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Catalytic kinetic resolution (KR) and dynamic kinetic asymmetric transformation (DyKAT) are alternative and complementary avenues to access chiral stereoisomers of both starting materials and reaction products. The development of highly efficient chiral catalytic systems for kinetically controlled processes has therefore been one of the linchpins in asymmetric synthesis. N‐heterocyclic carbene (NHC)/copper cooperative catalysis has enabled highly efficient KR and DyKAT of racemic N‐tosylaziridines by [3+3] annulation with isatin‐derived enals, leading to highly enantioenriched N‐tosylaziridine derivatives (up to >99 % ee) and a large library of spirooxindole derivatives with high structural diversity and stereoselectivity (up to >95:5 d.r. >99 % ee). Mechanistic studies suggest that the NHC can bind reversibly to the copper catalyst without compromising its catalytic activity and regulate the catalytic activity of the copper complex to switch the chemoselection between KR and DyKAT. [ABSTRACT FROM AUTHOR]

Although ionic conductors have been thoroughly investigated, topological features of these materials' nanotextures have been surprisingly overlooked. Here, we report fabrication of a metal-oxide nanocomposite consisting of intertwined phases of platinum (Pt) metal and oxygen-ion conductive cerium oxide (CeO2), i.e., Pt#CeO2. Sectional TEM observations coupled with topological analysis demonstrated that Pt#CeO2 composites having different nanostructures can be classified with a topological measure that corresponds to the phase connectivity of CeO2, namely, the Betti number β 0 , and another that corresponds to holes of the Pt phase, namely, the Betti number β 1 . The samples' oxygen ionic conductivity Pt#CeO2 was measured at elevated temperatures in air by alternating current impedance spectroscopy. It was found that the nanostructure changed from a striped appearance to a maze-like appearance as the value of β 1 / β 0 decreased. Both the activation energy E and the pre-exponential factor σ 0 for the oxygen ionic conductivity were found to be independent of β 1 and exhibited linear, negative correlations with β 0 . The topological connectivity of the ion-conductive CeO2 phase, which was quantified with the Betti number β 0 , was suitable as a descriptor to correlate the image data of nanostructures with their ionic transport properties. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES Advanced-stage (Child-Pugh classes B and C) liver cirrhosis (LC) is a contraindication for oesophagectomy. However, the question as to whether Child-Pugh class A LC may have an impact on perioperative outcomes remains unanswered. This retrospective single-centre study was designed to address this issue. METHODS This was a single-centre, retrospective, propensity-matched study. The perioperative outcomes of patients with Child-Pugh class A LC were compared with those of patients without LC after propensity score matching. RESULTS Out of a cohort consisting of 811 patients, we identified 51 cases with Child-Pugh class A LC. After the application of propensity score matching, the LC and no-LC groups consisted of 50 and 100 patients, respectively. The presence of LC did not compromise the quality of surgical resection as attested to by similar lymph node yields and R0 rates. However, patients with LC patients were more prone to developing postoperative pneumonia (22% vs 9%, P  = 0.027), pleural effusion (38% vs 20%, P  = 0.018) and chylothorax (10% vs 1%, P  = 0.016) and had longer intensive care unit stay (mean: 6.10 vs 2.58 days, P  = 0.002) compared with the no-LC group. Multivariable analysis identified thoracic duct ligation [odds ratio (OR) 12.292, P  = 0.042] and a higher number of dissected nodes (OR 4.375, P  = 0.037) as independent risk factors for chylothorax and pleural effusion, respectively. The detrimental effect of these variables was limited to the LC group. CONCLUSIONS Oesophagectomy portends a higher morbidity in patients with Child-Pugh class A LC. A meticulous management of lymphatic ducts during mediastinal dissection may improve surgical outcomes in this high-risk group. [ABSTRACT FROM AUTHOR]

Photovoltaic device construct with a 2D nanomaterial atop a 3D wide bandgap semiconductor enables van Hove singularity induced enhanced light absorption on the front surface in close proximity (few atoms above) to the depletion region. Here, thin layers of tungsten disulfide (WS2) varying from mono to few layers were grown directly on both n-gallium nitride (GaN) and p-GaN via low pressure chemical vapor deposition. The conditions for WS2 growth were optimized for a larger coverage of the GaN substrate. The WS2 film was characterized using confocal Raman spectroscopy and x-ray photoelectron spectroscopy. Ultraviolet photoelectron spectroscopy measurement was conducted to elucidate the electronic band structures of WS2 on top of GaN. Afterwards, WS2/GaN heterojunction photovoltaic devices were fabricated. The current density–voltage (J–V) tests were conducted to illustrate the electrical performance. The device showed an open circuit voltage of 0.53 mV and a short circuit current density of 60 µA cm−2, 85% higher than that of a WS2/Si solar cell. An external quantum efficiency was measured to be near 60% for red and infrared, and above 50% in the violet region. [ABSTRACT FROM AUTHOR]

This study aims to investigate the postoperative cognitive function changes of infants who underwent endoscopic third ventriculostomy (ETV) or ventriculoperitoneal shunt (VPS) for the treatment of congenital hydrocephalus. Data of 70 hydrocephalus infants and children were retrospectively analyzed. Among these patients, 20 patients underwent ETV, 27 patients underwent VPS, and 23 patients did not undergo any operation (controls). All patients were routinely cared after discharge. The Gecell Developmental Diagnostic Scale was filled for all patients at 2 weeks, 2 months, and 6 months after diagnosis. A total of 20 patients in the ETV group were followed up for 6 months. Among these patients, the clinical symptoms of 18 patients significantly improved. Results determined at 6 months after surgery in the ETV group was statistically significant, compared with the control group (P < 0.05). Results determined at 2 and 6 months after surgery in the VPS group were statistically significant, compared with the control group (P < 0.05). Developmental quotient (DQ) values in these two operation groups increased after the operation (P < 0.01), and the differences were statistically significant. ETV and VPS can improve the cognitive function of infants with hydrocephalus. Improvement of cognitive function by VPS is more significant for infants. [ABSTRACT FROM AUTHOR]

Red blood cells (RBCs) stressed by high temperature are similar to senescent or damaged RBCs in pathological conditions. RBCs can be efficiently labelled with 18F-fluorodeoxyglucose (FDG). The aim of this study was to assess stressed RBCs erythrophagocytosis and organ distribution in vivo with the application of 18F-FDG PET/CT. RBCs were induced under high temperature (48 °C) to prepare stressed RBCs. Fluorescence-activated cell sorting (FACS) was used to analyse reactive oxygen species (ROS) generation, intracellular Ca2+ concentration and membrane phosphatidylserine (PS) externalization of RBCs. 18F-FDG was used to label RBCs and assess the erythrophagocytosis. Finally, 18F-FDG PET/CT was applied to reveal and measure the organ distribution of stressed RBCs in mice. Compared with untreated RBCs, stressed RBCs decreased in cell volume and increased in ROS level, intracellular Ca2+ concentration, and PS exposure. RBCs could be labelled by 18F-FDG. Stressed RBCs tended to be phagocytosed by macrophages via assessment of FACS and radioactivity. 18F-FDG PET/CT imaging showed that stressed RBCs were mainly trapped in spleen, while untreated RBCs remained in circulation system. Thus, stressed RBCs can be effectively labelled by 18F-FDG and tend to be trapped in spleen of mice as assessed by PET/CT. [ABSTRACT FROM AUTHOR]

Background: DNA methylation of Cadherin 13 (CDH13), a tumor suppressor gene is associated with gene repression and carcinogenesis. We determined the relation of dietary fat and sex with CDH13 cg02263260 methylation in Taiwanese adults. Methods: Data of 870 eligible participants (430 men and 440 women) between 30 and 70 years were obtained from the Taiwan Biobank (TWB) database. The association of dietary fat and sex with CDH13 cg02263260 methylation was determined using multiple linear regression. Results: The association between sex and cg02263260 methylation was significant: beta-coefficient (β) = 0.00532; 95% confidence interval (CI) = 0.00195–0.00868. Moreover, the interaction between sex and dietary fat on cg02263260 methylation was significant (P-value = 0.0145). After stratification by sex, the association of dietary fat with cg02263260 methylation was significant only in women. Specifically, high dietary fat was positively associated with cg02263260 methylation in women (β = 0.00597; 95% CI = 0.00061–0.01133) and the test for trend was significant (P-value = 0.0283). Conclusion: High fat intake was significantly associated with higher cg02263260 methylation in women and the test for trend was significant. These findings suggest that the association of fat intake and CDH13 cg02263260 might vary by sex and CDH13 cg02263260 methylation levels in women might increase as fat intake increases. [ABSTRACT FROM AUTHOR]

Nerve growth factor (NGF) contributes to the progression of malignancy. However, the functional role and regulatory mechanisms of NGF in the development of neuroendocrine prostate cancer (NEPC) are unclear. Here, we show that an androgen-deprivation therapy (ADT)-stimulated transcription factor, ZBTB46, upregulated NGF via ZBTB46 mediated-transcriptional activation of NGF. NGF regulates NEPC differentiation by physically interacting with a G-protein-coupled receptor, cholinergic receptor muscarinic 4 (CHRM4), after ADT. Pharmacologic NGF blockade and NGF knockdown markedly inhibited CHRM4-mediated NEPC differentiation and AKT-MYCN signaling activation. CHRM4 stimulation was associated with ADT resistance and was significantly correlated with increased NGF in high-grade and small-cell neuroendocrine prostate cancer (SCNC) patient samples. Our results reveal a role of the NGF in the development of NEPC that is linked to ZBTB46 upregulation and CHRM4 accumulation. Our study provides evidence that the NGF-CHRM4 axis has potential to be considered as a therapeutic target to impair NEPC progression. Here, the authors discover that NGF, upregulated by transcription factor ZBTB46 in prostate cancer exposed to androgen therapy, promotes neuroendocrine differentiation. They show that NGF interacts with the GPCR CHRM4, that both NGF and CHRM4 are upregulated in highly metastatic prostate cancer and that targeting NGF reduces therapy resistance in a mouse xenograft model. [ABSTRACT FROM AUTHOR]

Previous studies have shown that BMPR1B promotes follicular development and ovarian granulosa cell proliferation, thereby affecting ovulation in mammals. In this study, the expression and polymorphism of the BMPR1B gene associated with litter size in small-tail Han (STH) sheep were determined. The expression of BMPR1B was detected in 14 tissues of STH sheep during the follicular phase as well as in the hypothalamic–pituitary–gonadal (HPG) axis of monotocous and polytocous STH sheep during the follicular and luteal phases using quantitative polymerase chain reaction (qPCR). Sequenom MassARRAY® single nucleotide polymorphism (SNP) technology was also used to detect the polymorphism of SNPs in seven sheep breeds. Here, BMPR1B was highly expressed in hypothalamus, ovary, uterus, and oviduct tissue during the follicular phase, and BMPR1B was expressed significantly more in the hypothalamus of polytocous ewes than in monotocous ewes during both the follicular and luteal phases (P<0.05). For genotyping, we found that genotype and allele frequencies of three loci of the BMPR1B gene were extremely significantly different (P<0.01) between the monotocous and polytocous groups. Association analysis results showed that the g.29380965A > G locus had significant negative effects on the litter size of STH sheep, and the combination of g.29380965A > G and FecB (Fec – fecundity and B – Booroola; A746G) at the BMPR1B gene showed that the litter size of AG–GG, AA–GG, and GG–GG genotypes was significantly higher compared with other genotypes (P<0.05). This is the first study to find a new molecular marker affecting litter size and to systematically analyze the expression of BMPR1B in different fecundity and physiological periods of STH sheep. [ABSTRACT FROM AUTHOR]

This paper explores the relationship between cultural identity and foreign policy formation by conducting a qualitative analysis of Malaysia. Different from the existing literature that focuses on a leader's personality and international factors for explaining foreign policy formation, this paper contends that cultural identity matters for the making of foreign policy. Focusing on the trajectories of Malaysia's foreign policy over time, the paper argues that Islamic identity serves as an essential norm as well as a main guideline for the decision makers of Malaysia's foreign policy. The case studies of the Iraqi invasion of Kuwait (1990-1991), the War on Terror (2001-2003), and the Moro Muslim conflict in the Southern Philippines (1969-2012) support my argument. [ABSTRACT FROM AUTHOR]

This study aims to investigate the postoperative cognitive function changes of infants who underwent endoscopic third ventriculostomy (ETV) or ventriculoperitoneal shunt (VPS) for the treatment of congenital hydrocephalus. Data of 70 hydrocephalus infants and children were retrospectively analyzed. Among these patients, 20 patients underwent ETV, 27 patients underwent VPS, and 23 patients did not undergo any operation (controls). All patients were routinely cared after discharge. The Gecell Developmental Diagnostic Scale was filled for all patients at 2 weeks, 2 months, and 6 months after diagnosis. A total of 20 patients in the ETV group were followed up for 6 months. Among these patients, the clinical symptoms of 18 patients significantly improved. Results determined at 6 months after surgery in the ETV group was statistically significant, compared with the control group (P < 0.05). Results determined at 2 and 6 months after surgery in the VPS group were statistically significant, compared with the control group (P < 0.05). Developmental quotient (DQ) values in these two operation groups increased after the operation (P < 0.01), and the differences were statistically significant. ETV and VPS can improve the cognitive function of infants with hydrocephalus. Improvement of cognitive function by VPS is more significant for infants. [ABSTRACT FROM AUTHOR]

Background/Objectives: Relapsed B-cell acute lymphoblastic leukemia (B-ALL) remains an unresolved matter of concern regarding adverse outcomes. This case study aimed to evaluate the effectiveness of blinatumomab, with or without door lymphocyte infusion (DLI), in treating measurable residual disease (MRD)-positive B-ALL. Methods: All patients who received blinatumomab salvage therapy were included in this study. Eleven patients were included in the study. All patients were evaluated for MRD-negativity. Results: Before starting blinatumomab therapy, seven patients tested positive for MRD, three tested negative, and one had refractory disease. Hematopoietic cell transplantation (HCT) was reserved for five patients with persistent MRD. Six patients became MRD-negative and subsequent HCT was not performed. Only two patients relapsed; one patient died of relapse, and the other one received carfilzomib-based therapy and was MRD-negative thereafter. Nine patients were MRD-negative at a median follow-up of 28 months (15–52 months). Two of three MRD-positive post-transplant patients remained in complete molecular remission after preemptive DLI at the last follow-up date. In the first salvage, blinatumomab may achieve complete remission and bridging to HCT in pediatric patients with end-of-induction MRD-positive B-cell precursor ALL. Conclusions: The decision on how to treat post-transplant relapse continues to affect survival outcomes. Blinatumomab combined with DLI may extend the armamentarium of release options for high-risk pediatric patients. This approach is encouraging for high-risk ALL patients who are MRD-positive post-transplantation. [ABSTRACT FROM AUTHOR]

Background: To compare the clinical outcomes of two treatment modalities, initial surgery and primary definitive radiotherapy (RT), in Taiwanese patients diagnosed with cT1−2N0M0 oral cavity squamous cell carcinoma (OCSCC). Methods: Between 2011 and 2019, we analyzed data for 13,542 cT1−2N0M0 patients who underwent initial surgery (n = 13,542) or definitive RT with a dosage of at least 6600 cGy (n = 145) for the treatment of OCSCC. To account for baseline differences, we employed propensity score (PS) matching, resulting in two well‐balanced study groups (initial surgery, n = 580; definitive RT, n = 145). Results: Before PS matching, the 5‐year disease‐specific survival (DSS) rates were 88% for the surgery group and 58% for the RT group. After PS matching, the 5‐year DSS rates of the two groups were 86% and 58%, respectively. Similarly, the 5‐year overall survival (OS) rates before PS matching were 80% for the surgery group and 36% for the RT group, whereas after PS matching, they were 73% and 36%, respectively. All these differences were statistically significant (p < 0.0001). A multivariable analysis identified treatment with RT, older age, stage II tumors, and a higher burden of comorbidities as independent risk factors for both DSS and OS. We also examined the 5‐year outcomes for various subgroups (margin ≥5 mm, margin <5 mm, positive margins, RT combined with chemotherapy, and RT alone) as follows: DSS, 89%/88%/79%/63%/51%, respectively, p < 0.0001; OS, 82%/79%/68%/39%/32%, respectively, p < 0.0001. Conclusions: In Taiwanese patients with cT1−2N0M0 OCSCC, a remarkably low proportion (1.1%) completed definitive RT. A significant survival disparity of 30% was observed between patients who underwent initial surgery and those who received definitive RT. Interestingly, even patients from the surgical group with positive surgical margins exhibited a significantly superior survival compared to those in the definitive RT group. [ABSTRACT FROM AUTHOR]

Patients with Aarskog–Scott syndrome (AAS) have short stature, facial anomalies, skeletal deformities, and genitourinary malformations. FYVE, RhoGEF, and PH domain-containing 1 (FGD1) is the only known causative gene of AAS. However, the diagnosis of AAS remains difficult, and specific treatments are still absent. Patients suspected with AAS were recruited, and clinical information was collected. Genetic testing and functional analysis were carried out for the diagnosis. By literature review, we summarized the clinical and genetic characteristics of FGD1-related AAS and analyzed the genotype–phenotype correlation. Five patients were recruited, and four novel FGD1 variants were identified. The diagnosis of AAS was confirmed by genetic analysis and functional study. Three patients treated with growth hormone showed improved heights during the follow-up period. By literature review, clinical features of AAS patients with FGD1 variants were summarized. Regarding FGD1 variations, substitutions were the most common form, and among them, missense variants were the most frequent. Moreover, we found patients with drastic variants showed higher incidences of foot and genitourinary malformations. Missense variants in DH domain were related to a lower incidence of cryptorchidism. Conclusion: We reported four novel pathogenic FGD1 variations in AAS patients and confirmed the efficacy and safety of growth hormone treatment in FGD1-related AAS patients with growth hormone deficiency. Additionally, our literature review suggested the crucial role of DH domain in FGD1 function. What is Known: • Aarskog–Scott syndrome is a rare genetic disease, and the only known cause is the variant in FGD1 gene. The typical clinical manifestations of AAS include facial, skeletal, and urogenital deformities and short stature. What is New: • We reported four novel FGD1 variants and reported the treatment of growth hormone in FGD1-related AAS patients. Our genotype–phenotype correlation analysis suggested the crucial role of DH domain in FGD1 function. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionUveitis is a common, sight-threatening inflammatory ocular disease and is the main cause of blindness, which is caused by autoimmune response, infection, and injury. The contribution of 14-3-3ζ in uveitis remains obscure. This study aims to investigate the role of 14-3-3ζ in regulating ferroptosis in retinal inflammation and its contribution to uveitis.A lipopolysaccharide (LPS)-induced uveitis mouse model and BV-2 cell line were used to examine the effect of LPS stimulation on the expression of 14-3-3ζ and ferroptosis in microglia. The expression of heme oxygenase-1 (HO-1) was also analyzed to understand its role in promoting microglial ferroptosis.We found that LPS stimulation increased the expression of 14-3-3ζ and promoted ferroptosis in microglia. Additionally, 14-3-3ζ was found to promote microglial ferroptosis by stabilizing the expression of HO-1. These findings suggest that the 14-3-3ζ/HO-1 axis plays a crucial role in promoting microglial ferroptosis in retinal inflammation.The study provides valuable insights into the mechanisms underlying uveitis and highlights the potential of the 14-3-3ζ/HO-1 axis as a therapeutic target for the disease. Further research in this area could lead to the development of preventive and therapeutic strategies for uveitis. [ABSTRACT FROM AUTHOR]

As a result of the advantages of the steel fiber reinforced concrete pavement structure, which includes high strength, high stiffness, and high stability, a large number of steel fiber concrete pavements will be used for highway construction in China. As a result, numerous cracks develop, which significantly reduces the life of the road; therefore, the study of the jointing problem is vital. As concrete research on the influence of the load transfer capacity and service life of prefabricated steel fiber reinforced concrete joints on the structural design and use function of the whole and pavement panels, the paper proposes two joint forms, tongue-and-groove and overlap. Using experiments and software, the stress and reflection of prefabricated road panels of the two joint forms are analyzed for different axial loads. The analysis reveals that the maximum tensile stress, shear stress, and deflection of the precast panels of both joint forms increase linearly as the axle load of the vehicle increases, while the service life decreases relatively. The load transfer capacity is independent of the axle load magnitude, and the load transfer capacity difference between the two types of joints is minimal and excellent. [ABSTRACT FROM AUTHOR]

The intracellular sensor protein complex known as the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome plays a crucial role in regulating inflammatory diseases by overseeing the production of interleukin (IL)-1β and IL-18. Targeting its abnormal activation with drugs holds significant promise for inflammation treatment. This study highlights LCZ696, an angiotensin receptor-neprilysin inhibitor, as an effective suppressor of NLRP3 inflammasome activation in macrophages stimulated by ATP, nigericin, and monosodium urate. LCZ696 also reduces caspase-11 and GSDMD activation, lactate dehydrogenase release, propidium iodide uptake, and the extracellular release of NLRP3 and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) in ATP-activated macrophages, suggesting a potential mitigation of pyroptosis. Mechanistically, LCZ696 lowers mitochondrial reactive oxygen species and preserves mitochondrial integrity. Importantly, it does not significantly impact NLRP3, proIL-1β, inducible nitric oxide synthase, cyclooxygenase-2 expression, or NF-κB activation in lipopolysaccharide-activated macrophages. LCZ696 partially inhibits the NLRP3 inflammasome through the induction of autophagy. In an in vivo context, LCZ696 alleviates NLRP3-associated colitis in a mouse model by reducing colonic expression of IL-1β and tumor necrosis factor-α. Collectively, these findings suggest that LCZ696 holds significant promise as a therapeutic agent for ameliorating NLRP3 inflammasome activation in various inflammatory diseases, extending beyond its established use in hypertension and heart failure treatment. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Fu et al paper. To view this article, visit https://doi.org/10.1111/apt.17397 [ABSTRACT FROM AUTHOR]

Fibroblast growth-factor receptor (FGFR) is a potential target for cancer therapy. We designed three novel series of FGFR1 inhibitors bearing indazole, benzothiazole, and 1H-1,2,4-triazole scaffold via fragment-based virtual screening. All the newly synthesised compounds were evaluated in vitro for their inhibitory activities against FGFR1. Compound 9d bearing an indazole scaffold was first identified as a hit compound, with excellent kinase inhibitory activity (IC50 = 15.0 nM) and modest anti-proliferative activity (IC50 = 785.8 nM). Through two rounds of optimisation, the indazole derivative 9 u stood out as the most potent FGFR1 inhibitors with the best enzyme inhibitory activity (IC50 = 3.3 nM) and cellular activity (IC50 = 468.2 nM). Moreover, 9 u also exhibited good kinase selectivity. In addition, molecular docking study was performed to investigate the binding mode between target compounds and FGFR1. [ABSTRACT FROM AUTHOR]

Objectives: Whether a relationship between fish consumption and non-Hodgkin lymphoma (NHL) risk exists is an open issue. We carried out a meta-analysis to explore this association according to the published observational studies. Methods: We performed a search of databases in MEDLINE and EMBASE to identify relevant studies. We derived meta-analytic estimates using random-effects models, and assessed between-study heterogeneity using the Cochran's Q and I2 statistics. Results: We identified a total of seven case–control and two prospective cohort studies, including 7696 subjects with NHL. The summary relative risks (SRRs) estimated for NHL were 0.80 (95% confidence intervals (CIs): 0.68–0.94) for those in the highest fish consumption category compared with those in the lowest consumption category. There was evidence of significant heterogeneity across studies (Q = 26.72, Pheterogeneity = 0.002, I2 = 66.3%). Stratified analysis by study design indicated that a significant risk association between fish consumption and NHL was observed in case–control studies, but not in cohort studies. Based on the dose–response meta-analysis, the SRRs of NHL were 0.85 (95% CIs: 0.71–1.01) for three servings increased per week of fish consumed with evidence of significant heterogeneity (Pheterogeneity = 0.007, I2 = 63.9%). Conclusions: Findings from our meta-analysis indicate that consumption of fish may be not related to NHL risk. [ABSTRACT FROM AUTHOR]

Two new Zn(II)-based coordination polymers {[Zn3(L1)6(H2O)]∙(H2O)4}n (1, HL1 = 4-(tetrazol-5-yl)phenyl-4,2′:6′,4″-terpyridine) and [Zn2Cl2(L2)2H2O]n (2, HL2 = 4-([2,2′:6',2″'-terpyridin]-4′-yl)benzoic acid) have been successfully prepared using two similar organic ligands with distinct donor groups under similar reaction conditions. The distinct structural features and donor atoms make the two complexes show different water stability, and the complex 1 with good water stability, which can be utilized as the sensor for Fe3+ ion detection in water. The value of Stern–Volmer quenching constant of 1 to the Fe3+ is 5.77 × 104 M− 1, which lies in the top region of the reported CP-based sensors. The mechanism investigation reveals that the energy transfer of resonance from the complex 1 to the Fe3+ ion can account for its fluorescent quenching behavior. The treatment activity of compounds 1 and 2 on the postpartum hemorrhage (PPH) was assessed. First, the cytotoxicity of compounds 1 and 2 on human umbilical vein endothelial cells was assessed with Cell Counting Kit-8 detection kit. Then, to evaluate the prevention of compounds 1 and 2 on the PPH, we conducted the Lowry method and detected the clotting factor IX and anticoagulant factor III contents after the indicated treatment. Finally, the inflammatory response in mice was determined by ELISA method, and the IL-6 and IL-8 levels were determined. [ABSTRACT FROM AUTHOR]

Radiotherapy plays a major role in the curative treatment of head and neck cancer, either as a single modality therapy, or in combination with surgery or chemotherapy, or both. Despite advances to limit radiation-induced side-effects, the major salivary glands are often affected. This frequently leads to hyposalivation which causes an increased risk for xerostomia, dental caries, mucositis, and malnutrition culminating in a significant impact on patients' quality of life. Previous research demonstrated that loss of salivary function is associated with a decrease in polarity regulators and an increase in nuclear Yap localization in a putative stem and progenitor cell (SPC) population. Yap activation has been shown to be essential for regeneration in intestinal injury models; however, the highest levels of nuclear Yap are observed in irradiated salivary SPCs that do not regenerate the gland. Thus, elucidating the inputs that regulate nuclear Yap localization and determining the role that Yap plays within the entire tissue following radiation damage and during regeneration is critical. In this study, we demonstrate that radiation treatment increases nuclear Yap localization in acinar cells and Yap-regulated genes in parotid salivary tissues. Conversely, administration of insulin-like growth factor 1 (IGF1), known to restore salivary function in mouse models, reduces nuclear Yap localization and Yap transcriptional targets to levels similar to untreated tissues. Activation of Rho-associated protein kinase (ROCK) using calpeptin results in increased Yap-regulated genes in primary acinar cells while inhibition of ROCK activity (Y-27632) leads to decreased Yap transcriptional targets. These results suggest that Yap activity is dependent on ROCK activity and provides new mechanistic insights into the regulation of radiation-induced hyposalivation. [ABSTRACT FROM AUTHOR]

A new algorithm named the eight-section (ES) method for carrying out the interpolation for a magneto-resistive (MR) encoder is successfully developed and fabricated in a digital chip. It is known that a conventional magneto-resistive (MR) encoder employs the interpolation method, which converts incoming front-end analog signals in harmonics in sinusoids/co-sinusoids to moving displacement via calculating arc-tangents. This conventional interpolation requires divisions to be carried out for the displacement, which often leads to large noises while conducting digital computation, eventually undermining significantly the accuracy of the MR sensor. The proposed interpolation of eight-section (ES) is designed specially without divisions in the digital computation, leading to higher precision than the conventional interpolation conducting the computation of arc-tangents. The digital computation chip designed by this study consists of a cycle counter, two decimators for incoming analog signals of the MR sensor, a correcting circuit, and the proposal ES interpolation unit. The designed chip is successfully fabricated by TSMC 0.18-μm CMOS process, the area of which is 1643 × 1676 μm. The chip is than calibrated by a reference interferometer by experiments for further improving the measurement accuracy. The precision finally results in measuring displacement reaches as accurate as within 1.065 μm, which is much favorable to the existing performance around 2 μm by the conventional interpolation. [ABSTRACT FROM AUTHOR]

Aims: To determine deficiencies in the Food and Drug Administration (FDA)'s guidance for assessing acarbose bioequivalence (BE) and to explore optimal pharmacodynamic (PD) metrics for better evaluation of acarbose BE. Methods: Three clinical trials with branded acarbose were conducted in healthy subjects, including a pilot study (Study I, n = 11, 50 and 100 mg), a 2×2 crossover BE study (Study II, n = 36, 100 mg) and a 4×4 Williams study (Study III, n = 16, 50/100/150 mg). Serum glucose concentrations were measured by the glucose oxidase method. Results: In Study I, compared with 50 mg acarbose, only 100 mg acarbose had a significantly lower Cmax0–4h than that of sucrose administration alone (7.96 ± 0.83 mmol/L vs 6.78 ± 1.02 mmol/L, P <.05). In Study II, the geometric mean ratios of the test formulation to the reference formulation (both formulations were the branded drug) for FDA PD metrics, ΔCmax0–4h and ΔAUC0–4h, were 0.903 and 0.776, respectively, and the 90% confidence intervals were 67.44–120.90 and 53.65–112.13, respectively. The geometric mean ratios (confidence interval) for possible optimal evaluation PD metrics (Cmax0–2h and AUC0–2h) were 1.035 (94.23–112.68) and 0.982 (89.28–107.17), respectively. Further, Cmax0–2h and AUC0–2h also met the sensitivity requirements for BE evaluation in Study III. Conclusion: Considering the mechanisms of action of acarbose, the PD effect was shown to be dose independent during the 2–4 hours postadministration of acarbose. Hence PD metrics based on the serum glucose concentration from 0 to 2 hours (Cmax0–2h and AUC0–2h) are more sensitive than the FDA‐recommended PD metrics for acarbose BE evaluation from 0–4 hours (ΔCmax0–4h and ΔAUC0–4h). The trial has been registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn, ChiCTR1800015795, ChiCTR‐IIR‐17013918, ChiCTR‐IIR‐17011903). All subjects provided written informed consent before screening. [ABSTRACT FROM AUTHOR]

Bacteria‐mediated tumor therapy (BMTT) has been known for decades; however, its clinical use is inhibited by its association with infections. To address this issue, a spiky, bacterium‐like metal–organic framework (MOF), which can replicate the functional responses of BMTT without its adverse side‐effects, is proposed. MOFs are synthesized in a solvothermal reaction of aluminum sulfate, ruthenium chloride hydrate, and 2‐aminoterephthalic acid; they have a spherical morphology or many nanospikes on their surfaces, depending on the reaction temperature. Both spherical and spiky MOFs can function as photothermal agents, converting absorbed optical energy into local heat. Owing to their higher surface area of interaction, spiky MOFs are more easily phagocytosed by macrophages than are spherical MOFs, strengthening their immune responses. Moreover, when injected intratumorally, spiky MOFs reside significantly longer than spherical ones, enabling their use in repeated photothermal treatments. The combination of in situ vaccination with intratumorally injected bacterium‐like MOFs under exposure to an near‐infrared laser and the immune checkpoint blockade of systemically administered αPD‐1 is evaluated in tumor‐bearing mice. The results indicate that the checkpoint blockade acts synergistically with in situ vaccination to provide diverse antitumor functions of BMTT, destroying a primary tumor and suppressing tumor recurrence and metastasis. [ABSTRACT FROM AUTHOR]

To facilitate the cell-based experiment for pulsed electromagnetic field biological effect study, a novel TEM-cell-integrated CO2 incubator was developed. The integrated experimental system could simultaneously meet the requirement of standard cell culture condition and the various Transient Electromagnetic Field (TEF) exposure, which made it possible to study the relationship between different electromagnetic pulse exposure and the cellular responses in a reliable way. During the research, a comparison experiment was carried out to evaluate the necessity of the integrated incubator system: firstly, two different types of cell lines, which are the human prostate cancer cell line (PC3) and the pancreatic β cell line (MIN6) were chosen and exposed in the TEM-cell which located in the open area and the integrated system, respectively, with the same EFT radiation conditions; then, the cells' viability, the cellular ROS level and the mitochondrial membrane potential (MMP) were detected, respectively. The results showed that in the same parameter of the EFT radiation, the processes of the cells had a significant difference and even opposite in the incubator and open area, and all the results could be reproducible. The phenomenon indicated the stability of the TEM-cell-integrated CO2 incubator, and also demonstrated the necessity to strictly control the cell culture condition when carrying out the precise mechanism study of the TEF bioresponse at the cellular levels. [ABSTRACT FROM AUTHOR]

Complexity and abundant dynamics may arise in locally-active systems only, in which locally-active elements are essential to amplify infinitesimal fluctuation signals and maintain oscillating. It has been recently found that some memristors may act as locally-active elements under suitable biasing. A number of important engineering applications would benefit from locally-active memristors. The aim of this paper is to show that locally-active memristor-based circuits can generate periodic and chaotic oscillations. To this end, we propose a non-volatile locally-active memristor, which has two asymptotically stable equilibrium points (or two non-volatile memristances) and globally-passive but locally-active characteristic. At an operating point in the locally-active region, a small-signal equivalent circuit is derived for describing the characteristics of the memristor near the operating point. By using the small-signal equivalent circuit, we show that the memristor possesses an edge of chaos in a voltage range, and that the memristor, when connected in series with an inductor, can oscillate about a locally-active operating point in the edge of chaos. And the oscillating frequency and the external inductance are determined by the small-signal admittance Y(iω). Furthermore, if the parasitic capacitor in parallel with the memristor is considered in the periodic oscillating circuit, the circuit generates chaotic oscillations. [ABSTRACT FROM AUTHOR]

A selective recovery process for cobalt from the cathode materials of Li-ion batteries is demonstrated in this report. First, acid leaching was applied to dissolve the metals from the lithium-metal oxides. It was found out that with the assistance of probe type ultrasonication, manganese could be simultaneously separated by precipitation. This phenomenon would reduce the difficulty for later separation. Next, water-in-oil microemulsion extraction was applied for direct extraction of cobalt from the other metals. The cobalt extraction yield was 98% and purity was 96%. Moreover, the microemulsion system could be reused for 100 times without losing its extraction ability. [ABSTRACT FROM AUTHOR]

In2O3@Cu2MoS4 nanocomposite with superior photoelectrochemical (PEC) performance is used for the first time as a photoactivity material, and a signal-off PEC biosensing platform for miRNA detection has been successfully constructed. Firstly, the Cu2MoS4 nanosheets are synthesized by a hydrothermal method, and then, the homogeneous In2O3 nanoparticles (In2O3 NPs) are synthesized by calcination in the air. The In2O3@Cu2MoS4 nanocomposite is constructed with the Cu2MoS4 nanosheets as matrix and In2O3 NPs as sensitizer through a layer-by-layer assembly strategy. The nanocomposite with a tight interface and the matched band structure restrains the electron-hole pair recombination. Under visible light (400–700 nm), the nanocomposite exhibits a strong initial signal. With the catalyzed hairpin assembly, dozens of PbS quantum dots (QDs) are introduced on the surface of an electrode, significantly reducing the photocurrent of n-type In2O3@Cu2MoS4. Since PbS QDs can compete with the nanocomposite for light energy and electron donors, the signal decreased. Under optimal conditions, the biosensor manifests a broad linear range (1 fM–1 nM) and a low detection limit of about 0.57 fM, at a working potential of 0 V (vs. Ag/AgCl). The recovery of spiked human serum is between 94.0 and 102%, and the relative standard deviation (RSD) is between 1.3 and 2.7%. Therefore, the as-fabricated biosensor exhibits a potential for the determination of miRNA-21 in practical applications. Graphical abstract [ABSTRACT FROM AUTHOR]

The inhibition of soluble epoxide hydrolase (sEH) is regarded as a promising therapeutic approach to treat inflammation and its related disorders. In present work, we investigated inhibitory effects of forty-nine kinds of traditional Chinese medicines against sEH. Inula helenium showed significant inhibitory effect against sEH, and the extract of I. helenium was isolated to obtain eight compounds, including 4 H -tomentosin (1), xanthalongin (2), linoleic acid (3), 8-hydroxy-9-isobutyryloxy-10(2)-methylbutyrylthymol (4), dehydrocostus lactone (5), alantolactone (6), costunolide (7), and isoalantolactone (8). Among them, 4 H -tomentosin (1), xanthalongin (2), and linoleic acid (3) showed significantly inhibitory activities on sEH with half maximal inhibitory concentration (IC 50) from 5.88 ± 0.97 μM to 11.63 ± 0.58 μM. The inhibition kinetics suggested that 4 H -tomentosin (1) and xanthalongin (2) were mixed-competitive type inhibitors with inhibition constants (K i) of 7.02 and 6.57 μM, respectively, and linoleic acid (3) was a competitive type inhibitor with a K i values of 3.52 μM. The potential interactions of 4 H -tomentosin (1), xanthalongin (2), and linoleic acid (3) with sEH were analyzed by molecular docking, which indicated that these bioactive compounds had interactions with key amino acid residues Tyr343, Ile363, Tyr383, and His524. • Eight compounds were isolated from I. helenium. • Compounds 1-3 could inhibit sEH activity with IC 50 values from 5.88 ± 0.97 μM to 11.63 ± 0.58 μM. • They were all mixed-competitive type inhibitor with Ki values from 3.52 μM to 7.02 μM • Molecular docking revealed interaction of compounds 1-3 with sEH. [ABSTRACT FROM AUTHOR]

Arabidopsis AINTEGUMENTA (ANT), an AP2 transcription factor, is known to control plant growth and floral organogenesis. In this study, our transcriptome analysis and in situ hybridization assays of maize embryonic leaves suggested that maize ANT1 (ZmANT1) regulates vascular development. To better understand ANT1 functions, we determined the binding motif of ZmANT1 and then showed that ZmANT1 binds the promoters of millet SCR1, GNC, and AN3, which are key regulators of Kranz anatomy, chloroplast development, and plant growth, respectively. We generated a mutant with a single-codon deletion and two frameshift mutants of the ANT1 ortholog in the C4millet Setaria viridis by the CRISPR/Cas9 technique. The two frameshift mutants displayed reduced photosynthesis efficiency and growth rate, smaller leaves, and lower grain yields than wild-type (WT) plants. Moreover, their leaves sporadically exhibited distorted Kranz anatomy and vein spacing. Conducting transcriptomic analysis of developing leaves in the WT and the three mutants we identified differentially expressed genes (DEGs) in the two frameshift mutant lines and found many downregulated DEGs enriched in photosynthesis, heme, tetrapyrrole binding, and antioxidant activity. In addition, we predicted many target genes of ZmANT1 and chose 13 of them to confirm binding of ZmANT1 to their promoters. Based on the above observations, we proposed a model for ANT1 regulation of cell proliferation and leaf growth, vascular and vein development, chloroplast development, and photosynthesis through its target genes. Our study revealed biological roles of ANT1 in several developmental processes beyond its known roles in plant growth and floral organogenesis. [ABSTRACT FROM AUTHOR]

A disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) family are widely implicated in tissue remodeling events manifested in cancer development. ADAMTS1, the most fully characterized ADAMTS, plays conflicting roles in different cancer types; however, the role of ADAMTS1 in renal cell carcinoma (RCC) remains unclear. Herein, we found that ADAMTS1 is highly expressed in RCC tissues compared to normal renal tissues, and its expression was correlated with an advanced stage and a poor prognosis of RCC patients. In vitro, we observed higher expression of ADAMTS1 in metastatic (m)RCC cells compared to primary cells, and manipulation of ADAMTS1 expression affected cell invasion and clonogenicity. Results from protease array showed that ADAMTS1 is modulated by melatonin through mechanisms independent of the MT1 receptor in mRCC cells, and overexpression of ADAMTS1 relieved the invasion/clonogenicity and growth/metastasis inhibition imposed by melatonin treatment in vitro and in an orthotopic xenograft model. The human microRNA (miR) OneArray showed that miR‐181d and miR‐let‐7f were induced by melatonin and, respectively, targeted the 3'‐UTR and non‐3'‐UTR of ADAMTS1 to suppress its expression and mRCC invasive ability. Clinically, RCC patients with high levels of miR‐181d or miR‐let‐7f and a low level of ADAMTS1 had the most favorable prognoses. In addition, ubiquitin/proteasome‐mediated degradation of ADAMTS1 can also be triggered by melatonin. Together, our study indicates that ADAMTS1 may be a useful biomarker for predicting RCC progression. The novel convergence between melatonin and ADAMTS1 post‐transcriptional and post‐translational regulation provides new insights into the role of melatonin‐induced molecular regulation in suppressing RCC progression. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID-19) epidemic met coincidentally with massive migration before Lunar New Year in China in early 2020. This study is to investigate the relationship between the massive migration and the coronavirus disease 2019 (COVID-19) epidemic in China. Methods: The epidemic data between January 25th and February 15th and migration data between Jan 1st and Jan 24th were collected from the official websites. Using the R package WGCNA, we established a scale-free network of the selected cities. Correlation analysis was applied to describe the correlation between the Spring Migration and COVID-19 epidemic. Results: The epidemic seriousness in Hubei (except the city of Wuhan) was closely correlated with the migration from Wuhan between January 10 and January 24, 2020. The epidemic seriousness in the other provinces, municipalities and autonomous regions was largely affected by the immigration from Wuhan. By establishing a scale-free network of the regions, we divided the regions into two modules. The regions in the brown module consisted of three municipalities, nine provincial capitals and other 12 cities. The COVID-19 epidemics in these regions were more likely to be aggravated by migration. Conclusions: The migration from Wuhan could partly explain the epidemic seriousness in Hubei Province and other regions. The scale-free network we have established can better evaluate the epidemic. Three municipalities (Beijing, Shanghai and Tianjin), eight provincial capitals (including Nanjing, Changsha et al.) and 12 other cities (including Qingdao, Zhongshan, Shenzhen et al.) were hub cities in the spread of COVID-19 in China. [ABSTRACT FROM AUTHOR]

Brain function has been implicated to control the aging process and modulate lifespan. However, continuous efforts remain for the identification of the minimal sufficient brain region and the underlying mechanism for neuronal regulation of longevity. Here, we show that the Drosophila lifespan is modulated by rab27 functioning in a small subset of neurons of the mushroom bodies (MB), a brain structure that shares analogous functions with mammalian hippocampus and hypothalamus. Depleting rab27 in the α/βp neurons of the MB is sufficient to extend lifespan, enhance systemic stress responses, and alter energy homeostasis, all without trade‐offs in major life functions. Within the α/βp neurons, rab27KO causes the mislocalization of phosphorylated S6K thus attenuates TOR signaling, resulting in decreased protein synthesis and reduced neuronal activity. Consistently, expression of dominant‐negative S6K in the α/βp neurons increases lifespan. Furthermore, the expression of phospho‐mimetic S6 in α/βp neurons of rab27KO rescued local protein synthesis and reversed lifespan extension. These findings demonstrate that inhibiting TOR‐mediated protein synthesis in α/βp neurons is sufficient to promote longevity. [ABSTRACT FROM AUTHOR]

microRNA‐3607 (miR‐3607) has been identified as an important biomarker, and its aberrant expression exerts a significant role in tumorigenesis. However, the biological function of miR‐3607 in hepatocellular carcinoma (HCC) needs to be deciphered comprehensively. Clinical samples of HCC patients, as well as normal cases, were derived from The Cancer Genome Atlas database. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) and Western blotting analyses were utilized to detect the expression levels of indicated genes. Cell counting kit‐8 (CCK‐8), colony formation, and transwell assays were performed to assess the effect of miR‐3607 in HCC cell viability, migration, and invasion. Bioinformatics analysis and luciferase reporter gene assay was applied to screen the target genes of miR‐3607 and verified the association between miR‐3607 and its potential target gene. Our study showed that miR‐3607 expression was decreased in HCC tissues and cell lines, and its downregulation was linked with poor outcomes of HCC patients. miR‐3607 was noted to inhibit HCC cell growth, colony formation, migration, and invasion. Besides, minichromosome maintenance (MCM5) was a possible target gene of miR‐3607 in HCC. Overexpression of MCM5 was observed in HCC and induced unfavorable prognosis. MCM5 expression had a negative correlation with miR‐3607. MCM5 can abolish the suppressive impacts of miR‐3607 on HCC cell malignant behaviors and the epithelial‐mesenchymal transition (EMT) process. To sum up, our results unveiled that miR‐3607 could inhibit HCC cell growth, migration, and invasion by regulating MCM5 and mediating EMT process, suggesting a new probable biomarker for further treatment of HCC. [ABSTRACT FROM AUTHOR]

Background: It has previously been shown that bevacizumab, when added to chemotherapy, improved overall survival in several cancers. In glioblastoma multiforme (GBM), bevacizumab increased progression-free survival and it is widely used for tumor recurrence, though it has failed to improve overall survival (OS) in controlled trials. However, an effective biomarker for predicting the prognosis of bevacizumab treatment has yet to be identified. This study, therefore, aimed to retrospectively analyze the polymorphisms of p53 codon 72 and the clinical characteristics of GBM specimens from Taiwanese patients.Methods: The polymorphisms of p53 codon 72 in 99 patients with GBM treated at Taichung Veterans General Hospital in Taiwan from 2007 to 2017 were analyzed using direct DNA sequencing and PCR-RFLP analysis.Results: We found that among these GBM patients, the distribution of codon 72 polymorphisms was 28.3% for proline homozygotes (Pro/Pro), 38.4% for arginine homozygotes (Arg/Arg), and 33.3% for proline/arginine heterozygotes (Pro/Arg). Although the polymorphisms of p53 codon 72 were not directly associated with the overall survival of GBM, both the Arg/Arg and Arg/Pro genotypes were associated with significant benefits in terms of overall survival in patients treated with CCRT plus bevacizumab compared to patients treated with CCRT alone.Conclusions: This pilot study suggests that both the Arg/Arg and Arg/Pro genotypes of p53 codon 72 polymorphism may have value as independent prognostic or predictive parameters for bevacizumab treatment response and failure. Relatedly, the results of the study further demonstrate the utility of stratifying GBM patients according to bevacizumab sensitivity. [ABSTRACT FROM AUTHOR]

Aims: To explore the concerns and experiences of parents of children scheduled to receive allogeneic haematopoietic stem cell transplantation. Design: A qualitative secondary analysis of interview data from an intervention study. Methods: A total of 28 parents (4 fathers and 24 mothers) were recruited from a children's hospital, which performs approximately one‐third of all paediatric haematopoietic stem cell transplantation cases in Taiwan. Data were collected between September 2015–August 2018 by one researcher with face‐to‐face interviews, which were tape‐recorded and transcribed verbatim. The data were analysed using inductive content analysis to extract the main themes. Results: Five themes describing parental concerns prior to paediatric haematopoietic stem cell transplantation were identified: the child became their first priority, seeking solutions, an interweaving of hope and uncertainty, grateful for the chance of a cure and the long road to recovery. Conclusion: Understanding the concerns and experiences of our participants as they navigated the pre‐transplantation period could reduce parents' uncertainty and improve the care of their child. Impact: These experiences provide information that could be used by healthcare professionals to develop support interventions and strategies tailored to the individual needs of each parent, which could prepare parents for their child's haematopoietic stem cell transplantation. [ABSTRACT FROM AUTHOR]

Objectives: Peripheral arterial disease (PAD) is characterised by arterial occlusion and fibrosis in the lower extremities. Extracellular volume matrix fraction (ECV) is a biomarker of skeletal muscle fibrosis, but has not been applied to the lower extremities with PAD. This study investigated the clinical feasibility of using ECV for calf muscle fibrosis quantification by comparing normal controls (NC) and PAD patients.Methods: From October 2016 to December 2017, we recruited patients with PAD, and patients with head and neck cancer receiving fibular flap as NC group. All participants underwent magnetic resonance imaging (MRI) to determine the ECV of the calves and the differences between the NC and PAD groups. ECV was calculated from T1 values at steady-state equilibrium, defined as the point in time after contrast agent injection when the variance of T1 relaxation time in blood and muscle becomes less than 5%.Results: A total of 46 patients (18 in the NC group and 28 in the PAD group) were recruited. Steady-state equilibrium was reached at 11-12 min after contrast agent injection. The NC group had significantly lower mean ECV than the PAD group (12.71% vs. 31.92%, respectively, p < 0.001). In the PAD group, the mean ECV was slightly lower in patients with collateral vessels than in those without (26.58% vs. 34.88%, respectively, p = 0.047).Conclusion: Evaluation of skeletal fibrosis in PAD using ECV is feasible. ECV can help identify PAD patients with collateral vessel formation and lay the foundation for future research in PAD management.Key Points: • Steady-state equilibrium for ECV measurement of the lower limbs can be reached at around 11-12 min. • Quantification of lower limb muscle fibrosis by measuring ECV is clinically feasible and can be used to differentiate between patients with PAD and histologically proven normal controls. • ECV can differentiate PAD patients with or without visible collateral vessels, further expanding its role in identifying the presence of collateral supply in clinical decision-making. [ABSTRACT FROM AUTHOR]

In this paper, a half-space fast multipole BEM is developed for the simulation of three-dimensional acoustic problems above an infinite impedance plane. The half-space impedance Green's function involving a complex line source is used, so that both mass-like and spring-like impedance boundary conditions on the infinite plane can be explicitly satisfied and the infinite plane is not required to be discretized. The Burton–Miller method is employed to tackle the fictitious eigenfrequency problem involved in the conventional boundary integral equation method. Image relations of the multipole expansion coefficients are used and the half-space impedance Green's function is modified to apply such relations to avoid calculating, translating and saving the multipole/local expansion coefficients in the image domain. An automatic integrator with adaptive interval subdivision is further adopted to calculate the line integral contained in the M2L translation formula accurately and efficiently. Numerical examples are given to show the validity and potential of the method. [ABSTRACT FROM AUTHOR]

We demonstrate the transmission of a microwave frequency signal at 10 GHz over a 112-km urban fiber link based on a novel simple-architecture electronic phase compensation system. The key element of the system is the low noise frequency divider by 4 to differentiate the frequency of the forward signal from that of the backward one, thus suppressing the effect of Brillouin backscattering and parasitic reflection along the link. In terms of overlapping Allan deviation, the frequency transfer instability of 4.2 × 10−15 at 1-s integration time and 1.6 × 10−18 at one-day integration time was achieved. In addition, its sensitivity to the polarization mode dispersion in fiber is analyzed by comparing the results with and without laser polarization scrambling. Generally, with simplicity and robustness, the system can offer great potentials in constructing cascaded frequency transfer system and facilitate the building of fiber-based microwave transfer network. [ABSTRACT FROM AUTHOR]

aimed to investigate the tumor-suppressive role of miR-199a-3p targeted ZEB1. Materials and Methods: A549 cells were transfected with ZEB1 and/or miR-199a-3p. Then, tumor growth was investigated in xenograft mice. Stem-like property, proliferation and mitochondria injury were further validated in vitro. Results: Overexpression of miR-199a-3p with premiRNAs significantly reduced tumor growth inhibited CD44 and Ki67 and increased Caspase-3 in A549 xenograft mice. Sphere formation and protein expression of stem-like markers showed that miR-199a-3p inhibited stemness of A549 cell. miR-199a-3p reduced proliferation of A549 cells, as showed with EdU staining and reduced expression of Ki67. Transfection of miR-199a-3p also promoted apoptosis, as indicated with increased apoptotic cells with flow cytometry, and increased cleaved Caspase-3/Caspase3 and Bcl-2/Bax. Apoptosis was further validated to be induced with mitochondria dysfunction, which indicated with JC-1 labeled loss of mitochondrial membrane potential, reduced activity of SOD, and increased MDA and LDH. All these effects were inverted with overexpression of ZEB1. Conclusion: Altogether, the findings suggested that the up-regulation of miR-199a-3p significantly inhibited NSCLC growth in vivo, and reduced A549 cell proliferation and promoted mitochondrial-mediated apoptosis, through down-regulation of ZEB1. The findings supported ZEB1 down-expression with miR-199a-3p as a novel therapeutic target for NSCLC treatment. [ABSTRACT FROM AUTHOR]

This paper develops a Hamiltonian state space approach for analytic determination of deformation and stress fields in multilayered monoclinic angle-ply laminates under the combined action of extension, bending, and torsion. The present solution satisfies the equations of anisotropic elasticity, the end conditions, the traction-free boundary conditions on the four edge surfaces of the rectangular section, and the interfacial continuity conditions in multilayered laminates. The proposed method only requires the solutions of matrix and eigen equations, regardless of the number or lamination of the layers. The finite element analyses are used to validate the accuracy of the analysis. The analytical solution and the numerical solutions are in excellent agreement. [ABSTRACT FROM AUTHOR]

In the U.S., since the 2000s, with the strong growth of China's economy and military, China has become a threat to U.S. interests in the Indo-Pacific region. Due to a breakthrough in U.S.-India relations has pushed Washington to devote more attention to this region, President Obama articulated the concepts of "pivot" or "rebalance" to Asia, and Secretary of State Hillary Clinton published an article in 2011 ("America's Pacific Century"), in which she argued that the U.S. would build a multipronged approach of military cooperation, diplomatic engagement, and free trade negotiation to establish its position in the Indo-Pacific region. [ABSTRACT FROM AUTHOR]

Proper amounts of copper supplemented in livestock feed improve the physical growth and traits of farm animals. The pancreas is an important organ with both exocrine and endocrine portions. To investigate the role and mechanism of copper in the sheep pancreas, we first established sheep pancreatic duct organoids (sPDOs). We found that an appropriate amount of copper benefited the formation and growth of sPDOs, whereas excess or deficient copper damaged sPDOs. We found that the proliferation-stimulating effect of copper was related to the copper chaperone antioxidant protein 1 (ATOX1)-dependent activation of MEK-ERK1/2 signaling. Atox1 knockdown suppressed the cell proliferation of sPDOs, even in the presence of the MEK activator. These results indicate that moderate concentrations of copper promote sPDO growth through ATOX1-regulated cell proliferation by activation of MEK-ERK. Moreover, our study indicates that organoids may be a useful model to study organ growth mechanisms in livestock. [ABSTRACT FROM AUTHOR]

We developed ultrathin dual-mesoporous polymer nanosheets by combining co-assembly of different templates with in situ synthesis of functional polymers, which featured inherent smaller and template-directed larger mesopores (2.6 nm and 15 nm, respectively), ultrathin nanolayers (20 nm), high surface area (268 m2 g−1), intrinsic fluorescent properties and effective detectability for organophosphates. [ABSTRACT FROM AUTHOR]

Background: Surrogates often do not accurately predict older people's preferences about end-of-life (EOL) care. Few studies have examined the impact of advance care planning (ACP) on EOL decision-making consistency between older people and their surrogates, and these studies have yielded conflicting results. Objectives: To evaluate the effectiveness of ACP in improving EOL decision-making consistency between older people and their surrogates. Design: The intervention in this pre–post quasi-experimental design included an informative video, a brochure about ACP, and a guided discussion about EOL wishes. Setting: Two geriatric wards in a medical center in northern Taiwan. Subjects: One hundred eight participants, as 54 pairs of older people and their surrogates, were randomly assigned to either the experimental or control group. The experimental group received an intervention, while the control group received usual care. Measurements: Life-Support Preferences Questionnaire. Results: The intervention did not improve decision-making consistency between older people and their surrogates. This was the first time that most pairs discussed specific EOL decisions, so additional preparation may improve comfort with this topic. This study also found that some older people had difficulty concentrating on the educational brochure or understanding the related terms. Conclusions: Preparation for ACP discussion is needed for older people and their surrogates. Longer-term effects of ACP should be monitored because ACP interventions may have enhanced empathy between older people and their surrogates. Additionally, a culturally sensitive illustrated questionnaire that explains life-support preferences and ACP topics may improve communication between older people and their surrogates. [ABSTRACT FROM AUTHOR]

The development and demonstration of a high-bandwidth two-color temperature sensor for high-pressure environments using intensity-modulation spectroscopy (IMS) is presented. The sensor utilized rapid intensity modulation, beam coalignment, and frequency multiplexing to deal with common challenges for laser absorption spectroscopy systems at high pressures and achieved a sensor bandwidth of 100 kHz. The P(16) and R(6) transitions of the H 2 O fundamental antisymmetric stretch rovibrational band near 2.5 μ m were chosen for initial development of this temperature diagnostic concept. Temperature validation experiments were conducted with shock tubes for both reactive and non-reactive environments. Shock tube experiments were first conducted with H 2 O and N 2 mixtures at pressures of around 8.2 atm, yielding temperature measurements with a standard deviation of 2.9 K within the steady-state test time. The performance of this system was then validated at 36.9 atm, yielding temperature measurements with a standard deviation of 8.4 K . By comparing the measured temperatures with calculated temperatures based on ideal shock jump relations, the sensor achieved an average accuracy within 4.3 K of the known temperatures across multiple experiments spanning a range of 1030–1450 K, 8–38 atm. These results demonstrate that the IMS-based sensor enables high-precision measurements of temperature at high pressures. [ABSTRACT FROM AUTHOR]

Alopecia areata (AA) is thought to be an autoimmune process. In other autoimmune diseases, the innate immune system and Toll‐like receptors (TLRs) can play a significant role. Expression of TLR7, TLR9 and associated inducible genes was evaluated by quantitative PCR in peripheral blood mononuclear cells (PBMCs) from 10 healthy individuals and 19 AA patients, categorized according to disease duration, activity and hair loss extent. Microdissected scalp biopsies from five patients and four controls were also assessed by quantitative PCR and immunohistology. TLR9 was significantly upregulated 2.37 fold in AA PBMCs. Notably, TLR9 was most significantly upregulated in patients with active AA, as shown by a positive hair pull test, compared to stable AA patients. In hair follicle bulbs from AA patients, IFNG and TLR7 exhibited statistically significant 3.85 and 2.70 fold increases in mRNA, respectively. Immunohistology revealed TLR7 present in lesional follicles, while TLR9 positive cells were primarily observed peri‐bulbar to AA affected hair follicles. The increased expression of TLR7 and TLR9 suggest components of the innate immune system may be active in AA pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Wake-up stroke (WUS) accounts for up to 25% of all new ischemic strokes, but debate exists regarding whether WUS differs from non-WUS in previous studies. Our study aimed to investigate the proportion of WUS cases and to examine differences in clinical characteristics and outcomes in these two groups. Methods: Data from acute ischemic stroke patients who presented to the First Affiliated Hospital of Chongqing Medical University between April 2017 and September 2017 were prospectively collected. Admission demographic information, clinical and radiological characteristics, and 3-month functional outcomes were assessed and compared between patients with WUS and those with non-WUS. Poor functional outcome was defined as modified Rankin Scale ≥ 3 at the 90-day follow-up. Risks of poor outcomes for WUS were estimated with logistic regression analysis. Results: A total of 473 eligible patients were included, of which 132 had been diagnosed with WUS (27.9%). Forty WUS patients had poor functional outcomes and 92 WUS patients had good functional outcomes. WUS and non-WUS patients were similar in regard to stroke risk factors, severity, etiology, and prognosis at 90 days (p > 0.05), but WUS patients were more likely to have had previous stroke (p < 0.001) and a tendency of higher albumin levels (p = 0.051). WUS patients show significant differences in terms of age, gender, prior stroke, atrial fibrillation, impaired consciousness at admission, levels of albumin and triglycerides, stroke severity, and stroke etiology between the good outcome group and the poor outcome group (p < 0.05). Multivariate logistic regression analysis showed that age (odds ratio [OR] 1.079, 95% confidence interval [CI] 1.021–1.141; p < 0.05), previous stroke (OR 4.017, 95% CI 1.197–13.484; p < 0.05), and admission National Institutes of Health Stroke Scale (NIHSS) score ≥5 (OR 5.453, 95% CI 1.510–19.696; p < 0.05) were independently associated with an unfavorable outcome of WUS. Conclusions: WUS accounts for 27.9% of 473 ischemic strokes in the Chinese population. WUS and non-WUS patients were similar in terms of stroke risk factors, severity, etiology, and early outcomes. Age, previous stroke, and a high admission NIHSS score were independent risk factors for unfavorable outcomes in patients with WUS. [ABSTRACT FROM AUTHOR]

Background: Physical violence against women is a major public health problem in African countries; however, no studies have focused on factors associated with violent injuries to women in Africa.Objectives: A matched case-control study was conducted to investigate risk factors for injuries from physical violence against African women in The Gambia.Methods: Over a 12-month study period, study participants were recruited from emergency departments of eight government-managed health care facilities. Cases were female patients aged ≥ 15 years who had been violently injured. Matched by the health facility, date of injury, sex, and age, a control patient for each case was selected from those injured due to nonviolent mechanisms.Results: In total, 194 case-control pairs were recruited. Results of a conditional logistic regression showed that being a Fula (odds ratio [OR] 2.45; 95% confidence interval [CI] 1.06-5.66), living in an extended family compound (OR 3.07; 95% CI 1.22-7.72), having six or more female siblings (OR 3.10; 95% CI 1.38-6.97), having been raised by grandparents (OR 3.34; 95% CI 1.06-10.51), and having been verbally (OR 3.04; 95% CI 1.56-5.96) or physically abused (OR 3.36; 95% CI 1.34-8.39) in the past 12 months were significantly associated with injury from physical violence.Conclusion: Most risk factors identified for violent injury among African women are unique to the studied geography. Violence prevention programs, if designed based on these identified risk factors, may be more effective for this population. [ABSTRACT FROM AUTHOR]