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Drought (water shortage) can substantially limit the yield and economic value of rose plants (Rosa spp.). Here, we characterized the effect of exogenous calcium (Ca2+) on the antioxidant system and photosynthesis-related properties of rose under polyethylene glycol 6000 (PEG6000)-induced drought stress. Chlorophyll levels, as well as leaf and root biomass, were significantly reduced by drought; drought also had a major effect on the enzymatic antioxidant system and increased concentrations of reactive oxygen species. Application of exogenous Ca2+ increased the net photosynthetic rate and stomatal conductance of leaves, enhanced water-use efficiency, and increased the length and width of stomata following exposure to drought. Organ-specific physiological responses were observed under different concentrations of Ca2+. Application of 5 mmol · L−1 Ca2+ promoted photosynthesis and antioxidant activity in the leaves, and application of 10 mmol · L−1 Ca2+ promoted antioxidant activity in the roots. Application of exogenous Ca2+ greatly enhanced the phenotype and photosynthetic capacity of potted rose plants following exposure to drought stress. Overall, our findings indicate that the application of exogenous Ca2+ enhances the drought resistance of roses by promoting physiological adaptation and that it could be used to aid the cultivation of rose plants.

With technological progress, how to efficiently process and retrieve large amounts of multi-modal multimedia data has become a challenge. Although multi-modal hash algorithms have been applied in this field, their performance potential has not been fully realized. To fully leverage the performance of the model, a supervised discrete multi-modal hash algorithm has been proposed to improve the efficiency of multi-modal retrieval. The adaptive online multi-modal hash algorithm is used to dynamically adapt to changes in query samples. The topological semantic multi-modal hash algorithm is applied to further improve the retrieval performance of multi-modal hashes. According to the results, in the MIR Flickr dataset, the Mean Average Precision (MAP) reaches 0.8048, 0.8155, and 0.8185 at 32-bit, 64-bit, and 128-bit, respectively. Fusion Graph Convolutional multi-modal Hashing (FGCMH) exhibits the bestin different datasets. From this, the designed method has high processing power in handling large-scale and high-dimensional multimedia data.

Abstract Rechargeable calcium (Ca) metal batteries are promising candidates for sustainable energy storage due to the abundance of Ca in Earth’s crust and the advantageous theoretical capacity and voltage of these batteries. However, the development of practical Ca metal batteries has been severely hampered by the current cathode chemistries, which limit the available energy and power densities, as well as their insufficient capacity retention and low-temperature capability. Here, we describe the rechargeable Ca/Cl2 battery based on a reversible cathode redox reaction between CaCl2 and Cl2, which is enabled by the use of lithium difluoro(oxalate)borate as a key electrolyte mediator to facilitate the dissociation and distribution of Cl-based species and Ca2+. Our rechargeable Ca/Cl2 battery can deliver discharge voltages of 3 V and exhibits remarkable specific capacity (1000 mAh g−1) and rate capability (500 mA g−1). In addition, the excellent capacity retention (96.5% after 30 days) and low-temperature capability (down to 0 °C) allow us to overcome the long-standing bottleneck of rechargeable Ca metal batteries.

The design and development of highly efficient electrocatalysts for oxygen evolution reaction (OER) are critical for renewable energy generation. Ni‐based electrocatalysts are widely used in the water electrolysis process. In this work, heterostructure consisting of selenides and layered double hydroxides (LDH) named (Co, Ni)Se4@NiFe‐LDH, are prepared by an LDH‐based strategy, in which the electronic structure of Ni active sites is regulated by interfacial electron interaction. The (Co, Ni)Se4@NiFe‐LDH shows an optimized charge distribution of Ni sites and excellent catalytic activity. The effective charge modulation results in lowering the energy barrier of OOH* intermediate formation and adequate adsorption strength of the intermediates on Ni‐active sites, which improves the kinetics of OER. Specifically, the (Co, Ni)Se4@NiFe‐LDH only requires an overpotential of 237 mV to reach the current density of 10 mA cm−2 under alkaline conditions. The results of this work demonstrate that reasonable engineering of heterostructure is an effective strategy to improve the intrinsic property of OER electrocatalysts for water splitting.

BackgroundNormal hepatic functional reserve is the key to avoiding liver failure after liver surgery. This study investigated the assessment of hepatic functional reserve using liver shear wave velocity (LSWV) combined with biochemical indicators, tumor volume, and portal vein diameter.MethodsIn this single-center prospective study, a total of 123 patients with hepatocellular carcinoma (HCC) were divided into a test group (n=92) and a validation group (n=31). All patients were Child-Pugh grade A. The indocyanine green retention rate at 15 min (ICG-R15), liver shear wave velocity (LSWV), portal vein diameter (Dpv), alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GGT), albumin (ALB), prothrombin time (PT), and also liver tumor volume (maximum diameter ≤5 cm) were measured. In the test group, multiple parameters were used to evaluate hepatic functional reserve, and the multiparametric model was established. Receiver operating characteristic (ROC) curve analysis was conducted to assess the diagnostic performance of the multiparametric model. In the validation group, the predictive effectiveness of the multiparametric model was analyzed using consistency tests.ResultsIt was revealed that LSWV, ALB, and PT were statistically significant in evaluation of the hepatic functional reserve (P

ABSTRACT Purpose: To compare the effectiveness and safety of marketed oral drugs for overactive bladder based on a systematic review and network meta-analysis approach. Methods: Pubmed, Embase, Web of Science, and the Cochrane Register of Clinical Trials databases were systematically searched. The search time frame was from database creation to June 2, 2022. Randomized controlled double-blind trials of oral medication for overactive bladder were screened against the protocol's entry criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 software. Result: A total of 60 randomized controlled double-blind clinical trials were included involving 50,333 subjects. Solifenacin 10mg was the most effective in mean daily micturitions and incontinence episodes, solifenacin 5/10mg in mean daily urinary urgency episodes and nocturia episodes, fesoterodine 8mg in urgency incontinence episodes/d and oxybutynin 5mg in voided volume/micturition. In terms of safety, solifenacin 5mg, ER-tolterodine 4mg, mirabegron, vibegron and ER-oxybutynin 10mg all showed a better incidence of dry mouth, fesoterodine 4mg, ER-oxybutynin 10mg, tolterodine 2mg, and vibegron in the incidence of constipation. Compared to placebo, imidafenacin 0.1mg showed a significantly increased incidence in hypertension, solifenacin 10mg in urinary tract infection, fesoterodine 4/8mg and darifenacin 15mg in headache. Conclusion: Solifenacin showed better efficacy. For safety, most anticholinergic drugs were more likely to cause dry mouth and constipation, lower doses were better tolerated. The choice of drugs should be tailored to the patient's specific situation to find the best balance between efficacy and safety.

Abstract The integrins and G protein-coupled receptors are both fundamental in cell biology. The cross talk between these two, however, is unclear. Here we show that β3 integrins negatively regulate G protein-coupled signaling by directly inhibiting the Gα13-p115RhoGEF interaction. Furthermore, whereas β3 deficiency or integrin antagonists inhibit integrin-dependent platelet aggregation and exocytosis (granule secretion), they enhance G protein-coupled RhoA activation and integrin-independent secretion. In contrast, a β3-derived Gα13-binding peptide or Gα13 knockout inhibits G protein-coupled RhoA activation and both integrin-independent and dependent platelet secretion without affecting primary platelet aggregation. In a mouse model of myocardial ischemia/reperfusion injury in vivo, the β3-derived Gα13-binding peptide inhibits platelet secretion of granule constituents, which exacerbates inflammation and ischemia/reperfusion injury. These data establish crucial integrin-G protein crosstalk, providing a rationale for therapeutic approaches that inhibit exocytosis in platelets and possibly other cells without adverse effects associated with loss of cell adhesion.

Abstract Platelets, small hemostatic blood cells, are derived from megakaryocytes. Both bone marrow and lung are principal sites of thrombopoiesis although underlying mechanisms remain unclear. Outside the body, however, our ability to generate large number of functional platelets is poor. Here we show that perfusion of megakaryocytes ex vivo through the mouse lung vasculature generates substantial platelet numbers, up to 3000 per megakaryocyte. Despite their large size, megakaryocytes are able repeatedly to passage through the lung vasculature, leading to enucleation and subsequent platelet generation intravascularly. Using ex vivo lung and an in vitro microfluidic chamber we determine how oxygenation, ventilation, healthy pulmonary endothelium and the microvascular structure support thrombopoiesis. We also show a critical role for the actin regulator Tropomyosin 4 in the final steps of platelet formation in lung vasculature. This work reveals the mechanisms of thrombopoiesis in lung vasculature and informs approaches to large-scale generation of platelets.

IntroductionLung cancer is the primary cause of cancer-related deaths worldwide, with high rates of morbidity and mortality. The most effective treatment for early stage (I-II) non-small cell lung cancer (NSCLC) is surgical resection. However, the extent of mediastinal lymph nodes removal required and the impact of their removal remains controversial. This systematic review and meta-analysis aimed to evaluate the postoperative complications in patients with stage I-II NSCLC who received mediastinal lymph node dissection (MLND) or mediastinal lymph node sampling (MLNS).Methods and analysisAccording to the predefined inclusion criteria, we will conduct a comprehensive search for randomized controlled trials (RCTs) and observational studies examining the postoperative complications of MLND compared to MLNS in patients with stage I-II NSCLC. The search will be performed across multiple databases including PubMed, Embase, the Cochrane Library, CNKI, WanFang, Sinomed, VIP, Duxiu, and Web of Science from inception to February 2024. Additionally, relevant literature references will be retrieved and hand searching of pertinent journals will be conducted. Screening, data extraction, and quality assessment will be performed by two independent reviewers. Review Manager 5.4 will be applied in analyzing and synthesizing. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) will be used to assess the quality of evidence for the whole RCTs and used Newcastle-Ottawa scale to assess the methodologic quality of observational studies.Ethics and disseminationThis study did not include personal information. Ethical approval was not required for this study. This study is based on a secondary analysis of the literature, so ethical review approval is not required. The final report will be published in a peer-reviewed journal.ConclusionThis systematic review will contribute to compare the safety and survival benefits of these two surgical techniques for the treatment of early stage NSCLC, to further guide the selection of surgical approaches.Trial registrationThe protocol of the systematic review has been registered on Open Science Framework, with a registration number of DOI https://doi.org/10.17605/OSF.IO/N2Y5D.

ObjectiveIntermittent energy restriction (IER) is an effective weight loss strategy. However, little is known about the dynamic effects of IER on the brain-gut-microbiome axis.MethodsIn this study, a total of 25 obese individuals successfully lost weight after a 2-month IER intervention. FMRI was used to determine the activity of brain regions. Metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways in from fecal samples.ResultsOur results showed that IER longitudinally reduced the activity of obese-related brain regions at different timepoints, including the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit. IER longitudinally reduced E. coli abundance across multiple timepoints while elevating the abundance of obesity-related Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis. Correlation analysis revealed longitudinally correlations between gut bacteria abundance alterations and brain activity changes.ConclusionsThere was dynamical alteration of BGM axis (the communication of E. coli with specific brain regions) during the weight loss under the IER.

[Objective] The performance of microbial induced calcium carbonate precipitation (MICP) to stabilize aeolian sand soil was studied in order to providing a theoretical basis for MICP technology in stabilize aeolian sand soil and restoring ecology. [Methods] The microstructure of aeolian sand soil was analyzed by use of scanning electron microscopy and optical microscopy on an aeolian sand soil stabilized with MICP. The test analyzed the basic physical properties and water retention of stabilized specimens. [Results] The aeolian sand soil treated with MICP had calcium carbonate crystals generated between the aeolian sand particles that cemented the sand particles together and solidified the loose aeolian sand into a whole with a certain strength. As curing time increased, the thickness, dry density, and calcium carbonate content of cured aeolian sand gradually increased, the permeability coefficient gradually decreased, the stabilized thickness increased from 3.38 mm to 11.28 mm, the dry density increased from 1.61 g/cm3 for the original sand to 2.05 g/cm3, the calcium carbonate content increased from 8.99% to 13.08%, and the permeability coefficient decreased from 1.06×10-3 cm/s for the original sand to 2.35×10-4 cm/s. When the number of curing treatments was not more than five times, the water retention rate increased with increasing number of curing treatments, and the water retention of the stabilized specimen increased. After more than five curing treatments, water retention decreased. [Conclusion] Aeolian sand soil stabilized by MICP technology can significantly improve the physical and mechanical properties and water retention of aeolian sand soil. Considering this stabilizing effect, water retention, and economics, the best stabilizing treatment time is three times. Thus, we can effectively prevent wind erosion, maintain soil moisture, and facilitate ecological restoration.

IntroductionChimeric antigen receptors (CARs) can redirect T cells against antigen-expressing tumors, and each component plays an important role in the function and anti-tumor efficacy. It has been reported that using human sequences or a low affinity of CAR single-chain variable fragments (scFvs) in the CAR binding domains is a potential way to enhance the function of CAR-T cells. However, it remains largely unknown how a lower affinity of CARs using humanized scFvs affects the function of CAR-T cells until recently.MethodsWe used different humanized anti-HER2 antibodies as the extracellular domain of CARs and further constructed a series of the CAR-T cells with different affinity.ResultsWe have observed that moderately reducing the affinity of CARs (light chain variable domain (VL)-based CAR-T) could maintain the anti-tumor efficacy, and improved the safety of CAR therapy both in vitro and in vivo compared with high-affinity CAR-T cells. Moreover, T cells expressing the VL domain only antibody exhibited long-lasting tumor elimination capability after multiple challenges in vitro, longer persistence and lower cytokine levels in vivo.DiscussionOur findings provide an alternative option for CAR-T optimization with the potential to widen the use of CAR T cells.

Abstract Colorectal cancer (CRC) is a major leading cause of cancer mortality worldwide in which dysregulated protein synthesis plays an etiologic role. The eukaryotic elongation factor 1 A1 (eEF1A1) exerts significant effects on protein synthesis by contributing to peptide chain extension. Whereas its role in CRC remains to be investigated. In this study, we found that the mRNA and protein levels of eEF1A1 were significantly upregulated in CRC cell lines and tissues. Elevated expression of eEF1A1 was correlated with shorter overall survival in 94 CRC patients. The inhibition of proliferation and cell cycle block were observed in CRC cells after eEF1A1 downregulation. Mechanistically, weighted gene correlation network analysis and further Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that mitogen‐activated protein kinases (MAPKs) signaling pathways were significantly enriched in high‐eEF1A1 expression group, and the levels of phosphorylated p38/JNK/ERK MAPK were dramatically decreased after eEF1A1 downregulation. Overexpression of eEF1A1 in CRC correlated with a poor prognosis. Collectively, this study determined the oncogenic role of eEF1A1 in CRC proliferation and tumorigenesis. eEF1A1 might be a promising therapeutic target and prognostic biomarker in CRC.

BackgroundIntermittent energy restriction (IER) is an effective weight loss strategy. However, the accompanying changes in spontaneous neural activity are unclear, and the relationship among anthropometric measurements, biochemical indicators, and adipokines remains ambiguous.MethodsThirty-five obese adults were recruited and received a 2-month IER intervention. Data were collected from anthropometric measurements, blood samples, and resting-state functional magnetic resonance imaging at four time points. The regional homogeneity (ReHo) method was used to explore the effects of the IER intervention. The relationships between the ReHo values of altered brain regions and changes in anthropometric measurements, biochemical indicators, and adipokines (leptin and adiponectin) were analyzed.ResultsResults showed that IER significantly improved anthropometric measurements, biochemical indicators, and adipokine levels in the successful weight loss group. The IER intervention for weight loss was associated with a significant increase in ReHo in the bilateral lingual gyrus, left calcarine, and left postcentral gyrus and a significant decrease in the right middle temporal gyrus and right cerebellum (VIII). Follow-up analyses showed that the increase in ReHo values in the right LG had a significant positive correlation with a reduction in Three-factor Eating Questionnaire (TFEQ)-disinhibition and a significant negative correlation with an increase in TFEQ-cognitive control. Furthermore, the increase in ReHo values in the left calcarine had a significant positive correlation with the reduction in TFEQ-disinhibition. However, no significant difference in ReHo was observed in the failed weight loss group.ConclusionOur study provides objective evidence that the IER intervention reshaped the ReHo of some brain regions in obese individuals, accompanied with improved anthropometric measurements, biochemical indicators, and adipokines. These results illustrated that the IER intervention for weight loss may act by decreasing the motivational drive to eat, reducing reward responses to food cues, and repairing damaged food-related self-control processes. These findings enhance our understanding of the neurobiological basis of IER for weight loss in obesity.

The high levels of bile acids are a critical factor in hepatorenal syndrome. Organic solute transporter α/β (Ostα/β) participate in bile acids reabsorption in the kidney. Fucoidan has the great potential in protecting against liver and kidney injury. However, whether Ostα/β increase bile acids reabsorption in bile duct ligature (BDL)-induced hepatorenal syndrome and the blockade of fucoidan are still not clear. Male mice that received BDL were given to fucoidan (at 12.5, 25 and 50 ​mg/kg) through intraperitoneal injection once daily for three weeks. The serum, liver and kidney samples of these experimental mice were collected to carry out biochemical, pathological and Western blot analysis. In this study, fucoidan significantly lowered serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), decreased serum levels of uric acid, creatinine and uric nitrogen, restored the deregulation of the renal urate transporter 1 (URAT1), organic anion transporter 1 (OAT1), and organic cation/carnitine transporter 1/2 (OCTN1/2), consistence with alleviation BDL-induced liver and kidney dysfunction, inflammation and fibrosis in mice. Furthermore, fucoidan significantly hampered Ostα/β and reduced bile acids reabsorption in BDL-induced mice, protected against AML12 and HK-2 ​cells injury in vitro. These results demonstrate that fucoidan alleviates BDL-induced hepatorenal syndrome through inhibition Ostα/β to reduce bile acids reabsorption in mice. Therefore, suppression of Ostα/β by fucoidan may be a novel strategy for attenuating hepatorenal syndrome.

Microplastics are ubiquitous in the natural environment, especially in waters, and their potential impact is also a key issue of concern. In this study, we used 1 µm, 1000 μg/L, polystyrene (PS-MPs) particles to analyze the effects after exposure for 14 and 28 days in rare minnow (Gobiocypris rarus). Results indicated that PS-MPs induce structural alterations in the intestinal tissue, including epithelial damage, villi damage and the inflammatory cell infiltration, while the changes were severer after exposure for 28 days. Polystyrene microplastics also significantly increased the activities of catalase (CAT, increased 142 % and 385 % in 14d and 28d), superoxide dismutase (SOD, increased 17.76 % and 23.43 % in the 14d and 28d) and the content of malondialdehyde (MDA, increased 14.5 % and 442 % in the 14d and 28d), glutathione (GSH, increased 146 % and 298 % in the 14d and 28d). The results not only showed the characterization of gut microbial communities in rare minnow, but also indicated that microbial diversity and composition were altered in gut of fish exposed to PS-MPs. In the control groups, Proteobacteria (31.36–54.54 %), Actinobacteriota (39.99–52.54 %), Fusobacteriota (1.43–1.78 %), Bacteriadota (0.31–0.57 %) were the four dominant bacterial phyla in the intestinal of rare minnow. After exposure to microplastics, In the gut microbiota, the proportion of Proteobacteria increased 9.27 % and 30 % with exposure time, while Actinobacteria decreased 37.89 % and significantly different after 28 days. In addition, metabolomic analysis suggested that exposure to PS-MPs induced alterations of metabolic profiles in rare minnow and differential metabolites were involved in energy metabolism, inflammatory responsible secretion, oxidative stress, nucleotide and its metabolomics. In conclusion, our findings suggest that long-term exposure to microplastics could induce intestinal inflammation, oxidative stress, microbiota dysbiosis and metabolic disorder in rare minnow, and the alterations and severity were exacerbated by prolonged exposure. This study has extended our cognition of the toxicity of polystyrene, and enriched theoretical data for exploring the toxicological mechanism of microplastics.

BackgroundChromosome 8p11.2 includes several key genes in development such as the FGFR1, ANK1, KAT6A, and SLC20A2 genes. Deletion of this fragment causes a contiguous gene syndrome. Currently, few cases of interstitial deletion of whole 8p11.2 have been reported. We report a rare case of 8p11.2 deletion syndrome with the unique phenotypes, presenting with early-onset diabetes.Case DescriptionA 20-year-old man with a 1-year history of diabetes mellitus was admitted to the Endocrinology Clinic. Physical examination revealed the dysmorphic facial features, and broad and foreshortened halluces. Laboratory examination indicated spherocytosis anemia, and hypogonadotropic hypogonadism. Bone mineral density analysis showed decreased bone density in the lumbar vertebrae. Brain CT showed calcification. Whole-exome sequencing revealed a 7.05-Mb deletion in 8p11 containing 43 OMIM genes, and a large in-frame deletion of exons 48–55 in the DMD gene. Metformin was given to the patient after which his blood glucose was well controlled. HCG was injected subcutaneously and was supplemented with calcium and vitamin D, which led to an improvement in the patient’s quality of life.ConclusionWe report a rare case of 8p11.2 deletion syndrome with unique phenotypes, and early-onset diabetes. It is challenging for endocrinologists to simultaneously reconcile a combination of these diseases across multiple disciplines. We discussed the influencing factors of early-onset diabetes in this patient and speculated that it was caused by complex interactions of known and unknown genetic backgrounds and environmental factors.

In order to solve the problem that the existing graph attention mechanism tends to cause attention distribution to certain relations with high frequency when performing link prediction related tasks, a new link prediction model based on hierarchical attention mechanism was proposed.In the link prediction task, a hierarchical attention mechanism was designed to give different attention to the relationships of different relationship types connected to a given entity in the knowledge graph according to the relationship in the prediction task.While the characteristics of multi-hop neighbor entities were pay attention to, the relationship characteristics was pay more attention to find the relationship type that matches the target relationship.Through comparison experiments with the mainstream models on multiple benchmark data sets, the results show that the performance of the model is better than the mainstream models and has good robustness.

Objective To compare the identification effect of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, rpoB gene sequencing and VITEK 2 Compact on Staphylococci. Methods Three methods were used to identify 59 isolates of Staphylococci from food simultaneously. Results The result consistency of MALDI-TOF MS and rpoB gene sequencing was 100. 00%, while the consistency of MALDI-TOF MS with VITEK 2 Compact was 83. 05%(49/59). Seven isolates were misidentified by VITEK 2 Compact because of out of identification range. The MALDI-TOF MS method could quickly identify 59 strains as 17 species of Staphylococci, and the identification score was related to the species. The identification score of Staphylococcus aureus is the highest(> 2. 300), and the identification score of Staphylococcus squirrel, S. piscifermentans and S. succinus was relatively low(1. 700-2. 000). Conclusion Compared with rpoB gene sequencing and VITEK 2 Compact method, MALDI-TOF MS method is more rapid and accurate. In order to achieve a better identification effect, the existing database still needs to be further optimized.

Carbonic anhydrase (CA) inhibitors have a long history of safe clinical use as mild diuretics, in the treatment of glaucoma and for altitude sickness prevention. In this study, we aimed to determine if CA inhibition may be an alternative approach to control thrombosis. We utilized a high-resolution dynamic imaging approach to provide mechanistic evidence that CA inhibitors may be potent anti-procoagulant agents in vitro and effective anti-thrombotics in vivo. Acetazolamide and methazolamide, while sparing platelet secretion, attenuated intracellular chloride ion entry and suppressed the procoagulant response of activated platelets in vitro and thrombosis in vivo. The chemically similar N-methyl acetazolamide, which lacks CA inhibitory activity, did not affect platelet procoagulant response in vitro. Outputs from rotational thromboelastometry did not reflect changes in procoagulant activity and reveal the need for a suitable clinical test for procoagulant activity. Drugs specifically targeting procoagulant remodeling of activated platelets, by blockade of carbonic anhydrases, may provide a new way to control platelet-driven thrombosis without blocking essential platelet secretion responses.

The principal demonstrated role of the nonvisual arrestins in vivo is to limit G protein-coupled receptor (GPCR) signaling. Nonetheless, a direct demonstration of this fundamental ability in platelets remains lacking, despite the prominent role played by GPCRs in platelet activation. This paper describes the basic characterization of the activatory responses of platelets from mice lacking arrestin-3 (arr3-/-), revealing pleiotropic roles dependent on GPCR ligand. Functionally, arrestin-3 acts as a brake on platelet aggregation regardless of ligand tested. Downstream of P2Y receptors, arr3-/- mice show increased secretion and integrin activation mirrored by enhanced intracellular calcium signaling and global PKC-dependent phosphorylation. Furthermore, P2Y12 receptor (P2Y12R) activity as assessed by ADP-mediated reduction of VASP phosphorylation is enhanced in arr3-/-mice. Downstream of PAR receptors there are similar increases in secretion and integrin activation in arr3-/- mice, together with enhanced PKC activity. Last, in arr3-/- mice the TP receptor displays unaltered PKC activity but markedly reduced calcium responses, which together with the kinetics of the aggregation response suggested a unique positive regulatory role for arrestin-3 in TP signaling. Overall, this paper reveals pleiotropic roles for arrestin-3 dependent on GPCR ligand describing for the first time a negative regulatory function for arrestin-3 in platelets.

The conversion of flavonoid glycosides and their analogs to their lipophilic ester derivatives was developed by nanobiocatalysts from immobilizing Thermomyces lanuginosus lipase (TLL) on polydopamine-functionalized magnetic Fe3O4 nanoparticles (Fe3O4-PDA-TLL). The behavior investigation revealed that Fe3O4-PDA-TLL exhibits a preference for long chain length fatty acids (i.e., C10 to C14) with higher reaction rates of 12.6–13.9 mM/h. Regarding the substrate specificity, Fe3O4-PDA-TLL showed good substrate spectrum and favorably functionalized the primary OH groups, suggesting that the steric hindrances impeded the secondary or phenolic hydroxyl groups of substrates into the bonding site of the active region of TLL to afford the product.

In this paper, our aim is to study the following fuzzy system: xn+1=Axn−1xn−2+Bxn−3D+Cxn−4, n=0,1,2,⋯, where {xn} is a sequence of positive fuzzy numbers and the initial conditions x−4,x−3,x−2,x−1,x0 and the parameters A,B,C,D are positive fuzzy numbers. Firstly, the existence and uniqueness of positive fuzzy solutions of the fuzzy system are proved. Secondly, the dynamic behavior of the equilibrium points for the fuzzy system are studied by means of the fuzzy sets theory, linearization method and mathematical induction. Finally, the results obtained in this paper are simulated by using the software package MATLAB 2016, and the numerical results not only show the dynamic behavior of the solutions for the fuzzy system, but also verify the effectiveness of the proposed results.

Abstract Background Although the genetic spectrum of human colorectal cancer (CRC) is mainly characterized by APC, KRAS and TP53 mutations, driver genes in tumor initiation have not been conclusively demonstrated. In this study, we aimed to identify novel markers for CRC. Methods We performed exome analysis of sporadic colorectal cancer (sCRC) coding regions to screen loss of function (LoF) mutation genes, and carried out systems-level approaches to confirm top rank gene in this study. Results We identified loss of BMP5 is an early event in CRC. Deep sequencing identified BMP5 was mutated in 7.7% (8/104) of sCRC samples, with 37.5% truncating mutation frequency. Notably, BMP5 negative expression and its prognostic value is uniquely significant in sCRC but not in other tumor types. Furthermore, BMP5 expression was positively correlated with E-cadherin in CRC patients and its dysregulation play a vital role in epithelial-mesenchymal transition (EMT), thus triggering tumor initiation and development. RNA sequencing identified, independent of BMP/Smads pathway, BMP5 signaled though Jak-Stat pathways to inhibit the activation of oncogene EPSTI1. Conclusions Our result support a novel concept that the importance of BMP5 in sCRC. The tumor suppressor role of BMP5 highlights its crucial role in CRC initiation and development.

Zinc–ion hybrid supercapacitors are a promising energy storage device as they simultaneously combine the high capacity of batteries and the high power of supercapacitors. However, the practical application of Zinc–ion hybrid supercapacitors is hindered by insufficient energy density and poor rate performance. In this study, a symmetrical zinc–ion hybrid supercapacitor device was constructed with hollow mesoporous-carbon nanospheres as electrode materials, and aqueous ZnSO4 adopted as an electrolyte. Benefiting from the mesoporous structure and high specific area (800 m2/g) of the hollow carbon nanospheres, fast capacitor-type ion adsorption/de-adsorption on both the cathode and the anode can be achieved, as well as additional battery-type Zn/Zn2+ electroplating/stripping on the anode. This device thus demonstrates outstanding electrochemical performance, with high capacity (212.1 F/g at 0.2 A/g), a high energy density (75.4 Wh/kg at 0.16 kW/kg), a good rate performance (34.2 Wh/kg energy density maintained at a high power density of 16.0 kW/kg) and excellent cycling stability with 99.4% capacitance retention after 2,500 cycles at 2 A/g. The engineering of this new configuration provides an extremely safe, high-rate, and durable energy-storage device.

Zinc-based electrochemistry attracts significant attention for practical energy storage owing to its uniqueness in terms of low cost and high safety. In this work, we propose a 2.0-V high-voltage Zn–MnO2 battery with core@shell Co3O4@MnO2 on carbon cloth as a cathode, an optimized aqueous ZnSO4 electrolyte with Mn2+ additive, and a Zn metal anode. Benefitting from the architecture engineering of growing Co3O4 nanorods on carbon cloth and subsequently deposited MnO2 on Co3O4 with a two-step hydrothermal method, the binder-free zinc-ion battery delivers a high power of 2384.7 W kg−1, a high capacity of 245.6 mAh g−1 at 0.5 A g−1, and a high energy density of 212.8 Wh kg−1. It is found that the Mn2+ cations are in situ converted to Mn3O4 during electrochemical operations followed by a phase transition into electroactive MnO2 in our battery system. The charge-storage mechanism of the MnO2-based cathode is Zn2+/Zn and H+ insertion/extraction. This work shines light on designing multivalent cation-based battery devices with high output voltage, safety, and remarkable electrochemical performances.

Financing by patent pledge is an important way for small- and medium-sized pharmaceutical enterprises to address financing problems. In this study, eight indexes are analyzed considering both the pledge patent value and pledger credit value. And a prediction model for the patent pledge financing amount for pharmaceutical enterprises is constructed for the first time using the analytic hierarchy process and the fuzzy comprehensive evaluation method. Three levels of financing amount are concluded through the prediction model and prediction results corresponding with the financing amount are displayed. This model was designed to help small- and medium-sized pharmaceutical enterprises get access to financing through patent pledge to relieve their financial stress. At the same time, it provides guides for pledgees and policymakers to improve the efficiency and quality of patent pledge. This work is reliable and valid in that it constructs this prediction model based on systematical data from official data sources.

We analyzed surveillance data for 2 sentinel hospitals to estimate the influenza-associated severe acute respiratory infection hospitalization rate in Beijing, China. The rate was 39 and 37 per 100,000 persons during the 2014–15 and 2015–16 influenza seasons, respectively. Rates were highest for children

One of the mechanisms by which PI3 kinase can regulate platelet function is through phosphorylation of downstream substrates, including glycogen synthase kinase-3 (GSK3)α and GSK3β. Platelet activation results in the phosphorylation of an N-terminal serine residue in GSK3α (Ser21) and GSK3β (Ser9), which competitively inhibits substrate phosphorylation. However, the role of phosphorylation of these paralogs is still largely unknown. Here, we employed GSK3α/β phosphorylation-resistant mouse models to explore the role of this inhibitory phosphorylation in regulating platelet activation. Expression of phosphorylation-resistant GSK3α/β reduced thrombin-mediated platelet aggregation, integrin αIIbβ3 activation, and α-granule secretion, whereas platelet responses to the GPVI agonist collagen-related peptide (CRP-XL) were significantly enhanced. GSK3 single knock-in lines revealed that this divergence is due to differential roles of GSK3α and GSK3β phosphorylation in regulating platelet function. Expression of phosphorylation-resistant GSK3α resulted in enhanced GPVI-mediated platelet activation, whereas expression of phosphorylation-resistant GSK3β resulted in a reduction in PAR-mediated platelet activation and impaired in vitro thrombus formation under flow. Interestingly, the latter was normalised in double GSK3α/β KI mice, indicating that GSK3α KI can compensate for the impairment in thrombosis caused by GSK3β KI. In conclusion, our data indicate that GSK3α and GSK3β have differential roles in regulating platelet function.

Dysplasia and intramucosal esophageal squamous cell carcinoma (ESCC) frequently go unnoticed with white-light endoscopy and, therefore, progress to invasive tumors. If suitable targets are available, fluorescence molecular endoscopy might be promising to improve early detection. Microarray expression data of patient-derived normal esophagus (n = 120) and ESCC samples (n = 118) were analyzed by functional genomic mRNA (FGmRNA) profiling to predict target upregulation on protein levels. The predicted top 60 upregulated genes were prioritized based on literature and immunohistochemistry (IHC) validation to select the most promising targets for fluorescent imaging. By IHC, GLUT1 showed significantly higher expression in ESCC tissue (30 patients) compared to the normal esophagus adjacent to the tumor (27 patients) (p < 0.001). Ex vivo imaging of GLUT1 with the 2-DG 800CW tracer showed that the mean fluorescence intensity in ESCC (n = 17) and high-grade dysplasia (HGD, n = 13) is higher (p < 0.05) compared to that in low-grade dysplasia (LGD) (n = 7) and to the normal esophagus adjacent to the tumor (n = 5). The sensitivity and specificity of 2-DG 800CW to detect HGD and ESCC is 80% and 83%, respectively (ROC = 0.85). We identified and validated GLUT1 as a promising molecular imaging target and demonstrated that fluorescent imaging after topical application of 2-DG 800CW can differentiate HGD and ESCC from LGD and normal esophagus.

In most of the cognitive radio (CR) network scenarios,there are multiple primary users (PU) with intense traffic.A novel multi-PU multi-state CR access mechanism and the corresponding multi-power access strategy based on the primary user traffic were proposed to address this problem.The method enabled the secondary user (SU) to access the optimal channel and adopt an appropriate power to transmit data,which could maximize the throughput of the CR system.Numerical simulation results show that the proposed method can enable the SU to take advantage of the information and resource of the multi-PU.The method not only minimizes the interference to the primary user,but also improves the achievable throughput of the CR system.

Abstract Herein we propose a new equivalent circuit including double heterojunctions in series to simulate the current–voltage characteristic of P–I–N planar structure perovskite solar cells. This new method can theoretically solve the dilemma of the parameter diode ideal factor being larger than 2 from an ideal single heterojunction equivalent circuit, which usually is in the range from 1 to 2. The diode ideal factor reflects PN junction quality, which influences the recombination at electron transport layer/perovskite and perovskite/hole transport layer interface. Based on the double PN junction equivalent circuit, we can also simulate the dark current–voltage curve for analyzing recombination current (Shockley–Read–Hall recombination) and diffusion current (including direct recombination), and thus carrier recombination and transportation characteristics. This new model offers an efficacious and simple method to investigate interfaces condition, film quality of perovskite absorbing layer and performance of transport layer, helping us further improve the device efficiency and analyze the working mechanism.

The cage and ladder structured phosphorus-containing polyhedral oligomeric silsesquioxanes (DOPO-POSS) have been synthesized through the hydrolytic condensation of 9,10-dihydro-9-oxa-10-phosphenanthrene-10-oxide (DOPO)-vinyl triethoxysilane (VTES). The unique ladder and cage–ladder structured components in DOPO-POSS endowed it with good solubility in vinyl epoxy resin (VE), and it was used with tetrabutyl titanate (TBT) to construct a phosphorus-silicon-titanium synergy system for the flame retardation of VE. Thermal stabilities, mechanical properties, and flame retardancy of the resultant VE composites were investigated by thermal gravimetric analysis (TGA), dynamic mechanical analysis (DMA), three-point bending tests, limiting oxygen index (LOI) measurement, and cone calorimetry. The experimental results showed that with the addition of only 4 wt% DOPO-POSS and 0.5 wt% TBT, the limiting oxygen index value (LOI) increased from 19.5 of pure VE to 24.2. With the addition of DOPO-POSS and TBT, the peak heat release rate (PHRR), total heat release (THR), smoke production rate (SPR), and total smoke production (TSP) were decreased significantly compared to VE-0. In addition, the VE composites showed improved thermal stabilities and mechanical properties comparable to that of the VE-0. The investigations on pyrolysis volatiles of cured VE further revealed that DOPO-POSS and TBT exerted flame retardant effects in gas phase. The results of char residue of the VE composites by SEM and XPS showed that TBT and DOPO-POSS can accelerate the char formation during the combustion, forming an interior char layer with the honeycomb cavity structure and dense exterior char layer, making the char strong with the formation of Si-O-Ti and Ti-O-P structures.

Metastasis is a well-known poor prognostic factor and primary cause of mortality in patients with colorectal cancer (CRC). Recently, with the progress of high through-put sequencing, aberrantly expressed non-coding RNAs (ncRNAs) were found to participate in the initiation and development of cancer. However, the mechanisms of ncRNA-mediated regulation of metastasis in CRC remain largely unknown. In this study, we systematically analyzed the expression network of microRNAs (miRNAs) and genes in CRC metastasis using bioinformatics, and discovered that the miR-581/SMAD7 axis could be a potential factor that drives CRC metastasis. A dual luciferase report assay and protein analysis confirmed the binding relationship between miR-581 and SMAD7. Further functional assays revealed that miR-581 inhibition could suppress cell proliferation and induce apoptosis in SW480 cells. Up-regulation or down-regulation of miR-581 could both affect cell invasion capacity and modulate epithelial to mesenchymal transition (EMT) via a SMAD7/TGFβ signaling pathway. In conclusion, our findings elucidated that miR-581/SMAD7 could be essential for CRC metastasis, and may serve as a potential therapeutic target for CRC patients.

Pseudomonas putida (P. putida) MnB1 is a widely used model strain in environment science and technology for determining microbial manganese oxidation. Numerous studies have demonstrated that the growth and metabolism of P. putida MnB1 are influenced by various environmental factors. In this study, we investigated the effects of hydrogen peroxide (H2O2) and manganese (Mn2+) on proliferation, Mn2+ acquisition, anti-oxidative system, and biofilm formation of P. putida MnB1. The related orthologs of 4 genes, mco, mntABC, sod, and bifA, were amplified from P. putida GB1 and their involvement were assayed, respectively. We found that P. putida MnB1 degraded H2O2, and quickly recovered for proliferation, but its intracellular oxidative stress state was maintained, with rapid biofilm formation after H2O2 depletion. The data from mco, mntABC, sod and bifA expression levels by qRT-PCR, elucidated a sensitivity toward bifA-mediated biofilm formation, in contrary to intracellular anti-oxidative system under H2O2 exposure. Meanwhile, Mn2+ ion supply inhibited biofilm formation of P. putida MnB1. The expression pattern of these genes showed that Mn2+ ion supply likely functioned to modulate biofilm formation rather than only acting as nutrient substrate for P. putida MnB1. Furthermore, blockade of BifA activity by GTP increased the formation and development of biofilms during H2O2 exposure, while converse response to Mn2+ ion supply was evident. These distinct cellular responses to H2O2 and Mn2+ provide insights on the common mechanism by which environmental microorganisms may be protected from exogenous factors. We postulate that BifA-mediated biofilm formation but not intracellular anti-oxidative system may be a primary protective strategy adopted by P. putida MnB1. These findings will highlight the understanding of microbial adaptation mechanisms to distinct environmental stresses.

Tunable properties prompt the development of different “tailor-made” functional ionic liquids (FILs) for specific tasks. FILs with an ether group are good solvents for many organic compounds and enzymatic reactions. However, ionic composition influences the solubility by affecting the physiochemical properties of these FILs. To address the structure effect, a series of novel FILs with a mono-ether group (ME) based on imidazole were prepared through cationic functionalization and anionic exchange reactions, and characterized by NMR, mass spectroscopy, and Thermogravimetric analysis (TGA). The effect of ionic composition (cationic structure and anions) on density, viscosity, ionic conductivity, electrochemical window, and thermal properties of these ME-FILs were systematically investigated. In general, the viscosity and heat capacity increases with the bigger cationic volume of ME-FILs; in particular, the 2-alkyl substitution of imidazolium enhances the viscosity remarkably, whereas the density and conductivity decrease on the condition of the same [NTf2]− anion; For these ME-FILs with the same cations, the density follows the order of [NTf2]− > [PF6]− > [BF4]−. The viscosity follows the order of [PF6]− > [BF4]− > [NTf2]−. Ion conductivity follows the order of [NTf2]− ≈ [BF4]− > [PF6]−. It is noted that the dynamic density has a good linear relationship with the temperature, and the slopes are the same for all ME-FILs. Furthermore, these ME-FILs have broad electrochemical windows and glass transition temperatures in addition to a cold crystallization and a melt temperature for ME-FIL7. Therefore, the cationic structure and counter anion affect the physicochemical properties of these ME-FILs together.

Research on hMLH1 and hMSH2 mutations tend to focus on Lynch syndrome (LS) and LS-like colorectal cancer (CRC). No studies to date have assessed the role of hMLH1 and hMSH2 genes in mass sporadic CRC (without preselection by MSI or early age of onset). We aimed to identify novel hMLH1 and hMSH2 DNA variants, to determine the mutation frequencies and sites in both sporadic and LS CRC and their relationships with clinicopathological characteristics of CRC in Northeast of China. 452 sporadic and 21 LS CRC patients were screened for germline and somatic mutations in hMLH1 and hMSH2 genes with PCR-SSCP sequencing. We identified 11 hMLH1 and seven hMSH2 DNA variants in our study cohort. Six of them were novel: four in hMLH1 gene (IVS8-16 A>T, c.644 GAT>GTT, c.1529 CAG>CGG and c.1831 ATT>TTT) and two in hMSH2 gene (-39 C>T, insertion AACAACA at c.1127 and deletion AAG at c.1129). In sporadic CRC, germline and somatic mutation frequencies of hMLH1/hMSH2 gene were 15.59% and 17.54%, respectively (p = 0.52). Germline mutations present in hMLH1 and hMSH2 genes were 5.28% and 10.78%, respectively (pTTT (3.90%), a polymorphism. Somatic mutation frequency of hMLH1/hMSH2 gene was significantly different in proximal, distal colon and rectal cancer (p = 0.03). Our findings elucidate the mutation spectrum and frequency of hMLH1 and hMSH2 genes in sporadic and LS CRC, and their relationships with clinicopathological characteristics of CRC.

von Willebrand factor (VWF) is essential for normal hemostasis. VWF gene mutations cause the hemorrhagic von Willebrand disease (VWD). In this study, a 9-year-old boy was diagnosed as type 2A VWD, based on a history of abnormal bleeding, low plasma VWF antigen and activity, low plasma factor VIII activity, and lack of plasma high-molecular-weight (HMW) VWF multimers. Sequencing analysis detected a 6-bp deletion in exon 28 of his VWF gene, which created a mutant lacking D1529V1530 residues in VWF A2 domain. This mutation also existed in his family members with abnormal bleedings but not in >60 normal controls. In transfected HEK293 cells, recombinant VWF ΔD1529V1530 protein had markedly reduced levels in the conditioned medium (42±4% of wild-type (WT) VWF, p

In the title complex, [Co(C10H11N2O2)2(C5H5N)2], the CoII atom lies on a centre of symmetry and adopts a distorted cis-CoO2N4 octahedral geometry. The two acetone salicyloylhydrazone ligands are deprotonated and act as N,O-bidentate monoanionic ligands, forming the equatorial plane, while the axial positions are occupied by two N atoms of two pyridine molecules. The complex presents O—H...N and C—H...N intramolecular hydrogen bonds. Intermolecular C—H...N and C—H...O interactions are also present in the crystal.

Objective • This study aims to investigate the relationship between folic acid (FA) metabolic gene polymorphisms, homocysteine (Hcy), vitamin B12 (Vit B12), and red blood cell folate (RBCF) with adverse pregnancy. The findings of this study can help in the prevention and treatment of adverse pregnancy in the future. Methods • 118 pregnant women admitted to Qingdao Central Hospital between August 2020 and October 2022 were selected for retrospective analysis, including 62 cases of normal delivery (control group, CG) and 56 cases of adverse pregnancy (research group, RG). The single nucleotide polymorphisms of MTHFR C677T, MTHFR A1298C, and MTRR A66G gene loci were tested in both cohorts. Besides, differences in Hcy, Vit B12, and RBCF levels were observed, as well as Hcy, Vit B12, and RBCF alterations in different genotype carriers in the research group. Results • An elevated proportion of MTHFR 677TT-type gene and MTRR 66GG-type gene carriers and a lower proportion of MTRR 66GG-type gene carriers were found in the research group (χ2 = 4.458, 4.238, 4.206, P = .035, .040, .040). As indicated by the Logistic regression analysis, carriers of MTHFR 677TT and MTRR 66GG gene had an increased risk of adverse pregnancy outcomes (95%CI=2.881-5.942, 1.427-3.809, P < .001), while MTRR 66AG carriers had a decreased risk (95%CI=0.124-1.849, P < .001). Finally, Hcy levels of MTHFR 677TT and MTRR 66GG gene carriers increased, while Vit B12 and RBCF decreased; the opposite was true for MTRR 66AG gene carriers (P < .001). Conclusions • FA metabolic gene polymorphisms, Hcy, Vit B12, and RBCF are closely related to adverse pregnancy outcomes, which is of great significance for future clinical evaluation of adverse pregnancy. [ABSTRACT FROM AUTHOR]