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Abstract Background Low-intensity cognitive behavioural therapy (LICBT) has been recommended as a primary intervention in the tiered care for mild to moderate generalised anxiety disorder. However, LICBT for generalised anxiety disorder are markedly diverse and efficacy data on various outcomes have not been systematically reviewed. This meta-analysis aimed to synthesise effect sizes of three NICE-recommended LICBT for generalised anxiety disorder: non-facilitated self-help, guided self-help, and psychoeducational groups. Methods A systematic literature review of randomised controlled trials (RCTs) examining LICBT for generalised anxiety disorder in the last 23 years (2000–2023) was conducted. Efficacy data for anxiety, depression, and worry outcomes were separately meta-analysed. The study was reported following the PRISMA guidelines. Results The systematic review identified 12 RCTs out of 1205 papers. The three meta-analyses consisted of 12 (anxiety), 11 (depression), and 9 (worry) effect sizes respectively, including total sample sizes of 1201 (anxiety), 1164 (depression), and 908 (worry). The adjusted effect sizes for reductions in anxiety (g = -0.63), depression (g = -0.48), and worry (g = -0.64) were all in the medium range, favouring LICBT over control conditions. Between-study heterogeneity was significant on anxiety and worry, with no specific moderators identified by meta-regression. Conclusions LICBT has shown promise as an effective and efficient treatment modality for individuals with generalised anxiety disorder. Future research comparing various LICBT subtypes and treatment components will further inform clinical practice. Trial registration This systematic review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO; record ID CRD42021285590).

Accurate and prompt determination of fire types is essential for effective firefighting and reducing damage. However, traditional methods such as smoke detection, visual analysis, and wireless signals are not able to identify fire types. This paper introduces FireSonic, an acoustic sensing system that leverages commercial speakers and microphones to actively probe the fire using acoustic signals, effectively identifying fire types. By incorporating beamforming technology, FireSonic first enhances signal clarity and reliability, thus mitigating signal attenuation and distortion. To establish a reliable correlation between fire type and sound propagation, FireSonic quantifies the heat release rate (HRR) of flames by analyzing the relationship between fire-heated areas and sound wave propagation delays. Furthermore, the system extracts spatiotemporal features related to fire from channel measurements. The experimental results demonstrate that FireSonic attains an average fire type classification accuracy of 95.5% and a detection latency of less than 400 ms, satisfying the requirements for real-time monitoring. This system significantly enhances the formulation of targeted firefighting strategies, boosting fire response effectiveness and public safety.

Background: Cholestasis is a common pathological manifestation dominated by accumulation of potentially toxic biliary compounds. Na+-taurocholate cotransporting polypeptide (NTCP) plays a critical role in protection from cholestasis and can be targeted therapeutically. Chishao (Paeoniae Radix Rubra) is a clinically efficacious agent for treating cholestasis, but the underlying mechanism has not been fully clarified.Objective: To evaluate the effects of Chishao on the expression of NTCP in rats with alpha-naphthylisothiocyanate (ANIT)-induced cholestasis.Methods: Chishao extracts were obtained by water decoction. Cholestasis model induced by ANIT in rats were established. Thirty rats were divided into five groups: control group (C), ANIT model group (M), 10 g/kg Chishao group (LD), 20 g/kg Chishao group (MD) and 40 g/kg Chishao group (HD). The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), direct bilirubin (DB), alkaline phosphatase (ALP) and total bile acid (TBA) were detected. The mRNA and protein expression of NTCP, multidrug resistance associated protein 2 (MRP2) and bile salt export pump (BSEP) were detected by reverse transcription qPCR and Western blotting respectively. To assess the effects of Chishao on NTCP, MRP2 and BSEP localized at the membrane of hepatocytes, an in vitro experiment involving primary hepatocytes was conducted via the utilization of laser scanning confocal microscopy.Results: The extracts of Chishao significantly improved serum ALT, AST, ALP, TB, DB and TBA (p < 0.05), especially ALP in the HD group (p < 0.01). The histological pathological findings were also reversed in LD, MD and HD groups. The mRNA level of MRP2 was significantly downregulated after treatment with ANIT, whereas it was reversed in MD and HD groups (p < 0.05). The mRNA expression of NTCP was significantly downregulated after ANIT treatment, but dramatically upregulated in the HD group. The expressions of BSEP and MRP2 were similar, but that of NTCP decreased after ANIT treatment, which was reversed significantly by Chishao extracts in a dose-dependent manner. The expression of NTCP in hepatocytes from rats increased dose-dependently after Chishao treatment in vitro.Conclusion: Chishao extracts can improve the serum and histological performances of intra-hepatic cholestasis caused by ANIT, probably by working on transport proteins in liver cell membranes.

Introduction:Corydalis yanhusuo total alkaloids (CYTA) are the primary active ingredients in yanhusuo, known for their analgesic and cardioprotective effects. However, the mechanisms underlying the treatment of Myocardial ischemia (MI) with CYTA have not been reported. The purpose of this study was to explore the protective effect of CYTA on MI and its related mechanisms.Methods: A network pharmacology was employed to shed light on the targets and mechanisms of CYTA’s action on MI. The protective effect of CYTA against hypoxia damage was evaluated in H9c2 cells. Furthermore, the effects of CYTA on L-type Ca2+ current (ICa-L), contractile force, and Ca2+ transient in cardiomyocytes isolated from rats were investigated using the patch clamp technique and IonOptix system. The network pharmacology revealed that CYTA could regulate oxidative stress, apoptosis, and calcium signaling. Cellular experiments demonstrated that CYTA decreased levels of CK, LDH, and MDA, as well as ROS production and Ca2+ concentration. Additionally, CYTA improved apoptosis and increased the activities of SOD, CAT, and GSH-Px, along with the levels of ATP and Ca2+-ATPase content and mitochondrial membrane potential. Moreover, CYTA inhibited ICa-L, cell contraction, and Ca2+ transient in cardiomyocytes.Results: These findings suggest that CYTA has a protective effect on MI by inhibiting oxidative stress, mitochondrial damage, apoptosis and Ca2+ overload.Discussion: The results prove that CYTA might be a potential natural compound in the field of MI treatment, and also provide a new scientific basis for the its utilization.

Abstract Objective To summarize the effect of adding Lactobacillus reuteri in the treatment plan for diarrheal disease in children, and analyze the potential of probiotics in preventing the occurrence of diarrheal disease. Methods Search for randomized controlled trials of Lactobacillus reuteri for the treatment and prevention of diarrhea in the Pubmed, Web of science, Medline, and Cochrane databases. Data such as the number of diarrhea patients, time, length of stay, clinical symptoms and effect of diarrhea prevention were extracted for meta-analysis. Relative risk and confidence interval (RR and 95% CI) were used as outcome indicators. Results 963 participants in the 9 RCTs came from multiple countries/regions. Compared with placebo/no intervention, the number of diarrhea patients in the Lactobacillus reuteri group was significantly reduced on the day 1 (RR = 0.87, 95%CI: 0.78–0.97) and day 2 (RR = 0.61, 95%CI: 0.44–0.83). Cumulative statistics analysis showed that the effect was stable and significant starting on the 4th day after treatment. A few studies have shown that Lactobacillus reuteri can reduce the time of diarrhea, the number of days with watery stools, and days of hospital stay. However, it has no effect on the occurrence of nosocomial diarrhea (RR = 1.11, 95%CI: 0.68–1.83), rotavirus diarrhea (RR = 1.46, 95%CI: 0.78–2.72), antibiotic-related diarrhea (RR = 1.76, 95%CI: 0.77–4.05), and diarrhea (RR = 1.35, 95%CI: 0.95–1.92). Conclusion Addition of Lactobacillus reuteri in the treatment plan has a significant effect on reducing the number of diarrhea and reducing the symptoms of diarrhea, but has no obvious effect on the prevention of diarrhea. Combining probiotics and improving the ability of probiotics to respond is the focus of attention.

Macrofungi are well-known as edible-medicinal mushrooms, which belong mostly to Basidiomycota, with a few from Ascomycota. In recent years, macrofungi have been recognized as a rich resource of structurally unique secondary metabolites, demonstrating a wide range of bioactivities, including anti-tumor, antioxidant, anti-inflammatory, antimicrobial, antimalarial, neuro-protective, hypoglycemic, and hypolipidemic activities. This review highlights over 270 natural products produced by 17 families of macrofungi covering 2017 to 2023, including their structures, bioactivities, and related molecular mechanisms.

In order to predict the temperature change of Laoshan scenic area in Qingdao more accurately, a new back propagation neural network (BPNN) prediction model is proposed in this study. Temperature change affects our lives in various ways. The challenge that neural networks tend to fall into local optima needs to be addressed to increase the accuracy of temperature prediction. In this research, we used an improved genetic algorithm (GA) to optimize the weights and thresholds of BPNN to solve this problem. The prediction results of BPNN and GA-BPNN were compared, and the prediction results showed that the prediction performance of GA-BPNN was much better. Furthermore, a screening test experiment was conducted using GA-BPNN for multiple classes of meteorological parameters, and a smaller number of parameter sets were identified to simplify the prediction inputs. The values of running time, root mean square error, and mean absolute error of GA-BPNN are better than those of BPNN through the calculation and analysis of evaluation metrics. This study will contribute to a certain extent to improve the accuracy and efficiency of temperature prediction in the Laoshan landscape.

6-Gingerol (6G) is the main phenolic active component of ginger, which has a certain protective effect against liver injury induced by drugs, and chemical pollutants. However, the mechanism of protection of 6G against arsenic trioxide (ATO)-induced liver injury remains unclear. The network pharmacology and animal experiment results respectively indicated that oxidative stress and inflammatory responses were closely related to ATO-induced liver injury. 6G can alleviate ATO-induced liver injury and oxidative stress. Furthermore, 6G can attenuate the release of pro-inflammatory factors induced by ATO and reduce the expressions of NLRP3, ASC, Caspase-1 and gasdermin-D. The results showed that the activation of NLRP3 inflammatory and its induced pyroptosis play critical roles in liver injury caused by ATO. Furthermore, 6G can suppress the ROS-NLRP3 inflammasome signaling pathway, which may be an effective strategy for the treatment of ATO-induced liver injury.

In order to accelerate the construction of a clean, low-carbon, safe and efficient energy system, China set the provincial weight of responsibility for renewable energy power consumption and established a renewable energy power absorption guarantee mechanism in 2019. As a market incentive policy, it has enduring effect on the low-carbon transformation of the power industry. Firstly, the operation mechanism of the renewable energy consumption guarantee mechanism is analyzed. The general framework, core elements and supporting measures are clarified. Secondly, a stock-flow diagram is constructed based on the system dynamics method. It contains the green electricity market sub-module, the green-certificate market sub-module and the excess power absorption market sub-module. Finally, multiple scenarios are set up to simulate the impact of the green-certificate market and excess power absorption market improvements on the installed capacity and tariff of China’s green power market. The renewable energy guarantee mechanism is an effective means to promote the consumption of green electricity in China. In addition, in the short term the cost of electricity for users has increased, but in the long term the cost of electricity shows a fluctuating downward trend. This study provides theoretical references for the formulation of clean and low-carbon policy objectives in the power industry and the optimization of market mechanisms.

Abstract Acute graft-versus-host disease (aGVHD) is the main complication of and cause of death after allogeneic hematopoietic stem cell transplantation. Baicalin can protect the small intestinal epithelial cells of rats against TNF-α-induced injury and alleviate enteritis-related diarrhea. To verify whether baicalin can protect the small intestinal mucosal barrier by regulating abnormal autophagy and interfering with intestinal aGVHD, a mouse model of aGVHD was established. CB6F1 micewere intravenously injected with a suspension of mononuclear cells derived from BALB/c donor mouse bone marrow and splenic tissue after treatment with 60Co X-rays. After treatment with different doses of baicalin for 15 days, the survival time, serum TNF-α and IL-10 levels, and autophagy markers levels in the intestine were assessed. A cell model of intestinal barrier dysfunction was also used to verify the effect of baicalin. The results showed that baicalin significantly prolonged the survival time, significantly reduced the aGVHD pathology score and clinical score by decreasing the TNF-α level with increasing the IL-10 level compared with the control. Transmission electron microscopy examination showed that baicalin treatment increased the number of autophagic vacuoles and led to the recovery of mitochondrial structures in the intestinal mucosal epithelial cells of mice and in Caco-2 cells. Western blotting results showed that baicalin treatment enhanced autophagy in vivo by regulating the AMPK/mTOR autophagy pathway. Similar results were observed in vitro in Caco-2 cells. Furthermore, the effect of baicalin was reduced after combination treatment with the autophagy inhibitor 3-methyladenine(3-MA). Baicalin can decrease the severity of small intestinal aGVHD by regulating autophagy by influencing imbalances in inflammatory cytokine levels and mucosal barrier damage, thus baicalin may have potential as a new treatment for aGVHD.

In this study, a tobramycin concentration-dependent whole-cell micro-biosensor (tob-HHAz) was constructed by fusing a tobramycin aptamer with a hammerhead ribozyme (HHR) from Schistosoma mansoni. The biosensor was obtained by integrating all the modules into one complete RNA sequence, which was easily introduced into E. coli without suffering from harsh external environments. Three independent tobramycin-sensitive RNA structures were identified via high-throughput screening in vivo and were further verified in vitro to undergo the desired self-cleavage reaction. The computation prediction of the RNA structure was performed to help analyze the mechanisms of various conformations by performing a qualitative and rapid detection of tobramycin in practical samples; two sensors exhibited high responsiveness to spiked milk, with a detection limit of around 40 nM, which is below the EU’s antibiotic maximum residual level. One of the structures provides a linear range from 30 to 650 nM with a minimum detection limit of 30 nM and showed relatively good selectivity in spiked urine. This study is the first in which in vivo screening was combined with computation analysis to optimize the pivotal structure of sensors. This strategy enables researchers to use artificial ribozyme-based biosensors not only for antibiotic detection but also as a generally applicable method for the further detection of substances in living cells.

Background: Bladder cancer (BLCA) has a high rate of morbidity and mortality, and is considered as one of the most malignant tumors of the urinary system. Tumor cells interact with surrounding interstitial cells, playing a key role in carcinogenesis and progression, which is partly mediated by chemokines. CXC chemokines exert anti-tumor biological roles in the tumor microenvironment and affect patient prognosis. Nevertheless, their expression and prognostic values patients with BLCA remain unclear. Methods: We used online tools, including Oncomine, UALCAN, GEPIA, GEO databases, cBioPortal, GeneMANIA, DAVID 6.8, Metascape, TRUST (version 2.0), LinkedOmics, TCGA, and TIMER2.0 to perform the relevant analysis. Results: The mRNA levels of C-X-C motif chemokine ligand (CXCL)1, CXCL5, CXCL6, CXCL7, CXCL9, CXCL10, CXCL11, CXCL13, CXCL16, and CXCL17 were increased significantly increased, and those of CXCL2, CXCL3, and CXCL12 were decreased significantly in BLCA tissues as assessed using the Oncomine, TCGA, and GEO databases. GEO showed that high levels of CXCL1, CXCL6, CXCL10, CXCL11, and CXCL13 mRNA expression are associated significantly with the poor overall survival (all p < 0.05), and similarly, those of CXCL2 and CXCL12 in the TCGA database (p < 0.05). The predominant signaling pathways involving the differentially expressed CXC chemokines are cell cycle, chemokine, and cytokine-cytokine receptor interaction. Moreover, transcription factors such as Sp1 transcription factor (SP1), nuclear factor kappa B subunit 1 (NFKB1), and RELA proto-oncogene, NF-KB subunit (RELA) were likely play critical roles in regulating CXC chemokine expression. LYN proto-oncogene, src family tyrosine kinase (LYN) and LCK proto-oncogene, src family tyrosine kinase (LCK) were identified as the key targets of these CXC chemokines. MicroRNAs miR200 and miR30 were identified as the main microRNAs that interact with several CXC chemokines through an miRNA-target network. The expression of these chemokines is closely associated with the infiltration of six categories of immune cells. Conclusion: We explored the CXC chemokines superfamily-based biomarkers associated with BLCA prognosis using public databases, and provided possible chemokine targets for patients with BLCA.

The flexible structural design of organic materials make them promising candidates for cathode in rechargeable batteries. Here, the authors report a tetraamino-p-benzoquinone cathode which realizes facile proton conduction by the Grotthuss-type mechanism and shows excellent electrochemical performance.

IntroductionLoneliness is a negative experience arising from a mismatch between perceived and actual social relationships. Several dimensions of loneliness have been suggested, namely intimate, relational and collective loneliness. Loneliness has been linked to poorer mental health, with its co-occurrence with depression, social anxiety, and paranoia most widely reported. While expressions of these symptoms are heterogeneous across individuals in the non-clinical population, it remains unclear how these symptoms co-occur with one another and with various dimensions of loneliness. It is also of interest how trait factors such as core schemas about self/others may moderate these relationships between loneliness and co-occurring symptoms.MethodsA demographically diverse sample of young adults was recruited from multiple sources. The validated sample consisted of 2,089 participants (68.4% female), who completed an online survey consisting of questionnaires assessing levels of multidimensional loneliness, depression, social anxiety, paranoia, core schemas, and demographic characteristics. Latent profile analysis (LPA) was used to identify distinct profiles of loneliness and the three symptoms. Positive and negative core schemas about self and others were modeled as predictors of these profiles.ResultsFive distinct profiles were identified. Profile 1 had low levels across all symptoms and dimensions of loneliness (n = 1,273, 60.9%). Profiles 2–5 were elevated on dimensions of loneliness, and were heightened in depression (n = 189, 9.0%), social anxiety (n = 206, 9.9%), paranoia (n = 198, 9.5%), and all symptoms (n = 223, 10.7%), respectively. Relative to Profile 1, the other four profiles scored higher on negative-self (adjusted ORs = 1.36–1.49, ps < 0.001) and negative-other schemas (adjusted ORs = 1.24–1.44, ps < 0.001), and lower on positive-self (adjusted ORs = 0.82–0.85, ps < 0.001) and positive-other schemas (adjusted ORs = 0.81–0.90, ps < 0.001).ConclusionMore marked intimate, relational and collective loneliness were evident across profiles that had heightened depression, social anxiety and/or paranoia, suggesting that loneliness may serve as a general risk factor for these psychopathologies. Our findings shed light on the heterogeneity of the co-occurrence of loneliness and various mental health difficulties in non-clinical young adults. Core schemas are suggested to be putative psychological mechanisms underlying their co-occurrence and even development.

In the era of globalization, industries of critical metals are organized through the global supply chain. However, the global supply chains have been disrupted since 2020 by the outbreak of COVID-19 and a series of geopolitical crises. To better address the supply chain challenges of critical metals, a review is needed about the sources, propagation, and responses of the supply chain risks. Firstly, this review provides an overview about the research progress in identifying the risk sources and assessing the risks and then proposes a new supply chain framework, categorizing relevant risk factors into upstream risks, middle-stream risks, downstream risks, and general risks, for risk analysis of critical metals. Secondly, this review offers a comprehensive understanding about how the risks propagate horizontally and vertically. Finally, responses such as supply diversification, stockpiling, material substitution, recycling and circular economy strategy, price volatility hedging, and supply chain traceability are reviewed. This survey features the supply chain perspective, overviews on network-based studies, and affirms the urgency and need for further studies on supply chain risks and resilience, which may contribute to a smooth clean energy transition.

Abstract Background BCOR-CCNB3 sarcoma (BCS) is a group of undifferentiated small round cell sarcomas harboring the BCOR gene rearrangement which shares morphology with the Ewing sarcoma family as well as other malignant round blue cell tumors, thus making them difficult to diagnose. The aim of this study was to explore the role of molecular techniques in the diagnosis of BCS. Methods Twenty-three cases of EWSR1 rearrangement-negative undifferentiated small round cell sarcomas (Ewing-like sarcoma) were analyzed for the presence of BCOR gene rearrangement by Fluorescence in situ hybridization (FISH) and Reverse Transcription -Polymerase Chain Reaction (RT-PCR). The clinicopathological features of the positive cases were also reviewed. Fifteen additional cases were used as negative controls. Results Eight cases were found with BCOR gene rearrangement by FISH and reappraised as BCS. The patients ranged in age from 8 to 20 years old, with a male predominance (M:F = 6:2). All tumors were located in the lower extremities. The tumor locations were more common in bone (n = 6) than deep soft tissue (n = 2). Histologically, 7 of 8 tumors were predominately composed of spindle or ovoid cells. The tumor cells were usually arranged in solid hypercellular sheets without a distinct architectural pattern. IHC showed expression of TLE1 (100%), CCNB3 (88%), BCOR (71%). RT-PCR for BCOR-CCNB3 fusion transcript was positive in 7 of 8 cases. Pre-operative chemotherapy resulted in eradication of tumors in 5 patients after a follow-up of 7 to 42 months. Conclusions Efficient diagnosis of BCOR rearranged sarcomas is achieved by the using a combination of FISH and RT-PCR assays.

Abstract Introduction Myocardial damage is a mostly incurable complication of multiple myeloma (MM) that seriously affects the treatment outcome and quality of life of patients. Exosomal circular RNAs (exo-circRNAs) play an important role in tumor occurrence and development and are considered key factors in MM pathogenesis. However, the role and mechanism of action of exo-circRNAs in MM-related myocardial damage are still unclear. This study aimed to investigate correlations between exo-circRNAs and MM and to preliminarily explore the role of exo-circRNAs in MM-related myocardial damage. Methods Six MM patients and five healthy controls (HCs) were included in the study. High-throughput sequencing and qRT-PCR verification were used to obtain a profile of abnormally expressed exo-circRNAs. GO, KEGG, miRanda, TargetScan and Metascape were used for bioinformatics analyses. H9C2 cells treated with exosomes from U266 cells were used in cell experiments. CCK-8, PCR, immunofluorescence and western blotting assays were used to detect cell proliferation and expression of autophagy-related indicators. Electron microscopy was used to observe the number of autophagic vesicles. Results Bioinformatics analysis showed that circRNAs with upregulated expression had the potential to promote MM-related myocardial damage. In addition, PCR results confirmed that circ-G042080 was abundantly expressed in the serum exosomes of 20 MM patients. Correlation analysis showed that the expression level of circ-G042080 was positively correlated with the clinical level of MM and MM-related myocardial damage and that circ-G042080 might interfere with MM-related myocardial damage through a downstream miRNA/TLR4 axis. Cell experiments demonstrated that the circ-G042080/hsa-miR-4268/TLR4 axis might exist in H9C2 cells incubated with exosomes and cause abnormal autophagy. Conclusion Abnormal expression of serum exo-circRNAs was found to be associated with MM-related myocardial damage, suggesting that exo-circRNAs might become a new diagnostic marker of MM-related myocardial damage and a therapeutic target.

IntroductionWisdom has been empirically researched as a complex psychological characteristic that is associated with many mental health outcomes. However, its association with psychotic-like experiences (PLEs) remains unclear. This is the first work to assess wisdom, explore its association with PLEs, and test its moderating effect on the relation between the frequency of PLEs and their associated distress in the general population.MethodsFrom January 29th to February 5th, 2021, our online self-administered survey recruited 927 participants (ages 14 to 65) from thirteen Chinese provinces. Convenience sampling was employed. We measured wisdom with the 12-item three-dimensional wisdom scale (3D-WS-12) and PLEs with the 15-item positive subscale of the Community Assessment of Psychic Experiences (CAPE-P15).ResultsUsing the cut-off value of 1.47 in the mean frequency score, we divided our participants into high-PLEs group (188, 22.1%) and low-PLEs group (663, 77.9%). Three-dimensional wisdom score was decreased in the high-PLEs group compared to the low-PLEs group (Kruskal-Wallis t = 59.9, p < 0.001). Wisdom was associated with less frequent PLEs (Spearman’s rho = −0.21, p < 0.01) and lower distress related to PLEs (Spearman’s rho = −0.28) in the high-PLEs group (all above p < 0.001), which were replicated in the low-PLEs group. Notably, wisdom significantly attenuated the distress associated with PLEs [coefficient = −0.018, Bootstrap 95% CI (−0.029, −0.008)], but only in the low-PLEs group.ConclusionOur results implicated that wisdom could protect individuals from distressful subclinical psychotic symptoms and wiser individuals have better general mental health.

Abstract Infectious bronchitis virus (IBV) is a pathogenic coronavirus with high morbidity and mortality in chicken breeding. Macrophages with normal biofunctions are essential for host immune responses. In this study, the HD11 chicken macrophage cell line and chicken peripheral blood mononuclear cell-derived macrophages (PBMCs-Mφ) were infected with IBV at multiplicity of infection (MOI) of 10. The dynamic changes of their biofunctions, including cell viability, pathogen elimination function, phagocytic ability, and gene expressions of related proteins/mediators in innate and acquired immunity, inflammation, autophagy and apoptosis were analyzed. Results showed that IBV infection decreased chicken macrophage viability and phagocytic ability, and increased pathogen elimination function. Moreover, IBV augmented the gene expressions of most related proteins in macrophages involved in multiple host bioprocesses, and the dynamic changes of gene expressions had a close relationship with virus replication. Among them, MHCII, Fc receptor, TLR3, IFN-α, CCL4, MIF, IL-1β, IL-6, and iNOS showed significantly higher expressions in IBV-infected cells. However, TLR7, MyD88, MDA5, IFN-γ, MHCII, Fc receptor, MARCO, CD36, MIF, XCL1, CXCL12, TNF-α, iNOS, and IL-10 showed early decreased expressions. Overall, chicken macrophages play an important role in host innate and acquired immune responses to resist IBV infection, despite early damage or suppression. Moreover, the IBV-induced autophagy and apoptosis might participate in the virus-host cell interaction which is attributed to the biological process.

Hypoxia is a typical feature of solid tumors, which highly limits the application of the oxygen-dependent therapy. Also, the dense and hyperbaric tumor tissues impede the penetration of nanoparticles into the deep tumor. Thereby, we designed a novel localized injectable hydrogel combining the photothermal therapy (PTT) and the thermodynamic therapy (TDT), which is based on the generation of free radicals even in the absence of oxygen for hypoxic tumor therapy. In our study, gold nanorods (AuNRs) and 2,2′-Azobis[2-(2-imidazalin-2-yl)propane] dihydrochlaride (AIPH) were incorporated into the hydrogel networks, which were formed by the copolymerization of hydrophobic N-isopropyl acrylamide (NIPAM) and hydrophilic glycidyl methacrylate modified hyaluronic acid (HA-GMA) to fabricate an injectable and near-infrared (NIR) responsive hydrogel. The crosslinked in situ forming hydrogel could not only realize PTT upon the NIR laser irradiation, but also generate free radicals even in hypoxic condition. Meanwhile the shrink of hydrogels upon thermal could accelerate the generation of free radicals to further damage the tumors, achieving the controlled drug release on demand. The designed hydrogel with a sufficient loading capacity, excellent biocompatibility and negligible systemic toxicity could serve as a long-acting implant for NIR-triggered thermo-responsive free radical generation. The in vitro cytotoxicity result and the in vivo antitumor activity illustrated the excellent therapeutic effect of hydrogels even in the absence of oxygen. Therefore, this innovative oxygen-independent platform combining the antitumor effects of PTT and TDT would bring a new insight into hypoxic tumor therapy by the application of alkyl free radical.

Mortierella alpina has a strong capacity for lipid accumulation. Isocitrate dehydrogenase (IDH) plays an important role in affecting the flow of intracellular carbon sources and reducing power NADPH for lipid biosynthesis. In this study, the effect of various IDHs (NAD+- and NADP+-specific) in M. alpina on the lipid accumulation was investigated through homologous overexpression. The results showed that the transcription level and enzyme activity of the IDHs from M. alpina (MaIDHs) in homologous overexpressing strains were higher than those of the control strain, but that their biomass was not significantly different. Among the various NAD+-specific MaIDH1/2/3 overexpression, NAD+-MaIDH3 reduced total lipid content by 12.5%, whereas overexpression NAD+-MaIDH1 and NAD+-MaIDH2 had no effect on fatty acid content. Intracellular metabolites analysis indicated that the overexpression NAD+-MaIDH3 strain had reduced the fatty acid accumulation, due to its greater carbon flux with the tricarboxylic acid cycle and less carbon flux with fatty acid biosynthesis. For the NADP+-MaIDH4/5/6 recombinant strains overexpressing only NADP+-MaIDH4 enhanced the total fatty acid content by 8.2%. NADPH analysis suggested that this increase in lipid accumulation may have been due to the great reducing power NADPH is produced in this recombinant strain. This study provides theoretical basis and guidance for the analysis of the mechanism of IDH function and the potential to improve lipid production in M. alpina.

The prevention and treatment of cerebral ischemia/reperfusion injury has become a key link in the treatment of ischemic cerebrovascular diseases. In this study, Wistar rats were randomly divided into Sham, low-dose ginsenoside (L-CK), high-dose ginsenoside (H-CK) and nimodipine groups, and the rats in the L-CK, H-CK, and nimodipine groups were intragastrically given the corresponding agents successively once a day for 15 days before surgery. At 1 h after the last administration, a rat cerebral ischemia/reperfusion model was established by suture-occluded method and the effects of ginsenoside CK on the neurological scores, brain tissue water content, brain infarct volume, oxidative stress and inflammation were investigated. The results showed that, compared with those in the model group, the neurological behaviour scores in the L- and H-CK groups, the brain tissue water content in the H-CK group, and the brain infarct volume ratios in the L- and H-CK groups were significantly reduced. Compared with those in the model group, the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities increased, whereas the malondialdehyde (MDA) content decreased significantly in the brain tissue of the rats in the L- and H-CK groups. Compared with that in the model group, the content of TNF-α in the H-CK group, the content of IL-1β and the expression of HMGB1 protein in the L- and H-CK groups were significantly reduced. These results suggest that ginsenoside CK can protect against cerebral ischemia reperfusion injury in rats, which may be related to its anti-oxidative, anti-inflammatory and HMGB1-expression inhibitory activity.

Objectives: It is common, among clinical and non-clinical populations alike, for paranoia and anxiety to co-occur. It has been suggested that anxiety and its related appraisal styles may contribute to development of paranoia. We aimed to evaluate different aspects of risk perception in relation to paranoia and anxiety and to identify specific aspects that may differentiate paranoia from anxiety. This paper consists of two inter-related studies. Methods: Study 1 compared 30 patients with persecutory delusions, 21 patients with generalized anxiety disorder and 52 healthy controls. Study 2 compared 30 non-clinical individuals with high levels of paranoia and anxiety, 28 individuals with high anxiety only and 36 healthy controls. Within each study, the two symptomatic groups were matched on level of anxiety. Four dimensions of risk perception (i.e. likelihood, harm, controllability, and intentionality) were compared across groups, as measured by the locally validated Risk Perception Questionnaire. Results: In both studies, the paranoia and the anxiety groups reported an elevated perceived likelihood of negative events than controls respectively. Only the paranoia groups reported an elevated perceived harm of neutral events than controls. In Study 2, the two at-risk groups attributed more harm and intentionality to negative events than controls. Conclusion: Although perception of negative events was characteristic in anxiety (with or without paranoia), a biased perception of neutral events as risky was unique to the addition of paranoia. Implications to the transdiagnostic and continual view of psychopathology, and mechanism-based interventions were discussed.

The potential implications of digital currencies and electronic payment (DC/EP) have become a hot global research area. To present the knowledge bases and research fronts of this field, we apply a scientometric approach to analyze 454 publications obtained from the Web of Science core collection. Results show that, first, the knowledge bases can be classified into three main topics: (1) the usage and diversification effect of private digital currencies from the point of investment and asset allocation; (2) the price dynamics and market efficiency of private digital currencies; and (3) other economic roles of digital currencies and corresponding change brought into the monetary system. Second, several research trends can be inferred using sliding window analysis and burst detection, namely, how the introduction of digital currencies changes consumers’ choice in payment instrument and their money demand; how social media and investor sentiment affect the market of digital currencies; and the impact of digital currencies on the central bank, monetary policy, and central bank digital currency. Third, core scholars and countries involved in the research of DC/EP are identified, and it is found that collaboration has been rising especially among European scholars and countries. With these systematic analyses, we offer recommendations for scholars and practitioners in future research of DC/EP.

Hypericum perforatum L., also known as Saint John’s Wort, has been well studied for its chemical composition and pharmacological activity. In this study, the antiviral activities of H. perforatum on infectious bronchitis virus (IBV) were evaluated in vitro and in vivo for the first time. The results of in vitro experiments confirmed that the antiviral component of H. perforatum was ethyl acetate extraction section (HPE), and results showed that treatment with HPE significantly reduced the relative messenger ribonucleic acid (mRNA) expression and virus titer of IBV, and reduced positive green immunofluorescence signal of IBV in chicken embryo kidney (CEK) cells. HPE treatment at doses of 480–120 mg/kg for 5 days, reduced IBV induced injury in the trachea and kidney, moreover, reduced the mRNA expression level of IBV in the trachea and kidney in vivo. The mRNA expression levels of IL-6, tumor necrosis factor alpha (TNF-α), and nuclear factor kappa beta (NF-κB) significantly decreased, but melanoma differentiation-associated protein 5 (MDA5), mitochondrial antiviral signaling gene, interferon alpha (IFN-α), and interferon beta (IFN-β) mRNA levels significantly increased in vitro and in vivo. Our findings demonstrated that HPE had significant anti-IBV effects in vitro and in vivo, respectively. In addition, it is possible owing to up-regulate mRNA expression of type I interferon through the MDA5 signaling pathway and down-regulate mRNA expression of IL-6 and TNF-α via the NF-κB signaling pathway. Moreover, the mainly active compositions of HPE analyzed by high-performance liquid chromatography/electrospray ionization–mass spectroscopy (ESI-MS) are hyperoside, quercitrin, quercetin, pseudohypericin, and hypericin, and a combination of these compounds could mediate the antiviral activities. This might accelerate our understanding of the antiviral effect of H. perforatum and provide new insights into the development of effective therapeutic strategies.

MnO2 nanostructures are promising TME-responsive theranostic agents in cancer. Here, the authors develop a nano-platform based on hollow H-MnO2 nanoshells able to modulate the tissue microenvironment, release a drug and inhibit tumor growth alone or in combination with check-point blockade therapy.

Advanced oxidation processes (AOPs) are effective ways to degrade refractory organic contaminants, relying on the generation of inorganic radicals (e.g., •OH and SO4•−). Herein, a novel AOP with organic radicals (R-O•) was reported to degrade contaminants. Lanthanum cobaltite perovskite (LaCoO3) was used to activate peracetic acid (PAA) for organic radical generation to degrade sulfamethoxazole (SMX). The results show that LaCoO3 exhibited an excellent performance on PAA activation and SMX degradation at neutral pH, with low cobalt leaching. Meanwhile, LaCoO3 also showed an excellent reusability during PAA activation. In-depth investigation confirmed CH3C(O)O• and CH3C(O)OO• as the key reactive species for SMX degradation in LaCoO3/PAA system. The presence of Cl− (1–100 mM) slightly inhibited the degradation of SMX in the LaCoO3/PAA system, whereas the addition of HCO3− (0.1–1 mM) and humic aid (1–10 mg/L) could significantly inhibit SMX degradation. This work highlights the generation of organic radicals via the heterogeneous activation of PAA and thus provides a promising way to destruct contaminants in wastewater treatment.

It is well understood that liver cytochrome p450 enzymes are responsible for AFB1 bioactivation, while phase-II enzymes regulated by the transcription factor nuclear factor-erythroid-2-related factor 2 (Nrf2) are involved in detoxification of AFB1. In this study, we explored the potential of curcumin to prevent AFB1-induced liver injury by modulating liver phase-I and phase-II enzymes along with Nrf2 involved in AFB1 bioactivation and detoxification. Arbor Acres broiler were divided into four groups including control group (G1; fed only basal feed), curcumin alone-treated group (G2; 450 mg/kg feed), AFB1-fed group (G3; 5 mg/kg feed), and curcumin plus AFB1 group (G4; 5 mg AFB1+450 mg curcumin/kg feed). After 28 days, liver and blood samples were collected for different analyses. Histological and phenotypic results revealed that AFB1-induced liver injury was partially ameliorated by curcumin supplementation. Compared to AFB1 alone-treated group, serum biochemical parameters and liver antioxidant status showed that curcumin supplementation significantly prevented AFB1-induced liver injury. RT-PCR and western blot results revealed that curcumin inhibited CYP enzymes-mediated bioactivation of AFB1 at mRNA and protein level. Transcription factor Nrf2, its downstream genes such as GSTA3, and GSTM2 mRNA, and protein expression level significantly upregulated via dietary curcumin. In addition, GSTs enzyme activity was enhanced with dietary curcumin which plays a crucial role in AFB1-detoxification. Conclusively, the study provided a scientific basis for the use of curcumin in broiler’s diet and contributed to explore the multi-target preventive actions of curcumin against AFB1-induced liver injury through the modulation of phase-I and phase-II enzymes, and its potent anti-oxidative effects.

Pantographs are important devices on high-speed trains. When a train runs at a high speed, concave and convex parts of the train cause serious airflow disturbances and result in flow separation, eddy shedding, and breakdown. A strong fluctuation pressure field will be caused and transformed into aerodynamic noises. When high-speed trains reach 300 km/h, aerodynamic noises become the main noise source. Aerodynamic noises of pantographs occupy a large proportion in far-field aerodynamic noises of the whole train. Therefore, the problem of aerodynamic noises for pantographs is outstanding among many aerodynamics problems. This paper applies Detached Eddy Simulation (DES) to conducting numerical simulations of flow fields around pantographs of high-speed trains which run in the open air. Time-domain characteristics, frequency-domain characteristics, and unsteady flow fields of aerodynamic noises for pantographs are obtained. The acoustic boundary element method is used to study noise radiation characteristics of pantographs. Results indicate that eddies with different rotation directions and different scales are in regions such as pantograph heads, hinge joints, bottom frames, and insulators, while larger eddies are on pantograph heads and bottom frames. These eddies affect fluctuation pressures of pantographs to form aerodynamic noise sources. Slide plates, pantograph heads, balance rods, insulators, bottom frames, and push rods are the main aerodynamic noise source of pantographs. Radiated energies of pantographs are mainly in mid-frequency and high-frequency bands. In high-frequency bands, the far-field aerodynamic noise of pantographs is mainly contributed by the pantograph head. Single-frequency noises are in the far-field aerodynamic noise of pantographs, where main frequencies are 293 Hz, 586 Hz, 880 Hz, and 1173 Hz. The farther the observed point is from the noise source, the faster the sound pressure attenuation will be. When the distance of two adjacent observed points is increased by double, the attenuation amplitude of sound pressure levels for pantographs is around 6.6 dB.

Microscopic factors are the basis of macroscopic phenomena. We proposed a network analysis paradigm to study the macroscopic financial system from a microstructure perspective. We built the cointegration network model and the Granger causality network model based on econometrics and complex network theory and chose stock price time series of the real estate industry and its upstream and downstream industries as empirical sample data. Then, we analysed the cointegration network for understanding the steady long-term equilibrium relationships and analysed the Granger causality network for identifying the diffusion paths of the potential risks in the system. The results showed that the influence from a few key stocks can spread conveniently in the system. The cointegration network and Granger causality network are helpful to detect the diffusion path between the industries. We can also identify and intervene in the transmission medium to curb risk diffusion.

As a kind of potent stimulus, lipopolysaccharide (LPS) has the ability to cause cell damage by activating toll-like receptor(TLR)4, then nuclear factor kappa B (NF-κB) translocates into the nucleus and changes the expression of related inflammatory genes. Baicalin is extracted from Radix Scutellariae, which possesses anti-inflammation, antioxidant and antibacterial properties. However, the effects of it on LPS-induced liver inflammation have not been fully elucidated. This study aims to investigate the anti-inflammatory effects of Baicalin on the LPS-induced liver inflammation and its underlying molecular mechanisms in chicken. The results of histopathological changes, serum biochemical analysis, NO levels and myeloperoxidase activity showed that Baicalin pretreatment ameliorated LPS-induced liver inflammation. ELISA and qPCR assays showed that Baicalin dose-dependently suppressed the production of IL-1β, IL-6, and TNF-α. Furthermore, the mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were significantly decreased by Baicalin. TLR4 is an important sensor in LPS infection. Molecular studies showed that the expression of TLR4 was inhibited by Baicalin pretreatment. In addition, Baicalin pretreatment inhibited NF-kB signaling pathway activation. All results demonstrated the protective effects of Baicalin pretreatment against LPS-induced liver inflammation in chicken via negative regulation of inflammatory mediators through the down-regulation of TLR4 expression and the inhibition of NF-kB activation.

Orexins are hypothalamic neuropeptides that regulate feeding, reward, wakefulness and energy homeostasis. The present study sought to characterize the involvement of orexin A in glucose metabolism in HepG2 human hepatocellular carcinoma cells, and investigated the role of hypoxia-inducible factor-1α (HIF-1α) in the response. HepG2 cells were exposed to different concentrations of orexin A (10-9 to 10-7 M) in vitro, without or with the orexin receptor 1 (OX1R) inhibitor (SB334867), HIF-1α inhibitor (YC-1) or a combination of both inhibitors. Subsequently, OX1R, HIF-1α expression and localization, glucose uptake, glucose transporter 1 (GLUT1) expression and ATP content were measured. We further investigated the intracellular fate of glucose by measuring the gene expression of pyruvate dehydrogenase kinase 1 (PDK1), lactate dehydrogenase (LDHA) and pyruvate dehydrogenase B (PDHB), as well as metabolite levels including lactate generation and mitochondrial pyruvate dehydrogenase (PDH) activity. The activity of phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway was also assessed. Our results showed that the expression of OX1R was predominantly located in the nucleus in HepG2 cells. Orexin A oxygen-independently promoted the mRNA and protein expression of HIF-1α as well as its nuclear accumulation in HepG2 cells and the elevated HIF-1α protein was associated, at least partly, with the activation of the PI3K/Akt/mTOR pathway. Orexin A stimulated GLUT1 expression, glucose uptake as well as ATP generation in HepG2 cells via OX1R acting through the HIF-1α pathway. Moreover, orexin A inhibited LDHA, PDK1 expression and lactate production, stimulated PDHB expression and PDH enzyme activity independent of HIF-1α. Our results indicated that orexin signaling facilitated the glucose flux into mitochondrial oxidative metabolism rather than glycolysis in HepG2 cells. These findings provide new insight into the regulation of glucose metabolism by orexin A in hepatocellular carcinoma cells.

Objective: To determine the astragaloside content in Qishen Huoxue Granule (QHG) by HPLC and to investigate the protective effect of astragaloside in septic rats. Methods: Dikma DiamonsilTM C18 column was used. Mobile phase was methanol: acetonitrile (42:58) and detection was performed at 205 nm. Healthy rats were randomly divided into three groups, group A: sham operation (SO) group; group B: cecal ligation and puncture (CLP) group; and group C: CLP QHG treatment group. 72 h after model establishment, plasma tumor necrosis factor-α (TNF-α), plasma and peritoneal albumin concentrations, as well as mesenteric venular flow velocity in each group were measured and degree of intestinal mucosal injury was observed. Results: Average recovery was 100.7%, with a RSD of 2.20%. Sample concentration exhibited good linearity with peak area within a 0.01~0.2 mg/mL range. After CLP, plasma TNF-α concentration and albumin leakage in rats increased markedly; such increases were more significant in group B than group C (P