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Background Frailty is an age-associated state of increased vulnerability to stressors that strongly predicts poor health outcomes. Epidemiological evidence on frailty is limited during the COVID-19 pandemic, and whether frailty is associated with the risk of infection is unknown. Objectives We derived a robust Frailty Index (FI) to measure the prevalence of frailty and its risk factors in community-dwelling older adults in Southern Switzerland (Ticino), and we explored the association between frailty and serologically confirmed SARS-CoV-2 infection. Methods In September 2020, we recruited a random sample of community-dwelling older adults (65 +) in the Corona Immunitas Ticino prospective cohort study (CIT) and assessed a variety of lifestyle and health characteristics. We selected 30 health-related variables, computed the Rockwood FI, and applied standard thresholds for robust (FI Results Complete data for the FI was available for 660 older adults. The FI score ranged between zero (no frailty) and 0.59. The prevalence of frailty and pre-frailty were 10.3% and 48.2% respectively. The log-transformed FI score increased by age similarly in males and females, on average by 2.8% (p p = 0.236). Conclusion Advanced age increases the risk of frailty. The risk of COVID-19 infection in older adults may not differ by frailty status.

Carbon coated Si core–shell structures have been proposed to solve the adverse effects of Si-based anode. However, designing ideal core–shell architecture with excellent surface and interface properties is still a significant challenge. Herein, a novel peanut-like structure of B-doped silicon/carbon nanoparticle (Si@B-C) synthesized by sol–gel process and subsequent thermal reduction is reported. The peanut-like Si@B-C electrode demonstrates a superior cyclability of 534 mAh·g−1 after 1000 cycles at high current density of 1000 mA·g−1. The exceptional electrochemical performance is attributed to the boric acid-induced highly interconnected peanut-like structure and boron heteroatom framework could provide a continuous electron pathway to reduce the irreversible lithium ion loss during rapid cycling. This work provides insight into the development of the heteroatom-doped Si-based anodes with stable cycling performance for LIBs.

The liver has recently been identified as a major organ for destruction of desialylated platelets. However, the underlying mechanism remains unclear. Kupffer cells, which are professional phagocytic cells in the liver, comprise the largest population of resident tissue macrophages in the body. Kupffer cells express a C-type lectin receptor, CLEC4F, that recognizes desialylated glycans with an unclear in vivo role in mediating platelet destruction. In this study, we generated a CLEC4F-deficient mouse model (Clec4f−/−) and found that CLEC4F was specifically expressed by Kupffer cells. Using the Clec4f−/− mice and a newly generated platelet-specific reporter mouse line, we revealed a critical role for CLEC4F on Kupffer cells in mediating destruction of desialylated platelets in the liver in vivo. Platelet clearance experiments and ultrastructural analysis revealed that desialylated platelets were phagocytized predominantly by Kupffer cells in a CLEC4F-dependent manner in mice. Collectively, these findings identify CLEC4F as a Kupffer cell receptor important for the destruction of desialylated platelets induced by bacteria-derived neuraminidases, which provide new insights into the pathogenesis of thrombocytopenia in disease conditions such as sepsis.

Although numerous efforts have been made in direct syngas conversion to higher alcohols via Fischer–Tropsch synthesis, the higher alcohols distribution remains a challenge. Here, we introduce alkaline earth metal oxide as promoter into activated carbon supported cobalt catalyst to tune distribution of higher alcohols. With the addition of Mg, the distribution of C2-5 alcohols increase from 41.2 to 75.8% accompanying with distribution of C6-18 alcohols decrease from 52.8 to 14.0%. Ba-promoted Co based catalyst (CoBa/AC) presents similar alcohols distribution to un-promoted catalyst, while the alcohol selectivity over CoBa/AC is higher than Co/AC. For promoted catalysts, the distribution of C6-18 alcohols increased in the order of Mg

Spin–orbit torque magnetization switching is an efficient method to control magnetization. In perpendicularly magnetized films, two types of spin–orbit torque are induced by driving a current: a damping-like torque and a field-like torque. The damping-like torque assists magnetization switching, but a large field-like torque pushes the magnetization towards the in-plane direction, resulting in a larger critical switching current density and making deterministic switching challenging. Control of the field-like torque strength is difficult because it is intrinsic to the material system used. Here, we show that the field-like term can be suppressed in a spin–orbit ferromagnetic single layer of (Ga,Mn)As by a current-induced Oersted field due to its non-uniform current distribution, making the damping-like torque term (the result of strong Dresselhaus spin–orbit coupling) dominant. The Oersted field can be controlled by the film thickness, resulting in an extremely low switching current density of 4.6 × 104 A cm–2. This strategy can thus provide an efficient approach to spin–orbit torque magnetization switching. A spin–orbit ferromagnetic single layer of (Ga,Mn)As can have a magnetization switching current density as low as 4.6 × 104 A cm−2 by suppressing the field-like torque via control of the current direction and film thickness.

Recently, graphene oxide (GO), MXene, carbon nanotubes (CNTs) have been used for compounding with other materials as anodes and cathodes to achieve excellent electrochemical properties for metal-ion batteries. However, few researches have focused on the differences between the three additives. Herein, silicon, as a typical anode, is selected to integrate with MXene, GO and CNTs in carbon nanofibers (CNFs) and form Si/MXene@CNFs, Si/GO@CNFs and Si/CNTs@CNFs, respectively. Together with the results, it can be realized that these CNFs with a significant improved performance compared with pure Si@CNFs show superiority in different aspects of electrochemical properties. Additionally, the reasons for the superiority are also discussed in this work. The addition of MXene can improve the cycle stability of the electrodes, thereby obtaining a high capacity retention rate, CNTs are favorable for the enhancement of rate performance, and the electrodes reversible capacity can be increased due to the addition of GO. Consequently, the studies on three additives may contribute to the rational design of silicon-based and other anode materials.

Gefitinib (Iressa), is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), used in the targeted treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). Skin toxicity is the major adverse effect observed in patients treated with EGFR-targeted TKIs such as gefitinib and erlotinib. To date, a corresponding skin animal model has not been established to address the mechanisms of these effects. Therefore, we analyzed the skin rash phenotype and its pathological features in Brown Norway (BN) rats treated with gefitinib 2.5 mg, 5.0 mg, or 10 mg/100 g/day for 4 weeks. We found that treatment with gefitinib led to weight loss, rash, itching, and hair loss in a dose-dependent manner. We also investigated the skin pathology and found that the animal model showed thickening of the epidermis, loss of moisture, and apoptosis of keratinocytes. Immunohistochemistry, flow cytometry, and analysis of monocytes and leukocytes in the blood revealed increased macrophage infiltration was associated with the cutaneous toxicities induced by gefitinib in the BN rats. Finally, we found that gefitinib-induced cutaneous toxicity is significantly associated with three inflammatory cytokines known to be secreted by activated macrophages, TREM-1, CINC-2, and CINC-3.

Background An increasing number of studies have shown the merits of endoscopic retrograde appendicitis therapy (ERAT) in diagnosing and treating acute uncomplicated appendicitis. However, no related prospective controlled studies have been reported yet. Our aim is to assess the feasibility and safety of ERAT in the treatment of acute uncomplicated appendicitis. Methods In this open-label, randomized trial, participants were randomly allocated to the ERAT group, laparoscopic appendectomy (LA) group and open appendectomy (OA) group. The primary outcome was the clinical success rate of the treatment. Intention-to-treat analysis was used in the study. Results The study comprised of 99 patients, with 33 participants in each group. The clinical success rate was 87.88% (29/33), 96.97% (32/33) and 100% (33/33) in the ERAT, LA and OA group, respectively. In the ERAT group, 4 patients failed ERAT due to difficult cannulation. In LA group, 1 patient failed because of abdominal adhesion. There were no significant differences among the three treatment groups regarding the clinical success rate (P = 0.123). The median duration of follow-up was 22 months. There were no significant differences (P = 0.693) among the three groups in terms of adverse events and the final crossover rate of ERAT to surgery was 21.21% (7/33). Conclusion ERAT can serve as an alternative and efficient method to treat acute uncomplicated appendicitis. Trial registration The study is registered with the WHO Primary Registry-Chinese Clinical Trial Registry (ChiCTR1900025812).

Long non-coding RNAs (lncRNAs) play critical functions in various cancers. Firre intergenic repeating RNA element (FIRRE), a lncRNA located in the nucleus, was overexpressed in colorectal cancer (CRC). However, the detailed mechanism of FIRRE in CRC remains elusive. Results of RNA sequence and qPCR illustrated overexpression of FIRRE in CRC cell lines and tissues. The aberrant expression of FIRRE was correlated with the migration, invasion, and proliferation in cell lines. In accordance, it was also associated with lymphatic metastasis and distant metastasis in patients with CRC. FIRRE was identified to physically interact with Polypyrimidine tract-binding protein (PTBP1) by RNA pull-down and RNA immunoprecipitation (RIP). Overexpression of FIRRE induced the translocation of PTBP1 from nucleus to cytoplasm, which was displayed by immunofluorescence and western blot. In turn, delocalization of FIRRE from nucleus to cytoplasm is observed after the loss of PTBP1. The RNA-protein complex in the cytoplasm directly bound to BECN1 mRNA, and the binding site was at the 3' end of the mRNA. Cells with FIRRE and PTBP1 depletion alone or in combination were treated by Actinomycin D (ACD). Results of qPCR showed FIRRE stabilized BECN1 mRNA in a PTBP1-medieated manner. In addition, FIRRE contributed to autophagy activity. These findings indicate FIRRE acts as an oncogenic factor in CRC, which induces tumor development through stabilizing BECN1 mRNA and facilitating autophagy in a PTBP1-mediated manner.

In 2020, a new coronavirus, SARS-CoV-2, quickly spread worldwide within a few months. Although coronaviruses typically infect the upper or lower respiratory tract, the virus RNA can be detected in plasma. The risk of transmitting coronavirus via transfusion of blood products remains. As more asymptomatic infections are identified in COVID-19 cases, blood safety has become particularly important. Methylene blue (MB) photochemical technology has been proven to inactivate lipid-enveloped viruses with high efficiency and safety. The present study aimed to investigate the SARS-CoV-2 inactivation effects of MB in plasma. The SARS-CoV-2 virus strain was isolated from Zhejiang University. The live virus was harvested from cultured VERO-E6 cells, and mixed with MB in plasma. The MB final concentrations were 0, 1, 2, and 4 μM. The “BX-1 AIDS treatment instrument” was used at room temperature, the illumination adjusted to 55,000 ± 0.5 million Lux, and the plasma was irradiated for 0, 2, 5, 10, 20, and 40 mins using light at a single wavelength of 630 nm. Virus load changes were measured using quantitative reverse transcription- PCR. BX-1 could effectively eliminate SARS-CoV-2 within 2 mins in plasma, and the virus titer declined to 4.5 log10 TCID50 (median tissue culture infectious dose)/mL. BX-1 is based on MB photochemical technology, which was designed to inactivate HIV-1 virus in plasma. It was proven to be safe and reliable in clinical trials of HIV treatment. In this study, we showed that BX-1 could also be applied to inactivate SARS-CoV-2. During the current outbreak, this technique it has great potential for ensuring the safety of blood transfusions, for plasma transfusion therapy in recovering patients, and for preparing inactivated vaccines.

Saline lakes represent a particularly interesting aquatic environment for harboring high microbial diversity. However, the microbial diversity in different states and locations of saline lake is often overlooked. We studied for the first time the diversity and relative composition of the microbial communities in the Chagan Lake, NE China, and investigated the differences in microbial species and physical and chemical factors in different geographical localities of the lake. After extracting the total DNA of the sample, we tested the library with the established library, sequenced the qualified library with Illumina HiSeq 2500, and studied the bacterial diversity by 16S rRNA targeted metagenomics analysis. Results reveal that the highest microbial abundance in Chagan Lake at genus level was Proteobacterium followed by Actinomycetes and Bacteroides. In addition, we compared the microbial composition within the lake using alpha- and beta-diversity indices, showing that both diversity and evenness were the highest in the middle of the lake and lowest in the west of lake areas, and in the upper, middle, and lower depth of water columns, the low water column had the highest species number in the whole water environment, but the difference was not significant. We believe that physicochemical factors contribute to the formation of microbial community composition and diversity. In aquaculture industry, it is impossible apply horticulture for making full use of the spatial differences in the microbial composition of the water. Therefore, combining cultured aquatic animal with the most suitable microbial species is a good way to boost the breeding effect for greater economic value.

Post-traumatic stress disorder (PTSD) is a mental disease associated with the exposure of traumatic stress, and results in the structural and functional changes of hippocampus. Calcineurin (CaN), a calcium/calmodulin-regulated protein phosphatase ubiquitously expressed in brain, has a very important role in the fear extinction, neuronal structure and neuronal excitability. With CaN activation, its down target nuclear factor of activated T cells (NFATs) dephosphorylated and then translocated from the cytoplasm to the nucleus to affect neuronal function, resulting in the function changes of brain structure such as hippocampus. Increasing evidence has suggested that CaN/NFATs signaling are involved in the regulation of mental disorders like Alzheimer's disease, depression, while little is known about its effects on the molecular mechanisms on PTSD. This study seek to know the relationship between PTSD and CaN/NFATc4 pathway, and to detect whether CaN/NFATc4 pathway are involved in the hippocampus dysfunctions in a single-prolonged stress (SPS)-based rat model of PTSD. Our results have showed that after 4 days exposed to SPS, the protein expression of CaN up-regulated and the NFATc4 dephosphorylated and imported into the nucleus; while at the 7 and 14 day exposed to SPS, with the down-regulation of CaN, the expression of phosphorylate-NFATc4 increased. Our results show that CaN/NFATc4 pathway were involved in the development of PTSD model, which suggested that the changes of CaN/NFATc4 pathway may be one of the pathological molecular mechanism in the dysfunction of hippocampus in PTSD.

Background In 2020, a new coronavirus, SARS-CoV-2, quickly spread worldwide within a few months. Although coronaviruses typically infect the upper or lower respiratory tract, the virus RNA can be detected in plasma. The risk of transmitting coronavirus via transfusion of blood products remains. As more asymptomatic infections are identified in COVID-19 cases, blood safety has become particularly important. Methylene blue (MB) photochemical technology has been proven to inactivate lipid-enveloped viruses with high efficiency and safety. The present study aimed to investigate the SARS-CoV-2 inactivation effects of MB in plasma. Methods The SARS-CoV-2 virus strain was isolated from Zhejiang University. The live virus was harvested from cultured VERO-E6 cells, and mixed with MB in plasma. The MB final concentrations were 0, 1, 2, and 4 μM. The “BX-1 AIDS treatment instrument” was used at room temperature, the illumination adjusted to 55,000 ± 0.5 million Lux, and the plasma was irradiated for 0, 2, 5, 10, 20, and 40 mins using light at a single wavelength of 630 nm. Virus load changes were measured using quantitative reverse transcription- PCR. Results BX-1 could effectively eliminate SARS-CoV-2 within 2 mins in plasma, and the virus titer declined to 4.5 log10 TCID50 (median tissue culture infectious dose)/mL. Conclusion BX-1 is based on MB photochemical technology, which was designed to inactivate HIV-1 virus in plasma. It was proven to be safe and reliable in clinical trials of HIV treatment. In this study, we showed that BX-1 could also be applied to inactivate SARS-CoV-2. During the current outbreak, this technique it has great potential for ensuring the safety of blood transfusions, for plasma transfusion therapy in recovering patients, and for preparing inactivated vaccines.

To identify the commonalities between rheumatoid arthritis (RA) and diabetes mellitus (DM) to understand the mechanisms of Chinese medicine (CM) in different diseases with the same treatment. A text mining approach was adopted to analyze the commonalities between RA and DM according to CM and biological elements. The major commonalities were subsequently verified in RA and DM rat models, in which herbal formula for the treatment of both RA and DM identified via text mining was used as the intervention. Similarities were identified between RA and DM regarding the CM approach used for diagnosis and treatment, as well as the networks of biological activities affected by each disease, including the involvement of adhesion molecules, oxidative stress, cytokines, T-lymphocytes, apoptosis, and inflammation. The Ramulus Cinnamomi-Radix Paeoniae Alba-Rhizoma Anemarrhenae is an herbal combination used to treat RA and DM. This formula demonstrated similar effects on oxidative stress and inflammation in rats with collagen-induced arthritis, which supports the text mining results regarding the commonalities between RA and DM. Commonalities between the biological activities involved in RA and DM were identified through text mining, and both RA and DM might be responsive to the same intervention at a specific stage.

Lectin receptor-like kinases (LecRKs) are a class of membrane proteins found in higher plants. They play important roles in defense against of pathogens, perception of insect feeding, and stress tolerance. LecRK-VII.1 (AT4G04960) is one member of the LecRK family, which contains a conserved lectin domain and a kinase domain. In this study, the lecrk-VII.1 mutants (lecrk-VII.1-1 and lecrk-VII.1-2) showed increased seed germination rates and primary root length compared to ecotype Columbia-0 (Col-0) when treated with different concentrations of NaCl and methyl jasmonate (MeJA). To further confirm the possible role of LecRK-VII.1 in salt and jasmonic acid (JA) responses, we performed a comparative proteomic analysis of Arabidopsis Col-0 and lecrk-VII.1-1 mutant seedlings. In total, 312 proteins were differentially expressed of which 75 were related to stress responses including salt stress and JA response. Among them, decreased expressions of lipoxygenase (LOX) and annexin were confirmed by RT-PCR analyses. Activity of LOX was accordingly reduced in lecrk-VII.1 mutants. These results provide some valuable data to understand the role of LecRK-VII.1 in the response to salt stress and MeJA. In order to understand the role of LecRK-VII.1 in the response to salt stress and MeJA, we studied the phenotypes and expression patterns between the lecrk-VII.1 mutants and wild type. Comparative proteomic analysis of differentially expressed proteins of the lecrk-VII.1 mutants and wild type in Arabidopsis was performed.

Spin–orbit torque (SOT), which is induced by an in-plane electric current via large spin-orbit coupling, enables an innovative method of manipulating the magnetization of ferromagnets by means of current injection. In conventional SOT bilayer systems, the magnetization switching efficiency strongly depends on the interface quality and the strength of the intrinsic spin Hall Effect. Here, we demonstrate highly efficient full SOT switching achieved by applying a current in a single layer of perpendicularly magnetized ferromagnetic semiconductor GaMnAs with an extremely small current density of ∼3.4 × 105 A cm−2, which is two orders of magnitude smaller than that needed in typical metal bilayer systems. This low required current density is attributed to the intrinsic bulk inversion asymmetry of GaMnAs as well as its high-quality single crystallinity and large spin polarization. Our findings will contribute to advancements in the electrical control of magnetism and its practical application in semiconductor devices., Spin orbit torque enables an innovative method of manipulating the magnetization of ferromagnets by current injection. Here, Jiang et al. demonstrate efficient full spin–orbit torque switching with an activation current density of ∼3.4 × 105 A cm−2 in a single layer ferromagnetic semiconductor GaMnAs.

A series of iridium-rhenium catalysts with different impregnation sequences were prepared and the catalytic properties of these catalysts for glycerol hydrogenolysis were evaluated. The catalyst prepared by the impregnation of Ir prior to Re afforded the best selectivity to 1,3-propanediol of 49.2 % with 43.7 % glycerol conversion. These catalysts were also characterized by temperature programmed reduction (TPR), X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), NH3-temperature programmed desorption (NH3-TPD), Fourier transform infrared spectroscopy (FT-IR) and H2-chemisorption. It was found that Ir0 species played a key role on the activities of glycerol conversion, and Re species might act as an efficient promoter to improve the dispersive state of Ir species as well as the reducibility. Kinetic studies have also been conducted and it was observed that the number of Ir0 may affect the extent of consecutive hydrogenolysis of 1,3-propanediol over catalysts, and an appropriate number of Ir0 was of importance to 1,3-propanediol selectivity.

This article studied the difference between two 3V-PPh3 polymer (POL-PPh3) supported Rh catalysts synthesized via different synthetic strategies, one-pot and post-synthesis, respectively. The catalytic performance of the two catalysts was further evaluated for the hydroformylation of propylene on a fixed-bed reactor. The catalyst prepared through post-synthesis (Rh/POL-PPh3) showed better catalytic activity compared to the one-pot sample (Rh-POL-PPh3), and exhibited excellent long-term stability. N-2 sorption, SEM, EXAFS and FT-IR characterization results suggested that the possible reasons for the different catalytic performance of two catalysts can be ascribed to the fact that part of Rh species was probably embedded into the framework of POL-PPh3 in the Rh-POL-PPh3 catalyst. Moreover, it might restrict the accessibility of reagents to Rh species and block the flexible coordination between Rh species and POL-PPh3. The Rh/POL-PPh3 catalyst synthesized via post-synthesis and the Rh species were uniformly distributed on the surface of PO-LPPh3, which might have a positive effect on the improvement of the mass transfer and the flexible coordination of Rh species with POL-PPh3.

Guizhi-Shaoyao-Zhimu decoction (GSZ), a traditional Chinese medicine (TCM) herbal formula, has been shown effective in the treatment of diabetic peripheral neuropathy (DPN). In this study, network analysis was performed to decipher the molecular mechanisms of GSZ in the treatment of DPN. The chemical components of the 3 herbs forming GSZ, ie, Ramulus Cinnamomi (Guizhi), Paeonia lactiflora (Shaoyao) and Rhizoma Anemarrhenae (Zhimu), were searched in Chinese medicine dictionaries, and their target proteins were identified in PubChem. DPN genes were searched in PubMed gene databases. Ingenuity Pathway Analysis (IPA) was used to build the GSZ pharmacological network and DPN molecular network. The canonical pathways between the two networks were compared to decipher the molecular mechanisms of GSZ in the treatment of DPN. Sixty-one protein targets for Guizhi, 31 targets for Shaoyao, 47 targets for Zhimu, as well as 23 genes related to DPN were identified and uploaded to IPA. The primary functions of the DPN molecular network were inflammatory response, metabolic disease, cellular assembly and organization. As far as the pharmacological network functions were concerned, Guizhi target proteins were involved in neurological disease, inflammatory disease, cellular growth and proliferation, cell signaling, molecular transport, and nucleic acid metabolism, Shaoyao target proteins were related to neurological disease, inflammatory disease, and Zhimu target proteins focused on cell death and survival, cellular movement, immune cell trafficking, DNA replication, recombination and repair, and cell cycle. In the three-herb combination GSZ, several new network functions were revealed, including the inflammatory response, gene expression, connective tissue development and function, endocrine system disorders, and metabolic disease. The canonical pathway comparison showed that Shaoyao focused on IL-12 signaling and production in macrophages, and Zhimu focused on TNFR2 signaling, death receptor signaling, ILK signaling, IL-17A in gastric cells, IL-6 signaling, IL-8 signaling, the role of JAK1, JAK2, and TYK2 in interferon signaling, IL-9 signaling, HMGB1 signaling, NO production and ROS production in macrophages, whereas GSZ focused aryl hydrocarbon receptor signaling and apoptosis signaling in addition to those pathways induced by Guizhi, Shaoyao and Zhimu. Although each single herb can affect some DPN-related functions and pathways, GSZ exerts more effects on DPN-related functions and pathways. The effects of GSZ on aryl hydrocarbon receptor signaling and apoptosis signaling pathways may be the key components of its total molecular mechanisms.

Some cytokines, such as interleukin-2 (IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), produced by lymphocytes might play an important role in anti-tumor immunity and their production is possibly suppressed by cancer. Amelioration of the suppression of cytokine production might contribute to cancer control. Ganoderma lucidum polysaccharides (Gl-PS), a versatile group of a component of G. lucidum and one with various bioactivities, might have this potential. In this study, analyses including reverse transcription and the polymerase chain reaction (RT-PCR), immunocytochemistry and Western blot were used to test the effects of Gl-PS on the production of IL-2, IFN-γ and TNF-α in mononuclear lymphocytes by incubating Gl-PS with mouse splenic mononuclear lymphocytes in the presence of B16F10 cell culture supernatant following activation by phytohemagglutinin. The RT-PCR, immunocytochemistry and Western blot assays showed that the production of IL-2, IFN-γ and TNF-α in mononuclear lymphocytes was suppressed by B16F10 cell culture supernatant at both the mRNA and protein levels, whereas the suppression was fully or partially ameliorated by Gl-PS. The amelioration by Gl-PS against the suppression of the production of IL-2, IFN-γ and TNF-α in mononuclear lymphocytes by B16F10 cell culture supernatant might contribute to cancer control.

To explore the effectiveness related indicators which might help identify the indications of Tongxinluo Capsule () and Kangxin Capsule () targeting on qi deficiency and blood stasis pattern in Chinese medicine (CM) in the treatment of angina pectoris.The data from a multicenter, randomized and double-blinded study conducted at 5 centers in China were obtained for the analysis. A total of 239 patients with angina pectoris and CM syndrome of qi deficiency and blood stasis were randomly assigned in a 1:1 ratio to Tongxinluo Capsule group (119 cases) and Kangxin Capsule group (120 cases). Angina effectiveness and electrocardiogram (ECG) improvement were selected as the therapeutic outcomes.After a 4-week treatment, the effective rates of Tongxinluo Capsule and Kangxin Capsule were 43.70% and 25.00%, respectively (P0.05). Serum low-density lipoprotein (LDL) level was found to influence the effectiveness of Tongxinluo Capsule which had higher effective rate in the patients with lower level of LDL. Heart rate was found to influence the effectiveness in the patients treated with Kangxin Capsule which had higher effective rate in the patients with heart rate [Symbol: see text]80 beats/min.LDL level and heart rate were the indicators which help indentify the indications of Tongxinluo Capsule and Kangxin Capsule, respectively, in the treatment of angina pectoris with CM syndrome of qi deficiency and blood stasis.

Dysregulation of β-catenin turnover due to mutations of its regulatory proteins including adenomatous polyposis coli (APC) and p53 is implicated in the pathogenesis of cancer. Thus, intensive effort is being made to search for alternative approaches to reduce abnormally activated β-catenin in cancer cells. Nur77, an orphan member of the nuclear receptor superfamily, has a role in the growth and apoptosis of cancer cells. Here, we reported that Nur77 could inhibit transcriptional activity of β-catenin by inducing β-catenin degradation via proteasomal degradation pathway that is glycogen synthase kinase 3β and Siah-1 independent. Nur77 induction of β-catenin degradation required both the N-terminal region of Nur77, which was involved in Nur77 ubiquitination, and the C-terminal region, which was responsible for β-catenin binding. Nur77/ΔDBD, a Nur77 mutant lacking its DNA-binding domain, resided in the cytoplasm, interacted with β-catenin, and induced β-catenin degradation, demonstrating that Nur77-mediated β-catenin degradation was independent of its DNA binding and transactivation, and might occur in the cytoplasm. In addition, we reported our identification of two digitalis-like compounds (DLCs), H-9 and ATE-i2-b4, which potently induced Nur77 expression and β-catenin degradation in SW620 colon cancer cells expressing mutant APC protein in vitro and in animals. DLC-induced Nur77 protein was mainly found in the cytoplasm, and inhibition of Nur77 nuclear export by the CRM1-dependent nuclear export inhibitor leptomycin B or Jun N-terminal kinase inhibitor prevented the effect of DLC on inducing β-catenin degradation. Together, our results demonstrate that β-catenin can be degraded by cytoplasmic Nur77 through their interaction and identify H-9 and ATE-i2-b4 as potent activators of the Nur77-mediated pathway for β-catenin degradation.

Clinical manifestations of rheumatoid arthritis (RA) are diversified, and based on the manifestations, the patients with RA could be classified into different patterns under traditional Chinese medicine. These patterns decide the selection of herbal prescription, and thus they can help find a subset of rheumatoid arthritis patients for a type of therapy. In the present study, we combine genome-wide expression analysis with methods of systems biology to identify the functional gene networks for the sets of clinical symptoms that comprise the major information for pattern classification. Clinical manifestations in rheumatoid arthritis were clustered with factor analysis, and two factors (similar to cold and hot patterns in traditional Chinese medicine) were found. Microarray technology was used to reveal gene expression profiles in CD4(+) T cells from 21 rheumatoid arthritis patients. Protein-protein interaction information for these genes from databases and literature data was searched. The highly-connected regions were detected to infer significant complexes or pathways in this protein-protein interaction network. The significant pathways and function were extracted from these subnetworks using the Biological Network Gene Ontology tool. The genes significantly related to hot and cold patterns were identified by correlations analysis. MAPK signalling pathway, Wnt signaling pathway, and insulin signaling pathway were found to be related to hot pattern. Purine metabolism was related to both hot and cold patterns. Alanine, aspartate, and tyrosine metabolism were related to cold pattern, and histindine metabolism and lysine degradation were related to hot pattern. The results suggest that cold and hot patterns in traditional Chinese medicine were related to different pathways, and the network analysis might be used for identifying the pattern classification in other diseases.

Serving as recycled coarse aggregate, the pretreated rural building waste was added into the concrete hollow bricks in the varying replacement of 0, 20%, 40%, 60%, 80% and 100%. By testing its compressive strength, flexural strength, mass and strength loss after freeze-thaw cycles, the impact of the different replacement on mechanical and frost-resistance properties of concrete hollow bricks was presented through SEM analysis. The experimental results show that, with the increase in recycled coarse aggregate replacement rate, the mechanical and frost-resistance properties show a downward trend; when the replacement rate is 40%, 28 d compressive strength and flexural strength of concrete hollow brick demonstrate the good peak value which meet the requirement of the national standard for ordinary small concrete hollow bricks; the interfacial structures of the pretreated recycled concrete is more complicated than those of concrete made of natural aggregate, but the former enjoys better interface bonding and tight structure.

The abnormal expression of Annexin II (AnxA2, A2) has been associated with the development of tumors; however, its expression and function in multiple myeloma (MM) is less known. We compared the expression of AnxA2 in primary myeloma cells from MM patients with that in normal plasma cells from normal subjects and found that myeloma cells from patients had higher expression of AnxA2. Expression of AnxA2 was also significantly higher in MM cell lines U266 and RPMI8226, compared with other hematologic tumor cell lines. Transfecting U266 and RPMI8226 cells with the small interfering RNA (siRNA) that targets human AnxA2 led to significant downregulation of AnxA2 expression, which resulted in the decreased proliferation, invasive potential and increased apoptosis of U266 and RPMI8226 cell lines. Silencing AnxA2 gene by siRNA also inhibited the expression of pro-angiogenic molecules including VEGF-C, VEGF-R2, MMP-2, MMP-9, MT1-MMP and TIMP-2 in the two cell lines. Our data suggested that the AnxA2 is overexpressed in MM patients and myeloma cell lines U266 and RPMI8226, and that AnxA2 overexpression appeared to affect the proliferation, apoptosis, invasive potential and production of pro-angiogenic factors in MM cell lines U266 and RPMI8226.

Tripterygium wilfordii Hook F. (TwHF) based therapy has been proved as effective in treating rheumatoid arthritis (RA), yet the predictors to its response remains unclear. A two-stage trial was designed to identify and verify the baseline symptomatic predictors of this therapy. 167 patients with active RA were enrolled with a 24-week TwHF based therapy treatment and the symptomatic predictors were identified in an open trial; then in a randomized clinical trial (RCT) for verification, 218 RA patients were enrolled and classified into predictor positive (P+) and predictor negative (P−) group and were randomly assigned to accept the TwHF based therapy and Methotrexate and Sulfasalazine combination therapy (M&S) for 24 weeks, respectively. Five predictors were identified (diuresis, excessive sweating, night sweats for positive; and yellow tongue-coating, thermalgia in the joints for negative). In the RCT, The ACR 20 responses were 82.61% in TwHF/P+ group, significantly higher than that in TwHF/P− group (P = 0.0001) and in M&S/P+ group (P < 0.05), but not higher than in M&S/P− group. Similar results were yielded in ACR 50 yet not in ACR 70 response. No significant differences were detected in safety profiles among groups. The identified predictors enable the TwHF based therapy more efficiently in treating RA subpopulations.

The presence of macrolide antibiotics in aquatic environments causes serious antibiotic resistance propagation in microorganisms. In this study, the use of porous resins as adsorbents for the removal of tylosin from aqueous solutions was evaluated. The effectiveness of the resins (macroporous resin XAD-4, hypercross-linked resin MN-202, and aminated polystyrene resin MN-150) was compared with commercial hydroxylated multiwall carbon nanotubes (H-MWCNTs). Similar patterns of pH-dependent adsorption were observed despite the different surface properties and pore structures of the three resins, implying the importance of the tylosin molecular form in the adsorption process. Tylosin adsorption onto the four adsorbents showed different ionic strengths and temperature dependence consistent with the tylosin speciation and corresponding adsorption mechanism. The adsorption of tylosin onto the XAD-4 and MN-202 is mainly controlled by the intermolecular interactions between the matrix of the adsorbents and the tylosin molecule, whereas specific bonds among multiple surface functional groups are the predominant contributors to MN-150 and H-MWCNTs. The pore size is the key parameter in tylosin adsorption onto the surface of the adsorbents. The adsorption kinetics of the four adsorbents followed the pseudo-second-order model. The adsorption isotherm data well fit the Langmuir models, indicating surface coverage by a monomolecular layer.

Background The common randomized controlled trial design has distinct limitations when applied to Chinese medicine, because Chinese medicine identifies and treats 'Chinese medicine patterns' rather than diagnosed diseases. Chinese medicine patterns are a group of associated symptoms, tongue appearances and pulse characteristics. These limitations could be overcome by developing new strategies to evaluate the effect of Chinese medicine. The idea behind pattern-based efficacy evaluations may optimize clinical trial design by identifying the responsiveness-related Chinese medicine patterns. Methods/Design This is a two-stage multi-center trial of Chinese herbal medicine for the management of rheumatoid arthritis. The stage one trial is an open-label trial and aims to explore what groups of Chinese medicine information (such as symptoms) correlates with better efficacy, and the stage two trial is a randomized, controlled, double-blind, double-dummy clinical trial that incorporates the efficacy-related information identified in the stage-one trial into the inclusion criteria. Discussion The indication of a Chinese herbal formula is a specific Chinese medicine pattern and not a single disease and stratifying a disease into several patterns with a group of symptoms is a feasible procedure in clinical trials. This study is the first to investigate whether this approach in the design of Chinese herbal medicine trials can improve responses. Trial registration ChiCTR-TRC-10000989

Ethnopharmacological relevance Fufangkushen colon-coated capsule (FCC) was a newly developed herbal drug for treating ulcerative colitis (UC) patients with traditional Chinese medicine (TCM) pattern of damp-heat accumulating in the interior. Objective To explore the efficacy and safety of FCC in the treatment of active UC compared with Huidi (HD, mesalazine enteric-coated tablets) were evaluated in a double-blinded and randomized clinical trial. Materials and Methods In the double-blind, double-dummy, multicenter, randomized and controlled study, 320 active UC patients with TCM pattern of damp-heat accumulating in the interior were assigned to two groups: 240 treated with FCC plus HD placebo treatment, 80 with HD plus FCC placebo. The drugs and their corresponding placebos were administrated at advised dosage for 8 weeks. The primary endpoint was a positive clinical response at week 8, and Mayo scoring system was employed for assessment of UC activity. Results At the 8th week, 72.50 % of patients in FCC group (170 of 234) and 65.00 % of patients in HD group (52 of 80) had achieved a clinical response. There was no statistically significance between the 2 groups (P > 0.05). The proportions of patients who had a clinical remission was similar in 2 groups (41.50 % in FCC group, 41.25 % in HD group, P > 0.05), mucosal healing rate at week 8 in the two groups were also without significant difference (55.13 % in FCC group, 55.00 % in HD group, P > 0.05). Mayo scores at week 8 showed no statistically difference in the two groups. No significant differences were observed between the safety profiles of the 2 groups (P > 0.05). No severe AEs were reported in either group. The latent class analysis indicated that FCC was superior applicable for the left hemicolon involved patients than HD. Conclusions Compared with HD, a mesalamine enteric-coated tablet, FCC is similarly effective and safe in the treatment of active UC with TCM pattern of damp-heat accumulation interior pattern. In addition, FCC indicates superior effect in the treatment of UC with inflamed area of the left hemicolon than HD.