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The present study systematically investigated the influence of forging strategies on the microstructures and deformation behaviors of a Ti–5Al–5Mo–5V–1Cr–1Fe (Ti-55511) near β-titanium alloy. Microstructure analysis revealed that the as-cast alloy exhibited a basket-weave structure predominantly comprised of lamellar α phase. Three different forging methods were used to adjust the morphology of the primary α phase during the final two forging steps: 1) dual-phase (825 °C) + dual-phase forging (DD sample), 2) dual-phase + β single-phase (900 °C) forging (DS sample), and 3) β single-phase + dual-phase forging (SD sample). After standard heat treatment, the DD samples exhibited equiaxed αp due to sufficient deformation in dual-phase region, while DS samples transformed into lamellar shape due to αp reforming during the cooling process of the final β single-phase forging. In contrast, the SD samples displayed short-rod αp due to reforming in the single-phase region and insufficient deformation in the dual-phase region. All these αp and βt phases can hinder dislocation motion to enhance the strength. The DS sample exhibited the best combination of strength, ductility, and impact toughness. During tensile deformation, planar dislocation slip and {101‾1} twinning were dominant in the αp, while wave slip occurred in the βt phase. The fracture behavior transitioned from brittle to ductile after forging and heat treatment. Overall, this study offers a practical and effective method for optimizing the mechanical properties of the Ti-55511 alloy.

Background and objective: Thyroidectomy, followed by postoperative thyroid-stimulating hormone (TSH) suppression therapy, is the established therapeutic approach for low-risk differentiated thyroid carcinoma (DTC). Recently, there has been a growing body of research dedicated to postoperative TSH suppression therapy in low-risk DTC. This study aims to conduct a comprehensive literature review concerning the necessity of TSH suppression therapy in DTC after hemithyroidectomy. Methods: A systematic search of publicly available literature on postoperative TSH suppression therapy in DTC was conducted by querying databases such as PubMed, Embase, Cochrane, and Web of Science. Patients were stratified into two groups: the experimental group (patients who received TSH suppression therapy) and the control group (patients who did not receive TSH suppression therapy). Concurrently, the five selected studies were categorized into two groups based on the average follow-up period (5–8.6 years). Results: A total of five eligible studies, involving 2964 participants, were included in the analysis. The analysis of these five studies indicated low heterogeneity (I2 = 40 %). During the follow-up period, patients who received TSH suppression therapy had similar recurrence rate (P = 0.13) compared to those who did not. In both average follow-up period less than 6 years group (P = 0.85) and more than or equal to 6 years group (P = 0.07), postoperative TSH suppression therapy did not affect the recurrence of DTC after hemithyroidectomy. Conclusion: This study demonstrates that postoperative TSH suppression therapy does not reduce the recurrence rate of low-risk DTC patients after hemithyroidectomy.

CoCrMoW alloys with different nitrogen (N) additions (0, 0.05, 0.1, and 0.2 ​wt%) were prepared via laser powder bed fusion (LPBF). The effects of N content on the microstructure and mechanical properties were investigated. The results indicate that the LPBFed CoCrMoW alloy with 0.1 ​wt% N addition (0.1 ​N alloy) shows the best combination of mechanical properties with a yield strength of ∼983 ​MPa and an elongation of ∼19 ​%. Both the LPBF process and the N addition impose great effects on suppressing the γ to ε martensitic transformation, resulting in a decrease in the width and amount of ε laths/stacking faults. Besides, the N addition promotes the segregation of elements Mo, W, and Si along the cellular sub-grain boundaries (CBs), forming fine and discontinuous precipitates rich in Mo, W and Si along the CBs in the 0.1 ​N alloy, but dense and continuous (Mo,W)5Si3 precipitates along the CBs in the 0.2 ​N alloy. The (Mo,W)5Si3 precipitates with a tetragonal structure were observed and characterized for the first time in the Co–Cr based alloys. The negative mixing enthalpy between the non-metallic elements N, Si and the metallic elements Mo, W, Cr, and the rapid solidification induced segregation of high melting point elements such as Mo and W along CBs during LPBF process, synergistically contribute to the chemical heterogeneity in the alloys. The pure FCC matrix, the slightly increased segregation of Mo, W, Si elements and fine precipitates along the CBs contribute to the good combination of strength and elongation of the 0.1 ​N alloy. However, though pure FCC phase was present in the 0.2 ​N alloy, the dense and continuous (Mo,W)5Si3 precipitates along CBs acted as nucleation sites for cracks, deteriorating the elongation of the alloy. Overall, it is possible to tune the mechanical properties of the LPBFed CoCrMoW alloy by adjusting the local chemical heterogeneity.

With the development of surface engineering, porous surfaces have emerged as a significant research subject in boiling heat transfer. The latter, in turn, plays a crucial role in various industries such as power plants, distillation plants, and microelectronic technology. In this paper, the Molecular Dynamics method is adopted to investigate the wicking dynamics and boiling dynamics of two porous surfaces: foam, which exhibits randomly distributed pores, and mesh, composed of ordered square wires with relatively uniform pore sizes. Three wettability, namely hydrophilic, neutral, and hydrophobic wetting states, are assigned to the two porous surfaces de-coupling the effect of wettability from surface structure. Results reveal that, during the wicking process, the foam surface shows better wetting ability as it absorbs liquid under both hydrophilic and neutral wettability. Comparatively, the mesh surface has the fastest wicking speed under hydrophilic wettability yet it becomes non-wetting under neutral wettability. During the boiling process, the boiling dynamics differ greatly under three wettability. More importantly, the difference in surface structure makes the foam surface possess a better heat transfer whereas the mesh surface causes gentle pressure variation. Our findings provide insights into the design of artificial porous surfaces for certain purpose and their potential application.

Abstract Background The poor targeting delivery efficiency and limited efficacy of single therapeutic approach have consistently posed significant challenges in tumor management. Results In this research, we have conceived and synthesized a dual-targeting nanodrug delivery system denoted as PDA-DEM-Fe3O4@M, which incorporates a polydopamine nanoparticle (PDA) with photothermal properties, diethyl maleate (DEM) as a chemotherapy agent accelerating tumor apoptosis, iron oxide nanoparticles (Fe3O4) eliciting magnetic targeting effects, and tumor cell membranes (M) contributing to homologous targeting capabilities. The synergistic effect of PDA-induced photothermal therapy and DEM-mediated chemotherapy has been demonstrated in this study to exert a robust inhibitory and cytotoxic influence on tumor cells. Additionally, the biocompatibility of this system has also been demonstrated. Conclusions Through the synergistic effects of PDA’s photothermal therapy and DEM’s chemotherapy, this system demonstrated excellent inhibition and killing effects on tumor cells. Furthermore, we established its excellent biological safety profile. This study demonstrated the potential of this nanomaterial for clinical application in tumor therapy.

The formability and mechanical properties of magnesium (Mg) alloys are strongly related to the crystallographic basal texture. Twins play critical roles in adjusting crystallographic orientation of grains during both deformation and annealing treatment via deformation twinning and twinning-assisted recrystallization. In this study, cold rolling and subsequent annealing were conducted on a Mg-5.9Gd-3.3Y-0.5Zr alloy to investigate the recrystallization behavior and texture evolution. Electron backscatter diffraction and transmission electron microscopy techniques were applied to characterize the nucleation of recrystallized grains, especially the twinning-assisted recrystallization, at multi-scales. The results indicated that a large number of {101‾2}, {101‾1} twins and {101‾1}‐{101‾2} double twins were introduced after cold rolling. The {101‾1}‐{101‾2} double twins, double twin - grain boundary intersections and dense twin-twin intersections acted as the preferential nucleation sites for recrystallization during annealing treatment, while the coarse and parallel {101‾2} twins were unfavorable for the nucleation of recrystallized grains. Although {101‾2} tension twins are the most common twins in Mg alloys, the interface of this type of twin has strong mobility and is easy to expand. Therefore, it is generally difficult for a single {101‾2} twin to recrystallize. However, the {101‾1} compression twins and {101‾1}‐{101‾2} double twins are generally difficult to expand and can store high deformation energy, so they are conducive to becoming nucleation sites for recrystallization. During the recrystallization process, the texture type (basal texture) of the cold rolled sample remained unchanged, but the overall texture intensity was significantly reduced due to the dispersion of grain orientations brought by new grains generated by twinning recrystallization.

Abstract Background The presence of high-volume lymph node metastasis (LNM) and extranodal extension (ENE) greatly increases the risk of recurrence in patients with low-risk papillary thyroid microcarcinoma (PTMC). The goal of this research was to analyze the factors that contribute to high-risk lymph node metastasis in patients with low-risk PTMC. Methods We analyzed the records of 7344 patients who were diagnosed with low-risk PTMC and treated at our center from January 2013 to June 2018.LNM with a high volume or ENE was classified as high-risk lymph node metastasis (hr-LNM). A logistic regression analysis was conducted to identify the risk factors associated with hr-LNM. A nomogram was created and verified using risk factors obtained from LASSO regression analysis, to predict the likelihood of hr-LNM. Results The rate of hr-LNM was 6.5%. LASSO regression revealed six variables that independently contribute to hr-LNM: sex, age, tumor size, tumor location, Hashimoto’s thyroiditis (HT), and microscopic capsular invasion. A predictive nomogram was developed by integrating these risk factors, demonstrating its excellent performance. Upon analyzing the receiver operating characteristic (ROC) curve for predicting hr-LNM, it was observed that the area under the curve (AUC) had a value of 0.745 and 0.730 in the training and testing groups showed strong agreement, affirming great reliability. Conclusion Sex, age, tumor size, tumor location, HT, and microscopic capsular invasion were determined to be key factors associated with hr-LNM in low-risk PTMC. Utilizing these factors, a nomogram was developed to evaluate the risk of hr-LNM in patients with low-risk PTMC.

The temperature of the water wall in the furnace chamber is extremely important for the daily operation of a boiler. Considering the high temperature and dusty environment in the furnace, a temperature measurement device mainly composed of four parts (armored temperature sensor, in-furnace heat-collecting block, out-furnace fixing base, and protective cannula) was designed in this study, which could be used to directly obtain the temperature of the in-furnace water-wall. Numerical simulations of temperature measurement devices with different heat-collecting block structures were carried out using the computer fluid dynamics method. After comparing the measurement accuracy and considering the practical application scenarios, the optimized heat-collecting block structure with a specific expansion gap (0.5 mm wide and 4 mm deep) was selected for practical application. Such a temperature measurement device was then applied to a 1000 MW ultra-supercritical coal-fired boiler in China, and the tested in-furnace water-wall temperature data were in good agreement with relevant research. Compared with the conventional temperature measurement device arranged outside the furnace, the in-furnace water-wall temperature-measurement device adopted in this study has a more sensitive response characteristic and can directly reflect the temperature of the water wall inside the furnace. In addition, it can also reflect the local slag formation state of the water wall and has a long service life.

【Objective】 Rotating winter wheat and summer maize is a common cultivation method in northern and central China. Their water consumption and the occurrence of water deficit vary with prediction. Taking Shangqiu in easter Henan province as an example, this paper investigates the relationship between them with meteorological factors. 【Method】 The analysis was based on meteorological data measured from 1954 to 2019, and crop index data measured from 1999 to 2019 at the National Agro-ecological System Observation and Research Station of Shangqiu. The evapotranspiration used in the analysis was those measured from 2011 to 2018 from a large lysimeter. Statistics and the Mann-Kendall trend test were used to analyze the changing in crop water requirement and water deficit; the dominant analysis was used to elucidate the influence of the meteorological factors on water requirement of the two crops. 【Result】 On average, the annual effective precipitation has been increasing over the past 65 years, at a rate of 3.09 mm/10a during the wheat growing season and 5.23 mm/10a during the maize growing season, despite that in wet years the effective precipitation during the wheat season declined. In contrast, the annual crop water requirement showed a decline (P

Abstract Background Identifying risk factors for occult lateral lymph node metastasis (LLNM) in papillary thyroid microcarcinoma (PTMC) can provide valuable insights into the necessity of lateral neck dissection (LND). The objective of this study was to develop a nomogram for predicting the probability of LLNM in patients with cN0 unifocal PTMC. Methods We conducted a retrospective analyzed a total of 4872 patients with cN0 unifocal PTMC who were treated at our center from January 2013 to June 2018. Logistic regression analysis was used to determine the risk factors for LLNM, and a nomogram was constructed based on these risk factors. Results The rate of LLNM was 3.2%. Tumors located in the upper lobe(odds ratio [OR] = 2.56, 95% confidence interval [CI] 1.80–3.62; p

【Background and objective】 Evapotranspiration from managed and natural ecosystems is an important process in hydrological cycle but not trivial to measure at large scales. The eddy covariance developed over the past decade is a technique to measure atmospheric turbulent fluxes which can be used to estimate evapotranspiration and fluxes of other gases. Calculating evapotranspiration from the measurements of eddy covariance is complicated, and the aim of this paper is to experimentally investigate the areas in a farmland system that contribute to the fluxes measured from an eddy covariance. 【Method】 Atmospheric fluxes were measured from October 2019 to June 2020 using the closed-path eddy covariance system installed in a winter wheat field at Xinxiang comprehensive experimental station in Henan province. Distribution and variation of the measured flux sources were analyzed using the footprint models and FFP and KM methods. 【Result】 ①Southwest-northeast wind was the dominant wind during the experimental period, following by northeast-southwest wind. ②The results calculated under different growth stages and atmospheric conditions revealed that the areas that contributed to the fluxes measured from the device were larger under stable atmospheric conditions than under less stable atmospheric conditions. The direction and length of the areas were affected by wind direction and speed. ③The results calculated by the FFP and KM models showed a linear relationship between the source areas with SKM=0.93SFFP-1962.5 and R2=0.96, and that, in the general, the areas calculated by the KM method were greater than that calculated by the FFP model. 【Conclusion】 The flux source areas calculated by the FFP and KM methods differed, and the wind direction and speed were the main factors affecting the flux source distribution. For our experiment, the winter wheat was the main contributor to the fluxes measured from the eddy covariance system.

BackgroundMedullary thyroid cancer (MTC) can only be cured by surgery, but the management of lateral lymph nodes is controversial, especially for patients with cN0+cN1a. To address this challenge, we developed a multivariate logistic regression model to predict lateral lymph node metastases (LNM).MethodsWe retrospectively collected clinical data from 124 consecutive MTC patients who underwent initial surgery at our institution. The data of 82 patients (from 2010 to 2018) and 42 patients (from January 2019 to November 2019) were used as the training set for building the model and as the test set for validating the model, respectively.ResultsIn the training group, the multivariate analyses indicated that male and MTC patients with higher preoperative basal calcitonin levels were more likely to have lateral LNM (P = 0.007 and 0.005, respectively). Multifocal lesions and suspected lateral LNM in preoperative ultrasound (US) were independent risk factors (P = 0.032 and 0.002, respectively). The identified risk factors were incorporated into a multivariate logistic regression model to generate the nomogram, which showed good discrimination (C-index = 0.963, 95% confidence interval [CI]: 0.9286–0.9972). Our model was validated with an excellent result in the test set and even superior to the training set (C-index = 0.964, 95% CI: 0.9121–1.000).ConclusionHigher preoperative basal calcitonin level, male sex, multifocal lesions, and lateral lymph node involvement suspicion on US are risk factors for lateral LNM. Our model and nomogram will objectively and accurately predict lateral LNM in patients with MTC.

【Objective】 Analyzing the temporal and spatial distribution of crop water demand and irrigation water demand.This study provides basic data and technical support for irrigation water management and the implementation of the strictest water resources management system in Xinjiang. 【Method】 We constructe the NDVI multi temporal sequence was based on the GF-1 satellite data. Used the supervised classification method to extract the crop planting structure in Aksu River Oasis. Combined with penman Monteith formula and GIS spatial analysis function, the temporal and spatial distribution characteristics of crop water demand and gross irrigation water demand in Oasis were analyzed. 【Result】 Under the multi temporal NDVI sequence, the maximum likelihood method was the best, with an overall accuracy of 93.08% and Kappa coefficient of 0.913, which could meet the requirements of large area classification. The results showed that the grain crops (rice, corn, wheat) were mainly distributed in Wushi and Wensu in the upper reaches of the basin, economic crops (cotton) were mainly distributed in Aksu, Alar and some farms of the first agricultural division, and fruit trees were mainly distributed in Aksu and Awati. The temporal and spatial distribution of crop water requirement and irrigation amount in the watershed is quite different. In terms of time, the water demand in spring and summer accounted for about 70% of the annual water demand; in terms of space, the water demand and irrigation amount in the area near Wensu county were significantly higher than those in other areas. At the same time, the water demand of the same crop is also different in different regions. The range of water demand of cotton is 704.4～808.8 mm, and the difference of water demand in different regions is about 100 mm in crops. 【Conclusion】 The method of combining multi temporal NDVI and supervised classification based on GF-1 data can realize the extraction of crop planting structure in large area. There are obvious differences in crop irrigation requirement in space and time in oasis area of Aksu basin. The spatial distribution map of crop water demand and irrigation amount can provide reference for the formulation of irrigation schedule and the optimization of agricultural water resources pattern.

Abstract Our study presents the genetic landscape betel quid chewing‐associated tongue carcinomas (BQ‐TCs). We compared the genetic landscape and mutational signatures of 15 BQ‐TCs, five nonbetel quid chewing‐associated tongue carcinomas (nBQ‐TCs), and 82 tongue carcinomas in general population from the TCGA (TCGA‐TCs) project. The highlights of this research mainly include: (a) The genetic landscape of BQ‐TC was characterized with frequent mutations in RASA1 gene and in CpG islands throughout the genome. (b) The BQ‐TC had a distinct mutational signature from that of nBQ‐TC and tongue carcinomas in the general population, and this signature was associated with the mutations in RASA1 and in CpG islands. (c) Our study indicates that betel quid (BQ) chewing classifies a distinct group of tongue carcinoma. The BQ chewing might not contribute to the tumorigenesis of tongue carcinomas as a mutagen.

Gradient structures were introduced via torsional treatment to Cu and CuAl alloys with different starting grain sizes and stacking fault energies (SFEs). Systematic investigations showed that the original grain sizes and SFEs of these materials play vital roles in affecting the formation of gradient structures and their corresponding mechanical properties. Large grain size and relatively low SFE are two critical requirements for the formation of the optimum gradient structure. A superior combination of high strength and good ductility can be achieved by torsional treatment in ultra-coarse-grained materials with low SFEs, which is attributed to the hierarchical structures that led to the simultaneous activations of different deformation mechanisms from full dislocation activities to partial dislocation slip and nano-twinning along the radial direction. Keywords: Gradient structure, Strength, Ductility, Twinning, Stacking fault energy

The mechanical properties, texture and microstructural evolution of a 6111 aluminum alloy during hot rolling and cold rolling deformation were systematically investigated in this article. The results show that cold rolling and hot rolling have significant effects on the tensile behaviors of the alloy. The shear texture and recrystallization texture mainly formed during the hot rolling deformation process, while the rolling texture mainly formed during the cold rolling deformation. The grain refinement mechanisms depend significantly on the rolling process. Movement of shear zone and recrystallization are the main grain refinement mechanisms during the hot rolling process, while dislocations tangling is the main grain refinement mechanism during the cold rolling process. The recrystallization textures and shear textures affect the anisotropy in elongation but the rolling textures affect significantly the anisotropy in yield strength.

Mechanical properties and microstructural evolution of Cu-10wt.%Zn and Cu-30wt.%Zn alloys after pre-torsional deformation have been investigated in this study. The results indicated that pre-torsional deformation can significantly enhance the strength of both Cu-10wt.%Zn and Cu-30wt.%Zn alloys without changing their shape and size, but with the sacrifice of the ductility. The pre-torsion deformation can introduce gradient hardness and microstructures along the radial direction, with the microstructures along the radial direction in Cu-30wt.%Zn alloy being "dislocations→stacking faults→twins (low density)". The stacking fault energy affects significantly the microstructure along the radial direction.

This work studied the effect of irrigation measures on water changes and crop growth in wheat fields during extreme drought years with rainfall of only 47.7 mm during the wheat growth period. Field investigation was carried out in the low plains of Hebei Province. In the experiment, six water-saving wheat varieties were used, and five irrigation levels (0 mm, 75 mm, 150 mm, 225 mm and 300 mm designated as T0, T1, T2, T3 and T4, respectively) were set in the spring. Results showed that wheat yield ranged from 70.5 kg/hm2 to 7053.0 kg/hm2. With the increase in irrigation times, yield level gradually increased and was highest under the T4 treatment. The effect of irrigation mode on panicle number was different from that on yield. The T0 treatment group had the smallest panicle number, whereas the other treatment groups showed slight differences and no discernible trend. The range of 1000-grain weight of different varieties of wheat was 33.36–46.68 g. Except for the T0 treatment, all other treatments increased with the increase in irrigation times. The difference between panicle and grain number was irregular and related to varieties. When population difference was large, yield was related to population size. When the population difference was small, yield was correlated with 1000-grain weight. From the perspective of soil water changes, in the late growth stage, the water content of deep soil under T0 and T4 treatments was higher, whereas that under T1 and T2 treatments was lower. This result indicated that T1 and T2 irrigation modes were conducive for the full utilisation of water in deep soil and were efficient water use modes. T1 and T2 were water saving irrigation models in this study. These conclusions can provide a theoretical basis for guiding the selection of irrigation patterns for wheat cultivation during spring.

Abstract Background The pygopus gene of Drosophila encodes an essential component of the Armadillo (β-catenin) transcription factor complex of canonical Wnt signaling. To better understand the functions of Pygopus-mediated canonical Wnt signaling in kidney development, targeted mutations were made in the two mammalian orthologs, Pygo1 and Pygo2. Results Each mutation deleted >80% of the coding sequence, including the critical PHD domain, and almost certainly resulted in null function. Pygo2 homozygous mutants, with rare exception, died shortly after birth, with a phenotype including lens agenesis, growth retardation, altered kidney development, and in some cases exencephaly and cleft palate. Pygo1 homozygous mutants, however, were viable and fertile, with no detectable developmental defects. Double Pygo1/Pygo2 homozygous mutants showed no apparent synergy in phenotype severity. The BAT-gal transgene reporter of canonical Wnt signaling showed reduced levels of expression in Pygo1-/-/Pygo2-/- mutants, with tissue-specific variation in degree of diminution. The Pygo1 and Pygo2 genes both showed widespread expression in the developing kidney, with raised levels in the stromal cell compartment. Confocal analysis of the double mutant kidneys showed disturbance of both the ureteric bud and metanephric mesenchyme-derived compartments. Branching morphogenesis of the ureteric bud was altered, with expanded tips and reduced tip density, probably contributing to the smaller size of the mutant kidney. In addition, there was an expansion of the zone of condensed mesenchyme capping the ureteric bud. Nephron formation, however, proceeded normally. Microarray analysis showed changed expression of several genes, including Cxcl13, Slc5a2, Klk5, Ren2 and Timeless, which represent candidate Wnt targets in kidney development. Conclusion The mammalian Pygopus genes are required for normal branching morphogenesis of the ureteric bud during kidney development. Nevertheless, the relatively mild phenotype observed in the kidney, as well as other organ systems, indicates a striking evolutionary divergence of Pygopus function between mammals and Drosophila. In mammals, the Pygo1/Pygo2 genes are not absolutely required for canonical Wnt signaling in most developing systems, but rather function as quantitative transducers, or modulators, of Wnt signal intensity.

Purpose: The survival rate of patients with medullary thyroid carcinoma (MTC) who fail to achieve a biochemical cure after surgery is reduced. This study aimed to investigate the prognostic factors affecting the survival of MTC patients who do not achieve a biochemical cure after surgery. Methods: Cox univariate and multivariate proportional hazard models were used to determine the influence of different variables on overall survival (OS). Pearson's chi-square test was used for categorical variables, and paired t-test was used for continuous variables. Results: In our study of 277 MTC patients treated between 2012 and 2022, there were 96 with raised postoperative 1-month calcitonin (Ct) levels (0–9.52 pg/ml). The overall survival (OS) rates of patients with high postoperative 1-month Ct values at 1, 3, and 5 years were 97.9%, 94.6%, and 86.8%, respectively. The univariate analysis revealed that patients with a postoperative 1-month Ct > 441.9 pg/ml had a greater risk of mortality than patients with postoperative 1-month Ct values ranging from 9.52 to 73.4 pg/ml (p = 0.043). Subsequent analyses revealed that receiving targeted therapy did not improve the OS of patients with distant metastasis among those with high postoperative 1-month Ct values (p = 0.527). Conclusion: This study confirmed that MTC patients who did not achieve biochemical remission after surgery had an increased risk of death when the Ct level was > 441.9 pg/ml 1 month after surgery. Additionally, for MTC patients who have not achieved biochemical remission and have experienced disease progression or distant metastasis after surgery, the use of targeted therapy does not prolong survival. [ABSTRACT FROM AUTHOR]

The cinnamoyl lipid compound youssoufene A1 (1), featuring a unique dearomatic carbon‐bridged dimeric skeleton, exhibits increased inhibition against multidrug resistant Enterococcus faecalis as compared to monomeric youssoufenes. However, the formation process of this intriguing dearomatization/dimerization remains unknown. In this study, an unusual "gene‐within‐gene" thioesterase (TE) gene ysfF was functionally characterized. The gene was found to naturally encodes two proteins, an entire YsfF with α/β‐hydrolase and 4‐hydroxybenzoyl‐CoA thioesterase (4‐HBT)‐like enzyme domains, and a nested YsfFHBT (4‐HBT‐like enzyme). Using an intracellular tagged carrier‐protein tracking (ITCT) strategy, in vitro reconstitution and in vivo experiments, we found that: i) both domains of YsfF displayed thioesterase activities; ii) YsfF/YsfFHBT could accomplish the 6π‐electrocyclic ring closure for benzene ring formation; and iii) YsfF and cyclase YsfX together were responsible for the ACP‐tethered dearomatization/dimerization process, possibly through an unprecedented Michael‐type addition reaction. Moreover, site‐directed mutagenesis experiments demonstrated that N301, E483 and H566 of YsfF are critical residues for both the 6π‐electrocyclization and dimerization processes. This study enhances our understanding of the multifunctionality of the TE protein family. [ABSTRACT FROM AUTHOR]

Gas therapy, represented by nitric oxide (NO), has shown a powerful anti-tumor effect. However, current NO therapy relies on NO precursors, which are often released prematurely during in vivo delivery, resulting in poor targeting and obvious toxic side effects. Herein, a core/shell-structured nanocatalyst is designed and prepared to catalyze the generation of NO in tumor without introduction of NO donor. In this system, C-Z@CM is prepared by coating the octahedron of Cu-MOF with a nano-ZnO, and camouflaging homologous tumor cell membrane. After the nanomedicine is taken up by tumor cells, ZnO reacts in situ with endogenous S-nitrosoglutathione (GSNO), which is highly expressed in tumors, to continuously and stably generate NO. In addition, the dispersed copper ions in C-Z@CM acts as the catalytic active centers of the Fenton-like reaction, which catalyzes H2O2 to generate a large number of hydroxyl radicals (*OH). Importantly, the cascade of NO and reactive oxygen species (ROS) leads to the massive production of more lethal reactive nitrogen species (RNS), further enhancing the therapeutic effect. Catalytic production of high concentrations of NO in situ in the tumor, combined with the cascade generation of ROS and RNS, accompanied by glutathione (GSH) depletion, achieving effective tumor suppression. [ABSTRACT FROM AUTHOR]

Thymoma is a rare thymic tumor but is the most common anterior mediastinal tumor. Currently, there are still limitations regarding to its screening and the pathology remains elusive. In this study, nontargeted metabolomic analysis of serum was performed to study the metabolic characteristics of thymoma using ultra-performance liquid chromatography—high resolution mass spectrometry (UPLC-HRMS) in positive and negative ionization modes. The metabolites that were differentially abundant in thymoma were identified by MS/MS and matching to chemical standards. Forty-one metabolic features differentially abundant in thymoma were identified in the corresponding age groups, including uridine, dipeptides, arachidonic acid (AA)/8,11,14,17-eicosatetraenoic acid, lactic acid and its dimer, acylcarnitines, lysophosphatidylcholines (LPCs), and ceramide 1-phosphate (Cer1P) (d18:0/3:0). Among these metabolites, lactic acid and 9-decenoylcarnitine also had significant abundance changes between thymoma patients with and without myasthenia gravis (MG). Uridine, lactic acid and Cer1P (d18:0/3:0) may also be associated with the aberrant immune status in thymoma. Orthogonal partial least squares—discriminant analysis (oPLS-DA) showed that classification between thymoma and thymic hyperplasia was possible with 94.7% sensitivity, 100% specificity and 96.8% accuracy for all patient samples. The discriminant feature panel included uridine, AA/8,11,14,17-eicosatetraenoic acid, lactic acid dimer, and N-(1-deoxy-1-fructosyl)tryptophan. The distinct serum metabolic characteristics of thymoma identified in this study may offer insights into improvement of the diagnosis and discovery of new therapeutic strategies for thymoma, in addition to providing information for study of the underlying molecular mechanism of thymoma pathogenesis. [ABSTRACT FROM AUTHOR]