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LS I +61° 303 is one of the rare gamma-ray binaries that emit most of their luminosity in photons with energies beyond 100 MeV (ref. ). It is well characterized—the ~26.5 day orbital period is clearly detected at many wavelengths—and other aspects of its multifrequency behaviour make it the most interesting example of its class. The morphology of high-resolution radio images changes with orbital phase, displaying a cometary tail pointing away from the high-mass star component and LS I +61° 303 also shows superorbital variability. A couple of energetic (~10 erg s), short, magnetar-like bursts have been plausibly ascribed to it. Although the phenomenology of LS I +61° 303 has been the subject of theoretical scrutiny for decades, there has been a lack of certainty regarding the nature of the compact object in the binary that has hampered our understanding of the source. Here, using observations with the Five-hundred-meter Aperture Spherical radio Telescope, we report the existence of transient radio pulsations from the direction of LS I +61° 303 with a period P = 269.15508 ± 0.00016 ms at a significance of >20σ. These pulsations strongly argue for the existence of a rotating neutron star within LS I +61° 303., This work made use of the data from FAST. FAST is a Chinese national mega-science facility, operated by National Astronomical Observatories, Chinese Academy of Sciences. We acknowledge the use of the ATNF Pulsar Catalogue. S.-S.W. and B.-J.W. thank Z. Pan for discussions on the FAST data analysis. S.-S.W. thanks Z.-X. Wang, S.-N. Zhang and K. Lee for many valuable discussions. J.L., D.F.T. and A.P. acknowledge discussions with the international team on ‘Understanding and unifying the gamma rays emitting scenarios in high mass and low mass X-ray binaries’ of the ISSI (International Space Science Institute), Beijing. We acknowledge support from National Key R&D programme of China grant numbers 2017YFA0402602 and 2021YFA0718500, National SKA Program of China grant numbers 2020SKA0120100 and 2020SKA0120201, National Natural Science Foundation of China grant numbers U2038103, 11733009, U2031205, U1938109 and 11873032, the Youth Innovation Promotion Association of the CAS (grant id 2018075), the Chinese Academy of Sciences Presidential Fellowship Initiative 2021VMA0001, National Foreign Experts Program of Ministry of Science and Technology of the People’s Republic of China grant number G2021200001L and the International Visiting Professorship programme of the University of Science and Technology of China grant number 2021BVR05. S.-S.W. acknowledges financial support from the Jiangsu Qing Lan Project. D.F.T. also acknowledges grants PID2021-124581OB-I00, PGC2018-095512-B-I00 and Spanish programme Unidad de Excelencia ‘María de Maeztu’ grant number CEX2020-001058-M. A.P. acknowledges financial support from the Italian Space Agency (ASI) and National Institute for Astrophysics (INAF) under grant agreement numbers ASI-INAF I/037/12/0 and ASI-INAF n.2017-14-H.0, from INAF ’Sostegno alla ricerca scientifica main streams dell’INAF’, Presidential Decree 43/2018 and from PHAROS COST Action number 16214.

Hepatic ischemia followed by reperfusion (I/R), a major clinical problem during liver surgical procedures, can induce liver injury with severe cell death including ferroptosis which is characterized by iron-dependent accumulation of lipid peroxidation. The HECT domain-containing ubiquitin E3 ligase HUWE1 (also known as MULE) was initially shown to promote apoptosis. However, our preliminary study demonstrates that high expression of HUWE1 in the liver donors corelates with less injury and better hepatic function after liver transplantation in patients. Thus, we investigate the role of HUWE1 in acute liver injury, and identify HUWE1 as a negative ferroptosis modulator through transferrin receptor 1(TfR1). Deficiency of Huwe1 in mice hepatocytes (HKO) exacerbated I/R and CCl

Many anticancer agents induce apoptosis, mitotic catastrophe or cellular senescence. Here, we report the functional characterization of an experimental inducer of tumor necrosis factor (TNF)-independent necrosis, necrocide-1 (NC1). NC1 (but not its stereoisomer) killed a panel of human cancer cells (but not normal cells) at nanomolar concentrations and with a non-apoptotic, necrotic morphotype, both in vitro and in vivo. NC1-induced killing was not inhibited by caspase blockers, anti-apoptotic BCL2 overexpression or TNFα neutralization, suggesting that NC1 elicits a bona fide necrotic pathway. However, pharmacological or genetic inhibition of necroptosis, pyroptosis and ferroptosis failed to block NC1-mediated cell death. Instead, NC1 elicited reactive oxygen species (ROS) production by mitochondria, and elimination of mitochondrial DNA, quenching of mitochondrial ROS, as well as blockade of mitochondrial permeability transition with cyclosporine A, interfered with NC1-induced cell death. NC1 induced hallmarks of immunogenic cell death incurring calreticulin (CALR) exposure, ATP secretion and high mobility group box 1 (HMGB1) release. Taken together, these data identify a previously uncharacterized signaling cascade leading to an immunogenic variant of mitochondrion-regulated necrosis, supporting the notion that eliciting regulated necrosis may constitute a valid approach for anticancer therapy.

Dysfunction of cell cycle control and defects of primary ciliogenesis are two features of many cancers. Whether these events are interconnected and the driving mechanism coordinating them remains elusive. Here, we identify an actin filament branching surveillance system that alerts cells of actin branching insufficiency and regulates cell cycle progression, cytokinesis and primary ciliogenesis. We find that Oral-Facial-Digital syndrome 1 functions as a class II Nucleation promoting factor to promote Arp2/3 complex-mediated actin branching. Perturbation of actin branching promotes OFD1 degradation and inactivation via liquid-to-gel transition. Elimination of OFD1 or disruption of OFD1-Arp2/3 interaction drives proliferating, non-transformed cells into quiescence with ciliogenesis by an RB-dependent mechanism, while it leads oncogene-transformed/cancer cells to incomplete cytokinesis and irreversible mitotic catastrophe via actomyosin ring malformation. Inhibition of OFD1 leads to suppression of multiple cancer cell growth in mouse xenograft models. Thus, targeting OFD1-mediated actin filament branching surveillance system provides a direction for cancer therapy.

PURPOSE: Due to the recent rise in immunotherapy research to treat glioblastoma (GBM), immunocompetent mouse models have become increasingly crucial. However, the character and kinetics of the immune response against the most prevalent immunocompetent GBM models, GL261 and CT2A, have not been well studied, nor has the impact of commonly-used marker proteins and foreign antigens. METHODS: In this study, we compared the immune response in these models using flow cytometry and immunohistochemistry as well as investigated several factors that influence the immune response, including kinetics, tumor size, and expression of commonly-used marker proteins and foreign antigens. We hypothesize that these factors influence the immune response enough to warrant consideration when studying new immunotherapeutic approaches for GBM. RESULTS: CT2A-Luc, but not GL261-Luc2, drastically increased the number of T cells in the brain compared with wild-type controls, and significantly altered CT2A’s responsiveness to anti-PD-1 antibody therapy. Additionally, a larger cell inoculum size in the GL261 model increased the T cell response’s magnitude at day 28 post-injection. CT2A and GL261 models both stimulate a peak T cell immune response at day 21 post-injection. CONCLUSIONS: Our results suggest that the impact of foreign proteins like luciferase on the intracranial immune response is dependent upon the model, with CT2A being more sensitive to added markers. In particular, luciferase expression in CT2A could lead to meaningful misinterpretations of results from immune checkpoint inhibitor (ICI) studies.

Without smoke-free legislation in Wuhan, China, we investigated secondhand smoke (SHS) exposure at home, school, and public places for never-smoking school-going adolescents in 2019. A cross-sectional study was carried out within the Global Youth Tobacco Survey (GYTS) framework. Weighted univariate, bivariate and multivariable analyses were conducted. The prevalence of SHS exposure among never-smoking adolescents at home, school and public places was 25.7%, 31.9% and 48.9%, respectively. Multivariable logistic regression analysis showed that parents smoking, peers smoking and observing teachers smoking in school were all significantly related to a higher probability of SHS exposure at home, school, and public places. Never-smoking adolescents who had smoking parents had 14 times (adjusted odds ratio [aOR], 14.00; 95% confidence interval [CI], 11.37–17.24) higher odds of SHS exposure at home; Never-smoking adolescents who observed teachers smoking in school had about 10 (aOR = 9.76; 95% CI = 7.13–13.36) and four times (aOR = 3.55; 95% CI = 2.77–4.55) higher odds of SHS exposure in school and public places, respectively. Adopting comprehensive smoke-free legislation in public places and smoke-free home rules and implementing and supervising smoke-free school policies may further reduce SHS exposure among adolescents.

The systemic inflammatory response caused by host-tumor interactions is currently recognized as a hallmark feature of cancer. No study has confirmed which systemic inflammatory factors can accurately predict the progression and long-term prognosis of gastric cancer (GC). Through the analysis of receiver operating characteristic curve (ROC), in the discovery cohort, a variety of indicators composed of usual inflammatory factors were compared. Fibrinogen-albumin ratio (FAR), which can accurately predict the long-term survival of GC patients was selected and was further verified in the test cohort and the external validation cohort. The ROC curve analysis showed that the area under curve (AUC) value of FAR on the overall survival (OS) of GC patients was higher than that of other combined markers (P < 0.01). Patients in the high FAR group showed more advanced pathological stages, larger tumor diameters, and more poorly differentiated pathological type than those in the low FAR group (P < 0.05). Logistic regression analysis elucidated that, FAR was an independent risk factor for LN metastasis and tumor invasion of GC. High FAR was an independent risk factor for poor prognosis of GC patients. The relationship between FAR and pathological stage of GC and long-term prognosis of patients was verified in the test cohort and the external validation cohort with the same FAR cutoff value. The results are consistent with those of the discovery cohort. As a new developed inflammation-related marker, FAR can independently and effectively predict the tumor burden and long-term prognosis of patients with advanced GC.

A new process of AlN removal from secondary aluminum dross (SAD) by pyrometallurgical treatment with added cryolite was applied for solving the problem of recycling the secondary aluminum dross. The response surface methodology (RSM) was used to design experiments and optimize parameters. The results show that adding the appropriate amount of cryolite can effectively promote the oxidation of AlN in the SAD, and too much cryolite will reduce the promotion effect. The effects of roasting temperature and cryolite on the denitrification rate are the most significant (p < 0.0001) followed by holding time. Predicted values of the denitrification rate are found to be in good agreement with experimental values (R2 = 0.9894 and $$R_{\text{adj}}^2=0.9775$$ , which confirms the validity of the model employed. The optimum conditions of roasting temperature of 750 °C, holding time of 194 min, mass fraction of cryolite of 17.7% are obtained according to the quadratic model. Under these conditions, the maximum actual denitrification rate reaches 94.71% and the AlN content in the SAD is only 0.55 wt%. The unfired brick with compressive strength of 18.62 MPa (GB/T 2542-2012) was prepared based on the roasted SAD.

To detect abnormal eye movements in Parkinson’s disease and explore its correlation with clinical characteristics and their value for diagnosis. We recruited forty-nine Parkinson’s disease patients, including 35 early Parkinson’s disease patients (Hoehn-Yahr: 1 to 2 stage) and 14 advanced Parkinson’s disease patients (Hoehn-Yahr: 3 to 5 stage) and 23 healthy controls. Clinical manifestations in Parkinson’s disease patients were recorded. Oculomotor performances including fixation, gaze, saccade in horizontal and vertical direction, and smooth pursuit in horizontal and vertical direction were measured by video-oculography. We found that five oculomotor parameters, namely square wave jerk frequency, latency of downward saccade, latency of upward saccade, accuracy of upward saccade, and gain of horizontal smooth pursuit were significantly different in Parkinson’s disease patients and controls. When combining all these five parameters, we got the diagnostic sensitivity of 78.3% and specificity of 95.2%. More deficits in upward saccade than in other directions were associated with disease duration and progression of Parkinson’s disease. Our primary study suggests that oculomotor examination might serve as an aid in the clinical assessment of Parkinson’s disease patients and differentiating between early Parkinson’s disease and normal controls.

Aconitine (ACO), a main active ingredient of Aconitum, is well-known for its cardiotoxicity. However, the mechanisms of toxic action of ACO remain unclear. In the current study, we investigated the cardiac effects of ACO and mesaconitine (MACO), a structurally related analog of ACO identified in Aconitum with undocumented cardiotoxicity in guinea pigs. We showed that intravenous administration of ACO or MACO (25 μg/kg) to guinea pigs caused various types of arrhythmias in electrocardiogram (ECG) recording, including ventricular premature beats (VPB), atrioventricular blockade (AVB), ventricular tachycardia (VT), and ventricular fibrillation (VF). MACO displayed more potent arrhythmogenic effect than ACO. We conducted whole-cell patch-clamp recording in isolated guinea pig ventricular myocytes, and observed that treatment with ACO (0.3, 3 μM) or MACO (0.1, 0.3 μM) depolarized the resting membrane potential (RMP) and reduced the action potential amplitude (APA) and durations (APDs) in a concentration-dependent manner. The ACO- and MACO-induced AP remodeling was largely abolished by an INa blocker tetrodotoxin (2 μM) and partly abolished by a specific Na+/K+ pump (NKP) blocker ouabain (0.1 μM). Furthermore, we observed that treatment with ACO or MACO attenuated NKP current (INa/K) and increased peak INa by accelerating the sodium channel activation with the EC50 of 8.36 ± 1.89 and 1.33 ± 0.16 μM, respectively. Incubation of ventricular myocytes with ACO or MACO concentration-dependently increased intracellular Na+ and Ca2+ concentrations. In conclusion, the current study demonstrates strong arrhythmogenic effects of ACO and MACO resulted from increasing the peak INa via accelerating sodium channel activation and inhibiting the INa/K. These results may help to improve our understanding of cardiotoxic mechanisms of ACO and MACO, and identify potential novel therapeutic targets for Aconitum poisoning.

Background Application of indocyanine green (ICG) fluorescence imaging is effective in guiding laparoscopic radical lymphadenectomy for gastric cancer. However, the optimal approach for indocyanine green injection is controversial. Therefore, the objective of this study was aimed to compare the efficacy and ICG injection between the preoperative submucosal and intraoperative subserosal approaches for lymph node (LN) tracing during laparoscopic gastrectomy. Method This randomized controlled trial (ClinicalTrials.gov, NCT04219332) included 266 patients with potentially resectable gastric cancer (cT1–T4a, N0/+, M0) enrolled from a tertiary teaching center between December 2019 and October 2020. The primary endpoint was total number of retrieved LNs. Results In total, 259 patients (n = 130 and n = 129 in the submucosal and subserosal groups, respectively) were included in the per-protocol analysis. There are no significant differences in total number of retrieved LNs between the two groups (49.8 vs. 49.2, P = 0.713). The rate of LN noncompliance in the submucosal group was comparable to that in the subserosal group (32.3% vs. 33.3%, P = 0.860). No significant difference was found between the submucosal and subserosal groups in terms of the incidence (17.7% vs. 16.3%; P = 0.762) or severity of postoperative complications. The mean fluorescence cost in the submucosal group was higher than that in the subserosal group ($335.3 vs. $182.4; P < 0.001). The overall treatment satisfaction score was lower in the submucosal group than in the subserosal group (70.5 vs. 76.1%, P = 0.048). Conclusion ICG administered by subserosal injection was comparable to that administered by submucosal injection for lymph node tracing in gastric cancer. However, the former approach imposed a lower economic and mental burden on patients undergoing laparoscopic D2 lymphadenectomy. Trial registration ClinicalTrials.gov, NCT04219332.

Lysosome–autophagosome fusion is critical to autophagosome maturation. Although several proteins that regulate this fusion process have been identified, the prefusion architecture and its regulation remain unclear. Herein, we show that upon stimulation, multiple lysosomes form clusters around individual autophagosomes, setting the stage for membrane fusion. The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein on lysosomes—vesicle-associated membrane protein 8 (VAMP8)—plays an important role in forming this prefusion state of lysosomal clusters. To study the potential role of phosphorylation on spontaneous fusion, we investigated the effect of phosphorylation of C-terminal residues of VAMP8. Using a phosphorylation mimic, we observed a decrease of fusion in an ensemble lipid mixing assay and an increase of unfused lysosomes associated with autophagosomes. These results suggest that phosphorylation not only reduces spontaneous fusion for minimizing autophagic flux under normal conditions, but also preassembles multiple lysosomes to increase the fusion probability for resuming autophagy upon stimulation. VAMP8 phosphorylation may thus play an important role in chemotherapy drug resistance by influencing autophagosome maturation.

Alternating current electrical dynamometer is a common device to measure the torque of engines, such as the gasoline engine. In order to solve the problems such as high cost, high energy consumption and complicated measurement system which exists in the direct measurement on the torque of alternating current electrical dynamometer, copper loss and iron loss are taken as two key factors and a soft-sensing model on the torque of alternating current electrical dynamometer is established using the fuzzy least square support vector machine (FLS-SVM). Then, the FLS-SVM parameters such as penalty factor and kernel parameter are optimized by adaptive genetic algorithm, torque soft-sensing is investigated in the alternating current electrical dynamometer, as well as the energy feedback efficiency and energy consumption during the measurement phase of a gasoline engine loading continual test is obtained. The results show that the minimum soft-sensing error of torque is about 0.0018, and it fluctuates within a range from −0.3 to 0.3 N-m. FLS-SVM soft-sensing method can increase by 1.6% power generation feedback compared with direct measurement, and it can save 500 kJ fuel consumption in the gasoline engine loading continual test. Therefore, the estimation accuracy of the soft measurement model on the torque of alternating current electrical dynamometer including copper loss and iron loss is high and this indirect measurement method can be feasible to reduce production cost of the alternating current electrical dynamometer and energy consumption during the torque measurement phase of a gasoline engine, replacing the direct method of torque measurement.

While a number of optimization models have been proposed for siting refueling/recharging stations for alternative fuel/electric vehicles, many of these approaches require detailed origin–destination (OD) data of refueling trips that are often very costly or challenging to obtain. This paper introduces two new arc-based coverage models for locating alternative fuel stations for regions where OD data are unavailable or unsuitable. Station spacing parameters are proposed to reduce redundant coverage while helping fill in regional coverage gaps. The first model is more suitable for early stages of planning, while the second addresses coverage overlap issues during later stages when a denser station network is formed. Both models can handle cases with a set of pre-existing stations. The new models are applied to planning a network of compressed natural gas (CNG) fueling stations for heavy-duty CNG-powered trucking in the Southwest USA. The models are generalizable to other regions, fuels, and vehicle types when applicable OD data are lacking.

Three-dimensional (3D) systems for laparoscopy provide surgeons with additional information on spatial depth not found in two-dimensional (2D) systems. This study enrolled 156 spleen-preserving splenic hilar lymphadenectomy (LSPSHL) patients in a randomized controlled trial (ClinicalTrials.gov Identifier NCT02327481) at the department of gastric surgery at Fujian Medical University Union Hospital between January 2015 and April 2016. The short-term efficacies were compared between the treatment groups. The unedited videos of 80 LSPSHL (40 procedures each for 3D and 2D) were rated for technical performance using the Generic Error Rating Tool. The data for 156 LSPSHL patients indicate that the estimated blood loss (EBL) (3D vs 2D = 66.3 vs. 99.0, P = 0.046) was significantly less in the 3D group. The postoperative recovery and complication rates were similar (P > 0.05). And there were no deaths within 30 days of surgery. Two observers analyzed 80 videos of LSPSHL. The results showed that there were fewer grasping-errors made in the 3D group than in the 2D group when dissecting the inferior pole region of spleen (IPRS) (P = 0.016) and the superior pole region of spleen (SPRS) (P = 0.022). Additionally, the inter-rater reliability was high regarding grasping-errors in the IPRS (intraclass correlation coefficient (ICC) 0.92) and in the SPRS (ICC 0.83). The ICC for the total number of errors was 0.82. The mean of errors in the 3D group (3D vs. 2D = 20.7 vs. 23.5, P = 0.022) was less than the 2D group. Compared with 2D LSPSHL, 3D technology reduces EBL and technical errors during splenic hilar dissection.

Few reports have examined the prognosis of or possible remedial treatments for patients with noncompliant D2 lymphadenectomy. We investigated the effect of noncompliance in lymph node (LN) dissection on long-term survival in gastric cancer (GC) patients after radical gastrectomy and explored intervention measures. Clinicopathological data were retrospectively analyzed in 2401 patients who underwent radical gastrectomy for GC. Noncompliance was defined as patients with more than one empty LN station, as described in the protocol of the Japanese GC Association. The overall noncompliance rate was 49.1%. The 3-year overall survival (OS) rate was significantly better in compliant than noncompliant patients (74.0% vs. 60.1%, P

With the growth of new energy economy, proton exchange membrane fuel cell (PEMFC) has great potential to be success. However, the lack of high-performance catalyst layer (CL) especially at cathode limits its applications. It is becoming increasingly important to understand interface property during electrocatalytic oxygen reduction reaction (ORR). Here, the rotating disk electrode (RDE) method is developed to study the temperature and Nafion ionomer content effects on interface formed between Nafion and Pt/C. The results show that the temperature has the significant influence on electrochemical active sites, charging double capacitance, and reaction polarization resistance at low Nafion content region. Excess Nafion loaded in CLs will turn to self-reunion and increase the exposed active sites. We find that the optimum Nafion loading is in the range of 30 to 40 wt.%. The highest specific activity we achieve is 107.8 μA/cm2.Pt at 60 °C with 0.4 of ionomer/catalyst weight ratio, corresponding to the kinetic current 283.5 μA at 0.9 V. This finding provides new insights into enhancing the Pt utilization and designing high-efficiency catalysts for ORR.

Soft and medium-hard rocks are subjected to high rheology under high stress, and they are prone to a relatively large-degree of deformation when perturbed by external impacting loads. The phenomenon where rock deformation is developed due to external impacting perturbation in the rheological state is defined as the rock rheological perturbation effect. This work presents a new experimental system for investigating the rock rheological perturbation effect with experiments on medium-hard red sandstone. Results from our analysis show that red sandstone changes under two mechanical mechanisms: deformation-hardening effects at low stress states, and damage-fracture effects at high stress states when impacted by certain external impacting loads. Red sandstone tested in our experiments has a strain threshold of about 90% of the ultimate strain under the perturbation effect; the red sandstone is sensitive to a perturbed load when its actual strain exceeds the threshold. The perturbed deformation process of the rock can be divided into three phases: decline, approximately constant speed and acceleration. The rock will be rapidly destroyed when the perturbed deformation accumulates to a certain degree. The perturbation effect of rock deformation under uniaxial compression is more obvious than that under axial compression. Based on our experiment, a constitutive relation of the rock rheological perturbation effect is developed.

To observe the efficacy of auricular acupoint sticking based on conventional treatment in treating pain in early-stage extremity trauma. A hundred eligible patients with acute soft tissue injury or acute closed fracture were randomized into an observation group and a control group by their admission sequence, 50 cases in each group. The two groups both received routine management including routine checking, external fixing, traction, raising up the affected limb, etc., as well as cold compress with Chinese medication (Xiao Zhong Zhi Tong Powder). In addition to the routine management, the control group was given oral administration of amidopyrine and phenacetin compound tablet, 1 tablet per dose, twice a day, which was then taken only when necessary or terminated after pain subsided. The observation group was given auricular acupoint sticking in addition to the routine management. The two groups were compared in terms of numerical rating scale (NRS) score, therapeutic efficacy and adverse reactions after pain was relieved. After the intervention, the NRS scores dropped significantly in both groups (P

Folate-containing dextran ligand (FA-Dextran-DTPA) was synthesized by the incorporation of diethylenetriaminepentaacetic acid (DTPA) and folate (FA) as a tumor-targeting group into dextran as a polymer carrier. This ligand was further reacted with gadolinium chloride to make a dextran gadolinium complex FA-Dextran-DTPA-Gd. The ligand and its gadolinium complex were characterized by 1H-NMR, FTIR, UV-Vis, average particle sizes and zeta potential, as well. In vitro properties including relaxivity, cytotoxicity assay, cellular uptake assay, and magnetic resonance imaging (MRI) were also evaluated. Compared with Gd-DTPA, FA-Dextran-DTPA-Gd possessed obviously higher relaxation effectiveness and lower cytotoxicity to HeLa cells. FA-Dextran-DTPA-Gd had a high affinity to the H460 and MDA-MB-231 tumor cells and can be taken up selectively by these tumor cells. Moreover, FA-Dextran-DTPA-Gd showed enhanced signal intensities (SI) of MRI and enhanced the contrast of MR images of tumor cells. These results indicated that FA-Dextran-DTPA-Gd showed the potential as a tumor-targeting contrast agent in MRI.

Metabolic profiling, gene cloning, enzymatic analysis, ectopic expression, and gene silencing experiments demonstrate that the anthocyanidin reductase (ANR) pathway is involved in the biosynthesis of proanthocyanidins in upland cotton. Proanthocyanidins (PAs) are oligomeric or polymeric flavan-3-ols, however, the biosynthetic pathway of PAs in cotton remains to be elucidated. Here, we report on an anthocyanidin reductase (ANR) gene from cotton fibers and the ANR pathway of PAs. Phytochemical analysis demonstrated that leaves, stems, roots, and early developing fibers produced PAs and their monomers, including (−)-epicatechin, (−)-catechin, (−)-epigallocatechin, and (−)-gallocatechin. Crude PA extractions from different tissues were boiled in Butanol:HCl. Cyanidin, delphinidin, and pelargonidin were produced, indicating that cotton PAs include diverse extension unit structures. An ANR cDNA homolog (named GhANR1) was cloned from developing fibers. The open reading frame, composed of 1,011 bp nucleotides, was expressed in E. coli to obtain a recombinant protein. In the presence of NADPH, the recombinant enzyme catalyzed cyanidin, delphinidin, and pelargonidin to (−)-epicatechin and (−)-catechin, (−)-epigallocatechin and (−)-gallocatechin, and (−)-epiafzelechin and (−)-afzelechin, respectively. The ectopic expression of GhANR11 in an Arabidopsis ban mutant allowed for the reconstruction of the ANR pathway and PA biosynthesis in the seed coat. Virus-induced gene silencing (VIGS) of GhANR11 led to a significant increase in anthocyanins and a decrease in the PAs, (−)-epicatechin, and (−)-catechin in the stems and leaves of VIGS-infected plants. Taken together, these data demonstrate that the ANR pathway contributes to the biosynthesis of flavan-3-ols and PAs in cotton.

Microscopy image data of human cancers provide detailed phenotypes of spatially and morphologically intact tissues at single-cell resolution, thus complementing large-scale molecular analyses, e.g., next generation sequencing or proteomic profiling. Here we describe a high-resolution tissue microarray (TMA) image dataset from a cohort of 71 prostate tissue samples, which was hybridized with bright-field dual colour chromogenic and silver in situ hybridization probes for the tumour suppressor gene PTEN. These tissue samples were digitized and supplemented with expert annotations, clinical information, statistical models of PTEN genetic status, and computer source codes. For validation, we constructed an additional TMA dataset for 424 prostate tissues, hybridized with FISH probes for PTEN, and performed survival analysis on a subset of 339 radical prostatectomy specimens with overall, disease-specific and recurrence-free survival (maximum 167 months). For application, we further produced 6,036 image patches derived from two whole slides. Our curated collection of prostate cancer data sets provides reuse potential for both biomedical and computational studies., Scientific Data, 4, ISSN:2052-4463

Anthocyanidin reductase (ANR) is an NADPH-/NADH-dependent enzyme that transfers two hydrides to anthocyanidins to produce three types of isomeric flavan-3-ols. This reductase forms the ANR pathway toward the biosynthesis of proanthocyanidins (PAs, which are also called condensed tannins). Here, we report cloning and functional characterization of an ANR (called VbANR) homolog from the leaves of Vitis bellula, a newly developed grape crop in southern China. The open reading frame (ORF) of VbANR is 1,017 bp in length and encodes 339 amino acids. A phylogenetic analysis and an alignment using 17 sequences revealed that VbANR is approximately 99.9 % identical to the ANR homolog from Vitis vinifera. The VbANR ORF is fused to the Trx gene containing a His-tag in the pET32a(+) vector to obtain a pET32a(+)-VbANR construct for expressing the recombinant VbANR. In vitro enzyme assays show that VbANR converts cyanidin, delphinidin, and pelargonidin to their corresponding flavan-3-ols. Enzymatic products include 2S,3R-trans- and 2R,3R-cis-flavan-3-ols isomers, such as (−)-catechin and (−)-epicatechin. In addition, the third compound that is observed from the enzymatic products is most likely a 2S,3S-cis-flavan-3-ol. To analyze the kinetics and optimize pH and temperature values, a UV spectrometry method was developed to quantify the concentrations of total enzymatic products. The optimum pH and temperature values are 4.0 and 40 °C, respectively. The K m , K cat, V max, and K cat/K m values for pelargonidin and delphinidin were similar. In comparison, VbANR exhibits a slightly lower affinity to cyanidin. VbANR uses both NADPH and NADH but prefers to employ NADPH. GFP fusion and confocal microscopy analyses revealed the cytosolic localization of VbANR. The overexpression of VbANR in ban mutants reconstructed the biosynthetic pathway of PAs in the seed coat. These data demonstrate that VbANR forms the ANR pathway, leading to the formation of three types of isomeric flavan-3-ols and PAs in the leaves of V. bellula.

Pear is a fruit species with worldwide distribution belonging to the Rosaceae family. In this study, transcriptomes of 12 different tissues of pear were newly assembled, with a total of 17,353 SSR loci identified. Within these, repetitive sequences with dinucleotide and trinucleotide motifs were more abundant than other types. We developed 194 EST-SSR makers from the assembled sequences to test on seven pear varieties from different genetic backgrounds, on which 132 EST-SSR primers had amplicons. There were 108 primers with dinucleotide and trinucleotide motifs detecting a total of 311 alleles, with an average per primer of 2.88 and 2.86, respectively. These had better quality than primers with tetranucleotides, pentanucleotides, and hexanucleotides. Fifty polymorphic markers divided 36 pear genotypes into two groups with a similarity coefficient of 0.62. Results showed that Japanese pears had a comparatively close relationship with Chinese pears, indicating the great potential of the novel EST-SSR makers in future evaluations of pear germplasm. Furthermore, 54 EST-SSR markers were selected to test transferability to 96 other Rosaceae cultivars from eight species, including Japanese apricot, plum, apricot, peach, cherry, apple, strawberry, and loquat. Seventeen EST-SSR primers had PCR amplification products in at least one of the 96 accessions, with the highest transferability was from pear to apple at 29.63 %. Transferability from pear to Japanese apricot, plum, apricot, peach, cherry, strawberry, and loquat was 9.26, 14.81, 11.11, 12.96, 5.56, 3.7, and 12.96 %, respectively. Therefore, the newly developed EST-SSR markers can contribute to exploring the genetic relationship, evolution and comparative genomics, and gene introgressions in the Rosaceae family.

To improve the energetics in the life cycle of an ideal baroclinic instability case, we develop a Physical Conserving Fidelity model (F-model), and we compare the simulations from the F-model to those of the traditional global spectral semi-implicit model (control model). The results for spectral kinetic energy and its budget indicate different performances at smaller scales in the two models. A two-way energy flow emerges in the generation and rapid growth stage of the baroclinic disturbance in the Fmodel. However, only a downscale mechanism dominates in the control model. In the F-model, the meso- and smaller scales are energized initially, and then an active upscale nonlinear cascade occurs. Thus, disturbances at prior scales are forced by both downscale and upscale energy cascades and by conversion from potential energy. An analysis of the eddy kinetic energy budget also shows remarkable enhancement of the energy conversion rate in the F-model. As a result, characteristics of the ideal baroclinic wave are greatly improved in the F-model, in terms of both intensity and time of formation.

Air-cooled steam condensers (ACSCs) have been extensively utilized to reject waste heat in power industry to save water resources. However, ACSC performance is so sensitive to ambient wind that almost all the air-cooled power plants in China are less efficient compared to design conditions. It is shown from previous research that the influence of ambient wind on the cell performance differs from its location in the condenser. As a result, a numerical model including two identical ACSC cells are established, and the different influence on the performance of the cells is demonstrated and analyzed through the computational fluid dynamics method. Despite the great influence from the wind speeds, similar cell performance is obtained for the two cells under both windless and wind speed conditions when the wind parallels to the steam duct. Fan volumetric effectiveness which characterizes the fan performance, as well as the exchanger heat transfer rate, drops obviously with the increasing wind speed, and performance difference between the exchanger pair in the same A-frame also rises continuously. Furthermore, different flow and heat transfer characteristics of the windward and leeward cell are obtained at different wind angles, and ambient wind enhances the performance of the leeward cell, while that of the windward one changes little.

This study identified eight S-haplotype-specific F-box genes (SFB alleles) and one S-haplotype-specific F-box-like gene (SFB-like gene) from genomic DNA by PCR combined with cleaved amplified polymorphic sequence markers in Prunus pseudocerasus and Prunus speciosa. The unknown sequences of C-termini were obtained by thermal asymmetric interlaced PCR. The whole nucleotide sequences of these genes were submitted to the EMBL/GenBank database. The SFBs shared typical structural features with SFBs from other Prunus species exhibiting gametophytic self-incompatibility. The deduced amino acid identity ranged from 77.1% to 82.4% among the four PpsSFBs and from 70.4% to 80.2% among the four PspeSFBs. The typical structural features were also detected in the PpsFB, but the sequence polymorphism was lower. The nucleotide identities ranged from 71.3% to 90.3% among the eight introns of the SFBs, the length of these introns varied from 95 to 121 bp and showed few polymorphisms. The distance between these SFBs and the corresponding S-RNases (S-ribonucleases) varied from 33 to 956 bp. Moreover, sequence analysis showed that interspecific amino acid identities in comparison with some other Prunus species were often higher than intraspecific identities, similar to S-RNase alleles. In addition, a similarity comparison found that the deduced amino acid identities among SFB alleles were higher than among S-RNase alleles, and the similarity data showed that the relationships among SFB alleles differed among S-RNase alleles, suggesting that the S-RNase and SFB alleles were separated but correlated during the coevolutionary process.

The aim was to investigate three dextran gadolinium complexes Dextran-DTPA-Gd as the potential MRI contrast agents in lymphatic system. Three dextran gadolinium complexes Dextran-DTPA-Gd containing differing amounts of Gd-DTPA were synthesized by the incorporation of Gd-DTPA to the hydroxyl groups of dextran. These dextran ligands and gadolinium complexes were characterized, and their properties in vitro and in vivo were also evaluated. Dextran-DTPA-Gd demonstrated obviously higher relaxation effectiveness than that of Gd-DTPA. The result of in vitro cytotoxicity assay showed that these macromolecular ligands and their corresponding gadolinium complexes had low cytotoxicity to HeLa cells. Dextran-DTPA-Gd greatly enhanced the contrast of MR images of normal politeal lymph nodes and reactive hyperplasia of politeal lymph nodes in rabbits and provided prolonged duration in lymphatic system with lower injection doses than that of Gd-DTPA. However, Dextran-DTPA-Gd displayed low signal enhancements in MR images of politeal lymph nodes with VX2 carcinoma in rabbits during the detection time. These dextran gadolinium complexes Dextran-DTPA-Gd can be taken up selectively by lymphatic system and showed the potential as MRI contrast agents in lymphatic system.

With the development of numerical weather prediction technology, the traditional global hydrostatic models used in many countries of the world for operational weather forecasting and numerical simulations of general circulation have become more and more unfit for high-impact weather prediction. To address this, it is important to invest in the development of global nonhydrostatic models. Few existing nonhydrostatic global models use consistently the grid finite difference scheme for the primitive equations of dynamical cores, which can subsequently degrade the accuracy of the calculations. A new nonhydrostatic global spectral model, which utilizes the Eulerian spectral method, is developed here from NCAR Community Atmosphere Model 3.0 (CAM3.0). Using Janjic’s hydrostatic/nonhydrostatic method, a global nonhydrostatic spectral method for the primitive equations has been formulated and developed. In order to retain the integrity of the nonhydrostatic equations, the atmospheric curvature correction and eccentricity correction are considered. In this paper, the Held-Suarez idealized test and an idealized baroclinic wave test are first carried out, which shows that the nonhydrostatic global spectral model has similar climate states to the results of many other global models for long-term idealized integration, as well as better simulation ability for short-term idealized integration. Then, a real case experiment is conducted using the new dynamical core with the full physical parameterizations of subgrid-scale physical processes. The 10-day numerical integration indicates a decrease in systematic error and a better simulation of zonal wind, temperature, and 500-hPa height.

Glutamic acid gamma-methyl ester (GAME) was used as substrate for theanine synthesis catalyzed by Escherichia coli cells possessing gamma-glutamyltranspeptidase activity. The yield was about 1.2-fold higher than with glutamine as substrate. The reaction was optimal at pH 10 and 45 degrees C, and the optimal substrate ratio of GAME to ethylamine was 1:10 (mol/mol). With GAME at 100 mmol, 95 mmol theanine was obtained after 8 h.

The relationship between plant absorption and accumulation of heavy metals and the effect of iron plaque on roots of wetland plants are unknown, especially for plants grown in heavy metal-contaminated soil. This experiment was designed to study the effects of iron addition on the formation of iron plaque in the rhizosphere of the wetland plant species Iris pseudacorus L. in artificial Pb-contaminated soil and the effects of iron plaque on Pb accumulation by plants. Soil was collected from 0- to 30-cm depth of a clayey illitic thermic typic epiaqualfs in an abandoned paddy field in Jiaxing of Zhejiang Province, China. The seeds of yellow flag (I. pseudacorus L.) were germinated in soil mixed with vermiculite and grown for 30 days. Three treatments of iron (0, 100, and 500 mg Fe kg−1 as FeSO4) were added when uniform seedlings were transplanted into plastic pots filled with 1.0-kg soil, which had been previously treated with four treatments of Pb [0, 100, 500, and 1,000 mg Pb kg−1 as Pb(NO3)2] and waterlogged for 72 days. The yellow flags were grown in a greenhouse for 60 days. The plaque on roots was extracted using the cold DCB (dithionite–citrate–bicarbonate) technique. The plant samples were digested with 10 mL concentrated nitric acid by microwave digestion. The concentration of Fe and Pb were determined using atomic spectrophotometry (NovAA300, Germany). The amount of iron plaque on the roots of yellow flag (I. pseudacorus L.) was markedly affected by Fe addition but not by Pb addition. The total Pb accumulated in plants was increased initially and then decreased with the addition of Fe in three lower Pb treatments (0, 100, and 500 mg Pb kg−1) but decreased with more Fe addition in the 1,000 mg Pb kg−1 treatment. The pH value was decreased with the addition of more iron, which increases Pb availability, and heavy doses of iron caused iron toxicity. Plant growth decreased due to iron toxicity at higher iron additions (500 mg kg−1), while Pb accumulation decreased. Intermediate levels of iron supply (100 mg kg−1) enhanced Pb absorption in roots, which improved phytoremediation effectiveness. Iron supply enhanced the amount of iron plaque and increased both Pb adsorbed on the roots and Pb uptake by plants. However, plant growth was inhibited by iron toxicity at high iron dose (500 mg kg−1) and biomass decreased. The intermediate iron dose (100 mg kg−1) generally enhanced Pb absorption and accumulation, which enhances the ability of yellow flag to remove Pb from Pb-contaminated soils.

Patients with localized prostate cancer can usually achieve initial response to conventional treatment. However, most of them will inevitably progress to advanced disease stage. There is a clear need to develop innovative and effective therapeutics for prostate cancer. Mouse survivin T34A (mS-T34A) is a phosphorylation-defective Thr34 → Ala dominant negative mutant, which represents a potential promising target for cancer gene therapy. This study was designed to determine whether mS-T34A plasmid encapsuled by DOTAP-chol liposome (Lip-mS) has the anti-tumor activity against prostate cancer, if so, to further investigate the possible mechanisms. In vitro, TRAMP-C1 cells were transfected with Lip-mS and examined for apoptosis by PI staining and flow cytometric analysis. In vivo, subcutaneous prostate cancer models were established in C57BL/6 mice, which were randomly assigned into three groups to receive i.v. administrations of Lip-mS, pVITRO2-null plasmid complexed with DOTAP-chol liposome (Lip-null) or normal saline every 2 days for eight doses. Tumor volume was measured. Tumor tissues were inspected for apoptosis by TUNEL assay. Microvessel density (MVD) was determined by CD31 immunohistochemistry. Alginate-encapsulated tumor cell test was conducted to evaluate the treatment effect on angiogenesis. Administration of Lip-mS resulted in significant inhibition in the growth of mouse TRAMP-C1 tumors. The anti-tumor response was associated with increased tumor cell apoptosis and decreased microvessel density. The present study may be of importance in the exploration of the potential application of Lip-mS in the treatment of a broad spectrum of tumors.

Self-incompatibility has been studied extensively at the molecular level in Solanaceae, Rosaceae, and Scrophulariaceae, all of which exhibit gametophytic self-incompatibility. In the present study, we successfully isolated nine S-RNase alleles from cultivars of Chinese cherry by PCR amplification from genomic DNA and stylar cDNA combining with cleaved amplified polymorphic sequence marker. Analysis of amino acid sequences revealed five novel S-alleles, S 2 , S 4 , S 6 , S 8 , and S 9 , with respective accession numbers in the NCBI database of EF541168, EF541173, EF541172, FJ628598, and FJ628599. Results showed that “Dongtang” and “Yinzhu” contained six S-alleles (S 1 , S 3 , S 5 , S 7 , S 8 , and S 9 ); “Taishanganying” contained four S-alleles (S 1 , S 2 , S 4 , and S 6 ); “Daiba”, “Dayingzui”, and “Xiaomizi” contained four S-alleles (S 1 , S 2 , S 5 , and S 8 ); “Laiyangduanzhi”, “Shuangquanchangba”, and “Daqingye” contained three S-alleles (S 1 , S 2 , and S 8 ). It is interesting that different cultivars collected from the same place hold the same S-genotypes. Moreover, pollination tests and pollen tube growth assays showed that nine cultivars were self-compatible. Chinese cherry presented in this article are naturally polyploidy, which is a very useful material for the study of self-compatibility, and much of this information will be valuable for further work on self-(in)compatibility of fruit tree in Rosaceae.

A Gram-positive, endospore-forming, catalase- and oxidase-positive, motile, rod-shaped, aerobic bacterium, designated strain JSM 079157(T), was isolated from surface seawater off the coastline of Naozhou Island in South China Sea. The organism was able to grow with 1-15% (w/v) total salts (optimum, 4-7%), and at pH 6.0-10.0 (optimum, pH 7.5) and 10-45 degrees C (optimum, 30 degrees C). meso-Diaminopimelic acid was present in the cell-wall peptidoglycan. The predominant menaquinone was MK-7, and the polar lipids were diphosphatidylglycerol and phosphatidylglycerol. The major cellular fatty acids were anteiso-C(15:0) (45.1%) and anteiso-C(17:0) (16.2%), and the DNA G + C content was 39.5 mol%. A phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that strain JSM 079157(T) should be assigned to the genus Virgibacillus, being related most closely to the type strains of Virgibacillus litoralis (97.4% sequence similarity), Virgibacillus necropolis (97.3%) and Virgibacillus carmonensis (97.1%). These four strains formed a distinct subcluster in the phylogenetic tree. The levels of DNA-DNA relatedness between the new isolate and the type strains of V. litoralis, V. necropolis and V. carmonensis were 30.4, 19.3 and 12.6%, respectively. The results of the phylogenetic analysis, combined with DNA-DNA relatedness data, phenotypic characteristics and chemotaxonomic information, support the suggestion that strain JSM 079157(T) represents a new species of the genus Virgibacillus, for which the name Virgibacillus zhanjiangensis sp. nov. is proposed. The type strain is JSM 079157(T) (=DSM 21084(T) = KCTC 13227(T)).