Molecular characterization and expression changes of cytoglobin genes in response to hypoxia in a Tibetan schizothoracine fish, Schizopygopsis pylzovi.

Schizopygopsis pylzovi, an endemic fish of the subfamily Schizothoracinae, is comparatively well adapted to dissolved oxygen fluctuations in the aqueous environments of the Qinghai-Tibetan Plateau. Here, we cloned the complete cDNA of cytoglobin 1 and 2 (Cygb1 and Cygb2) from S. pylzovi and then investigated transcriptional changes of both genes in the selected tissues in response to hypoxia. Both the two genes had the standard exon-intron structure of vertebrate Mb genes but lacked an exon at downstream of the H helix (HC11.2) as seen in mammals. We applied severe hypoxia (4 h at PO2 = 3.6% saturation) and moderate hypoxia (72 h at PO2 = 36.0% saturation) to adult S. pylzovi. Under severe hypoxia, the Cygb1 mRNA levels decreased significantly in the liver, kidney, and brain, but increased significantly in the heart, while the Cygb2 mRNA levels downregulated significantly in the muscle and liver. But, the transcriptional activity of Cygb1 in muscle and that of Cygb2 in the kidney, brain, and heart remained almost unchanged. Under moderate hypoxia, the transcriptional activities of both genes in muscle and brain were turned down quickly after onset hypoxia, while in the liver, kidney, and heart, the transcriptional activities of both genes showed a short-term upregulation in different time periods of hypoxia exposure. Our data suggest that both the Cygb1 and Cygb2 in S. pylzovi are hypoxia-induced genes, and the responses of the transcription regulation of Cygb1 and Cygb2 genes to hypoxia are tissue specific and also depend on the hypoxia regime, which are different from that of other fish species.

Importance of the Correlation between Width and Length in the Shape Analysis of Nanorods: Use of a 2D Size Plot To Probe Such a Correlation.

Analysis of nanoparticle size through a simple 2D plot is proposed in order to extract the correlation between length and width in a collection or a mixture of anisotropic particles. Compared to the usual statistics on the length associated with a second and independent statistical analysis of the width, this simple plot easily points out the various types of nanoparticles and their (an)isotropy. For each class of nano-objects, the relationship between width and length (i.e., the strong or weak correlations between these two parameters) may suggest information concerning the nucleation/growth processes. It allows one to follow the effect on the shape and size distribution of physical or chemical processes such as simple ripening. Various electron microscopy pictures from the literature or from the authors' own syntheses are used as examples to demonstrate the efficiency and simplicity of the proposed 2D plot combined with a multivariate analysis.

One-Step Synthesis of Hybrid Liquid-Crystal ZnO Nanoparticles: Existence of a Critical Temperature Associated with the Anisotropy of the Nanoparticles.

Zinc oxide nanoparticles were obtained from the hydrolysis of an organometallic precursor in pure hexadecylamine. Interestingly, we demonstrate that the final (anisotropic or isotropic) shape of the nanoparticles is strongly correlated to the existence of a critical temperature. This suggests that the organization of the fatty amines is a paramount parameter in this synthesis. Moreover, the final hybrid ZnO materials systematically exhibit a liquid-crystal smectic phase, whereas no liquid-crystal phase was observed in the pristine reaction media. This simple process is, therefore, a direct and straightforward method to synthesize liquid-crystal hybrid materials.

Single-molecule tracking of PprI in D. radiodurans without interference of autoblinking.

Autoblinking is a widespread phenomenon and exhibits high level of intensity in some bacteria. In Deinococcus radiodurans (D. radiodurans), strong autoblinking was found to be indistinguishable from PAmCherry and greatly prevented single-molecule tracking of proteins of interest. Here we employed the bright photoswitchable fluorescent protein mMaple3 to label PprI, one essential DNA repair factor, and characterized systematically the fluorescence intensity and bleaching kinetics of both autoblinking and PprI-mMaple3 molecules within cells grown under three different conditions. Under minimal media, we can largely separate autoblinking from mMaple3 molecules and perform reliably single-molecule tracking of PprI in D. radiodurans, by means of applying signal-to-noise ratio and constraining the minimal length for linking the trajectories. We observed three states of PprI molecules, which bear different subcellular localizations and distinct functionalities. Our strategy provides a useful means to study the dynamics and distributions of proteins of interest in bacterial cells with high level of autoblinking.

The efficacy of thoracic radiotherapy in extensive stage small cell lung cancer with baseline brain metastases: a multi-institutional retrospective cohort study.

Background: Thoracic radiotherapy (TRT) had been shown to improve overall survival (OS) in extensive-stage small cell lung cancer (ES-SCLC) patients. However, approximately one fourth of SCLC harbored baseline brain metastases (BMs) and were excluded from previous TRT trials. Thus, the role of TRT in this sub-cohort of ES-SCLC requires elucidation. In this study, we evaluated the efficacy of TRT in ES-SCLC patients with clinically controlled baseline BMs. Methods: In this retrospective, multi-institutional cohort study, 49 patients fully staged as ES-SCLC with baseline BM, had their disease controlled at all sites with no BM symptoms for three months since treatment initiation were included. The patients were allocated to TRT or no-TRT groups according to whether they received consolidative TRT before progression. Their baseline characteristics were compared using the χ2 test. OS was selected as the primary observational endpoint. Survival and the incidence of cumulative progression between the groups were compared using log-rank analysis, and the interaction between TRT and selected factors was assessed via Cox proportional hazard analysis. Subgroup analysis was performed in oligo-metastasis patients (defined as five or fewer metastatic lesions in two or fewer organs). Results: Seventeen (34.7%) patients received TRT, with a median dose of 54 Gy. The failure pattern analysis revealed initial intrathoracic progression in 31.3% and 66.7% of patients in the TRT no-TRT groups, respectively. Also, the TRT group had a significantly longer OS than the no-TRT group [hazard ratio (HR) 0.426, P=0.011]. Clinical covariates including age, gender, performance status, smoking, metastatic state, response after chemotherapy, and TRT, were included in multivariate regression analysis. TRT remained significantly correlated with better OS (HR 0.430, P=0.029). Twenty-three (46.9%) patients had oligo-metastasis at baseline. Subgroup analyses showed that TRT was significantly correlated with better OS in oligo-metastatic patients but not in non-oligo metastatic patients. Conclusions: TRT improved the prognosis of select ES-SCLC patients with baseline BMs and should be considered in this sub-cohort, which has not been covered by previous randomized trials.

Manipulating the Li-S reaction kinetics via the V8C7/phosphorus defect-integrated carbon promoter.

V8C7/phosphorus defect-integrated carbon (VPC) is proposed as a dual-function promoter for Li-S chemistry. The well-dispersed V8C7 and phosphorus defects exhibit ample polar sites and remarkable electron conductivity. Such rational integration of dual active centers simultaneously suppresses the shuttle effect and propels the Li-S redox reaction kinetics. Therefore, the S/VPC cathode shows an initial capacity of 1090.0 mA h g-1 and a high retention of 83.5% at 0.2C after 100 cycles and a low decay rate of 0.076% at 2C over 600 cycles.

Ultra-fast and ultra-efficient removal of Cr (VI) by the aqueous solutions of monolayer MXene (Ti3C2Tx).

Chromium (VI) removal is crucial to the safety of water resources, but there is still a lack of effective and fast dislodge methods, especially the on-site rapid remediation and emergency removal technology. Herein, the monolayer (ML) Ti3C2Tx nanosheets (NSs) were prepared to remove Cr (VI) from water. The solution sample of the two-dimensional (2D) Ti3C2Tx NSs demonstrate ultrafast adsorption kinetics (the concentration decreasing from 300 to 3 mg L-1 in 10 min) and impressively high capacity (1483 mg g-1), which is several times higher than that of the most reported Cr (VI) adsorption by Ti3C2Tx. The analysis of the adsorption kinetics and isotherm models indicates that the adsorption reaction is endothermic, with physical and chemical adsorption coexisting (mainly monolayer chemical adsorption). The joint study of the experimental analysis and theoretical calculation based on the density functional theory (DFT) demonstrates that the extraordinary removal performance of Cr (VI) is due to the synergetic effect of reduction reaction removal and electrostatic adsorption. It is found that the Cr (VI) is mainly reduced by the OH- terminals on Ti3C2, and the detoxified Cr (III) is anchored on the surface of Ti3C2Tx through complexation reaction with O terminal. The advantages of ultrafast adsorption kinetics and extra-high adsorption capacity of the single-layered Ti3C2Tx for Cr (VI) removal make it a remarkable candidate for rapid and urgent removal of Cr (VI) wastewater.

Neuroendocrine transformation from EGFR/ALK-wild type or TKI-naïve non-small cell lung cancer: An under-recognized phenomenon.

INTRODUCTION: Neuroendocrine transformation (NET) is a resistance mechanism for epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). We aimed to elucidate whether NET develops in TKI-naïve NSCLC by using molecular fingerprinting in paired pre- and post-NET tissues. PATIENTS AND METHODS: NET cases were identified based on the following criteria: the pre- and post-NET lesions must harbor mutual somatic mutations; neuroendocrine component should be absent in the sampled specimens of pre-NET lesions; and re-biopsy should be performed in either previously biopsied baseline lesions or newly developed lesions, but not in baseline-existing non-biopsied lesions, excluding synchronous neuroendocrine malignancy. p53 and Rb expression were evaluated via immunohistochemistry. Clinical characteristics, treatments, and outcomes were recorded and analyzed. RESULTS: Fifteen NET cases were identified, including five EGFR/ALK wild-type, three EGFR-mutant TKI-naïve, and seven TKI-treated cases. All cases harbored mutual somatic mutations in paired pre- and post-NET lesions. Recurrent pre-NET mutations were detected in TP53 (44.4%), RB1 (33.3%), and PDGFRA (33.3%), but two of the three PDGFRA mutations were lost after NET, whereas pre-NET TP53 and RB1 mutations were retained in the corresponding post-NET lesions. Immunohistochemistry revealed inactivated p53/Rb in 90.9% and 72.7% of the pre-NET lesions, respectively. CONCLUSIONS: This proof-of-concept study demonstrated that NET develops in NSCLCs without TKI targets or treatments. This phenomenon could be under-recognized, because re-biopsy was less frequently performed in these patients. Tissue re-biopsy should be preferred over liquid biopsy at the time of progression to account for histology transformation. p53/Rb IHC should be considered in addition to genomic TP53/RB1 evaluation for NET risk prediction.

Atypical Response in Metastatic Non-Small Cell Lung Cancer Treated with PD-1/PD-L1 Inhibitors: Radiographic Patterns and Clinical Value of Local Therapy.

PURPOSE: To explore the clinical characteristics, management, and survival outcomes of advanced NSCLC patients treated with PD-1/PD-L1 inhibitors who presented with an atypical response (AR). METHODS: A total of 926 PD-1/PD-L1-inhibitor-treated patients with metastatic NSCLC from three academic centers were retrospectively reviewed. All measurable lesions were evaluated by RECIST version 1.1. RESULTS: Fifty-six (6.1%) patients developed AR. The median time to the occurrence of AR was 2.0 months. Patients with no fewer than 3 metastatic organs at baseline were more prone to develop AR in advanced NSCLC (p = 0.038). The common sites of progressive lesions were lymph nodes (33.8%) and lungs (29.7%). The majority (78.2%) of patients with AR had only 1-2 progressive tumor lesions, and most (89.1%) of the progressive lesions developed from originally existing tumor sites. There was no significance in terms of survival between patients with AR and those with typical response (TR). Local therapy was an independent predictor for PFS of patients with AR (p = 0.025). CONCLUSIONS: AR was not an uncommon event in patients with metastatic NSCLC treated with PD-1/PD-L1 inhibitors, and it had a comparable prognosis to those with TR. Proper local therapy targeting progressive lesions without discontinuing original PD-1/PD-L1 inhibitors may improve patient survival.

Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts.

Bone is a frequent metastatic site of non-small cell lung cancer (NSCLC), and bone metastasis (BoM) presents significant challenges for patient survival and quality of life. Osteolytic BoM is characterised by aberrant differentiation and malfunction of osteoclasts through modulation of the TGF-ß/pTHrP/RANKL signalling pathway, but its upstream regulatory mechanism is unclear. In this study, we found that lncRNA-SOX2OT was highly accumulated in exosomes derived from the peripheral blood of NSCLC patients with BoM and that patients with higher expression of exosomal lncRNA-SOX2OT had significantly shorter overall survival. Additionally, exosomal lncRNA-SOX2OT derived from NSCLC cells promoted cell invasion and migration in vitro, as well as BoM in vivo. Mechanistically, we discovered that NSCLC cell-derived exosomal lncRNA-SOX2OT modulated osteoclast differentiation and stimulated BoM by targeting the miRNA-194-5p/RAC1 signalling axis and TGF-ß/pTHrP/RANKL signalling pathway in osteoclasts. In conclusion, exosomal lncRNA-SOX2OT plays a crucial role in promoting BoM and may serve as a promising prognostic biomarker and treatment target in metastatic NSCLC.

Responses of Root Endophytes to Phosphorus Availability in Peach Rootstocks With Contrasting Phosphorus-Use Efficiencies.

Phosphorus (P) is an important macronutrient for all lives, but it is also a finite resource. Therefore, it is important to understand how to increase the P availability and plant uptake. The endophytes can help host plants to improve P uptake and will be apparently affected by plant genotypes. To investigate the mechanism of root endophytes in promoting P uptake of peach rootstocks, we analyzed the variations of the root endophytic fungal and bacterial communities of peach rootstocks with different P efficiencies under high or low level of P addition. Results showed that Proteobacteria was the dominant bacterial phylum in the roots of all rootstocks under the two levels of P addition. At low P level, the abundance of Actinoplanes in phosphorus-inefficiency root system was apparently higher than that at high P level. Actinoplanes produced important secondary metabolites, improving the stress resistance of plants. Under high P condition, the abundance of Ferrovibrio was higher in Qing Zhou Mi Tao than in Du Shi. Fe oxides considerably reduced the availability of applied P, which partially explained why the P utilization in Qing Zhou Mi Tao is inefficient. Further, Ascomycota was the dominant fungal phylum in the roots of all rootstocks under different levels of P addition. The fungi community of roots varied in different rootstocks at each P level, but was similar for the same rootstock at different P levels, which indicated that genotype had a greater effect than P addition on the fungal community of peach rootstocks.

A nomogram to predict the overall survival of patients with symptomatic extensive-stage small cell lung cancer treated with thoracic radiotherapy.

BACKGROUND: Small cell lung cancer (SCLC) makes up 13% of lung malignancies. Only one-third of SCLC patients received their diagnosis at the limited stage. Treatment for symptomatic extensive-stage (ES) SCLC with persistent intrathoracic disease is still controversial. The present research aimed to analyze the impact of palliative thoracic radiotherapy (TRT) as a treatment for this patient group and build a prognostic nomogram. METHODS: In this retrospective, multi-center study, we analyzed 120 patients with ES-SCLC and a World Health Organization performance status of 1-2 who were diagnosed between March 2014 and September 2019. A nomogram was formulated to predict the patients' 1- and 2-year overall survival (OS). RESULTS: The study cohort had a median age of 62 years, and males accounted for 85% of enrollees. A significant extension was observed in the median OS in the TRT group compared to the no TRT group (P<0.001). When the patients were stratified by TRT dose, no significant differences in OS were noted (P=0.530). However, higher levels of inflammatory markers prior to TRT were associated with a shorter OS (neutrophil-to-lymphocyte ratio, P=0.002; platelet/lymphocyte ratio, P=0.023). The nomogram's Harrell's concordance (C)-statistic reached 0.70, and the calibration curve analysis revealed goodness of fit. CONCLUSIONS: The neutrophil-to-lymphocyte ratio is an independent factor predicting survival in ES-SCLC patients treated with palliative TRT. Our nomogram, which incorporates immunological markers, has higher accuracy than existing models for the prediction of individuals' chances of survival, and it could be a significant tool for clinicians in the development of tailored therapeutic strategies.

Study on the effect of oxidation-ultrasound treatment on the electrochemical properties of activated carbon materials.

Activated carbon (AC) has been widely used in water treatment because of its rich pore structure, large specific surface area, simple production process, low preparation cost and wide source of raw materials. In this paper, the regeneration efficiency of low-frequency ultrasonic pretreatment (40 kHz, 115Μw/cm3) on biological activated carbon (BAC) is investigated, and its principle is discussed. The results show that the micro-jet and micro-liquid flow with high temperature and pressure produced by micro-bubble rupture during ultrasonic cavitation play an important role in the regeneration of activated carbon. And optimum ultrasonic treatment time is determined (5 min). In addition, the preparation of cu-loaded activated carbon by ultrasound-microwave method is investigated to pretreat wastewater produced in paracetamol production. The results show that Cu and Cu oxides can be loaded on activated carbon surface by ultrasonic-microwave pretreatment. Finally, the pretreatments of activated carbon by physical, chemical and physical-chemical method are investigated. The effects of the above different pretreatment methods on the structure and adsorption properties of activated carbon are compared and evaluated.

Supraclavicular Recurrence in Completely Resected (y)pN2 Non-Small Cell Lung Cancer: Implications for Postoperative Radiotherapy.

Background: The clinical value and delineation of clinical target volume (CTV) of postoperative radiotherapy (PORT) in completely resected (y)pN2 non-small cell lung cancer (NSCLC) remain controversial. Investigations specifically focusing on the cumulative incidence and prognostic significance of initial disease recurrence at the supraclavicular region (SCR) in this disease population are seldom reported. Methods: Consecutive patients with curatively resected (y)pN2 NSCLC who received adjuvant chemotherapy from January 2013 to December 2018 at our cancer center were retrospectively examined. Disease recurrence at the surgical margin, ipsilateral hilum, and/or mediastinum was defined as loco-regional recurrence (LRR). Disease recurrence beyond LRR and SCR, was defined as distant metastasis (DM). Overall survival (OS1 and OS2) were calculated from surgery and disease recurrence to death of any cause, in the entire cohort and in patients with recurrent disease, respectively. Results: Among the 311 patients enrolled, PORT without elective supraclavicular nodal irradiation (ESRT) was performed in 94 patients and neoadjuvant chemotherapy was administered in 31 patients. With a median follow-up of 26 months, 203 patients developed recurrent disease, including 27 SCRs, among which 16 were without DM and 22 involved the ipsilateral supraclavicular region. The 1, 3, and 5-year cumulative incidence of SCR were 6.53, 13.0, and 24.7%, respectively. Chosen DM as a competing event, cN2, ypN2, not receiving lobectomy, and negative expression of CK7 were significantly associated with SCR using the univariate competing risk analysis, while ypN2 was identified as the only independent risk factor of SCR (p = 0.012). PORT significantly reduced LRR (p = 0.031) and prolonged OS1 (p = 0.018), but didn't impact SCR (p = 0.254). Pattern of failure analyses indicated that the majority of LRRs developed within the actuarial or virtual CTV of PORT, and 15 of the 22 ipsilateral SCRs could be covered by the virtual CTV of proposed ESRT. In terms of OS2, patients who developed SCR but without DM had intermediate prognosis, compared with those who had DM (p = 0.009) and those who had only LRR (p = 0.048). Conclusions: SCR is not uncommon and has important prognostic significance in completely resected (y)pN2 NSCLC. The clinical value of PORT and ESRT in such patients need to be further investigated.

Risk factors of postoperative recurrence and potential candidate of adjuvant radiotherapy in lung adenosquamous carcinoma.

BACKGROUND: Adenosquamous carcinoma (ASC) is a rare and aggressive histologic subtype of non-small cell lung cancer (NSCLC). Little is known about the prognostic significance of routine immunohistochemical (IHC) markers and clinical value of adjuvant radiotherapy in completely resected lung ASC. METHODS: Consecutive patients with pathologically confirmed lung ASC receiving curative resection from January 2007 to December 2017 at our center were retrospectively reviewed. The prognostic significance of 14 routine IHC markers and potential candidate of adjuvant radiotherapy were investigated. RESULTS: With a median follow up of 35 (range, 3.0-138) months, 95 out of the 176 enrolled patients had disease recurrence. The 1-, 3- and 5-year cumulative rate of recurrence was 25.8%, 55.8% and 63.1%, respectively. Using the Cox proportional hazard regression model, T stage, N stage, lymphovascular invasion (LVI), expression of CEA, expression of p53, but not EGFR mutations or expression of the other 12 IHC markers (CK20, CK5/6, PE10, ERCC1, Napsin A, RRM1, Ki67, CK7, P63, EGFR, HER2, TTF1), were significantly associated with postoperative recurrence. N stage, expression of CEA and LVI were identified as independent prognosticators of overall recurrence. Using competing risk methodology and distant recurrence chosen as a competing risk, T stage and N stage were identified as significant risk factors of loco-regional recurrence. Moreover, adjuvant radiotherapy significantly improved disease-free survival (DFS) (P=0.002) and was associated with non-significant longer overall survival (OS) (P=0.078) among 95 patients with either pathological T3-4 or N+ disease (collectively defined as pT3-4/N+ disease). CONCLUSIONS: This study provides the proof of concept for using routine IHC markers, along with common clinic-pathological parameters, in predicting postoperative recurrence and identifying potential candidate for adjuvant radiotherapy in completely resected lung ASC.

Polydopamine-coated chitosan/calcium pyrophosphate hybrid microflowers as an effective hemostatic agent.

In this study, polydopamine (PDA) coated chitosan/calcium pyrophosphate hybrid microflowers (PDA@CS-CaP) were prepared using a facile approach and evaluated as a hemostatic agent. The surface morphology and elements, chemical groups, porous structure, thermostability, zeta potential, as well as surface wettability were systematically characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), N2 adsorption-desorption, thermogravimetry (TGA) and contact angle apparatus. Due to the synergistic effects of the high hydrophilicity (water contact angel nearly 0), chemical activation (the amino and phenol group of PDA), and the flower-like porous hierarchical structure, the prepared PDA@CS-CaP could induce hemocytes and platelets aggregation, promote the blood clotting and achieve bleeding control in vitro and in vivo. Furthermore, the PDA@CS-CaP had no exothermic adverse effects and exhibited better biocompatibility (no cytotoxicity against fibroblasts cells). Thus, the PDA@CS-CaP were expected to be a promising candidate for a safe and promising hemostatic agent because of its porous and hierarchical structures as well as the active PDA coating.

Transcriptome Analysis Provides Insights Into the Adaptive Responses to Hypoxia of a Schizothoracine Fish (Gymnocypris eckloni).

The schizothoracine fish endemic to the Qinghai-Tibetan Plateau are comparatively well adapted to aquatic environments with low oxygen partial pressures. However, few studies have used transcriptomic profiling to investigate the adaptive responses of schizothoracine fish tissues to hypoxic stress. This study compared the transcriptomes of Gymnocypris eckloni subjected to 72 h of hypoxia (Dissolved oxygen, DO = 3.0 ± 0.1 mg/L) to those of G. eckloni under normoxia (DO = 8.4 ± 0.1 mg/L). To identify the potential genes and pathways activated in response to hypoxic stress, we collected muscle, liver, brain, heart, and blood samples from normoxic and hypoxic fish for RNA-Seq analysis. We annotated 337,481 gene fragments. Of these, 462 were differentially expressed in the hypoxic fish as compared to the normoxic fish. Under hypoxia, the transcriptomic profiles of the tissues differed, with muscle the most strongly affected by hypoxia. Our data indicated that G. eckloni underwent adaptive changes in gene expression in response to hypoxia. Several strategies used by G. eckloni to cope with hypoxia were similar to those used by other fish, including a switch from aerobic oxidation to anaerobic glycolysis and the suppression of major energy-requiring processes. However, G. eckloni used an additional distinct strategy to survive hypoxic environments: a strengthening of the antioxidant system and minimization of ischemic injury. Here, we identified several pathways and related genes involved in the hypoxic response of the schizothoracine fish. This study provides insights into the mechanisms used by schizothoracine fish to adapt to hypoxic environments.