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Purpose: Most blunt thoracic aortic injuries (BTAIs) may be treated using thoracic endovascular aortic repair (TEVAR), and most blunt abdominal traumas (BATs) are managed conservatively. We hypothesized that severe trauma that needs TEVAR may increase the risk of delayed intra-abdominal hemorrhage in patients with concomitant BTAI and BAT because of the potential hemorrhagic shock, disseminated intravascular coagulopathy, blood loss, consequent need for blood transfusion, and procedure-associated heparinization.Materials and Methods: From 2015 to 2019, blunt trauma patients with concomitant severe chest trauma and abdominal trauma who could be managed conservatively were studied. The probability of delayed intra-abdominal hemorrhage was compared between patients with concomitant BTAI who received or did not undergo TEVAR. Propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and multivariate logistic regression (MLR) were used to eliminate discrepancies between these 2 groups.Results: Among the 341 studied patients, there were 26 patients with BTAI, and 19 of them underwent TEVAR. Delayed intra-abdominal hemorrhage was observed in 4 patients (21.1%, 4/19) who underwent TEVAR. Both PSM and IPTW showed that patients who underwent TEVAR for concomitant BTAI had a greater delayed need for blood transfusions and a larger proportion of delayed intra-abdominal hemorrhage than patients who did not undergo the procedure. The MLR analysis showed that TEVAR for BTAI was an independent risk factor for delayed intra-abdominal hemorrhage (odds ratio: 10.534, 95%, p<0.001).Conclusion: An increased probability of delayed intra-abdominal hemorrhage in patients with BAT (who could be managed conservatively) was observed in patients who underwent TEVAR for concomitant BTAI.Clinical Impact More attention should be give in patients with high grade aortic injuries and concomitant abdominal trauma.

The influences of different strategies involving designing advanced electrode structure, artificial solid electrolyte interphase (SEI) on Zn anode and electrolyte engineering to regulate zinc ion solvated sheath structure and transport behavior were elaborated.

Continuously monitoring neurotransmitter dynamics can offer profound insights into neural mechanisms and the etiology of neurological diseases. Here, we present a miniaturized implantable fluorescence probe integrated with metal–organic frameworks (MOFs) for deep brain dopamine sensing. The probe is assembled from physically thinned light-emitting diodes (LEDs) and phototransistors, along with functional surface coatings, resulting in a total thickness of 120 μm. A fluorescent MOF that specifically binds dopamine is introduced, enabling a highly sensitive dopamine measurement with a detection limit of 79.9 nM. A compact wireless circuit weighing only 0.85 g is also developed and interfaced with the probe, which was later applied to continuously monitor real-time dopamine levels during deep brain stimulation in rats, providing critical information on neurotransmitter dynamics. Cytotoxicity tests and immunofluorescence analysis further suggest a favorable biocompatibility of the probe for implantable applications. This work presents fundamental principles and techniques for integrating fluorescent MOFs and flexible electronics for brain-computer interfaces and may provide more customized platforms for applications in neuroscience, disease tracing, and smart diagnostics.

ABSTRACTThe aim of this study was to explore the effect and mechanism of Sirt6 on DNA damage repair in OA chondrocytes. Cartilage tissues were collected from OA patients with knee arthroplasty and traumatic amputation patients without OA. Besides, 7-week-old male C57BL/6 mice were randomly divided into Control and OA groups; CHON-001 cells of corresponding groups were treated with 10 ng/ml interleukin (IL)-1β, respectively. Subsequently, Sirt6 or siNrf2 was over-expressed in CHON-001 cells to observe the effect of Sirt6 on DNA damage and senescence of chondrocytes by IL-1β through the nuclear factor E2-related factor 2 (Nrf2) signaling pathway. The expression level of Sirt6 in human and mouse OA cartilage tissues was significantly decreased. However, 24 h of treatment with IL-1β significantly decreased the expression of Sirt6 in chondrocytes, induced DNA damage, and promoted cellular senescence. In addition, over-expression of Sirt6 promoted DNA damage repair and inhibited cellular senescence in IL-1β-induced chondrocytes. Moreover, the overexpression of Sirt6 activated the Keap1/Nrf2/HO-1 signaling pathway in chondrocytes, while knockdown of Nrf2 expression inhibited the DNA damage repair and anti-senescence effects of Sirt6 on IL-1β-treated chondrocytes. Sirt6 may reduce DNA damage and cellular senescence in OA chondrocytes induced by IL-1β through activating the Keap1/Nrf2/HO-1 signaling pathway.

Background: We investigated the understudied influence of maternal diet quality, food timing, and their interactions during pregnancy on offspring metabolic health. Methods: Maternal diet at 26–28 weeks’ gestation was assessed using a 24-h recall and adherence to the modified-healthy-eating-index (HEI-SGP) reflects diet quality. Predominant night-eating (PNE) was defined as consuming >50% of total daily energy intake from 19:00 to 06:59. Outcomes were offspring composite metabolic syndrome score and its components measured at age 6 years. Multivariable linear regressions adjusted for relevant maternal and child covariates assessed associations of diet quality and PNE with these outcomes. Results: Up to 758 mother-child pairs were included. The mean(SD) maternal HEI-SGP score was 52.3(13.7) points (theoretical range: 0-100) and 15% of the mothers demonstrated PNE. Maternal diet quality showed inverse relationship with offspring Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) [β(95% CI): –0.08(–0.15, –0.02) per-10-point HEI-SGP increment; P= 0.012]. Maternal PNE was associated with a higher offspring HOMA-IR [0.28(0.06, 0.50); P= 0.012], with similar estimates after adjustment for children’s BMI and diet quality; the association was stronger for boys (P-interaction&lt;0.001) and among mothers with lower diet quality (&lt;median HEI-SGP) (P-interaction = 0.062). Conclusions: Maternal PNE and low dietary quality were associated with a higher level of insulin resistance in early childhood, especially among boys. Impact:

We demonstrated that maternal predominant night-eating behavior and low-quality diet are associated with higher offspring insulin resistance.

Maternal low-quality diet and predominant night-eating behavior synergistically interact to influence offspring insulin resistance, particularly among boys.

While maternal diet quality and food timing impact the mother’s health, their influence on offspring long-term health outcomes through developmental programming is not well understood.

Our findings highlight the significance of maternal food timing and calls for further studies on its influence on child health through developmental programming. Targeting both dietary quality and food timing during pregnancy could be a promising intervention strategy.

It is known that the efficiency of the hydrogen evolution reaction (HER) can be promoted by the presence of proton relay groups neighboring a catalytic metal center. This work reports the synthesis of two new Co(iii) corroles (2and 3) with hangman proton relay groups for the electrocatalytic HER. When using trifluoroacetic acid (TFA) as a proton source, complexes 2and 3exhibited turnover frequencies (TOFs) of 219.36 s−1and 199.57 s−1, respectively. The catalytic HER undergoes viathe EECEC or EECC pathway (E: electron transfer; C: charge transfer) depending on the acidity and concentration of the proton source. Moreover, complex 2and 3also showed good HER activity in aqueous media with Faraday efficiencies (FEs) of 93.6% and 89.2% respectively.

Synergistic drug combinations can extend the use of poly(ADP-ribose) polymerase inhibitors (PARPi) such as Olaparib to BRCA-proficient tumors and overcome acquired or de novo drug resistance. To identify new synergistic combinations for PARPi, we screened a “micro-library” comprising a mix of commercially available drugs and DNA-binding ruthenium(II) polypyridyl complexes (RPCs) for Olaparib synergy in BRCA-proficient triple-negative breast cancer cells. This identified three hits: the natural product Curcumin and two ruthenium(II)-rhenium(I) polypyridyl metallomacrocycles. All combinations identified were effective in BRCA-proficient breast cancer cells, including an Olaparib-resistant cell line, and spheroid models. Mechanistic studies indicated that synergy was achieved via DNA-damage enhancement and resultant apoptosis. Combinations showed low cytotoxicity toward non-malignant breast epithelial cells and low acute and developmental toxicity in zebrafish embryos. This work identifies RPC metallomacrocycles as a novel class of agents for cancer combination therapy and provides a proof of concept for the inclusion of metallocompounds within drug synergy screens.

Purpose Adequate resuscitation and definitive hemostasis are both important in the management of hemorrhage related to pelvic fracture. The goal of this study was to analyze the relationship between the amount of blood transfused before transcatheter arterial embolization (TAE) and the clinical outcome later in the disease course.Methods Patients with pelvic fractures who underwent TAE for hemostasis from January 2018 to December 2019 were studied. The characteristics of patients who received blood transfusions of >2 U (1000 mL) and ≤2 U before TAE were compared. The mortality rate, blood transfusion-related complications, and length of stay were compared between these two groups.Results Among the 75 studied patients, 39 (52.0%) received blood transfusions of ≤2 U before TAE, and the other 36 (48.0%) patients received blood transfusions of >2 U before TAE. The incidence rates of systemic inflammatory response syndrome, sepsis, and coagulopathy were significantly higher in the >2 U group (97.2% vs 81.1%, P= .027; 50.0% vs 27.0%, P= .045; and 44.4% vs 5.4%, P< .01, respectively). After nonsurvivors were excluded, the >2 U group had a significantly higher proportion (43.8% vs 14.7%, P< .001) of prolonged intensive care unit (ICU) length of stay (7 days or more) and a longer hospital length of stay (33.8 ± 15.1 vs 21.9 ± 94.0, P< .01) than the ≤2 U group. Pre-TAE blood transfusion >2 U serves as an independent risk factor for prolonged ICU length of stay and increased hospital length of stay.Conclusion Early hemostasis for pelvic fracture-related hemorrhage is suggested to prevent pre-TAE blood transfusion-associated adverse effects of blood transfusion.

Early-life nutritional exposures may contribute to offspring epigenetic modifications. However, few studies have evaluated parental dietary quality effects on offspring DNA methylation (DNAm).

The existing aeroengine instability precursor detection methods can be summarized as applying advanced signal processing technologies to various signals from the compressor test rig rather than the whole engine. Besides, these methods seriously depend on the artificial designed feature and threshold and also ignore the limit on the sensors onboard. Thus, with the help of the powerful feature extraction ability of the deep neural network, a real-time surge prediction method based on the multi-branch feature fusion neural network (MBFFNN) is proposed. First, the dataset can be obtained by using overlapping slices to divide surge test data into a sample sequence and using complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) to label each sample precisely. Second, for each sample, the time-domain statistical parameters are calculated and the recurrence plot is obtained by using phase space reconstruction. Finally, the MBFFNN with mixed data type input is designed, and its performance is evaluated by the generated dataset. The experimental results show that compared with multilayer perceptron (MLP), long short-term memory (LSTM), and deep residual network (DRN), MBFFNN has the best performance on two datasets for different surge tests, which demonstrates that the proposed method for surge prediction can accurately judge the state of the aeroengine, identify the instability precursor before the surge, and give an early warning in advance.

Shaping modulation formats in multi-dimensional (MD) space is an effective approach to harvest spectral efficiency gains in both the additive white Gaussian noise (AWGN) channel and the optical fiber channel. In the first part of this paper, existing MD geometrically-shaped modulations for fiber optical communications are reviewed. It is shown that large gains can be obtained by exploiting correlation in the dimensions or/and by increasing the cardinality of the modulation format. Practical limitations and challenges are also discussed together with efficient solutions. In the second part, we extend the recently proposed four-dimensional (4D) modulation format family based on the constraint of orthant-symmetry to high spectrum efficiencies up to 10 b/4D-sym by maximizing generalized mutual information for AWGN channel. Reach increases of up to 25% for a multi-span optical fiber transmission system are reported. Lastly, with the help of a recently introduced nonlinear interference (NLI) model, an optimization for designing nonlinear-tolerant 4D modulation formats is introduced for a single-span optical fiber system. Simulation results show that the proposed NLI model-based 4D modulation format could increase the effective SNRs by 0.25 dB with respect to the AWGN channel-optimal 4D modulation format.

A reversible MnNO cathode fabricated via dual enhancement mechanisms of nitridation and electrochemical oxidation from the industrial-scale Mn2O3, exhibiting promising electrochemical performances with improved electrochemical reaction kinetics.

In order to simulate the effects of reconstructing misconnected nodes in the drainage system and quantify sewage routing paths during the rainy season, we have selected a specific region in Fangchenggang City as our study area. All misconnected nodes have been divided into 10 areas based on their respective blocks and streets. COD, NH4+-N, TN, and TP are chosen as evaluation indexes, and we have utilized SWMM for modelling purposes. The results indicate that nodes located upstream within the drainage watershed tend to have a broader influence scope, with a maximum pollutant load reduction rate of 8.6%. However, it is worth noting that the normalization effect could worsen if a reconstruction scheme contains more nodes. Our methodology for calculating the pollutant load reduction rate of pipelines presents a novel approach for quantifying pollutant reduction effects, sewage flow paths, and geographical visualization. This approach has the potential to address the knowledge gap in exploring pollutant transfer routes.

Irritable bowel syndrome (IBS) is characterized by visceral hypersensitivity (VH) associated with abnormal serotonin/5-hydroxytryptamine (5-HT) metabolism and neurotrophin-dependent mucosal neurite outgrowth. The underlying mechanisms of VH remain poorly understood. We investigated the role of 5-HT7receptor in mucosal innervation and intestinal hyperalgesia. A high density of mucosal nerve fibres stained for 5-HT7was observed in colonoscopic biopsy specimens from IBS patients compared with those from healthy controls. Staining of 5-HT3and 5-HT4receptors was observed mainly in colonic epithelia with comparable levels between IBS and controls. Visceromotor responses to colorectal distension were evaluated in two mouse models, one postinfectious with Giardiaand subjected to water avoidance stress (GW) and the other postinflammatory with trinitrobenzene sulfonic acid-induced colitis (PT). Increased VH was associated with higher mucosal density of 5-HT7-expressing nerve fibres and elevated neurotrophin and neurotrophin receptor levels in the GW and PT mice. The increased VH was inhibited by intraperitoneal injection of SB-269970 (a selective 5-HT7antagonist). Peroral multiple doses of CYY1005 (a novel 5-HT7ligand) decreased VH and reduced mucosal density of 5-HT7-expressing nerve fibres in mouse colon. Human neuroblastoma SH-SY5Y cells incubated with bacteria-free mouse colonic supernatant, 5-HT, nerve growth factor, or brain-derived neurotrophic factor exhibited nerve fibre elongation, which was inhibited by 5-HT7antagonists. Gene silencing of HTR7also reduced the nerve fibre length. Activation of 5-HT7upregulated NGFand BDNFgene expression, while stimulation with neurotrophins increased the levels of tryptophan hydroxylase 2 and 5-HT7in neurons. A positive-feedback loop was observed between serotonin and neurotrophin pathways via 5-HT7activation to aggravate fibre elongation, whereby 5-HT3and 5-HT4had no roles. In conclusion, 5-HT7-dependent mucosal neurite outgrowth contributed to VH. A novel 5-HT7antagonist could be used as peroral analgesics for IBS-related pain.

Purpose Whole-body computed tomography (WBCT) scans are frequently used for trauma patients, and sometimes, nontraumatic findings are observed. We aimed to investigate the characteristics of patients with nontraumatic findings on WBCT.Methods From 2013 to 2016, adult trauma patients who underwent WBCT were enrolled. The proportions of nontraumatic findings in different anatomical regions were studied. Nontraumatic findings were classified and evaluated as clinically important findings and findings that needed no further follow-up or treatment. The characteristics of the patients with nontraumatic findings were analyzed and compared with those of patients without nontraumatic findings.Results Two hundred seventeen patients were enrolled in this study during the 3-year study period, and 89 (41.0%) patients had nontraumatic findings. Nontraumatic findings were found more frequently in the abdomen (69.2%) than in the head/neck (17.3%) and chest regions (13.5%). In total, 31.3% of the findings needed further follow-up or treatment. Patients with nontraumatic findings that needed further management were significantly older than those without nontraumatic findings (57.3 vs. 38.9; P< .001), particularly those with abdominal nontraumatic findings (57.9 vs. 41.3; P< .001). A significantly higher proportion of women were observed in the group with head/neck nontraumatic findings that needed further management than in the group without nontraumatic findings (56.3% vs 24.9%; P= .015).Conclusions Whole-body computed tomography could provide alternative benefits for nontraumatic findings. Whole-body computed tomography images should be read carefully for nontraumatic findings, particularly for elderly patients or the head/neck region of female patients. A comprehensive program for the follow-up of nontraumatic findings is needed.

Coking wastewater, characterized by its complex composition, high pollutant concentration, and poor biodegradability, poses a significant challenge for wastewater treatment. In this study, a chitosan-based mesoporous carbon (CPC) and microporous carbon (ZPC) dual-cathode Electro-Fenton system was developed to enhance the in-situ Fe2+/Fe3+cycle efficiency for the degradation of coking wastewater. The optimal preparation conditions for both electrodes were investigated, as well as the primary factors affecting the degradation performance of the dual-cathode Electro-Fenton system. When the functional carbon loading was 17.5 mg/cm2and a current of 600 mA was applied, the CPC electrode produced 842 mg/L of H2O2within 30 min, and the Fe2+/Fe3+cycle efficiency of the ZPC electrode reached 85.23 %. The initial pH and current intensity had the most significant impact on the degradation efficiency of coking wastewater, achieving a COD degradation rate of 78 % at an initial pH of 3.5 and a current intensity of 600 mA. GC-MS analysis indicated that under 600 mA, nitrogen-containing organics, ethers, and alcohols in the coking wastewater were completely removed. The degradation of simulated wastewater showed that the presence of oxygen-containing compounds inhibited the degradation of nitrogen-containing organics. However, the dual-cathode system experienced significant electrode wear, with reduced hydrophobicity and agglomeration of Fe3+on the electrode surface impacting its cyclic stability.

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The present study investigates the chemical composition and antioxidant capacity of juice from the Gannan navel orange, which is harvested at one- to two-week intervals during the ripening period. The total soluble solid (TSS), total polyphenol content (TPC), total flavonoid content (TFC), sucrose and hesperidin contents gradually increase with the ripening of the fruit, followed by slight declines at the late maturity stage. Contrary to these observations, the contents of titratable acid (TA), vitamin C (Vc), and limonin trend downward throughout the ripening period. However, the contents of fructose, glucose, and narirutin fluctuate throughout the harvest time. Three in vitroantioxidant assays consistently indicate that the harvest time exerts no significant influence (P>0.01) on the antioxidant capacity. Furthermore, principal component analysis (PCA) and Pearson's correlation test are performed to provide an overview of the complete dataset. This study provides valuable information for evaluating the fruit quality and determining when to harvest the fruit in order to meet the preferences of consumers. Meanwhile, our observations suggest that the fruits subjected to juice processing should be harvested at the late maturity stage to alleviate the “delayed bitterness” problem without compromising the antioxidant capacity and the flavonoid content in the juice.

Background: Acute cholecystitis (AC) is a common surgical emergency. The Tokyo Guidelines 2018 (TG18) provides a reliable algorithm for the treatment of AC patients to achieve optimal outcomes. However, the economic benefits have not been validated. We hypothesize that good outcomes and cost savings can both be achieved if patients are treated according to the TG18. Method: This retrospective study included 275 patients who underwent cholecystectomy in a 15-month span. Patients were divided into three groups (group 1: mild AC; group 2: moderate AC with American Society of Anesthesiologists (ASA) physical status class ≤ 2 and Charlson Comorbidity Index (CCI) score ≤ 5; and group 3: moderate AC with ASA class ≥ 3, CCI score ≥ 6, or severe AC). Each group was further divided into two subgroups according to management (followed or deviated from the TG18). Patient demographics, clinical outcomes, and hospital costs were compared. Results: For group 1 patients, 77 (81%) were treated according to the TG18 and had a significantly higher successful laparoscopic cholecystectomy (LC) rate (100%), lower hospital cost ($1896 vs $2388), and shorter hospital stay (2.9 vs 8 days) than those whose treatment deviated from the TG18. For group 2 patients, 50 (67%) were treated according to the TG18 and had a significantly lower hospital cost ($1926 vs $2856), shorter hospital stay (3.9 vs 9.9 days), and lower complication rate (0% vs 12.5%). For group 3 patients, 62 (58%) were treated according to the TG18 and had a significantly lower intensive care unit (ICU) admission rate (9.7% vs 25%), but a longer hospital stay (12.6 vs 7.8 days). However, their hospital costs were similar. Early LC in group 3 patients did not have economic benefits over gallbladder drainage and delayed LC. Conclusion: The TG18 are the state-of-the-art guidelines for the treatment of AC, achieving both satisfactory outcomes and cost-effectiveness.

Seven new tropane alkaloids, including five monomeric (1–5), one dimeric (6), and one trimeric (7) 3α-nortropane ester, along with two known monomeric nortropane alkaloids (8and 9), were isolated from the leaves and bark of Pellacalyx saccardianus. Their structures, including the absolute configuration of the enantiomeric pair of (±)-6, were elucidated by comprehensive spectroscopic analyses. Alkaloids 6and 7showed cytotoxicity toward human pancreatic cancer cell lines (AsPC-1, BxPC3, PANC-1, and SW1990). Alkaloids 1, 4, and 9induced a smooth muscle relaxation effect comparable to that of atropine (Emax106.1 ± 7.5%, 97.0 ± 5.2%, 100.9 ± 1.4%, 111.7 ± 1.7%, respectively) on isolated rat tracheal rings.

AbstractThis work proposes the development of a system that will automatically evaluate quality honey bee queen species for breeding based on bee behavior. The queen breeding stages are set as the evaluation guidelines for queen bee and drone sources; the guidelines are then quantified using mathematical formulae. The work will also use sound sensors and database technology to complement JSP language and eclipse programming for system development. System functions will be designed based on actual operational needs, including establishing basic user information, the input of bee information, a blood relations structure, premium combinations and real-time monitoring. The system will integrate databases and real-time sound monitoring information to offer supervision of the queen breeding process in every bee breeding box. Using this system, honey bee queen breeding processes may be shortened by almost one month, which will increase the productivity of queen bee breeding.

The Three-River-Source is regarded as China's water tower. The protection of the source of three rivers, the Lancang River, the Yellow River and the Yangtze River, is related to the overall situation of China ecological security. It has been attached so much significance to the long-term interests and sustainable development of China. Since the construction of Three-River-Source National Park System Pilot Area was incorporated into the national strategy of China, outstanding achievements have been obtained. This paper has analyzed the path to constructing Three -River-Source National Park System Pilot Area. It has been concluded that Three -River-Source National Park System Pilot Area has provided much replicable and referential experiences on management system, operation mechanism and ecological protection.

In order to improve the quality of high‐moisture fermented rice cake (FRC) and analyze its staling mechanism, the texture, amylopectin retrogradation, water status and microstructure of FRCs with carrageenan (CA), locust bean gum (LBG), arabic gum (AG), xanthan gum (XT), and hydroxypropylmethylcellulose (HPMC) during 4 days of storage at 25°C were analyzed. The addition of 0.2% AG and 0.2% HPMC increased the softness of FRCs during storage. The specific gravity and pH values of rice batters were not affected by hydrocolloid, but their apparent viscosities were higher than that of the control. LBG and CA led greater effects on specific volume than AG, XT, and HPMC. AG and HPMC decreased the firming rate of the FRC crumb, retarded the amylopectin retrogradation, and effectively inhibited the increase of bound water in FRC for 4 days of storage. The selection of hydrocolloids as ingredients that can improve the physical properties of FRC. Additionally, high water‐binding strength and water content could decrease significantly the firming rate of FRC during storage. Arabic gum was the most effective in reducing the amount of bound water in the FRC. The reduction in firming rate of FRC was mainly due to the decrease in bound water.

Background: In animal studies early life antibiotic exposure causes metabolic abnormalities including obesity through microbiota disruption, but evidence from human studies is scarce. We examined involvement of gut microbiota in the associations between infant antibiotic exposure and childhood adiposity. Methods: Infant antibiotic exposure in the first year of life was ascertained using parental reports during interviewer-administered questionnaires. Primary outcomes were childhood obesity [body mass index (BMI) z-score > 95th percentile] and adiposity [abdominal circumference (AC) and skinfold (triceps + subscapular (SST)) measurements] determined from ages 15–60 months. At age 24 months, when the gut microbiota are more stable, stool samples (n= 392) were collected for the gut microbiota profiling using co-abundancy networks. Associations of antibiotic exposure with obesity and adiposity (n= 1016) were assessed using multiple logistic and linear mixed effects regressions. Key bacteria associated with antibiotics exposure were identified by partial redundancy analysis and multivariate association with linear models. Results: Antibiotic exposure was reported in 38% of study infants. In a fully adjusted model, a higher odds of obesity from 15–60 months of age was observed for any antibiotic exposure [OR(95% CI) = 1.45(1.001, 2.14)] and exposure to ≥3 courses of antibiotics [2.78(1.12, 6.87)]. For continuous adiposity indicators, any antibiotic exposure was associated with higher BMI z-score in boys [β= 0.15(0.01, 0.28)] but not girls [β= −0.04(−0.19, 0.11)] (Pinteraction = 0.026). Similarly, exposure to ≥3 courses of antibiotics was associated with higher AC in boys [1.15(0.05, 2.26) cm] but not girls [0.57(−1.32, 2.45) cm] (Pinteraction not significant). Repeated exposure to antibiotics was associated with a significant reduction (FDR-corrected Pvalues &lt; 0.05) in a microbial co-abundant group (CAG) represented by Eubacterium hallii, whose proportion was negatively correlated with childhood adiposity. Meanwhile, a CAG represented by Tyzzerella 4was positively correlated with the repeated use of antibiotics and childhood adiposity. Conclusions: Infant antibiotic exposure was associated with disruption of the gut microbiota and the higher risks of childhood obesity and increased adiposity.

Our previous study shows that nicotinamide adenine dinucleotide phosphate (NADPH) plays an important role in protecting against cerebral ischemia injury. In this study we investigated whether NADPH exerted cardioprotection against myocardial ischemia/reperfusion (I/R) injury. To induce myocardial I/R injury, rats were subjected to ligation of the left anterior descending branch of coronary artery for 30 min followed by reperfusion for 2 h. At the onset of reperfusion, NADPH (4, 8, 16 mg· kg−1· d−1, iv) was administered to the rats. We found that NADPH concentrations in plasma and heart were significantly increased at 4 h after intravenous administration. Exogenous NADPH (8−16 mg/kg) significantly decreased myocardial infarct size and reduced serum levels of lactate dehydrogenase (LDH) and cardiac troponin I (cTn-I). Exogenous NADPH significantly decreased the apoptotic rate of cardiomyocytes, and reduced the cleavage of PARP and caspase-3. In addition, exogenous NADPH reduced mitochondrial vacuolation and increased mitochondrial membrane protein COXIV and TOM20, decreased BNIP3L and increased Bcl-2 to protect mitochondrial function. We conducted in vitro experiments in neonatal rat cardiomyocytes (NRCM) subjected to oxygen–glucose deprivation/restoration (OGD/R). Pretreatment with NADPH (60, 500 nM) significantly rescued the cell viability and inhibited OGD/R-induced apoptosis. Pretreatment with NADPH significantly increased the phosphorylation of AMPK and downregulated the phosphorylation of mTOR in OGD/R-treated NRCM. Compound C, an AMPK inhibitor, abolished NADPH-induced AMPK phosphorylation and cardioprotection in OGD/R-treated NRCM. In conclusion, exogenous NADPH exerts cardioprotection against myocardial I/R injury through the activation of AMPK/mTOR pathway and inhibiting mitochondrial damage and cardiomyocyte apoptosis. NADPH may be a potential candidate for the prevention and treatment of myocardial ischemic diseases.

We synthesized an oxidation-responsive polycaprolactone (O-PCL) bearing pendant arylboronic esters as H2O2-responsive motifs. H2O2induces fast depolymerization of O-PCL within days. Nanoparticles formulated from O-PCL disintegrate and release payload in response to concentrations of H2O2(50 μM) that are relevant to human disease.

Sepsis initiates an inflammatory response that causes widespread injury, and candidates for related myocardial depressant factors include cytokines and nitric oxide (NO). Nuclear factor kappa-B (NF-κB) stimulated by toll-like receptor 4 activation in sepsis mediates the transcription of multiple proinflammatory genes. These inflammatory mediators can cause myocardial dysfunction, which may deteriorate sepsis outcomes. To address this risk, we investigated the potential beneficial effects of a novel isoquinolines derivative, CYY054c, in LPS-induced inflammatory response leading to endotoxemia.

Owing to the advantages of low cost, high safety, and a desirable cycling lifetime, vanadium redox flow batteries (VRFBs) have attracted great attention in the large-scale energy storage field. However, graphite felts (GFs), widely used as electrode materials, usually possess an inferior catalytic activity for the redox reaction of vanadium ions, largely limiting the energy efficiency and rate performance of VRFBs. Here, an in situ growth of amorphous MnO2on graphite felt (AMO@GF) was designed for application in VRFBs via mild and rapid etching engineering (5 min). After the etching process, the graphite felt fibers showed a porous and defective surface, contributing to abundant active sites toward the redox reaction. In addition, formed amorphous MnO2can also serve as a powerful catalyst to facilitate the redox couples of VO2+/VO2+based on density functional theoretical (DFT) calculations. As a result, the VRFB using AMO@GF displayed an elevated energy efficiency and superior stability after 2400 cycles at 200 mA cm–2, and the maximum current density can reach 300 mA cm–2. Such a high-efficiency and convenient design strategy for the electrode material will drive the further development and industrial application of VRFBs and other flow battery systems.

The cycling stability of a thin zinc anode under high zinc utilization has a critical impact on the overall energy density and practical lifetime of zinc ion batteries. In this study, an ion sieve protection layer (ZnSnF@Zn) was constructed in situon the surface of a zinc anode by chemical replacement. The ion sieve facilitated the transport and desolvation of zinc ions at the anode/electrolyte interface, reduced the zinc deposition overpotential, and inhibited side reactions. Under a 50% zinc utilization, the symmetrical battery with this protection layer maintained stable cycling for 250 h at 30 mA cm–2. Matched with high-load self-supported vanadium-based cathodes (18–20 mg cm–2), the coin battery with 50% zinc utilization possessed an energy density retention of 94.3% after 1000 cycles at 20 mA cm–2. Furthermore, the assembled pouch battery delivered a whole energy density of 61.3 Wh kg–1, surpassing the highest mass energy density among reported mild zinc batteries, and retained 76.7% of the energy density and 85.3% (0.53 Ah) of the capacity after 300 cycles.

This paper presents a single-lever control method based on Power Management System (PMS) and improved Twin Delayed Deep Deterministic Policy Gradient (TD3) algorithm for turboprop engines. In this approach, power level angle command, which is the single-lever command, is decoupled into controlled variable commands by PMS, and the controller based on improved TD3 algorithm can ensure that controlled variables track their commands rapidly and accurately. To achieve the optimal conversion relationship between different commands, an offline optimization process is used to design PMS. By optimization, specific fuel consumption and propeller efficiency are both improved after conversion. To deal with strong interactions between different control loops of a turboprop engine, TD3 algorithm which is a deep reinforcement learning algorithm is adopted. Two improvements which are the design method of observation state and prioritized experience replay are made to enhance the tracking accuracy. Simulation results show that improved TD3 algorithm can learn an optimal control policy to guarantee good control effect with fast response and small overshoot. The maximum settling time is less than 0.25s and the maximum overshoot is less than 0.1%. It also has a good robustness performance when the plant exists model uncertainties. The maximum fluctuations are less than 0.05%.

The histopathological hallmark of type 2 diabetes is islet amyloid implicated in the developing treatment options. The major component of human islet amyloid is 37 amino acid peptide known as amylin or islet amyloid polypeptide (IAPP). Amylin is an important hormone that is co-localized, copackaged, and co-secreted with insulin from islet β cells. Physiologically, amylin regulates glucose homeostasis by inhibiting insulin and glucagon secretion. Furthermore, amylin modulates satiety and inhibits gastric emptying via the central nervous system. Normally, human IAPP is soluble and natively unfolded in its monomeric state. Pathologically, human IAPP has a propensity to form oligomers and aggregate. The oligomers show misfolded α-helix conformation and can further convert themselves to β-sheet-rich fibrils as amyloid deposits. The pathological findings and physiological functions of amylin have led to the introduction of pramlintide, an amylin analog, for the treatment of diabetes. The history of amylin’s discovery is a representative example of how a pathological finding can translate into physiological exploration and lead to pharmacological intervention. Understanding the importance of transitioning from pathology to physiology and pharmacology can provide novel insight into diabetes mellitus and Alzheimer's disease.

Findings on the relations of maternal dietary patterns during pregnancy and risk of preterm birth and offspring birth size remain inconclusive. We aimed to systematically review and quantify these associations. We searched MEDLINE, Embase, CENTRAL, and CINAHL up to December 2017. Three authors independently conducted a literature search, study selection, data extraction, and quality assessment. Summary effect sizes were calculated with random effects models and studies were summarized narratively if results could not be pooled. We included 36 studies and pooled results from 25 observational studies (167,507 participants). Two common dietary patterns—“healthy” and “unhealthy”—were identified. Healthy dietary patterns—characterized by high intakes of vegetables, fruits, wholegrains, low-fat dairy, and lean protein foods—were associated with lower risk of preterm birth (OR for top compared with bottom tertile: 0.79; 95% CI: 0.68, 0.91; I2= 32%) and a weak trend towards a lower risk of small-for-gestational-age (OR: 0.86; 95% CI: 0.73, 1.01; I2= 34%). Only statistically data-driven healthy dietary patterns, and not dietary index-based patterns, were associated with higher birth weight (mean difference: 67 g; 95% CI: 37, 96 g; I2= 75%). Unhealthy dietary patterns—characterized by high intakes of refined grains, processed meat, and foods high in saturated fat or sugar—were associated with lower birth weight (mean difference: −40 g; 95% CI: −61, −20 g; I2= 0%) and a trend towards a higher risk of preterm birth (OR: 1.17; 95% CI: 0.99, 1.39; I2= 76%). Data from observational studies indicate that greater adherence to healthy dietary patterns during pregnancy is significantly related to lower risk of preterm birth. No consistent associations with birth weight and small- or large-for-gestational-age were observed.

DNA mismatch repair (MMR) deficiency has been associated with a higher risk of developing colorectal, endometrial, and ovarian cancer, and confers resistance in conventional chemotherapy. In addition to the lack of treatment options that work efficaciously on these MMR-deficient cancer patients, there is a great need to discover new drug leads for this purpose. In this study, we screened through a library of commercial and semisynthetic natural compounds to identify potential synthetic lethal drugs that may selectively target MLH1mutants using MLH1isogenic colorectal cancer cell lines and various cancer cell lines with known MLH1status. We identified a novel diarylpentanoid analogue, 2-benzoyl-6-(2,3-dimethoxybenzylidene)-cyclohexenol, coded as AS13, that demonstrated selective toxicity toward MLH1-deficient cancer cells. Subsequent analysis suggested AS13 induced elevated levels of oxidative stress, resulting in DNA damage where only the proficient MLH1cells were able to be repaired and hence escaping cellular death. While AS13 is modest in potency and selectivity, this discovery has the potential to lead to further drug development that may offer better treatment options for cancer patients with MLH1deficiency.

Boron neutron capture therapy and Y-90 radioembolization are emerging therapeutic methods for uncontrolled brain cancers and hepatic cancers, respectively. These advanced radiation therapies are heavily relied on theranostic nuclear medicine imaging before the therapy for the eligibility of patients and the prescribed-dose simulation, as well as the post-therapy scanning for assessing the treatment efficacy. In Taiwan, the Taipei Veterans General Hospital is the only institute performing the BNCT and also the leading institute performing Y-90 radioembolization. In this article, we present our single institute experiences and associated theranostic nuclear medicine approaches for these therapies.

Background:The treatment of relapsed or refractory acute myeloid leukemia ( AML) remains challenging. Measurable residual disease (MRD) persistence at transplantation or post-transplantation has been identified as the strongest risk factor for relapse and poor outcomes for patients with hematological malignancies (HMs). Chidamide, a novel oral histone deacetylase inhibitor, has shown potential therapeutic effects in various types of HMs by inducing cell apoptosis and regulating immunity. This study aimed to evaluate the efficacy and safety of Chidamide-based prophylactic or pre-emptive treatment for patients who are MRD positive before or who have sustained MRD positive after transplantation.

Introduction:

In this work, a porous copper fiber sintered sheet (PCFSS) is fabricated by using a low-temperature solid-phase sintering method. Copper fiber is a raw material that is produced by a cutting method with a multi-tooth tool. A novel reference plate method (RPM) with a steady state heat transfer process is introduced to measure the thermal conductivity of PCFSS. The study involves experimentally investigating the effects of reference plate materials as well as the porosity and porosity gradients of PCFSS on thermal conductivity. The findings indicate that reasonable measurement results of thermal conductivity of PCFSS are obtained when 304 stainless steel is selected as a reference plate material when compared with that in the case of a red copper plate. The thermal conductivity increases with a decrease in the porosities of PCFSS in the approximate range of 70%–90%. With respect to the approximate measuring temperature range of 34°C~58°C, the thermal conductivities of PCFSSs with 70%, 80% and 90% porosities correspond to 25.35 W/(m·°C), 15.01 W/(m·°C) and 11.24 W/(m·°C), respectively. The thermal conductivity of PCFSS with 70%-80%-90% gradient porosity corresponds to 13.43 W/(m·°C), and this value is between 80% and 90% porosity of PCFSS.

Molecular dynamics (MD) simulations were conducted to investigate the structural and chemical environment of aluminum in aluminophosphate glasses. Such glasses have the potential for application in the disposal of radioactive fluoride waste from molten salt reactors (MSR). Due to the risks of studying these materials and the limitations of realistic research conditions, MD simulations were used as an alternative method to study the vitrification of radioactive fluoride waste. In the past decades, aluminophosphate glasses have been studied and they exhibit certain favorable properties for high-level radioactive waste management. This work focuses on the effects of fluorine addition on structural changes in the glass. We observed that glass with composition P2O5–Al2O3–Na2O–CaO exhibited a good performance in immobilizing fluoride at low F concentrations (approximately under 25 mol%). Significant changes were observed where PO3F2units replaced PO3F units in the glass. The four-coordinated AlO4units were increasingly converted into five-coordinated [AlOxFy] with the increasing F content. The radionuclide Sr in the simulation had the tendency to form six-coordinated octahedrons in the glass. We conclude that the structural changes resulting from the fluoride waste added to aluminophosphate glasses does not adversely affect their chemical stability at relatively low F concentrations, i.e., under 25 mol%. Hence, the use of phosphate glasses is a potential alternative method of fluoride waste disposal.

A mild and simple synthesis process for large-scale vanadium redox flow batteries (VRFBs) energy storage systems is desirable. A graphite felt/MnO2(GF-MNO) composite electrode with excellent electrocatalytic activity towards VO2+/VO2+redox couples in a VRFB was synthesized by a one-step hydrothermal process. The resulting GF-MNO electrodes possess improved electrochemical kinetic reversibility of the vanadium redox reactions compared to pristine GF electrodes, and the corresponding energy efficiency and discharge capacity at 150 mA cm−2are increased by 12.5% and 40%, respectively. The discharge capacity is maintained at 4.8 A h L−1at the ultrahigh current density of 250 mA cm−2. Above all, 80% of the energy efficiency of the GFMNO composite electrodes is retained after 120 charge-discharge cycles at 150 mA cm−2. Furthermore, these electrodes demonstrated that more evenly distributed catalytic active sites were obtained from the MnO2particles under acidic conditions. The proposed synthetic route is facile, and the raw materials are low cost and environmentally friendly. Therefore, these novel GFMNO electrodes hold great promise in large-scale vanadium redox flow battery energy storage systems.