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Abstract Background There are a variety of causes of left ventricular aneurysm, but it is rarely due to a disturbance in intraventricular hemodynamics. To the best of our knowledge, there have been no reports of ventricular aneurysm at the left ventricular apex caused by an abnormal left ventricular muscle bundle. Case presentation We report two cases of patients with congenital abnormal left ventricular muscle bundles which caused disturbances in intraventricular hemodynamics. This process eventually led to a left ventricular aneurysm at the apex of the heart. In both cases, transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) indicated ventricular aneurysm formation at the apex of the left ventricle. There were also abnormal muscular bundles connecting the ventricular septum and the posterior wall of the left ventricle. The only differences between these two cases were the comorbidities and severity of symptoms. Conclusion Ventricular aneurysm at the apex of the left ventricle is common. However, it is rare for a ventricular aneurysm to form due to intraventricular hemodynamic disturbances caused by an abnormal muscle bundle as opposed to that due to original ventricular wall damage, which is more common. There is currently a lack of relevant studies on the treatment and prognosis of such patients. Whether surgical resection of a ventricular aneurysm leads to a better prognosis remains uncertain.

Abstract Background Bartonella henselae is a Gram-negative bacterium transmitted to humans by a scratch from cat in the presence of ectoparasites. Humans infected with B. henselae can result in various clinical diseases including local lymphadenopathy and more serious systemic disease such as persistent bacteremia and endocarditis. The current treatment of persistent B. henselae infections is not very effective and remains a challenge. To find more effective treatments for persistent and biofilm Bartonella infections, in this study, we evaluated a panel of drugs and drug combinations based on the current treatment and also promising hits identified from a recent drug screen against stationary phase and biofilm recovered cells of B. henselae. Results We evaluated 14 antibiotics and 25 antibiotic combinations for activity against stationary phase B. henselae (all antibiotics were at 5 μg/ml) and found that ciprofloxacin, gentamicin, and nitrofurantoin were the most active agents, while clofazimine and miconazole had poor activity. Drug combinations azithromycin/ciprofloxacin, azithromycin/methylene blue, rifampin/ciprofloxacin, and rifampin/methylene blue could rapidly kill stationary phase B. henselae with no detectable CFU after 1-day exposure. Methylene blue and rifampin were the most active agents against the biofilm B. henselae after 6 days of drug exposure. Antibiotic combinations (azithromycin/ciprofloxacin, azithromycin/methylene blue, rifampin/ciprofloxacin, rifampin/methylene blue) completely eradicated the biofilm B. henselae after treatment for 6 days. Conclusions These findings may facilitate development of more effective treatment of persistent Bartonella infections in the future.

Ferrous iron and polysulfide (Fe(II)Sn aq) is a nano‐decoction. It is usually prepared from the suspension of iron sulfide nanomaterial, using autoclave and centrifugation. A previous study conducted in our laboratory revealed that Fe(II)Sn aq was highly antibacterial, and it could efficiently kill more than 90% population of Escherichia coli and Staphylococcus aureus, within 5 min of the treatment. Our study reported that the intravenous administration of Fe(II)Sn aq provided effective treatment against epididymis infection, caused by S. aureus. The results of the study further highlighted its potential for clinical application. However, its effects on the reproductive system and overall health of mammals have not been investigated earlier. The present study assessed the impacts of Fe(II)Sn aq on reproductive health and other aspects of male mice. Briefly, male mice were exposed to Fe(II)Sn aq, either intravenously at the dose of 0.7 mM, 1.4 mM, and 2.8 mM of Fe2+or orally at the dose of 1.4 mM, 2.8 mM, and 5.6 mM of Fe2+. Following this, body weight, organs index, quality of sperm, blood biochemical markers, histopathology of organs, oxidative stress and apoptosis were evaluated, after 1 day and 30 days of exposure. In addition, male reproductivity was evaluated in terms of mating with female mice, and the body weight of the resulting offspring was recorded. Our results showed that the mice processed with Fe(II)Sn aq exhibited normal physiological status and reproductive capability. The present study illustrated the short‐ and long‐term influences of Fe(II)Sn aq on the fertility of male mice for the first time. The findings of the study provided a valuable reference for the application of Fe(II)Sn aq, particularly in terms of reproductive safety.

Objective. Dengue virus (DENV), Japanese encephalitis virus (JEV), and Zika virus (ZIKV) are several important flaviviruses, and infections caused by these flaviviruses remain worldwide health problems. Different flaviviruses exhibit different biological characteristics and pathogenicity. Metabolomics is an emerging research perspective to uncover and observe the pathogenesis of certain infections. Methods. To improve the understanding of the specific metabolic changes that occur during infection with different flaviviruses, considering the principle of noninvasive sampling, this article describes our comprehensive analysis of metabolites in urine samples from the three kinds of flavivirus-infected mice using a liquid chromatography tandem mass spectrometry method to better understand their infection mechanisms. Results. The urine of DENV-, JEV-, and ZIKV-infected mice had 68, 64, and 47 different differential metabolites, respectively, compared with the urine of control mice. Among the metabolic pathways designed by these metabolites, ABC transporters, arginine and proline metabolism, and regulation of lipolysis play an important role. Furthermore, we predicted and fitted potential relationships between metabolites and pathways. Conclusions. These virus-specific altered metabolites may be associated with their unique biological properties and pathogenicity. The metabolomic analysis of urine is very important for the analysis of flavivirus infection.

Luminescent molecular aggregates have attracted worldwide attention because of their potential applications in many fields. The luminescent properties of organic aggregates are complicated and highly morphology-dependent, unraveling the intrinsic mechanism behind is urgent. This review summarizes recent works on investigating the structure–property relationships of organic molecular aggregates at different environments, including crystal, cocrystal, amorphous aggregate, and doped systems by multiscale modeling protocol. We aim to explore the influence of intermolecular non-covalent interactions on molecular packing and their photophysical properties and then pave the effective way to design, synthesize, and develop advanced organic luminescent materials.

Biochar is a low-cost adsorbent for sorptive removal of antibiotics from wastewater, but the adsorption efficiency needs to be improved. In this study, coconut-shell biochar was activated with KOH to improve the adsorption efficiency and magnetically modified with FeCl3 to enable recycling. The amount of KOH and the concentration of FeCl3 were optimized to reduce the pollution and production cost. The KOH-activated and FeCl3-magnetized biochar gave good sulfonamide antibiotic (SA) removal. The maximum adsorption capacities for sulfadiazine, sulfamethazine and sulfamethoxazole were 294.12, 400.00 and 454.55 mg g−1, respectively, i.e., five to seven times higher than those achieved with raw biochar. More than 80% of the adsorption capacity was retained after three consecutive adsorption-desorption cycles. A combination of scanning electron microscopy, Brunauer-Emmett-Teller analysis, X-ray diffraction, Fourier-transform infrared and Raman spectroscopies, and magnetic hysteresis analysis showed that KOH activation increased the specific surface area, porosity, and number of oxygen-rich functional groups. Iron oxide particles, which were formed by FeCl3 magnetization, covered the biochar surface. The SAs were adsorbed on the modified biochar via hydrogen bonds between SA molecules and -OH/-COOH groups in the biochar. Investigation of the adsorption kinetics and isotherms showed that the adsorption process follows a pseudo-second-order kinetic model and a monolayer adsorption mechanism. The adsorption capacity at low pH was relatively high because of a combination of π+-π electron-donor-acceptor, charge-assisted hydrogen-bonding, electrostatic, and Lewis acid-base interactions, pore filling, van der Waals forces and hydrophobic interactions. The results of this study show that magnetically modified biochar has potential applications as an effective, recyclable adsorbent for antibiotic removal during wastewater treatment.

Hedgehog (Hh) and Bone Morphogenetic Proteins (BMPs) pattern the developing Drosophila wing by functioning as short- and long-range morphogens, respectively. Here, we show that a previously unknown Hh-dependent mechanism fine-tunes the activity of BMPs. Through genome-wide expression profiling of the Drosophila wing imaginal discs, we identify nord as a novel target gene of the Hh signaling pathway. Nord is related to the vertebrate Neuron-Derived Neurotrophic Factor (NDNF) involved in congenital hypogonadotropic hypogonadism and several types of cancer. Loss- and gain-of-function analyses implicate Nord in the regulation of wing growth and proper crossvein patterning. At the molecular level, we present biochemical evidence that Nord is a secreted BMP-binding protein and localizes to the extracellular matrix. Nord binds to Decapentaplegic (Dpp) or the heterodimer Dpp-Glass-bottom boat (Gbb) to modulate their release and activity. Furthermore, we demonstrate that Nord is a dosage-dependent BMP modulator, where low levels of Nord promote and high levels inhibit BMP signaling. Taken together, we propose that Hh-induced Nord expression fine-tunes both the range and strength of BMP signaling in the developing Drosophila wing.

Capillaria hepatica is a seriously neglected zoonotic parasite, which infects the liver of mammalian hosts, causing fibrosis or even hepatic failure. At present, the immune responses elicited by C. hepatica are not fully understood, and the role(s) of the programmed death 1 (PD-1) signaling pathway in the context of C. hepatica-induced pathology are not known. In this study, we identify that the late stage of infection with C. hepatica—especially the egg-derived antigens—modulates the host immune responses to promote alternatively activated macrophage (M2) polarization and programmed death ligand 2 (PD-L2) expression. The PD-L2-expressing alternatively activated M2 macrophages play an important role in maintaining Th2-biased regulatory immune responses, which may facilitate the survival of parasitic worms or eggs within the infected liver and reduce the liver pathology caused by the egg granulomas. Treatment with anti-PD-L2 antibody had no effect on the survival of parasitic eggs but deteriorated the pathology of egg granulomas. The obtained results suggest that PD-1/PD-L2 signaling, which is involved in alternative macrophage polarization, determines the immune response pattern and the immunopathology, consequently determining the outcome of the parasitic infection.

Extraction methods directly affect pectin extraction yield and physicochemical and structural characteristics. The effects of acid extraction (AE), ultrasonic-assisted acid extraction (UA), steam explosion pretreatment combined with acid extraction (SEA) and ultrasonic-assisted SEA (USEA) on the yield, structure, and properties of passion fruit pectin were studied. The pectin yield of UA was 6.5%, equivalent to that of AE at 60 min (5.3%), but the emulsion stability of UA pectin was poor. The pectin obtained by USEA improved emulsion stability. Compared with UA, it had higher protein content (0.62%), rhamnogalacturonan I (18.44%) and lower molecular weight (0.72 × 105 Da). In addition, SEA and USEA had high pectin extraction yields (9.9% and 10.7%) and the pectin obtained from them had lower degrees of esterification (59.3% and 68.5%), but poor thermal stability. The results showed that ultrasonic-assisted steam explosion pretreatment combined with acid extraction is a high-efficiency and high-yield method. This method obtains pectin with good emulsifying stability from passion fruit peel.

Background Visceral leishmaniasis (VL) could progress to secondary hemophagocytic lymphohistiocytosis (HLH), which is a rare but life-threatening condition with poor prognosis. So far, the clinical and laboratory characteristics of VL associated HLH have not been well elucidated. Method and findings In this study, we retrospectively analyzed the clinical and laboratory profiles between 17 patients with VL associated HLH and 27 patients with VL alone admitted at the Beijing Friendship Hospital, Capital Medical University from May 2016 to March 2021. In addition to the identification of Leishmania infection, hemophagocytosis was identified in bone marrow in the most cases of VL associated HLH (15/17). The patients with VL associated HLH had higher chances of bleeding, hepatomegaly, thrombocytopenia, hypertriglyceridemia, hyperferritinemia, hypofibrinogenemia, elevated secretion of soluble IL-2 receptor or lower NK cell activity compared to patients with VL only. Furthermore, patients with VL associated HLH had higher inflammation status associated with higher levels of Th1 (TNF-α, IFN-γ, IL-1beta, IL-6, IL-8, IL-12p70), Th2 (IL-4) and Th17 cytokines (IL-17, IL-23) in the peripheral blood, and higher parasite load (qPCR and parasite culture). All 27 VL cases were totally recovered after being treated with Sodium Stibogluconate, five of the 17 patients with VL associated HLH died even after timely treatment with anti-parasite and immunosuppressive chemotherapy. Conclusion Without appropriate treatment, visceral leishmaniosis could develop to secondary HLH. The parasite culturing and qPCR detection of bone marrow samples facilitates the diagnosis of VL associated HLH in addition to other findings of HLH. Prompt treatment with anti-Leishmania and immunosuppressive chemotherapy is critical to reduce the mortality of VL associated HLH. Author summary Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening syndrome characterized by pro-inflammatory cytokine secretion, hyperinflammatory and multiple organ damages. Visceral leishmaniasis (VL) is a well-known cause of infection associated HLH and result in fatal consequence. However, it is not well characterized for the clinical and laboratory features of the visceral leishmaniasis associated HLH. In this study, we presented that, compared to the VL alone, patients with VL associated HLH had higher chances of bleeding, hepatomegaly, thrombocytopenia, hypertriglyceridemia, hyperferritinemia, hypofibrinogenemia, elevated secretion of soluble IL-2 receptor or lower NK cell activity. Moreover, patients with VL associated HLH also had higher levels of Th1, Th2 and Th17 cytokines in the sera and had higher parasite load in the bone marrow specimen. More cases with VL associated HLH had hepatosplenomegaly with iron overload in the magnetic resonance imaging. In the therapeutic strategy, besides the anti-Leishmania treatment, anti-inflammatory therapy to reduce cytokine storm and excessive immune responses facilitated the remission in the VL associated HLH cases.

Ultrasonic treatment combined with resveratrol modification was used to improve banana starch’s solubility, thermal stability, and digestion resistance. The solubility and freeze-thaw stability of the modified starch complex significantly increased. The oil-absorption capacity increased by 20.52%, and the gelatinization temperatures increased from 64.10–73.92 °C to 70.77–75.83 °C. The storage modulus (G′) and loss modulus (G″) increased after ultrasound and resveratrol treatment, and the proportion of viscosity was increased after composition with resveratrol. Additionally, the in vitro digestibility decreased from 44.12% to 40.25%. The modified complexes had release-control ability for resveratrol. X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) spectroscopy demonstrated that complex structures became more compact and organized, whereas crystalline patterns were unchanged. Scanning electron microscopy (SEM) showed that the resveratrol modification caused physical change on the granular surface by creating pores and fissures. The findings can help develop antioxidant functional foods using banana starch.

Wood–plastic composite (WPC) is a kind of composite material that is made of plastic and wood fiber or wood powder. Because it is mothproof, is resistant to corrosion, and has plasticity, among other advantages, it has been researched and used increasingly in building materials. The flexural property of WPC is an important subject in evaluating its mechanical properties. In this paper, wood–plastic raw materials and processing technology are introduced; the internal and external factors of WPC which affect the flexural properties are analyzed; the different ways of enhancing the bending capacity, including the surface pretreatment, addition of different modifiers (compatibility agent and coupling agent) etc. are summarized; and the methods of operation and strengthening effect are analyzed. This work provides a reference for further research in related fields.

Designing materials with large thermal expansion is highly desirable to fabricate microscale devices. The authors report unusually large anisotropic negative and positive thermal expansion in a simple crystalline material, through temperature-driven orientation of imidazole cations acting as molecular wheels.

Molecular systems displaying aggregation-induced emission (AIE) have important biomedical and optoelectronic applications. Here the authors report a further mechanism for AIE, through aromaticity reversal from the ground state to the excited state, in the non-aromatic annulene derivative of cyclooctatetrathiophene.

Abstract Background Knee osteoarthritis (KOA) is common in elderly people, causes pain, loss of physical functioning, and disability. This was a two-arm, superiority, quasi-experimental trial. The aim of this study was to evaluate the effectiveness of a home-based exercise intervention (HBEI) to reduce KOA symptoms and improve the physical functioning of elderly patients. Methods A total of 171 elderly patients (60 years of age or older) with KOA were recruited from four community centers. Patients from two community centers were randomly assigned to the intervention group (IG) and the other two centers were randomly assigned to the control group (CG). Participants in the IG received a 12-week HBEI (including four 2-h sessions supervised by a physiotherapist and fortnightly telephone support) combined with health education, while patients in the CG only received health education. The participants and physiotherapists were aware of the group assignment and alternative treatment components, but the study’s hypotheses were not disclosed to the participants. Pain intensity, joint stiffness, lower-limb muscle strength, balance, mobility, and quality of life were measured before and after the intervention by the same blinded assessor. Results A total of 171 patients (IG: n = 84, CG: n = 87) were enrolled. Data were obtained from 141 patients with an average age of 68 (range, 60–86 years) who completed the 12-week study (IG: n = 71, CG: n = 70). No significant group differences were found in any outcome measures at baseline. At week 12, the pretest/posttest changes 3significant between-group differences in decreases in pain intensity (− 1.60 (CI, − 2.75 to − 0.58)) and stiffness (− 0.79 (CI, − 1.37 to − 0.21)), with the IG exhibiting significantly larger improvements on both measures than the CG. The IG also showed significantly greater improvements on all the secondary outcomes than the CG did. Conclusions HBEI may be effective for relieving KOA symptoms, increasing the physical functioning, and improving quality of life in community-dwelling KOA elderly patients. A large randomized controlled trial with long-term follow-up is needed to confirm these findings. Trial registration Chinese Clinical Trails Registry number ChiCTR1800017026 (retrospectively registered). Registered 9 July 2018.

For a better understanding of the metabolic adaptations to sulfonamide (SA) stress in submerged macrophytes, the alterations of nutrient element uptake and secondary metabolism were studied in the leaves of Vallisneria natans (Lour.) Hara exposed to 0 and 50 mg/L of SA for 15 d. The results showed that, under a treatment of 50 mg/L SA, the malondialdehyde and superoxide anion (O2•−) contents in V. natans leaves significantly increased, 1.77–3.32 times higher than the control group, respectively, while the chlorophyll concentration showed a 36.99% reduction at the end of experiment. Simultaneously, V. natans showed a removal effect on SA and SA dramatically affected the nutrient removal efficiency by V. natans. Our results suggest that high SA levels can damage V. natans tissue and in turn that results in a stimulation of the antioxidant response. V. natans significantly improved the removal efficiency of SA, meanwhile SA resulted in less removal of TN and TP from the water column.

Cerium (Ce), the most abundant of rare earth elements in the earth's crust, has received much health concerns due to its wide application in industry, agriculture, and medicine. The current study aims to evaluate whether there is an association between Ce exposures and the risk of developing oral cancer. Serum Ce level of 324 oral cancer patients and 650 matched healthy controls were measured by inductively coupled plasma mass spectrometry. Association between Ce level and the risk of oral cancer was estimated with an unconditional logistic regression model. Serum Ce concentrations in the oral cancer patients and controls were 0.57 (0.21–3.02) μg/L and 2.27 (0.72–4.26) μg/L, respectively. High level of Ce was associated with a decreased risk of oral cancer (OR: 0.60, 95% CI: 0.43–0.84). Stronger inverse associations between high level of Ce and oral cancer risk were observed among those with smoking (OR: 0.46, 95% CI: 0.27–0.79), drinking (OR: 0.50, 95% CI: 0.26–0.96), limited intake of leafy vegetables (OR: 0.40, 95% CI: 0.22–0.71) and fish (OR: 0.52, 95% CI: 0.33–0.83). There were significant multiplicative interactions between Ce level and alcohol drinking or intake of leafy vegetables and fish (all Pinteraction

Hedgehog (Hh) signaling patterns embryonic tissues and contributes to homeostasis in adults. In Drosophila, Hh transport and signaling are thought to occur along a specialized class of actin-rich filopodia, termed cytonemes. Here, we report that Interference hedgehog (Ihog) not only forms a Hh receptor complex with Patched to mediate intracellular signaling, but Ihog also engages in trans-homophilic binding leading to cytoneme stabilization in a manner independent of its role as the Hh receptor. Both functions of Ihog (trans-homophilic binding for cytoneme stabilization and Hh binding for ligand sensing) involve a heparin-binding site on the first fibronectin repeat of the extracellular domain. Thus, the Ihog-Ihog interaction and the Hh-Ihog interaction cannot occur simultaneously for a single Ihog molecule. By combining experimental data and mathematical modeling, we determined that Hh-Ihog heterophilic interaction dominates and Hh can disrupt and displace Ihog molecules involved in trans-homophilic binding. Consequently, we proposed that the weaker Ihog-Ihog trans interaction promotes and stabilizes direct membrane contacts along cytonemes and that, as the cytoneme encounters secreted Hh ligands, the ligands trigger release of Ihog from trans Ihog-Ihog complex enabling transport or internalization of the Hh ligand-Ihog-Patched -receptor complex. Thus, the seemingly incompatible functions of Ihog in homophilic adhesion and ligand binding cooperate to assist Hh transport and reception along the cytonemes.

Background: Activated hepatic stellate cells (aHSCs) regulate the function of immune cells during liver fibrosis. As major innate cells in the liver, macrophages have inducible plasticity. Nevertheless, the mechanisms through which aHSCs regulate macrophages' phenotype and function during liver fibrosis and cirrhosis remain unclear. In this study, we examined the immunoregulatory function of aHSCs during liver fibrosis and explored their role in regulating macrophage phenotype and function.Methods: A total of 96 patients with different stages of chronic hepatitis B-related liver fibrosis were recruited in the study. Metavir score system was used to evaluate the degree of fibrosis. The expression of hepatic CCL2 and M2 phenotype macrophage marker CD163 were detected by immunohistochemistry, and the relationship among hepatic CD163, CCL2, and fibrosis scores were also explored. In the in vitro model, the aHSCs isolated from human liver tissues and THP-1-derived M0-type macrophages (M0MΦ) were co-cultured to observe whether and how aHSCs regulate the phenotype and function of macrophages. To explore whether CCL2/CCR2 axis has a crucial role in macrophage phenotypic changes during liver fibrosis, we treated the M0MΦ with recombinant human CCL2 or its specific receptor antagonist INCB-3284. Furthermore, we used LX2 and TGF-β-activated LX2 to mimic the different activation statuses of aHSCs to further confirm our results.Results: In patients, the infiltration of M2 macrophages increased during the progression of liver fibrosis. Intriguingly, as a key molecule for aHSC chemotactic macrophage aggregation, CCL2 markedly up-regulated the expression of CD163 and CD206 on the macrophages, which was further confirmed by adding the CCR2 antagonist (INCB 3284) into the cell culture system. In addition, the TGF-β stimulated LX2 further confirmed that aHSCs up-regulate the expression of CD163 and CD206 on macrophages. LX2 stimulated with TGF-β could produce more CCL2 and up-regulate other M2 phenotype macrophage-specific markers, including IL-10, ARG-1, and CCR2 besides CD163 and CD206 at the gene level, indicating that the different activation status of aHSCs might affect the final phenotype and function of macrophages.Conclusions: The expression of the M2 macrophage marker increases during liver fibrosis progression and is associated with fibrosis severity. AHSCs can recruit macrophages through the CCL2/CCR2 pathway and induce M2 phenotypic transformation.

The excessive use and disposal of plastic packaging materials have drawn increasing concerns from the society because of the detrimental effect on environment and ecosystems. As the most widely used fruit packing material, polyethylene (PE) film is not suitable for long-term preservation of some tropical fruits, such as mangos, due to its inferior gas permeability. Cellulose based film can be made from renewable resources and is biodegradable and environmental-friendly, which makes it a promising alternative to PE as a packaging material. In this study, cellulose film synthesized from delignified banana stem fibers via an ionic liquid 1-Allyl-3-methylimidazolium chloride ([AMIm][Cl]) were evaluated as packing material for mangos preservation. The moisture vapor transmission rate and gas transmission rate of the synthesized cellulose film were 1,969.1 g/(m2⋅24 h) and 10,015.4 ml/(m2⋅24 h), respectively, which are significantly higher than those of commercial PE films. The high permeability is beneficial to the release of ethylene so that contribute to extend fruit ripening period. As a result, cellulose film packaging significantly decreased the disease and color indexes of mangos, while prolonged the storage and shelf life of marketable fruits. In addition, the cellulose film was decomposed in soils in 4 weeks, indicating an excellent biodegradability as compared to the PE plastic film.

Deltamethrin (DLM) is widely used in agriculture and the prevention of human insect-borne diseases. However, the molecular mechanism of DLM induced liver injury remains unclear to date. This study investigated the potential molecular mechanism that DLM induced liver fibrosis in quails. Japanese quails received resveratrol (500 mg/kg) daily with or without DLM (45 mg/kg) exposure for 12 weeks. Histopathology, transmission electron microscopy, biochemical indexes, TUNEL, quantitative real-time PCR, and western blot analysis were performed. DLM exposure induced hepatic steatosis, oxidative stress, inflammation, and apoptosis. Most importantly, the Nrf2/TGF-β1/Smad3 signaling pathway played an important role on DLM-induced liver fibrosis in quails. Interestingly, the addition of resveratrol, an Nrf2 activator, alleviates oxidative stress and inflammation response by activating Nrf2, thereby inhibits the liver fibrosis induced by DLM in quails. Collectively, these findings demonstrate that chronic exposure to DLM induces oxidative stress via the Nrf2 expression inhibition and apoptosis, and then results in liver fibrosis in quails by the activation of NF-κB/TNF-α and TGF-β1/Smad3 signaling pathway.

The new generation of information technology (IT) promotes the integration of fintech with the real economy. Existing studies emphasize the relationship between fintech and the real economy over the development level of fintech-served real economy (FtRE). To fill up the gap, this paper explores the evaluation of FtRE based on fintech improvement (FtI). Firstly, an evaluation index system (EIS) was established for fintech service efficiency (FtSE), and FtSE was measured through data envelopment analysis (DEA). Then, fuzzy c-means (FCM) clustering was performed to discretize continuous indices. Drawing on matter-element theories, the authors created the classic domain and node domain of FtRE, as well as the evaluation objects of real economy, calculated the correlation between each factor affecting development level and evaluated development level, and computed the weight coefficient of each index. Finally, the influence of FtI-based FtRE development was empirically analyzed through experiments.

In a low-visibility environment, the speed of traffic flow is more discrete on highways, which easily causes traffic accidents. To improve the safety and efficiency level of low-visibility zones on highways, a comprehensive optimization control method is proposed. The method uses formations of a low-visibility zone to queue discrete vehicles from the upstream intersection. Then, according to the relationship between the arrival time of the fleet and the phase state of the intersection, speed guidance and trajectory optimization are carried out to improve the traffic efficiency of the fleet that enters the low-visibility zone. Finally, a low-visibility zone of a highway segment is analysed with different traffic flows for the main road and the secondary roads, and the results show that the proposed optimization control method can prevent trajectory overlap and effectively decrease traffic delays on highways.

Laminitis in cattle is an important underlying cause of lameness, which leads to a significant reduction in economic and animal welfare. Nevertheless, the disordered pathological processes of laminitis remain unclear. Several proteinases are probably involved in the disorder of basement membrane (BM) metabolism in laminitis, for instance, matrix metalloproteinases (MMPs), neutrophil elastase (NE), and myeloperoxidase (MPO). This study aimed to investigate the change in proteolytic profile in circulating and lamellar tissues using an oligofructose (OF) overload-induced laminitis model in heifers. Twelve clinically healthy and nonlame Chinese Holstein heifers were recruited and randomly divided into two groups: OF-induced and control (CON). The OF-induced heifers group (n = 6) was administered 17 g/kg of body weight (BW) of OF dissolved in 2 L/100 kg of BW of tap water via the oral-rumen tube. The CON group (n = 6) was given an equal volume of tap water. The plasma samples were collected 0, 6, 12, 18, 24, 36, 48, 60, and 72 h after administration, and the lamellar samples were collected 72 h after euthanasia. The plasma samples were analyzed by zymography and reverse zymography. Histological examination, zymography, reverse zymography, and Western blot of lamellar samples were conducted. In the plasma of the OF-induced group, the pro-MMP9 activity increased from 36 h (P < 0.001) to 60 h (P < 0.05). Moreover, the plasma tissue inhibitors of metalloproteinase 1 (TIMP1) activity decreased after 18 h (P < 0.05), while the ratio of pro-MMP9 to TIMP1 and TIMP2 increased after 18 h (P < 0.001) and 48 h (P < 0.05), respectively. The act-MMP2, pro-MMP9, and act-MMP9 activities increased in the lamellar tissue of the OF-induced group compared with the CON group (P < 0.05). In addition, the expression of lamellar NE protein was higher in the OF-induced group (P < 0.01), while no change was found in lamellar MPO protein compared with the CON group. In conclusion, increased pro-MMP9 combined with decreased TIMP1 activity in the circulation might have caused the activation of blood neutrophils, while the activation of proteolytic enzymes in lamellar tissue probably led to the dysfunction of BM in the OF-induced group.

Significantly increased imported schistosomiasis cases have been reported in China as the economy grows. The aim of this study is to review and summarize the current status, clinical features, and transmission risk of imported infections of Schistosoma mansoni and Schistosoma haematobium in China. A retrospective study was performed to review all information regarding the imported cases of schistosomiasis collected from published literature and the database of the National Notifiable Disease Report System from 1979 to 2019. The characterization of epidemiological and clinical features was analyzed. A total of 355 cases of imported schistosomiasis have been reported in 15 provinces (autonomous regions, municipalities) in China since 1979, including 78 cases of infection with S. mansoni (21.97%), 262 cases with S. haematobium (73.80%), and 15 cases with unidentified Schistosoma species. Eosinophilia was the most common sign of the infection with S. mansoni (91.03%). The parasitological findings were confirmed in 89.74% (70/78) of cases infected with S. mansoni and 32.06% (84/262) of cases infected with S. haematobium. There was no imported case of infection of Schistosoma japonicum, Schistosoma intercalatum, or Schistosoma mekongi reported in China during this period. Praziquantel is the best therapeutic drug for curing imported schistosomiasis. In addition, Biomphalaria straminea, the intermediate host of S. mansoni, has already been found in Guangdong province in south China. There is a rising risk that the existence of the intermediate host B. straminea and the imported cases of S. mansoni infection could cause the spread of the infections and make these endemic. Thus, better understanding of the clinical features and the transmission pattern of these Schistosoma infections would assist Chinese physicians in the diagnosis and treatment of these imported schistosomiasis cases.

Background and aims: Aging-induced bone loss is a multifactorial, age-related, and progressive phenomenon among the general population and may further progress to osteoporosis and increase the risk of fractures. Cycloastragenol (CAG), currently the only compound reported that activates human telomerase, is thought to be able to alleviate or delay the symptoms of aging and chronic diseases. Previous research has suggested that CAG may have the potential to alleviate age-related bone loss. However, to date, no research has specifically focused on this aspect. In this study, we aimed to investigate whether CAG could prevent senile osteoporosis, and further reveal its underlying mechanism. Methods: CAG treatment was administrated into two bone loss rat models (D-galactose administration and aging) for 20 weeks and 33 weeks, respectively. Serum biomarkers analyses, bone biomechanical tests, micro-computed tomography assessment, and bone histomorphometry analyses were performed on the bone samples collected at the endpoint, to determine whether CAG could prevent or alleviate age-related bone loss. Proteomic analysis was performed to reveal the changes in protein profiles of the bones, and western blot was used to further verify the identity of the key proteins. The viability, osteoblastic differentiation, and mineralization of MC3T3-E1 cells were also evaluated after CAG treatment in vitro. Results: The results suggest that CAG treatment improves bone formation, reduces osteoclast number, alleviates the degradation of bone microstructure, and enhances bone biomechanical properties in both d-galactose- and aging-induced bone loss models. CAG treatment promotes viability, osteoblastic differentiation, and mineralization in MC3T3-E1 cells. Proteomic and western blot analyses revealed that CAG treatment increases osteoactivin (OA) expression to alleviate bone loss. Conclusion: The results revealed that CAG alleviates age-related bone loss and improves bone microstructure and biomechanical properties. This may due to CAG-induced increase in OA expression. In addition, the results support preclinical investigations of CAG as a potential therapeutic medicine for the treatment of senile osteoporosis.

Retinal progenitor cells (RPCs) remain in the eye throughout life and can be characterized by their ability for self-renewal as well as their specialization into different cell types. A recent study has suggested that metabotropic glutamate receptors (mGluRs) participate in the processes of multiple types of stem cells. Therefore, clarifying the functions of different subtypes of mGluRs in RPCs may provide a novel treatment strategy for regulating the proliferation and differentiation of endogenous RPCs after retinal degeneration. In this study, we observed that mGluR4 was functionally expressed in RPCs, with an effect on cell viability and intracellular cAMP concentration. The activation of mGluR4 by VU0155041 (VU, mGluR4 positive allosteric selective modulator) reduced the number of BrdU+/Pax6+ double-positive cells and Cyclin D1 expression levels while increasing the number of neuron-specific class III beta-tubulin (Tuj1)- and Doublecortin (DCX)-positive cells. The knockdown of mGluR4 by target-specific siRNA abolished the effects of VU on RPC proliferation and neuronal differentiation. Further investigation demonstrated that mGluR4 activation inhibited AKT phosphorylation and up-regulated PTEN protein expression. Moreover, the VU0155041-induced inhibition of proliferation and enhancement of neuronal differentiation in RPCs were significantly hampered by Forskolin (adenylyl cyclase activator) and VO-OHpic trihydrate (PTEN inhibitor). In contrast, the effect of LY294002 (a highly selective Akt inhibitor) on proliferation and differentiation was similar to that of VU. These results indicate that mGluR4 activation can suppress proliferation and promote the neural differentiation of cultured rat RPCs through the cAMP/PTEN/AKT pathway. Our research lays the foundation for further pharmacological work exploring a novel potential therapy for several retinal diseases.

Dengue virus (DENV) is the causative agent of dengue, and its incidence has increased 30-fold in the past five decades. Among the four cocirculating serotypes, DENV3 is associated with an increased number of severe infections and has become widespread. Vaccination is the mainstay of prevention in reducing disease burden. Previously, the protective efficacy of DNA vaccine candidates toward DENV1, 2, and 4 was confirmed in mice. In this study, a DNA vaccine candidate (pVAX1-D3ME) expressing the prM and E proteins of DENV3 was constructed, and then the immunogenicity and protection were assessed in mice to further develop a tetravalent dengue vaccine. Moreover, the cross-reactive immune responses against the other three serotypes were investigated. The results showed that three doses of 50 μg of pVAX1-D3ME were sufficient to induce strong antigen-specific T cell responses and robust and consistent neutralizing antibodies. Additionally, immunization with pVAX1-D3ME offered protective immunity against not only DENV3 but also the other three serotypes, which could be observed even after 12 months. This study shows great promise for the further evaluation of a dengue tetravalent DNA vaccine candidate in large animal models, including non-human primates.

Molecular aggregation is a widespread and important process in physiological metabolism, but details regarding conformational changes during the process are hard to probe. Here, the authors use circular dichroism to monitor in-situ the conformational changes occurring during molecular aggregation.

The demonstration of pure organic room temperature phosphorescence (RTP) luminogens with complementary emission is a key requirement for developing low-cost white light emitters. Here, the authors construct RTP-active organic salt compounds by exchanging the counterion with a heavy halide ion.

The range of Hedgehog (Hh) signalling in the Drosophila imaginal disc is limited by Hh/receptor degradation at the anterior/posterior (A/P) compartment boundary. Here, the authors show that degradation is mediated by co-receptor proteins Ihog/Boi, whose cell adhesion functions also contribute to A/P cell segregation.

Hydrophobic interactions occur between nonpolar molecules in water and their experimental quantification can help the understanding of biological self-assembly. Here Jianget al. examine the kinetics and thermodynamics of hydrophobic aggregation in a bulk environment and characterize its cooperativity.

Cytomegalovirus (CMV) is a ubiquitous β-herpesvirus that establishes life-long latent infection in a high percentage of the population worldwide. CMV induces the strongest and most durable CD8+ T cell response known in human clinical medicine. Due to its unique properties, the virus represents a promising candidate vaccine vector for the induction of persistent cellular immunity. To take advantage of this, we constructed a recombinant murine CMV (MCMV) expressing an MHC-I restricted epitope from influenza A virus (IAV) H1N1 within the immediate early 2 (ie2) gene. Only mice that were immunized intranasally (i.n.) were capable of controlling IAV infection, despite the greater potency of the intraperitoneally (i.p.) vaccination in inducing a systemic IAV-specific CD8+ T cell response. The protective capacity of the i.n. immunization was associated with its ability to induce IAV-specific tissue-resident memory CD8+ T (CD8TRM) cells in the lungs. Our data demonstrate that the protective effect exerted by the i.n. immunization was critically mediated by antigen-specific CD8+ T cells. CD8TRM cells promoted the induction of IFNγ and chemokines that facilitate the recruitment of antigen-specific CD8+ T cells to the lungs. Overall, our results showed that locally applied MCMV vectors could induce mucosal immunity at sites of entry, providing superior immune protection against respiratory infections.

Abstract Hospital‐acquired infection causes many deaths worldwide and calls for the urgent need for antibacterial biomaterials used in clinic that can selectively kill harmful bacteria. The present study rationally designs fusion peptides capable of undergoing 2D self‐assembly on the poly(methyl methacrylate) surface to form a smart surface, which can maintain a desirable orientation via electrostatic interactions. The in vitro assay shows that the smart surface can recognize bacteria to exert antibacterial activity and is nontoxic toward mouse bone mesenchymal stem cells. Excitingly, the smart surface can distinguish different bacterial strains. This selective feature, from being broad‐spectrum to being highly selective against S. aureus, can be altered by varying the number of amino acids in the recognition sequences. By all‐atom molecular dynamics simulations, it is also found that the recognition sequence in the peptide is critical for the selectivity toward specific bacterial strains, in which a less accessible surface area for the bacteria in the antimicrobial peptide sequence is responsible for such selectivity. Finally, the smart surface can inhibit S. aureus infection in vivo with much more rapid tissue‐healing compared to the control.

The development of a safe and effective tetravalent dengue vaccine that elicits protection against all dengue virus (DENV) serotypes is urgently needed. The consensus sequence of the ectodomain of envelope (E) protein of DENV (cE80) has been examined as an immunogen previously. In the current study, a cE80 DNA (D) vaccine was constructed and evaluated in conjunction with the cE80 protein (P) vaccine to examine whether both vaccines used together can further improve the immune responses. The cE80 DNA vaccine was administrated using either a homologous (DNA alone, DDD) or heterologous (DNA prime-protein boost: DDP or DPP) regimen, and evaluated for immunogenicity and protective efficacy in mice. Among the three DNA-based immunization regimens tested, DDP immunization is the optimal immunization regimen that elicited the greatest systemic immune response and conferred protection against all four DENV serotypes. This work provides innovative ideas for the development of consensus E-based dengue vaccines and the testing of optimal immunization regimens.

This paper investigates energy use efficiency at the province level in China using the stochastic frontier panel data model approach. The stochastic frontier model is a parametric model which allows for the modeling of the relationship between energy use and its determinants using different control variables. The main control variables in this paper are energy policy and environmental and regulatory variables. This paper uses province level data from all provinces in China for the period 2010–2017. Three different models are estimated accounting for the panel nature of the data; province-specific heterogeneity and province-specific energy inefficiency effects are separated. The models differ because of their underlying assumptions, but they also complement each other. The paper also explains the degree of inefficiency in energy use by its possible determinants, including those related to the public energy policy and environmental regulations. This research supplements existing research from the perspective of energy policy and regional heterogeneity. The paper identifies potential areas for improving energy efficiency in the western and northeastern regions of China. Its findings provide new empirical evidence for estimating and evaluating China’s energy efficiency and a transition to cleaner energy sources and production.

Advanced glycation end products (AGEs) generated from glycation can cause inflammation-related diseases such as diabetes and cancer. The bioactive compounds of rosemary extract (RE) were extracted and incubated with sugar-protein rich food and breast cancer cell MCF-7 to investigate its inhibitory effect on glycation and cancer cell proliferation, respectively. The diabetic rat was dosed with RE to investigate its effect on blood glucose, serum malondialdehyde (MDA), cholesterol (CHO), triglycerides (TG), low-density lipoproteins (LDLs), anti-oxidation capacity (T-AOC), superoxide dismutase (SOD) activity, anti-oxidation capacity alkaline phosphatase (ALP), glutamate pyruvate transaminase (GPT), and glutamate oxaloacetate transaminase (GOT). The results show that RE contained seven major phenolics ranging from 17.82 mg/g for rosemarinic acid to 0.01 mg/g for ferulic acid on dry weight basis. It significantly lowered AGEs, carboxymethyl lysine (CML), and protein glycation in a sugar-protein rich intermediate-moisture-food (IMF) model. Furthermore, the survival rates of MCF-7 cells decreased to 6.02 and 2.16% after 96 h of incubation with 1.0 and 2.0 mg/mL of RE, respectively. The blood glucose, MDA, CHO, TG, and LDLs in diabetic rats of RE treatment were decreased. The RE treatment also enhanced the T-AOC and SOD activity. Furthermore, the RE treatment improved liver function through improving ALP, GPT, and GOT activities in diabetic rats. The results provide important information for the nutriaceutical and pharmaceutical application of rosemary extract.

The soy protein isolate (SPI) was combined with tea saponin as an emulsifier to prepare camellia oil nanoemulsion, and the stability of camellia oil nanoemulsion was compared with that of soybean protein isolate or tea saponin as emulsifier. The effects of different pH, ionic strength, heating temperature and storage time on the average particle size, ξ-potential and microstructure of camellia oil nanoemulsion prepared by three emulsifiers were studied. The results showed that the nanoemulsions prepared by combining natural emulsifiers (SPI-TS) in the pH range of 5-9 were stable and remained stable in the range of 0-300mm NaCl concentration, but had poor tolerance to high salt environment. After heating at different temperatures (30 °C-90 °C) for 30min, the average particle size, ξ-potential and microstructure of the three emulsions did not change significantly, showing good heating stability. At different storage temperatures (4, 25, 50°C) SPI-TS and TS emulsion could exist stably about four weeks, and had good storage stability. In addition, we performed in vitro simulated gastrointestinal digestion studies on the digestive properties of camellia oil nanoemulsions. The results showed that the particle size, the ξ-potential of the nanoemulsion changes depend on the type of emulsifier during digestion. The release rate of free fat acids (FFAs) of nanoemulsions after gastrointestinal digestion were all higher than that of the control group. The results showed that the nanoemulsion delivery system could effectively improve the digestion of camellia oil, It was important to improve the bioavailability of camellia oil.

Asian pear plays an important role in the world pear industry, accounting for over 70% of world total production volume. Commercial Asian pear production relies on four major pear cultivar groups, Japanese pear (JP), Chinese white pear (CWP), Chinese sand pear (CSP), and Ussurian pear (UP), but their origins remain controversial. We estimated the genetic diversity levels and structures in a large sample of existing local cultivars to investigate the origins of Asian pears using twenty-five genome-covering nuclear microsatellite (simple sequence repeats, nSSR) markers and two non-coding chloroplast DNA (cpDNA) regions (trnL-trnF and accD-psaI). High levels of genetic diversity were detected for both nSSRs (HE = 0.744) and cpDNAs (Hd = 0.792). The major variation was found within geographic populations of cultivated pear groups, demonstrating a close relationship among cultivar groups. CSPs showed a greater genetic diversity than CWPs and JPs, and lowest levels of genetic differentiation were detected among them. Phylogeographical analyses indicated that the CSP, CWP, and JP were derived from the same progenitor of Pyrus pyrifolia in China. A dissemination route of cultivated P. pyrifolia estimated by approximate Bayesian computation suggested that cultivated P. pyrifolia from the Middle Yangtze River Valley area contributed the major genetic resources to the cultivars, excluding those of southwestern China. Three major genetic groups of cultivated Pyrus pyrifolia were revealed using nSSRs and a Bayesian statistical inference: (a) JPs; (b) cultivars from South-Central China northward to northeastern China, covering the main pear production area in China; (c) cultivars from southwestern China to southeastern China, including Yunnan, Guizhou, Guangdong, Guangxi, and Fujian Provinces. This reflected the synergistic effects of ecogeographical factors and human selection during cultivar spread and improvement. The analyses indicated that UP cultivars might be originated from the interspecific hybridization of wild Pyrus ussuriensis with cultivated Pyrus pyrifolia. The combination of uniparental DNA sequences and nuclear markers give us a better understanding of origins and genetic relationships for Asian pear groups and will be beneficial for the future improvement of Asian pear cultivars.

Glioblastoma multiforme (GBM) is the most lethal glioma variant in the adult brain and among the deadliest of human cancers. Increasing evidence has shown that metabotropic glutamate receptor subtype 4 (mGluR4) expression may play roles in regulating the growth of neural stem cells as well as several cancer cell lines. Here, we investigated the effects of mGluR4 on the growth and apoptosis of the LN229 GBM cell line. Involvement of Gli-1, one of the key transcription factors in the sonic Hedgehog (SHH) signaling pathway, was further explored. In this study, mGluR4 was activated using selective agonist VU0155041; and gene-targeted siRNAs were used to generate loss of function of mGluR4 and Gli-1 in LN229 cells. The results demonstrated that LN229 cells expressed mGluR4 and the agonist VU0155041 decreased cell viability in a dose- and time-dependent manner. Activation of mGluR4 inhibited cyclin D1 expression, activated pro-caspase-8/9/3, and disrupted the balance of Bcl-2/Bax expression, which indicated cell cycle arrest and apoptosis of LN229 cells, respectively. Furthermore, Gli-1 expression was reduced by mGluR4 activation in LN229 cells, and downregulation of Gli-1 expression by gene-targeted siRNA resulted in both inhibition of cell proliferation and promotion of apoptosis. Moreover, VU0155041 treatment substantially blocked SHH-induced cyclin D1 expression and cell proliferation, while increasing TUNEL-positive cells and the activation of apoptosis-related proteins. We concluded that activation of mGluR4 expressed in LN229 cells could inhibit GBM cell growth by decreasing cell proliferation and promoting apoptosis. Further suppression of intracellular Gli-1 expression might be involved in the action of mGluR4 on cancer cells. Our study suggested a novel role of mGluR4, which might serve as a potential drug target for control of GBM cell growth.

Abstract A novel, star‐shaped electron acceptor, DMTPA‐PDI3, derived from a planar dimethylmethylene‐bridged triphenylamine core with three acetylene‐linked perylene diimide (PDI) units is developed as a nonfullerene acceptor for organic solar cells (OSCs). DMTPA‐PDI3 manifests significantly reduced intramolecular twisting, enabling sufficient system‐wide π‐electron delocalization leading to broadened spectral absorption and raised lowest unoccupied molecular orbital level. As a result, higher and more balanced hole and electron transport properties are observed. Active layers for OSCs comprising DMTPA‐PDI3 acceptor and PBT7‐Th donor exhibit suppressed intermolecular aggregation, giving rise to uniform nanophase network formation. These OSC devices have afforded respectably high power‐conversion efficiency of about 5%.

Dengue virus (DV) is the causal pathogen of dengue fever, which is one of the most rapidly spread mosquito-borne disease worldwide and has become a severe public health problem. Currently, there is no specific treatment for dengue; thus, a vaccine would be an effective countermeasure to reduce the morbidity and mortality. Although, the chimeric Yellow fever dengue tetravalent vaccine has been approved in some countries, it is still necessary to develop safer, more effective, and less costly vaccines. In this study, a DNA vaccine candidate pVAX1-D1ME expressing the prME protein of DV1 was inoculated in BALB/c mice via intramuscular injection or electroporation, and the immunogenicity and protection were evaluated. Compared with traditional intramuscular injection, administration with 50 μg pVAX1-D1ME via electroporation with three immunizations induced persistent humoral and cellular immune responses and effectively protected mice against lethal DV1 challenge. In addition, immunization with a bivalent vaccine consisting of pVAX1-D1ME and pVAX1-D2ME via electroporation generated a balanced IgG response and neutralizing antibodies against DV1 and DV2 and could protect mice from lethal challenge with DV1 and DV2. This study sheds new light on developing a dengue tetravalent DNA vaccine.

Lignocellulosic biomass is a renewable source with great potential for biofuels and bioproducts. However, the cost of cellulolytic enzymes limits the utilization of the low-cost bioresource. This study aimed to develop a consolidated bioprocessing without the need of supplementary cellulase for butyric acid production from lignocellulosic biomass. A stirred-tank reactor with a working volume of 21 L was constructed and operated in batch and semi-continuous fermentation modes with a cellulolytic butyrate-producing microbial community. The semi-continuous fermentation with intermittent discharging of the culture broth and replenishment with fresh medium achieved the highest butyric acid productivity of 2.69 g/(L•d). In semi-continuous operation mode, the butyric acid and total carboxylic acid concentrations of 16.2 and 28.9 g/L, respectively, were achieved. Over the 21-day fermentation period, their cumulative yields reached 1189 and 2048 g, respectively, corresponding to 41% and 74% of the maximum theoretical yields based on the amount of NaOH pretreated rice straw fed in. This study demonstrated that an undefined mixed culture-based consolidated bioprocessing for butyric acid production can completely eliminate the cost of supplementary cellulolytic enzymes.

A fundamental question of biology is what determines organ size. Despite demonstrations that factors within organs determine their sizes, intrinsic size control mechanisms remain elusive. Here we show that Drosophila wing size is regulated by JNK signaling during development. JNK is active in a stripe along the center of developing wings, and modulating JNK signaling within this stripe changes organ size. This JNK stripe influences proliferation in a non-canonical, Jun-independent manner by inhibiting the Hippo pathway. Localized JNK activity is established by Hedgehog signaling, where Ci elevates dTRAF1 expression. As the dTRAF1 homolog, TRAF4, is amplified in numerous cancers, these findings provide a new mechanism for how the Hedgehog pathway could contribute to tumorigenesis, and, more importantly, provides a new strategy for cancer therapies. Finally, modulation of JNK signaling centers in developing antennae and legs changes their sizes, suggesting a more generalizable role for JNK signaling in developmental organ size control.

Recent evidence indicated that interspecific hybridization was the major mode of evolution in Pyrus. The genetic relationships and origins of the Asian pear are still unclear because of frequent hybrid events, fast radial evolution, and lack of informative data. Here, we developed fluorescent sequence-specific amplification polymorphism (SSAP) markers with lots of informative sites and high polymorphism to analyze the population structure among 93 pear accessions, including nearly all species native to Asia. Results of a population structure analysis indicated that nearly all Asian pear species experienced hybridization, and originated from five primitive genepools. Four genepools corresponded to four primary Asian species: P. betulaefolia, P. pashia, P. pyrifolia, and P. ussuriensis. However, cultivars of P. ussuriensis were not monophyletic and introgression occurred from P. pyrifolia. The specific genepool detected in putative hybrids between occidental and oriental pears might be from occidental pears. The remaining species, including P. calleryana, P. xerophila, P. sinkiangensis, P. phaeocarpa, P. hondoensis, and P. hopeiensis in Asia, were inferred to be of hybrid origins and their possible genepools were identified. This study will be of great help for understanding the origin and evolution of Asian pears.

Ciliary accumulation of signaling proteins must result from a rate of ciliary entry that exceeds ciliary exit, but approaches for distinguishing ciliary entry vs. exit are lacking. Using a photoconvertible fluorescent protein tag, we establish an assay that allows a separate but simultaneous examination of ciliary entry and exit of the Hedgehog signaling protein Smoothened in individual cells. We show that KAAD-cyclopamine selectively blocks entry, whereas ciliobrevin interferes initially with exit and eventually with both entry and exit of ciliary Smoothened. Our study provides an approach to understanding regulation of ciliary entry vs. exit of Hedgehog signaling components as well as other ciliary proteins.

BACKGROUND AND PURPOSE: Systemic upregulation of inflammatory cytokines is characteristic of critical severe hand, foot, and mouth disease (HFMD) with pulmonary edema. Thus, immunomodulatory medicines such as steroids, including methylprednisolone, have been proposed to treat patients with severe HFMD in China, because it is postulated that inflammatory cytokines play a role in the development of severe complications. This study is to further investigate the inflammatory response in the relatively mild HFMD patients, and whether steroid treatment has a beneficial effect on the suppression of inflammation in HFMD patients. METHOD: We measured the levels of 50 kinds of chemokines, cytokines, growth factors and soluble receptors in serum samples from control patients without HFMD and the HFMD patients with or without prior treatment of intravenous methylprednisolone. RESULTS: Our present study found that even relatively mild HFMD patients without central nervous system (CNS) complications had elevated serum levels of inflammatory cytokines, including interleukin (IL)-3, IL-6, IL-12p40, and tumor necrosis factor (TNF)-α, which suggested systemic inflammation. In contrast, these patients also have decreased levels of other serum biomarkers, including IL-1Ra, IL-8, IL-16, soluble ICAM-1, CXCL-1, and CCL27. The dysregulation of cytokine and chemokine expression may be involved in CNS complications and unbalanced circulating leukocytes in HFMD patients. Surprisingly, patients treated with methylprednisolone had no difference in the expression levels of HFMD-associated biomarkers instead had slightly increased levels of IL-17A, which was not associated with the occurrence of HFMD. CONCLUSION: Whether steroid treatment has any beneficial effect on the prognosis of HFMD patients requires to be further investigated.