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Coagulation disorders are common in Kawasaki disease (KD). The main objectives of the present study were to probe the associations of coagulation profiles with clinical classification, IVIG responsiveness, coronary artery abnormalities (CAAs) in the acute episode of KD. A total of 313 KD children were recruited and divided into six subgroups, including complete KD (n = 217), incomplete KD (n = 96), IVIG-responsive KD (n = 293), IVIG-nonresponsive KD (n = 20), coronary artery noninvolvement KD (n = 284) and coronary artery involvement KD (n = 29). Blood samples were collected within 24-h pre-IVIG therapy and 48-h post-IVIG therapy. Coagulation profiles, conventional inflammatory mediators and blood cell counts were detected. Echocardiography was performed during the period from 2- to 14-day post-IVIG infusion. In addition, 315 sex- and age-matched healthy children were enrolled as the controls. (1) Before IVIG therapy, coagulation disorders were more prone to appear in KD patients than in healthy controls, and could be overcome by IVIG therapy. FIB and DD significantly increased in the acute phase of KD, whereas reduced to normal levels after IVIG therapy. (2) PT and APTT were significantly longer in patients with complete KD when compared with their incomplete counterparts after IVIG therapy. (3) The larger δDD, δFDP and the smaller δPT, δINR predicted IVIG nonresponsiveness. (4) The higher δDD and δFDP correlated with a higher risk for CAAs (DD: r = −0.72, FDP: r = −0.54). Coagulation disorders are correlated with complete phenotype, IVIG nonresponsiveness and CAA occurrence in the acute episode of KD, and can be rectified by synergistic effects of IVIG and aspirin. [ABSTRACT FROM AUTHOR]

Ultrasound has expanded into the therapeutic field as a medical imaging and diagnostic technique. Low-intensity pulsed ultrasound (LIPUS) is a kind of therapeutic ultrasound that plays a vital role in promoting fracture healing, wound repair, immunomodulation, and reducing inflammation. Its anti-inflammatory effects are manifested by decreased pro-inflammatory cytokines and chemokines, accelerated regression of immune cell invasion, and accelerated damage repair. Although the anti-inflammatory mechanism of LIPUS is not very clear, many in vitro and in vivo studies have shown that LIPUS may play its anti-inflammatory role by activating signaling pathways such as integrin/Focal adhesion kinase (FAK)/Phosphatidylinositol 3-kinase (PI3K)/Serine threonine kinase (Akt), Vascular endothelial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS), or inhibiting signaling pathways such as Toll-like receptors (TLRs)/Nuclear factor kappa-B (NF-κB) and p38-Mitogen-activated protein kinase (MAPK). As a non-invasive physical therapy, the anti-inflammatory and immunomodulatory effects of LIPUS deserve further exploration. [ABSTRACT FROM AUTHOR]

The microstructures of the ionomer–catalyst interfaces in the catalyst layers are important for the fuel cell performance because they determine the distribution of the active triple-phase boundaries. Here, we investigate the ionomer–catalyst interactions in hydroxide exchange membrane fuel cells (HEMFCs) using poly(aryl piperidinium) and compare them with proton exchange membrane fuel cells (PEMFCs). It is found that different catalyst layer microstructures are between the two types of fuel cell. The ionomer/carbon (I/C) ratio does not have a remarkable impact on the HEMFC performance, while it has a strong impact on the PEMFC performance, indicating the weaker interaction between the HEMFC ionomer and catalyst. Molecular dynamics simulations demonstrate that the HEMFC ionomer tends to distribute on the carbon support, unlike the PEMFC ionomer, which heavily covers the Pt nanoparticles. These results suggest that the poisoning effect of the ionomer on the catalyst is much weaker in HEMFCs, and the improved ionomer/catalyst interaction is beneficial for the HEMFC performances. [ABSTRACT FROM AUTHOR]

Purpose: The principal objective of this project was to review and thoroughly examine the chemical characteristics, pharmacological activity, and quantification methods associated with contezolid. Methods: The article was based on published and ongoing preclinical and clinical studies on the application of contezolid. These studies included experiments on the physicochemical properties of contezolid, in vitro antimicrobial research, in vivo antimicrobial research, and clinical trials in various phases. There were no date restrictions on these studies. Results: In June 2021, contezolid was approved for treating complicated skin and soft tissue infections. The structural modification of contezolid has resulted in better efficacy compared to linezolid. It inhibits bacterial growth by preventing the production of the functional 70S initiation complex required to translate bacterial proteins. The current evidence has indicated a substantial decline in myelosuppression and monoamine oxidase inhibition without impairing its antibacterial properties. Contezolid was found to have a more significant safety profile and to be metabolised by flavin monooxygenase 5, reducing the risk of harmful effects due to drug–drug interactions. Adjusting doses is unnecessary for patients with mild to moderate renal or hepatic insufficiency. Conclusion: As an oral oxazolidinone antimicrobial agent, contezolid is effective against multi-drug resistant Gram-positive bacteria. The introduction of contezolid provided a new clinical option. [ABSTRACT FROM AUTHOR]

Wheat (Triticum aestivum) is one of the most important food crops with an urgent need for increase in its production to feed the growing world. Triticum timopheevii (2n = 4x = 28) is an allotetraploid wheat wild relative species containing the At and G genomes that has been exploited in many pre-breeding programmes for wheat improvement. In this study, we report the generation of a chromosome-scale reference genome assembly of T. timopheevii accession PI 94760 based on PacBio HiFi reads and chromosome conformation capture (Hi-C). The assembly comprised a total size of 9.35 Gb, featuring a contig N50 of 42.4 Mb and included the mitochondrial and plastid genome sequences. Genome annotation predicted 166,325 gene models including 70,365 genes with high confidence. DNA methylation analysis showed that the G genome had on average more methylated bases than the At genome. In summary, the T. timopheevii genome assembly provides a valuable resource for genome-informed discovery of agronomically important genes for food security. [ABSTRACT FROM AUTHOR]

Introduction: This study assessed the safety, tolerability, and PK/PD of HSK7653 tablets in Chinese patients with type 2 diabetes mellitus (T2DM). Methods: This was a Phase IIa, multicenter, randomized, double-blind, placebo-controlled, and dose-increasing study with 48 Chinese diabetes patients. Subjects were randomly assigned to placebo and 10/25/50 mg dose groups, and they received oral administration once every two weeks for a total of six times. Safety and tolerability were assessed throughout this study, and PK/PD parameters were analyzed using non-compartment model with WinNonlin. Results: The three doses of HSK7653 were well tolerated, and the incidence of TEAE and ADR was not significantly increased compared with the placebo group. Cmax increased linearly with the increasing dose, and the mean t1/2 was 64.0–87.0 h. The first dose and last dose PK parameters were similar. After oral administration of 10–50 mg HSK7653 every two weeks, the average Rac_Cmax and Rac_AUC were 0.9–1.0 and 1.0–1.1 respectively; therefore, HSK7653 was not accumulated in vivo. All three doses significantly inhibited DPP-4 activity and increased plasma GLP-1 level and serum insulin levels. When the plasma concentration of HSK7653 was ≥ 20.0 ng/mL, the DPP-4 inhibition rate in all subjects was maintained at > 80.0%. In 10 and 25 mg dose groups, the HbA1c levels maintained a downward trend compared with the placebo group. Discussion: HSK7653 showed desirable pharmacokinetic and pharmacodynamic properties with good safety and tolerability in Chinese T2DM patients. DPP-4 inhibition rate and plasma GLP-1 levels were higher in each dose group than in placebo group. Trial Registration Number: CTR20182505 (Drug Clinical Trial Registration and Information Disclosure Platform, www.chinadrugtrials.org.cn). [ABSTRACT FROM AUTHOR]

This paper addresses the challenge of accurately describing the boundary of deep cavern-type reservoirs. A method is developed to extract diffraction information from the cavern and its boundaries from full wavefield seismic data using PCA wavefield separation technology. The paper describes a method for extracting diffraction information based on post-stack seismic data, and demonstrates the validity of this method in identifying cavern's boundaries via forward modeling. Subsequently, the method is applied to actual seismic data to extract diffraction information from deep caverns. By separating wavefield information at different scales, the extracted diffraction information can effectively identify the characteristics of cavernous reservoirs and their boundaries. It is verified by examples that the diffraction wave information separation method can provide a more accurate description of the distribution of deep cavern-type reservoirs, which can provide a basis for predicting this type of reservoir. [ABSTRACT FROM AUTHOR]

Background: It has been acknowledged that the tumour immune microenvironment (TIME) plays a critical role in determining therapeutic responses and clinical outcomes in breast cancer (BrCa). Thus, the identification of the TIME features is essential for guiding therapy and prognostic assessment for BrCa. Methods: The heterogeneous cellular composition of the TIME in BrCa by single-cell RNA sequencing (scRNA-seq). Two subtype-special genes upregulated in the tumour-rich subtype and the immune-infiltrating subtype were extracted, respectively. The CRABP2/CD69 signature was established based on CRABP2 and CD69 expression, and its predictive values for the clinical outcome and the neoadjuvant chemotherapy (NAT) responses were validated in multiple cohorts. Moreover, the oncogenic role of CRABP2 was explored in BrCa cells. Results: Based on the heterogeneous cellular composition of the TIME in BrCa, the BrCa samples could be divided into the tumour-rich subtype and the immune-infiltrating subtype, which exhibited distinct prognosis and chemotherapeutic responses. Next, we extracted CRABP2 as the biomarker for the tumour-rich subtype and CD69 as the biomarker for the immune-infiltrating subtype. Based on the CRABP2/CD69 signature, BrCa samples were re-divided into three subtypes, and the CRABP2highCD69low subtype exhibited the worst prognosis and the lowest chemotherapeutic response, while the CRABP2lowCD69high subtype showed the opposite results. Furthermore, CARBP2 functioned as a novel oncogene in BrCa, which promoted tumour cell proliferation, migration, and invasion, and CRABP2 inhibition triggered the activation of cytotoxic T lymphocytes (CTLs). Conclusion: The CRABP2/CD69 signature is significantly associated with the TIME features and could effectively predict the clinical outcome. Also, CRABP2 is determined to be a novel oncogene, which could be a therapeutic target in BrCa. [ABSTRACT FROM AUTHOR]

Male breast cancer (MBC) is a rare but aggressive malignancy with cellular and immunological characteristics that remain unclear. Here, we perform transcriptomic analysis for 111,038 single cells from tumor tissues of six MBC and thirteen female breast cancer (FBC) patients. We find that that MBC has significantly lower infiltration of T cells relative to FBC. Metastasis-related programs are more active in cancer cells from MBC. The activated fatty acid metabolism involved with FASN is related to cancer cell metastasis and low immune infiltration of MBC. T cells in MBC show activation of p38 MAPK and lipid oxidation pathways, indicating a dysfunctional state. In contrast, T cells in FBC exhibit higher expression of cytotoxic markers and immune activation pathways mediated by immune-modulatory cytokines. Moreover, we identify the inhibitory interactions between cancer cells and T cells in MBC. Our study provides important information for understanding the tumor immunology and metabolism of MBC. Male breast cancer may involve different populations of immune cells. Here the authors use single cell transcriptomics to show that infiltration of T cells is lower in male breast cancer relative to female breast cancer, and find that this is accompanied by distinct metabolic changes. [ABSTRACT FROM AUTHOR]

In oil and gas engineering, non-Newtonian fluids are universal. Thus, studies on the seepage laws of non-Newtonian power-law fluids are of great importance and significance. In this paper, we introduced the definition of elastic coefficient based on the establishing elastic outer boundary conditions. We then set up a homogeneous well test model for non-Newtonian power-law fluids under elastic outer boundary conditions, considering wellbore reservoir and skin effect. The Laplace space solution of the bottom hole pressure was obtained using the similar structure method, and the double logarithmic characteristic curve was drawn using the Stehfest numerical inversion technique. Furthermore, the main parameters affecting the characteristic curve were analyzed. The experimental results showed that the early phase of the homogeneous well test curve can be affected by the wellbore storage coefficient. In addition, the mid-term seepage is greatly influenced by the power-law flow exponent and the skin factor, while the elastic coefficient predominantly acts on the later phase of fluid flow. We concluded that the introduction of the elastic outer boundary expands the traditional fixed form of ideal outer boundary conditions, enabling a more general representation of the seepage model. This approach provides a more effective theoretical basis for further exploration of the seepage law of the reservoir. Meanwhile, we simplify the calculation process of the solution model by the use of the similar structure method of the solution and point out a new research direction for solving the more complex seepage model. [ABSTRACT FROM AUTHOR]

Objective: We aimed to examine the influence of sleep disturbances on the risk of oligo/astheno/teratozoospermia (OAT) in men attending an infertility clinic. Methods: We consecutively enrolled men attending an infertility clinic from July 2020 to June 2021. Semen parameters were obtained at initial presentation, and the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale score, and the STOP-BANG Questionnair were completed to assess sleep quality. Embryo outcomes were evaluated after infertility treatment. Results: Of 466 men enrolled, 119 had OAT (OAT group) and 347 had normozoospermia (NS group). There were no differences between the two groups regarding Epworth Sleepiness Scale and STOP-BANG Questionnaire scores. The prevalence of poor sleep quality (Pittsburgh Sleep Quality Index score ≥ 5) in the OAT group was significantly higher than that in the NS group (42% vs. 29%, p = 0.009). A higher rate of poor subjective sleep quality was observed in the OAT group compared with the NS group (p = 0.005) and Pearson's correlations revealed a negative relationship between subjective sleep quality and semen quality. Logistic regression found that subjective sleep quality was independently associated with an increased risk of OAT (adjusted odds ratio = 0.610, p = 0.007). Conclusions: Men with OAT attending an infertility clinic exhibited poor subjective sleep quality. Improving sleep disturbances may be a target intervention to reduce the risk of OAT. This possibility warrants further investigation. [ABSTRACT FROM AUTHOR]

A letter to the editor of the journal Angiogenesis discusses the potential link between systemic glucocorticoids and long-term microvascular injury in COVID-19 patients. The authors note that a study found damaged microcirculation in COVID-19 patients, but did not include information on the use of systemic glucocorticoids. Glucocorticoids have been widely used in the treatment of COVID-19 and have been shown to have direct effects on microcirculation, including inhibiting angiogenesis, inducing endothelial dysfunction, and enhancing the constrictive tone of vascular smooth muscle cells. The authors also mention that systemic glucocorticoids may indirectly contribute to microvascular injury through metabolic disarrangements. Further research is needed to determine the relationship between systemic glucocorticoids and long-term microvascular injury in COVID-19. [Extracted from the article]

The multi-field compound polishing method based on the shear thickening has been applied to the processing of various hard materials due to its characteristics of low damage and adaptability to complex surface shapes. The surface defects on the carbide twist drill are usually produced during the grinding. This paper proposes a magnetic field-assisted shear thickening polishing (MASTP) method based on shear thickening and pumping effect, aiming to enhance surface quality of twist drill and passivate cutting edges to improve its cutting performance. The microscopic material removal mechanism of the twist drill and the rheological properties of magnetic shear thickening fluid were analyzed. The magnetic field intensity distribution in the polishing area for two types of magnetic pole arrangements is simulated. A numerical simulation was used to investigate the effect regularity of the polishing gap and spindle speed on the flow field shear stress. Experimental validation was carried out based on the processing platform. The results show the effects of processing parameters on twist drill surface roughness improvement rate and edge radius correspond to the simulated shear stress. After 60 min of polishing, the surface roughness improvement rate reached 94.7% and 80.4% at the body clearance and margin of the twist drill, respectively. The passivating radius of the major cutting edge can reach 12.92 μm, while the passivating radius of the minor cutting edge can reach 15.73 μm. At the same time, the edge defects caused by the grinding are also removed. [ABSTRACT FROM AUTHOR]

Aims: Circulating peripheral helper T (Tph) cells are shown to promote the progression of autoimmune diseases. However, the role of Tph cells in inflammatory diseases such as type 2 diabetes mellitus (T2DM) and the differences between T2DM and autoimmune diabetes remain unclear. Methods: We recruited 92 T2DM patients, 106 type 1 diabetes mellitus (T1DM) patients and 84 healthy control individuals. Peripheral blood mononucleated cells were isolated and examined by multicolor flow cytometry. We further evaluated the correlations between circulating Tph cells and clinical biochemical parameters, islet function, disease progression and islet autoantibodies. Results: Circulating Tph cells were significantly higher in both T2DM and T1DM patients than in healthy control individuals. A significant positive correlation was observed between Tph cells and B cells in T1DM patients and overweight T2DM patients. Furthermore, Tph cells were negatively correlated with the area under the C-peptide curve (C-PAUC), and Tph cells were significantly positively correlated with fasting glucose and glycated hemoglobin levels in T2DM patients. However, no correlation was found between Tph cells and the above clinical indicators in T1DM patients. The frequency of Tph cells positively correlated with the titer of GAD autoantibodies and duration of disease in T1DM patients. In addition, we demonstrated that the frequency of Tph cells was decreased after rituximab therapy in T1DM patients. Conclusions: Circulating Tph cells are associated with blood glucose levels and islet function in T2DM patients. In T1DM patients, circulating Tph cells are associated with B cells and islet autoantibodies. This may suggest that Tph cells have different pathogenic mechanisms in the two types of diabetes. Clinical trial information: http://ClinicalTrials.gov NCT01280682 (registered July, 2010). [ABSTRACT FROM AUTHOR]

Purpose: Patients with obstructive sleep apnoea (OSA) have a high incidence of vascular endothelial injury. The most important pathophysiological feature of OSA is chronic intermittent hypoxia (CIH). This study aimed to investigate the mechanisms of CIH-related vascular endothelial injury. Methods: IH exposure was applied to human umbilical vein endothelial cells (HUVECs). After modeling, cell viability, the expression levels of peroxisome proliferator activated receptor γ (PPARγ), apoptosis-associated proteins and mitochondrial division fusion proteins, and the levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were assessed via Cell Counting Kit-8 (CCK-8), western blotting, fluorescent microscope, and flow cytometry, respectively. Rosiglitazone (PPARγ agonist), tempo (the mitochondrial-specific antioxidant), and tempo combined with PPARγ interfering RNA were used to treat HUVECs, respectively. Results: After IH exposure, cell viability and levels of MMP decreased, cell apoptosis and ROS levels increased, and the expression levels of PPARγ decreased. Both tempo and rosiglitazone pretreatment ameliorated cell apoptosis and improved cell viability. In addition, mitochondrial function became better after tempo pretreatment. PPARγ interference reversed the protective effects of tempo on IH-related mitochondrial function injury and cell injury. Conclusions: PPARγ regulated the apoptosis and cell viability of IH-treated HUVECs by altering mitochondrial function. This finding clarifies the mechanism of CIH-related vascular endothelial injury. [ABSTRACT FROM AUTHOR]

Background: COVID-19 put older individuals at high risk for morbidity and mortality, isolation, reduced coping, and lower satisfaction with life. Many older adults experienced social isolation, fear, and anxiety. We hypothesized that successful coping with these stressors would maintain or improve satisfaction with life, a crucial psychological outcome during the pandemic. Our study investigated relationships between older people's coping and life satisfaction during the pandemic and their optimism, sense of mastery, closeness with spouse, family, and friends, and vulnerabilities from frailty, comorbid diseases, memory problems, and dependencies in instrumental activities of daily living (IADL). Methods: The study was based on a special COVID-19 sample of 1351 community-dwelling older adults who participated in the 2020 Health and Retirement Survey. A comprehensive structural equation modeling was used to test direct and indirect effects, with life satisfaction as the main outcome and coping as a mediator between the other variables and coping. Results: Most survey respondents were female and between the ages of 65–74 years. They averaged 1.7 chronic conditions, one in seven was frail, about one-third rated their memory as fair or poor, and about one in seven reported one or more difficulties in IADL. As hypothesized—older people with increased sense of mastery and optimism were better able to cope and had greater life satisfaction. In addition, close relationships with friends and with other family members besides the spouse/partner or children contributed to more successful coping, while the interpersonal closeness of all types contributed directly to greater life satisfaction. Finally, older people with more IADL limitations reported greater difficulty coping and lower life satisfaction, and those older people who were frail or had multiple comorbid diseases reported lower life satisfaction. Conclusions: Optimism, sense of mastery and closeness with family/friends promotes coping and life satisfaction, whereas frailty and comorbidities make coping more challenging and lead to lower life satisfaction particularly during a pandemic. Our study improves on prior research because of its nationally representative sample and formal specification and testing of a comprehensive theoretical framework. [ABSTRACT FROM AUTHOR]

Radix Astragali is one of the most famous and frequently used health food supplements and herbal medicines. Among more than 227 components of Radix Astragali, Astragaloside IV (AG IV) is famous functional compound and is commonly used as a quality marker for Radix Astragali. However, the relatively low content of AG IV in Radix Astragali (< 0.04%, w/w) severely limits its application. The purpose of this study is to improve the biotransformation of AG IV and its bioaccessibility during in vitro digestion by Poria cocos solid fermenting Radix Astragali. The optimum fermentation conditions were as follows: Inoculation amount 8 mL; fermentation time 10 d; fermentation humidity 90%. Through fermentation, the content of AG IV was increased from 384.73 to 1986.49 μg/g by 5.16-fold. After in vitro digestion, the contents of genistin, calycosin, formononetin, AG IV, Astragaloside II (AG II) and total flavonoids in fermented Radix Astragali (FRA) of enteric phase II (ENTII) were 34.52 μg/g, 207.32 μg/g, 56.76 μg/g, 2331.46 μg/g, 788.31 μg/g, 3.37 mg/g, which were 2.08-fold, 2.51-fold, 1.05-fold, 8.62-fold, 3.22-fold and 1.50-fold higher than those of control, respectively. The Scanning electron microscopy (SEM) of FRA showed rough surface and porous structure. The DPPH and ABTS radical scavenging rate of FRA were higher than those of control. These results showed that the Poria cocos solid fermentation could increase the content of the AG IV in Radix Astragali and improve the bioaccessibility and antioxidant activity of Radix Astragali, which is providing new ideas for future development and utilization of Radix Astragali. [ABSTRACT FROM AUTHOR]

Recent researches in the development of in-plane micro-supercapacitor (MSC) have been dedicated to advancing its energy density in a finite storage area. However, the low ion-accessible surface area of plane electrode material has been the bottleneck limiting the energy output of MSC. Herein, we design a stable ionic liquid (IL)-MXene microemulsion system in virtue of tween-20 (TW20), gathering IL-TW20 microdroplets around MXene nanosheets. The microemulsion can adhere on the current collector and form the dense MXene-TW20-IL film. The IL as spacer and electrolyte is retained in the interlamination of MXene with the elimination of the TW20 during heat treatment, which enlarges the ion-accessible surface area of the MXene electrode. Thus, the MSC based on the flexible MXene-IL film exhibits a high areal capacitance (44.6 mF·cm−2), a high areal and volumetric energy density (50.7 µW·h·cm−2 and 39 mW·h·cm−3), surpassing most of the reported MXene-based MSCs. And the MSC unit can be arbitrarily integrated in terms of various energy and voltage requirements. For instance, the integrated array with thirty MSC units in series realizes a high voltage output of 90 V, widening the range of application in next-generation microelectronic devices. [ABSTRACT FROM AUTHOR]

Uniform monodispersed mesoporous silica nanospheres with vertical pores were successfully synthesized using chiral amphiphilic small molecule L-16Ala5PyClO4 and solvents as dual templates via solgel transcription. The morphologies and pore sizes of silicas are adjustable by changing the type and amount of solvents in the reaction systems. With the increase of the organic solvent content, the morphologies of the obtained silica changed from nanospheres with vertical pore structures to nanosheets structures. When 1 mL of benzene, cyclohexane or toluene were used as solvents, only silica nanospheres were obtained, the BET surface areas of silica nanospheres reached 600.7, 669.5, and 560.8 m2/g, respectively. The pore sizes were 3.51, 3.54, and 3.46 nm, respectively. Significantly, these ordered silica nanospheres/poly(vinyl alcohol-co-ethylene) (PVA-co-PE) nanofiber membranes have high separation efficiencies (>99%) for n-hexane/water mixtures. [ABSTRACT FROM AUTHOR]

Photo composition is one of the most important factors in the aesthetics of photographs. As a popular application, composition recommendation for a photo focusing on a specific subject has been ignored by recent deep-learning-based composition recommendation approaches. In this paper, we propose a subject-aware image composition recommendation method, SAC-Net, which takes an RGB image and a binary subject window mask as input, and returns good compositions as crops containing the subject. Our model first determines candidate scores for all possible coarse cropping windows. The crops with high candidate scores are selected and further refined by regressing their corner points to generate the output recommended cropping windows. The final scores of the refined crops are predicted by a final score regression module. Unlike existing methods that need to preset several cropping windows, our network is able to automatically regress cropping windows with arbitrary aspect ratios and sizes. We propose novel stability losses for maximizing smoothness when changing cropping windows along with view changes. Experimental results show that our method outperforms state-of-the-art methods not only on the subject-aware image composition recommendation task, but also for general purpose composition recommendation. We also have designed a multistage labeling scheme so that a large amount of ranked pairs can be produced economically. We use this scheme to propose the first subject-aware composition dataset SACD, which contains 2777 images, and more than 5 million composition ranked pairs. The SACD dataset is publicly available at https://cg.cs.tsinghua.edu.cn/SACD/. [ABSTRACT FROM AUTHOR]

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The use of additive is an effective approach to optimize the active layer morphology and improve the power conversion efficiency (PCE) of organic solar cells (OSCs). However, residual solvent additives always lead to undesirably compromise the stability of OSCs. In this work, an organic small molecule BBT-Cl was designed and used as a novel solid additive to partly replace solvent additive to fabricate highperformance OSCs. The synergistic effect of the dual additives on the optical property, morphology and photovoltaic characteristics of the PM6:Y6 based non-fullerene OSCs have been systematically characterized. The introduction of BBT-Cl could effectively enhance the crystallinity of the blend and promote charge extraction and transport. Consequently, the OSCs processed by the dual additives exhibit a high PCE of 17.73%, which is obviously higher than OSCs with CN additive (16.48%). Meanwhile, BBT-Cl based dual additives treatment has also been successfully introduced into another two non-fullerene OSCs to verify its general applicability. Furthermore, 20% PCE aging is significantly prolonged from 720 min to 2880 min for the devices proceeded with the dual additives. This work highlights the great potential of solid additive in the fabrication of efficient OSCs with excellent stability. [ABSTRACT FROM AUTHOR]

Bioprosthetic heart valves (BHVs) are important for transcatheter valve replacement. Current commercial BHVs on the market are basically porcine or bovine pericardium (BP) crosslinked with glutaraldehyde (GA). Simply applying GA to BHVs can enhance mechanical stability, but cannot alleviate in vivo calcification. In this work, we developed a two-step decellularization (TSD) strategy to modify this biomacromolecular network, in which BP was post-treated, as the second step of decellularization, with a mild biosurfactant n-dodecyl-β-D-maltoside in a mixture of isopropanol and phosphate-buffered saline after the first step of traditional decellularization and GA cross-linking. The TSD-treated BP exhibited not only low cytotoxicity and excellent mechanical properties in vitro, but also low immune responses and significant anticalcification in vivo. After 60 days of subcutaneous implantation in the back of Wistar rats, the calcium content was, as quantified with an inductively coupled plasma optical emission spectrometer, only 1.1 µg/mg compared to 138.6 µg/mg in the control group without the post-treatment. In addition, collagen fibrils were observed with field emitting scanning electron microscopy (SEM), and the morphology and composition of the calcified sites resulting from in vivo biomineralization were studied with SEM with energy dispersive spectroscopy and also X-ray diffraction. This study proposes a facile yet effective anticalcification strategy for the modification of the bovine pericardial bioprosthetic heart valve, a natural biomacromolecular network. [ABSTRACT FROM AUTHOR]

Background: To report three cases of autoimmune cerebellar ataxia related to anti-delta/notch-like epidermal growth factor-related receptor (Tr/DNER) antibodies. Case presentation: Patients with unknown cerebellar ataxia were screened with autoimmune cerebellar ataxia (ACA)-related antibody panel. The anti-Tr antibody was positive in three female patients in whom the onset ages were 43 years, 35 years and 43 years old. The antibody titres of serum and cerebrospinal fluid were all 1:32. Cerebral ataxia was the most prominent presentation. Mild cerebellar atrophy was found in one of the patients. Immunotherapy was effective in all three patients. Conclusion: The Tr antibody is associated with autoimmune ataxia, and it has been suggested that the anti-Tr antibody should be tested in patients with cerebellar ataxia who are negative for routine ACA antibodies. Early immunotherapy may improve patient prognoses. [ABSTRACT FROM AUTHOR]

In this study, we investigate atom–dimer scattering within the framework of hyperspherical coordinates. The coupled-channel Schrödinger equation is solved using the R-matrix propagation technique combined with the smooth variable discretization method. In the matching procedure, the asymptotic wave functions are expressed in the rotated Jacobi coordinates. We apply this approach to the elastic scattering 3 He(T ↑ ) + 4 He 2 and H ↑ +LiH ↑ processes for testing. The convergence of the scattering length as a function of the propagation distance is studied. We find that the method is reliable and can provide considerable savings over previous propagators, so it is suitable for solving the atom–dimer scattering problem for important quantities such as the phase shift, cross section and scattering length. [ABSTRACT FROM AUTHOR]

Ship black carbon emissions have caused great harm to ecological environment. In order to estimate the black carbon emissions, thereby reducing the cost of black carbon experiments, here, we introduced four machine learning algorithms which are lasso regression, support vector machine, extreme gradient boosting, and artificial neural network to predict ship black carbon emissions. The prediction models were established with using the datasets acquired from similar marine engines under various steady-state conditions. The results show that SVM, XGB, and ANN have higher prediction accuracy than lasso regression, and the adjusted R2 of each model is 0.9810, 0.9850, 0.9885, and 0.6088. Although ANN shows the best prediction performance, it is inferior to SVM and XGB in terms of model stability and training cost. Then, in order to simplify the optimization process of hyperparameters and improve the prediction accuracy of the model at the same time, we use three different swarm intelligence algorithms to automatically optimize the hyperparameters of SVM and XGB. In addition, we applied mutual information to measure the correlation between the characteristics of the prediction models and black carbon concentration and found that the characteristics which related to in-cylinder combustion have a strong correlation with the black carbon concentration. The findings in this paper prove the feasibility of machine learning in ship black carbon emission prediction and could provide references for reducing ship black carbon emissions and the formulation of emission regulations. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer (OC) as the most fatal gynecological malignancy worldwide, with epithelial ovarian cancer (EOC) being the predominant and most lethal form, poses a serious threat to human health. LC3-positive extracellular vesicles (LC3+ EVs) promote tumorigenesis by educating CD4+ T cells in a murine melanoma model. However, regulation of LC3+ EVs in human EOC remains largely unknown. Methods: Differential analysis of Rab8a, Hsp90α and Il6 expression was performed using GEPIA2. The number of LC3+ EVs and the frequency of Heat shock protein 90α+ LC3+ EVs (HSP90α+ LC3+ EVs) in the ascites of EOC patients were tested by flow cytometry. IL-6, IL-10, IFN-γ, IL-4 and TGF-β were measured by ELISA. CD4+ T cells were isolated from peripheral blood of healthy human donors using MACS magnetic bead technology. Results: Higher Rab8a, Hsp90a and Il6 expression of cancer tissues compared with normal adjacent tissues in OC were found. The level of IL-6 was positively correlated with LC3+ EVs number, HSP90α+ LC3+ EVs percentage in the ascites, and ROMA index of the patient. In addition, elevated IL-6 production by CD4+ T cells induced by LC3+ EVs was observed, which was suppressed by anti-HSP90α or anti-TLR2. Conclusions: LC3+ EVs level and HSP90α+ LC3+ EVs percentage were associated with elevated IL-6 in the ascites of EOC patients. HSP90α on LC3+ EVs from human EOC could stimulate CD4+ T cell production of IL-6 via TLR2. [ABSTRACT FROM AUTHOR]

A three-compartment culture system was used to study the mechanism by which the AM fungus Funneliformis mosseae influences host plant growth and soil organic carbon (SOC) content in a northwest China coal mining area. A 13CO2 pulse tracing technique was used to trace the allocation of maize photosynthetic C in shoots, roots, AM fungus, and soil. Carbon accumulation and allocation in mycorrhizal (inoculated with Funneliformis mosseae) and non-mycorrhizal treatments were detected. AM fungal inoculation significantly increased the 13C concentration and content in both above- and below-ground plant parts and also significantly enhanced anti-aging ability by increasing soluble sugars and catalase activity (CAT) in maize leaves while reducing foliar malondialdehyde content (MDA) and leaf temperature and promoted plant growth. AM fungi also increased P uptake to promote maize growth. Soil organic carbon (SOC), glomalin, microbial biomass carbon (MBC), and nitrogen (MBN) contents increased significantly after inoculation. A mutually beneficial system was established involving maize, the AM fungus and the microbiome, and the AM fungus became an important regulator of C flux between the above- and below-ground parts of the system. Inoculation with the AM fungus promoted plant growth, C fixation and allocation belowground to enhance soil quality. A positive above-belowground feedback appeared to be established. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancer (EOC) exhibits strong dependency on the tricarboxylic acid (TCA) cycle and oxidative phosphorylation to fuel anabolic process. Here, we show that malate dehydrogenase 2 (MDH2), a key enzyme of the TCA cycle, is palmitoylated at cysteine 138 (C138) residue, resulting in increased activity of MDH2. We next identify that ZDHHC18 acts as a palmitoyltransferase of MDH2. Glutamine deprivation enhances MDH2 palmitoylation by increasing the binding between ZDHHC18 and MDH2. MDH2 silencing represses mitochondrial respiration as well as ovarian cancer cell proliferation both in vitro and in vivo. Intriguingly, re-expression of wild-type MDH2, but not its palmitoylation-deficient C138S mutant, sustains mitochondrial respiration and restores the growth as well as clonogenic capability of ovarian cancer cells. Notably, MDH2 palmitoylation level is elevated in clinical cancer samples from patients with high-grade serous ovarian cancer. These observations suggest that MDH2 palmitoylation catalyzed by ZDHHC18 sustains mitochondrial respiration and promotes the malignancy of ovarian cancer, yielding possibilities of targeting ZDHHC18-mediated MDH2 palmitoylation in the treatment of EOC. [ABSTRACT FROM AUTHOR]

Lithium-sulfur batteries have attracted great attention due to their high capacity and energy density. However, sulfur cathode suffers from poor cycle stability during the electrochemical process. Fe3C materials are promising sulfur hosts for lithium-sulfur batteries due to their high catalytic effect. In this work, we present Fe3C nanoparticles combined with porous carbon as host materials for lithium-sulfur batteries to overcome these issues. In this hybrid structure, the presence of carbon could act as conductive network for the rapid transport of electrons and ions, while Fe3C could facilitate trapping lithium polysulfide due to its high catalytic effect. As a result, the Fe3C/C@S composites exhibit high specific capacity and stable cycle performance. This work provides a new and effective way for the sulfur host design of high performance lithium-sulfur batteries. [ABSTRACT FROM AUTHOR]

(±)-Decumicorine A (1) and (±)-epi-decumicorine A (2), two pairs of enantiomeric isoquinoline alkaloids featuring a novel phenylpropanoid-conjugated protoberberine skeleton, were isolated and purified from the rhizomes of Corydalis decumbens. The separation of (±)-1 and (±)-2 was achieved by chiral HPLC to produce four optically pure enantiomers. The structures and absolute configurations of compounds (−)-1, (+)-1, (−)-2, and (+)-2 were elucidated by spectroscopic analysis, ECD calculations, and X-ray crystallographic analyses. The two racemates were generated from a Diels-Alder [4 + 2] cycloaddition between jatrorrhizine and ferulic acid in the proposed biosynthetic pathways, which were fully verified by a biomimetic synthesis. Moreover, compound (+)-1 exhibited an antiviral entry effect on SARS-CoV-2 pseudovirus by blocking spike binding to the ACE2 receptor on HEK-293T-ACE2h host cells. [ABSTRACT FROM AUTHOR]

Drought stress is one of the main limiting factors in apple (Malus domestica Borkh.) cultivation. Rootstock plays an important role in the drought tolerance of apple plants. 'M.9-T337' is a novel apple rootstock that was recently introduced and widely cultivated in China. In this study, we selected the new, widely promoted Chinese apple variety 'Huashuo' as the scion and grafted it onto 'M.9-T337' (HM9). Another combination, 'Huashuo'/'M.26'/Malus robusta Rehd. (HM26), served as the experimental control to analyse drought resistance in the two hybrids. We believe that this empirical approach is more representative than merely studying rootstock seedlings. After sustained drought stress for over 1 month, the leaf relative water content had decreased in both types of plants, but to a lesser extent in HM26 than in HM9. The SPAD values increased in both plants, but without significant difference. Drought stress reduced photosynthetic activity in both plants, and the net photosynthetic rate was higher in HM26 than in HM9. The observed changes in the chlorophyll fluorescence parameters indicated that drought had damaged the PSII activity centres of both plants, photosynthetic electron transfer was inhibited, and excessive excitation energy accumulated. However, compared to HM26, HM9 displayed lower maximal PSII quantum photochemical efficiency and potential PSII activity. Moreover, HM9 showed lower antioxidant enzyme activity than HM26 under drought stress. A membership function analysis confirmed that 'M.9-T337' was less drought resistant than 'M.26'. Nevertheless, 'M.9-T337' could still recover after prolonged drought stress, indicating it also had good drought resistance. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: In the present study, we aimed to compare the efficacy and safety of quinolones with trimethoprim-sulfamethoxazole (TMP/SMX), nitrofurantoin, fosfomycin, and β-lactams for the treatment of uncomplicated urinary tract infections (UTIs) in adults. Methods: All controlled clinical trials assessing quinolones for uncomplicated UTIs in adults were searched from PubMed, Embase, and Cochrane Library databases. Meta-analyses were used to evaluate the efficacy and safety in randomized controlled trials (RCTs). Results: A total of 47 RCTs consisting of 8992 patients were included in the present analysis. The clinical and bacteriological remission rates of quinolones were significantly higher (P < 0.01) compared with β-lactams and nitrofurantoin, while quinolones showed similar clinical and bacteriological remission rates compared with TMP/SMX and fosfomycin. Moreover, the bacterial resistance and relapse rates of quinolones were significantly lower (P < 0.01) compared with TMP/SMX, β-lactams, and nitrofurantoin. Regarding the adverse drug reactions (ADRs), quinolones did not bring higher risks, while the incidence of ADRs in the quinolone group was also even significantly lower (P < 0.01) compared with the TMP/SMX and nitrofurantoin groups, including the most reported ADRs associated with the gastrointestinal tract. Conclusions: Compared with other anti-UTI drugs, quinolones exerted an excellent effect on clinical remission and bacteriological eradication, and the application of quinolones did not bring a higher risk of ADRs. [ABSTRACT FROM AUTHOR]

Nb3Al nanoparticles were directly synthesized by metallothermic reduction process in the molten salts with mNbCl5–nAlCl3 powders as raw materials and sodium as reducing reagent. The effects of different feeding material orders, soaking time, Nb content in raw materials, and 3NbCl5–AlCl3 content in molten salts on the obtained Nb3Al powder were discussed. The as-prepared samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). It is found that the only phase Nb3Al nanoparticles are obtained by controlling the variation of the feeding material orders, soaking time, and Nb content in raw materials. And the morphologies of as-prepared nanoparticles change owning to different 3NbCl5–AlCl3 contents in molten salts. [ABSTRACT FROM AUTHOR]

As mobile devices become more and more popular, mobile traffic demands are increasing exponentially. To deal with such challenge, caching at small cell base stations (SBSs) is one of the most effective techniques for reducing the transmission delay of mobile applications. However, due to the limitation of the SBS storages, the improvement of reducing transmission delay is limited in small cell networks. In this paper, we propose a novel cooperative caching framework in a small cell network in which SBSs are grouped into disjoint clusters and cooperate through backhaul links to make use of SBS storages. A backhaul-based cooperative caching (BCC) scheme is introduced, and the problem for content placement is formulated to minimize the average download delay in small cell networks. Then, we show that the problem is equivalent to the maximization of a monotone submodular function subject to matroid constraints and propose a low-complexity greedy strategy with 1/2 performance guarantee. Simulation results demonstrate that the proposed scheme achieves lower download delay and better cache hit rate than other schemes. [ABSTRACT FROM AUTHOR]

As an important form of sustainable agriculture, rice-crab (Eriocheir sinensis) co-culture is rapid developing worldwide. However, the knowledge on the bacterial communities of the different components of the system is limited. In this study, we investigated the bacterial community structure in paddy soil and ditch sediment by using high-throughput sequencing technology. The results showed that compared with the ditch sediment, the content of NH4+-N in paddy soil decreased by 62.31%, and the content of AP (available phosphorus) increased by 172.02% (P < 0.05). The most abundant phyla in paddy soil and ditch sediment were Proteobacteria, Bacteroidetes and Chloroflexi, whose relative abundance was above 65%. Among the dominant genera, the relative abundance of an uncultured bacterium genus of Saprospiraceae and an uncultured bacterium genus of Lentimicrobiaceae in paddy soil was significantly lower than ditch sediment (P < 0.05). Alpha diversity indicated that the bacterial diversity of paddy soil and ditch sediment was similar. The bacterial community structure was affected by the relative abundance of bacteria, not the species of bacteria. Redundancy analysis (RDA) showed that the bacterial communities in paddy soil and ditch sediment were correlated with physicochemical properties. Our findings showed that the bacterial community structure was distinct in paddy soil and ditch sediment under rice-crab co-culture probably due to their different management patterns. These results can provide theoretical support for improving rice-crab co-culture technology. [ABSTRACT FROM AUTHOR]

Phyllite fragments are essential for accumulating and generating talus slope at the toes of hillslopes, however, how they are linked to slope failure remains unknown. This paper reports the directional arrangement of phyllite fragments (DAPF) in phyllite talus slope at the eastern margin of the Tibetan Plateau. Field investigation, mathematical statistics and model experiments were performed in order to systematically understand the influencing factors, which include fragment shape, flat ratio, dip angle (α), and fine particle content (c). The results show that the quadrilateral fragment generates a similar imbricate structure more easily than the triangular and rod fragments in the phyllite talus slope. Additionally, the flat phyllite fragments easily accumulate as imbricated structures on the phyllite talus slope. When the dip angle (α) is in the range of 20°–30°, the minimum orientation ratio (P) is more than 50%, which means that the DAPF phenomenon is more obvious in the phyllite talus slope. For the fine particle content (c) at the same dip angle (α), the minimum orientation ratio (P) is 54%, and the minimum orientation ratio (P) correlates positively with the fine particle content (c). Therefore, compared with the homogeneous talus slope, the phyllite talus slope displays a special DAPF phenomenon. This study provides a valuable reference and presents novel knowledge for risk assessment and engineering design against the phyllite talus slope failure mechanism. [ABSTRACT FROM AUTHOR]

SP 1 sp H NMR (500 MHz, CDCl SB 3 sb , , ppm, J/Hz): 7.52 (1H, dd, J = 8.4, 2.0, H-6'), 7.34 (1H, d, J = 2.0, H-2'), 6.98 (1H, d, J = 8.4, H-5'), 6.61 (1H, s, H-8), 6.59 (1H, s, H-3), 4.05 (3H, s, OMe), 3.99 (3H, s, OMe), 3.97 (3H, s, OMe). SP 1 sp H NMR (500 MHz, CDCl SB 3 sb , , ppm, J/Hz): 6.57 (4H, s, H-2, 6, 2', 6'), 5.58 (2H, s, OH), 4.72 (2H, d, J = 3.9, H-7, 7'), 4.27 (2H, m, H-9 , 9' ), 3.90 (2H, overlapped, H-9 , 9' ), 3.89 (12H, 4 × OMe), 3.09 (2H, q, J = 4.1, H-8, 8'). 6 Guanqigerupan Wangbu, Zhe Dui Pan De Ning Bu, Inner Mongolia People's Press, Huhehaote, 1987, p. 80. 7 Wang QH, Wu JS, Wu XL, Han N, Tai WQ, Dai N, Wu RJ, Ao W. Monatsh. SP 1 sp H NMR (500 MHz, CD SB 3 sb OD, , ppm, J/Hz): 6.71 (1H, d, J = 8.0, H-5), 6.69 (1H, d, J = 8.0, H-5'), 6.68 (1H, d, J = 2.0, H-2'), 6.67 (1H, d, J = 2.0, H-2), 6.60 (1H, dd, J = 8.0, 2.0, H-6), 6.57 (1H, dd, J = 8.0, 2.0, H-6'), 3.98 (2H, d, J = 8.0, H-9), 3.81 (3H, s, 3-OMe), 3.78 (3H, s, 3'-OMe), 3.12 (1H, d, J = 13.6, H-7' ), 2.85 (1H, d, J = 13.6, H-7' ), 2.79 (1H, dd, J =13.2, 4.6, H-7 ), 2.45 (2H, m, H-7 , 8). [Extracted from the article]

Demand for simple and effective gas sensing sensors is growing rapidly due to the growing threat of triethylamine (TEA). Semiconductor tin oxide (SnO2) is one of the most widely used sensing materials for metal oxide gas sensors. In recent years, a lot of binary ternary compound researches have been carried out. In this paper, five different SnO2 samples were synthesized by simple synthesis method to understand the internal relationship and obtain different gas sensing characteristics. Based on the low temperature nitrogen adsorption tests and the atomic arrangement model, it can be inferred that different exposed surfaces play a key role in TEA sensing properties. In addition, the TEA sensing activity relationship of SnO2 exposed crystal faces is proposed as listed: (200) > (101) > (110). [ABSTRACT FROM AUTHOR]

The meta-analysis aimed to systematically evaluate all the available pieces of evidence concerning the clinical effectiveness of Er,Cr:YSGG lasers (erbium, chromium, yttrium scandium gallium garnet laser) in the non-surgical treatment of patients with chronic periodontitis, and provide guidance for clinicians about the application of Er,Cr:YSGG lasers during the process of non-surgical periodontal treatments. The meta-analysis was conducted with data extracted from 16 randomized controlled clinical trials (RCTs) that compare Er,Cr:YSGG lasers adjunct/substitute to scaling and root planing (SRP) with SRP alone for the treatment of chronic periodontitis published in English or Chinese from January 2000 to January 2020. The weighted mean differences (WMDs) and 95% confidence intervals (CIs) were counted for probing depth (PD) reduction, clinical attachment level (CAL) gain, and visual analogue scale (VAS) score. Heterogeneity of each study was evaluated with the Q test. The publication bias was measured using Begg's adjusted rank correlation test. Sixteen RCTs with 606 patients were included in the meta-analysis. There were statistically significant differences between Er,Cr:YSGG lasers adjunct/substitute to SRP and SRP alone in the PD reduction at 1-month follow-up (WMD = ‑ 0.35, 95% CI [− 0.63, ‑ 0.07], P = 0.013), 3-month follow-up (WMD = − 0.342, 95% CI [− 0.552, − 0.132], P = 0.001), CAL gain at 3-month follow-up (WMD = − 0.17, 95% CI [− 0.31, 0.03], P = 0.017), and VAS score (WMD = − 2.395, 95% CI [− 3.327, − 1.464], P = 0.000) immediately after treatment. There were no significant differences of PD reduction and CAL change at 6-month follow-up. The present meta-analysis indicated that Er,Cr:YSGG lasers provided additional effectiveness in PD reduction and CAL gain at short-term follow-ups and there was less pain compared with SRP alone. [ABSTRACT FROM AUTHOR]

Introduction: N6-methyladenosine (m6A), the most prominent mRNA modification, plays a critical role in many physiological and pathological processes. However, the roles of m6A RNA modification in hepatocellular carcinoma (HCC) remain largely unknown. Materials and Methods: We investigated the mRNA expression and clinical significance of m6A-related genes using data from The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma cohort. Mutation, copy number variation (CNV), methylation, differential expression, and gene ontology analyses, gene set enrichment analysis and the construction of a competing endogenous RNA (ceRNA) regulatory network were performed to investigate the underlying mechanisms of the aberrant expression of m6A-related genes. Results: m6A-related genes were frequently dysregulated in cancers but with a cancer-specific pattern. METTL3, YTHDF2, and ZC3H13 were found to be independent prognostic factors of overall survival (OS); however, only METTL3 was found to be an independent prognostic factor of recurrence-free survival (RFS). Joint effects analysis showed the predictive capacity of combining METTL3, YTHDF2, and ZC3H13 for HCC OS. Then the potential mechanisms of METTL3 were further explored due to its prognostic role in both OS and RFS. CNV and DNA methylation, but not somatic mutations, might contribute to the abnormal upregulation of METTL3 in HCC. Significantly altered genes, microRNAs, and lncRNAs were identified, and a ceRNA regulatory network was constructed to explain the upregulation of METTL3 in HCC. Conclusions: Our study identified several m6A-related genes, especially METTL3, that could be potential prognostic biomarkers in HCC. [ABSTRACT FROM AUTHOR]

Background and Objective: At present, the deficiency of β-cell function is progressive in patients with type 2 diabetes mellitus. Exenatide cannot only control blood glucose well, but also promotes the regeneration and proliferation of islet β-cells and improves the function of β cells. However, it needs to be given twice a day, and there are many adverse reactions such as nausea. PEGylated exenatide (study code: PB-119) needs to be administered only once a week. The purpose of this experiment was to evaluate the safety, pharmacokinetics and pharmacodynamics of an escalating dose regimen of subcutaneous PEGylated exenatide injections in healthy subjects. Methods: Twelve healthy young adult subjects in each group received once-weekly subcutaneous injections of 165 μg, 330 μg, and 660 μg PEGylated exenatide for 6 weeks. Plasma drug concentration was determined in venous blood collected across selected time points. Safety and tolerability were evaluated by monitoring adverse events, laboratory parameters, and electrocardiogram. Blood glucose, insulin, glucagon and C peptide were monitored at different time points to evaluate the pharmacodynamics of PEGylated exenatide. Results: A total of 11, 10, and 12 subjects completed the study in 165 µg, 330 µg, and 660 µg dose groups, respectively. After 6 consecutive weeks of administration, the t1/2 in the 165 μg, 330 μg, and 660 µg dose groups was 55.67 ± 11.03 h, 56.99 ± 21.37 h, and 54.81 ± 13.87 h, respectively. The Cavg was 4.22 ± 0.78 ng/ml, 6.03 ± 1.43 ng/ml, and 10.50 ± 3.06 ng/ml, respectively. AUCss was 708.59 ± 131.87 h•ng/ml, 1012.63 ± 240.79 h•ng/ml, and 1763.81 ± 514.50 h•ng/ml, respectively. The accumulation index was 1.15 ± 0.07, 1.17 ± 0.11, and 1.14 ± 0.07. The CLss/F was 241.25 ± 51.13 ml/h, 341.53 ± 73.62 ml/h, and 450.06 ± 313.76 ml/h, respectively. A total of 10 of 36 (27.78%) subjects in the three dose groups developed specific antibodies after consecutive subcutaneous injections of PEGylated exenatide. The Cavg and Cmax were higher than those of antibody-negative subjects. Furthermore, in antibody-positive subjects, CLss/F, t1/2, AUCτ, accumulation index, MRT(0–inf) and other parameters were lower than those of antibody-negative subjects. In the 165 μg dose group, two subjects (16.67%) experienced 4 adverse events. In the 330 μg dose group, no subjects reported adverse events. In the 660 μg dose group, 8 subjects (66.67%) reported 16 adverse events, which were mostly gastrointestinal. There were no significant changes in the pharmacodynamic parameters except the glucagon level at day 36 in the 660 µg dose group, the 2h postprandial insulin and C peptide levels at day 36 and day 50 in the 165 μg dose group compared with baseline (− 1 day). Conclusion: A once-weekly subcutaneous injection of 165 µg and 330 µg PEGylated exenatide is safe. No significant effects on blood glucose or pancreatic hormone levels were observed in the subjects within these dose groups. The pharmacokinetic parameters of PEGylated exenatide may be affected by immunogenicity. Clinical Trials Registration: The study is registered at clinicaltrials.gov (No. NCT03062774). [ABSTRACT FROM AUTHOR]

Iron deficiency anemia (IDA) is a common micronutrient deficiency among pregnant women with severe consequences including impaired immuno-inflammatory system, premature birth, fetal death etc. The present study aimed to investigate the effects of three iron supplements on IDA female rats and their offspring. The IDA female rat model was established with low iron diet and the rats were then mated. After pregnancy, rats were fed diets containing different iron supplements (iron polysaccharide complex, iron protein succinylate and ferrous sulfate) until their offspring were 42 days old. Pregnancy outcomes, haematological, iron metabolism, physical and neurological development indexes were determined. The results showed that all three iron supplements improved the levels of hematological parameters of both mother and offspring rats. After iron supplementation, serum iron, transferrin saturation and serum ferritin levels were increased compared with the IDA group. The level of ferritin light chain in the liver and spleen of both mother and offspring rats in iron supplemented groups was significantly higher than that of the IDA group. The average number of born alive per litter in the iron treatment groups was significantly higher than that in the IDA group. Iron supplements also improved the physical growth and neurobehavioral development of offspring rats. It was also found that iron supplementation improved the expression of ferritin light chain and the synaptic growth associated proteins in the brain and hippocampus. No significant difference was found in the efficacy of three iron supplements. These results suggest that pregnant and postpartum IDA affects pregnancy outcomes, offspring physical development and causes neural impairment. Sufficient iron supplementation can significantly improve IDA and its adverse effects on both mother and offspring. [ABSTRACT FROM AUTHOR]

Periodic chemical cleaning with sodium hypochlorite (NaClO) is essential to restore the membrane permeability in a membrane bioreactor (MBR). However, the chlorination of membrane foulants results in the formation of disinfection by-products (DBPs), which will cause the deterioration of the MBR effluent and increase the antibiotic resistance in bacteria in the MBR tank. In this study, the formation of 14 DBPs during chemical cleaning offouled MBR membrane modules was investigated. Together with the effects of biofilm extracellular polymeric substances (EPS), influences of reaction time, NaClO dosage, initial pH, and cleaning temperature on the DBP formation were investigated. Haloacetic acids (HAAs) and trichloromethane (TCM), composed over 90% of the DBPs, were increasingly accumulated as the NaClO cleaning time extended. By increasing the chlorine dosage, temperature, and pH, the yield of TCM and dichloroacetic acid (DCAA) was increased by up to a factor of 1–14, whereas the yields of haloacetonitriles (HANs) and haloketones (HKs) were decreased. Either decreasing in the chlorine dosage and cleaning temperature or adjusting the pH of cleaning reagents toward acidic or alkaline could effectively reduce the toxic risks caused by DBPs. After the EPS extraction pretreatment, the formation of DBPs was accelerated in the first 12 h due to the damage of biofilm structure. Confocal laser scanning microscopy (CLSM) images showed that EPS, particularly polysaccharides, were highly resistant to chlorine and might be able to protect the cells exposed to chlorination. [ABSTRACT FROM AUTHOR]