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Abstract Septic cardiomyopathy is a life-threatening heart dysfunction caused by severe infection. Considering the complexity of pathogenesis and high mortality, the identification of efficient biomarkers are needed to guide clinical practice. Based on multimicroarray analysis, this study aimed to explore the pathogenesis of septic cardiomyopathy and the related immune landscape. The results showed that septic cardiomyopathy resulted in organ dysfunction due to extreme pro- and anti-inflammatory effects. In this process, KLRG1, PRF1, BCL6, GAB2, MMP9, IL1R1, JAK3, IL6ST, and SERPINE1 were identified as the hub genes regulating the immune landscape of septic cardiomyopathy. Nine transcription factors regulated the expression of these genes: SRF, STAT1, SP1, RELA, PPARG, NFKB1, PPARA, SMAD3, and STAT3. The hub genes activated the Th17 cell differentiation pathway, JAK-STAT signaling pathway, and cytokine‒cytokine receptor interaction pathway. These pathways were mainly involved in regulating the inflammatory response, adaptive immune response, leukocyte-mediated immunity, cytokine-mediated immunity, immune effector processes, myeloid cell differentiation, and T-helper cell differentiation. These nine hub genes could be considered biomarkers for the early prediction of septic cardiomyopathy.

BackgroundThere are a variety of microorganisms in ambient air, and susceptible people can be infected once contact with pathogenic microorganisms in the environment. In order to avoid the spread of pathogenic bacteria, disinfection is the simplest and most effective way of killing pathogenic bacteria in the environment to block the contact between pathogenic bacteria and humans. Sodium hypochlorite (NaClO) is the most widely used disinfectant, but its safety in ambient air disinfection is not clear yet. ObjectiveTo establish a model of bronchial epithelial cell (BEAS-2B) injury induced by NaClO, and to explore the mechanism of the toxic effect of NaClO disinfectants on BEAS-2B. MethodsCells were treated with concentration gradients of 0, 25, 50,100, 200, and 400 μmol·L−1 of the diluted NaClO (100 mmol·L−1) standard solution, respectively, and cell activity was measured by cell counting kit-8 (CCK-8) assay after 15 and 30 min. Cells treated with 0, 25, and 50 μmol·L−1 NaClO were selected to observe the cell morphology under an inverted microscope, apoptosis was determined by flow cytometry Annexin V FITC / PI double staining to determine the final experimental concentration. The morphology of organelles such as mitochondria was observed under a transmission electron microscope. Mitochondrial membrane potential of the cells was detected by JC-1 staining. Intracellular Ca2+ concentration was measured with a Fluo-4 AM fluorescent probe. Total cellular reactive oxygen species (ROS) was detected with a 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe, cell mitochondrial ROS with a dihydroethidium (DHE) fluorescent probe, and lipid peroxidation intermediate malondialdehyde (MDA) with a commercial kit. ResultsCompared with 0 μmol·L−1, NaClO treatment group, cell morphology did not change a lot after 25 μmol·L−1 NaClO treatment for 30 min, and the cells began to wrinkle and become round after 30 min treatment with 50 μmol·L−1 NaClO, showing about 70% of normal cell viability (P

Abstract The causal relationship between Packed red blood cell (RBC) transfusion and necrotizing enterocolitis (NEC) remains uncertain. This study aims to provide an exploration of transfusion and NEC in very preterm infants. Using data from the Chinese Neonatal Network cohort study between 2019 and 2021, the analysis focused on very preterm infants (with a birth weight of

BackgroundIn China, over 5 million people have been identified and registered by the public security institutions for using illicit drugs. The aim of this study is to compare the influence of different types of illicit drugs on the self-reported mental health of Chinese people. In particular, we want to assess the damage of Heroin, Methamphetamine and Ketamine to mental health in a social environment where drug use is strictly regulated.MethodsThe study is based on survey with 6,906 people who use drugs in Guangdong province, China. Risk of mental health issue is measured using the Brief Symptoms Inventory 18 (BSI-18) Scale, and a higher BSI-18 score indicates more severe mental health problems. The data was analyzed through multilevel regression analysis, propensity score matching analysis and mediation analysis.ResultsThe three major types of illicit drugs have both moderating and mediating effects on the length of drug-use history, that Heroin use leads to longer drug-use duration, while Ketamine use causes more damage on mental health per unit time of drug-use duration. Average duration of Methamphetamine use is 0.7 year shorter than average duration of Heroin use, and average duration of Ketamine use is 1.7 year shorter than average duration of Heroin use. For each year of increase of drug-use duration, Ketamine use leads to 1.2 times more of BSI score increase than Heroin use, and 2.3 times more of BSI score increase than Methamphetamine use.ConclusionThese three drugs are associated with severe mental health issue in a society with strict drug regulation. Attention should be paid to the mental health of people regardless of the type of drugs they use.

IntroductionIntra-aortic balloon pump (IABP) is sometimes coupled with Venoarterial extracorporeal membrane oxygenation (VA-ECMO) to treat patients with cardiogenic shock. In this study, we attempted to evaluate the association of the IABP approach on survival and vascular complication rates in adults with cardiogenic shock undergoing VA-ECMO.MethodsWe performed a systematic search of original studies on VA-ECMO with and without IABP in PubMed, EMBASE, and the Cochrane Library.ResultsA total of 42 studies with 8,759 patients were included. The pooled in-hospital deaths of patients on VA-ECMO with and without IABP were 2,962/4,807 (61.61%) versus 2,666/3,952 (67.45%). VA-ECMO with IABP presents lower in-hospital mortality (risk ratio, 0.88; 95% CI, 0.86-0.91; P

Background & aims: Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) has long been recognized as an adipokine. However, the exact role of eNAMPT in alcoholic liver disease (ALD) and its relevance to brown adipose tissue (BAT) remain largely unknown. This study aimed to evaluate the impact of eNAMPT on liver function and the underlying mechanisms involved in BAT-Liver communication. Methods: Serum eNAMPT levels were detected in the serum of both ALD patients and mice. Chronic and binge ethanol feeding was used to induce alcoholic liver injury in mice. An eNAMPT antibody, a coculture model of brown adipocytes and hepatocytes, and BAT-specific Nampt knockdown mice were used to investigate the role of eNAMPT in ALD. Results: Serum eNAMPT levels are elevated in ALD patients and are significantly positively correlated with the liver injury index. In ALD mice, neutralizing eNAMPT reduced the elevated levels of circulating eNAMPT induced by ethanol and attenuated liver injury. In vitro experiments revealed that eNAMPT induced hepatocyte ferroptosis through the TLR4-dependent mitochondrial ROS-induced ferritinophagy pathway. Furthermore, ethanol stimulated eNAMPT secretion from brown adipocytes but not from other adipocytes. In the coculture model, ethanol-induced release of eNAMPT from brown adipocytes promoted hepatocyte ferroptosis. In BAT-specific Nampt-knockdown mice, ethanol-induced eNAMPT secretion was significantly reduced, and alcoholic liver injury were attenuated. These effects can be reversed by intraperitoneal injection of eNAMPT. Conclusion: Inhibition of ethanol-induced eNAMPT secretion from BAT attenuates liver injury and ferroptosis. Our study reveals a previously uncharacterized critical role of eNAMPT-mediated BAT-Liver communication in ALD and highlights its potential as a therapeutic target.

Abstract Objectives To explore the efficacy and safety of Transarterial chemoembolization (TACE) in combination with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) in patients with unresectable hepatocellular carcinoma (uHCC). Methods 456 patients with HCC receiving either TACE in combination with ICIs and TKIs (combination group, n = 139) or TACE monotherapy (monotherapy group, n = 317) were included from Apr 2016 to Dec 2021 in this retrospective study. We employed propensity score matching (PSM), performed 1:2 optimal pair matching, to balance potential bias. Results The mean follow-up time is 24.7 months (95% CI 22.6–26.8) for matched patients as of March 2022. After matching, the combination group achieved longer OS and PFS (median OS:21.9 vs. 16.3 months, P = 0.022; median PFS: 8.3 vs. 5.1 months, P

IntroductionThe prevention and mitigation of intestinal immune challenge is crucial for poultry production. This study investigated the effects of dietary Macleaya cordata extract (MCE) supplementation on the prevention of intestinal injury in broiler chickens challenged with lipopolysaccharide (LPS).MethodsA total of 256 one-day-old male Arbor Acres broilers were randomly divided into 4 treatment groups using a 2×2 factorial design with 2 MCE supplemental levels (0 and 400 mg/kg) and 2 LPS challenge levels (0 and 1 mg/kg body weight). The experiment lasted for 21 d.Results and discussionThe results showed that MCE supplementation increased the average daily feed intake during days 0-14. MCE supplementation and LPS challenge have an interaction on the average daily gain during days 15-21. MCE supplementation significantly alleviated the decreased average daily gain of broiler chickens induced by LPS. MCE supplementation increased the total antioxidant capacity and the activity of catalase and reduced the level of malondialdehyde in jejunal mucosa. MCE addition elevated the villus height and the ratio of villus height to crypt depth of the ileum. MCE supplementation decreased the mRNA expression of pro-inflammatory cytokines interleukin (IL)-6 and IL-8 in the jejunum. MCE addition mitigated LPS-induced mRNA up-expression of pro-inflammatory factors IL-1β and IL-17 in the jejunum. MCE supplementation increased the abundance of probiotic bacteria (such as Lactobacillus and Blautia) and reduced the abundance of pathogenic bacteria (such as Actinobacteriota, Peptostretococcaceae, and Rhodococcus), leading to alterations in gut microbiota composition. MCE addition altered several metabolic pathways such as Amino acid metabolism, Nucleotide metabolism, Energy metabolism, Carbohydrate metabolism, and Lipid metabolism in broilers. In these pathways, MCE supplementation increased the levels of L-aspartic acid, L-Glutamate, L-serine, etc., and reduced the levels of phosphatidylcholine, phosphatidylethanolamine, thromboxane B2, 13-(S)-HODPE, etc. In conclusion, dietary supplementation of 400 mg/kg MCE effectively improved the growth performance and intestinal function in LPS-challenged broiler chickens, probably due to the modulation of gut microbiota and plasma metabolites.

Abstract Background Venovenous extracorporeal membrane oxygenation (VV ECMO) has been widely used for severe acute respiratory distress syndrome (ARDS) in recent years. However, the role of hemoadsorption in ARDS patients requiring VV ECMO is unclear. Methods Therefore, we conducted a systematic review to describe the effect of hemoadsorption on outcomes of ARDS patients requiring VV ECMO and elucidate the risk factors for adverse outcomes. We conducted and reported a systematic literature review based on the principles derived from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The systematic review searched Embase, CINHAL, and Pubmed databases for studies on ARDS patients receiving hemoadsorption and VV ECMO. The demographic data, clinical data and biological data of the patients were collected. Results We ultimately included a total of 8 articles including 189 patients. We characterized the population both clinically and biologically. Our review showed most studies described reductions in inflammatory markers and fluid resuscitation drug dosage in ARDS patients with Coronavirus disease 2019 (COVID-19) or sepsis after hemoadsorption. Conclusion Because most of the studies have the characteristics of high heterogeneity, we could only draw very cautious conclusions that hemoadsorption therapy may enhance hemodynamic stability in ARDS patients with COVID-19 or sepsis receiving VV ECMO support. However, our results do not allow us to draw conclusions that hemoadsorption could reduce inflammation and mortality. Prospective randomized controlled studies with a larger sample size are needed in the future to verify the role of hemoadsorption in ARDS patients requiring VV ECMO.

Multilevel diffractive lenses (MDLs) has undergone considerable advancements, marked by their exceptional efficiency and diverse focusing capabilities, resulting in their widespread use in optical systems. In recent times, MDLs have consistently been juxtaposed with metalenses, which have experienced swift progress over the last decade. Concurrently, MDLs have continued to evolve, propelled by their distinct advantages, such as cost-effective production and adaptability for mass manufacturing. This article explores the evolution and foundational concepts of MDLs, highlighting the advantages of their circular symmetry in enhancing simulation and optimization efficiency. Furthermore, we present several innovative fabrication methods for MDLs that capitalize on the latest advancements in 3D printing technology. We also show the practical applications and potential future developments of MDLs.

IntroductionClostridium perfringens α toxin is a main virulence factor responsible for gut damage in animals. Arginine is a functional amino acid exhibiting significant immunoregulatory activities. However, the effects and immunoregulatory mechanisms of arginine supplementation on α toxin-induced intestinal injury remain unclear.MethodsIn vivo, 256 male Arbor Acres chickens were randomly assigned to a 2×2 factorial arrangement, involving diet treatments (with or without 0.3% arginine supplementation) and immunological stress (with or without α toxin challenge). In vitro, IEC-6 cells were treated with or without arginine in the presence or absence of α toxin. Moreover, IEC-6 cells were transfected with siRNA targeting mTOR and SLC38A9 to explore the underlying mechanisms.Results and discussionThe results showed that in vivo, arginine supplementation significantly alleviated the α toxin-induced growth performance impairment, decreases in serum immunoglobulin (Ig)A and IgG levels, and intestinal morphology damage. Arginine supplementation also significantly reduced the α toxin-induced increase in jejunal proinflammatory cytokines interleukin (IL)-1β, IL-6 and IL-17 mRNA expression. Clostridium perfringens α toxin significantly decreased jejunal mechanistic target of rapamycin (mTOR) and solute carrier family 38 member 9 (SLC38A9) mRNA expression, while arginine supplementation significantly increased mTOR and SLC38A9 mRNA expression. In vitro, arginine pretreatment mitigated the α toxin-induced decrease in cell viability and the increase in cytotoxicity and apoptosis. Arginine pretreatment also alleviated the α toxin-induced upregulation of mRNA expression of inflammation-related cytokines IL-6, C-X-C motif chemokine ligand (CXCL)10, CXCL11 and transforming growth factor-β (TGF-β), as well as apoptosis-related genes B-cell lymphoma-2 associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-extra large (Bcl-XL) and cysteinyl aspartate specific proteinase 3 (Caspase-3) and the ratio of Bax to Bcl-2. Arginine pretreatment significantly increased the α toxin-induced decrease in mTOR, SLC38A9, eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4EBP1) and ribosomal protein S6 kinase (S6K) mRNA expression. Knockdown SLC38A9 and mTOR largely abrogated the positive effects of arginine pretreatment on α toxin-induced intracellular changes. Furthermore, SLC38A9 silencing abolished the increased mTOR mRNA expression caused by arginine pretreatment. In conclusion, arginine administration attenuated α toxin-induced intestinal injury in vivo and in vitro, which could be associated with the downregulation of inflammation via regulating SLC38A9/mTORC1 pathway.

To mitigate the impact of tropospheric radio-duct interference on 5G network, 3GPP has defined functionalities for remote interference management.Based on this functionality, an automated scheme for SetID and gNBID was developed, enabling the reuse of SetID in different tropospheric radio-duct interference regions, striking a balance between efficiency and uniqueness.By analyzing remote interference measurement data from base stations, an intelligent localization and identification method for tropospheric radio-duct interference was summarized.An intelligent network optimization process for identifying the aggressor base stations was created and successfully validated in the network.An effective operational plan was provided for management of 5G tropospheric radio-duct interference, alleviating the constraints on the development of the 5G industry caused by the interference.

Challenges remain in large-scale and successive preparation of porous polymer composite component, which limits its practical applications for high-performance electromagnetic interference (EMI) shielding. Herein, a scalable and efficient method based on mold-opening foam injection molding was developed to fabricate carbon fiber (CF) reinforced polymer composite foams for EMI shielding applications. Thanks to the novel foaming process and heterogeneous nucleation effect of CF, real microcellular poly(ether-block-amide) (PEBA)/CF composite foams with an average cell size of 6.6 μm and a cell density of up to 109 cells/cm3 were achieved. Due to the significantly refined cellular morphology, the PEBA/CF composite foams exhibit superior EMI shielding performance over the unfoamed composites which was characterized by absorption-dominated shielding characteristics and significantly enhanced EMI shielding effectiveness. Furthermore, compared with the unfoamed case, the foamed PEBA/CF composites with refined cellular morphology shows greatly improved cold toughness and duality, and the tensile strain at break and specific tensile toughness are increased by 88.6% and 109.1%, respectively. Moreover, real-microcellular PEBA/CF composite foams have remarkably enhanced surface quality than those fabricated by regular foam injection molding process, and the surface roughness can be maximumly increased by 91.6%. Thus, this study provides a promising strategy for producing lightweight and strong components for high-performance EMI shielding applications.

Automated milking systems (AMS) are increasingly adopted for dairy cow production, promoting individualized cow management dependent on factors like lactation stage, age, and productivity. The study objective was to investigate the effects of early lactation milking frequency on cows milked via AMS. Multiparous Holstein cows blocked by parity and due date were randomly assigned to treatments (n = 8 per treatment): three (3X) or six (6X) milkings per day (MPD). The experimental phase (EXP) was defined as 4 to 29 days in milk (DIM). The AMS settings were programed so 3X cows were limited to three MPD while 6X cows were allowed six MPD. Afterwards was the carry over phase (CO) ranging from 30 to 90 DIM; all cows were allowed up to six MPD. Measurements by the AMS included bodyweight, milk yield (MY), and pellet intake. Weekly composite milk samples were analyzed for macronutrient composition and fatty acid (FA) profile. Coccygeal blood was sampled at 3, 8 ± 1, and 13 ± 1 DIM; concentrations of blood plasma analytes were quantified. Greater MPD was achieved for 6X cows versus 3X cows during EXP, but similar during the CO. Daily MY was non-separable during the EXP while 6X cows in their third or greater lactation group (3 + LG) had greater MY than 3X cows of the same LG during the CO. Milk fat content and 4% fat-corrected MY were both greater for 6X, 3 + LG cows during the EXP compared to 3X, 3 + LG cows. Milk FA methyl esters (FAME) proportions were different between MPD groups, with 6X, 3 + LG cows having the lowest short, even-chain FA from de novo or post-absorptive origin. Differences in analytes indicated that 6X, 3 + LG cows experienced metabolic stress and incorporated greater FA from adipose tissue. Greater early lactation MPD in AMS may shift cow nutrient partitioning to support greater production in 3+ parity cows.

Tungsten and its alloys have a high atomic number, high melting temperature, and high thermal conductivity, which make them fairly appropriate for use in nuclear applications in an extremely harsh radioactive environment. In recent years, there has been growing research interest in using additive manufacturing techniques to produce tungsten components with complex structures. However, the critical bottleneck for tungsten engineering manufacturing is the high melting temperature and high ductile-to-brittle transition temperature. In this study, laser powder bed fusion has been studied to produce bulk pure tungsten. And finite element analysis was used to simulate the temperature and stress field during laser irradiation. The as-printed surface as well as transverse sections were observed by optical microscopy and scanning electron microscopy to quantitatively study processing defects. The simulated temperature field suggests small-sized powder is beneficial for homogenous melting and provides guidelines for the selection of laser energy density. The experimental results show that ultra-dense tungsten bulk has been successfully obtained within a volumetric energy density of 200–391 J/mm3. The obtained relative density can be as high as 99.98%. By quantitative analysis of the pores and surface cracks, the relationships of cracks and pores with laser volumetric energy density have been phenomenologically established. The results are beneficial for controlling defects and surface quality in future engineering applications of tungsten components by additive manufacturing.

The application of alginate fibers is limited by relatively low mechanical properties. Herein, a self-reinforcing strategy inspired by nature is proposed to fabricate alginate fibers with minimal changes in the wet-spinning process. By adapting a coagulation bath composing of CaCl2 and ethanol, the secondary structure of sodium alginate (SA) was regulated during the fibrous formation. Ethanol mainly increased the content of β-sheet in SA. Rheological analysis revealed a reinforcing mechanism of stiff β-sheet for enhanced modulus and strength. In combination with Ca2+ crosslinking, the self-reinforced alginate fibers exhibited an increment of 39.0% in tensile strength and 71.9% in toughness. This work provides fundamental understanding for β-sheet structures in polysaccharides and a subsequent self-reinforcing mechanism. It is significant for synthesizing strong and tough materials. The self-reinforcing strategy involved no extra additives and preserved the degradability of the alginate. The reinforced alginate fibers exhibited promising potentials for biological applications.

Three new cyclic lipopeptides, olenamidonins A-C (1–3), in addition to two previously reported metabolites (4 and 5), were accumulated in the ΔdtxRso deletion mutant of deepsea-derived Streptomyces olivaceus SCSIO 1071. The structures of these cyclic lipopeptides were determined by a combination of spectroscopic methods and circular dichroism (CD) measurement. The antibacterial assay results showed that compounds 1–5 displayed different degrees of growth inhibition against multidrug-resistant (MDR) bacterial strains Enterococcus faecalis CCARM 5172 and Enterococcus faecium CCARM 5203 with minimum inhibitory concentrations (MICs) of 1.56−6.25 μg/mL.

Abstract Planar super-oscillatory lens (SOL), a far-field subwavelength-focusing diffractive device, holds great potential for achieving sub-diffraction-limit imaging at multiple wavelengths. However, conventional SOL devices suffer from a numerical-aperture-related intrinsic tradeoff among the depth of focus (DoF), chromatic dispersion and focusing spot size. Here, we apply a multi-objective genetic algorithm (GA) optimization approach to design an apochromatic binary-phase SOL having a prolonged DoF, customized working distance (WD), minimized main-lobe size, and suppressed side-lobe intensity. Experimental implementation demonstrates simultaneous focusing of blue, green and red light beams into an optical needle of ~0.5λ in diameter and DOF > 10λ at WD = 428 μm. By integrating this SOL device with a commercial fluorescence microscope, we perform, for the first time, three-dimensional super-resolution multicolor fluorescence imaging of the “unseen” fine structures of neurons. The present study provides not only a practical route to far-field multicolor super-resolution imaging but also a viable approach for constructing imaging systems avoiding complex sample positioning and unfavorable photobleaching.

E-commerce is a typical form of retail digitalization that introduces online uncertainty and product returns. To decrease the negative influence of online uncertainty, the largest Chinese e-commerce company, the Alibaba Group, invited an insurance company to develop return-freight insurance (RFI), a new kind of insurance, to compensate for consumers' losses in the event of online product returns. Complimentary RFI can increase consumer confidence in the retailer and attract more demand. Retailers who offer complimentary RFI demonstrate to consumers that their products and services are too good to incur excessive product returns. However, some low-quality online retailers can mimic competitors’ behavior by offering complimentary RFI to consumers. This study aims to introduce an innovative online return policy based on RFI and to explore whether low-quality online retailers would use complimentary RFI as their return strategy to mislead consumers. Using signaling theory, we built a conceptual economic model that includes three exogenous pricing variables: RFI, insurance premium, and compensation. These variables play different roles in the model because consumers cannot observe the insurance premium, but the compensation can be. The main finding of this study is that innovative complimentary RFI could be abused by low-type retailers when the premium and compensation are appropriate. Interestingly, compensation plays different roles for retailers with different product values: low-type retailers use complimentary RFI as a noise tool. When the product works for the consumer and the insurance profit is not too high, the compensation for the low-quality product should be larger than that for the high-quality product, which is different from conventional wisdom. Although high-type online retailers may use complimentary RFI as a product quality signal, there is still a significant risk that nefarious elements will use it to create product quality noise.

Clostridium perfringens α toxin is generated by all types of C. perfringens and is closely related to necrotic enteritis in poultry. This study was conducted to investigate the effects of α toxin on immune function, antioxidant capacity, intestinal health and the underlying mechanisms in broiler chickens. A total of 144 twenty-day-old broiler chickens were randomly assigned to four treatments. On d 21, the birds were intraperitoneally injected with PBS (control group) or α toxin at 0.025, 0.1 or 0.4 U/kg of body weight. Samples were collected at 3 h and 24 h post injection (p.i.). Results showed that α toxin challenge linearly decreased the average daily gain during the 3 days after infection and decreased plasma IgA and IgM levels 3 h p.i. Plasma diamine oxidase and d-lactate levels were linearly elevated by α toxin challenge at 3 h p.i. and 24 h p.i. Alpha toxin challenge linearly decreased plasma and jejunal mucosal catalase, glutathione peroxidase and total superoxide dismutase activities at 3 h p.i. and linearly decreased glutathione peroxidase and total superoxide dismutase activities at 24 h p.i. The ileal villus height to crypt depth ratio decreased linearly with increasing α toxin levels at 3 h p.i. and 24 h p.i. Alpha toxin challenge linearly elevated jejunal IL-1β, IL-6, IL-8 and tumor necrosis factor α mRNA expression at 3 h p.i. Additionally, α toxin challenge linearly reduced the jejunal claudin-1, claudin-3 and zonula occludens 1 mRNA expression at 3 h p.i. and the claudin-3, occludin and zonula occludens 1 mRNA expression at 24 h p.i. What's more, α toxin linearly increased the jejunal PLCγ1, AMPKα1 and ATG5 mRNA expression and linearly decreased the mTOR mRNA expression. In conclusion, C. perfringens α toxin challenge decreased body weight gain, impaired immune function, antioxidant capacity and intestinal health, and induced PLCγ1/AMPK/mTOR pathway-mediated autophagy. The recommended intraperitoneal injection dose for moderate injury was 0.1 U/kg of body weight and the recommended sampling time was 3 h p.i. in broiler chickens.

IntroductionWith the goal to maximize intake of high-fermentable diet needed to meet energy needs during weaning period, calves are at risk for ruminal acidosis. Using the calves from previously established model of feed-induced, ruminal acidosis in young calves, we aimed to investigate the changes in rumen epimural transcriptome and its microbial metatranscriptome at weaning (8-week) and post-weaning (17-week) in canulated (first occurred at 3 weeks of age) Holstein bull calves with feed-induced subacute ruminal acidosis.MethodsEight bull calves were randomly assigned to acidosis-inducing diet (Treated, n = 4; pelleted, 42.7% starch, 15.1% neutral detergent fiber [NDF], and 57.8% nonfiber carbohydrates), while texturized starter was fed as a control (Control, n = 4; 35.3% starch, 25.3% NDF, and 48.1% nonfiber carbohydrates) starting at 1 week through 17 weeks. Calves fed acidosis-inducing diet showed significantly less (p

Ciprofol is a novel short-acting intravenous anaesthetic developed in China that is mainly metabolized by cytochrome P450 2B6 (CYP2B6) and uridine diphosphate glucuronosyltransferase 1A9 (UGT1A9). Currently, insufficient evidence is available to support drug‒drug interactions between ciprofol and CYP2B6 inactivators. Here, we established a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method to assess the concentration of ciprofol and investigated the effects of psoralen and clopidogrel on the metabolism of ciprofol in liver microsomes and rats. In rat and human liver microsomes, the median inhibitory concentration (IC50) values of psoralen were 63.31 μmol·L-1 and 34.05 μmol·L-1, respectively, showing mild inhibitory effects on ciprofol metabolism, whereas the IC50 values of clopidogrel were 6.380 μmol·L-1 and 2.565 μmol·L-1, respectively, with moderate inhibitory effects. SD rats were randomly divided into three groups: psoralen (27 mg·kg-1), clopidogrel (7.5 mg·kg-1), and the same volume of 0.5% carboxy methyl cellulose. After 7 days, all rats were injected with 2.4 mg·kg-1 ciprofol. Compared with the control group, the AUC and MRT values of ciprofol in the psoralen and clopidogrel groups were significantly greater, whereas the CL values were significantly lower. In addition, the durations of loss of righting reflex (LORR) in the psoralen and clopidogrel groups were 16.1% and 23.0% longer than that in the control group, respectively. In conclusion, psoralen and clopidogrel inhibit ciprofol metabolism to different degrees and prolong the duration of LORR in rats.

[Objective] The water resource carrying capacity of Yulin City, Shaanxi Province, was studied in order to provide a scientific reference for the development and utilization of water resources and regional coordinated development. [Methods] An evaluation system was constructed from the perspective of water-economy-society-ecology. Analytic hierarchy process, entropy, and TOPSIS methods were used to evaluate the carrying capacity of water resources in Yulin City. Coupled coordination degree and obstacle degree models were introduced to analyze the regional coordinated development level and the main obstacles to carrying capacity. Evolution analysis and prediction of carrying capacity were conducted based on development planning. [Results] The water resource carrying capacity indices of all districts and counties in Yulin City were at medium and weak levels, while the development of Yuyang District, Shenmu County, and Dingbian County were not coordinated. High population density and high agricultural water consumption were the main obstacles to increasing carrying capacity in Yuyang District. Ecological environment water demand was the main obstacle factor in Shenmu County. Weak water resources background, low availability, and soil erosion were the main obstacles limiting the carrying capacity of eastern counties. The overall regional water resource carrying capacity in 2020 has increased since 2016. Under future economic and social development and the implementation of water diversion projects, the water resource carrying capacity indices of Yuyang District, Shenmu County, Fugu County, and Hengshan County are expected to increase, while the water resource carrying capacity indices of other districts and counties are expected to weaken because of economic and social development and other factors. [Conclusion] Water resource carrying capacity and regional coordinated development in Yulin City are somewhat fragile and unbalanced. Therefore, it is necessary to further adjust the water use structure, optimize the allocation of water resources, and make coordinated plans to protect the water-food-safety-ecological resources.

Observing the fast development of livestreaming, this paper investigates its adoption on the retail platform and examines its impact on merchants. We develop a game-theoretic model in which a leading retailer and a third-party seller engage in price competition. Our model fully considers the initiative of live streamers in this asymmetric competition. We find that the streamer’s cost and the seller’s initial awareness are two key factors affecting the adoption of livestreaming. Specifically, when the streamer’s cost is low, or it is intermediate and the seller’s initial awareness is high, the retailer adopts and opens livestreaming and the seller also adopts it; when both factors are intermediate, the retailer adopts livestreaming but does not open it to the seller; when both factors are high, the retailer adopts and opens livestreaming but the seller does not adopt it; otherwise, the retailer does not adopt livestreaming. Our results also suggest that the presence of livestreaming benefits the retailer but may hurt the seller especially when the seller’s initial awareness is high. Our findings provide relevant and useful implications for both the platform retailer and third-party seller in their livestreaming decisions.

Abstract Photothermal therapy has shown great promise for cancer treatment and second near-infrared (NIR-II) -absorbing particles could further improve its precision and applicability due to its superior penetration depth and new imaging ability. Herein, high NIR-II-absorbing polymer particles were prepared by using soluble isobutyl-substituted diammonium borates (P-IDI). The P-IDI showed stronger absorption at 1000–1100 nm, which exhibited excellent photostability, strong photoacoustic imaging ability and high photothermal conversion efficiency (34.7%). The investigations in vitro and in vivo demonstrated that the excellent photothermal effect facilitated complete tumor ablation and also triggered immunogenic cell death in activation of the immune response. The high solubility and excellent photothermal conversion ability demonstrated that polymer IDI particles were promising theranostic agents for treatment of tumors with minor side effects.

ObjectiveWe investigated the association between bronchopulmonary dysplasia (BPD) and 3 years death or neurodevelopmental impairment (NDI) in very preterm infants without severe brain injury.MethodOur prospective cohort study recruited preterm infants who were born prior to 32 weeks of gestational age and survived in the neonatal intensive care unit until 36 weeks of corrected age. Upon reaching 3 years of age, each infant was assessed for death or NDI such as cerebral palsy, cognitive deficit, hearing loss, and blindness. Correlations between BPD and death or NDI were determined using multiple logistic regression analyses adjusted for confounding factors.ResultA total of 1,417 infants without severe brain injury who survived until 36 weeks of corrected age were initially enrolled in the study. Over the study period, 201 infants were lost to follow-up and 5 infants were excluded. Our final dataset, therefore, included 1,211 infants, of which 17 died after 36 weeks of corrected age and 1,194 were followed up to 3 years of age. Among these infants, 337 (27.8%) developed BPD. Interestingly, by 3 years of age, BPD was demonstrated to be independently associated with death or NDI, with an adjusted odds ratio of 1.935 (95% confidence interval: 1.292–2.899, p = 0.001), in preterm infants without severe neonatal brain injury.ConclusionOur findings indicate that BPD is strongly associated with death or NDI in preterm infants without severe neonatal brain injury at 3 years of age. Further research is needed to understand the mechanisms linking the development of BPD with death or NDI and whether appropriate treatment of BPD may ameliorate or prevent the development of neurological complications.

IntroductionIn the dairy industry, calves are typically fed diets rich in highly fermentable carbohydrates and low in fibrous feeds to maximize ruminal papillae and tissue development. Calves on such diets are vulnerable at developing ruminal acidosis. Prevalent in cattle, liver abscess (LA) is considered a sequela to ruminal acidosis. LAs can cause significant liver function condemnation and decreased growth and production. Currently, we know little about the liver microbiome in calves with feed-induced acidosis.MethodsUsing our established model of ruminal acidosis, where young calves were fed an acidosis-inducing (AC) or -blunting (control) diet starting at birth until 17-week of age, we investigated microbial community changes in the liver resultant from ruminal acidosis. Eight calves were randomly assigned to each diet, with four animals per treatment. Rumen epithelium and liver tissues were collected at 17 weeks of age right after euthanasia. Total RNAs were extracted and followed by whole transcriptome sequencing. Microbial RNA reads were enriched bioinformatically and used for microbial taxonomy classification using Kraken2.ResultsAC Calves showed significantly less weight gain over the course of the experiment, in addition to significantly lower ruminal pH, and rumen degradation comparison to the control group (p < 0.05). In the liver, a total of 29 genera showed a significant (p < 0.05) abundance change (> 2-fold) between the treatments at 17-week of age. Among these, Fibrobacter, Treponema, Lactobacillus, and Olsenella have been reported in abscessed liver in cattle. Concurrent abundance changes in 9 of the genera were observed in both the liver and rumen tissues collected at 17-week of age, indicating potential crosstalk between the liver and rumen epithelial microbial communities. Significant association was identified between host liver gene and its embedded microbial taxa. Aside from identifying previously reported microbial taxa in cattle abscessed liver, new repertoire of actively transcribed microbial taxa was identified in this study.DiscussionBy employing metatranscriptome sequencing, our study painted a picture of liver microbiome in young calves with or without feed induced acidosis. Our study suggested that liver microbiome may have a critical impact on host liver physiology. Novel findings of this study emphasize the need for further in-depth analysis to uncover the functional roles of liver resident microbiome in liver metabolic acidosis resultant from feed-related ruminal acidosis.

ABSTRACT: The aim of this work was to investigate the effects of dietary vitamin K3 (VK3) supplementation on production performance, egg quality, vitamin K-dependent proteins, and antioxidant properties in breeding geese during the laying period. A total of one hundred twenty 82-wk-old Wulong geese with similar body weights were randomly divided into 6 groups with 4 replicates and 5 geese each (1 male and 4 female). The geese in the control group were fed a basal diet, and the geese in the treatment groups were fed diets supplemented with different levels of VK3 (2.5, 5.0, 7.5, 10.0, and 12.5 mg/kg) for 11 wk. Dietary VK3 supplementation linearly and quadratically increased feed intake, egg mass, egg weight, and egg production (P < 0.05). Increasing VK3 levels linearly and quadratically increased albumen height, shell thickness and Haugh unit of eggs (P < 0.05). VK3 reduced osteocalcin (OC) and uncarboxylated osteocalcin (ucOC) levels in the serum. Dietary VK3 addition linearly decreased serum malondialdehyde (MDA) levels (P < 0.01). There was linear and quadratic effect in the activity of serum total superoxide dismutase (T-SOD) (P < 0.01), and linear effect in serum total antioxidant capacity (T-AOC) (P < 0.01). In conclusion, dietary VK3 supplementation enhanced the production performance, egg quality, vitamin K-dependent proteins, and antioxidant properties in breeding geese during the laying period. The optimal dose of dietary VK3 supplementation was 10.0 mg/kg.

Abstract Product recovery is an important business because of its great economic, social, and environmental benefits in practice. In this paper, a location-inventory problem (LIP) in a closed-loop supply chain (CLSC) is investigated to optimize facility location and inventory control decisions by considering product recovery. The objective is to optimize facility location and inventory control decisions to minimize the total cost of business operations in a closed-loop supply chain system. We formulate this problem as a mixed-integer nonlinear programming model and design a modified hybrid differential evolution algorithm (MHDE) to solve it efficiently. Finally, numerical results are presented to validate the performance of the new algorithm. The results show that MHDE is more efficient and effective than Lingo and other algorithms for the research problem under study. Managerial insights are also derived for business managers to improve their supply chain performance.

Abstract Background Lysine (Lys) is the first limiting amino acid for pigs fed corn-soybean meal diets. Three experiments were conducted to estimate the optimal standardized ileal digestible (SID) Lys requirement for growing (Exp. 1), early finishing (Exp. 2), and late finishing (Exp. 3) pigs under commercial conditions. Results and conclusions In Exp. 1, a total of 650 growing pigs (32.21 ± 0.33 kg bodyweight), were allocated to 5 dietary treatments supplemented with 0.75, 0.85, 0.94, 1.03, and 1.13% SID Lys. Each treatment had 5 replicate pens with 26 pigs per pen. The lowest feed to gain ratio (F:G) was obtained by pigs fed the 1.03% Lys diet and F:G showed both a linear and a quadratic response with increasing Lys (P

Abstract In nursing homes using technologies such as IoT, big data, cloud computing, and machine learning, there is a constant risk of attacks such as Brute Force FTP, Brute Force SSH, Web Attack, Infiltration, and Botnet during data communication between individual terminals and the cloud server. Therefore, effectively identifying network communication data is essential to protect data communication security between individual terminals and the cloud server. Aiming at the data mentioned above regarding communication security issues, we propose an intelligent intrusion detection model NIDD (Network Intelligent Data Detection) model that combines deep convolution generation adversarial network (DCGAN) with Light Gradient Boosting Machine (LightGBM) and Shapley Additive exPlanations (SHAP). The NIDD model first generates new attack samples by learning the feature distribution of the existing attack sample data and effectively expands the rare attack samples. Secondly, we use the Light Gradient Boosting Machine (LightGBM) algorithm as the base classifier to train the dataset and start to build the intrusion detection model. Then use Shapley Additive exPlanations (SHAP) to analyze the contribution of the classification results, and adjust the model parameters according to the analysis results. Finally, we obtain the optimal model for the intelligent detection model of network intrusion. This paper conducts experimental tests on the NSL-KDD dataset. The experimental results show that the NIDD model built based on Light Gradient Boosting Machine can detect Brute Force FTP, Brute Force SSH, DoS, Heartbleed, Web Attack, Infiltration, Botnet, PROBE, R2L, and U2R attacks with an accuracy of 99.76%. Finally, we re-verified the NIDD model on the CIC-IDC-2018 dataset. The results once again proved that the NIDD model could solve the data communication security between the nursing robot and the cloud server and the data before the IoT terminal and the cloud server. Communication security provides a sufficient guarantee.

In the present work, nanoporous carbon (NPC) was prepared from a metal–organic framework (zeolite imidazolate framework 8, ZIF-8). Different concentrations of graphene oxide (GO) were used to make NPC/reduced graphene oxide (NPC/rGO-x, x = 0.5, 1.0, 1.5, and 2.0) composites, and then γ-MnS/NPC/rGO-1 composite was synthesized via a simple hydrothermal technique. The electrochemical characteristics of porous carbon composites (NPC/rGO-x) and γ-MnS/NPC/rGO-1 electrodes were investigated by galvanostatic charge and discharge, cyclic voltammetry, and electrochemical impedance spectroscopy. NPC/rGO-1 showed the highest specific capacitance of 207 F/g at 0.5 A/g. Also, the γ-MnS/NPC/rGO-1 electrode demonstrates exceptional electrochemical performance with a high specific capacitance of 300 F/g at 0.5 A/g and impressive cyclic stability of 70% capacitance retention after 10,000 cycles at 1 A/g. As a result, this study demonstrates that γ-MnS/NPC/rGO-1 electrode can be considered a promising candidate for high-performance supercapacitors.

ABSTRACT: This study investigated the effects of dietary arginine supplementation on the production performance, serum biochemicals, antioxidant capacity, and immunity of laying Wulong geese. A total of 150 Wulong geese (34-wk old) with similar body weights were randomly divided into 6 groups with 5 replicates and 5 geese each (1 male and 4 female). The geese in the control group were fed a corn-rapeseed meal basal diet, and the geese in the treatment groups were fed the basal diet supplemented with 0.1, 0.2, 0.3, 0.4, and 0.5% arginine. The experiment lasted for 17 wk. Our results showed that dietary arginine increased the egg production rate (LR) and average egg weight (AEW) of geese in a quadratic manner (P < 0.05). Dietary arginine had a quadratic effect on the contents of total protein (TP) and triglyceride (TG) (P < 0.05) in the serum. Dietary arginine quadratically decreased the content of malondialdehyde (MDA) and increased the activity of total superoxide dismutase (T-SOD) (P < 0.05). Dietary arginine supplementation linearly and quadratically increased the contents of immunoglobulin A (IgA) and immunoglobulin G (IgG), and linearly increased the content of nitric oxide (NO) (P < 0.05). In conclusion, dietary arginine supplementation can significantly improve the production performance, serum biochemicals, antioxidant capacity, and immunity of laying Wulong geese. Therefore, 0.3% arginine (actual content: 1.02%) is recommended in the diet.

Three experiments were conducted to evaluate paddy rice as an alternative energy feedstuff in low-protein diets for pigs. In Experiment 1, a total of 400 growing pigs (20.68 ± 0.29 kg initial bodyweight), were randomly allocated four dietary treatments with 0, 10, 15, and 20% paddy rice for 30 days. Feeding 10% or 15% paddy rice had no adverse impacts on average daily gain (ADG) and feed to gain ratio (F:G), while the inclusion of 20% rice in diets significantly influenced the growth performance of pigs. In Experiment 2, 364 early-finishing pigs (42.25 ± 0.47 kg) were divided into four treatments with 0, 15, 20, and 25% paddy rice for 35 days. Feeding 15% or 20% paddy rice had no negative consequences on growth performance, while pigs fed with 25% rice had the lowest ADG and the greatest F:G. In Experiment 3, 364 late-finishing pigs (79.52 ± 1.28 kg) were divided into four treatments with 0, 20, 25, and 30% paddy rice for 60 days. Paddy rice can be included at up to 30% in diets without compromising growth performance, while feeding with 25% rice significantly improved the performance for pigs compared with the corn-fed control.

This experiment was conducted to evaluate the effects of dietary supplementation level of a two-strain Bacillus subtilis probiotic on growth performance, blood parameters, fecal metabolites, and microbiome in nursery pigs. A total of 54 weaned piglets were allotted to three treatments in three replicate pens with six pigs/pen for a 28 d feeding trial. The treatments were as follows: control: no probiotic supplementation; Pro1x: B. subtilis supplementation at 1.875 × 105 CFU/g diet; and Pro10x: B. subtilis supplementation at 1.875 × 106 CFU/g diet. Body weight at d 14 postweaning (p = 0.06) and average daily gain for d 0 to 14 postweaning (p < 0.05) were greater in the Pro1x treatment than in the other treatments. Blood glucose levels were greater in both probiotic treatments than in the control treatment at d 14 postweaning (p < 0.05). In the fecal short-chain fatty acid (SCFA) concentrations, the butyrate concentrations were greater in the Pro1x treatment than in the other treatments (p < 0.05), and the acetate, propionate, and total SCFA concentrations were greater in the Pro1x treatment than in the Pro10x treatment (p < 0.05). The beta diversity of fecal microbiome composition at d 14 postweaning based on Unweighted Unifrac analysis was dissimilar between the Pro1x and Pro10x treatments (p < 0.05). In conclusion, dietary B. subtilis supplementation of two strains selected to reduce effects of pathogenic Escherichia coli to nursery diets at 1.875 × 105 CFU/g diet improved the growth rate in the early postweaning period, increased fecal SCFA concentrations and altered the fecal microbial community composition. A higher dose of B. subtilis did not improve the performance parameters over those of the control piglets.

Abstract Many individual herbs and herbal formulae have been demonstrated to provide safe and effective treatment for pancreatic ductal adenocarcinoma (PDAC); however, the therapeutic mechanisms underlying their effects have not been fully elucidated. A total of 114 herbal formulae comprising 216 single herbal medicines used to treat PDAC were identified. Cluster analysis revealed a core prescription including four herbs [Glycyrrhizae Radix et Rhizome (Gan Cao), Codonopsis Radix (Dang Shen), Citri Reticulatae Pericarpium (Chen Pi), and Pinelliae Rhizoma (Ban Xia)] in combination to treat PDAC, and 295, 256, 141, and 365 potential targets were screened for each of these four herbs, respectively. PDAC-related proteins (n = 2940) were identified from the DisGeNET database. Finally, 44 overlapping targets of herbs and PDAC were obtained, representing potential targets of the herbal medicines for PDAC treatment. GO enrichment analysis indicated that targets common to herbs and PDAC primarily functioned in response to steroid hormones. KEGG pathway enrichment analysis indicated that the herbs may prevent PDAC by influencing apoptotic, p53, and PI3K/Akt signaling pathways. Further, molecular docking analysis indicated that of identified bioactive compounds, stigmasterol, phaseol, perlolyrine, shinpterocarpin, and licopyranocoumarin have good binding ability with proteins involved in responses to steroid hormones, while stigmasterol, phaseol, perlolyrine, and DIOP have good binding ability with PTGS2(also known as COX-2), ESR1, ESR2, AR, and PGR. The anti-PDAC activity of herbal medicines may be mediated via regulation of proteins with roles in responses to steroid hormones. This study provides further evidence supporting the potential for use of herbal medicines to treat PDAC.

Extracorporeal membrane oxygenation (ECMO) played an important role in the treatment of patients with critical care such as cardiac arrest (CA) and acute respiratory distress syndrome. ECMO is gradually showing its advantages in terms of speed and effectiveness of circulatory support, as it provides adequate cerebral blood flow (CBF) to the patient and ensures the perfusion of organs. ECMO enhances patient survival and improves their neurological prognosis. However, ECMO-related brain complications are also important because of the high risk of death and the associated poor outcomes. We summarized the reported complications related to ECMO for patients with CA, such as north–south syndrome, hypoxic–ischemic brain injury, cerebral ischemia–reperfusion injury, impaired intracranial vascular autoregulation, embolic stroke, intracranial hemorrhage, and brain death. The exact mechanism of ECMO on the role of brain function is unclear. Here we review the pathophysiological mechanisms associated with ECMO in the protection of neurologic function in recent years, as well as the ECMO-related complications in brain and the means to improve it, to provide ideas for the treatment of brain function protection in CA patients.

Abstract High-throughput transcriptomics has revolutionised the field of transcriptome research by offering a cost-effective and powerful screening tool. Standard bulk RNA sequencing (RNA-Seq) enables characterisation of the average expression profiles for individual samples and facilitates identification of the molecular functions associated with genes differentially expressed across conditions. RNA-Seq can also be applied to disentangle splicing variants and discover novel transcripts, thus contributing to a comprehensive understanding of the transcriptome landscape. A closely related technique, single-cell RNA-Seq, has enabled the study of cell-type-specific gene expressions in hundreds to thousands of cells, aiding the exploration of cell heterogeneity. Nowadays, bulk RNA-Seq and single-cell RNA-Seq serve as complementary tools to advance and accelerate the development of transcriptome-based resources. This Collection illustrates how the current global research community makes use of these techniques to address a broad range of questions in life sciences. It demonstrates the usefulness and popularity of high-throughput transcriptomics and presents the best practices and potential issues for the benefit of future end-users.

Abstract Objective Immune-mediated necrotising myopathy (IMNM) is a subset of idiopathic inflammatory myopathies (IIM) characterized by significantly elevated creatine kinase level, muscle weakness and predominant muscle fibre necrosis in muscle biopsy. This study aimed to investigate the clinical and pathological characteristics of patients with IMNM in a single-centre muscle biopsy cohort. Methods A total of 860 patients who had muscle biopsy reports in our centre from May 2008 to December 2017 were enrolled in this study. IMNM was diagnosed according to the 2018 European Neuromuscular Centre (ENMC) clinicopathological diagnostic criteria for IMNM. Results The muscle biopsy cohort consisted of 531 patients with IIM (61.7%), 253 patients with non-IIM (29.4%), and 76 undiagnosed patients (8.8%). IIM cases were classified as IMNM (68[7.9%]), dermatomyositis (346[40.2%]), anti-synthetase syndrome (82[9.5%]), polymyositis (32[3.7%]), and sporadic inclusion body myositis (3[0.3%]). Limb girdle muscular dystrophy (LGMD) 2B and lipid storage myopathy (LSM) are the two most common non-IIM disorders in our muscle biopsy cohort. IMNM patients had a higher onset age (41.57 ± 14.45 vs 21.66 ± 7.86 and 24.56 ± 10.78, p

Background/purpose: Oral squamous cell carcinoma (OSCC) is a highly malignant tumor, and the overall survival (OS) time of patients with OSCC varies considerably. This study aimed to identify reliable biomarkers for OSCC and construct a new prognostic signature, which may guide personalized precision treatment. Materials and methods: Transcriptome array data of 317 patients with OSCC from The Cancer Genome Atlas Project (TCGA) cohort were retrospectively analyzed. Single-sample gene set enrichment analysis (ssGSEA) and univariate Cox regression were performed to identify the prognostic significance of the hallmarks of each tumor in OSCC. Subsequently, lncRNAs related to glycolysis were identified through co-expression analysis. A glycolysis-related prognostic signature was constructed by combining univariate Cox regression, least absolute shrinkage and selection operator (Lasso) regression, and multivariate Cox regression analyses. Additionally, the infiltration of immune cells in OSCC was evaluated based on data from ssGSEA and TIMER databases. Results: Glycolysis was identified as the main risk factor for OS in a variety of cancer hallmarks. The 4-lncRNA glycolysis prognostic signature could distinguish high and low-risk patients. This risk signature was found to be an independent prognostic risk factor for OSCC, showing good predictive power compared with other clinicopathological indicators. Immune correlation analysis showed that patients in the low-risk group exhibited higher levels of immune cell infiltration. Conclusion: The novel 4-lncRNA prognostic signature can predict the clinical outcome of patients with OSCC well, and it is expected to become a promising prognostic biomarker as well as a potential therapeutic target in the future.

Abstract Background This study aims to construct a new prognostic gene signature in survival prediction and risk stratification for patients with Head and neck squamous cell carcinoma (HNSCC). Method The transcriptome profiling data and hallmark gene sets in the Molecular Signatures Database was used to explore the cancer hallmarks most relevant to the prognosis of HNSCC patients. Differential gene expression analysis, weighted gene co-expression network analysis, univariate COX regression analysis, random forest algorithm and multiple combinatorial screening were used to construct the prognostic gene signature. The predictive ability of gene signature was verified in the TCGA HNSCC cohort as the training set and the GEO HNSCC cohorts (GSE41613 and GSE42743) as the validation sets, respectively. Moreover, the correlations between risk scores and immune infiltration patterns, as well as risk scores and genomic changes were explored. Results A total of 3391 differentially expressed genes in HNSCC were screened. Glycolysis and hypoxia were screened as the main risk factors for OS in HNSCC. Using univariate Cox analysis, 97 prognostic candidates were identified (P 0.66). Subsequently, the predictive ability of the risk score was verified in the validation sets. Moreover, the two-factor survival analysis combining the cancer hallmarks and risk scores suggested that HNSCC patients with the high hypoxia or glycolysis & high risk-score showed the worst prognosis. Besides, a nomogram based on the nine-gene signature was established for clinical practice. Furthermore, the risk score was significantly related to tumor immune infiltration profiles and genome changes. Conclusion This nine-gene signature associated with glycolysis and hypoxia can not only be used for prognosis prediction and risk stratification, but also may be a potential therapeutic target for patients with HNSCC.

Improving dairy cow feed efficiency is critical to the sustainability and profitability of dairy production, yet the underlying mechanisms that contribute to individual cow variation in feed efficiency are not fully understood. The objectives of this study were to (1) identify genes and associated pathways that are altered in cows with high- or low-residual feed intake (RFI) using RNA sequencing, and (2) determine if rumen-protected choline supplementation during mid-lactation would influence performance or feed efficiency. Mid-lactation (134 ± 20 days in milk) multiparous Holstein cows were randomly assigned to either supplementation of 0 g/d supplementation (CTL; n = 32) or 30 g/d of a rumen-protected choline product (RPC; 13.2 g choline ion; n = 32; Balchem Corp., New Hampton, NY, USA). Residual feed intake was determined as dry matter intake regressed on milk energy output, days in milk, body weight change, metabolic body weight, and dietary treatment. The 12 cows with the highest RFI (low feed efficient; LE) and 12 cows with the lowest RFI (high feed efficient; HE), balanced by dietary treatment, were selected for blood, liver, and muscle analysis. No differences in production or feed efficiency were detected with RPC supplementation, although albumin was greater and arachidonic acid tended to be greater in RPC cows. Concentrations of β-hydroxybutyrate were greater in HE cows. Between HE and LE, 268 and 315 differentially expressed genes in liver and muscle tissue, respectively, were identified through RNA sequencing. Pathway analysis indicated differences in cell cycling, oxidative stress, and immunity in liver and differences in glucose and fatty acid pathways in muscle. The current work indicates that unique differences in liver and muscle post-absorptive nutrient metabolism contribute to sources of variation in feed efficiency and that differences in amino acid and fatty acid oxidation, cell cycling, and immune function should be further examined.

Abstract Background Targeted modification of the dairy calf ruminal microbiome has been attempted through rumen fluid inoculation to alter productive phenotypes later in life. However, sustainable effects of the early life interventions have not been well studied, particularly on the metabolically active rumen microbiota and its functions. This study investigated the sustained effects of adult-derived rumen fluid inoculations in pre-weaning dairy calves on the active ruminal microbiome of post-weaned dairy calves analyzed via RNA-sequencing. Results Two different adult-derived microbial inocula (bacterial- or protozoal-enriched rumen fluid; BE or PE, respectively) were administered in pre-weaned calves (3–6 weeks) followed by analyzing active rumen microbiome of post-weaned calves (9 weeks). The shared bacterial community at the genus level of 16S amplicon-seq and RNA-seq datasets was significantly different (P = 0.024), 21 out of 31 shared major bacterial genera differed in their relative abundance between the two analytic pipelines. No significant differences were found in any of the prokaryotic alpha- and beta-diversity measurements (P > 0.05), except the archaeota that differed for BE based on the Bray–Curtis dissimilarity matrix (P = 0.009). Even though the relative abundances of potentially transferred microbial and functional features from the inocula were minor, differentially abundant prokaryotic genera significantly correlated to various fermentation and animal measurements including butyrate proportion, body weight, and papillae length and counts. The overall microbial functions were affected quantitatively by BE and qualitatively by PE (P

Background Perifascicular atrophy is a unique pathological hallmark in dermatomyositis (DM)-affected muscles; however, the mechanism underlying this process remains unclear. In this study, we aimed to investigate the potential role of the immunoproteasome subunit β5i and retinoic acid-inducible gene-I (RIG-I) in DM-associated muscle atrophy.Methods The expression of β5i and RIG-I in the muscles of 16 patients with DM was examined by PCR, western blotting and immunohistochemistry. The associations between β5i and RIG-I expression levels and muscle disease severity were evaluated. Lentivirus transduction was used to overexpress β5i in human skeletal muscle myoblasts (HSMMs) and consequent cell functional changes were studied in vitro.Results β5i and RIG-I expression in the muscle of patients with DM was significantly increased and closely associated with muscle disease severity. Immunohistochemistry and immunofluorescence analyses showed the marked colocalised expression of β5i and RIG-I in perifascicular myofibres. β5i overexpression in HSMMs significantly upregulated RIG-I, the muscle atrophy marker MuRF1, type I IFN-related proteins (MxA and IFNβ) and NF-κB pathway-related proteins (pIκBα, pIRF3 and pNF-κBp65). In addition, the viability of HSMMs decreased significantly after β5i overexpression and was partly recovered by treatment with a β5i inhibitor (PR957). Moreover, activation of RIG-I by pppRNA upregulated IFNβ and MuRF1 and reduced the cell viability of HSMMs.Conclusion The immunoproteasome subunit β5i promotes perifascicular muscle atrophy in DM via RIG-I upregulation; our findings suggest a pathomechanistic role of β5i and RIG-I in DM-associated muscle damage, highlighting these components as potential therapeutic targets for the treatment of DM.

BackgroundExposure to disasters in early life may induce lifetime health risk, but investigation on earthquake exposure and DM in later life is still limited. The aim of the current study is to evaluate the association between exposure to the Tangshan Earthquake in early life and diabetes mellitus (DM) incidence in adulthood, and explore the modification of lifestyles on DM development.MethodsParticipants who were free of DM at baseline from the Kailuan Study were included in this study. All participants were divided into fetal-exposed, infant-exposed, early childhood-exposed and nonexposed group. The effect of earthquake exposure on DM and modification of lifestyles were examined by multivariable-adjusted Cox proportional hazard model.ResultsThe exposed group had a higher risk of DM than nonexposed group, especially in infant-exposed and early childhood-exposed group, with hazard ratio (HR) of 1.62 [95% confidence intervals (CI), 1.21–2.17] and 1.46 (95% CI, 1.06–1.99), respectively. After stratifying by lifestyles, a significant modification was observed in alcohol consumption.ConclusionExposing to earthquake in early life could increase DM incidence in later life, and alcohol consumption might modify the effect of earthquake exposure on DM development. More attention should be paid on the preventions of DM among adults who exposed to earthquake in their early life.

At present, the existing influence evaluation algorithms often ignore network structure attributes, user interests and the time-varying propagation characteristics of influence. To address these issues, this work comprehensively discusses users’ own influence, weighted indicators, users’ interaction influence and the similarity between user interests and topics, thus proposing a dynamic user influence ranking algorithm called UWUSRank. First, we determine the user’s own basic influence based on their activity, authentication information and blog response. This improves the problem of poor objectivity of initial value on user influence evaluation when using PageRank to calculate user influence. Next, this paper mines users’ interaction influence by introducing the propagation network properties of Weibo (a Twitter-like service in China) information and scientifically quantifies the contribution value of followers’ influence to the users they follow according to different interaction influences, thereby solving the drawback of equal value transfer of followers’ influence. Additionally, we analyze the relevance of users’ personalized interest preferences and topic content and realize real-time monitoring of users’ influence at various time periods during the process of public opinion dissemination. Finally, we conduct experiments by extracting real Weibo topic data to verify the effectiveness of introducing each attribute of users’ own influence, interaction timeliness and interest similarity. Compared to TwitterRank, PageRank and FansRank, the results show that the UWUSRank algorithm improves the rationality of user ranking by 9.3%, 14.2%, and 16.7%, respectively, which proves the practicality of the UWUSRank algorithm. This approach can serve as a guide for research on user mining, information transmission methods, and public opinion tracking in social network-related areas.