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Background Neutrophil-to-lymphocyte (NLR) ratio can predict survival outcome and assess response to chemotherapy in several tumors. However, the values of NLR in acute myeloid leukemia (AML) remains unknown. Methods A retrospective review of 181 patients with de novo AML excluding acute promyelocytic leukemia (M3) was conducted in our institute. We categorized the patients into two groups by defining NLR =2.0 as the cut-off point. NLR was calculated by the ratio of the number of neutrophils to lymphocytes in the peripheral blood (PB). The baseline clinicopathologic parameters were compared using Chi-squared test or Kruskal-Wallis H test. Kaplan-Meier analysis was used to assess survival, and overall survival (OS) and disease-free survival (DFS) were analyzed using the Cox regression with log-rank tests. Results We found AML patients with low NLR (

Purpose: Clonal architecture is fundamental for the understanding of cancer biology and therapy; however, multiregional sampling in advanced-stage cancers is not always applicable. This prospective clinical trial was to investigate whether paired tissue and circulating tumor DNA (ctDNA) could describe the clonal architecture of advanced non–small cell lung cancer (NSCLC) and its association with clinical outcome (NCT03059641). Patients and Methods: Paired tumor and plasma ctDNA samples were sequenced by target-capture deep sequencing of 1,021 genes. Clonal dominance analysis was performed on the basis of PyClone. Results: Overall, 300 treatment-naïve patients with stage IIIB–IV NSCLC were recruited from 14 centers. Of the 94 patients with available ctDNA data for EGFR clonal architecture analysis, 72 (76.6%) showed EGFR as the dominant clone. The median progression-free survival was longer for these patients than for the 22 patients whose EGFR was nondominant clone [11 vs. 10 months; HR, 0.46; 95% confidence interval (CI), 0.24–0.88; P = 0.02]. The difference was more significant if both tissue and ctDNA defined EGFR as dominant clone (n = 43) versus those not (n = 8; 11 vs. 6 months; HR, 0.13; 95% CI, 0.04–0.50; P = 0.003). Moreover, multivariate Cox proportional HR analysis demonstrated EGFR clonal architecture as an independent prognostic indicator of the efficacy of EGFR-tyrosine kinase inhibitors (TKIs). Conclusions: Paired tissue and ctDNA could be analyzed for clonal architecture in advanced cancer. EGFR mutations do not always make up a dominant clone in advanced NSCLC, which was associated with the efficacy of EGFR-TKIs in NSCLC.

Splicing of plant organellar group II introns from precursor-RNA transcripts requires the assistance of nuclear-encoded splicing factors. Maturase (nMAT) is one such factor, as its three homologs (nMAT1, 2 and 4) have been identified as being required for the splicing of various mitochondrial introns in Arabidopsis. However, the function of nMAT in maize (Zea mays L.) is unknown. In this study, we identified a seed development mutant, empty pericarp 2441 (emp2441) from maize, which showed severely arrested embryogenesis and endosperm development. Positional cloning and transgenic complementation assays revealed that Emp2441 encodes a maturase-related protein, ZmnMAT3. ZmnMAT3 is highly expressed during seed development and its protein locates to the mitochondria. The loss of function of ZmnMAT3 resulted in the reduced splicing efficiency of various mitochondrial group II introns, particularly of the trans-splicing of nad1 introns 1, 3 and 4, which consequently abolished the transcript of nad1 and severely impaired the assembly and activity of mitochondrial complex I. Moreover, the Zmnmat3 mutant showed defective mitochondrial structure and exhibited expression and activity of alternative oxidases. These results indicate that ZmnMAT3 is essential for mitochondrial complex I assembly during kernel development in maize.

Brain metastasis (BM) is a common malignant event in lung cancer. Here, we recruited 33 lung cancer patients with brain oligo-metastasis to explore the genomic features and tumor immune microenvironment (TIME) of the lung and BM independently. For genomic profiling, targeted sequencing was performed. We found that high-frequent ZFHX3 occurred in the lung (40%) and brain tumor (28%), which might relate to brain metastasis event; the vast majority of patients had lesions-shared mutations in primary tumor and BM, confirming the common clonal events; and EGFR was the most frequently clonal gene in both lung and BM, indicating its driver capability. To characterize TIME status, we also sequenced the T cell receptor (TCR) repertoires and performed immunohistochemistry (IHC) on CD8+ tumor-infiltrating lymphocytes (TILs) and PD-L1 expression in 28 patients who had paired samples. Through the comparison, the TCR clonality of BM was higher than lung tumor, indicating the distinct pattern of the stronger oligoclonal T cell expansion in BM; the primary tumor had a higher TMB than oligo-BM (13.9 vs 8.7 mutations, p = 0.019); CD8 + TILs of BM were significantly lower than lung tumor (10% vs 30%, p = 0.015), revealing the lower level of cytotoxic T cell infiltration; BM showed statistically equivalent level of PD-L1 compared with lung tumor (p = 0.722). We further investigated the potential biomarkers associated with overall survival (OS) after brain surgery. We found that higher TCR clonality was related to prolonged OS in EGFR-treated patients (HR 0.175, p p = 0.034). More CD8+ TILs were an independently positive indicator for OS, in EGFR-treated (HR 0.160, p = 0.001) and non-EGFR-treated patients (HR 0.308, p = 0.009). These findings provide a meaningful molecular and clinical understanding of lung carcinoma and brain oligo-metastasis.

Composite engineering has played an integral role in the development of new artificial materials with excellent properties, which has triggered a new revolution in high-performance optoelectronic devices. Herein, a Bi/flower-like structured Bi5O7I/acrylate fluoroboron polymer (AFBP) as a BBFP composite was fabricated in situ. Furthermore, the Bi/Bi5O7I flower system was uniformly distributed on the surface and interior of AFBP that boosted the interfacial charge transfer. The resultant spatial charge separation in the BBBF composite ameliorated via SPR and piezoelectric effect significantly enhanced the photocatalytic H2 evolution (835 μmol h−1 g−1), 8.26-fold that of Bi5O7I. In addition, the non-biological toxicity and self-cleaning function of the composite coating were proved from the regular growth rate of Nitzschia closterium and higher efficiency of the TOC removal. Furthermore, it exhibited an excellent diatom anti-settling performance, which was ascribed to the self-renewal process and hydrogen evolution, which formed a gas barrier between the substrate surface and fouling organisms. The self-renewed surfaces of AFBP can be gradually peeled off to create a piezoelectric effect without external mechanical disturbance. Similarly, compared to the antifouling methods of electrochemical hydrogen production, composite coatings can achieve outstanding antifouling performance without consuming extra energy. The strategy will provide a potential application in marine engineering in the future.

Based on the situation of marine biofouling and the ecological crisis caused by toxic antifouling paints, a series of environmental carbon nitride (C3N4) nanocomposite films (CNPs) were prepared by incorporating C3N4 into a self-polishing acrylate boron fluorinated polymer (ABFP). The antifouling performance was evaluated by the diatom anti-attachment test, photocatalytic antibacterial measurements and a mussel settlement assay. The results showed that the optimal content of C3N4 to inhibit the adhesion of diatoms was 3–7 wt%, the antibacterial rate of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) reached 98.10% and 96.94% in the presence of 7 wt% C3N4 under irradiation with visible light for 90 min. In addition, the CNPs and ABFP showed an ability to expel mussels. As a synergistic effect, the self-renewable polymer surfaces could also strip the attached fouling organisms without light. The undifferentiated growth rates between the CNPs and blank proved the environmental properties of the prepared films. The chemical oxygen demand (COD) values showed that the addition of C3N4 contributed to the eco-friendly properties of the CNPs.

A neutral extractant, tetra(tert-butyl)-calix[4]bis[(4,4′-dimethyl-1,2-phenelyene)-crown-6] (TTCalixB6), was prepared. The extraction equilibrium of Cs(I), Na(I), K(I), and Rb(I) and some coexistin...

Because depression is highly prevalent among Chinese undergraduates, it is crucial to develop an approach for early intervention and prevention. Cognitive bias modification of interpretation (CBM-I) has been shown to be an effective approach to alleviate anxiety. However, its utility in improving depression needs further verification. The current study sought to evaluate the efficacy of a four-session CBM-I program of depression prevention for Chinese undergraduates. Forty Chinese participants with depressive symptoms (Self-Rating Depression Scale, SDS ≥ 50) were randomly assigned to receive either a CBM-I training or a waitlist control condition. Test results of Ambiguous Scenarios Test for Depression-Related Bias and SDS indicate that the CBM-I training group have more positive interpretations and fewer symptoms of depression after the training compared to the control group. In addition, significant correlation was found between changes in depressive symptoms and changes in interpretation bias. The effect of the CBM-I on depressive symptoms was partially mediated by the change in interpretation bias. The study findings highlight the potential of CBM-I protocol as a brief, simple, and accessible approach for preventing depression.

New ambient sound absorption material, lightweight isocyanate-based polyimide foam (IBPIF), was fabricated by operable combination between different distinctive acoustic IBPIF. Cellular structure of IBPIF was facilely and obviously adjusted by increased slurry temperature corresponding to change in distinctive acoustic properties. Moreover, density of all IBPIF kept at only 12–17 kg/m3. With increasing slurry temperature from 0 °C to 40 °C, cell size and window opening rate gradually increased from 553 µm to 791 µm and from 6.85% to 58.46%, respectively. In this study, IBPIF generated by slurries at 0 °C (marked as PIF-2) and 40 °C (marked as PIF-6) showed best and distinctive acoustic behavior in 315–800 Hz and 800–6300 Hz regions, respectively. After acoustic behavior study of combined IBPIF prepared by stitching combination between two distinctive acoustic IBPIFs, results showed that only when PIF-6 sheet used as sound receiving surface even though with thickness of only 10 mm could the combined IBPIF possess the best acoustic level in 800–6300 Hz region as PIF-6. Furtherly, acoustic behavior in 315–800 Hz region could be significantly enhanced by increasing thickness of PIF-2 and could reach or close to the best acoustic level.

In this study, a hyperbranched chelated hydrophilic swollen-layer was constructed on the surface of polyacrylonitrile (PAN) fiber with amino trimethylene phosphoric acid (ATMP) as a terminal group, which applied as an adsorbent for seawater uranium U(VI) extraction. This shows that U(VI) enter the gel-like swollen-layer to form a more complex body structure. The molecular chain conformational extension in the swollen-layer reduces the resistance of the uranyl ion to enter the swollen-layer, which is conducive to the adsorption behavior. The adsorption performance on the U(VI) by the adsorption experiment were found to be consistent with the Langmuir isotherm adsorption model and the pseudo-second-order kinetics, indicating that the adsorption of U(VI) by this material is uniform single-layer chemical adsorption. Ion competition experiments and cyclic adsorption experiments verify the practical application potential of the materials. In the dynamic simulation of seawater adsorption experiments, the adsorption capacity of the adsorbent reached 7.4 mg/g. Studies on the adsorption mechanism have found that a large number of hydroxyl groups in the swollen-layer and ATMP as an end machine have a chelation effect on U(VI).

The accurate magnetoresistance (MR) measurement of individual nanostructures is essential and important for either the enrichment of fundamental knowledge of the magnetotransport mechanism or the facilitation of desired design of magnetic nanostructures for various technological applications. Herein, we report a deep investigation on the magnetotransport mechanism of a single CoCu/Cu multilayered nanowire via direct MR measurement using our invented magnetotransport instrument in situ scanning electron microscope. Off-axis electron holography experiments united with micromagnetic simulation prove that the CoCu layers in CoCu/Cu multilayered nanowires form a single-domain structure, in which the alignment of magnetic moments is mainly determined by shape anisotropy. The MR of the single CoCu/Cu multilayered nanowire is measured to be only 1.14% when the varied external field is applied along the nanowire length axis, which matches with the theoretical prediction of the granular film model. Density functional theory calculations further disclose that spin-dependent scattering at the interface between magnetic and nonmagnetic layers is responsible for the intrinsic magnetotransport mechanism.

Constructing a slippery lubricant-infused surface (SLIS) whose internal microstructure and surface properties can be fully repaired helps to improve its property stability and extend technological implications but has presented a huge challenge. A class of fully repairable slippery organogel surfaces (SOSs), which uses microstructured paraffin as reconfigurable supporting structure and silicone oil as lubricant dispersion medium, is reported here. Attributed to nearly 90 wt % of silicone oil stored in the slippery organogel system and good compatibility with the paraffin-based framework, SOSs combine continuous lubricity and reliable lubricant storage stability. Furthermore, the thermally sensitive paraffin-based framework can quickly switch between solid supporting structure and liquid solution according to the ambient temperature, thereby achieving rapid regeneration of microstructure. This unique system consisting of reconfigurable framework and flowable lubricant derives two types of repairs aimed at varying degrees of damage. Significantly, the easy-to-prepare SOS, on the other hand, allows the adoption of various substrate surfaces for different purposes to form an antiadhesion coating and exhibits excellent antistain, antialgae, and anti-icing performance, thus greatly improving the flexibility of such materials in practical applications.

The urgent demands of energy storage for wearable electronics necessitates the development of flexible supercapacitors (FSCs). However, the service environment of portable/wearable devices requires supercapacitors to possess excellent mechanical properties to withstand harsh straining conditions, such as bending, rolling, and twisting. Hence, to develop a high-performance flexible supercapacitor (FSC) that possesses both superior electrochemical properties and remarkable mechanical capacities is still a formidable challenge. In this paper, we successfully fabricate a 3D heterostructured electrode with bulge structured polypyrrole (PPy) wrapped NiMoO4 nanowires on carbon cloth (CC). Benefiting from the 3D heterostructure and the synergistic effect between NiMoO4 and PPy, the PPy/NiMoO4/CC electrode shows a high areal capacitance of 3.4 F cm−2 and cyclic stability (94% capacitance retention). Moreover, the assembled PPy/NiMoO4/CC//activated carbon (AC)/CC device exhibits a high energy density (0.5 mW cm−2 at a power density of 3.7 mWh cm−2). Furthermore, the CV curves of PPy/NiMoO4/CC//AC/CC show no obvious change under miscellaneous deformation conditions, indicating good flexibility. This work demonstrates that the assembled PPy/NiMoO4/CC//AC/CC FSC possesses notable electrochemical properties and exhibits great potential for application in future wearable energy-storage devices.

Background Rearranged during transfection (RET) has been proven to be a tumorigenic target in non-small cell lung cancers (NSCLCs). In RET-rearranged NSCLCs, molecular features and their impact on prognosis were not well illustrated, and the activity of mainstay therapeutics has not currently been well compared. Methods Patients diagnosed with NSCLCs with RET rearrangements were analyzed for concomitant mutations, tumor mutation burden (TMB), PD-L1 expression, T cell receptor repertoire and clinical outcomes with chemotherapy, immune checkpoint inhibitors (ICIs), and multikinase inhibitors (MKIs). Results Among 129 patients with RET-rearranged NSCLC who were analyzed, 41.1% (53/129) had co-occurring genetic alterations by next-generation sequencing, and concomitant TP53 mutation appeared most frequently (20/53, 37.7%). Patients with concurrent TP53 mutation (n = 15) had shorter overall survival than those without (n = 30; median, 18.4 months [95% CI, 8.6–39.1] vs 24.8 months [95% CI, 11.7–52.8]; P < 0.05). Patients with lower peripheral blood TCR diversity (n = 5) had superior overall survival compared with those with higher diversity (n = 6; median, 18.4 months [95% CI, 16.9–19.9] vs 4.8 months [95% CI, 4.5–5.3]; P = 0.035). An association with overall survival was not observed for PD-L1 expression nor for tumor mutation burden level. Median progression-free survival was not significantly different across chemotherapy, ICIs, and MKIs (median, 3.5 vs 2.5 vs 3.8 months). For patients treated with ICIs, the disease control rate was 60% (6/10) and the objective response rate was 20% (2/10). Conclusions RET-rearranged lung cancers can be heterogeneous in terms of concomitant genetic alterations. Patients with concurrent TP53 mutation or high peripheral blood TCR repertoire diversity have relatively inferior overall survival in this series. Outcomes with traditional systemic therapies in general are suboptimal.

Objectives The 3rd generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR TKI) osimertinib has shown promising efficacy both in EGFR-mutant, T790M positive non-small cell lung cancer (NSCLC) patients who have become resistant to 1st or 2nd generation EGFR TKIs and patients with sensitizing EGFR mutations as the first line therapy. However, the degree and duration of response to osimertinib are heterogeneous. We hypothesized that the concurrent genomic landscape of these tumors could play a role in clinical outcomes and/or mechanisms of resistance. Materials and methods We conducted a retrospective multicenter study of lung cancer patients who had developed resistance to osimertinib. Genomic profiling was done for all the patients by using targeted next-generation sequencing encompassing 59–1021 cancer-related genes. Results and conclusion Known EGFR-dependent resistant mutations and activation of alternative pathways were identified in 44 % of all the patients with great heterogeneity. Gain-of-function mutations of CTNNB1 were highly enriched in our cohort. Some other putative resistance mechanisms to osimertinib, such as the recurrent EGFR V834 L mutation, were also identified. Moreover, pathogenic mutations of TP53 were negatively related to the efficacy of osimertinib. To sum up, heterogeneity of resistance to osimertinib was not only manifested by inter-individual differences, but also embodied in its intra-individual diversity.

Introduction Human c-ros oncogene 1 (ROS1) rearrangement is a distinctive molecular subtype identified in 1-2% of non-small-cell lung cancer (NSCLC) tumors. Since the first gene rearrangement involving the ROS1 gene was described in 2003, multiple ROS1 fusion partner genes have been reported. Crizotinib, a multi-targeted MET/ALK/ROS1 tyrosine kinase inhibitor approved by the FDA, shows efficacy in the treatment of NSCLC patients with common ROS1 fusions. However, its efficacy in patients with rare ROS1 fusions remains unknown. Case presentation Here, we report a 16-year-old boy diagnosed with advanced lung adenocarcinoma. Paired tumor-normal next-generation sequencing was performed on DNA derived from pericardial effusion and peripheral blood with simultaneous analyses of genetic alterations, microsatellite instability (MSI), and tumor mutation burden (TMB). A total of 34 somatic variations, including a novel RBPMS-ROS1 (Exon 1:Exon 32) fusion, were identified. In addition, the sample was found to exhibit MSI-H and TMB-H. The patient was administered crizotinib and showed a rapid, favorable response in both intracranial and primary lung lesions. Conclusion This case supports the use of crizotinib in NSCLC patients with RBPMS-ROS1 rearrangement. Broader molecular profiling is strongly recommended for patients with NSCLC to identify novel actionable fusions.

Research in Information Science and interdisciplinary areas suggested the formation of a growing network of international research collaboration. The massive transmission of COVID-19 worldwide especially after the identification of the Omicron variant could fundamentally alter the factors shaping the network's development. This study employs network analysis methods to analyze the structure of the COVID-19 research collaboration from 2020 to 2022, using two major academic publication databases and the VOSviewer software. A novel temporal view is added by examining the dynamic changes of the network, and a fractional counting method is adopted as methodological improvements to previous research. Analysis reveals that the COVID-19 research network structure has undergone substantial changes over time, as collaborating countries and regions form and re-form new clusters. Transformations in the network can be partly explained by key developments in the pandemic and other social-political events. China as one of the largest pivots in the network formed a relatively distinct cluster, with potential to develop a larger Asia-Pacific collaboration cluster based on its research impact.

Background: This article is performed to assess the significance of minimal residual disease (MRD) after one course of therapy in patients with chronic myelomonocytic leukemia (CMML). Methods: From January 2010 to January 2022, a total of 158 patients who were newly diagnosed with CMML were enrolled, in which 58/158 (37%) patients were conducted by multiparameter flow cytometry (FCM) assessed MRD analysis after on cycle treatment and were included in this study. MRD was detected by six- to eight- colour FCM. Result: After one course of therapy, twenty-one (36%) patients achieved MRD0.01% (MRD1+). The patients in the MRD1+ group had lower platelet counts, higher 𝛽2-microglobulin, ferritin and BM1 myeloblasts (bone marrow myeloblasts after one cycle of therapy) than that of the MRD1- group (P=0.005, P=0.023, P=0.026 and P=0.007, respectively). Furthermore, a greater propotion of patients had JCK2 and SETBP1 mutation in MRD1- patients than in MRD1+ group (both P=0.037). At a median follow up time of 25.8 months (95%CI, 15.01-36.59), those patients who achieved MRD0.01%, and 2-year OS rate (90% vs. 30%; PConclusion: MRD is highly predictive of prognosis, and it may help identify patients at increased risk for progression to further improve the management of patients with CMML. Large-scaled investigations are warranted to validate our conclusions and its potential in clinical practice.

Background Lysine methyltransferase 2 (KMT2) family proteins methylate lysine 4 on histone H3 (H3K4) to promote genome accessibility and transcription. Dysregulation or mutation of KMT2 family have been observed frequently in various types of human cancers. Colorectal cancer is the third most common cancer worldwide. However, few studies have evaluated the role of KMT2 family mutations in colorectal cancer. The present study aimed to explore the impact of KMT2 family mutations on clinicopathological, molecular characteristics and prognosis in colorectal cancer. Methods A total of 316 colorectal cancer patients were enrolled; tumor tissue and matched peripheral blood samples were collected and subjected to targeted sequencing with a panel of 1021 cancer-related genes. The association of clinical pathological features and molecular characteristics in patients were then analyzed. The cBioPortal dataset was used for investigating the KMT2 family mutations data and their correlation with clinical outcomes. Results The overall mutation frequencies of KMT2A-D were 9.5%, 0.5%, 13%, and 13%, respectively, which were more often present at right-sided primary and earlier stage tumors. KMT2A-D mutations are associated with enhanced genomic instability, including a higher level of microsatellite instability (MSI-H) and tumor mutational burden (TMB-H). In addition, our results highlight the co-occurring gene mutations within the Wnt signaling, ERBB2/4, TGF-β superfamily pathway, and PI-3-kinase pathway in KMT2-mutant colorectal cancer. KMT2 family mutations were predictive biomarker for better overall survival in metastatic colorectal cancer. Conclusions Collectively, we identified that KMT2 family mutations were correlated with higher-TMB and higher-MSI, thus resulting in a better outcome for colorectal cancer patients.

Efficiently capturing of uranium (VI) [U(VI)] from seawater elicits unparalleled attraction for sustaining the uplifted requirement for nuclear fuel. However, obtaining the abundant U(VI) resource from seawater has always seriously restricted by competitive adsorption from higher concentrations of competitors, especially vanadium (V) [V(V)]. Herein, based on amidoximized natural bamboo strips with hierarchical porous structure, the molecular-level uranyl-specific "nano-holes" was co-constructed by the intramolecular hydrogen bonds for specifically trapping U(VI) from seawater. Manipulating the branched degrees of amino groups enabled the creation of a series of the molecular-level uranyl-specific "nano-holes" that exhibit ultrahigh affinity and selective adsorption of U(VI) with a adsorption capacity 1.8 fold higher compared to that of V(V) after 30 days floating in the Yellow Sea basin, conquering the long-term challenge of the competitive adsorption of V(V) for amidoxime-based adsorbents applied to extract U(VI) from seawater. The diameter of the molecular-level uranyl-specific "nano-holes" is approximately 12.07 Å, significantly larger than (UO

Purpose The present study aims to explore the clinical features, imaging manifestations, pathologic characteristics, treatment, and prognosis of aggressive splenic lymphoma (ASL) patients.Methods From January 2001 to March 2021, patients who were histologically proven splenic lymphoma were enrolled in this study. The survival curves of overall survival (OS) and progressive-free survival (PFS) were calculated by the Kaplan–Meier survival analysis and log-rank test. Univariate and multivariate Cox regression analyses were performed to estimate the potential prognostic factors.Results Sixty-nine patients who were histologically proven ASL in this study. The median follow-up time was 76.3 months (95%CI, 60.194-92.406). Patients with ASL underwent the splenectomy had better PFS and OS than that of patients who did not (OS 61% vs 35%, P=0.084; PFS 57% vs 25%, P=0.061), yet the difference was not remarkably significant. In addition, splenic lymphomas of T-cell origin (OS HR, 3.398[95%CI, 1.327-8.704], P=0.011; PFS HR, 2.776[95%CI, 1.107-6.959], P=0.029) and present with B symptoms (OS HR, 2.703[95%CI, 1.219-5.994], P=0.014; PFS HR, 2.890[95%CI, 1.348-6.194], P=0.006) were independent risk factors correlated with OS and PFS. After establishing a risk-stratified model in combination with cell of origin (COO) and B symptom to divide patients into three risk subgroups: 36 were in low-risk group, 28 were in intermediate-risk group, and 5 were in high-risk group. The differences between each group were statistically significant (OS: χ2=41.000, PConclusion Splenic T-cell lymphoma patients with B symptom at initial diagnosis had the worst outcome among aggressive splenic lymphoma.

In order to explore the impact of pegylated liposomal doxorubicin (PLD) dose intensity on survival outcomes of newly diagnosed elderly patients with diffuse large B-cell lymphoma (DLBCL), we performed a retrospective study to compare the efficacy and adverse effects of RCEOP (70 mg/mA total of 335 DLBCL patients (60-85 years old) who were newly diagnosed and completed at least four cycles of RCE(D)OP were selected. The patients were mainly divided into RCEOP (126 cases) (epirubicin 70 mg/mOur study showed that PLD and epirubicin had similar efficacy (overall survival (OS) p = 0.776; progression-free survival (PFS) p = 0.959). RCDOP (30-45 mg/mIn the general population, the CR rate in the RCDOP group was significantly higher than that in the RCdOP group (p = 0.018). For elderly DLBCL patients with cardiovascular disease, the effect benefit brought by the PLD dose was more obvious, and the PFS of the RCDOP group was significantly better than that of the RCdOP group (p = 0.043). Full dose of PLD is an efficient alternative in the treatment of patients with preexisting cardiovascular diseases.

The characteristics, sources and risk assessment of heavy metal pollution in community garden soil of Lin'an District were evaluated. The 28 soil samples from community garden were collected for determination of 7 heavy metal elements. The Geostatistical analysis, Spearman correlation coefficient, Principal component analysis and PMF model have explored sources of heavy metal pollution. The health risk assessment model has assessed ecological risk of heavy metals. The results revealed that average concentration of As, Cd, Cr, Cu, Ni, Pb and Zn were 16.0, 0.158, 76.1, 34.6, 45.8, 20.9 and 166 mg kg

Background The potential for acute exercise to enhance attention has been discussed in the literature. However, the neural mechanisms by which acute exercise affects attention remain elusive. Method In this study, we first identified an optimized acute Tai Chi Chuan (ATCC) exercise protocol that enhances sustained attention performance and then aimed to determine the neural substrates of exercise-enhanced attention. Reaction time (RT) from the psychomotor vigilance test (PVT) was used to evaluate sustained attention. In Experiment 1, improvements in RTs were compared among six different exercise protocols. In Experiment 2, the participants completed the PVT in an MRI scanner on both rest and exercise days. Results Experiment 1 showed that practicing TCC 3 times for a total of 20 minutes, followed by 10-minute rest periods, resulted in the largest improvements in RTs. Experiment 2 showed that ATCC enhanced sustained attention, as evidenced by shorter RTs, and resulted in greater cuneus/precuneus activation after exercise than in the rest condition. Exercise-induced changes in brain activities across a distributed network exhibited significant correlations with attention. Conclusion Therefore, this study indicates that ATCC effectively enhances sustained attention and underscores the key role of the cuneus/precuneus and frontoparietal-cerebellar regions in facilitating vigilance among young adults.

Nucleocapsid protein (N protein) is an appropriate target for early determination of viral antigen-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have found that β-cyclodextrin polymer (β-CDP) has shown a significant fluorescence enhancement effect for fluorophore pyrene via host–guest interaction. Herein, we developed a sensitive and selective N protein-sensing method that combined the host–guest interaction fluorescence enhancement strategy with high recognition of aptamer. The DNA aptamer of N protein modified with pyrene at its 3′ terminal was designed as the sensing probe. The added exonuclease I (Exo I) could digest the probe, and the obtained free pyrene as a guest could easily enter into the hydrophobic cavity of host β-CDP, thus inducing outstanding luminescent enhancement. While in the presence of N protein, the probe could combine with it to form a complex owing to the high affinity between the aptamer and the target, which prevented the digestion of Exo I. The steric hindrance of the complex prevented pyrene from entering the cavity of β-CDP, resulting in a tiny fluorescence change. N protein has been selectively analyzed with a low detection limit (11.27 nM) through the detection of the fluorescence intensity. Moreover, the sensing of spiked N protein from human serum and throat swabs samples of three volunteers has been achieved. These results indicated that our proposed method has broad application prospects for early diagnosis of coronavirus disease 2019.

Background: ERBB2 (HER2) insertions and point mutations are oncogenic drivers in non-small cell lung cancer (NSCLC) and now has approved targeted therapy for this patient population. Here, we present the landscape of ERBB2 genetic alterations (alts) and co-mutations, and the comparison between ERBB2 and EGFR exon 20 insertions in NSCLC. Methods: Two large retrospective cohorts were analyzed. In the Geneplus (China) cohort, 1,281 newly diagnosed NSCLC patients (pts) harboring ERBB2 alt were analyzed based on tissue and/or ctDNA. In the Guardant360 (Guardant Health, Redwood City, USA) cohort, 1719 ctDNA profiles of newly diagnosed NSCLC samples harboring ERBB2 alts were evaluated, with clonal alterations defined as those with ≥50% ratio of the maximum somatic variant allele fraction. Results: In the Geneplus cohort of 1,281 pts with ERBB2 alts, 55% were female with a median age of 58 years. ERBB2 mutations or insertions were identified in 930 pts, ERBB2 amplification(amp)-only in 351 pts, with mutation and co-amp at 7.5%. Most common alterations were in the tyrosine kinase domain exon 20 (85%), with Y772_A775dupYVMA to be the most frequent (57.4%), followed by G776delinsVC/LC/VV/IC (10.6%), and S310X (10.4%). EBRR2-mutation NSCLC were frequently having PDL1 Conclusion: In two large independent cohorts, Chinese and Western, ERBB2 mutation and co-mutation patterns were similar. ERBB2 exon 20 insertions/mutations were dominant at over 80% with Y772_A775dupYVMA being the most common driver mutation; TP53 and EGFR were the most frequently co-occurred genes. ERBB2 mutation lung cancers had low TMB and PDL1, as expected in female dominant lung adenocarcinomas, similar to EGFR exon 20 NSCLC. Clonal VUSs may represent a novel subset of mutations to functionally characterize. Citation Format: Lingzhi Hong, Leylah Drusbosky, Yinyi Wang, Yuanyuan Xiong, Rongrong Chen, Simon Heeke, Monique B. Nilsson, Jianjun Zhang, John V. Heymach, Xiuning Le. Mutation and co-mutation landscape ofERBB2 alterations in advanced NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6087.

Aberrant mesenchymal-epithelial transition/hepatocyte growth factor (MET/HGF) regulation presented in a wide variety of human cancers.We retrospectively analyzed 564 patients with MET alterations.Six hundred thirty-twoHalf of the

PURPOSE MET exon 14 skipping alterations ( METex14) comprise a diverse set of actionable oncogene drivers in non–small-cell lung cancer (NSCLC). Recent studies have established the efficacy of tyrosine kinase inhibitors for this patient population. The landscape of co-occurring genetic alterations in METex14 NSCLC and their potential impact to therapeutic sensitivities has not yet been fully described. MATERIALS AND METHODS METex14 NSCLC cases were collected from three cohorts: the VISION trial, and data sets from Guardant360 and GenePlus. Clinicopathologic characteristics and METex14 mutation sites were analyzed and compared across data sets. Co-occurring genetic alterations and the clonality relationships to METex14 were evaluated. RESULTS Of 40,824 NSCLCs, 692 METex14 cases (1.7%) were identified, including 332 in Guardant360, 188 in VISION, and 172 in GenePlus. The demographics and mutation type and/or sites were similar in the Asian versus Western cohorts. MET amplification, which were found to be associated with sensitivity to MET kinase inhibitors, co-occurs in 7.6%-13.8% of cases, whereas kinase domain secondary mutation of MET co-occurs in 5%-6%. When co-occurring with METex14, EGFR mutations were often identified as the dominant clone (78%, 7 of 9), whereas when co-occurring, METex14 (39%, 7 of 18) and KRAS (44%, 8 of 18) had similar rates of clonal dominance. PIK3CA and PTEN mutations were almost always subclones (89%, 16 of 18) to METex14. Moreover, RET-CCDC6 fusion and EGFR mutation were detected following crizotinib treatment in two patients, suggesting novel mechanisms of resistance. CONCLUSION METex14 mutations frequently co-occur with other potential driver oncogenes with differing patterns of clonal dominance observed among the drivers. This cellular context can provide insights into whether METex14 is acting as a primary oncogenic driver or resistance mechanism and help guide treatment choices.

To evaluate the efficacy and safety of Traditional Chinese Medicine (TCM) in the treatment of epilepsy.A comprehensive search of the database in both Chinese and English was performed. Data from the selected studies were extracted and analyzed independently by two authors.30 randomized controlled trials (RCTs) were included in the meta-analysis with a total of 2471 patients. Among them, 4 trials (n = 235) focused on TCM monotherapy, while the other 26 trials (n = 2236) assessed the benefit of TCM as an add-on therapy to antiseizure medications (ASMs). For the efficacy, the meta-analysis found (1) The effective rate in TCM monotherapy group was higher than that in control group (OR = 4.92, 95 % CI: 2.29-10.57, Z = 4.08, P 0.0001); (2) The add-on of TCM also increased the effective rate (OR = 3.37, 95 % CI: 2.65-4.30, Z = 9.85, P 0.00001) and seizure freedom rate (OR = 1.93, 95 % CI: 1.53-2.44, Z = 5.58, P 0.00001). In terms of safety, the add-on of TCM reduced the rate of total adverse events (OR = 0.46, 95 % CI: 0.31-0.67, Z = 3.96, P 0.0001) as well as adverse events of the gastrointestinal and nervous system. 26 different TCM prescriptions were used in these included RCTs. Among them, the 5 most frequently used herbs were Acorus tatarinowii (19 out of 26), Glycyrrhiza uralensis (13 out of 26), Gastrodia elata (12 out of 26), Pinellia ternata (11 out of 26) and Poria cocos (11 out of 26).This study suggested that TCM may be a relatively efficacious and safe clinical strategy for the treatment of epilepsy. Several limitations still exist, such as the risk of bias in the included studies, the diversified composition of TCM prescriptions, and the relatively low quality of study design.

In this paper, the failure mechanism of the piston in the pneumatic down the hole (DTH) impactor has been studied. Failed piston microstructure has been analyzed using the light optical microscopy (OM) and scanning electron microscope (SEM). Impact toughness test and the Rockwell hardness test were conducted. Results showed the following: a) The carburizing layer of IQCT failed piston is mainly composed of acicular martensite and lower bainite after the carburizing-tempering-isothermal quenching-cryogenic treatment-tempering (IQCT), and there are collapses on the impact side and outer surface of the piston, mainly fatigue failure. b) IQT failed piston samples are subject to carburizing-tempering-isothermal quenching-tempering treatment (IQT). The carburized layer is mainly composed of high-carbon martensite, carbide and retained austenite. The transition layer is still composed of lower bainite and acicular martensite, but the volume fraction of lower bainite increases significantly and the core is mainly composed of lower bainite. It has the best impact toughness, up to 61.5 J/cm2, which is mainly fatigue failure. c) OQT failed piston sample is subject to carburizing-tempering-oil quenching-tempering (OQT). The carburized layer is mainly composed of acicular martensite, the transition layer is composed of acicular martensite (AM) and lath martensite (LM), and the core is mainly composed of LM. The impact toughness of the sample is the worst. Therefore, fatigue fracture failure is caused.

BackgroundEpidemiological surveys have suggested that lung cancer has inherited susceptibility and shows familial aggregation. However, the distribution and prevalence of epidermal growth factor receptor (EGFR) germline variants and their roles in lung cancer genetic predisposition in Chinese population remain to be elucidated.MethodsIn this study, EGFR germline and somatic variants were retrospectively reviewed from the next-generation sequencing results of 31,906 patients with lung cancer. Clinical information was also collected for patients with confirmed EGFR germline mutations.ResultsA total of 22 germline EGFR variants were identified in 64 patients with lung cancer, accounting for 0.2% of the total cases studied. Five patients were diagnosed as multiple primary carcinomas. Family history was documented in 31.3% (20/64) of patients, 55% of which were diagnosed as lung cancer. G863D was the most frequent EGFR germline mutation, followed by P848L, D1014N, and K757R. Somatic EGFR-sensitive mutations were identified in 51.6% of patients with germline EGFR mutations. The proportion of L858R mutation, exon 19 deletion, and rare sensitive mutation was 50%, 17.6%, and 32.4%, respectively. D1014N and T790M mutations were common in young patients. The family members of patients with P848L, R776H, V769M, and V774M mutations were more commonly diagnosed with cancers. A total of 19 patients were confirmed to have received EGFR tyrosine kinase inhibitors (TKIs), but the response to EGFR-TKIs differed among patients with different EGFR mutations.ConclusionChinese patients with lung cancer harbored unique and dispersive EGFR germline mutations and showed unique clinical and genetic characteristics, with varied response patterns to EGFR-TKI treatment.

Objective: We aimed to investigate the chemical basis and mechanism of angiogenesis regulation by a multicomponent Chinese medicine Danhong injection (DHI). Methods: A chemical fraction library of DHI was screened and validated for angiogenesis activities by tube formation and migration assays. Mouse ischemic and tumor vascular models were used to verify the angiogenesis effects in vivo. Migration ability of the main monomers of proangiogenic component (PAC) and antiangiogenic component (AAC) in EA.hy926 cells were determined by migration assay. qPCR analyses were performed to access whether the main monomers of PAC or AAC could affect the expression of angiogenesis-related genes in ECs. Western blotting was used to verify the main monomers PAC and AAC effects on CXCR4 protein expression. Results: Two chemically-distinct fractions, including promotion and inhibition of angiogenesis, were identified in DHI. PAC enhanced angiogenesis and improved recovery of ischemic limb perfusion while AAC reduced Lewis lung tumor growth in vivo in VEGFR-2-Luc mice. CA and RA upregulated the expression of TSP1 and downregulated the expression of KDR and PECAM genes. CXCR4 expression was significantly decreased by CA and RA, but increased by PAI, consistent with their differential effects on EC migration. Conclusion: DHI is capable of bi-directional regulation of angiogenesis in a disease-specific manner. The proangiogenesis activity of DHI promotes ischemic vascular injury repair, whereas the anti-angiogenesis activity inhibits tumor growth. The best pro- and anti-angiogenesis activities are composed of unique chemical combinations that differentially regulate angiogenesis-related gene network.

Underwater facilities are often perplexed by severe and ubiquitous biofouling. The widely applied commercial antifouling materials still have several challenges in static applications. Herein, a polymer containing isoborneol and borane (PBABs), the borneol derivative structure and grafted pyridine-triphenylborane (PTPB) as antifouling groups were prepared by radical polymerization. PBABs showed high antibacterial rates for Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) of up to 95.1% and 81.1%, respectively, confirming superior antibacterial adhesion propertys. More importantly, PBABs effectively reduced the expression of mussel adhesion protein, indicating superior antifouling propertys, resulting from the synergistic effect of multiple antifouling functional groups on the material's surface. Therefore, the PBABs have been evaluated as noncytotoxic, low-cost, easily synthesized, and mass-produced, which demonstrates their great potential for actual marine applications.

Background Precision medicine highlights the importance of incorporating molecular genetic testing into standard clinical care. Next-generation sequencing can detect cancer-specific gene mutations, and molecular-targeted drugs can be designed to be effective for one or more specific gene mutations. For patients with special site metastases, it is particularly important to use appropriate samples for genetic profiling. This study aimed to determine whether genomic profiling using ASC and PE is effective in detecting genetic mutations. Methods Tissues, plasma, ascites (ASC) supernatants, and pleural effusion (PE) samples from gastrointestinal cancer patients with peritoneal metastasis and lung cancer patients with pleural metastasis were collected for comprehensive genomic profiling. The samples were subjected to next-generation sequencing using a panel of 59 or 1021 cancer-relevant genes panel. Results A total of 156 tissues, 188 plasma samples, 45 ASC supernatants, and 1 PE samples from 304 gastrointestinal cancer patients and 446 PE supernatants, 122 tissues, 389 plasma samples, and 45 PE sediments from 407 lung cancer patients were analyzed. The MSAF was significantly higher in ASC and PE supernatant than that in plasma ctDNA (50.00% vs. 3.00%, p p p Conclusion ASC and PE supernatants could be better alternative samples when tumor tissues are not available, especially in patients with only peritoneal or pleural metastases.

RNA helicase catalyzes the denaturation of DNA or the unwinding of double-stranded RNA. It is vital to RNA splicing, transport, editing, degradation and the initiation of protein translation. However, the function of RNA helicase in Medicago truncatula has rarely been reported. In this study, 170 putative RNA helicase genes were identified in the M. truncatula genome, and classified into three subfamilies based on the presence of either a DEAD-box (52 genes), DEAH-box (38 genes), or DExD/H-box (80 genes) in their coding regions. Additionally, conserved helicase_C domains and other functional domains (e.g., the HA2, DUF, and ZnF domains) were also present in these genes. Chromosomal mapping and synteny analyses showed that there were tandem and segment duplications of RNA helicase genes. Furthermore, transcriptome and real-time PCR analysis showed that the expression of 35 RNA helicase genes was affected by abiotic stress. To be specific, 17, 12 and 19 genes were regulated by salt, drought and cold stress, respectively. It is worth noting that MtDEAD8, MtDEAH3, MtDExD/H18 and MtDExD/H23 responded to all three types of stress. These results provide valuable information for understanding the RNA helicase genes in M. truncatula and their abiotic stress-related functions. Supplementary information The online version contains supplementary material available at 10.1007/s12298-021-01087-y.

Centipedegrass [Eremochloa ophiuroides(Munro) Hack.], a member of the Panicoideae subfamily, is one of the most important warm-season turfgrasses originating from China. This grass has an extremely developed prostrate growth habit and has been widely used in transitional and warm climatic regions. To better understand the genetic basis of important biological characteristics, such as prostrate growth and seed yield, in warm-season turfgrasses, we present a high-quality reference genome for centipedegrass and use PacBio, BioNano, and Hi-C technologies to anchor the 867.43 Mb genome assembly into nine pseudochromosomes, with a scaffold N50 of 86.05 Mb and 36,572 annotated genes. Centipedegrass was most closely related to sorghum and diverged from their common ancestor ~16.8 Mya. We detected a novel chromosome reshuffling event in centipedegrass, namely, the nest chromosome fusion event in which fusion of chromosomes 8 and 10 of sorghum into chromosome 3 of centipedegrass likely occurred after the divergence of centipedegrass from sorghum. The typical prostrate growth trait in centipedegrass may be linked to the expansion of candidatePROSTRATE GROWTH 1(PROG1) genes on chromosome 2. Two orthologous genes ofOsPROG1,EoPROG1,andEoPROG2, were confirmed to increase the stem number and decrease the stem angle inArabidopsis. Collectively, our assembled reference genome of centipedegrass offers new knowledge and resources to dissect the genome evolution of Panicoideae and accelerate genome-assisted breeding and improvement of plant architecture in turf plants.

Objectives Anaplastic lymphoma kinase (ALK) fusion counts for 5% non-small cell lung cancer (NSCLC) and sensitive to ALK-TKIs. The most common fusion partner with ALK is echinoderm microtubule-associated protein-like4 (EML4), and a variety of other fusion partners have been found in recent years. In this study we report a intergenic fusion of ALK which involved exon 18 in a 52-year-old female lung adenocarcinoma. Materials and Methods CtDNA was used for genetic analysis by Next-generation sequencing (NGS). Immunohistochemistry (IHC) was performed on the tumor tissue to test ALK expression. Results NGS revealed a chr2 30297612-ALK fusion in ctDNA, which retained exon18-29 of ALK. And ALK protein was strongly expression in tumor by IHC. The patient received crizotinib (250mg, bid) and achieved long-term partial response. Conclusion Intergenic fusion of ALK which involved exon 18 can also benefit from crizotinib. NGS can detect and expose the detail of ALK fusion. This discovery extended the understanding of ALK fusion in NSCLC.