Transcription factors MhDREB2A/MhZAT10 play a role in drought and cold stress response crosstalk in apple.

Drought and cold stresses seriously affect tree growth and fruit yield during apple (Malus domestica) production, with combined stress causing injury such as shoot shriveling. However, the molecular mechanism underlying crosstalk between responses to drought and cold stress remains to be clarified. In this study, we characterized the zinc finger transcription factor ZINC FINGER OF ARABIDOPSIS THALIANA 10 (ZAT10) through comparative analysis of shoot-shriveling tolerance between tolerant and sensitive apple rootstocks. MhZAT10 responded to both drought and cold stresses. Heterologous expression of MhZAT10 in the sensitive rootstock 'G935' from domesticated apple (Malus domestica) promoted shoot-shriveling tolerance, while silencing of MhZAT10 expression in the tolerant rootstock 'SH6' of Malus honanensis reduced stress tolerance. We determined that the apple transcription factor DEHYDRATION RESPONSE ELEMENT-BINDING PROTEIN 2A (DREB2A) is a direct regulator activating the expression of MhZAT10 in response to drought stress. Apple plants overexpressing both MhDREB2A and MhZAT10 genes exhibited enhanced tolerance to drought and cold stress, while plants overexpressing MhDREB2A but with silenced expression of MhZAT10 showed reduced tolerance, suggesting a critical role of MhDREB2A-MhZAT10 in the crosstalk between drought and cold stress responses. We further identified drought-tolerant MhWRKY31 and cold-tolerant MhMYB88 and MhMYB124 as downstream regulatory target genes of MhZAT10. Our findings reveal a MhDREB2A-MhZAT10 module involved in crosstalk between drought and cold stress responses, which may have applications in apple rootstock breeding programs aimed at developing shoot-shriveling tolerance.

Pulse buildup dynamics in a self-starting Mamyshev oscillator.

The Mamyshev oscillator (MO) can generate high-performance pulses. However, due to their non-resonant cavities, they usually are not self-starting, and there is almost no effort to reveal the pulse buildup dynamics of the MO. This paper investigates the dynamic of single pulse (SP) and multi-pulse formation in a self-starting MO. It indicated that both SP self-starting and multi-pulse self-starting can be obtained by adjusting the oscillator parameters. More importantly, increasing pump power could only result in bound state pulses (BSPs) if SP self-starting was formed. With the increase of the pump power, the pulse number in BSPs would increase. However, multiple pulses could not be formed only by increasing the pump power, and the BSPs obtained here underwent SP generated from noise, amplified, and then bounded, which is different from conventional passive mode-locked fiber lasers (CPMLFLs). On the other hand, if multiple pulses were self-initiated, BSPs, pulse bunch, and harmonic mode-locked pulses (HMLPs) could be obtained by adjusting the polarization state and pump power in the cavity. Furthermore, once any of the above states are formed, if the oscillator polarization state and filter interval are unchanged, only increasing the pump power from zero, the original state can still be obtained, which is consistent with the characteristics of the CPMLFLs. These findings will provide new insights into the pulse dynamics of self-starting MO, which will be significant for studying ultrafast laser technology and nonlinear optics.

Insulin resistance, coronary artery lesion complexity and adverse cardiovascular outcomes in patients with acute coronary syndrome.

BACKGROUND: Insulin resistance (IR) is linked to both the complexity of coronary artery lesions and the prognosis of acute coronary syndrome (ACS). However, the precise extent of this correlation and its impact on adverse cardiovascular outcomes in ACS patients remain unclear. Therefore, this study aims to investigate the intricate relationship between IR, coronary artery lesion complexity, and the prognosis of ACS through a cohort design analysis. METHOD: A total of 986 patients with ACS who underwent percutaneous coronary intervention (PCI) were included in this analysis. IR was assessed using the triglyceride-glucose (TyG) index, while coronary artery lesion complexity was evaluated using the SYNTAX score. Pearson's correlation coefficients were utilized to analyze the correlations between variables. The association of the TyG index and SYNTAX score with major adverse cardiovascular events (MACEs) in ACS was investigated using the Kaplan-Meier method, restricted cubic splines (RCS), and adjusted Cox regression. Additionally, a novel 2-stage regression method for survival data was employed in mediation analysis to explore the mediating impact of the SYNTAX score on the association between the TyG index and adverse cardiovascular outcomes, including MACEs and unplanned revascularization. RESULTS: During a median follow-up of 30.72 months, 167 cases of MACEs were documented, including 66 all-cause deaths (6.69%), 26 nonfatal myocardial infarctions (MIs) (2.64%), and 99 unplanned revascularizations (10.04%). The incidence of MACEs, all-cause death, and unplanned revascularization increased with elevated TyG index and SYNTAX score. Both the TyG index (non-linear, P = 0.119) and SYNTAX score (non-linear, P = 0.004) displayed a positive dose-response relationship with MACEs, as illustrated by the RCS curve. Following adjustment for multiple factors, both the TyG index and SYNTAX score emerged as significant predictors of MACEs across the total population and various subgroups. Mediation analysis indicated that the SYNTAX score mediated 25.03%, 18.00%, 14.93%, and 11.53% of the correlation between the TyG index and MACEs in different adjusted models, respectively. Similar mediating effects were observed when endpoint was defined as unplanned revascularization. CONCLUSION: Elevated baseline TyG index and SYNTAX score were associated with a higher risk of MACEs in ACS. Furthermore, the SYNTAX score partially mediated the relationship between the TyG index and adverse cardiovascular outcomes.

Correlation of mir-221-3p differential expression with clinical characteristics of gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is one of the most common digestive malignancies. Although miR-221-3p was defined as a novel biomarker in many types of cancer, the relationship between its expression differences and the clinicopathological characteristics and prognosis of GC patients was yet to be fully understood. METHODS AND RESULTS: TCGA database was utilized to predict the potential biological function of miR-221-3p in GC. QRT-PCR and RNA FISH were performed to detect the expression levels of miR-221-3p in GC. The miR-221-3p expression levels in GC tissues and cells were significantly higher than those in paracancerous tissues (p < 0.001) and normal gastric mucosal cells (p < 0.05). Higher expression levels of miR-221-3p were associated with tumor diameter ≥ 4 cm (χ2 = 5.519, p = 0.019), cTNM stage (III + IV) (χ2 = 28.013, p = 0.000), lymph node metastasis (χ2 = 23.272, p = 0.000) and distant metastasis (χ2 = 7.930, p = 0.005). Kaplan-Meier survival analysis showed a better prognosis for GC patients with miR-221-3p low expression(HR = 4.520, 95% CI: 1.844-11.075). CONCLUSIONS: miR-221-3p is highly expressed in GC tissues, which plays an important role in tumorigenesis, invasion and metastasis. miR-221-3p may become an important biomarker and potential molecular therapeutic target for patients with GC.

Efficient Nitrate Generation through Electrochemical N2 Oxidation with Nickel Oxyhydroxide Decorated Copper Hydroxide Driven by Solar Cells.

Electrocatalytic nitrogen oxidation reaction (NOR) into nitrate under ambient conditions, as an alternative to replace traditional industrial method, is a promising artificial N2 fixation strategy, especially powered by renewable energy. Here, through skillfully balancing competitive relationships between NOR and oxygen evolution reaction (OER), the nickel oxyhydroxide decorated Cu(OH)2 hybrid electrocatalyst with Cu:Ni molar ratio of 1:1 is developed, which achieves outstanding Faradaic efficiency (FE) of 18.7% and yield rate of 228.24 µmol h-1  gcat -1 at 2.0 V versus reversible hydrogen electrode (RHE) in the electrolyte of 0.1 m Na2 SO4 . Also, the hybrid catalyst maintained over five cycles (10 h each cycle) with negligible decay in performance. The synergetic effect between the components of nickel oxyhydroxide and Cu(OH)2 is found to remarkably activate N2 and suppress the activity of competitive OER, which enhances NOR performance eventually. Moreover, the conversion efficiency of solar-to-nitrate (STN) with 0.025% was obtained by coupling with a commercial solar cell. This work provides a novel avenue of rational catalysts design strategies and realizes solar-to-nitrate synthesis.

Methylome and transcriptome analyses of three different degrees of albinism in apple seedlings.

BACKGROUND: Leaf colour mutations are universally expressed at the seedling stage and are ideal materials for exploring the chlorophyll biosynthesis pathway, carotenoid metabolism and the flavonoid biosynthesis pathway in plants. RESULTS: In this research, we analysed the different degrees of albinism in apple (Malus domestica) seedlings, including white-leaf mutants (WM), piebald leaf mutants (PM), light-green leaf mutants (LM) and normal leaves (NL) using bisulfite sequencing (BS-seq) and RNA sequencing (RNA-seq). There were 61,755, 79,824, and 74,899 differentially methylated regions (DMRs) and 7566, 3660, and 3546 differentially expressed genes (DEGs) identified in the WM/NL, PM/NL and LM/NL comparisons, respectively. CONCLUSION: The analysis of the methylome and transcriptome showed that 9 DMR-associated DEGs were involved in the carotenoid metabolism and flavonoid biosynthesis pathway. The expression of different transcription factors (TFs) may also influence the chlorophyll biosynthesis pathway, carotenoid metabolism and the flavonoid biosynthesis pathway in apple leaf mutants. This study provides a new method for understanding the differences in the formation of apple seedlings with different degrees of albinism.

SnRK2 subfamily I protein kinases regulate ethylene biosynthesis by phosphorylating HB transcription factors to induce ACO1 expression in apple.

Ethylene (ETH) controls climacteric fruit ripening and can be triggered by osmotic stress. However, the mechanism regulating ETH biosynthesis during fruit ripening and under osmotic stress is largely unknown in apple (Malus domestica). Here, we explored the roles of SnRK2 protein kinases in ETH biosynthesis related to fruit ripening and osmoregulation. We identified the substrates of MdSnRK2-I using phosphorylation analysis techniques. Finally, we identified the MdSnRK2-I-mediated signaling pathway for ETH biosynthesis related to fruit ripening and osmoregulation. The activity of two MdSnRK2-I members, MdSnRK2.4 and MdSnRK2.9, was significantly upregulated during ripening or following mannitol treatment. Overexpression of MdSnRK2-I increased ETH biosynthesis under normal and osmotic conditions in apple fruit. MdSnRK2-I phosphorylated the transcription factors MdHB1 and MdHB2 to enhance their protein stability and transcriptional activity on MdACO1. MdSnRK2-I also interacted with MdACS1 and increased its protein stability through two phosphorylation sites. The increased MdACO1 expression and MdACS1 protein stability resulted in higher ETH production in apple fruit. In addition, heterologous expression of MdSnRK2-I or manipulation of SlSnRK2-I expression in tomato (Solanum lycopersicum) fruit altered fruit ripening and ETH biosynthesis. We established that MdSnRK2-I functions in fruit ripening and osmoregulation, and identified the MdSnRK2-I-mediated signaling pathway controlling ETH biosynthesis.

Efficient method to improve the distribution probability of dissipative soliton and noise-like pulse in all-normal-dispersion fiber lasers.

Inspired by the chirped pulse amplification technique, herein, we show an efficient method to improve the distribution probability of dissipative soliton and noise-like pulse in all-normal-dispersion fiber lasers by using an intracavity pulse power editing (PPE) technique for the first time. The dissipative-soliton fiber laser is thus simplified into three parts: a PPE link, a saturable absorber (SA), and a spectral filter. Pulse with different peak powers can be edited in the PPE link, then undergo the positive- or reverse-saturable absorption of the SA, and finally pass through the filter. Further, just by assigning the length of single-mode fiber (SMF) at different positions in the PPE link with a fixed cavity length, four pulse patterns, including dissipative soliton (DS), DS molecules, a bound pattern of DS and noise-like pulse (NLP), and pure NLP, can be controllably produced in fiber lasers. The observed bound pattern of DS and NLP is a new addition to the pulse dynamic pattern family. It is found that the longer the SMF after the gain fiber is, the pulse will be severely broadened. This pulse can easily enter the positive-saturable absorption region of most saturated absorption curves, which will increase the probability of DS radiation; if the SMF behind the gain fiber is shorter, the pulse is not severely broadened. The pulse has a high probability of entering the reverse-saturable absorption range of most saturated absorption curves, resulting in a higher likelihood of generating NLP. In experiments, it is only necessary to increase the SMF length between the gain fiber and the isolator to build a DS fiber laser; however, to construct an NLP fiber laser, only the SMF length between the gain fiber and the isolator needs to be shortened. The experimental results agree well with the numerical predictions. The results significantly broaden the design possibilities for pulse lasers, making them much more accessible to produce specific pulse patterns.

Wavelength and bandwidth tunable filter and its application in a dissipative soliton fiber laser.

A wavelength and bandwidth tunable filter and its application in a dissipative soliton (DS) Yb-doped fiber laser are demonstrated. The spectral filter consisting of six cascaded temperature-sensitive long-period fiber gratings is designed and fabricated for the first time, to the best of our knowledge. The corresponding spectral characteristics of the filter are also characterized with temperature. Its 3-dB bandwidth can be adjusted from 4.84 to 11.02 nm, and the center wavelength is continuously adjustable from 1036 to 1045 nm. The sensitivity of the variation of the center wavelength and the linearity of the center wavelength variation are 32 pm/°C and 99.53%, respectively. This home-made spectral filter has two notable features: i) with regard to the tunable spectrum, the 3-dB bandwidth of the spectrum filter can be unchanged; ii) with regard to the spectral tunability, the 3-dB bandwidth of the spectral filter can also be quantitatively changed as needed by changing the heating mode. The home-made spectral filter is used in the DS fiber laser to further realize the continuous adjustment of DS with a tuning accuracy of 0.03 nm by a step size of 1°C. Such a wavelength-tunable DS fiber laser greatly enhances the design flexibility of the coherent anti-Stokes Raman scattering source.

Insights into the spontaneous multi-scale supramolecular assembly in an ionic liquid-based extraction system.

Herein, we report a four-step mechanism for the spontaneous multi-scale supramolecular assembly (MSSA) process in a two-phase system concerning an ionic liquid (IL). The complex ions, elementary building blocks (EBBs), [EBB]n clusters and macroscopic assembly (MA) sphere are formed step by step. The porous large-sized [EBB]n clusters in the glassy state can hardly stay in the IL phase and they transfer to the IL-water interface due to both electroneutrality and amphiphilicity. Then, the clusters undergo random collision in the interface driven by the Marangoni effect and capillary force thereafter. Finally, a single MA sphere can be formed owing to supramolecular interactions. To our knowledge, this is the first example realizing spontaneous whole-process supramolecular assembly covering microscopic, mesoscopic and macroscopic scales in extraction systems. The concept of multi-scale selectivity (MSS) is therefore suggested and its mechanism is revealed. The selective separation and solidification of metal ions can be realized in a MSSA-based extraction system depending on MSS. In addition, insights into the physicochemical characteristics of ILs from microscopic, mesoscopic to macroscopic scales are provided, and especially, the solvation effect of ILs on the large-sized clusters leading to the phase-splitting is examined. It is quite important that the polarization of uranyl in its complex, the growing of uranyl clusters in an IL as well as the glassy material of uranyl are investigated systematically on the basis of both experiment and theoretical calculations in this work.

Efficacy and Safety of a Naphthoquine-Azithromycin Coformulation for Malaria Prophylaxis in Southeast Asia: A Phase 3, Double-blind, Randomized, Placebo-controlled Trial.

BACKGROUND: A prophylactic antimalarial drug that is both effective for protection and improves compliance is in high demand. METHODS: We conducted a randomized, placebo-controlled, double-blinded phase 3 trial to evaluate the 1:1 fixed-dose combination of naphthoquine-azithromycin (NQAZ) for safety and protection against Plasmodium infections in villages along the China-Myanmar border. A total of 631 residents, 5-65 years of age, were randomized into the drug group (n = 319) and the placebo group (n = 312) to receive NZAQ and placebo, respectively, as a single-dose monthly treatment. Follow-ups were conducted weekly to monitor for adverse events and malaria infections. RESULTS: Of the 531 subjects completing the trial, there were 46 and 3 blood smear-positive Plasmodium infections in the placebo and treatment groups, respectively. For the intent-to-treat analysis, the single-dose monthly NQAZ treatment had 93.62% protective efficacy (95% confidence interval [CI]: 91.72%-95.52%). For the per-protocol analysis, NQAZ treatment provided a 93.04% protective efficacy (95% CI: 90.98%-95.1%). Three smear-positive cases in the NQAZ group were all due to acute falciparum malaria. In comparison, NQAZ treatment provided 100% protection against the relapsing malaria Plasmodium vivax and Plasmodium ovale. The treatment group had 5.6% of participants experiencing transient elevation of liver aminotransferases compared with 2.2% in the placebo group (P > .05). CONCLUSIONS: Monthly prophylaxis with NQAZ tablets was well tolerated and highly effective for preventing Plasmodium infections. It may prove useful for eliminating P. vivax in areas with a high prevalence of glucose-6-phosphate dehydrogenase deficiency in the population. CLINICAL TRIALS REGISTRATION: ChiCTR1800020140.

The lncRNA XIST/miR-150-5p/c-Fos axis regulates sepsis-induced myocardial injury via TXNIP-modulated pyroptosis.

Myocardial injury is a severe complication of sepsis and contributes substantially to the death of critically ill patients. Long non-coding RNAs (lncRNAs) participate in the pathogenesis of sepsis-induced myocardial injury. In this study, we investigated the role of lncRNA X-inactive specific transcript (XIST) in septic myocardial injury and explored its mechanism. Lipopolysaccharide (LPS)-stimulated H9C2 cells and rats subjected to cecal ligation and puncture (CLP) were used as the in vitro and in vivo models. After exposure to LPS, XIST and c-Fos levels were upregulated, but miR-150-5p was downregulated in H9C2 cardiomyocytes and myocardial tissues. XIST affected viability, apoptosis, and pyroptosis in LPS-challenged H9C2 cells. Moreover, XIST knockdown attenuated LPS-induced injury in H9C2 cells by targeting the miR-150-5p/c-Fos axis. c-Fos could bound to the promoter of the TXNIP/XIST gene and enhanced TXNIP/XIST expression. Silencing of XIST improved cardiac function and survival rate and reduced apoptosis and pyroptosis by regulating the miR-150-5p/c-Fos axis in septic rats in vivo. Taken together, our data show that XIST/miR-150-5p/c-Fos axis affected septic myocardial injury, which may indicate a novel therapeutic strategy for sepsis-induced myocardial injury.

Pulse dynamic patterns in a self-starting Mamyshev oscillator.

The pulse dynamics of a self-starting Yb-doped fiber Mamyshev oscillator without external seed pulses or additional starting arms is demonstrated experimentally. Multiple dynamic patterns of pulses, including single pulses, bound-state pulses, and harmonic mode-locking pulses, are observed at different pump powers and filter spectral separations. The generation and evolution of bound states have also been simulated by establishing the corresponding theoretical model. This is the first systematic theoretical and experimental study of the formation and evolution of bound states in Yb-doped Mamyshev oscillators. The numerical results are in excellent agreement with experiment results, providing validation of both the measurements and the numerical model.

Symbiotic coexistence of noise-like pulses.

Noise-like pulse (NLP) can split and then self-assemble into dynamic bound states, named NLP polymer. Here, we reported the first observation, to the best of our knowledge, of the buildup process of bound NLPs in all-normal-dispersion Yb-doped fiber lasers. By designing two NLP fiber lasers, the distinct autocorrelation trace property for the bound NLPs with a short time interval (around 30 ps), and the high-speed oscilloscope trace characterization for the bound NLPs with a relatively broad time interval (∼500 ps) have all been exhibited. Also, we have demonstrated that it was the Raman effect that mediated the NLP bound states. The experiment results showed that though the inter-interval between the NLPs and the NLP width in the bound states are constantly changing, the envelope of each NLP remained localized and the bound NLPs could maintain within a wide pump range. The dynamics of the experimentally observed bound NLPs have also been discussed with fitting models and numerical simulations. In addition, the experimental test results for the coherence of the NLPs and their bound states further indicated that the NLPs had low temporal coherence characteristics.

Spectral filtering effect-induced temporal rogue waves in a Tm-doped fiber laser.

We have experimentally and theoretically investigated optical rogue waves (ORWs) in a net negative dispersion Tm-doped fiber laser with a long cavity, adopting nonlinear polarization evolution as a mode-locker as well as a spectral filter. We obtained a state with numerous pulses bunched in a burst accompanied by perturbation within the burst, in which the spectrum was partially perturbed. After statistical analysis, we found that ORWs have existed in this bunching state. By adjusting the intra-cavity polarization controllers, the perturbed pulse bunching turned into a chaotic pulse bunching state, which gave rise to giant pulses with ultra-high amplitudes, and the giant pulses were a precursor of a broad-spectrum noise-like pulse. The probability of occurrence of ORWs was increased in the chaotic state, which is caused by multi-pulse instability induced by the spectral filtering effect. Simulation results confirm the experimental results and demonstrate that the spectral filter bandwidth (SFB) is directly related to the probability of the emergence of ORWs. When increasing the SFB across the range of multi-pulse instability at a fixed pump power, the frequency with which ORWs appear increases.

Complexation of Cyclic Glutarimidedioxime with Cerium: Surrogating for Redox Behavior of Plutonium.

The complexation of cerium with glutarimidedioxime (H2L) was studied by potentiometry, ESI-mass spectrometry, and cyclic voltammetry. Crystallization of [CeIV(HL)3]+ from Ce3+ starting reactant indicated spontaneous complexation-driven oxidation. In aqueous solution, Ce3+ ions form three successive complexes, Ce(HL)2+, Ce(HL)2+, and Ce(HL)3 (where HL- stands for the singly deprotonated ligand). The interactions of glutarimidedioxime with metal ions are dominantly electrostatic in nature, and the stability constants of the complexes are correlated to the charge density of metal ions. Extrapolations of predicted stability constant (log ß) values were made from plotting effective charge and the ionic radius of the metal ion for Pu3+ and Pu4+. The stability constants of PuIV(HL)3+ and PuIII(HL)2+ are estimated to be 27.74 and 19.75, respectively. The differences of stability constants mean that glutarimidedioxime selectively binds Pu4+ over Pu3+ by a factor of about 8 orders of magnitude, suggesting Pu4+ would be stabilized by chelation with glutarimidedioxime. The mechanism of reduction of Pu4+ to Pu3+ in acidic solution is explained by decomposition of glutarimidedioxime through acid hydrolysis rather than a chelation-driven mechanism.

Research Progress of Radiolabeled Asn-Gly-Arg (NGR) Peptides for Imaging and Therapy.

Asn-Gly-Arg (NGR) motifs have vasculature-homing properties via interactions with the aminopeptidase N (CD13) expressed on tumor neovasculature. Numerous NGR peptides with different molecular scaffolds have been exploited for targeted delivery of different compounds for imaging and therapy. When conjugated with NGR, complexes recognize the CD13 receptor expressed on the tumor vasculature, which improves the specificity to tumor and avoids systematic toxic reactions. Both preclinical and clinical studies performed with these products suggest that NGR-mediated vascular targeting is an effective strategy for delivering bioactive amounts of cytokines to tumor endothelial cells. For molecular imaging, radiolabeled peptides have been the most successful approach and have been translated into clinic. This review describes current data on radiolabeled tumor vasculature-homing NGR peptides for imaging and therapy.

Dynamics of rotating Laguerre-Gaussian soliton arrays.

Trajectory control of spatial solitons is an important subject in optical transmission field. Here we investigate the propagation dynamics of Laguerre-Gaussian soliton arrays in nonlinear media with a strong nonlocality and introduce two parameters, which we refer to as initial tangential velocity and displacement, to control the propagation path. The general analytical expression for the evolution of the soliton array is derived and the propagation properties, such as the intensity distribution, the propagation trajectory, the center distance, and the angular velocity are analyzed. It is found that the initial tangential velocity and displacement make the solitons sinusoidally oscillate in the x and y directions, and each constituent soliton undergoes elliptically or circularly spiral trajectory during propagation. A series of numerical examples is exhibited to graphically illustrate these typical propagation properties. Our results may provide a new perspective and stimulate further active investigations of multisoliton interaction and may be applied in optical communication and particle control.

ROS1-ADGRG6: a case report of a novel ROS1 oncogenic fusion variant in lung adenocarcinoma and the response to crizotinib.

BACKGROUND: ROS1 rearrangements are validated drivers in lung cancer, which have been identified in a small subset (1-2%) of patients with non-small cell lung cancer (NSCLC). To date, 18 fusion genes of ROS1 have been identified in NSCLC. The ALK inhibitor (crizotinib) exhibits therapeutic effect against ROS1-rearranged NSCLC. Next-generation sequencing (NGS) technology represents a novel tool for ROS1 detection that covers many fusion genes. CASE PRESENTATION: A 55-year-old female with EGFR mutation (L858R) was diagnosed with lung adenocarcinoma, who was responsive to first-generation EGFR-tyrosine kinase inhibitor (TKI). Afterwards, she developed acquired resistance accompanied with a ROS1 rearrangement. A NGS assay showed that the tumor had a novel ROS1-ADGRG6 rearrangement generated by the fusion of exons of 1-33 of ROS1 on chr6: q22.1 to exons of 2-26 of ADGRG6 on chr6: q24.2. The patient was obviously responsive to crizotinib. CONCLUSION: We firstly identified ROS1-ADGRG6 fusion variant in NSCLC by NGS, which should be considered in further ROS1 detecting assays.

Complexation of Light Trivalent Lanthanides with N-(2-Hydroxyethyl)ethylenediamine-N,N',N'-triacetic Acid in Aqueous Solutions: Thermodynamic Analysis and Coordination Modes.

N-(2-Hydroxyethyl)ethylenediamine-N,N',N'-triacetic acid (HEDTA, denoted as H3L) is a strong chelating ligand that is widely used in the separation of f elements as relevant to the nuclear fuel cycle. There is much to be known about the structure and composition of the coordination sphere of the complexes of HEDTA with lanthanides. The complexation of HEDTA with light lanthanides (La3+, Nd3+, and Eu3+) was investigated thermodynamically and structurally in aqueous solutions. Potentiometry and microcalorimetry were performed to acquire the complexation constants (25-70 °C) and enthalpies (25 °C), respectively, at I = 1.0 mol·L-1 NaClO4. Coordination modes of the complexes were analyzed by luminescence spectroscopy and NMR spectroscopy. The results indicate that there are two successive Ln3+/HEDTA complexes, LnLaq and Ln2(H-1L)22- (Ln3+ refers to La3+, Nd3+, and Eu3+; H-1L4- refers to deprotonation of the hydroxyl group) during titration. The hydroxyl group of HEDTA is coordinated in the Ln3+/HEDTA complex. The dinuclear Ln2(H-1L)22- complex is present as a carboxyl-bridged centrosymmetric dimer, and two carboxyl groups in bridging positions are coordinated to two adjacent Ln3+ cations. Complexation of NdLaq is exothermic, while formation of the hydrolytic complex Nd2(H-1L)22- is endothermic. Both NdLaq and Nd2(H-1L)22- complexes are driven by entropic force. These data will help to predict the behavior of lanthanides in the separation process, where HEDTA is used as the aqueous complexant.