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Abstract Fruit, as a source of antioxidants and phenolic compounds, is perishable. It also has an underutilized component. Fruit leather has a long shelf life in the form of thin sheets with a distinctive texture. This study aimed to investigate the effect of seaweed (Eucheuma cottonii) addition on the physicochemical and sensory quality of fruit leather made from the combination of red dragon fruit and watermelon rind. The physicochemical quality was characterized by measuring the critical quality parameters of fruit leathers, including proximate analysis, water activity, total phenol, antioxidant activity, texture, and organoleptic analysis. The statistical analysis of phenolic compound activity, antioxidant activity, vitamin C, moisture content, carbohydrates, and water activity (aw) was conducted using a one-way ANOVA test, while the analysis of ash content, protein, fat, tensile strength, elongation, and organoleptic properties was performed using the Kruskal–Wallis test. Increasing seaweed concentration significantly increased moisture, ash, protein, vitamin C, total phenol, water activity, and elongation but decreased fat content. Furthermore, the increase in seaweed concentration reduced liking toward taste and color significantly but increased texture liking. The best product was the F2 product with 10% seaweed. F2 has the following attributes: 11.07% of moisture content, 2.34% of ash, 1.53% of protein, 0.19% of fat, 84.86% of carbohydrate, 8.17 mg/100 g of vitamin C, 0.41 of water activity, 0.54 N/m2 of tensile strength, 22.22% of elongation, 107.39 ppm of IC50, 1.66 mg/GAE g of total phenolics.

Abstract In this paper we revisit the general phenomenon that scattering amplitudes of pions can be obtained from “dimensional reduction” of gluons in higher dimensions in a more general context. We show that such “dimensional reduction” operations universally turn gluons into pions regardless of details of interactions: under such operations any amplitude that is gauge invariant and contains only local simple poles becomes one that satisfies Adler zero in the soft limit. As two such examples, we show that starting from gluon amplitudes in both superstring and bosonic string theories, the operations produce “stringy” completion of pion scattering amplitudes to all orders in α′, with leading order given by non-linear sigma model amplitudes. Via Kawai-Lewellen-Tye relations, they give closed-stringy completion for Born-Infeld theory and the special Galileon theory, which are directly related to gravity amplitudes in closed-string theories. We also discuss how they naturally produce stringy models for mixed amplitudes of pions and colored scalars.

Summary: The dynamics of N6-methyladenosine (m6A) mRNA modification are tightly controlled by the m6A methyltransferase complex and demethylases. Here, we find that auxin treatment alters m6A modification on auxin-responsive genes. Mechanically, TRANSMEMBRANE KINASE 4 (TMK4), a component of the auxin signaling pathway, interacts with and phosphorylates FKBP12-INTERACTING PROTEIN 37 (FIP37), a core component of the m6A methyltransferase complex, in an auxin-dependent manner. Phosphorylation of FIP37 enhances its interaction with RNA, thereby increasing m6A modification on its target genes, such as NITRILASE 1 (NIT1), a gene involved in indole-3-acetic acid (IAA) biosynthesis. 1-Naphthalacetic acid (NAA) treatment accelerates the mRNA decay of NIT1, in a TMK4- and FIP37-dependent manner, which leads to inhibition of auxin biosynthesis. Our findings identify a regulatory mechanism by which auxin modulates m6A modification through the phosphorylation of FIP37, ultimately affecting mRNA stability and auxin biosynthesis in plants.

Summary: Cognitive dysfunction is a feature in multiple sclerosis (MS), a chronic inflammatory demyelinating disorder. A notable aspect of MS brains is hippocampal demyelination, which is closely associated with cognitive decline. However, the mechanisms underlying this phenomenon remain unclear. Chitinase-3-like (CHI3L1), secreted by activated astrocytes, has been identified as a biomarker for MS progression. Our study investigates CHI3L1’s function within the demyelinating hippocampus and demonstrates a correlation between CHI3L1 expression and cognitive impairment in patients with MS. Activated astrocytes release CHI3L1 in reaction to induced demyelination, which adversely affects the proliferation and differentiation of neural stem cells and impairs dendritic growth, complexity, and spine formation in neurons. Our findings indicate that the astrocytic deletion of CHI3L1 can mitigate neurogenic deficits and cognitive dysfunction. We showed that CHI3L1 interacts with CRTH2/receptor for advanced glycation end (RAGE) by attenuating β-catenin signaling. The reactivation of β-catenin signaling can revitalize neurogenesis, which holds promise for therapy of inflammatory demyelination.

Abstract Eukaryotic five-methylcytosine (m5C) is an important regulator of viral RNA splicing, stability, and translation. However, its role in HBV replication remains largely unknown. In this study, functional m5C sites are identified in hepatitis B virus (HBV) mRNA. The m5C modification at nt 1291 is not only indispensable for Aly/REF export factor (ALYREF) recognition to promote viral mRNA export and HBx translation but also for the inhibition of RIG-I binding to suppress interferon-β (IFN-β) production. Moreover, NOP2/Sun RNA methyltransferase 2 (NSUN2) catalyzes the addition of m5C to HBV mRNA and is transcriptionally downregulated by the viral protein HBx, which suppresses the binding of EGR1 to the NSUN2 promoter. Additionally, NSUN2 expression correlates with m5C modification of type I IFN mRNA in host cells, thus, positively regulating IFN expression. Hence, the delicate regulation of NSUN2 expression induces m5C modification of HBV mRNA while decreasing the levels of m5C in host IFN mRNA, making it a vital component of the HBV life cycle. These findings provide new molecular insights into the mechanism of HBV-mediated IFN inhibition and may inform the development of new IFN-α based therapies.

Amorphous alloys produced through rapid solidification offer a host of exceptional properties, with the caveat that achieving a fully amorphous structure. In our laboratory, the FeSiBPC alloy has demonstrated substantial industrial potential, but it contends with a persistent challenge in the form of surface crystallization during large-scale manufacturing. This study delves into the phenomenon of surface crystallization, variables influencing surface crystallization and elucidate its distinctive characteristics were studied. A noteworthy breakthrough emerges with the inaugural characterization of a high-quality fiber texture within an Fe-based amorphous alloy, achieved through Electron Backscattered Diffraction. Our findings underscore the remarkable sensitivity of air pressure within the chamber, revealing its significant impact on the intensity of Bragg peaks related to surface crystals. Moreover, the crucial role of an oxide atmosphere in effectively mitigating surface crystallization and offer insights into the mechanisms governing this preventive action. This study provides valuable insights into the intricate interplay of factors governing surface crystallization in amorphous alloys, offering promising avenues for enhanced industrial applications.

Abstract Background Abnormalities in the 5-HT system and synaptic plasticity are hallmark features of schizophrenia. Previous studies suggest that the human endogenous retrovirus W family envelope (ERVWE1) is an influential risk factor for schizophrenia and inversely correlates with 5-HT4 receptor in schizophrenia. To our knowledge, no data describes the effect of ERVWE1 on 5-HT neuronal plasticity. N6-methyladenosine (m6A) regulates gene expression and impacts synaptic plasticity. Our research aims to systematically investigate the effects of ERVWE1 on 5-HT neuronal plasticity through m6A modification in schizophrenia. Results HTR1B, ALKBH5, and Arc exhibited higher levels in individuals with first-episode schizophrenia compared to the controls and showed a strong positive correlation with ERVWE1. Interestingly, HTR1B was also correlated with ALKBH5 and Arc. Further analyses confirmed that ALKBH5 may be an independent risk factor for schizophrenia. In vitro studies, we discovered that ERVWE1 enhanced HTR1B expression, thereby activating the ERK-ELK1-Arc pathway and reducing the complexity and spine density of 5-HT neurons. Furthermore, ERVWE1 reduced m6A levels through ALKBH5 demethylation. ERVWE1 induced HTR1B upregulation by improving its mRNA stability in ALKBH5-m6A-dependent epigenetic mechanisms. Importantly, ALKBH5 mediated the observed alterations in 5-HT neuronal plasticity induced by ERVWE1. Conclusions Overall, HTR1B, Arc, and ALKBH5 levels were increased in schizophrenia and positively associated with ERVWE1. Moreover, ALKBH5 was a novel risk gene for schizophrenia. ERVWE1 impaired 5-HT neuronal plasticity in ALKBH5-m6A dependent mechanism by the HTR1B-ERK-ELK1-Arc pathway, which may be an important contributor to aberrant synaptic plasticity in schizophrenia.

Background: Sarcopenia, characterised by an ongoing loss of skeletal muscle mass and reduced strength and function, is frequently observed in patients with non-small cell lung cancer (NSCLC). However, the relationship between sarcopenia and the prognosis of NSCLC treated with immune checkpoint inhibitors (ICIs) remains unclear. This aimed to assess whether sarcopenia is an independent prognostic factor for survival in patients with advanced NSCLC receiving ICIs. Methods: For this retrospective cohort study, we analysed the medical records of patients attending our hospital aged 18–75 years who were newly diagnosed with stage IIIB to stage IV NSCLC, and who had received ICIs as first- or second-line therapy between May 2019 and April 2022. The skeletal muscle index (SMI) was calculated from computed tomography (CT) images and relevant clinical characteristics within 4 weeks of initiating treatment and used to diagnose sarcopenia status. The Kaplan-Meier method and log-rank test were used to calculate and compare patients' progression-free survival (PFS). Cox proportional hazard regression was used to examine the associations between sarcopenia and survival outcomes. The chi-square test was used to compare treatment response outcomes, such as the objective response rate (ORR), disease control rate (DCR), and immunotherapy-related adverse events (irAEs), between individuals with and without sarcopenia. Additionally, the Student's t-test was utilised to compare SMI values between patients by their objective response (OR) and disease control (DC). Finally, the Mann-Whitney U test was used to compare nutritional and inflammatory indicators between the sarcopenia groups. Results: The study enrolled 70 patients, of whom 34 (48.6%) were diagnosed with sarcopenia. The median PFS of patients with and without sarcopenia was 7.5 vs. 13.4 months, respectively (p = 0.006). The proportional hazards regression analysis showed sarcopenia to be an independent prognostic factor for shorter PFS (hazard ratio (HR): 0.504, 95% CI: 0.265–0.962, p = 0.038). Using chi square tests, we found significant differences in the ORR (20.59% vs. 58.33%, p = 0.001) and occurrence of any irAEs (44.1% vs. 22.2%, p = 0.028) between the sarcopenia and the non-sarcopenia groups, respectively. The Student's t-test showed a significant difference in SMI between the ORR group and the non-ORR group (49.99 ± 7.00 vs. 42.98 ± 2.18 cm2/m2, p = 0.0015). While the sarcopenia group were with significantly a lower CD4+/CD8+ ratios and a higher C-reactive protein (CRP) level (p = 0.026, p = 0.011, respectively). Conclusions: This study found that sarcopenia is a significant predictor of a poor prognosis for patients with advanced NSCLC receiving ICIs. Multiple inflammatory and immune functions related to prognosis also differ by sarcopenia status.

Research on food-derived immunoregulatory peptides has attracted increasing attention of scientists worldwide. However, the structure–activity relationship of rice immunopeptides was not clearly. Herein, 114 rice immunopeptides were obtained by simulating the enzymatic hydrolysis of rice proteins and were further analyzed by NetMHCIipan-4.0. Subsequently, the molecular docking was used to simulate the binding of immunoreactive peptides to major histocompatibility complex class II (MHC-II) molecules. Results show that S, R, D, E, and T amino acid could easily form hydrogen bonds with MHC-II molecules, thus enhancing innate and adaptive immunity. Finally, glucose-modified rice immunopeptides were to investigate the binding of the peptides with MHC-II molecules after glycosylation modification; this provided a theoretical basis for the targeted modification of the generated immunopeptides. All in all, the present study provides a theoretical foundation to further utilize rice processing byproducts and other food products to enhance immunity.

Background and Objectives: Connexin 43 (Cx43) is involved in the transfer of small signaling molecules between neighboring cells, thereby exerting a major influence on the initiation and progression of tumorigenesis. However, there is a lack of systematic research on Cx43 expression and its predictive role in clinical diagnosis and prognosis in pan-cancer. Materials and Methods: Several biological databases were used to evaluate the expression levels of GJA1 (encoding Cx43) and its diagnostic and prognostic significance in pan-cancer. We targeted kidney renal clear cell carcinoma (KIRC) and investigated the relationship between GJA1 expression and different clinical features of KIRC patients. Then, we performed cell-based experiments to partially confirm our results and predicted several proteins that were functionally related to Cx43. Results: The expression of GJA1 has a high level of accuracy in predicting KIRC. High GJA1 expression was remarkably correlated with a favorable prognosis, and this expression was reduced in groups with poor clinical features in KIRC. Cell experiments confirmed the inhibitory effects of increased GJA1 expression on the migratory capacity of human renal cancer (RCC) cell lines, and protein–protein interaction (PPI) analysis predicted that CDH1 and CTNNB1 were closely related to Cx43. Conclusions: GJA1 could be a promising independent favorable prognostic factor for KIRC, and upregulation of GJA1 expression could inhibit the migratory capacity of renal cancer cells.

Due to the complex environment and ground stress at depth, and the various cross-sectional shapes and sizes, the damage types of deep roadways are diversified. The maximum ground stress, maximum compressive strength, and the corresponding support methods are compared by systematically analyzing the influence of high stress and dynamic pressure on the deep weak surrounding rock of roadways. And the stress intensity ratio is proposed to evaluate the support difficulty of surrounding rock of roadways. Then, the concept of active-passive full space collaborative control is proposed, and the core of the concept is to control the deformation of the roadway through active support methods such as destressing, grouting and bolt-cable to bring the self-supporting capacity of the surrounding rock of roadway into play, forming an active support body, and restoring its partial bearing capacity. Using passive support methods such as concrete-filled steel tube sets and U-shaped steel sets with high support resistance to form a passive support ring to assist or mobilize the bearing capacity of the rock surrounding roadways. Additionally, the mechanical mechanism of the collaborative support for concrete-filled steel tube sets and bolt-cable were analyzed, and the active-passive full space collaborative control technology and construction technique were developed and applied in the field. The study shows that the bolt-cable can reduce the bending moment and shear force of the concrete-filled steel tube sets, while reducing the axial force of the support and protecting the steel tube and the core concrete with poor tensile properties. The active-passive full space cooperative control technology has been successfully applied in deep roadway subjected to dynamic pressure and weak rock roadway in Jincheng Hudi Coal Mine and Yangquan Xinyuan Coal Mine, which has further developed the theory and technology of equal-strength support in deep roadway.

Wind turbine towers experience complex dynamic loads during actual operation, and these loads are difficult to accurately predict in advance, which may lead to inaccurate structural fatigue and strength assessment during the structural design phase, thereby posing safety risks to the wind turbine tower. However, online monitoring of wind loads has become possible with the development of load identification technology. Therefore, an identification method for wind load exerted on wind turbine towers was developed in this study to estimate the wind loads using structural strain, which can be used for online monitoring of wind loads. The wind loads exerted on the wind turbine tower were simplified into six equivalent concentrated forces on the topside of the tower, and the initial mathematical model for wind load identification was established based on dynamic load identification theory in the frequency domain, in which many candidate sensor locations and directions were considered. Then, the initial mathematical model was expressed as a linear system of equations. A numerical example was used to verify the accuracy and stability of the initial mathematical model for the wind load identification, and the identification results indicate that the initial mathematical model combined with the Moore–Penrose inverse algorithm can provide stable and accurate reconstruction results. However, the initial mathematical model uses too many sensors, which is not conducive to engineering applications. Therefore, D-optimal and C-optimal design methods were used to reduce the dimension of the initial mathematical model and determine the location and direction of strain gauges. The C-optimal design method adopts a direct optimisation search strategy, while the D-optimal design method adopts an indirect optimisation search strategy. Then, four numerical examples of wind load identification show that dimensionality reduction of the mathematical model leads to high accuracy, in which the C-optimal design algorithm provides more robust identification results. Moreover, the fatigue damage calculated based on the load identification wind loads closely approximates that derived from finite element simulation wind load, with a relative error within 6%. Therefore, the load identification method developed in this study offers a pragmatic solution for the accurate acquisition of the actual wind load of a wind turbine tower.

Summary: Cognitive impairment has been associated with an age-related decline in adult hippocampal neurogenesis (AHN). The molecular basis of declining neurogenesis in the aging hippocampus remains to be elucidated. Here, we show that pleiotrophin (PTN) expression is decreased with aging in neural stem and progenitor cells (NSPCs). Mice lacking PTN exhibit impaired AHN accompanied by poor learning and memory. Mechanistically, we find that PTN engages with protein tyrosine phosphatase receptor type Z1 (PTPRZ1) to promote NSPC proliferation and differentiation by activating AKT signaling. PTN overexpression or pharmacological activation of AKT signaling in aging mice restores AHN and alleviates relevant memory deficits. Importantly, we also find that PTN overexpression improves impaired neurogenesis in senescence-accelerated mouse prone 8 (SAMP8) mice. We further confirm that PTN is required for enriched environment-induced increases in AHN. These results corroborate the significance of AHN in aging and reveal a possible therapeutic intervention by targeting PTN.

Summary: Mitochondria play important roles in angiogenesis. However, the mechanisms remain elusive. In this study, we found that mitochondrial ubiquinol-cytochrome c reductase complex assembly factor 3 (UQCC3) is a key regulator of angiogenesis. TALEN-mediated knockout of Uqcc3 in mice caused embryonic lethality at 9.5–10.5 days postcoitum, and vessel density was dramatically reduced. Similarly, knockout of uqcc3 in zebrafish induced lethality post-fertilization and impaired vascular development. Knockout of UQCC3 resulted in slower tumor growth and angiogenesis. Mechanistically, UQCC3 was upregulated under hypoxia, promoted reactive oxygen species (ROS) generation, enhanced HIF-1α stability and increased VEGF expression. Finally, higher expression of UQCC3 was associated with poor prognosis in multiple types tumors, implying a role for UQCC3 in tumor progression. In conclusion, our findings highlight the important contribution of UQCC3 to angiogenesis under both physiological and pathological conditions, indicating the potential of UQCC3 as a therapeutic target for cancer.

In order to alleviate the shortage of natural sand and gravel resources, an orthogonal test was used to study the mechanics of recycled concrete from gold tailings. Four influencing factors of water-cement ratio, gold tailing sand substitution rate, recycled coarse aggregate substitution rate and fly ash content were selected, and two performance indicators of compressive strength and tensile strength of gold tailing sand recycled concrete were obtained. The performance was also researched on the ratio optimization combination. Results showed that the water-cement ratio and the content of fly ash have significant effects on the two evaluation indexes, followed by the replacement rate of gold tailing sand, while the reclaimed coarse aggregate of secondary crushing has little effect on the two indexes. The optimal factor level scheme for the preparation of recycled concrete with gold tailing sand is the water-cement ratio of 0.45, the replacement rate of gold tailing sand, the replacement rate of recycled coarse aggregate of 30% and the content of fly ash of 10%. By comparing the strength of recycled concrete with ordinary concrete and recycled concrete with the best ratio of gold tailing sand, it can be seen that it is feasible to use gold tailing sand in recycled concrete.

Cluster states are essential quantum resources for one-way quantum computations and quantum networks. The reliable generation of cluster states in specific quantum systems is crucial for initializing complex quantum operations. In this paper, we introduce an efficient scheme for the deterministic preparation of a cluster state via circuit quantum electrodynamics (QED). Our scheme involves four individual microwave resonators, each of which is coupled to a superconducting transmon qutrit. We demonstrated that a four-cqubit cluster state can be achieved using three controlled-phase gate operations. The cluster state is prepared deterministically, eliminating the need for measurement-based feedback. Throughout these operations, the qutrit remains in its ground state, effectively minimizing decoherence from the qutrit. Numerical simulations suggest that our scheme can generate high-fidelity cluster states using current-circuit QED technology. We believe that our model will facilitate exploration of future large-scale continuous-variable quantum information processing systems.

Abstract Whether metabolites derived from injured renal tubular epithelial cells (TECs) participate in renal fibrosis is poorly explored. After TEC injury, various metabolites are released and among the most potent is adenosine triphosphate (ATP), which is released via ATP-permeable channels. In these hemichannels, connexin 43 (Cx43) is the most common member. However, its role in renal interstitial fibrosis (RIF) has not been fully examined. We analyzed renal samples from patients with obstructive nephropathy and mice with unilateral ureteral obstruction (UUO). Cx43-KSP mice were generated to deplete Cx43 in TECs. Through transcriptomics, metabolomics, and single-cell sequencing multi-omics analysis, the relationship among tubular Cx43, ATP, and macrophages in renal fibrosis was explored. The expression of Cx43 in TECs was upregulated in both patients and mice with obstructive nephropathy. Knockdown of Cx43 in TECs or using Cx43-specific inhibitors reduced UUO-induced inflammation and fibrosis in mice. Single-cell RNA sequencing showed that ATP specific receptors, including P2rx4 and P2rx7, were distributed mainly on macrophages. We found that P2rx4- or P2rx7-positive macrophages underwent pyroptosis after UUO, and in vitro ATP directly induced pyroptosis by macrophages. The administration of P2 receptor or P2X7 receptor blockers to UUO mice inhibited macrophage pyroptosis and demonstrated a similar degree of renoprotection as Cx43 genetic depletion. Further, we found that GAP 26 (a Cx43 hemichannel inhibitor) and A-839977 (an inhibitor of the pyroptosis receptor) alleviated UUO-induced fibrosis, while BzATP (the agonist of pyroptosis receptor) exacerbated fibrosis. Single-cell sequencing demonstrated that the pyroptotic macrophages upregulated the release of CXCL10, which activated intrarenal fibroblasts. Cx43 mediates the release of ATP from TECs during renal injury, inducing peritubular macrophage pyroptosis, which subsequently leads to the release of CXCL10 and activation of intrarenal fibroblasts and acceleration of renal fibrosis.

Abstract Cost‐effective and under‐exploited plant species as functional food ingredients represent alternatives to chemicals with safety concerns and potent toxicity. Staghorn sumac (Rhus typhina) is considered a good source of natural polyphenols, which can be introduced into food products to carry out some specific technological functions (e.g., antioxidation and preservation). However, sumac fruit as a spice is under‐explored for its diversified uses in various food products as a novel functional ingredient. This study explored the technological feasibility and sensory acceptability of two representative sumac‐fortified food systems, namely Cheddar cheese and ground beef. Extracts of sumac (0.5%−5%) dose‐dependently increased the total phenolic and anthocyanin contents, while reducing thiobarbituric acid reactive substance (up to 46%), total plate counts of bacteria (up to 4.5 log colony‐forming units [CFU]/g) and pH of the cheese. In fresh ground beef, sumac extract at concentrations of 1%−5% was effective in reducing the total aerobic counts of Escherichia coli inoculated fresh ground beef by 0.16−1.14 log CFU/g, while improving meat color and oxidative stability during a storage period of 7 days at 4°C. Phytochemical profiling by high‐performance liquid chromatography showed the presence of gallic acid, caffeic acid, ellagic acid, quercetin and anthocyanins in the sumac extracts. These compounds were possibly responsible for the antimicrobial and antioxidant activities in the evaluated food systems. Sensory acceptability of Cheddar cheese or cooked beef meatballs with sumac extract addition (0.5%−3%) were similar to their respective controls. This study provides a feasible approach to satisfy health‐conscious consumers who favor a natural multifunctional ingredient to preserve food products.

BackgroundProspective studies on the association between Helicobacter pylori (H. pylori) infection and subclinical hyperthyroidism are limited. We, therefore, designed a large-scale cohort study to explore the association between H. pylori infection and the risk of subclinical hyperthyroidism in women.MethodsThis prospective cohort study investigated 2,713 participants. H. pylori infection was diagnosed with the carbon 13 breath test. Subclinical hyperthyroidism was defined as serum thyroid-stimulating hormone levels are low or undetectable but free thyroxine and tri-iodothyronine concentrations are normal. Propensity score matching (PSM) analyses and Cox proportional hazards regression models were used to estimate the association between H. pylori infection and subclinical hyperthyroidism.ResultsA total of 1,025 PS-matched pairs of H. pylori infection women were generated after PSM. During 6 years of follow-up, the incidence rate of subclinical hyperthyroidism was 7.35/1,000 person-years. After adjusting potential confounding factors (including iodine intake in food and three main dietary patterns score), the multivariable hazard ratio (HR; 95% confidence intervals) of subclinical hyperthyroidism by H. pylori infection was 2.49 (1.36, 4.56). Stratified analyses suggested a potential effect modification by age, the multivariable HR (95% confidence intervals) was 2.85 (1.45, 5.61) in participants aged ≥ 40 years and 0.70 (0.08, 6.00) in participants aged < 40 years (P for interaction = 0.048).ConclusionOur prospective study first indicates that H. pylori infection is significantly associated with the risk of subclinical hyperthyroidism independent of dietary factors among Chinese women, especially in middle-aged and older individuals.Clinical Trial Registration:https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000031137, identifier UMIN000027174.

Theabrownins (TBs) in dark tea have received increasing attention for their multiple health benefits. In this study, ultrasound assisted extraction with deep eutectic solvent (UAE-DES) was developed for the extraction of TBs from Kangzhuan dark tea (KZDT). The highest yield (12.59%) of TBs was obtained using UAE-choline (ChCl)/malic acid (MA) with a liquid to solid ratio of 20:1 (v/w), ultrasonic power of 577 W, ultrasonic time of 25 min, and water content of 30%. TBs were further eluded by silica gel to obtain six theabrownine fractions (TBFs), namely, TBFs1, TBFs2, TBFs3, TBFs4, TBFs5, and TBFs6. LC-MS/MS revealed that flavonoids, terpenes, phenolic acids, alkaloids, lipids, and amino acids are the leading components of TBFs. The TBFs4, with the DPPH, ABTS, and FRAP values of 45.08 ± 0.42 μM Ascorbic acid/g DW, 178.52 ± 0.29 μM Trolox/g DW, and 370.85 ± 6.00 μM Fe(II)/g DW, respectively, showed the highest antioxidant activity among all the TBFs. Overall, this study first provided the evidence that UAE-ChCl/MA combining with silica gel was effective to extract TBs from KZDT, and the 6,7-dihydroxycoumarin-6-glucoside and neohesperidin were found as the leading compounds in the TBFs, providing a guidance for the chemical research and further utilization of dark tea and its TBs.

Ultrasonication has been identified as a particularly promising technology for homogenization of dairy products. Homogenization of cream, by reducing fat globule size, can be utilized to inhibit creaming. The homogenization of cream usually leads to increased viscosity. Cream with fat level greater than 17% cannot be homogenized with satisfactory results since conventional homogenization methods cause coalescence and mostly agglomeration. The aim of this study was to investigate the influence of ultrasonication on milk cream (5-30% fat) and to study the phenomenon of formation of fat clusters during sonication (0.5-15 mins) at low temperature (2°C). The results showed that ultrasonication can reduce the fat globule size, although it resulted in the formation of fat clusters at short time (

Alpha-fetoprotein-positive gastric cancer (AFPGC) is a type of gastric cancer with a high degree of malignancy. The disease is more common in the elderly, with a high prevalence in males and generally atypical clinical manifestations. For advanced patients, the current treatment options are limited and, to date, few cases of advanced AFPGC have been treated successfully with conventional chemotherapy. With the development of molecular biology and immunology, tumor immunotherapy offers more therapeutic options to patients with advanced gastric cancer. This study describes a case of advanced gastric cancer in a young woman with a high blood alpha-fetoprotein (AFP) level (>54,000 ng/mL). The patient showed initial promising results when programmed cell death-1 (PD-1) inhibitor treatment was combined with chemotherapy after systemic chemotherapy failed. When the disease progressed again after 129 days, adjustment of the treatment regimen to Atezolizumab in combination with Irinotecan and Surufatinib capsules achieved partial remission (PR). There were no immune-related pneumonia, myocarditis, or other adverse effects observed. The patient currently has an overall survival of more than 14 months. This case demonstrated that switching from PD-1 inhibitor to programmed cell death-Ligand 1 (PD-L1) inhibitor therapy may overcome potential resistance. It providing a reference for immunotherapy of patients with AFP-positive advanced gastric cancer.

Schizophrenia, a mental disorder, afflicts 1% of the worldwide population. The dysregulation of homeostasis in the endoplasmic reticulum (ER) has been implicated in schizophrenia. Moreover, recent studies indicate that ER stress and the unfolded protein response (UPR) are linked to this mental disorder. Our previous research has verified that endogenous retrovirus group W member 1 envelope (ERVW-1), a risk factor for schizophrenia, is elevated in individuals with schizophrenia. Nevertheless, no literature is available regarding the underlying relationship between ER stress and ERVW-1 in schizophrenia. The aim of our research was to investigate the molecular mechanism connecting ER stress and ERVW-1 in schizophrenia. Here, we employed Gene Differential Expression Analysis to predict differentially expressed genes (DEGs) in the human prefrontal cortex of schizophrenic patients and identified aberrant expression of UPR-related genes. Subsequent research indicated that the UPR gene called XBP1 had a positive correlation with ATF6, BCL-2, and ERVW-1 in individuals with schizophrenia using Spearman correlation analysis. Furthermore, results from the enzyme-linked immunosorbent assay (ELISA) suggested increased serum protein levels of ATF6 and XBP1 in schizophrenic patients compared with healthy controls, exhibiting a strong correlation with ERVW-1 using median analysis and Mann–Whitney U analysis. However, serum GANAB levels were decreased in schizophrenic patients compared with controls and showed a significant negative correlation with ERVW-1, ATF6, and XBP1 in schizophrenic patients. Interestingly, in vitro experiments verified that ERVW-1 indeed increased ATF6 and XBP1 expression while decreasing GANAB expression. Additionally, the confocal microscope experiment suggested that ERVW-1 could impact the shape of the ER, leading to ER stress. GANAB was found to participate in ER stress regulated by ERVW-1. In conclusion, ERVW-1 induced ER stress by suppressing GANAB expression, thereby upregulating the expression of ATF6 and XBP1 and ultimately contributing to the development of schizophrenia.

Local outlier detection is a hot area and great challenge in data mining, especially for large-scale datasets. On the one hand, traditional algorithms often achieve low-quality detection results and are sensitive to neighborhood size. On the other hand, they are infeasible for large-scale datasets due to at least O(N2) time and space complexity. In light of these, we propose a new local outlier detection algorithm, which is designed based on a new stable neighborhood strategy-dynamic references nearest neighbors (DRNN). Meanwhile, we present a new detection framework by combining the proposed approach and k-mean for large-scale datasets. Experimental results demonstrate that the proposed algorithm can produce higher quality and robust detection results compared to several classic methods. Meanwhile, the new detection framework is able to significantly improve detecting efficiency without sacrificing accuracy.

Abstract Human endogenous retrovirus (HERVs), originating from exogenous retroviral infections of germ cells millions of years ago, have the potential for human diseases. Syncytin-1, an envelope protein encoded by the HERV W family, participates in the contexts of schizophrenia, multiple sclerosis, diabetes, and several types of cancers. Nevertheless, there is no report on the expression pattern and potential mechanism of Syncytin-1 in HCC. Here we found Syncytin-1 expression was up-regulated in HCC compared to adjacent non-tumorous tissues, especially in advanced HCC. Syncytin-1 was an independent risk factor to predict vascular invasion, metastasis, larger tumor size, and poor prognosis in HCC patients. Further analysis discovered that Syncytin-1 overexpression positively associated with HCC patients with serum HBsAg positive. Functional experiments in vitro and in vivo demonstrated that Syncytin-1 enhanced cell proliferation, metastasis, and tumorigenicity in HCC. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that the mitogen-activated protein kinase (MEK)/extracellular signal-regulated protein kinase (ERK) pathway was involved in HCC. Our clinical data indicated that the levels of phosphorylation MEK1/2 and ERK1/2 were increased in HCC comparing with adjacent non-tumorous tissues. It showed the linear correlation between Syncytin-1 expression and upregulated MEK1/2 and ERK1/2 phosphorylation levels in HCC. Furthermore, Syncytin-1 activated MEK/ERK pathway in HCC cells. In-depth research showed that the inflammation-activated MEK/ERK pathway was essential in Syncytin-1 promoted hepatocarcinogenesis. Syncytin-1 suppressed doxorubicin-induced apoptosis via MEK/ERK cascade. In conclusion, Syncytin-1 promoted HCC progression and doxorubicin resistance via the inflammation-activated MEK/ERK pathway. Our findings revealed that Syncytin-1 was a potential prognostic biomarker and therapeutic target for HCC.

Hepatocellular carcinoma (HCC) is one of the most lethal human cancers. Hepatitis B virus (HBV) infection accounts for nearly 50% of HCC cases. Recent studies indicate that HBV infection induces resistance to sorafenib, the first-line systemic treatment for advanced HCC for more than a decade, from 2007 to 2020. Our previous research shows that variant 1 (tv1) of proliferating cell nuclear antigen clamp-associated factor (PCLAF), overexpressed in HCC, protects against doxorubicin-induced apoptosis. However, there are no reports on the relevance of PCLAF in sorafenib resistance in HBV-related HCC. In this article, we found that PCLAF levels were higher in HBV-related HCC than in non-virus-related HCC using bioinformatics analysis. Immunohistochemistry (IHC) staining of clinical samples and the splicing reporter minigene assay using HCC cells revealed that PCLAF tv1 was elevated by HBV. Furthermore, HBV promoted the splicing of PCLAF tv1 by downregulating serine/arginine-rich splicing factor 2 (SRSF2), which hindered the inclusion of PCLAF exon 3 through a putative cis-element (116–123), “GATTCCTG”. The CCK-8 assay showed that HBV decreased cell susceptibility to sorafenib through SRSF2/PCLAF tv1. HBV reduced ferroptosis by decreasing intracellular Fe2+ levels and activating GPX4 expression via the SRSF2/PCLAF tv1 axis, according to a mechanism study. Suppressed ferroptosis, on the other hand, contributed to HBV-mediated sorafenib resistance through SRSF2/PCLAF tv1. These data suggested that HBV regulated PCLAF abnormal alternative splicing by suppressing SRSF2. HBV caused sorafenib resistance by reducing ferroptosis via the SRSF2/PCLAF tv1 axis. As a result, the SRSF2/PCLAF tv1 axis may be a prospective molecular therapeutic target in HBV-related HCC, as well as a predictor of sorafenib resistance. The inhibition of the SRSF2/PCLAF tv1 axis may be crucial in the emergence of systemic chemotherapy resistance in HBV-associated HCC.

Schizophrenia is a severe neuropsychiatric disorder affecting about 1% of individuals worldwide. Increased innate immune activation and neuronal apoptosis are common findings in schizophrenia. Interferon beta (IFN-β), an essential cytokine in promoting and regulating innate immune responses, causes neuronal apoptosis in vitro. However, the precise pathogenesis of schizophrenia is unknown. Recent studies indicate that a domesticated endogenous retroviral envelope glycoprotein of the W family (HERV-W ENV, also called ERVWE1 or syncytin 1), derived from the endogenous retrovirus group W member 1 (ERVWE1) locus on chromosome 7q21.2, has a high level in schizophrenia. Here, we found an increased serum IFN-β level in schizophrenia and showed a positive correlation with HERV-W ENV. In addition, serum long intergenic non-protein coding RNA 1930 (linc01930), decreased in schizophrenia, was negatively correlated with HERV-W ENV and IFN-β. In vitro experiments showed that linc01930, mainly in the nucleus and with noncoding functions, was repressed by HERV-W ENV through promoter activity suppression. Further studies indicated that HERV-W ENV increased IFN-β expression and neuronal apoptosis by restraining the expression of linc01930. Furthermore, HERV-W ENV enhanced cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes protein (STING) expression and interferon regulatory factor 3 (IRF3) phosphorylation in neuronal cells. Notably, cGAS interacted with HERV-W ENV and triggered IFN-β expression and neuronal apoptosis caused by HERV-W ENV. Moreover, Linc01930 participated in the increased neuronal apoptosis and expression level of cGAS and IFN-β induced by HERV-W ENV. To summarize, our results suggested that linc01930 and IFN-β might be novel potential blood-based biomarkers in schizophrenia. The totality of these results also showed that HERV-W ENV facilitated antiviral innate immune response, resulting in neuronal apoptosis through the linc01930/cGAS/STING pathway in schizophrenia. Due to its monoclonal antibody GNbAC1 application in clinical trials, we considered HERV-W ENV might be a reliable therapeutic choice for schizophrenia.

Numerous artificial intelligence (AI) based approaches have been proposed for automatic Alzheimer's disease (AD) prediction with brain structural magnetic resonance imaging (sMRI). Previous studies extract features from the whole brain or individual slices separately, ignoring the properties of multi-view slices and feature complementarity. For this reason, we present a novel AD diagnosis model based on the multiview-slice attention and 3D convolution neural network (3D-CNN). Specifically, we begin by extracting the local slice-level characteristic in various dimensions using multiple sub-networks. Then we proposed a slice-level attention mechanism to emphasize specific 2D-slices to exclude the redundancy features. After that, a 3D-CNN was employed to capture the global subject-level structural changes. Finally, all these 2D and 3D features were fused to obtain more discriminative representations. We conduct the experiments on 1,451 subjects from ADNI-1 and ADNI-2 datasets. Experimental results showed the superiority of our model over the state-of-the-art approaches regarding dementia classification. Specifically, our model achieves accuracy values of 91.1 and 80.1% on ADNI-1 for AD diagnosis and mild cognitive impairment (MCI) convention prediction, respectively.

Vibration-energy harvesting is an effective strategy for replacing batteries and provides a long-term power supply to microelectronic devices. Harvesting vibration energy from human motions has attracted research attention in recent years. Here, a novel low-frequency hybrid piezoelectric and electromagnetic broadband harvester is proposed. Two parallel piezoelectric cantilever beams support the harvester and capture environmental vibration energy based on the piezoelectric effect. A permanent magnet is connected by springs to the two beams, and a fixed coil surrounds the moving permanent magnet, enabling energy conversion via the electromagnetic effect and the proof mass. The parameters influencing the output power of the harvester are optimized numerically to boost the harvester’s performance. The output power of the proposed hybrid harvester is compared with that of a piezoelectric harvester and an electromagnetic harvester. The simulation results show that the output power is significantly higher for the hybrid harvester than for the piezoelectric and electromagnetic harvesters, and the bandwidth is broader owing to the double cantilevers. An experiment is conducted using a prototype of the hybrid harvester to evaluate its output power. The results show multiple resonant peaks, an extended bandwidth, and a maximum power of 6.28 mW. In contrast, the maximum harvested power of the piezoelectric harvester is only 5.15 mW at 9.6 Hz.

Human endogenous retroviruses (HERVs) are remnants of ancestral germline infections by exogenous retroviruses. Human endogenous retroviruses W family envelope gene (HERV-W env, also called ERVWE1), located on chromosome 7q21-22, encodes an envelope glycoprotein from the HERV-W family. Mounting evidence suggests that aberrant expression of ERVWE1 involves the etiology of schizophrenia. Moreover, the genetic and morphological studies indicate that dendritic spine deficits may contribute to the onset of schizophrenia. Here, we reported that ERVWE1 changed the density and morphology of the dendritic spine through inhibiting Wingless-type (Wnt)/c-Jun N-terminal kinases (JNK) non-canonical pathway via miR-141-3p in schizophrenia. In this paper, we found elevated levels of miR-141-3p and a significant positive correlation with ERVWE1 in schizophrenia. Moreover, serum Wnt5a and actin-related protein 2 (Arp2) levels decreased and demonstrated a significant negative correlation with ERVWE1 in schizophrenia. In vitro experiments disclosed that ERVWE1 up-regulated miR-141-3p expression by interacting with transcription factor (TF) Yin Yang 1 (YY1). YY1 modulated miR-141-3p expression by binding to its promoter. The luciferase assay revealed that YY1 enhanced the promoter activity of miR-141-3p. Using the miRNA target prediction databases and luciferase reporter assays, we demonstrated that miR-141-3p targeted Wnt5a at its 3’ untranslated region (3′ UTR). Furthermore, ERVWE1 suppressed the expression of Arp2 through non-canonical pathway, Wnt5a/JNK signaling pathway. In addition, ERVWE1 inhibited Wnt5a/JNK/Arp2 signal pathway through miR-141-3p. Finally, functional assays showed that ERVWE1 induced the abnormalities in hippocampal neuron morphology and spine density through inhibiting Wnt/JNK non-canonical pathway via miR-141-3p in schizophrenia. Our findings indicated that miR-141-3p, Wnt5a, and Arp2 might be potential clinical blood-based biomarkers or therapeutic targets for schizophrenia. Our work also provided new insight into the role of ERVWE1 in schizophrenia pathogenesis.

Background: The promotion of a healthy diet via health education is a component of the “Healthy China 2030” plan. However, few studies have reported whether health knowledge about nutrition and diet has gained public attention, and whether it is needed by the public.Methods: The numbers of views, shares, and reads of articles published by the official WeChat account of a hospital in China were accessed. The influence index was obtained via the entropy analysis of these three indices. A questionnaire survey was developed based on the purpose of the study and the conclusion of the content analysis, which conducted to analyze users' requirements for health knowledge and their influencing factors. Moreover, risk factors were explored by logistic regression models.Results: Of the 103 articles considered in this study, four articles in the Top 10 were related to nutrition and diet. The influence index of nutrition and diet knowledge was found to be the highest in the content analysis (p < 0.05). The higher degrees of humor (β = 0.224, p = 0.027), nutrition and diet articles (β = 0.776, p = 0.034), and cover articles (β = 0.312, p = 0.021) have significant influences on the influence index. In total, 581 questionnaires were obtained, and 78.1% of the respondents reported believing that the health knowledge of greatest concern was that related to nutrition and diet. Multivariate logistic regression analyses were conducted to explore the associations between the features of the articles and users reading nutrition and diet knowledge; it was found that gender (female, OR: 4.651, 95%Cl: 2.598, 8.325, and p < 0.001), age (young adult, OR: 0.358, 95%Cl: 0.266, 0.481, and p < 0.001), cancer precaution knowledge (OR: 4.333, 95%Cl: 2.262, 8.299, and p < 0.001), traditional Chinese medicine (OR: 2.121, 95%Cl: 1.064, 4.230, and p = 0.033), the knowledge acquisition approach [circle of friends (OR: 2.586, 95%Cl: 1.373, 4.868, and p = 0.003), social media (OR: 2.183, 95%Cl: 1.204, 3.960, and p = 0.010)), hospitals (OR: 3.194, 95%Cl: 1.793, 5.692, and p < 0.001), television media (OR: 4.348, 95%Cl: 2.341, 8.077, and p < 0.001)], and social media strategies [professionalism and authority (OR: 2.354, 95%Cl: 1.231, 4.505, and p = 0.006)] have statistically significant relationships with users reading nutrition and diet knowledge.Conclusion: Nutrition and diet knowledge could contribute to WeChat user engagement of health information dissemination. Nutrition professionals should improve the scientific popularization ability and effectively use social media for health promotion.

As important decomposers and plant symbionts, soil fungal communities play a major role in remediating heavy-metal-polluted soils. However, the diversity and structures of fungal communities generally remain unclear in mining areas. This study aimed to assess the rhizospheric fungal-community composition of Masson pine (Pinus massoniana) in the lead-zinc mining area of Suxian District, Hunan Province, China. This experiment undertook the following three treatments: Masson pine inoculated with or not inoculated with Suillus luteus, and bulk soil without plants as a control. The results thereof showed that inoculation of ectomycorrhizal fungi could enlarge plants’ capability to absorb heavy metals and secrete soil enzymes. The richness and diversity of fungi in the rhizospheric soil were significantly higher than of those in the bulk soil (p < 0.05), but no significant difference was noted between the rhizospheric soils inoculated with and not inoculated with ectomycorrhizal (ECM) fungi as the community structure changed. The rhizospheric fungi belonged to 6 phyla, 25 classes, 65 orders, 115 families, and 150 genera, and the dominant phyla were Chytridiomycota (50.49%), Ascomycota (38.54%), and Basidiomycota (9.02%). Through use of LEfSe and heatmapping, the relative abundances of Suillus, Paraglomus, Agaricus, and Tulasnella were found to be the highest in the soil with ECM fungus inoculation. RDA showed that the community structure nearly changed with ECM-fungus inoculation; this was significantly related to soil water content, the carbon–nitrogen ratio, bulk density, available potassium, and soil enzymes. Altogether, inoculation with ECM fungi may change the habitation environments of microorganisms and dominant fungi in soil, providing keystone screenings in heavy-metal-contaminated mining areas.

(1) Objective: Evidence suggests that comprehensive sexuality education (CSE) can protect and empower younger generations to advocate for their reproductive health and wellbeing. This survey aims to investigate the current status and influencing factors of CSE among Chinese junior high school students, and to evaluate its correlation with the learning experience of sex education and subjective social status (SSS) to provide evidence for the implementation of CSE in the future. (2) Methods: A total of 4109 participants aged 11 to 16 years were recruited using data from a cross-sectional survey among junior high school students in China in 2021. CSE knowledge, attitude, and skills were used to generate the CSE comprehensive capacity by a principal component analysis. One-way ANOVA was used to assess the different effects of school sex education and family sex education. Multiple linear regression was used to assess the association between CSE comprehensive capacity and SSS. (3) Results: The average score of CSE comprehensive capacity was 82.44 ± 8.60 (with a total score of 100 points) among participants. After the adjustment, subjective social status was positively related to CSE comprehensive capacity (B = 0.28, 95% CI: 0.20–0.36), and SSS (School) (beta = 0.62) had a higher impact on CSE comprehensive capacity compared to SSS (Family) (beta = −0.10). School sex education was associated with the CSE knowledge level with a larger magnitude compared to family sex education (mean deviation = −0.53, p = 0.031), whereas family sex education was related to the CSE skill level with a greater magnitude (mean deviation =1.14, p = 0.005). (4) Conclusions: These findings suggest that sex education at school and within the family might have a different impact on CSE capacity, which was positively associated with SSS among junior high school students.

Abstract Background Keto-analogues administration plays an important role in clinical chronic kidney disease (CKD) adjunctive therapy, however previous studies on their reno-protective effect mainly focused on kidney pathological changes induced by nephrectomy. This study was designed to explore the currently understudied alternative mechanisms by which compound α-ketoacid tablets (KA) influenced ischemia–reperfusion (IR) induced murine renal injury, and to probe the current status of KA administration on staving CKD progression in Chinese CKD patients at different stages. Methods In animal experiment, IR surgery was performed to mimic progressive chronic kidney injury, while KA was administrated orally. For clinical research, a retrospective cohort study was conducted to delineate the usage and effects of KA on attenuating CKD exacerbation. End-point CKD event was defined as 50% reduction of initial estimated glomerular filtration rate (eGFR). Kaplan–Meier analysis and COX proportional hazard regression model were adopted to calculate the cumulative probability to reach the end-point and hazard ratio of renal function deterioration. Results In animal study, KA presented a protective effect on IR induced renal injury and fibrosis by attenuating inflammatory infiltration and apoptosis via inhibition of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. In clinical research, after adjusting basic demographic factors, patients at stages 4 and 5 in KA group presented a much delayed and slower incidence of eGFR decrease compared to those in No-KA group (hazard ratio (HR) = 0.115, 95% confidence interval (CI) 0.021–0.639, p = 0.0134), demonstrating a positive effect of KA on staving CKD progression. Conclusion KA improved IR induced chronic renal injury and fibrosis, and seemed to be a prospective protective factor in end stage renal disease.

The success of a robotic pick and place task depends on the success of the entire procedure: from the grasp planning phase, to the grasp establishment phase, then the lifting and moving phase, and finally the releasing and placing phase. Being able to detect and recover from grasping failures throughout the entire process is therefore a critical requirement for both the robotic manipulator and the gripper, especially when considering the almost inevitable object occlusion by the gripper itself during the robotic pick and place task. With the rapid rising of soft grippers, which rely heavily on their under-actuated body and compliant, open-loop control, less information is available from the gripper for effective overall system control. Tackling on the effectiveness of robotic grasping, this work proposes a hybrid policy by combining visual cues and proprioception of our gripper for the effective failure detection and recovery in grasping, especially using a proprioceptive self-developed soft robotic gripper that is capable of contact sensing. We solved failure handling of robotic pick and place tasks and proposed (1) more accurate pose estimation of a known object by considering the edge-based cost besides the image-based cost; (2) robust object tracking techniques that work even when the object is partially occluded in the system and achieve mean overlap precision up to 80%; (3) contact and contact loss detection between the object and the gripper by analyzing internal pressure signals of our gripper; (4) robust failure handling with the combination of visual cues under partial occlusion and proprioceptive cues from our soft gripper to effectively detect and recover from different accidental grasping failures. The proposed system was experimentally validated with the proprioceptive soft robotic gripper mounted on a collaborative robotic manipulator, and a consumer-grade RGB camera, showing that combining visual cues and proprioception from our soft actuator robotic gripper was effective in improving the detection and recovery from the major grasping failures in different stages for the compliant and robust grasping.

Kiwifruit (Actinidia chinensis) is a nutrient-dense fruit abundant in vitamin C and phenolic compounds, and it exhibits strong antioxidant capacity. However, the antioxidants in ‘Jinfeng’ kiwifruit have seldom been extracted and analyzed, and the conditions for the extraction of kiwifruit antioxidants by ultrasound-assisted extraction (UAE) have seldom been investigated. In this study, response surface methodology (RSM) was used to optimize UAE conditions to extract antioxidants from ‘Jinfeng’ kiwifruit. In addition, the antioxidant capacity, contents of total phenolics and total flavonoids, ascorbic acid, and the profiles of antioxidants were also analyzed. The results showed that the optimal UAE conditions included 68% ethanol, liquid/solid ratio at 20 mL/g, extraction time at 30 min, extraction temperature at 42 °C, and ultrasonic power at 420 W. Under these conditions, the ABTS value of kiwifruit was 70.38 ± 1.38 μM TE/g DW, which was 18.5% higher than that of the extract obtained by conventional solvent extraction. The total phenolic and flavonoid contents were 15.50 ± 0.08 mg GAE/g DW and 5.10 ± 0.09 mg CE/g DW, respectively. Moreover, 20 compounds were tentatively identified by UPLC–MS/MS, and the content of main compounds, such as procyanidin B2, neochlorogenic acid, and epicatechin, were determined by HPLC–DAD. This research revealed the profiles of antioxidant phytochemicals in ‘Jinfeng’ kiwifruit, which can be a good dietary source of natural antioxidants with potential health functions.

Lead–zinc (Pb–Zn) mine tailings pose a great risk to the natural environment and human health because of their high toxicity. In this study, the responses of photosynthesis, chlorophyll fluorescence, and antioxidative enzyme of Melia azedarach and Ligustrum lucidum in the soil contaminated by Pb–Zn mine tailings were investigated. Results showed that Pb–Zn mine tailings significantly reduced net photosynthetic rates and leaf photosynthetic pigment content of both trees, and the reduction of net photosynthetic rates was mainly caused by their biochemical limitation (BL). The chlorophyll fluorescence parameters from Pb–Zn tailing stressed leaves indicated that Pb–Zn tailings affected PSII activity which was evident from the change values of energy fluxes per reaction center (RC): probability that an electron moves further than QA− (ETO/TRO), maximum quantum yield for primary photochemistry (TRO/ABS), the density of PSII RC per excited cross-section (RC/CSO), the absorption of antenna chlorophylls per PSII RC (ABS/RC), and the turnover number of QA reduction events (N). Pb–Zn mine tailings also affected the oxidation and reduction of PSI, which resulted in a great increase of reactive oxygen species (ROS) contents and then stimulated the rate of lipid peroxidation. Both trees exhibited certain antioxidative defense mechanisms as elevated superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities, then declined under high level of Pb–Zn tailing treatment. Comparatively, L. lucidum showed less extent effect on photosynthesis and higher antioxidative enzyme activities than M. azedarach; thus L. lucidum was more tolerant than M. azedarach at least under the described Pb–Zn tailing treatment. These results indicate that the effect of Pb–Zn mine tailings on photosynthesis performance mainly related to imbalance of the PSII activity and PSI redox state in both trees. We propose that M. azedarach and L. lucidum could relieve the oxidative stress for phytoremediation under the appropriate Pb–Zn mine tailing content.

An increasing number of studies have begun considering human endogenous retroviruses (HERVs) as potential pathogenic phenomena. Our previous research suggests that HERV-W Envelope (HERV-W ENV), a HERV-W family envelope protein, is elevated in schizophrenia patients and contributes to the pathophysiology of schizophrenia. The dopamine (DA) hypothesis is the cornerstone in research and clinical practice related to schizophrenia. Here, we found that the concentration of DA and the expression of DA receptor D2 (DRD2) were significantly higher in schizophrenia patients than in healthy individuals. Intriguingly, there was a positive correlation between HERV-W ENV and DA concentration. Depth analyses showed that there was a marked consistency between HERV-W ENV and DRD2 in schizophrenia. Studies in vitro indicated that HERV-W ENV could increase the DA concentration by regulating DA metabolism and induce the expression of DRD2. Co-IP assays and laser confocal scanning microscopy indicated cellular colocalization and a direct interaction between DRD2 and HERV-W ENV. Additionally, HERV-W ENV caused structural and functional abnormalities of DA neurons. Further studies showed that HERV-W ENV could trigger the PP2A/AKT1/GSK3 pathway via DRD2. A whole-cell patch-clamp analysis suggested that HERV-W ENV enhanced sodium influx through DRD2. In conclusion, we uncovered a relationship between HERV-W ENV and the dopaminergic system in the DA neurons. Considering that GNbAC1, a selective monoclonal antibody to the MSRV-specific epitope, has been promised as a therapy for treating type 1 diabetes and multiple sclerosis (MS) in clinical trials, understanding the precise function of HERV-W ENV in the dopaminergic system may provide new insights into the treatment of schizophrenia.

Directly relating the mechanical properties of metallic glasses to their atomic structure remains a challenge. Here, the authors use high resolution microscopy to show many mechanical properties of metallic glasses depend on a single structural parameter, the characteristic length of spatial heterogeneity.

Background/Aims: Migraine is a disabling condition that severely impacts socioeconomic function and quality of life. The focus of this study was to develop a mouse model of trigeminal pain that mimics migraine. Methods: After undergoing dural cannulation surgery, mice were treated with repeated dural doses of an acidic solution to induce trigeminal pain. Results: The method elicited intermittent, head-directed wiping and scratching as well as the expression of both the c-FOS gene in the spinal trigeminal nucleus caudalis and calcitonin gene related peptide (CGRP) in the periaqueductal grey matter. Interestingly, the acid-induced trigeminal pain behaviour was inhibited by amiloride, an antagonist of acid-sensing ion channels (ASICs), but not by AMG-9810, an inhibitor of transient receptor potential cation channel V1(TRPV1). In addition, the relative mRNA and protein expression levels of ASIC1a and ASIC3 were increased in the acid-induced trigeminal nociceptive pathways. Furthermore, blocking CaMKII with KN-93 significantly reduced the acid-induced trigeminal pain behaviour and c-FOS gene expression. Conclusion: The data suggested that chronic intermittent administration of an acidic solution to mice resulted in trigeminal hypersensitivity and that dural acid-induced trigeminal pain behaviour in mice may mechanistically mimic migraine. The observations here identify an entirely novel treatment strategy for migraine.

Spinal and bulbar muscular atrophy (SBMA), a progressive degenerative disorder, is caused by a CAG/glutamine expansion in the androgen receptor (polyQ AR). Recent studies demonstrate that skeletal muscle is an important site of toxicity that contributes to the SBMA phenotype. Here, we sought to identify critical pathways altered in muscle that underlie disease manifestations in AR113Q mice. This led to the unanticipated identification of gene expression changes affecting regulators of carbohydrate metabolism, similar to those triggered by denervation. AR113Q muscle exhibits diminished glycolysis, altered mitochondria, and an impaired response to exercise. Strikingly, the expression of genes regulating muscle energy metabolism is rescued following peripheral polyQ AR gene silencing by antisense oligonucleotides (ASO), a therapeutic strategy that alleviates disease. Our data establish the occurrence of a metabolic imbalance in SBMA muscle triggered by peripheral expression of the polyQ AR and indicate that alterations in energy utilization contribute to non-neuronal disease manifestations.

Rheumatoid arthritis patients respond differently to anti-TNF treatment. Using community-based challenge, the authors show that currently available data does not reveal meaningful genetic predictors of response to anti-TNF therapy, thus confirming clinical observations.

Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome. Recent studies have considered HERVs as potential pathogenic factors. The majority of HERV genes are mutated and not capable of encoding functional proteins; regardless, some HERV genes, such as HERV-W envelope (env) glycoprotein, are known to have intact open reading frames. The HERV-W element on 7q21.2, which encodes a protein referred to as Syncytin-1, participates in human placental morphogenesis and can activate a pro-inflammatory and autoimmune cascade. Neuropsychological disorders are typically linked to inflammatory abnormalities. In this study, we review that Syncytin-1 has been increasingly involved in the development of neuropsychological disorders, such as schizophrenia and multiple sclerosis (MS). This study also presents inflammation imbalances in schizophrenia and MS. More importantly, we discuss the potential role and molecular mechanisms by which Syncytin-1 regulates inflammatory abnormalities in neuropsychological diseases. In summary, Syncytin-1 activity may represent a novel molecular pathogenic mechanism in neuropyschological diseases, such as schizophrenia and MS.

Pseudomonas aeruginosa causes devastating chronic pulmonary infections in cystic fibrosis (CF) patients. Although the CF airway is inhabited by diverse species of microorganisms interlaced within a biofilm, many studies focus on the sole contribution of P. aeruginosa pathogenesis in CF morbidity. More recently, oral commensal streptococci have been identified as cohabitants of the CF lung, but few studies have explored the role these bacteria play within the CF biofilm. We examined the interaction between P. aeruginosa and oral commensal streptococci within a dual species biofilm. Here we report that the CF P. aeruginosa isolate, FRD1, enhances biofilm formation and colonization of Drosophila melanogaster by the oral commensal Streptococcus parasanguinis. Moreover, production of the P. aeruginosa exopolysaccharide, alginate, is required for the promotion of S. parasanguinis biofilm formation and colonization. However, P. aeruginosa is not promoted in the dual species biofilm. Furthermore, we show that the streptococcal adhesin, BapA1, mediates alginate-dependent enhancement of the S. parasanguinis biofilm in vitro, and BapA1 along with another adhesin, Fap1, are required for the in vivo colonization of S. parasanguinis in the presence of FRD1. Taken together, our study highlights a new association between streptococcal adhesins and P. aeruginosa alginate, and reveals a mechanism by which S. parasanguinis potentially colonizes the CF lung and interferes with the pathogenesis of P. aeruginosa.

This study presents a two-dimensional micro-/nanoradian angle generator (2D-MNAG) that achieves high angular displacement resolution and repeatability using a piezo-driven flexure hinge for two-dimensional deflections and three capacitive sensors for output angle monitoring and feedback control. The principal error of the capacitive sensor for precision microangle measurement is analyzed and compensated for; so as to achieve a high angle output resolution of 10 nrad (0.002 arcsec) and positioning repeatability of 120 nrad (0.024 arcsec) over a large angular range of ±4363 μrad (±900 arcsec) for the 2D-MNAG. The impact of each error component, together with the synthetic error of the 2D-MNAG after principal error compensation are determined using Monte Carlo simulation for further improvement of the 2D-MNAG.

We previously reported that TR2 and TR4 orphan nuclear receptors bind to direct repeat (DR) elements in the ε- and γ-globin promoters, and act as molecular anchors for the recruitment of epigenetic corepressors of the multifaceted DRED complex, thereby leading to ε- and γ-globin transcriptional repression during definitive erythropoiesis. Other than the ε- and γ-globin and the GATA1 genes, TR4-regulated target genes in human erythroid cells remain unknown. Here, we identified TR4 binding sites genome-wide using chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-seq) as human primary CD34(+) hematopoietic progenitors differentiated progressively to late erythroid precursors. We also performed whole transcriptome analyses by RNA-seq to identify TR4 downstream targets after lentiviral-mediated TR4 shRNA knockdown in erythroid cells. Analyses from combined ChIP-seq and RNA-seq datasets indicate that DR1 motifs are more prevalent in the proximal promoters of TR4 direct target genes, which are involved in basic biological functions (e.g., mRNA processing, ribosomal assembly, RNA splicing and primary metabolic processes). In contrast, other non-DR1 repeat motifs (DR4, ER6 and IR1) are more prevalent at gene-distal TR4 binding sites. Of these, approximately 50% are also marked with epigenetic chromatin signatures (such as P300, H3K27ac, H3K4me1 and H3K27me3) associated with enhancer function. Thus, we hypothesize that TR4 regulates gene transcription via gene-proximal DR1 sites as TR4/TR2 heterodimers, while it can associate with novel nuclear receptor partners (such as RXR) to bind to distant non-DR1 consensus sites. In summary, this study reveals that the TR4 regulatory network is far more complex than previously appreciated and that TR4 regulates basic, essential biological processes during the terminal differentiation of human erythroid cells.

Background & aimsThe natural course of chronic hepatitis B virus (HBV) infection is characterized by different immune responses, ranging from immune tolerant (IT) to immune activated (IA) stages. In our study, we investigated the natural killer (NK) cells activity in patients at different immunological stages of chronic HBV infection.MethodsBlood samples obtained from 57 HBeAg positive patients with chronic hepatitis B (CHB), including 15 patients in the immune tolerant (IT) stage, 42 patients in the immune activated (IA) stage, and 18 healthy individuals (HI). The analyses included flow cytometry to detect NK cells, the determination of cytokine levels as well as of surface receptor expression and cytotoxicity.ResultsNK cells in peripheral blood were significantly lower in patients in the IA stage of CHB compared to HI (pConclusionNK cells activity was lower in CHB patients, especially in those in the IA stage.

This study was to investigate the bidirectional estrogen-like effects of genistein on murine experimental autoimmune ovarian disease (AOD). Female BALB/c mice were induced by immunization with a peptide from murine zona pellucida. The changes of estrous cycle, ovarian histomorphology were measured, and the levels of serum sex hormone were analyzed using radioimmunoassay. Proliferative responses of the ovary were also determined by immunohistochemistry. Administration of 25 or 45 mg/kg body weight genistein enhanced ovary development with changes in serum sex hormone levels and proliferative responses. Meanwhile, the proportions of growing and mature follicles increased and the incidence of autoimmune oophoritis decreased, which exhibited normal ovarian morphology in administration of 25 or 45 mg/kg body weight genistein, while a lower dose (5 mg/kg body weight genistein) produced the opposite effect. These findings suggest that genistein exerts bidirectional estrogen-like effects on murine experimental AOD, while a high dose (45 mg/kg body weight) of genistein may suppress AOD.