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No specific antiviral agent against hand foot and mouth disease (HFMD) is available for clinical practice today. To evaluate the efficacy and safety of Jinzhen oral solution in treating uncomplicated HFMD. In this randomized, double-blind, placebo-controlled trial, 399 children aged 1 to 7 years with laboratory confirmed HFMD were randomized to receive Jinzhen oral liquid or placebo 3 times daily for 7 days with a 3-day follow-up. The primary outcomes were time to the first disappearance of oral ulcers and vesicles on hand or foot and time to the first normalization of temperature (fever clearance). There were 199 children enrolling into the Jinzhen group including 79 with fever and 200 into the placebo group including 93 with fever. Jinzhen reduced the time to the first disappearance of oral ulcers and vesicles on hand or foot to 4.9 days (95% CI, 4.6 to 5.2 days), compared with 5.7 days (95% CI, 5.4 to 6.0 days) in the placebo group (P = 0.0036). The median time of fever clearance was shorter in the 79 children who received Jinzhen (43.41 hrs, 95% CI, 37.05 to 49.76) than that in the 93 children who received placebo (54.92 hrs, 95% CI, 48.16 to 61.68) (P = 0.0161). Moreover, Jinzhen reduced the risk of symptoms by 28.5% compared with placebo (HR, 0.7150, 95% CI, 0.5719 to 0.8940, P = 0.0032). More importantly, treatment failure rate was significantly lower in the Jinzhen group (8.04%) compared with that in the placebo group (15.00%) (P = 0.0434). The incidence of serious adverse events did not differ significantly between the two groups (9 in Jinzhen group vs. 18 in placebo, P = 0.075). Children with HFMD may benefit from Jinzhen oral liquid treatment as compared with placebo. Chinese Clinical Trial Registry (http://www.chictr.org/en/) ChiCTR-TRC-10000937.

Background： Fat grafting technologies are popularly used in plastic and reconstructive surgery. Due to its size limitation, it is hard to directly inject untreated iht tissue into the dermal layer. Nanolht, which was introduced by Tonnard, solves this problem by mechanically emulsifying fat tissue. However, the viability of the cells was greatly destroyed. In this study, we reported a new method by ＂gently＂ digesting the fat tissue to produce viable adipocytes, progenitors, and stromal stem cells using collagenase I digestion and centrifugation. This was named ＂Vivo nanofat＂. Methods： Human liposuction aspirates were obtained from five healthy female donors with mean age of 28.7±5.6 years. Colony-forming assay, flow cytometry analysis, and adipogenic and osteogenic induction of the adherent cells from the Vivo nanofat were used to characterize the adipose mesenchymal stem cells （MSCs）. To investigate in vivo survival, we respectively injected Vivo nanofat and nanofat subcutaneously to the back of 8-week-old male BALB/c nude mice. Samples were harvested 2 days, 2 weeks, and 4 weeks postiniection for measurement, hematoxylin and eosin staining, and immunostaining. Results： Our results showed that the Vivo nanofat contained a large number ofcolony-fbrming cells. These cells expressed MSC markers and had multi-differentiative potential. In vivo transplantation showed that the Vivo nanofat had lower resorption ratio than that of nanofat. The size of the transplanted nanofat was obviously smaller than that of Vivo nanofat 4 weeks postinjection （0.50±0.17 cm vs. 0.81 ± 0.07 cm, t = -5783, P- 0.01）. Conclusion： Vivo nanofat may serve as a cell fraction injectable through a fine needle; this could be used for cosmetic applications.

Energy-coupling factor （ECF） transporters are a large family of ATP-binding cassette transporters recently iden- tified in microorganisms. Responsible for micronutrient uptake from the environment, ECF transporters are mod- ular transporters composed of a membrane substrate-binding component EcfS and an ECF module consisting of an integral membrane scaffold component EcfT and two cytoplasmic ATP binding/hydrolysis components EcfA/A＇. ECF transporters are classified into groups I and II. Currently, the molecular understanding of group-I ECF transport- ers is very limited, partly due to a lack of transporter complex structural information. Here, we present structures and structure-based analyses of the group-I cobalt ECF transporter CbiMNQO, whose constituting subunits CbiM/ CbiN, CbiQ, and CbiO correspond to the EcfS, EctT, and EcfA components of group-II ECF transporters, respec- tively. Through reconstitution of different CbiMNQO subunits and determination of related ATPase and transporter activities, the substrate-binding subunit CbiM was found to stimulate CbiQO＇s basal ATPase activity. The structure of CbiMQO complex was determined in its inward-open conformation and that of CbiO in p, y-methyleneadenosine 5＇-triphosphate-bound closed conformation. Structure-based analyses revealed interactions between different compo- nents, substrate-gating function of the L1 loop of CbiM, and conformational changes of CbiO induced by ATP bind- ing and product release within the CbiMNQO transporter complex. These findings enabled us to propose a working model of the CbiMNQO transporter, in which the transport process requires the rotation or toppling of both CbiQ and CbiM, and CbiN might function in coupling conformational changes between CbiQ and CbiM.

Lithium-ion batteries （LIBs） are currently recognized as one of the most popular power sources available. To construct advanced LIBs exhibiting long-term endurance, great attention has been paid to enhancing their poor cycle stabilities. As the performance of LIBs is dependent on the electrode materials employed, the most promising approach to improve their life span is the design of novel electrode materials. We herein describe the rational design of a three-dimensional （3D） porous MnO/C-N nanoarchitecture as an anode material for long cycle life LIBs based on their preparation from inexpensive, renewable, and abundant rapeseed pollen （R-pollen） via a facile immersion-annealing route. Remarkably, the as-prepared MnO/C-N with its optimized 3D nanostructure exhibited a high specific capacity （756.5 mAh·g^-1 at a rate of 100 mA·g^-1）, long life span （specific discharge capacity of 513.0 mAh·g^-1, -95.16% of the initial reversible capacity, after 400 cycles at 300 mA·g^-1）, and good rate capability. This material therefore represents a promising alternative candidate for the high-performance anode of next-generation LIBs.

Aim： To assess the spatiotemporal changes in the expression of extracellular signal-regulated kinases 1 and 2 （ERK1/ 2）, c-Jun N-terminal kinases （JNK） and p38 mitogen-activated protein kinases （MAPK） in response to heat stress in the cryptorchid testis, and to investigate a possible relation to Sertoli cell dedifferentiation. Methods： Immunohistochemistry and western blot were used to examine the expression and activation of ERK1/2, p38 and JNK in the cryptorchid testis at various stages after experimental cryptorchidism. Results： The abdominal temperature did not obviously change the total ERK1/2 expression but significantly activated phospho-ERK1/2 in the Sertoli cells of the cryptorchid testis. Heat stress increased total JNK expression in the Sertoli cells of the cryptorchid testis but did not activate phospho-JNK. Neither total p38 nor phospho-p38 was induced by heat stress in the Sertoli cells of the cryptorchid testis. Changes in the spatiotemporal expression of cytokeratin 18 （CK18）, a marker of immature or undifferentiated Sertoli cells, were induced in the cryptorchid testis in a pattern similar to the activation of ERK1/2. Condusion： The activation of ERK1/2 in the testis may be related to dedifferentiation of Sertoli cells under heat stress induced by experimental cryptorchidism.

Gut microbial transformations of flavonoids, an enormous class of polyphenolic compounds abundant in plant-based diets, are closely associated with human health. However, the enzymes that initiate the gut microbial metabolism of flavones and flavonols, the two most abundant groups of flavonoids, as well as their underlying molecular mechanisms of action remain unclear. Here, we discovered a flavone reductase (FLR) from the gut bacterium, Flavonifractor plautii ATCC 49531 (originally assigned as Clostridium orbiscindens DSM 6740), which specifically catalyses the hydrogenation of the C2–C3 double bond of flavones/flavonols and initiates their metabolism as a key step. Crystal structure analysis revealed the molecular basis for the distinct catalytic property of FLR. Notably, FLR and its widespread homologues represent a class of ene-reductases that has not been previously identified. Genetic and biochemical analyses further indicated the importance of FLR in gut microbial consumption of dietary and medicinal flavonoids, providing broader insight into gut microbial xenobiotic transformations and possible guidance for personalized nutrition and medicine. Flavonoids are abundant polyphenols in plants but it is not well understood how their metabolism is initiated by microbes in the human gut. Here, the authors identify and characterise an ene-reductase from the gut bacterium, Flavonifractor plautii ATCC 49531 that catalyses the hydrogenation of the C2–C3 double bond of flavones and flavonols and present its crystal structure.

Gastric cancer (GC) is one of the leading causes of cancer death in the world. The role of histone deacetylase 4 (HDAC4) in specific cell and tissue types has been identified. However, its biological roles in the development of gastric cancer remain largely unexplored. Quantitative real time PCR (qRT-PCR) and western blot were used to analyze the expression of HDAC4 in the clinical samples. siRNA and overexpression of HDAC4 and siRNA p21 were used to study functional effects in a proliferation, a colony formation, a adenosine 5'-triphosphate (ATP) assay and reactive oxygen species(ROS) generation, cell cycle, cell apoptosis rates, and autophagy assays. HDAC4 was up-regulated in gastric cancer tissues and several gastric cancer cell lines. The proliferation, colony formation ability and ATP level were enhanced in HDAC4 overexpression SGC-7901 cells, but inhibited in HDAC4 knockdown SGC-7901 cells. HDAC4 knockdown led to G0/G1 phase cell arrest and caused apoptosis and ROS increase. Moreover, HDAC4 was found to inhibit p21 expression in gastric cancer SGC-7901 cells. p21 knockdown dramatically attenuated cell proliferation inhibition, cell cycle arrest, cell apoptosis promotion and autophagy up-regulation in HDAC4-siRNA SGC-7901 cells. We demonstrated that HDAC4 promotes gastric cancer cell progression mediated through the repression of p21. Our results provide an experimental basis for understanding the pro-tumor mechanism of HDAC4 as treatment for gastric cancer.

Rice blast disease is one of the most destructive rice diseases worldwide. Rice MicroRNAs (miRNAs) play an essential role in immunity against blast fungus Magnaporthe oryzae . However, it remains unclear which miRNAs are involved in the three layers of rice- M. oryzae interaction, including pathogen associated molecular patterns (PAMPs)-triggered immunity (PTI), effector-triggered susceptibility (ETS), and effector-triggered immunity (ETI). In this study, we performed small RNA-sequencing to systemically identify miRNAs regulating PTI, ETS, and ETI in rice- M. oryzae interaction. A totally 441 miRNAs were identified, with 13, 30, and 14 miRNAs screened out and classified as regulators of PTI, ETS, and ETI, respectively. We investigated and confirmed the roles of 9 previously reported miRNAs and an uncharacterized miRNA, miR408-5p, in the three interaction processes. We demonstrated that miR1320-5p positively regulated PTI; miR396 family members and miR164a improved, whereas miR171b and miR172a suppressed ETS; miR166a enhanced, whereas miR169a and miR396 family members suppressed ETI. Moreover, we demonstrated that miR397b and miR408-5p enhanced rice susceptibility by promoting ETS and suppressing ETI; miR398b enhanced rice resistance by promoting both PTI and ETI while suppressing ETS. Our findings figured a miRNA-mediated regulatory network in which distinct miRNAs modulate PTI, ETS, and ETI against M. oryzae . This study provides new sight into the regulation mechanism of plant disease resistance.

Background Few prognostic risk scores (PRSs) have been routinely used in acute decompensated heart failure (ADHF). We, therefore, externally validated three published PRSs (3A3B, AHEAD, and OPTIME-CHF) and derived a new PRS to predict the short-term prognosis in ADHF. Methods A total of 4550 patients from the Heb-ADHF registry in China were randomly divided into the derivation and validation cohorts (3:2). Discrimination of each PRS was assessed by the area under the receiver operating characteristic curve (AUROC). Logistic regression was exploited to select the predictors and create the new PRS. The Hosmer–Lemeshow goodness-of-fit test was used to assess the calibration of the new PRS. Results The AUROCs of the 3A3B, AHEAD, and OPTIME-CHF score in the derivation cohort were 0.55 (95% CI 0.53–0.57), 0.54 (95% CI 0.53–0.56), and 0.56 (95% CI 0.54–0.57), respectively. After logistic regression analysis, the new PRS computed as 1 × (diastolic blood pressure < 80 mmHg) + 2 × (lymphocyte > 1.11 × 10 9 /L) + 1 × (creatinine > 80 μmol/L) + 2 × (blood urea nitrogen > 21 mg/dL) + 1 × [BNP 500 to < 1500 pg/mL (NT-proBNP 2500 to < 7500 pg/mL)] or 3 × [BNP ≥ 1500 (NT-proBNP ≥ 7500) pg/mL] + 3 × (QRS fraction of electrocardiogram < 55%) + 4 × (ACEI/ARB not used) + 1 × (rhBNP used), with a better AUROC of 0.67 (95% CI 0.64–0.70) and a good calibration (Hosmer–Lemeshow χ 2  = 3.366, P  = 0.186). The results in validation cohort verified these findings. Conclusions The short-term prognostic values of 3A3B, AHEAD, and OPTIME-CHF score in ADHF patients were all poor, while the new PRS exhibited potential predictive ability. We demonstrated the QRS fraction of electrocardiogram as a novel predictor for the short-term outcomes of ADHF for the first time. Our findings might help to recognize high-risk ADHF patients.

PurposeThe present study is intended to develop an effective approach to the real-time modeling of general dynamic nonlinear systems based on the multidimensional Taylor network (MTN).Design/methodology/approachThe authors present a detailed explanation for modeling the general discrete nonlinear dynamic system by the MTN. The weight coefficients of the network can be obtained by sampling data learning. Specifically, the least square (LS) method is adopted herein due to its desirable real-time performance and robustness.FindingsCompared with the existing mainstream nonlinear time series analysis methods, the least square method-based multidimensional Taylor network (LSMTN) features its more desirable prediction accuracy and real-time performance. Model metric results confirm the satisfaction of modeling and identification for the generalized nonlinear system. In addition, the MTN is of simpler structure and lower computational complexity than neural networks.Research limitations/implicationsOnce models of general nonlinear dynamical systems are formulated based on MTNs and their weight coefficients are identified using the data from the systems of ecosystems, society, organizations, businesses or human behavior, the forecasting, optimizing and controlling of the systems can be further studied by means of the MTN analytical models.Practical implicationsMTNs can be used as controllers, identifiers, filters, predictors, compensators and equation solvers (solving nonlinear differential equations or approximating nonlinear functions) of the systems of ecosystems, society, organizations, businesses or human behavior.Social implicationsThe operating efficiency and benefits of social systems can be prominently enhanced, and their operating costs can be significantly reduced.Originality/valueNonlinear systems are typically impacted by a variety of factors, which makes it a challenge to build correct mathematical models for various tasks. As a result, existing modeling approaches necessitate a large number of limitations as preconditions, severely limiting their applicability. The proposed MTN methodology is believed to contribute much to the data-based modeling and identification of the general nonlinear dynamical system with no need for its prior knowledge.