, and wavelength division multiplexing systems. In this Letter, we propose a tunable double notch filter on thin-film lithium niobate using dual microring architecture. This unique integrated filter is essential for complex photonic integrated circuits, along with multiple channels and various frequency spacing. With only one loaded voltage, the device demonstrates a wide frequency spacing tunability from 16.1 to 89.9 GHz by reversely tuning the resonances of the two microrings while the center wavelength between the two resonances remains unaltered. Moreover, by utilizing the pronounced electro-optic properties of lithium niobate associated with the tight light confined nanophotonic waveguides, the device demonstrates a spacing tunability of 0.82 GHz/V and a contrast of 10-16 dB. In addition, the device has an ultracompact footprint of 0.0248 mm2.

Photosensitized 1,2-Difunctionalization of Alkenes to Access ß-Amino Sulfonamides.

A metal-free photosensitized 1,2-imino-sulfamoylation of olefins by employing a tailor-made sulfamoyl carbamate as the difunctionalization reagent has been established. This protocol exhibits versatility across a broad substrate scope, including aryl and aliphatic alkenes, leading to the synthesis of diverse ß-imino sulfonamides in moderate to good yields. This method is characterized by its metal-free reaction system, mild reaction conditions, excellent regioselectivity, and high atom economy, serving as a promising platform for the preparation of ß-amino sulfonamide-containing molecules, particularly in the context of drug discovery.

Dual inhibitors of DNMT and HDAC induce viral mimicry to induce antitumour immunity in breast cancer.

The existing conventional treatments for breast cancer, including immune checkpoint blockade, exhibit limited effects in some cancers, particularly triple-negative breast cancer. Epigenetic alterations, specifically DNMT and HDAC alterations, are implicated in breast cancer pathogenesis. We demonstrated that DNMTs and HDACs are overexpressed and positively correlated in breast cancer. The combination of DNMT and HDAC inhibitors has shown synergistic antitumour effects, and our previously designed dual DNMT and HDAC inhibitor (termed DNMT/HDACi) 15a potently inhibits breast cancer cell proliferation, migration, and invasion and induces apoptosis in vitro and in vivo. Mechanistically, 15a induces a viral mimicry response by promoting the expression of endogenous retroviral elements in breast cancer cells, thus increasing the intracellular level of double-stranded RNA to activate the RIG-I-MAVS pathway. This in turn promotes the production of interferons and chemokines and augments the expression of interferon-stimulated genes and PD-L1. The combination of 15a and an anti-PD-L1 antibody had an additive effect in vivo. These findings indicate that this DNMT/HDACi has immunomodulatory functions and enhances the effectiveness of immune checkpoint blockade therapy. A novel dual DNMT and HDAC inhibitor induces viral mimicry, which induces the accumulation of dsRNA to activate tumoral IFN signalling and cytokine production to enhance the immune response in breast cancer.

Bosea beijingensis sp. nov., Telluria beijingensis sp. nov. and Agrococcus beijingensis sp. nov., isolated from baijiu mash.

The baijiu fermentation environment hosts a variety of micro-organisms, some of which still remain uncultured and uncharacterized. In this study, the isolation, cultivation and characterization of three novel aerobic bacterial strains are described. The cells of strain REN20T were Gram-negative, strictly aerobic, motile and grew at 26-37 °C, at pH 6.0-9.0 and in the presence of 0-5.0   % (w/v) NaCl. The cells of strain REN29T were Gram-negative, strictly aerobic, motile and grew at 15-30 °C, at pH 6.0-9.0 and in the presence of 0-10.0   % (w/v) NaCl. The cells of strain REN33T were Gram-positive, strictly aerobic, motile and grew at 15-37 °C, at pH 5.0-10.0 and in the presence of 0-7.0   % (w/v) NaCl. The digital DNA-DNA hybridization and average nucleotide identity by orthology values between type strains in related genera and REN20T (20.3-36.8 % and 79.8-89.9  %), REN29T (20.3-36.8  % and 74.5-88.5  %) and REN33T (22.6-48.6  % and 75.8-84.2  %) were below the standard cut-off criteria for the delineation of bacterial species, respectively. Based on polyphasic taxonomy analysis, we propose three new species, Bosea beijingensis sp. nov. (=REN20T=GDMCC 1.2894T=JCM 35118T), Telluria beijingensis sp. nov. (=REN29T=GDMCC 1.2896T=JCM 35119T) and Agrococcus beijingensis sp. nov. (=REN33T=GDMCC 1.2898T=JCM 35164T), which were recovered during cultivation and isolation from baijiu mash.

CyanoStrainChip: A Novel DNA Microarray Tool for High-Throughput Detection of Environmental Cyanobacteria at the Strain Level.

Detecting cyanobacteria in environments is an important concern due to their crucial roles in ecosystems, and they can form blooms with the potential to harm humans and nonhuman entities. However, the most widely used methods for high-throughput detection of environmental cyanobacteria, such as 16S rRNA sequencing, typically provide above-species-level resolution, thereby disregarding intraspecific variation. To address this, we developed a novel DNA microarray tool, termed the CyanoStrainChip, that enables strain-level comprehensive profiling of environmental cyanobacteria. The CyanoStrainChip was designed to target 1277 strains; nearly all major groups of cyanobacteria are included by implementing 43,666 genome-wide, strain-specific probes. It demonstrated strong specificity by in vitro mock community experiments. The high correlation (Pearson's R > 0.97) between probe fluorescence intensities and the corresponding DNA amounts (ranging from 1-100 ng) indicated excellent quantitative capability. Consistent cyanobacterial profiles of field samples were observed by both the CyanoStrainChip and next-generation sequencing methods. Furthermore, CyanoStrainChip analysis of surface water samples in Lake Chaohu uncovered a high intraspecific variation of abundance change within the genus Microcystis between different severity levels of cyanobacterial blooms, highlighting two toxic Microcystis strains that are of critical concern for Lake Chaohu harmful blooms suppression. Overall, these results suggest a potential for CyanoStrainChip as a valuable tool for cyanobacterial ecological research and harmful bloom monitoring to supplement existing techniques.

Usefulness of KIT mutant transcript levels for monitoring measurable residual disease in t (8;21) acute myeloid leukemia.

In addition to RUNX1::RUNX1T1 transcript levels, measurable residual disease monitoring using KIT mutant (KITmut ) DNA level is reportedly predictive of relapse in t (8; 21) acute myeloid leukemia (AML). However, the usefulness of KITmut transcript levels remains unknown. A total of 202 bone marrow samples collected at diagnosis and during treatment from 52 t (8; 21) AML patients with KITmut (D816V/H/Y or N822K) were tested for KITmut transcript levels using digital polymerase chain reaction. The individual optimal cutoff values of KITmut were identified by performing receiver operating characteristics curve analysis for relapse at each of the following time points: at diagnosis, after achieving complete remission (CR), and after Course 1 and 2 consolidations. The cutoff values were used to divide the patients into the KITmut -high (KIT_H) group and the KITmut -low (KIT_L) group. The KIT_H patients showed significantly lower relapse-free survival (RFS) and overall survival (OS) rates than the KIT_L patients after Course 1 consolidation (p = 0.0040 and 0.021, respectively) and Course 2 consolidation (p = 0.018 and 0.011, respectively) but not at diagnosis and CR. The <3-log reduction in the RUNX1::RUNX1T1 transcript levels after Course 2 consolidation was an independent adverse prognostic factor for RFS and OS. After Course 2 consolidation, the KIT_H patients with >3-log reduction in the RUNX1::RUNX1T1 transcript levels (11/45; 24.4%) had similar RFS as that of patients with <3-log reduction in the RUNX1::RUNX1T1 transcript levels. The combination of KITmut and RUNX1::RUNX1T1 transcript levels after Course 2 consolidation may improve risk stratification in t (8; 21) AML patient with KIT mutation.