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Abstract KDM6A (lysine demethylase 6A) has been reported to undergo inactivating mutations in colorectal cancer, but its function in the progression of colorectal cancer has not been evaluated using animal models of colorectal cancer. In this study, we found that knocking out KDM6A expression in mouse intestinal epithelium increased the length of villus and crypt, promoting the development of AOM (azoxymethane)/DSS (dextran sulfate sodium salt)-induced colorectal cancer. On the other hand, knocking down KDM6A expression promoted the growth of colorectal cancer cells. In molecular mechanism studies, we found that KDM6A interacts with HIF-1α; knocking down KDM6A promotes the binding of HIF-1α to the LDHA promoter, thereby promoting LDHA expression and lactate production, enhancing glycolysis. Knocking down LDHA reversed the malignant phenotype caused by KDM6A expression loss. In summary, this study using animal models revealed that KDM6A loss promotes the progression of colorectal cancer through reprogramming the metabolism of the colorectal cancer cells, suggesting that restoring the function of KDM6A is likely to be one of the strategies for colorectal cancer treatment.

Abstract Background Casuarina equisetifolia (C. equisetifolia) is a woody species with many excellent features. It has natural resistance against drought, salt and saline-alkali stresses. WRKY transcription factors (TFs) play significant roles in plant response to abiotic stresses, therefore, molecular characterization of WRKY gene family under abiotic stresses holds great significance for improvement of forest trees through molecular biological tools. At present, WRKY TFs from C. equisetifolia have not been thoroughly studied with respect to their role in salt and saline-alkali stresses response. The current study was conducted to bridge the same knowledge gap. Results A total of 64 WRKYs were identified in C. equisetifolia and divided into three major groups i.e. group I, II and III, consisting of 10, 42 and 12 WRKY members, respectively. The WRKY members in group II were further divided into 5 subgroups according to their homology with Arabidopsis counterparts. WRKYs belonging to the same group exhibited higher similarities in gene structure and the presence of conserved motifs. Promoter analysis data showed the presence of various response elements, especially those related to hormone signaling and abiotic stresses, such as ABRE (ABA), TGACG (MeJA), W-box ((C/T) TGAC (T/C)) and TC-rich motif. Tissue specific expression data showed that CeqWRKYs were mainly expressed in root under normal growth conditions. Furthermore, most of the CeqWRKYs were up-regulated by NaCl and NaHCO3 stresses with few of WRKYs showing early responsiveness to both stresses while few others exhibiting late response. Although the expressions of CeqWRKYs were also induced by cold stress, the response was delayed compared with other stresses. Transgenic C. equisetifolia plants overexpressing CeqWRKY11 displayed lower electrolyte leakage, higher chlorophyll content, and enhanced tolerance to both stresses. The higher expression of abiotic stress related genes, especially CeqHKT1 and CeqPOD7, in overexpression lines points to the maintenance of optimum Na+/K+ ratio, and ROS scavenging as possible key molecular mechanisms underlying salt stress tolerance. Conclusions Our results show that CeqWRKYs might be key regulators of NaCl and NaHCO3 stresses response in C. equisetifolia. In addition, positive correlation of CeqWRKY11 expression with increased stress tolerance in C. equisetifolia encourages further research on other WRKY family members through functional genomic tools. The best candidates could be incorporated in other woody plant species for improving stress tolerance.

Abstract Background Iatrogenic complications of endovascular treatment for central venous stenosis have not yet been reported. Here we present a case of a patient on maintenance hemodialysis who developed catheter-related superior vena cava syndrome and subsequently suffered from hemorrhagic pericardial tamponade after undergoing percutaneous transluminal angioplasty and stenting. Case presentation A 72-year-old male patient presented with uremia, and had been receiving maintenance hemodialysis for the past five years. The patient initially presented with dysfunction of the dialysis catheter (a cuffed tunneled double-lumen catheter in the right internal jugular vein). Imaging examination revealed a segmental occlusion of the superior vena cava stretching from the distal end of the dialysis catheter up to right atrium entrance, apparent compensatory dilatation of the azygos vein, and abundant subcutaneous collaterals. The patient underwent percutaneous transluminal balloon dilatation and stenting (covered stent) of the superior vena cava in the Cath Lab. During the procedure, with forceful advancement of the guidewire, it was observed to progress for a distance before a “smoke” appeared, and an outward spillage of contrast agent was visible, which suggested a possible vessel puncture leading into the mediastinum. Unfortunately, postoperative hemorrhagic pericardial tamponade occurred and the patient developed cardiogenic shock. He experienced symptoms included chest tightness and breath shortness with a recorded blood pressure of 84/60mmHg. After draining 600 ml of bloody fluid through pericardiocentesis, the patient’s symptoms alleviated and his condition improved. Conclusions The case emphasizes the need for increased attention to iatrogenic endovascular injuries during catheter placement and endovascular treatment, such as causing pericardial hemorrhage leading to cardiac tamponade.

Effectively combining various evolutionary computing algorithms and leveraging the advantages of each can significantly enhance the convergence speed and solution quality of the algorithm. However, a mere combination of evolutionary computing algorithms may not comprehensively improve optimization performance and may even lead to poorer performance in certain optimization problems. The aim of the paper is to provide a fundamental integrating platform and method based on species explode and deracinate algorithm. Utilizing the species explode and deracinate algorithm as a foundation, this study presents a hybrid algorithm named SED-PSO algorithm by utilizing the particle swarm optimization algorithm as an exemplar. The outcomes of the simulations conducted on 27 benchmark functions published by the Competition on Evolutionary Constrained demonstrate that the SED-PSO algorithm exhibits exceptional convergence accuracy, robust stability, and rapid convergence speed. The simulation results comprehensively illustrate that the species explode and deracinate algorithm serves as a fundamental integrating platform for diverse evolutionary computing algorithms, while also incorporating the strengths of each algorithm. Additionally, the outcomes of the optimization of sensor network coverage reveal that the SED-PSO algorithm exhibits superior solution quality, minimal occurrence of local extremum, and enhanced stability and efficacy.

Summary: CD8+ T cells are rendered exhausted in tumor and chronic infection. Among heterogeneous exhausted T cells, a subpopulation of progenitor-like (Tpex) cells have been found important for long-term tumor or pathogen control and are also the main responders in immunotherapy. Using an RFP reporter mouse for the orphan nuclear receptor NR4A1, originally characterized as critical in T cell dysfunction, we discover that the reporter is highly expressed in Tpex cells in tumor and chronic infection. Enforced expression of Nr4a1 promotes Tpex cell accumulation, whereas tumor control is improved after Nr4a1 deletion, associated with increased effector function but decreased long-term maintenance of CD8+ T cells. Integrating chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) analysis, NR4A1 is found to bind and promote the expression of Tpex-related genes, as well as suppress terminal differentiation-associated genes. This study therefore has identified a key role of NR4A1 in Tpex regulation and provides a promising target for immunotherapy.

The single-event effects (SEEs) of frequency divider circuits and the radiation tolerance of the hardened circuit are studied in this paper. Based on the experimental results of SEEs in InP HBTs, a transient current model for sensitive transistors is established, taking into account the influence of factors such as laser energy, base-collector junction voltage, and radiation position. Moreover, the SEEs of the (2:1) static frequency divider circuit with the InP DHBT process are simulated under different laser energies by adding the transient current model at sensitive nodes. The effect of the time relationship between the pulsed laser and clock signal are discussed. Changes in differential output voltage and the degradation mechanism of unhardened circuits are analyzed, which are mainly attributed to the cross-coupling effect between the transistors in the differential pair. Furthermore, the inverted output is directly connected to the input, leading to a feedback loop and causing significant logic upsets. Finally, an effective hardened method is proposed to provide redundancy and mitigate the impacts of SEEs on the divider. The simulation results demonstrate a notable improvement in the radiation tolerance of the divider.

In this work, we demonstrate the surface functionalization of cellulose triacetate membrane with co-deposition of polydopamine (PDA)/polyethyleneimine (PEI) and silver nanoparticles (AgNPs) for antifouling property in municipal wastewater treatment. PDA/PEI was first coated on the membrane surface by single-step co-deposition, while AgNPs were formed in situ through catechol groups of PDA immobilizing silver ions and subsequently reducing. The successful surface modification was verified by different membrane characterization techniques. The modified PDA/PEI-nAg CTA membrane exhibits enhanced hydrophilicity and improved antiadhesion and antimicrobial activity. Furthermore, the functional layer had an indistinctive effect on the membrane transport parameters. In addition, dynamic forward osmosis (FO) fouling experiment with raw municipal wastewater as feed solution indicated that the PDA/PEI-nAg CTA membrane exhibited notably lower water flux decrease compared to the nascent CTA membrane. The results of confocal laser scanning microscopy (CLSM) showed that PDA/PEI-nAg CTA membranes effectively reduced the adsorption of organic foulants (proteins and polysaccharides) and inhibited the formation and development of the fouling layer. The membrane surface modification of the CTA membrane with PDA/PEI and AgNPs efficiently mitigated membrane fouling in municipal wastewater treatment. HIGHLIGHTS AgNPs were in situ immobilized on a CTA FO membrane with PDA/PEI coating layer.; The PDA/PEI coating and Ag in situ generation had no considerable impact on the mass transport coefficients of the CTA FO membrane.; The PDA/PEI-nAg CTA-modified membrane exhibited excellent antifouling performance for raw municipal wastewater treatment.;

Abstract Purpose In recent years, considerable research has been conducted on the use of plant growth regulators (PGRs) to improve crop yields. Large amounts of PGRs are applied to regulate crop growth. However, few studies have assessed the impact of PGRs, which leave soil residues, on soil microorganisms, especially rhizobia. Methods In this study, the influence of inoculation of soybean roots with Sinorhizobium fredii and Bradyrhizobium japonicum exposed to gibberellin A3 (GA3) and mepiquat chloride (MC) on nodule number, nitrogenase activity, and a symbiotic nitrogen fixation gene (fixA) expression was studied. The nitrate content, free amino acids, and nitrate reductase activity of the roots, and seed yield and quality of soybean were measured. Result Nodulation was promoted to some extent, whereas nitrogenase activity and fixA expression were inhibited to some extent by treatment with GA3; however, these effects were reversed by treatment with MC. In a pot experiment to study phenotypic characteristics, rhizobia treatment in combination with GA3 or MC significantly improved soybean yield and seed nitrogen content, and increased the root nitrate content, free amino acid content, and nitrate reductase activity. Conclusion The results indicated that PGRs, which leave soil residues, have significant positive effects on the growth and activity of soybean and rhizobia.

Hulless barley (Hordeum vulgare L. var. nudum Hook. f.), belonging to the genus Gramineae, has high and steady output and thus considered as a principal food crop by Tibetan people. Hulless barley grain can be used for food, brewing, and functional health product development, while its straw serves as an essential supplementary forage and is a crucial cereal crop. Lodging can reduce the yield and quality of barley grain and straw, and it hinders mechanical harvesting. It is a significant factor affecting high and stable yields of barley. Unlike other Poaceae plants (such as rice, wheat), hulless barley is mainly grown in high-altitude regions, where it is susceptible to low temperatures, strong winds, and heavy rainfall. As a result, its stem lodging resistance is relatively weak, making it prone to lodging during the growth period. In this study, we observed that the lignin concentration and the contents of lignin monomers (H, S, and G), and neutral detergent fibre of the lodging-resistant variety Kunlun14 were substantially greater than those of the lodging-sensitive variety Menyuanlianglan. We performed the weighted gene co-expression network analysis (WGCNA) and Short Time-series Expression Miner (STEM) analysis of both the lodging-resistant and lodging-sensitive varieties. Through transcriptome sequencing analysis at different developmental stages, combined with the previously annotated genes related to lodging resistance, a total of 72 DEGs were identified. Among these DEGs, 17 genes were related to lignin, cellulose, and hemicellulose synthesis or regulation, including five transcription factors about NAC, MYB and WRKY. Our results provide a basis for further exploring the molecular mechanism of stem lodging resistance in hulless barley and provide valuable gene resources for stem lodging resistance molecular breeding.

Abstract This study evaluated epidemic temporal aspects of Japanese encephalitis (JE) and investigated the weather threshold of JE response across eight climate subtypes between 2005 and 2019 in Gansu Province, China. Epidemiological data were collected from the China Information System for Disease Control and Prevention (CISDCP). Three epidemic temporal indices [frequency index (α), duration index (β), and intensity index (γ)] were adopted for the comparison of epidemic features among different climate subtypes. In addition, the local indicators of spatial association (LISA) technique was used to detect the hot-spot areas. The category and regression tree (CART) model was used to detect the response threshold of weather variables in hot-spot areas across climate subtypes. Among eight climate subtypes in Gansu, in most hot-spot areas (i.e., high–high clusters), α, β, and γ were detected in the climate subtypes of subtropical winter dry (Cwa), temperate oceanic continental (Cwb), and continental winter dry (Dwa and Dwb). According to the CART analysis, a minimum monthly temperature is required for Japanese encephalitis virus (JEV) transmission, with different threshold values among the climatic subtypes. In temperate climate zones (Cwa and Cwb), this threshold is 19 °C at a 1-month lag. It is lower in continental winter dry climate zones: 18 °C in Dwa (snow climate, dry winter, and hot summer) and 16 °C in Dwb (snow climate, dry winter, and warm summer). Additionally, some areas of the areas with temperate arid (BWk and BSk) had the first JE cases. Further studies to detect whether the climate change influence the JEV’s distribution in Gansu Province are needed.

Abstract Background Cell therapy is a key technology to prevent sacrificing normal skin. Although some studies have shown the promise of human epidermal stem cells (EpiSCs), the efficacy, biosafety and quality control of EpiSC therapy have not been systematically reported. Methods The biosafety, stemness maintenance and wound repair of EpiSC were systematically verified by in vitro and in vivo experiments. EpiSC were prepared from the foreskin using a collagen type IV rapid adherence method. The EpiSCs were identified by flow cytometry, immunofluorescence staining and cell morphology. The well-growing passage 1 (P1) EpiSCs were used to determine the proliferation curve (counting method). EpiSC clone formation assay was performed by Giemsa staining. Nude mice were used to prepare a full-thickness skin defect wound model to detect the repair effect of EpiSCs. The biosafety of EpiSCs was double tested in vitro and in vivo. Results The results showed that the expression of specific markers and clone formation efficiency was stable when passage 1 (P1) to P8 cells were cultured, and the stemness rate of P8 cells was close to 85.1%. EpiSCs were expanded in vitro for 25 days, the number of cells reached 2.5 × 108, and the transplantable area was approximately 75% of the total body surface area (TBSA). At 45 days, the total number of cells was approximately 30 billion, and the transplantable area was approximately the size of a volleyball court. A nude mouse wound model indicated that EpiSCs could rapidly close a wound. On postinjury day 7, the wound epithelialization rate in the cell transplantation group was significantly higher than that in the NaCl group (P

IntroductionAs one of the most common malignant tumors in clinical practice, hepatocellular carcinoma (HCC) is a major threat to human health, where alpha-fetoprotein (AFP) is widely used for early screening and diagnoses. However, the level of AFP would not elevate in about 30-40% of HCC patients, which is clinically referred to as AFP-negative HCC, with small tumors at an early stage and atypical imaging features, making it difficult to distinguish benign from malignant by imaging alone.MethodsA total of 798 patients, with the majority being HBV-positive, were enrolled in the study and were randomized 2:1 to the training and validation groups. Univariate and multivariate binary logistic regression analyses were used to determine the ability of each parameter to predict HCC. A nomogram model was constructed based on the independent predictors. ResultsA unordered multicategorical logistic regression analyses showed that the age, TBIL, ALT, ALB, PT, GGT and GPR help identify non-hepatic disease, hepatitis, cirrhosis, and hepatocellular carcinoma. A multivariate logistic regression analyses showed that the gender, age, TBIL, GAR, and GPR were independent predictors for the diagnosis of AFP-negative HCC. And an efficient and reliable nomogram model (AUC=0.837) was constructed based on independent predictors.DiscussionSerum parameters help reveal intrinsic differences between non-hepatic disease, hepatitis, cirrhosis, and HCC. The nomogram based on clinical and serum parameters could be used as a marker for the diagnosis of AFP-negative HCC, providing an objective basis for the early diagnosis and individualized treatment of hepatocellular carcinoma patients.

Aiming at the multiobjective topology optimization design of the structure, this paper proposes a method to establish the comprehensive objective function based on the normalized subobjective of the compromise programming method and to determine the weight coefficient of the subobjective of the comprehensive objective function by the analytic hierarchy process (AHP). By using statistical analysis and modal analysis, the static and dynamic characteristics of the gear can be obtained. The single objective topology optimization is used to reduce the compliance of the gear and elevate the low-order natural frequency, and the frequency weighting method is used to suppress the oscillation phenomenon in the frequency-single-objective optimization. AHP was used to determine the weight coefficient of each subtarget. The compromise programming method is used for multiobjective topology optimization, and the gear design is improved according to the optimization results. By analyzing the improved gear structure, the weight of the optimized gear is reduced by 25.3%. The overall stiffness performance and strength performance are enhanced, and the natural frequencies of each order are improved to different degrees.

In this study, the enzymatic method was used to prepare Se-containing peptides (SeCPPs) with antioxidant activity from Cardamine enshiensis. The extraction conditions of protein of C. enshiensis (SeCP) were optimized by single-factor experiments and orthogonal test with protein extraction rate as the index. The enzymatic parameters of SeCP were optimized with DPPH∙ and ABTS+∙ scavenging rate as the investigated index, and ultrafiltration equipment was used to determine the best protocol for the SeCPPs. The reducing power and Fe2+ chelating ability of Se-containing peptides were investigated. The results showed that the optimal conditions for the extraction of SeCP were: 0.1 mol/L NaOH solution, liquid to material ratio 45:1 mL/g, extraction temperature 60 °C, extraction time 3 h, twice. Under this condition, the extraction rate of SeCP was 72.91%. The optimum conditions for the enzymatic preparation of antioxidant SeCPPs were: 4% substrate concentration, 1.0% enzyme substrate ratio, 1 h digestion time, 1 kDa molecular weight retained by ultrafiltration membrane. The Se content in SeCPP was 362.378 mg/kg, and the EC50 values of DPPH∙ and ABTS+∙ scavenging rate were 0.435 and 0.399 mg/mL, respectively. Besides, SeCPPs showed better reducing power and Fe2+ chelating ability.

Inosine 5′-monophoaphate (IMP) is a food additive that promotes serious lipohyperplasia in the liver of C57/KsJ-db/db (db/db) mice. Thus, IMP taken orally by healthy mice might also damage their health. To date, how IMP affects health after being taken by healthy animals is still unclear. Therefore, we investigated the health of C57BL/6J mice affected by IMP intake. Our data revealed that C57BL/6J mice administered 255 μM IMP daily via oral gavage for 4 months caused hyperlipidemia and an increase in body fat rate. The expressions of acetyl-CoA carboxylase 1 (ACC1) and phosphorylated acetyl-CoA carboxylase 2 (ACC2) in hepatocytes increased though the administration of IMP, promoting the phosphorylation of adenosine 5′-monophosphate-activated protein kinase (AMPK). The conversion of acetyl-CoA into triglycerides (TGs) was promoted by ACC1. These TGs were transported from the hepatocytes to avoid the development of non-alcoholic fatty liver disease (NAFLD), causing a deficiency of acetyl-CoA in the liver, and then, the increased phosphorylated ACC2 promoted the cytoplasm fatty acids entering the mitochondria and conversion into acetyl-CoA through the fatty acid β-oxidation pathway, causing a deficiency in fatty acids. Therefore, the liver showed enhanced absorption of exogenous fatty acids, which were converted into TGs, causing lipohyperplasia. In conclusion, an excessive IMP intake promotes metabolic dysfunction in adipose tissue.

The Sup35 prion protein of budding yeast has been reported to undergo phase separation to form liquid droplets both at low pH in vitro and when energy depletion decreases the intracellular pH in vivo. It also has been shown using purified proteins that this phase separation is driven by the prion domain of Sup35 and does not re-quire its C-terminal domain. In contrast, we now find that a Sup35 fragment consisting of only the N-terminal prion domain and the M-domain does not phase separate in vivo; this phase separation of Sup35 requires the C-terminal domain, which binds Sup45 to form the translation termination complex. The phase-separated Sup35 not only colocalizes with Sup45 but also with Pub1, a stress granule marker protein. In addition, like stress granules, phase separation of Sup35 appears to require mRNA since cycloheximide treatment, which inhibits mRNA release from ribosomes, prevents phase separation of Sup35. Finally, unlike Sup35 in vitro, Sup35 condensates do not disassemble in vivo when the intracellular pH is increased. These results suggest that, in energy-depleted cells, Sup35 forms supramolecular assemblies that differ from the Sup35 liquid droplets that form in vitro.

The earth surface in the Sichuan Basin and its periphery is geologically complex, which causes low signal-to-noise ratio of seismic data, poor imaging quality of seismic profiles and great difficulty in data acquisition. In order to ensure high-quality operation of the seismic survey project in the complex surface of the Sichuan Basin, researchers have been working continuously to solve the bottleneck problems in the seismic acquisition technology for complex surface in recent years. In addition, the upgrading of acquisition technology and operation capacity is promoted effectively by means of technical innovation, and a series of key technologies for seismic acquisition are developed. And the following application results of this series of technologies are obtained. First, the optimization design technology of the geometry based on wave equation forward modeling and actual data, combined with prestack migration imaging can show the influence of different acquisition schemes on the prestack imaging effect of complex targets more directly, which makes the seismic acquisition scheme more economic and effective. Second, by extracting landform risks and surface obstacle information intelligently, combined with field fine reconnaissance, landform risk identification and hierarchical evaluation and indoors intelligent optimization of well-shot physical point deployment are conducted, and thus the GIS+ intelligent deployment technology of shot point in complex surface is formed, which effectively reduces the risks of operation. Third, the cavity excitation technology which reduces the initial pressure of explosive pulse and extends the explosive action time of explosives can increase the conversion rate of rock excitation energy into effective elastic wave energy and the reflected energy and improve the quality of seismic single shot data. Fourth, combination of the automatic evaluation technology for field seismic data acquired in mountainous regions and the KL-GMLiveQC1.0 software can improve the evaluation efficiency, reduce the evaluation cost and ensure the high-quality acquisition of seismic data in complex surface. In conclusion, this series of key seismic acquisition technologies greatly improve the signal-to-noise ratio and resolution of seismic data, lay a foundation for fine reservoir prediction, and ensure the continuous important breakthrough of three-dimensional natural gas exploration and development in the gas fields of marine carbonate rock, shale gas, volcanic rock and shallow tight sandstone gas in the Sichuan Basin.

Introduction Mechanical thrombectomy (MT) using stent retrievers or a direct aspiration first-pass technique has proven to yield better results over intravenous thrombolysis in treating acute ischaemic stroke caused by large vessel occlusion (LVO). However, the treatment of intracranial atherosclerotic stenosis-related LVO remains unclear and has been a critical problem in daily clinical practice, as it can cause a relatively high failure rate for MT. Whether direct angioplasty and/or stenting is clinically feasible and shows advantage in reducing delay to revascularisation with better functional outcome compared with MT with rescue angioplasty and/or stenting remains unclear. This study seeks to provide direct and practical clinical evidence for clinicians.Methods and analysis The main databases of PubMed, the Cochrane library, Embase and Web of Science will be screened for related studies published after1 January 2015. Primary outcomes include successful recanalisation and 90-day favourable outcome. Secondary outcomes include puncture to revascularisation time, vascular complication (perforation, dissection and vasospasm), intracerebral haemorrhage, hospital-related complications and 90-day mortality. The Newcastle-Ottawa Scale will be adopted to assess risk bias of observational studies. The I2 statistic will be used to assess heterogeneity.Ethics and dissemination No primary data of patients are needed. Therefore, ethics approval is unnecessary. The results of this systematic review and meta-analysis will be published in a peer-reviewed journal.PROSPERO registration number CRD42021268061.

The unsaturated zone is the critical zone of the earth, which is closely related to the human living environment and health safety. Carbon dioxide plays a crucial role in the ecological environment and global climate change. In order to explore the potential risk of high concentration CO2 invasion into the unsaturated zone to the ecological environment, and based on CO2 simulation platform of in situ research filed of water and environment of the Chang’an University, we present a controlled experiment, in which 5%, 10% and 15% pure CO2 was respectively injected into the local soil planted with five typical plants (ryegrass, wheat, corn, pea and amaranth) to assess the potential impact of CO2 invasion on the environment, specifically on soil and plants. Botanical investigation and chemical analyses of soil samples (at depth from 20 to 30 cm) shows a significant adverse impact of CO2 injection on plant growth, including declining plant height, number of leaves and fruit weight. Small changes were observed in mineralogy and bulk chemistry, showing the change of soil pH and reduction of nitrogen, available potassium, available phosphorus, etc. Different plants show different and complicated responses to CO2 stress, depending on plant life history, including photosynthetic pathways, osmoregulation and antioxidant systems. On the whole, C3 monocotyledon ryegrass and C4 monocotyledon corn show greater sensitivity than other plants, suggesting their potential as indicator plants for evaluation of CO2 impact on ecological environment.

Forkhead box O transcriptional factors, especially FoxO1 and FoxO3a, play critical roles in physiologic and pathologic immune responses. However, the function of FoxO4, another main member of the FoxO family, in lymphoid cells is still poorly understood. Here, we showed that loss of FoxO4 in T cells augmented IFN-γ production of Th1 cells in vitro. Correspondingly, conditional deletion of FoxO4 in CD4+ T cells enhanced T cell–specific responses to Listeria monocytogenes infection in vivo. Genome-wide occupancy and transcriptomic analyses identified Dkk3 (encoding the Dickkopf-3 protein) as a direct transcriptional target of FoxO4. Consistent with the FoxO4-DKK3 relationship, recombinant DKK3 protein restored normal levels of IFN-γ production in FoxO4-deficient Th1 cells through the downregulation of lymphoid enhancer–binding factor 1 (Lef1) expression. Together, our data suggest a potential FoxO4/DKK3 axis in Th1 cell differentiation, providing what we believe to be an important insight and supplement for FoxO family proteins in T lymphocyte biology and revealing a promising target for the treatment of immune-related diseases.

The yeast Sup35 protein misfolds into the infectious [PSI+] prion, which is then propagated by the severing activity of the molecular chaperone, Hsp104. Unlike other yeast prions, this prion is unique in that it is efficiently cured by the overexpression as well as the inactivation of Hsp104. However, it is controversial whether curing by overexpression is due to the dissolution of the prion seeds by the trimming activity of Hsp104 or the asymmetric segregation of the prion seeds between mother and daughter cells which requires cell division. To answer this question, we conducted experiments and found no difference in the extent of curing between mother and daughter cells when half of the cells were cured by Hsp104 overexpression in one generation. Furthermore, curing was not affected by the lack of Sir2 expression, which was reported to be required for asymmetric segregation of the [PSI+] seeds. More importantly, when either hydroxyurea or ethanol were used to inhibit cell division, the extent of curing by Hsp104 overexpression was not significantly reduced. Therefore, the curing of [PSI+] by Hsp104 overexpression is not due to asymmetric segregation of the prion seeds, but rather their dissolution by Hsp104.

Alum sludge is an inevitable by-product from the water purification process, which had been applied as substrates in some constructed wetlands with good performance, especially for phosphorus (P) adsorption. The raw alum sludge is similar to a clay lump with an irregular shape, and there is a concern of it leaching into water. For better reuse, herein, some sludge was fired to produce alum sludge ceramsite (ASC) with a uniform spherical shape via a four-step process of kneading the sludge ball, air drying, preheating at 400 °C for 10 min, and firing at 600 °C for 5 min. Meanwhile, an air-dried alum sludge ball (adASB) was manufactured for comparison. The physicochemical properties and P adsorption ability of ceramsite were investigated subsequently. Through XRD and FT-IR tests, there was no obvious difference between ASC and adASB on the phase structure, but there was a certain amount of Al-OH group loss on the surface of ASC. The structure of ASC was still amorphous, similar to adASB, while ASC possessed more micropore structure and a bigger specific surface area than adASB. Adsorption experiments showed the P adsorption behaviors of ASC and adASB were much similar, and their adsorption kinetics were in accordance with the two-step adsorption kinetics rate equation and pseudo-second-order kinetics equation. The maximum adsorption capacities of ASC and adASB fitted by the Langmuir model were 1.66 mg/g and 1.89 mg/g, respectively. It should be pointed out that, compared with other adsorbents, the ASC produced in this study still had a greater ability to adsorb P. Therefore, ASC should have a great application potential for P removal in wastewater treatment in China.

Abstract Objective Epidermal stem cells (EpSCs) can self-renew, which are responsible for the long-term maintenance of the skin, and it also plays a critical role in wound re-epithelization, but the mechanism underlying EpSCs proliferation is unclear. GDF-5, also known as BMP-14, is a member of the BMP family and can be used as a self-renewal supporter. Here, we studied the effects of GDF-5 on mouse EpSCs proliferation mechanism in wound healing. Methods Firstly, the effects of GDF-5 on EpSCs proliferation was tested by using CCK8 reagent and PCNA expression was analyzed by Western blotting. Secondly, we screened genes that promote EpSCs proliferation in the FOX and cyclin family by qPCR, and then the protein expression level of the selected genes was further analyzed by Western blotting. Thirdly, siRNA plasmids and pAdEasy adenovirus were transfected or infected, respectively, into mouse EpSCs to detect the effect of target genes on GDF-5-induced cell proliferation. Furthermore, we injected GDF-5 to a deep partial thickness burn mouse model for finding out whether EpSCs proliferation can be detected by immunohistochemical. Finally, the relevant target genes were analyzed by qPCR, immunoblotting, and dual-luciferase reporter gene detection. Results We discovered that 100 ng/ml recombinant mouse GDF-5 was the optimal concentration for promoting mouse EpSCs proliferation. Through preliminary screened by qPCR, we found that Foxg1 and cyclin D1 could be the downstream molecules of GDF-5, and the results were confirmed by Western blotting. And the effect of GDF-5 on mouse EpSCs proliferation was adjusted by Foxg1/cyclin D1 in vitro and in vivo. Besides, GDF-5-induced transcription of cyclin D1 was regulated by Foxg1-mediated cyclin D1 promoter activity. Conclusion This paper showed that GDF-5 promotes mouse EpSCs proliferation via Foxg1-cyclin D1 signal pathway. It is suggested that GDF-5 may be a new approach to make EpSCs proliferation which can be used in wound healing.

HIV-1 maturation is the final step in the retroviral lifecycle that is regulated by the proteolytic cleavage of the Gag precursor protein. As a first-in-class HIV-1 maturation inhibitor (MI), bevirimat blocks virion maturation by disrupting capsid-spacer peptide 1 (CA-SP1) cleavage, which acts as the target of MIs. Previous alterations of beesioside I (1) produced (20S,24S)-15ꞵ,16ꞵ-diacetoxy-18,24; 20,24-diepoxy-9,19-cyclolanostane-3ꞵ,25-diol 3-O-3′,3′-dimethylsuccinate (3, DSC), showing similar anti-HIV potency compared to bevirimat. To ascertain the binding modes of this derivative, further modification of compound 1 was conducted. Three-dimensional quantitative structure–activity relationship (3D-QSAR) analysis combined with docking simulations and molecular dynamics (MD) were conducted. Five new derivatives were synthesized, among which compound 3b showed significant activity against HIV-1NL4-3 with an EC50 value of 0.28 µM. The developed 3D-QSAR model resulted in great predictive ability with training set (r2 = 0.99, q2 = 0.55). Molecular docking studies were complementary to the 3D-QSAR analysis, showing that DSC was differently bound to CA-SP1 with higher affinity than that of bevirimat. MD studies revealed that the complex of the ligand and the protein was stable, with root mean square deviation (RMSD) values

Casuarina equisetifolia is widely used in agroforestry plantations for soil stabilization, ecosystem rehabilitation, reclamation, and coastal protection. Moreover, C. equisetifolia has remarkable resistance to typhoons, desert, low soil fertility, drought, and salinity, but not cold. Therefore, it is significant to breed high-quality Casuarina varieties to improve the tolerance and adaptability to cold weather by molecular techniques. The establishment of a rapid and efficient callus induction and regeneration system via tissue culture is pre-requisite for the genetic transformation of C. equisetifolia, which is so far lacking. In this study, we reported an efficient and rapid regeneration system using stem segment explants, in which callus induction was found to be optimal in a basal medium supplemented with 0.1 mg⋅L–1 TDZ and 0.1 mg⋅L–1 NAA, and proliferation in a basal medium containing 0.1 mg⋅L–1 TDZ and 0.5 mg⋅L–1 6-BA. For bud regeneration and rooting, the preferred plant growth regulator (PGR) in basal medium was 0.5 mg⋅L–1 6-BA, and a combination of 0.02 mg⋅L–1 IBA and 0.4 mg⋅L–1 IAA, respectively. We also optimized genetic a transformation protocol using Agrobacterium tumefaciens harboring the binary vector pCAMBIA1301 with β-glucuronidase (GUS) as a reporter gene. Consequently, 5 mg L–1 hygromycin, 20 mg L–1 acetosyringone (As), and 2 days of co-cultivation duration were optimized to improve the transformation efficiency. With these optimized parameters, transgenic plants were obtained in about 4 months. Besides that, Agrobacterium rhizogenes-mediated transformation involving adventitious root induction was also optimized. Our findings will not only increase the transformation efficiency but also shorten the time for developing transgenic C. equisetifolia plants. Taken together, this pioneer study on tissue culturing and genetic transformation of C. equisetifolia will pave the way for further genetic manipulation and functional genomics of C. equisetifolia.

Summary: Inflammatory bowel disease (IBD) is multi-factorial chronic intestinal inflammation driven by pathogenic T cells, among which a large portion of patients are resistant to current anti-inflammatory regimes. The mechanisms underlying colitis pathogenicity and drug resistance are not fully understood. Here, we demonstrate that RORα is highly expressed in active UC patients, particularly in those non-responsive to anti-TNF treatment. Rorα deficiency in CD4+ T cells greatly reduced colitis development. Mechanistically, RORα regulated T cell infiltration in colon and inhibited T cell apoptosis. Meanwhile, genome-wide occupancy and transcriptome analysis revealed that RORα promoted mTORC1 activation. mTORC1 signaling, also hyperactivated in active UC patients, is necessary for T cell-mediated colitis. Our results thus demonstrate a crucial role of the RORα-mTORC1 axis in CD4+ T cells in promoting IBD, which may be targeted in human patients.

Novel alum sludge-based floating treatment wetland (FTW) was developed to enhance the purification performances of natural water bodies, i.e., rivers, lakes, and ponds. Polyurethane was applied to foam the lightweight alum sludge based-substrate (PU-AL) of FTW through the response surface method. Three FTWs configurations were created for a half-year lab-scale operation, and the PU-AL FTW presents the greatest purification performance in the removal rate of chemical oxygen demand (COD) of 62.58 ± 6.65%, total nitrogen (TN) of 53.31 ± 4.65%, and total phosphorus (TP) of 45.39 ± 4.69%. PU-AL substrate could enhance the nutrient removal performance of existing FTW by providing a proper media for microbial and plants’ growth. This study provides a good solution and showcase not only from a natural water restoration point of view but also from the waterworks sludge management view for a better understanding of FTWs and good applications in engineering practice.

Despite significant progress in the treatment of patients with diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), the prognosis of patients with relapsed disease remains poor due to the emergence of drug resistance and subsequent disease progression. Identification of novel targets and therapeutic strategies for these diseases represents an urgent need. Here, we report that both MCL and DLBCL are exquisitely sensitive to transcription-targeting drugs, in particular THZ531, a covalent inhibitor of cyclin-dependent kinase 12 (CDK12). By implementing pharmacogenomics and a cell-based drug screen, we found that THZ531 leads to inhibition of oncogenic transcriptional programs, especially the DNA damage response pathway, MYC target genes and the mTOR-4EBP1-MCL-1 axis, contributing to dramatic lymphoma suppression in vitro. We also identified de novo and established acquired THZ531-resistant lymphoma cells conferred by over-activation of the MEK-ERK and PI3K-AKT-mTOR pathways and upregulation of multidrug resistance-1 (MDR1) protein. Of note, EZH2 inhibitors reversed resistance to THZ531 by competitive inhibition of MDR1 and, in combination with THZ531, synergistically inhibited MCL and DLBCL growth in vitro. Our study indicates that CDK12 inhibitors, alone or together with EZH2 inhibitors, offer promise as novel effective approaches for difficult-to-treat DLBCL and MCL.

Modern human activities have resulted in the indiscriminate exploitation of land resources, which has exerted increasingly negative influences on soil quality. Critically, these effects are seen in already ecologically fragile areas. In this study, a total of 48 soil samples were obtained at 0–20 cm depth (surface soil) and 20–40 cm depth (subsurface soil) from five types of land uses in a typical watershed in northwest China, Qinghai-Tibet Plateau. A comprehensive fuzzy mathematical model combined with soil quality index (SQI) was used to evaluate and calculate soil quality in the study area. Results showed that the SQI value was highest in mountain cropland, with values of 0.520 and 0.421 for surface and subsurface areas, respectively. Comparatively, values were lowest in grassland, with 0.447 and 0.364 for surface and subsurface areas, respectively. Then we assessed the sensitivity index (SI) to understand the effects of different physicochemical soil properties on soil quality under different land use types, and the SI values of mountain cropland and grassland with a large variations of soil quality were analyzed. Results showed that among the 15 evaluating indices, SI values for alkali-hydrolyzed nitrogen (AN), available phosphorus (AP), and total nitrogen (TN) in the surface soil layer meanwhile AN and TN in subsurface soil were higher than 1.5, indicating the sensitivity of these properties increased in mountain cropland. Surface soil is more vulnerable to land use changes driven by a variety of human activities, given this, surface and subsurface soil samples had recognizable differences. We next calculated the stratification ratio (SR), with results showing that SR values for most soil properties were higher in mountain cropland relative to grassland soil, with AP in mountain cropland was a maximum at 1.94, indicating these properties were more important indicators of the effects of land use changes. These analyses, provide a better explanation of why the soil quality was better in mountain cropland with specific physical and chemical properties. Collectively, the outcomes of this study indicated the potential for assessing soil quality covered by five land use types along with soil stratifications in a region with a sensitive and fragile ecological environment.

(1) Background: To better carry out air pollution control and to assist in accurate investigations of air pollution, in this study, we fully explore the spatial distribution characteristics of air pollution complaint results and provide guidance for air pollution control by combining regional air monitoring data. (2) Methods: By selecting the air pollution complaint information in Beijing from 2019 to 2020, in this study, we extract the names and addresses of complaint points, as well as the complaint times and types by adopting the BERT (bidirectional encoder representations from transformers) + CRF (conditional random field) model deep learning method. Moreover, through further filtering and processing of the complaint points’ address information, we achieve address matching and spatial positioning of the complaint points, and realize the regional spatial representation of air pollution complaints in Beijing in the form of a heat map. (3) Results: The experimental results are compared and analyzed with the ranking data of total suspended particulate (TSP) concentration of townships (streets) in Beijing during the same period, indicating that the key areas of air pollution complaints have a high correlation with the key polluted township (street) areas. The distribution of complaints and the types of complaints in each township (street) differ according to the population density in each township (street), the level of education, and economic activity. (4) Conclusions: The results of this study show that the public, as the intuitive perceiver of air pollution, is sensitive to the air pollution situation at a smaller spatial scale; furthermore, complaints can provide guidance and reference for the direction of air pollution control and law enforcement investigations when coupled with geographical features and economic status.

Hulless barley (Hordeum vulgare L. var. nudum), also called naked barley, is a unique variety of cultivated barley. The genome-wide specific length amplified fragment sequencing (SLAF-seq) method is a rapid deep sequencing technology that is used for the selection and identification of genetic loci or markers. In this study, we collected 300 hulless barley accessions and used the SLAF-seq method to identify candidate genes involved in plant height (PH) and tiller number (TN). We obtained a total of 1407 M paired-end reads, and 228,227 SLAF tags were developed. After filtering using an integrity threshold of >0.8 and a minor allele frequency of >0.05, 14,504,892 single-nucleotide polymorphisms (SNP) loci were screened out. The remaining SNPs were used for the construction of a neighbour-joining phylogenetic tree, and the three subcluster members showed no obvious differentiation among regional varieties. We used a genome wide association study approach to identify 1006 and 113 SNPs associated with TN and PH, respectively. Based on best linear unbiased predictors (BLUP), 41 and 29 SNPs associated with TN and PH, respectively. Thus, several of genes, including Hd3a and CKX5, may be useful candidates for the future genetic breeding of hulless barley. Taken together, our results provide insight into the molecular mechanisms controlling barley architecture, which is important for breeding and yield.

Since the output torque of the rotary reducer of the ZYL-15000D-kilometer directional drill is proportional to the gear train transmission ratio, the output torque is large enough when the input speed and output speed meet the design goal. This paper selects the method of reducing the transmission ratio to optimize the size parameters of the reducer. MATLAB genetic algorithm is used in the optimization design, and the minimum volume of the rotary part reducer is taken as the objective of optimization design, while the design variables and constraints are determined. The optimal value of design variables was obtained through optimization, and the parameter values of each gear were determined accordingly. Through analysis, the total volume of the optimized gear reducer was reduced by 49.6%. Then, the 3D model of the optimized gear was created, and the analysis of the transient dynamics of the optimized gear was carried out with ANSYS Workbench software. According to the analysis results, the optimized gear met the strength requirements and provided a reference for the subsequent optimization design of other types of gear reducers.

Retinoid-related orphan receptor alpha (RORα) is involved in tumor development. However, the mechanisms underlying RORα inhibiting epithelial-to-mesenchymal transition (EMT) and invasion are poorly understood in gastric cancer (GC). This study revealed that the decreased expression of RORα is associated with GC development, progression, and prognosis. RORα suppressed cell proliferation, EMT, and invasion in GC cells through inhibition of the Wnt/β-catenin pathway. RORα overexpression resulted in the decreased Wnt1 expression and the increased RORα interaction with β-catenin, which could lead to the decreased intranuclear β-catenin and p-β-catenin levels, concomitant with downregulated T-cell factor-4 (TCF-4) expression and the promoter activity of c-Myc. The inhibition of Wnt/β-catenin pathway was coupled with the reduced expression of Axin, c-Myc, and c-Jun. RORα downregulated vimentin and Snail and upregulated E-cadherin protein levels in vitro and in vivo. Inversely, knockdown of RORα attenuated its inhibitory effects on Wnt/β-catenin pathway and its downstream gene expression, facilitating cell proliferation, EMT, migration, and invasion in GC cells. Therefore, RORα could play a crucial role in repressing GC cell proliferation, EMT, and invasion via downregulating Wnt/β-catenin pathway.

Abstract Background In a previous study, we found that titrating clopidogrel maintenance doses (MDs) according to vasodilator-stimulated phosphoprotein (VASP) monitoring minimised the rate of major adverse cardiovascular and cerebral events (MACCE) after percutaneous coronary intervention (PCI) without increasing bleeding in patients with high on-treatment platelet reaction to clopidogrel. This study aimed to investigate whether VASP-guided clopidogrel MD could reduce thromboembolism and bleeding in atrial fibrillation (AF) patients requiring anticoagulation and scheduled for PCI. Methods AF patients scheduled for PCI were recruited between July 2014 and July 2016. These patients were allocated into VASP-guided (n = 250) and control (n = 253) groups depending on the clopidogrel MD profile. In the VASP-guided group, clopidogrel MD was titrated by the platelet reactivity index (PRI), whereas in the control group, clopidogrel MD was fixed at 75 mg per day. The primary endpoint was MACCE and secondary endpoints were thrombolysis in myocardial infarction (TIMI) major and minor bleeding 1 year after PCI. Results Five hundred and three patients were included in the present study, with 1-year data available for 95.6% patients. The average CHA2DS2-VASc score of the whole population was 3.7 ± 0.7 and the average HAS-BLED score was 3.2 ± 0.4. MACCE was less in the VASP-guided group than in the control group (2.5% vs. 5.0%, P = 0.02). The incidence of major bleeding was comparable between both groups (3.0% vs. 2.8%, P = 0.72) and minor bleeding was higher in the VASP-guided group than in the control group (15.3% vs. 9.7%, P = 0.03). Kaplan-Meier analysis indicated that there was no difference in survival between both groups (log-rank test, P = 0.68). Conclusions In AF patients requiring anticoagulation and scheduled for PCI, VASP-guided antiplatelet therapy reduced major cardiovascular and cerebral adverse events, accompanied by increased minor bleeding events. Trial registration The present study was retrospectively registered in the Chinese Clinical Trial Registry, A Primary Registry of the International Clinical Trial Registry Platform, World Health Organisation (Registration no: ChiCTR-IOR-17013854). The registered date was December 11, 2117.

Programmed cell death (PCD) is a process intended for the maintenance of cellular homeostasis by eliminating old, damaged, or unwanted cells. In plants, PCD takes place during developmental processes and in response to biotic and abiotic stresses. In contrast to the field of animal studies, PCD is not well understood in plants. Calcium (Ca2+) is a universal cell signaling entity and regulates numerous physiological activities across all the kingdoms of life. The cytosolic increase in Ca2+ is a prerequisite for the induction of PCD in plants. Although over the past years, we have witnessed significant progress in understanding the role of Ca2+ in the regulation of PCD, it is still unclear how the upstream stress perception leads to the Ca2+ elevation and how the signal is further propagated to result in the onset of PCD. In this review article, we discuss recent advancements in the field, and compare the role of Ca2+ signaling in PCD in biotic and abiotic stresses. Moreover, we discuss the upstream and downstream components of Ca2+ signaling and its crosstalk with other signaling pathways in PCD. The review is expected to provide new insights into the role of Ca2+ signaling in PCD and to identify gaps for future research efforts.

Abstract One of the major concerns for CO2 capture and storage (CCS) is the potential risk of CO2 leakage from storage reservoirs on the shallow soil property and vegetation. This study utilizes a naturally occurring CO2 leaking site in the Qinghai-Tibet Plateau to analog a “leaking CCS site”. Our observations from this site indicates that long-term CO2 invasion in the vadose zone results in variations of soil properties, such as pH fluctuation, slight drop of total organic carbon, reduction of nitrogen and phosphorus, and concentration changes of soluble ions. Simultaneously, XRD patterns of the soil suggest that crystallization of soil is enhanced and mineral contents of calcite and anorthite in soil are increased substantially. Parts of the whole ecosystem such as natural wild plants, soil dwelling animals and microorganisms in shallow soil are affected as well. Under a moderate CO2 concentration (less than 110000 ppm), wild plant growth and development are improved, while an intensive CO2 flux over 112000 ppm causes adverse effects on the plant growth, physiological and biochemical system of plants, and crop quality of wheat. Results of this study provide valuable insight for understanding the possible environmental impacts associated with potential CO2 leakage into shallow sediments at carbon sequestration sites.

Ibrutinib has demonstrated high response rates in B-cell lymphomas but a lot of ibrutinib-treated patients relapse with resistance. This study unified TME-mediatedde novoand acquired drug resistance through B-cell receptor signalling and PI3K-AKT-mTOR axis and provides a combination therapeutic strategy against B-cell malignancies.

Underwater fishing nets represent a danger faced by autonomous underwater vehicles (AUVs). To avoid irreparable damage to the AUV caused by fishing nets, the AUV needs to be able to identify and locate them autonomously and avoid them in advance. Whether the AUV can avoid fishing nets successfully depends on the accuracy and efficiency of detection. In this paper, we propose an object detection multiple receptive field network (MRF-Net), which is used to recognize and locate fishing nets using forward-looking sonar (FLS) images. The proposed architecture is a center-point-based detector, which uses a novel encoder-decoder structure to extract features and predict the center points and bounding box size. In addition, to reduce the interference of reverberation and speckle noises in the FLS image, we used a series of preprocessing operations to reduce the noises. We trained and tested the network with data collected in the sea using a Gemini 720i multi-beam forward-looking sonar and compared it with state-of-the-art networks for object detection. In order to further prove that our detector can be applied to the actual detection task, we also carried out the experiment of detecting and avoiding fishing nets in real-time in the sea with the embedded single board computer (SBC) module and the NVIDIA Jetson AGX Xavier embedded system of the AUV platform in our lab. The experimental results show that in terms of computational complexity, inference time, and prediction accuracy, MRF-Net is better than state-of-the-art networks. In addition, our fishing net avoidance experiment results indicate that the detection results of MRF-Net can support the accurate operation of the later obstacle avoidance algorithm.

Background: We studied the consistency between two classification systems for categorizing patients: traditional Chinese medicine (TCM) constitution-based methods, versus genetic clustering. Genetic classification in constitutional identification was also evaluated. Methods: A TCM physician evaluated the constitution of each patient, according to four examinations (inspection, auscultation-olfaction, interrogation, and palpation). Those who met the criteria for Yang-deficient, Yin-deficient, and balanced constitutions were enrolled in the study. Peripheral blood samples were obtained from the participants, and peripheral blood mononuclear cells were separated from the samples within 2 hours. Total RNA extraction from the white blood cells was performed; and an Affymetrix HG-U133 Plus2.0 array was used to determine the peripheral blood gene expression profiles. The samples were classified using a support vector machine genetic classifier, and the “leave-one-out” method was used for validation. Results: The global gene expression profiles of 32 samples were grouped into three categories, and the samples in each of the gene categories corresponded with the three constitution categories. The three constitution types were distinguished using the genetic classifier with 165 genes. The accuracy of the prediction classification was greater than 95% using mathematical method. Conclusions: Participants with Yin-deficient, Yang-deficient, and balanced constitutions have varying physical characteristics and gene expression patterns. Additionally, the results from TCM constitution classification matched those obtained by genetic classification. Finally, our preliminary gene classifier distinguishes among Yin-deficient, Yang-deficient, and balanced constitutions, and provides a methodological basis for identifying the different constitutions.

Prions are infectious proteins that self-propagate by changing from their normal folded conformation to a misfolded conformation. The misfolded conformation, which is typically rich in β-sheet, serves as a template to convert the prion protein into its misfolded conformation. In yeast, the misfolded prion proteins are assembled into amyloid fibers or seeds, which are constantly severed and transmitted to daughter cells. To cure prions in yeast, it is necessary to eliminate all the prion seeds. Multiple mechanisms of curing have been found including inhibiting severing of the prion seeds, gradual dissolution of the prion seeds, asymmetric segregation of the prion seeds between mother and daughter cells during cell division, and degradation of the prion seeds. These mechanisms, achieved by using different protein quality control machinery, are not mutually exclusive; depending on conditions, multiple mechanisms may work simultaneously to achieve curing. This review discusses the various methods that have been used to differentiate between these mechanisms of curing.

Dalbergia odorifera, a critically endangered tree species, produces heartwood containing a vast variety of flavonoids. This heartwood, also known as Chinese rosewood, has high economic and medicinal value, but its formation takes several decades. In this study, we showed that discolored wood induced by pruning displays similar color, structure, and flavonoids content to those of natural heartwood, suggesting that wounding is an efficient method for inducing flavonoid production in D. odorifera. Transcriptome analysis was performed to investigate the mechanism underlying wounding-induced flavonoids production in D. odorifera heartwood. Wounding upregulated the expression of 90 unigenes, which covered 19 gene families of the phenylpropanoid and flavonoid pathways, including PAL, C4H, 4CL, CHS, CHI, 6DCS, F3’5’H, F3H, FMO, GT, PMAT, CHOMT, IFS, HI4’OMT, HID, IOMT, I2’H, IFR, and I3’H. Furthermore, 47 upregulated unigenes were mapped to the biosynthesis pathways for five signal molecules (ET, JA, ABA, ROS, and SA). Exogenous application of these signal molecules resulted in the accumulation of flavonoids in cell suspensions of D. odorifera, supporting their role in wounding-induced flavonoid production. Insights from this study will help develop new methods for rapidly inducing the formation of heartwood with enhanced medicinal value.

Background Frailty associated with aging increases the risk of falls, disability, and death. We investigated gender-associated factors for frailty. Methods Data of 3,079 geriatric subjects were retrieved from the National Health and Nutrition Examination Survey (NHANES) 2007–2010 database. After excluding 1,126 subjects with missing data on frailty, medical history and survival, data of 1,953 patients were analyzed. Main endpoints were frailty prevalence, mortality rates and causes of death. Results Frailty prevalence was 5.4% in males, 8.8% in females. Significant risk factors for geriatric frailty in males were being widowed/divorced/separated, low daily total calorie intake, physical inactivity, sleeping >9 h, smoking and hospitalization history; and in females were obesity, physical inactivity, sleeping

Acquired resistance to standard chemotherapy is the common and critical limitation for cancer therapy. Hematopoietic cell-specific protein 1-associated protein X-1 (HAX-1) has been reported to be upregulated in numerous cancers. However, the role of HAX-1 in oncotherapy remains unclear. In this study, we established MDA-MB-231 cell lines which were resistant to cisplatin (MDA-MB-231/CR) or doxorubicin (MDA-MB-231/DR) to study the chemoresistance in breast cancer. As a result, the HAX-1 which is an apoptosis-associated protein was observed to be overexpressed in both MDA-MB-231/CR and MDA-MB-231/DR compared with the routine MDA-MB-231 cells. Moreover, knockdown of HAX-1 via RNA interference decreased IC50 level of cisplatin by 70.91% in MDA-MB-231/CR cells, and the IC50 level of doxorubicin was decreased by 76.46% in MDA-MB-231/DR cells when the HAX-1 was downregulated. Additionally, we found that the knockdown of HAX-1 induced the release of cytochrome C from mitochondria, resulting in the activation of caspases. Taken together, our study indicates that the overexpression of HAX-1 is essential in the development of chemoresistance in breast cancer. Furthermore, we identify that HAX-1 may become the target for cancer therapy.

The damage mechanism of proton irradiation in InP/InGaAs heterostructures was studied. The deep level traps were investigated in detail by deep level transient spectroscopy (DLTS), capacitance−voltage (C−V) measurements and SRIM (the stopping and range of ions in matter, Monte Carlo code) simulation for non-irradiated and 3 MeV proton-irradiated samples at a fluence of 5 × 1012 p/cm2. Compared with non-irradiated samples, a new electron trap at EC-0.37 eV was measured by DLTS in post-irradiated samples and was found to be closer to the center of the forbidden band. The trap concentration in bulk, the interface trap charge density and the electron capture cross-section were 4 × 1015 cm−3, 1.8 × 1012 cm−2, and 9.61 × 10−15 cm2, respectively. The deep level trap, acting as a recombination center, resulted in a large recombination current at a lower forward bias and made the forward current increase in InP/InGaAs heterostructures for post-irradiated samples. When the deep level trap parameters were added into the technology computer-aided design (TCAD) simulation tool, the simulation results matched the current−voltage measurements data well, which verifies the validity of the damage mechanism of proton irradiation.

Background It is unclear whether ideal cardiovascular health (CVH), and particularly cumulative exposure to ideal CVH (cumCVH), is associated with incident diabetes. We aimed to fill this research gap. Methods and Results The Kailuan Study is a prospective cohort of 101 510 adults aged 18 to 98 years recruited in 2006–2007 and who were subsequently followed up at 2‐ (Exam 2), 4‐ (Exam 3), and 6 (Exam 4)‐year intervals after baseline. The main analysis is restricted to those individuals with complete follow‐up at all 4 examinations and who had no history of diabetes until Exam 3. Cumulative exposure to ideal CVH (cumCVH) was calculated as the summed CVH score for each examination multiplied by the time between the 2 examinations (score×year). Logistic regression models were used to assess the association between cumCVH and incident diabetes. In fully adjusted models, compared with the lowest quintile of cumCVH, individuals in the highest quintile had ~68% (95% confidence interval [CI] 60‐75) lower risk for incident diabetes (compared with 61% [95% CI 52‐69] lower risk when using baseline CVH). Every additional year lived with a 1‐unit increase in ideal CVH was associated with a 24% (95% CI 21‐28) reduction in incident diabetes. Conclusions Ideal CVH is associated with a reduced incidence of diabetes, but the association is likely to be underestimated if baseline measures of CVH exposure are used. Measures of cumulative exposure to ideal CVH are more likely to reflect lifetime risk of diabetes and possibly other health outcomes. Clinical Trial Registration URL: https://www.chictr.org. Unique identifier: ChiCTRTNC‐11001489.

Background and objective Cyclooxygenases (COX), the key enzymes in the conversion of arachidonic acid (AA) to prostaglandins (PGs), are involved in initiation and progression of cancer. The aim of this study is to explore the relationship between the expressions of COX-2 and several transcription factors in non-small cell lung cancer. Methods Immunohistochemistry was performed to assay the expression levels of COX-2, c-Fos, c-Jun and nuclear factor of activated T cells 3 (NFAT3) in tissue microarray containing 159 tumor tissues of non-small cell lung cancer. Results The positive rate of COX-2 expression was 42.8%, and the expression of COX-2 was significantly higher in squamous cell carcinoma than that in adenocarcinoma (52.9% vs 31.3%, χ2=7.723, P=0.005). The expression of COX-2 was significantly associated with differentiation grade, with the lower level in the poorer differentiation grade group (χ2=7.600, P=0.022). In this panel of samples, the expression of COX-2 was significantly correlated with c-Fos expression (r=0.456, P < 0.001) and NFAT3 level (r=0.294, P < 0.001). The correlation between the expressions of NFAT3 and c-Fos were also observed (r=0.231, P=0.003). Conclusion The expression of COX-2 was significantly associated with the expressions of transcription factors NFAT3 and c-Fos in nonsmall cell lung cancer.

Acylated lignins with substituents consisting of different lengths of carbon chains were prepared by a mechanical activation-assisted solid phase synthesis (MASPS) technology with a customized stirring ball mill as a reactor. The structures and properties were analyzed by UV/Vis, FTIR, NMR, SEM, DSC, and TG. The results showed that the acylated lignins were successfully prepared with either non-cyclic or cyclic anhydrides as the acylating agents. Both aliphatic hydroxyl and phenolic hydroxyl groups of lignin reacted with non-cyclic anhydrides, and different reactivity of acylating agents resulted in different relative contents of phenolic and aliphatic substituents in the products. The reactivity of the cyclic anhydrides was weaker than that of the non-cyclic anhydrides, and the reactivity of the acylating agents decreased with increasing carbon chain length and unsaturated bonds of acyl groups. All of the acylated lignins except maleylated lignin had a lower glass transition temperature (Tg) than the original lignin. The acylated lignins prepared with non-cyclic anhydrides had better thermal stability than original lignin, and the thermal stability increased, but Tg decreased with an increasing chain length of the acyl groups. The acylated lignins prepared with cyclic anhydrides had higher a Tg than those with non-cyclic anhydrides with the same carbon number, and the thermal stability was not obviously improved.