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Analyzing the mechanical deformation of the hydrate-bearing layer during hydrate exploitation requires the establishment of a robust model for the isotropic compression behavior of methane hydrate-bearing sediment (MHBS), which is of utmost importance. However, few research involves developing the isotropic compression model. In this paper, a novel simplified isotropic compression model of MHBS is developed according to the isotropic compression characteristics of MHBS. To address the effect of temperature and pore pressure condition (P-T condition) on the isotropic compression curve (ICC) of MHBS, the phase state parameter, as a representative for P-T condition, is used to characterize the ICC of MHBS with varying P-T condition. The fact that the predicted and measured ICCs display a strong agreement indicates that the simplified compression model developed in this study can effectively capture the isotropic compression behavior of MHBS under various hydrate saturation, temperature, and pore pressure conditions. • A novel simplified isotropic compression model is developed for MHBS. • The influences of hydrate saturation on ICCs are addressed. • The effects of temperature and pore pressure on ICCs are addressed. [ABSTRACT FROM AUTHOR]

Hydrogels have broad application prospects in drug delivery due to their biocompatibility, high water content and three-dimensional structure. However, the regulation of drug release from hydrogels is an important issue in medical applications. At the same time, water also has an important impact on drug release. In this study, a hydrogel with hydrogen bond and ion dipole interaction (PAHDP) was prepared by introducing catechol group into polymer to regulate drug release. Ten model drugs were selected to explore the relationship and mechanism of action among polymer, drug and water. The results showed that PAHDP had excellent adhesion and safety. Drug release test showed that 10 kinds of drugs had different drug release trends, and the release amount was negatively correlated with drug polarizability and LogP. In addition, in vitro transdermal test and pharmacokinetic results showed that the hydrogel based on PAHDP achieved increased or decreased blood drug concentration, and the area under the concentration-time curve (AUC) of >1.5 times showed its potential to regulate drug release. The mechanism study showed that the hydrogen bond and ion dipole interaction between polymer and drug were affected by drug polarizability and LogP, and the distribution of water in different states was changed. Hydrogen bond and ion dipole interactions synergistically control drug release. Therefore, the mussel inspired PAHDP hydrogel has the potential to become a controllable drug delivery system. [Display omitted] [ABSTRACT FROM AUTHOR]

Graphical diagram illustrating the function and mechanism of Nrf2 in Pb-induced kidney injury. [Display omitted] • Lead (Pb)-induced persistent Nrf2 activation contributes to kidney injury. • Persistent Nrf2 activation promotes apoptosis and autophagic blockage. • Nrf2 is persistently activated in a p62-dependent non-canonical manner. Lead (Pb) is an environmental toxicant that poses severe health risks to humans and animals, especially renal disorders. Pb-induced nephrotoxicity has been attributed to oxidative stress, in which apoptosis and autophagy are core events. Nuclear factor erythroid 2-related factor 2 (Nrf2) acts as a major contributor to counteract oxidative damage, while hyperactivation or depletion of Nrf2 pathway can cause the redox imbalance to induce tissue injury. This study was performed to clarify the function and mechanism of Nrf2 in Pb-triggered kidney injury. First, data showed that Pb exposure activates Nrf2 pathway in primary rat proximal tubular cells. Next, Pb-induced Nrf2 activation was effectively regulated by pharmacological modulation or siRNA-mediated knockdown in vitro and in vivo assays. Notably, Pb-triggered cytotoxicity, renal injury and concomitant apoptosis were improved by Nrf2 downregulation, confirming that Pb-induced persistent Nrf2 activation contributes to nephrotoxicity. Additionally, Pb-triggered autophagy blockage was relieved by Nrf2 downregulation. Mechanistically, we found that Pb-induced persistent Nrf2 activation is attributed to reduced Nrf2 ubiquitination and nuclear-cytoplasmic loss of Keap1 in a p62-dependent manner. In conclusion, these findings highlight the dark side of persistent Nrf2 activation and potential crosstalk among Pb-induced persistent Nrf2 activation, apoptosis and autophagy blockage in Pb-triggered nephrotoxicity. [ABSTRACT FROM AUTHOR]

When using a classic lumboperitoneal shunt, laparotomy is inevitable for peritoneal catheter implantation, which is time consuming and difficult for unskilled neurosurgeons. A minimally invasive technique of percutaneous abdominal puncture for catheterization with the assistance of guidewire is introduced in this paper. Ten patients with communicating hydrocephalus received a lumboperitoneal shunt through percutaneous abdominal puncture for catheterization. The safety and effectiveness of percutaneous abdominal puncture for catheterization were followed up for more than 6 months. The surgery was successfully completed in 10 patients. The average operation time was nearly 30 minutes. No patients reported abdominal organ damage. None of the 10 patients had other complications such as peritonitis and obstruction of abdominal catheters caused by the percutaneous peritoneal puncture technique. One patient presented with intracranial aseptic inflammation postoperatively, which was controlled after repeated lumbar puncture. Another patient confirmed that the lumbar catheter was folded in 6 months postoperatively. The technique of percutaneous abdominal puncture for catheterization with the assistance of a guidewire is a simple, safe, and effective way to treat communicating hydrocephalus. [ABSTRACT FROM AUTHOR]

Vertically aligned carbon nanotube (VACNT) arrays are considered promising thermal interface materials (TIM) due to their superior vertical thermal conductivity. However, the weak interaction between adjacent carbon nanotubes (CNT) leads to the change in orientation of the CNT during polymer infiltration. Therefore, the thermal conductivity of a CNT array/polymer composite does not reach the expected value. Simultaneously, the air gap between adjacent CNT hinders the in-plane heat transfer, and both of the above aspects significantly reduce the thermal conductivities of VACNT-based TIM. In this study, we proposed a novel three-dimensional CNT (3DCNT) network structure comprising VACNT crosslinked by randomly-oriented secondary CNT to provide several in-plane phonon paths and maintain the structural stability of the CNT arrays during polymer infiltration. The network structures formed by the secondary CNT were compared for two different growth times: 10 and 20 min. The 3DCNT network that grew for 20 min exhibited a denser network structure compared to the network that grew for 10 min. The vertical thermal conductivity and horizontal thermal conductivity of the 3DCNT20/Polydimethylsiloxane (3DCNT20/P) composite was 544.77% and 56.06% higher than those of the IVACNT/P composites, respectively. A novel three-dimensional CNT (3DCNT) network structure comprising VACNT crosslinked by randomly-oriented secondary CNT to provide several in-plane phonon paths and maintain the structural stability of the CNT arrays. [Display omitted] [ABSTRACT FROM AUTHOR]

• Candidate proposal model provides detailed mitotic candidates, reducing missed detections. • Joint training of classification and clustering capture representative RBF centers. • RBF subcategorization scheme guides feature learning, making members in each subcategory closer in feature space. • RBF subcategorization scheme handles the intra-class diversity and inter-class similarity. Due to the intra-class diversity of mitotic cells and the morphological overlap with similarly looking imposters, automatic mitosis detection in histopathology slides is still a challenging task. In this paper, we propose a novel mitosis detection model in a weakly supervised way, which consists of a candidate proposal network and a verification network. The candidate proposal network based on patch learning aims to separate both mitotic cells and their mimics from the background as candidate objects, which substantially reduces missed detections in the screening process of candidates. These obtained candidate results are then fed into the verification network for mitosis refinement. The verification network adopts an RBF-based subcategorization scheme to deal with the problems of high intra-class variability of mitosis and the mimics with similar appearance. We utilize the RBF centers to define subcategories containing mitotic cells with similar properties and capture representative RBF center locations through joint training of classification and clustering. Due to the lower intra-class variation within a subcategory, the localized feature space at subcategory level can better characterize a certain type of mitotic figures and can provide a better similarity measurement for distinguishing mitotic cells from nonmitotic cells. Our experiments manifest that this subcategorization scheme helps improve the performance of mitosis detection and achieves state-of-the-art results on the publicly available mitosis datasets using only weak labels. [ABSTRACT FROM AUTHOR]

The anterior pituitary plays a critical role in the endocrine system, contains gonadotrophs, which regulate reproductive efficiency by secreting follicle-stimulating hormone (FSH) and luteinizing hormone (LH). PPP2R2A is a serine-threonine phosphatase that regulates reproductive functions in both females and males, its function in pituitary cells remain unclear. Hu sheep is a highly prolific breed, which makes it suitable for studying reproductive mechanisms. In this study, the relative abundances of PPP2R2A mRNA expression were higher in the pituitary of high-prolificacy (HF) Hu sheep compared to those of low-prolificacy (LF) Hu sheep. Additionally, we demonstrated that PPP2R2A promotes pituitary cell proliferation and gonadotropin secretion using the EdU assay and ELISA, respectively. Moreover, it inhibits pituitary cell apoptosis using flow cytometry. Furthermore, PPP2R2A may affect pituitary cell function by regulating the AKT/mTOR signaling pathway. In summary, our findings suggest that PPP2R2A may play a role in regulating pituitary function and influencing the secretion of gonadotropins. • The expression of PPP2R2A is higher in the pituitary of high-prolificacy Hu sheep compared to low-prolificacy. • PPP2R2A promotes the proliferation and secretion of gonadotropins, while inhibiting pituitary cell apoptosis. • PPP2R2A may affect the function of pituitary cell by regulating AKT/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Biochar has demonstrated the potential in mitigating pollutant gaseous emission during composting. However, little is known about the difference among biochars derived from different plant feedstocks on the critical genes' expression and microbial communities' succession for gaseous emissions. In this study, the effects of biochar (from wood chips, cornstalks, and rice husks) on gaseous emissions during chicken manure composting were investigated. Environmental factors, bacterial communities, and functional genes related to CH 4 , N 2 O, NH 3 , and H 2 S emissions were analyzed to reveal the reduction pathways of different biochar amendments during composting. Results showed that all biochar treatments improved the seed germination index of the compost from unmature (55.74%) to mature (70.28–75.23%). The CH 4 , N 2 O, NH 3 , and H 2 S emissions from all biochar-treated composts were reduced by 18.93–27.47%, 35.74–52.82%, 1.26–36.38%, and 8.57–24.14%, respectively, and the cornstalk biochar had the highest emission reduction performance. Temperature, pH, and NH 4 + were the major environmental factors that affected Lactobacillus and Bacillus activities, which critically influenced the CH 4 , N 2 O, NH 3 , and H 2 S emissions during composting. Furthermore, cornstalk biochar mainly improved pmoA for CH 4 reduction, whereas wood chip biochar increased amoA for NH 3 oxidation. Rice husk biochar mostly decreased nirS and nirK and increased norB , narG , and nosZ during N 2 O reduction. Cornstalk biochar also increased dsrB and decreased aprA during H 2 S reduction. Overall, cornstalk biochar was determined to be an optimal additive for simultaneously improving compost maturity and reducing gaseous pollutant emissions during chicken manure composting. This study verified the mechanisms of three plant derived biochars in pollutant gas control in composting, and thus provided evidence for facilitating the sustainable development of composting technologies. [Display omitted] • Cornstalk biochar emitted the lowest CH 4 , N 2 O, NH 3 , and H 2 S in composting. • Temperature, pH, and NH 4 + regulated Lactobacillus and Bacillus to reduce emissions. • Cornstalk biochar increased pmoA and decreased mcrA abundances for lower CH 4 emissions. • Rice husk biochar reduced nirS and nirK and increased norB , narG , and nosZ to lower N 2 O. • Cornstalk biochar increased dsrB and decreased aprA abundances for lower H 2 S emissions. [ABSTRACT FROM AUTHOR]

First-phase ejection fraction (EF1) is a novel measure of early changes in left ventricular systolic function. This study was to investigate the prognostic value of EF1 in heart transplant recipients. Heart transplant recipients were prospectively recruited at the Union Hospital, Wuhan, China between January 2015 and December 2019. All patients underwent clinical examination, biochemistry measures [brain natriuretic peptide (BNP) and creatinine] and transthoracic echocardiography. The primary endpoint was a combined event of all-cause mortality and graft rejection. In 277 patients (aged 48.6 ± 12.5 years) followed for a median of 38.7 [26.8–45.0] months, there were 35 (12.6%) patients had adverse events including 20 deaths and 15 rejections. EF1 was negatively associated with BNP (β = −0.220, p < 0.001) and was significantly lower in patients with events compared to those without. EF1 had the largest area under the curve in ROC analysis compared to other measures. An optimal cut-off value of 25.8% for EF1 had a sensitivity of 96.3% and a specificity of 97.1% for prediction of events. EF1 was the most powerful predictor of events with hazard ratio per 1% change in EF1: 0.628 (95%CI: 0.555–0.710, p < 0.001) after adjustment for left ventricular ejection fraction and global longitudinal strain. Early left ventricular systolic function as measured by EF1 is a powerful predictor of adverse outcomes after heart transplant. EF1 may be useful in risk stratification and management of heart transplant recipients. • EF1 is a novel measure of early LV systolic function, our study found a strong association between EF1 and adverse outcomes in patients post HT. • EF1 is a powerful predictor of adverse outcomes post HT, which is superior to LVGLS and other measures of systolic function. • EF1 is a novel but simple marker of early left ventricular systolic function, which can be easily measured in clinical routine examinations. [ABSTRACT FROM AUTHOR]

The contribution of recycled oceanic crust to the mantle source of mid-ocean ridge basalts (MORBs) remains a subject of debate, as radiogenic isotopes alone yield ambiguous insights. Here, we present comprehensive data on whole-rock major element, trace element, and Mo–Nd–Hf isotopic compositions for MORB samples from International Ocean Discovery Program Expedition 349 sites U1431E and U1433B in the eastern (ESB) and southwestern (SWB) subbasins, respectively, of the South China Sea (SCS). The δ98/95Mo values of the SCS MORBs exhibit a significant range (from −0.80‰ to +0.05‰), in contrast to the restricted composition observed in MORBs (δ98/95Mo = −0.19‰ ± 0.01‰). The ESB MORBs display extremely light Mo isotopic compositions (δ98/95Mo = −0.80‰ to −0.24‰) with Nd Hf isotopic compositions similar to those of Pacific MORB, whereas the SWB MORBs show higher δ98/95Mo values (−0.44‰ to +0.05‰) and depleted Nd Hf isotopic compositions. The δ98/95Mo values of the SCS MORBs are negatively correlated with Ce/Mo ratios and positively correlated with ε Hf values, suggesting the incorporation of dehydrated slab components into the source of the SCS MORBs. The subbasin-scale mantle heterogeneity in the SCS can be best explained by varying degrees of interaction between a mantle plume and stagnant slabs in the mantle transition zone, as suggested by mantle tomography. The rigid stagnant slab in the mantle transition zone beneath the SWB largely impeded the upwelling of the mantle plume, whereas the slab beneath the ESB was disrupted by the plume and subsequently transported into the upper mantle. This study, therefore, provides compelling evidence for the involvement of recycled oceanic slabs in generating MORB and the influence of an ascending mantle plume on seafloor spreading in a continental marginal sea. Mantle recycling processes in marginal sea basins exhibit distinct characteristics compared to those occurring in open oceans. • The SCS MORBs mainly show much lower δ98/95Mo values than global MORB. • Extremely light Mo isotopes in the SCS MORBs result from abundant ROC in the source. • The Mo isotopic compositions of the SCS MORBs exhibit subbasin-scale variations. • Plume-stagnant slab interaction leads to large-scale mantle heterogeneity in the SCS. [ABSTRACT FROM AUTHOR]

Betaine, a highly valuable feed additive, has been observed to alter the distribution of protein and fat in the bodies of ruminants and to exhibit strong antioxidant properties. However, the effects of dietary betaine supplementation on the biochemical parameters of blood and on testicular oxidative stress remain unknown. This study aimed to investigate the effects of dietary betaine supplementation on lipid metabolism, immunity, and testicular oxidative status in Hu sheep. Experimental sheep (n=3, three sheep per group) were fed betaine-containing diets, a basal diet supplemented with 0 g/day (control group), 1 g/day (B1), and 3 g/day betaine (B2). There were no differences in the serum concentrations of triglycerides and cholesterol in Hu sheep receiving diets supplemented with betaine. The ratio of basophils significantly increased in the B1 and B2 groups. ELISA (enzyme-linked immunosorbent assay) results showed that testicular superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity were significantly higher, whereas malondialdehyde (MDA) content significantly decreased, after feeding betaine-supplemented diets. qPCR results showed that the mRNA expression levels of CAT , SOD2 , and GSH-Px were significantly upregulated in both the B1 and B2 groups compared to those in the control group. Furthermore, the expression of proliferating cell nuclear antigen (PCNA) was significantly lower in the testes of betaine-treated Hu sheep than in the control group. Moreover, LKB1 (liver kinase B1) expression significantly increased, and mRNA expression of AMPK (AMP-activated serine/threonine protein kinase) significantly decreased in the B1 group. The relative gene expression of mTOR (mechanistic target of rapamycin) was significantly higher in the B2 group than in the control group. RAPTOR expression significantly increased in the B1 group. Western blot revealed that the ratio of P-mTOR and mTOR significantly increased after feeding betaine-supplemented diets. In conclusion, betaine supplementation improved serum lipid metabolism, immune response, and increased the testicular antioxidant capacity of Hu sheep, which might be regulated via mTOR signaling pathway. • Dietary betaine supplementation improved concentrations of high-density lipoprotein cholesterol (HDL-C) and granulocytes of Hu sheep. • Testicular antioxidant capacity is increased with betaine-containing diets of Hu sheep. • Dietary betaine supplementation regulated mTOR signaling pathway in Hu sheep. [ABSTRACT FROM AUTHOR]

As a new form of crude slices of traditional Chinese medicine (TCM), traditional Chinese medicine dispensing granules (TCMDGs) have been used for clinical formula. It is necessary to evaluate whether the chemical composition and biological activity are consistent among the different batches. Angelica Sinensis Radix (ASR), the root of Angelica sinensis (Oliv.) Diels, is one of the most frequently used medicinal materials in gynecology, senile and cardiovascular diseases. In this paper, the quality of TCMDGs is examined taking the Angelica Sinensis Radix dispensing granules (ASRDGs) as a typical case. In this study, integrating bioequivalence and chemical analysis was used to evaluate the quality of dispensing granules taking ASRDGs as a typical case. According to the clinical efficacy of ASR, the intestinal absorption liquid of ASRDGs (IAL-ASRDGs) in 15 batches prepared by the everted gut sac (EGS) method was used to evaluate its effects of vasodilatation on isolated vascular rings. Then, the chemical profiling analysis of IAL-ASRDGs from the 15 batches was carried out by ultra-high performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS). The components in IAL-ASRDGs were identified using mass spectrometry data and the obtained reference standards. Pearson correlation analysis was further performed for the selection of quality control markers based on the extracted ion chromatograms of the identified compounds and vasodilatory activities of different batches of IAL-ASRDGs. Moreover, the selected chemical components in ASRDGs were further verified by vasodilatory activities and quantitatively analyzed by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-QQQ-MS). The IAL-ASRDGs showed favorable vasodilatory activities. There were significant differences among the 15 batches. The ranges of maximum vasodilation rate (%) and EC 50 were 69.33 ± 7.16 to 19.52 ± 5.05 and 0.07–25.58 g raw materials/mL, respectively. A total of 46 compounds in IAL-ASRDGs were identified based on accurate mass measurements, fragmentation behavior and the reference standards. Among them, 8 compounds including butylidenephthalide, butylphthalide and senkyunolide A showed positive correlation with vasodilatory effect of IAL-ASRDGs. The 8 compounds were further verified, showing obvious vasodilatory activities. The content of the 8 compounds also showed some differences in 15 batches of ASRDGs. Among them, the content of ferulic acid, senkyunolide I and senkyunolide H varied the most in different batches of ASRDGs. By Pearson correlation analysis, the total content of senkyunolides (senkyunolide A, senkyunolide I and senkyunolide H) in ASRDGs was found to reflect the vasodilatory activity of ASRDGs mostly. This study provides new strategies for the quality assessment by bioequivalence and explore the chemical quality control markers for ASRDGs. [Display omitted] [ABSTRACT FROM AUTHOR]

Wound healing remains challenging due to posttraumatic pain. At present, most wound dressings ignore the importance of wound pain. In this study, a temperature-sensitive multifunctional intelligent hydrogel patch (CPAG) containing lidocaine has developed for wound healing. CPAG hydrogel was prepared by grafting N-isopropylacrylamide and acrylamide onto carboxymethyl agarose (CMA) modified by agarose and encapsulating gallic acid and lidocaine. FTIR, 1H NMR spectroscopy, SEM and rheology were used to investigate its structure and temperature-sensitive properties. The contraction force generated by the temperature response characteristics of CPAG at 30 °C can accelerate wound healing. In vitro release assays demonstrated that CPAG directly controlled the same amount of lidocaine release at different temperatures through the competition between polymer-polymer and polymer-water interactions. In addition, MTT, H&E staining and stimulation test further proved its biological safety. The pain behavior study showed that the pain inhibition rates of the lidocaine cataplasms and LID@CPAG were 51.16 % and 67.83 %, respectively. In vitro and in vivo studies have shown that compared with the blank group, the bleeding volume of LID@CPAG decreased by 54.3 %, and the wound healing rate reached 97 %. CPAG hydrogel can play a comprehensive therapeutic role in accelerating wound closure by controlling drug release, analgesia, antioxidation and hemostasis. [ABSTRACT FROM AUTHOR]

Enhancer of zeste homolog 2 (EZH2) is a histone H3 lysine 27 (H3K27) methyltransferase that plays vital roles in mouse spermatogenesis. However, the expression pattern and role of EZH2 in goat spermatogonial stem cells (SSCs) is unknown. In the present study, we investigated EZH2 expression in the testis of postpubertal goats and its effect on the biological characteristics of goat SSCs. We found that EZH2 mRNA (P < 0.01) and protein (P < 0.05) expression was increased in the testes of postpubertal goats compared to that of prepubertal goats. Moreover, EZH2 was more highly expressed in goat SSCs than in Leydig cells (P < 0.01) and Sertoli cells (P < 0.01) as determined by qPCR, Western blot, and immunofluorescence. Compared to a negative control (NC), cell proliferation (P < 0.01) and viability (P < 0.01) were decreased in SSCs in which EZH2 was knocked down, and the G2/M phase of the cell cycle was blocked (P < 0.01), as determined by Edu staining, CCK-8 assay, and flow cytometry analysis. Additionally, the expression of CASP3 , CASP9 , and BAX was significantly increased (P < 0.01) while BCL2 expression was decreased (P < 0.01) in EZH2 knockdown SSCs. Notably, the expression of GDNF , a SSCs marker gene, and DAZL , a spermatogenesis-related gene, were significantly decreased (P < 0.01) while GFRA1 expression was significantly up-regulated (P < 0.01) in EZH2 knockdown SSCs. Our data suggest that EZH2 plays a pivotal role in the self-renewal of goat SSCs, and knockdown of EZH2 might impair spermatogenesis in goats. • Increased expression of EZH2 in the testis of postpuberal goats and goat SSCs. • Knockdown of EZH2 compromised proliferation, and blocked G2/M phase in goat SSCs. • Knockdown of EZH2 elevated cell apoptosis of goat SSCs. • Knockdown of EZH2 impaired self-renewal of goat SSCs. • EZH2 serves an important role in the spermatogenesis of goat. [ABSTRACT FROM AUTHOR]

Paper-based analytical device (PAD) has received more and more attention in the field of point-of-care test (POCT) due to its low cost, portability and simple operation. Sensitivity and selectivity are two important aspects in clinical diagnostic analysis. However, low sensitivity of a PAD limits its wider application for POCT. Here we introduced a PAD that can clean and enrich the protein content from salty media with both electric field (E) and pH gradient (double E/pH gradients), with which 100-fold enrichment effect could be achieved within 70 s as demonstrated by fluorescein isothiocyanate labeled bovine serum albumin (FITC-BSA) from artificial urine media. With post staining of the protein stacking band with bromophenol blue (BPB), selective colorimetric detection of human serum albumin (HSA) was achieved simply with smartphone camera in the clinically significant range of 10–300 mg‧L−1 (R2 = 0.99) with a limit of detection (LOD) of 4.9 mg‧L−1. Detection of microalbuminuria (MAU) of diabetic patients was demonstrated with this method without difference (ɑ = 0.01) to that by the clinical method (immunoturbidimetry). This work demonstrated the potential of this PAD method in online sample pretreatment and detection of target component from complex physiological samples. Image 1 • Both electric field and pH gradient (E/pH double gradients) can be established and sustained on a paper fluidic channel. • Ampholytic content from salty sample media can be stacked/separated from other types of species. • Proteins from urine can be cumulatively stacked on the double gradient interface without intensive pre-treatment. • Sensitive and selective colorimetric detection of microalbuminuria (MAU) from clinical samples was successfully demonstrated. [ABSTRACT FROM AUTHOR]

Field-amplified stacking (FAS) is a commonly used method for enhancing the sensitivity of charged species from low conductive media in capillary electrophoresis. FAS also showed significant sensitivity enhancement effect on a uniform paper fluidic channel by proper design of the electrolyte. In this paper, a novel method of introducing electric field gradient is proposed by geometry design of a 2D paper fluidic channel, and field amplification effect was successfully demonstrated with reduced requirement on the sample's conductivity. Sensitive colorimetric detection of microalbuminuria (MAU) from urine samples was demonstrated by mobile phone camera. Experimental results showed that, with active electric field motivation, up to 93.5% of the loaded protein probe could be effectively transferred and stacked into a narrow band on the newly designed paper fluidic channel. A limit of detection (LOD) of 6.5 mg‧L−1 HSA was achieved with a dynamic range of 10–300 mg‧L−1 (linear in the range of 10–100 mg‧L−1, R2 = 0.991). Combined with selective staining of albumin with bromophenol blue (BPB), the established method was applied to the detection of MAU from clinical urine samples, and consistent results with that of the clinical method were obtained. With this paper-based analytical device (PAD), MAU from highly conductive urine samples can be directly loaded and detected without any pretreatment. This method provides a way to develop highly sensitive point-of-care test (POCT) for rapid screening of some diseases. Image 1 • Novel field amplification achieved mainly by the change of paper channel geometry, rather than the conductivity difference. • Protein probe was actively transported with a high transfer rate up to 93.5%, vs. less than 50% only by capillary force. • Sensitivity was enhanced by 2 orders of magnitude as demonstrated by colorimetric detection of human serum albumin (HSA). • Detection of microalbuminuria (MAU) from clinical urine samples was successfully demonstrated. [ABSTRACT FROM AUTHOR]

• Chinese higher education is experiencing unprecedented growth. • The current student loan arrangements may pose repayment difficulties for many borrowers. • As such, the existing loan arrangement could jeopardize on-going enrolment needs. • An income-contingent loan system has the potential to resolve these concerns. Currently China is experiencing unprecedented growth in higher education enrolments, with this trend set to continue. Whether higher education financing policy is able to facilitate this expansion is a critical issue for both education outcomes and economic growth. Using cross-sectional earnings data from the Chinese Household Income Project we find that a significant proportion of low-income graduates have a high likelihood of experiencing financial difficulties with current loan arrangements, implying high levels of financial hardship, a reliance on family members to meet repayments in order to avoid difficulties, and for some, default. In contrast we show that a properly designed income-contingent loan scheme has the potential to significantly mitigate, even eliminate, these concerns without attendant high budgetary costs. Our findings have important policy implications for Chinese higher education financing. [ABSTRACT FROM AUTHOR]

The steel-concrete composite structure using the high-strength steel (HSS) is featured with high strength, lightweight and economic benefits. In this study, a finite element model was established to simulate the compressive behavior of concrete-filled double-skin steel tubular (CFDST) stub column using high-strength steel. The material nonlinearity, the confinement effect and the contact behavior were considered. A total of four large-scale CFDST stub columns using HSS in the outer tube were tested under axial compression. The model was validated using both current and previous test results. The verified numerical model was then used to analyze the influences of various parameters, such as the yield stress of steel, the hollow ratio and the confinement factor. Furthermore, the feasibility of current design equations for CFDST columns using HSS was assessed. It was found that the HSS tube worked well with the sandwiched concrete, and the current methods could provide reasonable yet conservative predictions on the compressive strength of CFDST stub columns using HSS. • We provide new test data for the compressive behavior of the CFDST stub column using high-strength steel (HSS). • We establish the FE model and discuss influences of key parameters on the performance of CFDST stub column using HSS. • We verify the feasibility of the current method on the prediction of compressive strength of CFDST stub column using HSS. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs), as post-transcriptional gene mediators, regulate the biological characteristics of spermatogonial stem cells (SSCs), including proliferation, differentiation and apoptosis. However, the potential roles and mechanisms by which miR-101–5p affected the biological characters of goat SSCs have not been fully elucidated. Herein, we reported that miR-101–5p overexpression decreased cell viability (P < 0.01), arrested cell cycle in the G1 phase (P < 0.05), and aggravated apoptosis of goat SSCs (P < 0.01) compared with negative control (NC), as determined by CCK-8 assay and flow cytometry analysis. Additionally, PCNA protein expression was attenuated by miR-101–5p overexpression (P < 0.05). Notably, the expression of SSCs specific genes Oct4 (P < 0.05), PLZF (P < 0.01) and DAZL (P < 0.01) were decreased in miR-101–5p overexpressed SSCs. Furthermore, the dual luciferase reporter assay showed that, when co-transfected with miR-101–5p mimics, the relative luciferase activity of EZH2 wide-type (WT) was inhibited (P < 0.05) compared with the transfection of EZH2 mutant (MUT). EZH2 expression was negatively correlated with miR-101–5p expression in goat SSCs. Collectively, our data implicates that miR-101–5p overexpression aggravates cell apoptosis, and suppresses cell proliferation of goat SSCs via targeting EZH2, which may impair spermatogenesis. • miR-101–5p overexpression aggravated cell apoptosis of goat SSCs. • miR-101–5p overexpression blocked cell cycle progression with reduced PCNA expression of goat SSCs. • miR-101–5p overexpression compromised spermatogenesis-related gene expression of goat SSCs. • miR-101–5p targeted EZH2 and inhibited its expression. [ABSTRACT FROM AUTHOR]

Graphical abstract A Ge4+-based coordination complex was obtained via a simple hydrothermal synthesis, which contains 8-Hydroxyquinoline and hydroxyl group as ligands, forms a dense 0-D structure which shows interesting photoluminescence both at room temperature and 14 K. Highlights • A new Ge-based coordination complex was hydrothermally synthesized. • 8-Hydroxyquinoline and hydroxyl group were employed as ligands. • The photoluminescence of the title complex was studied under room temperature and at low temperature. Abstract A new germanium hydroxide coordinated by 8-Hydroxyquinoline (8-HQ), C 18 H 14 GeN 2 O 4 (Hereafter, GeHQ1) was synthesized via either a hydrothermal or common solution approach. Its structure was determined with both powder XRD and single crystal X-ray diffraction techniques. GeHQ1 crystallizes in orthorhombic symmetry, space group Pbca (No. 61) with unit-cell parameters: a = 8.7537(5) Å, b = 13.9817(7) Å, c = 24.8775(13) Å, and V = 3044.8(3) Å3, Z = 8, R = 0.0337 for reflections with I >2 sigma(I) and w R = 0.0803. The structure of GeHQ1 is built up from one germanium metal center octahedrally coordinating with two 8-Hydroxyquinoline anions (8-Q) and two hydroxyl groups and each two adjacent building units are held into a dimer via extensive hydrogen-bonding interaction between two relatively closer hydroxyl groups (2.936 Å) of two adjacent molecules. The crystals were also studied by SEM (scanning electron microscopy), EDS (energy dispersive analysis of X-rays spectroscopy), FT-IR spectrum and TGA (Thermogravimetric analysis). The photoluminescence properties were investigated in room temperature as well as lower temperature (14 K). [ABSTRACT FROM AUTHOR]

Highlights • We firstly find heavy ion-induced all pixel clusters in APS. • We demonstrate that shape and number of the pixel cluster change with the integration time. • We propose a simple model predicting charge collected by APS. Abstract The complementary metal-oxide-semiconductor (CMOS) active pixel sensors (APSs) can easily be susceptible to heavy-ion radiation in space applications. In this paper, the single event effects (SEEs) of pinned photodiode (PPD) active pixel sensor array exposed to heavy ion (Tantalum, Xenon, Krypton) with linear energy transfer (LET) (37, 50.34 and 81.35 MeV·cm2/mg) have been studied. During the heavy ion exposure, all devices were fully functional and integration time was changed, no single event latch-up (SEL) and single event functional interrupt (SEFI) happened. However, dark background with pixel clusters in a frame, which indicates the single event transient (SET) effect were observed. The number of the pixel clusters, total collected charge and cluster size were analyzed in detail. Finally, SRIM simulations were conducted on a PPD in order to predict the number of the electron-hole pairs generated by a heavy ion. [ABSTRACT FROM AUTHOR]

Highlights • Ag-ZnO cored nanotube have been firstly synthesized by CVD. • The morphologies and structure of Ag-ZnO cored nanotube are investigated. • The PL properties of Ag-ZnO cored nanotube are investigated. • The mechanism of growth and PL for Ag-ZnO cored nanotube is analyzed. Abstract In this paper, Ag-ZnO cored nanotubes were synthesized by a simple chemical vapor deposition method. The morphology and elemental components of the core inside and the nanotube outside of Ag-ZnO cored nanotube were characterized. The X-ray diffraction result showed two series of characteristic peaks, which were connected with hexagonal wurtzite ZnO and face-centered cubic Ag. The growth behaviour of Ag-ZnO cored nanotubes was explained by vapor-liquid-solid mechanism. The optical absorption spectrum showed an absorption peak at 378 nm and the photoluminescence results demonstrated a weak emission peak in the ultraviolet region which was due to the near-band-edge emission as well as three emission peaks in the visible region which were due to the defect level emission. [ABSTRACT FROM AUTHOR]

Abstract Purpose To assess the value of susceptibility-weighted imaging (SWI) for staging of liver fibrosis (F), necroinflammatory activity (A), and steatosis (S) of chronic hepatitis. Methods 100 Sprague-Dawley (SD) male rats were randomly divided into a chronic hepatitis model group (n = 88) and a control group (n = 12). The chronic hepatitis model rats were induced by intraperitoneal injection of 40% (v/v) of carbon tetrachloride (CCl 4) diluted in olive oil. All rats were examined by magnetic resonance imaging (MRI) and then killed immediately to detect pathologic staging as liver fibrosis (F), necroinflammatory activity (A), and steatosis (S). Liver-to-muscle signal intensity ratios (SIRs) of SWI were analyzed and associated with histopathologic findings. Results There were ultimately 11 normal control rats and 60 chronic hepatitis model rats. Statistical data were as follows: F0 (n = 11), F1 (n = 18), F2 (n = 16), F3 (n = 13), F4 (n = 13); A0 (n = 11), A1 (n = 29), A2 (n = 21), A3 (n = 10); S0 (n = 11), S1 (n = 12), S2 (n = 12), S3 (n = 18), and S4 (n = 18). The liver-to-muscle SIR of the SWI was related to hepatic fibrosis (P < 0.05) and liver steatosis (P < 0.05) but not to necroinflammatory activity (P > 0.05). By partial correlation analysis, a significant negative correlation was shown between the liver-to-muscle SIR and staging of liver fibrosis (r = −0.68, P < 0.05) as well as a low correlation with liver steatosis (r = 0.30, P < 0.05). Except for F0–F1 and F1–F2, there were statistical differences between each of the stages of hepatic fibrosis (P < 0.05), with an area under the ROC of 0.87 for F3 or above and of 0.96 for F4. Conclusion SWI can be a reliable method for staging hepatic fibrosis. Highlights • The liver-to-muscle SIR of SWI were related to fibrosis and steatosis but not to necroinflammatory activity. • The SIR of SWI could differentiate moderate to severe liver fibrosis. • There was no difference for liver-to-muscle SIR of SWI between stage of steatosis. [ABSTRACT FROM AUTHOR]

Two types of chicken broth, broiler broth (BB) and native chicken broth (NCB), were used to analyse their differences in aroma by gas chromatography–olfactometry/mass spectrometry (GC-O/MS). NCB contained more complex volatiles and exhibited a richer aromatic profile compared with BB. Results from aroma extract dilution analysis showed that ( E , E )-2,4-decadienal was the odorant with highest flavour dilution (FD) factor in both broths. The FD factors of 10 odorants in NCB were greater than those in BB, and 13 odorants with almond, citrus, vegetable, cucumber and sweet smells were only found in NCB. Moreover, 16 aroma compounds had average odor activity values (OAVs) greater than 1, among which ( E , Z )-2,4-decadienal (OAV BB  = 181, OAV NCB  = 1067), ( E , E )-2,4-decadienal (OAV BB  = 175, OAV NCB  = 1065), ( E , E )-2,4-nonadienal (OAV BB  = 28, OAV NCB  = 169), and ( E )-2-nonenal (OAV BB  = 39, OAV NCB  = 120) exhibited the highest values. Omission tests corroborated the importance of dienals to the overall aroma of chicken broth; nevertheless, omitting either ( E , E )-2,4-decadienal or ( E , E )-2,4-nonadienal individually did not result in significant aroma change. [ABSTRACT FROM AUTHOR]

While membrane fouling has been studied for decades, it remains challenging to obtain direct information about the dominant mechanism of fouling in a specific scenario. Here, we employed a high-throughput particle-tracking approach, which enabled the visualization of particle transport in actual microfiltration membranes under flow conditions and provided direct evidence for distinct fouling mechanisms under different operating conditions. Our results suggest that the “stickiness” of particles can qualitatively change the dominant fouling mechanism. In particular, the evolutions of effective flux, particle velocity and pathway tortuosity were found to be systematically different under “sticking” vs “reduced-sticking” conditions in two different microfiltration membranes, composed of PVDF and PTFE, respectively. Under “sticking” conditions, fouling was rapid, and individual pathways were observed to disappear with the reduction of flux. However, the average particle velocity and the tortuosity of particle trajectories were unchanged throughout the fouling process, consistent with the complete blocking of random pathways. Conversely, under “reduced-sticking” conditions, the average particle velocity decreased and the tortuosity of particle pathways increased systematically with fouling, consistent with the gradual narrowing of pathways causing increased resistance. The comprehensive information about particle dynamics in membranes achieved with this approach will assist design and optimization of reduced-fouling separation processes as well as advance the understanding of complex mass transport. [ABSTRACT FROM AUTHOR]

Babesiosis has become a new global threat impacting human health, and most human babesiosis cases are caused by Babesia microti . Until now few antigens of B. microti have been described which can be used for the diagnosis of human babesiosis. In the present study, we report on the bioinformatic analysis, cloning and expression of the sequence encoding the B. microti seroreactive antigen 5-1-1 to investigate its potential incorporation in serologic diagnostic tools for babesiosis. Bioinformatic analysis and recombinant gene expression were performed to molecularly characterize seroreactive antigen 5-1-1. Enhanced chemiluminescence (ECL)-Western blot methods were used to detect specific antibodies in infected mice. Immunofluorescence antibody assays (IFA) were performed to detect the localization of BmSA5-1-1 in B. microti parasites. ELISA and immunochromatographic (ICT) tests were developed using recombinant BmSA5-1-1 to evaluate its potential use in rapid detection methods for B. microti antibodies and for the diagnosis of babesiosis. A recombinant expression plasmid was constructed by inserting the target gene fragment in the pET28a vector after double digestion with BamHI and XhoI restriction enzymes. The recombinant BmSA5-1-1 protein was expressed in Escherichia coli (rBmSA5-1-1) and purified by means of Ni-nitrilotriacetic acid (NTA) agarose columns. Polyclonal antibodies were generated against rBmSA5-1-1. Based on indirect immunofluorescence assay results, BmSA5-1-1 appeared to localize on the surface of B. microti . ELISA tests using the rBmSA5-1-1 antigen detected specific antibodies from infected mice as early as 4 days post-infection. Our results indicate that the two methods we developed can detect specific antibodies in mice at different stages of infection with sensitivities of 100% (rBmSA5-1-1 ELISA) and 90% (ICT). The specificity of the two methods was 100%. Sera of patients suffering from other closely related parasitic diseases, such as malaria and toxoplasmosis, produced negative results. In conclusion, seroreactive antigen 5-1-1, a member of the BMN1 protein family, is expressed on the outer surface of B. microti and is a promising candidate antigen for the early diagnosis of babesiosis. rBmSA5-1-1 ELISA and ICT methods show good potential for detecting specific antibodies in mice at different stages of infection. [ABSTRACT FROM AUTHOR]

Poly(lactic acid) (PLA), as a biodegradable material, finds wide applications in packaging, automotive, and biological industries. However, achieving high strength, toughness, ultra-transparency, and heat resistance simultaneously in pure PLA through continuous one-step manufacturing remains a significant challenge. In this study, we addressed this challenge by utilizing the eccentric rotor extruder (ERE) in combination with cooling rolls to manufacture PLA sheets with outstanding mechanical performance. The ERE's elongational flow field combined with the cooling roller's weak stretching action induced orientation in the PLA molecular chains and promoted the formation of more mesophase, significantly improving mechanical properties. When the extrusion-stretch ratio (λ) value was 3.5, the tensile yield strength, Young's modulus, and elongation at break of ERE-fabricated samples ER-3.5 reached 86.2 MPa, 1777 MPa, and 57.9 %, respectively. Compared to the SE-3.5 samples manufactured with traditional methods, the increases were 38.8 %, 25.8 %, and 9.4 times, respectively. Additionally, the ERE manufactured samples maintained ultra-transparency and high heat resistance, making them suitable for food packaging, biomedicine, and other related fields. This methodology provides an efficient industrial-scale approach for manufacturing neat, biodegradable PLA with outstanding mechanical performance and ultra-transparency. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synergistic hydrogen bonding in the quaternary system hydrogel improves bio-adhesion by significantly enhancing cohesion. • The drug-loaded hydrogel patch significantly enhances the biological adhesion and is more suitable for transdermal drug delivery system. • The hydrogel has excellent stability, flexibility, and high drug release. • Polydopamine affects drug release by altering polymer chain-drug interaction and polymer chain relaxation. Low adhesion to skin remains a significant challenge for most hydrogel based transdermal drug delivery systems. Meanwhile, most of the methods to improve bio-adhesion often ignore the effect of the cohesion. Inspired by the adhesion mechanism of natural mussels and the synergistic balance theory based on cohesion and adhesion, we designed a poly (acrylamide- co -hydroxyethyl acrylate)-polydopamine-polyvinylpyrrolidone (PAHDP) quaternary composite hydrogel to enhance the cohesion and adhesion through the synergistic effect of multiple hydrogen bonds to achieve strong bio-adhesion to skin. The structure of PAHDP was characterized by FTIR, 1H NMR, SEM and TGA. The peeling adhesion force of PAHDP on porcine skin was improved by 9-fold compared with PAH hydrogel. At the same time, the adhesion force of drug-loaded PAHDP was 1.3 times that of Voltaren® EX. The rheological test further demonstrated that the synergistic hydrogen bonding can significantly improve the PAHDP cohesion. In addition, in vitro release, skin permeation and pharmacokinetics test of PAHDP hydrogel containing diclofenac sodium (DIC) showed that monomer dopamine (DA) could promote drug release. FTIR and molecular modeling were utilized to further demonstrate the enhanced drug release mechanism of DA. MTT assay, H&E staining and skin erythema analysis demonstrated that PAHDP was non-irritant to the skin. In conclusion, the innovatively prepared PAHDP hydrogel exhibits high skin adhesion, excellent mechanical properties, non-irritation and high drug release ability. This study also provides a simple and efficient strategy and theoretical basis for the preparation of high adhesion and high drug release hydrogels for transdermal drug delivery system. [ABSTRACT FROM AUTHOR]

Medical anomaly detection is a crucial yet challenging task aimed at recognizing abnormal images to assist in diagnosis. Due to the high-cost annotations of abnormal images, most methods utilize only known normal images during training and identify samples deviating from the normal profile as anomalies in the testing phase. Many readily available unlabeled images containing anomalies are thus ignored in the training phase, restricting the performance. To solve this problem, we introduce one-class semi-supervised learning (OC-SSL) to utilize known normal and unlabeled images for training, and propose Dual-distribution Discrepancy for Anomaly Detection (DDAD) based on this setting. Ensembles of reconstruction networks are designed to model the distribution of normal images and the distribution of both normal and unlabeled images, deriving the normative distribution module (NDM) and unknown distribution module (UDM). Subsequently, the intra-discrepancy of NDM and inter-discrepancy between the two modules are designed as anomaly scores. Furthermore, we propose a new perspective on self-supervised learning, which is designed to refine the anomaly scores rather than directly detect anomalies. Five medical datasets, including chest X-rays, brain MRIs and retinal fundus images, are organized as benchmarks for evaluation. Experiments on these benchmarks comprehensively compare a wide range of anomaly detection methods and demonstrate that our method achieves significant gains and outperforms the state-of-the-art. Code and organized benchmarks are available at https://github.com/caiyu6666/DDAD-ASR. • The first anomaly detection method that exploits unlabeled data. • Discrepancies of reconstruction ensembles are designed as anomaly scores. • Self-supervised refinement is proposed to further improve the prediction. • Five benchmark datasets with three different image modalities for evaluation. • A comprehensive comparison of various anomaly detection methods. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effect of lipo-PGE1 on renal hypoxia in patients with DKD by BOLD-MRI. Materials and methods All patients were divided into DKD group and CKD-without-diabetes group. All patients received intravenous 10 μg lipo-PGE1 once daily for 14 days. BOLD-MRI was performed before and after lipo-PGE1 administration to acquire renal CR2* and MR2* values. Results Renal MR2* value in DKD group after lipo-PGE1 treatment were significantly decreased compared with the baseline. However, no significant differences in MR2* values were found in the CKD-without-diabetes group. Conclusions Lipo-PGE1 was shown to improve kidney medullary oxygenation in patients with DKD. [ABSTRACT FROM AUTHOR]

We previously reported that Smad ubiquitin regulatory factor 2 (Smurf2) activity was decreased in human fibrotic livers. Here, we overexpressed Smurf2 in livers of transgenic mice and observed inhibited collagen deposition and hepatic stellate cell activation in fibrotic model induced by carbon tetrachloride treatment or bile duct ligation. Hepatic Smurf2 overexpression also inhibited the production of connective tissue growth factor (CTGF), a central mediator of liver fibrosis. Using miRNA array and bioinformatics analyses, we identified miR-132 as a mediator of this inhibitory effect. miR-132 directly targets the 3′-untranslated region of CTGF and was transcriptionally upregulated by cAMP-PKA-CREB signaling. In addition, Smurf2 activated cAMP-PKA-CREB pathway by interacting with phosphodiesterase 4B (PDE4B) and facilitating its degradation. Thus, we have demonstrated a previously unrecognized anti-fibrotic pathway controlled by Smurf2. [ABSTRACT FROM AUTHOR]

Lake ice is a sensitive indicator of climate change. Based on the disparities between the brightness temperatures of lake ice and water, passive microwave data can be used to monitor the ice variations of a lake. With focus on the analysis of long time series variability of lake ice, this study extracts four characteristic dates related to lake ice (the annual freeze start, freeze completion, ablation start and ablation completion dates) for Qinghai Lake from 1979 to 2016 using Scanning Multichannel Microwave Radiometer (SMMR) and Special Sensor Microwave Imager (SSM/I) passive microwave brightness temperature data. The corresponding freezing duration, ablation duration, complete freezing duration and ice coverage duration are calculated. Applying Moderate Resolution Imaging Spectroradiometer (MODIS) daily snow products, the accuracy of the results derived from passive microwave data is validated. The validation analysis shows a strong agreement (R 2 ranges from 0.70 to 0.85, mean absolute error (MAE) ranges from 2.25 to 3.94 days) in the freeze start, ablation start, and ablation completion dates derived from the MODIS data and passive microwave data; the ice coverage duration also has a small error (relative error (RE) = 2.95%, MAE = 3.13 days), suggesting that the results obtained from passive microwave data are reliable. The results show that the freezing dates of Qinghai Lake have been delayed and the ablation dates have advanced. Over 38 years, the freeze start date and freeze completion date have been pushed back by 6.16 days and 2.27 days, respectively, while the ablation start date and ablation completion date have advanced by 11.24 days and 14.09 days, respectively. The freezing duration and ablation duration have shortened by 3.89 days and 2.85 days, respectively, and the complete freezing duration and ice coverage duration have shortened by 14.84 days and 21.21 days, respectively. There is a significant negative correlation between the ice coverage duration and the mean air temperature in winter. [ABSTRACT FROM AUTHOR]

Synthesis of photodynamic and photothermal agents with absorption in the near-infrared (NIR) region and featuring excellent photostability, high singlet oxygen generation efficiency, good photothermal conversion efficiency, and good biocompatibility is necessary for the application of photodynamic therapy (PDT) and phtothermal therapy (PTT). Three NIR absorption compounds based on thieno[2,3- b ]indole (TI) and diketopyrrolopyrrole (DPP) were designed and synthesized. Their UV-vis-NIR absorption, photoluminescence, electronic distribution, energy levels and thermally induced phase transitions have been carefully determined. As structural analogues, only DPP-TI possesses excellent singlet oxygen quantum yield ( 1 O 2 , Φ Δ = 48.5%), which displays effective photothermal conversion efficiency (η = 15.8%) as nanoparticles in water. The potential of DPP-TI nanoparticles as fluorescence imaging therapeutic agent for synergetic PDT and PTT in vitro using only one wavelength light were explored preliminarily. [ABSTRACT FROM AUTHOR]

Liver fibrosis is characterized by proliferation and activation of hepatic stellate cells (HSCs). Transforming growth factor-β1 (TGFβ1) is crucial for liver fibrogenesis, and gut-derived endotoxin (LPS) also plays an important role in liver fibrogenesis. In the present study, we found that microRNA-146a-5p (miR-146a-5p) could regulate TGFβ1/Smad and LPS/NF-κB/Bambi pathways to attenuate liver fibrosis. Downregulated miR-146a-5p and upregulated level of LPS were found in liver of CCl4-treated rats. On cellular level, expression of miR-146a-5p is reduced during primary rat HSCs naturally activation and changed in response to TGFβ1 and/or LPS stimulation in primary rat HSCs and human HSC line LX-2. Further overexpression of miR-146a-5p suppresses proliferation and activation of HSCs. The underlying mechanism involved that miR-146a-5p directly suppresses profibrogenic effects of TGFβ1 by down-regulating the expression of Smad4 and phosphorylation of Smad2. Moreover, miR-146a-5p indirectly suppresses TGFβ1/Smad pathway by targeting IL-1 receptor-associated kinase 1 (IRAK1) and TNF receptor associated factor-6 (TRAF6), two major components of LPS/NF-κB/Bambi pathway, to reduce inhibition of TGFβ pseudoreceptor Bambi. These results indicate that miR-146a-5p abrogate hepatic fibrosis by suppressing both TGFβ/Smad and LPS/NF-κB/Bambi signaling pathway in HSCs and suggest that miR-146a-5p is a potential therapeutic target for liver fibrosis. [ABSTRACT FROM AUTHOR]

A paper-based colorimetric sensor array with an integrated smartphone was developed to detect a wide range of volatile organic compounds (VOCs) and used for an exhaled-breath analysis of VOCs associated with gastric cancer (GC). The sensor array combines functionalized nanoplasmonic materials and chemically responsive organic dyes which change color when they come in chemical contact with VOCs. Parts per billion (ppb)-level detection is achieved based on color changes of the array. Gas chromatography-mass spectroscopy (GC-MS) analysis of the exhaled gas from GC patients and healthy candidates indicated 25 different VOCs which may be used as the biomarkers. The paper-based smartphone nano-optoelectronic nose, used in combination with orthogonal partial least squares discriminant analysis (OPLS-DA), was able to differentiate between VOCs associated with GC patients and healthy candidates with an accuracy of 90 %. This cost-effective sensor platform paves a way for further clinical breath analysis on the noninvasive screening of GC and potentially other gas detection in medical diagnosis and environmental monitoring. • A paper-based colorimetric sensor with a smartphone is designed to detect VOCs. • The sensor array contains dyes and plasmonic materials modified with various thiols. • GC-MS analysis shows 25 VOCs as potential biomarkers for gastric cancer. • The sensor achieves the noninvasive screening of gastric cancer using exhaled gas. [ABSTRACT FROM AUTHOR]

Six new alkaloids (1 – 6) and six known alkaloids (7 – 12) were obtained from the stems of Sinomenium acutum. Among them, compounds 1 – 3 and 6 were four N -oxide alkaloids. The structures and absolute configurations of these new alkaloids were elucidated through comprehensive data of 1D and 2D NMR, HRESIMS and ECD spectra. All isolated compounds were evaluated in vitro for their inhibitory activities against nitric oxide (NO) production and inhibitory effects on AChE. Among them, the sinomenine N -oxide (9) was the most potent NO production inhibitor, with an IC 50 value of 23.04 μM. [Display omitted] • Six new alkaloids (1 – 6) were isolated from the the stems of Sinomenium acutum. • Compounds 1 – 3 are morphinane N -oxides, while 6 is an isoquinoline N -oxide. • Compounds 1 and 2 are a pair of axial chiral isomers with a rare dimeric morphinane N -oxide scaffold. [ABSTRACT FROM AUTHOR]

• An lens-flare-free computational imaging method is proposed. • The data throughput of the proposed method is low. • Video frame-rate imaging is available for the method. Lens flare, the photographic artifact produced by reflecting and scattering a powerful incident light within a camera lens group, can severely degrade image quality and mislead the image-based processing task. Existing solutions typically depend on sophisticated optics design or complex image postprocessing algorithms to reduce lens flare. This paper demonstrates a direct reconstruction of the target feature by single-pixel imaging with a simple optics design and no image postprocessing. A novel sampling strategy is proposed for spacecraft docking, which utilizes Fourier single-pixel imaging methods to capture a specific feature at an ultralow sampling ratio. Simulation and experiments demonstrate that the proposed method can image the feature with a sampling ratio of 4.8% at a video frame rate while almost eliminating the impact of the ring effect. This paper provides a new perspective for achieving lens-flare-free, video-framerate and low-data-throughput imaging in space tasks, which has potential in many imaging-based applications. [ABSTRACT FROM AUTHOR]

Objective Bleomycin (BLM) has been found safe and highly effective in the treatment of the mucoceles by intralesional injection in our previous study. The present research was designed to investigate whether epithelial-to-mesenchymal transition (EMT) contributes to the therapeutic effects of BLM for mucoceles of the salivary glands. Material and methods The cell proliferation and apoptosis of human submandibular gland cells (HSG cells) were examined by Cell Counting Kit-8 assay and Annexin V binding assay respectively. Epithelial and mesenchymal markers of HSG cells were measured by real-time quantitative PCR and Western blot analysis. Acinar differentiation and cell migration assays were performed to evaluate HSG cells function. Results High-dose BLM (≥0.5 μg/mL) significantly inhibited the cell proliferation and induced the cell apoptosis, while the treatment with low-dose BLM (0.05 and 0.1 μg/mL) for 48 h induced EMT in HSG cells. Furthermore, Akt/mTOR pathway, rather than MAPK pathway, was activated through treated with 0.05 and 0.1 μg/mL BLM, as well as activation of the transcription factor Slug and Zeb 1. The migration of HSG cells was also enhanced through 0.05 and 0.1 μg/mL BLM, but the ability of acinar differentiation was diminished. Conclusion Our results indicated that an EMT process was involved in the BLM-induced therapeutic effects on the HSG cells through the Akt/mTOR pathway. Importantly, the results indicated the potential role of this process in the BLM sclerotherapy of mucoceles of the salivary glands. [ABSTRACT FROM AUTHOR]

Background: Cancer is a disease that involves abnormal cell growth and can invade or metastasize to other tissues. It is known that several factors are related to its initiation, proliferation, and invasiveness. Recently, it has been reported that long non-coding RNAs (lncRNAs) can participate in specific functional pathways and further regulate the biological function of cancer cells. Studies on lncRNAs are therefore helpful for uncovering the underlying mechanisms of cancer biological processes.Methods: We investigated cancer-related lncRNAs using gene ontology (GO) terms and KEGG pathway enrichment scores of neighboring genes that are co-expressed with the lncRNAs by extracting important GO terms and KEGG pathways that can help us identify cancer-related lncRNAs. The enrichment theory of GO terms and KEGG pathways was adopted to encode each lncRNA. Then, feature selection methods were employed to analyze these features and obtain the key GO terms and KEGG pathways.Results: The analysis indicated that the extracted GO terms and KEGG pathways are closely related to several cancer associated processes, such as hormone associated pathways, energy associated pathways, and ribosome associated pathways. And they can accurately predict cancer-related lncRNAs.Conclusions: This study provided novel insight of how lncRNAs may affect tumorigenesis and which pathways may play important roles during it. These results could help understanding the biological mechanisms of lncRNAs and treating cancer. [ABSTRACT FROM AUTHOR]

• Croconic Acid (CA) materials are easily designed into near-infrared (NIR) region. • The development of CA materials is significant for future clinical transformation. • The design of CA materials for better optical imaging or therapy are introduced. • All current biomedical applications of CA materials are summarized. • The perspectives and challenges of CA materials for biomedicine are discussed. Croconic acid (CA), an organic pseudo-oxocarbon molecule with a highly strong electron-withdrawing character, can efficiently react with electron-rich groups and form a donor–acceptor-donor (D-A-D) conjugated structure. CA-based molecules have excellent photobleaching resistance, thermal stability, high molar absorption coefficient, and favorable spectral tunability. Consequently, the development of CA-based functional materials in various biomedical applications is significant for potential clinical transformation. Herein, we thoroughly review the development of CA-based near-infrared (NIR) materials in biomedical fields. Primarily, we introduce the rational structure design of CA molecules for excellent NIR optical properties, and the formation of CA dye-based nanomaterials for better bioavailability and stability. Subsequently, the biomedical applications such as photothermal therapy, photoacoustic imaging, phototheranostics, and multimodal treatment of CA-based functional materials are summarized. Finally, the perspectives and potential drawbacks of CA-based materials for future clinical transformation are systematically discussed. [ABSTRACT FROM AUTHOR]

• Realize direct electron transfer of native glucose oxidase based on PEDOT:PSS hydrogel decorated electrode. • Achieve glucose detection in deoxygenated solution with no extra auxiliary electron mediator. • Propose a model that mixture forms of GOx contribute to the DET-related electro performance. Direct electron transfer (DET) is the critical issue in developing the third-generation glucose biosensor. However, the DET of glucose oxidase (GOx) is hard to realize because the redox center of GOx is located deeply within the enzyme molecule. Here, we have studied DET of GOx on a poly(3,4-ethylene dioxythiophene): poly(styrene sulfonate) (PEDOT:PSS) hydrogels decorated carbon nanotube fiber (CNTF) electrode with oxygen-independence glucose determination performance. PEDOT:PSS hydrogels modified on carbon nanotube fiber by electrogelation might play a key role in keeping the catalytic activity and DET for GOx simultaneously. The cyclic voltammetric result of the biosensor shows a pair of well-defined and quasi-reversible redox peaks with a formal potential of −0.431 V and a peak-to-peak separation of 69 mV. The constructed biosensor shows a linear range from 0.05 to 0.5 mM and a sensitivity of 43.52 μA mM−1 cm−2 toward glucose via a constant potential of −0.3 V in an N 2 -saturated solution. Three GOx models on the electrode surface are proposed to explain these DET-related electrochemical performances of the biosensor. We demonstrate the DET for the native GOx with catalytic activity in PEDOT:PSS hydrogels, which takes a step towards developing the third-generation glucose biosensor with conductive hydrogels. [ABSTRACT FROM AUTHOR]

[Display omitted] • 1. π-conjugated organic electrode: 1,4-Dicyanobenzene (DCB) polymer DCB-COF is successfully synthesized. • 2. DCB-COF applied as an organic electrode in Li-ion batteries exhibit high reversible capacities and rate performance. • 3. Density functional theory (DFT) theoretical calculations explain the lithium storage mechanism of the DCB-COF electrode. • 4. In-situ FTIR spectroscopy and ex-situ XPS further validate the active site of the DCB-COF electrode in the battery process. Covalent organic frameworks (COFs) have attracted widespread attention for gas storage, separation, catalysis, and sensors applications. We report a simple, inexpensive, and abundant aromatic nitrile 1,4-dicyanobenzene (1,4-DCB) as a lithium-ion battery anode material through the synthesis of a DCB triazine-based covalent organic framework (DCB-COF) under ionic thermal conditions. An investigation of the lithium storage mechanism of the active groups in the DCB-COF by in-situ Fourier-transform infrared spectroscopy, ex-situ X-ray photoelectron spectroscopy, and density functional theory calculations demonstrates that DCB-COF had a high initial capacity of 2100 mAh g−1, and good structural and cycling stability. This work provides an effective strategy for the subsequent fabrication of novel COF electrode materials. [ABSTRACT FROM AUTHOR]

Scutellariae Radix (SR) has been extensively prescribed in folk medicines due to its notable beneficial activities. The flavonoid glucuronides baicalin (BG), wogonoside (WG), oroxylin A 7- O -β- d -glucuronide (OG) and their aglycones baicalein, wogonin and oroxylin A, are the main components of the herb. So far, majority of previous studies failed to report the pharmacokinetics and none offered an explanation for the systemic exposures of these six flavonoids when the herbal extract was orally administered. In this study, when a SR extract was orally dosed to rats (800 mg/kg, equivalent to BG 324.80, WG 124.00, OG 43.04, baicalein 25.36, wogonin 24.40, and oroxylin A 5.79 mg/kg), all six flavonoids were detectable throughout the experimental period (48 h) using an LC–MS/MS method with the Cmax and AUC 0–48 h of the glucuronides 10–130 times that of respective aglycones. As the lowest among the three glucuronides in the herb, OG was the most abundant in vivo , while the systemic exposure of wogonin was the highest amongst the three aglycones. The dose-normalized AUC 0–48 h descended in orders of OG/oroxylin A, WG/wogonin and BG/baicalein. Two di-conjugates of baicalein (BG glucuronide and BG glucoside), two BG isomers (minor BM1 and major BM2), and one WG isomer (wogonin 5- O -glucuronide) were detected in rat plasma. Semi-quantitation of the isomers with peak area data revealed that the AUPs (area under peak area ratio-time curves) of BG isomers were ∼3 times that of BG, yet the AUP of wogonin 5- O -glucuronide was only one seventh of WG. BM2, tentatively assigned as baicalein 6- O -glucuronide, was formed from both microbial isomerization of BG and hepatic glucuronidation of baicalein. Wogonin 5- O -glucuronide was only formed in hepatic glucuronidation of wogonin. Demethylated wogonin was observed in gut bacteria, offering an optional origin of BM1 apart from baicalein glucuronidation. Microbial isomerization of BG and extensive hepatic glucuronidation of baicalein to form BM2 as well as a poorer intestinal permeability of baicalein ( P app × 10 −6 cm/s) should account for the lower systemic exposures of BG and baicalein. Faster microbial hydrolysis of WG, high intestinal permeability ( P app × 10 −5 cm/s) and less hepatic glucuronidation of wogonin explain the relatively high systemic exposure of wogonin. Sole microbial deglycosylation of OG, high intestinal permeability ( P app × 10 −5 cm/s) and extensive hepatic glucuronidation of oroxylin A supported the highest systemic exposure of OG. Taken together, the oral kinetics of six flavonoid glucuronides and aglycones in the SR extract were simultaneously obtained. Microbial conversion, intestinal epithelial permeability and hepatic glucuronidation are determinant factors for their systemic exposures. [ABSTRACT FROM AUTHOR]

Porphyromonas gingivalis causes inflammation, and leads to the periodontitis in gingival tissue damage and bone resorption. Epigallocatechin-3-gallate (EGCG) is a major polyphenol extract from green tea with plenty of pharmacological functions. The aim of this study was to determine whether continuous oral intake of EGCG would alleviate P. gingivalis -induced periodontitis. Eight-week BALB/c mice were administered with EGCG (0.02%) or vehicle in drinking water. They were fed normal food and orally infected with P. gingivalis every 2 days, up to a total of 20 times, and then sacrificed at 15 weeks of age. The P. gingivalis -challenged group markedly increased alveolar bone resorption of the maxillae in BALB/c mice by Micro-CT detection, and administration of EGCG resulted in a significant reduction in bone loss. Inflammation cytokine antibody array and enzyme linked immunosorbent assay revealed that some inflammatory mediators in serum were increased by P. gingivalis infection, but were lowered after EGCG treatment. High positive areas of IL-17 and IL-1β in the gingival tissue were observed in the P. gingivalis -challenged mice, and were reduced by EGCG treatment. Real-time polymerase chain reaction (PCR) analyses also showed the expressions of IL-1β, IL-6, IL-17, IL-23, TNF-α and other mediators in gingival tissue were higher in P. gingivalis -challenged mice, and were down-regulated with EGCG treatment, except IL-23. Our results suggest that EGCG, as a natural healthy substance, probably alleviates P. gingivalis -induced periodontitis by anti-inflammatory effect. [ABSTRACT FROM AUTHOR]

Aroma extract dilution analysis (AEDA) is widely used for the screening of aroma-active compounds in gas chromatography–olfactometry (GC–O). In this study, three aroma dilution methods, (I) using different test sample volumes, (II) diluting samples, and (III) adjusting the GC injector split ratio, were compared for the analysis of volatiles by using HS-SPME–AEDA. Results showed that adjusting the GC injector split ratio (III) was the most desirable approach, based on the linearity relationships between Ln (normalised peak area) and Ln (normalised flavour dilution factors). Thereafter this dilution method was applied in the analysis of aroma-active compounds in Japanese soy sauce and 36 key odorants were found in this study. The most intense aroma-active components in Japanese soy sauce were: ethyl 2-methylpropanoate, ethyl 2-methylbutanoate, ethyl 3-methylbutanoate, ethyl 4-methylpentanoate, 3-(methylthio)propanal, 1-octen-3-ol, 2-methoxyphenol, 4-ethyl-2-methoxyphenol, 2-methoxy-4-vinylphenol, 2-phenylethanol, and 4-hydroxy-5-ethyl-2-methyl-3(2H)-furanone. [ABSTRACT FROM AUTHOR]

Traditional aircraft conceptual design primarily involves determination of top-level sizing parameters, resulting in an initial design which satisfies specified point-performance constraints while flying the so-called design mission. In practical scenarios, commercial aircraft are also expected to operate optimally in the actual missions they fly which may drastically differ from the design mission. To improve performance and reduce operating costs, optimization shall be performed using specific objectives from the on-design mission and from one or more representative off-design reference mission(s). Such multi-mission optimizations may result in different designs for the same performance constraints. Moreover, the size of aircraft and choice of reference mission(s) may also have an effect in the difference resulting from such multi-mission optimizations. This paper solves a series of multi-objective on-design and multi-mission optimization problems in the conceptual design phase on aircraft spanning a range of size-classes, using the Non-dominated Sorting Genetic Algorithm II (NSGA-II). Results shed light on the design differences between formulations that exclusively consider design mission metrics of interest from the ones that consider metrics of interest from disparate, as-flown, i.e., off-design missions. In addition, results also reveal the impact of off-design mission weightings on the designs obtained from the optimization problems. [ABSTRACT FROM AUTHOR]

• Two substituted piperidinium salts tetrahalogenated copper(II) with chirality were synthesized and characterized. • The HOMO-LUMO energy gap explains the charge transfer interactions in the molecules. • The nonlinear optical properties were studied using DFT calculations. • Two salts exhibit good bactericidal activity on S. aureus and E. coli. This paper presents the syntheses, composition analysis and structural characterization of two ionic complexes, [4NO 2 BzPid] 2 [CuX 4 ] ([4-NO 2 BzPid]+= 4-nitro-1-benzylpiperidinium, X = Cl(1) and Br(2)). Two complexes crystallize in chiral space group P 6(4)(No. 172), and comprise two [4NO 2 BzPid]+cations and a [CuX 4 ]2– anion in which the piperidine ring shows a boat structure while the [CuX 4 ]2– anion exhibits a tetrahedron geometry. The intermolecular energy, the energy gap between the HOMO and LUMO orbitals, and the first hyperpolarizability were carried out based on the DFT calculation. The low energy gap (2.24 ev for 1 and 2.01 ev for 2) explains the eventual charge transfer interactions taken place between the [CuX 4 ]2−anion and [4NO 2 BzPid]+cation. The first hyperpolarisability (β tot) of two salts is 9.3 and 16.0 times greater than that of the standard KDP crystal showing that two complexes are good materials for NLO application. The results of antibacterial experiments show that two complexes exhibit good bactericidal activity for S. aureus and E. coli. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to compare the effectiveness of percutaneous needle aspiration ( PNA) and percutaneous catheter drainage ( PCD) in the management of liver abscess. Methods Electronic searches (Cochrane Library, MEDLINE, EMBASE, SCIE) were conducted to identify randomized controlled trials ( RCTs) comparing PNA and PCD. A meta-analysis was subsequently performed. Results A total of five RCTs covering 306 patients were included. The meta-analysis showed that outcomes in patients treated with PCD were superior to those in patients treated with PNA in terms of success rate [relative risk ( RR): 0.81, 95% confidence interval ( CI) 0.66-0.99; P = 0.04], clinical improvement [standardized mean difference ( SMD): −0.73, 95% CI 0.36-1.11; P = 0.0001] and days to achieve a 50% reduction in abscess cavity size ( SMD: −1.08, 95% CI 0.64-1.53; P < 0.00001). No significant differences were found in duration of hospitalization (mean difference: −0.17, 95% CI −2.10 to 1.75; P = 0.86) or procedure-related complications ( RR: 0.50, 95% CI 0.10-2.63; P = 0.41). Days to achieve the total or near total resolution of the abscess cavity and mortality were not calculated because data in the RCTs in the meta-analysis were insufficient. Conclusions Both PNA and PCD are safe methods of draining liver abscesses. However, PCD is more effective than PNA because it facilitates a higher success rate, reduces the time required to achieve clinical relief and supports a 50% reduction in abscess cavity size. However, among successfully treated patients, the outcomes of PNA are comparable with those of PCD. [ABSTRACT FROM AUTHOR]