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Since the initial discovery of metamaterial absorbers (MAs), they generate significant interest across the electromagnetic device industry due to their capacity to attain subwavelength magnitudes, adaptable design, and almost complete absorption. In recent years, there has been a growing focus on incorporating active materials into MAs, making it a current focal point of investigation. In the past few years, MAs have seen the integration of various active materials and configurations thanks to continuous exploration and innovation. Herein, comprehensive and systematic research on different tuning methods of MAs is reviewed, highlighting innovative materials and unique designs to accurately control the electromagnetic absorption characteristics of MAs. Key parameters, such as the operating frequency and relative tuning range, are summarized and compared to provide guidance for optimization design. Finally, the challenges of tunable MAs and their future prospects are also summarized. [ABSTRACT FROM AUTHOR]

Objective: To evaluate response to anti‐calcitonin gene–related peptide (CGRP) migraine preventives in a real‐world community cohort of persons living with migraine and to identify clinical and genetic characteristics associated with efficacious response. Background: Erenumab‐aooeb, fremanezumab‐vrfm, and galcanezumab‐gnlm target CGRP or its receptor; however, many patients are non‐responsive. Methods: In this retrospective clinical and genetic study, we identified 1077 adult patients who satisfied the International Classification of Headache Disorders, 3rd edition, criteria for migraine without aura, migraine with aura, or chronic migraine and who were prescribed an anti‐CGRP migraine preventive between May 2018 and May 2021. Screening of 558 patients identified 289 with data at baseline and first follow‐up visits; data were available for 161 patients at a second follow‐up visit. The primary outcome was migraine days per month (MDM). In 198 genotyped patients, we evaluated associations between responders (i.e., patients with ≥50% reduction in MDM at follow‐up) and genes involved in CGRP signaling or pharmacological response, and genetic and polygenic risk scores. Results: The median time to first follow‐up was 4.4 (0.9–22) months after preventive start. At the second follow‐up, 5.7 (0.9–13) months later, 145 patients had continued on the same preventive. Preventives had strong, persistent effects in reducing MDM in responders (follow‐up 1: η2 = 0.26, follow‐up 2: η2 = 0.22). At the first but not second follow‐up: galcanezumab had a larger effect than erenumab, while no difference was seen at either follow‐up between galcanezumab and fremanezumab or fremanezumab and erenumab. The decrease in MDM at follow‐up was generally proportional to baseline MDM, larger in females, and increased with months on medication. At the first follow‐up only, patients with prior hospitalization for migraine or who had not responded to more preventive regimens had a smaller decrease in MDM. Reasons for stopping or switching a preventive varied between medications and were often related to cost and insurance coverage. At both follow‐ups, patient tolerance (1: 92.2% [262/284]; 2: 95.2% [141/145]) and continued use (1: 77.5% [224/289]; 2: 80.6% [116/145]) were high and similar across preventives. Response consistency (always non‐responders: 31.7% [46/145]; always responders: 56.5% [82/145], and one‐time only responders: 11.7% [17/145]) was also similar across preventives. Non‐responder status had nominally significant associations with rs12615320‐G in RAMP1 (odds ratio [95% confidence interval]: 4.7 [1.5, 14.7]), and rs4680‐A in COMT (0.6[0.4, 0.9]). Non‐responders had a lower mean genetic risk score than responders (1.0 vs. 1.1; t(df) = −1.75(174.84), p = 0.041), and the fraction of responders increased with genetic and polygenic risk score percentile. Conclusions: In this real‐world setting, anti‐CGRP preventives reduced MDM persistently and had similar and large effect sizes on MDM reduction; however, clinical and genetic factors influenced response. [ABSTRACT FROM AUTHOR]

Introduction: Sickle cell trait (SCT) is common in African descendants. Its association with several adverse pregnancy outcomes (APOs) has been reported but remains inconsistent. The objectives of this study are to test associations of SCT with APOs in non‐Hispanic Black women, including (1) validate the associations of SCT with previously reported APOs, (2) test novel associations of SCT with broad spectrum of APOs, and (3) estimate the attributable risk of SCT for implicated APOs. Material and methods: This is a retrospective analysis of a prospectively designed population‐based cohort. Women/participants were self‐reported non‐Hispanic Black women from the UK Biobank (UKB). SCT status was determined based on heterozygous Glu6Val in the HBB gene. Several APOs were studied, including four previously reported SCT‐associated APOs (preeclampsia, bacteriuria, pregnancy loss, and preterm delivery), and broad conditions related to pregnancy, childbirth, and the puerperium. APOs were curated by experts' peer review and consensus processes. Associations of SCT with APOs were tested by estimating its relative risk and 95% confidence interval (95% CI), adjusting for number of live births and age at first birth. Attributable risk proportion (ARP) and population attributable risk proportion (PARP) of SCT to APOs were estimated. Results: Among the 4057 self‐reported non‐Hispanic Black women with pregnancy records in the UKB, 581 (14.32%) were SCT carriers. For four previously reported SCT‐associated APOs, two were confirmed at a nominal P < 0.05; relative risk (RR) was 2.39 (95% CI 1.09–5.23) for preeclampsia, and 4.85 (95% CI 1.77–13.27) for bacteriuria. SCT contributed substantially to these two APOs among SCT carriers, with attributable risk proportion estimated at 61.00% and 68.96% for preeclampsia and bacteriuria, respectively. SCT also contributed substantially to these two APOs in the population (self‐reported Black UK women), with population attributable risk proportion estimated at 18.30% and 24.14% for preeclampsia and bacteriuria, respectively. In addition, novel associations were found for seven other APOs (nominal P < 0.05). Conclusions: SCT is significantly associated with APOs in this study and contributes substantially to APOs among self‐reported Black women in the UK. Confirmation of these findings in independent study populations is required. [ABSTRACT FROM AUTHOR]

A durable and environmentally‐friendly superhydrophobic coatings for liquid‐food residue reduction were prepared by using stearic acid (SA) modified organic montmorillonite (SA@OMMT) and poly(dimethylsiloxane) (PDMS). Due to the natural hydrophobicity of SAs, SA@OMMT provides low surface energy as well as roughness for the coating. PDMS not only provided low surface energy in the coating but also contributed to the bonding of SA@OMMT as a result of its high adhesive properties. In addition, PDMS has good physical properties after curing, which can effectively improve the physical properties and durability of a superhydrophobic coating by the self‐assembly method using a PDMS/n‐hexane solution. For 1 wt.% SA@OMMT and 5 wt.% PDMS, the resulting SA@OMMT/PDMS (SOP) coating showed the water contact angle (WCA) and water sliding angle (WSA) of 156.3°and 2°, respectively. The prepared coatings have good physical and chemical stability, and they still have superhydrophobicity after physical abrasion tests and exposure to the corrosion solutions. In the meanwhile, the prepared coating also has flexibility and superhydrophobicity after bending and folding. Finally, the coating surface shows highly effective antifouling ability to liquid and solid pollutants. The coating can be applied against different substrates and has potential application in the field of liquid‐food residue reduction. [ABSTRACT FROM AUTHOR]

Aims: Numerous genes have been proposed as causal for maturity‐onset diabetes of the young (MODY). Scoring systems to annotate mutation pathogenicity have been widely used; however, statistical evidence for being a highly penetrant MODY gene has not been well‐established. Methods: Participants were from the UK Biobank with whole‐exome sequencing data, including 14,622 with and 185,509 without diagnosis of diabetes. Pathogenic/likely pathogenic (P/LP) mutations in 14 reported and 3 possible MODY genes were annotated using American College of Medical Genetics criteria. Evidence for being a high‐penetrant MODY gene used two statistical criteria: frequency of aggregate P/LP mutations in each gene are (1) significantly more common in participants with a diagnosis of diabetes than without using the SKAT‐O (p <.05) and (2) lower than the maximum credible frequency in the general population. Results: Among the 17 genes, 6 (GCK, HNF1A, HNF4A, NEUROD1, KCNJ11 and HNF1B) met both criteria, 7 (ABCC8, KLF11, RFX6, PCBD1, WFS1, INS and PDX1) met only one criterion, and the remaining 4 (CEL, BLK, APPL1 and PAX4) failed both criteria, and were classified as 'consistent', 'inconclusive' and 'inconsistent' for being highly penetrant diabetes genes, respectively. Diabetes participants with mutations in the 'consistent' genes had clinical presentations that were most consistent with MODY. In contrast, the 'inconclusive' and 'inconsistent' genes did not differ clinically from non‐carriers in diabetes‐related characteristics. Conclusions: Data from a large population‐based study provided novel statistical evidence to identify 6 MODY genes as consistent with being highly penetrant. These results have potential implications for interpreting genetic testing results and clinical diagnosis of MODY. [ABSTRACT FROM AUTHOR]

Background: B7 homolog 3 (B7‐H3) is an immunomodulatory molecule that is highly expressed in prostate cancer (PCa) and belongs to the B7 superfamily, which includes PD‐L1. Immunotherapies (antibodies, antibody‐drug conjugates, and chimeric antigen receptor T cells) targeting B7‐H3 are currently in clinical trials; therefore, elucidating the molecular and immune microenvironment correlates of B7‐H3 expression may help to guide trial design and interpretation. The authors tested the interconnected hypotheses that B7‐H3 expression is associated with genetic racial ancestry, immune cell composition, and androgen receptor signaling in PCa. Methods: An automated, clinical‐grade immunohistochemistry assay was developed by to digitally quantify B7‐H3 protein expression across 2 racially diverse cohorts of primary PCa (1 with previously reported transcriptomic data) and pretreatment and posttreatment PCa tissues from a trial of intensive neoadjuvant hormonal therapy. Results: B7‐H3 protein expression was significantly lower in self‐identified Black patients and was inversely correlated with the percentage African ancestry. This association with race was independent of the significant association of B7‐H3 protein expression with ERG/ETS and PTEN status. B7‐H3 messenger RNA expression, but not B7‐H3 protein expression, was significantly correlated with regulatory (FOXP3‐positive) T‐cell density. Finally, androgen receptor activity scores were significantly correlated with B7‐H3 messenger RNA expression, and neoadjuvant intensive hormonal therapy was associated with a significant decrease in B7‐H3 protein expression. Conclusions: The current data underscore the importance of studying racially and molecularly diverse PCa cohorts in the immunotherapy era. This study is among the first to use genetic ancestry markers to add to the emerging evidence that PCa in men of African ancestry may have a distinct biology associated with B7‐H3 expression. Lay Summary: B7‐H3 is an immunomodulatory molecule that is highly expressed in prostate cancer and is under investigation in clinical trials.The authors determined that B7‐H3 protein expression is inversely correlated with an individual's proportion of African ancestry.The results demonstrate that B7‐H3 messenger RNA expression is correlated with the density of tumor T‐regulatory cells.Finally, in the first paired analysis of B7‐H3 protein expression before and after neoadjuvant intensive hormone therapy, the authors determined that hormone therapy is associated with a decrease in B7‐H3 protein levels, suggesting that androgen signaling may positively regulate B7‐H3 expression.These results may help to guide the design of future clinical trials and to develop biomarkers of response in such trials. B7‐H3 protein expression was significantly lower in self‐identified Black patients and was inversely correlated with the percentage African ancestry. Androgen receptor activity scores were significantly correlated with B7‐H3 messenger RNA expression, and neoadjuvant intensive hormonal therapy was associated with a significant decrease in B7‐H3 protein expression, consistent with a presumed androgen receptor binding site upstream of the B7‐H3 promoter. [ABSTRACT FROM AUTHOR]

Aims: GSK3640254 is a next‐generation maturation inhibitor likely to be coadministered with combined oral contraceptives in HIV‐positive women. Methods: This phase I, open‐label, 1‐way study assessed pharmacokinetic and pharmacodynamic interactions of GSK3640254 200 mg and ethinyl oestradiol 0.03 mg/levonorgestrel 0.15 mg once daily in healthy female participants who received ethinyl oestradiol/levonorgestrel for 10 days with a moderate‐fat meal after which GSK3640254 was added from Days 11 to 21. Primary endpoints were area under the plasma concentration–time curve to the end of the dosing interval (AUC0‐t), maximum observed concentration (Cmax) and plasma concentration at the end of the dosing interval (Cτ) for ethinyl oestradiol and levonorgestrel. Serum follicle‐stimulating hormone, luteinizing hormone and progesterone concentrations were determined. Adverse events were monitored. Results: Among 23 enrolled participants, 17 completed the study. Geometric least squares mean ratios (with vs. without GSK3640254) of AUC0‐t, Cmax and Cτ were 0.974, 0.970 and 1.050 for ethinyl oestradiol and 1.069, 1.032 and 1.083 for levonorgestrel, respectively. Three participants had elevated progesterone levels, which occurred before GSK3640254 administration in 2 participants. No participants had elevated follicle‐stimulating hormone or luteinizing hormone values. Fourteen participants (61%) reported adverse events. Four participants reported asymptomatic elevated transaminase levels meeting liver‐stopping criteria; of these, 3 events occurred before GSK3640254 administration and led to study withdrawal. Conclusion: Ethinyl oestradiol/levonorgestrel plus GSK3640254 coadministration did not affect steady‐state pharmacokinetics or pharmacodynamics of ethinyl oestradiol and levonorgestrel in healthy female participants. No major tolerability findings were reported. Elevated liver transaminase levels were probably due to ethinyl oestradiol/levonorgestrel. [ABSTRACT FROM AUTHOR]

Aims: GSK3640254, a novel, next‐generation maturation inhibitor effective against a range of HIV polymorphisms with no cross‐resistance to current antiretroviral therapy, could potentially be coadministered with dolutegravir as a 2‐drug regimen. In this phase I study, pharmacokinetics and tolerability of GSK3640254 plus dolutegravir were assessed. Methods: Healthy participants received dolutegravir 50 mg once daily (QD) on Days 1–5 in period 1, GSK3640254 200 mg QD on Days 1–7 in period 2, and dolutegravir 50 mg plus GSK3640254 200 mg QD on Days 1–7 in period 3. All treatments were administered with a moderate‐fat meal 30 minutes prior to dosing. Pharmacokinetics parameters were derived by noncompartmental methods, and geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were derived using linear mixed effects models. Adverse events, laboratory measurements, electrocardiography and vital signs were monitored. Results: Sixteen participants completed the study. GMRs (90% CIs) for dolutegravir area under the plasma concentration–time curve from time 0 to the end of the dosing interval at steady state, maximum observed concentration and plasma concentration at the end of the dosing interval were 1.17 (1.118–1.233), 1.09 (1.044–1.138) and 1.24 (1.160–1.315), respectively. The GMRs (90% CIs) for GSK3640254 were 1.04 (0.992–1.094), 0.99 (0.923–1.065) and 0.10 (0.939–1.056), respectively. Dolutegravir plus GSK3640254 coadministration did not meaningfully alter steady‐state exposure to dolutegravir or GSK3640254. No clinically significant trends in tolerability or safety were observed. Conclusion: Coadministration of GSK3640254 with dolutegravir did not result in clinically significant drug interaction and was well tolerated. [ABSTRACT FROM AUTHOR]

Malnutrition in patients with gastric cancer (GC) with normal body mass index (BMI) is often ignored. This study aimed to explore the role of sarcopenia in predicting postoperative complication and long‐term survival in patients with GC with normal BMI. We included patients with normal BMI (18.5 kg/m2 ≤ BMI < 23 kg/m2) who underwent radical gastrectomy between July 2014 and December 2016. Sarcopenia was assessed by muscle mass, handgrip strength, and gait speed. Kaplan–Meier survival analysis was used to analyze the association between sarcopenia and the prognosis of patients with GC. Univariate and multivariate analyses were used to identify risk factors contributing to postoperative complications and long‐term survival. Overall, 267 patients with GC with normal BMI were included in this study; of which 49 (18.35%) patients were diagnosed with sarcopenia. Patients with sarcopenia had higher incidence of a major postoperative complication, longer postoperative hospital stays, and greater hospital costs. The Kaplan–Meier survival analysis showed that patients with sarcopenia had poorer overall survival than non‐sarcopenia patients. Univariate and multivariate analyses showed that sarcopenia was an independent predictor for postoperative complication and long‐term survival in such patients. Sarcopenia is an independent predictor for postoperative complications and long‐term survival in patients with normal BMI after radical gastrectomy for GC. We recommend that patients with normal BMI should perform nutritional risk screening by sarcopenia. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) carriers carrying one defective copy of a CFTR germline mutation are common in the general population. A recent study reported associations of CF carriers with risk for cancers of digestive organs and pancreatic cancer. In the current study, we assessed associations of CFTR F508del carriers with the risk for 54 types of cancers in the UK Biobank, a large population‐based study. In Caucasians, compared to the carrier rate of 3.15% (12 357/392274) in noncancer subjects, the rate was significantly higher in cancer patients overall (2621/79619 = 3.29%), especially in patients with colorectal cancer (247/6667 = 3.70%), cancers of gallbladder and biliary tract (21/351 = 5.98%), thyroid cancer (30/665 = 4.51%) and unspecified non‐Hodgkin's lymphoma (74/1805 = 4.10%), all P ≤.05. In contrast, the carrier rate in patients with cancers of lung and bronchus was significantly lower (89/3463 = 2.57%), P =.05. The association of CFTR F508del carriers with these types of cancer remained significant after adjusting for respective cancer‐specific risk factors. For pancreatic cancer, although a higher carrier rate (38/1004 = 3.78%) was found in patients with this cancer, the difference was not statistically significant (P =.26). This null association was unlikely due to lack of statistical power; the large sample size of our study had >80% power, at a significance level of.05, to detect an association of >1.5‐fold increased risk. In conclusion, the identified associations of CFTR F508del carriers with multiple types of cancer may have potential biological and clinical implications if confirmed in independent study populations. What's new? Cystic fibrosis (CF) carriers have only one defective copy of the CFTR gene. While this means that carriers do not develop CF, they may be at increased risk of CF‐related conditions, including cancer. Here, using data from the population‐based UK Biobank study, the authors investigated potential associations between CFTR F508del, the most common CFTR mutation, and risk of 54 cancer types. The CFTR F508del carrier rate was found to be significantly elevated in several types of cancer, including colorectal and gallbladder/biliary tract cancers, thyroid cancer, and unspecified non‐Hodgkin's lymphoma. The findings may be relevant for risk stratification among CF carriers. [ABSTRACT FROM AUTHOR]

Background: The causal relationship between adiponectin (ADPN) and estimated glomerular filtration rate (eGFR) is unclear. This study adopts a two‐sample bidirectional Mendelian randomization (MR) study to explore the causal relationship between ADPN and eGFR. Methods: Using eight single nucleotide polymorphisms (SNP) of ADPN and 26 SNP of eGFR as instrumental variables, the study performs a two‐sample bidirectional MR study using MR inverse‐variance weighted (IVW), MR‐Egger and weighted median approach to evaluate the causal relationship between ADPN and eGFR. Using the genetic risk score (GRS) of ADPN and eGFR as instrumental variables, the study performs a second MR analysis to assess the association between ADPN and eGFR. Results: In ADPN to eGFR MR analysis, the IVW, weighted median and GRS analysis all showed that ADPN had a causal effect on eGFR after removing potential confounders of the ADPN‐eGFR relation (IVW: β =.016, P =.002; weighted median: β =.012, P =.022; GRS: β =.016, P = 1.48E‐05). As both ADPN and eGFR were natural log‐transformed in the corresponding GWAS, eGFR increased by 0.15% for any 10% increase in ADPN. In eGFR to ADPN MR analysis, eGFR had no causal effect on ADPN after removing potential confounders of the eGFR‐ADPN relation (All P values > 0.05). The heterogeneity test and sensitivity analysis indicated some heterogeneity, but no directional pleiotropy. Conclusion: Adiponectin has a causal effect on eGFR, while eGFR has no causal effect on ADPN. ADPN may be a clinical target for improving eGFR and treating chronic kidney disease caused by decreased eGFR. SUMMARY AT A GLANCE: This Mendelian randomization study analysed interaction between single nucleotide polymorphisms separately associated with adiponectin levels and estimated glomerular filtration rate (eGFR). Adiponectin level exhibited a causal effect on eGFR, but the reverse was not true. This is important in future discovery and therapeutic approaches to chronic kidney disease. [ABSTRACT FROM AUTHOR]

A novel waterborne hyperbranched polyacrylate (HBPA) dispersed organo‐montmorillonite (OMMT) emulsion was synthesized in laboratory. The sapwood of Cathay poplar (Populus cathayana Rehd.) was modified with the emulsion via vacuum treatment for polymer impregnated wood composite with cross section sealing off. Some surface characterization was carried out to analyze the impregnation depth. The results showed that OMMT and HBPA successfully penetrated into the wood cell wall with completely exfoliated OMMT and formed a hydrophobic film covering on the inner surface of cell wall lumen, which improved the surface hydrophobicity and mechanical properties of wood cell wall. With increasing impregnation depth, the improvements decreased, which was associated with the limited impregnation ability of the modifiers only with the pathway of radial and tangential sections. Thus, for better modification, the cross section of the wood must be unobstructed. [ABSTRACT FROM AUTHOR]

Reconstructing the chemical and structural characteristics of the plant cell wall represents a promising solution to overcoming lignocellulosic biomass recalcitrance to biochemical deconstruction. This study aims to leverage hydroxyproline (Hyp)‐O‐glycosylation, a process unique to plant cell wall glycoproteins, as an innovative technology for de novo design and engineering in planta of Hyp‐O‐glycosylated biopolymers (HypGP) that facilitate plant cell wall reconstruction. HypGP consisting of 18 tandem repeats of "Ser–Hyp–Hyp–Hyp–Hyp" motif or (SP4)18 was designed and engineered into tobacco plants as a fusion peptide with either a reporter protein enhanced green fluorescence protein or the catalytic domain of a thermophilic E1 endoglucanase (E1cd) from Acidothermus cellulolyticus. The engineered (SP4)18 module was extensively Hyp‐O‐glycosylated with arabino‐oligosaccharides, which facilitated the deposition of the fused protein/enzyme in the cell wall matrix and improved the accumulation of the protein/enzyme in planta by 1.5–11‐fold. The enzyme activity of the recombinant E1cd was not affected by the fused (SP4)18 module, showing an optimal temperature of 80°C and optimal pH between 5 and 8. The plant biomass engineered with the (SP4)18‐tagged protein/enzyme increased the biomass saccharification efficiency by up to 3.5‐fold without having adverse impact on the plant growth. [ABSTRACT FROM AUTHOR]

Summary: Background: To date, 14 single‐nucleotide polymorphisms (SNPs) have been identified as susceptibility loci for chronic hepatitis B (CHB). Aim: To investigate if these SNPs are associated with treatment response of hepatitis B e antigen (HBeAg)‐positive CHB patients. Methods: We performed a retrospective analysis of 1623 Han Chinese HBeAg‐positive CHB patients (782 patients treated with pegylated interferon alpha [PegIFNα] for 48 weeks plus 24 weeks follow‐up, and 841 patients treated with nucleos(t)ide analogues [NUCs] for 104 weeks) included in four phase‐IV multicentre randomised controlled trials. All 14 SNPs were genotyped for each CHB patient. A polygenic score (PGS) was used to evaluate the cumulative effect of multiple SNPs. The associations of SNPs or PGS with combined response (CR) and hepatitis B s antigen (HBsAg) loss were assessed. Results: We found that rs12614, a missense variant of complement factor B (CFB), was significantly associated with CR in PegIFNα‐treated patients, and the CR rate in patients with the rs12614 TT/CT genotype was less than one‐third of that in patients with the CC genotype (7.4% vs 22.6%, P = 0.009). Moreover, a PGS integrating CFB rs12614 and STAT4 rs7574865 (previously reported to be associated with response to PegIFNα) was significantly associated with both CR (P‐trend = 4.000 × 10−4) and HBsAg loss (P‐trend = 0.010) in PegIFNα‐treated patients. However, none of the SNPs were associated with treatment response in NUCs‐treated patients. Conclusions: CFB rs12614 is an independent predictor of response to PegIFNα therapy in Chinese HBeAg‐positive CHB patients. A PGS integrating CFB rs12614 with STAT4 rs7574865 can effectively discriminate responders to PegIFNα from nonresponders. [ABSTRACT FROM AUTHOR]

Cell‐free metabolic engineering is an emerging and promising alternative platform for the production of fuels and chemicals. In recent years, macromolecular crowding effect, which is an important function in living cells but ignored in cell‐free systems, has been transferred to cell‐free protein synthesis (CFPS). However, inhibitory effects of crowding agents on CFPS were frequently observed, and the mechanism is unclear. In this study, free Mg2+ was found to be a key factor that can regulate the macromolecular crowding effect on in vitro transcription, in vitro translation, and coupled transcript/translation. Addition of crowding agents (20% of Ficoll‐70 or Ficoll‐400) enhanced in vitro transcription at an index of free Mg2+ concentration (IFMC) below 2 mM but inhibited the transcription when the IFMC was higher than 2 mM. Similarly, Ficoll‐400 enhanced in vitro translation and coupled transcription/translation at a lower IFMC (0.1–2 mM) and inhibited the reactions at higher IFMC (>2 mM). Based on the results, CFPS systems could be further optimized by adjusting the content of crowding agents and the IFMC. Besides, the results also indicate that macromolecular crowding effect is important for maintaining the efficiency of in vivo transcription and translation which occur at a low intracellular IFMC (<1 mM). [ABSTRACT FROM AUTHOR]

Nano‐ZnO was applied to modify the yellow polyurethane‐acrylic UV ink by physically blending and then the modified ink composites were used for wood printing. The color and gloss of the printed samples before and after aging were tested at periods. The aging mechanism of the ink composites was investigated was analyzed by XPS and FTIR analyses, and the morphologies were observed by AFM analysis. The results showed that the UV ink composite underwent oxidation during aging. Cromatism and gloss changed, and bulges existed on the surface in both untreated and nano‐ZnO modified samples. However, the situation of the nano‐ZnO modified UV ink composite printed samples after aging test was not as server as that printed with the unmodified one. During light aging, the primary amine, CO2, and carboxylic acid were yielded, and NH radicals were generated, which promoted the formation of conjugated structure and the chromogenic enamine. As expected, these reactions were inhibited by adding of nano‐ZnO. Consequently, the light‐resistant of the UV ink composite was improved. 1.0% nano‐ZnO offered the lowest chromatism and the gloss changes among all, showing the best light‐resistant performance. POLYM. COMPOS., 40:3533–3540, 2019. © 2019 Society of Plastics Engineers [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the pharmacokinetics of baicalin after intravenous and intramuscular administration of sodium baicalin at 50 mg/kg to piglets. Plasma baicalin levels were determined by high‐performance liquid chromatography. The plasma concentration–time data of baicalin for both administration routes were best described by two‐compartmental open model. The area under the plasma concentration–time curve and the elimination half‐lives were 77.47 ± 6.14 µg/ml × h and 1.73 ± 0.16 hr for intravenous and 64.85 ± 5.67 µg/ml × h and 2.42 ± 0.15 hr for intramuscular administration, respectively. The apparent volume of distribution and body clearance were 1.63 ± 0.23 L/kg and 2.74 ± 0.30 L h−1 kg−1 for intravenous and 0.51 ± 0.10 L/kg and 0.78 ± 0.08 L h−1 kg−1 for intramuscular routes, respectively. An intramuscular injection of sodium baicalin in piglets resulted in rapid and complete absorption, with a mean maximal plasma concentration of 77.28 ± 7.40 µg/ml at 0.17 hr and a high absolute bioavailability of 83.73 ± 5.53%. [ABSTRACT FROM AUTHOR]

Purpose: Depth of interaction (DOI) decoding capability is of great importance for positron emission tomography (PET) requiring high resolution. In this study, we presented a novel low‐cost DOI detector design with four crystals coupling to one SiPM, based on the method of rectangular light‐sharing window (RLSW). A prototype detector was constructed, calibrated, and assessed using the methods of homogeneous radiation and flood map analysis. Methods: The DOI detector was constructed with a 4 × 4 array of lutetium‐yttrium oxyorthosilicate (LYSO) crystals (2.95 mm × 2.95 mm × 20 mm3), barium sulfate (BaSO4) reflectors, and optical glues. A RLSW 7 mm in height was deployed in the BaSO4 reflectors. A non‐DOI detector with identical dimensions and without RLSW was also constructed for comparison. The light‐output surface of the detector was air‐coupled with a 4 × 4 array of SiPMs (3 mm × 3 mm2). The signals generated from the 16 SiPMs were read out by a custom‐designed electronic system, and the signals from four adjacent 3 mm SiPMs were summed into one signal to emulate a 2 × 2 array of 6 mm SiPMs. The RLSW caused the DOI‐related position shifts of the crystal spots in the flood map. A homogeneous radiation method was used to establish the transfer functions to convert the spot shifts measured from the flood map into DOI measurements. The accuracy of the DOI measurements was assessed with data acquired using the conventional collimated radiation method. Results: All 16 crystals are distinctly separated from each other in the flood map. Twelve crystals, including four central crystals and eight edge crystals, have the DOI capability. The full width half maximum (FWHM) of the DOI measurements of the central crystals and the edge crystals are 3.06 ± 0.08 and 3.79 ± 0.15 mm, respectively, for the configuration with four crystals coupling to one SiPM. By contrast, the FWHMs (3.98 ± 0.16 and 5.12 ± 0.38 mm, respectively) are slightly worse for the configuration with one crystal coupling to one SiPM. The average and standard deviation (STD) of the FWHM energy resolutions of the DOI detector and non‐DOI detector were 10.2% ± 0.7% and 10.7% ± 1.7%, respectively. Their FWHM coincidence timing resolutions were 197.0 ± 9.6 and 206.4 ± 13.3 ps, respectively. The RLSW had no significant impact on the energy resolutions and timing resolutions of the DOI detector. Conclusions: The novel four‐crystals‐to‐one‐SiPM coupling technology is a cost‐efficient approach to construct high‐performance detector modules with DOI capability. The methods of homogeneous radiation and flood map analysis are easy to perform and of good performance. Those methods can be adapted in the clinic PET scanners to enable the capability of DOI measurements. [ABSTRACT FROM AUTHOR]

Background: Genetic risk score (GRS) is an odds ratio (OR)‐weighted and population‐standardized method for measuring cumulative effect of multiple risk‐associated single nucleotide polymorphisms (SNPs). We hypothesize that GRS is a valid tool for risk assessment of most common cancers. Methods: Utilizing genotype and phenotype data from The Cancer Genome Atlas (TCGA) and Electronic Medical Records and Genomics (eMERGE), we tested 11 cancer‐specific GRSs (bladder, breast, colorectal, glioma, lung, melanoma, ovarian, pancreatic, prostate, renal, and thyroid cancer) for association with the respective cancer type. Cancer‐specific GRSs were calculated, for the first time in these cohorts, based on previously published risk‐associated SNPs using the Caucasian subjects in these two cohorts. Results: Mean cancer‐specific GRS in the population controls of eMERGE approximated the expected value of 1.00 (between 0.98 and 1.02) for all 11 types of cancer. Mean cancer‐specific GRS was consistently higher in respective cancer patients than controls for all 11 types of cancer (P < 0.05). When subjects were categorized into low‐, average‐, and high‐risk groups based on cancer‐specific GRS (<0.5, 0.5‐1.5, and >1.5, respectively), significant dose‐response associations of higher cancer‐specific GRS with higher OR of respective type of cancer were found for nine types of cancer (P‐trend < 0.05). More than 64% subjects in the population controls of eMERGE can be classified as high risk for at least one type of these cancers. Conclusion: Validity of GRS for predicting cancer risk is demonstrated for most types of cancer. If confirmed in larger studies, cancer‐specific GRS may have the potential for developing personalized cancer screening strategy. [ABSTRACT FROM AUTHOR]

Summary: The key technical bottleneck for exploiting plant hairy root cultures as a robust bioproduction platform for therapeutic proteins has been low protein productivity, particularly low secreted protein yields. To address this, we engineered novel hydroxyproline (Hyp)‐O‐glycosylated peptides (HypGPs) into tobacco hairy roots to boost the extracellular secretion of fused proteins and to elucidate Hyp‐O‐glycosylation process of plant cell wall Hyp‐rich glycoproteins. HypGPs representing two major types of cell wall glycoproteins were examined: an extensin module consisting of 18 tandem repeats of 'Ser‐Hyp‐Hyp‐Hyp‐Hyp' motif or (SP4)18 and an arabinogalactan protein module consisting of 32 tandem repeats of 'Ser‐Hyp' motif or (SP)32. Each module was expressed in tobacco hairy roots as a fusion to the enhanced green fluorescence protein (EGFP). Hairy root cultures engineered with a HypGP module secreted up to 56‐fold greater levels of EGFP, compared with an EGFP control lacking any HypGP module, supporting the function of HypGP modules as a molecular carrier in promoting efficient transport of fused proteins into the culture media. The engineered (SP4)18 and (SP)32 modules underwent Hyp‐O‐glycosylation with arabino‐oligosaccharides and arabinogalactan polysaccharides, respectively, which were essential in facilitating secretion of the fused EGFP protein. Distinct non‐Hyp‐O‐glycosylated (SP4)18‐EGFP and (SP)32‐EGFP intermediates were consistently accumulated within the root tissues, indicating a rate‐limiting trafficking and/or glycosylation of the engineered HypGP modules. An updated model depicting the intracellular trafficking, Hyp‐O‐glycosylation and extracellular secretion of extensin‐styled (SP4)18 module and AGP‐styled (SP)32 module is proposed. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphism (SNP)‐based genetic risk score (GRS) and APOE genotype are both important in risk prediction of Alzheimer's disease (AD); however, the interaction between GRS and APOE has not been extensively investigated. Our objective was to determine whether GRS modifies the APOE effect on AD risk and age at onset (AAO). The study included 774 AD cases and 767 controls of European descent. Population standardized GRS was calculated based on 17 previously implicated AD risk‐associated SNPs. Association was analyzed using logistic regression, Cox proportional hazards model and Kaplan‐Meier curve. We found that GRS was significantly associated with AD risk and the association was stronger among APOE ε4 carriers. Compared to ε4 non‐carriers, the Odds Ratio (OR) for AD was 8.09 (95% Confidence Interval [CI]: 4.98‐13.63) for ε4 carriers with high‐GRS (≥1.5). In contrast, the OR was 2.55 (95% CI: 1.46‐4.49) for ε4 carriers with low‐GRS (<0.6). In conclusion, these results suggest SNP‐based GRS may supplement APOE for better assessment of inherited risk and age of onset of AD. Individuals with APOE ε4 allele and high GRS (>1.5) carry the greatest risk (OR=8.09) of Alzheimer's disease and have the earliest onset age (median disease‐free survival age=73). [ABSTRACT FROM AUTHOR]

Objectives: To perform a systematic evaluation of whether germline DNA repair gene mutations in bladder cancer (BCa) are associated with increased risk of BCa and aggressive disease. Materials and Methods: Germline DNA from 98 patients with BCa was analysed for 54 DNA repair genes using a customized targeted sequencing panel. Population control data were obtained from the public databases the Exome Aggregation Consortium database and the Genome Aggregation Database. Mutation pathogenicity was annotated based on American College of Medical Genetics criteria, mutation frequencies in the general population and the ClinVar database. Mutation frequencies were compared based on case–control and case–case designs for disease risks, disease aggressiveness and outcomes. Results: The frequency of pathogenic/likely pathogenic germline DNA repair gene mutations was 10.2% among patients with BCa. Within the subset of patients with carcinoma invading the bladder muscle, the frequency was 15.8%, ~2.4‐fold higher than in patients with non‐muscle invasive BCa (6.67%). The mutation frequency among patients with early‐onset disease (at age <45 years) was ~3‐fold higher than among those diagnosed after age 45 years (28.57% vs 8.79%). Mutation carriers had a significantly higher frequency of unfavourable clinical outcomes (disease recurrence or progression to metastatic BCa) than non‐carriers (50.0% vs 13.64%; P = 0.013). Conclusion: Pathogenic and likely pathogenic mutations in DNA repair genes were associated with unfavourable prognosis of BCa. [ABSTRACT FROM AUTHOR]

Purpose: In brain imaging, the spherical PET system achieves the highest sensitivity when the solid angle is concerned. However, it is not practical. In this work, we designed an alternative sphere‐like scanner, the dodecahedral scanner, which has a high sensitivity in imaging and a high feasibility to manufacture. We simulated this system and compared the performance with a few other dedicated brain PET systems. Methods: Monte Carlo simulations were conducted to generate data of the dedicated brain PET system with the dodecahedral geometry (11 regular pentagon detectors). The data were then reconstructed using the in‐house developed software with the fully three‐dimensional maximum‐likelihood expectation maximization (3D‐MLEM) algorithm. Results: Results show that the proposed system has a high‐sensitivity distribution for the whole field of view (FOV). With a depth‐of‐interaction (DOI) resolution around 6.67 mm, the proposed system achieves the spatial resolution of 1.98 mm. Our simulation study also shows that the proposed system improves the image contrast and reduces noise compared with a few other dedicated brain PET systems. Finally, simulations with the Hoffman phantom show the potential application of the proposed system in clinical applications. Conclusions: In conclusion, the proposed dodecahedral PET system is potential for widespread applications in high‐sensitivity, high‐resolution PET imaging, to lower the injected dose. [ABSTRACT FROM AUTHOR]

Abstract: An expeditious and straightforward approach for the synthesis of 4H‐pyrido[1,2‐a][1,3,5]triazin‐4‐ones starting from readily available imidazo[1,2‐a]pyridines and sodium azide has been presented under aerobic oxidative conditions. The reaction proceeded well with the promotion of potassium persulfate/potassium permanganate with good functional group tolerance. A wide range of biologically valuable 4H‐pyrido[1,2‐a][1,3,5]triazin‐4‐one scaffolds were assembled by this methodology. The gram‐scale reaction was also achieved. A cascade nitrogenation and oxidative recyclization sequence could be involved in the reaction. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to demonstrate the accuracy and feasibility of using single nucleotide polymorphism (SNP) array-based preimplantation genetic haplotyping (PGH) in Chinese population, as the currently short tandem repeat method is labor-intensive and time-consuming.Method: Six pedigrees with thalassemia who underwent preimplantation genetic diagnosis in the First Affiliated Hospital of Sun Yat-sen University in China were included in this study. In vitro fertilization (IVF) cycles and embryo biopsies were performed in clinics. All embryos were diagnosed using both a polymerase chain reaction-based method with short tandem repeat and an SNP-based PGH (SNP microarray) method blindly.Results: SNP-based PGH was successfully conducted for six pedigrees. Our result was concordant with the initial diagnosis based on the mutation detection (96.4%) and human leukocyte antigen matching (100%). All of the embryos detected to be suitable for IVF with PGH were also diagnosed as suitable using initial methods.Conclusion: This simple SNP-based PGH method offers simultaneous haplotyping and human leukocyte antigen matching, which facilitates the determination of optimal embryos for IVF with high accuracy. Further studies are needed to help improve this method into clinic utility. © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lnc RNAs), a novel class of transcripts that have critical roles in carcinogenesis and progression, have emerged as important gene expression modulators. Recent evidence indicates that lnc RNA taurine-upregulated gene 1 ( TUG1) functions as an oncogene in numerous types of human cancers. However, its function in the development of cervical cancer remains unknown. The aim of this research was to investigate the clinical significance and biological functions of TUG1 in cervical cancer. TUG1 was found to be significantly upregulated in cervical cancer tissues and four cervical cancer cell lines by quantitative real-time polymerase chain reaction ( qRT- PCR). Elevated TUG1 expression was correlated with larger tumor size, advanced international federation of gynecology and obstetrics ( FIGO) stage, poor differentiation, and lymph node metastasis. Furthermore, knockdown of TUG1 suppressed cell proliferation with activation of apoptosis, in part by regulating the expression of Bcl-2 and caspase-3. Silencing of TUG1 inhibited cell migration and invasion via the progression of epithelial-mesenchymal transition ( EMT). Taken together, our findings indicate that TUG1 acts as an oncogene in cervical cancer and may represent a novel therapeutic target. [ABSTRACT FROM AUTHOR]

The first genome-wide association study (GWAS) for bladder cancer has identified a susceptibility locus at 3q28 in the European ancestry. However, the causal variant at 3q28 remains unknown. We conducted a three-stage fine mapping study to identify potential causal variants in the region. A total of 41 single nucleotide polymorphisms (SNPs) across 120 kb at 3q28 were tested for association with bladder cancer risk among 3,094 bladder cancer cases and 3,738 controls. Resequencing and functional assays were further evaluated. The SNP rs35592567 in the 3′-UTR of TP63 was consistently associated with bladder cancer risk in all three stages. In the combined analysis, the T allele of rs35592567 was significantly associated with a decreased risk for bladder cancer (OR = 0.82, 95% CI = 0.75-0.90, P = 9.797 × 10−6 in the additive model). Biochemical assays revealed that the T allele reduced the post-transcriptional levels of TP63 mediated by interfering binding efficiency of miR-140-5p. In addition, overexpression of miR-140-5p inhibited bladder cancer cell proliferation and attenuated cell migration, invasion and G1 cell-cycle arrest. Together, these results suggest that rs35592567 in TP63 may be a novel causal variant contributing to the susceptibility to bladder cancer, which provides additional insight into the pathogenesis of bladder carcinogenesis. [ABSTRACT FROM AUTHOR]