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A previous 1H-NMR method allowed the quantification of ephedrine alkaloids; however, there were some disadvantages. The cyclized derivatives resulted from the impurities of diethyl ether were identified and benzene was selected as the better extraction solvent. The locations of ephedrine alkaloids were confirmed with 2D NMR. Therefore, a specific 1H-NMR method has been modified for the quantification of ephedrine alkaloids. Accordingly, twenty Ephedrae Herba samples could be classified into three classes: (I) E. sinica-like species; (II) E. intermedia-like species; (III) others (lower alkaloid contents). The results indicated that ephedrine and pseudoephedrine are the major alkaloids in Ephedra plants, but the concentrations vary greatly determined by the plant species and the collection locations.

The Hutoubi Reservoir and its mainstream, Huyuan Stream, in the southern mountainous region of Taiwan, have experienced riverbed sedimentation and flood disasters for the past 150 years. In addition to climate change, it is necessary to scientifically consider its regulation for the next hundred years. This study adopted a collaborative approach, involving industry, government, and academia, using Nature-based Solutions (NbS) to enhance ecosystem services. The solution layout is constructed by widening the channel and constructing additional farm ponds and wetlands. An hydraulic simulation indicated that flood control was addressed. The restoration project would create diverse aquatic habitats by simulating and evaluating the distribution of ecological biotopes, using porous materials as revetments. It provided urban residents with forest leisure and recreational sites and supported the local agricultural and forestry products. The restoration has propagated local culture and created environmental and professional education. Therefore, ecological services are enhanced regarding regulation, support, provision, and culture. This pilot study, led by researchers, aimed to promote comprehensive management concepts considering all stakeholders and their active participation. We integrated NbS into the watershed and its river system as a pathway for facing the challenges of rapid urbanization and climate change and improving ecosystem services.

Inflammation is a cancer hallmark. NSAIDs improve overall survival (OS) in certain cancers. Real-world studies explored here whether NSAIDs improve non–small cell lung cancer (NSCLC) OS. Analyses independently interrogated clinical databases from The University of Texas MD Anderson Cancer Center (MDACC cohort, 1987 to 2015; 33,162 NSCLCs and 3,033 NSAID users) and Georgetown-MedStar health system (Georgetown cohort, 2000 to 2019; 4,497 NSCLCs and 1,993 NSAID users). Structured and unstructured clinical data were extracted from electronic health records using natural language processing (NLP). Associations were made between NSAID use and NSCLC prognostic features (tobacco use, gender, race, and body mass index, BMI). NSAIDs were statistically significantly (P < 0.0001) associated with increased NSCLC survival (5-year OS 29.7% for NSAID users vs. 13.1% for nonusers) in the MDACC cohort. NSAID users gained 11.6 months over nonusers in 5-year restricted mean survival time. Stratified analysis by stage, histopathology, and multicovariable assessment substantiated benefits. NSAID users were pooled independent of NSAID type and by NSAID type. Landmark analysis excluded immortal time bias. Survival improvements (P < 0.0001) were confirmed in the Georgetown cohort. Thus, real-world NSAID usage was independently associated with increased NSCLC survival in the MDACC and Georgetown cohorts. Findings were confirmed by landmark analyses and NSAID type. The OS benefits persisted despite tobacco use and did not depend on gender, race, or BMI (MDACC cohort, P < 0.0001). These real-world findings could guide future NSAID lung cancer randomized trials. Significance: NLP and real-world studies conducted in large cohorts explored whether NSAIDs improved survival across NSCLC stages, histopathology, gender, smoking history, or demographic groups. A statistically significant association between NSAID use and NSCLC survival was found. This provides a rationale for future NSAID randomized NSCLC trials.

Supplementary Table 6: The MD Anderson cohort 5-year survival rate and difference of 5-year restricted mean survival time in months between NSAID users and non-users by gender, race, and smoking status corresponding to Figure 2. Comparisons are made to the Georgetown cohort.

Supplemental Figure 2. The Kaplan-Meier analysis of overall survival and NSAID use in lung cancer cases within the MedStar-Georgetown University database (Georgetown cohort).

Inflammation is a cancer hallmark. NSAIDs improve overall survival (OS) in certain cancers. Real-world studies explored here whether NSAIDs improve non–small cell lung cancer (NSCLC) OS. Analyses independently interrogated clinical databases from The University of Texas MD Anderson Cancer Center (MDACC cohort, 1987 to 2015; 33,162 NSCLCs and 3,033 NSAID users) and Georgetown-MedStar health system (Georgetown cohort, 2000 to 2019; 4,497 NSCLCs and 1,993 NSAID users). Structured and unstructured clinical data were extracted from electronic health records using natural language processing (NLP). Associations were made between NSAID use and NSCLC prognostic features (tobacco use, gender, race, and body mass index, BMI). NSAIDs were statistically significantly (P < 0.0001) associated with increased NSCLC survival (5-year OS 29.7% for NSAID users vs. 13.1% for nonusers) in the MDACC cohort. NSAID users gained 11.6 months over nonusers in 5-year restricted mean survival time. Stratified analysis by stage, histopathology, and multicovariable assessment substantiated benefits. NSAID users were pooled independent of NSAID type and by NSAID type. Landmark analysis excluded immortal time bias. Survival improvements (P < 0.0001) were confirmed in the Georgetown cohort. Thus, real-world NSAID usage was independently associated with increased NSCLC survival in the MDACC and Georgetown cohorts. Findings were confirmed by landmark analyses and NSAID type. The OS benefits persisted despite tobacco use and did not depend on gender, race, or BMI (MDACC cohort, P < 0.0001). These real-world findings could guide future NSAID lung cancer randomized trials.Significance:NLP and real-world studies conducted in large cohorts explored whether NSAIDs improved survival across NSCLC stages, histopathology, gender, smoking history, or demographic groups. A statistically significant association between NSAID use and NSCLC survival was found. This provides a rationale for future NSAID randomized NSCLC trials.

OBJECTIVE: Conventional ultrafiltration (CUF) during cardiopulmonary bypass (CPB) serves to hemoconcentrate blood volume to avoid allogeneic blood transfusions. Previous studies have determined weight-indexed CUF volumes as a continuous variable are associated with postoperative AKI after cardiac surgery but optimal weight-indexed volumes that predict AKI have not been described. DESIGN: Retrospective cohort SETTING: Single-center university hospital PARTICIPANTS: 1,641 consecutive patients that underwent elective cardiac surgery between June 2013-December 2015. INTERVENTIONS: CUF volume was removed during CPB in all participants as part of our routine practice. We investigated the association of dichotomized weight indexed CUF volume removal with postoperative AKI development to provide pragmatic guidance for clinical practice at our institution. MEASUREMENTS AND MAIN RESULTS: Primary outcomes of postoperative AKI was defined by the KDIGO staging criteria and dichotomized, weight indexed CUF volumes (ml/kg) were defined by (i) extreme quartiles (Q3) and by (ii) Youden’s criterion that best predicted AKI development. Multivariable logistic regression models were developed to test the association of these dichotomized indices with AKI status. Postoperative AKI occurred in 827 patients (50.4%). Higher CUF volumes were associated with AKI development by quartiles (CUF >Q(3)=32.6 vs. CUF 32 mL/kg increased the risk for postoperative AKI development. Importantly, CUF volume removal of any amount did not mitigate allogeneic blood transfusion during elective cardiac surgery. Prospective studies are needed to validate these findings.

Pines evolve with fire and have diverged into fire-avoiders and fire-adapters. Pine needles are resistant to microbial decomposition, and their accumulation serves as a major fuel source for forest fires. Facilitated needle decomposition reduces forest fuel loads and probably interacts with the adaptive strategies of pines. However, there is little information available regarding differences in microbiomes associated with needle decomposition of the two types of pine. In this study, we monitored the microbial communities in three compartments associated with needle decomposition, namely, fresh needles, needle litter, and humus, along altitudinal gradients at three sites of the fire-tolerator Pinus taiwanensis and one site of the fire-avoider Pinus morrisonicola in Taiwan. The humus microbiome was dominated by an overwhelming proportion of bacteria. As a reservoir of decomposers, humus bacteria accounted for > 70% of the litter communities and showed marked differences in composition between the two Pinus species, as determined by non-metric multidimensional scaling. Such differences were associated with the abundance of bacterial genes encoding lignin-degrading enzymes, which were highest in the P. morrisonicola stand. Additionally, the humus accumulating under this fire-avoider was characterized by low ammonium concentrations and lower pH compared with that under the fire-tolerator, which is indicative of conditions conducive to litter decomposition. Conclusively, our findings suggested that P. morrisonicola grows in more favorable conditions for needle decomposition compared with the habitats where the P. taiwanensis lives.

Migration of placental extravillous trophoblast (EVT) cells into uterine decidua facilitates the establishment of blood circulation between mother and fetus and is modulated by EVT-decidual cell interaction. Poor or excessive EVT migration is associated with pregnancy complications such as preeclampsia or placenta accreta. Glial cells missing 1 (GCM1) transcription factor is essential for placental development, and decreased GCM1 activity is detected in preeclampsia. To study whether GCM1 regulates trophoblast cell migration, here we showed that GCM1 promotes BeWo and JAR trophoblast cell migration through a novel target gene, WNT10B. Moreover, WNT10B signaling stimulated cytoskeletal remodeling via Rac1 and frizzled 7 (FZD7) was identified as the cognate receptor for WNT10B to up-regulate cell migration. We further showed that secreted frizzled-related protein 3 (SFRP3) is expressed in uterine decidual cells by immunohistochemistry and that SFRP3 expression in telomerase-transformed human endometrial stromal cells (T-HESCs) is elevated under decidualization stimuli and further enhanced by bone morphogenetic protein 2 via SMAD1. SFRP3 blocked the interaction between FZD7 and WNT10B to decrease BeWo cell migration, which corroborated the elevated BeWo cell migration when cocultured with decidualized and SFRP3-knockdown T-HESC monolayer. Our results suggest that GCM1 up-regulates EVT cell migration through WNT10B and FZD7, which is negatively modulated by decidual SFRP3.-Wang, L.-J., Lo, H.-F., Lin, C.-F., Ng, P.-S., Wu, Y.-H., Lee, Y.-S., Cheong, M.-L., Chen, H. SFRP3 negatively regulates placental extravillous trophoblast cell migration mediated by the GCM1-WNT10B-FZD7 axis.

Four new sesquiterpenes (1–4), one new alkaloid (5), and one new benzenoid glycoside (6) were characterized from Lindera aggregata, and their structures were elucidated according to their spectrometric analytical data. Among these isolates, 3 and 4 were constructed as possessing unprecedented carbon skeletons from the natural source. Some of these purified constituents were examined for their anti-inflammatory bioactivity. Among the tested compounds, linderaggredin C (3), (+)-N-methyllaurotetanine, and (+)-isoboldine displayed the significant inhibition of superoxide anion generation in human neutrophils with IC50 values of 7.45 ± 0.74, 8.36 ± 0.11, and 5.81 ± 0.59 μM, respectively.

Objectives To determine whether precardiopulmonary bypass (CPB) normalization of antithrombin levels in infants to 100% improves heparin sensitivity and anticoagulation during CPB and has beneficial effects into the postoperative period. Design Randomized, double-blinded, placebo-controlled prospective study. Setting Multicenter study performed in 2 academic hospitals. Participants The study comprised 40 infants younger than 7 months with preoperative antithrombin levels Interventions Antithrombin levels were increased with exogenous antithrombin to 100% functional level intraoperatively before surgical incision. Measurements and Main Results Demographics, clinical variables, and blood samples were collected up to postoperative day 4. Higher first post-heparin activated clotting times (sec) were observed in the antithrombin group despite similar initial heparin dosing. There was an increase in heparin sensitivity in the antithrombin group. There was significantly lower 24-hour chest tube output (mL/kg) in the antithrombin group and lower overall blood product unit exposures in the antithrombin group as a whole. Functional antithrombin levels (%) were significantly higher in the treatment group versus placebo group until postoperative day 2. D-dimer was significantly lower in the antithrombin group than in the placebo group on postoperative day 4. Conclusion Supplementation of antithrombin in infants with low antithrombin levels improves heparin sensitivity and anticoagulation during CPB without increased rates of bleeding or adverse events. Beneficial effects may be seen into the postoperative period, reflected by significantly less postoperative bleeding and exposure to blood products and reduced generation of D-dimers.

d -Allulose 3-epimerase (DAEase) catalyzes the epimerization between d -fructose and d -allulose. We had PCR-cloned and overexpressed the gene encoding Agrobacterium sp. ATCC 31749 DAEase (AsDAEase) in Escherichia coli. A high yield of active AsDAEase, 35,300 U/L or 1350 U/g of wet cells, was acquired with isopropyl β- d -1-thiogalactopyranoside induction at 20 °C for 20 h. Although only six residues including residue 234 located in tetrameric interface are different between AsDAEase and A. tumefaciens DAEase (AtDAEase), the specific activity of purified AsDAEase is much larger than that of AtDAEase. The optimal pHs and optimal temperatures of the purified recombinant AsDAEase are 7.5–8.0 and 55–60 °C, respectively. The half-life of the enzyme is 267 min at 55 °C in the presence of 0.1 mM Co2+, and the equilibrium ratio between d -allulose and d -fructose is 30:70 at 55 °C. Besides characterizing AsDAEase, mutation N234D was constructed to assess its influence on activity. The specific activity of the purified N234D AsDAEase is only 25.5% of wil d -type's activity, suggesting residue N234 is an important interfacial residue which substantially affects enzyme activity. The high specific activity and high expression yield of AsDAEase suggest its prospect to be applied in d -allulose production.

Introduction: Postoperative acute kidney injury (AKI) confers poor outcomes after cardiac surgery. Conventional ultrafiltration (CUF) is performed on cardiopulmonary bypass (CPB) to raise hematocrit, avoid intraoperative blood transfusion, and provide renal protection. These protective effects remain unclear with high CUF volumes, which may cause hypovolemia and renal hypoperfusion. Hypothesis: Higher CUF volumes will be associated with increased AKI and poor outcomes. Methods: Retrospective analysis of 1,791 consecutive patients undergoing cardiac surgery (CABG, CABG/Valve, Valve only) was performed between June 2013 and December 2015. Institutional CPB protocol with CUF was used during all cases. Uni- and multivariable logistic regression analyses determined predictors for AKI. CUF volume analyses were performed, defined by two extreme quartiles or by Youden index derived from ROC analysis, and compared for their effect on AKI rate. Mortality data was acquired from the Social Security Administration’s Death Master File through 1 year after index surgery. Results: CUF volume independently predicted AKI (prd quartile, was > 2,900 ml (OR=1.72, 95% CI 1.25, 2.38) and defined by Youden index, was > 2,239 ml, (OR=1.52, 95% CI 1.22, 1.89). While associated with increased intraoperative blood transfusion volume (p=0.002), CUF volume in AKI patients (N=903) predicted increased ICU (p Conclusions: CUF volume removal during CPB predicted blood transfusion requirements, postoperative AKI, and ICU/Hospital LOS, while AKI predicted 30-day mortality.

Glial cell missing 1 (GCM1) transcription factor regulates placental cell fusion into the syncytiotrophoblast. Caspase-14 is proteolytically activated to mediate filaggrin processing during keratinocyte differentiation. Interestingly, altered expression of nonactivated caspase-14 proenzyme is associated with tumorigenesis and diabetic retinopathy, suggesting that caspase-14 may perform physiological functions independently of its protease activity. Here, we performed tandem affinity purification coupled with mass spectrometry analysis to identify caspase-14 proenzyme as a GCM1-interacting protein that suppresses GCM1 activity and syncytiotrophoblast differentiation. Immunohistochemistry revealed that caspase-14 and GCM1 colocalize to placental cytotrophoblast cells at 8 wk of gestation and syncytiotrophoblast layer at term. Further, we demonstrated that caspase-14 mRNA level is decreased by 40% in placental BeWo cells treated with forskolin (FSK). To the contrary, stimulation of GCM1-regulated placental cell fusion and human chorionic gonadotropin β (hCGβ) expression by FSK is enhanced by caspase-14 knockdown. Indeed, GCM1 protein level is increased by 40% in the caspase-14-knockdown BeWo cells. Because GCM1 is stabilized by acetylation, we subsequently showed that caspase-14 impedes the interaction between GCM1 and cAMP response element-binding protein (CREB)-binding protein (CBP) to suppress CBP-mediated acetylation and transcriptional coactivation of GCM1. Therefore, caspase-14 can suppress placental cell differentiation through down-regulation of GCM1 activity.

Two new diterpenoids, 14,18-dihydroxyabieta-8,11,13-trien-7-one (1) and 13-acetyl-14,18-dihydroxy-podocarpa-8,11,13-triene (2), together with eight known compounds, i.e., gaultheric acid (3), vanillic acid (4), 4-hydroxybenzoic acid (5), cinnamic acid (6), stearic acid (7), palmitic acid (8), beta-sitosterol (9), and stigmasterol (10), were isolated from the MeOH extract of the whole plant of Gaultheria itoana Hayata (Ericaceae). The structures of the new constituents were elucidated by spectroscopic methods (UV, IR, and 1D- and 2D-NMR) and by mass spectrometry (HR-ESI-MS). Among them, 1 and 2 were demonstrated to exhibit significant cytotoxic activity against the LNCaP cell line.

Fractionation of an ethanol-soluble extract of the seeds of Swietenia macrophylla yielded six new limonoids, swielimonoids A-F (1-6), along with 20 known compounds. Compounds 1 and 2, mexicanolide-type limonoids, were assigned with an α,β-unsaturated δ-lactone moiety (ring D) and a C═C bond between C-8 and C-30. Compounds 3-6 could be categorized as highly oxygenated phragmalin-type limonoids. The structures of these new compounds were elucidated through the interpretation of spectroscopic data. The antidengue virus 2 activities of the isolated components from S. macrophylla were investigated, and of 12 compounds subjected to bioassay, compounds 2 and 7-10 were found to show inhibitory activity in the range 3.5 to 12.5 μM. Among these, the new limonoid 2 exhibited significant antiviral activity (EC50 = 7.2 ± 1.33 μM) with a selectivity index (CC50/EC50) value of >27.7.

Ridesharing has the great opportunity to reduce the consumption of energy and the emission of harmful gases, and to let people share the traffic costs with others. Most of the current ridesharing systems simply provide a number of candidates for users to choose. Time-consuming negotiation often discourages people from ridesharing. We propose a novel approach that assigns users to form ridesharing groups according to their routes and payments. Given a driver, our goal is to find a group of passengers who will pay the driver the most. Under the payment scheme, the passengers who share rides on the same route will equally share the expense with the driver. For the prompt response to an online system, our approach aims for the near-optimal group, where the available seats on the driver route are occupied by passengers as many as possible. Compared with the previous methods, the experiment results show that our approach incurs a little overhead but obtains answers of good quality, measured by the driver's saving, under various parameter settings.

In the conventional bench-top approach, the DNA recombination process is time- and effort-consuming due to laborious procedures lasting from several hours to a day. A novel DNA selection and direct extraction process has been proposed, integrated and tested on chip. The integrative microfluidic chip can perform the whole procedure of DNA recombination, including DNA digestion, gel electrophoresis, DNA extraction and insert-vector ligation within 1 h. In this high-throughput design, the manual gel cutting was replaced by an automatic processing system that performed high-quality and high-recovery efficiency in DNA extraction process. With no need of gel-dissolving reagents and manipulation, the application of selection and direct extraction process could significantly eliminate the risks from UV and EtBr and also facilitate DNA recombination. Reliable output with high success rate of cloning has been achieved with a significant reduction in operational hazards, required materials, efforts and time.