Effects of temperature (mesophilic (35 °C) vs. thermophilic (55 °C)) and dissolved oxygen (DO) concentration (under thermophilic conditions) on sludge properties and their role in bioflocculation and ...settling were studied using well-controlled sequencing batch reactors fed with a synthetic wastewater comprised of glucose and inorganic nutrients. Under a similar DO level, thermophilic sludge had a poorer bioflocculating ability and settleability than that of mesophilic sludge. Under a thermophilic condition, an increase in DO level led to a poorer settleability and a slightly improved bioflocculating ability. A poorer settleability was related to a higher level of filaments. Analysis of bound extracellular polymeric substances (EPS) indicates that thermophilic sludge had a higher level of total bound EPS content than that of mesophilic sludge under a similar DO level, and an increase in DO resulted in an increase in total bound EPS content in thermophilic sludge. Surface analysis of sludge by X-ray photoelectron spectroscopy (XPS) suggests that significant differences in the surface concentrations of elements N, C, O were observed between thermophilic and mesophilic sludge, implying significant differences in bound EPS composition. The results of gel permeation chromatography indicate that the weight-averaged molecular weight (Mw) of bound EPS covered a range of 1159 Da to 13220 Da. The distribution of EPS “species” at floc surfaces was shown by transmission electron microscopy (TEM) to be uneven; different kinds of nanoscale materials were distributed in a patchy manner at the floc–water interface. The results suggest that it is the role of specific EPS molecules rather than the quantity of bound EPS that determine the difference in bioflocculation behavior between thermophilic and mesophilic sludge. The strategy of increasing the DO level could not solve the biomass separation problems associated with thermophilic sludge.
We consider an additional fine-tuning problem which afflicts scalar-driven models of inflation. The problem is that successful reheating requires the inflaton be coupled to ordinary matter, and ...quantum fluctuations of this matter induce Coleman-Weinberg potentials which are not Planck suppressed. Unlike the flat space case, these potentials depend upon a still-unknown, nonlocal functional of the metric which reduces to the Hubble parameter for de Sitter. Such a potential cannot be completely subtracted off by any local action. In a simple model we numerically consider one possible subtraction scheme in which the correction is locally subtracted at the beginning of inflation. For fermions the effect is to make the Universe approach de Sitter with a smaller Hubble parameter. For gauge bosons the effect is to make inflation end almost instantly unless the gauge charge is unacceptably small.
Combined analyses of the natural occurrence of fusarium head blight (FHB), mycotoxins and mycotoxin‐producing isolates of Fusarium spp. in fields of wheat revealed FHB epidemics in 12 of 14 regions ...in Hubei in 2009. Mycotoxin contamination ranged from 0·59 to 15·28 μg g⁻¹ in grains. Of the causal agents associated with symptoms of FHB, 84% were Fusarium asiaticum and 9·5% were Fusarium graminearum, while the remaining 6·5% were other Fusarium species. Genetic chemotyping demonstrated that F. asiaticum comprised deoxynivalenol (DON), 3‐acetyldeoxynivalenol (3‐AcDON), 15‐acetyldeoxynivalenol (15‐AcDON) and nivalenol (NIV) producers, whereas F. graminearum only included DON and 15‐AcDON producers. Compared with the chemotype patterns in 1999, there appeared to be a modest shift towards 3‐AcDON chemotypes in field populations during the following decade. However, isolates genetically chemotyped as 3‐AcDON were present in all regions, whereas the chemical 3‐AcDON was only detected in three of the 14 regions where 3‐AcDON accounted for 15–20% of the DON and acetylated forms. NIV mycotoxins were detected in seven regions, six of which also yielded NIV chemotypes. The number of genetic 3‐AcDON producers was positively correlated with amounts of total mycotoxins (DON, NIV and acetylated forms) or DON in wheat grains. Chemical analyses of wheat grains and rice cultures inoculated with different isolates from the fields confirmed their genetic chemotypes and revealed a preferential biosynthesis of 3‐AcDON and 4‐AcNIV in rice. These findings suggest the importance of chemotyping coupled with species identification for improved prediction of mycotoxin contamination in wheat.
The bilayer-based Antiferroelectric Tunneling Junction (AFTJ) with ferroelectric (FE) HfZrO 2 (HZO) and dielectric (DE) Al 2 O 3 demonstrates a current ratio of <inline-formula> <tex-math ...notation="LaTeX">> 100\times </tex-math></inline-formula>, a TER (tunneling electroresistance) of <inline-formula> <tex-math notation="LaTeX">> 50\times </tex-math></inline-formula>, multilevel states, <inline-formula> <tex-math notation="LaTeX">> 10^{4} </tex-math></inline-formula> sec retention, and a cycling endurance as high as 10 8 . The concept of tunneling current through DE in an antiferroelectric (AFE) system enhances the capacity to modulate the current/TER ratio and makes the AFTJ feasible for low-power crossbar eNVM (embedded nonvolatile memory) applications.
Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy ...(nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC).
Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596).
A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P = 0.28, with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P = 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P = 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P = 0.063), while the recurrence pattern was similar (P = 0.802).
NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.
•The CMISG1701 trial assessed the safety and efficacy of nCRT versus nCT followed by MIE for locally advanced bulky ESCC.•The nCRT followed by MIE strategy could not improve survival significantly compared with the nCT strategy.•The best strategy of neoadjuvant therapy for locally advanced bulky ESCC remains a pending issue.
Abstract
Male C57BL/6J mice treated with D-galactose (DG) were used to examine the effects of ergothioneine (EGT), melatonin (MEL), or their combination (EGT+MEL) on learning and memory abilities. ...The mice were divided into five groups and injected subcutaneously with DG (0.3 mL of 1% DG/mouse) except for group 1 (normal controls). Group 3 was orally supplemented with EGT 0.5 mg/kg body weight (bw), group 4 with MEL (10 mg/kg bw, p.o.), and group 5 with EGT+MEL. EGT and MEL were provided daily for 88 days, while DG was provided between days 7 to 56. Active avoidance task and Morris water-maze task were used to evaluate learning and memory abilities. DG treatment markedly increased escape latency and decreased the number of avoidance in the active avoidance test, whereas EGT and MEL alone significantly improved the performance. DG also impaired the learning and memory abilities in the water-maze task, and EGT and MEL alone also significantly improved the performance. EGT+MEL produced the strongest effects in both tasks. EGT and MEL alone markedly decreased β-amyloid protein accumulation in the hippocampus and significantly inhibited lipid peroxidation and maintained glutathione/glutathione disulfide ratio and superoxide dismutase activity in brain tissues of DG-treated mice. MEL alone completely prevented the rise in brain acetylcholine esterase activity induced by DG, whereas EGT and EGT+MEL were only partially effective. Overall, EGT, MEL, and, in particular, the combination of EGT and MEL effectively protect against learning and memory deficits in C57BL/6J mice treated with DG, possibly through attenuation of oxidative damage.
Thyroid hormone (TH) and TH receptors (TRs) α and β act by binding to TH response elements (TREs) in regulatory regions of target genes. This nuclear signaling is established as the canonical or type ...1 pathway for TH action. Nevertheless, TRs also rapidly activate intracellular second-messenger signaling pathways independently of gene expression (noncanonical or type 3 TR signaling). To test the physiological relevance of noncanonical TR signaling, we generated knockin mice with a mutation in the TR DNA-binding domain that abrogates binding to DNA and leads to complete loss of canonical TH action. We show that several important physiological TH effects are preserved despite the disruption of DNA binding of TRα and TRβ, most notably heart rate, body temperature, blood glucose, and triglyceride concentration, all of which were regulated by noncanonical TR signaling. Additionally, we confirm that TRE-binding–defective TRβ leads to disruption of the hypothalamic–pituitary–thyroid axis with resistance to TH, while mutation of TRα causes a severe delay in skeletal development, thus demonstrating tissue- and TR isoform-specific canonical signaling. These findings provide in vivo evidence that noncanonical TR signaling exerts physiologically important cardiometabolic effects that are distinct from canonical actions. These data challenge the current paradigm that in vivo physiological TH action is mediated exclusively via regulation of gene transcription at the nuclear level.
The glucagon-like peptide (GLP)-1 receptor (GLP-1R) is a class B G protein-coupled receptor (GPCR) that mediates the action of GLP-1, a peptide hormone secreted from three major tissues in humans, ...enteroendocrine L cells in the distal intestine, α cells in the pancreas, and the central nervous system, which exerts important actions useful in the management of type 2 diabetes mellitus and obesity, including glucose homeostasis and regulation of gastric motility and food intake. Peptidic analogs of GLP-1 have been successfully developed with enhanced bioavailability and pharmacological activity. Physiologic and biochemical studies with truncated, chimeric, and mutated peptides and GLP-1R variants, together with ligand-bound crystal structures of the extracellular domain and the first three-dimensional structures of the 7-helical transmembrane domain of class B GPCRs, have provided the basis for a two-domain-binding mechanism of GLP-1 with its cognate receptor. Although efforts in discovering therapeutically viable nonpeptidic GLP-1R agonists have been hampered, small-molecule modulators offer complementary chemical tools to peptide analogs to investigate ligand-directed biased cellular signaling of GLP-1R. The integrated pharmacological and structural information of different GLP-1 analogs and homologous receptors give new insights into the molecular determinants of GLP-1R ligand selectivity and functional activity, thereby providing novel opportunities in the design and development of more efficacious agents to treat metabolic disorders.
LUX-ZEPLIN (LZ) is a next-generation dark matter direct detection experiment that will operate 4850 feet underground at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, USA. ...Using a two-phase xenon detector with an active mass of 7 tonnes, LZ will search primarily for low-energy interactions with weakly interacting massive particles (WIMPs), which are hypothesized to make up the dark matter in our galactic halo. In this paper, the projected WIMP sensitivity of LZ is presented based on the latest background estimates and simulations of the detector. For a 1000 live day run using a 5.6-tonne fiducial mass, LZ is projected to exclude at 90% confidence level spin-independent WIMP-nucleon cross sections above 1.4 × 10−48 cm2 for a 40 GeV/c2 mass WIMP. Additionally, a 5 σ discovery potential is projected, reaching cross sections below the exclusion limits of recent experiments. For spin-dependent WIMP-neutron(-proton) scattering, a sensitivity of 2.3 × 10−43 cm2 (7.1 × 10−42 cm2) for a 40 GeV/c2 mass WIMP is expected. With underground installation well underway, LZ is on track for commissioning at SURF in 2020.
Background and purpose
No study has established a prediction dementia model in the Asian populations. This study aimed to develop a prediction model for dementia in Chinese type 2 diabetes patients.
...Methods
The retrospective cohort study included 27 540 Chinese type 2 diabetes patients (aged 50–94 years) enrolled in the Taiwan National Diabetes Care Management Program. Participants were randomly allocated into derivation and validation sets at a 2:1 ratio. Cox proportional hazards regression models were used to identify risk factors for dementia in the derivation set. Steps proposed by the Framingham Heart Study were used to establish a prediction model with a scoring system.
Results
The average follow‐up was 8.09 years, with a total of 853 incident dementia cases in the derivation set. The dementia risk score summed up the individual scores (from 0 to 20). The areas under the curve of 3‐, 5‐ and 10‐year dementia risks were 0.82, 0.79 and 0.76 in the derivation set and 0.84, 0.80 and 0.75 in the validation set, respectively.
Conclusions
The proposed score system is the first dementia risk prediction model for Chinese type 2 diabetes patients in Taiwan.
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