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Background: Despite advances in treatments for gastric cancer (GC), new targets are needed to enhance treatment, especially when mesenchymal‐epithelial transition (MET) amplification is involved. Therefore, we investigated the genomic features of MET‐amplified GC and efficacy of anti‐MET therapy. Methods: Genomic features were investigated in 2284 patients (cohort 1) and 438 patients in the Cancer Genome Atlas (TCGA cohort). RNA data were obtained from TCGA for expression analysis. Clinical responses of 71 patients (cohort 2) were investigated. Survival rates were compared by Kaplan–Meier and log‐rank tests. Results: In cohort 1, 95 (4.2%) exhibited MET amplifications. In TCGA cohort, 15 (3.4%) exhibited MET amplifications. The five top mutated genes were TP53, CDH1, ARID1A, KMT2D and PIK3CA in cohort 1 and TTN, TP53, MUC16, LRP1B and SYNE1 in TCGA cohort. TP53, PIK3CA, KRAS and GNAS showed significant single nucleotide variants (SNVs) in cohort 1, and TP53 SNVs were significant in TCGA cohort. Fifteen and 18 genes showed significant copy number variations (CNVs) between the MET‐ and non‐MET‐amplified groups in cohort 1 and TCGA cohort, respectively. The PI3K pathway was significantly activated in Chinese patients with MET‐amplified GC (p = 0.002). TP53 expression is negatively associated with MET amplification. Real‐world data obtained with cohort 2 revealed that anti‐MET treatment significantly affected overall survival (OS) (p = 0.002), whereas CNVs did not affect progression‐free or OS even when treatment lines were considered. Conclusions: MET‐amplified GC has a distinctive mutation landscape. Our findings provide valuable information for clinicians who treat patients with MET‐amplified GC. [ABSTRACT FROM AUTHOR]

To effectively control nonpoint source pollution and predict its transport and load, understanding water and solute transport processes, patterns and mechanisms is essential. However, the measurement of water movement and solute transport parameters is usually a laborious and time‐consuming task. It is important to predict water movement and solute transport parameters from more readily available soil physical and chemical properties. In this study, a database of soil hydraulic and solute transport parameters containing information retrieved from 83 published studies on soil properties, land use, management measures, etc. was established to characterize and simulate soil water movement and solute transport processes. Our results showed that the soil particle composition was closely related to all soil hydraulic and solute transport parameters. As the soil texture changed from sand to clay, the soil residual water content (θr) obviously increased. The soil porosity was significantly positively correlated with θr, saturated water content (θs), van Genuchten parameter α, dispersity (λ) and retardation factor (R) and negatively correlated with van Genuchten parameter n (p < 0.01). The use of random forest models allowed the prediction of soil hydraulic and solute transport parameters by inputting common or even incomplete soil property parameters. The bulk density and particle composition jointly contributed 66% to the prediction of the soil hydraulic parameters and 44% to the prediction of the solute transport parameters. The pH exerted a notable impact on the solute transport parameters, especially dispersion coefficient (D), λ and R. The results may be useful in providing data support and facilitating the development of watershed nonpoint source pollution models. [ABSTRACT FROM AUTHOR]

Tumor‐associated macrophages (TAMs) are key components of the tumor microenvironment, and their different polarization states play multiple roles in tumors by secreting cytokines, chemokines, and so on, which are closely related to tumor development. In addition, the enrichment of TAMs is often associated with poor prognosis of tumors. Thus, targeting TAMs is a potential tumor treatment strategy, in which therapeutic approaches such as reducing TAMs numbers, remodeling TAMs phenotypes, and altering their functions are being extensively investigated. Meanwhile, the ubiquitin–proteasome system (UPS), an important mechanism of protein hydrolysis in eukaryotic cells, participates in cellular processes by regulating the activity and stability of key proteins. Interestingly, UPS plays a dual role in the process of tumor development, and its role in TAMs deserve to be investigated in depth. This review builds on this foundation to further explore the multiple roles of UPS on TAMs and identifies a promising approach to treat tumors by targeting TAMs with UPS. [ABSTRACT FROM AUTHOR]

The relationship between single nucleotide polymorphisms (SNPs) at various loci and adverse drug reactions (ADRs) in patients with gynecologic cancer receiving platinum‐based chemotherapy (PPCT) remains unexplored. This research aimed to investigate the correlation between SNPs at several loci (e.g., GSTP1 rs1695, MTHFR rs1801133, XPC rs2228001, TP53 rs1042522, and ERCC1 rs3212986) and ADRs in patients with gynecologic cancer receiving PPCT. A total of 244 patients with gynecologic cancer who received first‐line PPCT were included in this retrospective study. Blood fluorescence quantitative polymerase chain reaction was used to detect genotypes. Logistic regression, Pearson's Chi‐square test, and Fisher's exact test were used to explore the correlations between these SNPs and the occurrence of ADRs. The logistic regression results showed that different genotypes of the five genes had no statistical significance in the overall grade greater than or equal to 3 ADRs. The results of Pearson's Chi‐square test showed the same results. On specific adverse reactions, we found that the rs1042522 GG genotype significantly increased the risk of grade greater than or equal to 3 leucopenia compared with the CG and the CC genotypes (p = 0.002). The rs1695 AG genotype showed higher correlation for grade greater than or equal to 3 neutropenia (p = 0.020). The rs2228001 CC genotype also had a higher risk for grade greater than or equal to 3 neutropenia (p = 0.003). This study found that whereas the overall grade greater than or equal to 3 adverse reactions in patients with gynecologic cancer receiving PPCT were not associated with SNPs, specific SNPs (rs1042522 GG, rs1695 AG, and rs2228001 CC) were linked to higher risks of leucopenia and neutropenia, indicating their potential as predictors of hematotoxicity in PPCT‐treated patients with gynecologic cancer. [ABSTRACT FROM AUTHOR]

A quinine‐derived thiourea‐catalyzed enantioselective double annulation strategy using alkylidene Meldrum′s acid as an acceptor‐donor‐acceptor with salicylaldehyde‐derived azomethine ylide is reported. The methodology is realized via a (3+2) cycloaddition/transesterification/decarboxylation sequence, giving chromeno[4,3‐b]pyrrolidines within 15–420 minutes at room temperature in 51–97% yields with 92–99% ee under 1–10 mol% catalyst loading. A plausible activation model is proposed for the excellent stereoinduction by H‐bond interaction between the catalyst and the Meldrum′s acid motif according to control experiments. [ABSTRACT FROM AUTHOR]

The future vehicle‐to‐everything (V2X) scenarios greatly call for reliable and efficient communication links between roadside units (RSUs) and vehicles. Integrated sensing and communication (ISAC) represents one of the key candidate technologies for 6G, which provides new solutions for this problem. In this paper, the beam tracking design for V2X communication is investigated by exploiting the ISAC technique, where the RSU uses the echoes of the ISAC signals to estimate the motion parameters of the vehicles. Compared with traditional feedback‐based beam tracking, the proposed method can reduce the overall signaling costs and improve communication robustness. Furthermore, to achieve high accuracy and low latency for beam alignment, a Trajectory Adaptive Unscented Kalman Filter (TA‐UKF) beam tracking algorithm is proposed, which obtains the optimal state transition model following the change of the vehicle state. Considering practical application scenarios, an ISAC‐based adaptive beam coverage (ISAC‐AC) scheme is further developed for the beam tracking of extended targets, which can achieve the beam misalignment of vehicles in practical scenarios. Numerical results demonstrate that the proposed beam tracking and coverage strategies outperform baseline approaches. [ABSTRACT FROM AUTHOR]

BACKGROUND: Walnut proteins display poor solubility and dispersity under acidic pH conditions, which limits their application in acidic beverages and foods. This study aimed to fabricate stable nanocomplexes between phosphorylated walnut protein (PWPI) and chitosan (CS) in an acidic pH and to investigate the encapsulation capacity of the complexes. RESULTS: The PWPI/CS nanocomplexes prepared at a mass ratio of 2:1 showed small Z‐average sizes (approximately 285 nm at pH 5.5 and 222 nm at pH 3.5) with a narrow particle distribution (polydispersity index <0.3). Caffeic acid phenethyl ester (CAPE) can be effectively encapsulated into PWPI/CS with improved solubility. Circular dichroism analysis indicated that PWPI/CS and CAPE‐loaded PWPI/CS (PWPI/CS‐CAPE) had reduced α‐helical content and increased β‐sheet content. Fourier transform infrared spectroscopy analysis further identified the different driving forces for the complexation of PWPI and CS at pH 3.5 and 5.5 and confirmed the successful encapsulation of CAPE. The rheological results revealed that the PWPI/CS and PWPI/CS‐CAPE formed at pH 3.5 (PWPI/CS‐CAPE‐3.5) had a higher apparent viscosity and better viscoelasticity than the complexes formed at pH 5.5. The PWPI/CS‐CAPE‐3.5 also showed good stability under heat treatment, salt treatment, and long‐term storage. The PWPI/CS‐CAPE complexes showed controlled release of CAPE. CONCLUSION: Walnut protein and chitosan nanocomplexes prepared at acidic pH levels were stable and promising carriers for CAPE, which could expand the application of walnut proteins in the food industry. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE). The chronic graft versus host disease (cGVHD) mouse model is a well‐established model of SLE. LC3‐associated autophagy plays a critical role in extracellular particle clearance, including pathogens and apoptotic cells. Lupus Recipe (LR) is a Chinese herbal compound that has been proven to be effective in treating SLE. In the study, we investigated the protective effects of LR or LR combined with prednisone on cGVHD mouse model and LC3‐associated autophagy in the kidney. The mice were subjected to six groups. The LR treatment group received LR at the dosage of 1.15 and 2.3 g/kg/day, respectively. The corticosteroid treatment group received prednisone at a dosage of 5 mg/kg/day. The combination treatment group received LR at a dosage of 2.3 g/kg/day, and prednisone at 2.5 mg/kg/day. LR treatment reduced proteinuria and serum triglyceride levels, as well as spleen weight. LR also alleviated pathologic damage and immunoglobulin G deposition in the kidney. LR combined with a low dose of prednisone significantly improved kidney function and decreased serum triglyceride, total cholesterol, and spleen weight. In addition, combination treatment relieved kidney injury more effectively than LR alone. Western blot revealed that LR treatment or LR combined with prednisone increased the LC3‐associated autophagy protein of Rubicon and Nox2, as well as LC3I levels in the kidney tissues. In conclusion, LR inhibited the manifestation of cGVHD‐induced LN, which may attribute to the increased levels of LC3‐associated autophagy. [ABSTRACT FROM AUTHOR]

Summary: Background: Natural killer (NK) cells exhibit a selective deficiency of IFN‐γ production in chronic hepatitis B (CHB). Toll‐like receptor 8 (TLR8) agonists could induce IFN‐γ production in immune cells, although their effects on the deficiency in NK cells remain unclear. Aims: To investigate TLR8 expression in NK cells and the effect of TLR8 agonists in patients with CHB Methods: We enrolled 32 patients with CHB and 19 healthy controls to assess TLR8 expression and IFN‐γ production in NK cells. The sorted NK cells and monocytes were co‐cultured to compare the extent of IFN‐γ and IL‐10 production after TLR8 agonist ssRNA40 stimulation. The synergic effect of NK cells and monocytes was assessed by blocking IL‐12 and IL‐18. We recruited another 22 patients with CHB undergoing nucleotide analogue (NA) therapy to explore the impact of antiviral treatment on the ssRNA40‐mediated response of NK cells. Results: In patients with CHB, TLR8 expression in NK cells was up‐regulated, accompanied by insufficient IFN‐γ production. The enhanced IFN‐γ secretion by ssRNA40 in NK cells depended on monocyte‐derived IL‐12 and IL‐18. NK cells displayed an imbalanced response to ssRNA40 in patients with CHB with a weak increase in IFN‐γ despite a higher IL‐10 production. The response was improved in patients with CHB undergoing NA therapy. Conclusions: In patients with CHB, targeting TLR8 partially rescues the IFN‐γ insufficiency in NK cells. However, NK cells show an inhibitory response to TLR8 agonist stimulation. TLR8 agonist combined with NA may enhance the antiviral effect of NK cells. [ABSTRACT FROM AUTHOR]

The fomite transmission of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has drawn attention because of its highly contagious nature. Therefore, surfaces that can prevent coronavirus contamination are an urgent and unmet need during the coronavirus disease 2019 (COVID‐19) pandemic. Conventional surfaces are usually based on superhydrophobic or antiviral coatings. However, these coatings may be dysfunctional because of biofouling, which is the undesired adhesion of biomolecules. A superhydrophobic surface independent of the material content and coating agents may serve the purpose of antibiofouling and preventing viral transmission. Doubly reentrant topology (DRT) is a unique structure that can meet the need. This study demonstrates that the DRT surfaces possess a striking antibiofouling effect that can prevent viral contamination. This effect still exists even if the DRT surface is made of a hydrophilic material such as silicon oxide and copper. To the best of our knowledge, this work first demonstrates that fomite transmission of viruses may be prevented by minimizing the contact area between pathogens and surfaces even made of hydrophilic materials. Furthermore, the DRT geometry per se features excellent antibiofouling ability, which may shed light on the applications of pathogen elimination in alleviating the COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

Aim: To investigate the relationship between erythrocyte folate levels and cervical lesions. Methods: Using a case–control method, patients with cervical lesions from September 2021 to February 2022 in the Department of Obstetrics and Gynecology, Jiangnan University Hospital were selected as study subjects. After cervical biopsy, 40 cases of cervical intraepithelial neoplasia (CIN) CIN3 and 65 cases of cervical cancer as case group. The normal population of 120 cases attending the same period served as the control group. A competitive model was used to establish a chemiluminescence immunoassay (CLIA) for human erythrocyte folate. Erythrocyte folate levels of 225 subjects were determined. Results: Serum folate levels were 7.82 ± 3.13, 8.04 ± 3.58, and 7.58 ± 4.30 ng/ml in the control, CIN3, and cervical cancer groups, with no statistically significant differences (p = 0.959). Erythrocyte folate levels were 307.27 ± 122.95, 306.52 ± 189.77, and 285.42 ± 125.74 ng/ml, respectively, with statistically significant differences (p = 0.03). Conclusions: In a population of middle‐aged Chinese women, the lower the erythrocyte folate value, the greater the risk of cervical cancer. In addition, serum folate levels were not associated with cervical lesions. [ABSTRACT FROM AUTHOR]

BACKGROUND: The low solubility and poor dispersion of alkaline‐extracted walnut protein isolate (AWPI) limit its application as a protein‐based carrier for the delivery of poorly soluble nutraceuticals, including curcumin. This work investigated the physicochemical characteristics of phosphorylated walnut protein isolate (PWPI) extracted using sodium tripolyphosphate (STP) and evaluated its encapsulation ability. RESULTS: The results of phosphorus determination, X‐ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FTIR) spectroscopy confirmed the phosphorylation of the extracted PWPI. Circular dichroism (CD) analysis indicated that PWPI contained higher α‐helix and lower β‐sheet contents than AWPI. The PWPI prepared at pH 9.0 and 11.0 showed significantly improved solubility, similar surface hydrophobicity, and increased surface charges compared to the AWPI. Fluorescence quenching experiments indicated that the binding affinity of curcumin to PWPI was significantly higher than that of AWPI. When bound to PWPI, the solubility of curcumin in aqueous solution was greatly enhanced, with an 8700‐fold increase at a nanocomplex concentration of 10 mg mL−1. The complexation of curcumin with PWPI significantly improved the storage stability of curcumin. Additionally, the PWPI–curcumin nanocomplexes showed significantly increased antioxidant capacity. CONCLUSION: Phosphorylated walnut protein isolate showed greatly improved solubility and strong encapsulation ability, making it a promising nanocarrier for curcumin. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Understanding how natural and anthropogenic factors affects the watershed runoff and sediment yield at event scale can provide useful insights into watershed hydrological processes to guide watershed management. This article investigates the nonlinear relationships between natural and anthropogenic factors and event runoff and sediment yield with a boosted regression tree (BRT) model for 38 watersheds within the Loess Plateau in China during 2006 to 2016. The BRT model captures the relative importance of each natural and anthropogenic factors to the variability in runoff and sediment yield. The results show that these relationships are complex and highly nonlinear. The event runoff was most related to NDVI in the grass land (NDVI_g), with a 21.3% contribution, followed by 3‐day antecedent precipitation index (AP3), 10‐day antecedent precipitation index (AP10), precipitation (P), and 7‐day antecedent precipitation index (AP7). For event sediment yield, the strongest factor is AP3, with contribution of 33.3%, followed by P, NDVI in the forest land (NDVI_f), AP7, and NDVI in the crop land (NDVI_c). The marginal effect curves produced by the BRT are often characterized by thresholds. For instance, NDVI_f has the greatest effect on event sediment yield reduction when NDVI_f = 0.42, suggesting that a very intense green coverage is not necessary to achieve maximal soil erosion control. Vegetation coverage and meteorological factors can explain 54.7% of event runoff variation and 55.6% of event sediment yield variation. Our study identify the nonlinear relationships between runoff and sediment yield with vegetation cover and meteorological factors and provide scientific support for the planning of subsequent reforestation projects in the Loess Plateau. [ABSTRACT FROM AUTHOR]

N‐heterocyclic carbene (NHC) catalysis has become a versatile catalysis strategy for building molecules via unique reaction modes. Dual catalytic processes using NHCs in combination with additional modulating agents such as another organocatalyst or transition‐metal catalyst have also been studied. The clear selection of cocatalysts has led to enhanced reactivity, increased yields, and/or improved stereoselectivity. This minireview is to provide readers with a brief overview of the development and applications of NHC and hydrogen‐bond donor for dual catalytic reactions. [ABSTRACT FROM AUTHOR]

Apolipoprotein B mRNA‐editing enzyme catalytic polypeptide like (APOBEC) DNA cytidine deaminases convert cytosine to uracil in pathogen‐related single‐stranded DNAs. Aberrant activation of APOBEC enzymes in tumour cells leads to hypermutations that drive heterogeneity and clonal evolution, which results in tumour progression and treatment adaptation. APOBEC3 family member APOBEC3B (A3B) is a promising drug target to combat drug resistance, but the discovery of potent lead compounds remained challenging. Here, we devised a BspH1 restriction enzyme‐based biosensor to measure APOBEC deaminase activity, with superior simplicity and without the need of counter assays. Using this method, we performed a proof‐of‐concept screening using series of flavonoids and dihydrochalcones, from which bona fide inhibitors of recombinant A3B were identified and further validated by isothermal titration calorimetry. Our results demonstrate the capability of the BspH1‐based biosensor as a method for HTS, and prospects of developing potent A3B inhibitors using flavonoid and dihydrochalcone backbones. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are rounded vesicles enclosed by a lipid bilayer membrane, released by eukaryotic cells and by bacteria. They carry various types of bioactive substances, including nucleic acids, proteins, and lipids. Depending on their cargo, EVs have a variety of well‐studied functions in mammalian systems, including cell‐to‐cell communication, cancer progression, and pathogenesis. In contrast, EVs in plant cells (which have rigid walls) have received very little research attention for many decades. Increasing evidence during the past decade indicates that both plant cells and plant pathogens are able to produce and secrete EVs, and that such EVs play key roles in plant–pathogen interactions. Plant EVs contains small RNAs (sRNAs) and defence‐related proteins, and may be taken up by pathogenic fungi, resulting in reduced virulence. On the other hand, EVs released by gram‐negative bacteria contain a wide variety of effectors and small molecules capable of activating plant immune responses via pattern‐recognition receptor‐ and BRI1‐ASSOCIATED RECEPTOR KINASE‐ and SUPPRESSOR OF BIR1‐mediated signalling pathways, and salicylic acid‐dependent and ‐independent processes. The roles of EVs in plant–pathogen interactions are summarized in this review, with emphasis on important molecules (sRNAs, proteins) present in plant EVs. [ABSTRACT FROM AUTHOR]

Clip‐domain serine proteases (CLIPs) play important roles in insect innate immunity and development. Our previous studies indicated that CLIP13, an epidermis‐specific gene, was involved in cuticle remodeling during molting and metamorphosis in the silkworm, Bombyx mori. However, the transcriptional regulatory mechanism and regulatory pathways of CLIP13 remained unclear. In the present study, we investigated CLIP13 expression and the regulation pathway controlled by 20‐hydroxyecdysone (20E) in the silkworm. At the transcriptional level, expression of CLIP13 exhibited pronounced spatial and temporal specificity in different regions of the epidermis; homeodomain transcription factors POU‐M2, antennapedia (Antp), and abdominal‐B (Abd‐B) showed similar expression change trends as CLIP13 in the head capsule, thorax, and abdomen, respectively. Furthermore, results of cell transfection assays, electrophoretic mobility shift assays, and chromatin immunoprecipitation demonstrated that POU‐M2, Antp, and Abd‐B were involved in the transcriptional regulation of CLIP13 by directly binding to their cis‐response elements in CLIP13 promoter. RNA interference‐mediated silencing of POU‐M2, Antp, and Abd‐B led to a decrease of CLIP13 expression in the head capsule, the epidermis of the 1st to 3rd thoracic segments and the 7th to 10th abdominal segments, respectively. Consistent with CLIP13, 20E treatment significantly upregulated expression of POU‐M2, Antp, and Abd‐B in the silkworm epidermis. Taken together, these data suggest that 20E positively regulates transcription of CLIP13 via homeodomain proteins POU‐M2, Antp, and Abd‐B in different regions of the silkworm epidermis during metamorphosis, thus affecting the molting process. Our findings provide new insight into the functions of homeodomain transcription factors in insect molting. [ABSTRACT FROM AUTHOR]

Introduction: Low‐concentration oxygen is an established way for the treatment of chronic obstructive pulmonary disease (COPD) with Type II respiratory failure. Hypercapnia can complicate both COPD exacerbations and stable COPD. Treating with noninvasive ventilation (NIV) can reduce carbon dioxide tension in arterial (PaCO2) in hypercapnic COPD. As an open system, high‐flow nasal cannula oxygen (HFNC) is easy to tolerate and use. More researches are needed to focus on how HFNC is used to treat COPD patients with hypercapnic respiratory failure. Methods: The Cochrane Library, Medline, EMBASE, and CINAHL database were retrieved from inception to October 2019. Eligible trials were clinical randomized controlled trials comparing the effects of HFNC and conventional oxygen on hypercapnic COPD patients. Two researchers assessed the quality of each study and extracted the data into RevMan 5.3 independently. The primary outcome was PaCO2 and the secondary outcome was PaO2. Results: Four RCTs with 329 patients were included. The research results indicated that PaCO2 in the HFNC group was similar to the conventional oxygen group. No significant difference were observed in PaCO2 (MD −0.98, CI: −2.67 to 0.71, Z = 1.14, p = 0.25) and PaO2 (MD −0.72, CI: −6.99 to 5.55, Z = 0.23, p = 0.82) between the HFNC group and conventional oxygen group. Conclusions: Our meta‐analysis showed no difference in PO2 and PCO2 between the HFNC and conventional oxygen. But we should treat this conclusion with caution because the number of studies and participants is small and, there is heterogeneity in the PaO2 and PCO2 measurements between stable and AECOPD. [ABSTRACT FROM AUTHOR]

Aminoacyl‐tRNA synthetase‐interacting multifunctional protein‐3 (AIMP3) is a tumour suppressor, however, the roles of AIMP3 in non‐small cell lung cancer (NSCLC) are not explored yet. Here, we reported that AIMP3 significantly inhibited the cell growth and metastasis of NSCLC (lung adenocarcinoma) in vitro and in vivo. We have firstly identified that AIMP3 was down‐regulated in human NSCLC tissues compared with adjacent normal lung tissues using immunohistochemistry and western blot assays. Overexpression of AIMP3 markedly suppressed the proliferation and migration of cancer cells in a p53‐dependent manner. Furthermore, we observed that AIMP3 significantly suppressed tumour growth and metastasis of A549 cells in xenograft nude mice. Mechanically, we identified that AIMP3 was a direct target of miR‐96‐5p, and we also observed that there was a negative correlation between AIMP3 and miR‐96‐5p expression in paired NSCLC clinic samples. Ectopic miR‐96‐5p expression promoted the proliferation and migration of cancer cells in vitro and tumour growth and metastasis in vivo which partially depended on AIMP3. Taken together, our results demonstrated that the axis of miR‐96‐5p‐AIMP3‐p53 played an important role in lung adenocarcinoma, which may provide a new strategy for the diagnosis and treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Buried salt bridges widely exist in protein structures but are rarely used in synthetic systems for molecular recognition in water. By mimicking the binding pocket of bioreceptors, we designed and synthesized a pair of endo‐functionalized macrocyclic hosts with secondary ammonium groups in a hydrophobic cavity. We found that these macrocycles are able to selectively recognize carboxylic acids in water through salt bridges and the hydrophobic effect. Moreover, it was demonstrated that these macrocyclic receptors can be used in circular‐dichroism‐based optical chirality sensing of chiral carboxylic acids and fluorescent sensing of phenylpyruvic acid—a biomarker for phenylketonuria. This research showcases that buried salt bridges can be effectively used by endo‐functionalized macrocyclic hosts for molecular recognition in water, where solvent screening on polar noncovalent interactions is high. [ABSTRACT FROM AUTHOR]

Melatonin (N‐acetyl‐5‐methoxytryptamine) plays important roles in plant defences against a variety of biotic and abiotic stresses, including UV‐B stress. Molecular mechanisms underlying functions of melatonin in plant UV‐B responses are poorly understood. Here, we show that melatonin effect on molecular signalling pathways, physiological changes and UV‐B stress resistance in Arabidopsis. Both exogenous and endogenous melatonin affected expression of UV‐B signal transduction pathway genes. Experiments using UV‐B signalling component mutants cop1‐4 and hy5‐215 revealed that melatonin not only acts as an antioxidant to promote UV‐B stress resistance, but also regulates expression of several key components of UV‐B signalling pathway, including ubiquitin‐degrading enzyme (COP1), transcription factors (HY5, HYH) and RUP1/2. Our findings indicate that melatonin delays and subsequently enhances expression of COP1, HY5, HYH and RUP1/2, which act as central effectors in UV‐B signalling pathway, thus regulating their effects on antioxidant systems to protect the plant from UV‐B stress. Several studies have demonstrated that melatonin plays a role in UV‐B responses, however, the molecular mechanism whereby melatonin affects the UV‐B pathway was not clear. This study examined the function of melatonin in molecular signaling pathways, physiological changes, and UV‐B stress resistance under UV‐B radiation in Arabidopsis. Exogenous melatonin treatment experiment indicated that melatonin could enhance the transcriptional level of genes on UV‐B signaling pathway and ameliorate ROS damage caused by UV‐B stress. This result was verified in SNAT overexpressing lines and knock‐down mutant. [ABSTRACT FROM AUTHOR]

Tumour‐associated macrophages (TAMs), which possess M2‐like characters and are derived from immature monocytes in the circulatory system, represent a predominant population of inflammatory cells in solid tumours. TAM infiltration in tumour microenvironment can be used as an important prognostic marker in many cancer types and is a potential target for cancer prevention or treatment. VEGI‐251 not only is involved in the inhibition of tumour angiogenesis, but also participates in the regulation of host immunity. This work aimed to investigate the involvement of VEGI‐251 in the regulation of specific antitumour immunity. We found that recombinant human VEGI‐251(rhVEGI‐251) efficiently mediated the elimination of TAMs in tumour tissue in mice, and induced apoptosis of purified TAMs in vitro. During this process, caspase‐8 and caspase‐3 were activated, leading to PARP cleavage and apoptosis. Most importantly, we further elucidated the mechanism underlying VEGI‐251‐triggered TAM apoptosis, which suggests that ASK1, an intermediate component of the VEGI‐251, activates the JNK pathway via TRAF2 in a potentially DR3‐dependent manner in the process of TAM apoptosis. Collectively, our findings provide new insights into the basic mechanisms underlying the actions of VEGI‐251 that might lead to future development of antitumour therapeutic strategies using VEGI‐251 to target TAMs. [ABSTRACT FROM AUTHOR]

Aim: Disturbances in mineral metabolism markers are common in patients with chronic kidney disease but there is no consensus on the association between these markers and clinical outcomes. This study investigated associations between mineral metabolism parameters and mortality in Chinese peritoneal dialysis (PD) patients. Methods: This was a single‐centre retrospective cohort study. Incident PD patients between 1 January 2006 and 31 December 2013 with baseline phosphate, albumin‐corrected calcium, and calcium‐phosphate product data were enrolled. Associations between these parameters and all‐cause and cardiovascular mortality were assessed using multivariable‐adjusted Cox models. Results: Of 1662 patients (mean age: 47.4 ± 15.3 years), 59.3% were male and 23.8% had diabetes. Over a median 38.1 month (interquartile range: 21.3–59.7 months) follow‐up period, 382 (23.0%) patients died. After adjusting for confounders, the higher serum phosphate level (>1.78 mmol/L) and calcium‐phosphate product level (≥4.4 mmol2/L2) were significantly associated with an increased risk for all‐cause mortality (hazards ratio (HR) = 1.818, 95% CI = 1.379–2.396 and HR = 1.735, 95% CI = 1.261–2.386) and cardiovascular mortality (HR = 2.069, 95% CI = 1.428–2.998 and HR = 2.175, 95% CI = 1.450–3.262), respectively. While each 1 mmol/L higher baseline albumin‐corrected calcium level was associated with an 14.3% (95% CI = 0.749–0.981) lower risk for all‐cause mortality after adjusting for potential confounders. Conclusion: Abnormalities in mineral metabolism markers, particularly higher serum phosphate and calcium‐phosphate product levels, at the commencement of PD were independently associated with increased all‐cause and cardiovascular mortality in this cohort of PD patients. SUMMARY AT A GLANCE: The authors showed that high serum phosphate at the commencement of peritoneal dialysis was independently associated with increased all‐cause and cardiovascular mortality in a sizeable cohort of over 1,600 patients. [ABSTRACT FROM AUTHOR]

Selective intrauterine growth restriction (sIUGR), which affects approximately 10%‐15% of monochorionic (MC) twin pregnancies, is highly associated with intrauterine foetal death and neurological impairment in both twins. Data suggest that unequal sharing of the single placenta is the main contributor to birth weight discordance. While MC twins and their placenta derive from a single zygote and harbour almost identical genetic material, the underlying mechanisms of phenotypic discrepancies in MC twins remain unclear. MicroRNAs are small non‐coding RNA molecules that regulate gene expression but do not change the DNA sequence. Our preliminary study showed that microRNA‐210‐3p (miR‐210‐3p) was significantly upregulated in the placental share of the smaller sIUGR twin. Here, we investigate the potential role of miR‐210‐3p in placental dysplasia, which generally results from dysfunction of trophoblast cells. Functional analysis revealed that miR‐210‐3p, induced by hypoxia‐inducible factor 1α (HIF1α) under hypoxic conditions, suppressed the proliferation and invasiveness of trophoblast cell lines. Further RNA sequencing analysis and luciferase reporter assays were performed, revealing that fibroblast growth factor 1 (FGF1) is an influential target gene of miR‐210‐3p. Moreover, correlations among miR‐210‐3p levels, HIF1α and FGF1 expression and the smaller placental share were validated in sIUGR specimens. These findings suggest that upregulation of miR‐210‐3p may contribute to impaired placentation of the smaller twin by decreasing FGF1 expression in sIUGR. [ABSTRACT FROM AUTHOR]

Vanadium (V) can induce cell apoptosis in layers' oviduct resulting in egg quality reduction. In this study, we investigated the relationship between the mitogen‐activated protein kinase (MAPK)‐signaling pathway and V‐induced apoptosis in poultry oviduct magnum epithelial cells (OMECs). Cultured OMECs were divided into 8 treatment groups: 0 μmol/L V (control), 100 μmol/L V (V100), V100 + P38MAPK inhibitor (SB203580), SB203580, V100 + extracellular signal‐regulated kinases 1 and 2 (ERK1/2) inhibitor (U0126), U0126, V100 + c‐JUN NH2‐terminal kinase (JNK) inhibitor (SP600125), and SP600125. The OMECs were pretreated with the MAPK inhibitors before their treatment with V100 for 12 h. V100 increased the apoptosis of OMECs (P <.05), while 3 MAPK inhibitors suppressed V100‐induced apoptosis P <.05); V100 enhanced the depolarization of △ψm (P <.05), and SB203580 and U0126 alleviated the V100‐induced △ψm decrease (P <.05); V100 downregulated B‐cell lymphoma‐2 (Bcl‐2) and poly [Adenosine diphosphate ribose] polymerase 1 (PARP1) mRNA expression (P <.05), meanwhile it upregulated Bcl‐2 associated x (Bax), Apaf1, cytochrome C (CytC) and cysteine aspartase (caspase) 3, 8, 9 mRNA expression (P <.05). All MAPKs inhibitors alleviated the up‐regulation of V100 for Bax and caspase 3 mRNA expression and down‐regulation of V100 for Bcl‐2 expression (P <.05). SB203580 and U0126 upregulated CytC expression treated by V100 (P <.05), except SP600125, while SB203580 administration resulted in a similar upregulation of PARP1 expression (P <.05). SP600125 can alleviated V triggered p‐P38MAPK (phosphor‐P38), p‐ERK1/2 (phosphor‐ERK1/2), p‐JNK (phosphor‐JNK) increase on OME cells, and SB203580 and U0126 had a similar response to phosphor‐P38 and p‐JNK (P <.05). It concluded that V‐induced apoptosis in OMECs through the activation of P38 and ERK1/2, and by increasing the ratio of Bax/Bcl‐2, which resulted in △ψm decrease, CytC release into the cytosol; consequently caspase 3 is recruited and activated, PARP1 is cleaved, eventually leading to apoptosis. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Pallister‐Killian syndrome (PKS) is often incidentally diagnosed prenatally due to ultrasound abnormalities or advanced maternal age. Severely shortened limbs could be the most outstanding abnormal observation in a fetus with PKS. PKS can be detected with the highest mosaic ratio by chromosomal microarray analysis (CMA) on uncultured amniocytes prenatally. [ABSTRACT FROM AUTHOR]

Hand‐foot syndrome (HFS) is the most common adverse effect of capecitabine‐containing chemotherapy. The purpose of this study was to assess the efficacies of various prevention and treatment strategies for capecitabine‐induced HFS. Searches of the PubMed and Embase databases were performed to identify relevant studies. The risk ratio (RR) with the corresponding 95% confidence interval (CI) was used as an effect measure to evaluate the efficacies of these prevention and treatment strategies. Publication bias was evaluated using Begg's and Egger's tests. Overall and subgroup analyses were conducted. All statistical analyses were conducted with Stata software version 12.0. Seventeen eligible studies were included. Our results indicated that celecoxib was significantly associated with a lower incidence of grade ≥2 capecitabine‐induced HFS without heterogeneity (RR = 0.43, 95% CI = 0.23–0.81, I2 = 0.0%). However, pyridoxine and topical urea/lactic acid were not effective toward preventing capecitabine‐induced grade 1, 2, 3, ≥1 or ≥2 HFS. Moreover, pyridoxine was not effective in treating capecitabine‐induced HFS. Similar results were obtained by subgroup analysis. Our results indicate that celecoxib has potential prophylactic efficacy for capecitabine‐induced HFS. However, pyridoxine and topical urea/lactic acid are not associated with a decrease in the incidence of capecitabine‐induced HFS. [ABSTRACT FROM AUTHOR]

Objective: To investigate the types of cardiovascular anomalies and the results of invasive prenatal diagnosis in twin fetuses.Methods: A total of 298 fetuses in 149 twin pairs were enrolled, in which 1 or 2 fetuses of a twin pair had cardiovascular anomalies. Prenatal diagnosis was performed on 290 fetuses of 149 twin pairs, including 150 monochorionic diamniotic (MCDA) fetuses (79 pairs) and 140 dichorionic diamniotic (DCDA) fetuses (70 pairs). G-Banding karyotyping and/or chromosomal microarray analysis were performed. The types of cardiovascular anomalies and the results of prenatal diagnosis were analyzed.Results: Fifty percent (79/158) fetuses in MCDA group and 52.1% (73/140) fetuses in DCDA group were diagnosed with cardiovascular anomalies by ultrasound. Primary cardiac structural defects such as septal defects and tetralogy of Fallot were more common in DCDA group than in MCDA group, while acardiac anomaly was the most common in MCDA group. Chromosomal aberrations were identified in 7.7% fetuses (11/142) of MCDA group and in 18.3% fetuses (22/120) of DCDA group by G-banding karyotyping. Except benign copy number variations (CNVs), 37 CNVs (pathogenic, likely pathogenic, and variant of uncertain significance) and chromosomal aberrations were detected in 21.3% (32/150) fetuses of MCDA group and 47 CNVs (pathogenic, likely pathogenic, and variant of uncertain significance) and chromosomal aberrations were detected in 32.1% (45/140) fetuses of DCDA group by chromosomal microarray analysis.Conclusions: Most of cardiovascular anomalies were identified in one fetus of a twin pair no matter in MCDA or DCDA twin. Primary cardiac structural defects were more common in DCDA group. Monozygotic twins may have discordant phenotypes, karyotypes, and CNVs between 2 fetuses of each pair. [ABSTRACT FROM AUTHOR]

It has been recently reported that CD38 was highly expressed in adipose tissues from obese people and CD38-deficient mice were resistant to high-fat diet ( HFD)-induced obesity. However, the role of CD38 in the regulation of adipogenesis and lipogenesis is unknown. In this study, to explore the roles of CD38 in adipogenesis and lipogenesis in vivo and in vitro, obesity models were generated with male CD38−/− and WT mice fed with HFD. The adipocyte differentiations were induced with MEFs from WT and CD38−/− mice, 3T3-L1 and C3H10T1/2 cells in vitro. The lipid accumulations and the alternations of CD38 and the genes involved in adipogenesis and lipogenesis were determined with the adipose tissues from the HFD-fed mice or the MEFs, 3T3-L1 and C3H10T1/2 cells during induction of adipocyte differentiation. The results showed that CD38−/− male mice were significantly resistant to HFD-induced obesity. CD38 expressions in adipocytes were significantly increased in WT mice fed with HFD, and the similar results were obtained from WT MEFs, 3T3-L1 and C3H10T1/2 during induction of adipocyte differentiation. The expressions of PPARγ, AP2 and C/ EBPα were markedly attenuated in adipocytes from HFD-fed CD38−/− mice and CD38−/− MEFs at late stage of adipocyte differentiation. Moreover, the expressions of SREBP1 and FASN were also significantly decreased in CD38−/− MEFs. Finally, the CD38 deficiency-mediated activations of Sirt1 signalling were up-regulated or down-regulated by resveratrol and nicotinamide, respectively. These results suggest that CD38 deficiency impairs adipogenesis and lipogenesis through activating Sirt1/ PPARγ- FASN signalling pathway during the development of obesity. [ABSTRACT FROM AUTHOR]

Objective The mutant γ-aminobutyric acid type A ( GABAA) receptor γ2(Q390X) subunit (Q351X in the mature peptide) has been associated with the epileptic encephalopathy, Dravet syndrome, and the epilepsy syndrome genetic epilepsy with febrile seizures plus ( GEFS+). The mutation generates a premature stop codon that results in translation of a stable truncated and misfolded γ2 subunit that accumulates in neurons, forms intracellular aggregates, disrupts incorporation of γ2 subunits into GABAA receptors, and affects trafficking of partnering α and β subunits. Heterozygous Gabrg2 +/Q390X knock-in ( KI) mice had reduced cortical inhibition, spike wave discharges on electroencephalography (EEG), a lower seizure threshold to the convulsant drug pentylenetetrazol ( PTZ), and spontaneous generalized tonic-clonic seizures. In this proof-of-principal study, we attempted to rescue these deficits in KI mice using a γ2 subunit gene ( GABRG2) replacement therapy. Methods We introduced the GABRG2 allele by crossing Gabrg2 +/Q390X KI mice with bacterial artificial chromosome ( BAC) transgenic mice overexpressing HA (hemagglutinin)-tagged human γ2 HA subunits, and compared GABAA receptor subunit expression by Western blot and immunohistochemical staining, seizure threshold by monitoring mouse behavior after PTZ-injection, and thalamocortical inhibition and network oscillation by slice recording. Results Compared to KI mice, adult mice carrying both mutant allele and transgene had increased wild-type γ2 and partnering α1 and β2/3 subunits, increased miniature inhibitory postsynaptic current ( mIPSC) amplitudes recorded from layer VI cortical neurons, reduced thalamocortical network oscillations, and higher PTZ seizure threshold. Significance Based on these results we suggest that seizures in a genetic epilepsy syndrome caused by epilepsy mutant γ2(Q390X) subunits with dominant negative effects could be rescued potentially by overexpression of wild-type γ2 subunits. [ABSTRACT FROM AUTHOR]

Novel supramolecular vesicles based on host-guest systems were coassembled from carboxylate-substituted pillar[6]arene (CPA[6]) and disulfide-linked benzimidazolium amphiphiles, and the microstructures of the CPA-based supramolecular vesicles were clearly elaborated. The supramolecular vesicles showed controlled drug release in response to five stimuli, with glutathione, pH, CO2, Zn2+ ions, and hexanediamine, leading to cleavage of the disulfide bonds, protonation of the carboxylate groups, metal chelation, and competitive binding. This is the first case of a smart pillararene-based supramolecular vesicle being integrated with five stimuli-responsive functions to meet the diverse requirements of controlled drug release. Importantly, each of the five stimuli is closely related to microenvironments of tumors and diseases of the human body. The smart stimuli-responsive supramolecular vesicles have promising applications in drug therapy of tumors and relevant diseases. [ABSTRACT FROM AUTHOR]

Objective To determine the safety and clinical efficacy of two anti-angiogenic agents, bevacizumab and lenalidomide, with docetaxel and prednisone. Patients and methods Eligible patients with metastatic castration-resistant prostate cancer enrolled in this open-label, phase II study of lenalidomide with bevacizumab (15 mg/kg), docetaxel (75 mg/m2) and prednisone (10 mg daily). Docetaxel and bevacizumab were administered on day 1 of a 3-week treatment cycle. To establish safety, lenalidomide dosing in this combination was escalated in a conventional 3 + 3 design (15, 20 and 25 mg daily for 2 weeks followed by 1 week off). Patients received supportive measures including prophylactic pegfilgrastim and enoxaparin. The primary endpoints were safety and clinical efficacy. Results A total of 63 patients enrolled in this trial. Toxicities were manageable with most common adverse events ( AEs) being haematological, and were ascertained by weekly blood counts. Twenty-nine patients (46%) had grade 4 neutropenia, 20 (32%) had grade 3 anaemia and seven (11%) had grade 3 thrombocytopenia. Despite frequent neutropenia, serious infections were rare. Other common non-haematological grade 3 AEs included fatigue (10%) and diarrhoea (10%). Grade 2 AEs in >10% of patients included anorexia, weight loss, constipation, osteonecrosis of the jaw, rash and dyspnoea. Of 61 evaluable patients, 57 (93%), 55 (90%) and 33 (54%) had PSA declines of >30, >50 and >90%, respectively. Of the 29 evaluable patients, 24 (86%) had a confirmed radiographic partial response. The median times to progression and overall survival were 18.2 and 24.6 months, respectively. Conclusions With appropriate supportive measures, combination angiogenesis inhibition can be safely administered and potentially provide clinical benefit. These hypothesis-generating data would require randomized trials to confirm the findings. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical value of chromosomal microarray analysis (CMA) in the prenatal diagnosis of chromosomal abnormalities in fetal growth restriction (FGR) cases.Method: The ultrasound findings of 107 FGR cases subjected to invasive prenatal diagnostic testing from March 2013 to October 2015 were retrospectively reviewed. Karyotyping was performed in all cases, and CMA was performed in 80 cases.Results: In our study, karyotype analysis identified chromosomal aberrations in 9.3% (10/107) of the cases, while CMA detected abnormalities in 18.8% (15/80) of the cases. CMA achieved a 11.4% detection rate of chromosomal abnormalities among FGR cases with a normal karyotype. Among 53 FGR cases without malformations, CMA increased (9.4%; 95%CI, 1.6%-17.3%) the detection rate of chromosomal abnormalities. CMA identified more chromosomal abnormalities (50.0%; 95%CI, 19.0%-81.0%) than karyotyping (30.0%; 95%CI, 7.0%-65.0%) among the cases diagnosed during the second trimester. Further, the detection rate in cases with asymmetric FGR was higher with CMA (33.3%; 95%CI, 10.0%-65.0%) than with karyotyping (16.7 %; 95%CI, 2.0%-48.0%).Conclusion: Our study highlights the added value of CMA compared with karyotyping in evaluation of asymmetric FGR cases diagnosed during the second trimester without sonographic anomalies. © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Myocardin is frequently repressed during human malignant transformation, and restoration of myocardin expression in sarcoma cells contributes to the inhibition of malignant growth. However, its role in breast carcinoma has barely been addressed. Here, we reported that myocardin could inhibit the proliferation of MCF-7 cells. Notably, we show that myocardin inhibited ERα-mediated proliferation of breast cancer MCF-7 via impairing ER-dependent transcriptional activation, mainly through the inhibition of the activity of ERα. Importantly, the molecular mechanism for the inhibition of the ERα-mediated proliferation is that myocardin inhibited the transcription and expression of ERα-induced PCNA, Ki-67, and E2F1 to impair ERα-mediated proliferation of breast cancer MCF-7. Interestingly, myocardin significantly enhanced the transcription and expression of miR-885 depending on the CArG box in miR-885 promoter, and miR-885 targeted the 3′ untranslated regions (UTR) of E2F1 to silence the expression of E2F1. Thus, our data provided important and novel insights into how myocardin may deeply influence ERα-mediated breast cancer proliferation. In conclusion, myocardin could be seen as a breast cancer tumor suppressor so that it will provide new ideas for the treatment of breast cancer. © 2016 IUBMB Life, 68(6):477-487, 2016 [ABSTRACT FROM AUTHOR]

Objectives Micro RNAs (mi RNAs) are endogenous small non-coding RNAs that regulate proteins and mRNAs for degradation or translational suppression. Up to now, the role of miR-372 in renal cell carcinoma has remained unknown; in this study, we have aimed to reveal its functional importance in this tumour. Materials and methods qRT- PCR was performed to measure expression levels of miR-372 in renal cell carcinoma cell lines and tissues. CCK-8 and an invasion assay were performed to measure its functional role. Luciferase assays, qRT- PCR and western blotting were performed to discover miR-372′s target gene. Results We demonstrated that mi RNA-372 was down-regulated in renal cell carcinoma cell lines and tissue specimens; its over-expression inhibited cell proliferation and invasion. Moreover, we showed that mi RNA-372 repressed insulin-like growth factor 2 mRNA-binding protein 1 ( IGF2 BP1) expression by directly interacting with its putative binding site at the 3′- UTR. Furthermore, ectopic expression of IGF2 BP1 significantly reversed suppression of cell proliferation and invasion caused by miR-372 over-expression. Conclusions Our data indicated that miR-372 seemed to function as a tumour suppressor in renal cell carcinoma progression by inhibiting the IGF2 BP1 expression. [ABSTRACT FROM AUTHOR]

To synthesize 18F-labeled positron emission tomography (PET) ligands, reliable labeling techniques inserting 18F into a target molecule are necessary. The 18F-fluorobenzene moiety has been widely utilized in the synthesis of 18F-labeled compounds. The present study utilized [18F]-labeled aniline as intermediate in [18F]-radiolabeling chemistry for the facile radiosynthesis of 4-amino- N-(3-chloro-4-fluorophenyl)- N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide ([18F]IDO5L) as indoleamine 2,3-dioxygenase 1 (IDO1) targeted tracer. IDO5L is a highly potent inhibitor of IDO1 with low nanomolar IC50. [18F]IDO5L was synthesized via coupling [18F]3-chloro-4-fluoroaniline with carboximidamidoyl chloride as a potential PET probe for imaging IDO1 expression. Under the optimized labeling conditions, chemically and radiochemically pure (>98%) [18F]IDO5L was obtained with specific radioactivity ranging from 11 to 15 GBq/µmol at the end of synthesis within ~90 min, and the decay-corrected radiochemical yield was 18.2 ± 2.1% ( n = 4). [ABSTRACT FROM AUTHOR]

We present a parallel matrix-free implicit finite volume scheme for the solution of unsteady three-dimensional advection-diffusion-reaction equations with smooth and Dirac-Delta source terms. The scheme is formally second order in space and a Newton-Krylov method is employed for the appearing nonlinear systems in the implicit time integration. The matrix-vector product required is hardcoded without any approximations, obtaining a matrix-free method that needs little storage and is well-suited for parallel implementation. We describe the matrix-free implementation of the method in detail and give numerical evidence of its second-order convergence in the presence of smooth source terms. For nonsmooth source terms, the convergence order drops to one half. Furthermore, we demonstrate the method's applicability for the long-time simulation of calcium flow in heart cells and show its parallel scaling. © 2014 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq31: 143-167, 2015 [ABSTRACT FROM AUTHOR]

ABSTRACT Objective The aim of this article is to investigate the prevalence, clinical presentation, prenatal management, and prognosis of mirror syndrome associated with twin-twin transfusion syndrome (TTTS) treated by amnioreduction or selective fetocide. Method A retrospective study of twin pregnancies with TTTS was conducted. The prevalence of mirror syndrome, defined as severe maternal edema related to fetal hydrops and placental edema, was calculated for TTTS, and data on clinical characteristics, treatment, and outcomes of the patients were reviewed. Results We observed mirror syndrome in 4.85% (5/103) of pregnancies with TTTS and 26.32% (5/19) of pregnancies with TTTS Stage IV. Most cases (4/5) of mirror syndrome associated with TTTS were diagnosed before 24 weeks of gestation. The patients manifested edema, anemia, hemodilution, and hypoproteinemia (5/5); proteinuria (4/5); complicated postpartum hemorrhage (4/5); and pulmonary edema and congestive heart failure (2/5). Maternal hemoglobin, hematocrit, and plasma protein dropped after amnioreduction. The perinatal survival rate at 28 days was 28.57% (2/7), and only one infant born after selective feticide survived beyond 18 months. Conclusion TTTS carries a high risk of mirror syndrome, a disease with significant materno-fetal mortality and morbidity. Amnioreduction alone or with selective feticide in mirror syndrome may transiently aggravate anemia and hemodilution and lead to severe maternal complications. © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Autocorrelation or nonstationarity may seriously impact the performance of conventional Hotelling's T2 charts. We suggest modeling processes with multivariate autoregressive integrated moving average time series models and propose two model-based monitoring charts. One monitors the predicted value and provides information about the need for mean adjustments. The other is a Hotelling's T2 control chart applied to the residuals. The average run length performance of the residual-based Hotelling's T2 chart is compared with the observed data-based Hotelling's T2 chart for a group of first-order vector autoregressive models. We show that the new chart in most cases performs well. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective The objective of this study is to assess the performance of noninvasive prenatal testing for trisomies 21 and 18 on the basis of massively parallel sequencing of cell-free DNA from maternal plasma in twin pregnancies. Method A double-blind study was performed over 12 months. A total of 189 pregnant women carrying twins were recruited from seven hospitals. Maternal plasma DNA sequencing was performed to detect trisomies 21 and 18. The fetal karyotype was used as gold standard to estimate the sensitivity and specificity of sequencing-based noninvasive prenatal test. Results There were nine cases of trisomy 21 and two cases of trisomy 18 confirmed by karyotyping. Plasma DNA sequencing correctly identified nine cases of trisomy 21 and one case of trisomy 18. The discordant case of trisomy 18 was an unusual case of monozygotic twin with discordant fetal karyotype (one normal and the other trisomy 18). The sensitivity and specificity of maternal plasma DNA sequencing for fetal trisomy 21 were both 100% and for fetal trisomy 18 were 50% and 100%, respectively. Conclusion Our study further supported that sequencing-based noninvasive prenatal testing of trisomy 21 in twin pregnancies could be achieved with a high accuracy, which could effectively avoid almost 95% of invasive prenatal diagnosis procedures. © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

SERPINA3 K, also known as kallikrein-binding protein ( KBP), is a serine proteinase inhibitor with anti-inflammatory and anti-angiogenic activities. Our previous studies showed that SERPINA3 K inhibited proliferation in a dose-dependent manner and induced apoptosis of endothelial cells but had no influence on SGC-7901 gastric carcinoma cells or Hep G2 hepatocarcinoma cells. However, it is unknown whether SERPINA3 K has a direct impact on other carcinoma cells and which mechanisms are involved. In this study, we report for the first time that SERPINA3 K not only decreased cell viability but also induced apoptosis in the colorectal carcinoma cell lines SW480 and HT-29. SERPINA3 K-induced apoptosis of SW480 and HT-29 was rescued by interference with Fas ligand ( Fas L) small hairpin RNA. Moreover, SERPINA3 K increased the expression of Fas L and activated caspase-8. Peroxisome proliferator-activated receptor γ ( PPARγ), a transcription factor of Fas L, was also upregulated by SERPINA3 K in a dose-dependent manner. The upregulation effect of Fas L induced by SERPINA3 K was reversed after interference with PPARγ small interfering RNA. These results demonstrated that SERPINA3 K-induced SW480 and HT-29 cell apoptosis was mediated by the PPARγ/ Fas/ Fas L signaling pathway. Therefore, our study provides additional insight into the direct anti-tumor function by inducing tumor cell apoptosis of SERPINA3 K in colorectal tumors. [ABSTRACT FROM AUTHOR]

Macht hoch die Tür: Eine Fracht (rosa Würfel) kann gezielt aus den durch Lectin (blaue Quadrate) verschlossenen Nanoporen eines mit Mannose (grüne Schlaufen) funktionalisierten mesoporösen Siliciumdioxids freigesetzt werden (siehe Schema). Die Proteinnanogatter können entweder durch pH ‐ Senkung des Puffers oder durch Zusatz von Glucose (gelbe Ringe) als konkurrierendes Agens geöffnet werden, um die Fracht aus den Poren zu entlassen. [ABSTRACT FROM AUTHOR]

Weniger stabil, aber natürlich: Die asymmetrische Totalsynthese von Leucosceptroid B (siehe Schema) gelang in 19 Schritten. Dieser Naturstoff erweist sich als thermodynamisch weniger stabil als sein C11 ‐ Epimer, das ein synthetisches Intermediat ist. Die Synthese zeichnet sich durch ein hohes Maß an Flexibilität aus, was ihre Anwendung auf die Herstellung eines breiten Spektrums natürlicher Derivate ermöglicht. [ABSTRACT FROM AUTHOR]