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Background: The vivid red, purple, and blue hues that are observed in a variety of plant fruits, flowers, and leaves are produced by anthocyanins, which are naturally occurring pigments produced by a series of biochemical processes occurring inside the plant cells. The purple-stalked Chinese kale, a popular vegetable that contains anthocyanins, has many health benefits but needs to be investigated further to identify the genes involved in the anthocyanin biosynthesis and translocation in this vegetable. Results: In this study, the purple- and green-stalked Chinese kale were examined using integrative transcriptome and metabolome analyses. The content of anthocyanins such as cyanidin-3-O-(6″-O-feruloyl) sophoroside-5-O-glucoside, cyanidin-3,5-O-diglucoside (cyanin), and cyanidin-3-O-(6″-O-p-hydroxybenzoyl) sophoroside-5-O-glucoside were considerably higher in purple-stalked Chinese kale than in its green-stalked relative. RNA-seq analysis indicated that 23 important anthocyanin biosynthesis genes, including 3 PAL, 2 C4H, 3 4CL, 3 CHS, 1 CHI, 1 F3H, 2 FLS, 2 F3'H, 1 DFR, 3 ANS, and 2 UFGT, along with the transcription factor BoMYB114, were significantly differentially expressed between the purple- and green-stalked varieties. Results of analyzing the expression levels of 11 genes involved in anthocyanin production using qRT-PCR further supported our findings. Association analysis between genes and metabolites revealed a strong correlation between BoGSTF12 and anthocyanin. We overexpressed BoGSTF12 in Arabidopsis thaliana tt19, an anthocyanin transport mutant, and this rescued the anthocyanin-loss phenotype in the stem and rosette leaves, indicating BoGSTF12 encodes an anthocyanin transporter that affects the accumulation of anthocyanins. Conclusion: This work represents a key step forward in our understanding of the molecular processes underlying anthocyanin production in Chinese kale. Our comprehensive metabolomic and transcriptome analyses provide important insights into the regulatory system that controls anthocyanin production and transport, while providing a foundation for further research to elucidate the physiological importance of the metabolites found in this nutritionally significant vegetable. [ABSTRACT FROM AUTHOR]

Background: Peanut is an economically-important oilseed crop and needs a large amount of calcium for its normal growth and development. Calcium deficiency usually leads to embryo abortion and subsequent abnormal pod development. Different tolerance to calcium deficiency has been observed between different cultivars, especially between large and small-seed cultivars. Results: In order to figure out different molecular mechanisms in defensive responses between two cultivars, we treated a sensitive (large-seed) and a tolerant (small-seed) cultivar with different calcium levels. The transcriptome analysis identified a total of 58 and 61 differentially expressed genes (DEGs) within small-seed and large-seed peanut groups under different calcium treatments, and these DEGs were entirely covered by gene modules obtained via weighted gene co-expression network analysis (WGCNA). KEGG enrichment analysis showed that the blue-module genes in the large-seed cultivar were mainly enriched in plant-pathogen attack, phenolic metabolism and MAPK signaling pathway, while the green-module genes in the small-seed cultivar were mainly enriched in lipid metabolism including glycerolipid and glycerophospholipid metabolisms. By integrating DEGs with WGCNA, a total of eight hub-DEGs were finally identified, suggesting that the large-seed cultivar concentrated more on plant defensive responses and antioxidant activities under calcium deficiency, while the small-seed cultivar mainly focused on maintaining membrane features to enable normal photosynthesis and signal transduction. Conclusion: The identified hub genes might give a clue for future gene validation and molecular breeding to improve peanut survivability under calcium deficiency. [ABSTRACT FROM AUTHOR]

• Plasma osteoprotegerin levels were elevated in patients with severe/critical hemorrhagic fever with renal syndrome. • Tumor necrosis factor-α synergizes with the Hantaan virus to promote osteoprotegerin production in endothelial cells. • Plasma osteoprotegerin correlated with hemorrhagic disorder indicators of hemorrhagic fever with renal syndrome. The bleeding tendency is a hallmark of hemorrhagic fever with renal syndrome (HFRS) after Hantaan virus (HTNV) infection. Growing reports indicate the importance of osteoprotegerin (OPG) in vascular homeostasis, implying OPG might be involved in the pathogenesis of coagulopathy in patients with HFRS. Acute and convalescence plasmas of 32 patients with HFRS were collected. Enzyme-linked immunosorbent assays (ELISA) were used to detect plasma OPG levels and other parameters. The human umbilical vein endothelial cells were stimulated with HTNV and/or tumor necrosis factor-α (TNF-α) to explore the source of OPG. Plasma OPG levels of patients with HFRS were elevated and correlated positively with the severity of HFRS and negatively with platelet counts. Abundant OPG was released from endothelial cells in response to TNF-α stimuli, along with HTNV infection, which was in accordance with the findings of positive correlations between plasma OPG and TNF-α or c-reactive protein. Importantly, plasma OPG levels correlated positively with activated partial thromboplastin time and the content of d-dimer. These findings suggested that increased plasma OPG levels induced by HTNV might be an important factor for the severity of HFRS, and was likely involved in endothelium dysfunction and hemorrhagic disorder of HFRS, which might contribute to the pathogenesis of hemorrhage in HFRS. [ABSTRACT FROM AUTHOR]

Background: This study aimed to clarify the significance of the crosstalk between hypoxia-inducible factor-1α (HIF-1α) and the Wnt/β-catenin pathway in oesophageal squamous cell carcinoma (ESCC).Methods: The oncogenic role of HIF-1α in ESCC was investigated using in vitro and in vivo assays. The clinicopathological significance of HIF-1α, β-catenin and TCF4/TCF7L2 in ESCC were evaluated using quantitative real-time PCR and immunohistochemistry.Results: The expression level of HIF-1α, β-catenin, and TCF4/TCF7L2 in T.Tn and TE1 cell lines were elevated under hypoxia in vitro. HIF-1α knockdown suppressed proliferation, migration/invasion and epithelial-mesenchymal transition (EMT) progression, induced G0/G1 cell cycle arrest, promoted apoptosis and inhibited 5-fluorouracil chemoresistance in vitro. In vivo assays showed that HIF-1α is essential in maintaining tumour growth, angiogenesis, and 5-fluorouracil chemoresistance. Mechanically, we identified the complex between HIF-1α and β-catenin, HIF-1α can directly bind to the promoter region of TCF4/TCF7L2. The mRNA level of HIF-1α, β-catenin and TCF4/TCF7L2 were increased in ESCC tumour tissues compared to the corresponding non-tumour tissues. High levels of HIF-1α and TCF4/TCF7L2 expression were correlated with aggressive phenotypes and poor prognosis in ESCC patients.Conclusions: HIF-1α serves as an oncogenic transcriptional factor in ESCC, probably by directly targeting TCF4/TCF7L2 and activating the Wnt/β-catenin pathway. [ABSTRACT FROM AUTHOR]

The current outbreak of mpox presents a significant threat to the global community. However, the lack of mpox-specific drugs necessitates the identification of additional candidates for clinical trials. In this study, a network medicine framework was used to investigate poxviruses-human interactions to identify potential drugs effective against the mpox virus (MPXV). The results indicated that poxviruses preferentially target hubs on the human interactome, and that these virally-targeted proteins (VTPs) tend to aggregate together within specific modules. Comorbidity analysis revealed that mpox is closely related to immune system diseases. Based on predicted drug-target interactions, 268 drugs were identified using the network proximity approach, among which 23 drugs displaying the least side-effects and significant proximity to MPXV were selected as the final candidates. Lastly, specific drugs were explored based on VTPs, differentially expressed proteins, and intermediate nodes, corresponding to different categories. These findings provide novel insights that can contribute to a deeper understanding of the pathogenesis of MPXV and development of ready-to-use treatment strategies based on drug repurposing. [ABSTRACT FROM AUTHOR]

Hantaan virus infection may cause severe lethal hemorrhagic fever with renal syndrome (HFRS) in humans. The chemokine fractalkine (CX3CL1) acts as a proinflammatory cytokine, and it is elevated in several infectious diseases. However, little is known about the contributions of CX3CL1 to HFRS pathogenesis. Present study detected plasma CX3CL1 levels and expression of the receptor CX3CR1 in HFRS patients and discussed the possible effects of CX3CL1 on pathogenesis of HFRS. Plasma CX3CL1 in acute phase and Critical/Severe groups of HFRS patients were significantly increased compared to that in normal controls (p < 0.001 and p < 0.01, respectively). High plasma CX3CL1 was negatively correlated with platelet count (r = −0.5844, p < 0.0001) and positively correlated with blood urea nitrogen (r = 0.3668, p = 0.0039), creatinine (r = 0.42, p = 0.0008), and white blood cells (r = 0.2646, p = 0.0411). Expression of CX3CR1 on nonclassical and intermediate monocytes was also increased in the acute phase (p < 0.01 for both the cells) and Critical/Severe groups (p < 0.05 and p < 0.01, respectively) of HFRS patients compared to that in normal controls. Taken together, elevation of plasma CX3CL1 in HFRS patients and expression of CX3CR1 on nonclassical and intermediate monocyte subsets might provide new insights into the potential role of CX3CL1/CX3CR1 in pathogenesis of HFRS. [ABSTRACT FROM AUTHOR]

This study investigated the effects of fermented rice bran (FRB) on modulating intestinal aryl hydrocarbon receptor (AhR) expression, innate lymphoid cell (ILC)3 populations, the fecal microbiota distribution, and their associations with dextran sodium sulfate (DSS)-induced acute colitis. C57BL/6 mice were assigned to four groups: 1) NC group, normal mice fed the AIN-93M diet; 2) FRB group, normal mice fed a diet supplemented with 5% FRB; 3) NCD group, DSS-treated mice fed AIN-93M; 4) FRBD group, DSS-treated mice fed a 5% FRB-supplemented diet. DSS was administered for 5 d and followed by 5 d for recovery. At the end of the experiment, mice were sacrificed. Their blood and intestinal tissues were collected. Results showed that there were no differences in colonic biological parameters and function between the NC and FRB groups. Similar fecal microbiota diversity was noted between these two groups. Compared to the non-DSS-treated groups, DSS administration led to increased intestinal permeability, enhanced inflammatory cytokine production and disease severity, whereas tight junctions and AhR, interleukin (IL)-22 expressions were downregulated, and the ILC3 population had decreased. Also, gut microbiota diversity differs from the non-DSS-treated groups and more detrimental bacterial populations exist when compared to the FRBD group. FRB supplementation in DSS-treated mice attenuated fecal microbial dysbiosis, decreased intestinal permeability, improved the barrier integrity, upregulated AhR and IL-22 expression, maintained the ILC3 population, and pathologically mitigated colonic injury. These findings suggest enhanced ILC3- and AhR-mediated functions may be partly responsible for the anti-colitis effects of FRB supplementation in DSS-induced colitis. [ABSTRACT FROM AUTHOR]

• Host immune changes at different stages of chronic HBV infection were systematically summarized and analyzed from the perspective of cytokines. • Luminex multiplex analysis was used to detect serum cytokines of patients. • The combination of IL-6, IL-8, CXCL9 and CXCL13 was closely correlated with HCC during chronic HBV infection. • Current antiviral therapy (NAs) was beneficial for killing the virus but had no significant effect on immune recovery. The characteristics of cytokine/chemokine(CK) profiles across different courses of chronic hepatitis B virus infection and the effects of NAs antiviral therapy on cytokine profiles remain unclear. This report provides evidence from 383 patients with chronic HBV infection. The Luminex multiple cytokine detection technology was used to detect CK profiles. The predictive power of CKs across course of disease was assessedusing univariate analyses and with receiver operating characteristic (ROC) curves. Compared to healthy control (HC), expression levels of interleukin 6 (IL)-6, IL-8, IL-21, matrix metalloproteinases (MMP)-2 and tumor necrosis factor receptor (TNFR)-1 showed a significant increasing trend during chronic HBV infection. IL-23 and IL-33 increased respectively in chronic hepatitis B patients (CHB). interferon (IFN)-gamma and TNF-α changed significantly only in liver cirrhosis (LC) patients. Whereas, myeloid-related markers decreased dramatically in those with hepatocellular carcinoma (HCC). The ROC result suggests that combining IL-6, IL-8, CXCL9 and CXCL13 into a nomogram has closely correlation with HCC during chronic HBV infection. In addition, nucleotide analogues (NAs) antiviral treatments are capable of recoveringnormal liver functions and significantly reducing the viral loads, however, they seem to have a limited effect in changing CKs, especially specific antiviral factors. The differential CK and virological markers may serve as potential indicators of distinct immune statuses in chronic HBV infection. They also underscore the varying efficacy and limitations of NAs antiviral therapies. This next step would to break new ground in the optimization of current anti-HBV treatment programs although this requires further research. [ABSTRACT FROM AUTHOR]

Reliable determination of hydrogen peroxide (H2O2) and glucose is vital in various fields, especially implicated in diagnosis of diabetes and oxidative stress-related diseases. Herein, yolk–shell hollow Ni/NiO@C microspheres were template-synthesized with well-defined Ni-MOF (metal–organic framework) and further worked as a bifunctional electrocatalyst for glucose oxidation in alkaline solution and H2O2 reduction in neutral solution, of which the unique structure and rich pore openings provide large accessible surface areas, while the uniformly distributed Ni, NiO and C efficiently catalyze and facilitate the reaction of glucose and H2O2, thus achieving a wide linear range of 0.01 to 10 mM with a sensitivity of 1291 μA mM−1 cm−2 and a detection limit of 0.116 μM for glucose and offering a sensitivity of 32.09 μA mM−1 cm−2, a detection limit of 0.9 μM and a linear range up to 80.7 mM for H2O2, as well as good selectivity, excellent reproducibility and long-term stability for two analytes. What's more, the as-constructed sensors realize quantitative detection glucose in blood serum with satisfying results and can use to monitor H2O2 in neutral situation. This work opens an avenue to design high-performance sensoring materials but also becomes a great candidate in practical application. [ABSTRACT FROM AUTHOR]

Pumpkin-like CuO/Cu2O composites with different ratios were successfully fabricated by adjusting the hydrothermal reaction time and then their bifunctional catalyst capability was explored in glucose oxidation and H2O2 reduction. By comparing the peak potentials and peak currents, the CuO/Cu2O composites obtained at 24 and 30 h displayed the relatively highest performance for glucose and H2O2, respectively, and the corresponding mechanisms were also explained. Benefiting from the large active surface area and the synergistic effect of the optimal binary composition interfaces, the constructed sensors showed superior performance, with a sensitivity of 880 μA mM−1 cm−2, detection limit of 0.108 μM, and linear range of up to 15 mM for glucose together with a sensitivity of 5154 μA mM−1 cm−2, detection limit of 0.018 μM, and linear range from 0.005 to 1.05 mM for H2O2, as well as good selectivity, reproducibility, and stability, which were sufficient to meet the concentration requirements, enabling realizing the quantitative detection glucose in blood serum and H2O2 released from cells. This work provides a strategy to enhance the electrocatalytic activity of sensors and a promising platform for practical application. [ABSTRACT FROM AUTHOR]

Micro-supercapacitors (MSCs) with excellent electrochemical behaviours and flexibility possess great promise for portable and wearable electronic devices. A novel type of hybrid-dimensional Fe2O3/graphene/Ag ink is developed and extruded into MSC electrodes through the direct ink writing-based three-dimensional (3D) printing. The optimal solid-state MSC device exhibits a maximum areal capacitance of 412.3 mF cm−2 at 2 mA cm−2, a correspondingly high energy density of 65.4 μWh cm−2 and 89% capacitance retention for over 5000 charge and discharge cycles. The superior electrochemical performance is profited by the high electron transport synergistically boosted by two-dimensional graphene nanosheets and one-dimensional Ag nanowires, and the high pseudocapacitive behaviours of Fe2O3 nanoparticles. The 3D printed MSC exhibits reliable flexibility with remarkable retention of 90.2% of its original capacitance after 500 bending cycles. The current 3D printing fabrication demonstrates an efficient route for advanced miniaturised electrochemical energy storage. [ABSTRACT FROM AUTHOR]

Peanut is a leguminous crop with an indeterminate growth habit that will continuously flower during the entire reproductive development stage. Flowering redundancy adversely affects the yield and quality of peanut. In this study, eight flowering and five yield-related traits were collected and comprehensively evaluated from a diverse germplasm panel consisting of 232 peanut accessions, aiming to provide a theoretical basis for improving the flowering habit and yield for future peanut breeding efforts. As a result, large phenotypic diversity was observed in 13 traits. Most of the traits suggested high heritability, except high effective flowering duration (HEFD), days to 100% flower cessation (DTC100), and yield per plant (YPP). Days to 90% flower cessation (DTC90), days to DTC100, flowering duration (FD), and low effective flowering duration (LEFD) showed significant negative correlations with 100-seed weight, 100-pod weight, YPP, average weight per pod, and shelling percentage. Principal component analysis (PCA) suggested that flowering redundancy traits as well as yield-related traits contributed more to the first three PCs when compared to other traits. This study addresses the lack of peanut flowering phenotypic and genetic diversity and lays the foundation for in-depth research on redundancy-related genes in peanut flowering. [ABSTRACT FROM AUTHOR]

Background: Hantaan virus (HTNV) can cause hemorrhagic fever with renal syndrome (HFRS) in humans with severe morbidity and high mortality. Although inactivated HFRS vaccines are given annually for prevention in populations, China still has the highest number of HFRS cases and deaths worldwide. Consequently, vaccination for HFRS requires the development of novel, more effective vaccines. Epitope peptide vaccines have been developed rapidly in recent years and are considered a novel approach for the prevention of infection. Specifically, the multiple antigenic peptide (MAP) design with preferable immunogenicity can arouse a satisfactory immune response for vaccination. However, there are few reports on the design and evaluation of MAP for HTNV. Methods: Three HLA-A*02-restricted 9-mer cytotoxic T lymphocyte (CTL) epitopes on HTNV glycoprotein and one HLA-A*02-restricted 9-mer CTL epitope on the HTNV nucleocapsid, which have been proven to be immunoprotective in our previous study, were selected for the design of HTNV MAP. A four-branched HTNV MAP was evaluated by the IFN-γ-secreting enzyme-linked immunospot assay and proliferation induction capacity of CD8+ T cells and compared with the single HTNV CTL epitope in 17 HLA-A*02+ patients with HFRS. The Mann–Whitney U test was used for comparison of parameters between different subject groups. Results: The macromolecular HTNV MAP was designed with a polylysine core and four radially branched single CTL epitope chains. Importantly, HTNV MAP could stimulate CD8+ T cell secretion of IFN-γ in HLA-A*02+ patients with HFRS. The frequency of IFN-γ-secreting CD8+ T cells in the MAP stimulation group was significantly higher than that in the single HTNV CTL epitope stimulation groups (P < 0.005). Meanwhile, the activity of IFN-γ-secreting CD8+ T cells in the HTNV MAP group was also higher than that of the single CTL epitope groups (P < 0.05). Moreover, there was a much stronger ability of HTNV MAP to stimulate CD8+ T cell proliferation compared with that of a single HTNV CTL epitope. Conclusions: The designed HTNV MAP could induce CTL responses ex vivo and may be considered a candidate for the design and development of novel HTNV peptide vaccines. [ABSTRACT FROM AUTHOR]

Micro-pseudocapacitors (MPCs) are prospective power source candidates with compatible sizes as well as superior power densities for miniaturized electronic devices; however, their limited capacitive charge storage characteristics are still hindering their further development. Herein, an optimized 3D printing technique is employed to build remarkable reduced holey graphene oxide (rHGO) supported MPC microelectrodes. In such microelectrodes, the presence of macroscale pores introduced through freeze drying is beneficial to the accessibility to electrolyte ions. Moreover, with two additional pore modals including the microscale pores from pseudocapacitive nanoparticles stacking and nanoscale in-plane holes formed by rational HGO engineering, the MPC microelectrodes offer an enhancement in both electrical and ionic transports. The resultant 3D-printed planar MPCs exhibit a remarkable device specific charge storage capacity of 241.3 mC cm−2, which is approximately 1.7-fold that of a non-optimized one and much higher than most reported planar micro-supercapacitors. Superior rate capability and high capacity retention (91% capacity retention after 11000 charge and discharge cycles) are also achieved. Our porosity engineering strategy combined with 3D printing is expected to serve as a facile and general design in the roadmap for next-generation state-of-the-art customized electrochemical energy storage devices. Image 1 [ABSTRACT FROM AUTHOR]

Background: Haemorrhagic fever with renal syndrome (HFRS) is characterized by an uncontrolled cytokine storm that causes vascular leakage and kidney injury. The cytokine interleukin 34 (IL-34) enhances proliferation and differentiation of myeloid cells and secretion of pro-inflammatory cytokines, which is involved in the pathogenesis of some inflammatory and infectious diseases, including acute kidney injury. To date, however, the role of IL-34 in patients with HFRS is unclear. This study aims to determine the plasma IL-34 levels of HFRS patients and discuss the possible effects of IL-34 in the pathogenesis of HFRS. Methods: Plasma levels of IL-34 in 52 HFRS patients and 20 healthy controls were quantified using enzyme-linked immunosorbent assay. Results: Compared with healthy controls, the plasma IL-34 levels in HFRS patients were significantly elevated in acute phase [37.92 (0–215.45) pg/ml vs. 7.13 (0–19.44) pg/ml, p <.0001], and then decreased to the normal levels in convalescent phase. Importantly, IL-34 levels correlated positively with white blood cell counts and mononuclear cell counts (r = 0.592, p <.0001 and r = 0.458, p <.0001, respectively), and correlated negatively with platelet counts and serum albumin levels (r = −0.430, p <.0001 and r = −0.479, p =.0001, respectively). Conclusions: Plasma levels of IL-34 in HFRS patients were significantly elevated in acute phase and correlated with disease severity-reflecting parameters, which suggests a potential role of IL-34 in HFRS and should be future explored. [ABSTRACT FROM AUTHOR]

We evaluated cellular immune responses induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in an immunized population based on HLA-E-restricted CD8+ T cell epitope identification. HLA-E-restricted SARS-CoV-2 CD8+ T cell nonamer peptides were predicted with software. An HLA-E-transfected K562 cell binding assay was used to screen for high-affinity peptides. IFN-γ enzyme-linked immunospot assays were used to identify HLA-E-restricted epitopes. An HLA-E/epitope tetramer was employed to detect the frequencies of epitope-specific CD8+ T cells. Four CD8+ T cell epitopes on the spike protein of SARS-CoV-2 restricted by both HLA-E*0101 and E*0103 were identified. HLA-E-restricted epitope-specific IFN-γ-secreting CD8+ T cell responses could be detected in individuals vaccinated with SARS-CoV-2 vaccines. Importantly, the frequencies of epitope-specific CD8+ T cells in Ad5-nCoV vaccinated individuals were higher than in individuals vaccinated with recombinant protein or inactivated vaccines. Moreover, the frequencies of epitope-specific CD8+ T cells could be maintained for at least 120 days after only one dose of Ad5-nCoV vaccine, while the frequencies of epitope-specific CD8+ T cells decreased in individuals after two doses of Ad5-nCoV vaccine. These findings may contribute to a more comprehensive evaluation of the protective effects of vaccines for SARS-CoV-2; meanwhile, they may provide information to characterize HLA-E-restricted CD8+ T cell immunity against SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Stage IIIc Kienböck's disease is a clinical challenge to treat collapse of the lunate bone. A new reconstructive surgery was described in one patient using 3D printing lunate prosthesis. The prosthesis shape was designed by tomographic image processing and segmentation using technology compared with the intact side matched by mirror symmetry and 3D post-processing technologies. The patient recovered nearly full range of motion of the wrist after 12 months. The visual analog scale scores and Cooney scores were 2 points and 91 points. We demonstrated that an anatomical reconstruction to Kienböck's Disease is possible using 3D printing lunate prosthesis. [ABSTRACT FROM AUTHOR]

Flowering Chinese cabbage (Brassica rapa var. parachinensis) is one of the most popular vegetables in the south of China. As an antioxidant, anthocyanin is an important quality trait in vegetables, and the gene related to anthocyanin biosynthesis in purple flowering Chinese cabbage is also important. In this study, two flowering Chinese cabbage with extreme colors in the stem were used as materials for transcriptome analysis. RNA-seq analysis showed that 6811 differentially expressed genes (DEGs) were identified, including 295 transcription factors. Phenylpropanoid biosynthesis, flavone and flavanol biosynthesis, and flavonoid biosynthesis pathways were found to be significantly enriched in the purple flowering Chinese cabbage. A total of 25 DEGs associated with anthocyanin biosynthesis were found at a higher expression in purple flowering Chinese cabbage than in green flowering Chinese cabbage. Bioinformatics analysis shows that BrMYB114 is a candidate gene for the regulation of anthocyanin biosynthesis, and heterologous expression analysis of BrMYB114 in Nicotiana benthamiana indicates that BrMYB114 functions in anthocyanin biosynthesis. Therefore, our findings provide vital evidence for elucidating the molecular mechanism in the purple stem in flowering Chinese cabbage. [ABSTRACT FROM AUTHOR]

Haemorrhagic fever with renal syndrome (HFRS) is characterised by an uncontrolled immune response that causes vascular leakage. Adiponectin (APN) is an adipocytokine involved in prorevascularisation and immunomodulation. To investigate the possible effects of APN in the pathogenesis of HFRS, total and high molecular weight (HMW) APN levels in the plasma of patients with HFRS were quantified using enzyme-linked immunosorbent assay (ELISA). Compared with those in healthy controls, the plasma total and HMW APN levels in patients were elevated to different degrees from the fever onset and remained high at the convalescent phase. Consistent with these results, western blot analysis additionally showed that low molecular weight (LMW), middle molecular weight (MMW), and HMW APN levels were all elevated and contributed to the elevation of the total APN level. Importantly, sustained high levels of total and HMW APN at the convalescent phase were significantly higher in patients with critical disease than those in patients with mild or moderate disease. Moreover, total and HMW APN levels negatively correlated with white blood cell count and positively correlated with platelet count and serum albumin level. These results may provide insights into understanding the roles of total and HMW APN in the pathogenesis of HFRS. [ABSTRACT FROM AUTHOR]

Peanut is vulnerable under waterlogging stress, and it is important to explore efficient agronomic practices to reduce adverse effects induced by waterlogging stress. In this study, the effects of waterlogging stress on plant morphology, physiological and biochemical characters in peanut seedlings were studied. It was founded waterlogging stress posted adverse effects on plant growth and development and triggered the activities of antioxidant enzymes and osmotic adjustment substances to improve the plant tolerance under stress. It was also found that exogenous calcium fertilization could significantly improved root growth and development under stress. Moreover, higher dose of calcium fertilizer (1600 mg/kg) showed better performance on improving waterlogging tolerance than lower dose one (800 mg/kg) in peanut seedlings. This study explored positive effects of exogenous calcium on recovering damages especially in roots caused by waterlogging stress, providing a theoretical guidance in agronomic practice to improve waterlogging tolerance, and laying a foundation for agronomic practice when further discovering molecular mechanisms in response to waterlogging stress. [ABSTRACT FROM AUTHOR]

Hantaan virus (HTNV) infection can cause severe hemorrhagic fever with renal syndrome (HFRS) in humans. CD14, a pattern recognition receptor recognizing lipopolysaccharide, is highly expressed on monocytes and can be shed as soluble CD14 (sCD14) upon monocyte activation. To understand the role of sCD14 in HFRS, the sCD14 plasma concentrations from 45 HFRS patients were quantified, and the relationships between the plasma sCD14 level and the monocyte response status and clinical parameters were analyzed. The plasma sCD14 levels were significantly higher in the HFRS patients and they correlated with monocyte expansion and activation, which were characterized by increased blood monocyte counts, the proportion of CD14++CD16+ intermediate monocytes, as well as elevated plasma tumor necrosis factor- α (TNF- α) and soluble CD163 (sCD163) levels. Additionally, the high plasma sCD14 levels positively correlated with white blood cell counts and blood urea nitrogen levels and negatively correlated with platelet counts in the HFRS patients. Taken together, our data indicate that elevated plasma sCD14 levels are associated with the monocyte response status during HTNV infection in humans. [ABSTRACT FROM AUTHOR]

Introducing heterostructures combined by different building blocks (transition metal chalcogenides) enables the regulation of composition and architecture towards boosting electrocatalytic sensing performance. Herein, a successful transformation from well-defined Cu 2 O microcubes to hollow core-shell CuS@CuSe heteromicrocubes are performed via a template-directed in-situ sulfuration and selenization reaction at room temperature and further defined as bifunctional nanozymes to detect H 2 O 2 reduction and DA oxidation, of which the ultrathin CuSe nanosheets vertically wrapping on hollow CuS microcube-like core created plenty of exposed active sites, rich ion-transfer channels, as well as remarkable structural stability, while the existence of interfacial effect between two components can facilitate fast ion/electron transfer to execute cooperative catalytical capacity, thus harvesting highly efficient electrochemical sensor features for catalyzing H 2 O 2 and DA, as reflected by high sensitivity (1005.2 μA mM−1 cm−2 and 60.44 μA μM−1 cm−2), low LOD (30 nM and 0.38 nM), favorable working potential (−0.25 V and 0.20 V) as well as excellent selectivity, powerful long-term stability and outstanding repeatability/reportability. Such preeminent performance is not only superior to single CuS and CuSe counterparts and most designed nanozymes, but also creates satisfactory recoveries and expected accuracy in real human serum samples. Then, designing heterogeneous nanomaterials with matching functions and structures and investigating their potential prospects in electrocatalytic biosensors would guide the exploitation of nanozymes to fulfill the versatile requirements. • Hierarchical core-shell CuS@CuSe hollow microcubes has been constructed. • CuS@CuSe affords abundant active sites, fast reaction kinetics as well as admirable configuration stability. • CuS@CuSe/GCE displayed significantly enhanced biosensing properties for H 2 O 2 reduction and DA oxidation. • Powerful tolerance and satisfactory accuracy towards H 2 O 2 and DA determination achieved in real samples. [ABSTRACT FROM AUTHOR]

Aims: To validate the perfusion, extent, depth, infection and sensation (PEDIS) classification system and to make the clinical practice easier, we created a score system and compared this system with two previously published common score systems. Methods: A retrospective cohort study was conducted on patients with diabetic foot ulcer (DFU) attending our hospital (n=364) from May 2007 to September 2013. Participants’ characteristics and all variables composing the PEDIS classification system were assessed. Results: During a median follow-up of 25 months (range 6-82), ulcers healed in 217 of the 364 patients (59.6%), remained unhealed in 37 patients (10.2%), and were resolved by amputation in 62 patients (17.0%); 48 patients (13.2%) died. When measured using the PEDIS classification system, the outcome of DFU deteriorated with increasing severity of each subcategory. Additionally, longer ulcer history, worse perfusion of lower limb, a larger extent of the ulcer, a deeper wound, more severe infection, and loss of protective sensation were independent predictors of adverse outcome. More importantly, the new PEDIS score system showed good diagnostic accuracy, especially when compared with the SINBAD and Wagner score systems. Conclusions: The PEDIS classification system, which encompasses relevant variables that contribute to the outcome of DFU and has excellent capacity for predicting the ulcer outcome, demonstrated acceptable accuracy. The PEDIS classification system might be useful in clinical practice and research both for the anticipation of health care costs and for comparing patient subgroups. [ABSTRACT FROM AUTHOR]

The zinc(II) coordination polymer [Zn3(BPT)2(μ2-H2O)2(H2O)2] n · n(DMA) ( 1) (H3BPT = biphenyl-3,4′,5-tricarboxylic acid, DMA = N,N′-dimethylactamide) was obtained by the solvothermal reaction of H3BPT with Zn(NO3)2 in DMA/H2O mixed solvent. Single crystal X-ray analysis reveals that compound 1 has a complicated 3D framework containing linear trinuclear [Zn3(COO)4(μ2-H2O)2] clusters as building subunits, which can be simplified into a (3,6)-connected rtl topological network with the Schläfli symbol {4.62}2{42.610.83}. The calculated results of total and partial density of states (DOS) indicate that the luminescence of 1 mainly originates from intraligand charge transfer. [ABSTRACT FROM AUTHOR]

The titanosilicate zeolite catalyzed epoxidation of propylene with hydrogen peroxide (H 2 O 2 , HP) to propylene oxide (PO), the so-called HPPO, is more eco-efficient, compared to the chlorohydrin process and the epoxidation using organic hydroperoxides. However, the zeolite catalysts used in the HPPO process are easily deactivated, because the main byproduct propylene glycol (PG) and other heavy byproducts with high boiling points, derived from the solvolysis of PO, are deposited inside the zeolite micropores. In the present work, trimethylsilylated Ti-MWW zeolites, named Si–Ti-MWW, were developed for the HPPO process. In combination with the results from extensive characterizations for the prepared zeolites, it is found that the trimethylsilylation merely occurs on the external surface of Ti-MWW crystals and can significantly enhance the hydrophobicity, but not alter the coordination states of the Ti species and textural properties of the zeolites. The catalytic properties of Ti-MWW and Si–Ti-MWW were compared in propylene epoxidation. The results show that the solvolysis of PO to the byproducts can be effectively inhibited over the hydrophobic zeolite surface, making Si–Ti-MWW exhibit a much higher selectivity for PO and a much better stability and reusability than the parent Ti-MWW in the HPPO process. The current study, therefore, provides a new approach to develop efficient catalysts for the HPPO process. [Display omitted] • Develop trimethylsilylated Ti-MWW zeolites for propylene epoxidation. • Trimethylsilylation can significantly enhance the zeolite hydrophobicity. • Solvolysis of PO effectively inhibited due to the hydrophobic surface. • Developed catalyst shows a high activity, selectivity, stability, and reusability. [ABSTRACT FROM AUTHOR]

Background: Fibrosis is a significant pathological feature of chronic skeletal muscle injury, profoundly affecting muscle regeneration. Fibro-adipogenic progenitors (FAPs) have the ability to differentiate into myofibroblasts, acting as a primary source of extracellular matrix (ECM). the process by which FAPs differentiate into myofibroblasts during chronic skeletal muscle injury remains inadequately explored. Method: mouse model with sciatic nerve denervated was constructed and miRNA expression profiles between the mouse model and uninjured mouse were analyzed. qRT/PCR and immunofluorescence elucidated the effect of miR-27b-3p on fibrosis in vivo and in vitro. Dual-luciferase reporter identified the target gene of miR-27b-3p, and finally knocked down or overexpressed the target gene and phosphorylation inhibition of Smad verified the influence of downstream molecules on the abundance of miR-27b-3p and fibrogenic differentiation of FAPs. Result: FAPs derived from a mouse model with sciatic nerves denervated exhibited a progressively worsening fibrotic phenotype over time. Introducing agomiR-27b-3p effectively suppressed fibrosis both in vitro and in vivo. MiR-27b-3p targeted Transforming Growth Factor Beta Receptor 1 (TGF-βR1) and the abundance of miR-27b-3p was negatively regulated by TGF-βR1/Smad. Conclusion: miR-27b-3p targeting the TGF-βR1/Smad pathway is a novel mechanism for regulating fibrogenic differentiation of FAPs. Increasing abundance of miR-27b-3p, suppressing expression of TGF-βR1 and inhibiting phosphorylation of smad3 presented potential strategies for treating fibrosis in chronic skeletal muscle injury. [ABSTRACT FROM AUTHOR]

The CCT gene family is present in plants and is involved in biological processes such as flowering, circadian rhythm regulation, plant growth and development, and stress resistance. We identified 87, 62, 46, and 40 CCTs at the whole-genome level in B. napus, B. rapa, B. oleracea, and A. thaliana, respectively. The CCTs can be classified into five groups based on evolutionary relationships, and each of these groups can be further subdivided into three subfamilies (COL, CMF, and PRR) based on function. Our analysis of chromosome localization, gene structure, collinearity, cis-acting elements, and expression patterns in B. napus revealed that the distribution of the 87 BnaCCTs on the chromosomes of B. napus was uneven. Analysis of gene structure and conserved motifs revealed that, with the exception of a few genes that may have lost structural domains, the majority of genes within the same group exhibited similar structures and conserved domains. The gene collinearity analysis identified 72 orthologous genes, indicating gene duplication and expansion during the evolution of BnaCCTs. Analysis of cis-acting elements identified several elements related to abiotic and biotic stress, plant hormone response, and plant growth and development in the promoter regions of BnaCCTs. Expression pattern and protein interaction network analysis showed that BnaCCTs are differentially expressed in various tissues and under stress conditions. The PRR subfamily genes have the highest number of interacting proteins, indicating their significant role in the growth, development, and response to abiotic stress of B. napus. [ABSTRACT FROM AUTHOR]

Objective: To explore therapeutic efficacy and mechanism of puerarin (PUE) in treating of ulcerative colitis (UC). Methods: Network pharmacology and molecular docking technique were used to screen and analyze targets of PUE in regulating UC. C57BL/6 mice were given free access to 2.5%DSS aqueous solution for 7 days, and influence of PUE on changes in body weight and disease activity index (DAI) score were subsequently observed. Histopathological alterations of colon tissue were observed by HE staining, changes of goblet cell population in colon tissue were evaluated through Alcian blue staining; expressions of inflammatory factors in colon tissue were detected by qRT-PCR and ELISA. Effect of PUE on MODE-K cell viability and apoptosis were assessed by CCK-8 and flow cytometry. Results: A total of 38 common targets of PUE in modulating UC, such as AKT1, TNF, STAT3, CASP3, HIF1A and etc, mainly involving TNF, IL-17 and PI3K-Akt signaling pathway. In vivo experiments confirmed that PUE ameliorated degree of colon shortening, body weight and DAI scores and reduced inflammatory cell infiltration in mice. Besides, expressions of inflammatory factors in colon, such as TNF-α and IL-1β, were inhibited by PUE. Furthermore, in vitro experiments validated that PUE relieved DSS-induced apoptosis of epithelial cells. Conclusion: PUE alleviates occurrence and development of DSS-induced UC in mice. [ABSTRACT FROM AUTHOR]

(−)clausenamide is a compound isolated from Clausena lansium (lour) Skeel with nootropic effects. At the present study, we investigated the clausenamide induced Ca2+ signaling in primary cultures of rat cortical neurons by using laser confocal microscopy. The mean amplitude of (−)clausenamide (1 μM) induced Ca2+ transient was similar in extracellular solution with or without calcium; and (−)clausenamide failed to trigger calcium transient after treatment with endoplasmic reticulum Ca2+ pumps inhibitor BHQ to exhaust intracellular Ca2+ stores. This result suggested that the primary source of (−)clausenamide induced Ca2+ transient was from internal stores. Application of IP3 receptor inhibitor MgCl2 and PLC-γ inhibitor U73122 suppressed (−)clausenamide induced Ca2+ transient, suggesting that the major source of (−)clausenamide induced Ca2+ transient was from IP3 receptor pathway. We also found that mitochondria were involved in (−)clausenamide triggered Ca2+ transient. The distinctive spatial and temporal characteristic of (−)clausenamide induced Ca2+ transient may play an important role in its action. [Copyright &y& Elsevier]

CX3CL1, also named fractalkine or neurotactin, is the only known member of the CX3C chemokine family that can chemoattract several immune cells. CX3CL1 exists in both membrane-anchored and soluble forms, with each mediating distinct biological activities. CX3CL1 signals are transmitted through its unique receptor, CX3CR1, primarily expressed in the microglia of the central nervous system (CNS). In the CNS, CX3CL1 acts as a regulator of microglia activation in response to brain disorders or inflammation. Recently, there has been a growing interest in the role of CX3CL1 in regulating cell adhesion, chemotaxis, and host immune response in viral infection. Here, we provide a comprehensive review of the changes and function of CX3CL1 in various viral infections, such as human immunodeficiency virus (HIV), SARS-CoV-2, influenza virus, and cytomegalovirus (CMV) infection, to highlight the emerging roles of CX3CL1 in viral infection and associated diseases. [ABSTRACT FROM AUTHOR]

Background: An effective vaccine that prevents disease caused by hantaviruses is a global public health priority, but up to now, no vaccine has been approved for worldwide use. Therefore, novel vaccines with high prophylaxis efficacy are urgently needed. Methods: Herein, we designed and synthesized Hantaan virus (HTNV) linear multi-epitope peptide consisting of HLA-A*02-restricted HTNV cytotoxic T cell (CTL) epitope and pan HLA-DR-binding epitope (PADRE), and evaluated the immunogenicity, as well as effectiveness, of multi-epitope peptides in HLA-A2.1/Kb transgenic mice with interferon (IFN)-γ enzyme-linked immunospot assay, cytotoxic mediator detection, proliferation assay and HTNV-challenge test. Results: The results showed that a much higher frequency of specific IFN-γ-secreting CTLs, high levels of granzyme B production, and a strong proliferation capacity of specific CTLs were observed in splenocytes of mice immunized with multi-epitope peptide than in those of a single CTL epitope. Moreover, pre-immunization of multi-epitope peptide could reduce the levels of HTNV RNA loads in the liver, spleen and kidneys of mice, indicating that specific CTL responses induced by multi-epitope peptide could reduce HTNV RNA loads in vivo. Conclusions: This study may provide an important foundation for the development of novel peptide vaccines for HTNV prophylaxis. [ABSTRACT FROM AUTHOR]

Polymer memory devices based on a π-conjugated poly [9,9-bis(4-diphenylaminophenyl)-2,7-fluorene] covalently bridged, Disperse Red 1 (a dye) triad were fabricated. The devices exhibit electrical bistability in the I-V characteristics and can be used to perform read-write-erase memory functions. The memory devices exhibit good performance with an on/off current ratio up to 103 and stable on and off states under a constant voltage stress and read pulses. Furthermore, memory retention tests show that it is possible to preserve both states at 150 °C under ambient atmosphere for about 1 h when using Cu as the top electrode. [ABSTRACT FROM AUTHOR]

Taro is a plant in the Araceae family, and its leafstalk possesses significant botanical and culinary value owing to its noteworthy medicinal and nutritional attributes. Leafstalk colour is an essential attribute that significantly influences its desirability and appeal to both breeders and consumers. However, limited information is available about the underlying mechanism responsible for the taro plant's colouration. Thus, the purpose of the current study was to elucidate the information on purple leafstalks in taro through comprehensive metabolome and transcriptome analysis. In total, 187 flavonoids, including 10 anthocyanins, were identified. Among the various compounds analysed, it was observed that the concentrations of five anthocyanins (keracyanin chloride (cyanidin 3-O-rutinoside chloride), cyanidin 3-O-glucoside, tulipanin (delphinidin 3-rutinoside chloride), idaein chloride (cyanidin 3-O-galactoside), and cyanidin chloride) were found to be higher in purple taro leafstalk compared to green taro leafstalk. Furthermore, a total of 3330 differentially expressed genes (DEGs) were identified by transcriptome analysis. Subsequently, the correlation network analysis was performed to investigate the relationship between the expression levels of these differentially expressed genes and the content of anthocyanin. There were 18 DEGs encoding nine enzymes detected as the fundamental structural genes contributing to anthocyanin biosynthesis, along with seven transcription factors (3 MYB and 4 bHLH) that may be promising candidate modulators of the anthocyanin biosynthesis process in purple taro leafstalk. The findings of the current investigation not only provide a comprehensive transcriptional code, but also give information on anthocyanin metabolites as well as beneficial insights into the colour mechanism of purple taro leafstalk. [ABSTRACT FROM AUTHOR]

• Stannosilicate zeolites with different topologies used in the Baeyer–Villiger (B-V) oxidation. • Zeolites' pore structure and hydrophobicity play a crucial role in B-V oxidation. • Sn-MCM-68 has large three-dimensional pore-opening channels and relatively high hydrophobicity. • Sn-MCM-68 shows superior catalytic performance in B-V oxidation. Although stannosilicate zeolites are active and selective in Baeyer–Villiger (B-V) oxidation because of their unique Lewis acidity, which is useful to activate the carbonyl group of ketone rather than peroxide, the role of their pore-opening structure and hydrophobicity in selective oxidation still needs to be explored. In the present work, stannosilicate zeolites with different topologies were synthesized and characterized in detail, especially in terms of the coordination states of the Sn species in the isomorphically substituted Sn zeolite Sn-MSE (Sn-MCM-68). The catalytic properties of the synthesized zeolites were evaluated in B-V oxidation. The results show that Sn-MCM-68 possesses some superior catalytic properties in B-V oxidation in comparison with other zeolites, because of its three-dimensional 12 × 10 × 10-membered ring (MR) pore-opening channels and relatively higher hydrophobicity. [ABSTRACT FROM AUTHOR]

Magnesium phosphate (MgP) has garnered growing interest in hard tissue replacement processes due to having similar biological characteristics to calcium phosphate (CaP). In this study, an MgP coating with the newberyite (MgHPO4·3H2O) was prepared on the surface of pure titanium (Ti) using the phosphate chemical conversion (PCC) method. The influence of reaction temperature on the phase composition, microstructure, and properties of coatings was systematically researched with the use of an X-ray diffractometer (XRD), a scanning electron microscope (SEM), a laser scanning confocal microscope (LSCM), a contact angle goniometer, and a tensile testing machine. The formation mechanism of MgP coating on Ti was also explored. In addition, the corrosion resistance of the coatings on Ti was researched by assessing the electrochemical behavior in 0.9% NaCl solution using an electrochemical workstation. The results showed that temperature did not obviously affect the phase composition of the MgP coatings, but affected the growth and nucleation of newberyite crystals. In addition, an increase in reaction temperature had a great impact on properties including surface roughness, thickness, bonding strength, and corrosion resistance. Higher reaction temperatures resulted in more continuous MgP, larger grain size, higher density, and better corrosion resistance. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract N -methyl- d -aspartate receptors (NMDARs) have multiple prominent roles in CNS function but their excessive or insufficient activity contributes to neuropathological/psychiatric disorders. Consequently, a variety of positive and negative allosteric modulators (PAMs and NAMs, respectively) have recently been developed. Although these modulators bind to extracellular domains, in the present report we find that the NMDAR's intracellular C-terminal domains (CTDs) significantly influence PAM/NAM activity. GluN2 CTD deletion robustly affected NAM and PAM activity with both enhancing and inhibiting effects that were compound-specific and NMDAR subunit-specific. In three cases, individual PAMs became NAMs at specific GluN2-truncated receptors. In contrast to GluN2, GluN1 CTD removal only reduced PAM activity of UBP684 and CIQ, and did not affect NAM activity. Consistent with these findings, agents altering phosphorylation state or intracellular calcium levels displayed receptor-specific and compound-specific effects on PAM activity. It is possible that the GluN2′s M4 domain transmits intracellular modulatory signals from the CTD to the M1/M4 channel gating machinery and that this site is a point of convergence in the direct or indirect actions of several PAMs/NAMs thus rendering them sensitive to CTD status. Thus, allosteric modulators are likely to have a marked and varied sensitivity to post-translational modifications, protein-protein associations, and intracellular ions. The interaction between PAM activity and NMDAR CTDs appears reciprocal. GluN1 CTD-deletion eliminated UBP684, but not pregnenolone sulfate (PS), PAM activity. And, in the absence of agonists, UBP684, but not PS, was able to promote movement of fluorescently-tagged GluN1-CTDs. Thus, it may be possible to pharmacologically target NMDAR metabotropic activity in the absence of channel activation. [ABSTRACT FROM AUTHOR]

The rapid spread of multidrug-resistant bacteria has called for effective antimicrobial agents which work on a more direct mechanism of killing. Cationic peptidopolysaccharides are developed in the present work to mimic the peptidoglycan structure of bacteria and to enhance the membrane-compromising bactericidal efficacy. Antimicrobial CysHHC10 peptide was grafted to the C-2 (amino) or C-6 (hydroxyl) position of chitosan backbone via thiol-maleimide “click” conjugation, utilizing the maleimidohexanoic linkers. The peptidopolysaccharide with primary amino backbone intact (CSOHHC) exhibited higher bactericidal activity toward Gram-positive and Gram-negative bacteria, in comparison to that with amino backbone grafted with the peptide (CSNHHC). Both peptidopolysaccharides also exhibited lower hemolytic activity and cytotoxicity than free CysHHC10 peptide due to the moderation effect contributed by the chitosan backbone. For targeting the Gram-positive bacteria in particular, the CSOHHC expressed 4- and 2-fold increases in hemo- and cytoselectivity, respectively, as compared to the CysHHC10 peptide. In an extended application, peptidopolysaccharide antibacterial coatings were formed via layer-by-layer assembly with tannic acid. The peptidopolysaccharide coatings readily killed the adhered bacteria upon contact while being cytocompatible by maintaining more than 60% viability for the adhered fibroblasts. Therefore, the peptidoglycan-mimetic peptidopolysaccharides are potential candidates for anti-infective drugs in biomedical applications. [ABSTRACT FROM AUTHOR]

Understanding protein adsorption behaviors on solid surfaces constitutes an important step toward development of efficacious and biocompatible medical devices. Both surface charge and wettability have been shown to influence protein adsorption attributes, including kinetics, quantities, deformation, and reversibility. However, determining the dominant interaction in these surface-induced phenomena is challenging because of the complexity of inter-related mechanisms at the liquid/solid interface. Herein, we reveal the dominant interfacial forces in these essential protein adsorption attributes under the influence of a combination of surface charge and wettability, using quartz crystal microbalance with dissipation monitoring and atomic force microscopy-based force spectroscopy on a series of model surfaces. These surfaces were fabricated via layer-by-layer assembly, which allowed two-dimensional control of surface charge and wettability with minimal cross-parameter dependency. We focused on a soft globular protein, bovine serum albumin (BSA), which is prone to conformational changes during adsorption. The information obtained from the two techniques shows that both surface charge and hydrophobicity can increase the protein-surface interaction forces and the adsorbed amount. However, surface hydrophobicity triggered a greater extent of deformation in the adsorbed BSA molecules, leading to more dehydration, spreading, and resistance to elution by ionic strength changes regardless of the surface charge. The role played by the surface charge in the adsorbed protein conformation and extent of desorption induced by changes in the ionic strength is secondary to that of surface hydrophobicity. These findings advance the understanding of how surface chemistry and properties can be tailored for directing protein-substrate interactions. [ABSTRACT FROM AUTHOR]

Hantaan virus (HTNV) infection causes an epidemic of hemorrhagic fever with renal syndrome (HFRS) mainly in Asia. Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes known to play an important role in innate host defense during virus infection. However, their roles and phenotypes during HTNV infection have not yet been explored. We characterized CD8+MAIT cells from HFRS patients based on scRNA-seq data combined with flow cytometry data. We showed that HTNV infection caused the loss and activation of CD8+MAIT cells in the peripheral blood, which were correlated with disease severity. The production of granzyme B and IFN-γ from CD8+MAIT cells and the limitation of HTNV replication in endothelia cells indicated the anti-viral property of CD8+MAIT cells. In addition, in vitro infection of MAIT cells by HTNV or HTNV-exposed monocytes showed that the activation of MAIT cells was IL-18 mediated. In conclusion, this study identified, for the first time, gene expression profiles of MAIT cells, provided underlying molecular mechanisms for activation of MAIT cells during HTNV infection, and suggested a potential anti-viral role of MAIT cells in HFRS. HTNV infection caused the activation and deficiency of MAIT cells in the peripheral blood. The production of IFN-γ from MAIT cells can limit the replication of HTNV. The activation of MAIT cells was mediated by IL-18, which was sourced from monocytes infected by HTNV. [ABSTRACT FROM AUTHOR]

Objective: Precise classification of mass-forming intrahepatic cholangiocarcinoma (MF-ICC) and hepatocellular carcinoma (HCC) based on magnetic resonance imaging (MRI) is crucial for personalized treatment strategy. The purpose of the present study was to differentiate MF-ICC from HCC applying a novel deep-learning-based workflow with stronger feature extraction ability and fusion capability to improve the classification performance of deep learning on small datasets. Methods: To retain more effective lesion features, we propose a preprocessing method called semi-segmented preprocessing (Semi-SP) to select the region of interest (ROI). Then, the ROIs were sent to the strided feature fusion residual network (SFFNet) for training and classification. The SFFNet model is composed of three parts: the multilayer feature fusion module (MFF) was proposed to extract discriminative features of MF-ICC/HCC and integrate features of different levels; a new stationary residual block (SRB) was proposed to solve the problem of information loss and network instability during training; the attention mechanism convolutional block attention module (CBAM) was adopted in the middle layer of the network to extract the correlation of multi-spatial feature information, so as to filter the irrelevant feature information in pixels. Results: The SFFNet model achieved an overall accuracy of 92.26% and an AUC of 0.9680, with high sensitivity (86.21%) and specificity (94.70%) for MF-ICC. Conclusion: In this paper, we proposed a specifically designed Semi-SP method and SFFNet model to differentiate MF-ICC from HCC. This workflow achieves good MF-ICC/HCC classification performance due to stronger feature extraction and fusion capabilities, which provide complementary information for personalized treatment strategy. [ABSTRACT FROM AUTHOR]

Background: Fascia lata has been used for arthroscopic superior capsule reconstruction (ASCR) and verified to achieve a good clinical outcome. However, it is still not known about revascularization character of the fascia lata after ASCR. This study was performed to evaluate the revascularization of autologous fascia lata grafts after ASCR by enhanced magnetic resonance imaging (MRI). Methods: A prospective study of 19 patients with irreparable rotator cuff tears underwent ASCR with autologous fascia lata grafts from September 2019 to April 2021. Radiography examinations and clinical evaluations were performed preoperatively and postoperatively at 6 weeks and 3, 6, and 12 months. The signal-to-noise quotient (SNQ) value and enhancement index (EI) of autologous fascia lata grafts in the great tubercle insertion (GTI), midpoint of the graft (MG), and glenoid insertion (GI) were compared for radiography examination. Clinical evaluation included the American Shoulder and Elbow Surgeons (ASES) score, University of California Los Angeles (UCLA) shoulder score, and Visual Analog Scale (VAS) score. Results: The SNQ values in T1WI enhancement at GI and GTI were significantly higher than those at the plain MRI scan at all postoperative observation timepoints; however, the SNQ values in T1WI enhancement at MG did not show a significant difference until 3 months postoperation. EI values at GTI and GI were significantly higher than those at MG at 6 weeks and 3 months postoperation, while there was no significant difference in the EI value between GTI and GI. At 6 months postoperation, the EI value at GI was significantly higher than those at MG. At 12 months postoperation, the EI value at GI was significantly higher than those at MG and GTI; however, there was no significant difference between GTI and MG. The EI values at GTI and MG peaked at 3 months and 6 months postoperation, respectively, and then plateaued at 12 months postoperation. However, there was no significant difference in the EI value among the different postoperative timepoints at GI. The EI value did not correlate with the VAS and ASES, UCLA scores at any time point or any postoperative observation location. Conclusion: Revascularization of the fascia lata was dependent on the location of the fascia lata and plateaus at 12 months postoperation. The EI value did not correlate with the VAS and ASES, UCLA scores during12 months postoperation. [ABSTRACT FROM AUTHOR]

Nanoparticles of transition metals, particularly noble metals, have been widely used in nanocatalysis. However, enhancing their stability and reusability during catalytic reactions has been a challenge that has limited the full use of the benefits associated with their miniature size. The encapsulation of noble metal nanocores as guest species into the hollow polymeric shells has emerged with the promise to solve this problem, which usually arises from a combined effect of the properties from their inorganic and polymeric components. In the present study, template-assisted synthesis of monodispersed hairy hybrid nanorattles, consisting of a movable platinum nanocluster and a hairy temperature- and pH-responsive polymer shell (Pt@air@P[MAA-co-(PMA-click-βCD-guest-PVCL)] HHNs; PMAA: poly(methacrylic acid); PPMA: poly(propargyl methacrylate); βCD: β-cyclodextrin; PVCL: poly(N-vinylcaprolactam)), was carried out and preformed as nanocatalyst. The novelty of this approach lies in the use of click chemistry and supramolecular assembly (referred to as "grafting to" approaches) to assist the creation of a protective and stimuli-responsive polymer shell to promote efficient mass transfer to encapsulated metal nanoparticles. The polymer shell not only acts as a physical barrier that prevents the coalescence of Pt nanocores but also provides a void space where organic transformation occurs on the surface of the ligand-free Pt nanocluster in a controlled manner. The as-synthesized HHNs were found to perform as a robust and reusable heterogeneous catalyst for catalytic reactions. One may find the present study a general and effective way for the synthesis of monodispersed hollow nanomaterials in a controllable and green manner. [ABSTRACT FROM AUTHOR]

Hantaan virus (HTNV) infection causes an epidemic of hemorrhagic fever with renal syndrome (HFRS) mainly in Asia. It is well known that T cells mediated anti-viral immune response. Although previous studies showed that double positive T (DP T) cells, a little portion of T lymphocytes, were involved in adaptive immune response during virus infection, their kinetic changes and roles in HTNV infection have not yet been explored. In this study, we characterized DP T cells from HFRS patients based on flow cytometry data combined with scRNA-seq data. We showed that HTNV infection caused the upregulation of DP T cells in the peripheral blood, which were correlated with disease stage. The scRNA-seq data clustered DP T cells, unraveled their gene expression profile, and estimated the ordering of these cells. The production of granzyme B and CD107a from DP T cells and the abundant TCR distribution indicated the anti-viral property of DP T cells. In conclusion, this study identified, for the first time, an accumulation of DP T cells in the peripheral blood of HFRS patients and suggested these DP T cells belonging to CD8+T cells lineage. The DP T cells shared the similar characteristics with cytotoxic T cells (CTL) and exerted an anti-viral role in HFRS. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19) has become a global pandemic and continues to prevail with multiple rebound waves in many countries. The driving factors for the spread of COVID‐19 and their quantitative contributions, especially to rebound waves, are not well studied. Multidimensional time‐series data, including policy, travel, medical, socioeconomic, environmental, mutant and vaccine‐related data, were collected from 39 countries up to 30 June 2021, and an interpretable machine learning framework (XGBoost model with Shapley Additive explanation interpretation) was used to systematically analyze the effect of multiple factors on the spread of COVID‐19, using the daily effective reproduction number as an indicator. Based on a model of the pre‐vaccine era, policy‐related factors were shown to be the main drivers of the spread of COVID‐19, with a contribution of 60.81%. In the post‐vaccine era, the contribution of policy‐related factors decreased to 28.34%, accompanied by an increase in the contribution of travel‐related factors, such as domestic flights, and contributions emerged for mutant‐related (16.49%) and vaccine‐related (7.06%) factors. For single‐peak countries, the dominant ones were policy‐related factors during both the rising and fading stages, with overall contributions of 33.7% and 37.7%, respectively. For double‐peak countries, factors from the rebound stage contributed 45.8% and policy‐related factors showed the greatest contribution in both the rebound (32.6%) and fading (25.0%) stages. For multiple‐peak countries, the Delta variant, domestic flights (current month) and the daily vaccination population are the three greatest contributors (8.12%, 7.59% and 7.26%, respectively). Forecasting models to predict the rebound risk were built based on these findings, with accuracies of 0.78 and 0.81 for the pre‐ and post‐vaccine eras, respectively. These findings quantitatively demonstrate the systematic drivers of the spread of COVID‐19, and the framework proposed in this study will facilitate the targeted prevention and control of the ongoing COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

[Display omitted] • Sn-Ti-MWW development for the oxidative hydration of ethylene with H 2 O 2. • Synergetic effects of the Sn and Ti species on promoting the oxidative hydration. • Sn-doping makes the Ti species more electropositive. • Sn-doping results in the stronger acidity of the zeolite. • Reconciliation of experimental data and molecular simulations. Although the titanosilicate zeolite catalyzed one-pot oxidative hydration of ethylene with hydrogen peroxide (H 2 O 2) to ethylene glycol (EG) takes advantages of step-saving and facile operation, both H 2 O 2 utilization efficiency and EG yield are relatively low. In the present work, Sn-doped Ti-MWW zeolites, named Sn-Ti-MWW, were developed for this oxidative hydration, showing the much higher H 2 O 2 utilization efficiency and EG yield, compared to Ti-MWW. The extensive characterizations of Sn-Ti-MWW zeolites, in combination with Density Functional Theory (DFT) calculations, verify that the doping of Sn into Ti-MWW leads to the higher electropositivity of the Ti species, resulting in the stronger acidity of the zeolite, which is helpful to the H 2 O 2 utilization and EG production. In addition, although the catalyst deactivation is observed due to the deposition of the bulky byproducts onto the active sites and/or into the zeolite micropores, the simple calcination of the used catalyst readily restores its catalytic activity. Therefore, it is anticipated that the developed Sn-Ti-MWW catalyst might be applicable in the one-pot oxidative hydration of ethylene with H 2 O 2 to EG industrially. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinomas (HNSCCs) are a type of cancer originating in the mucosal epithelium of the mouth, pharynx, and larynx, the sixth most common cancer in the world. However, there is no effective treatment for HNSCCs. More than 90% of HNSCCs overexpress epidermal growth factor receptors (EGFRs). Although small molecule inhibitors and monoclonal antibodies have been developed to target EGFRs, few EGFR-targeted therapeutics are approved for clinical use. Ferroptosis is a new kind of programmed death induced by the iron catalyzed excessive peroxidation of polyunsaturated fatty acids. A growing body of evidence suggests that ferroptosis plays a pivotal role in inhibiting the tumor process. However, whether and how ferroptosis-inducers (FINs) play roles in hindering HNSCCs are unclear. In this study, we analyzed the sensitivity of different HNSCCs to ferroptosis-inducers. We found that only tongue squamous cell carcinoma cells and laryngeal squamous cell carcinoma cells, but not nasopharyngeal carcinoma cells, actively respond to ferroptosis-inducers. The different sensitivities of HNSCC cells to ferroptosis induction may be attributed to the expression of KRAS and ferritin heavy chain (FTH1) since a high level of FTH1 is associated with the poor prognostic survival of HNSCCs, but knocked down FTH1 can promote HNSCC cell death. Excitingly, the ferroptosis-inducer RSL3 plays a synthetic role with EGFR monoclonal antibody Cetuximab to inhibit the survival of nasopharyngeal carcinoma cells (CNE-2), which are insensitive to both ferroptosis induction and EGFR inhibition due to a high level of FTH1 and a low level of EGFR, respectively. Our findings prove that FTH1 plays a vital role in ferroptosis resistance in HNSCCs and also provide clues to target HNSCCs resistant to ferroptosis induction and/or EGFR inhibition. [ABSTRACT FROM AUTHOR]

Hantaan orthohantavirus (HTNV) can cause hemorrhagic fever with renal syndrome (HFRS) characterized by acute kidney injury and hemorrhage. Neutrophils are the most abundant innate immune cell and the body's first line of defense against pathogens. Currently, an increasing number of studies have shown that neutrophils may be a mixed blessing in terms of viral infections. However, the role of neutrophils in HFRS patients with HTNV infection has not been fully declared. In this study, we analyzed plasma levels of both myeloperoxidase (MPO) and MPO-DNA in HFRS patients, together with the clinical parameters. Neutrophil-platelet aggregates (NPAs) during the acute and convalescent phases of HFRS were also assessed. The results showed that plasma MPO-DNA levels had no change in different disease phases or severities of HFRS patients. Whereas plasma MPO significantly increased in the acute phase and critical/severe groups of HFRS patients. Furthermore, plasma MPO was positively correlated with inflammatory clinical parameters, such as white blood cell counts, neutrophil counts, and renal injury-related parameters, such as blood urea nitrogen, blood uric acid, and serum creatinine, as well as negatively correlated with and platelet counts. In addition, NPAs increased both in acute and convalescent phase in HFRS patients compared with normal controls. These results suggested that elevated plasma MPO in HFRS patients correlated with disease severity, together with the increases of NPAs in HFRS patients, which may provide new insights into potential role of neutrophils in the pathogenesis of HFRS. [ABSTRACT FROM AUTHOR]

Background/Aims: Tendon injuries are common, difficult to cure and usually healed with fibrosis and scar tissue. The aim of this study was to evaluate tendon derived stem cells (TDSCs) and platelet rich plasma (PRP) in the treatment of collagenase induced Achilles tendinopathy in rat. Methods: Four and 8 weeks (n=18) after TDSCs, PRP, PRP with TDSC or PBS (control) injection into collagenase or saline (sham) injected rat Achilles tendon, tendon tissue was harvested and tendon quality was evaluated by histology and biomechanical testing. TDSCs were cultured and treated by 10% PRP, and the FAK/ERK1/2 signaling pathway and tenocyte-related genes were detected by western blot analysis. Results: Compared to the control, PRP treatment resulted in better healing of injured tendons with improved histological outcomes and biomechanical functions. The addition of TDSCs to PRP treatment significantly enhanced the effects of PRP treatment alone. TDSC injection alone had little effect on tendon healing. PRP and PRP with TDSC treatments of collagenase induced tendon injuries also increased the mRNA and protein expression of tenocyte-related genes (type I collagen, SCX, Tenascin C) and activated the focal adhesion kinase (FAK) and extracellular-regulated kinase (ERK) 1/2 signaling pathways. Treatment of TDSCs in vitro with 10% PRP significantly increased the phosphorylation levels of FAK and ERK1/2 and the protein levels of tenocyte-related genes (Col I, SCX and Tenascin C). Inhibition of the FAK and ERK1/2 signaling pathways abolished the effect of PRP. Conclusion: This study concludes that PRP combined with TDSCs is potentially effective for the treatment of tendinopathy. The PRP induced, FAK and ERK1/2 dependent activation of tenocyte related genes in TDSCs in vitro suggests that the beneficial healing effect of the PRP with TDSC combination might occur by means of an improved TDSC differentiation toward the tenocyte lineage. Thus, a PRP with TDSC combination therapy may be clinically useful. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: A range of strict nonpharmaceutical interventions (NPIs) were implemented in many countries to combat the coronavirus 2019 (COVID-19) pandemic. These NPIs may also be effective at controlling seasonal influenza virus infections, as influenza viruses have the same transmission path as severe acute respiratory syndrome coronavirus 2. The aim of this study was to evaluate the effects of different NPIs on the control of seasonal influenza.Methods: Data for 14 NPIs implemented in 33 countries and the corresponding influenza virological surveillance data were collected. The influenza suppression index was calculated as the difference between the influenza positivity rate during its period of decline from 2019 to 2020 and during the influenza epidemic seasons in the previous 9 years. A machine learning model was developed using an extreme gradient boosting tree regressor to fit the NPI and influenza suppression index data. The SHapley Additive exPlanations tool was used to characterize the NPIs that suppressed the transmission of influenza.Results: Of all NPIs tested, gathering limitations had the greatest contribution (37.60%) to suppressing influenza transmission during the 2019-2020 influenza season. The three most effective NPIs were gathering limitations, international travel restrictions, and school closures. For these three NPIs, their intensity threshold required to generate an effect were restrictions on the size of gatherings less than 1000 people, ban of travel to all regions or total border closures, and closing only some categories of schools, respectively. There was a strong positive interaction effect between mask-wearing requirements and gathering limitations, whereas merely implementing a mask-wearing requirement, and not other NPIs, diluted the effectiveness of mask-wearing requirements at suppressing influenza transmission.Conclusions: Gathering limitations, ban of travel to all regions or total border closures, and closing some levels of schools were found to be the most effective NPIs at suppressing influenza transmission. It is recommended that the mask-wearing requirement be combined with gathering limitations and other NPIs. Our findings could facilitate the precise control of future influenza epidemics and other potential pandemics. [ABSTRACT FROM AUTHOR]

Background: Periodontitis is characterized by progressive inflammation and alveolar bone loss resulting in tooth loss finally. Macrophages including pro-inflammatory M1-like macrophages and reparative M2-like macrophages play a vital role in inflammation and tissue homeostasis in periodontitis. Among them, reparative M2-like macrophages have been shown to promote tissue repair and prevent bone loss. However, the mechanism of reparative M2 macrophages-induced osteoprotective effect remains elusive. Results: Exosomes from reparative M2-like macrophages (M2-Exos) were isolated and identified successfully. M2-Exos could promote bone marrow stromal cells (BMSCs) osteogenic differentiation while suppressing bone marrow derived macrophage (BMDM) osteoclast formation, and prohibit pathological alveolar bone resorption because of the intercellular communication via exosomes. High expression level of IL-10 mRNA was detected not only in reparative M2-like macrophages but also in M2-Exos. Meanwhile, IL-10 expression level in BMSCs or BMDM was also upregulated significantly after co-culturing with M2-Exos in a concentration-dependent manner. In vitro, recombinant IL-10 proteins had the ability to selectively promote osteogenic differentiation of BMSCs and hinder osteoclast differentiation of BMDM. Moreover, after treatment with M2-Exos and IL-10R antibody together, the capacity of promoting osteogenesis and suppressing osteoclastogenesis of M2-Exos was significantly reversed. In vivo experiments further showed that M2-Exos reduced alveolar bone resorption in mice with periodontitis via IL-10/IL-10R pathway. Conclusion: In conclusion, our results demonstrate that the reparative M2-like macrophages could promote osteogenesis while inhibiting osteoclastogenesis in vitro as well as protect alveolar bone against resorption in vivo significantly. M2-Exos could upregulate the IL-10 cytokines expression of BMSCs and BMDM via delivering exosomal IL-10 mRNA to cells directly, leading to activation of the cellular IL-10/IL-10R pathway to regulate cells differentiation and bone metabolism. These results might partly account for the mechanism of osteoprotective effect of reparative M2-like macrophages and provide a novel perspective and a potential therapeutic approach on improving alveolar resorption by M2-Exos. [ABSTRACT FROM AUTHOR]