Search

Abstract Background Phosphorus is a macronutrient necessary for plant growth and development and its availability and efficient use affect crop yields. Leaves are the largest tissue that uses phosphorus in plants, and membrane phospholipids are the main source of cellular phosphorus usage. Results Here we identify a key process for plant cellular phosphorus recycling mediated by membrane phospholipid hydrolysis during leaf senescence. Our results indicate that over 90% of lipid phosphorus, accounting for more than one-third of total cellular phosphorus, is recycled from senescent leaves before falling off the plants. Nonspecific phospholipase C4 (NPC4) and phospholipase Dζ2 (PLDζ2) are highly induced during leaf senescence, and knockouts of PLDζ2 and NPC4 decrease the loss of membrane phospholipids and delay leaf senescence. Conversely, overexpression of PLDζ2 and NPC4 accelerates the loss of phospholipids and leaf senescence, promoting phosphorus remobilization from senescent leaves to young tissues and plant growth. We also show that this phosphorus recycling process in senescent leaves mediated by membrane phospholipid hydrolysis is conserved in plants. Conclusions These results indicate that PLDζ2- and NPC4-mediated membrane phospholipid hydrolysis promotes phosphorus remobilization from senescent leaves to growing tissues and that the phospholipid hydrolysis-mediated phosphorus recycling improves phosphorus use efficiency in plants.

The ductile-to-brittle transition (DBT) is an important characteristic that restricts the use of body-centered cubic metals as structural materials at low temperatures. This study shows a design of heterogenous lamellar microstructure (HLM), which is implemented in a low-density steel to promote the occurrence of delamination parallel to the direction of the main crack propagation, and result in delamination toughening effect. When the Charpy impact test temperature was reduced from room temperature to −196°C, the impact absorbed energy displayed a linear decline. The design of HLM brings a new pathway for developing economical BCC-structured metal plates with reliable low-temperature toughness.

Background The urban community health service centers in China have developed for nearly 20 years, but there is a lack of systematic research on their development, progress made, and existing problems. Objective To propose suggestions for the high-quality development of urban community health services centers in China by analyzing their development situation. Methods In October 2022, 50 community health service centers were selected from 13 provinces in the eastern, central and western regions by convenience sampling method. A self-developed research questionnaire based on the key core indicators for the assessment of urban community health services centers included two parts of basic data and evaluation content. Basic data included jurisdictional area, number of employees, number of outpatient visits, etc; the evaluation content included 4 gradeⅠindicators (institutional configuration, service function, service mode, and service support), 13 GradeⅡindicators and 33 GradeⅢindicators. The data of year 2006 (or the first year of the hospital's establishment and data) and 2021 were compared, and the survey results were reported in through "sojump". Results (1) Basic data: the number of community health service centers established before 2006 were 24 (accounting for 48.00%), and 26 after 2006 (accounting for 52.00%) ; comparing the year of 2006 or the first year of establishment, and the year of 2021, the number of employees was 67.00 (40.00, 101.00) and 94.00 (62.00, 162.00) respectively; the number of outpatient visits was 39 324.00 (22 620.00, 118 384.00) and 106 259.00 (44 999.00, 225 851.00) respectively; the total score of the questionnaire was 36.50 (28.13, 46.00) and 69.00 (56.38, 76.00), respectively. (2) The median scores of Grade I indicators institutional configuration, service mode and service function in 2021 were all higher than those in 2006 or the first year of establishment. The relative scoring rate of Grade I indicators in 2021, institutional configuration was 77.27% (25.50/33.00), service mode was 61.84% (23.50/38.00), service function was 76.92% (10.00/13.00), service support was 47.37% (9.00/19.00). The median score of structure area in the institutional configuration indicators was 0; among the service function indicators, the relative scoring rate of the diagnosis and treatment of common and chronic diseases in the community, and the inpatient service content were all 100.00%; the relative scoring rate of inpatient bed utilization rate was 25.00% (1.00/4.00). (3) Score of GradeⅡ、Ⅲ evaluation indicators of service function, service mode, and service support: The median score of public health items in service function increased from 2.00 points in 2006 or the first year of establishment to 9.50 points in 2021. The differences were statistically significant (P

Abstract Aim Patients with diabetes mellitus have poor prognosis after myocardial ischemic injury. However, the mechanism is unclear and there are no related therapies. We aimed to identify regulators of diabetic myocardial ischemic injury. Methods and results Mass spectrometry-based, non-targeted metabolomic approach was used to profile coronary sinus blood from diabetic and non-diabetic Bama-mini pigs at 0.5-h post coronary artery ligation. Six metabolites had a |log2 (Fold Change)|> 1.3. Among them, the most changed is arachidonic acid (AA), levels of which were 32 times lower in diabetic pigs than in non-diabetic pigs. The AA-derived products, PGI2 and 6-keto-PGF1α, were also significantly reduced. AA treatment of cultured cardiomyocytes protected against cell death by 30% at 48 h of high glucose and oxygen deprivation, which coincided with increased mitophagic activity (as indicated by increased LC3II/LC3I, decreased p62 and increased parkin & PINK1), improved mitochondrial renewal (upregulation of Drp1 and FIS1), reduced ROS generation and increased ATP production. These cardioprotective effects were abolished by PINK1(a crucial mitophagy protein) knockdown or the autophagy inhibitor 3-Methyladenine. The protective effect of AA was also inhibited by indomethacin and Cay10441, a prostacyclin receptor antagonist. Furthermore, diabetic Sprague Dawley rats were subjected to coronary ligation for 40 min and AA treatment (10 mg/day per animal gavaged) decreased myocardial infarct size, cell apoptosis index, inflammatory cytokines and improved heart function. Scanning electron microscopy showed more intact mitochondria in the border zone of infarcted myocardium in AA treated rats. Lastly, diabetic patients after myocardial infarction had lower plasma levels of AA and 6-keto-PGF1α and reduced cardiac ejection fraction, compared with non-diabetic patients after myocardial infarction. Plasma AA level was inversely correlated with fasting blood glucose. Conclusions AA protects against diabetic ischemic myocardial damage by promoting mitochondrial autophagy and renewal, which is related to AA derived PGI2 signaling. AA may represent a new strategy to treat diabetic myocardial ischemic injury.

K subgroup of Avian leukemia virus (ALV-K), as the latest reported exogenous ALV subgroup, can cause severe immunosuppression and tumorigenesis in infected chickens and bring serious threats to the poultry. Culling the positive chickens from breeder flocks is the most effective measurement for controling its infection at present. To setup a specific and rapid method for detecting ALV-K, an immunochromatographic strip (ICS) based on colloidal gold nanoparticles and double monoclonal antibodies (MAbs) immunochemical reaction was successfully developed. The solution containing colloidal gold particles (colloidal 20 nm) was prepared by sodium citrate reduction, and the ascites MAbs against ALV-K were purified and identified. The antibody concentration of the colloidal gold-MAb complex reaction system was 9.6 μg/mL, and the optimum pH was 7.5. The optimum coating concentrations of the captured antibody and quality control antibody on the NC membrane were 1.2 mg/mL and 0.6 mg/mL, respectively. The results showed that the prepared ICS could specifically detect ALV-K and had no cross reaction with exogenous ALV-A/B/J strains. Its sensitivity was 64 TCID50/mL against ALV-K and 0.25 μg/mL against ALV-K gp85 protein. The ICS stored at 4 °C for 180 d, at 25 °C for 45 d, and at 37 °C for 15 d could stably detect ALV-K in the samples. In comparision detection of 128 clinical samples, the coincidence rates in cloacal swab samples, serum samples, egg albumen samples and tissue homogenate samples between the ICS and the commercial ALV p27 antigen ELISA kit were 100 %, 100 %, 96.7 % and 96.9 %, respectively; moreover, the prepared ICS in operations was simpler and more convenient. This study supplies a new specific and rapid method for detecting ALV-K in clinics. This is the first report on the application of nano-colloidal gold ICS in ALV-K differential detection.

Abstract Enteral nutrition (EN) is important for critically ill patients. This study investigated the current situation of EN treatment in SHANGHAI intensive care units (ICUs). We hypothesized that improving EN practice in SHANGHAI may benefit the prognosis of ICU patients. Clinical information on EN use was collected using clinic information forms in 2019. The collected data included the patient’s general clinical information, EN prescription status, EN tolerance status, and clinical outcomes. The observation time points were days 1, 3, and 7 after starting EN. A total of 491 patients were included. The proportion of EN intolerance (defined as 0.5 g/kg/day on day 3 or day 7 might affect the 28-day mortality. Risk factors with EN tolerance on day 7 by logistic regression showed that the AGI grade on day 1 was a major factor against EN tolerance. The proportion of EN tolerance in SHANGHAI ICU patients was low. Achieving tolerance on day 7 after the start of EN is a protective factor for 28-day survival. Improving EN tolerance and protein intake maybe beneficial for ICU patients.

The hot-working behavior of high-Mn austenitic steel for liquefied natural gas carriers at the deformation temperature in the range of 1073–1273 K and the strain rate in the range of 0.01–10 s−1 was studied on a Gleeble-3800 thermomechanical simulator using a compression test. Electron backscatter diffraction was used to study the microstructure after deformation. Under each deformation condition, a peak stress appears in the stress-strain curve, which conforms to traditional dynamic recrystallization hot-working flow stress curves. A hyperbolic sine-law-type constitutive equation was established to predict the peak stress. The thermal deformation activation energy was 414.19 kJ/mol, and the stress index n was 4.94. The texture of the deformed grains consisted of strong and weak fibers along the compression direction. The main recrystallization mechanism was discontinuous dynamic recrystallization. The grain size of the discontinuous dynamic recrystallization grains tended to increase with increasing deformation temperature or decreasing strain rate. Processing maps were drawn based on the dynamic material model. At high deformation temperatures, the power consumption factor of dynamic recovery was greater than that of dynamic recrystallization, whereas at low deformation temperatures, the power consumption factor of discontinuous dynamic recrystallization was greater than that of dynamic recovery. There are two flow instability regions in the processing maps, 1243–1273 K/1-10 s−1 and 1073–1203 K/0.05–10 s−1. The formation of a ‘necklace microstructure’ was the main cause of deformation instability. The optimized process parameters for industrial production were 1243–1273 K/1-10 s−1.

Utilizing the ultrasonic nonlinear coefficient, the fatigue damage state of specimens can be accurately determined. This study rapidly assessed the fatigue damage of selective laser melting(SLM) GH4169 nickel-based alloy layers through higher harmonic detection techniques. Results showed that obvious second harmonics were detected when the frequency increased to 10MPa, and the second harmonics formed an amplitude lower than the fundamental wave. Compared with the initial specimen, the amplitude signal was more obvious in the specimen after 20,000 fatigue tests. There were equiaxed crystals, fusion lines, and columnar crystals in the samples, and many columnar crystals were arranged in regular directions. After the fatigue test, there were many fatigue cracks in the substrate, and the second harmonic amplitude also increased significantly. With the extension of the fatigue period, the β/β0 ratio increased. Different from test point 1, the ultrasonic nonlinear coefficients at point 2 and point 3 only showed a small increase trend relative to the fatigue cycle number. The research has a good theoretical support value for improving the fatigue damage detection accuracy of laser melting samples.

BackgroundOat (Avena sativa L.) belongs to the early maturity grass subfamily of the Gramineae subfamily oats (Avena) and has excellent characteristics, such as tolerance to barrenness, salt, cold, and drought. Aquaporin (AQP) proteins belong to the major intrinsic protein (MIP) superfamily, are widely involved in plant growth and development, and play an important role in abiotic stress responses. To date, previous studies have not identified or analyzed the AsAQP gene family system, and functional studies of oat AQP genes in response to drought, cold, and salt stress have not been performed.MethodsIn this study, AQP genes (AsAQP) were identified from the oat genome, and various bioinformatics data on the AQP gene family, gene structure, gene replication, promoters and regulatory networks were analyzed. Quantitative real-time PCR technology was used to verify the expression patterns of the AQP gene family in different oat tissues under different abiotic stresses.ResultsIn this study, a total of 45 AQP genes (AsAQP) were identified from the oat reference genome. According to a phylogenetic analysis, 45 AsAQP were divided into 4 subfamilies (PIP, SIP, NIP, and TIP). Among the 45 AsAQP, 23 proteins had interactions, and among these, 5AG0000633.1 had the largest number of interacting proteins. The 20 AsAQP genes were expressed in all tissues, and their expression varied greatly among different tissues and organs. All 20 AsAQP genes responded to salt, drought and cold stress. The NIP subfamily 6Ag0000836.1 gene was significantly upregulated under different abiotic stresses and could be further verified as a key candidate gene.ConclusionThe findings of this study provide a comprehensive list of members and their sequence characteristics of the AsAQP protein family, laying a solid theoretical foundation for further functional analysis of AsAQP in oats. This research also offers valuable reference for the creation of stress-tolerant oat varieties through genetic engineering techniques.

The effect of a high-fat diet (HFD) on mood is a widely debated topic, with the underlying mechanisms being poorly understood. This study explores the anxiolytic effects of a four-week HFD in C57BL/6 mice. Five-week-old mice were exposed to either an HFD (60% calories from fat) or standard chow diet (CD) for four weeks, followed by cannula implantation, virus infusion, behavioral tests, and biochemical assays. Results revealed that four weeks of an HFD induced anxiolytic-like behaviors and increased the protein levels of mature brain-derived neurotrophic factor (mBDNF) and phosphorylated tyrosine kinase receptor B (p-TrkB) in the medial prefrontal cortex (mPFC). Administration of a BDNF-neutralizing antibody to the mPFC reversed HFD-induced anxiolytic-like behaviors. Elevated BDNF levels were observed in both neurons and astrocytes in the mPFC of HFD mice. Additionally, these mice exhibited a higher number of dendritic spines in the mPFC, as well as upregulation of postsynaptic density protein 95 (PSD95). Furthermore, mRNA levels of the N6-methyladenosine (m6A) demethylase, fat mass and obesity-associated protein (FTO), and the hydrolase matrix metalloproteinase-9 (MMP9), also increased in the mPFC. These findings suggest that an HFD may induce FTO and MMP9, which could potentially regulate BDNF processing, contributing to anxiolytic-like behaviors. This study proposes potential molecular mechanisms that may underlie HFD-induced anxiolytic behaviors.

Summary: The circadian clock regulates temporal metabolic activities, but how it affects lipid metabolism is poorly understood. Here, we show that the central clock regulators LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) regulate the initial step of fatty acid (FA) biosynthesis in Arabidopsis. Triacylglycerol (TAG) accumulation in seeds was increased in LHY-overexpressing (LHY-OE) and decreased in lhycca1 plants. Metabolic tracking of lipids in developing seeds indicated that LHY enhanced FA synthesis. Transcript analysis revealed that the expression of genes involved in FA synthesis, including the one encoding β-ketoacyl-ACP synthase III (KASIII), was oppositely changed in developing seeds of LHY/CCA1-OEs and lhycca1. Chromatin immunoprecipitation, electrophoretic mobility shift, and transactivation assays indicated that LHY bound and activated the promoter of KASIII. Furthermore, phosphatidic acid, a metabolic precursor to TAG, inhibited LHY binding to KASIII promoter elements. Our data show a regulatory mechanism for plant lipid biosynthesis by the molecular clock.

Non-specific phospholipase C (NPC) is a plant-specific phospholipid-hydrolyzing enzyme. Here, the authors define the molecular basis of how Arabidopsis NPC works, and provide new mechanistic insights into the members of phospholipase family.

As there is a small amount of deformation in the center during the rolling process of ultra-heavy plates, it is extremely easy to cause poor mechanical properties in the center. Increasing the deformation in the center is the most feasible method to eliminate the deformation effects in the cross-section of ultra-heavy plates. In this study, the gradient temperature rolling (GTR) process is compared with the traditional uniform temperature rolling (UTR) process. It is found that the GTR process can significantly increase the deformation in the center and thereby refine the grains. The room temperature tensile test and instrumented Charpy impact test are used to test the strength at room temperature and impact energy at low temperature. Combined with the obtained impact load/energy displacement curve, the deformation and damage process under impact load are analyzed. The microstructure morphology and impact fracture obtained by different rolling processes in the center are analyzed by experimental methods such as OM, SEM, EBSD, etc. The prior austenite grain (PAG) boundary morphology is analyzed and the densities of grain boundaries are statistically quantified. The results showed that the strength, plasticity, and low-temperature toughness of the GTR process are improved compared to the UTR process, with increased dislocation density in the center microstructure, the density of PAG boundaries, and the density of packet boundaries. The size of the PAG in the center is refined by ~49%, the density of PAG boundaries increased by ~140%, the density of high-angle packet boundaries increased by ~39%, and the density of low-angle packet boundaries increased by ~49%. The crack propagation in the instrumented Charpy impact test of the GTR process showed stable expansion, indicating a ductile fracture compared to the semi-brittle fracture of the UTR process. The densities of PAG boundaries and high-angle packet boundaries are the most important factors affecting the strength and low-temperature toughness.

The efficient synthesis of nanosheets containing two metal ions is currently a formidable challenge. Here, we attempted to dope lanthanide-based bimetals into porphyrin-based metal-organic skeleton materials (MOFs) by microwave-assisted heating. The results of the EDX, ICP, and XPS tests show that we have successfully synthesized porphyrin-based lanthanide bimetallic nanosheets (Tb-Eu-TCPP) using a household microwave oven. In addition, it is tested and experimentally evident that these nanosheets have a thinner thickness, a larger BET surface area, and higher photogenerated carrier separation efficiency than bulk porphyrin-based bimetallic materials, thus exhibiting enhanced photocatalytic activity and n-type semiconductor properties. Furthermore, the prepared Tb-Eu-TCPP nanomaterials are more efficient in generating single-linear state oxygen under visible light irradiation compared to pristine monometallic nanosheets due to the generation of bimetallic nodes. The significant increase in catalytic activity is attributed to the improved separation and transfer efficiency of photogenerated carriers. This study not only deepens our understanding of lanthanide bimetallic nanosheet materials but also introduces an innovative approach to improve the photocatalytic performance of MOFs.

Abstract As a third‐generation infrared detector, the quantum cascade detector (QCD) exhibits an accurately adjustable wavelength, low noise, and ultrafast response characteristics. By introducing an additional doping layer, QCD also shows excellent application prospects in the broadband response. Herein, a coupled doped‐well QCD with an array structure located at very long‐wave infrared (VLWIR, ≈15 µm) is prepared. Based on the energy levels interaction and carrier distribution, the regulatory mechanism of the applied bias on the response characteristics is explored. At zero bias, the detector exhibits dual‐wavelength detection owing to the splitting of the energy levels, then transforms into single‐wavelength detection with the bias increasing. Simultaneously, the QCD device exhibits a broadband response (≈13–16 µm) from 15 to 300 K and an excellent detectivity of 1.52 × 1012 cm Hz1/2 W−1 at 15 K. A high R0A (>106 Ω cm2) and robust detectivity (>109 cm Hz1/2 W−1) are obtained at room temperature. The results of the response characteristics presented in this work provide a strategy for the flexible application of QCD in infrared detection.

Summary: To detect novel endometrial cancer risk variants, we leveraged information from endometrial cancer risk factors in a multi-trait GWAS analysis. We first assessed causal relationships between established and suspected endometrial cancer risk factors, and endometrial cancer using Mendelian randomization. Following multivariable analysis, five independent risk factors (waist circumference, testosterone levels, sex hormone binding globulin levels, age at menarche, and age at natural menopause) were included in a multi-trait Bayesian GWAS analysis. We identified three potentially novel loci that associate with endometrial cancer risk, one of which (7q22.1) replicated in an independent endometrial cancer GWAS dataset and was genome-wide significant in a meta-analysis. This locus may affect endometrial cancer risk through altered testosterone levels. Consistent with this, we observed colocalization between the signals for endometrial cancer risk and expression of CYP3A7, a gene involved in testosterone metabolism. Thus, our findings suggest opportunities for hormone therapy to prevent or treat endometrial cancer.

BackgroundIn the past few decades, heat waves and seasonal variation linked with global warming are causing frequent fluctuations of water temperature in aquatic environments, resulting in further challenges for marine organisms. As a poikilothermic marine animal and a temperate species, sea cucumber A. japonicus is also very sensitive to temperature variation and shows a limited ability to adapt to environmental temperature changes. However, the molecular mechanisms by which A. japonicus perceives signals from such a diverse environment including the trigger of aestivation still remain unclear. TRP (transient receptor potential) superfamily, as the great potential “sentinel” of the organism in response to the changes of the external environment signals, perceived little attention and will be the future great candidates for sensory function research in echinoderm.MethodsBLAST program was applied to identify the AjTRPs based on A. japonicus transcriptome database. Gene structure analysis of AjTRPs and phylogenetic analysis of TRPs were performed. The expression profiles of AjTRPs in different tissues and in response to different heat stress treatments (chronic/ acute) were measured using qRT-PCR.ResultsA total of 54 TRPs were identified in A. japonicus. Gene structure analysis showed that the exon numbers and the domains of AjTRPs varied greatly. Phylogenetic analysis indicated that AjTPRs were mainly grouped into six subfamilies: TRPA, TRPM, TRPC, TRPV, TRPML, and TRPP. Copy numbers of each TRP member in marine invertebrates including A. japonicus were more than those in vertebrates, however some TRP channel members were lost in invertebrates. Expression profile detection suggested that the representative 15 AjTRP genes belonging to 6 subfamilies were expressed in all tissues examined.ConclusionOur findings indicate that the plastic evolutionary history of TRP channel genes and suggest that TRPM2-1, TRPM2-2, TRPM3, and TRPC3-1 are potential thermo-TRP proteins involved in thermal regulation in A. japonicus. This work facilitates the knowledge of TRP-mediated sensory systems in echinoderms, provides new insights into the mechanisms of aestivation and global warming adaptation in marine invertebrates.

The hot working behavior of Al-alloyed δ-ferritic/martensitic dual-phase steel was investigated using a Gleeble-3800 thermomechanical simulator and compression tests at deformation temperatures and strain rates ranging from 800 to 1100 °C and 0.1 to 3 s−1, respectively. The shape of the flow stress curve of the experimental steel resembled that of traditional dynamic recovery (DRV) flow stress curves produced by work hardening, ferritic DRV, ferritic dynamic recrystallization (DRX), and austenitic dynamic phase transformation (DPT). Additionally, constitutive equations were established to predict the steady-state stress. The apparent deformation activation energy of the steel was approximately 264.7 kJ/mol. Moreover, the microstructure following deformation was investigated using electron backscatter diffraction. The primary dynamic restoration mechanisms of δ-ferrite comprised DRV and DRX at temperatures below and above 900 °C, respectively. However, with increasing deformation temperature and strain rate, the primary dynamic restoration mechanism of δ-ferrite shifted from continuous DRX (CDRX) to discontinuous DRX (DDRX). Additionally, the processing maps of the steel were established using the dynamic materials model. Further, based on the microstructure results, it was found that the power dissipation efficiency of ferritic CDRX, ferritic DDRX, ferritic DRV, and austenitic DPT gradually decreased. Additionally, only one domain of flow instability was identified, and it was located at 1025–1075 °C/0.6–3 s−1. Thus, to avoid unstable deformation regions, a two-stage design of the optimal process parameters for industrial processing is highly essential.

In severe low-visibility environments full of smoke, because of the performance degeneration of the near-infrared (NIR) collimation system of quantum drones communication networks, the improved dual-threshold method based on trend line analysis for long-wave infrared (LWIR) quantum cascade lasers (QCLs) is proposed, to achieve target acquisition. The simulation results show that smoke-scattering noise is a steeply varying medium–high-frequency modulation. At particle sizes less than 4 μm, the traditional dual-threshold method can effectively distinguish the target information from the smoke noise, which is the advantage of the LWIR laser compared to the NIR laser. For detecting lasers with high signal-to-noise ratios (SNRs), the method can achieve good target acquisition, by setting reasonable conventional thresholds, such as 0.7 times the peak intensity and 0.8 times the peak rising velocity. At low SNRs and steep intensity variation, the method can also achieve good target acquisition, by adaptively resetting new thresholds after filtering the detecting laser, such as 0.6 times the peak intensity and 0.6 times the peak rising velocity. The results of this paper will provide a reference for the performance improvement and refinement of the collimation system for wireless quantum communication networks in low visibility.

Abstract Background Whether different embolic particles with comparable diameter lead to similar beneficial effects in endovascular embolization of hemorrhoidal disease remains to be established. We sought to evaluate the efficacy and safety of different types of agents for superior rectal arterial embolization (SRAE) in patients with bleeding hemorrhoids. Methods Patients with recurrent episodes of internal hemorrhoidal bleeding and chronic anemia treated by SRAE in three tertiary hospitals between March 2017 and June 2020 were retrospectively evaluated. The patients were divided into two study groups based on the embolic materials: embolization with coils (2–3 mm) + gelfoam particles at 350–560 μm (Group A, n = 23), embolization with coils (2–3 mm) + microparticles at 300–500 μm (Group B, n = 18). The technical success, preliminary clinical efficacy (percentage of patients without hematochezia), postoperative complications and short-term follow-up outcomes were analysed. Results A total of 41 patients (27 males) with symptomatic hemorrhoids were included in the study, mean age was 47 ± 12 years (range 25–72). 39% (16) patients with grade II hemorrhoids while 61% (25) patients with grade III. The technical success rate of the embolization procedure was 100%, and the preliminary clinical efficacy (87.0% vs 88.9%) showed no significant difference between the 2 groups (p = 0.098). No patients reported post-procedural and short-term serious complications, such as infection, intestinal ischemia or massive hemorrhage during the follow-up period (range 6–15 months). Conclusions Both gelfoam particles and microparticles with comparable diameter in the endovascular treatment of hemorrhoidal bleeding demonstrated similarly good short-term efficacy and safety profile.

Pik Fang Kho et al. conduct multi-tissue transcriptome-wide association studies of endometrial cancer risk. Their results identify potential susceptibility genes for endometrial cancer, and provide avenues for the development of future treatments for this disease.

Abstract Background Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid cancer. The effect of traditional anti-tumor therapy is not ideal for the patients with recurrence, metastasis and radioiodine resistance. The abnormal expression of immune-related genes (IRGs) has critical roles in the etiology of PTC. However, the effect of IRGs on PTC prognosis remains unclear. Methods Based on The Cancer Genome Atlas (TCGA) and ImmPort databases, we integrated IRG expression profiles and progression-free intervals (PFIs) of PTC patients. First, we identified the differentially expressed IRGs and transcription factors (TFs) in PTC. Subsequently, an IRG model that can predict the PFI was constructed by using univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses of the differentially expressed IRGs in the TCGA. Additionally, a protein–protein interaction (PPI) network showed the interactions between the differentially expressed genes (DEGs), and the top 30 genes with the highest degree were extracted from the network. Then, the key IRG was identified by the intersection analysis of the PPI network and univariate Cox regression, which was verified the differential expression of by western blotting and immunohistochemistry (IHC). ssGSEA was performed to understand the correlation between the key IRG expression level and immune activity. Results A total of 355 differentially expressed IRGs and 43 differentially expressed TFs were identified in PTC patients. Then, eight IRGs were finally utilized to construct an IRG model. The respective areas under the curve (AUCs) of the IRG model reached 0.948, 0.820, and 0.831 at 1, 3 and 5 years in the training set. In addition, lactotransferrin (LTF) was determined as the key IRG related to prognosis. The expression level of LTF in tumor tissues was significantly lower than that in normal tissues. And the results of ssGSEA showed the expression level of LTF is closely related to immune activity. Conclusions These findings show that the prognostic model and key IRG may become promising molecular markers for the prognosis of PTC patients.

In this study, steels with different volume fraction of bainite and ferrite were obtained by tuning the rolling process to change the austenitic state before ferrite transformation. The volume fraction of bainite in the steel when the austenite was undeformed was ~83%, and in the steel when the austenite was deformed was ~36%. The yield strength at room temperature of the experimental steel with undeformed austenite was ~63.5 MPa higher than the experimental steel with deformed austenite, while the yield strength at 600 °C of the former was ~104.8 MPa higher than the latter. The main strengthening methods that led to difference in yield strength at elevated temperature are precipitation strengthening, dislocation strengthening and grain boundary strengthening. The experimental steel with higher volume fraction of bainite was characterized by higher Young's modulus and dislocation density at 600 °C, while the volume fraction of precipitates was relatively lower. The higher Young's modulus was mainly because of higher volume fraction of alloyed cementite precipitated from steel with higher volume fraction of bainite at 600 °C. Furthermore, the boundary densities of packet boundaries, block boundaries and sub-block boundaries had an important influence on the yield strength of steel at 600 °C.

Abstract Background Immune cells account for a large proportion of the tumour microenvironment in anaplastic thyroid carcinomas (ATCs). However, the expression pattern of immune-related genes (IRGs) in ATCs is unclear. Our study aimed to identify an immune-related signature indicating the dedifferentiation of thyroid cells. Methods We compared the differences in thyroid differentiation score (TDS), infiltration of immune cells and enriched pathways between ATCs and papillary thyroid carcinomas (PTCs) or normal thyroid tissues in the Gene Expression Omnibus database. Univariate and multivariable Cox analyses were used to screen prognosis-associated IRGs in The Cancer Genome Atlas database. After constructing a risk score, we investigated its predictive value for differentiation and survival by applying receiver operating characteristic and Kaplan–Meier curves. We further explored its associations with important immune checkpoint molecules, infiltrating immune cells and response to immunotherapy. Results Compared with PTCs or normal thyroid tissues, ATCs exhibited lower TDS values and higher enrichment of immune cells and activation of the inflammatory response. The quantitative analyses and immunohistochemical staining validated that most ATC cell lines and ATC tissues had higher expression of MMP9 and lower expression of SDC2 than normal thyroid samples and PTC. Higher risk scores indicates dedifferentiation and a worse prognosis. Additionally, the risk score was positively correlated with the immune checkpoint molecules PDL1, CTLA4, IDO1, and HAVCR2 and infiltration of multiple immune cells. Importantly, we found that the samples with higher risk scores tended to have a better response to immunotherapy than those with lower scores. Conclusion Our findings indicate that the risk score may not only contribute to the determination of differentiation and prognosis of thyroid carcinomas but also help the prediction of immune cells infiltration and immunotherapy response.

Nitrogen is a key macronutrient to plant growth. We found previously that increased expression of phospholipase Dε (PLDε), which hydrolyzes phospholipids into phosphatidic acid (PA), enhanced plant growth under nitrogen deficiency in Brassicaceae species Arabidopsis and canola. The present study investigated the effect of AtPLDε-overexpression (OE) on soybean (Glycine max), a species capable of symbiotic nitrogen fixation. AtPLDε-OE soybean plants displayed increased root length and leaf size, and the effect of AtPLDε-ΟΕ on leaf size was greater under nitrogen-deficient than -sufficient condition. Under nitrogen deficiency, AtPLDε-OE soybean plants had a higher chlorophyll content and activity of nitrogen assimilation-related enzymes than wild-type soybean plants. AtPLDε-OE led to a higher level of specific PA species in roots after rhizobium inoculation than wild type. AtPLDε-OE soybean plants also increased seed production under nitrogen deprivation with and without nodulation and decreased seed germination in response to high humidity storage and artificial aging. These results suggest that PLDε promotes nitrogen response and affects adversely seed viability during storage.

Abstract Background Lipid transporters play an essential role in lipid delivery and distribution, but their influence on seed oil production in oilseed crops is not well studied. Results Here, we examined the effect of two lipid transporters, FAX1 (fatty acid export1) and ABCA9 (ATP-binding cassette transporter subfamily A9) on oil production and lipid metabolism in the oilseed plant Camelina sativa. Overexpression (OE) of FAX1 and ABCA9 increased seed weight and size, with FAX1-OEs and ABCA9-OEs increasing seed length and width, respectively, whereas FAX1/ABCA9-OEs increasing both. FAX1-OE and ABCA9-OE displayed additive effects on seed oil content and seed yield. Also, OE of FAX1 and ABCA9 affected membrane lipid composition in developing pods, especially on phosphatidylcholine, phosphatidylethanolamine, and phosphatidylglycerol. The expression of some genes involved in seed oil synthesis, such as DGAT2, PDAT1, and LEC1, was increased in developing seeds of FAX1- and/or ABCA9-OEs. Conclusion These results indicate that increased expression of FAX1 and ABCA9 can potentially be applied to improving camelina oil production.

There was an error in the original publication [...]

Given the strong association between obesity and endometrial cancer risk, dietary factors may play an important role in the development of this cancer. However, observational studies of micro- and macronutrients and their role in endometrial cancer risk have been inconsistent. Clarifying these relationships are important to develop nutritional recommendations for cancer prevention. We performed two-sample Mendelian randomization (MR) to investigate the effects of circulating levels of 15 micronutrients (vitamin A (retinol), folate, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, β-carotene, calcium, copper, iron, magnesium, phosphorus, selenium, and zinc) as well as corrected relative macronutrient intake (protein, carbohydrate, sugar and fat) on risks of endometrial cancer and its subtypes (endometrioid and non-endometrioid histologies). Genetically predicted vitamin C levels were found to be strongly associated with endometrial cancer risk. There was some evidence that genetically predicted relative intake of macronutrients (carbohydrate, sugar and fat) affects endometrial cancer risk. No other significant association were observed. Conclusions: In summary, these findings suggest that vitamin C and macronutrients influence endometrial cancer risk but further investigation is required.

Summary: Endometrial cancer is a common gynaecological cancer with increasing incidence and mortality. In the last decade, endometrial cancer genome-wide association studies (GWAS) have provided a resource to explore aetiology and for functional interpretation of heritable risk variation, informing endometrial cancer biology. Indeed, GWAS data have been used to assess relationships with other traits through correlation and Mendelian randomisation analyses, establishing genetic relationships and potential risk factors. Cross-trait GWAS analyses have increased statistical power and identified novel endometrial cancer risk variation related to other traits. Functional analysis of risk loci has helped prioritise candidate susceptibility genes, revealing molecular mechanisms and networks. Lastly, risk scores generated using endometrial cancer GWAS data may allow for clinical translation through identification of patients at high risk of disease. In the next decade, this knowledge base should enable substantial progress in our understanding of endometrial cancer and, potentially, new approaches for its screening and treatment.

SQUAMOSA Promoter-binding protein-Like (SPL) genes affect a broad range of plant biological processes and show potential application in crop improvement by genetic modification. As the most widely planted forage crop in the world, biomass and abiotic stresses tolerance are important breeding targets for alfalfa (Medicago sativa L.). Nevertheless, the systematic analysis of SPL genes in alfalfa genome remains lacking. In the present study, we characterized 22 putative non-redundant SPL genes in alfalfa genome and uncovered the abundant structural variation among MsSPL genes. The phylogenetic analysis of plant SPL proteins separated them into 10 clades and clade J was an alfalfa-specific clade, suggesting SPL genes in alfalfa might have experienced gene duplication and functional differentiation within the genome. Meanwhile, 11 MsSPL genes with perfect matches to miRNA response elements (MREs) could be degraded by miR156, and the cleavage sites were gene specific. In addition, we investigated the temporal and spatial expression patterns of MsSPL genes and their expression patterns in response to multiple treatments, characterizing candidate SPL genes in alfalfa development and abiotic stress tolerant regulation. More importantly, overexpression of the alfalfa-specific SPL gene (MsSPL20) showed stable delayed flowering time, as well as increased biomass. Further studies indicated that MsSPL20 delayed flowering time by regulating the expression of genes involved in floret development, including HD3A, FTIP1, TEM1, and HST1. Together, our findings provide valuable information for future research and utilization of SPL genes in alfalfa and elucidate a possibly alfalfa-specific flowering time regulation, thereby supplying candidate genes for alfalfa molecular-assisted breeding.

Stress conditions can induce translocation of glyceraldehyde-3-phosphate dehydrogenase (GAPC) to the nucleus. Here Kim et al. show that in Arabidopsis, GAPC can interact with the NF-YC transcription factor subunit, enhance expression of heat-inducible genes and promote heat tolerance.

Abstract In this paper, we consider a class of nonautonomous discrete p-Laplacian complex Ginzburg–Landau equations with time-varying delays. We prove the existence and uniqueness of pullback attractor for these equations. The existing results of studying attractors for time-varying delay equations require that the derivative of the delay term should be less than 1 (called slow-varying delay). By using differential inequality technique, our results remove the constraints on the delay derivative. So, we can deal with the equations with fast-varying delays (without any constraints on the delay derivative).

Abstract Background α-Tocopherol is one of the most important vitamin E components present in plant. α-Tocopherol is a potent antioxidant, which can deactivate photoproduced reactive oxygen species (ROS) and prevent lipids from oxidation when plants suffer drought stress. γ-Tocopherol methyltransferase (γ-TMT) catalyzes the formation of α-tocopherol in the tocopherol biosynthetic pathway. Our previous studies showed that over-expression of γ-TMT gene can increase the accumulation of α-tocopherol in alfalfa (Medicago sativa). However, whether these transgenic plants confer increased drought tolerance and the underlying mechanism are still unknown. Results In the present study, we further evaluate transgenic alfalfa lines, and found that over-expression of MsTMT led to an increase in α-tocopherol and total tocopherol level in the transgenic lines compared with the control plant. It was revealed that drought tolerance of the transgenic alfalfa was remarkably increased, with alleviated oxidative damage and accumulation of more osmolytic substances. The stomatal development in transgenic plants was significantly inhibited on both sides of leaves, which may be resulted from the repression of MsSPCHLESS (MsSPCH) gene. The reduced stomatal density of transgenic plants contributes to a lower stomatal conductance and higher water use efficiency (WUE). Moreover, both RNA-seq and qRT-PCR analyses indicate that regulatory mechanism of MsTMT in drought involved in both ABA-dependent and ABA-independent pathways. Conclusion Our results suggest that MsTMT gene plays a positive role in regulating alfalfa response to PEG-simulated drought stress, which might involve complex mechanisms, including ROS scavenging system, stomatal development and multiple phytohormone signaling pathways. This study will broaden our view on the function of γ-TMT gene and provide new strategy for genetic engineering in alfalfa breeding.

Abstract Background Eukaryotic elongation factor-2 kinase (eEF2K) is a Ca 2+ /calmodulin (CaM)-dependent protein kinase that inhibits protein synthesis. However, the role of eEF2K in cancer development was reported paradoxically and remains to be elucidated. Methods Herein, A549 cells with eEF2K depletion or overexpression by stably transfected lentivirus plasmids were used in vitro and in vivo study. MTT and colony assays were used to detect cell proliferation and growth. Extracellular glucose and lactate concentration were measured using test kit. Immunoblot and co-immunoprecipitation assays were used to examine the molecular biology changes and molecular interaction in these cells. LC-MS/MS analysis and [γ- 32 P] ATP kinase assay were used to identify combining protein and phosphorylation site. Nude mice was utilized to study the correlation of eEF2K and tumor growth in vivo. Results We demonstrated that eEF2K inhibited lung cancer cells proliferation and affected the inhibitory effects of EGFR inhibitor gefitinib. Mechanistically, we showed that eEF2K formed a complex with PKM2 and STAT3, thereby phosphorylated PKM2 at T129, leading to reduced dimerization of PKM2. Subsequently, PKM2 impeded STAT3 phosphorylation and STAT3-dependent c-Myc expression. eEF2K depletion promoted the nuclear translocation of PKM2 and increased aerobic glycolysis reflected by increased lactate secretion and glucose. Conclusions Our findings define a novel mechanism underlying the regulation of cancer cell proliferation by eEF2K independent of its role in protein synthesis, disclosing the diverse roles of eEF2K in cell biology, which lays foundation for the development of new anticancer therapeutic strategies.

Abstract Background Lignocellulosic biomass has been commonly regarded as a potential feedstock for the production of biofuels and biochemicals. High sugar yields and the complete bioconversion of all the lignocellulosic sugars into valuable products are attractive for the utilization of lignocelluloses. It is essential to pretreat and hydrolyze lignocelluloses at high solids loadings during industrial processes, which is more economical and environmentally friendly as capital cost, energy consumption, and water usage can be reduced. However, oligosaccharides are inevitably released during the high solids loading enzymatic hydrolysis and they are more recalcitrant than monosaccharides for microorganisms. Results A fed-batch enzymatic hydrolysis of corn stover pretreated by the sodium hydroxide–methanol solution (SMs) at high solids loading was demonstrated to reach the high concentrations and yields of fermentable sugars. Glucose, xylose, cello-oligosaccharides, and xylo-oligosaccharides achieved 146.7 g/L, 58.7 g/L, 15.6 g/L, and 24.7 g/L, respectively, when the fed-batch hydrolysis was started at 12% (w/v) solids loading, and 7% fresh substrate and a standardized blend of cellulase, β-glucosidase, and hemicellulase were fed consecutively at 3, 6, 24, and 48 h to achieve a final solids loading of 40% (w/v). The total conversion of glucan and xylan reached 89.5% and 88.5%, respectively, when the oligosaccharides were taken into account. Then, a fed-batch culture on the hydrolysates was investigated for lipid production by Cutaneotrichosporon oleaginosum. Biomass, lipid content, and lipid yield were 50.7 g/L, 61.7%, and 0.18 g/g, respectively. The overall consumptions of cello-oligosaccharides and xylo-oligosaccharides reached 74.1% and 68.2%, respectively. Conclusions High sugars concentrations and yields were achieved when the enzyme blend was supplemented simultaneously with the substrate at each time point of feeding during the fed-batch enzymatic hydrolysis. Oligosaccharides were co-utilized with monosaccharides during the fed-batch culture of C. oleaginosum. These results provide a promising strategy to hydrolyze alkaline organosolv-pretreated corn stover into fermentable sugars with high concentrations and yields for microbial lipid production.

Energy level interaction and electron concentration are crucial aspects that affect the response performance of quantum cascade detectors (QCDs). In this work, two different-structured array QCDs are prepared, and the detectivity reaches 109 cm·Hz1/2/W at room temperature. The overlap integral (OI) and oscillator strength (OS) between different energy levels under a series of applied biases are fitted and reveal the influence of energy level interaction on the response performance. The redistribution of electrons in the cascade structure at room temperatures is established. The coupled doped-well structure shows a higher electron concentration at room temperature, which represents a high absorption efficiency in the active region. Even better responsivity and detectivity are exhibited in the coupled doped-well QCD. These results offer a novel strategy to understand the mechanisms that affect response performance and expand the application range of QCDs for long-wave infrared (LWIR) detection.

Inflammation caused by viral or bacterial infection is a major threat to human health globally. Blood C-reactive protein (CRP) has been proven to be a sensitive indicator for the occurrence and development of inflammation. Furthermore, a tiny change of blood CRP concentration may portend chronic diseases; therefore, high-sensitivity CRP (hs-CRP) detection in a quantitative, rapid, user-friendly, and low-cost manner is highly demanded. In this paper, we developed a europium-chelate polystyrene microsphere (EuPSM)-based lateral flow immunoassay (LFIA) integrating with a benchtop fluorescence analyzer for hs-CRP detection. The optimization of the EuPSM-based LFIA was implemented through adjusting the antibody density on EuPSM from 100% to 60% of the saturated density. Finally, the limit of detection of 0.76 pg/mL and detection range of 0.025–250 ng/mL were obtained. Moreover, the clinical application capability of the proposed platform was validated through detecting CRP in clinical serum samples, showing high consistency with the results obtained from the clinical standard method. Hence, the proposed EuPSM-based LFIA has been verified to be well suitable for hs-CRP detection, while also showing great applicability for sensitively and rapidly detecting other biomarkers.

Squamous cell carcinoma of the head and neck (HNSCC) is one of the six most common malignancies. HNSCC has both a high incidence and poor prognosis, and its prognostic factors remain unclear. Ferroptosis is a newly discovered form of programmed cell death that is iron-dependent. Increasing evidence indicates that targeting ferroptosis may present a new form of anti-tumor treatment. However, the prognostic value of ferroptosis-related genes (FRGs) in HNSCC is unclear. This study was designed to identify molecular markers associated with ferroptosis that influence prognosis in patients with HNSCC. We used HNSCC tumor and normal data from The Cancer Genome Atlas (TCGA) to identify prognosis-related FRGs. An FRG-based prognostic risk score was constructed, and its prognostic value for patients with HNSCC was evaluated using receiver operating characteristic curve (ROC) and nomogram analyses. The model was validated using the Gene Expression Omnibus (GEO) database. Univariate Cox regression analysis in patients with HNSCC revealed 11 FRGs that were significantly associated with overall survival (OS). We constructed a ferroptosis risk score model based on five genes and divided the patients into different risk groups based on its median value. Kaplan-Meier curve analysis showed that patients with a higher ferroptosis risk score had shorter OS (TCGA training set: P < 0.001, TCGA validation set: P < 0.05,GEO validation set: P < 0.001), and Gene Expression Profiling Interactive Analysis (GEPIA) further verified the relationships between these five genes and prognosis in patients with HNSCC. Multivariate Cox regression analysis showed that the risk score remained an independent predictor of OS after the exclusion of clinical confounders (HR > 1, P < 0.01). Significant differences in gene function enrichment analysis and immune cell infiltration status were identified between the two groups. The prognostic model can be used to predict the prognosis of patients with HNSCC. Moreover, the five FRGs may affect ferroptosis in HNSCC and thereby represent potential treatment targets. These results provide new directions for HNSCC treatment.

Summary: Studies investigating whether there is a causative link between the gut microbiota and lifespan have largely been restricted to invertebrates or to mice with a reduced lifespan because of a genetic deficiency. We investigate the effect of early-life antibiotic exposure on otherwise healthy, normal chow-fed, wild-type mice, monitoring these mice for more than 700 days in comparison with untreated control mice. We demonstrate the emergence of two different low-diversity community types, post-antibiotic microbiota (PAM) I and PAM II, following antibiotic exposure. PAM II but not PAM I mice have impaired immunity, increased insulin resistance, and evidence of increased inflammaging in later life as well as a reduced lifespan. Our data suggest that differences in the composition of the gut microbiota following antibiotic exposure differentially affect host health and longevity in later life.

Primary central nervous system lymphoma (PCNSL) is a rare but highly aggressive non-Hodgkin lymphoma. Treatment-related cardiovascular lesion has become one of the most common complications in patients with tumor. However, very little is known about the cardiovascular death (CVD) of the patients with PCNSL. This study aims at identifying the cardiovascular outcomes of PCNSL patients and making comparison on CVD with extra central nervous system lymphoma (ECNSL). Clinical information of PCNSL and ECNSL was retrieved from the Surveillance, Epidemiology and End Results database. The risk factors of CVD in PCNSL patients and the comparison on the CVD hazard between PCNSL and ECNSL were assessed with the competing risks regression. A 1:2 propensity score matching was used to reduce the imbalanced baseline characteristics between PCNSL and ECNSL. Four thousand thirty-eight PCNSL subjects and 246,760 ECNSL subjects were enrolled in this retrospective study. CVD was the leading cause (41.2%) of non-cancer death in PCNSL patients and mostly occurred within the first year of diagnosis. Age over 60s and diagnosis in 2000–2008 were significantly associated with the elevated risk of CVD in PCNSL patients, while chemotherapy and radiotherapy play no role on the cardiovascular outcomes. Compared with ECNSL patients, the risk of CVD in PCNSL patients were 40% approximately lower. The risk of CVD in the patients with PCNSL still remains unclear currently. Clinicians ought to pay more attention on the risk of CVD in PCNSL patients, especially the elder patients within the first year of diagnosis.

This study aimed to explore whether microRNA (miR) 223 affects microglial autophagy by targeting autophagy-related 16-like 1 (ATG16L1) in the kainic acid (KA) model of temporal lobe epilepsy (TLE). The miRNA and mRNA expression levels were quantified using quantitative real-time polymerase chain reaction (qRT-PCR), and the protein expression was investigated using western blotting. A dual-luciferase reporter assay was used to test the direct interaction between miR 223 and ATG16L1. In situ hybridization was performed to measure the hippocampal expression of miR 223. We used immunofluorescence staining to assess the expression of ATG16L1 and microtubule-associated protein light chain 3 (LC3) in the murine hippocampal microglia. Inhibitor of miR 223 was utilized to investigate the role of miR 223 in TLE, and the epileptic activity was assessed using electroencephalography (EEG). The autophagosomes were observed by transmission electron microscopy. In patients with TLE, the murine KA model of TLE, and the KA-stimulated BV2 cells, miR 223, and sequestosome 1 (SQSTM1/P62) expressions were remarkably increased, whereas ATG16L1 and LC3 levels were significantly decreased. Using a dual-luciferase reporter assay, ATG16L1 was determined as a direct target of miR 223. Treatment with antagomir 223 alleviated epilepsy, prevented abnormalities in EEG recordings and increased the ATG16L1 and LC3 levels in KA-treated mice. Inhibition of miR 223 induced increased autophagy in BV2 cells upon Rapamycin stimulation. These findings show that miR 223 affects microglial autophagy via ATG16L1 in the KA model of TLE. The miR 223/ATG16L1 pathway may offer a new treatment option for TLE.