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Abstract Background Salmonella Typhimurium (S. Typhimurium) is a common pathogenic microorganism and poses a threat to the efficiency of poultry farms. As signaling molecules regulating the interaction between the host and gut microbiota, bile acids (BAs) play a protective role in maintaining gut homeostasis. However, the antibacterial effect of BAs on Salmonella infection in broilers has remained unexplored. Therefore, the aim of this study was to investigate the potential role of feeding BAs in protecting against S. Typhimurium infection in broilers. Methods A total of 144 1-day-old Arbor Acres male broilers were randomly assigned to 4 groups, including non-challenged birds fed a basal diet (CON), S. Typhimurium-challenged birds (ST), S. Typhimurium-challenged birds treated with 0.15 g/kg antibiotic after infection (ST-ANT), and S. Typhimurium-challenged birds fed a basal diet supplemented with 350 mg/kg of BAs (ST-BA). Results BAs supplementation ameliorated weight loss induced by S. Typhimurium infection and reduced the colonization of Salmonella in the liver and small intestine in broilers (P

Subacute ruminal acidosis (SARA) is a common metabolic disease due to feeding high-concentrate (HC) diets to ruminants, especially dairy cows, in intensive farming system. Long term feeding HC diets commonly induce damages to hindgut barrier, leading to the translocation of harmful substances such as endotoxins (LPS) from lumen to blood, which results in a low-grade inflammation and stress response. Secondary bile acids (SBAs) play an important role in maintaining intestinal homeostasis. However, the function of SBAs on the intestinal epithelial barrier in SARA remains unclear. In this study, 15 growing goats were randomly divided into 3 groups, control group (30 % concentrate of dry matter, CON), SARA group (70 % concentrate of dry matter, SARA), and SARA+BAs group (70 % concentrate of dry matte, supplemented with 3 g/d/goat of BAs, SARA+BAs). The changes of mucosal permeability, gut microbiota and bile acids (BAs) profile was measured in the colon. The results showed that compared to CON group, the level of plasma D-lactate and diamine oxidase activity (DAO) (P < 0.05) was elevated in SARA group, while BAs supplementation significantly decreased plasma DAO (P < 0.05). The thickness of colonic mucosa, goblet cells (GCs) number (P < 0.01) and the abundance of MUC2 and occludin expression (P < 0.05) were significantly decreased in SARA group, while BAs supplementation markedly increased GCs number and improved mucosal barrier. BAs effectively reduced the content of LPS and volatile fatty acids (VFAs) in the colonic digesta (P < 0.05). Furthermore, BAs ameliorated SARA-induced reduction of total BAs (P < 0.001), primary BAs (P < 0.05), and conjugated BAs (P < 0.05) including taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA) and taurodeoxycholic acid (TDCA), as well as significantly increased hyodeoxycholic acid (HDCA) and lithocholic acid (LCA) contents in colonic digesta. 16S rRNA gene sequence analysis revealed that BAs decreased the abundance of Prevotella and Treponema, but increased the abundance of Akkermansia which was positively correlated with GCs number and MUC2 abundance. BAs supplementation improved the changes in the abundance of Roseburia, Negativibacillus, Lactobacillus, and unclassified_f_prevotellaceae, which were correlated with TCA, TCDCA, and TDCA levels. RNA-Seq results showed that, compared to SARA group, BAs activated the PPAR signaling pathway which was positively correlated with the number of GCs. In summary, BAs supplementation remodels the profiles of gut microbiota and metabolites, activates the PPAR signaling pathway, and eventually ameliorates intestinal mucosal barrier damage.

Objective: To clarify the structural characteristics of selenium polysaccharides from Morchella esculenta, and their ameliorative effects on exercise-fatigued rats. Methods: Polysaccharides from Morchella esculenta were extracted using ultrasound-assisted hot water extraction. Purified polysaccharides (Msp-1) were obtained through DEAE cellulose column chromatography and Sephadex G-100 column chromatography. Nitric acid-sodium selenite method was used to prepare selenized polysaccharide (Se-Msp1) from purified polysaccharides. The structures of Msp-1 and Se-Msp1 were characterized. The swimming time of rats was measured by exhaustive swimming test, and the weighted swimming model was established at the same time. The rats were randomly divided into quiet control group, exercise fatigue control group, positive control group (salidroside, 100 mg/kg), normal polysaccharide group (Msp-1, 100 mg/kg), and selenized polysaccharide low, medium, and high dose groups (Se-Msp1, 50, 100, and 200 mg/kg, respectively). The rats were orally administered with 0.1 mL/(10 g·bw) for 5 weeks. The content of blood lactic acid (BLA), blood urea nitrogen (BUN), hepatic glycogen (HG), and muscular glycogen (MG), as well as malondialdehyde (MDA) content, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities in skeletal muscle mitochondria, were measured to evaluate the anti-exercise fatigue effect of Se-Msp1. Results: The major component of the purified polysaccharides from Morchella esculenta was Msp-1, which accounted for 85.25%. Infrared spectroscopy showed that the heteromeric carbon of Se-Msp1 was α configuration, and characteristic absorption peaks of selenium were observed, indicating that Se-Msp1 was successfully selenided. The Se content in Se-Msp1 was 9.56 mg/g, the polysaccharide content was 56.34%, with uronic acid content of 36.82%, and the weight average molecular weight was 3.482×105 Da, particle size of 384.71 nm, zeta potential was −45.78 mV, indicating that Se-Msp1 had a high selenium content and good stability. The monosaccharide composition of Se-Msp1 consisted of mannose, glucose, galactose, galacturonic acid, and rhamnose, with molar ratios of 1:0.42:3.57:3.34:1.86. The anti fatigue results of rats showed that compared with the control group (Con), both Msp-1 and Se-Msp1 significantly increased the exhausted swimming time (P

Cardiotoxicity and QT interval prolongation have been a common cause of withdrawal of drugs from the market. FCN-437c is an oral, second-generation, potent, and selective CDK4/6 inhibitor for the treatment of patients with HR+/HER2- metastatic breast cancer. A single-center, double-blind, randomized, and placebo-controlled clinical study in healthy subjects was conducted to investigate the QTc prolongation potential of FCN-437c utilizing Concentration-QTc (C-QTc) modeling approach. FCN-437c was administered at doses of 300, and 400 mg with single oral administration, along with placebo, in 18 healthy subjects. Electrocardiograms (ECGs) through 24 h holter monitor and blood samples were collected. The Cmax of 400 mg single dose in healthy subjects is similar to that from therapeutic dose 200 mg QD at steady state in patients with cancer. The 90% CI upper limit of ΔΔQTcF at the Cmax geometric mean in both dose groups were

Abstract The continued miniaturization of chips demands highly thermally conductive materials and effective thermal management strategies. Particularly, the high‐field transport of the devices built with 2D materials is limited by self‐heating. Here a systematic control of heat flow in single‐side fluorinated graphene (FG) with varying degrees of fluorination is reported, revealing a superior room‐temperature thermal conductivity as high as 128 W m−1 K−1. Monolayer graphene/FG lateral heterostructures with seamless junctions are approached for device fabrication. Efficient in‐plane heat removal paths from graphene channel to side FG are created, contributing significant reduction of the channel peak temperature and improvement in the current‐carrying capability and power density. Molecular dynamics simulations indicate that the interfacial thermal conductance of the heterostructure is facilitated by the high degree of overlap in the phonon vibrational spectra. The findings offer novel design insights for efficient heat dissipation in micro‐ and nanoelectronic devices.

Abstract The oral delivery of nano-drug delivery systems (Nano-DDS) remains a challenge. Taking inspirations from viruses, here we construct core–shell mesoporous silica nanoparticles (NPs, ~80 nm) with virus-like nanospikes (VSN) to simulate viral morphology, and further modified VSN with L-alanine (CVSN) to enable chiral recognition for functional bionics. By comparing with the solid silica NPs, mesoporous silica NPs and VSN, we demonstrate the delivery advantages of CVSN on overcoming intestinal sequential barriers in both animals and human via multiple biological processes. Subsequently, we encapsulate indomethacin (IMC) into the nanopores of NPs to mimic gene package, wherein the payloads are isolated from bio-environments and exist in an amorphous form to increase their stability and solubility, while the chiral nanospikes multi-sited anchor and chiral recognize on the intestinal mucosa to enhance the penetrability and ultimately improve the oral adsorption of IMC. Encouragingly, we also prove the versatility of CVSN as oral Nano-DDS.

Sustainable development is a key issue of global concern, and countries around the world are striving to promote green development. From the perspective of financial asset allocation motivation, this paper explores the impact of financial asset allocation on green innovation based on the data of A-share listed non-financial companies from 2011 to 2021. First, there is an inverted U-shaped relationship between the proportion of financial asset allocation and the green innovation of physical enterprises, that is, as the proportion of financial asset allocation increases, the green innovation output of enterprises first increases and then decreases. After robustness testing, the conclusion still holds. Second, further testing of the intermediary mechanism shows that the moderate holding of short-term financial assets by real enterprises can increase the output of green innovation by alleviating financing constraints, which is manifested as the "reservoir" effect. The "crowding out" effect plays a leading role when overallocation of financial assets reduces liquidity supply and capital expenditure, which in turn reduces green innovation output. Third, in the test of financial asset allocation preference, it is found that the short-term financial assets held by enterprises mainly play a "reservoir" effect, that is, they tend to be "preventive" motives. Holding long-term financial assets mainly exerts a "crowding out" effect, that is, tends to "seek profits" motives. Finally, there are differences in the impact of financial asset allocation on green innovation output among enterprises with different property rights, different monetary policies and different social responsibilities.

Global attention toward environmental sustainability and economic green transformation is on the rise. Green technology innovation plays a crucial role in achieving green economic development, making the study of enterprises' sustainable green innovation highly valuable. This paper aims to examine the influence mechanism of green finance on enterprises' sustainable green innovation. To achieve this, panel data from A-share-listed enterprises in Shanghai and Shenzhen between 2012 and 2020 are utilized as the basis for analysis. The results show that: (1) Green finance plays an important role in encouraging enterprises' sustainable green innovation. (2) The test of the intermediary effect reveals that green finance can stimulate enterprises' sustainable green innovation by increasing continued R & D investment. (3) The moderating mechanism test reveals that enterprise financing restrictions and enterprise debt default risk moderate the influence of green finance on enterprises' sustainable green innovation. Furthermore, for enterprises with high financial constraints and a high risk of debt default, the development of green finance is particularly important in fostering their long-term green innovation. (4) The study concludes that all four types of sustainable green innovation, namely, strategic, substantive, independent and cooperative, exhibit the promotion effect of green financial development, the intermediary effect of continuous R & D investment and the moderating effect of financing constraints. Enterprises with a higher risk of defaulting on their debt are more likely to make significant, independent and sustainable green innovations.

Key Clinical Message Brucellosis, caused by gram‐negative coccobacilli of the genus Brucella, is a zoonotic disease with bone and joint complications being common. However, acute abdomen with intestinal perforation is rare. We present a case of a 69‐year‐old man diagnosed with acute diffuse peritonitis and intestinal perforation due to Brucella infection. Surgical intervention revealed ileocecal perforation with wheel spoke‐like necrosis. The patient underwent partial resection, ileum closure, and ileostomy. Positive blood culture and Brucella agglutination confirmed the diagnosis. Targeted tetracycline and aminoglycoside treatment led to recovery.

The group-transfer polymerization (GTP) of N,N-bis(2-methoxyethyl)acrylamide (MOEAm) initiated by Me2EtSiH in the hydrosilylation-promoted method and by silylketene acetal (SKA) in the conventional method proceeded in a controlled/living manner to provide poly(N,N-bis(2-methoxyethyl)acrylamide) (PMOEAm) and PMOEAm with the SKA residue at the α-chain end (MCIP-PMOEAm), respectively. PMOEAm-b-poly(N,N-dimethylacrylamide) (PDMAm) and PMOEAm-s-PDMAm and PMOEAm-b-poly(N,N-bis(2-ethoxyethyl)acrylamide) (PEOEAm) and PMOEAm-s-PEOEAm were synthesized by the block and random group-transfer copolymerization of MOEAm and N,N-dimethylacrylamide or N,N-bis(2-ethoxyethyl)acrylamide. The homo- and copolymer structures affected the thermoresponsive properties; the cloud point temperature (Tcp) increasing by decreasing the degree of polymerization (x). The chain-end group in PMOEAm affected the Tcp with PMOEAmx > MCIP-PMOEAmx. The Tcp of statistical copolymers was higher than that of block copolymers, with PMOEAmx-s-PDMAmy > PMOEAmx-b-PDMAmy and PMOEAmx-s-PEOEAmy > PMOEAmx-b-PEOEAmy.

Lacking of substantial physiological activity and low utilization remains a problem for most conventional drug carriers. Polyprenol with beneficial medical effects and high availability could be an ideal candidate for solving this issue. Here, Ginkgo biloba leaves polyprenol (GBP)-based derivative was prepared by Michael addition reaction of poly (β-amino esters) (PBAE) with GBP and galactose (Gal). The intervention of poly (β-amino ester) and galactose promoted GBP-PBAE-Gal to depict as micellar carrier, enhancing the loading of hydrophobic DOX and the sensitivity to the specific tumor microenvironment, with the largest DOX loading of 28.62 ± 1.49 % and the efficient DOX release rate of 90.30 %. In the meantime, GBP-PBAE-Gal exhibited enhanced colloidal stability at 640-folds of dilution and in the presence of serum and realized the possibility of long-term storage at room temperature. Additionally, GBP-PBAE-Gal was safe for human red blood cells and human normal liver cells HL-7702. When applied for DOX delivery to HepG2 cells, GBP-PBAE-Gal increased the targeting of DOX to intensify its inhibition on HepG2 cells. Compared to free DOX, the DOX loaded into GBP-PBAE-Gal presented stronger anticancer activity, with IC50 of 0.56 μg/mL at 72 h. Besides, the anticancer mechanism study revealed that GBP-PBAE-Gal arrested the cell cycle in HepG2 cells, suggesting the potential of GBP-based carrier for intensive treatment. This research evidenced the feasibility and high availability of the GBP to use as a drug carrier, providing a novel candidate for drug delivery systems.

Abstract Background Medical information has rapidly increased on the internet and has become one of the main targets of search engine use. However, medical information on the internet is subject to the problems of quality and accessibility, so ordinary users are unable to obtain answers to their medical questions conveniently. As a solution, researchers build medical question answering (QA) systems. However, research on medical QA in the Chinese language lags behind work on English-based systems. This lag is mainly due to the difficulty of constructing a high-quality knowledge base and the underutilization of medical corpora in the Chinese language. Results This study developed an end-to-end solution to implement a medical QA system for the Chinese language with low cost and time. First, we created a high-quality medical knowledge graph from hospital data (electronic health/medical records) in a nearly automatic manner that trained a supervised model based on data labeled using bootstrapping techniques. Then, we designed a QA system based on a memory-based neural network and attention mechanism. Finally, we trained the system to generate answers from the knowledge base and a QA corpus on the internet. Conclusions Bootstrapping and deep neural network techniques can construct a knowledge graph from electronic health/medical records with satisfactory precision and coverage. Our proposed context bridge mechanisms perform training with a variety of language features. Our QA system can achieve state-of-the-art quality in answering medical questions with constrained topics. As we evaluated, complex Chinese language processing techniques, such as segmentation and parsing, were not necessary for practice and complex architectures were not necessary to build the QA system. Lastly, we created an application using our method for internet QA usage.

Members of the high-affinity potassium transporter (HKT) protein family regulate the uptake and homeostasis of sodium and potassium ions, but little research describes their roles in response to abiotic stresses in rapeseed (Brassica napus L.). In this study, we identified and characterized a total of 36 HKT genes from the species comprising the triangle of U model (U-triangle species): B. rapa, B. nigra, B. oleracea, B. juncea, B. napus, and B. carinata. We analyzed the phylogenetic relationships, gene structures, motif compositions, and chromosomal distributions of the HKT family members of rapeseed. Based on their phylogenetic relationships and assemblage of functional domains, we classified the HKT members into four subgroups, HKT1;1 to HKT1;4. Analysis of the nonsynonymous substitutions (Ka), synonymous substitutions (Ks), and the Ka/Ks ratios of HKT gene pairs suggested that these genes have experienced strong purifying selective pressure after duplication, with their evolutionary relationships supporting the U-triangle theory. Furthermore, the expression profiles of BnaHKT genes varies among potassium, phytohormone and heavy-metal treatment. Their repression provides resistance to heavy-metal stress, possibly by limiting uptake. Our results systematically reveal the characteristics of HKT family proteins and their encoding genes in six Brassica species and lay a foundation for further exploration of the role of HKT family genes in heavy-metal tolerance.

Background: Ambient sulfur dioxide (SO2) has been associated with morbidity and mortality of respiratory diseases, however, its effect on length of hospital stays (LOS) and cost for these diagnoses remain unclear. Methods: We collected hospital admission information for respiratory diseases from all 11 cities in the Shanxi Province of China during 2017–2019. We assessed individual-level exposure by using an inverse distance weighting approach based on geocoded residential addresses. A generalized additive model was built to delineate city-specific effects of SO2 on hospitalization, hospital expenditure, and length of hospital stay for respiratory diseases. The overall effects were obtained by random-effects meta-analysis. We further estimated the respiratory burden attributable to SO2 by comparing different reference concentrations. Results: We observed significant effects of SO2 exposure on respiratory diseases. At the provincial level, each 10 μg/m3 increase in SO2 on lag03 was associated with a 0.63% (95% CI: 0.14–0.11) increase in hospital admission, an increase of 4.56 days (95% CI: 1.16–7.95) of hospital stay, and 3647.97 renminbi (RMB, Chinese money) (95% CI: 1091.05–6204.90) in hospital cost. We estimated about 6.13 (95% CI: 1.33–11.10) thousand hospital admissions, 65.77 million RMB (95% CI: 19.67–111.87) in hospital expenditure, and 82.13 (95% CI: 20.87–143.40) thousand days of hospital stay could have potentially been avoided had the daily SO2 concentrations been reduced to WHO’s reference concentration (40 µg/m3). Variable values in correspondence with this reference concentration could reduce the hospital cost and LOS of each case by 52.67 RMB (95% CI: 15.75–89.59) and 0.07 days (95% CI: 0.02–0.117). Conclusion: This study provides evidence that short-term ambient SO2 exposure is an important risk factor of respiratory diseases, indicating that continually tightening policies to reduce SO2 levels could effectively reduce respiratory disease burden in Shanxi Province.

Poly(ether ether ketone) (PEEK) is an important engineering plastic and evaluation of its local crystallinity in composites is critical for producing strong and reliable mechanical parts. Low wavenumber Raman spectroscopy and X-ray diffraction are promising techniques for the analysis of crystal ordering but a detailed understanding of the spectra has not been established. Here, we use molecular dynamics combined with a newly developed approximation to simulate local vibrational features to understand the effect of intermolecular ordering in the Raman spectra. We found that intermolecular ordering does affect the low wavenumber Raman spectra and the X-ray diffraction as observed in the experiment. Raman spectroscopy of intermolecular vibration modes is a promising technique to evaluate the local crystallinity of PEEK and other engineering plastics, and the present technique offers an estimation without requiring heavy computational resources.

Physical parameters (i.e., extraction yield, oil content), chemicals (i.e., fatty acids, phenolics) and oxidative stability associated with virgin olive oil (VOO) from ten varieties in Wudu, China, were analyzed as a function of maturity index and variety by multivariate analysis models. Most of the analytical parameters were significantly affected by the variety and maturity index, and the former was more influential than the latter. Phenolics were the principal factor dividing the ten varieties into four groups. High phenolic levels were observed in the ‘Koroneiki’ group and ‘Manzanilla’ group, but the oil extractability index differentiated between them, being the highest and lowest, respectively. The ‘Koroneiki’ group demonstrated high oil productivity and oil quality, which was worthy of promotion in large-scale cultivation. High amounts of linoleic enhanced the VOO health benefits of ‘Ascolana tenera, Arbequina and Zhongshan24’ group, but brought the risk of shortening the shelf-life. The ‘Ulliri Bardhe, Empeltre, Ezhi8, Yuntai14 and Picual’ group clustered for the higher relative value of oleic acid. The maturity index had significant negative effects on the content of total phenolics, oleacein, oleocanthal, and oleic acid, but had a positive effect on the extractability index, which suggested that varieties with low phenolics and oleic acid levels should be harvested early.

Herein, a kind of novel multi-layer core-shell nanocomposites (NSPN) was prepared by employing SiO2 and polyvinylpyrrolidone (PVP) polymers as modifiers and amino-functionalized metal-organic frameworks (NH2-MIL101(Fe)) as coating. It was referred to as the NSPN and ILs-based effervescence-assisted dispersive solid-phase microextraction, hereafter abbreviated as NIE-DSM. In terms of extraction efficiency, SiO2 and PVP as modifiers and NH2-MIL(Fe) as coating onto the surface of NiFe2O4 cores played a synergistically enhancing effect on adsorption/extraction. Effervescent tablets were prepared by integrating the NSPN magnetic nanoparticles as adsorbents with imidazolium-based ionic liquids (ILs) as extractants as well as acidic and alkaline sources. Under vigorous dispersion of CO2 bubbles, the NIE-DSM method realized the goal of rapidly diffusing and separating the adsorbent/extractant (~3 min) without needing conventional vortexing or centrifugation step. Consequently, the NIE-DSM approach combined dispersion and adsorption/extractant in a synchronous way. Under optimized conditions, the NIE-DSM/HPLC-FLD method gave low limits of detection (0.008–0.034 μg kg−1) and satisfactory extraction recoveries (74.1–101.6%) for five polycyclic aromatic hydrocarbons (PAHs; fluorene, anthracene, pyrene, chrysene and benzo(a)pyrene) in milk samples. The intra-day and inter-day precision, expressed as relative standard deviations, was

Sesquiterpenes are common small-molecule natural products with a wide range of promising applications and are biosynthesized by sesquiterpene synthase (STS). Basidiomycetes are valuable and important biological resources. To date, hundreds of related sesquiterpenoids have been discovered in basidiomycetes, and the biosynthetic pathways of some of these compounds have been elucidated. This review summarizes 122 STSs and 2 fusion enzymes STSs identified from 26 species of basidiomycetes over the past 20 years. The biological functions of enzymes and compound structures are described, and related research is discussed.

R&D alliances and knowledge networks are vital to the innovation process. Based on the multilevel network approach, our study comprehensively investigates several knowledge attributes of interorganizational knowledge networks and explores how R&D alliance networks are relevant for the relationship between knowledge attributes and organizational innovation capability. Samples in our research include 86 cliques from 2010 to 2015 in five Chinese high-tech industries’ R&D alliance networks. Results from the negative binomial regression model show that different knowledge attributes show a distinct effect on organizational innovation capability, including linear relationship, inverted U-shaped curve relationship, and inverted S-shaped curve relationship. Besides, our results identify that the central position within R&D alliance networks plays a limited role in the relationship between knowledge attributes and organizational innovation capability. Our findings could be used to help organizations sort out their knowledge attributes of knowledge bases, come to understand the impact of the interaction between the interorganizational knowledge network and R&D alliance network on the organizational innovation capability, and then make a targeted strategy to carry out innovation activities.