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Abstract Alkali-activated materials (AAMs) possess several advantages, such as high strengths and low carbon emissions. However, their application is hindered due to their significant shrinkage. This study explored the effect of borax-modified sodium silicate activator and metakaolin (MK) on the mechanical properties and drying shrinkage (DS) of alkali-activated slag (AAS) and AAS/MK (AASM) mortars. X-ray diffraction, scanning electron microscopy, and Fourier-transform infrared spectroscopy were used to characterize the hydration products. The results showed that the DS reduction of the AAS mortar was related to decreased Na2O content, a reduction in the proportion of mesopores, and the formation of moisture-retaining borate compounds. The DS reduction of the AASM mortar was attributed to the ultra-fine differential effect induced by MK, reducing the connected pores. The modified activator combined with MK increased the chemically bound water content in the matrix. Additionally, the B–O bond and highly active MK improved compactness of the AASM mortar. The use of borax-modified activators and MK provides a new solution to address the significant shrinkage issue in AAMs. This sets the stage for AAMs to potentially replace OPC, contributing to low-carbon emissions and promoting environmental protection.

BackgroundOrnithine transcarbamylase deficiency (OTCD), a rare hereditary disease caused by gene mutation of ornithine transcarbamylase (OTC), is the most prevalent type among urea cycle disorders. OTCD typically leads to mitochondrial enzyme dysfunction, preventing the synthesis of citrulline from carbamoyl phosphate and ornithine, and is characterized by a remarkable increase in blood ammonia. Specific symptoms may include neurological abnormalities, growth retardation, and other manifestations.MethodsWe presented a case of a child diagnosed with OTCD (OMIM: 311250). By using whole-genome sequencing (WGS) for the pedigree and in-depth whole-exome sequencing (WES), we aimed to identify the disease-causing genes. Gene mutation prediction tools were employed to verify the pathogenicity, and the molecular dynamics simulation method was utilized to assess the impact of this mutation on the activity and structural stability of the OTC protein.ResultsWhole-exome sequencing detected an OTC variant [NM_000531: c.622 (exon6) G > A, p.A208T]. Through comprehensive analysis with various gene mutation prediction tools and in line with the ACMG guidelines, this mutation site was firmly established as a pathogenic site. Moreover, the molecular dynamics simulation results clearly demonstrated that this mutation would significantly compromise the stability of the OTC protein structure.ConclusionThis study deepens our understanding of the clinical manifestations and characteristics of OTCD, especially the OTC A208T gene mutation site. Given the lack of specific clinical manifestations in OTCD patients, early and accurate diagnosis is crucial for effective treatment and prognosis improvement. To our knowledge, this is the first case of this mutation site reported in China.

Phytoplankton has been used as a paradigm for studies of coexistence of species since the publication of the “paradox of the plankton.” Although there are a wealth of studies about phytoplankton assemblages of lakes, reservoirs and rivers, our knowledge about phytoplankton biodiversity and its underlying mechanisms in mountain headwater stream ecosystems is limited, especially across regional scales with broad environmental gradients. In this study, we collected 144 phytoplankton samples from the Xijiang headwater streams of the Pearl River across low altitude (< 1,000 m) located in Guangxi province, intermediate altitude (1,000 m 2,000 m) in Yunnan province of China. Our study revealed high phytoplankton diversity in these streams. Freshwater phytoplankton, including cyanobacteria, Bacillariophyta, Chlorophyta, Rhodophyta, Chrysophyta, Euglenophyta, Glaucophyta, Phaeophyta and Cryptophyta, were all detected. However, phytoplankton alpha diversity exhibited a monotonic decreasing relationship with increasing altitude. High altitudes amplified the “isolated island” effect of headwater streams on phytoplankton assemblages, which were characterized by lower homogeneous selection and higher dispersal limitation. Variability and network vulnerability of phytoplankton assemblages increased with increasing altitudes. Our findings demonstrated diversity, variability and co-occurrence patterns of phytoplankton assemblages linked to environmental factors co-varying with altitude across regional scales.

Abstract Metabolic reprogramming has been observed in cancer metastasis, whereas metabolic changes required for malignant cells during lymph node metastasis of esophageal squamous cell carcinoma (ESCC) are still poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq) of paired ESCC tumor tissues and lymph nodes to uncover the reprogramming of tumor microenvironment (TME) and metabolic pathways. By integrating analyses of scRNA-seq data with metabolomics of ESCC tumor tissues and plasma samples, we found nicotinate and nicotinamide metabolism pathway was dysregulated in ESCC patients with lymph node metastasis (LN+), exhibiting as significantly increased 1-methylnicotinamide (MNA) in both tumors and plasma. Further data indicated high expression of N-methyltransferase (NNMT), which converts active methyl groups from the universal methyl donor, S-adenosylmethionine (SAM), to stable MNA, contributed to the increased MNA in LN+ ESCC. NNMT promotes epithelial–mesenchymal transition (EMT) and metastasis of ESCC in vitro and in vivo by inhibiting E-cadherin expression. Mechanically, high NNMT expression consumed too much active methyl group and decreased H3K4me3 modification at E-cadherin promoter and inhibited m6A modification of E-cadherin mRNA, therefore inhibiting E-cadherin expression at both transcriptional and post-transcriptional level. Finally, a detection method of lymph node metastasis was build based on the dysregulated metabolites, which showed good performance among ESCC patients. For lymph node metastasis of ESCC, this work supports NNMT is a master regulator of the cross-talk between cellular metabolism and epigenetic modifications, which may be a therapeutic target.

Thermal pollution from the cooling system of the nuclear power plants greatly changes the environmental and the ecological conditions of the receiving marine water body, but we know little about their impact on the steady-state transition of marine bacterioplankton communities. In this study, we used high-throughput sequencing based on the 16S rRNA gene to investigate the impact of the thermal pollution on the bacterioplankton communities in a subtropical bay (the Daya Bay). We observed that thermal pollution from the cooling system of the nuclear power plant caused a pronounced thermal gradient ranging from 19.6°C to 24.12°C over the whole Daya Bay. A temperature difference of 4.5°C between the northern and southern parts of the bay led to a regime shift in the bacterioplankton community structure. In the three typical scenarios of regime shifts, the steady-state transition of bacterioplankton community structure in response to temperature increasing was more likely consistent with an abrupt regime shift rather than a smooth regime or a discontinuous regime model. Water temperature was a decisive factor on the regime shift of bacterioplankton community structure. High temperature significantly decreased bacterioplankton diversity and shifted its community compositions. Cyanobium and Synechococcus of Cyanobacteria, NS5 marine group of Bacteroidota, and Vibrio of Gammaproteobacteria were found that favored high temperature environments. Furthermore, the increased water temperature significantly altered the community assembly of bacterioplankton in Daya Bay, with a substantial decrease in the proportion of drift and others, and a marked increase in the proportion of homogeneous selection. In summary, we proposed that seawater temperature increasing induced by the thermal pollution resulted in an abrupt regime shift of bacterioplankton community in winter subtropical bay. Our research might broad our understanding of marine microbial ecology under future conditions of global warming.

Abstract Dihydroquercetin (DHQ) is a natural occurring dihydroflavonol that has strong antioxidant and antibacterial activities. However, its application is limited due to its poor solubility. This study aims to improve the aqueous solubility of DHQ by complexing DHQ with β-cyclodextrin (β-CD) to boost its biological activity. DHQ was encapsulated with β-CD by freeze drying at a 1:1-M ratio. The structure of DHQ/β-CD complex prepared was elucidated by using Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, and 1H nuclear magnetic resonance (1H NMR). In addition, molecular docking further revealed two energetically favorable conformations of the DHQ/β-CD complex, in which DHQ interacted with β-CD via hydrogen bonds. Experimental results showed that the solubility of the DHQ increased 22.63-fold by encapsulating with β-CD. Also the dissolution rate, antioxidant activity and antibacterial activity of the DHQ were significantly improved by encapsulating. The encapsulating with β-CD solves the problem of the poor aqueous solubility of DHQ, and broadens the path for a more optimal use of the health promoting effect of DHQ in pharmaceutical and food products.

Pseudomonas fragi (P. fragi) is usually detected in low-temperature meat products, and seriously threatens food safety and human health. Therefore, the study investigated the antibacterial mechanism of linalool against P. fragi from membrane damage and metabolic disruption. Results from field-emission transmission electron microscopy (FETEM) and atomic force microscopy (AFM) showed that linalool damage membrane integrity increases surface shrinkage and roughness. According to Fourier transform infrared (FTIR) spectra results, the components in the membrane underwent significant changes, including nucleic acid leakage, carbohydrate production, protein denaturation and modification, and fatty acid content reduction. The data obtained from amino acid metabolomics indicated that linalool caused excessive synthesis and metabolism of specific amino acids, particularly tryptophan metabolism and arginine biosynthesis. The reduced activities of glucose 6-phosphate dehydrogenase (G6PDH), malate dehydrogenase (MDH), and phosphofructokinase (PFK) suggested that linalool impair the respiratory chain and energy metabolism. Meanwhile, genes encoding the above enzymes were differentially expressed, with pfkB overexpression and zwf and mqo downregulation. Furthermore, molecular docking revealed that linalool can interact with the amino acid residues of G6DPH, MDH and PFK through hydrogen bonds. Therefore, it is hypothesized that the mechanism of linalool against P. fragi may involve cell membrane damage (structure and morphology), disturbance of energy metabolism (TCA cycle, EMP and HMP pathway) and amino acid metabolism (cysteine, glutamic acid and citrulline). These findings contribute to the development of linalool as a promising antibacterial agent in response to the food security challenge.

Direct barrier discharge (DBD) plasma is a potential antibacterial strategy for controlling Fusarium oxysporum (F. oxysporum) in the food industry. The aim of this study was to investigate the inhibitory effect and mechanism of action of DBD plasma on F. oxysporum. The result of the antibacterial effect curve shows that DBD plasma has a good inactivation effect on F. oxysporum. The DBD plasma treatment severely disrupted the cell membrane structure and resulted in the leakage of intracellular components. In addition, flow cytometry was used to observe intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potential, and it was found that, after plasma treatment, intracellular ROS accumulation and mitochondrial damage were accompanied by a decrease in antioxidant enzyme activity. The results of free fatty acid metabolism indicate that the saturated fatty acid content increased and unsaturated fatty acid content decreased. Overall, the DBD plasma treatment led to the oxidation of unsaturated fatty acids, which altered the cell membrane fatty acid content, thereby inducing cell membrane damage. Meanwhile, DBD plasma-induced ROS penetrated the cell membrane and accumulated intracellularly, leading to the collapse of the antioxidant system and ultimately causing cell death. This study reveals the bactericidal effect and mechanism of the DBD treatment on F. oxysporum, which provides a possible strategy for the control of F. oxysporum.

ObjectiveTo explore the influence of serum metabolites on the risk of psoriasis.MethodsIn the initial stage, we applied Mendelian randomization to evaluate the association between 1,400 serum metabolites and the risk of psoriasis. Causal effects were primarily assessed through the Inverse-Variance Weighted method and Wald Ratio’s odds ratios, and 95% confidence intervals. False Discovery Rate was used for multiple comparison corrections. Sensitivity analyses were conducted using Cochran’s Q Test, MR-PRESSO. MR-Steiger Test was employed to check for reverse causality. In the validation stage, we sought other sources of psoriasis GWAS data to verify the initial results and used meta-analysis to combine the effect sizes to obtain robust causal relationships. In addition, we also conducted metabolic pathway enrichment analysis on known metabolites that have a causal relationship with the risk of psoriasis in both stages.ResultsIn the initial stage, we identified 112 metabolites causally associated with psoriasis, including 32 metabolite ratios and 80 metabolites (69 known and 11 unknown). In the validation stage, 24 metabolites (16 known, 1 unknown, and 7 metabolite ratios) were confirmed to have a causal relationship with psoriasis onset. Meta-analysis results showed that the overall effect of combined metabolites was consistent with the main analysis in direction and robust in the causal relationship with psoriasis onset. Of the 16 known metabolites, most were attributed to lipid metabolism, with 5 as risk factors and 8 as protective factors for psoriasis. Peptidic metabolite Gamma-glutamylvaline levels had a negative causal relationship with psoriasis, while exogenous metabolite Catechol sulfate levels and amino acid 3-methylglutaconate levels had a positive causal relationship with the disease onset. The metabolites associated with psoriasis risk in the two stages are mainly enriched in the following metabolic pathways: Glutathione metabolism, Alpha Linolenic Acid and Linoleic Acid Metabolism, Biosynthesis of unsaturated fatty acids, Arachidonic acid metabolism, Glycerophospholipid metabolism.ConclusionCirculating metabolites may have a potential causal relationship with psoriasis risk, and targeting specific metabolites may benefit psoriasis diagnosis, disease assessment, and treatment.

In buildings that experience fires, cement mortar is subjected to high-temperature environments and not only the weight of the structure above but also blast loads, leading to structural damage and loss of load-bearing capacity. To investigate the static and dynamic mechanical properties of thermally damaged mortar, a series of tests utilizing modified split Hopkinson pressure bar were conducted. These tests included quasi-static, conventional dynamic and coupled static-dynamic loading tests on mortar specimens that were subjected to seven temperature levels: 20°C, 100°C, 200°C, 300°C, 400°C, 500°C, and 600°C. The test results revealed that both the thermal damage and loading method had an impact on the mechanical properties and damage characteristics of the mortar specimens. The compressive strength, elastic modulus and absorbed energy ratio of mortar decreased as temperature increased. Notably, the quasi-static strength loss rate was 60% when the temperature reached 600°C. Under coupled static-dynamic loading, the specimens exhibited higher strength, elastic modulus, reflected energy ratio, and transmitted energy ratio. Conversely, they had lower average strain rates and absorbed energy ratios. Intriguingly, the dynamic growth factor had a relative increase of 0.7–2.0 compared with other loading methods. Furthermore, the higher temperature, the higher fragmentation of the specimens in the fragmentation pattern. Conventional dynamic loading resulted in the greatest degree of fragmentation. The findings provide a scientific basis for the design and evaluation of concrete shockproof and explosion-resistant structures.

Background: Psoriasis, a chronic skin condition characterized by systemic inflammation and altered gut microbiota, has been a target of Traditional Chinese Medicine (TCM) for centuries. Shenling Baizhu Powder (SLBZP), a TCM formulation, holds promise for treating inflammatory diseases, but its specific role in psoriasis and impact on gut microbiota is not fully understood.Objective: This study aims to elucidate the mechanism of SLBZP in treating psoriasis, integrating component analysis, network pharmacology, and experimental validation in mice models.Methods: We commenced with a detailed component analysis of SLBZP using liquid chromatograph and mass spectrometer (LC-MS). Network pharmacology analysis was used to predict the potential action targets and pathways of SLBZP in psoriasis. An in vivo experiment was conducted with psoriasis mice models, treated with SLBZP. Therapeutic effects were assessed via symptomatology, histopathology, and immunohistochemical analysis. Gut microbiota composition was analyzed using 16S rRNA gene sequencing.Results: A total of 42 main components and quality markers were identified, primarily from licorice and ginseng, including flavonoids, saponins and other markers. PPI topology analysis showed that TNF, IL-6, IL-1β, TP53 and JUN were the core DEPs. 168 signaling pathways including lipid and atherosclerosis, AGE-RAGE signaling pathway, IL-17 signaling pathway and Th17 cell differentiation were enriched by KEGG. SLBZP demonstrated significant therapeutic effects on psoriasis in mice, with alterations in skin pathology and biomarkers. Additionally, notable changes in gut microbiota composition were observed post-treatment, indicating a possible gut-skin axis involvement.Conclusion: This research has pinpointed lipid metabolism as a key pathway in the treatment of psoriasis with SLBZP. It explores how SLBZP’s modulation of gut microbiota and lipid metabolism can alleviate psoriasis, suggesting that balancing gut microbiota may reduce inflammation mediators and offer therapeutic benefits. This underscores lipid metabolism modulation as a potential new strategy in psoriasis treatment.

Psoriasis vulgaris is a chronic dermatological disease with a high global prevalence. It significantly reduces patients' quality of life and is associated with a substantial economic burden. Conventional therapies for mild-to-moderate psoriasis are often associated with insufficient long-term symptomatic relief and side effects. Chinese herbal medicine (CHM) is commonly used for psoriasis management. A CHM formula, namely Fu zheng he fu zhi yang (FZHFZY), has shown promising treatment effects in clinical practice when used as a bath therapy. However, its efficacy and safety has not been evaluated by a rigorous randomized controlled trial (RCT). Therefore, we designed a double-blinded pilot RCT embedded with a qualitative study on CHM formula FZHFZY plus topical urea for mild-to-moderate psoriasis vulgaris to advance the evidence development and practice of CHM external application for psoriasis. This will be a mixed-method design consisting of a pilot RCT and a qualitative study. The pilot RCT is a two-arm, parallel, placebo-controlled, double-blinded trial. Sixty eligible participants will be randomized at a 1:1 ratio to receive eight weeks' treatment of either FZHFZY plus 10% urea cream, or placebo plus 10% urea cream, with 12-week follow-up visits after the treatment phase. The CHM or placebo will be administered externally as a bath therapy. Outcome measures include trial feasibility, efficacy and safety. The primary efficacy outcome will be Psoriasis Area Severity Index (PASI). Secondary efficacy outcomes include Physician Global Assessment, PASI-75, PASI-50, Body Surface Area, Dermatology Life Quality Index, Skindex-16, itch visual analogue scale and relapse. The qualitative study will be conducted to collect participants' feedback on CHM external application and their experience with the pilot RCT. This study will advance the evidence-based clinical practice of using CHM for psoriasis vulgaris and then to support translation of findings into clinical practice in the future. Trial registration number: ChiCTR2200064092.

Primary care physicians (PCPs) suffered from heavy workloads and health problems during COVID-19 pandemics, and building their confidence in pandemic response has great potential to improve their well-being and work performance. We identified the organizational factors associated with their confidence in pandemic response and proposed potential management levers to guide primary care response for the pandemic. We conducted a cross-sectional survey with 224 PCPs working in 38 community health centers in China. Guided by self-efficacy theory, organization-level factors (organizational structure and organizational culture) and physician-level factors (job skill variety, perceived organizational support, work-family conflict, and professional fulfillment) were selected, and two-level ordinal logit models were built to examine their association with PCPs' confidence in pandemic response. We found that hierarchical culture (OR = 3.51, P

The collapsible loess will rapidly soften and lose its bearing capacity when soaked in water. Under a mild condition (20 °C), the biomimetic inorganic agent, diammonium phosphate (DAP), reacts with calcite in the collapsible loess, producing a stronger bonding material, hydroxyapatite (HAP), to modify and stabilize the soil. Uniaxial compression, permeability tests, and morphological analysis using X-ray diffraction and scanning electron microscopy equipped with an energy X-ray dispersive system were used to assess the effectiveness of DAP stabilization on the collapsible loess. The results indicated that HAP improved the inter-particle bonding within the loess, filled the pores within particles, reduced the permeability, and consequently mitigated the collapsibility of the loess. The compressive strength of the DAP-treated loess increased as DAP concentration increased. Following 28 days of curing, the compressive strength of the loess treated with a 3.0 mol/L DAP solution was six times greater than that of the untreated group. DAP’s reinforcement effect on the loess was superior to that of cement. The compressive strength of the DAP-treated loess was about double that of the cement-treated loess and the permeability coefficient was reduced by more than 50% at equivalent solid content. Furthermore, DAP generated 82% fewer carbon emissions compared to Portland cement. Considering eco-friendly and sustainable development, DAP offers a more competitive alternative for modification and stabilization of loess.

This research aimed to investigate the effects of protein concentration (0.2 %-1.0 %), ionic strength (100–500 mM NaCl), and heat treatment (temperature: 80 and 90℃; time: 15 and 30 min) on the interfacial and emulsifying properties of coconut globulins (CG). When protein concentration was set at 0.2–0.6 %, the interfacial adsorption increased with the increasing of protein concentration. However, the lowest interfacial viscoelasticity was found when CG concentration was 0.6 %. When the protein concentration was higher than 0.6 %, the dilatational viscoelasticity increased with the increasing of protein concentration. The protein concentration showed positive effect on the emulsion stability of CG. The ionic strength showed positive effect on the interfacial adsorption but negative effects on the interfacial viscoelasticity and emulsion stability. Higher temperature and longer heating time brought worse interface behavior. The heated CG (90℃, 30 min) had the worst interfacial behavior but the best emulsion stability.

Endowing a robust pressure-sensitive adhesive (PSA) with sensable properties is of great significance for in-situ stress detection and information encryption in the fields of electronics, energy storage, flexible sensing, etc. However, it remains great challenge due to the difficulty in balancing interfacial wetting and cohesive strength. Herein, a microphase-separated strategy is proposed to construct an ionogel with a lower modulus of 1.96MPa, a strength of 728kPa as well as a remarkable toughness of 2258.9kJ/m3, which can be used as a sturdy PSA bonded to various substrates (metals, polar plastics, non-polar plastics) under gentle pressure. The comparable modulus and cohesive strength give it an excellent adhesion strength of 1340kPa, which far exceeds most of reported high-performance PSAs. Furthermore, due to the orientation of a large number of ionic groups, the adhesion strength increases by 31.3% once a voltage of 20V is applied. Finally, the sensitive force-resistance response of such PSA that can be used for encrypted messaging was demonstrated.

LEDBAT++ is a novel less-than-best-effort congestion control algorithm. However, it still shows aggressiveness when competing with CUBIC in shallow buffer networks or with BBRv2 in low latency networks. In order to maintain its low-priority performance over diversified network environments, we propose PeaceKeeper, which combines reinforcement learning algorithm to dynamically adjust the target based on the network state. Extensive simulations show that, compared to LEDBAT++, the throughput of the primary flow competing with PeaceKeeper improved by 30.76% to 173.63%. Additionally, compared to heuristics adjusting the target, PeaceKeeper increases the link bandwidth utilization by 50.91%.

Meat is often contaminated by food-borne pathogens, resulting in significant economic losses. Linalool from plant essential oils (EOs) has been reported to have excellent antibacterial properties. Therefore, this study aims to elucidate the mechanism of linalool against Shigella sonnei (S. sonnei) based on proteomic and physiological indicators. The results indicated that linalool severely perturbed the expression levels of intracellular proteins, of which 208 were up-regulated and 49 were down-regulated. Moreover, linalool exerted its inhibitory effect mainly through the induction of amino acid limitation and insufficient energy levels based on the pathways involved in differential expressed proteins (DEPs). After 8 h, alkaline phosphatase (AKP) leakage increased 20.96 and 21.52-fold in the MIC and 2MIC groups while protein leakage increased 2.17 and 2.50-fold, respectively, which revealed the potential of linalool on cell structure damage combined with nucleic acid leakage. In addition, the ATP content decreased to 36.92% and 18.84% in the MIC and 2MIC groups, respectively when processed for 8 h. In particular, linalool could effectively control the quality change of fresh beef by measuring pH, total volatile basic nitrogen (TVB-N), total viable counts (TVC) while not affecting its sensory acceptability based on the result of sensory evaluation. This research provides theoretical insights for the development of linalool as a new natural antibacterial agent.

Abstract Background Little evidence suggests that trauma centres are associated with a lower risk of mortality in severely injured patients (Injury Severity Score (ISS) ≥16) with multiple injuries in China. The objective of this study was to determine the association between the establishment of trauma centres and mortality among severely injured patients with multiple injuries and to identify some risk factors associated with mortality. Methods A retrospective single-centre study was performed including trauma patients admitted to the First Affiliated Hospital of Nanchang University (FAHNU) between January 2016 and December 2021. To determine whether the establishment of a trauma centre was an independent predictor of mortality, logistic regression analysis and propensity score matching (PSM) were performed. Results Among 431 trauma patients, 172 were enrolled before the trauma centre was built, while 259 were included after the trauma centre was built. A higher frequency of older age and traffic accident injury was found in patients diagnosed after the trauma centre was built. The times for the completion of CT examinations, emergency operations and blood transfusions in the “after trauma centre” group were shorter than those in the “before trauma centre” group. However, the total expenditure of patients was increased. In the overall group, univariate and multivariate logistic regression analyses showed that a higher ISS was an independent predictor for worse mortality (OR = 17.859, 95% CI, 8.207–38.86, P

In satellite networks, existing congestion resolution methods do not consider the predictability and stability of paths, leading to frequent path switches and high maintenance costs. In this regard, we propose a novel congestion resolution approach, named MOLM, which introduces a continuous neighbor set during path updates. This set includes nodes capable of establishing sustainable connections with the predecessors and successors of congested nodes. Combined with a multi-objective simulated annealing framework, MOLM iteratively derives an optimal selection from this set to replace congested nodes. Additionally, we employ a Fast Reroute mechanism based on backup paths (FRR-BP) to address node failures. The simulation results indicate that the optimal node endows the new path with optimal path stability and path latency.

With the vigorous development of the Internet of Things, 5G technology, and artificial intelligence, flexible wearable sensors have received great attention. As a simple and low-cost power supply in wearable sensors, the triboelectric nanogenerator (TENG) has a wide range of applications in the field of flexible electronics. However, most polymers are thermally poor conductors (less than 0.1 W/(m·K)), resulting in insufficient heat dissipation performance and limiting the development of TENG. In this study, a high-performance non-woven fabric TENG with strong thermal conductivity (0.26 W/m·K) was achieved by introducing ZrB2 into the polyurethane (PU) matrix. The excellent output performance with an open circuit voltage (Voc) of 347.6 V, a short circuit current (Isc) of 3.61 μA, and an accumulated charge of 142.4 nC endows it with good sensitivity. The electrospun PU/ZrB2 composites exhibit excellent sensing performance to detect body movements in situ, such as pressing, clapping, running, and walking. Moreover, the generated power can light up 224 LED bulbs as a demonstration of self-powering ability.

Abstract Internet of Things (IoT) is made up with growing number of facilities, which are digitalized to have sensing, networking and computing capabilities. Traditionally, the large volume of data generated by the IoT devices are processed in a centralized cloud computing model. However, it is no longer able to meet the computational demands of large-scale and geographically distributed IoT devices for executing tasks of high performance, low latency, and low energy consumption. Therefore, edge computing has emerged as a complement of cloud computing. To improve system performance, it is necessary to partition and offload some tasks generated by local devices to the remote cloud or edge nodes. However, most of the current research work focuses on designing efficient offloading strategies and service orchestration. Little attention has been paid to the problem of jointly optimizing task partitioning and offloading for different application types. In this paper, we make a comprehensive overview on the existing task partitioning and offloading frameworks, focusing on the input and core of decision engine of the framework for task partitioning and offloading. We also propose comprehensive taxonomy metrics for comparing task partitioning and offloading approaches in the IoT cloud-edge collaborative computing framework. Finally, we discuss the problems and challenges that may be encountered in the future.

Obesity and hyperlipidemia have become serious public health problems in today's society. Studies have found that edible and medicinal fungi polysaccharides can promote the proliferation of probiotics in the intestines, inhibit the growth of harmful bacteria, improve the intestinal flora, and play a role in regulating lipid metabolism. But at present, its specific mechanism has not been determined and unified in regulating lipid metabolism. This article mainly focused on the interaction and effects between polysaccharides of edible and medicinal bacteria, gut microbiota and lipid metabolism, as well as the possible mechanism of edible and medicinal fungi polysaccharides in regulating lipid metabolism through gut microbiota, mainly including the short-chain fatty acid pathway and the activity of reducing inflammation are reviewed. The aim of this study would provide a reference for the utilization of active ingredients of edible and medicinal fungi and the research and development of nutritional functional foods.

The most notable side-effect of apatinib, a novel antiangiogenic agent for the treatment of cancer, is hypertension, but there are few published studies regarding the use of apatinib to treat patients with cancer and severe hypotension. Here, the cases of three patients with tumours and severe hypotension are described: case 1, a 73-year-old male patient with lung squamous cell carcinoma who initially received radiotherapy and chemotherapy, and developed pneumonia and severe hypotension after 6 months; case 2, a 56-year-old male patient with nasopharyngeal carcinoma who was treated with chemotherapy and presented with fever and persistent hypotension; and case 3, a 77-year-old male patient with oesophageal cancer who was admitted with deglutition difficulty and severe hypotension. Apatinib was added to the treatment regimen of all three patients for antitumor therapy. Pneumonia, tumour progression, and severe hypotension improved noticeably in all patients within 1 month after receiving apatinib. Apatinib was associated with a positive effect on blood pressure stability, in synergy with other means of therapy, and the patients achieved satisfactory short-term clinical results. The role of apatinib in treating patients with cancer and hypotension merits further investigation.

Abstract Background Multiple myeloma (MM) patients have variable responses to mRNA vaccination to COVID‐19. Little is known regarding their vaccine‐induced antibody levels over time. Methods We monitored spike IgG antibody levels over 24 weeks among a subset of 18 MM patients who showed a full response after two mRNA vaccinations. Results MM patients had a more rapid decline in antibody levels as compared to eight healthy controls, with power law half‐lives of 72 days (vs. 107 days) and exponential half‐lives of 37 days (vs. 51 days). The patients with longer SARS‐CoV‐2 antibody half‐lives were more likely to have undetectable monoclonal protein than those with shorter half‐lives, suggesting better disease control may correlate with longer duration of vaccine‐induced antibodies. Regardless, by 16 weeks post‐second dose of mRNA vaccination, the majority of patients had antibody levels below 250 binding arbitrary units per milliliter, which would be unlikely to contribute to preventing COVID‐19. Conclusions Thus, even MM patients who respond adequately to vaccination are likely to require more frequent booster doses than the general population.

ObjectiveThe constant changes in the control strategies of the Corona Virus Disease 2019 (COVID-19) pandemic have greatly affected the prevention and control of nosocomial infections (NIs). This study assessed the impact of these control strategies on the surveillance of NIs in a regional maternity hospital during the COVID-19 pandemic.MethodsThis retrospective study compared the observation indicators of nosocomial infections and their changing trends in the hospital before and during the COVID-19 pandemic.ResultsIn total, 2,56,092 patients were admitted to the hospital during the study. During the COVID-19 pandemic, the main drug-resistant bacteria in hospitals were Escherichia coli, Streptococcus agalactiae, Staphylococcus aureus, Klebsiella pneumoniae, and Enterococcus faecalis. The detection rate of S. agalactiae increased annually, while that of E. faecalis remained the same. The detection rate of multidrug-resistant bacteria decreased during the pandemic (16.86 vs. 11.42%), especially that of CRKP (carbapenem-resistant Klebsiella pneumoniae 13.14 vs. 4.39, P < 0.001). The incidence of nosocomial infections in the pediatric surgery department decreased significantly (OR: 2.031, 95% CI: 1.405–2.934, P < 0.001). Regarding the source of infection, a significant reduction was observed in respiratory infections, followed by gastrointestinal infections. In the routine monitoring of the ICU, the incidence of central line-associated bloodstream infection (CLABSI) decreased significantly (9.4/1,000 catheter days vs. 2.2/1,000 catheter days, P < 0.001).ConclusionThe incidence of nosocomial infections was lower than that before the COVID-19 pandemic. The prevention and control measures for the COVID-19 pandemic have reduced the number of nosocomial infections, especially respiratory, gastrointestinal, and catheter-related infections.

Hyperplasia of epidermal keratinocytes that depend on glycolysis is a new hallmark of psoriasis pathogenesis. Our previous studies demonstrated that PSORI-CM02 could halt the pathological progression of psoriasis by targeting inflammatory response and angiogenesis, but its effect(s) and mechanism(s) on proliferating keratinocytes remained unclear. In this study, we aim to identify components of PSORI-CM02 that are absorbed into the blood and to determine the effect(s) of PSORI-CM02 on keratinocyte proliferation and its molecular mechanism(s). We used the immortalized human epidermal keratinocyte cell line, HaCaT, as an in vitro model of proliferating keratinocytes and the imiquimod-induced psoriasis mouse (IMQ) as an in vivo model. Metabolite profiles of vehicle pharmaceutic serum (VPS), PSORI-CM02 pharmaceutic serum (PPS), and water extraction (PWE) were compared, and 23 components of PSORI-CM02 were identified that were absorbed into the blood of mice. Both PPS and PWE inhibited the proliferation of HaCaT cells and consequently reduced the expression of the proliferation marker ki67. Additionally, PPS and PWE reduced phosphorylation levels of mTOR pathway kinases. Seahorse experiments demonstrated that PPS significantly inhibited glycolysis, glycolytic capacity, and mitochondrial respiration, thus reducing ATP production in HaCaT cells. Upon treatments of PPS or PWE, hexokinase 2 (HK2) expression was significantly decreased, as observed from the set of glycolytic genes we screened. Finally, in the IMQ model, we observed that treatment with PSORI-CM02 or BPTES, an inhibitor of mTOR signaling, reduced hyperproliferation of epidermal keratinocytes, inhibited the expression of p-S6 and reduced the number of proliferating cell nuclear antigen (PCNA)-positive cells in lesioned skin. Taken together, we demonstrate that PSORI-CM02 has an anti-proliferative effect on psoriatic keratinocytes, at least in part, by inhibiting the mTOR/HK2/glycolysis axis.

Abstract Background To evaluate the safety and efficacy of bilateral balloon pulmonary angioplasty (BPA) as compared with unilateral BPA for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Method We reviewed 210 consecutive BPA sessions for 92 CTEPH patients, including 124 unilateral BPA sessions and 86 bilateral BPA sessions. Radiation exposure, operation details, lesions characteristics and the occurrence of complications were compared between unilateral BPA and bilateral BPA. 131 BPA sessions with a hemodynamics follow-up were included for efficacy analysis, in which hemodynamics changes were compared. Logistic regression analysis was used to identify factors associated with the occurrence of complications. Result Bilateral BPA treated more lobes, arteries and lesions [3 (2, 4) vs. 2 (1, 3) lobes, p

We have reported that IgG antibody responses following two mRNA COVID-19 vaccinations are impaired among patients with multiple myeloma (MM). In the current study, sixty-seven patients with MM were tested for anti-spike IgG antibodies 0–60 days prior to their first vaccination, 14–28 days following the second dose, and both before and 14–28 days after their third dose of the mRNA-1273 or BNT162b2 vaccines. After the first two doses, most patients' (93 %) antibody levels declined to ineffective levels ( 10-fold change from baseline for the two-dose series, switching from BNT162b2 to mRNA-1273 for D3, and treatment with elotuzumab and an immunomodulatory agent. Lower antibody levels prior to D3, poorer overall response to first two doses, and ruxolitinib or anti-CD38 monoclonal antibody treatment negatively correlated with D3 response. Our results show encouraging activity of the third vaccine, even among patients who failed to respond to the first two vaccinations. The finding of specific factors that predict COVID-19 antibody levels will help advise patients and healthcare professionals on the likelihood of responses to further vaccinations.

Unmanned Surface Vehicles (USVs) generate a large amount of data that needs to be processed in real time when they work, but they are usually limited by computational and battery resources, so they need to offload their tasks to the edge for processing. However, when numerous USVs offload their tasks to the edge nodes, some offloaded tasks may be thrown due to queuing timeouts. Existing task offloading methods generally consider the latency or the overall system energy consumption caused by the collaborative processing at the edge and end layers, and do not consider the wasted energy when the tasks are thrown. Therefore, to address the above situation, this paper establishes a task offloading model to minimize long-term task latency and energy consumption by jointly considering the requirments of latency and energy-sensitive tasks and the overall load dynamics in the cloud, edge, and end layers. A deep reinforcement learning (DRL)-based Task Offloading with Cloud Edge Jointly Load Balance Optimization algorithm (TOLBO) is proposed to select the best edge server or cloud server for offloading. Simulation results show that the algorithm can improve the utilization of energy consumption of the cloud edge nodes compared with other algorithms. At the same time, it can significantly reduce the task throw rate, average latency, and energy consumption of end devices.

It has been reported that in an oxidative environment, the flavonoid 2R,3R-dihydroquercetin (2R,3R-DHQ) oxidizes into a product that rearranges to form quercetin. As quercetin is a very potent antioxidant, much better than 2R,3R-DHQ, this would be an intriguing form of targeting the antioxidant quercetin. The aim of the present study is to further elaborate on this targeting. We can confirm the previous observation that 2R,3R-DHQ is oxidized by horseradish peroxidase (HRP), with H2O2 as the oxidant. However, HPLC analysis revealed that no quercetin was formed, but instead an unstable oxidation product. The inclusion of glutathione (GSH) during the oxidation process resulted in the formation of a 2R,3R-DHQ-GSH adduct, as was identified using HPLC with IT-TOF/MS detection. GSH adducts appeared on the B-ring of the 2R,3R-DHQ quinone, indicating that during oxidation, the B-ring is oxidized from a catechol to form a quinone group. Ascorbate could reduce the quinone back to 2R,3R-DHQ. No 2S,3R-DHQ was detected after the reduction by ascorbate, indicating that a possible epimerization of 2R,3R-DHQ quinone to 2S,3R-DHQ quinone does not occur. The fact that no epimerization of the oxidized product of 2R,3R-DHQ is observed, and that GSH adducts the oxidized product of 2R,3R-DHQ on the B-ring, led us to conclude that the redox-modulating activity of 2R,3R-DHQ quinone resides in its B-ring. This could be confirmed by chemical calculation. Apparently, the administration of 2R,3R-DHQ in an oxidative environment does not result in ‘biotargeting’ quercetin.

Extracellular vesicles (EVs) play critical roles in intercellular communication by transporting bioactive cargo to recipient cells. EVs have been implicated in a range of physiological and pathological processes, including tumor progression, metastasis, immune modulation, and drug resistance. The objective of this review is to present a thorough overview of recent studies focusing on EVs in hepatocellular carcinoma (HCC), with an emphasis on their potential utility as diagnostic biomarkers as well as therapeutic agents. Initially, we explore the utility of EVs as diagnostic biomarkers for HCC, followed by a discussion of their potential as carriers of therapeutic payloads. Additionally, we delve into the emerging field of therapeutic EVs for modulating tumor immune responses. Through this review, our ultimate aim is to provide a comprehensive understanding of the opportunities and challenges in the clinical translation of EV research in the domain of HCC.

Ordinary Portland concrete (OPC) is characterized by low tensile strength and low toughness. These properties can be improved by adding glass fiber (GF). However, the alkaline environment of the pore solutions adversely affects the durability of GF. First, the effect of GF addition on the mechanical properties and fluidity of cement mortar was investigated. It was found that the fluidity decreased, and the flexural strength increased with an increase in the GF content. The incorporation of GF had little effect on the compressive strength of mortar. The optimal volume dosage of GF was 2 %. Then, Experiments were conducted to study the effects of glass powder (GP) characterized by different particle sizes and dosages on the fluidity, mechanical properties, and strength activity index (SAI) of glass-fiber-reinforced cementitious composites (GFRC). The results revealed that the fluidity, flexural strength, and compressive strength of GFRC containing GP increased with a decrease in the GP particle size. The flexural and compressive strength of GFRC first increased and then decreased with an increase in the GP content. The SAIs values of all GFRC specimens were more than 75 %, except GPI-25. Finally, the effect of the GPIV (GP of the optimal particle sizes) content on the drying shrinkage and pore structure of GFRC was studied. It was observed that the addition of GP into GFRC resulted in a reduction in the drying shrinkage, and the drying shrinkage of GFRC decreased with an increase in the GPIV content. The pore volume (0.5–50 nm) of GFRC decreased with an increase in the GPIV content. GP in GFRC consumed calcium hydroxide (CH) to produce calcium silicate gel. This helped reduce the extent of corrosion of GF by CH. Waste glass is processed into GP and added into mortar or concrete to replace parts of cement to reduce cement consumption and carbon dioxide emission. This helps protect the environment. GP is a promising agent for the fabrication of glass-fiber-reinforced cementitious composites.

Mango juice (MJ) was co-inoculated with Lactobacillus plantarum + Rhodotorula glutinis or Metschnikowia pulcherrima (LP + RG or LP + MP, respectively) and Lactobacillus casei + Rhodotorula glutinis or Metschnikowia pulcherrima (LC + RG or LC + MP, respectively) to evaluate their effect on the physicochemical characteristics, antioxidant capacity, and aroma compounds of MJ after 72 h of fermentation at 28 °C. Results indicated that among the fermented MJ, that which was fermented with LC + RG yielded the highest content of total acid (15.05 g/L). The pH values of MJ fermented with LC + MP, LC + RG, LP + RG, and LP + MP were 3.36, 3.33, 3.26, and 3.19, respectively, and were lower than that of CK (4.79). The juice fermented with LP + MP culture had the lowest sugar content (73.52 g/L), and those fermented with LP + RG and LP + MP had higher total phenol contents and stronger DPPH radical scavenging activity, ABTS radical scavenging activity, iron-reducing antioxidant capacity, and copper reducing antioxidant capacity than the others. Carotenoids in MJ had varying degrees of degradation after mixed fermentation by using all four combinations. Volatile compounds revealed that the co-fermentation of LP + RG produced increased norisoprenoid aroma compounds. The mixed co-inoculation method is a strategy to contemplate for MJ fermentation, but the modalities of inoculation need further investigation. Success depends on the suitable combination of non-Saccharomyces and lactic acid bacteria and consideration of strain variation.

In this paper, we report the preparation of a gas diffusion layer (GDL) with different gradient pore size structures. The pore structure of microporous layers (MPL) was controlled by the amount of pore-making agent sodium bicarbonate (NaHCO3). We investigated the effects of the two-stage MPL and the different pore size structures in the two-stage MPL on the performance of proton exchange membrane fuel cells (PEMFC). The conductivity and water contact angle tests showed that the GDL had outstanding conductivity and good hydrophobicity. The results of the pore size distribution test indicated that introducing a pore-making agent altered the pore size distribution of the GDL and increased the capillary pressure difference within the GDL. Specifically, there was an increase in pore size within the 7–20 μm and 20–50 μm ranges, which improved the stability of water and gas transmission within the fuel cell. The maximum power density of the GDL03 was increased by 37.1% at 40% humidity, 38.9% at 60% humidity, and 36.5% at 100% humidity when compared to the commercial GDL29BC in a hydrogen-air environment. The design of gradient MPL ensured that the pore size between carbon paper and MPL changed from an initially abrupt state to a smooth transition state, which significantly improved the water and gas management capabilities of PEMFC.

The areca nut is one of the most important cash crops in the tropics and has substantial economic value. However, the research information about the edible quality of different areca nuts is still insufficient. This study compared the composition, texture characteristics and flavor release behaviors of four different areca nuts (AN1, AN2, AN3 and AN4) and two commercially dried areca nuts (CAN1 and CAN2). Results showed that AN1 had higher soluble fiber and lower lignin, which was the basis of its lower hardness. Meanwhile, the total soluble solid (TSS) of AN1 was the highest, which indicated that AN1 had a moister and more succulent mouthfeel. After the drying process, the lignification degree of AN1 was the lowest. Through textural analyses, the hardness of AN1 was relatively low compared to the other dried areca nuts. AN1, CAN1 and CAN2 had higher alkaline pectin content and viscosity, and better flavor retention, which indicated better edible quality. The present study revealed the differences of various areca nuts and provided vital information to further advance the study of areca nuts.

The development of functional edible films is promising for the food industry, and improving the water barrier of edible films has been a research challenge in recent years. In this study, curcumin (Cur) was added to zein (Z) and shellac (S) to prepare an edible composite film with a strong water barrier and antioxidant properties. The addition of curcumin significantly reduced the water vapor permeability (WVP), water solubility (WS), and elongation at break (EB), and it clearly improved the tensile strength (TS), water contact angle (WCA), and optical properties of the composite film. The ZS–Cur films were characterized by SEM, FT-IR, XRD, DSC, and TGA; the results indicated that hydrogen bonds were formed among the curcumin, zein, and shellac, which changed the microstructure and improved the thermal stability of the film. A test of curcumin release behavior showed controlled release of curcumin from the film matrix. ZS–Cur films displayed remarkable pH responsiveness, strong antioxidant properties, and inhibitory effects on E. coli. Therefore, the insoluble active food packaging prepared in this study provides a new strategy for the development of functional edible films and also provides a possibility for the application of edible films to extend the shelf life of fresh food.

Abstract Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive pulmonary vascular disease characterized by pulmonary artery stenosis or obstructions resulting from insufficient thrombus resolution. Chemokine (C‐X‐C motif) ligand 10 (CXCL10) is a chemokine that contributes to the pathogenesis of many autoimmune diseases and cancers. The present study aims to investigate the levels of CXCL10 in patients with CTEPH throughout balloon pulmonary angioplasty (BPA) and its correlation with the improvement of pulmonary hemodynamics. Plasma CXCL10 levels were measured in 38 CTEPH patients with 100 BPA sessions and in 28 healthy controls. Correlations between CXCL10 and pulmonary hemodynamics were investigated. Receiver operating characteristic (ROC) curves were plotted to display the diagnostic value and the predictive ability for perioperative complications of CXCL10 and CXCL10‐related models. Nomograms were plotted to visualize the diagnostic value and the predictive ability for perioperative complications of CXCL10 and CXCL10‐related models. CXCL10 levels are higher in CTEPH patients compared with healthy controls (36.5 [95% confidence interval {CI}: 25.0–51.1] vs. 14.8 [95% CI: 11.1–30.9], p

A novel neutral polysaccharide designated as PAP1b was isolated from Areca catechu L. by hot water extraction, ethanol precipitation, and column chromatography. PAP1b was mainly composed of mannose, galactose, xylose, and arabinose in a ratio of 4.1:3.3:0.9:1.7, with an average molecular weight of 37.3 kDa. Structural characterization indicated that the backbone of PAP1b appeared to be composed mainly of → 6-β-Manp-(1 →, → 4)-α-Galp-(1 → and → 3,6)-β-Manp-(1 →) residues with some branches, and terminal of (1 →)-linked-β-Manp residues. The results of bioactivity experiments showed that PAP1b had antioxidant in vitro, esspecially on scavenging DPPH and hydroxyl radicals. Therefore, the polysaccharide from Areca catechu L. could be used as a potential antioxidant in functional food.

Abstract Background Early‐stage lung adenocarcinoma that radiologically manifests as part‐solid nodules, consisting of both ground‐glass and solid components, has distinctive growth patterns and prognosis. The characteristics of the tumour microenvironment and transcriptional features of the malignant cells of different radiological phenotypes remain poorly understood. Methods Twelve treatment‐naive patients with radiological part‐solid nodules were enrolled. After frozen pathology was confirmed as lung adenocarcinoma, two regions (ground‐glass and solid) from each of the 12 part‐solid nodules and 5 normal lung tissues from 5 of the12 patients were subjected to single‐cell sequencing by 10x Genomics. We used Seurat v3.1.5 for data integration and analysis. Results We comprehensively dissected the multicellular ecosystem of the ground‐glass and solid components of part‐solid nodules at the single‐cell resolution. In tumours, these components had comparable proportions of malignant cells. However, the angiogenesis, epithelial‐to‐mesenchymal transition, KRAS, p53, and cell‐cycle signalling pathways were significantly up‐regulated in malignant cells within solid components compared to those within ground‐glass components. For the tumour microenvironment, the relative abundance of myeloid and NK cells tended to be higher in solid components than in ground‐glass components. Slight subtype composition differences existed between the ground‐glass and solid components. The T/NK cell subsets’ cytotoxic function and the macrophages’ pro‐inflammation function were suppressed in solid components. Moreover, pericytes in solid components had a stronger communication related to angiogenesis promotion with endothelial cells and tumour cells. Conclusion The cellular landscape of ground‐glass components is significantly different from that of normal tissue and similar to that of solid components. However, transcriptional differences exist in the vital signalling pathways of malignant and immune cells within these components.

Psoriasis is chronic skin disease and an important health concern. Traditional Chinese Medicine (TCM) has shown great promise in the treatment of psoriasis. However, the correlation between TCM Syndromes and genomics of psoriasis has not been evaluated. Here, we analyzed gene expression profiling of monocytes from psoriasis vulgaris patients with different TCM syndrome types to reveal the molecular basis of different psoriasis syndromes. Of the 62 cases of psoriasis vulgaris recruited, 16, 23, and 23 cases were of blood-heat syndrome, blood stasis syndrome, and blood-dryness syndrome, respectively; 10 healthy controls were recruited as controls. Affymertix’s Gene Chip ®clariom D gene chip was used to detect the gene expression profile of peripheral blood monocytes collected from recruited individuals. Compared with the healthy control group, 1570 genes were up-regulated and 977 genes were down-regulated in the psoriasis vulgaris patients group; 798 genes and 108 genes were up- and down-regulated in the blood-heat syndrome group respectively; 319 and 433 genes were up- and down-regulated in the blood-dryness syndrome group, respectively; and 502 and 179 genes were up-and down-regulated in the blood-stasis syndrome group. Our analyses indicated not only common differential genes and pathways between psoriasis syndrome groups and healthy controls, but also syndrome-specific genes and pathways. The results of this study link the three syndromes at the gene level and will be useful for clarifying the molecular basis of TCM syndromes of psoriasis.Clinical Trial Registration: (http://www.chictr.org.cn/showproj.aspx?proj=4390), identifier (ChiCTR-TRC-14005185).

Psoriasis is a chronic and refractory inflammatory and autoimmune-mediated cutaneous disease affecting approximately 2%–3% of the global population. Most of the current therapies could relieve symptoms rapidly, while the side effects cannot be negligible. Hence, it is urgent to explore much safer and more effective treatments. In the current work, we evaluated the potential beneficial effect of Punica granatum peel polysaccharides (PPPs) in an imiquimod-elicited psoriasis-like mouse model and unraveled their mechanism of action. Firstly, PPPs were isolated from P. granatum peels, and then the molecular weight was determined and monosaccharide analysis was performed. The results revealed that PPPs significantly ameliorated psoriasis-like skin lesions and reduced the Psoriasis Area and Severity Index (PASI) scores and transepidermal water loss (TEWL). PPPs also attenuated the expressions of CD3 and Ki67 in psoriasis-like mouse skin and suppressed the serum or skin levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), IL-1β, IL-8, IL-17, and IL-23. Moreover, PPPs were able to upregulate the mRNA and protein expressions of aquaporin-3 (AQP3) and filaggrin (FLG) in the skin of mice. In addition, PPPs inhibited the NF-κB and STAT3 signaling pathways. Overall, these results indicated that PPPs ameliorated the symptoms of psoriasis through inhibition of the inflammatory cytokines by suppressing the NF-κB and STAT3 signaling pathways and improved skin barrier protection via enhancing AQP3 and FLG. These observations potentially contribute to providing theoretical and experimental evidence for the clinical application of PPPs for psoriasis.

Abstract Background To analyze the expression of miRNA (microRNA) in peripheral blood mononuclear cells in patients with Psoriasis vulgaris with different TCM syndromes by miRNA chip. It further revealed the micromaterial basis of different syndrome types of psoriasis at the miRNA level. Methods Peripheral blood monocytes were collected and prepared from 30 patients with Psoriasis vulgaris (including 9 patients of blood heat syndrome, 8 patients of blood stasis syndrome, and 13 patients of blood dry syndrome) and 9 healthy controls. The miRNA expression profile of peripheral blood monocytes was detected by Agilent Hum miRNA chip. Results Compared to the healthy control group, 156 upregulated and 242 downregulated miRNAs were detected in all psoriasis patients. Compared to the healthy control group, 40 miRNAs were upregulated and 44 were downregulated in the blood heat syndrome group. Furthermore, there were 49 upregulated miRNAs and 44 downregulated miRNAs in the dry syndrome group as compared to the healthy control group. Also, 67 miRNAs were upregulated and 154 miRNAs were downregulated in the blood stasis syndrome group as compared to the healthy control group. Conclusions There are common different miRNAs and pathways, as well as specific miRNAs between the psoriasis and the healthy control groups. Trial registration ChiCTR-TRC-14005185 registered on August 8, 2014.

Summary: Every human somatic cell inherits a maternal and a paternal genome, which work together to give rise to cellular phenotypes. However, the allele-specific relationship between gene expression and genome structure through the cell cycle is largely unknown. By integrating haplotype-resolved genome-wide chromosome conformation capture, mature and nascent mRNA, and protein binding data from a B lymphoblastoid cell line, we investigate this relationship both globally and locally. We introduce the maternal and paternal 4D Nucleome, enabling detailed analysis of the mechanisms and dynamics of genome structure and gene function for diploid organisms. Our analyses find significant coordination between allelic expression biases and local genome conformation, and notably absent expression bias in universally essential cell cycle and glycolysis genes. We propose a model in which coordinated biallelic expression reflects prioritized preservation of essential gene sets.

In this study, tender coconuts were treated with high-intensity ultrasound (US) for 20 min at a frequency of 20 kHz and a power of 2400 W. Compared with control group, US treated coconut water had a higher content of total soluble solid and sugar/acid ratio along with a lower pH value and conductivity, and the contents of sucrose, fructose and glucose were also higher. Results from HS-SPME/GC–MS showed that there was no significant difference in the content of volatile compounds in coconut water before and after US treatment. The activities of sugar metabolism enzymes such as sucrose phosphate synthase, sucrose synthase, acid invertase (AI) and neutral invertase were inhibited by US, of which AI had the strongest inactivation. Circular dichroism and fluorescence spectra showed that the secondary and tertiary structure of AI molecule were destroyed with the increase of US intensity and time, which was confirmed by the change of particle size distribution pattern and scanning electron microscopy. Molecular docking and molecular dynamics showed that US treatment prevented the recognition and binding of sucrose and AI molecules, thereby inhibiting the decomposition of sucrose. In conclusion, our results indicate that US can inhibit the activity of AI and maintain the sugar content to increase the quality as well as extend the shelflife of coconut water, which will bring more commercial value.

Arecanut (Areca catechu L.) is one of the most important industrial crops in tropical Asia and parts of east Africa. However, the arecanut industry has suffered pandemic loss caused by negative reports such as carcinogenic effect. The healthy development of arecanut industry is of great significance. Our previous study found that arecanut (Areca catechu L.) seed polyphenol (ACP) can increase bone mass in ovariectomized rats which is closely related to metabolism of tryptophan. Here, we investigated the relationship among ACP, bone metabolism and serum metabolism in ovariectomized osteoporosis rat. We observed the bone structure of femur and analyzed the LDL-receptor relater protein 5 (LRP5), 5-hydroxytryptophan initial synthetase enzyme 1 (Tph1) and gut-derived serotonin (5-HT) in the gut, bone alkaline phosphatase (BALP), osteocalcin (OCN), Runt-related transcription factor 2 (RUNX2), osteoprotegerin (OPG) and receptor activator of nuclear factor NF-κB ligand (RANKL) in serum, 5-hydroxytryptophan receptor protein (Htr1b), bone morphogenetic protein-2 (BMP2) and β-catenin expression in bone and serum metabolites. The results indicated that compared with osteoporosis rats, ACP significantly improved the damaged bone structure, increased the ratio of OPG/RANKL, Lrp5, BMP2 and β-catenin. The ACP and E2 remarkably enhanced the expression of the metabolites such as 7-Ketodeoxycholic acid, indole and 15-Deoxy-Δ12, 14-prostaglandin, which were deeply linked with 5-HT synthesis via Lrp5 and tryptophan metabolism. Altogether, these studies shown that the ACP could downregulate 5-HT, which were implicated in serum metabolism and promoted bone mass by controlling the bone resorption and formation.

Psoriasis is a chronic proliferative skin disorder characterised by abnormal epidermal differentiation. The Fuzhenghefuzhiyang (FZHFZY) formula created by Chuanjian Lu, a master of Chinese medicine in dermatology, has been external used in the Guangdong Provincial Hospital of Chinese Medicine for the treatment of psoriasis, but its mechanisms of action against psoriasis remain poorly understood. This study involved an exploration of the effects of FZHFZY on epidermal differentiation and its underlying mechanisms in interleukin (IL)-17A/IL-22/interferon (IFN)-γ/tumour necrosis factor (TNF)-α–stimulated HaCaT cells and in a mouse model of imiquimod (IMQ)-induced psoriasis. Cell viability was assessed by MTT assay. Epidermal differentiation was detected by reverse-transcription polymerase chain reaction and western blotting. Histological evaluation of the skin tissue was performed via haematoxylin and eosin staining, and the Akt/mTORC1/S6K1 pathway was analysed by western blotting. FZHFZY inhibited proliferation and improved epidermal differentiation in IL-17A/IL-22/IFN-γ/TNF-α–induced HaCaT cells. FZHFZY ameliorated symptoms of psoriasis, regulated epidermal differentiation and inhibited phosphorylation of the Akt/mTORC1/S6K1 pathway in the skin of mice with imiquimod-induced psoriasis. Our results suggest that FZHFZY may exhibit therapeutic action against psoriasis by regulating epidermal differentiation via inhibition of the Akt/mTORC1/S6K1 pathway.

Non-alcoholic fatty liver disease (NAFLD) is one of the most widespread chronic diseases. Previous reports showed that Ganoderma amboinense polysaccharide (GAP) could protect the liver. In this study, high-fat diet (HFD) mice were given GAP for 8 weeks to evaluate the feasibility of GAP to prevent NAFLD and explore its mechanism of action. The results showed that GAP effectively prevented the development of NAFLD, at the same time, reduced the body weight, liver weight and blood lipid levels. Through the serum biochemical analysis and metabolomics analysis, it was found that GAP promoted fat transport in the liver by regulating the phosphatidylcholine content in the blood. At the same time, GAP regulated some metabolic pathways and protected the mitochondrial function of HFD-mouse liver cells, which is the basis for the rapid catabolism of lipids. These results indicated that GAP could be used as a potential preventive and therapeutic agent for NAFLD.

Linalool showed a broad-spectrum antibacterial effect, but few studies have elucidated the antibacterial mechanism of linalool on Pseudomonas fragi (P. fragi) to date. The present study aimed to uncover the antimicrobial activity and potential mechanism of linalool against P. fragi by determining key enzyme activities and metabolites combined with a high-throughput method and metabolomic pathway analysis. As a result, linalool had excellent inhibitory activity against P. fragi with MIC of 1.5 mL/L. In addition, the presence of linalool significantly altered the intracellular metabolic profile and a total of 346 differential metabolites were identified, of which 201 were up-regulated and 145 were down-regulated. The highlight pathways included beta-alanine metabolism, pantothenic acid and CoA metabolism, alanine, aspartate and glutamate metabolism, nicotinate and nicotinamide metabolism. Overall, linalool could cause metabolic disorders in cells, and the main metabolic pathways involved energy metabolism, amino acid metabolism and nucleic acid metabolism. In particular, the results of intracellular ATP content and related enzymatic activities (ATPase, SDH, and GOT) also highlighted that energy limitation and amino acid disturbance occurred intracellularly. Together, these findings provided new insights into the mechanism by which linalool inhibited P. fragi and theoretical guidance for its development as a natural preservative.